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11-03-2020 | Biologics | News

More research needed on biologic safety during pregnancy

Author: Claire Barnard


medwireNews: Findings from a systematic review and meta-analysis suggest that biologic use during pregnancy may be linked to an increased risk for maternal and neonatal adverse outcomes, but some associations lose significance after adjustment for confounding factors.

“We are currently limited by the dearth of studies that have attempted to control for potential confounding,” and based on the available data “it is inconclusive whether biologics are safe when used during pregnancy,” say Mary De Vera (University of British Columbia, Vancouver, Canada) and study co-authors.

The meta-analysis included 24 studies involving a total of 57,298 women with systemic inflammatory diseases; one-third of the studies included women with inflammatory arthritis, one-third comprised women with inflammatory bowel disease, and the remaining third involved a mixture of both patient populations. The majority (79.2%) of studies focused on tumor necrosis factor (TNF) inhibitors only, while 20.8% included other biologic agents.

In unadjusted analyses, infants born to women who were exposed to biologics during pregnancy had a significant 1.3-fold increased risk for congenital abnormalities relative to those born to unexposed women, as well as a significant 1.61-fold increased risk for preterm delivery and a 1.68-fold increased risk for low birthweight.

In all, congenital abnormalities occurred in 5.65% of 1963 infants exposed to biologics compared with 4.67% of 23,874 non-exposed infants, while preterm deliveries occurred in 16.53% of 1428 and 9.53% of 24,627 cases, respectively, and low birthweight in a corresponding 15.04% of 452 and 8.96% of 2299 deliveries.

De Vera and team note that “[m]ost studies reported only crude proportions of the outcomes of interest, without controlling for confounding,” with adjusted analyses reported in just five of 16 studies investigating congenital abnormalities, four of 16 evaluating preterm delivery, and one of six on low birthweight. Moreover, they point out that “there was no standardization in methodological approaches employed to control confounding.”

When analyzing the studies that were adjusted for confounding factors, the association between biologic exposure and congenital abnormalities lost statistical significance, and the researchers say that the association with preterm delivery “differed dramatically” depending on whether one large study was included or not.

“Altogether, differences in findings from pooled unadjusted and adjusted risk estimates suggest that observed elevated risks from unadjusted estimates may be explained by confounding due to disease activity or other pregnancy related factors not accounted for in studies reporting crude estimates,” write the study authors in Rheumatology.

“As such, this study highlights the need for subsequent studies to better control potential confounding, especially that related to disease activity, as well as increased consistency and transparency in reporting of confounder selection and methodological approaches,” they add.

The team identified no significant associations between biologic use and risk for stillbirth or serious infant infections in the crude and adjusted analyses.

medwireNews is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature group

Rheumatology 2020; doi:10.1093/rheumatology/keaa064