Introduction:
Chronic inflammatory diseases (CIDs) are a group of autoimmune diseases which affect between 5-7% of the population and include rheumatoid arthritis (RA), psoriatic arthritis and inflammatory bowel disease (IBD).1,2 Many CIDs have a female preponderance and are often associated with activity during reproductive years.3–5 They share a similar pathophysiology centring on dysregulation of the systemic immune response mediated by cytokines including tumour necrosis factor (TNF), interleukin 1 (IL-1), and interleukin 6 (IL-6) which are known to affect pregnancy and embryogenesis.6,7 Modulation of these cytokines with the introduction of biologic agents over two decades ago was a revolution in the care for these patients and are increasingly used to manage chronic autoimmune diseases during pregnancy.
CID activity is inherently associated with an increased risk of a range of adverse pregnancy outcomes.8–10 Women with active IBD during pregnancy have higher rates of miscarriage, preterm delivery, low birth weight, congenital anomalies and Caesarean section compared to a general population.8 Likewise, there is a strong correlation with activity in RA and adverse outcomes such as miscarriage, low birth weight, pre-eclampsia and Caesarean section.9 Disease flares are associated with a greater magnitude of risk for both women and their pregnancy with balancing the risk of disease flare with fears regarding adverse effects of biologic medications.10
Randomised control trials on biologic medications during pregnancy are lacking and the majority of data regarding safety in pregnancy arises from case series, population data review and cohort studies. One of the most recent meta-analysis by Tsao et al11 focused solely on studies that had a disease matched control group thus limiting their review to 24 studies including 10 published as abstracts only. The other most recent meta-analysis by Komaki et al included 13 studies and compared outcomes in the treatment group to the general population only, with no disease matched cohort included.12
The primary aim of this systematic review and meta-analysis was to examine a range of maternal and neonatal adverse pregnancy outcomes in pregnant women exposed to biologics for the management of underlying CID compared with disease matched cohorts and women without CID.