Health outcomes of 1000 children born to mothers with inflammatory bowel disease in their first 5 years of life

Summary Background Data about thiopurines or anti‐TNF use during pregnancy in women with inflammatory bowel diseases (IBD) are reassuring. However, many studies are based upon small sample sizes. Aims To assess IBD medication safety during pregnancy. Methods Using the French national health database, which covers more than 99% of the French population, around 65 000 000 people, we identified pregnancies ending with a birth in IBD patients in France between 2010 and 2018. Pregnancy outcomes (vital status at birth, birth term, and weight for gestational age) were compared according to treatment exposure during pregnancy using propensity score‐weighted marginal logistic regression models. Results 27 729 pregnancies were included: 3554 were exposed to thiopurines monotherapy, 3525 to anti‐TNF monotherapy, 839 to combination therapy, and 19 811 unexposed. Pregnancies exposed to thiopurines monotherapy compared to unexposed pregnancies more frequently resulted in stillbirths (1.0% vs 0.5%, aOR 2.04; 95%CI: 1.18‐3.55), preterm birth (12.3% vs 7.1%, aOR 1.76; 95%CI: 1.55‐2.00), large for gestational age (10.6% vs 8.4%, aOR 1.32; 95%CI: 1.13‐1.53) and less frequently in small for gestational age (9.6% vs 11.1%, aOR 0.79; 95%CI: 0.67‐0.92). By contrast, pregnancies exposed to anti‐TNF monotherapy were not different from unexposed pregnancies as regards to these outcomes. Compared to unexposed pregnancies, those exposed to combination therapy more frequently resulted in preterm births (aOR 1.55; 95%CI: 1.15‐2.11) and larger for gestational age (aOR 1.61; 95%CI: 1.13‐2.29) but did not differ as regards to stillbirths. Conclusions Pregnancies exposed to thiopurines more frequently resulted in stillbirths, preterm births and large for gestational age compared to pregnancies exposed to anti‐TNF or unexposed pregnancies. By contrast, pregnancies exposed to anti‐TNF monotherapy were not associated with these outcomes.

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Comparative study of pregnancy outcomes in women with inflammatory bowel disease treated with thiopurines and/or anti‐TNF: a French nationwide study 2010–2018

Meyer

Drouin

Weill

et al. 2021

“…An increased risk of infection during the first year of life has been reported among infants exposed to anti-TNF or combination therapy with anti-TNF and a thiopurine, 5,[11][12][13] although this was not seen in other studies. 6,14,15 Risk of infant infections after intrauterine exposure to combination or monotherapy with vedolizumab has received little attention. Furthermore, there is a paucity of data concerning the impact of intrauterine exposure to vedolizumab on child development and growth.…”

Section: Introductionmentioning

confidence: 99%

Vedolizumab clearance in neonates, susceptibility to infections and developmental milestones: a prospective multicentre population‐based cohort study

Julsgaard¹,

Baumgart²,

Baunwall³

et al. 2021

Background:Little is known about the consequences of intrauterine exposure to, and the post-natal clearance of, vedolizumab. Aims:To investigate the levels of vedolizumab in umbilical cord blood of newborns and rates of clearance after birth, as well as how these correlated with maternal drug levels, risk of infection and developmental milestones during the first year of life Methods: Vedolizumab-treated pregnant women with inflammatory bowel disease were prospectively recruited from 12 hospitals in Denmark and Canada in 2016-2020. Demographics were collected from medical records. Infant developmental milestones were evaluated by the Ages and Stages Questionnaire (ASQ-3).Vedolizumab levels were measured at delivery and, in infants, every third month until clearance. Non-linear regression analysis was applied to estimate clearance. Results:In 50 vedolizumab-exposed pregnancies, we observed 43 (86%) live births, seven (14%) miscarriages, no congenital malformations and low risk of adverse pregnancy outcomes. Median infant:mother vedolizumab ratio at birth was 0.44 (95% confidence interval [CI], 0.32-0.56). The mean time to vedolizumab clearance in infants was 3.8 months (95% CI, 3.1-4.4). No infant had detectable levels of vedolizumab at 6 months of age. Developmental milestones at 12 months were normal or above average. Neither vedolizumab exposure in the third trimester (RR 0.54, 95% CI, 0.28-1.03) nor combination therapy with thiopurines (RR 1.29, 95% CI, 0.60-2.77) seemed to increase the risk of infections in the offspring.Conclusions: Neonatal vedolizumab clearance following intrauterine exposure is rapid. Infant vedolizumab levels did not correlate with the risk of infections during the first year of life. Continuation of vedolizumab throughout pregnancy is safe.

“…The majority of the reproductive research on medication safety on thiopurines in women with different autoimmune diseases focuses on adverse pregnancy and birth outcomes, 12,16‐20,22,23,25,38 and in general, there is a lack of data in examining the long‐term consequences after in utero drug exposure. Furthermore, most of the studies on the maternal safety of thiopurines during conception and pregnancy concern IBD, Systemic Lupus Erythematosus (SLE) and renal transplantation recipients 26‐28,39,40 . This study thus adds important evidence to this area, and it is the first and most comprehensive study on the risk of long‐term chronic diseases and congenital malformations with almost 9 years of follow‐up in the children exposed in utero to thiopurines.…”

Section: Discussionmentioning

confidence: 92%

The risk of chronic diseases and congenital malformations during childhood and adolescence after in utero exposure to thiopurines

Jølving

Anru

Nielsen

et al. 2021

Summary Background Women with autoimmune diseases, particularly inflammatory bowel disease (IBD), often need to continue immunomodulatory therapies during pregnancy. While the evidence of birth and short‐term outcomes in children exposed in utero to these medicines is reassuring, long‐term safety data are lacking. Aim To assess any association between in utero exposure to thiopurines and diagnoses of chronic diseases (type 1 diabetes, coeliac disease, thyroid disease, rheumatoid arthritis, IBD and asthma) and congenital malformations during childhood and adolescence. Methods This nationwide cohort study was based on information using Danish registers and comprised all live‐born children from 1995 to 2015 (N = 1 308 778). Children exposed in utero to thiopurines were followed for a median of 8.9 years (25%‐75% percentiles 5.5‐12.4 years); children not exposed were followed for 13.9 years (25%‐75% percentiles 8.7‐19.0 years). Analyses were adjusted for a number of confounders including the type of maternal underlying disease. Results A total of 1047 children had been exposed to thiopurines in utero; 96 developed a chronic disease and 126 were diagnosed with congenital malformations during follow‐up. The adjusted hazard ratio for rheumatoid arthritis was 0.78 (95% CI 0.35‐1.73); for IBD, it was 1.45 (95% CI 0.64‐3.27); for asthma 0.94 (95% CI 0.73‐1.21), and for congenital malformations, it was 0.95 (95% CI 0.78‐1.15). For type 1 diabetes, coeliac disease, thyroid disease and ulcerative colitis, we had insufficient data to perform adjusted analysis. Conclusion We found no increased risk of seven common chronic diseases or congenital malformations during childhood and adolescence after gestational exposure to thiopurines.