Year: 2025
Type: article
Abstract: 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.
Source: BMC Medicine
Institutions: The University of Queensland, University of Exeter, Institute for Molecular Bioscience, Sahlgrenska University Hospital, Region Västra Götaland, Haukeland University Hospital, University of Bergen, Norwegian Institute of Public Health, University of Gothenburg, Northwestern University, University of Bristol, MRC Integrative Epidemiology Unit
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,190
Funders: Stiftelsen Kristian Gerhard Jebsen, Wellcome Trust, Trond Mohn stiftelse, National Institute for Health and Care Research, Department of Health and Social Care, University of Exeter, University of Bristol, Svenska Forskningsrådet Formas, Novo Nordisk, Vetenskapsrådet, Universitetet i Bergen, Norges Forskningsråd, Sahlgrenska Universitetssjukhuset, Novo Nordisk Fonden, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, Sahlgrenska Akademin, NIHR Exeter Clinical Research Facility, Norwegian Institute of Public Health, National Center for Research Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Developing and Applying Mendelian Randomization Methods to Facilitate Drug Discovery and Solve Intractable Problems in Medical Research, General Clinical Research Center, G1542875509, G1684393010, G1793884970, G205230472, Integrating genomic studies of gestational duration and birth weight to understand maternal and fetal causes of adverse pregnancy outcomes and links with later diseases, G2694757618, G3507283293, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi- generation, longitudinal resource focusing on life course health and well- being., G3723918320, Using genetics to understand how the maternal intrauterine environment influences fetal growth., G3987754321, G4521018072, G4670997888, Using genetics to identify optimal times to intervene on early life growth and reduce future risk of cardio-metabolic disease, G4895042318, G4931922774, G4985203053, G5313676757, G5730485479, G6667305214, HAPO: DATA COORDINATING CENTER, Using genetics to understand how the maternal intrauterine environment influences fetal growth., G7095874527, G7702317272, G7762657818, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi-generation, longitudinal resource focusing on life course health and well-being., GENERAL CLINICAL RESEARCH CENTER, Hyperglycemia and Adverse Pregnancy Outcome (HAPO), Harvesting genomic data to advance the understanding of pregnancy duration and preterm birth
OpenAlex ID: W4415917603