Strengths and limitations
Studies examining the use of biologics in pregnancy have been limited due to small sample size and the rare outcomes of interest. To our knowledge this is the largest cohort of pregnancies exposed to biologics collated to date. This review was based on a pre-published protocol on PROSPERO and followed the PRISMA guidelines. This review allows areas of future research to be highlighted that are currently lacking, primarily elucidating the links with preterm birth, maternal infection risk as well as exploring likely protective effects of these medications against uncontrolled disease activity. There are several limitations to this study, our search included English only literature. Disparities in the measurement criteria e.g.: birth weight, infection criteria and even the diagnostic criteria for congenital malformation make meta-analysis on this topic difficult with an already small sample being made smaller by misusing the appropriate definition and criteria. Additionally, the recording of concomitant medications, particularly corticosteroids, dosing and pregnancy outcomes which can differ between studies is imprecise at best. Pregnancy outcomes in this population can be influenced by the activity of the underlying disease state peri-conceptually and during pregnancy which can be difficult to accurately collate in these observational studies and difficult to control for by using a “disease matched cohort” when matched by diagnosis only.
We have expanded on the previous reviews by increasing the pool of data to include peer reviewed cohort studies and case series11,12,21 with statistical analysis of proportions rather than odds ratio. Another novel approach that we have taken was allowing comparisons across three populations; the treated, disease matched and disease free. We also performed sub analysis by biologic type and disease type where appropriate.