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. 2025 Jan 8:10.14309/ajg.0000000000003306.
doi: 10.14309/ajg.0000000000003306. Online ahead of print.

Inflammatory Bowel Disease, Periconceptional Disease Activity, and Risk of Major Congenital Anomalies: A Nationwide Cohort Study

Karl Mårild  1   2 , Jonas Söderling  3   4 , Olof Stephansson  4 , Jordan Axelrad  5 , Jonas Halfvarson  6 , Gabriella Bröms  4   7 , Jan Marsal  8   9 , Martin Neovius  4 , Björn Pasternak  4   10 , Ola Olén  4   11 , Jonas F Ludvigsson  3   12   13 ; SWIBREG Study Group
Affiliations

Inflammatory Bowel Disease, Periconceptional Disease Activity, and Risk of Major Congenital Anomalies: A Nationwide Cohort Study

Karl Mårild et al. Am J Gastroenterol. .

Abstract

Introduction: It is uncertain whether the risk of major congenital anomalies (mCAs) is increased in children of women with inflammatory bowel disease (IBD).

Methods: We aimed to determine the risk of mCAs in a Swedish nationwide cohort of 13,131 singleton live births from 1997 to 2020 to women with IBD and 61,909 matched children to women without IBD from the general population. We additionally examined mCAs according to periconceptional histological inflammation (vs remission: 1,124 and 646 births, respectively) or clinically active IBD (vs quiescent: 3,380 and 6,603 births, respectively). Adjusted risk ratios (aRRs) for overall and organ-specific mCAs were estimated using generalized linear models. These models adjusted for maternal sociodemographics, comorbidities, body mass index, and smoking.

Results: There were 38.0 (n = 499) mCAs per 1,000 births to women with IBD vs 33.9 (n = 2,101) in matched comparators and a risk difference of 1 extra mCA per 246 births to women with IBD (aRR 1.11; 95% confidence interval [CI] 1.01-1.23). Risks of heart defects and mCAs of the urinary system partly drove estimates. The risk of mCAs was similar in children of women with ulcerative colitis and Crohn's disease. Periconceptional histological inflammation (vs remission) or clinically active (vs quiescent) IBD did not further influence the risk of mCA in the child (aRR 0.87 [95% CI 0.55-1.40] and aRR 1.04 [95% CI 0.85-1.27], respectively).

Discussion: Children of women with IBD had a heightened susceptibility to mCAs, although absolute and relative risks were lower than previously reported. IBD activity was not linked to mCA risks, but those analyses included relatively few events.

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Conflict of interest statement

Potential competing interests:

Dr Mårild is a sub-investigator at a clinical trial financed by Pfizer.

Dr Ludvigsson has coordinated an unrelated study on behalf of the Swedish Quality Registry for IBD (SWIBREG). That study received funding from the Janssen Corporation. Dr Ludvigsson has also received financial support from MSD, developing a paper reviewing national healthcare registers in China. Dr Ludvigsson is currently collaborating on celiac disease research with Takeda.

Dr Olén has been PI for projects at Karolinska Institutet financed by Janssen, Takeda, AbbVie, Ferring, Galapagos, Bristol Myers Squibb, and Pfizer grants. Karolinska Institutet has received fees for lectures (OO) and participation on advisory boards (OO) from Janssen, Ferring, Bristol Myers Squibb, Galapagos, and Takeda.

Dr Halfvarson has served as a speaker or advisory board member for AbbVie, BMS, Celgene, Celltrion, Eli Lilly, Dr Falk Pharma and the Falk Foundation, Ferring, Galapagos, Gilead, Hospira, Index Pharma, Janssen, MEDA, Medivir, Medtronic, MSD, Novartis, Olink Proteomics, Pfizer, Prometheus Laboratories Inc., Sandoz, Shire, STADA, Takeda, ThermoFisher Scientific, Tillotts Pharma, Vifor Pharma, and UCB. He has also received grant support from Janssen, MSD, and Takeda.

Dr Axelrad has received research grants from BioFire Diagnostics and Genentech; consultancy fees, advisory board member, or honorarium from Adiso, Bristol-Myers Squibb, bioMérieux, Abbvie, Pfizer, Ferring, Celltrion, Vedanta, and Janssen.

Dr Bröms has participated in projects at Karolinska Institutet financed by grants from Janssen, Pfizer, and UCB—lecturer for Takeda and Janssen.

Dr Marsal has served as a speaker, consultant, or advisory board member for AbbVie, Bayer, Bristol-Myers Squibb, Galapagos, Hospira, Janssen-Cilag, Merck Sharp & Dohme, Pfizer, Sandoz, Takeda, and Union Chimique Belge and has received grant support from AbbVie, Calpro AS, Fresenius Kabi, Pfizer, SVAR Life Science, and Takeda.

The other authors report no conflicts of interest.

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