Download The newborn thyroid stimulating hormone levels in

Moksliniai darbai
The newborn thyroid stimulating
hormone levels in relation to maternal
age and gestation at birth
naujagimio tirostimuliuojančio hormono ryšys su motinos amžiumi
bei nėštumo trukme
Ingrida Mockutė1, Eimantas Švedas1, Nijolė Raškauskienė2, Narseta Mickuvienė2,
Robertas Bunevičius2
1
Department of Obstetric and Gynaecology of Lithuanian University of Health Sciences,
2
Institute of Psychophysiology and Rehabilitation of Lithuanian University of Health Sciences
Summary. Thyroid stimulating hormone (TSH) is used as a compulsory newborn screening assay to evaluate for
congenital hypothyroidism. Understanding of confounding factors that affect newborn TSH levels remains the scope
of research and requires further investigation. Aims. Our aim was to examine the relationship between newborn TSH
levels and maternal age, newborn birth weight, gestational age and gender. Methods. We studied 170 newborns born
between 35 and 41 weeks of gestation. The neonates were tested for thyroid function by measurement of TSH level
from dried filter paper blood spots on the 3rd day of life. We conducted multivariate analyses
to simultaneously examine the relationship between neonatal TSH levels and maternal age,
newborn gender, gestational age, and birth weight. Results. For the study population, median
and mean maternal age was 28 years and ranged from 19 to 41 years. All neonates were born
at 40 median gestational weeks (range from 35 to 41 weeks). The study sample consisted of
96 male and 74 female births. Median birth weight was 3540 g (range from 2176 to 4700 g).
There were 2 (1.2%) males born at <37 weeks’ of gestation. The mean newborn TSH concentration was within normal physiological reference range (mean 3.12 mIU/L (SD 1.04 mIU/L);
Ingrida Mockutė 1995–2001 m. studijavo KMU Medicinos fakultete, dalį laiko Kalundborgo
ligoninėje, Danijoje. Pirminę rezidentūrą baigė Šiaulių miesto ligoninėje bei Granados universitetinėje ligoninėje, Ispanijoje. Nuo 2006 m. tęsia doktorantūros studijas „Skydliaukės
disfunkcijos įtaka nėštumui, gimdymui ir ankstyvajai vaisiaus raidai“. Dirba KMU Akušerijos ir ginekologijos klinikoje. El. paštas [email protected]
Doc. Eimantas Švedas 1994 m. baigė KMU Gydomąjį fakultetą, 1999 m. – akušerijos
ir ginekologijos rezidentūrą. 1999–2003 m. studijavo doktorantūrą Karolinska instituto
Huddinge universitetinės ligoninės Moterų klinikoje (Stokholmas, Švedija). 2003 m. apgynė
medicinos daktaro disertaciją „Endotelio ląstelių funkcija smulkiose arterijose, izoliuotose
iš moterų reprodukciniame amžiuje ir po menopauzės – galimybės pagerinimui“. Dirba
KMU Akušerijos ir ginekologijos klinikoje gydytoju. Stažavosi Švedijoje, Danijoje, UK, JAV.
Nijolė Raškauskienė, jaunesnioji mokslo darbuotoja, Kauno medicinos universiteto Psichofiziologijos ir reabilitacijos institutas. Pagrindinė darbo kryptis – matematinė statistika.
Dr. Narseta Mickuvienė, gydytoja endokrinologė. 1983 metais baigė KMI, apginta daktaro
disertacija KMU 2000 m. Kauno medicinos universiteto Psichofiziologijos ir reabilitacijos
instituto vyresnioji mokslo darbuotoja, direktoriaus pavaduotoja klinikai, endokrinologė
konsultantė.
Habil. dr. Robertas Bunevičius, mokslo darbuotojas, 1982 m. baigė KMI, 1983 m. – psichiatrijos internatūrą. 1992 m. apgynė disertaciją „Ph.D.Afektinė patologija ir pogumburio-hipofizės – skydliaukės sistemos funkcija sergant autoimuniniu tireoiditu“, 1999 m. – habilitacinį
darbą „Emociniai sutrikimai sergant skydliaukės ligomis: klinikiniai ir neuroendokrininiai
aspektai“. Lietuvos biologinės psichiatrijos draugijos prezidentas ir Pasaulinės biologinės
psichiatrijos draugijų federacijos valdybos narys.
278
2010 rugsėjis, tomas XIII, Nr. 3
Lietuvos akušerija ir ginekologija
Moksliniai darbai
range: 0.23–6.03 mIU/L). In our study age-specific 2SD range (mean ± 2SD) necessary for interpretation of newborn
TSH levels on the third day of life was 0.4–5.2 mIU/L. We performed crude and multivariate analyses adjusting for
newborn gender, birth weight, gestational age, maternal age. A model showed significant adjusted associations with
TSH levels for both maternal age (p = 0.022) and gestational age (p = 0.035), but not for birth weight (p = 0.267)
and newborn gender (p = 0.086). Gestational age was associated with TSH levels in multivariate but not univariate
models. Positive association between maternal age and newborn TSH persisted in both univariate and multivariate
models. The model accounted for 6.9% of the total variation. Conclusion: Maternal age and gestational age were
related to neonatal thyroid function, as measured by neonatal TSH levels. Therefore, careful consideration of these
factors should be drawn while assessing blood spot TSH levels and providing antenatal care.
Key words: pregnancy, blood spot thyroid stimulating hormone (TSH), newborn screening, maternal age, gestational age.
Santrauka. Tirostimuliuojančio hormono testas (TSH) naudojamas naujagimių patikros programoje, diagnozuojant įgimtą hipotireozę. Veiksniai, įtakojantys naujagimio TSH koncentraciją, yra aktuali mokslinių tyrimų sritis.
Tikslas. Ištirti naujagimių TSH koncentracijos ryšį su motinos amžiumi, gimimo svoriu, nėštumo trukme ir naujagimio
lytimi. Metodai. Ištyrėme 170 naujagimių, gimusių tarp 35-os iki 41-os nėštumo savaitės. Naujagimių skydliaukės funkcija buvo vertinta, atliekant sauso kraujo lašo TSH testą trečią dieną po gimimo. Nepriklausomus kintamuosius įtraukus
į skaičiavimą vienu metu, atlikome daugiamatę regresinę analizę, siekdami nustatyti ryšį tarp naujagimių TSH kiekio
ir motinos amžiaus, nėštumo trukmės, naujagimio lyties ir gimimo svorio. Rezultatai. Tiriamojoje grupėje, vidutinis
gimdyvių amžius buvo 28 metai bei svyravo nuo 19 iki 41 metų. Naujagimiai gimė vidutiniškai 40 nėštumo savaičių
(nuo 35 iki 41 savaitės). Tyrimo grupę sudarė 96 vyriškos ir 74 moteriškos lyties naujagimiai. Vidutinis naujagimio svoris
buvo 3540 g (nuo 2176 iki 4700 g). Du (1,2 proc.) berniukai gimė <37 nėštumo savaičių. Naujagimių TSH koncentracijos
vidurkis buvo fiziologinės normos ribose (vidurkis 3,12 (SD 1,04); intervalas: 0,23–6,03 mIU/L). Tyrime nustatytas naujagimių TSH koncentracijos 2SD intervalas (vidurkis ± 2SD) pagal amžių, kuris trečią gyvenimo dieną svyravo nuo 0,4
iki 5,2 mIU/L. Atlikome vienmatės ir daugiamatės tiesinės regresijos analizę, kontroliuojant duomenis pagal naujagimio
lytį, gimimo svorį, nėštumo trukmę, motinos amžių. Statistiškai reikšmingame modelyje motinos amžius (p = 0,022) ir
nėštumo trukmė (p = 0,035) turėjo statistiškai reikšmingą įtaką naujagimių TSH koncentracijai, tačiau statistiškai reikšmingos sąsajos su naujagimio gimimo svoriu (p = 0,267) ir lytimi (p = 0,086) nebuvo. Gestacinis amžius buvo susijęs su
naujagimio TSH koncentracija tik daugiamatėje analizėje. Teigiamas ryšys tarp motinos amžiaus ir naujagimio TSH
koncentracijos nustatytas ir vienmatėje, ir daugiamatėje analizėje. Modelis paaiškino 6,9 proc. TSH koncentracijos kitimo.
Išvada. Motinos amžius ir nėštumo trukmė yra susiję su naujagimių TSH koncentracija. Veiksniai, įtakojantys TSH
tyrimo rezultatus, turėtų būti atidžiai įvertinami, teikiant antenatalinę priežiūrą.
Reikšminiai žodžiai: nėštumas, sauso kraujo lašo tirostimuliuojantis hormonas (TSH), naujagimių patikra,
motinos amžius, gestacinis amžius.
INTRODUCTION
The development and maturation of the
brain and central nervous system and other
target tissues have a critical dependence on
thyroid hormones [1–2], beginning before
birth and extending through the first 2–3
years of life [3–4]. Incidence of congenital
hypothyroidism (CH) ranges from 1 in
3000 to 1 in 4000 newborn infants [5–6]
and is a common preventable cause of
mental retardation. Elevated thyroid stimulating hormone (TSH) concentration
in a newborn’s blood is the earliest available laboratory manifestation of primary
hypothyroidism. Owing to its superior
specificity and sensitivity TSH testing is
preferred over thyroxin testing [7].
Elevated neonatal serum TSH level
indicate insufficient supply of thyroid
hormones to the neonatal pituitary, hypot-
Lietuvos akušerija ir ginekologija
halamus as well as other parts of the brain,
and therefore constitute a major indicator
that allows prediction of brain impairment
[8]. There is a known association between
CH and other congenital malformations
cardiac, neural tube defects (NTD) and
dysmorphic features being predominant
ones [9–10]. From the obstetrical point of
view, the risk for congenital malformations
and chromosomal abnormalities increases
with advanced maternal age. Childbearing
period in the reproductive life cycle is generally defined in the studies as between
the ages of 15 and 44 years in the studies
[11]. Maternal age as influencing neonatal
TSH levels is of particular interest, especially over the recent decades, since the
demography of parenting has changed due
to delayed decisions to motherhood [12].
Neonatal screening TSH values may vary
2010 rugsėjis, tomas XIII, Nr. 3
279
Moksliniai darbai
depending on the influence of multiple methodological sample collection factors, including timing of specimen collection, the TSH
assay and collection paper used [13]. There
are, however, very little data available on perinatal factors potentially affecting neonatal
blood spot TSH levels. Whether evaluation
of TSH levels in newborns is ordered as a
screening test or in response to symptoms,
the understanding of confounding factors
has to be further explored. Therefore the aim
of this study was to examine the relationship
between neonatal TSH levels and possible
confounding factors, such as maternal age,
newborn birth weight, gestational age and
gender. Since birth statistics over the recent
decades in Europe have shifted foward delaying motherhood until thirties and beyond
[12] it is of interest to assess neonatal TSH
levels in relation to maternal age in healthy
newborns with no signs of CH or congenital
malformations.
MATERIAL AND METHODS
Subjects and measures
Pregnant women who signed for antenatal care in Kaunas University of Medicine
Hospital, as well as in the Primary Health
Care Center between 2003 and 2005, were
randomly invited to participate in the study: ”Effect of psychoendocrine challenge
during gestation and delivery to the wellbeing of mother and child: multi-central
study” [14–15]. The study and its consent
procedures were approved by the Regional
Committee of Ethics in Biomedical Research at the Kaunas University of Medicine,
Kaunas, Lithuania.
322 pregnant women signed an informed
consent for participation. After applying
exclusion criteria (extragenital and thyroid
disease, including thyroid autoimmune
disease assessed by the elevated levels of
thyroid antibodies and singleton pregnancy) data from 184 pregnant women were
included in the study. Dry blood spot TSH
was obtained from 177 newborns. Data on
blood spot TSH levels were obtained from
the National Neonatal Screening Program
for congenital hypothyroidism. Recommended timing of taking blood from a heel
prick is after 24 hours of minimize the false
positive high TSH due to the physiological
neonatal TSH surge that elevates TSH levels
and causes dynamic during in thyroxine
(T4) and triiodo thyroxine concentration
280
2010 rugsėjis, tomas XIII, Nr. 3
(T3) changes in the first 1 or 2 days after
birth [16]. Therefore our blood spot TSH
samples were obtained on the third day after
birth according to the institutional regulations by a nurse-neonatologist. All measures of TSH level in blood specimens dried
on filter paper were analyzed at the Centre
for Medical Genetics, Vilnius University
Hospital. Dry blood spot TSH level data
of 7 newborns was not found among the
records from the Human Genetics Center.
Detailed information on neonatal factors
was obtained from medical records from
three delivery centers in Kaunas. Lithuania
Information on neonatal birth weight (in
grams) gestational age at birth (in weeks),
and maternal age was collected from the
medical documentation.
Statistical methods
Mean, median and standard deviations
(SD) of TSH values of the neonates were
considered to report the result of the
screening. Seven records with missing descriptive information were removed before
statistical analysis. The Mann-Whitney test
was used to detect difference in median
by groups defined by neonatal gender.
TSH levels complied with assumptions of
normality of the dependent variable. The
effects of maternal age, gestational age,
gender and birth weight on newborn TSH
levels were assessed by analysis of variance
(ANOVA), multiple correlation coefficient
and Spearman‘s correlation coefficients.
Multiple linear regressions were performed
to quantify the associations between the
above parameters and changes in TSH level.
A probability level of p < 0.05 was taken
as significant. All statistical analyses were
performed using the statistical software
package SPSS, version 15.0. (SPSS Inc.,
Chicago, Illinois).
RESULTS
We studied a total of 170 newborns. For
the study population, median and mean
maternal age was 28 years (range from 19
to 41 years). All neonates were born at median 40 of gestational weeks (range from 35
to 41 weeks). The study sample consisted
of 96 male and 74 female births. Median
birth weight was 3540 g (range from 2176
to 4700 g). There were 2 (1.2%) males born
at <37 weeks’ of gestation (maternal age 21
years, gestational age 35 weeks, birth weight
Lietuvos akušerija ir ginekologija
Moksliniai darbai
Table 1.
Descriptive continuous data showing median, IQRa and range (minimum and maximum
values) for TSH, birth weight and gestational age in male and female infants
All
median
TSH, mIU/l
Birth weight, g
Gestation, weeks
a
IQR (range)
Males (M) N=96
Females (F) N=74
median
median
IQR (range)
pb
M vs. F
IQR (range)
3.23
2.55–3.79
(0.23–6.03)
3.38
3.26–3.95
(0.23–6.03)
3.12
2.28–3.59
(1.05–5.37)
0.054
3540
3265–3832
(2176–4700)
3602
3307–3880
(2176–3722)
3,500
3230–3722
(2176–4700)
0.075
40
39–40
(35–41)
40
39–40
(35–41)
40
39–40
(36–41)
0.284
IQR, interquartile range, the range from the 25th to 75th percentile; b Mann-Whitney tests.
2176 g, TSH 2.21 mIU/L in one case; 27
years, 36 weeks, 3000 g, 2.67 mIU/L in the
other one).
Mean newborn TSH level was 3.12 (SD
1.04) mIU/L. Descriptive data, medians and
interquartile ranges (IRQ) are presented in
table 1. The distribution of TSH level was
not significantly different between male and
female newborns, although male newborns
tended have higher median TSH levels (3.38
mIU/L compared with 3.12 mIU/L in females, p=0.054). Male newborns also tended
heavier at birth (p=0.075). Both groups had
an identical median and IQR of gestational
age (p=0.284).
An effect of gestational age on TSH levels
was established at the p-value below 0.1
(b = 0.14, p = 0.07) (Figure). Gender specific analyses showed that gestational age
was not correlated with TSH levels when
stratified by gender (p = 0.41 and 0.33 for
males and females, respectively).
There were also no effects of birth weight
on TSH levels (b = 0.02, p = 0.871). Two
newborns were lighter than 2500 grams at
birth. The values of TSH were 2.21 (female,
gestation age 39 weeks, birth weight 2176 g)
and 3.47 mIU/L (male, 36 weeks, 2176 g).
Mean (SD) maternal age was 28 (6) years.
Newborn TSH levels were associated with
maternal age (b=0.17, p=0.029). Spearman
rank correlation analysis showed significant
positive correlation between birth weight
and gestational age (r = 0.398, p < 0.001).
Gender-specific analyses showed similar
correlation coefficients as for the combined
analysis (p < 0.001 and p = 0.006 for male
newborns and female newborns, respectively). There was no effect of neonates on
birth weight (F(1,168) = 2.4; p = 0.121) and
on maternal age (F(1,168) = 1.1; p = 0.287).
Lietuvos akušerija ir ginekologija
Table 2.
Adjusted coefficients for factors included in a
multiple linear regression model with the TSH as
the outcome variable
Factor
Beta β
p
Maternal age, year
0.18
0.022
Gestational age, week
0.18
0.035
Gender (1, female; 2, male)
0.13
0.086
–0.09
0.267
Birth weight, g
Dependent variable: newborn TSH; R adjusted = 0.069; adjusted for maternal age,
child gender, gestational age, and birth weight.
2
Figure.
Thyroid stimulating hormone (TSH) values in
infants of different gestational age
Gestational age correlated significantly with
maternal age (r = 0.15 p = 0.032) and birth
weight (r = 0.33 p<0.001).
Multivariate analysis
Since birth weight is dependent on gestational age, we conducted a multivariate
analysis simultaneously to examine the
2010 rugsėjis, tomas XIII, Nr. 3
281
Moksliniai darbai
relationship between neonatal TSH, levels
and maternal age (modeled continuously),
newborn gender, gestational age, and birth
weight. The outcome variable in the analysis
was the TSH level and the results are shown
in table 2. A significant (F3,167=2.99, p =
0.020) model showed significant adjusted
associations with TSH levels for maternal
age (p = 0.022) and gestational age (p =
0.035), but not for birth weight (p = 0.267),
and newborn gender (p = 0.086).
Gestational age was associated with TSH
level in multivariate but not in univariate
models. Positive association between
maternal age and newborn TSH levels
persisted in both univariate and multivariate models. In this model for TSH levels,
the inclusion of all predictive covariates
accounted 6.9% of the total variation.
Linear multivariate regression analysis performed in order to test the relation between
TSH level, newborn birth weight, newborn
gender, and gestational age yielded the following regression equation: TSH (mIU/L)
= [–0.00022 (p=0.27) × birth weight (g)] +
[0.182 (p=0.035) × gestational age (weeks)]
+ [0.038 (p=0.022) × maternal age (years)]
+ [0.279 (p=0.086) × gender (1, female;
2, male)] – 4.86 (r2 = 0.069). The effect of
birth weight and newborn gender was not
significant.
Age-specific 2SD range (mean ± 2SD)
necessary for interpretation of newborn
TSH levels during the third day of life was
0.4–5.2 mIU/L.
DISCUSSION
In our study we found that maternal age
and gestational age were independently
related to neonatal TSH levels in newborns
without CH in the region of mild iodine
deficiency [17–19]. We observed that older
maternal age in pregnancy and newborn
gestational age were associated with elevated newborn bloodspot TSH levels on the
third day of life. Therefore careful consideration of these factors should be drawn
while assessing blood spot TSH levels and
providing antenatal care.
There is scanty research data available on
the dynamics of neonatal thyroid func­tion
during the perinatal period and the factors
potentially influencing newborn TSH levels.
We found only one study, assessing the relation between newborn TSH levels and maternal age. Our data on this issue is in close
282
2010 rugsėjis, tomas XIII, Nr. 3
agreement with the study by Herbstman et
al. where older maternal age was independently associated with lower umbilical cord,
total T4 levels. Nevertheless, they did not the
same association with umbilical cord serum
TSH levels TSH in multivariate analysis
[20]. We can only speculate on the different
study design as well as different geographical
region and nutrition environment of the
newborns and their mothers studied. We
can also hypothesize, that cord blood TSH
levels could have been influenced by a wide
range of delivery factors, while 3rd day blood spot TSH measures could reflect the for
basal TSH level in the newborn.
It is noted that maternal age is increasing among pregnant Lithuanian women.
Acording to statistics of 2001 and 2008 the
proportion of delivering women over 30
years of age was 30.9 and 37.7 percent, respectively [21]. In our study 31.1 percent of
delivering women were more than 30 years
of age. It is well known that older pregnant
women carry a higher risk of having a baby
with a genetic abnormality, such as Down’s
syndrome, Edwards’ syndrome or Patau’s
syndrome [22]. According to the worldwide
database, The International Clearinghouse
for Birth Defects [23] and EUROCAT [24]
collecting information on infants born with
congenital malformations, and Italian study
from the Italian Registry for Congenital
Hypothyroidism [25], anomalies of heart,
nervous system, eyes (representing precocious structures in the developing embryo)
and multiple congenital malformations are
significantly associated with CH [26–27].
These findings strongly suggest a very early
impairment in the first stages of embryo development with a consequent involvement
of different organs and structures. As the fetus progresses into the third trimester, it develops the ability to produce its own thyroid
hormones but is still dependent on maternal
iodine for hormone synthesis [28]. While
most women in Europe are classified as iodine – deficient during preg­nancy (achieving
only approximately half of the recommended l daily iodine intake), only 13–50% of
them receive iodine supplementation [29].
Therefore we presume that maternal age and
elevated neonatal TSH levels acting jointly
might have a significant impact on fetal
intrauterine development and hormonal
status of the newborn. There are known
benefits of folic acid supplementation three
Lietuvos akušerija ir ginekologija
Moksliniai darbai
months before and during early stages of
pregnancy in terms of preventing neural
tube defects (NTDs) alone and reducing the
incidence of other birth abnormalities such
as congenital heart disease, urinary tract
problems, oral facial clefts, limb defects, and
some early pediatric cancers [30–31]. On the
other hand, there are recommendations that
women should increase their daily iodine intake to 250 µg on average during pregnancy
and breastfeeding [32–33].
We suggest, health care providers to be
cautious when providing antenatal care
to the older women in terms of fetal and
neonatal thyroid function, especially, because there is no consensus on universal
screening for hypothyroidism in pregnancy
[32]. A case finding approach is recommended [32] in case of women at high risk for
thyroid dysfunction, but maternal age is
not included in the criteria. Although data
on associations between maternal age and
neonatal TSH levels is scanty, we propose
to be alert while providing antenatal care to
older pregnant women and evaluating TSH
levels during the first days postpartum. We
suppose maternal age factor could also be
taken into account while deciding on iodine
supplementation during pregnancy.
In our study we observed that gestational
age was associated with increased bloodspot
TSH levels in multivariate but not univariate models. In agreement with our study,
a relationship between gestational age and
TSH concentrations was shown by Korada
et al. [34], but multiple regression analysis
confirmed that this was a reflection of the
close link between gestational age and birth
weight [34]. On the contrary, Herbstman et
al. concluded that gestational age was independently associated with lower cord TSH,
higher cord total T4, and higher neonatal
and subsequent bloodspot total T4 [20].
In the study by Miyamoto et al. TSH levels
varied widely and had no correlation with
gestational age because they were affected by
the mode of delivery [35]. It is known however, that as gestational age increases, the
fetus elevates the synthesis of both T4 and
TSH [28]. That statement was confirmed in
the study by McElduff et al., where higher
TSH values had been associated with older
gestational age [36]. Studies of fetal and
neonatal thyroid function show that thyroid
hormone levels rise as pregnancy advances
[37–38] with levels of TSH in cord blood
Lietuvos akušerija ir ginekologija
and neonatal blood spot samples positively
related to gestational age [20].
Still we have to acknowledge some limitations of our study due to relatively small
sample size, omitted data on maternal thyroid status, assessment of iodine adequacy,
non-multiregional involvement, also prematurity and CH being out of the scope of
the research too. Even though Lithuania is
considered to be a region of mild iodine deficiency [19] with 22% of pregnant women
having a severe iodine deficiency [18] and
3 of newborns having TSH values above 5
mIU/L [17], our sample size represents only
one country region. Therefore a multiregional study design would be of interest.
The limitation of our study is that we can
not currently provide the data on iodine
status during pregnancy. The evaluation of
iodine in urine of pregnant women, as well
as data on multivitamin pill use during pregnancy, could broaden the spectrum of the
analysis and help to research in depth the
effect of iodine on the changes of neonatal
TSH in relation to maternal age and gestational age. The assessment of maternal and
neonatal thyroid hormones could provide
additional information on the interaction
of two different economies in terms of confounding factors. Prematurity effect issue on
thyroid function has been left out, since it has
the exceptional role in obstetrics as well as
in endocrinology. Therefore it opens a new
scope for research in this area. In our study
there were no newborns with CH, therefore
we suppose setting a study for evaluating
mother‘s age effects on the presence of CH
would be of interest in the further research.
CONCLUSION
Maternal age and gestational age were
related to neonatal TSH levels in newborns
without CH in the region of mild Iodine
deficiency. We found older maternal age in
pregnancy and longer gestation at birth were
associated with elevated newborn bloodspot
TSH levels. Therefore, we should carefully
consider these factors while assessing blood
spot TSH levels and providing antenatal care.
Refference
1. Bernal J. Action of thyroid hormone in brain. J
Endocrinol Invest 2002;25(3):268-88.
2. Bunevicius R. Thyroid disorders in mental patients. Curr Opin Psychiatry 2009;22(4):391-5.
3. Porterfield SP, Hendrich CE. The role of thyroid
hormones in prenatal and neonatal neurological
development--current perspectives. Endocr Rev
2010 rugsėjis, tomas XIII, Nr. 3
283
Moksliniai darbai
1993;14(1):94-106.
4. Zoeller RT, Rovet J. Timing of thyroid hormone
action in the developing brain: clinical observations
and experimental findings. J Neuroendocrinol
2004;16(10):809-18.
5. Haddow JE, Palomaki GE, Allan WC, Williams
JR, Knight GJ, Gagnon J, et al. Maternal thyroid
deficiency during pregnancy and subsequent
neuropsychological development of the child. N
Engl J Med 1999;341(8):549-55.
6. Waller DK, Anderson JL, Lorey F, Cunningham
GC. Risk factors for congenital hypothyroidism:
an investigation of infant’s birth weight, ethnicity,
and gender in California, 1990-1998. Teratology
2000;62(1):36-41.
7. LaFranchi S. Congenital hypothyroidism: etiologies, diagnosis, and management. Thyroid
1999;9(7):735-40.
8. Delange F. Neonatal thyroid screening as a monitoring tool for the control of iodine deficiency. Acta
Paediatr Suppl 1999;88(432):21-4.
9. Reddy PA, Rajagopal G, Harinarayan CV,
Vanaja V, Rajasekhar D, Suresh V, et al. High
prevalence of associated birth defects in congenital hypothyroidism. Int J Pediatr Endocrinol
2010;2010:940980.
10. Cassio A, Tatò L, Colli C, Spolettini E, Costantini
E, Cacciari E. Incidence of congenital malformations in congenital hypothyroiidsm. Screening
1994(3):125-30.
11. Boivin J, Bunting L, Collins JA, Nygren KG.
International estimates of infertility prevalence
and treatment-seeking: potential need and demand for infertility medical care. Hum Reprod
2007;22(6):1506-12.
12. Boivin J, Rice F, Hay D, Harold G, Lewis A,
van den Bree MM, et al. Associations between
maternal older age, family environment and parent and child wellbeing in families using assisted
reproductive techniques to conceive. Soc Sci Med
2009;68(11):1948-55.
13. Copeland DL, Sullivan KM, Houston R, May W,
Mendoza I, Salamatullah Q, et al. Comparison of
neonatal thyroid-stimulating hormone levels and
indicators of iodine deficiency in school children.
Public Health Nutr 2002;5(1):81-7.
14. Bunevicius R, Kusminskas L, Bunevicius A, Nadisauskiene RJ, Jureniene K, Pop VJ. Psychosocial
risk factors for depression during pregnancy. Acta
Obstet Gynecol Scand 2009;88(5):599-605.
15. Bunevicius R, Kusminskas L, Mickuviene N,
Bunevicius A, Pedersen CA, Pop VJ. Depressive
disorder and thyroid axis functioning during pregnancy. World J Biol Psychiatry 2009;10(4):324-9.
16. Buyukgebiz A. Newborn screening for congenital hypothyroidism. J Pediatr Endocrinol Metab
2006;19(11):1291-8.
17. Mockute I, Svedas E, Kusminskas L, Raskauskiene N. Iodine deficiency assessed by the newborn
thyrotropin concentrations. Lietuvos akuserija ir
ginekologija 2010;13(2):131-2.
18. Bėrontienė R. Vaikų skydliaukės struktūriniai
ir funkciniai pokyčiai jodo trūkumo sąlygomis:
daktaro disertacija. Kaunas: Kauno Medicinos
Universitetas; 2002.
19. Elimination of Iodine Deficiency Disorders (IDD)
in Central and Eastern Europe, the Commonwealth
of independant states, and the Baltic States. WHO/
EURO/NUT/981; 1997 3-6 september. Miunich;
1997.
20. Herbstman J, Apelberg BJ, Witter FR, Panny
S, Goldman LR. Maternal, infant, and delivery
factors associated with neonatal thyroid hormone
status. Thyroid 2008;18(1):67-76.
21. Naujagimių registro duomenys [database on the
Internet]. Lietuvos sveikatos informacijos centras.
Available from: http://www.lsic.lt/.
22. Cunningham FG, Norman FG, Kenneth JL. Fetal
abnormalities: inherited and aquired disorders. In:
284
2010 rugsėjis, tomas XIII, Nr. 3
Seils A, Noujaim SR, Davis K, editors. Williams
obstetrics. 21st ed. New York: The McGraw Hill
Companies, Inc; 2001. p. 941-86.
23. The International Cleringhouse for Birth Defects.
Available from: http://www.icbdsr.org.
24. European Surveillance of Congenital Anomalies.
Available from: http://www.eurocat-network.eu/
HomePage.
25. Olivieri A, Stazi MA, Mastroiacovo P, Fazzini C,
Medda E, Spagnolo A, et al. A population-based
study on the frequency of additional congenital
malformations in infants with congenital hypothyroidism: data from the Italian Registry for
Congenital Hypothyroidism (1991-1998). J Clin
Endocrinol Metab 2002;87(2):557-62.
26. Cassio A, Tatò L, Colli C, Spolettini E, Costantini
E, Cacciari E. Incidence of congenital malformations in congenital hypothyroidism. Screening
1994;3(3):125-30.
27. Gu YH, Harada S, Kato T, Inomata H, Aoki K,
Hirahara F. Increased incidence of extrathyroidal
congenital malformations in Japanese patients with
congenital hypothyroidism and their relationship
with Down syndrome and other factors. Thyroid
2009;19(8):869-79.
28. Burrow GN, Fisher DA, Larsen PR. Maternal and fetal thyroid function. N Engl J Med
1994;331(16):1072-8.
29. Zimmermann M, Delange F. Iodine supplementation of pregnant women in Europe: a review and
recommendations. Eur J Clin Nutr 2004;58(7):97984.
30. SOGC Clinical practice guidelines: the use of
folic acid for the prevention of neural tube defects
and other congenital anomalies [database on the
Internet]2003, November. Available from: http://
www.sogc.org/guidelines/public/138E-CPGNovember2003.pdf.
31. Periconceptional supplementation with folate
and/or multivitamins for preventing neural tube
defects [database on the Internet]. John Wiley &
Sons, Ltd; 2001. Available from: http://www.mrw.
interscience.wiley.com/cochrane/clsysrev/articles/
CD001056/frame.html.
32. Abalovich M, Amino N, Barbour LA, Cobin
RH, De Groot LJ, Glinoer D, et al. Management
of thyroid dysfunction during pregnancy and
postpartum: an Endocrine Society Clinical Practice
Guideline. J Clin Endocrinol Metab 2007;92(8
Suppl):S1-47.
33. Report of a WHO Technical Consultation on
prevention and control of iodine defficiency in
pregnancy, lactation, and in children less than 2
years of age (Geneva, 24-26 January 2005). Public
Health Nutr (Special Issue) 2007(10 (12A)):1527611.
34. Korada M, Pearce MS, Avis E, Turner S, Cheetham T. TSH levels in relation to gestation, birth
weight and sex. Horm Res 2009;72(2):120-3.
35. Miyamoto N, Tsuji M, Imataki T, Nagamachi N,
Hirose S, Hamada Y. Influence of mode of delivery
on fetal pituitary-thyroid axis. Acta Paediatr Jpn
1991;33(3):363-8.
36. McElduff A, McElduff P, Wiley V, Wilcken B.
Neonatal thyrotropin as measured in a congenital
hypothyroidism screening program: influence of
the mode of delivery. J Clin Endocrinol Metab
2005;90(12):6361-3.
37. Murphy N, Hume R, van Toor H, Matthews
TG, Ogston SA, Wu SY, et al. The hypothalamicpituitary-thyroid axis in preterm infants; changes in
the first 24 hours of postnatal life. J Clin Endocrinol
Metab 2004;89(6):2824-31.
38. LaFranchi S. Thyroid function in the preterm
infant. Thyroid 1999;9(1):71-8.
Gauta: 2010 m. rugpjūčio mėn.
Priimta spausdinti 2010 m. rugpjūčio mėn.
Lietuvos akušerija ir ginekologija