Download Long-Term Prognosis of Pregnancies

Long-Term Prognosis of Pregnancies
Complicated by Slow Embryonic Heart
Rates in the Early First Trimester
Peter M. Doubilet, MD, PhD, Carol B. Benson, MD, Jeanne S. Chow, MD
Slow embryonic heart rates at gestational age
7 weeks or less are associated with high risk of first
trimester death. Our goal was to determine the
prognosis for those embryos with slow early heart
rates who survive the first trimester. We prospectively recorded embryonic heart rates for all obstetrical sonograms obtained on singleton pregnancies
at or before 7.0 weeks’ gestation since 1993. We collected information about pregnancy outcome,
including date of live birth or in utero death and
presence and nature of congenital anomalies. First
trimester survival rate was 61.6% among 531
embryos with slow early heart rates (<100 bpm at
≤6.2 weeks, <120 bpm at 6.3 to 7.0 weeks), lower
than the survival rate of 91.5% among 1501 embryos
with normal heart rates (p < 10–8, Fisher’s exact test).
Among 299 pregnancies in which the early heart
rate was slow and the fetus was still alive at the end
of the first trimester, 277 (92.6%) resulted in liveborn
ABBREVIATIONS
bpm, Beats per minute; SD, Standard deviation
Received February 9, 1999, from the Department of Radiology,
Harvard Medical School and Brigham and Women’s Hospital,
Boston, Massachusetts. Revised manuscript accepted for publication
May 11, 1999.
Address correspondence and reprint requests to Peter M. Doubilet,
MD, PhD, Department of Radiology, Brigham and Women’s
Hospital, 75 Francis Street, Boston, MA 02115.
infants without congenital anomalies, similar to the
frequency of 95.1% in cases with normal early heart
rates (p > 0.10, Fisher’s exact test). Structural and
chromosomal anomalies, however, occurred more
than twice as frequently in cases with slow early
heart rates: 5.4% (16 of 299) of the first trimester survivors with slow early heart rates proved to have
anomalies, as compared to 2.4% (31 of 1281) of cases
with normal early heart rates (p < 0.05, Fisher’s exact
test). In conclusion, a pregnancy in which the
embryo has a slow heart rate at or before 7.0 weeks’
gestation and which continues beyond the first
trimester has a high likelihood (>90%) of resulting in
a liveborn neonate without congenital anomalies.
Embryos with slow early heart rates do, however,
have a greater risk of having anomalies than
embryos with normal early heart rates. KEY WORDS:
Embryo, heart rate; Pregnancy, outcome; Heart rate,
embryonic.
A
slow embryonic heart rate in the early
first trimester is associated with a poor
short-term prognosis.1–7 In particular,
rates below 100 bpm prior to 6.3 weeks’ gestation
and below 120 bpm between 6.3 weeks and
7.0 weeks carry an elevated risk of death by the
end of the first trimester. The risk of embryonic
death is close to 100% when the rate is less than 80
bpm below 6.3 weeks or less than 100 bpm
between 6.3 weeks and 7.0 weeks. The risk
declines progressively with increasing heart rates
until it plateaus for heart rates over 100 bpm at less
than 6.3 weeks or 120 bpm between 6.3 weeks and
7.0 weeks.5
 1999 by the American Institute of Ultrasound in Medicine • J Ultrasound Med 18:537–541, 1999 • 0278-4297/99/$3.50
538
PROGNOSIS WITH SLOW EMBRYONIC HEART RATE
Although the short-term prognosis for embryos
with slow heartbeats in the early first trimester has
been well documented, little is known about the
long-term prognosis for those embryos who survive
the first trimester. Most studies assessing the relationship between early embryonic heart rates and
outcome have followed pregnancies only until the
end of the first trimester. As a result, little or no data
exist on the liveborn rate and frequency of congenital anomalies in first trimester survivors who had
had slow early embryonic heart rates. We undertook
a study to assess pregnancy outcome in such
embryos.
MATERIALS AND METHODS
We prospectively recorded the results of all sonograms obtained at our institution between January
1993 and June 1998 demonstrating singleton pregnancies up to 7.0 weeks’ gestation with embryonic
cardiac activity. When a woman underwent sonography more than once at or prior to 7.0 weeks, the earliest sonogram demonstrating cardiac activity was
used in the study.
Data recorded for each case included gestational
age and heart rate (measured via M-mode) at the
time of the study sonogram, and the results of any
subsequent sonogram obtained during the pregnancy. Birth information was recorded, when available, including date of birth and neonatal discharge
diagnoses.
Embryonic heart rate was classified as “slow” if it
was less than 100 bpm at 6.2 weeks or earlier or less
than 120 bpm between 6.3 weeks and 7.0 weeks of
gestation.5 A heart rate above these cutoff points was
classified as normal.
First trimester outcome was classified as “live” if a
sonogram at or beyond 13 weeks’ gestation showed
a live fetus or if the pregnancy resulted in a liveborn
infant. It was classified as “dead” if, prior to 13
weeks, a sonogram showed no heartbeat or the
patient miscarried.
Final pregnancy outcome was classified as “liveborn with no anomaly” if a liveborn infant was delivered at or beyond 24 weeks’ gestation and no
anomaly was diagnosed either prenatally or during
the neonatal hospital stay. It was classified as “pregnancy loss with no anomaly” if delivery occurred
prior to 24 weeks or in utero death occurred at any
gestational age and no anomaly was diagnosed on
prenatal ultrasonogram, at delivery, or via fetopsy.
Pregnancy outcome was classified as “anomaly” if
an anomaly was present at birth or fetopsy. Minor
J Ultrasound Med 18:537–541, 1999
anomalies, such as hydrocele or pigmented skin
lesions, were ignored (i.e., neonates with such findings were classified as having no anomaly). Cases
lost to follow-up and those terminated electively
(other than terminations performed because of fetal
anomaly) were not assigned to any of these outcome
classifications.
RESULTS
The study population included 1392 singleton pregnancies scanned prior to 6.3 weeks’ gestation and
1425 scanned between 6.3 weeks and 7.0 weeks.
Mean heart rate (± SD) prior to 6.3 weeks was 109.2 ±
14.0 bpm and between 6.3 weeks and 7.0 weeks was
125.3 ± 15.9 bpm.
First trimester survival rate was lower in pregnancies with slow early embryonic heart rates than in
those with normal embryonic heart rates (Table 1). In
pregnancies in which the patients were scanned
prior to 6.3 weeks, the first trimester survival rate
was 53.8% among cases with slow embryonic heart
rates, significantly lower than the survival rate of
89.3% when the embryonic heart rate was normal
(p < 10–8, Fisher’s exact test). The lower the heart rate,
the lower the survival rate: 69.5% for heart rates of 90
to 99 bpm, 43.5% for rates of 80 to 89 bpm, and 8.8%
for rates less than 80 bpm. A similar relationship
between heart rate and survival was found in cases
scanned between 6.3 weeks and 7.0 weeks: embryos
with slow heart rates (less than 120 bpm) were less
likely than those with normal heart rates to survive
the first trimester (66.6% versus 93.8%; p < 10–8,
Fisher’s exact test), and the survival rate was poorer
with lower heart rates. Overall, cases with slow
embryonic heart rates at 7.0 weeks’ gestation or less
had a first trimester survival rate of 61.6%, lower
than the survival rate of 91.5% in cases with normal
embryonic heart rates (p < 10–8, Fisher’s exact test).
In those pregnancies in which the fetus survived
the first trimester, over 90% resulted in liveborn
neonates without congenital anomalies, regardless of
the early heart rate (Table 2). Among 299 pregnancies
in which the early heart rate was slow and the fetus
was still alive at the end of the first trimester, 277
(92.6%) resulted in normal liveborn infants (omitting
cases with unknown outcome). This was similar to
the frequency of 95.1% in cases with normal early
heart rates (p > 0.10, Fisher’s exact test).
Congenital anomalies, however, were more common in first trimester survivors with slow early heart
rates than in those with normal heart rates (Table 2).
Sixteen (5.4%) of the 299 first trimester survivors
J Ultrasound Med 18:537–541, 1999
DOUBILET ET AL
539
Table 1: Relationship Between Embryonic Heart Rate and First Trimester Outcome
First Trimester Outcome
Embryonic Heart Rate
Gestational age ≤6.2 weeks
Slow <100 bpm
<80 bpm
80–89 bpm
90–99 bpm
Normal ≥100 bpm
Gestational age 6.3 weeks to 7.0 weeks
Slow <120 bpm
<100 bpm
100–109 bpm
110–119 bpm
Normal ≥120 bpm
Total (gestational age ≤7.0 weeks)
Slow
Normal
N
Live
Dead
Survival Rate
208
34
46
128
774
112
3
20
89
691
96
31
26
39
83
53.8%*
8.8%
43.5%
69.5%
89.3%*
323
61
52
210
727
215
4
30
181
682
108
57
22
29
45
66.6%†
6.6%
57.7%
86.2%
93.8%†
531
1501
327
1373
204
128
61.6%‡
91.5%‡
N, Number of cases with known first trimester outcome.
*p < 10–8, Fisher’s exact test.
†p < 10–8, Fisher’s exact test.
‡p < 10–8, Fisher’s exact test.
with slow early heart rates proved to have anomalies, more than double the frequency of 2.4% (31 of
1281) in cases with normal early heart rates (p < 0.05,
Fisher’s exact test). Cardiac, chromosomal, and other
anomalies all occurred more frequently in fetuses
whose early heart rates had been slow than in those
with normal early heart rates (Table 3). In particular,
the frequency of aneuploidy in fetuses who survived
the first trimester was 1.3% among those whose early
embryonic heart rates had been slow, significantly
Table 2: Final Pregnancy Outcome Among First Trimester Survivors: Relationship to Embryonic Heart Rate
Final Pregnancy Outcome
Embryonic Heart Rate
N
Liveborn with No Anomaly
Pregnancy Loss* with No Anomaly
Anomaly
Gestational age ≤6.2 weeks
Slow <100 bpm
<80 bpm
80–89 bpm
90–99 bpm
Normal ≥100 bpm
Gestational age 6.3 weeks to 7.0 weeks
Slow <120 bpm
<100 bpm
100–109 bpm
110–119 bpm
Normal ≥120 bpm
98
3
18
77
639
91 (92.9%)
2
16
73
601 (94.1%)
2 (2.0%)
1
0
1
16 (2.5%)
5 (5.1%)
0
2
3
22 (3.4%)
201
4
29
168
642
186 (92.5%)
4
27
155
617 (96.1%)
4 (2.0%)
0
1
3
16 (2.5%)
11 (5.5%)
0
1
10
9 (1.4%)
Total (gestational age ≤7.0 weeks)
Slow
Normal
299
1281
277 (92.6%)†
1218(95.1%)†
6 (2.0%)
32 (2.5%)
16 (5.4%)‡
31 (2.4%)‡
N, Number of first trimester survivors with known final pregnancy outcome.
*Includes in utero deaths and fetuses delivered prior to 24 weeks.
†p > 0.10, Fisher’s exact test.
‡p < 0.05, Fisher’s exact test.
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PROGNOSIS WITH SLOW EMBRYONIC HEART RATE
J Ultrasound Med 18:537–541, 1999
Table 3: Anomalies Occurring in First Trimester Survivors: Relationship to Embryonic Heart Rate
Early Heart Rate
Type of Anomaly*
Slow
Normal
Cardiac
3 cases (incidence† = 1.0%; 3/299): VSD and
right aortic arch; transposition of great vessels;
coarctation
9 cases (incidence = 0.7%; 9/1281):
ventricular septal defect (3);
transposition of great vessels;
coarctation; DORV, TGV, HLV; hypoplastic
left ventricle; atrial septal defect (2)
Chromosomal
4 cases (incidence = 1.3%; 4/299): trisomy 21 (3); 47,XYY
4 cases (incidence = 0.3%; 4/1281): trisomy
21 (3); 48,XXYY
Other
9 cases (incidence = 3.0%; 9/299): hydrocephalus;
omphalocele; amniotic band syndrome; unilateral renal
agenesis; VATER syndrome; GI malrotation and SBO;
hemivertebrae; harlequin syndrome; hydrops
18 cases (incidence = 1.4%; 18/1281):
hydrocephalus; anencephaly (3); DandyWalker malformation; omphalocele;
unilateral renal agenesis (3); dysplastic left
kidney; pulmonary sequestration; facial
anomalies (2); polydactyly; Fanconi anemia;
clubfoot; hydrops (2)
Total (all anomalies)
16 cases (incidence = 5.4%; 16/299)
31 cases (incidence = 2.4%; 31/1281)
*Each pregnancy with an anomalous fetus is listed only once in the table. In the case of fetuses with multiple anomalies, the most
serious anomaly is listed.
†Incidence among first trimester survivors with known final pregnancy outcome.
VSD, Ventricular septal defect; DORV, double outlet right ventricle; TGV, transposition of the great vessels; HLV, hypoplastic left
ventricle; GI, gastrointestinal; SBO, small bowel obstruction; VATER, vertebral defects, anal atresia, tracheoesophageal fistula with
esophageal atresia, radial and renal dysplasia.
greater than the 0.3% in those whose early heart rates
had been normal (p < 0.05, Fisher’s exact test). Half
of all aneuploid fetuses (three of six with trisomy 21,
one of two with other chromosomal abnormalities)
had slow early heart rates. Maternal age was 35 years
or older in seven of the eight aneuploid fetuses,
including all four whose early heart rates had been
slow.
DISCUSSION
With transvaginal ultrasonography, the embryonic
heartbeat can be visualized beginning at approximately
6.0 weeks’ gestation, and its rate can be measured via Mmode sonography. The mean heart rate in early pregnancy increases progressively from approximately
100–120 bpm at 6.0 weeks to between 145–170 bpm at
9.0 weeks, after which it declines slowly for the rest of
the first trimester.7,12–15 The heart rate in an individual
embryo or fetus of less than 10 weeks’ gestational age
varies little from measurement to measurement, so that
reliable information about heart rate can be obtained
from a single measurement.16
Embryos with slow heart rates prior to 7.0 weeks have
a poor short-term prognosis, with a high chance of
death before the end of the first trimester.1–7 In particular, in comparison to embryos with normal heart rates,
the likelihood that an embryo will survive the first
trimester is lower when the heart rate is less than 100
bpm prior to 6.3 weeks or less than 120 bpm between 6.3
weeks and 7.0 weeks of gestation. Below these cutoffs
points, the slower the heart rate the poorer the prognosis for first trimester survival.5 Our study confirms this
relationship between a slow embryonic heart rate and
poor first trimester outcome.
When a slow early embryonic heart rate is found at
sonography, the parents should be advised that the risk
of miscarriage in the first trimester is high. If the fetus
survives the first trimester, however, counseling the parents is difficult, because the existing literature provides
little information about the long-term prognosis for
these pregnancies.
Our study addresses this issue. We assessed the
final outcome in pregnancies that continue beyond
the first trimester, comparing those with slow early
embryonic heart rates to those with normal early
embryonic heart rates. That is, we addressed the
J Ultrasound Med 18:537–541, 1999
question, ”If an embryo with a slow early heart rate
survives the first trimester, what is the likelihood that
the pregnancy will result in a normal neonate?”
Our study demonstrates that the prognosis for an
embryo with a slow early heart rate who survives the
first trimester is good, with a 92.6% likelihood that
the pregnancy will result in birth of a normal neonate.
This prognosis is similar to the 95.1% likelihood of a
good outcome for an embryo whose early embryonic
heart rate had been normal and who survives the first
trimester. That is, death occurring after a slow embryonic heart rate at 7.0 weeks of gestation or less is
likely to occur quickly—within the first trimester—or
not at all.
Our findings also indicate that a slow early embryonic heart rate is associated with an elevated risk of
congenital anomalies. The frequencies of cardiac,
chromosomal, and other anomalies are all increased
when an embryo has a slow early heart rate. Overall,
a pregnancy complicated by a slow heart rate at
7.0 weeks of gestation or less has at least twice the risk
of anomalies than one with a normal early heart rate.
Although the risk of aneuploidy is increased in
fetuses with slow early heart rates, all aneuploid
fetuses with slow early heart rates in our series were
born of women over the age of 35 years. These
women would have been offered amniocentesis
based on maternal age, independent of the heart rate
findings.
On the basis of our results, we suggest the following approach when a slow embryonic heart rate is
seen in the early first trimester. A 1–2 week follow-up
sonogram should be obtained and, unless embryonic
death is diagnosed, another scan should be performed in the late first trimester. If the fetus is still
alive at this time, the parents should be told that the
likelihood of subsequent death is now low, but that
the risk of anomalies is elevated. In view of this risk,
sonography should be performed at approximately
18 weeks to evaluate for fetal structural anomalies.
Karyotype testing is probably not indicated in the
absence of another risk factor for aneuploidy (e.g.,
maternal age of 35 years or greater, thickened nuchal
lucency on the late first trimester sonogram).
In summary, an embryo with a slow early heart rate
has a markedly increased chance of dying within the
first trimester. If it survives the first trimester, the likelihood of subsequent death is low, but the risk of
anomalies is elevated.
DOUBILET ET AL
541
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