Fetal sex differences in human chorionic gonadotropin fluctuate by maternal race, age, weight and by gestational age

Abstract

Circulating levels of the placental glycoprotein hormone human chorionic gonadotropin (hCG) are higher in women carrying female v. male fetuses; yet, the significance of this difference with respect to maternal factors, environmental exposures and neonatal outcomes is unknown. As a first step in evaluating the biologic and clinical significance of sex differences in hCG, we conducted a population-level analysis to assess its stability across subgroups. Subjects were women carrying singleton pregnancies who participated in prenatal and newborn screening programs in CA from 2009 to 2012 (1.1 million serum samples). hCG was measured in the first and second trimesters and fetal sex was determined from the neonatal record. Multivariate linear models were used to estimate hCG means in women carrying female and male fetuses. We report fluctuations in the ratios of female to male hCG by maternal factors and by gestational age. hCG was higher in the case of a female fetus by 11 and 8% in the first and second trimesters, respectively (P<0.0001). There were small (1-5%) fluctuations in the sex difference by maternal race, weight and age. The female-to-male ratio in hCG decreased from 17 to 2% in the first trimester, and then increased from 2 to 19% in the second trimester (P<0.0001). We demonstrate within a well enumerated, diverse US population that the sex difference in hCG overall is stable. Small fluctuations within population subgroups may be relevant to environmental and physiologic effects on the placenta and can be probed further using these types of data.

Keywords: placental hormones; pregnancy; sexual dimorphism.

Fig. 1

Placental-fetal sex differences in circulating hCG in first and second trimester pregnancies. The dots and lines are median and 25th/75th percentile values for each gestational day of prenatal screening. Female values are denoted in gray, and male values are denoted in black. hCG, human chorionic gonadotropin; MoM, multiple of the medians.

Fig. 2

Predicted means (± standard errors) in female and male placental hCG multiples of the median, normalized for ga-MoM, across categories of maternal race, weight and age in the first and second trimesters. All of these plots represent significant fluctuations in the female-to-male ratio across categories (P <0.01). hCG, human chorionic gonadotropin; ga-MoM, gestational age multiple of the median.

Fig. 3

Variability in female/male ratio in hCG by gestational age. Black dots represent the ratio calculated for each gestational day for the median female hCG to the median male hCG. hCG, human chorionic gonadotropin.