Unmeasured confounding in meta-analyses of observational studies evaluating maternal periodontitis and adverse birth outcomes

Abstract Background Maternal periodontitis has been consistently linked to adverse birth outcomes (ABOs). However, a causal relationship is not established due to potential unmeasured confounding factors in observational studies and inconclusive results from randomized controlled trials. This study aimed to assess the impact of unmeasured confounding factors in meta-analyses examining associations between maternal periodontitis and preterm birth (PTB) or low birth weight (LBW). Methods PubMed and MEDLINE, Cochrane, Embase, and Google Scholar were searched for systematic reviews with meta-analyses of observational studies between 2002 and 2023. Systematic reviews with meta-analyses of observational studies were included if either PTB or LBW were the outcome and were published in English. The E-value analogue method was used to evaluate possible unmeasured confounding effects in random effects meta-analyses. Results 62 original studies from nine meta-analyses met the inclusion criteria. In relation to the exposure and outcome, the random-effects meta-analysis showed that even with an unmeasured confounder having a relative risk (RR) of 3.00, 80% of cohort studies evaluating PTB and 90% evaluating LBW would have an RR > 2.00. Conclusions Associations between maternal periodontitis and ABOs in observational studies appear robust to unmeasured confounding factors, supporting the hypothesis that maternal periodontitis is causally related to ABOs.