Arch Gynecol Obstet (2006) 274:257–260 DOI 10.1007/s00404-006-0176-5

O R I G I N A L A RT I C L E

First trimester embryonic/fetal heart rate in normal pregnant women Tharangrut Hanprasertpong Æ Vorapong Phupong

Received: 20 November 2005 / Accepted: 14 April 2006 / Published online: 20 May 2006 Ó Springer-Verlag 2006

Abstract Objective: To establish reference ranges for first trimester embryonic/fetal heart rate in normal pregnant women. Materials and methods: This was a cross-sectional study. We performed ultrasonogram in 319 normal pregnant women, gestation age between 6+0 and 14+6 weeks and measured embryonic/fetal heart rates using M-mode. The embryonic/fetal heart rates were analyzed according to gestational ages (GA). Results: Data of 319 pregnancies were analyzed and the outcome revealed the mean of fetal heart rate according to gestational age. The mean embryonic heart rates during the 6th–7th week of gestation are lower when compared with the other gestational ages. At the 8th week of gestation, the embryonic heart rate is maximum. Then the embryonic/fetal heart rate gradually decreased to 161 beats/min at the 14th week of gestation. The regression equation for embryonic/fetal heart rate (beat/min) [y] according to GA (day) [x] was y = –53.124 + 6.1333x + (–0.0407)x 2 (r2 = 0.525; P < 0.001). Conclusion: Embryonic/fetal heart rates during the 6+0 and 14+6 week of gestation are related to GA. Our reference ranges may be useful for further studies such as for prediction of adverse pregnancy outcome in threatened abortion.

Introduction Heart is a vital organ of a human. Cardiovascular development in a human embryo occurs between 3 and 6 weeks after ovulation. Cardiac function is the first sign of independent cardiac activity that can be explored with non-invasive techniques such as Doppler ultrasound [7]. Previous studies on the embryonic heart rate normally measured about 100–200 beats per minute (bpm) when it was first visible on sonography at approximately 6 weeks’ gestation [4]. The rate increases progressively over the subsequent 2–3 weeks [4, 12]. Recent studies suggested that when slow embryonic/fetal heart rate is detected, the likelihood of subsequent first-trimester demise remains elevated [5, 11]. In addition, there was a report on the association between a slow embryonic/fetal heart rate and adverse pregnancy outcome in first trimester threatened abortion pregnancies [3]. However, there is no report on baseline fetal/embryonic heart rate of Thai population classified in each week of gestation age using M-mode measurement. The purpose of this study was to establish reference ranges for first trimester embryo/fetal heart rate in Thai pregnant women using M-mode measurement.

Keywords Embryo Æ Fetus Æ Heart rate Æ First trimester Æ Pregnancy Materials and methods

T. Hanprasertpong Æ V. Phupong (&) Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Rama IV Road, Pathumwan, Bangkok 10330, Thailand e-mail: [email protected]

The study was conducted as a prospective descriptive cross-sectional study including 319 pregnancies between 6+0 and 14+6 weeks according to their last menstrual period (LMP) who underwent ultrasound examination at the Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology,

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Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Informed consent was obtained from each participant and the Ethics Committee of the institution approved this study. Inclusion criterions were (1) singleton gestation; (2) accurate dating based on LMP and calculated gestational age (GA) by crown-rump length (CRL) measurement was in agreement; and (3) term delivery with normal birth weight fetus. Exclusion criterions were (1) vaginal bleeding at the time of ultrasound examination; (2) pregnancy complications (e.g. diabetes, hypertensive disorders); (3) miscarriage or fetal demise; (4) fetus with structural or chromosomal abnormalities; (5) fetus with growth restriction or macrosomia; and (6) lost to follow-up. All measurements were performed with an Aloka model Prosound 5000 (Aloka Co., Ltd., Tokyo, Japan) ultrasound machine with a 7.5 MHz vaginal or a 3.75 MHz abdominal transducer. CRL was measured from the cranial to caudal end of the body with the fetus in neutral position. The measurements of embryonic/fetal heart rates were measured by Mmode, at least ten regular cardiac cycles. The calculation of the heart rate was made by measuring the time interval of two cardiac cycles (Fig. 1). The average values obtained from two measurements were utilized for statistical analysis. Each woman was included only once and measurements were made by the first author. All of the newborns were proved to be normal at birth. Statistical analysis was performed with SPSS software package version 11.0 (SPSS Inc., Chicago, IL, USA). Mean and standard deviation (SD) for the embryonic/fetal heart rates were computed at weekly intervals for GA. Regression analysis was performed and the best-fit regression curve was established. Pvalue < 0.05 was considered statistically significant.

Arch Gynecol Obstet (2006) 274:257–260

Results During the study period, 335 pregnancies were recruited. Records of 16 patients were excluded on the following reasons: abnormal vaginal bleeding (n = 10), intrauterine fetal/embryonic death (n = 3), multiple gestations (n = 1) and loss to follow-up (n = 2). Thus, a total of 319 pregnancies were included in analysis. The mean ± SD of patients’ age was 29.3 ± 5.6 years, and the body mass index was 21.8 ± 3.5 kg/m2. Embryonic/ fetal heart rates according to GA are presented in Table 1. The mean embryonic heart rates at 6+0–6+6 week of gestation are 125.8 ± 12.5 bpm. After the 6th week of gestation, the embryonic heart rates gradually increase to 159.6 + /–17.4 bpm at 7+0–7+6 week of gestation. The maximal embryonic heart rates presented at 8+0–8+6 week of gestation were, 179.3 ± 9.5 bpm. Then the fetal heart rates gradually decrease to 160.0 ± 12.3 bpm at 14+0–14+6 week of gestation (Table 1, Fig. 2). The best fit regression equation for embryonic/fetal heart rate (beats/min) [y] according to GA (days) [x] was y = –53.124 + 6.1333x + (–0.0407) x 2 (r2 = 0.525; P < 0.001)

Discussion This study demonstrates that embryonic/fetal heart rates can be easily measured by M-mode ultrasonogram in the first trimester. M-mode is not too difficult to use in measuring the embryonic/fetal heart rate in the first trimester. The mean embryonic heart rates during the 6th–7th week of gestations are lower when compared with the other gestational ages. At the 8th week of gestation, the embryonic heart rates are maximal. Then the embryonic/fetal heart rates gradually decrease to161 bpm at the 14th week of gestation.

Table 1 Embryonic/fetal heart rate according to gestational age Week of gestation (weeks+days) N (319) Heart rate (bpm) Mean (bpm) SD (bpm)

Fig. 1 Ultrasonographic measurements of embryonic/fetal heart rate using M-mode

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6+0–6+6 7+0–7+6 8+0–8+6 9+0–9+6 10+0–10+6 11+0–11+6 12+0–12+6 13+0–13+6 14+0–14+6 SD standard deviation

32 40 32 38 42 33 36 34 32

125.8 159.6 179.3 177.6 174.9 168.8 164.0 161.9 160.0

12.5 17.4 9.5 7.9 7.7 7.7 8.4 9.7 12.3

Arch Gynecol Obstet (2006) 274:257–260

Fig. 2 Embryonic/fetal heart rates plotted on the scatter graph according to gestation age

The explanation about embryonic/fetal heart rate that gradually increases from 6th to 8th week of gestation in our study is a physiologic phenomenon related to the development of the embryonic heart and its conductive system [9]. The normal slower heart rate in early pregnancy may be due to the immaturity of the sinoatrial node or the slower intrinsic atrial pacemaker activity [10]. The reason behind the gradual decrease of fetal heart rate after 9 weeks is that it may be caused by the difference in balance of the sympathetic and parasympathetic components of the autonomic nervous outflow.Walker et al studied the sympathetic and parasympathetic control of heart rate in unanesthetic fetal and newborn lambs. Fetal lambs showed a progressive increase in parasympathetic restraint of heart rate and sympathetic stimulation of fetal heart rate declined toward term [13]. Our results were similar to those of earlier studies which showed lower embryonic heart rates during early gestation [4–6, 12]. This fetal heart rate reference could be used to determine the prognosis of pregnancies. Most studies on the first trimester embryonic/fetal heart rate showed that the likelihood ratio of subsequent first-trimester demise remain elevated if slow fetal heart was detected [3, 5, 11]. In contrast, the outcome of pregnancies with rapid embryonic heart rates in the early first trimester have a good prognosis, with a high likelihood of normal outcome [6]. From this advantage, we suggest to measure the embryonic and fetal heart rate in all pregnancies which are ultrasonically scanned in the first trimester. If the embryonic/fetal heart rate is below this reference, the

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patient should be closely followed-up. There will be a demise of pregnancy following a slow embryonic heart rate in early pregnancy and the demise often occurs within one week after the slow heart rate is first detected and in most cases always occur by the end of the first trimester [5]. When a slow heart rate is seen in the first trimester, a follow-up ultrasonogram should be performed approximately for one week. If the embryonic/fetal heart beat is normal or rapid heart rate, the patient should be reassured about good outcome of her baby. On the contrary, if the repeated embryonic/fetal heart rate is still slow, this may be due to an abnormal development of the heart or an arrest in the development of the conductive system which predicts subsequent miscarriage [9, 10]. Compared to an earlier study by Tannirandorn et al. on embryonic/fetal heart rate using duplex color Doppler ultrasonography [12], Pulsed Doppler examination creates higher intensities than conventional B mode imaging, and Doppler may have the capacity of thermally disturbing the embryological development [1, 2]. Although no haemopoietic changes have been found after frequent ultrasound exposure of embryonic structures during organogenesis in animal models, it is difficult to compare results obtained in vitro or in animal model setting to in vivo conditions as a result of the difference in cooling effects [8]. At this moment, there are no experimental data on the in vivo effects on the fetus of color and pulsed Doppler ultrasound when performed in the first trimester. We are concerned about higher energy exposure during the use of Doppler, thus we use the M-mode for measurement of the embryonic/fetal heart rate. There are similar in pattern of embryonic/fetal heart rates measured by both methods.We suggest using M-mode to avoid the effect to the embryo/fetus. If the embryonic/fetal heart rate cannot be measured by this method, Doppler should be substituted. Another difference from Tannirandorn et al. is the more number of cases in GA 6, 7 and 14 weeks and similar number of cases in each week of gestation (about 30 cases) in our study. In conclusion, our reference ranges for embryonic/ fetal heart rate serve as a normative data of normal pregnant women. It may be useful for further prospective studies at least in two viewpoints: firstly, for the prediction of adverse pregnancy outcomes such as miscarriage, pre-eclampsia or fetal growth disorders and secondly, as an ultrasound marker for fetal aneuploidy screening. Acknowledgment This work was supported by the Grant number 196/2548, Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University.

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