Maternal and neonatal outcomes associated with biologic exposure before and during pregnancy in women with inflammatory systemic diseases: a systematic review and meta-analysis of observational studies

Abstract Objective To determine the association between exposure to biologics in pregnant women with inflammatory systemic diseases and maternal and neonatal outcomes through a meta-analysis of findings from studies identified in a systematic review. Methods We conducted a systematic review of Medline, Embase, and Cochrane Database of Systematic Reviews to identify observational studies assessing the perinatal impacts of biologic in women with inflammatory systemic disease. Findings were meta-analysed across included studies with random-effects models. Crude risk estimates and, where possible, adjusted risk estimates were pooled to determine the impact on results when confounding is addressed. Results Overall, 24 studies were included in the meta-analysis. Meta-analyses of crude risk estimates resulted in pooled odds ratios (OR) for the association of biologic use during pregnancy and the following respective outcomes: congenital anomalies (1.30, 95% CI: 1.02, 1.67), preterm birth (OR 1.61, 95% CI: 1.37, 1.89), and low birth weight (OR 1.68, 95% CI: 1.21, 2.31). However, in pooled analyses of adjusted risk estimates we observed that the association between biologics use during pregnancy in disease-matched exposed and unexposed pregnant women was no longer statistically significant for congenital anomalies (adjusted OR 1.18, 95% CI: 0.88, 1.57). Conclusion Pooled results from studies reporting adjusted risk estimates showed no increased risk of congenital anomalies associated with biologics use, suggesting that increased rates of adverse outcomes may be due to disease activity itself or other confounders.