Sex differences in umbilical artery Doppler indices: a longitudinal study

Abstract

BackgroundSexual dimorphism in placental size and function has been described. Whether this influences the clinically important umbilical artery (UA) waveform remains controversial, although a few cross-sectional studies have shown sex differences in UA pulsatility index (PI). Therefore, we tested whether fetal sex influences the UA Doppler indices during the entire second half of pregnancy and aimed to establish sex-specific reference ranges for UA Doppler indices if needed.MethodsOur main objective was to investigate gestational age-associated changes in UA Doppler indices during the second half of pregnancy and compare the values between male and female fetuses. This was a prospective longitudinal study in women with singleton low-risk pregnancies during 19–40 weeks of gestation. UA Doppler indices were serially obtained at a 4-weekly interval from a free loop of the umbilical cord using color-directed pulsed-wave Doppler ultrasonography. Sex-specific reference intervals were calculated for the fetal heart rate (HR), UA PI, resistance index (RI), and systolic/diastolic ratio (S/D) using multilevel modeling.ResultsComplete data from 294 pregnancies (a total of 1261 observations from 152 male and 142 female fetuses) were available for statistical analysis, and sex-specific reference ranges for the UA Doppler indices and fetal HR were established for the last half of pregnancy. UA Doppler indices were significantly associated with gestational age (P < 0.0001) and fetal HR (P < 0.0001). Female fetuses had 2–8% higher values for UA Doppler indices than male fetuses during gestational weeks 20+0–36+6 (P < 0.05), but not later. Female fetuses had higher HR from gestational week 26+0 until term (P < 0.05).ConclusionsWe have determined gestational age-dependent sex differences in UA Doppler indices and fetal HR during the second half of pregnancy, and correspondingly established new sex-specific reference ranges intended for refining diagnostics and monitoring individual pregnancies.

Sex differences in fetal heart rate and variability assessed by antenatal computerized cardiotocography

“…In an analysis on 740 maternal‐fetal pairs, they reported a sex‐related difference of 2 bpm in the baseline FHR at term. A similar trend with no significant difference before 26 weeks and a difference of 1‐2 bpm at 26‐40 weeks of gestation was reported by Widnes et al in a longitudinal study of low‐risk pregnancies using umbilical arterty Doppler waveforms to calculate FHR. In addition to methodological differences (longitudinal vs cross‐sectional design, use of cCTG vs umbilical artery Doppler to record FHR), the smaller sex‐related absolute difference in the baseline FHR in our study could be explained by the inclusion of high‐risk pregnancies with suspected fetal compromise, in contrast to normal pregnancies.…”

“…Some studies reported no effect on the heart rate in early or late pregnancy. In a longitudinal study, Widnes et al reported that female fetuses had a significantly higher heart rate after 26 weeks of pregnancy, although the absolute difference was small. Visual analysis of antenatal fetal heart rate recording has been shown to have high inter‐ and intraobserver variability .…”

“…Fetal sex‐dependent differences are found in many aspects of pregnancy . Previous publications have shown sex‐related differences in fetal cardiac function . The effect of fetal sex on the heart rate is less clear.…”

Sex‐specific reference ranges of cerebroplacental and umbilicocerebral ratios: longitudinal study

“…22 While several reference ranges for CPR, including one longitudinal study of adequate sample size with terms for calculation of conditional ranges, have been published, 27 longitudinal reference intervals for the UCR are lacking. Furthermore, sex-differences are present in placental 28,29 and cerebral 30 circulations, but these have not been taken into account by any studies.…”

Third Trimester Umbilical Artery Doppler in Low-Risk Pregnancies and its Correlation to Estimated Fetal Weight and Birthweight

“…The role of UA-PI as a predictor of LGA babies in low-risk pregnancies was investigated in 2012 by Pilalis A et al, who demonstrated that third trimester UA-PI does not significantly improve the prediction of LGA babies in comparison to the EFW [20]. Interestingly, Widnes C et al showed that there is a sex-related difference in UA indices, where the mean UA-PI is higher in female fetuses than in male ones during pregnancy before 36 weeks of gestation [21]. This difference could be explained by the different mean estimated fetal weight between males and females [22].…”