Sex Specific Differences in Fetal Middle Cerebral Artery and Umbilical Venous Doppler

Abstract

BackgroundThe incidence of several adverse pregnancy outcomes including fetal growth restriction are higher in pregnancies where the fetus is male, leading to suggestions that placental insufficiency is more common in these fetuses. Placental insufficiency associated with fetal growth restriction may be identified by multi-vessel Doppler assessment, but little evidence exists regarding sex specific differences in these Doppler indices or placental function. This study aims to investigate sex specific differences in fetal and placental perfusion and to correlate these changes with intra-partum outcome.Methods and FindingsThis is a prospective cohort study. We measured Doppler indices of 388 term pregnancies immediately prior to the onset of active labour (≤3 cm dilatation). Fetal sex was unknown at the time of the ultrasound assessment. Information from the ultrasound scan was not made available to clinical staff. Case notes and electronic records were reviewed following delivery. We report significantly lower Middle Cerebral artery pulsatility index (1.34 vs. 1.43, p = 0.004), Middle Cerebral artery peak velocity (53.47 cm/s vs. 58.10 cm/s, p = <0.001), and Umbilical venous flow/kg (56 ml/min/kg vs. 61 ml/min/kg, p = 0.02) in male fetuses. These differences however, were not associated with significant differences in intra-partum outcome.ConclusionSex specific differences in feto-placental perfusion indices exist. Whilst the physiological relevance of these is currently unknown, the identification of these differences adds to our knowledge of the physiology of male and female fetuses in utero. A number of disease processes have now been shown to have an association with changes in fetal haemodynamics in-utero, as well as having a sex bias, making further investigation of the sex specific differences present during fetal life important. Whilst the clinical application of these findings is currently limited, the results from this study do provide further insight into the gender specific circulatory differences present in the fetal period.

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“…That analysis also establishes the directionality of the effect such that earlier fetal heart rate influences maternal heart rate. Variation in maternal physiological indicators, potentially as the result of fetal sex, may be less generally expected but aligned with the growing literature pointing to a differential role of fetal sex on the intrauterine milieu (Clifton, 2010; Ghidini & Salafia, 2005; Prior, Wild, Mullins, Bennett, & Kumar, 2013). Indeed, in the second century A.D., Soranus promoted the notion that women carrying male fetuses have better color as the result of the stimulation provided by the excessive movement of male fetuses and that pallor of women carrying female fetuses was the result of lack of such stimulation (Temkin 1991).…”

“…These include the use of Doppler technology to measure blood flow in specific areas of the brain, including the middle cerebral artery, in response to maternal vocalizations (Emory, 2010; Feng, Raynor, Fiano, Graham, & Emory, 1997). Doppler flow studies have revealed a previously unknown sex difference in perfusion of the developing fetal brain (Prior et al, 2013). New tools available to map the connectivity of the developing human brain from the molecular to the functional were heretofore unimaginable (Kang et al, 2011; Thomason et al, 2013).…”

The Disappearing Brain-Sparing Effect in Early-Onset Fetal Growth Restriction Fetuses Revisited

“…Second, MCA Doppler evaluation itself is an unreliable method under circumstances like fetal head movement, engagement and compression of the fetal head during scan. Even significant sex-specific differences were reported in the MCA PI and MCA PSV [34] and gender-specific normal ranges should be arranged. Third, MCA measurement is an indirect estimation of blood flow in fetal cranium.…”

Effects of Plasmodium falciparum infection on umbilical artery resistance and intrafetal blood flow distribution: a Doppler ultrasound study from Papua New Guinea

“…Previous research indicates that ethnic differences in fetoplacental flow may be limited [42], but sex-specific differences in umbilical and cerebral blood flow may exist [43]. …”