Embryonic Heart Rate in Early Pregnancy

Theodor I. Stefos, MD, Dimitrios E. Lolis, MD, Alexander J. Sotiriadis, MD, George V. Ziakas, MD

Department of Obstetrics-Gynecology, Maternal-Fetal Division, University of Ioannina, N. Papadopoulou3, 454 44 Ioannina, Greece

Received 4 April 1996; accepted 5 March 1997

ABSTRACT: Purpose. Heart rates in embryos (6–8weeks’ gestation) have rarely been studied. We at-tempted to identify embryonic heart rates at 4 stagesduring 6–8 weeks’ gestation and to relate our findingsto fetal outcome at the end of the first trimester. Wealso tried to determine the lower limit of the heart rateassociated with a favorable outcome for each group.

Methods. We prospectively studied 2,164 singletonpregnancies between 1992 and 1995. Gestational agewas calculated from the known date of the beginningof the last menstrual period and was confirmed bysonographic measurement of the crown-rump length.M-mode sonography was used to calculate the em-bryonic heart rate as the mean of at least 3 waves inbeats/minute.

Results. Mean embryonic heart rates (± standarddeviation) were 111 ± 14 beats/min for group 1 (42–45days), 125 ± 15 beats/min for group 2 (46–49 days), 145± 14 beats/min for group 3 (50–52 days), and 157 ± 13beats/min for group 4 (53–56 days). Statistically sig-nificant differences (p < 0.01) in the mean heart rateswere seen between all groups. A heart rate between116 and 125 beats/min was associated with the fewestlosses in groups 1 (10.8% losses) and 2 (8.6%). Ingroups 3 and 4, a heart rate of 146 beats/min or morewas associated with the fewest losses (5.5% and 3.3%,respectively). A highly significant (p < 0.01) linear de-crease was seen in fetal losses with increasing gesta-tional age. Embryos with heart rates below 85 beats/min during 6–8 weeks’ gestation did not survive.

Conclusions. The heart rate during 6–8 weeks’ ges-tation is associated with fetal outcome at the end ofthe first trimester and identifies those embryos thatare in jeopardy. © 1998 John Wiley & Sons, Inc. J ClinUltrasound 26:33–36, 1998.

Keywords: heart rate; embryo; early pregnancy; ultra-sonography

Previous publications from European andAmerican centers have shown a gradual in-

crease in embryonic heart rates between 6 and 9weeks of pregnancy.1–5 In other studies, the like-lihood of embryo demise in the first trimester hasvaried between 79% for heart rates of 80–90beats/min to 100% for heart rates below 70 beats/min.6–10 The prognosis for fetal outcome and thenormal limits of the heart rate at different gesta-tional ages in the first trimester are unknown forheart rates above 90 beats/min. We undertookthis study to describe the heart rates seen be-tween 6 and 8 weeks of pregnancy and to deter-mine the rates that could be considered normalfor each gestational age in association with fetaloutcome at the end of the first trimester as shownby the fetal loss rate for each studied group.

PATIENTS AND METHODS

This prospective study of consecutive singletonpregnancies was undertaken between 1992 and1995 in an epidemiologically and demographical-ly homogeneous population of 2,164 white womenaged 18–36 years [mean ± standard deviation(SD), 26 ± 4 years] from all social classes. A de-tailed medical history was recorded for eachwoman and included risk factors of hypertension,diabetes, anemia, hereditary diseases or congen-ital abnormalities in previous pregnancies, previ-ous spontaneous abortions, sterility, medication,and habits such as coffee and alcohol intake. Arisk factor was found in 476 (22%) cases. None ofthe women were abusers of drugs or alcohol.

In 2,098 cases (97%), the gestational age wascalculated from the known date of the beginningof the last menstrual period, which had beenregular for the previous 2 years. Gestational age

Correspondence to: T.I. Stefos

© 1998 John Wiley & Sons, Inc. CCC 0091-2751/98/010033-04

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was confirmed by sonographic measurement ofthe crown-rump length (CRL). In 33 cases (1.5%),the gestational age was considered to be the con-ceptual age plus 2 weeks, with the conceptualdate being based on body temperature and inter-course records. The date of embryo transfer wasknown in the remaining 33 cases (1.5%) becausethese women had undergone in vitro fertilization.Still, embryonic age was confirmed by sono-graphic measurement of the CRL.

The first sonographic examination was per-formed transvaginally in 45% of cases and trans-abdominally in 55% of cases.11–13 The nextsonographic examination was performed trans-abdominally in 90% of cases. Sonographic exami-nations done after the 8th week of pregnancywere always performed transabdominally.

We used a 5-MHz vaginal transducer for trans-vaginal examinations, a 3.5-MHz transducer forabdominal examinations, and a Toshiba SSA-270A ultrasound scanner (Tokyo, Japan). The Mmode was used to evaluate the embryonic heartrate, which was detected in all our cases and cal-culated as the mean of at least 3 displayed heartwaves in beats per minute as measured by elec-tronic calipers.

Each case in our study was evaluated every 2weeks until the end of the first trimester (12weeks). Spontaneous abortions or fetal losses de-tected by the absence of heart beats at subsequentserial scans were recorded. No pregnancy in thestudy was terminated electively or had an un-known outcome at the end of the first trimester.

The 2,164 cases included in the study were di-vided into 4 groups according to gestational age:group 1, 6 weeks to 6 weeks 3 days (42–45 days;CRL # 7.2 mm), group 2, 6 weeks 4 days to 7weeks (46–49 days; CRL, 7.6–10.5 mm), group 3,7 weeks 1 day to 7 weeks 3 days (50–52 days;CRL, 10.8–13.3 mm), and group 4, 7 weeks 4 daysto 8 weeks (53–56 days; CRL, 13.8–17.0 mm).

Statistical analysis was done with SPSS soft-ware for Windows as described by Ryan et al.14

The hypothesis of no difference among the meanheart rates in groups 1–4 was examined using theKruskal-Wallis test. The test value was found tobe significant, and therefore, multiple compari-sons were carried out to determine the differencesbetween pairs of groups. For this we used the non-parametric procedure known as Fisher’s least sig-nificant difference computed on ranks. For eachcase, we also analyzed the fit of all possible hier-archical log-linear models to find the one thatgave the most parsimonious summary. Finally,the fetal loss rate in connection with gestationalage was examined using the chi-squared test. Be-

cause the gestational-age categories were natu-rally ordered, a further investigation of the asso-ciation between heart rate and fetal loss wascarried out by testing for the trend in the propor-tions of fetal mortality across groups. Thus, theoverall chi-squared value was partitioned into 2trends, linear with 1 degree of freedom and cur-vilinear with 2 degrees of freedom. The findingsfrom the latter analysis were then fitted with the2-way saturated log-linear model to arrive at theinteraction term and to examine the adjusted re-siduals. A p value less than 0.01 was consideredhighly significant.

Evaluation of fetal loss as related to risk fac-tors identified in the mother was beyond the scopeof this study.

RESULTS

The mean (±SD) heart rates for each group arepresented in Table 1, which shows that the em-bryonic heart rate progressively increased be-tween 6 and 8 weeks of pregnancy. Significant (p< 0.01) differences in mean heart rates werefound when each group was compared with theothers.

Table 2 shows the number of spontaneouslosses and the fetal loss rates for groups 1 and 2with respect to embryonic heart rate. Fetal lossrates were 100% for embryos with heart rates lessthan 85 beats/min. The outcome progressively im-proved as heart rate increased, with heart rates of116–125 beats/min associated with the fewestlosses (10.8%). The increased loss rate (22.7%)seen in group 1 embryos at a heart rate of 126beats/min or more could have resulted from thesmall number of embryos in this subgroup. Ingroup 2, loss rates were 75–100% for embryoswith heart rates of 105 beats/min or less. A heartrate of 116–125 beats/min was associated with agood outcome (8.6% losses).

The fetal loss rates with respect to heart ratefor groups 3 and 4 are presented in Table 3. Aheart rate of 126–145 beats/min was associated

TABLE 1

Mean Heart Rates for Embryos at 6–8 Weeks’ Gestation

GroupGestationalAge (days)

Mean Heart Rate±SD (beats/min)*

1 (n = 456) 42–45 111 ± 142 (n = 522) 46–49 125 ± 153 (n = 558) 50–52 145 ± 144 (n = 628) 53–56 157 ± 13

*Statistically significant (p < 0.01) differences were seen betweenall groups.

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with fetal loss rates of 17.1% in group 3 embryosand 24.7% in group 4 embryos. A heart rate of 146beats/min or more in group 3 embryos reflected agood outcome (only 5.5% losses) and seemed to bethe normal cut-off value for group 4 embryos, witha fetal loss rate of 3.3%. No group 4 embryos sur-vived at heart rates of 125 beats/min or less.

For group 1 and 2 data, the only model thatprovided a good fit was the saturated model, in-dicating a strong third-order interaction amongfetal mortality, gestational age, and heart rate.On the other hand, a conditional independencemodel fit the data for groups 3 and 4 adequately.This model postulates that fetal mortality andgestational age are independent of each other ateach heart rate but that each is associated withheart rate.

The observed proportions in Table 4 indicate adecrease in fetal mortality as gestational age in-creased. Indeed, the tests resulting from parti-tioning the overall chi-squared value revealedstrong evidence (p < 0.01) that this decrease waslinear rather than curvilinear; the departure fromlinearity was represented by a test value that wasnot significant.

It was observed that 326 (78.4%) of the fetallosses occurred between 7 and 10 weeks’ gesta-tion, whereas 90 (21.6%) fetal losses occurred be-tween 10 and 12 weeks’ gestation.

DISCUSSION

Previous studies have shown that there is a rela-tionship between gestational age and fetal heartrate.1–5 Some of these studies revealed that aheart rate below 90 beats/min in early pregnancyis associated with a poor outcome3,4,9,10 and that aheart rate of 70 beats/min or less leads to theembryo’s death.9 The existing studies have deter-mined a 95% confidence range for heart rate as afunction of gestational age and suggested thatrates below this range should be consideredslow.1,2,7,10,11 However, the given ranges are not as-sociated with a prediction of subsequent fetal loss.

To the best of our knowledge, the present studyis the first to use a very large database. It wasundertaken to describe embryonic heart rates be-tween 6 and 8 weeks of pregnancy. We tried todetect probable differences in the heart rates withmaximum accuracy, so we studied our data ingroups by dividing each week of pregnancy into 2time periods. Another purpose of this study wasto give the heart rates that could be consideredfavorable for fetal outcome at the end of the firsttrimester.

The results of our study show that a heart ratebelow 85 beats/min at 6–8 weeks of pregnancy isassociated with fetal death in all cases. The meanheart rate progressively increased from the 6th tothe 8th week. The mean heart rates (±SD) were111 ± 14 beats/min for group 1 (42–45 days), 125± 15 beats/min for group 2 (46–49 days), 145 ± 14beats/min for group 3 (50–52 days), and 157 ± 13beats/min for group 4 (53–56 days). These resultsare very useful in evaluating the heart rate as afunction of gestational age. A heart rate above116 beats/min can be considered a good predictorof fetal outcome in the gestational age range ofgroup 1. The same rate is also a good predictor offetal outcome for group 2. The high loss rate(22.7%) for embryos with a heart rate of 126beats/min or more in group 1 should be explainedby the small number of cases (n 4 22) included inthis subgroup.

TABLE 2

Fetal Losses by Heart Rate for Group 1 and 2 Embryos*

Heart Rate(beats/min)

Spontaneous Fetal Losses/Number of Embryos(Fetal Loss Rate, %)

Group 1 Group 2

#85 16/16 (100) 12/12 (100)86–95 56/82 (68.3) 14/16 (87.5)96–105 36/104 (34.6) 24/32 (75.0)

106–115 13/74 (17.6) 36/68 (52.9)116–125 17/158 (10.8) 16/186 (8.6)

$126 5/22 (22.7) 19/208 (9.1)

*Group 1, 6 weeks to 6 weeks 3 days (42–45 days) of gestation;group 2, 6 weeks 4 days to 7 weeks (46–49 days) of gestation.

TABLE 3

Fetal Losses by Heart Rate for Group 3 and 4 Embryos*

Heart Rate(beats/min)

Spontaneous Fetal Losses/Number of Embryos(Fetal Loss Rate, %)

Group 3 Group 4

#85 6/6 (100) 0/0 (0)86–125 15/16 (93.7) 3/3 (100)

126–145 68/398 (17.1) 36/146 (24.7)$146 8/138 (5.5) 16/479 (3.3)

*Group 3, 7 weeks 1 day to 7 weeks 3 days (50–52 days) of gesta-tion; group 4, 7 weeks 4 days to 8 weeks (53–56 days) of gestation.

TABLE 4

Spontaneous Fetal Losses and Mean Mortality Rates for

Embryos in Groups 1–4

GroupGestationalAge (days)

SpontaneousFetal Losses

MeanMortality Rate*

(%)

1 (n = 456) 42–45 143 31.32 (n = 522) 46–49 121 23.23 (n = 558) 50–52 97 17.44 (n = 628) 53–56 55 8.8

*Mean mortality rates were calculated as the number of spontane-ous fetal losses divided by the total number of cases in each group.

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Another interesting result is that a heart rateof 146 beats/min or higher is associated with avery good outcome at the end of the first trimesterfor both groups 3 and 4 as shown by the fetal lossrates of 5.5% and 3.3%, respectively. Additionally,rates above 126 beats/min in group 3 indicated arelatively good fetal outcome (82.9% of the cases).Our results show that the majority of miscar-riages (31.3%) will occur at 42–45 days’ gestation,with the trend in fetal losses progressively de-creasing to 8.8% at 53–56 days’ gestation.

We believe that the results of our study provideuseful information to the obstetrician in the careand counseling of pregnant women, especially inregard to the likelihood of fetal death because ofvery low fetal heart rates. Therefore, intensivesurveillance and follow-up examinations shouldbe done at intervals of 1–2 weeks. Serial sono-graphic scans at these checkups in cases of abnor-mal heart rates could detect fetal death at anearly point, resulting in timely treatment withoutthe complications that may arise after a missedabortion.

It is also known that there is a relationshipbetween embryonic heart rate in early pregnancyand chromosomal disorders.15 Thus, an addi-tional benefit from our study is that cases of anabnormal heart rate combined with findings thatare suspicious for chromosomal abnormalitiescould be provided with a prenatal diagnosis (eg,chorionic villus sampling at 11–12 weeks).

In conclusion, the present study gives the em-bryonic heart rates seen during 6–8 weeks’ gesta-tion that indicate a normal or abnormal fetal out-come at the end of the first trimester. These heartrates are related to the fetal loss rates at the endof the first trimester and could be helpful for tak-ing special care of the embryo in jeopardy. Thisknowledge could also minimize the possible com-plications in cases of fetal loss because such casescould be diagnosed without delay.

ACKNOWLEDGMENT

We thank Dr. K. Adamidis of the Department ofMathematics, Section of Statistics, of the Univer-sity of Ioannina, for his contribution to the statis-tical analyses.

REFERENCES

1. Hertzberg BS, Mahony BS, Bowie JD: First trimes-ter fetal cardiac activity. Sonographic documenta-tion of a progressive early rise in heart rate. J Ul-trasound Med 1988;7:573.

2. Schats R, Jansen CAM, Wladimiroff JM: Embry-onic heart activity: appearance and development inearly human pregnancy. Br J Obstet Gynaecol1990;97:989.

3. van Heeswijk M, Nijhuis JG, Hollanders HMG: Fe-tal heart rate in early pregnancy. Early Hum Dev1990;22:151.

4. Howe RS, Isaacson KJ, Albert JI, et al: Embryonicheart rate in human pregnancy. J Ultrasound Med1991;10:367.

5. Moore KL: The Developing Human. Philadelphia,WB Saunders, 1982, pp. 70–104.

6. Laboda LA, Estroff JA, Benacerraf BR: First tri-mester bradycardia: a sign of impending fetal loss.J Ultrasound Med 1989;8:561.

7. Achiron R, Tadmor O, Mashiach S: Heart rate as apredictor of first trimester spontaneous abortionafter ultrasound proven viability. Obstet Gynecol1991;78:330.

8. Merchiers EH, Dhont M, De Sutter PA, et al: Pre-dictive value of early embryonic cardiac activity forpregnancy outcome. Am J Obstet Gynecol 1991;165:11.

9. Benson CB, Doubilet PM: Slow embryonic heartrate in early first trimester: indicator of poor preg-nancy outcome. Radiology 1994;192:343.

10. May DA, Sturtevant NV: Embryonic heart rate asa predictor of pregnancy outcome. J UltrasoundMed 1991;10:591.

11. Bonilla-Musoles F, Simon C, Sampaio M, et al:Transvaginal ultrasound in the first trimester ofpregnancy. Riv Obstet Gynecol 1989;1:247.

12. Kurjak A, Kupesic-Urek S, Predanic M, et al:Transvaginal color Doppler assessment of utero-placental circulation in normal and abnormal earlypregnancy. Early Hum Dev 1992;29:385.

13. Timor-Tritsch IE, Rottem S: Pathology of the earlyintrauterine pregnancy. In Timor-Tritsch IE, Rot-tem S, eds: Transvaginal Sonography, 2nd edn.New York, Elsevier, 1992, pp. 299–326.

14. Ryan TR Jr, Joiner BL, Ryan BL: Minitab StudentHandbook. Boston, Duxburg Press, 1976.

15. Van Lith JMM, Visser GHA, Mautingh A, et al:Fetal heart rate in early pregnancy and chromo-somal disorders. Br J Obstet Gynaecol 1992;99:741.

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