Prenatal alcohol consumption and placental outcomes: a systematic review and meta-analysis of clinical studies.

OBJECTIVE: A systematic review was conducted to determine placental outcomes following prenatal alcohol exposure in women.

DATA SOURCES: The search terms "maternal OR prenatal OR pregnant OR periconception" AND "placenta" AND "alcohol OR ethanol" were used across 5 databases (PubMed, Embase, Cochrane Library, Web of Science, and CINAHL) from inception until November 2020.

STUDY ELIGIBILITY CRITERIA: Articles were included if they reported placental outcomes in an alcohol exposure group compared with a control group. Studies were excluded if placentas were from elective termination before 20 weeks' gestation, animal studies, in vitro studies, case studies, or coexposure studies.

METHODS: Study quality was assessed by 2 reviewers using the Newcastle-Ottawa Quality Assessment Scale. Title and abstract screening was conducted by 2 reviewers to remove duplicates and irrelevant studies. Remaining full text articles were screened by 2 reviewers against inclusion and exclusion criteria. Placental outcome data were extracted and tabulated separately for studies of placentation, placental weight, placental morphology, and placental molecular studies. Meta-analyses were conducted for outcomes reported by >3 studies.

RESULTS: Database searching retrieved 640 unique records. Screening against inclusion and exclusion criteria resulted in 33 included studies. The quality assessment identified that 61% of studies were high quality, 30% were average quality, and 9% were low quality. Meta-analyses indicated that prenatal alcohol exposure increased the likelihood of placental abruption (odds ratio, 1.48; 95% confidence interval, 1.37-1.60) but not placenta previa (odds ratio, 1.14; 95% confidence interval, 0.84-1.34) and resulted in a reduction in placental weight of 51 g (95% confidence interval, -82.8 to -19.3). Reports of altered placental vasculature, placental DNA methylation, and gene expression following prenatal alcohol exposure were identified. A single study examined placentas from male and female infants separately and found sex-specific placental outcomes.

CONCLUSION: Prenatal alcohol exposure increases the likelihood of placental abruption and is associated with decreased placental weight, altered placental vasculature, DNA methylation, and molecular pathways. Given the critical role of the placenta in determining pregnancy outcomes, further studies investigating the molecular mechanisms underlying alcohol-induced placental dysfunction are required. Sex-specific placental adaptations to adverse conditions in utero have been well documented; thus, future studies should examine prenatal alcohol exposure-associated placental outcomes separately by sex.