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PERINATAL JOURNAL
Volume 14 / Issue 1 / 2006
The Official Publication of Turkish Perinatology Society
On behalf of the Turkish Perinatology Society: Murat Yayla
Managing Editor: Cihat fien
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Managing the patent ductus arteriosus in the premature neonate: a new
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— Article published in an only electronic journal: Lee J, Romero R,
Xu Y, Kim JS, Topping V, Yoo W, et al. A signature of maternal anti-fetal
rejection in spontaneous preterm birth: chronic chorioamnionitis, antihuman leukocyte antigen antibodies, and C4d. PLoS ONE 2011;6:e16806.
doi:10.1371/ journal.pone.0011846.
— Book: Jones KL. Practical perinatology. New York: Springer; 1990.
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Perinatal Journal
Volume 14 / Issue 1 / 2006
Contents
Research Articles
Case Reports
Perinatal Outcome of Pregnancy on Over Age 40
Ali Gedikbafl›, Alpaslan Akyol, Varujan Ma¤ar, Cemal Ark, Yavuz Ceylan
1
Evaluation of the Prenatal Care Usage of Mothers Giving Birth at the
Ministry of Health, Ankara Etlik Training and Research Hospital of
Obstetrics and Gynecology
Emine Dibek M›s›rl›o¤lu, Didem Aliefendio¤lu, Kibriya Fidan,
Fatma Nur Çakmak, Ali Haberal
7
The Correlation of Thyroid Hormone Levels and Gestasional Weeks in
Amniotic Fluid at Second Trimester
Ahmet Kale, Nurten Akdeniz, Ebru Kale, Ahmet Yal›nkaya, Murat Yayla
14
Second Trimester Termination of Pregnancy:
Comparing Intracervical Prostaglandin E2 (Dinoprostone) to
Intravaginal Misoprostol
Özgür Dündar, Ercüment Müngen, Levent Tütüncü, Murat Muhcu,
Serkan Bodur, Yusuf Z. Yergök
19
The effect of sex on fetal ultrasound measurements: is it necessary
sex-spesific nomograms?
Yeflim Bülbül Baytur, Hasan Y›ld›z, Ali Özler, Ümit Sungurtekin ‹nceboz,
Hüsnü Ça¤lar
26
Investigation of Folic Acid, Vitamin B12,Vitamin B6 and Homocysteine
Levels in Preeclamptic Pregnancies
Ahmet Kale, Ebru Kale, Nurten Akdeniz, Mahmut Erdemo¤lu,
Ahmet Yal›nkaya, Murat Yayla
31
A Case of Non-Immun Hydrops Fetalis Due to Placental Chorioangioma
Ener Ça¤r› Dinleyici, Neslihan Tekin, Mehmet Arif Akflit, Emine Dündar
37
Congenital large oropharyngeal immature teratoma
Figen K›r fiahin, Gülengül Nadir Köken, Serhan Çevrio¤lu, Önder fiahin,
Arif Saylan
40
Abruption placenta in adult Still’s disease with onset during pregnancy:
A case report
Cem Dane, Murat Yayla, Banu Dane, Ahmet Çetin
45
Prenatal diagnosis of osteogenes›s imperfecta: a case report
‹ncim Bezircio¤lu, Merve Biçer, Dilek Uysal, Seyran Yi¤it, Ali Balo¤lu
49
Cervical pregnancy: a case report
Cüneyt Eftal Taner, Tolga M›zrak, Semih Mun, ‹rem fienyuva, Yi¤it Özgenç,
Fatma Alt›ntaflo¤lu Çelimli
55
Perinatal Journal • Vol: 14, Issue: 1/March 2006
1
Perinatal Outcome of Pregnancy on Over Age 40
Ali Gedikbafl›, Alpaslan Akyol, Varujan Ma¤ar, Cemal Ark, Yavuz Ceylan
Clinics of Gynecology and Obstetrics, Ministery of Health Bak›rköy Training and Research Hospital for Gynecology,
Obstetrics and Pediatrics, ‹stanbul
Abstract
Objective: The aim of this study is to evaluate the gestational data and complications of pregnant women above 40 years old.
Methods: 337 pregnancies above 40 years were compared with 266 healthy pregnancies as control in our hospital in 2004.
Gestational complications as chronic hypertension, preeclampsia, intrauterine growth retardation, intrauterine fetal death,
APGAR scores, incidence of premature birth, type of birth and birth weights, perinatal morbidity and the need of neonatal care
unit of each group was compared.
Results: Pregnancies above 40 years constituted % 1.6 of all pregnancies in 2004. Chronic hypertension, preeclampsia, intrauterine fetal death, APGAR scores below 7 on the 5th minute, incidence of premature birth, ceserean sectio and postnatal need of
neonatal care unit was statistically higher in pregnancies above 40 years. Birth weight and intrauterine growth retardation was
not significantly different between groups.
Conclusion: Maternal and fetal complications occur in pregnancies above 40 years. We found similar rates about perinatal
mortalite, intrauterine fetal death, neonatal death, preterm birth rate, low birth weight, preeclampsia and gestational hypertansion data for 40 years and older pregnant women as in the literature. More studies should be performed about antenatal
and perinatal problems in older women and more guidelines should be developed about perinatal care.
Keywords: Pregnancy beyond 40 years, gestational complications.
40 yafl üstü gebeliklerin perinatal sonuçlar›
Amaç: Çal›flman›n amac› 40 yafl üstü gebelerin verilerini ve do¤um sonuçlar›n› de¤erlendirmektir.
Yöntem: 2004 y›l›nda hastanemizde gerçeklefltirilen do¤umlar›n 337’si 40 yafl ve üstündeki gebelere ait olup, veriler preeklamp-
si, süre¤en yüksek kan bas›nc›, rahim içi geliflme gerili¤i, rahim içi fetal ölüm, perinatal hastal›k ve yenido¤an yo¤un bak›m
gereklili¤i, APGAR skorlar›, erken eylem ve do¤um, do¤um flekilleri ve tart›lar› aç›s›ndan incelenmifltir; elde edilen veriler, 40 yafl
alt›nda rast gele seçilmifl 266 gebenin oluflturdu¤u kontrol grubunun bulgular› ile karfl›laflt›r›lm›flt›r.
Bulgular: 40 yafl üstündeki do¤umlar tüm do¤umlar›m›z›n %1,6’s›n› oluflturmaktad›r. ‹leri yafl gebeliklerde süre¤en yüksek kan
bas›nc›, preeklampsi, erken eylem ve do¤um, rahim içi fetal ölüm, sezaryen ile do¤um, beflinci dakika APGAR skorunun 7 ve
alt›nda olmas› ve yenido¤an yo¤un bak›m gereklili¤i genç yafl grubuna göre istatistiksel olarak daha s›k gözlendi. Do¤um a¤›rl›¤›
ve rahim içi geliflme gerili¤i aç›s›ndan istatistiksel olarak anlaml› fark bulunamad›.
Sonuç: Tüm parametreler dikkate al›nd›¤›nda, 40 yafl üstü gebeliklerin %25’ inde anne veya fetal sorun geliflmifltir. Literatürdeki
verilerle uyumlu olarak, 40 yafl ve üstündeki gebeliklerde perinatal ölüm, rahim içi fetal ölüm, yenido¤an ölümü, erken do¤um
oran›, düflük do¤um a¤›rl›¤›, preeklampsi, gestasyonel yüksek kan bas›nc› daha s›k gözlendi. ‹leri yafl gebeliklerde sorunlar ve
perinatal sonuçlar ile ilgili daha fazla çal›flma yap›lmal›, izlem protokolleri oluflturulmal›d›r.
Anahtar Sözcükler: 40 yafl üstü gebelik, gebelik sorunlar›.
Correspondence: Dr. Alpaslan Akyol, Sa¤l›k Bakanl›¤› Bak›rköy Kad›n Do¤um ve Çocuk Hastal›klar› E.A Hastanesi, Kad›n Hastal›klar› ve
Do¤um Klini¤i, ‹stanbul e-mail: [email protected]
2
Gedikbafl› A et al., Perinatal Outcome of Pregnancy on Over Age 40
Introduction
Recently it has been shown and highlighted
that the neonatal morbidity and mortality rate of
pregnant women at advanced age is similar to that
of young population by a good prenatal monitoring and care.1 There are several studies about the
impact of maternal age as a factor in pregnancy.
Although recent studies are mainly concerned about the pregnancies over 35 years of age, there are
several others, taking 40 and 45 ages as a threshold
value.2,3,4 Today many women, particularly the
ones in developed countries, delay childbearing
beyond their 40 age due to social, economic and
educational motives, which continue to become
increasingly common in our daily life.5
Childbearing women over the age of 35 are defined with “advanced maternal age”2 while some
other researchers define pregnancies over the age
of 40 as “very advanced maternal age”.6 This group includes infertile cases treated by the infertility
methods developed, specifically nulliparous cases.7,8 The age-related medical complications and
chronic disorders are much higher in this group of
pregnancies, which comprises the highest risk group.
It has been reported that chronic hypertension,
preeclampsia, low neonatal birth weight, malpresentation, premature delivery and fetal chromosome anomalies are higher in pregnancies at advanced maternal age.9,10 It has been also reported that
prolonged labor, perinatal disease and death and
cesarean section were more frequent in older
pregnant women.9,10 However, there are some studies suggesting that there is no such a difference
between old and young pregnant women in terms
of perinatal outcomes.11,12
Methods
A total of 344 pregnant women aged 40 years
or over, who delivered in 2004 (between
01.01.2004 and 31.12.2004) at the Bak›rköy
Training and Research Hospital for gynecology
Obstetrics and Pediatrics affiliated with the T.R.
Ministry of Health, was evaluated. Out of more
than 20.000 deliveries in our hospital within this
period, 267 cases under the age of 40 were randomized by their pregnancy monitoring findings,
and included in the study as a control group.
Miscarriages prior to the gestational week 24 and
lower than 500 grams were excluded. Also excluded are multiple pregnancies after assisted reproductive technologies or natural reproduction.
Perinatal mortality and morbidity rates related
with complications during pregnancy and delivery,
APGAR indexes, early labor (detection of pain or
cervical aperture during examination), early delivery, presence of chronic hypertension, presence of
preeclampsia and eclampsia were evaluated in 344
pregnant women in the study group in terms of
gestational week at delivery, mode of delivery and
birth weight. Data were assessed by comparison
with the control group.
A Kolmogroff-Smirnoff test was used to determine the normal distribution of data for statistical
evaluation. Student’s t test was used to determine
the differences between normally distributed data
while chi-square (X2) and Mann-Whitney-U Test
methods were used for determination of the differences between others. For statistical analysis,
p<0.05 was considered significant.
Results
The mean age of our patients was 41 years
(minimum 40, maximum 48) in the study group
and 25 years (minimum 17, maximum 39) in the
control group. Number of pregnancies (4,4 ± 2,4
vs. 2,0 ± 1,0; p=0,000) and number of deliveries
(2,4 ± 1,8 vs. 0,7 ± 0,8; p=0,000) were higher in the
study group, where the difference was statistically
significant (Table 1).
Table 1. Descriptive analysis of the group.
Demographical data
< 40 years (n: 267)
Mean ± Std. deviation
≥ 40 years (n: 344)
Mean ± Std. deviation
p
Age
Number of pregnancy
Number of delivery
Number of living child
Miscarriage
25,5 ± 4,7
2,0 ± 1,0
0,7 ± 0,8
0,7 ± 0,7
0,2 ± 0,5
41,1 ± 1,5
4,4 ± 2,4
2,4 ± 1,8
2,2 ± 1,6
0,8 ± 1,2
0.000
0.000
0.000
0.000
0.000
3
Perinatal Journal • Vol: 14, Issue: 1/March 2006
Preeclampsia was significantly higher in pregnant women over 40 years of age compared to the
control group (9.3% n=32; 1.5% n=4, p=0.000)
(Table 2). Similarly, chronic hypertension was also
more frequent in the pregnant women at advanced
age than in the younger women (2.5% n=43; 0.4%
n=1, p=0.000) (Table 2).
Table 2. Age-related complications of pregnancy and
delivery during gestation.
Preeclampsia and eclampsia
Chronic hypertension›
Intrauterine growth retardation
Intrauterine fetal death
Early labor
Early delivery
< 40 years
(n: 267) (%)
≥ 40 years
(n: 344) (%)
p
4 (%1,5)
1 (%0,4)
14 (%5,2)
1 (%0,4)
3 (%1,1)
2 (%0,7)
32 (%9,3)
43 (%12,5)
23 (%6,7)
12 (%3,5
22 (%6,4)
29 (%8,4)
0,000
0,000
0,458
0,008
0,001
0,000
No statistically difference was found between
two groups in intrauterine growth retardation
(6.7% n=23; 5.2% n=14; p=0.458) (Table 2).
Intrauterine fetal death was higher in pregnant
women at advanced age, and the difference was
statistically significant (0.4% n=1; 3.5% n=12,
p=0.008) (Table 2).
Preterm labor was higher in the study group
than in the control group (6.4% n=22; 1.1% n=3;
p=0.001) (Table 2). Based on this, preterm delivery
was also higher in pregnancies at advanced age
(8.4% n=29; 0.7% n=2; p=0.000) (Table 2).
At advanced maternal ages, the preferred mode
of delivery was mainly cesarean section. Delivery
by cesarean section was significantly higher in
study group compared to control group (44.8%
n=154; 30.2% n=81; p=0.000) (Table 3). Motives
and frequencies for cesarean section are shown at
Table 4.
Table 3. Distribution of mode of delivery by age groups
Mode of delivery < 40 years (n:267)
(grup içi oran %)
≥ 40 years (n:344)
(grup içi oran %)
Normal vaginal
delivery
186
(%69.7)
190
(%55.2)
C/S abdominals
81
(%30.3)
154
(%44.8)
p
0.001
Table 4. Distribution of cesarean indications by age.
Indication
Malpresentation
Fetal distress
Abnormal labor progress
Macrosomic baby (>4500gr)
Ablatio placenta
Placenta previa
Previous cesarean and elective
Primary infertility
Old nulliparous
Discrepancy between fetal
head and maternal pelvis
< 40 years (n)
≥ 40 years (n)
3
16
6
7
0
0
39
0
0
10
10
20
4
6
4
5
66
8
25
6
Table 5. Neonatal data.
Demographic
Characteristics
< 40 years
(n: 267)
≥ 40 years
(n: 344)
p
Delivery week›
Birth weight (gr)
40 hafta
3300 gr
39 hafta
3310 gr
0,000
0,492
Need for neonatal
intensive care
(rate in age group %)
16
(%6,0)
38
(%11,0)
0,029
Five-minute APGAR <7
(rate in age group %)
1
(%0.4)
14
(%4.2)
0,003
The gestational week at delivery was significantly lower in the study group (39 weeks in study
group; minimum 24, maximum 42 weeks; 40 weeks in control group, minimum 32, maximum 42
weeks; p=0.000) (Table 5).
No difference was found between the groups in
birth weight (mean 3310 gr in study group, minimum 520 gr, maximum 5050 gr; mean 3300 gr in
control group, minimum 1800, maximum 4570 gr,
p=0.492) (Table 5).
The five-minute APGAR scores were examined
in order to evaluate the perinatal status of the neonate, and seven and six were the accepted threshold values. Based on this, lower APGAR values
were higher at advanced maternal age (4.2% n=14;
0.4% n=1; p=0.003) (Table 5).
Postpartum intensive care need and neonatal
illnesses were higher in the group of advanced
maternal age (11% n=38; 6% n=16, p=0.029) (Table 5).
The statistical analyses carried out after combining all gestational data related with maternal, perinatal and fetal complications showed that frequency of complications was higher in the study
group than in the control group (24,7% n=85; 9,4%
n=25; p=0,000) (Figure 1).
4
Gedikbafl› A et al., Perinatal Outcome of Pregnancy on Over Age 40
p=0.000 olarak bulundu
100
9
25
90
91
80
75
70
60
50
40
30
20
Var
%
10
Yok
0
< 40
>= 40
Yafl grubu
Figure 1. Overall gestational complications by the age group.
Discussion
We have chosen to study a patient population
over 40 years of age as pregnancies beyond 40
years are increasing in frequency although there
are several studies on pregnancies over 35 years.
The trend of conceiving at an older age increases
to continue, where the main underlying factors are
socioeconomic status and developing infertility
techniques. The rate of initial pregnancies between
30 and 44 years of age has been doubled since
1987 compared to the data in 1970 and 1979,
which makes the overall rate of pregnancies at
older age accounting for 16% of all pregnancies.13
Consistent with the literature, the majority of our
cases was from the infertility group. Twenty-five of
our cases (7.26%) were initial pregnancies aged
over 40 years, and 18 of them were conceived with
assisted reproductive technologies. The rate of
pregnant women who delivered over 40 years of
age was 1.67% in our group (337 of 20108 deliveries in 2004), which is consistent with the foreign
literature.13 Göl et al found a pregnancy rate of
4.85% for pregnancies over 40 years of age.14
The diagnosis for preeclampsia was significantly higher in pregnant women aged over 40 years
compared to the control group in our study. It is
shown in the literature that preeclampsia peaked
at second trimester in early advanced ages.15
Although the etiology of preeclampsia is not
known in detail, it is sometimes difficult to distinguish an existing hypertension from a pregnancyinduced hypertension. Therefore, frequency of
preeclampsia was not found increased in older
pregnant women in some studies.16
Chronic hypertension was also found higher in
older pregnant women, and a study by Gilbert
reports that the chronic hypertension was five fold
in nulliparous older women while it was eight fold
in multiparous women.17 However, some studies
suggest that the increased perinatal death in older
pregnant women, and increased perinatal death
and intrauterine fetal death can not be explained
by the concomitant hypertension and pregnancy
complications.10,12
Consistent with the literature, there was no difference between the groups in the intrauterine
growth retardation. In a study by Abel et al18 low
5
Perinatal Journal • Vol: 14, Issue: 1/March 2006
birth rates were assessed rather than the growth,
including the teenage pregnant women, and it has
been reported that the neonatal birth weights were
lower in pregnant women at early ages and
advanced ages.
bution of concerns by physicians and patients into
the increasing number of operations is not known.
Relative causes like “advanced maternal age-first
pregnancy, precious pregnancy” increase the trend
to operate.17
Intrauterine fetal death was higher in our study
in consistency with the literature, and chromosomal and structural anomalies in the advanced ages
are held responsible for the increased intrauterine
death.17,19 As the maternal age increases, intrauterine loss is increased 2- fold in the pregnant women
aged 30 years and over, and 3-4 fold in the ones
aged 40 years and over.20
In the Gilbert study17 it has been indicated that
neonatal complications were increased in older
women, and rate of birth asphyxia, fetal growth retardation and intraventricular bleeding was higher.
Similarly, we have found that the 5-minute APGAR
scores were lower in pregnant women at advanced
age, and the neonates of this group required neonatal intensive care more frequently, which can
be considered secondary to the early deliveries caused by preeclampsia, being more common in this
group of patients and other complications.
Our data on early labor were consistent with
the literature in pregnant women aged 40 years
and over.17 Based on this, hospitalization and requirement for tocolytic treatment were more common
in these women compared to the control group. Similarly, it was observed that pregnant women at
advanced age delivered their babies one week before than the control group (mean gestational week; 39 in the study group vs. 30 in the control group). However, stimulation by oxytocin and particularly elective termination of pregnancy by cesarean delivery on request of the older women due
to concerns about the delivery played an important
role in this outcome.17
Delivery by cesarean section was higher in the
pregnant women aged over 40 years.21 Among the
most common causes are elective operation on request, previous history of cesarean operation, fetal
distress and fetal head and maternal pelvis discrepancy. The most common cause was request for
elective cesarean operation in nulliparous women
while it was previous history of cesarean delivery
in multiparous women. The rate of cesarean delivery was 44.8% in pregnant women aged 40 years
and over, and 30.2% in the control group. Probably, one of the major motives is that in our hospital we offer cesarean section as an option for
mode of delivery in nulliparous women aged over
40 years. In US, for women aged over 40 and 45
years, the rate of cesarean delivery was 22.3% and
31.7% respectively,22 and Göl et al14 listed malpresentation, abnormal labor progress and previous
delivery by cesarean section as the most common
causes in women aged over 40 years. The contri-
Perinatal and postpartum complications were
more frequent in women aged over 40 years in our
study. In this group, chronic hypertension and preeclampsia, intrauterine fetal loss, early membrane
rupture, early labor and early delivery were higher.
Rate of cesarean delivery and need for neonatal intensive care was higher in women aged over 40
years, particularly together with early delivery.
When all data about maternal, perinatal and fetal
complications were combined and evaluated, we
found that overall incidence of complications was
higher in the study group aged over 40 years, and
any maternal, perinatal or fetal complication was
potential at a mean rate of 25% in such pregnancies. Therefore, pregnant women aged over 40 years
should be informed of potential complications,
and they should be monitored more frequently
and attentively.
References
1.
Bianco A, Stone J, Lynch L, Lapinski R, Berkowitz G,Berkowitz RL. Pregnancy outcome at age 40 and older. Obstet
Gynecol 1996; 87: 917-22.
2.
Dildy GA, Jackson GM, Fowers GK, Oshiro BT, Varner MW,
Clark SL. Very advanced maternal age: pregnancy after age
45. Am J Obstet Gynecol 1996; 175: 668-74.
3.
Hansen JP. Older maternal age and pregnancy outcome: a
review of the literature. Obstet Gynecol Surv 1986; 41: 72642.
4.
Adams MM, Oakley GP Jr, Marks JS. Maternal age and
births in the 1980s. JAMA 1982 Jan 22-29; 247(4): 493-4.
5.
Ziadeh S, Yahaya A. Pregnancy outcome at age 40 and older. Arch Gynecol Obstet 2001; 265: 30-3.
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Gedikbafl› A et al., Perinatal Outcome of Pregnancy on Over Age 40
Annual vital statistics, Part 4. O¨rebro, Sweden: Statistics
Sweden; 2002.
Sauer MV, Paulson RJ, Lobo RA. Pregnancy after age 50:
application of oocyte donation to women after natural menopause. Lancet 1993; 341: 321-3
Sauer MV, Paulson RJ, Lobo RA. Pregnancy in women 50 or
more years of age: outcomes of 22 consecutively established pregnancies from oocyte donation. Fertil Steril 1995;
64: 11-5
Lagrew DC Jr, Morgan MA, Nakamoto K, Lagrew N. Advanced maternal age: perinatal outcome when controlling for
physician selection. J Perinatol 1996; 16: 256-60.
10. Windridge KC , Berryman JC (1999) Women’s experiences
of giving birth after 35. Birth 26: 16-25.
11. Berkowitz GS, Skovron ML, Lapinski RH, Berkowitz RL. Delayed childbearing and the outcome of pregnancy.N England Journal of Medicine 1990; 322: 659-64.
12. Forman MR, Meirik O, Berendes HW, (1984). Delayed
childbearing in Sweden. JAMA 252: 3135-9.
13. Center of Disease Control. Postponed childbearing-United
States, 1970-1987. MMWR Morb Mortal Wkly Rep 1989; 38:
810-2.
14. Göl M, Ayd›n C, Guven CM, Yensel U, Karc› L, Baloglu A.
Pregnancy outcome in women aged 40 or over. Gynecol
Obstet Reprod Med 2003; 9: 176-9.
15. Bo Jacobsson, MD, PhD, Lars Ladfors, MD, PhD, and Ian
Milsom, MD, PhD Advanced Maternal Age and Adverse Perinatal Outcome: Obstet Gynecol 2004; 104: 727–33
16. Beydoun, Hind MPH; Itani, Mohammad MBChB; Tamim,
Hala PhD; Aaraj, Alia MD; Khogali, Mustafa MD; Yunis,
Khalid MD; The National Collaborative Perinatal Neonatal
Network (NCPNN) Impact of Maternal Age on Preterm Delivery and Low Birthweight: A Hospital-Based Collaborative
Study of Nulliparous Lebanese Women in Greater Beirut.
Journal of Perinatology 2004; 24(4): 228-35.
17. Gilbert WM, Nesbitt TS, Danielsen B. Childbearing beyond
age 40: pregnancy outcome in 24,032 cases. Obstet Gynecol
1999; 93: 9-14.
18. Abel EL, Kruger M, Burd L. Effects of maternal and paternal
age on Caucasian and Native American preterm births and
birth weights. Am J Perinatol 2002; 19(1): 49-54.
19. Muhieddine A.-F. Seoud, M.D., Anwar H. Nassar, M.D.,
Ihab M. Usta, M.D.,Ziad Melhem, M.D., Alia Kazma, M.S.,
and Ali M. Khalil, M.D. Impact of Advanced Maternal Age
on Pregnancy Outcome American Journal of Perinatology,
Volume 19, Number 1, 2002. 2002; 19: 01-8.
20. Cnattingius S, Forman MR, Berendes HW, Isotalo L.Delayed
childbearing and risk of adverse perinatal outcome:a population-based study. JAMA 1992; 268: 886-90.
21. Dulitzki M, Soriano D, Schiff E, Chetrit A, Mashiach S,Seidman DS. Effect of very advanced maternal age on pregnancy outcome and rate of cesarean delivery. Obstet Gynecol 1998; 92: 935-9.
22. Ventura SJ, Martin JA, Taffel SM, Matthew TJ, Clarke SC. Advance report of final natality statistics, 1992. Hyattsville
(MD): National Center for Health Statistics, 1994. Monthly
Vital Statistics Report, Vol.43, no: 5 (Suppl)
Perinatal Journal • Volume: 14, Number: 1/March 2006
7
Evaluation of the Prenatal Care Usage of
Mothers Giving Birth at the Ministry of
Health, Ankara Etlik Training and
Research Hospital of Obstetrics and
Gynecology
Emine Dibek M›s›rl›o¤lu1, Didem Aliefendio¤lu1, Kibriya Fidan2, Fatma Nur Çakmak3, Ali Haberal2
1Department of Pediatrics, Faculty of Medicine, K›r›kkale University, Ankara
Ministry of Health Ankara Etlik Training and Research Hospital of Obstetrics and Gynecology, Ankara
3Ministry of Health Ankara D›flkap› Training and Research Hospital for Pediatrics, Ankara
2
Abstract
Objective: The aim of this study was to determine the prenatal care usage of mothers giving birth at the Ministry of Health, Ankara Etlik
Training and Research Hospital of Obstetrics and Gynecology, the influencing factors and the mother’s knowledge level regarding breastfeeding.
Methods: All mothers giving birth during a 3-month period (n=502) were included in this sectional study. The responses provided to a questionnaire were evaluated with chi-square and t-tests for statistical analysis.
Results: The percentage living in the city center or towns was 96.4% and 53.9% were primary school graduates with 87.1% not working. The
rate of consanguineous marriage was 16.3% and this rate was higher in the group of mothers who were primary school graduates or illiterate
than high school graduates (p<0.05). The number of pregnancies, births and living children was higher in the group with consanguineous marriages (p<0.05). When monitoring during the final pregnancy was checked, 95.6% had gone to a physician for a check-up at least once with
53.8% going for 6 or more follow-ups. The mother’s breastfeeding knowledge was also evaluated and 95.8 % knew that breastfeeding should
start after birth.
Conclusion: In conclusion, it is encouraging that a high percentage of mothers have gone for follow-ups at a health institution at least once
during pregnancy. Because only half had an adequate number of follow-ups more emphasis on prenatal care is still needed. The high rate of
birth and low educational level in the consanguineous marriage group indicates more should be done for training these women.
Keywords: Prenatal care, consanguineous marriage, breast milk.
Sa¤l›k Bakanl›¤› Ankara Etlik Do¤umevi ve Kad›n Hastal›klar› E¤itim ve Araflt›rma Hastanesinde do¤um yapan
annelerin antenatal bak›m hizmetlerinden yararlanma durumunun de¤erlendirilmesi
Amaç: Bu araflt›rma, Sa¤l›k Bakanl›¤› Ankara Etlik Do¤umevi ve Kad›n Hastal›klar› E¤itim ve Araflt›rma Hastanesinde do¤um yapan annelerin do¤um öncesi bak›m hizmetlerinden yararlanma durumlar›, bunu etkileyen faktörler ve anne sütü ile beslenme konusundaki bilgilerinin belirlenmesi amac›yla yap›lm›flt›r.
Yöntem: Kesitsel nitelikteki bu çal›flmada, üç ayl›k süre içersinde do¤um yapan tüm anneler (n=502) çal›flmaya al›nm›flt›r. Annelerin anket formundaki sorulara verdikleri yan›tlar de¤erlendirmeye al›narak istatistiksel de¤erlendirmede ki-kare ve student’s t-testi kullan›lm›flt›r.
Bulgular: Annelerin % 96.4’ü il merkezi ve ilçelerde yaflamakta olup % 53.9’u ilkokul mezunu ve % 87.1’i çal›flmamaktayd›. Akraba evlili¤i oran› % 16.3 olarak bulundu ve okur yazar olmayan veya 8 y›l alt›nda e¤itim alan annelerin akraba evlili¤i oran›, 8 y›l ve üzerinde e¤itim alanlara
göre daha fazla idi (p<0.05). Ayr›ca, akraba evlili¤i olan annelerin grubunda gebelik say›s›, do¤um say›s› ve yaflayan çocuk say›s› daha fazlayd›
(p<0.05). Son gebelik s›ras›ndaki izlemlerine bak›ld›¤›nda; % 95.6’s› kontrol amac›yla en az bir kez doktora baflvururken, 6 veya üstünde izlemi
olanlar›n oran› % 53.8 idi. Annelerin bebek beslenmesi konusundaki bilgileri de¤erlendirildi¤inde; % 95.8’i do¤umdan hemen sonra süt vermeye bafllanmas› gerekti¤ini biliyordu.
Sonuç: Annelerin gebelik s›ras›nda en az bir kez de olsa sa¤l›k kurulufluna baflvurma oran›n›n yüksek olmas› dikkat çekicidir. Ancak sadece yar›s›n›n yeterli say›da izleminin olmas›; do¤um öncesi izlemin sürdürülmesi için daha çok çaba gösterilmesi gerekti¤ini düflündürmektedir. Ayr›ca,
akraba evlili¤i olan grupta do¤urganl›k oran›n›n yüksekli¤i ve e¤itim düzeyinin düflüklü¤ü bu grupta, e¤itimle ilgili daha çok çal›flma yap›lmas› gerekti¤ini de düflündürmektedir.
Anahtar Sözcükler: Do¤um öncesi bak›m, akraba evlili¤i, anne sütü.
Correspondence: Dr. Emine Dibek M›s›rl›o¤lu, K›r›kkale Üniversitesi T›p Fakültesi, Pediatri, K›r›kkale, Türkiye
e-mail: [email protected]
8
Dibek M›s›rl›o¤lu E vet al., Evaluation of the Prenatal Care Usage of Mothers
Introduction
Raising healthy generations is possible by only
benefiting enough from healthcare services and
that is related to becoming conscious of the community about health. Because the healthcare services’ effectiveness is appreciated by the employability of the services that are offered, at first it is
necessary that the healthcare services must be
employable for everybody.
Existence of the healthcare services and the
incidence of usage are decisive in determining the
level and the quality of maternity&children welfare
services in community.1
As the indexes of maternity&children welfare in
a country reflect the maternity&children welfare
level in the community, they also reflect the country’s environmental conditions and the development status very well. That’s why the indexes of
maternity&children welfare show parallelism with
the development status of the countries. Being
able to speak of communities’ real economic and
social developments and composing a healthy
society, health problems of the mothers and the
children who are the most effected by the risk factors shall be taken in hand firstly and be healed.1,2
Because the health situations are not in the
desired levels, as many developing countries,
maternity&children welfare form one of the important and indispensable subjects of general health
problems in our country too.” Mother death rate”
which is one of the data in reflecting this level,
changes from country to country and our country
with the rate of 46.7 in one hundred, gets very
behind about maternity&children welfare services.
The first three reasons of mother deaths; bleedings
(30.3%), pregnancy and puerperium toxemias
(15.5%) and infections (9.6%) are among the preventable causes by the well-qualified follow-up of
the pregnants in prenatal and postnatal periods.3,4
Antenatal care (ANC) in the first trimester and
continuing with regular periods until the last of
pregnancy, appreciating the mother and the fetus’
health situations and abrogating the health problems, reduces perinatal, maternal mortality and
morbidity. Also with screening tests in the predefined terms, possible pregnancy complications can
be determined and can take precautions. Thereby
it is provided for mother passing a healthy pregnancy period and having a healthy baby. The
babies who are delivered following a healthy pregnancy period and taking care in optimal conditions
during the delivery are the basis of the community.5
Social structure of the community, the social
values relating to found a family which is the
smallest unit in community also concern society
health closely. For example, when a family is
founded, choosing the partner from the same
blood relation shipped indivuals, that means
inbreeding (consanguineus marriage) is still occurs
as an important problem in our country.
Consanguineus marriage, increases the incidence
of especially the genetic diseases in community
and therefore it has to be appreciated as an
important factor which effects the society health.6
As a conclusion of these realities, at Ankara’s
province center, in the hospital which the deliveries in Ankara are given by second frequently, this
research has planned and applied in the purpose
of following-up the mothers’ situation of using prenatal care cervices, the factors which effect that,
relative marriage incidence and the effect on taking ANC and also discover their information about
breastmilk.
Methods
In this cross-sectional qualified research, 502
mothers who have given birth in The Ministry of
Health Ankara Training and Research Hospital of
Obstetrics and Gynecology since last three months
period are included. Questions figured in the predefined polls were asked to these mothers just
after births and they were wanted to answer these
questions with the face to face questionnaire technic. The questionnaire sample is at the end of this
article.
By the questions in this poll, mothers’ sociodemographic data, obstetric information and their
knowledge about breastmilk are evaluated and
beside their situation of benefiting from healthcare
services related to their last pregnancy, by examining our hospital’s files, information about their
follow-up is gathered. While analyzing the data,
SPSS 10.0 package software has been used.
Comparisons has been done with square and the
student’s t tests and p value has been accepted as
<0.05 for the statistical significance.
9
Perinatal Journal • Volume: 14, Number: 1/March 2006
Results
Sociodemographic features of the mothers (n=
502) who are taken into the research are shown in
Table 1. Their ages vary between 16 and 41, and the
average pregnancy number was 2.1+1.4 (interval: 110), average delivery number was 1.7+0.9 (interval:
1-10).
The data belong to mothers’ second pregnancy
are shown in Table 2. 95.4% of the mothers (n=
480) are at least one time, 71.3% of them (n= 358)
are 4 times or more and 53.8% of them (n= 270) are
6 times or more than taken medical examination
during their pregnancy. Also 94.4% of the mothers
have at least one time ultrasonography and 91.4% of
them has been found normal. Triple screening tests
has been applied to 30.2% of the mothers and risky
results have been gained in the 0.6%. Hepatitis B
surface antigen (Hbs Ag) examination has done to
574% of the mothers and antigen positiveness has
been stated in the 0.6%.
In 25 (5%) of the mothers who don’t have any
problems before pregnancy, gestational diabetes
has been stated and in 38 of them (7.6%), hypertension has been stated.
Relative marriage incidence was 16.3%. The
comparison of making a relative marriage (n= 82)
and not making a relative marriage (n= 420) are
shown in Table 3.
• A statistical significant relation has been stated
between the education level of mother and making a relative marriage. While the relative marriage incidence is 19.7% in the group who are
uneducated and have taken education under 8
years, this incidence is 10.4% among the ones
who have taken 8 years and more education and
this difference was significant (p=0.004).
• In the group which has made relative marriages,
the average pregnancy number was 2.4+1.4, the
delivery number was 2.0+1.9 and the living children number were 1.7+0.9, in the ones who did
not make relative marriages the average pregnancy number was 2.0+1.3, the delivery number was
1.7+0.8 and the living children number were
1.5+0.8 and the difference between the groups
was significant (in turn; p=0.027, p=0.008,
p=0.043).
• There has not been found a statistical difference
according to mothers’ age, state of business, settling area, the time has passed since the last pregnancy and the follow-up number during the last
pregnancy (p=0.043).
When the information of the mothers about the
babies’ nutrition was investigated, it has been
found that the 95.8% knew it has to be started to
Table 1. The sociodemographic features of mothers.
Özellikler
Age
• 18 and under
• 19-24
• 25-29
• 30-34
• 35 and above
Marriage term
• 0-5 years
• 6-10 years
• 11-15 years
• 16-20 years
• 21 years and more
Education level
• Not literate
• Under 8 years educated
• More than 8 years educated or high school graduate
• Bachelor degree
Mother’s state of business
• Not working
• Unskilled worker
• Technician
• Licence owner
Father’s occupation
• Not working
• Unskilled worker
• Teknisyen
• Licence owner
Settling area
• Province center
• District
• Village
Time has passed since the last pregnancy
• Under 2 years
• Above 2 years
• First pregnancy
Living children number
Number
Percent
31
201
161
81
28
6.2
40.0
32.1
16.1
5.6
319
121
48
12
2
63.6
24.1
9.5
2.4
0.4
9
311
155
27
1.8
61.9
30.9
5.4
437
28
9
28
87.1
5.6
1.8
5.6
16
359
87
40
3.1
71.5
17.4
8.0
262
222
18
52.2
44.2
3.6
61
211
230
22.5
77.5
45.8
1.6+0.8 (average:1-6)
Table 2. The follow-ups during the last pregnancy.
Follow-up number
•0
• 1-5
• 6 or more
Having USG during the pregnancy
Appling screening tests (triple screening test)
Looking up for HBs Ag
Way of giving delivery
• Normal spontaneous delivery
• Cesarean section (C/S)
n
%
22
210
270
474
152
288
4.4
41.8
53.8
94.4
30.2
57.4
351
151
69.9
30.1
10
Dibek M›s›rl›o¤lu E vet al., Evaluation of the Prenatal Care Usage of Mothers
Table 3. Comparison between the ones made consanguineous marriage (CM) and
did not make CM.
Age
Not make
CM
(n:420)
Make
CM
(n:82)
190
140
90
42
21
19
0.451
257
163
63
19
0.004
366
54
71
11
0.255
220
200
42
40
0.427
49
170
201
12
41
29
0.129
19
167
232
3
41
38
0.517
2.0+1.3
1.7+ 0.8
1.5+0.8
2.4+1.4
2.0+0.9
1.7+0.9
0.027
0.008
0.043
• 24 and under
(n:232)
• 25-29
(n:161)
• 30 and above
(n:109)
Education level
• Uneducated or under 8 years (n:320)
• 8 years and more
(n:182)
State of business
• Not working
(n:437)
• Working
(n:65)
Settling area
• Province Center
(n:262)
• District or village
(n:240)
Time has passed since the last pregnancy
• Under 2 years
(n:61)
• Above 2 years
(n:211)
• First Pregnancy
(n:230)
Follow-up numbers during last pregnancy
•0
(n:22)
• 1-5
(n:210)
• 6 or more
(n:270)
Pregnancy number
Delivery number
Living children number
nurse just after the delivery and 94% of them knew
that giving brestmilk is necessary at least for 4-6
months.
Discussion
Each year, almost 520 thousand women die
from problems based on pregnancy. These deaths
can occur in prenatal, during delivery or postnatal
terms and most of them are preventable reasons.
Because of that in addition to the prenatal care,
giving delivery in suitable conditions and postnatal
care are important too.5,7,8
Although pregnancy is a physiological period,
because of the pathological circumstances can
develop easily, it is important to follow-up in regular periods. ANC is the follow-up of mother and
fetus during the whole pregnancy term in regular
periods with medical examination and recommendations by educated health personnel. Quality and
number of prenatal care follow-up is highly important. World Health Organisation announces that in
developing countries, antenatal follow-up 4 times
is enough for pregnants who have not any risk fac-
p
tors.9 In our studies, 71.3% of mothers have gotten
antenatal care 4 or more times. The ministry of
health made at least 6 times of antenatal follow-up
necessary, made arrangements about giving delivery with the help of a health personnel and in
healthy conditions and also recommended at least
3 times of follow up during the puerperal period.10
It is stated that the 95.4% of mothers who
joined our studies have consulted to a hospital at
least once during the pregnancy. This percentage
is more than the other percentages which have
been stated from our country. For example; in last
5 years, incidence of women which gave delivery
consulted to a health personnel at least once is
found as 81%, depends on Turkey’s Population
and Health Research data.11 In a study like this
made in Gaziantep, this percentage is reported as
75.9%.12
American Academy of Pediatrics and ACOG
1992 (American College of Obstetricians &
Gynecologist) recommends at least 6 times of prenatal follow-ups.7 In our studies percentage of
pregnants who had 6 times or more follow-ups has
been found as % 53.8.It’s seen that this incidence
Perinatal Journal • Volume: 14, Number: 1/March 2006
is also more than the others belong to the previous
studies. For example, in a study made in Erzurum,
it is stated that the incidence of pregnants who had
6 or more times follow-ups during their pregnancy
is 18.7%.13
Antenatal care varies from country to country
and while this rate is 98% in developed countries
it decreases until 68% in developing countries.14
The region that lived plays an important role in
reaching the prenatal care. In Turkey while
women living in cities are taking ANC at least one
time, this rate is decreases to 65% in women living
in rural area.11 Furthermore, it is reported that there
is differences in benefiting from prenatal care
according to demographic characteristics. It is
determined young mothers are more desirous in
taking prenatal care than mothers at 35 age or
above. As number of deliveries increases care taking rate decreases. Benefiting from prenatal care
increases also with the increase in mother’s educational level.11 But, in our studies, it could not be
set a relation between rate of prenatal care and this
factors. 80% of mothers included in our study are
below 30 years of age therefore, our study group
is constituted from young mothers who are having
a few number of children. It is considered that this
condition can cause that.
Early diagnosing of pregnancies at risk and giving the appropriate care reduces morbidity and
mortality of both mother and baby. Blood pressure
monitorization, blood and urine analysis are quite
important in determining diseases that risking
pregnancy and baby such as preeclampsia and
gestationel diabetes. It is recommended to make
gestational diabetes screening between 24th-28th
pregnancy weeks to all of the pregnants.7,9,14 In our
study, gestational diabetes is determined in 5% and
hypertension in 7.6% of our patients. It is reported
that gestational diabetes incidence varies from
1.2% to 6.5% and hypertension is seen in 5% to
10% of pregnancies in studies performed in different regions of our country.15, 16
Ultrasonography is quite important in evaluating the fetus morphology.7,9 According to data from
Turkey’s Population and Health Investigation 2003
it is reported that ultrasonography is made at least
one time in 91% of mothers taking ANC.11 It is seen
in our study that ultrasonography is made at least
for one time during pregnancy period in 94.4% of
mothers. It is frequently applied to ultrasonography in higher rates than other diagnose or scan
aimed investigations. The reasons for preference of
11
ultrasonographic investigation in higher rates are;
family considers ultrasonography as the most
important investigation among the others, willingness to learn the sex of baby, doctor's prefer to
comfort his patient, feeling himself in confidence
and besides those also doctor’s aiming to earn
money.
In our study, HBs antigen positivity rate is
found 1.04% (screening is made on 288 pregnant).
This rate is found as 7.3% in a study made previously in Sanl›urfa.17 Our country takes place in a
medium endemic region about Hepatitis B infection. Hepatitis B has a more risk in developing
chronicity when taken in the earlier period of life.
All pregnant women must be screened routinely
because of that reason and passive Hepatitis B
Immunoglobuline must be injected and active
immunization (Hepatitis B vaccine) must be applicated to newborn delivered from Hbs Ag (+) mothers.7,9,17
According to data from Turkey’s Population
and Health Investigation 2003 average number of
live deliveries is 3.5 in women who are at the end
of fertility period.11 In our study average number
of children is found (1.6+0.8) and it is lower than
the Turkey average. The reason for that lower
value can be mothers included in our study were
younger and didn’t come to the end of fertility
period yet.
Rate of consanguineous marriage is above 20%.
For example, in our two big cities, in Konya and
Istanbul these rates are determined as 23.2% and
24.8% respectively.6,18 This rate is found lower
(16.3%) in our study and it is indicative that consanguineous marriage rates are high in mothers
having low education level. Consanguineous marriage is quite important because of linkage of
genetic diseases from generation to generation and
increase in the number of diseased individuals.
Similar rates are preserved in spite of regional differences, consanguineous marriage is related to
education and it is seen in high rates in mothers
having low education level. Furthermore, in our
study, it is seen that fertility rates are higher in consanguineous marriage group in spite of that there
is no difference between age averages of two
groups. Increased number of delivery, effects
directly the health of the mother, in the other side
every child added to family will effect the health of
the other children indirectly because of his or her
effect on distribution of income. Supporting of
education of girls who will become mothers in the
12
Dibek M›s›rl›o¤lu E vet al., Evaluation of the Prenatal Care Usage of Mothers
future, will show a parallel relationship with the
reducing in consanguineous marriages and will be
a great step in having a healthy community.
Breastfeeding is the first choice in baby nutrition and can meet all the needs of the baby.
Nutrition with mother milk is ideal for babies especially in first months because it ensures adequate
growing and important in protection from infections. American Academy of Pediatrics offers
breastfeeding up to one year, moreover, offers as
longer as breastfeeding as how low is the mother's
social and economical level.19 In the study of Dallar
et al it is determined that 90% of mothers are
knowing that breastfeeding is a must in first 4 – 6
months.19 This rate is found high (94%) similarly in
our study. Furthermore, it is understood that again
in a high rate (95.8%) mothers are having information about the requirement of immediate starting
of breastfeeding after delivery. This rate is found
42% in a study made by Cin et al20 Being high of
these rates can be related to fact that mothers are
informed about mother milk in our hospital and
this continues uninterrupted.
In conclusion, high application rates of mothers
to the health institution at least one time during
pregnancy is attracting attention. But, it indicates
that more effort have to be spent when we consider that only half of the women have adequate
followings, benefiting from health services because
of social security and majority are residing in city
or peripheral towns where hospital are found.
Because, decreasing of perinatal and maternal
mortality and morbidity can be possible with
growing healthy generation; existence of a social
security system covering all of the health expenses, giving the easy and easy-reachable health service, increasing the education level and improving
the ANC. Additionally, informing the mothers
about mother milk and causing them to use is very
important in order to make breastfeeding become
widespread and continuous.
References
1.
Kaya S. Sa¤l›k bak›m hizmetlerinin kullan›labilirli¤i. Toplum
ve Hekim 1995; 66:101-106.
2.
Mihçiokur S, Ak›n A. Dünya’da ve Türkiye’de anne ölümleri. Sa¤l›k ve Toplum 1998; 8: 37-44.
3.
TC. Sa¤l›k Bakanl›¤› Ana Çocuk Sa¤l›¤› ve Aile Planlamas›
Genel Müdürlü¤ü Ana ve Çocuk Ölümlerini Önleme Projesi, 2005.
4.
Türkiye’de Anne-Çocuk durum analizi, T.C Hükümeti-UNICEF iflbirli¤i program›, Ankara, 1996:129-136.
5.
Ak›n A, Özvar›fl fiB. Ana Sa¤l›¤› ve Aile Planlamas›. Bertan
M, Güler Ç (ed): Halk Sa¤l›¤› Temel Bilgiler. Ankara, Günefl
Kitabevi, 1995;119-155.
6.
Baksu A, Ç›¤sar MS, Göker N, Kartal S, Hergin CE. Akraba
evlili¤i yapan kad›nlarda e¤itim düzeyi, evlilik yafl› ve do¤urganl›k oranlar›. fiEH T›p Bülteni 2000; 3: 35-40.
7.
Öndero¤lu L. Prenatal bak›m. Temel Yenido¤an Sa¤l›¤›, Ertogan F, Arsan S (ed), Öncü Ltd, Ankara 1999:1-7.
8.
Boz DG, Öztürk Y. Sivas Do¤umevi Hastanesinde do¤um
yapan kad›nlar›n do¤um öncesi bak›m ve do¤uma iliflkin
bilgi ve davran›fllar›n›n de¤erlendirilmesi. Erciyes Üniversitesi Sa¤l›k Bilimleri Dergisi 2003; 12: 62-68.
9.
Altunyurt S. Do¤um öncesi bak›m. 22-24 Eylül 2005 III. Ulusal Ana Çocuk Sa¤l›¤› Kongre Kitab› 79-81.
10. T.C Sa¤l›k Bakanl›¤›, Sa¤l›k Projesi Genel Koordinatörlü¤ü.
T.C. Sa¤l›k Bakanl›¤› veri toplama ve bildirim formlar› kullan›m k›lavuzu, Ankara 1996: 21-23.
11. Türkiye Nüfus ve Sa¤l›k Araflt›rmas› 2003. Hacettepe Üniversitesi Nüfus Etütleri Enstitüsü, Sa¤l›k Bakanl›¤› Ana Çocuk Sa¤l›¤› ve Aile Planlamas› Genel Müdürlü¤ü, Devlet
Planlama Teflkilat› ve Avrupa Birli¤i, Ankara, Türkiye, 2004.
12. Bozkurt A‹, fiahinöz S, Özç›rp›c› B, Özgür S. Gaziantep’te
sa¤l›k ocaklar›na herhangi bir nedenle baflvuran 15-49 yafl
evli kad›nlar›n do¤um öncesi, do¤um ve do¤um sonras› bak›m alma durumu ve etkileyen faktörlerin de¤erlendirilmesi. Erciyes T›p Dergisi 2001; 23: 59-67.
13. K›l›ç D. Erzurum il Merkezinde 15-49 Yafl Grubu Annelerin
Sa¤l›k Ocaklar› Taraf›ndan Verilen Ana Çocuk Sa¤l›¤› Hizmetlerini Kullanma Durumlar› ve Etkileyen Faktörler. Atatürk Üniversitesi Hemflirelik Yüksekokulu Halk Sa¤l›¤›
Hemflireli¤i Anabilim Dal›, Yüksek Lisans Tezi, 1998.
14. Günay T. Do¤um öncesi bak›mda durum. 22-24 Eylül 2005
III. Ulusal Ana Çocuk Sa¤l›¤› Kongre Kitab›: 89-92.
15. Harma M, Harma M, Kafal› H, Öksüzler C, Demir N. ‹lk Antenatal Muayenede Yap›lan Glukoz Tarama Testinin De¤eri. Perinatoloji Dergisi 2003; 11: 37-40.
16. Erata Y E. Preeklampsi: tan›-tedavi. 26-30 Ekim 2003, IX.
Ulusal Perinatoloji Kongre Kitab›: 28-32.
17. Harma M, Harma M, Kafal› H, Güngen N, Demir N. Gebelerde Hepatit B Tafl›y›c›l›¤› ve Yenido¤ana Vertikal Geçifl.
Perinatoloji Dergisi 2003; 11: 29-32.
18. Demirel S, Kaplano¤lu N, Acar A, Bodur S, Paydak F. The
frequency of consanguinity in Konya, Turkey and its medical effects. Genetic Counseling 1997; 8: 295-301.
19. Dallar Y, Er P, Ifl›klar Z. Annelerin bebek beslenmesi
konusuna iliflkin bilgi, tutum ve davran›fllar›. Ege Pediatri
Bülteni 2002; 9:175-180.
20. Cin A, Özkaya B, Ergin S, Yaprak I, Kansoy S, Engindeniz
E. 0-24 ayl›k bebek beslenmesi ve annelerin anne sütü ile
bebek beslenmesine iliflkin bilgi-tutum ve davran›fllar›. Optimal T›p Dergisi 2000; 13:3-9.
13
Perinatal Journal • Volume: 14, Number: 1/March 2006
Questionnaire Form
A SURVEY ON MOTHERS AND CHILDREN REGARDING MOTHER & CHILD HEALTH
1) No: ……………………
2) Mother’s age : ……………………
1) 18 years or less 2) 19-24 years
3) 25-29 years
4) 30-34 years
5) 35 years and older
3) Mother’s level of education:
1) Illiterate 2) Able to reads and write 3) Primary School 4) Secondary School 5) High School 6) College
4) Place of residence (city/district/village): ……………………
5) Baby’s gender:
1) Girl
2) Boy
6) Mother’s profession:
1) Housewife
2) Unqualified employee
3) Technician
4) Employee, holder of bachelor’s degree
7) Father’s profession:
1) Unemployed 2) Unqualified employee
3) Technician
4) Employee, holder of bachelor’s degree
8) Duration of marriage: …………………… years
1) 0-5 years
2) 6-10 years
3) 11-15 years
4) 16-20 years
5) 21 years and longer
9) Number of pregnancies: ……………………
10) Number of deliveries: ……………………
11) Interval with the last pregnancy: ……………………
1) First pregnancy
2) Less than 2 years
3) 2 years and longer
12) Number of miscarriages?:……………………
13) Number of children?: ……………………
14) How many times have you been checked during the pregnancy?: ………….
1) Never
2) Once
3) 2-3 times
4) 4-5 times
5) 6 times and more
15) Have you been subject to ultrasound examination?:
1) Yes, and the result is normal
2) Yes, and the result is not normal
3) No.
16) Have you been subject to triple test?:
1) Yes, and the result is positive
2) Yes, and the result is negative
3) No
17) Have you develop diabetes mellitus?:
1) Yes
2) No
18) Have you developed hypertension?:
1) Yes
2) No
19) Has HbsAg been examined?:
1) Yes, and the result is positive
20) Type of delivery:
1) Normal
2) C/S
2) Yes, and the result is negative
Weight at delivery : ……………………...gr
21) When should you start breast feeding?: ………………………
22) For how long should you continue breast feeding?: ………………………
3) No
14
Perinatoloji Dergisi • Cilt: 14, Say›: 1/Mart 2006
The Correlation of Thyroid Hormone Levels
and Gestasional Weeks in
Amniotic Fluid at Second Trimester
Ahmet Kale1, Nurten Akdeniz1, Ebru Kale2, Ahmet Yal›nkaya1, Murat Yayla1
Department of Gynecology and Obstetrics, Department of Biochemistry, Faculty of Medicine, Dicle University, Diyarbak›r
2Clinics of Gynecology and Obstetrics, Haseki Hospital, Istanbul
1
Abstract
Objective: The purpose of this study was to determine thyroid hormone levels of amniotic fluid and correlate with gestasional
ages.
Methods: 125 pregnant women underwent amniocentesis procedure for prenatal diagnosis were inclueded in study between
May 2004 and May 2005. Thyroid hormone levels were analyzed with using Roche E170 Modular analytics (Hitachi, Japan) system. Statistical analyses were performed by using One-Way Anova test. A value of p<0.05 was considered statistically significant.
Results: The mean age of patients was 34.5 ± 5.6 (21-40) The mean gestational age of patients who underwent amniocente-
sis was 17.88 ± 1.58 (16-20) Karyotype analysis of all patients was normal. Amniotic fluid levels of total and free T4 increased
progressively with gestasional age (p< 0.001). Although total T3 , free T3 and TSH levels did not increase with gestasional age
(p>0.05).
Conclusion: The levels of thyroxine (T4) hormone in amniotic fluid was higher than T3 and TSH hormones. The need of thyrox-
ine (T4) hormone increased with gestasional age.
Keywords: Thyroid hormone, amniotic fluid, gestational age.
Ikinci trimester amniotik s›v› tiroid hormon düzeyleri ile gestasyonel
hafta aras›ndaki iliflki
Amaç: Amniosentez uygulanan gebelerin amnion mayilerindeki tiroid hormon düzeylerini ölçmek ve bu de¤erlerin gestasyonel
hafta ile olan iliflkisini de¤erlendirmek.
Yöntem: Çal›flmaya, May›s 2004 ile May›s 2005 tarihleri aras›nda prenatal tan› amac›yla, klini¤imizde amniosentez yap›lan top-
lam 125 gebe dahil edildi. Tiroid hormon analizleri, 1ml amnion s›v›s›nda, Roche E170 Modular analytics (Hitachi, Japan) cihaz›
ile, Roche marka ticari kit kullan›larak gerçeklefltirildi. Veriler, istatistiksel olarak One-Way Anova testi kullan›larak karfl›laflt›r›ld›,
p<0.05 de¤eri istatistiksel anlaml› olarak kabul edildi.
Bulgular: Çal›flmaya al›nan hastalar›n ortalama yafl›, 34.5 ± 5.6 (21-40) y›l idi. Amniosentez uygulanan olgular›n ortalama gebelik haftas›, 17.88 ± 1.58 (16-20) olarak bulundu. Tüm hastalarn amniosentez sonucu normal karyotip olarak tesbit edildi. Olgular›n amnion s›v›s›ndaki total T4 ve serbest tiroksin (f T4) seviyeleri, gestasyonel hafta art›kça progresif olarak art›fl gösterdi (p<
0.001). Buna karfl›l›k total T4 , serbest triiodotronin (f T4) ve TSH seviyeleri gestasyonel hafta ile birlikte progresif olarak art›fl göstermedi (p>0.05).
Sonuç: Amnion s›v›s›ndaki tiroksin (Tv) hormonun miktar›n›n, T4 ve TSH’a göre daha fazla oldu¤unu bulduk ve bu hormona olan
ihtiyac›n gebelik haftas› artt›kça belirginleflti¤ini düflünüyoruz.
Anahtar Sözcükler: Tiroid hormon, amnion s›v›s›, gestasyonel hafta.
Correspondence: Dr. Ahmet Kale, Dicle Üniversitesi T›p Fakültesi, Kad›n Hastal›klar› ve Do¤um Anabilim Dal›, 21280 Diyarbak›r
e-mail: [email protected]
15
Perinatal Journal • Vol: 14, Issue: 1/March 2006
Introduction
Thyroid hormones that accelerate tissue growth
synthesis through DNA and RNA synthesis are necessary for normal growth and development.
Thyroid hormones are responsible for dendritic
and axonal development, synaptogenesis, neuronal migration, myelinization, and cerebral differentiation in fetal period.1
Thyroid follicles and T4 synthesis was detected
in 10 week-fetus. As from 10th week, a growth in
fetal serum TSH, T4 and Thyroid binding globulin
levels was detected. Total and free T4 level reaches the adolescent levels in 36th week. On the
fourth hour following the birth, serum T3 and T
hormones reach the peak level. Since iodotironin
deiodinaz activity was high in placenta, transforming T3 and T4 into the inactive metabolites T3
and T4, TSH, T3 and T4 trespass to the fetus at low
level.3
4
The purpose of this study was to determine
thyroid hormone levels of amniotic fluid and correlate with gestational ages.
povidine iodine, accompanied by the ultrasonography, transabdominal amniocentesis was applied.
Punctures were performed by single usage spinal
injectors varying 20-22 gauge. Thyroid hormone
analysis were studied in first two mP amnion fluid
before amnion fluid necessary for cytogenetic
analysis was taken. Total T3 and T4 free triiodothyronine (f T3), free thyroxine (f T4) and thyroid stimulant hormone (TSH) analysis were performed by
Roche E170 Modular analytics (Hitachi, Japan) system, Roche commercial kit. The cases were divided into 5 groups for amniocentesis. Group I; 16th
pregnancy week (n=25), group II; 17th pregnancy
week (n=25), group III 18th pregnancy week (n=
25), group IV 19th pregnancy week (n=25), group
V, 20th pregnancy week (n=25). During the pregnancy, the patients with thyroid or systemic diseases weren’t included into the study. All data
were transferred to the software and this study was
analyzed prospectively. Statistical analyses were
performed by using One-Way ANOVA test. A
value of p<0.05 was considered statistically significant.
Methods
125 pregnant women underwent amniocentesis
procedure for prenatal diagnosis were included in
study between May 2004 and May 2005. All 16-20
weeks pregnants who are suggested amniocentesis
accepted this suggestion. Before amniocentesis,
both mother and father filled and signed amniocentesis approval form. Pregnancy age was measured by Toshiba SSH-140A, 3.5 MHz convex
probe colored Doppler ultrasonography device,
according to the BPD (biparietal diameter) and AC
(abdominal circumference) measurements. After
abdominal cleaning and cleaning of probe with
Results
125 pregnant women underwent amniocentesis
procedure for prenatal diagnosis, were included in
study between May 2004 and May 2005. The mean
age of patients was 34.5 ± 5.6 (21-40). The mean
gestational age of patients who underwent amniocentesis was 17.88 ± 1.58 (16-20). A Positive triple
test applied to 82 cases (65.6), advanced age to 20
cases (16%), maternal anxiety to 18 cases (14.4%),
and amniocentesis applied to 5 cases because of
mal obstetric anamnesis. Karyotype analysis of all
patients was normal.
Tablo 1. Thyroid hormone values in amnion fluid, varying with gestational week.
Thyroid hormone
levels
Total T3 (ng/ml)
Total T4 (ug/ml)
Free T3 (ng/dl)
Free T4 (ng/dl)
(TSH) (uIU/ml)
16th week
Group 1
17th week
Group 2
18th week
Group 3
19th week
Group 4
20th week
Group 5
P*
0,49±0,15
0,78±0,18
0,068±0,004
0,13±0,032
0,42±0,15
0,51±0,18
1,02±0,17
0,069±0,001
0,28±0,05
0,38±0,1
0,51±0,15
1,06±0,23
0,080±0,002
0,27±0,16
0,37±0,15
0,45±0,14
1,36±0,25
0,073±0,002
0,31±0,06
0,36±0,13
0,52±0,16
1,42±0,41
0,070±0,005
0,34±0,03
0,43±0,14
>0.05
<0.001
>0.05
<0.001
>0.05
16
Kale A et al., The Correlation of Thyroid Hormone Levels and Gestasional Weeks in Amniotic Fluid at Second Trimester
Rajatipi et al7 observed the presence of the thyroid hormone receptors in fetus lung, on 13th gestational week. This situation proves that thyroid
hormones have a role in fetal lung development in
early gestational weeks.
Total T3 and T4 free triiodothyronine (f T3), free
thyroxine (f T4) and thyroid stimulant hormone
(TSH) values varying according to the gestational
weeks, are shown in Table 1. Amniotic fluid levels
of total and free T4 increased progressively with
gestational age (p<0.001) (Figure 1). Although total
T3, free T3 and TSH levels did not progressively
increase with gestational age (p>0.05) (Figures 2
and 3).
Fetal thyroid gland isn’t functional until 12th
week. Fetus is under the influence of maternal thyroid hormones within the first trimester.8 Pop et al9
showed that the level of free T4 in early gestational period are strong indicators for motor and mental development of the infant after the birth.
Discussion
Clinical and experimental researches proved
that thyroid hormones are essential for normal
cerebral development in early fetal period and that
has specific effects on olfactory bulbus, in sub ventricular zone of cerebral cortex, and in hippocampus.1-4 It affects thyroid hormones, mitochondrial
energy metabolism in short and long term.5 It
affects the lipid distribution of fetal thyroid hormones and bone differentiation in histological
level.6
Fetal thyroid hormones are also increased in
cases of vaginal delivery, prolongation of the second gestation period, fetal umbilical fetal distress,
painting amnion fluid by meconium, and forceps
and vacuum usage that the fetus is exposed to the
intrauterine stress.10,11 Ward et al12 noted that maternal cardiac diseases, preeclampsia, HIV infection,
diabetes mellitus have no effect on fetal thyroid
hormones.
2,0
1,5
1,0
,5
95% Cl
Total T4 (ug/ml)
Free T4 (ng/dl)
0,0
16,00
17,00
18,00
19,00
20,00
Gestational weeks
Figure 1. Total T4 and free thyroxin levels in amnion fluid, varying with gestational
week
17
Perinatal Journal • Vol: 14, Issue: 1/March 2006
,7
,6
,5
4
,3
95% Cl
,2
Total T3 (ng/ml)
,1
Free T3 (ng/dl)
0,0
16,00
17,00
18,00
19,00
20,00
Gestational weeks
Figure 2. Total T3 and free thyroxin levels in amnion fluid, varying with gestational week.
,6
95% Cl TSH (ulU/mL)
,5
4
,3
,2
16,00
17,00
18,00
19,00
20,00
Gestational weeks
Figure 3. Thyroid stimulant hormone TSH level in amnion fluid, varying with gestational week
A growth in fetal serum TSH, T4 and thyroid
binding globulin levels occurs. TH, T4 and T3 lev-
els reach the peak level in second trimester and
they tend to decrease until the next term. In last
18
Kale A et al., The Correlation of Thyroid Hormone Levels and Gestasional Weeks in Amniotic Fluid at Second Trimester
trimester, T4 and TSH levels are higher than maternal levels however total T4 and T3 are lower. For
Fetal thyroid hormone metabolism, second and
third trimesters are critical transition period.13
Polk et al14 showed that total T4, and free T4 levels are augment along with gestational weeks and
serum T3 levels are low. Klein et al15 observed that
fetal serum T4, free T4 and thyroid binding globulin levels are in a significant increase between 26th
and 33rd gestational weeks, as from 34th gestational
week; there isn’t any change in these parameters.
Sack et al determined that amniotic fluid T4 levels
are progressively elevated before 20th week, however T3 levels didn’t give a progressive increase.16
In our study, total T4 levels and free thyroxin (f
T4) levels in amniotic fluid increased progressively
between 16 and 20th gestational weeks (p<0.001).
Although total T3 , free T3 and TSH levels did not
increase with gestational week (p>0.05) In fetal
period, normal cerebral development, fetal bone
and lung differentiation and similar cases that thyroid hormones influence, thyroxin (T4) hormone is
effective and the need for this hormone increased
as gestational weeks go by. Although T3, free T3
and TSH levels did not progressively increase with
gestational age, their presence in amnion fluid
make us think that they contribute to the fetal
development.
1.
References
Lavado-Autric R, Auso E, Garcia-Velasco JV, Arufe Mdel C,
Escobar del Rey F, Berbel P. Early maternal hypothyroxinemia alters histogenesis and cerebral cortex cytoarchitecture
of the progeny. J Clin Invest 2003; 111: 1073-82.
mouse brain. Neurosci Lett 2000; 280: 79 82.
5.
Wrutniak-Cabello C, Casas F, Cabello G. Thyroid hormone
action in mitochondria. J Mol Endocrinol 2001; 26: 67-77.
6.
Geloso JP, Hemon P, Legrand J, Legrand C, Jost A. Some
aspects of thyroid physiology during the perinatal period.
General and Comparative Endocrinology Gen Comp Endocrinol 1986; 10: 191-7.
7.
Rajatapiti P, Kester MH, de Krijger RR, Rottier R, Visser TJ,
Tibboel D. Expression of glucocorticoid, retinoid, and
thyroid hormone receptors during human lung development. J Clin Endocrinol Metab 2005; 90: 4309-4314.
8.
Calvo RM, Jauniaux E, Gulbis B, Asuncion M, Gervy C,
Contempre B, Morreale de Escobar G. Fetal tissues are exposed to biologically relevant free thyroxine concentrations
during early phases of development. J Clin Endocrinol Metab 2002; 87: 1768 1777.
9.
Pop VJ, Kuijpens JL, van Baar AL, Verkerk G, van Son MM,
de Vijlder JJ, Vulsma T, Wiersinga WM, Drexhage HA, Vader HL. Low maternal free thyroxine concentrations during
early pregnancy are associated with impaired psychomotor
development in infancy. Clin Endocrinol 1999; 50: 149 155.
10. Fukuda S. Correlation between function of the pituitary
thyroid axis and metabolism of catecholamines by the fetus
at delivery. Clin Endocrinol 1987; 27: 331–338.
11. Chan LY, Leung TN, Lau TK Influences of perinatal factors
on cord blood thyroid-stimulating hormone level. Acta Obstet Gynecol Scand 2001; 80: 1014-8.
12. Ward LS, Kunii IS, de Barros Maciel RM. Thyroid-stimulating hormone levels in cord blood are not influenced by
non-thyroidal mothers’ diseases. Sao Paulo Med J 2000;
118:144-7.
13. Hume R, Simpson J, Delahunty C, van Toor H, Wu SY, Williams FL, Visser TJ. Human fetal and cord serum thyroid
hormones: developmental trends and interrelationships. J
Clin Endocrinol Metab 2004; 89: 4097-103.
14. Polk DH. Thyroid hormone metabolism during development. Reprod Fertil Dev 1995; 7: 469-77.
2.
Thorpe-Beeston JG, Nicolaides KH, McGregor AM. Fetal
thyroid function. Thyroid 1992; 2: 207-17.
3.
Roti E, Gnudi A, Braverman LE. The placental transport,
synthesis and metabolism of hormones and drugs which affect thyroid function. Endocr Rev 1983; 4: 131-49.
15. Klein AH, Oddie TH, Parslow M, Foley TP Jr, Fisher DA.
Developmental changes in pituitary-thyroid function in the
human fetus and newborn. Early Hum Dev 1982; 6: 321-30.
4.
Hadj-Sahraoui N, Seugnet I, Ghorbel MT, Demeneix B.
Hypothyroidism prolongs mitotic activity in the post-natal
16. Sack J, Fisher DA, Hobel CJ, Lam R. Thyroxine in human
amniotic fluid. J Pediatr 1975; 87: 364-8.
Perinatal Journal • Volume: 14, Number: 1/March 2006
19
Second Trimester Termination of Pregnancy:
Comparing Intracervical Prostaglandin E2
(Dinoprostone) to Intravaginal
Misoprostol
Özgür Dündar, Ercüment Müngen, Levent Tütüncü, Murat Muhcu, Serkan Bodur, Yusuf Z. Yergök
Clinics of Gynecology and Obstetrics, Haydarpafla Educational Hospital,
Gülhane Military Medicine Academy of Medicine, Istanbul
Abstract
Objective: The purpose of this study was to compare the efficiency and safety of intracervical prostaglandin E2 (dinoprostone)
and intravaginal misoprostol in second trimester termination of pregnancy.
Methods: Forty cases in which pregnancy were terminated by dinoprostone and 63 cases of pregnancy termination using misoprostol were evaluated retrospectively. The dinoprostone group received 0.5 mg prostaglandin E2 intracervically. Misoprostol
was used intravaginally in a dose of 200 µg every 6 h with a maximum of five doses. The success rate, induction to abortion
interval and the incidence of side effects were analyzed for both groups. Statistical analysis was performed using independent
samples t test, Pearson X2 and Fisher’s exact test, where appropriate. A p value <0.05 were considered significant.
Results: The pregnancy was terminated within 48 hours in 60 of 63 patients (95.2 %) in the misoprostol group and in 31 of 40
patients (77.5%) in the dinoproston group; the rate of pregnancy termination in the misoprostol group was signifacantly higher than that of the dinoproston group (p=0.01; OR, 5.81; %95 CI, 0.46-2.18). While womitting-nausea rate was significantly
higher in the dinoproston group, (p=0.01; OR, 0.09; %95 CI, 0.01-0.79) there were no significant differences in the rates of
incomplete abortion, diarrhea, febril morbidity, bleeding, transfusion and cervical laceration between the two groups.
Conclusion: Misoprostol is an effective, easy to use, safe and cheap drug then dinoprostone for termination of second trimester
pregnancy.
Keywords: Second trimester, pregnancy termination, misoprostol, dinoprostone.
‹kinci trimester gebelik sonland›r›lmas›nda intraservikal prostaglandin E2 (dinoproston) ve
intravaginal misoprostolün etkinli¤inin araflt›r›lmas›
Amaç: ‹kinci trimester gebelik sonland›r›lmas›nda intraservikal prostaglandin E2 (dinoproston) ve intravaginal misoprostolün etkinli¤ini araflt›rmak.
Yöntem: Çal›flmaya 1995-2006 tarihleri aras›nda, Klini¤imizde 14-28 gebelik haftalar›nda maternal veya fetal nedenlerle gebelik
sonland›rma endikasyonu al›p, intraservikal PGE2 (dinoproston) uygulanan 40 hasta ve intravaginal misoprostol uygulanan 63
hasta dahil edildi. Misoprostol 200 µg, vaginal olarak, 6 saat aralarla maksimum 5 doz uyguland›. Dinoproston (prostaglandin
E2) 0.5 mg intraservikal uyguland›. 48 saat içinde gebeli¤i sonlanmayan olgularda yöntem baflar›s›z kabul edildi. Her iki grubun
48 saatlik süreçte gebelik sonlanmas›ndaki baflar› oranlar› ile komplikasyon ve yan etkiler karfl›laflt›r›ld›. ‹statistiksel de¤erlendirmede student t, Fisher’s exact ve X2 testleri kullan›ld›. p de¤erinin 0.05’den küçük olmas› anlaml› kabul edildi.
Bulgular: Misoprostol uygulanan birinci gruptaki 63 hastan›n %95.2’inde (60 hasta), intraservikal dinoproston uygulanan 40 hastan›n %77.5’inde (31 hasta) gebelik 48 saat içinde sonland›; misoprostol grubunda gebelik sonlanma oran›, dinoproston grubuna göre anlaml› olarak daha yüksekti (p=0.01; OR, 5.81; %95 CI, 0.46-2.18). Bulant›-kusma, dinoproston grubunda anlaml› olarak daha yüksek oranda gözlenirken ( p=0.01; OR, 0.09; %95 CI, 0.01-0.79), tam olmayan düflük, diyare, febril morbidite, kanama, transfüzyon ve servikal y›rt›k yönünden gruplar aras›nda anlaml› farkl›l›k yoktu.
Sonuç: ‹kinci trimester gebeliklerin sonland›r›lmas›nda intravajinal misoprostol kullan›m›n›n, dinoproston kullan›m›na göre daha
etkin ve güvenli oldu¤u sonucuna var›ld›.
Anahtar Sözcükler: ‹kinci trimester, sonland›rma, misoprostol, dinoproston.
Correspondence: Dr. Özgür Dündar, GATA Haydarpafla E. H., Kad›n Hastal›klar› ve Do¤um Klini¤i, T›bbiye Cad. 34668 Üsküdar-‹stanbul
e-mail: [email protected]
20
Dündar Ö et al., Second Trimester Termination of Pregnancy
Introduction
In first trimester termination of pregnancy
dilatation and curettage (D&C) are used generally.
In second trimester termination of pregnancy surgical intervention can be used. However the
process is more complicated in second trimester
pregnancies since fetal-placental structures are
dilated, bleeding is increased and cervix is maturated and a special experience is required in this
subject. On account of these reasons prostaglandins (PG) are preferred in second trimester terminations of pregnancy rather than surgical intervention nowadays with the usage of prostaglandins
(Prostaglandin E and S).1 Another frequently used
method is oxytocin hormone which is used in different doses intravenously. Misoprostol peptic is a
synthetic PGE1 (15-deoksi-16-hidroksi-16-methyl
analog) analog used in treatment of ulcer2. It is
used as per oral (PO), rectal and vaginal methods.
It does not require special conditions for to be preserved, and can be preserved for years.2 It is used
in abortion induction, maturation of cervix, postpartum bleeding control and parturition induction
due to its effects of uterus contracting and cervix
maturating.2 Misoprostol PO can be determined
after two minutes it is taken.3 and leads to contraction in uterus.4 It does not lead to hypertension.5 Prostaglandins are agents which can be used
in vaginal and intracervical ways for provision of
pre-induction cervical maturation in second
trimester termination of pregnancy.1 Prostaglandin
E2 (PGE2, dinoproston) is used as intracervical.
PGE2 requires endocervical application and it is so
expensive and difficult to preserve since it is easily inactivated in normal room conditions.6
Methods
40 patients in whom PGE2 (dinoproston) had
been applied and 63 patients in whom intravaginal
misosprostol who had been applied pregnancy termination indications in their 14-28 pregnancy
weeks due to maternal or fetal reasons in our
Clinic between 1995 and 2006 were included in
the study. The group in which misoprostol has
been used was evaluated as Group 1 and the other
applied dinoproston was evaluated as Group 2.
data relating to the patients was obtained by examining patient files in the clinic archive retrospectively. Both groups of patient was passed through
a full systemic and gynecologic examination after
hospitalized and routine blood analyses and
obstetric ultrasonography USG) were applied. In
addition, fibrinogen, bleeding time, coagulation
time and protrombine time were examined in
inutero ex fetuses. Cases with severe lung and kidney disease, decompensate heart failure, placenta
previa, hydramnios, myoma, glocom, prostaglandin sensitivity, severe asthma, inflammatory intestinal disease, and those who passed caesarian or
operations which may cause uterine scar were not
included in the study.
The patients for whom dinoproston was
applied was brought in lithotomic position. After
vulva and vagina were disinfected, cannula is
pushed until internal osmium by putting specially
prepared cannula on the injector. While the gel
was given to cervical channel slowly cannula was
backed out. Special attention was paid in order to
prevent gel to extend internal osmium and to be
given in vagina. After the process the cases in
which discourse was not started were evaluated by
touching again. 1% oxytocin infusion was used in
those bishop score is above 6 and the repeat of the
process was applied in score below 6 and the technique was considered as successful in patients
whose pregnancy terminated in 48 hours. In cases
bishop score does not extend 6 despite 2 doses of
intracervical PGE2 application and in cases whose
pregnancy did not terminated in 48 hours, the
method was considered as unsuccessful.
In the groups for which misoprostol was
applied 200 µg misoprostol (Cytotec tablet 200 µg,
Searle®) serum was softened with physiological
and located on vagina posterior fornix in lithotomic position and maximum 5 doses were applied in
6 hour intervals. In cases whose pregnancy did not
terminated in 48 hours, the method was considered as unsuccessful.
After the process patients were passed from
fever, pulse, tension arterial controls in every 15
minutes during the first 2 hours, in every one hour
in following 8 hours and in every 4 hour until the
pregnancy terminated. After fetus and its supplements were discharged cavity control was applied
in patients for whom a suspicion about whether
the process was completed. Lactation inhibition
was applied in patients whose pregnancy terminated and the patients were followed up. After 24
hours the patients who had no problem were discharged from the hospital and called for a control
after 3-6 weeks.
21
Perinatal Journal • Volume: 14, Number: 1/March 2006
Age, parity, pregnancy week, USG data, reason
of pregnancy termination, application hour of the
method, amount of the medicine applied, blood
count after and before abortus, average duration of
termination of the pregnancy and complications
were determined and recorded. Diarrhea, vomiting, headache, fatigue, sensitivity in nozzles, fever
above 38 °C, febril mobidity were considered as
abnormal. Induction-abortion duration was defined as the duration beginning from the first misoprostol and dinoproston application until abortion.
Induction-abortion durations, successful abortion
rates fulfilled between 12-24 hour, 24-36 hour and
36-48 hour, incidence of adverse effects were compared between the groups. Statistical analyses of
the data were performed with SPSS 11.0 (Statistical
Package for Social Sciences Chicago, USA) package program which has been prepared for
Windows. Statistical calculations were performed
with Student’s t test, Fisher's exact and X2 tests. p
values below 0.05 in were considered as statistically meaningful.
Results
Ages of 103 patients participated in the study
differ between 17 and 41. Average age of two
groups was 26.28±5.10. Average age of the
patients participated in the first group of the study
was determined as 26.73±4.86, and the average
age of patients in second group as 25.57±5.41.
There is not any meaningful difference between
two groups in terms of age, gravida, parity and
gestational week. Demographic characteristics of
both groups were indicated in Table 1.
Majority of cases were composed of 21-25 age
group (43.7%), second frequent age group was 2630 age group (30.1%), and the third frequent was
31-35 age group (11.6%). The least number of
cases are composed of the groups of 36 and above
ages (%7.8). This sequence in total number of
Table 1. Demographic characteristics of the groups.
Maternal age
Gravida
Parity
Pregnancy week
Group 1
Group 2
p
26.73±4.86
2.01±0.97
1.05±1.02
18.01±3.52
25.57±5.41
1.75±0.97
0.75±0.98
18.02±3.02
0.19
0.11
0.78
0.99
Note: Values are stated as average ± standard deviation
patients is founded as the same if two groups are
evaluated separately.
All cases were in 14-28 weeks of pregnancy
according to examination and ultrasonography
results. Average pregnancy week of the patients in
the first group was determined as 18.01±3.52, and
average pregnancy week of the patients in the first
group determined as 18.02±3.02. When distribution of the patients according to pregnancy week,
majority of cases was composed of those in 14-16
weeks of their pregnancy (39.8%). Second frequent
was composed of those in 17-19 weeks of their
pregnancy (34.9%). The least number of cases was
determined in 26-28 week pregnancy terminations
(3.9%). This sequence in total number of patients
is founded as the same if two groups are evaluated separately.
When the patients are evaluated according to
their parities, nullipar ones constitute the majority
(43.7%), primiparas comes second (29.1%), and
multiparas come third (27.2%). This sequence is
founded as the same if two groups are evaluated
separately.
When indications of termination of pregnancy
were investigated in patients inutero exitus comes
first (59.2%), cases with fetal anomaly come second (29.1%). Indications of termination of pregnancy in both groups were stated in Table 2.
In 95.2% (60 patients) of 63 patients in the first
group for whom misoprostol was applied preg-
Table 2. Distribution of patients according to indications of termination of
pregnancy.
Group 1
Group 2
Total
Indications
n
%
n
%
n
%
‹nutero exitus
Fetal anomaly
Anhidramnios
Rubella infection
Severe preeclampsia
32
21
10
—
—
50.8
33.3
15.9
—
—
29
9
—
1
1
72.5
22.5
—
2.5
2.5
61
30
10
1
1
59.2
29.1
9.7
1
1
n: Number of cases
22
Dündar Ö et al., Second Trimester Termination of Pregnancy
nancy terminated in 48 hours. In one of three cases
in which this application was considered as unsuccessful pregnancy terminated after 13 dose misoprostol 200 µg given with intervals and in one
another pregnancy terminated after 18 doses misoprostol 200 µg. In the third case in which the
method was unsuccessful pregnancy terminated
after oxytocin infusion. Pregnancy terminated in 48
hour in 77.5% (31 patients) of 40 patients for
whom intracervical dinoproston was applied. In
nine patients this method was recognized as
unsuccessful pregnancy was terminated by applying extraamniotic rivanol. When the success rates
of both methods are compared success of misoprostal group has a statistically meaningful difference compare to dinoproston group (p=0.01; OR,
5.81; 95% CI, 0.46-2.18).
In dinoproston group pregnancy of 19 patients
terminated in the first 24 hours after a single dose
of intracervical dinoproston without any need to
another process, pregnancy of 9 patients terminated in 48 hours following a dose of intracervical
dinoproston, pregnancy of 3 patients terminated
after oxytocin infusion following two doses of
intracervical dinoproston. In 4 among 31 patients
whose pregnancy terminated cavity control was
applied with curette due to the incompletion of
discharge. In the group which used misoprostol,
pregnancy of 60 patients among 63 terminated in
24 hours with no necessity to another process,
oxytocin infusion was applied for 3 patients as
additional process.
Cavity control was applied with curette due to
the incompletion of discharge for 6 patients in the
first group. Minimum 1 and maxium 18 tablets were
used in the patients for whom misoprostol was
applied. Misoprostol dose applied was found in
average as 3.14±2.70 tablet (628±540 mg).
Misoprostol dose used in the first 12 hour duration
when misoprostol was found statistically meaningful compare to dinoprostol was determined as
1.5±0.51 tablet (300±102 mg).
When the rates of termination of pregnancy in
the first 24 hour are compared between two groups
there was a statistically meaningful difference in
misoprostol group (p=0.01; OR, 4.25; 95% CI, 1.7810.15). Success rates of groups in 24 hour durations
are stated in Table 3.
Any severe complication did not appear in the
patients of both groups. Minor complications
appeared are indicated in Table 4. In our study
minor complication appeared in 8 (12.7%) among
63 patients used minoprostol and 15 (37.5%)
among 40 patents used dinoproston. There was
determined a statistically meaningful difference in
complication arte appeared in dinoproston group
compare to misoprostol group (p=0.03; OR, 0.242;
95% CI, 0.091-0.646). While nausea/vomiting
appeared in only one patient among those in the
Table 3. Distribution of patients according to termination of pregnancy
indications
Group 1
Group 2
Duration
n
%
n
%
p
OR
95% CI
0-24
0-48
50
60
79.4
95.2
19
31
47.5
77.5
0.01
0.01
4.25
5.81
1.78-10.15
0.46-2.18
n: Number of cases
Table 4. Distribution of complications according to the groups
Group 1
Group 2
Complications
n
%
n
%
p
95% CI
OR
Nausea/Vomiting
Incomplete abortion
Diarrhea
Fever > 38°
Bleeding
Transfusion
Cervical rupture
1
6
—
—
1
1
—
1.6
9.5
—
—
1.6
1.6
—
6
4
2
1
1
1
1
15
7.5
2.5
2.5
2.5
2.5
2.5
0.01
1.0
0.15
0.39
1.0
1.0
0.39
0.01-0.79
0.25-3.59
0.98-1.13
0.98-1.08
0.04-10.35
0.04-10.35
0.98-1.08
0.09
0.95
1.05
1.03
0.63
0.63
1.03
n: Number of cases
Perinatal Journal • Volume: 14, Number: 1/March 2006
first group, nausea/vomiting appeared in six
among patients in the second group. When the
complaint of nausea/vomiting is evaluated between both groups the rate of appearance in dinoproston groups was determined as a statistically
meaningful difference (p=0.01; OR, 0.091; 95% CI,
0.011-0.791). Antiemetic was given to all patients
who complain about nausea/vomiting. These complaints of the patients remained in tolerable levels
with symptomatic treatment. The complaint of
diarrhea appeared in a patient in dinoproston
group which started after two hours from the
process and continued for 24 hours. A similar complication did not appear in any patient in the misoprostol group.
500 cc bleeding happened in one patent from
each group after discharge. When the patients
complained about bleeding after discharge were
examined again, retention was determined in placental tissues and cavity was cleaned with curette,
blood transfusion was applied in these patients. In
one of the patients included in the second group
fever above 38 °C appeared, a similar complication
did not occur in any of the patients in the first
group. Antipyretic treatment was applied in the
patient suffered from high fever and the fever did
not continue in this patient.
Cervical injury appeared in one of the patients
applied intracervical dinoproston. This process
was applied to this patient who is 17 week nullipara due to inutero exitus. Cervical laceration and
rupture were determined in the patient who suffered from bleeding after discharge. Cervical rupture was sutured duly.
Discussion
In parallel with improvements in diagnosis of
fetal anomaly there appears an increase in second
trimester terminations of pregnancy. There is not
already a consensus opinion concerning the most
ideal method for termination of second trimester
pregnancies. Advantages and disadvantages are
declared in methods compare to each other used
in the studies about this issue.1,4,6 While determining the most appropriate method, cheapness, easiness of application, efficiency, shortness of duration pregnancy termination, lowness of number
and tolerability of its complications are important
desired criteria. In addition to them special conditions and counter indications, and experiences and
preferences of doctors who will apply the method
should also be taken into consideration.
23
Extraamniotic rivanol, prostaglandin F2 alpha
or saline infusion, laminaria and mifeptriston,
gemeprost, dinoproston, misoprostol were used in
second trimester termination of pregnancy
processes until now.7-10
In the study we obtained 77% success in 40
patients we used intracervical dinoproston. This
rate was meaningfully low compare to success rate
in patients for whom misoprostol was used. Failure
rate of our study in dinoproston group was found
higher than the studies which had been published
in the literature before. Mungen et al. has reported
5.45% failure in patients with second and third
primester pregnancies with the combination of
intracervical dinoproston and oxytocin infusion.11
Karaman et al. has declared 5.5% failure in 20-36
week pregnant women with the same method.12
Gedikoglu et al. has reported that the process was
failed only in one patient among 30 postterm
patients (3.33%) on whom they applied the same
procedure, and they determined 8.8% failure in 45
inutero exitus cases with second trimester pregnancy with this method.13 Yilmaz et al has declared
failure only in one case among 13 term pregnant
women.14 Some studies were published which
were applied by combining with some other
abortive methods than oxytocin infusion in order
to increase the efficiency of intracervical dinaproston. Rath and Kunt reported that they obtained
97.5% success in 42 patients by combining intracervical dinaproston with extraamniotic PGF2-alpha
and oxytocin.15
The usage of misoprostol for the first time was
declared by Lehair et al who has used it as intravaginal in termination of second trimester death
fetuses. As a result of these studies; it was reported that misoprostol is in high efficiency, minor
adverse effect was determined and it did not lead
to any complication.16
Bugalho et al declared that average termination
duration as 14.3 hour and success rate in termination of pregnancies as 88.6% in their study held in
132 pregnant women with legal abortion by using
800-1600 µgr intravaginal misoprostol.17 In another
study about second trimester termination of pregnancy which was held by using misoprostol due to
intrauterine death 157.4 µgr misopostol intravaginal was used in average, average termination duration was reported as 13.2 hour and success rate as
77.8%.18 Contrarily in the study held by Yapar et al
by using five different methods in second trimester
termination of pregnancy; it was found that
24
exraamniotic ethacridin, intravenous oxytocin and
balloon insertion are more efficient than intracervical PGE2 gel and vaginal misoprostol. In this
study, success rate of misoprostol group was
reported as 77.5%.19 In our study on the other
hand, pregnancy was terminated in 48 hours in
95.2% (60 patients) among 63 patients in the first
group for whom misoprostol was applied and
77.5% (31 patients) among 40 patients in the second group for whom intracervical dinoproston was
applied and success rate between pregnancy termination of two groups showed a statistically
meaningful difference.
Misoprostol is used as oral, vaginal, sublingual,
buccal and rectal methods. Absorption becomes
more effective in sublingual usage of misoprostol
and it reaches to high concentrations in blood in a
short time. Vaginal solubility and vaginal absorption happen slowly in vaginal usage of misoprostol, and so misoprostol effect takes longer. Tang et
al reported that termination rate in the first 24 hour
is higher in vaginal usage of misoprostol compare
to oral and sublingual usage and termination rates
in 48 hours are the same in their study on second
trimester termination of pregnancy.20 In another
study it was indicated that vaginal usage of misoprostol is more effective in parturition induction
compare to its oral and sublingual usage.21 Any
severe complication did not observed in any of the
patients we included in the study. We calculated
observed minor complications as 12.7% in the first
group we have applied misoprostol and as 37.5%
in the second group we have applied intracervical
dinoproston. The most frequently observed complication in the patients who use misoprostol was
rest placenta (9.5%), and the second two minor
complications observed only in one patient were
nausea/vomiting and bleeding, on the other hand
the most frequently observed complication in the
group which used dinoproston was nausea/vomiting (15%). In addition some other complications
observed rest placenta 7.5%, diarrhea 2.5%, fever
above 38°C 2.5%, bleeding 2.5% and cervical rupture 2.5% also occurred.
Complications and rates exhibited in some
studies held with intracervical dinoproston before
are similar with our study. Karaman has reported
infection and bleeding happened with this
method.12 Gedikoglu has reported nausea/vomiting.13 Rath and Khun reported uterine in addition
to them.15 The complications observed in the
Dündar Ö et al., Second Trimester Termination of Pregnancy
group we have used misoprostol are similar with
the complications observed the studies held with
misoprostol before.7,16,17 Usage of misoprostol
which can be easily provided as a method to terminate undesired pregnancies without control of a
gynecologist is found so dangerous. For this reason some measures required to prevent usage of
misoprostol out of control of a gynecologist should
be taken.
Conclusion
Findings in our study and the results of
researches conducted before indicate that misoprostol is a method required to be preferred firstly
as a cheap, easily applicable, efficient and safe in
case second trimester pregnancies need to terminated. Intracervical dinoproston is considered as a
method which should not be consulted in the first
plan in termination of second trimester pregnancies since its success rate is low, it is expensive,
required to be combined with oxytocin despite its
advantages like being noninvasive and easily
applicable.
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Ramsey PS RK. Misoprostol, a prostaglandin E1 analog, for
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Collins PW. Misoprostol: discovery, development and clinical applications. Med Res Rev 1990; 10:149-72.
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El-Rafaey H,Hinshaw K, Templeton A. The abortifacient effect of misoprostol in the second trimester. Hum Reprod
1993; 8: 1744-6.
4.
Norman JE, Thong KJ, Baird DT. Uterine contractility and
induction of abortion in early pregnancy by misoprostol
and mifepristone. Lancet l99l; 338: l233-6.
5.
Pregnancy and childbirth Module. In: Keirse MJNC, Renfrew MJ, Neilson JP, Crowther C, editors. Cochrane
Database of systematic Reviews. The Cochrane Collaboration, Issue 2. Oxford: Update software, 1995: Review
Nos 2974, 2999, 5352.
6.
Miller AM, Rayburn WF, Smith CV. Patterns of uterine activity after intravaginal prostaglandine E2 during preinduction cervical ripening. Am J Obstet Gynecol 1991; 165:10069.
7.
Mohamed Nabil MG, Bassam A el H. Second-trimester termination of pregnancy by extra-amnioic prostaglandin F2
alfa or endocervical misoprostol. Acta Obstet Gynecol
Scand 1998; 77: 429-32.
8.
Daskalakis GJ, Mesogitis SA, Papantoniou NE, Moulopoulos
GG, Papapanagiotou AA, Antsaklisa AJ. Misoprostol for second trimester pregnancy termination in women with prior
caesarean section. BJOG 2005; 112: 97-9.
9.
Yongyoth H, Boonsri C, Piyaporn P. A randomised controlled trial of 6 and 12 hourly administration of vaginal misop-
Perinatal Journal • Volume: 14, Number: 1/March 2006
25
rostol for second trimester pregnancy termination. BJOG
2005; 112: 1297-1301.
lication in cases of intrauterin fetal death. Int J Gynaecol
Obstet 1985; 23: 387-94.
10. Chung YP, Hwa HL, Ko TM. Laminaria and sulprostone in
second trimester pregnancy termination of fetal abnormalities. Int J Obstet Gynaecol 1999; 65: 47-52.
16. Lehair J, Lemarie P, Helleringer M, Manini P. Expulsion of
arrested pregnancy product in the second trimester using a
prostaglandin E1 analog administered intravaginally. Apropos of 12 cases. Rev Fr Gynecol Obstet 1989; 84: 19-23.
11. Müngen E, Yergök YZ, Ertekin AA, Bilgin H, Ülgenalp ‹.
‹ntraservikal dinoproston (PGE2) jel ile 2. ve 3. trimester
gebeliklerde serviksin olgunlaflmas› ve/veya eylem indüksiyonu. Jinekoloji Obstetrik Dergisi 1994; 4: 173-7.
12. Karaman Afi, Uran B, Erler A, Vural AH. Gebeli¤in sonland›r›lmas›nda ‹ntraservikal dinoproston (PGE2) jeli ve intraamniyotik hipertonik NaCl solüsyonu ile yap›lan karfl›lflt›rmal› bir çal›flma. Jinekoloji ve Obstetrik Dergisi 1992; 6:
148-53.
13. Gediko¤lu V, ‹nan A, Bulgur M, Yücesoy ‹, Baysal C,
Karaosmano¤lu S. ‹ntraservikal PGE2 jel aplikasyonu ile
servikal olgunlaflma ve travay indüksiyonu. Jinekoloji ve
Obstetrik Dergisi 1994; 8: 46-50.
14. Y›lmaz H, Çapano¤lu R. Do¤um indüksiyonu için prostaglandin jel uygulamas›. Jinekoloji ve Obstetrik Dergisi 1992; 6:
174-6.
15. Rath W, Khun W. Cervical ripening and induction of labor
by intracervical and extra-amniotic prostaglandin gel app-
17. Bugalho A, Bique C, Almedia L, Bergstrom S. Pregnancy interruption by vaginal misoprostol. Gynecol Obstet Invest
1993; 34: 226-9.
18. Merrell DA, Koch MA. Induction of labour with intravaginal
misoprostol in the second trimesters of pregnancy. S Afr
Med J 1995; 85: 1088-90.
19. Yapar EG, Senöz S, Ürkütür M, Bat›o¤lu S, Gömen O.
Second trimester pregnancy termination including Fetal
death: comparison of five different methods. Eur J Obstet
Gynecol Reprod Biol 1996; 69: 97-102.
20. Tang OS, Lau WNT, Chan CCW, Ho PC. A prospective randomised comparison of sublingual and vaginal misoprostol
in second trimester termination of pregnancy. BJOG 2004;
111: 1001–05.
21. Bartusevicius A, Barcaite E, Nadisauskiene R. Oral, vaginal
and sublingual misoprostol for induction of labor. Int J
Gynecol and Obstet 2005; 91: 2-9.
26
Perinatal Journal • Volume: 14, Number: 1/March 2006
The Effect of Sex on Fetal Ultrasound
Measurements: Is It Necessary
Sex-Spesific Nomograms?
Yeflim Bülbül Baytur, Hasan Y›ld›z, Ali Özler, Ümit Sungurtekin ‹nceboz, Hüsnü Ça¤lar
Department of Gynecology and Obstetrics, Faculty of Medicine, Celal Bayar University, Manisa
Abstract
Objective: To investigate the effect of gender differences on fetal ultrasound measurements like biparietal diameter, head cir-
cumference, abdominal circumference, femur length and estimated fetal weight.
Methods: Between 2002 and 2005, 548 women admitted to our obstetrics department were enrolled in the study. 637 ultra-
sound examination including biparietal diameter, head circumference, abdominal circumference and femur length were performed by 4 different investigators in these women. Fetal weight was estimated using the Hadlock 4 formula. Ultrasound measurements were recorded for each gestational week. The differences in ultrasound measurements between male and female
fetuses were investigated using Student t-test. P<0,05 was considered statistically significant.
Results: The birth weight was not different between female and male fetuses (3311 ± 518 and 3269 ± 522 gr, respectively)
(p>0.05). Femur length and abdominal circumference was significantly higher in male fetuses than females between 15 and 22
weeks of gestation, whereas estimated fetal weight were significantly higher in female fetuses than males between 27-30
weeks of gestation (p<0.05). Furtermore, head circumference was significantly higher in males than females between 35 and
38 weeks of gestation. Other measurements were not different between males and females (p>0.05).
Conclusion: The use of sex-spesific nomograms may obtain to evaluate fetal growth and also making accurate diagnosis for
intrauterine growth restriction and macrosomia. It may be useful to repeat this preliminary study in a large and heterogenous
population.
Keywords: Gender differences, estimated fetal weight, head circumference, abdominal circumference, ultrasound.
Cinsiyetin fetal ultrason ölçümleri üzerine etkisi: cinsiyete özgü büyüme e¤rileri gerekli mi?
Amaç: Fetusun cinsiyetinin, biparietal çap, kafa çevresi, abdomen çevresi, femur uzunlu¤u ve tahmini fetal a¤›rl›k gibi fetal ultra-
son ölçümleri üzerine etkisini araflt›rmak.
Yöntem: 2002-2005 y›llar› aras›nda, obstetri ve perinatoloji poliklini¤imize rutin kontrol amac›yla baflvuran 15-40 hafta aras›nda
548 gebe çal›flmaya dahil edildi. Bu gebelerde 637 fetal ultrason, biparietal çap, kafa çevresi, abdomen çevresi ve femur uzunlu¤unu içerecek flekilde, dört farkl› araflt›rmac› taraf›ndan yap›ld›. Tahmini fetal a¤›rl›k hesaplamas›nda ultrasonografinin program›nda yer alan Hadlock 4 formülü kullan›ld›. Her gebelik haftas› için fetal ölçümler kaydedildi. 15. haftadan 40. haftaya kadar
yap›lan tüm ölçümler 15-22. hafta, 23-26 hafta, 27-30 hafta, 31-34 hafta, 35-38 hafta, 39-40 haftalar aras›nda gruplanarak
karfl›laflt›r›ld›. Fetal ölçümlerin k›z ve erkek fetuslar aras›nda farkl›l›k gösterip göstermedi¤i Student t- testi kullan›larak
karfl›laflt›r›ld›. P<0.05 istatistiksel olarak anlaml› kabul edildi.
Bulgular: K›z ve erkek bebeklerin do¤um a¤›rl›¤› aras›nda bir fark yoktu (s›ras›yla 3311 ± 518 ve 3269 ± 522 gr) (p>0.05). 1522. gebelik haftalar› aras›nda k›z fetuslarda femur uzunlu¤u ve abdomen çevresi erkek fetuslara göre anlaml› ölçüde k›sa iken,
27-30. gebelik haftalar› aras›nda tahmini do¤um a¤›rl›¤› k›z fetuslarda, erkek fetuslara göre anlaml› ölçüde fazla, 35-38. gebelik
haftalar›nda ise kafa çevresi erkek fetuslarda k›z fetuslara göre anlaml› ölçüde fazla idi (p<0.05). Di¤er ölçümlerde k›z ve erkek
fetuslar aras›nda istatistiksel olarak anlaml› bir fark saptanmad›.
Sonuç: K›z ve erkek fetuslar için farkl› büyüme e¤rilerinin kullan›lmas›, intrauterin büyümenin do¤ru de¤erlendirilmesini için önerilir. Bir ön çal›flma olarak planlanan bu çal›flman›n, daha genifl ve daha heterojen bir hasta
Anahtar kelimeler: Cinsiyet farkl›l›¤›, tahmini fetal a¤›rl›k, bafl çevresi, abdominal çevre, ultrason.
Correspondence: Dr. Yeflim Bülbül Baytur, Celal Bayar Üniversitesi T›p Fakültesi, Kad›n Hastal›klar› ve Do¤um Anabilim Dal›, Manisa
e-mail: [email protected]
27
Perinatal Journal • Volume: 14, Number: 1/March 2006
Introduction
Biparietal diameter (BPD), head circumference
(HC), abdominal circumference (AC), femur length
(FL) are used to measure the estimated birth
weight (EBW) and evaluate intrauterine fetal maturation.1 These measurements are used for fetal
maturation estimation as well as intrauterine
growth retardation (IGR) and pathologies like
macrosomia.1,2-5 Some of the researchers are trying
to estimate the fetal weight by using maternal
weight, length, parity and the sex of the fetus as
well as ultrasound monitoring.6-9 It is a known fact
that male fetuses are taller, heavier and have larger cranial diameter in comparison to the female
fetus.10-12 Some contends that this difference is
begun as from the early gestational weeks.10,13 And
also, for female and male infants, the length and
weight growth is accelerated in different timetables
of intrauterine period.14
The purpose in this study is to investigate the
effect of gender differences on fetal ultrasound
measurements like BPD, HC, AC, FL and EBW.
Methods
Between 2002 and 2005, 548 women admitted
to our obstetrics department were enrolled in the
study and 637 ultrasonography monitoring were
performed. The reason for ultrasonography monitoring is to implement fetal measurement for triple
scanning, and second level detailed USG, routine
uterine artery Doppler, fetal growth follow up or
amnion fluid assessment. Any of the patients didn’t get involved to ultrasonographic examination
without indications. The gestational week was estimated by the latest menstrual period, if not know,
by the first trimester ultrasonography. The patients
with endocrinal disorders, preeclampsia, hypertensive, smoking, fetal anomalies, preterm gestation,
were excluded from the study. Ultrasonographic
scanning was made by 2 different ultrasonic device
(Siemens Sonoline Sienna, Siemens Medical
System, Erlangen, Germany and Voluson 730
Expert, General Electric, Kretz Ultrasound Systems,
Austria) 2-7 megahertz frequency range, using convex probe, conducted by 4 scanner. Biparietal
diameter, head circumference, abdominal circum-
ference, at thalamus level, calvarium skull circumference except the soft tissues, transverse
abdomen section that umbilical vein intersects
with portal vein and the distance from proximal
edge to femoral cervix in proximity to the distal
metaphysis are measured in a way that includes
only ossified sections.15 TDA was measured
through Hadlock 4 formula in the ultrasonic
device. The sex of the fetuses, which was determined antenatally, was confirmed after the gestation. All measurement between 15th and 40th
weeks, were grouped in 15-22, 27-30, 31-34, 35-38,
39-40th weeks and compared.
Statistical research was performed by using
SPSS (SPSS for windows, version 13.0, USA) software. The difference between ultrasonic measurements of the male and female fetuses and that of
their birth weight was researched using Student-t
test, and the relation between birth weight and
fetal measurements was analyzed by Pearson
Correlation Analysis. P<0,05 was considered statistically significant.
Results
All measurements, birth weight and basal values were shown as average ± standard deviation
(SD).
The mean age of patients was 28.3 ± 5.3 and 28
± 4.8. 49. 8% of the fetuses were male, 50.2% were
female. 48.6% of the pregnant women delivered
the fetus by cesarean, 51.4% delivered with vaginal
modality. There wasn’t a significant difference
between male and female birth weights (consecutively 331 ± 518 and 3269 ± 522 gr) (p>0.05). 548
women admitted to our obstetrics department
were enrolled in the study and 637 ultrasonography monitoring were performed. The dispersion
of the ultrasonic scanning numbers to the gestational weeks is shown in Figure 1.
Between 15th and 22nd gestational weeks, FL
and AC were comparatively short in female fetuses, between 27 and 30th gestational weeks, EBW
was significantly greater than male fetuses,
between 35 and 38th gestational weeks, HC was
significantly greater in male fetuses than the female
fetuses (Table 1). In other measurements, no sta-
28
Baytur YB et al., The Effect of Sex on Fetal Ultrasound Measurements: Is It Necessary Sex-Spesific Nomograms?
70
60
50
40
30
20
Count
10
0
15.00
19.00
17.00
23.00
21.00
27.00
25.00
35.00
31.00
29.00
33.00
39.00
37.00
Week
Figure 1. Dispersion of the ultrasonic scanning numbers to the gestational weeks (n = measurement).
tistical difference between male and female fetuses has been found.
Considering the relation between birth weight
and fetal measurements, there is a slight but significant correlation between fetal measurements in
male and female fetuses and birth weight (Table
2).
Discussion
It is a known fact that male fetuses are taller,
heavier and have larger cranial diameter in comparison to the female fetus.10-12 These natal measurement differences between male and female
infants are theoretically depended on different
growth rates in intrauterine period. The growth
rate of the male and female fetuses differs in
intrauterine period, according to their gestational
weeks.14 The femoral length and weight growth of
the female infants are more symmetrical and their
legs that are growing faster, enable that the pon-
deral indexes are lower.14 In another study, noted
that the sex of the fetus influence on BPC, HC and
FU and that it should be appropriate to use as an
independent variable for estimating weight.
Supporting this opinion, noted that the measurements of female infants are lower than that of the
male infants as from the early periods of the pregnancy.16-18
In our study, despite the male fetuses grew
faster than female fetuses in early gestational
weeks, EBW of the female fetuses outstrips the
EBW of the male fetuses in early trimester period,
following gestational weeks this difference closed
down. Since the measurement differences
between male and female fetuses in early gestational weeks, may have effect on the results of the
triple scanning tests, these differences are important.
In contrary to our study, Schwarzler et al17
found that all measurements except FL were dif-
29
Perinatal Journal • Volume: 14, Number: 1/March 2006
Table 1. BPD, FL, AC, HC and EBW measurements for male and female fetus (*p value indicates the ones that
are statistically significant).
Week
15-22
(n=196)
23-26
(n=76)
27-30
(n=72)
31-34
(n=102)
35-38
(n=137)
39-40
(n=52)
BPD (mm)
Female
Male
p
48.6±7.4
49.2±6.2
0.241
59.8±5.4
60.3±4.4
0.278
76.7±6.5
72±4.9
0.460
82.3±4.2
81.3±7.4
0.596
89.1±4.1
89.1±3.3
0.206
94.5±2.7
94.1±3.3
0.284
FL (mm)
Female
Male
p
33.2±6.6
33.9±5.3
0.017*
42.4±3.9
42.3±3.1
0.609
53.5±7.3
54.1±4.8
0.118
62.2±3.9
63±3.5
0.482
69.9±3.4
70.7±3.4
0.766
76.1±2.7
74.6±3.6
0.962
AC (mm)
Female
Male
p
158±26
160±20
0.026*
197±15
209±18
0.561
249.7±29.8
242.8±19
0.113
280.3±19.5
287±18.4
0.482
326±45.3
322.5±19.7
0.275
345.5±17.5
353.1±16.8
0.649
HC (mm)
Female
Male
p
184±25
186±18
0.052
223±20
224±24
0.563
272±25.4
268±19.5
0.745
304.7±19.6
302.7±21.1
0.590
318±18
327±13.1
0.004*
340.7±11.1
339±9.8
0.578
EBW (gr)
Female
Male
p
395±166
407±123
0.354
684±140
695±178
0.387
1403±517
1236±289
0.006*
2005±347
2063±303
0.284
2914±533
2986±336
0.193
3684±394
3547±296
0.504
ferent between 15th and 40th gestational week.
Hindmarsh et al10 observed low risk group single
pregnancy cases, between 20-30 weeks and found
that the sex of the fetus influence HC, on the
other hand, AC is greater in male fetus than
female fetus however FL wasn’t changed. In the
extent of these studies which were performed in
different geographical areas, the ethnic particularities may affect the results. In fact, studies showed
that ethnic origin and geographical territory have
effects on the growth rate of the fetus.19 Moreover,
the weight, length, parity which was supposed to
influence the weight of the fetus, are exluded
from our study and their influence should be
examined.
Schild et al.20 developed a special formula for
estimating the ultrasonographic fetal weight and
claimed that it contains lower fault tolerances
comparing to other methods. In our study, no difference between male and female weight estimations. But, there isn’t ant significant difference
between birth weights within our study group.
Eventually, it is natural not to find any difference
in intrauterine period. Changing climate, nutrition,
and living conditions are anthropologically changing the human kind. In this extent, that fact that
female fetuses are delivered in smaller size compared to the male fetuses, may be a new research
subject.
Table 2. Relation between birth weight and fetal measurements for male
and female fetus (r = correlation coefficient, p = significance).
EBW
BPD
FL
AC
HC
Female
r=216
p=0.003
r=180
p=0.01
r=177
p=0.01
r=185
p=0.01
r=160
p=0.03
Male
r=199
p=0.009
r=185
p=0.01
r=160
p=0.03
r=194
p=0.01
r=157
p=0.04
30
Baytur YB ve ark., Cinsiyetin Fetal Ultrason Ölçümleri Üzerine Etkisi: Cinsiyete Özgü Büyüme E¤rileri Gerekli mi?
The significant but slight effects of the ultrasonographic measurements for estimating the
fetal weight strengthen the opinions that are
claiming the inadequacy of the ultrasonographic
scanning in order to estimate the birth weight.
Consequently, the sex of the fetus may be influencing the measurements in some gestational
weeks. But, since there are many factors including
maternal, genetic, ethnic and geographical differences that influence the growth of the fetus, fetal
maturation should be evaluated in single case
basis, and serial measurements should be preferred instead of single measurements. Using different growth curves for female and male fetuses
may ensure the exact evaluation of intrauterine
growth and be useful for diagnosing intrauterine
growth retardation and macrosomia. It would be
appropriate to repeat this study, which was
planned as preliminary and single centered, on
larger and heterogeneous patient group.
Conclusion
Using different growth curves for female and
male fetuses may ensure the exact evaluation of
intrauterine growth and be useful for diagnosing
intrauterine growth retardation and macrosomia.
We think that it would be appropriate to repeat
this study, which was planned as preliminary and
single centered, on larger and heterogeneous
patient group.
1.
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and symphysiofundal height. Aust N Z J Obstet Gynaecol
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mur measurements- a prospective study. Am J Obstet Gynecol 1985; 151: 333-7.
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Gardosi J, Chang A, Kalyan B, Sahota D, Symonds EM. Customised antenatal growth charts. Lancet 1992; 339: 283-7.
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Gardosi J, Mongelli M, Wilcox M, Chang A. An adjustable
fetal weight standard. Ultrasound Obstet Gynecol 1995; 6:
168-74.
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Owen P, Farrell T, Hardwick JC, Khan KS.Relationship between customised birthweight centiles and neonatal anthropometric features of growth restriction. BJOG 2002;
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10. Hindmarsh PC, Geary MP, Rodeck CH, Kingdom JP, Cole
TJ. Intrauterine growth and its relationship to size and
shape at birth. Ped Research 2002; 52: 263-8.
11. Cogswell ME, Yip R. The influence of fetal and maternal
factors on the distribution of birth weight. Semin Perinatol
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12. Copper RL, Goldenberg RL, Cliver SP, Dubard MB, Hoffman HJ, Davis RO. Anthropometric assessment of body size
differences of full-term male and female infants. Obstet
Gynecol 1993; 81: 161-4.
13. Pedersen JF. Ultrasound evidence of sexual difference in
fetal size in first trimester. BMJ 1980; 281: 1253.
14. Lampl M, Jeanty P. Timing is everything: a reconsideration
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15. Bowerman RA, Nyberg DA. Normal fetal anotomic survey.
In: Nyberg DA, McGahan JP, Pretorius DH, Pilu G(Ed).
Diagnostic Imaging of Fetal Anomalies. Philadelphia, Lippincott Williams&Wilkins; 2003; p: 1-30.
16. Schwarzler P, Bland JM, Holden D, Campbell S, Ville Y.
Sex-spesific antenatal growth charts for uncomplicated
singleton pregnancies at 15-50 weeks. Ultrasound Obstet
Gynecol 2004; 23: 23-9.
17. Wald N, Cuckle H, Nanchahal K, Turnbull AC. Sex difference in fetal size in pregnancy. BMJ 1986; 292: 137.
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SP, Brumfield CG. Fetal biparietal diameter, head circumference, abdominal circumference and femur length. A
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fetuses. Int J Gynecol Obstet 2005; 88: 173-8.
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Sex-spesific fetal weight prediction by ultrasound. Ultrasound Obstet Gynecol 2004; 23: 30-5.
Perinatal Journal • Volume: 14, Number: 1/March 2006
31
Investigation of Folic Acid, Vitamin B12,
Vitamin B6 and Homocysteine Levels in
Preeclamptic Pregnancies
Ahmet Kale1, Ebru Kale2, Nurten Akdeniz1, Mahmut Erdemo¤lu1, Ahmet Yal›nkaya1, Murat Yayla3
Department of Gynecology and Obstetrics, 2Department of Biochemistry, Faculty of Medicine, Dicle University, Diyabak›r
3Clinics of Gynecology and Obstetrics, Haseki Hospital, ‹stanbul
1
Abstract
Objective: To investigate the relationship between preeclampsia and serum folic acid, serum B12, plasma vitamin B6 (pyridoxal-5’-phosphate) and plasma homocysteine levels.
Methods: 100 pregnant women with preeclampsia and 74 healthy pregnant women were included in the study from September
2004 to August 2005. Serum vitamin B12, folic acid and plasma vitamin B6 and homocysteine levels were measured in all
patients at their third trimester of pregnancy.
Results: Vitamin B12 serum levels in the preeclamptic and the control group were similar (117.44±42.03 pg/ml in the
preeclamptic group and 136.07±59.01 pg/ml in the control group, p>0.05 ). Vitamin B6 (pyridoxal-5’-phosphate) plasma levels
in preeclampsia group were lower than control group (6.40±2.91µg/l in preeclampsia group and 11.15±5.76 µg/l in the control group p<0.001). Folic acid serum levels in the preeclampsia group were lower (5.43±3.08 ng/ml in the control, 8.00±5.1
ng/ml, in the preeclamptic group, p<0.001). Homocysteine plasma levels were significantly higher in the preeclampsia group
than control group (10.50±6.21 µmol/L in the preeclamptic group and 6.54.±2.64 µmol/L in the control group, p<0.001).
Conclusion: High homocysteine level and low folic acid and vitamin B6 levels play a role in the pathogenesis of preeclampsia.
Keywords: Preeclampsia, homocysteine, folate, vitamin B6, vitamin B12.
Preeklamptik gebelerde folik asit, vitamin B12, vitamin B6 ve homosistein düzeylerinin
araflt›r›lmas›
Amaç: Preeklampsi ile serum folik asit, serum vitamin B12, plazma vitamin B6 (piridoksal 5 fosfat) ve plazma homosistein düzey-
leri aras›ndaki iliflkinin araflt›r›lmas›.
Yöntem: Eylül 2004-A¤ustos 2005 tarihleri aras›nda, klini¤imize baflvuran ve preeklampsi tan›s› alan 100 gebe ile herhangi bir
medikal problemi olmayan 74 sa¤l›kl› gebe çal›flmaya dahil edildi. Bütün hastalardan gebeli¤in 3. trimesterinde serum vitamin
B12, serum folik asit, plazma vitamin B6 ve plazma homosistein konsantrasyonlar› ölçüldü.
Bulgular: Vitamin B12 serum düzeyleri preeklampsi ve kontrol gruplar› aras›nda benzerdi (s›ras› ile; 117.44±42.03 pg/ml,
136.07±59.01 pg/ml, p>0.05). Vitamin B6 (piridoksal 5 fosfat) plazma düzeyi preeklampsi grubunda kontrol grubuna göre düflük bulundu (s›ras› ile; 6.40±2.91 µg/l, 11.15±5.76 µg/l, p<0.001). Folik asit serum düzeyi preeklampsi grubunda daha düflük
saptand› (s›ras› ile; 5.43±3.08 ng/ml, 8.00±5.1 ng/ml, p<0.001). Homosistein plazma düzeyi ise preeklampsi grubunda kontrol
grubuna göre anlaml› oranda yüksekti (s›ras› ile; 10.50±6.21 µmol/L, 6.54±2.64 µmol/L, p<0.001).
Sonuç: Yüksek homosistein konsantrasyonu ile düflük folik asit ve vitamin B6 düzeyleri preeklampsinin patogenezinde rol oyna-
yabilir.
Anahtar Sözcükler: Preeklampsi, homosistein, folik asit, vitamin B6 (piridoksal 5 fosfat), vitamin B12.
Correspondence: Dr. Ahmet Kale, Dicle Üniversitesi T›p Fakültesi, Kad›n Hastal›klar› ve Do¤um Anabilim Dal›, 21280 Diyarbak›r
e-mail: [email protected]
32
Kale A et al., Vitamin B12, Vitamin B6 and Homocysteine Levels in Preeclamptic Pregnancies
Introduction
Homocysteine is an aminoacid that forms during methionine metabolism. Homocysteine blood
levels are affected by genetic or many acquired
factors. The lack of enzymes added to the homocysteine metabolism or the cofactors necessary for
its metabolism (folate, B6 vitamin, B12 vitamin)
cause hyperhomocysteinemia.1 Mc Cully was the
first to suggest that high homocysteine leads to
atherosclerotic and thrombotic complications.2
Further studies showed disorder in endothelium
dependant relaxation in various isolated artery
preparations incubated with homocysteine.3 The
placental vascular changes in preeclamptic
patients: due to similar changes to those of atherosclerotic patients, various studies have been done
to investigate the relationship between preeclampsia and homocysteine, vitamin B6 (pyridoxal-5'phospate), vitamin B12 and folic acid levels, and it
was shown in these studies that preeclamptic
patients have higher homocysteine levels than
healthy pregnant women, and that there are
changes in parallel to this in vitamin B6 (pyridoxal-5’-phosphate), vitamin B12 and folic acid levels.4,5
The objective of this study is to research
whether there is any difference between
preeclamptic pregnant women and healthy normotensive pregnant women through the comparison of serum folic acid, serum vitamin B12, plasma vitamin B6 (pyridoxal-5’-phosphate) and plasma homocysteine levels.
Methods
This study was performed prospectively on a
total of 174 normotensive healthy pregnant women
and pregnant women diagnosed with preeclampsia who do not use any medication other than the
iron preparation and do not smoke and who contacted the Clinics of Gynecology and Obstetrics,
Faculty of Medicine, Dicle University between
September 2004 and August 2005. Ethical approval
was received to perform the study. Furthermore,
approval was also received from all patients that
their participation in the study is voluntary.
Preeclamptic pregnant women were classified as
the study group and healthy pregnant women as
the control group. The preeclampsia classification
was done according to ACOG (American College
of Obstetricians and Gynecologists) criteria.6 Blood
pressure ≥ 140/90 mmHg and proteinuria > 300
mg/dl in the 24 hour urine sample was considered
to be mild preeclampsia; blood pressure ≥ 160/110
mmHg and proteinuria (5 gr/more than 24 hours),
oliguria (500 ml/less than 24 hours), headache,
sight impairment, pain in the right upper quadrant,
liver function failure, and thrombocytopenia were
considered severe preeclampsia criteria.
In addition to the obstetric evaluation and laboratory examination in the 3rd trimester of gestation, blood was taken from all patients into EDTA
tubes for homocysteine and vitamin B6 (pyridoxal5’-phosphate) analysis, and into plain gel tubes for
folic acid and vitamin B12 analysis. After all samples were centrifuged at 3500 rpm for 10 minutes,
plasma was allocated for homocysteine and vitamin B6 (pyridoxal-5’-phosphate) and serum for
folic acid and vitamin B12. The samples acquired
were stored in the dark and at -24ºC until the day
of the study.
Homocysteine levels were studied using a DPC
brand "Immulate 2000 Homocysteine" kit (reference range 5.0-12 µmol/L), on the Immulate 2000
apparatus (DPC, Los Angeles) using the
immunoassay method.
Vitamin B6 (pyridoxal-5’phosphate) levels were
studied using a Recipe brand "ClinRep Complete
Kit for vitamin B6 (pyridoxal-5’phosphate) in
Plasma and Whole Blood" kit (reference range 8.627.2 µg/l), on the HPLC apparatus (Schimadzu,
Japan) using the chromatographic method.
Folic acid levels were studied using a Roche
brand kit (reference range 3.1-17.5 µg/l), on the
E170 system (Roche, Los Angeles) using the
chemiluminescence immunoassay method.
Vitamin B12 levels were studied using a Roche
brand kit (reference range 30-2000 pg/ml), on the
E170 system (Roche, Los Angeles) using the
chemiluminescence immunoassay method. The
student t test SPSS 10.0 for Windows computer
program was used in the statistical analysis of data,
and p<0.05 was accepted statistically significant.
Results
A total of 174 cases were included in the study
of which 100 were preeclampsia cases (Group 1)
and 74 were healthy pregnancy cases (Group 2).
33
Perinatal Journal • Volume: 14, Number: 1/March 2006
Table 1. The demographic, hematological and biochemical parameters of the groups and the
weights of the newborn.
Parameters
Age
Gravida
Parity
Systolic (mm/Hg)
Diastolic (mm/Hg)
Gestational week
White blood cell ( / mL)
Hemoglobin (g/dL)
Hematocrit (%)
Trombosis (K/uL)
LDH (U/L)
AST (U/L)
ALT(U/L)
Albumin (g/L)
Proteinuria (mg/dL)
Apgar 1
Apgar 5
Weight at birth (g)
Preeclampsia
(Average and SD)
Healthy pregnancy
(Average and SD)
P
30.28±6.40
5.00±3.54
3.37±3.34
158.30±16.57
96.45±11.74
34.15±4.09
13.812±5.0
11.3±2.0
38.68±5.91
215.2±103
509.2±395.7
94.39±20.30
67.73±17.82
2.76±0.60
365.3±189.1
4.65±2.65
6.42±3.05
2228.50±88.86
29.70±5.59
4.90±3.40
3.02±3.13
113.78±11.66
71.48±8.55
38.06±1.29
11.577±3.3
11.6±1.5
34.56±4.08
270±62
202.2±88.9
20.06±7.74
17.62±7.28
3.28±0.36
14.0±6.1
6.01±1.94
8.13±1.46
3245.54±398.68
p>0.05
p>0.05
p>0.05
*p<0.001
*p<0.001
*p<0.001
*p<0.001
p>0.05
p>0.05
*p<0.001
*p<0.001
*p<0.001
*p<0.001
*p<0.001
*p<0.001
*p<0.001
*p<0.001
*p<0.001
*Statistically significant.
Cases were separated into two groups: preeclamptic and healthy pregnant women. In group 1 cases
(n=100), mild preeclampsia was predicted in 74
cases (74%) and severe preeclampsia in 26 cases
(26%). The demographic, hematological and biochemical parameters, and newborn weights and
first and 5th minute Apgar scores of the cases are
shown in Table 1. No statistically significant difference was predicted between the age, gravid, parities between both groups (p>0.05). The week of
delivery, birth weight, first and 5th minute apgar
scores between both groups were statistically significant (p<0.001).
group (respectively, 10.50±6.21 µmol/L, 6.54±2.64
µmol/L, p<0.001) (Diagram 4) (Table 2).
No statistical difference could be predicted
between the preeclampsia and control groups in
terms of vitamin B12 serum level (respectively,
117.44±42.03 pg/ml, 136.07±59.01 pg/ml, p>0.05)
(Diagram 1).
Endothelial damage plays a role in the etiology
of preeclampsia. It leads to vascular endothelial
damage at high homocysteine levels. Therefore,
the relationship between high homocysteine levels
and preeclampsia has been shown in various studies.6 De Vries et al have predicted that 24% of
preeclamptic patients also have high homocysteine.8 It is considered that high homocysteine levels may also make vascular endothelia in
preeclamptic patients more sensitive towards oxidasive stress.9 In their study, Kassab et al have predicted that high homocysteine leads to maternal
hypotension, proteinuria, renal damage, intrauterine developmental retardation, and increased fetal
mortality.10 Patrick et al have shown that decreased
folic acid and B12 levels cause high homocysteine
concentrations in preeclamptic patients.11 In their
The vitamin B6 (pyridoxal-5’-phosphate) plasma level was found to be low in the preeclampsia
group in comparison to the control group (respectively, 6.40±2.91 µg/l, 11.15±5.76 µg/l p<0.001)
(Diagram 2).
Folic acid serum level was found to be lower in
the preeclampsia group (respectively, 5.43±3.08
ng/ml, 8.00±5.1 ng/ml, p<0.001) (Diagram 3).
And the homocysteine plasma level was found
to be at a significantly high ratio in the preeclampsia group in comparison to the healthy pregnancy
Furthermore, no statistical difference could be
predicted in terms of the vitamin B12, vitamin B6,
folic acid and homocysteine serum levels of mild
and severe preeclamptic patients (p>0.05).
Discussion
Homocysteine is methionine’s non-essential
amino acid derivative. High plasma homocysteine
levels are a risk factor for endothelial dysfunction,
vascular disease, aterosclerosis.1-5
34
Kale A et al., Vitamin B12, Vitamin B6 and Homocysteine Levels in Preeclamptic Pregnancies
160
%95 CI vitamin B12 (pg/ml)
150
140
130
120
110
100
N=
100
Preeclampsia (n=100)
74
Control (n=74)
Diagram 1. Vitamin B12 levels of the group of preeclampsia and healthy pregnant women.
study, Gürbüz et al have shown that there is a
prevalent degree of high homocysteine concentration in preeclamptic patients, and that high homo-
cysteine concentrations are in parallel with the bad
prognosis of preeclampsia.12 Calle et al have stated
that vitamin B6 (pyridoxal-5’-phosphate) and vita-
14
%95 CI vitamin B6 (µg/l)
12
10
8
6
4
N=
100
Preeclampsia (n=100)
74
Control (n=74)
Diagram 2. Vitamin B6 levels of the group of preeclampsia and healthy pregnant women.
35
Perinatal Journal • Volume: 14, Number: 1/March 2006
10
%95 CI folic acid (ng/ml)
9
8
7
6
5
4
N=
100
Preeclampsia (n=100)
74
Control (n=74)
Diagram 3. Folic acid levels of the group of preeclampsia and healthy pregnant women.
min B12 play a role in the homocysteine metabolism, and that the administration of these vitamins
during the term of gestation with a diet prevent
complications such as spontaneous low intrauterine developmental retardation, preeclampsia,
intrauterine morbidity linked to gestation.13 In their
13
%95 CI homosistein (µmolg/L)
12
11
10
9
8
7
6
5
N=
100
Preeclampsia (n=100)
74
Control (n=74)
Diagram 4. Homocysteine levels of the group of preeclampsia and healthy pregnant women.
36
Kale A et al., Vitamin B12, Vitamin B6 and Homocysteine Levels in Preeclamptic Pregnancies
study, while predicting homocysteine levels as
higher in the preeclampsia pregnancy group in
comparison to the healthy pregnancy group,
Üstüner et al have predicted that serum folic acid
levels are low and have stated that it is necessary
to correct the lack of nutritional folic acid during
the antenatal term.14 The lack of folic acid in pregnant women receiving folic acid treatment in the
second and third trimester of gestation was predicted to be less in comparison to those not receiving the treatment. Thence, with the consideration
that 30% of preeclamptic gestations will repeat, it
is suggested that folic acid treatment be started to
observe the homocysteine level in preeclamptic
pregnant women and to prevent its repetition in
subsequent pregnancies.15,16
According to data from this study, plasma
homocysteine concentrations being predicted as
higher and folic acid and vitamin B6 levels as
lower in preeclamptic pregnant women in comparison to healthy pregnant women gives rise to
the thought that high homocysteine concentration
and low folic acid and vitamin B6 levels may play
a role in the pathogenesis of preeclampsia. If
preeclampsia and high homocysteine level are predicted together during the gestational term, we
believe that it is necessary to inform the patient in
terms of possible risks and to closely monitor the
gestation.
1.
References
Kang SS, Zhou J, Wong PWK, Kowalisyn J, StrokoschG. Intermediate homocysteinemia: a termolabile variant of
methylenetetrahydrofolate reductase. Am J Hum Genet
1988, 43: 414-21.
2.
Mc Kully KS. Vascular pathology of homocysteinaemia:
implications for the pathogenesis of arterioslerosis. Am J
Pathol 1969; 56: 111-28.
3.
Lang D, Hussain SA, Lewis MJ. Homocysteine inhibits endothelium-dependent relaxation in isolated aortic rings. Br
J Pharmacol 1997; 120: 145-7.
4.
Sanchez SE, Zhang C, Rene Malinow M, Ware-Jauregui S,
Larrabure G, Williams MA. Plasma folate, vitamin B(12),
and homocyst(e)ine concentrations in preeclamptic and
normotensive Peruvian women. Am J Epidemiol 2001; 153:
474-80.
5.
Herrmann W, Hubner U, Koch I, Obeid R, Retzke U, Geisel
J. Alteration of homocysteine catabolism in pre-eclampsia,
HELLP syndrome and placental insufficiency. Clin Chem
Lab Med 2004; 42: 1109-16.
6.
The American College of Obstetricians and Gynecologist.
ACOG practice bulletin. Diagnosis and management of
preeclampsia and eclampsia. Int J Gynaecol Obstet 2002; 77:
67-75.
7.
Raijmakers MT, Zusterzeel PL, Steegers EA, Peters WH.
Hyperhomocysteinaemia: a risk factor for preeclampsia?
Eur J Obstet Gynecol Reprod Biol 2001; 95: 226-8.
8.
De Vries JI, Dekker GA, Huijgens PC, Jakobs C, Blomberg
BM, van Geijn HP. Hyperhomocysteinemia and protein S
deficiency in complicated pregnancies. Brit J Obstet
Gynecol 1997; 11: 1248-54.
9.
Powers RW, Evans RW, Majors AK, Ojimba JI, Ness RB,
Crombleholme WR, Roberts JM. Plasma homocysteine concentration is increased in preeclampsia and is associated
with evidence of endothelial activation. Am J Obstet
Gynecol 1998; 179: 1605-11.
10. Kassab SE, Abu-Hijleh MF, Al-Shaikh HB, Nagalla DS.
Hyperhomocysteinemia in pregnant rats: Effects on arterial
pressure, kidneys and fetal growth. Eur J Obstet Gynecol
Reprod Biol. 2005 Jul 25 Epub ahead of print.
11. Patrick TE, Powers RW, Daftary AR, Ness RB, Roberts JM.
Homocysteine and folic acid are inversely related in black
women with preeclampsia. Hypertension 2004; 43: 1279-82.
12. Gurbuz A, Karateke A, Mengulluoglu M. Elevated plasma
homocysteine levels in preeclampsia and eclampsia. International Journal of Gynecology & Obstetrics 2004; 87: 1656.
13. De Usandizaga R, Sancha M, Magdaleno F, Herranz A, Cabrillo E. Homocysteine, folic acid and B-group vitamins in
obstetrics and gynaecology. Eur J Obstet Gynecol Reprod
Biol 2003; 107: 125-34.
14. Üstüner I, Sönmezer M, Cengiz B, Kahraman K, Elhan A,
Söylemez F. Serum Folik Asit, Vitamin B12 ve Plazma
Homosistein Düzeylerinin Preeklampsi ile ‹liflkisi. Klinik
Bilimler & Doktor Kad›n Do¤um 2005; 11: 78-82.
15. De la Calle M. Hiperhomocisteinemia Preeclampsia Tesis
Doctoral. Madrid, 2000.
16. A. Rajkovic, P.M. Catalano and M.R. Malinow, Elevated
homocysteine levels with preeclampsia. Obstet. Gynecol
1997; 90: 168-71.
37
Perinatal Journal • Volume: 14, Number: 1/March 2006
A Case of Non-Immun Hydrops Fetalis Due to
Placental Chorioangioma
Ener Ça¤r› Dinleyici1, Neslihan Tekin1, Mehmet Arif Akflit1, Emine Dündar2
Department of Pediatrics, 2Department of Pathology, Faculty of Medicine, Osmangazi University, Eskiflehir
1
Abstract
Choriangioma of the placenta occurs in 1% of pregnancies but it is an extremely rare condition to be large enough to threat
viability of fetus or newborn due to nonimmune hydrops. A 3500 g female infant was born to a 32 year-old-woman at 36 weeks
of gestation by caeserean section. Pregnanacy was complicated by polyhydramnios and preterm PROM. Apgar scores were 2
and 3 at first and 5th minutes, she had pallor, generalised edema, ascites, hepatosplenomegaly, disseminated maculopapular
rash and cardiac failure. Laboratory examination revealed anemia, thrombocytopenia and leukocytosis, and increased number
of erythroblasts in peripheral blood film and consumption coagulopathy. She died at 40th hours of age. Placental weight was
920 g and histopathological examination revealed a large chorioangioma. The pathophysiology of hydrops fetalis due to choriangioma and proper management during pregnancy are discussed.
Keywords: Placental choriangioma, non-immune hydrops fetalis.
Plasental korioanjioma ba¤l› non-immün hidrops fetalis olgusu
Plasental korioanjiom tüm gebeliklerin %1’de görülmekle birlikte fetus ve yenido¤anda fatal seyirli non-immün hidrops fetalise
yol açabilmektedir. 3500 gram a¤›rl›¤›nda k›z bebek, 32 yafl›ndaki polihidramniosu ve erken membran rupturü olan annenin 1.
gebeli¤inde 36. gestasyon haftas›nda sezaryen ile, 2-3 apgar ile do¤du. Soluk görünümde olan hastada jeneralize ödem,
hepatosplenomegali, yayg›n makülopapüler döküntüleri ve kalp yetnezli¤i bulgular› saptand›. Laboratuar incelemesinde anemi,
trombositopeni, lökositoz, periferik yaymada normoblastlarda belirgin art›fl ve dissemine intravasküler koagülasyon saptanan
hasta takibinin 40. saatinde eksitus oldu. Plasenta a¤›rl›¤› 920 g olup, histopatolojik inceleme plasental koriyoanjiom ile uyumlu
idi. Bu çal›flmada koriyoanjioma ba¤l› hidrops patofizyolojisi ve gebelikteki tedavi yaklafl›mlar› tart›fl›lm›flt›r.
Anahtar Sözcükler: Plasentak korioanjiom, non-immün hidrops fetalis.
Background
Hydrops is generally a common end stage for a
variety of diseases that share any of the three
underlying mechanisms. These are the conditions
that lead to congestive heart failure or conditions
with obstructed lymphatic flow or decrease in
plasma osmotic pressure and increase in capillary
permeability.1 In the past, most cases of hydrops
were due to erythroblastosis from Rh alloimmunization, now non-immune hydrops makes up 7687% of all cases.2 Incidence of non-immune
hydrops fetalis (NIHF) at delivery ranges from 1 in
830 to 1 in 4600.3
Although chorioangiomas are the most common benign tumor of placenta, hydrops fetalis due
to chorioangioma is a rare condition that resulted
Correspondence: Dr. Ener Ça¤r› Dinleyici, Osmangazi Üniversitesi T›p Fakültesi, Çocuk Sa¤l›¤› ve Hastal›klar› Anabilim Dal›, Eskiflehir
e-mail: [email protected]
38
Perinatal Journal • Volume: 14, Number: 1/March 2006
from fetal cardiac failure because of hyperdynamic circulation and anemia.4-6 We present such a
case of hydrops fetalis with a review of the literature in order to emphasize the importance of follow-up in chorioangioma-detected cases.
Case
A 3500 g female infant was born to a 32-yearold unregistered gravida 1, para 0 mother at 36
weeks gestation by caesarean section. Pregnancy
was complicated by polyhydramnios and premature rupture of membranes. Apgar scores were 2
and 3 at 1st and 5th minutes, respectively. In
umbilical cord blood, pH was 7.18, base deficit
was –10.5. On physical examination weight was
3500 g, length was 47 cm, head circumference was
35 cm. She had pallor, generalized edema and
ascites. Cardiovascular system revealed tachycardia
and short systolic murmur in left parasternal area.
Liver was 4 cm and spleen was 3 cm palpable
below the costal margin. Disseminated maculopapular rash was observed over the trunk and
limbs. Laboratory examination revealed hemeglobine 11.8 g/dl, platelets 55000/mm3 and leucocyto-
sis 91100/mm3 with increased number of normoblasts (60%) in peripheral blood film. Blood
glucose 31 mg/dl, total bilirubin was 14.9 mg/dl
with a rise in direct bilirubin of 12,02 mg/dl. AST
was 785 IU/L, ALT 143 IU/L, BUN 9 mg/dl, Cr 0.4
mg/dl PT 160’’, PTT 82’’, Fibrinogen 63 mg/dl. In
urinalysis 3+ proteinuria, 2+ bilirubinemia were
detected. Chest X-ray demonstrated cardiomegaly
with a cardiothoracic index of 0.70. She died at
40th hour of birth. In pathological evaluation placental weight was 920 g. At dissection, a mass
9x6x5 cm in diameters was seen in maternal surface of the placenta. It was purplish-red in color
and well demarcated from surrounding parenchyma. Microscopically the tumor was composed of
numerous blood vessels capillary in type and supported by loose, scanty fibrous stroma. No areas of
necrosis, calcification or myxoid change were
identified (Figure 1).
Discussion
Chorioangioma is a benign and common neoplasm of placenta that does not metastasize.6 Fetal
complications such as hydramnios, congestive
Figure 1. Numerous capillary sized vessels are separated by inconspicuous stroma
(Hematoxyline and Eosin x200).
39
Dinleyici EÇ et al., A Case of Non-Immun Hydrops Fetalis Due to Placental Chorioangioma
heart failure, anemia, and prematurity and growth
retardation were rarely described.4,7-8 Among these
complications hydramnios is the most frequently
reported one. When anemia develops which is
severe enough to cause high output cardiac failure,
fetal cardiomegaly, and hydrops can be expected.
Development of anemia can be either due to
hemodilution or destruction of the red blood cells
in such cases.9 Our case had congestive heart failure with cardiomegaly, hepatomegaly, edema and
ascites with a hemoglobin level of 11 g/dl.
Consumptive coagulopathy was also present in our
case with disseminated purpuric rash and prolonged PT and PTT, low fibrinogen value and
reduced number of platelets. It was suggested that
trapped red cells and platelets in the vascular
channels of chorioangiomas resulted in consumptive coagulopathy and microangiopathic hemolytic
anemia.10
management alternative in patients with large
chorioangioma.13 If diagnosis cannot be made in
utero or in utero treatment fails, fluid restriction
with diuretics and blood transfusion is administered for the treatment of neonatal cardiac failure.
Consumptive coagulopathy can be managed by
fresh frozen plasma, and platelet transfusions.
Life expectancy is low among non-immun hydrops
fetalis cases, early in utero diagnosis of placental
chorioangiomas and management will improve
prognosis.
2.
Santolaya J, Alley D, Jaffe R et al. Antenatal classification of
hydrops fetalis. Obstet Gynecol 1992: 79: 256-9.
In most of the reported cases, it was emphasized that the size was important for the development of fetal hydrops.7,11 However Jauniaux et al.,12
evaluated 9 cases of chorioangiomas which in
those cases the diameter of the tumors ranged
between 3 and 10 cm, only one case was complicated by non immun hydrops. They concluded
that the vascularization of the tumor is a pivotal
determinant factor for the development of complications not the size. If the tumor is avascular no
specific complications are expected. Our patient
had a large placenta weighing 920 g with a large
chorioangioma, which was 9x6x5 cm in size. It
was also associated with increased vascularity.
3.
Hill LM. Non-immune hydrops. Ultrasound Obstet Gynecol
2001; 1: 248-55.
4.
Haak MC, Oosterhof H, Mouw RJ et al. Pathophysiology
and treatment of fetal anemia due to placental chorioangioma. Ultrasound Obstet Gynecol 1999; 14: 68-70.
5.
Montan S, Anandakumar C, Joseph R et al. Fetal and neonatal hemodilution associated with multipl placental
chorioangioma: case report. J Obstet Gynec Res 1996; 22: 436.
6.
Wallenburg HCS. Chorioangioma of the placenta. Obstet
Gynec Surv 1971; 26: 411-25.
7.
D’Ercole C, Cravello L, Boubli L et al. Large chorioangioma
associated with hydrops fetalis: prenatal diagnosis and
management. Fetal Diagn Ther 1996; 11: 357-60.
8.
Horigome H, Hamada H, Sohda S et al. Large placental
chorioangiomas as a cause of cardiac failure in two fetuses.
Fetal Diagn Ther 1997; 12: 241-3.
9.
Locham KK, Garg R, Goel S. Hydrops fetalis in placental
chorioangioma. Indian Pediatr 2001; 38: 112-3.
With the increasing use of ultrasound, prenatal
diagnosis of these tumors is becoming more common.5 In patients with fetal and/or maternal complications, color Doppler may play a role in
demonstrating the blood flow inside the mass.4,12
As for those without complications and with little
or no blood flow, it is of limited use. Management
includes umbilical blood sampling and intravascular transfusion that temporarily corrects the
hydrops and significantly pro- longs the pregnancy.9 Ablation of the blood supply of placental
chorioangioma via operative fetoscopy is another
1.
References
Etches PC, Demianczuk NN, Okun NB, Chari R. Nonimmune hydrops fetalis. In: Rennie JM, Roberton NRC, ed.
Textbook of Neonatology. 3rd ed. Edinburgh, England:
Churchill Livingstone, 1999.
10. Teaching files: The Placenta. Division of Neonatology,
Cedars-Sinai Medical Center, Los Angeles, California.
http://www.neonatology.org/syllabus/placenta.
11. Zoppini C, Acaia B, Lucci G et al. Varying clinical course of
large placental chorioangiomas. Report of 3 cases. Fetal
Diagn Ther 1997; 12: 61-4.
12. Jauniaux E, Ogle R. Color Doppler imaging in the diagnosis and management of chorioangiomas. Ultrasound Obstet
Gynecol 2000; 15: 463-7.
13. Quintero RA, Reich H, Romero R et al. In utero endo-scopic devascularization of a large chorioangioma. Ultrasound
Obstet Gynec 1996; 8: 48-52.
Perinatal Journal • Volume: 14, Number: 1/March 2006
40
Congenital Large Oropharyngeal Immature
Teratoma
Figen K›r fiahin1, Gülengül Nadir Köken1, Serhan Çevrio¤lu1, Önder fiahin2, Arif Saylan1
Kocatepe Üniversitesi, Kad›n Hastal›klar› ve Do¤um, 2Patoloji Anabilim Dal›, Afyon
1
Abstract
Epignathus is a congenital tumor and a rare type of teratoma. It is associated with midline abnormalities. In our case the teratoma was of oropharyngeal origin, extending to cervical region, inhibiting the growth of maxillary and mandibular bones and
tongue. No treatment could be applied. Although there are few cases of epignathus reported to be treated with ex-utero intrapartum treatment procedure, there are no reported cases in the literature with totally undeveloped bone and soft tissue of lower
and upper jaws as in our case.
Keywords: Epignathus, oropharyngeal mass, maxillo facial deformities.
Konjenital büyük orofaringeal immatür teratom
Epignathus konjenital bir tümördür ve nadir görülen bir teratom türüdür. Orta hat anomalileri ile iliflkilidir. Olgumuzda teratomun orofarenks kaynakl› olup servikal bölgeye kadar uzan›m gösterdi¤i, maksiller ve mandibular kemi¤in ve dilin geliflimine engel oldu¤u saptand› ve tedavi yap›lamad›. Literatürde eksutero intrapartum tedavi prosedürü ile tedavi edilebilen az say›da epignatus olgusu bulunmas›na ra¤men olgumuzda oldu¤u gibi alt ve üst çeneye ait kemik ve yumuflak dokunun tamamen geliflmedi¤i bir olguya rastlamad›k.
Anahtar Sözcükler: Epignathus, orofaringeal kitle, maksillo fasiyal deformiteler.
Introduction
Teratomas are congenital germ cell tumors that
contain tissues of variable maturity and have a
known malignant potential which is unpredictable
from their histological features or stage of development. Teratomas occur in approximately one in
4000 live births, show a female preponderance,
and have an 18% risk of other congenital malformations, some of which can be incompatible with
life.1 The most common sites of origin of teratomas
in children are the sacrococcigeal region, gonads
and mediastinum. Epignathus teratoma represents
a rare group of congenital neoplasms in the head
and neck. It has an incidence of 1/35.0001/200.000 births. The clinical presentation of this
tumor varies depending on size and location in the
oronasopharynx.2 In utero a tumor occluding the
foetal airway may not cause many significant problems because the foetus is perfused by the umbilical cord and placenta, but it may impede foetal
swallowing leading to the accumulation of amniotic fluid or ‘maternal polyhydramnios’.1 Epignathi
that arise from the palate or pharynx and protrude
from the mouth result in life-threatening airway
Yaz›flma adresi: Dr. Figen K›r fiahin, Kocatepe Üniversitesi, Kad›n Hastal›klar› ve Do¤um Anabilim Dal›, Afyon
e-posta: [email protected]
Perinatal Journal • Volume: 14, Number: 1/March 2006
obstruction and usually cause asphyxiation shortly
after birth.3 The large oropharyngeal teratoma can
cause airway obstruction and neonatal mortality.
Case
The patient was a 20-year-old healty woman
pregnant to her first child with a gestational age of
25 weeks. Questionning the family history it was
learned that all the family members were healthy.
Foetal heart activity was observed in three dimensional ultrasonography. Foetal measurements were
compatible with 25 weeks. Amniotic fluid index
was increased. A mass lesion of 73x76 mm, originating from the facial and neck region, containing
solid and cystic components was observed (Figure
1). The mass lesion was just below the eye level of
the foetal face so the nose and the mouth could
not be observed and foetal magnetic resonance
imaging (MRI) was performed. In the MRI a7x8x11
cm smooth lobulated contoured, septated multicystic mass lesion with a fibrous capsule occupying the anterior maxillofacial and cervical region
was detected. The mass lesion was unrelated with
the cervical spinal canal and and intracranial area
(Figure 2). Bilateral orbital development was normal. Bone and soft tissue of lower and upper jaws
were not developed. The family was informed
about the situation. The surgical procedures to be
performed after the birth because of the nondevelopment of maxillary and mandibular bone and soft
tissue due to the teratoma were consulted with
Figure 1. Ultrasound view of the foetus.
41
plastic and reconstructive surgerions and paediatric surgeons and the family was informed. As a
result of the consultations it was learned that a
functional jaw would be unable to be reconstructed in this case and the extrauterin intrapartum
treatment procedure after birth would be difficult.
As the mass lesion extends to cervical region respiratory and digestive tracts were completely
closed and the baby would face breathing and
nutrition problems. Family was informed about
these problems. The pregnancy was terminated via
vaginal route with the family’s decision. The
autopsy of the foetus revealed that the mass lesion
with a dimension of 7x8x11 cm was occupying the
whole oropharynx and was unrelated with any of
the oropharyngeal structures but the mass was
extending to cervical region. Cervical tissue and
organ development was normal. The upper border
of the mass was adjacent to the lower border of
the orbital bone but it was unrelated with the
sphenoid bone. Maxilary and mandibular bones
and the tongue were absent, there were some cartilage remnants which were thought to be belonging to the jaw (Figure 3). The mass was shown in
Figure 4 macroscopically. The mass was diagnosed
as immature teratoma histopathologically (Figure 5).
Discussion
Teratomas are composed various tissues of
ectodermal, endodermal and mesodermal origin.
These tissues exhibit various degrees of matura-
42
K›r fiahin F et al., Congenital Large Oropharyngeal Immature Teratoma
Figure 2. MRI view of the 7x8x11 cm mass occupying the
maxillofacial and cervical region.
tion.3 They are classified in four groups as dermoid
cyst, teratoid cyst, teratoma and epignathus.
Dermoid cyst derives from endodermal and mosedermal germ layers. Tumors composed of all three
germ layers that are poorly differentiated are called
teratoid cyst and those which are well differentiated are called teratoma. Epignathi are oral tumors
containing foetal organ and structures.4
Figure 3. View of the dead born foetus.
er places with the lack of regulation effects of adjacent cells and factors.4 In the recent studies epignathus teratomas were reported to have a neuroectodermal tissue dominance although cells of
three germ layers are seen, as seen in our case.3
Epignathus teratomas are rare congenital tumors
associated with midline abnormalities. They have an
incidence of 1/35.000-1/200.000.5 Epignathus teratomas are normally nonfamilial. It is 3 times more
prevelant among women.5 The reason of this predominance is yet unclear. Epignathus teratomas are
more common among the babies of young mothers
as in our case. Mean age of the mother is 24.6.5
There are no findings suggestive of an environmental factor or a karyotypic abnormality.3
Histopathologically 51% are mature teratoma,
49% are immature teratoma, 5.8% are yolk sac
tumors.3,6 Our case was reported as immature teratoma histopathologically.
(Vandenhaute) The aetiopathogenesis of epignathus is unclear. According to a theory, it developes due to insufficient fusion of midline tissues
during the embriogenesis at the 7-9th gestational
weeks.4-5 Another theory suggests that uncontrolled growth of primordial germ cells in improp-
In our case intraoral teratoma of oropahryngeal
origin was present. Although most of the cases
were reported to originate intraorally, the classical
epignathus tumor is of jaw or alveolar bone origin.7 According to the settling place, head-neck teratomas with palatal origin are called epipalatus,
In a review of Isaac Jr6 about the perinatal germ
cell tumors, it was mentioned that, in the literature
16 cases with hard palate origin, 14 cases with
nasopharyngeal origin, 6 cases with sphenoid origin and 6 cases with oropharyngeal origin were
reported.
Perinatal Journal • Volume: 14, Number: 1/March 2006
43
Figure 4. Macroscopic view of the mass.
those with sphenoidal origin are called episphenoid, those with cranial origin are called epicranium.4 Most of the epignathus tumors have a binding place to the cranial base in the posterior
nasopharyngeal region. Although most of them are
related with hard palate and sphenoid bone, there
are some developing from midline or laterally.5 In
our case the mass was not related with any
oropharyngeal region.
The clinical presentation is associated with the
settlment place and the size. Usually a great epignathus tumor fills the mouth and protrudes from the
oral cavity. A small one is usually pediculated and
may localize anywhere in the oropharyngel region.
A huge oropharyngeal mass compresses and
replaces the normal tissues in the lower part of the
face and jaw and frequently causes maxillary deformity.5 The teratoma of our case was localized intraorally. The mass was not protruding from the
mouth, however, it was extending to the cervical
region and additionally, maxillary and mandibular
bony structure and the tongue was not present. To
our knowledge, there are no cases of oropharyngeal
teratoma impeding the development of maxillary
and mandibular bone and the tongue.
Cranial base involvement of teratoma may
extend both intracranially and extracranially like a
sand watch.4,5 There exists a craniopharyngeal
extension in some cases. Intracranial extension is
often fatal.5 Intracranial extension shall be suspected in case of sphenoid base involvement and be
confirmed by CT or MRI.4,5 In our case there were
no sphenoid bone involvement and MRI scans
revealed no intracranial extension, that should be a
sign in our favor about the prognosis of the foetus.
As in our case, maternal polyhydramniosis can
be seen due to oropharyngeal obstruction by the
teratoma in the intrauterin period and difficulty in
swallowing or due to eosophageal compression.3,4
Epignathus can be diagnosed antenatally by
ultrasound and in appropriate cases multidiciplinary treatment can be applied.5 Antenatal diagnosis was achieved in our case, however, because of
nondevelopment of maxillary and mandibular
bones and the tongue, impossibility to reconstruct
these organs surgically the pregnancy was termi-
K›r fiahin F et al., Congenital Large Oropharyngeal Immature Teratoma
44
Figure 5. Histopathologic view of the mass compatible with immature teratoma.
nated with the decision of the family.
Embrional rabdomyosarcoma of the tongue,
retinoblastoma, nasal glioma, heterotopic thyroid,
cystic lymphangioma, nasoethmoidal meningoencephalocele, sphenoid meningoencephalocele and
giant epulis shall be considered in the differential
diagnosis.5
Although rarely seen, head and neck teratomas
are emergent cases during the neonatal period due
to airway obstruction and high mortality rates in
infants.3 Usually, those diagnosed antenatally have 3
folds higher mortality than those diagnosed neonatally.6
leaves the uterus and before the umblical cord is
cut, then the maternofoetal circulation is ceased
and the birth is completed.7
1.
2.
3.
Multiple surgical procedures can be needed to
obtain an optimal result in large tumors.
Intracranial extension must be excluded before the
surgery.6 In case of hydrocephaly or intracranial
mass in a neonate with epignathus, surgery is
avoided because the prognosis is poor.8 No recurrance was reported after complete resection.5
4.
In the exutero intrapartum treatment procedure, during the ceserian sectio of the term foetus,
airway patency is achieved with intraoperative
intubation or tracheostomy just after the foetus
7.
5.
6.
8.
Kaynaklar
Fautrel B, Le Moel G, Saint-Marcoux B, Taupin P. Diagnos1. Demajumdar R, Bhat N. Epignathus: A germ-cell tumour
presinting as neonatal respiratory distress. Int J Ped
Otolaryngol 1999; 47: 87-90.
Haghighi K, Milles M, Cleveland D, Ziccardi V. Epignathus
teratoma with bifid tongue and median glossal salivary
mass:report of a case. J Oral Maxillofac Surg 2004; 62: 37983.
Yoon JH, Kim J, Park C. Congenital immature teratoma of
the tongue: an autopsy case. Oral Sur Oral Med Oral Pathol
Oral Radiol Endod 2002; 94: 741-5.
Izadi K, Smith M, Askari M, Hackam D, Hameed AA,
Bradley JP. A patient with an epignathus: management of a
large orooharyngeal teratoma in a newborn. J Craniofac
Surg 2003; 14: 468-72.
Vandenhaute B, Leteurtre E, Lecomte-houcke M, Pelerin P,
Nuyts JP,Cuisset JM, Soto-ares G. Epignathus teratoma:
report of three cases with a review of the literature. Cleft
Palate-Craniofac J 2000; 37: 83-91.
Isaacs H. Perinatal (fetal and neonatal) germ cell tumors. J
Ped Surg 2004; 7: 1003-13.
Vega SJ, Losee JE. Epignathus teratoma. Images Surg 2003;
197: 332-3.
Smith NM, Chambers SE, Billson VR, West CP, Bell JE. Oral
teratoma (epignathus) with intracranial extension: a report
of two cases. Prenat Diagn 1993; 13: 945-52.
45
Perinatal Journal • Vol: 14, Issue: 1/March 2006
Abruptio Placentae in Adult Still’s Disease with
Onset During Pregnancy: A Case Report
Cem Dane, Murat Yayla, Banu Dane, Ahmet Çetin
Clinics of Gyneceology and Obstetrics, Haseki Training and Research Hospital, Istanbul
Abstract
Background: We investigated a woman who was presented fever of unknown origin, rash, artralji due to adult-onset Still's disease who developed abruption placenta.
Case: The patient was admitted at 20 weeks’ gestation with fever, malaise, sore throat, cervical lymphadenopathy and a dif-
fuse erythematous maculopapular rash for 10 days. After exclusion of an infectious or malignant disease, adult onset Still's disease was diagnosed according to the Yamaguchi criteria. After the exclusion of other infectious, malignant, and inflammatory
causes, a diagnosis of adult-onset Still disease meeting the Yamaguchi criteria was made. She was treated with prednisone and
had immediate improvement. Despite this, the dead fetus is delivered at 22 weeks of gestation with placental abruption.
Conclusion: To the best of our knowledge, this is the first case of AOSD who presented with placental abruption. Patients with
adult onset Still disease are usually subjected to multiple diagnostic procedures and laboratory tests as well as empiric treatment
with antibiotics and other medications. Corticosteroid therapy can achieve satisfactory response and perhaps better fetal outcome.
Keywords: Still’s disease, abruption placentae, hyperferritinemia.
Gebelikte bafllayan eriflkin tip still hastal›¤›nda dekolman plasenta: olgu sunumu
Amaç: Plasenta dekolman› geliflen bir Still hastal›¤› olgusu incelendi. Eriflkin tip Still hastal›¤› nedeni aç›klanamayan atefl, eklem
a¤r›s› ve döküntü özellikleri ile seyreden romatolojik bir rahats›zl›kt›r.
Olgu: Gebeli¤in 20. haftas›nda olan hasta atefl, yorgunluk, bo¤az a¤r›s›, servikal lenfadenomegali ve 10 gündür süren vücutta
yayg›n eritematö-makulopapüler döküntüyle baflvurdu. Enfeksiyöz, malign ve enflamatuar nedenlerin araflt›r›lmas› sonras›nda,
Yamaguchi kriterlerine dayan›larak eriflkin tip Still hastal›¤› tan›s› konuldu. Prednizolona cevap veren hastada iki hafta sonra geliflen dekolman plasentaya ba¤l› fetal ölüm olufltu.
Sonuç: Plasenta dekolman› ile ortaya ç›kan literatürdeki ilk eriflkin tip Still hastal›¤› olgusunu sunduk. Eriflkin tip Still hastalar› ta-
n› konulmadan önce genellikle birçok laboratuar ve klinik testlere maruz kal›rlar ve s›kl›kla antibiyotik ve baz› di¤er ilaçlarla ampirik olarak tedavi edilmeye çal›fl›l›rlar. Kortikosteroid tedavisi bu hastalarda tatmin edici sonuçlar›n al›nmas›n› sa¤layarak fetüsün
iyilik durumuna katk›da bulunabilir.
Anahtar Sözcükler: Still hastal›¤›, plasenta dekolman›, hiperferritinemi.
Backgrond
Adult-onset Still’s disease (AOSD) is an inflammatory condition that can involve internal organs,
joints and also sometimes other parts of the body.
The cause of the disease and occurrence mechanism is not understood clearly. Clinical properties
are intermittent raising body temperature, arthralgia, macular or maculo-papular skin eruption, sore
Correspondence: Dr. Cem Dane, Haseki E¤itim ve Araflt›rma Hastanesi, Kad›n Hastal›klar› ve Do¤um Klini¤i, ‹stanbul email: [email protected]
Presented as a poster at the 7th World Congress of Perinatal Medicine - Zagreb on 21.24.2005.
46
Dane C et al. Abruptio Placentae in Adult Still’s Disease with Onset During Pregnancy: A Case Report
throat, myalgia, lymphadenomegaly and splenomegaly. ETSH is rarely diagnosed during pregnancy. This disease has to be differentially diagnosed especially with infectious diseases with viral
ecsantemas, malignencies (lymphomas) and some
rheumatologic diseases. Mostly a lot of laboratory
and radiologic tests are done and these cause a delaying in diagnosis and therapy. Elevated serum
ferritine has a diagnostic value in acute progressing Adult type Still disease.1
daily; fever decreased and did not increase again,
myalgias and arthralgias disappeared, patient
could wake up from her bed without help. After 10
days of this nice improvements patient had a vaginal bleeding and placental detachment is diagnosed in ultrasonography, the patient who
intrauterine death occurred is delivered with
induction (Figure 1).
Adult type Still disease presenting with placental at pregnancy is studied with clinical and laboratory characteristics and reported in this article.
Adult type Still’s disease is rarely seen and estimated incidence is reported as 0.34 in 100.000
women.3 The disease which was first described at
year of 1896 by George Still is being named as
“juvenile idiopathic arthritis” in recent years.4 The
adult form of Still’s disease which is generally
seen in children is described by Bywaters.5 Stein
published first case appearing in pregnancy at
1980.6 In a study that was made at year of 2004,
22 pregnancies were followed up in 17 patients
with adult type Still’s disease.7 In ten patients Still’s
disease appeared in pregnancy for the first time,
relapses occurred in seven of 12 pregnancies seen
in previously diagnosed patients. Symptoms generally appeared in first trimester in the patients
that were diagnosed in pregnancy for the first
time. Although, it is reported that only three pregnancies resulted without problem, probably the
other patients who were not developed any problem are not reported. Abortus, premature birth,
retardation in intrauterine development and newborn death are reported related with pregnancy.
Premature birth and retardation in intrauterine
development are determined during relapses in
patients previously diagnosed. Recurrences
appeared most frequently in postpartum period.
Impaired glucose tolerance and preeclampsia are
reported for maternal morbidity. As understood
from the study pregnancy condition does not
affect the disease that is dragging on with recurrence and recovery periods. In another study
made at 2003, 33 pregnancies occurring in 24
patients were examined.8 According to this study
there was not stated expressly a clear evidence
about the effect of the pregnancy on adult type
Still’s disease or about the effect of adult type
Still’s disease on pregnancy. In the article, it is
reported that beginning of the disease could be
either in the antepartum or postpartum periods,
Case
A 25-year-old patient with 20 weeks pregnancy
(G3, P2) is admitted with fever, sore throat, cervical lymphadenomegaly and diffuse erithematomaculopapular eruptions lasting 10 days. An
anatomically normal fetus concordant with pregnancy week and normal placenta and amnion fluid
is found in obstetrical ultrasonography . Her body
temperature was 39.5°C when she admitted.
Parenteral fluid therapy and third generation
cephalosporin and erythromycin is started. There
has been no difference in patient’s condition during following three days. Fever of the patient was
usually raising on mornings. Eruptions were rising
while there was fever and then color of the eruptions were getting pale with decreasing of fever. In
the patient’s laboratory findings; anemia; Hb: 8.6
g/dl, Hct: % 23.6, ESR: 80 mm/hour, leukocytes:
19.500/mm3, platelets: 186,000/mm3, ALT 32 U/L,
AST 65 U/L and C-reactive protein (CRP) 10 mg/dl
(normal value < 0.6 mg/dl) were found. ANA, ACA
and rheumatoid factor and also blood, urine and
throat cultures were found negative. After discarding infectious, malignant and inflammatory reasons
that can cause this clinical disease, adult type Still’s
disease is diagnosed based upon Yamaguchi criteria.2 Significantly elevated serum ferritin level in
patient (> 13.000 mg/dl) is evaluated as a specific
sign (normal values 15-300). Lymph node analysis
from cervical region, reactive lymphocytosis is
determined consistent with Still’s disease. The
patient’s symptoms improved dramatically after 12
hours starting the treatment of 30 mg cortisone
Discussion
47
Perinatal Journal • Vol: 14, Issue: 1/March 2006
Figure 1. Retroplacental hematoma regions are seen at right and left.
Table 1. Major and minor criterion in adult type Still’s disease.
Major criteria
Minor criteria
Fever > 39°C
Arthralgia > 2 weeks
Still eruptions
Neutrophilic leukocytosis
Sore throat
Lymphadenomegaly or splenomegaly
Elevation in liver enzymes
Negative rheumatoid and antinuclear factor
and also disease symptoms could get improved,
did not change or recurrences were seen during
pregnancy or in postpartum period. In long term
follow-ups of children from mothers with adult
type Still’s disease there was no problem concerning education, job and social functions.9 Clinical
course is generally slight with recurrence and
relapse periods. Life threatening internal organ
involvement was not seen, however liver failure,
pericarditis, acute respiratory distress syndrome,
myocarditis causing heart failure, arrhythmias,
pancytopenia, thrombotic thrombocytopenic purpurae-hemolytic uremic syndrome and diffuse
intravessel coagulation were evident. In our case,
retroplacental hematoma and placental detachment was observed. The observed detachment is
interesting in the aspect that it shows a severe
form of the disease. It may possibly be an indication that the disease affects the placental arteries.
In recent studies, a relationship is found between
the activation of the adult Still’s disease and the
increased ferrite serum level.10 The increase of the
serum ferrite concentration over 10000 ng/ml is
considered to show the active period of the illness
and for this reason, it is suggested to be used not
only for the prediction of the illness but also the
for monitoring the activity of the illness. Although
many diagnosis criteria are suggested, it is accepted that criteria of Yamaguchi maintains the highest sensitivity (96.2%) and specificity (92.1%).2 The
adult type Still’s disease is diagnosed with 10 or
more points from 5 major criteria (2 points for
each) or combination of major and minor criteria
(one point each) (Table 1). Furthermore, there
must be five or more criteria and at least two of
them must be major criteria. The Adult Still’s disease criteria predicted in our case are as follows:
intermittent fever reaching peak points and then
decreasing, continuing for two weeks together
with sore throat, maculo-papular eruption seen
with the increase of the fever and disappearing
with the decrease of the fever, leukocytosis and
arthralgia. In addition, increased level of ferrite for
48
Dane C et al. Abruptio Placentae in Adult Still’s Disease with Onset During Pregnancy: A Case Report
the patient maintained the distinguishing from
other rheumatologic diseases and is consistent
with the laboratory results of this disease. As far as
we can understand from studies which we could
access, our case is the fist adult type Still’s disease
presented in the literature together with placental
detachment. This case shows an instance of the
adult type Still’s disease presented with severe
symptoms. ETSH should be considered in the
diagnosis of patients administered to the hospital
for fever with unknown reasons. Thus, the development of life threatening complications ETSH
can be prevented with early diagnosis and remedy.
1.
2.
References
Fautrel B, Le Moel G, Saint-Marcoux B, Taupin P. Diagnostic value of ferritin and glycosylated ferritin in adult onset
Still's disease. J Rheumatol 2001; 28: 322-8.
Yamaguchi M, Ohta A, Tsunematsu T. Preliminary criteria
for classification of adult Still’s disease. J Rheumatol 1992;
19: 424-30.
3.
Wakai K, Ohta A, Tamakoshi A. Estimated prevalence and
incidence of adult Still’s disease: findings by a nationwide
epidemiological survey in Japan. J Epidemiol 1997; 7:
221–5.
4.
Still GF. On a form of chronic joint disease in children. Med
Chir Trans 1897; 80:47. (Reprinted in: Arch Dis Child 1941;
6:56).
5.
Bywaters EGL. Still’s disease in the adult. Ann Rheum Dis
1971; 30:121–133.
6.
Stein GH, Cantor B, Panush RS. Adult Still’s disease associated with pregnancy. Arthritis Rheum 1980; 23:248–50.
7.
Mok MY, Lo Y, Leung PY, Lau CS. Pregnancy outcome in
patients with adult onset Still's disease. J Rheumatol 2004;
31: 2307-9.
8.
Pan VL, Haruyama AZ, Guberman C, Kitridou RC, Wing
DA. Newly Diagnosed Adult-Onset Still Disease in Pregnancy. Obstet Gynecol 2003; 101:1112– 6.
9.
Sampalis JS, Esdaile JM, Medsger TA, Partridge AJ, Yeadon
C, Senecal JL. A controlled study of the long term prognosis
of adult Still’s disease. Am J Med 1995; 98: 384–8.
10. Van Reeth C, Le Moel G, Lasne Y. Serum ferritin and isoferritius are tools for diagnosis of active adult Still’s disease. J
Rheumatol 1994; 21: 890–5
Perinatal Journal • Vol: 14, Issue: 1/March 2006
49
Prenatal Diagnosis Of Osteogenesis Imperfecta:
A Case Report
‹ncim Bezircio¤lu1, Merve Biçer1, Dilek Uysal1, Seyran Yi¤it2, Ali Balo¤lu1
First Clinic of Gynecology and Obstetrics, 2Pathology Department of ‹zmir Atatürk Training and Research Hospital, ‹zmir
1
Abstract
Background: Osteogenesis imperfecta is a heterogeneous group of genetic disorders characterized by severe bone fragility,
abnormal ossification and multiple fractures. We report here a terminated case of osteogenesis imperfecta diagnosed with
obstetric ultrasonography during sixteenth week of pregnancy.
Case: A 19 year-old gravida 2, para 1 patient was referred to our institution following a secreening ultrasound which demonstrated skeletal anomalies of the fetus. Sonographic evaluation revealed that all long bones were short and angulated with multiple fractures, the chest was narrow and bell-shaped, the echogenity of the skull was decreased and visualization of the intracranial structures were increased. Termination of the pregnancy was decided due to the ultrasonographic findings predicting lethality. The diagnosis of Osteogenezis Imperfecta type II was confirmed by postmortem radiography and autopsy examination.
Conclusion: Today with the advances in obstetric ultrasonography, the early prenatal diagnosis of lethal skeletal dysplasias is
possible. In existence of ultrasonographic findings predicting lethality, the choice of termination should be offered to parents
after giving a detailed information about the fetal prognosis even if the true ultrasonographic diagnosis is not available.
Keywords: Osteogenesis imperfecta, prenatal diagnosis.
Osteogenezis Imperfektan›n Prenatal Tan›s›: Olgu Sunumu
Amaç: Osteogenezis imperfekta kollagen maturasyonunda defekt nedeniyle kemik k›r›lganl›¤›nda art›fl, anormal kemikleflme ve
çok say›da k›r›klarla karakterize heterojen bir genetik hastal›kt›r. Bu çal›flmada gebeli¤in 16. haftas›nda yap›lan obstetrik ultrasonografi ile tan›s› konularak sonland›r›lan bir Osteogenezis imperfecta olgusu sunulmufltur.
Olgu: 19 yafl›nda gravida 2, parite1 olan olgu gebeli¤in 16. haftas›nda yap›lan ultrasonografisinde fetal iskelet anomalisi saptanmas› üzerine klini¤imize refere edildi. Olgunun yap›lan prenatal 2. düzey ultrasonografisinde tüm ekstremitelerde uzun kemiklerin k›sa bükülmüfl ve çok say›da k›r›k içerdi¤i, gö¤üs kafesinin k›sa dar oldu¤u, ayr›ca kafatas›n›n düflük ekodansitede olup kafa
içi yap›lar›n ola¤andan daha net görüldü¤ü saptand›. Letaliteyi gösteren ultrasonografi bulgular› nedeniyle gebeli¤in terminasyonuna karar verildi. Postnatal radyografi ve otopsi bulgular›yla Osteogenezis imperfekta tip II tan›s› kondu.
Sonuç: Günümüzde obstetrik ultrasonografideki geliflmelerle ölümcül iskelet displazilerinin erken prenatal tan›s› mümkün olabilmektedir. Spesifik ultrasonografik tan› konulamasa bile letaliteyi öngören ultrasonografik belirteçlerin varl›¤›nda aileye fetal prognoz hakk›nda bilgi verilerek terminasyon seçene¤i sunulmal›d›r.
Anahtar Sözcükler: Osteogenezis imperfekta, prenatal tan›.
Correspondence: Dr. ‹ncim Bezircio¤lu, ‹zmir Atatürk E¤itim ve Araflt›rma Hastanesi 1. Kad›n Hastal›klar› ve Do¤um Klini¤i, ‹zmir
e-mail: [email protected]
50
Bezircio¤lu ‹ et al., Prenatal Diagnosis of Osteogenesis Imperfecta: A Case Report
Background
An osteogenesis imperfecta type II case diagnosed with prenatal ultrasonography and aborted at
16th pregnancy week is presented. Because of the
case it is aimed to draw attention to the ultrasonographic diagnosis criteria of fatal prognosed osteogenesis imperfecta Type II and reviewing the
ultrasonographic markers preceding fatal prognosis.
Case
The case is 19 years old, G2P1, having a normal son; in the ultrasonography that was made for
the first time in this pregnancy at 16th week upon
determining a morphologic defect in fetus, the patient is referred to our clinic. In ultrasonographic
evaluation cranium echogenity is decreased, intracranial structures were seen more evident than
usual (Figure 1). Thorax diameter was decreased
significantly and increased to the favor of heart.
Spine was morphologically normal. Long bones in
extremities were short and curled, their measurement was below 5 % percentile, and some parts of
hand and foot bones could not be seen (Figure 2).
With these findings a fatal skeletal displasia prognosed with mineralization defect was considered
Figure 1. Ultrasonographic view of the cranium.
Figure 2. Ultrasonographic view of the limbs.
51
Perinatal Journal • Vol: 14, Issue: 1/March 2006
clinically and radiologically. After giving prenatal
the inspection after birth and postmortem radiog-
consultancy it is decided to end the pregnancy.
raphy (Figure 3).
With induction of misopristol dead male fetus was
delivered.
In autopsy examination caudo rectal length was
16, 5 cm, head to heel length was 20 cm (Figure
It is seen that cranium bones were not devel-
4). It was seen that cranial bones were not devel-
oped, Thorax was significantly short and thin, long
oped when the cranial cavity opened. There were
bones of extremities were fairly short and curled in
multifractures in costae and small nodular struc-
Figure 3. Postmortem radiographic view.
Figure 4. Morphological view.
52
Bezircio¤lu ‹ et al., Prenatal Diagnosis of Osteogenesis Imperfecta: A Case Report
Figure 5. View of the costal fractures.
tures made of callus tissue in thorax cavity (Figure
5). Fibrocartilagenous young repairment tissue was
observed in samples taken from costae. There was
microfractures and callus tissue in samples from
tibia. Furthermore bone spicules in metaphysis
could not be seen clearly and it showed marked
ossification defect (Figure 6). There were immature
organ findings in samples from the other organs.
Discussion
Osteogenesis imperfecta type 1 is a heterogen
genetic disease developing with collagen metabolism disorder and seen clinically in a broad spectrum. It is characterized with increase in bone
fragility, abnormal osteogenesis and multifractures.
Type II is the most severe form among four known
Figure 6. Ossification defects on microscopy.
Perinatal Journal • Vol: 14, Issue: 1/March 2006
clinical forms. Incidence is 0.4 in 10000 liveborns,
approximately half of them are (0,19 : 10000) type
II.1
Osteogenesis imperfecta type II is divided into
3 subgroups according to radiologic criteria. The
most severe and frequently seen type is type II A.
Severe micromelia, decreased thorax diameter and
short thorax length, decreased mineralization and
multifractures in bones are the mainly characteristics of the disease. There is normal bone echogenity in type II B and C and fractures are seen rarely.
There is shortness in all bones in type II B while
only an isolated shortness is found in femur in
type II C.2,3 Our case is consistent to Osteogenesis
imperfecta type II A with phenotypic and radiologic characteristics.
Most of osteogenesis imperfecta type II cases
occur with de novo otosomal dominant mutations.
It is also reported rare otosomal recessive and
germ line mosaism.4,5
Type 1 is developed as a result of a dominant
mutation in one of COL1A1 or COL1A2 genes responsible from collagen production. Disease type 1
occurs in collagen containing organs and tissues
(skin, ligament, tendon, demineralized bone, dentine) with clinical pathologic findings. In osteogenesis imperfecta, both intramembraneous production and enchondral bone production and repairment are effected from type 1 collagen production
defect.4 Failure in intramembranous bone production leads to diaphysial cortical bone production
and calvarial ossification defect. In our case, it is
shown that there is no ossification in sculp with
ultrasonography, radiography and autopsy findings. Failure in enchondral osteogenesis leads defect in bone growing and also in healing of bone
fracture.4 It showed severe micromelia in our case, long bone measurements are determined below the 5% percentile. Ossification defect is
showed histologically in slices taken from metaphysis.
Prenatal diagnose of osteogenesis imperfecta
type II can be done with ultrasonographic examination and DNA analysis on chorion villus samples.6 Most frequently described prenatal sonographic signs are being the long bones short thick
53
untidy margin, short thorax, being the skull in low
echogenity, seeing intracranial structures more evident. It can be diagnosed by ultrasonography from
beginning of the second trimester.3,7 It is reported
cases that are diagnosed in first trimester.8,9
At high risk patient population severe displasia
cases can be diagnosed early with transvaginal
fetal biometry followings. But, fetal biometry following is not found effective in early diagnosing of
mild form skeletal displasias.7
Since skeletal displasias are a quite heterogen
disease group, their spesific and differential diagnose is hard. The spesific diagnose can be done
with clinical findings, biochemistry analysis, radiography in postnatal period, and with radiography,
autopsy and biochemistry analysis on fibroclast
cultures of samples taken from fetus and autopsy
in fatal cases.10
Tretter et al confirmed specific antenatal diagnose of 13 cases (48%), 26 cases were fatal in postnatal period in a series of 27 cases that they are
determined fatal skeletal displasia.11
Parilla et al made a true specific antenatal diagnose to the 20 cases (65%) in a serie of 31 cases
that they diagnosed skeletal displasia by ultrasonography. They project its fatality is 100 % with
the findings such as severe shortness of long
bones, bone curlings and fractures, being the
FL/AC ratio smaller than 0.16, cloverleaf shaped
skull, hypoplastic thorax, short ribs. They did not
determine false positive sign showing it is fatal.10
Hers et al investigated that definite ultrasonographic findings are whether indicative or not in
cases of suspected skeletal displasia. They projected 23 of 26 cases who they diagnosed skeletal
displasia were fatal, specific diagnose of 11 of
them were confirmed postnatally. They found positive predictive value 92 % in determining the fatal
prognosis when evaluated with narrow thorax,
being femur percentile smaller than 1 and
decreased bone echogenity.12
In our case osteogenesis imperfecta Type II is
pre-diagnosed with short narrow thorax, lack of
ossification in cranium, severe micromelia and
fractures and pregnancy is ended because of the
presence of findings determining fatal prognosis.
54
Bezircio¤lu ‹ et al., Prenatal Diagnosis of Osteogenesis Imperfecta: A Case Report
Its prenatal diagnose is important because of its
fatality and osteogenesis imperfecta type II mostly
occurs with de novo mutations. Severe shortness
of long bones, multifractures in long bones and
angling, short and narrow thorax, decreased bone
echogenity, cloverloaf shaped sculp are the most
important ultrasonographic markers of fatal prognosis.
References
1.
Skeletal Dysplasias, Chapter15. In: Nyberg DA, McGahan
JP, Pretorius DH, Pilu G (Eds). Diagnostic imagines of fetal
anomalies. 1th Edition, Philadelphia, Lippincott Williams&Wilkins 2003; p: 696-8.
2.
Tongsong T, Wanapirak C, Siriangkul S. Prenatal diagnosis
of osteogenesis imperfecta type II. Int J Gynaecol Obstet
1998; 61(1): 33-8.
3.
Baytur YB, Nefle N, Uyar Y, Laçin S, ‹nceboz ÜS, Ça¤lar H.
Osteogenezis ‹mperfekta Tip II tan›s›nda prenatal ultrason,postmortem radyografi ve otopsinin yeri: Olgu sunumu. Perinatoloji Dergisi 2004; 12(3): 155.
4.
Kennon JC, Vitsky JL, Tiler GE, Jeanty P. Osteogenesis Imperfecta. The fetus net: 1994-07-07-15.
5.
Cole WG, Dalgleish R. Perinatal lethal osteogenesis imperfecta. J Med Genet 1995; 32(4): 284-9.
6.
Berge LN, Marton V, Tranebjaerg L, Kearney MS, Kiserud T,
Oian P. Prenatal diagnosis of osteogenesis imperfecta. Acta Obstet Gynecol Scand 1995; 74(4): 321-3.
7.
Gabrielli S, Falco P, Pilu G, Perolo A, Milano V, Bovicelli
L.Can transvaginal fetal biometry be considered a useful
tool for early detection of skeletal dysplasias in high-risk
patients? Ultrasound Obstet Gynecol 1999; 13: 107-111.
8.
Viora E, Sciarrone A, Bastonero S, Errante G, Botta G, Franceschini PG, Campogrande M. Osteogenesis imperfecta associated with increased nuchal translucency as a first ultrasound sign: report of another case. Ultrasound Obstet
Gynecol 2003; 21(2): 200-2.
9.
McEwing RL, Alton K, Johnson J, Scioscia AL, Pretorius DH.
First-trimester diagnosis of osteogenesis imperfecta type II
by three-dimensional sonography. J Ultrasound Med 2003;
22(3): 311-4.
10. Parilla BV, Leeth EA, Kambich MP, Chilis P, MacGregor SN.
Antenatal detection of skeletal dysplasias. J Ultrasound
Med. 2003;22(3):255-8.
11. Tretter AE, Saunders RC, Meyers CM, Dungan JS, Grumbach
K, Sun CC, Campbell AB, Wulfsberg EA. Antenatal diagnosis of lethal skeletal dysplasias. Am J Med Genet 1998;
75(5): 518-22.
12. Hersh JH, Angle B, Pietrantoni M, Cook VD, Spinnato JA,
Clark AL, Kurtzman JT, Bendon RW, Gerassimides A.
Predictive value of fetal ultrasonography in the diagnosis of
a lethal skelethal dysplasia. Southern Medical Journal 1998;
91(12): 1137-42.
55
Perinatal Journal • Vol: 14, Issue: 1/March 2006
Cervical Pregnancy: A Case Report
Cüneyt Eftal Taner, Tolga M›zrak, Semih Mun, ‹rem fienyuva, Yi¤it Özgenç, Fatma Alt›ntaflo¤lu Çelimli
SSK Ege Maternity Hospital. Obstetrics Clinic, Izmir
Abstract
Introduction: Cervical pregnancy constitutes 0.1% of all ectopic pregnancies. It is associated with a significant risk of life-threatening severe hemorrhage.
Case: A 33-years-old woman gravida 8, para 2, abortus 5 and living children 2 who had left oophorectomy operation due to
ovarian cyst was referred to our hospital with pelvic pain and delayed menstrual period. By vaginal ultrasonographic examination, cervical pregnancy sac which was 7.5x3 mm in diameter and compatible with 5 weeks and 1 day of gestation was found
in the cervical canal. There was no significant subchorionic bleeding area. The patient was hospitalised. Beta-human chorionic
gonadothropin (β-hCG) level was 4532 mIU/ml on admission. Since the pregnancy was very early, aspiration&curettage was
applied. Ultasonographic and physical findings after curettage were normal and the patient was discharged in the following
day.
Conclusion: Cervical pregnancy is associated with life-threating hemorrhage. Only in early pregnancy surgical interventions can
be applied safely.
Keywords: Cervical ectopic pregnancy.
Servikal gebelik: olgu sunumu
Girifl: Servikal gebelikler tüm ektopik gebeliklerin %0.1’ini oluflturur. Hayat› tehdit edebilecek kadar afl›r› kanama en önemli
komplikasyondur.
Olgu: 33 yafl›nda, gebelik 8, parite 2, abortus 5, yaflayan 2 çocu¤u olan olgunun 2 y›l önce over kisti nedeniyle geçirilmifl sol ooforektomi öyküsü mevcuttu. Adet gecikmesi ve kas›k a¤r›s› flikayeti ile baflvuran olguda yap›lan vaginal ultrasonografik incelemede servikal kanal içerisinde yaklafl›k 7.5x3 mm çapl›, konturlar› düzgün, içerisinde 3 mm’lik yolk sak ve milimetrik CRL‘si bulunan
5 hafta 1 gün ile uyumlu servikal gebelik izlendi. Belirgin subkoryonik kanama alan› yoktu. Hastaneye yat›r›lan olguda β-hCG düzeyi 4532 mIU/ml olarak ölçüldü. Erken gebelik saptanmas› nedeniyle aspirasyon küretaj uyguland›. Küretaj sonras› ve muayene
bulgular› normal olarak de¤erlendirilen olgu bir gün sonra taburcu edildi.
Sonuç: Servikal gebelikler hayat› tehdit edebilecek düzeyde kanama riski tafl›maktad›r. Ancak erken gebelik olgular›nda güvenli
cerrahi müdahale uygulanabilir.
Anahtar Sözcükler: Servikal ektopik gebelik.
Background
Cervical pregnancy constitutes 0.1% of ectopic
pregnancies and it is a life threatening condition.1
Correspondence: Dr. Semih Mun, SSK Ege Do¤umevi, ‹zmir
e-mail: [email protected]
Definite etiology of cervical pregnancy is not
known. There is a relation with past dilatation and
curettage, Asherman’s syndrome, cesarean section,
56
Taner CE et al., Cervical Pregnancy: A Case Report
infertility, invitro fertilization therapy, intrauterin
device usage history and embryonal chromosome
abnormalities.1 Sonographic findings of cervical
pregnancy are presence of pregnancy sac at endocervical localization and trophoblastic invasion.
Pathologic diagnostic criteria of cervical pregnancy are presence of endocervical glands against placental region, beginning the invasion of placenta
into cervix, being of some part or whole of the
placenta at under the uterine entry region or peritoneal foldings at the front or back face of uterine
and lack of fetal elements in endometrial cavity.
There is a living fetus in 60% of the cervical pregnancies.2 Most of the patients are low parity pregnants and the most important problem in conservative treatment is excessive bleeding. Conservative
treatment forms are chemotherapy with
methotrexate, KCl injection into the sac.
Hysterectomy is more offered in second or third
trimester of cervical pregnancies or uncontrolled
bleedings.1
Case
Case who is 33-years-old, married for 16 years,
had 8 pregnancy, 2 birth, 5 abortus, 2 living children had a history of left ooferectomy because of
ovarian cyst two years ago. She admitted with
complaints of menstrual delay and inguinal pain
and there was seen approximately 7.5x3 mm diameter, smoothly contoured, having inside 3 mm yolk
sac and millimetric CRL that is consistent with 5
week 1 day pregnancy in cervical canal in vaginal
ultrasonography. There was no marked subchorionic bleeding area (Figure 1). Endometrium thickness was 14 mm in our case and myometrium
echogenicity was normal. β-HCG level is measured
as 4532 mIU/ml. There was no vaginal bleeding in
her physical examination. Blood biochemistry and
hemogram parameters were normal. Aspiration
curettage is applied because of determined early
pregnancy. Ultrasonography was normal after
curettage and vital findings were normal during
following, there was no vaginal bleeding and case
is discharged at fist day after curettage. Pathology
results were nonproductive placental tissue as
pathology doctors reported.
Discussion
As ectopic pregnancy incidence was 16 over
1000 pregnancies in 1989 in USA, in recent years
this ratio increased to the levels of five folds compared to 1970s.3 We face the maximal ectopic
pregnancy incidence between 35-44 ages with a
rate of 20.8 pregnancies over 1000.3 Cervical preg-
Figure 1. Pregnancy sac at cervical canal.
57
Perinatal Journal • Vol: 14, Issue: 1/March 2006
nancy is a life-threatening and rarely seen type of
ectopic pregnancy. Cervical pregnancy incidence
is 1 over 2.400 to 50.000 pregnancies in USA.3 In
a study by Ushakov et al, it is reported that the
most seen symptom of cervical pregnancy is vaginal bleeding with a ratio of 91% and then inguinal
pain with a ratio of 2%.1 There was no vaginal
bleeding in the physical examination of our case.
There was only inguinal pain and menstrual delay
complaint. There is a relationship between cervical pregnancy and past dilatation and curettage
history, Asherman’s syndrome, cesarean section,
infertility, IVF treatment, intrauterine device usage
history and embryonic chromosomal abnormalities.1 There was no other risk factor except past
dilatation and curettage history in our case.
It is hard to diagnose cervical pregnancy clinically. Diagnose has been abortus imminens, incomplete abortus or missed abortus preoperatively in 50% of the patients in a study made by
Nelson et al.3 With the using of ultrasonography in
diagnosing cervical pregnancy can be differentially diagnosed from other types of abortus. Although 4.5% false diagnose is made, when ultrasonography is not used 46.2% case take false diagnose.3 Transvaginal ultrasonography must be preferred in cervical pregnancies but, the best results
are always made with a combination of transvaginal and abdominal sonography.2 In our case cervical pregnancy diagnose was made with transvaginal ultrasonography. Ushakov et al determined
live cervical pregnancy in a ratio of 62.5% while
they determine 10.8% early cervical pregnancy
and 13.8% missed cervical pregnancy.
Serum β-hCG levels are used in diagnose of
cervical pregnancy and in the following of conservative treatment. Ushakov et al reported serum βhCG levels as 54.1-137,000 mIU/ml at the moment
of diagnose in their study. In our case serum βhCG level was 4532 mIU/ml when it is diagnosed.
β-hCG followings are carrying importance especially in observation of medical treatment.
Main target in the treatment of cervical pregnancy is preventing bleeding by ending the pregnancy. Aspiration and curettage are the most frequently used choice in the treatment of cervical
pregnancy. Aspiration and curettage are performed in approximately half of the patients.1 Altho-
ugh aspiration and curettage seem as a benign treatment method severe bleeding can begin after
ablation of placenta as Schneider described.4 Some approaches in order to reduce the blooding of
cervices can be administered preoperatively to
solve this problem. This methods are ligation of
cervical branches of uterine artery transvaginally,
Shirodkar type cerclage, embolization of uterine
artery by angiography or intracervical vasopressine injection.1,5 However, in that case a preoperative administration to reduce cervical bleeding
was not done because of early cervical pregnancy
and unexpectation of deep trophoblastic invasion.
An excessive bleeding was not observed during or
after the operation.
In the treatment of cervical pregnancy hysterectomy, conservative abdominal surgery (ligation
of bilateral internal iliac or uterine arteries or cervical hysterectomy) and medical treatments can be
administered besides aspiration and curettage. Today hysterectomy is preferred in patients 45 years
and above, having high parity or having diagnose
of cervical pregnancy with uterine pathology.1
Methotrexate or potassium chloride can be administered in medical treatment. Methotrexate can
be administered in patients with a pregnancy age
of under 10 weeks and also hemodynamically stabile, with minimal or no bleeding and in patients
without active renal or liver disease, leucopenia or
trombositopenia.5 For this reason methotrexate is
an agent that can be used systemic or local. Pregnancy sac collapse due to local methotrexate administration; bone marrow depression, stomatitis,
anorexia, vomiting, nausea, diarrhea, acute or
chronic hepatotoxicity, pulmoner fibrosis, alopecia and photosensitivity are the side effects that
can be seen due to systemic administration of
methotrexate.6 Potassium chloride is an agent that
can be administered locally into the sac as injection.7
As a result cervical pregnancy is a type of ectopic pregnancy carrying excessive bleeding risk.
However, surgical intervention can be administered safely in early pregnancy cases.
1.
References
Ushakov FB, Elchalal U, Aceman PJ, Schenker JG. Cervical
pregnancy: Past and future. Obstet Gynecol Surv 1997; 52:
45-59.
58
Taner CE et al., Cervical Pregnancy: A Case Report
2.
Frates MC, Benson CB, Doubilet PM et al. Cervical ectopic
pregnancy: Results of conservative treatment. Radiology
1994; 191: 773-5.
3.
Ectopic pregnancy. In: Speroff L, Glass RH, Kase NG.
Editors. Clinical Endocrinology and Infertility. Baltimore:
Williams & Wilkins. 1994: 947-66.
4.
Nelson RM. Bilateral internal iliac artery ligation in cervical
pregnancy: conservation of reproductive function. Am J
Obstet Gynecol 1979; 15; 134: 145-50.
5.
Dreizin DH, Schneider P. Cervical pregnancy. Am J Surg
1957; 93: 27-40.
6.
Honey L, Leader A, Claman P. Uterine artery embolization:
A successful treatment to control bleeding cervical pregnancy with a simultaneous intrauterine gestation. Hum Reprod 1999; 14: 553-5.
7.
Bai SW, Lee JS, Park JH, Kim JY, Jung KA, Kim SK, Park
KH. Failed methotrexate treatment of cervical pregnancy.
Predictive factors. J Reprod Med 2002; 47: 483-8.
8.
Doubilet PM, Benson CB, Frates MC, Ginsburg E. Sonographically guided minimally invasive treatment of unusual
ectopic pregnancies. Ultrasound Med 2004; 23: 359-70.