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1 All authors: Department of Radiology, Harvard Medical School and Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115.
Received September 20, 1999;
accepted after revision December 7, 1999.
Address correspondence to P.M. Doubilet.
Abstract
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SUBJECTS AND METHODS. We recorded embryonic heart rates in 2817 sonograms at or before 7.0 weeks' gestation performed between January 1993 and June 1998. The upper limit of normal heart rate in two gestational age ranges (before 6.3 weeks and 6.3-7.0 weeks) was computed as the average of two values: mean heart rate + 1.96 standard deviations and the rate above which 2.5% of embryos in our population were measured. Pregnancy outcome in cases with rapid embryonic heart rates was compared with pregnancy outcome in a control group with normal rates.
RESULTS. The upper limit of normal heart rate was 134 beats per minute before 6.3 weeks' gestation and 154 beats per minute at 6.3-7.0 weeks' gestation. Forty-one embryos had rapid early heart rates and known first-trimester outcome, of which 37 (90.2%) were alive at the end of the first trimester. Pregnancy outcome was available in 33 of the 37 first-trimester survivors (four were lost to follow-up before delivery), and 30 of these 33 (90.9%) were healthy neonates. These short- and long-term outcomes were not significantly different from those of the control group of embryos with normal early heart rates (p > 0.20, Fisher's exact test).
CONCLUSION. A rapid early embryonic heart rate is one that is at least 135 beats per minute before 6.3 weeks or at least 155 beats per minute at 6.3-7.0 weeks. Pregnancies in which the embryo has a rapid early heart rate have a good prognosis, with a high likelihood of normal outcome.
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Slow embryonic heart rates and their prognostic significance have been well studied [2, 9,10,11,12,13,14,15]. A heart rate below 100 bpm before 6.3 weeks' gestation or below 120 bpm at 6.3-7.0 weeks carries a poor short-term prognosis, in that an embryo with such a rate is at an elevated risk of dying within the first trimester [9]. The short-term prognosis is especially bleak for heart rates below 80 bpm before 6.3 weeks or below 100 bpm at 6.3-7.0 weeks. The long-term prognosis among first-trimester survivors, on the other hand, is fairly good, in that an embryo with a slow early heart rate who is still alive at the end of the first trimester has a high likelihood of becoming a healthy neonate [15].
Much less is known about rapid heart rates in the early first trimester. In particular, the upper limits of normal heart rates at gestational ages up to 7.0 weeks have not been clearly established, and the short- and long-term prognoses of an embryo whose early heart rate exceeds this limit have not been delineated. We undertook a study to determine the upper limits of normal heart rates for gestational ages up to 7.0 weeks and to assess the prognosis of embryos with rapid early heart rates.
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Data recorded for each case included heart rate and gestational age at the time of the study sonogram, as well as findings on all subsequent sonograms obtained during the pregnancy. Delivery date and neonatal discharge diagnoses were recorded for all neonates delivered at our institution.
The upper limit of normal heart rate before 6.3 weeks' gestation was determined by taking the average of two values, each of which was derived from a method for estimating the upper limit of the 95% confidence interval. Method 1: Upper limit of normal heart rate = mean heart rate before 6.3 weeks' gestation + 1.96 (SD of heart rates before 6.3 weeks' gestation). Method 2: Upper limit of normal heart rate equals heart rate above which 2.5% of cases in our population fell.
Note that if heart rates are normally distributed, methods 1 and 2 will yield precisely the same value, because in a normally distributed sample 95% of cases are within 1.96 SDs of the mean, 2.5% are more than 1.96 SDs above the mean, and 2.5% are more than 1.96 SDs below the mean.
The upper limit of the normal heart rate at 6.3-7.0 weeks' gestation was determined in the same way.
First-trimester outcome was classified as "live" if a sonogram obtained at or beyond 13 weeks' gestation showed a live fetus or a neonate was delivered. It was classified as "dead" if, before 13.0 weeks, sonography showed no cardiac activity or a spontaneous miscarriage occurred. First-trimester outcome was considered to be unknown in all other cases, including pregnancies electively terminated before 13 weeks.
Final pregnancy outcome among first-trimester survivors was classified as "liveborn with no anomaly" if a neonate was delivered at or beyond 24 weeks' gestation and no anomaly was detected either prenatally or during the neonatal hospital stay. Outcome was classified as "pregnancy loss with no anomaly" if either delivery before 24 weeks or inutero demise at any gestational age occurred, and no anomaly was detected either prenatally or via autopsy. Outcome was classified as "anomaly" if an anomaly was diagnosed prenatally, at birth, or via autopsy. Final pregnancy outcome was considered to be unknown in all other cases, including elective pregnancy terminations after 13 weeks (unless the termination involved an anomalous fetus).
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In our study population, method 1 (mean + 1.96 SD) yielded a value of 136.6 bpm and method 2 (heart rate above which 2.5% of cases were measured) yielded 132 bpm. The values at 6.3-7.0 weeks were 156.4 bpm and 153 bpm for methods 1 and 2, respectively.
Averaging the values in each gestational age range yielded 134 bpm as the upper limit of normal heart rate before 6.3 weeks' gestation and 154 bpm as the upper limit at 6.3-7.0 weeks. That is, the criteria for rapid embryonic heart rates are before 6.3 weeks, greater than or equal to 135 bpm; 6.3-7.0 weeks, greater than or equal to 155 bpm.
Pregnancies with rapid early embryonic heart rates were compared with those with normal early heart rates (100-134 bpm before 6.3 weeks and 120-154 bpm at 6.3-7 weeks) with respect to short-term (Table 1) and long-term (Table 2) outcomes.
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Among 41 embryos with rapid early heart rates and known first-trimester outcome, 37 (90.2%) were alive at the end of the first trimester (Table 1). This is similar to the first-trimester survival rate of 91.5% among embryos with normal early heart rates (p = 0.77, Fisher's exact test). That is, a rapid early heart rate does not adversely affect short-term prognosis.
Four of the 37 first-trimester survivors of a rapid early heart rate were lost to follow-up before delivery. Among the remaining 33 pregnancies with known pregnancy outcome, more than 90% resulted in a healthy neonate (Table 2). The frequency of spontaneous loss without anomalies was similar in fetuses whose early heart rate had been rapid (3.0%) and those whose early heart rate had been normal (2.5%) (p = 0.57, Fisher's exact test). The frequency of anomalies was somewhat higher in fetuses whose early heart rate had been rapid than in those whose early heart rate had been normal (6.1% versus 2.3%), while the frequency of a good outcome (healthy neonate) was somewhat lower in the rapid early heart rate group (90.9% versus 95.2%), but the differences were not statistically significant (Table 2). Anomalies occurring in the rapid early heart rate group included one case each of trisomy 21 and double-outlet right ventricle. Those in the normal early heart rate group included two cases of trisomy 21, eight of cardiac anomalies, and 19 of other anomalies.
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Our findings suggest that an embryonic heart rate of 135 bpm or more before 6.3 weeks' gestation should be considered rapid, as should a rate of 155 bpm or more at 6.3-7 weeks. They also indicate that a rapid early embryonic heart rate is not associated with adverse short-term outcome, in contrast to the poor short-term prognosis after a slow early heart rate. In particular, 90.2% of embryos with a rapid heart rate at or before 7 weeks' gestation were alive at the end of the first trimester, similar to the first trimester survival rate of 91.5% for embryos with a normal early heart rate.
Our findings also indicate that the long-term prognosis after a rapid early embryonic heart rate is good, in that more than 90% of first-trimester survivors of a rapid early heart rate in our study became healthy neonates. We cannot, however, definitively exclude a small difference in long-term prognosis between pregnancies with rapid early heart rates and those with normal early heart rates because the observed frequency of major anomalies was higher in the rapid heart rate group (6.1% versus 2.3%), but not statistically significant in view of the small sample size. Notably, there was one fetus with trisomy 21 among the 33 first-trimester survivors of a rapid early heart rate (incidence rate of 3%), an occurrence that cannot be ignored in view of a previously suggested association between trisomy 21 and rapid heart rates later in the first trimester [20]. Further studies with larger sample sizes are needed to delineate more clearly the risk of anomalies, including aneuploidy, in embryos with rapid early heart rates. In particular, the 3% incidence rate of trisomy 21 in first-trimester survivors of a rapid early heart rate would have been statistically significant had our study population been twice as large (assuming that all frequencies, including that of trisomy 21 among fetuses with normal early heart rates, had remained the same).
In summary, a heart rate in early pregnancy is rapid if it is at least 135 bpm before 6.3 weeks' gestation, or at least 155 bpm at 6.3-7 weeks. Pregnancies with rapid early embryonic heart rates have a good prognosis, with a high likelihood of normal outcome.
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