Pediatric investigation study finds sex-based fetal responses to maternal hypertension

Hypertensive disorders in pregnancy (HDPs) are a group of complications marked by high blood pressure, including chronic hypertension—where elevated blood pressure is present before pregnancy or before 20 weeks—and gestational hypertension, which arises after 20 weeks. These conditions raise the risk of serious health problems or death for both mothers and babies. HDPs are also linked to premature birth, neonatal intensive care admission, and increased infant mortality.

In addition to these risks, HDPs may interfere with blood flow to the placenta, limiting the delivery of oxygen and nutrients to the fetus. This impaired circulation can restrict both fetal and placental growth, although existing research has produced mixed results. One possible reason for these inconsistencies is that fetal growth responses may differ based on sex. However, relatively few studies have investigated whether male and female fetuses respond differently to HDPs, leaving an important knowledge gap—especially as HDP rates continue to rise worldwide.

Against this backdrop, a team of researchers led by Ms. Alexandra R. Sitarik from the Department of Public Health Sciences at Henry Ford Health, USA, investigated whether the association between HDPs and birthweight and placental weight differs by fetal sex. Their study was published on 11 July 2025 in Pediatric Investigation.

Ms. Sitarik is a Biostatistician at Henry Ford Health whose research focuses on early-life exposures and their impact on long-term health, particularly in asthma, allergy, and obesity. She specializes in microbiome analysis, causal inference, and longitudinal data methods.

“According to the growth strategy hypothesis, male fetuses tend to prioritize growth and are less adaptable to prenatal stressors, while females focus more on placental development, which may help buffer adverse conditions,” Ms. Sitarik explains. “Based on this, we hypothesized that males and females would respond differently to the prenatal conditions of HDPs in terms of birthweight and placental weight.”

To test this hypothesis, the team analyzed data from the Wayne County Health Environment Allergy and Asthma Longitudinal Study (WHEALS), a Detroit-based birth cohort that followed 1,258 mother-child pairs. After applying selection criteria—such as availability of blood pressure measurements and singleton births—the researchers included 853 pregnancies in their primary analysis. A secondary analysis subset of 165 pregnancies, which had available placental pathology data, was also examined to focus on more complicated pregnancies.

HDP status was obtained from clinical records, birthweight from delivery data, and placental weight from pathology reports. Using linear regression while adjusting for confounders and accounting for selection bias, the team investigated whether the associations between HDPs and fetal or placental growth differed by fetal sex.

In the primary analysis group, male babies born to mothers with gestational hypertension had significantly higher birthweight than males whose mothers had normal blood pressure. This pattern was not observed among female babies. However, in the subset of complicated pregnancies, an opposite trend emerged: female babies exposed to gestational hypertension had lower birthweight, while male babies continued to show increased birthweight.

To further assess placental growth, the researchers calculated fetoplacental weight ratios—a comparison of birthweight to placental weight. They found that only female babies showed reduced ratios in the presence of any HDP, suggesting that females may prioritize placental development over fetal growth when exposed to prenatal stress. This sex-specific difference in growth strategy supports the hypothesis that male and female fetuses adopt different survival mechanisms in response to maternal hypertension.

“These findings help explain inconsistent results in previous research on HDPs and fetal growth,” says Ms. Sitarik. “They also show why fetal sex matters when assessing pregnancy risks.”

Hopefully, these insights encourage further investigation into the biological mechanisms behind sex-specific growth patterns, helping obstetricians and gynecologists to better predict complications and provide more personalized care for mothers and babies affected by HDPs.

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Reference
Authors: Alexandra R. Sitarik^1,2, Ganesa Wegienka^1,3, Christine C. Johnson^1,3, Raminder Khangura⁴, Jennifer K. Straughen^1,3, and Andrea E. Cassidy-Bushrow^1,5
DOI: 10.1002/ped4.70015
Affiliations: ¹Department of Public Health Sciences, Henry Ford Health, Detroit, Michigan
²Department of Epidemiology and Biostatistics, College of Human Medicine, Michigan State University, East Lansing, Michigan
³Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, East Lansing, Michigan
⁴Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Henry Ford Health, Detroit, Michigan
⁵Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, Michigan

About Ms. Alexandra R. Sitarik
Ms. Alexandra R. Sitarik is a Biostatistician at Henry Ford Health, Michigan, United States, where she has worked since 2013. She holds a master’s in biostatistics from the University of Michigan and a bachelor’s in mathematics from Wittenberg University. She works in the domain of asthma, allergy, and obesity. She particularly focuses on the Developmental Origins of Health and Disease (DOHaD) hypothesis to explore how exposures in early life can influence health outcomes later in life. She has co-authored over 40 research papers and specializes in microbiome analysis, latent class analysis, longitudinal data analysis, causal inference, and mediation analysis.