Response to Pre-Pregnancy Blood Pressure and Offspring Sex in the HUNT Study, Norway

We thank Haug et al. for their interest in our recent findings on maternal blood pressure prior to pregnancy and subsequent sex of the baby at delivery.1,2 As previously reported,1 in 1,411 women participating in a prospective preconception cohort study in China, we noted that maternal systolic blood pressure measured at median 26.3 weeks prior to pregnancy was higher in those who went on to deliver a boy, as compared to those who delivered a girl (both before and after covariate adjustment). Furthermore, on logistic regression analyses, maternal pregravid systolic blood pressure emerged as the only significant predictor of subsequently delivering a male baby.1 As this association certainly requires confirmation in other populations, we read with interest the letter by Haug et al. describing a comparable analysis in 2,427 women from Norway.2 They found no significant difference in blood pressure at median 3 years before pregnancy in those who delivered a boy as compared to those who delivered a girl. The question thus arises of how to reconcile these conflicting findings. In this regard, Haug et al. note 2 differences between the studies that may be relevant to the conflicting findings. The first is that the study populations are quite different in their ethnic composition, with one study performed in China and the other in Norway. We concur that one would not expect fundamental biologic relationships to differ between ethnic groups, although we cannot exclude the possibility of unrecognized differences between populations (particularly in the context of observational study designs). A more important difference may be the timing of the pregravid blood pressure assessment in relation to the pregnancy. Indeed, the studies differed considerably in this regard, in that pregravid blood pressure assessment was much closer to the pregnancy in the Chinese preconception cohort than in the Norwegian study (median 26.3 weeks vs. median 3 years prior to gestation). Although Haug et al. found that blood pressure was not a significant predictor of delivering a boy in the subset of 1,210 women in whom it was measured within 3 years prior to pregnancy,2 it is unclear how near to gestation the blood pressure measurement was performed in this subset and whether differences therein from the median 26.3 weeks in the Chinese cohort may be relevant. It is worth noting that we raised the question of whether there may be underlying physiologic features in a woman that relate to her likelihood of sex-specific fetal loss and hence her likelihood of delivering a boy or girl because of (i) recognition that the population sex ratio at birth can be affected by adverse societal conditions3 and (ii) the recent demonstration of sex-biased fetal loss at different timepoints across human gestation.4 In this context, maternal physiologic features near conception may better reflect the relevant physiology that bears upon subsequent sex-specific fetal loss during gestation. This may be particularly important for a dynamic measure such as blood pressure. While this model remains conjecture at this time, it requires further evaluation in future studies. The authors declared no conflict of interest.

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