The human placenta demonstrates sex-related differences at both structural and functional levels. However, the total mortality from conception to birth is greater among female fetuses. This has been referred to as “the male disadvantage” and the female neonatal survival advantage is well recognized. Male sex is an independent risk factor for unfavorable perinatal outcomes including fetal distress during labor, premature birth, adverse neonatal outcome, and early neonatal death. Previous studies have shown sex-specific differences in fetal development regarding growth and adaption to intrauterine environment. The importance of conducting longitudinal studies and analyzing data accounting for biological differences related to sex has been highlighted a decade ago. We 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. Female fetuses had higher HR from gestational week 26 +0 until term ( P < 0.05). 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. UA Doppler indices were significantly associated with gestational age ( P < 0.0001) and fetal HR ( P < 0.0001). ResultsĬomplete 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. 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. 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. This was a prospective longitudinal study in women with singleton low-risk pregnancies during 19–40 weeks of gestation. Our 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. 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. 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). Sexual dimorphism in placental size and function has been described.
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