Sex differences in growth and mortality in pregnancy-associated hypertension

by Jess C. Hercus, Katherine X. Metcalfe, Julian K. Christians

It is hypothesized that male fetuses prioritize growth, resulting in increased mortality, whereas females reduce growth in the presence of adversity. Preeclampsia reflects a chronic condition, in which fetuses have the opportunity to adjust growth. If females reduce their growth in response to preeclampsia, but males attempt to maintain growth at the cost of survival, we predict that differences in birthweight between preeclamptic and non-preeclamptic pregnancies will be greater among females, whereas differences in mortality will be greater among males.

We analysed data from the Centers for Disease Control and Prevention. We compared pregnancies with pregnancy-associated hypertension (PAH) and controls.

The difference in birthweight between pregnancies affected by PAH and controls varied by fetal sex and gestational age. Among pregnancies of White individuals, at 34–35 weeks, the difference between PAH and controls was higher among females, as predicted. However, this pattern was reversed earlier in pregnancy and around term. Such variation was not significant in Black pregnancies. In both Black and White pregnancies, early in gestation, males had lower odds of death in PAH pregnancies, but higher odds of death in control pregnancies, counter to our prediction. Later, males had higher odds of death in PAH and controls, although the increased odds of death in males was not higher in PAH pregnancies than in controls. Overall, the difference in birthweight between surviving and non-surviving infants was greater in males than in females, opposite to our prediction.

The impact of PAH on birthweight and survival varies widely throughout gestation. Differences in birthweight and survival between male and female PAH and controls are generally not consistent with the hypothesis that males prioritize fetal growth more than females, and that this is a cause of increased mortality in males.