Pre-pregnancy Blood Pressure and Offspring Sex in the HUNT Study, Norway

To the Editor: We read with great interest the recent paper by Retnakaran et al.1 describing an association between higher maternal pre-pregnancy systolic blood pressure and increased probability of delivering a boy. As the authors suggested this finding needs replication, which we aimed to do using the Norwegian HUNT Study. In the HUNT Study, the entire adult population of Nord-Trøndelag county, Norway, has been invited to health surveys since the 1980s.2 By linking HUNT Study data with the Medical Birth Registry of Norway,3 which has prospectively recorded all births in Norway since 1967, we identified 2,427 women with blood pressure recorded in the HUNT2 (1995–97) or HUNT3 (2006–08) surveys prior to a singleton first pregnancy. Blood pressure was measured at rest by trained staff 3 times at 1-minute intervals using an automatic oscillometric method (Dinamap, Critikon, FL). We used the mean of the second and third measurements, or the second measurement for women (n = 163) who did not have a third measurement. Associations between pre-first pregnancy systolic blood pressure and sex of the offspring of first pregnancy were analyzed with logistic and linear regression models using Stata. In a very similar fashion to Retnakaran et al., we adjusted for the highest obtained education level, age, current smoking, body mass index, waist circumference, nonfasting serum glucose, high-density and non-high-density lipoprotein cholesterol, and triglycerides. We also adjusted for HUNT survey occasion (HUNT2 or HUNT3). Overall, mean (SD) pre-pregnancy blood pressure among the 2,427 women was 121 (11) mm Hg systolic and 70 (9) mm Hg diastolic. There were 1,267 (52%) boys and 1,160 (48%) girls (sex ratio 1.09). Median time from blood pressure recording to pregnancy was 3 years. Unadjusted pre-pregnancy systolic and diastolic blood pressure was similar before pregnancies with male (121/70 mm Hg) and female (121/70 mm Hg) offspring. The adjusted differences in pre-pregnancy systolic and diastolic blood pressure between mothers of male and female offspring were 0.2 mm Hg (95% confidence interval, −0.6 to 1.1) and −0.1 mm Hg (95% confidence interval, −0.8 to 0.5), respectively. We found no meaningful association of systolic blood pressure with the probability of male offspring. Overall, each one mm Hg higher systolic blood pressure was associated with an adjusted odds ratio of male offspring of 1.002 (95% confidence interval, 0.994–1.010). The predicted probabilities of having a boy by quintiles of systolic blood pressure are shown in Figure 1. As time from blood pressure measurement to pregnancy was shorter (median: 26.3 weeks) in the study by Retnakaran et al., we repeated the analysis in a subgroup of females with blood pressure measurements taken less than 3 years before pregnancy (n = 1210); the odds ratio of having a boy per one mm Hg higher systolic blood pressure was 1.005 (95% confidence interval, 0.994–1.015). Findings were similar for diastolic blood pressure and sex of offspring. The blood pressure measurement protocol did not substantially differ between our study and the study by Retnakaran et al. Retnakaran et al. studied a Chinese population whilst our study population was predominantly Caucasian, included both planned and unintended pregnancies, and was restricted to first births. However, we do not expect that any causal effect of maternal blood pressure on offspring sex would differ by these characteristics. In summary, these results from a Norwegian population-based cohort of greater size than that of Retnakaran et al., do not support the suggestion that maternal pre-pregnancy blood pressure influences the probability of delivering a boy.