Abstract
Abstract
Study question
To determine pregnancy outcomes in women with chronic inflammatory disease exposed to biologics during conception and pregnancy.
Summary answer
Meta-analysis of 11172 pregnancies exposed to biologic medications show no evidence of harm for the fetus or the mother.
What is known already
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). Many CIDs have a female preponderance and are often associated with activity during reproductive years. Biologic medications, specifically the TNF-α inhibitors, have become increasingly prevalent in the treatment of chronic inflammatory disease (CID) in women of childbearing age.
Study design, size, duration
PubMed and EMBASE databases January 1998-July 2021.Peer reviewed, English language cohort, case-control, cross-sectional studies, and case series which contained original data. P- diagnosis of CID pregnancy. I- Biologic medication. C- diagnosis of CID without treatment with biologics and a CID free population. O- fetal:congenital malformations, preterm delivery (<37 weeks), severe neonatal infection requiring hospitalisation, low birth weight (<2.5Kg) and small for gestational age (<10th Centile). Maternal: severe maternal infection requiring hospitalisation, miscarriage and pre-eclampsia.
Participants/materials, setting, methods
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 described by McDonald et al. The GRADE approach was used to assess the overall certainty of evidence.
Main results and the role of chance
35 studies, 11172 pregnancies, were eligible for inclusion. Analysis showed pooled proportions for congenital malformations: treated 0.04(95% CI 0.03-0.04; I2 77) vs disease matched 0.04(0.03-0.05. I2 86) p = 0.238. Preterm delivery treated 0.04(0.10-0.14. I2 88) vs disease matched 0.10(0.09-0.12. I2 87) p = 0.250. Severe neonatal infection: treated 0.05(0.03-0.07. I2 88) vs disease matched 0.05(0.02-0.07. I2 94) p = 0.970. Low birth weight: treated 0.10(0.07-0.12. I2 93) vs disease matched 0.08(0.07-0.09. I2 0) p = 0.241. The pooled Miscarriage: treated 0.13(0.10-0.15. I2 77) vs disease matched 0.08(0.04-0.11. I2 5) p = 0.078. Pre-eclampsia; treated 0.01(0.01-0.02. I2 0) vs disease matched 0.01(0.00-0.01. I2 0). p = 0.193. No statistical differences in proportions were observed.
Limitations, reasons for caution
GRADE certainty of findings were low to very low.
Wider implications of the findings
We demonstrated comparable pregnancy outcomes in pregnancies exposed to biologics, disease matched controls and CID free pregnancies using the GRADE approach.
Trial registration number
NA