Fetal sex and maternal pregnancy outcomes: a systematic review and meta-analysis

Abstract

Background: Since the placenta also has a sex, fetal sex-specific differences in the occurrence of placenta-mediated complications could exist.

Objective: To determine the association of fetal sex with multiple maternal pregnancy complications.

Search strategy: Six 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 criteria: Observational studies that assessed fetal sex and the presence of maternal pregnancy complications within singleton pregnancies.

Data collection and analyses: Data were extracted by 2 independent reviewers using a predesigned data collection form.

Main results: From 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.

Conclusion: This 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.

Funding: None.

Keywords: Fetal sex; Pregnancy complications.

Fig. 1

Search strategy for the studies included in the current systematic review (search until April 5, 2019). PRISMA flow diagram of selection process of eligible studies

Fig. 2

Meta-analyses on the association between fetal sex and maternal pregnancy complications. The boxes are proportional to the weight of each study in the analysis, and the lines represent their 95% confidence intervals (CIs). Size of data markers are proportional to the inverse of the variance of the effect estimate. The open diamond represent the pooled odds ratio, and its width represents its 95% CI. The summary estimates presented were calculated using random-effects models (D + L) and fixed effects (I + V). Assessment of heterogeneity: gestational hypertension (I² = 74,8%, p < 0.001) (a); total pre-eclampsia (I² = 81,8%, p < 0.001) (b); preterm pre-eclampsia (I² = 93,5%, p < 0.001) (c); term pre-eclampsia (I² = 7,1%, p = 0.37) (d); postterm pre-eclampsia (I² = 84.4%, p = 0.011) (e); eclampsia (I² = 47.0%, p = 0.08) (f); gestational diabetes, (I² = 36,3%, p = 0.03) (g); placental abruption (I² = 92.9%, p < 0.001) (h)