Birthweight and PCOS: systematic review and meta-analysis

STUDY QUESTION: Are intrauterine conditions, reflected in birthweight, associated with the development of polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Our study indicates that a low birthweight as a summary measure of intrauterine environment may be associated with PCOS when diagnosed according to the Rotterdam criteria. WHAT IS ALREADY KNOWN: The etiology of PCOS is still largely unknown. Besides subfertility, women diagnosed with PCOS have an increased risk of chronic health issues. PCOS has been linked to adverse prenatal conditions, including a low birthweight. STUDY DESIGN, SIZE, DURATION: A systematic search of the literature and meta-analysis of pooled data was undertaken, according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) and meta-analysis of observational studies in epidemiology (MOOSE) guidelines. PARTICIPANTS/MATERIALS, SETTING, METHOD: The following online databases were systematically searched: PubMed, EMBASE, CINAHL (via EBSCO) and Cochrane library up to 10 June 2017, with no language or date restrictions. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1484 studies were identified of which 16 met the inclusion criteria and 14 provided data for meta-analysis. The exposure variable birthweight was either analyzed as a categorical variable using the birthweight categories <2.5, 2.5–4 and >4 kg, or as a continuous variable. We composed a birthweight category consisting of birthweights <2.5 kg plus birthweights >4 kg, reflecting extreme birthweights. In a subset analysis, we investigated the association between a low birthweight and PCOS while differentiating between Rotterdam and NIH criteria. When diagnosed according to the Rotterdam criteria, women born with birthweights lower than 2.5 kg had an odds ratio [95% CI] of 1.76 [1.14,2.70] for PCOS compared to women born with birthweights higher than 2.5 kg. For the latter analysis, we were able include 1252 women (I(2) = 16%). There was no significant effect of birthweight on PCOS when diagnosed according to NIH criteria. LIMITATIONS REASONS FOR CAUTION: The funnel plot of the studies providing data for the meta-analysis and the subset analysis indicates a publication bias. WIDER IMPLICATIONS OF THE FINDINGS: A low birthweight could be a risk factor for PCOS when diagnosed according to the Rotterdam criteria. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: The protocol of this study was registered at PROSPERO under registration number CRD42016048972.