Background
Pregnancy with a male compared to a female fetus carries a higher risk of term pre-eclampsia. Given evidence that maternal blood pressure (BP) may be raised in pregnancies with Beckwith-Wiedemann syndrome (fetal overgrowth), a possible contributor to the association between male sex and term pre-eclampsia is faster male growth (~ 130 g heavier than females). We hypothesized that male sex would be associated with higher maternal BP in a general population sample, explained by birth weight sex differences.
Methods
We tested the association between fetal sex and maternal systolic (SBP) and diastolic blood pressure (DBP), measured at ~ 28 weeks gestation, in a meta-analysis of five cohorts of mother–child pairs (n up to 109,842). Maternal BP was analyzed as a continuous and dichotomized (high BP yes/no) outcome. Linear regression models were constructed with and without adjustment for birth weight to assess whether any difference in maternal BP was explained by birth weight differences between male and female babies. Lastly, we constructed a fetal genetic score for birth weight using 186 own-birth-weight-associated single-nucleotide polymorphisms (SNPs) to test whether fetal birth-weight-raising-alleles were associated with maternal BP in pregnancy (n up to 32,232).
Results
Maternal SBP and DBP were higher in pregnancy when carrying a male compared to a female fetus (mean difference 0.35 mmHg [95% CI: 0.15–0.55] and 0.35 mmHg [95% CI: 0.21–0.49], for SBP and DBP, respectively). An independent effect of fetal sex remained when including birth weight but attenuated slightly (0.22 mmHg [95% CI: 0.02–0.42] and 0.31 mmHg [95% CI: 0.17–0.45], for SBP and DBP, respectively). While there was a positive direction of effect for odds of high maternal BP given pregnancy with a male fetus, confidence intervals included the null (OR 1.05 [95% CI: 0.98–1.12]). No evidence for an association was found between a fetal birth weight genetic score and SBP or DBP when conditioned on maternal genotype.
Conclusions
We found strong evidence to support a small effect of male fetal sex on higher maternal BP in pregnancy, without substantial contribution from larger fetal size at birth. Our findings do not indicate a difference in maternal BP that would warrant changes to routine clinical practice.
