The effects of probiotics administration during pregnancy on preeclampsia and associated maternal, fetal and newborn outcomes: a systematic review and meta-analysis

Objective: To synthesise the available evidence on probiotic administration during pregnancy for the prevention of pre-eclampsia, and its effects on related maternal, fetal and newborn outcomes.Data Sources: Six databases were systematically searched for eligible studies - Ovid Medline, Embase, CINAHL, Cochrane, Global Index Medicus and the Maternity and Infant Care Database – from inception to 2 August 2023.Study Eligibility Criteria: Randomised controlled trials that evaluated the effects of probiotic administration on women during any stage of pregnancy.Study Appraisal and Synthesis Methods: The protocol was registered on PROSPERO (CRD42023421613). Study eligibility, data extraction, risk of bias assessment (ROB-2 tool) and certainty rating (GRADE) were performed by two authors independently. The primary outcomes were incidence of pre-eclampsia, eclampsia and maternal mortality. Meta-analysis was performed, and results reported as risk ratios with 95% confidence intervals.Results: Twenty-nine trials (7,735 pregnant women) met the eligibility criteria. There was heterogeneity across trials in population of enrolled women and type of probiotic tested (20 different strains) though most used oral administration. Probiotics may make no difference to the risk of pre-eclampsia (RR 1.14, 95% CI: 0.84 to 1.53; 11 trials; 2,401 women; low certainty evidence;) preterm birth <37 weeks’ gestation (RR 0.93, 95% CI 0.66 to 1.30; 18 trials, 4,016 women; low certainty evidence) or gestational age at delivery (MD=-0.03 weeks (≈0.2 days), 95% CI -0.16 to 0.10 weeks (≈ -1.1 to 0.7 days); 13 trials, 2,194 women; low certainty evidence). It is difficult to assess the effects of probiotics on other secondary outcomes as the evidence was of very low certainty, though no benefits or harms were observed.Conclusion: Limited evidence suggests that probiotics supplementation does not affect the risk of pre-eclampsia. Further high-quality trials are needed to definitively assess the benefits and possible harms of probiotic supplementation during pregnancy. There is also lack of data from trials involving women who are undernourished or experiencing microbial dysbiosis, in whom probiotic supplementation might be useful.