Sexual Dimorphism in Adverse Pregnancy Outcomes - A Retrospective Australian Population Study 1981-2011.

Petra E Verburg,Claire Trelford Roberts,Jan Jaap H M Erwich,Gus A Dekker,Graeme Tucker,Wendy Scheil,Cornelis B Lambalk

doi:10.1371/journal.pone.0158807

Abstract

ObjectivesSexual inequality starts in utero. The contribution of biological sex to the developmental origins of health and disease is increasingly recognized. The aim of this study was to assess and interpret sexual dimorphisms for three major adverse pregnancy outcomes which affect the health of the neonate, child and potentially adult.MethodsRetrospective population-based study of 574,358 South Australian singleton live births during 1981–2011. The incidence of three major adverse pregnancy outcomes [preterm birth (PTB), pregnancy induced hypertensive disorders (PIHD) and gestational diabetes mellitus (GDM)] in relation to fetal sex was compared according to traditional and fetus-at-risk (FAR) approaches.ResultsThe traditional approach showed male predominance for PTB [20–24 weeks: Relative Risk (RR) M/F 1.351, 95%-CI 1.274–1.445], spontaneous PTB [25–29 weeks: RR M/F 1.118, 95%-CI 1.044–1.197%], GDM [RR M/F 1.042, 95%-CI 1.011–1.074], overall PIHD [RR M/F 1.053, 95%-CI 1.034–1.072] and PIHD with term birth [RR M/F 1.074, 95%-CI 1.044–1.105]. The FAR approach showed that males were at increased risk for PTB [20–24 weeks: RR M/F 1.273, 95%-CI 1.087–1.490], for spontaneous PTB [25–29 weeks: RR M/F 1.269, 95%-CI 1.143–1.410] and PIHD with term birth [RR M/F 1.074, 95%-CI 1.044–1.105%]. The traditional approach demonstrated female predominance for iatrogenic PTB [25–29 weeks: RR M/F 0.857, 95%-CI 0.780–0.941] and PIHD associated with PTB [25–29 weeks: RR M/F 0.686, 95%-CI 0.581–0.811]. The FAR approach showed that females were at increased risk for PIHD with PTB [25–29 weeks: RR M/F 0.779, 95%-CI 0.648–0.937].ConclusionsThis study confirms the presence of sexual dimorphisms and presents a coherent framework based on two analytical approaches to assess and interpret the sexual dimorphisms for major adverse pregnancy outcomes. The mechanisms by which these occur remain elusive, but sex differences in placental gene expression and function are likely to play a key role. Further research on sex differences in placental function and maternal adaptation to pregnancy is required to delineate the causal molecular mechanisms in sex-specific pregnancy outcome. Identifying these mechanisms may inform fetal sex specific tailored antenatal and neonatal care.

Highlights

The foundation for the health of children and both women and men is established during intrauterine life when the fetus is said to be programmed by the intrauterine environment
The FAR approach showed that males were at increased risk for preterm birth (PTB) [20–24 weeks: Relative Risk (RR) M/F 1.273, 95% Confidence Intervals (95%-CI) 1.087–1.490], for spontaneous PTB [25–29 weeks: risks for males versus females (RR M/F) 1.269, 95%-CI 1.143–1.410] and pregnancy induced hypertensive disorders (PIHD) with term birth [RR M/F 1.074, 95%-CI 1.044– 1.105%]
The traditional approach demonstrated female predominance for iatrogenic PTB [25–29 weeks: RR M/F 0.857, 95%-CI 0.780–0.941] and PIHD associated with PTB [25–29 weeks: RR M/F 0.686, 95%-CI 0.581–0.811]

Summary

Introduction

The foundation for the health of children and both women and men is established during intrauterine life when the fetus is said to be programmed by the intrauterine environment. The “developmental origins of health and disease” hypothesis indicates long-term health consequences for individuals with a low birth weight[1]. Adverse pregnancy outcomes, such as preterm birth (PTB), pregnancy induced hypertensive disorders (PIHD) and gestational diabetes mellitus (GDM) do have an immense influence on the mother, and on the baby. Pregnancy complications are associated with impaired development of the fetus, neonate and infant. Both women who had preeclampsia and the babies born to them are at increased risk for later adult onset diseases such as hypertension, cardiovascular disease and type 2 diabetes[2]. Offspring from mothers with GDM are at increased risk of developing obesity, impaired glucose tolerance, Type 2 Diabetes and cardio-vascular disease in adulthood[4]

Objectives

Methods

Results

Discussion

Conclusion