Fetal and maternal outcomes after maternal biologic use during conception and pregnancy: A systematic review and meta-analysis

Background Biologic medications, specifically tumour necrosis factor-alpha (TNF-alpha) inhibitors, have become increasingly prevalent in the treatment of chronic inflammatory disease (CID) in pregnancy. Objective To determine pregnancy outcomes in women with CID exposed to biologics during pregnancy. Search strategy PubMed and EMBASE databases were searched through January 1998-July 2021. Selection criteria Peer-reviewed, English-language cohort, case-control, cross-sectional studies, and case series that contained original data. Data collection and analysis Two authors independently conducted data extraction. A meta-analysis of proportions using a random-effects model was used to pool outcomes. Linear regression analysis was used to compare the mean of proportions of outcomes across exposure groups using the 'treated' group as the reference category. All studies were evaluated using an appropriate quality assessment tool. The GRADE approach was used to assess the overall certainty of evidence. Main results Thirty-five studies, describing 11 172 pregnancies, were eligible for inclusion. Analysis showed pooled proportions for congenital malformations as follows: treated 0.04 (95% CI 0.03-0.04; I-2 = 77) versus disease-matched 0.04 (95% CI 0.03-0.05. I-2 = 86; p = 0.238); preterm delivery treated 0.04 (95% CI 0.10-0.14; I-2 = 88) versus disease-matched 0.10 (95% CI 0.09-0.12; I-2 = 87; p = 0.250); severe neonatal infection: treated 0.05 (95% CI 0.03-0.07; I-2 = 88) versus disease-matched 0.05 (95% CI 0.02-0.07; I-2 = 94; p = 0.970); low birthweight: treated 0.10 (95% CI 0.07-0.12; I-2 = 93) versus disease-matched 0.08 (95% CI 0.07-0.09; I-2 = 0; p = 0.241); pooled miscarriage: treated 0.13 (95% CI 0.10-0.15; I-2 = 77) versus disease-matched 0.08 (95% CI 0.04-0.11; I-2 = 5; p = 0.078); pre-eclampsia; treated 0.01 (95% CI 0.01-0.02; I-2 = 0) versus disease-matched 0.01 (95% CI 0.00-0.01; I-2 = 0; p = 0.193). No statistical differences in proportions were observed. GRADE certainty of findings was low to very low. Conclusion We demonstrated comparable pregnancy outcomes in pregnancies exposed to biologics, disease-matched controls and CID-free pregnancies using the GRADE approach.