Abstract
BackgroundSince the placenta also has a sex, fetal sex–specific differences in the occurrence of placenta-mediated complications could exist.ObjectiveTo determine the association of fetal sex with multiple maternal pregnancy complications.Search strategySix electronic databases Ovid MEDLINE, EMBASE, Cochrane Central, Web-of-Science, PubMed, and Google Scholar were systematically searched to identify eligible studies. Reference lists of the included studies and contact with experts were also used for identification of studies.Selection criteriaObservational studies that assessed fetal sex and the presence of maternal pregnancy complications within singleton pregnancies.Data collection and analysesData were extracted by 2 independent reviewers using a predesigned data collection form.Main resultsFrom 6522 original references, 74 studies were selected, including over 12,5 million women. Male fetal sex was associated with term pre-eclampsia (pooled OR 1.07 [95%CI 1.06 to 1.09]) and gestational diabetes (pooled OR 1.04 [1.02 to 1.07]). All other pregnancy complications (i.e., gestational hypertension, total pre-eclampsia, eclampsia, placental abruption, and post-partum hemorrhage) tended to be associated with male fetal sex, except for preterm pre-eclampsia, which was more associated with female fetal sex. Overall quality of the included studies was good. Between-study heterogeneity was high due to differences in study population and outcome definition.ConclusionThis meta-analysis suggests that the occurrence of pregnancy complications differ according to fetal sex with a higher cardiovascular and metabolic load for the mother in the presence of a male fetus.FundingNone.
Highlights
Impaired placentation leading to abnormal placental perfusion and placental dysfunction is believed to be the foundation of several pregnancy complications such as pre-eclampsia [3, 4]
Statistical Analysis We evaluated the differences between pregnancies with a male and female fetus on maternal pregnancy complications (including gestational hypertension, preeclampsia, eclampsia, gestational diabetes, placental abruption, postpartum hemorrhage, and miscarriage)
Four of eight analyses showed high between-study heterogeneity, with an I2 estimate exceeding 75% (p < 0.05 for the Cochrane X2 statistic) (Fig. 2). This level of heterogeneity could be explained by differences between studies attributable to heterogeneous study populations, methods, and outcome definition. This is the first systematic review and meta-analyses investigating the association between fetal sex and multiple major pregnancy outcomes showing that sexual dimorphisms in maternal pregnancy complications exist
Summary
The placenta constitutes the active interface between the maternal and fetal blood circulation. It regulates important physiological changes during pregnancy and accounts for fetal development and nutrient supply. Maternal physiological changes include cardiovascular changes in vascular tone, cardiac output, and plasma volume, providing a better placental perfusion [1, 2]. Clear fetal sex-specific differences are noticeable in the occurrence of different pregnancy complications such as pre-eclampsia and gestational diabetes and even in maternal vascular adaptation to pregnancy [5]. Despite growing speculations that placentation and maternal adaptation to pregnancy are influenced by fetal sex, in most studies that assess these possible pathophysiological mechanisms, fetal sex is not being taken into account [6–9]. Since the placenta has a sex, fetal sex–specific differences in the occurrence of placentamediated complications could exist
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