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Observational Study
. 2015 Oct;80(4):727-39.
doi: 10.1111/bcp.12642. Epub 2015 May 28.

Pregnancy outcome after TNF-α inhibitor therapy during the first trimester: a prospective multicentre cohort study

Corinna Weber-Schoendorfer  1 , Marc Oppermann  1 , Evelin Wacker  1 , Nathalie Bernard  2 ; network of French pharmacovigilance centres; Delphine Beghin  3 , Benedikte Cuppers-Maarschalkerweerd  4 , Jonathan L Richardson  5 , Laura E Rothuizen  6 , Alessandra Pistelli  7 , Heli Malm  8 , Georgios Eleftheriou  9 , Debra Kennedy  10 , Mine Kadioglu Duman  11 , Reinhard Meister  12 , Christof Schaefer  1
Affiliations
Observational Study

Pregnancy outcome after TNF-α inhibitor therapy during the first trimester: a prospective multicentre cohort study

Corinna Weber-Schoendorfer et al. Br J Clin Pharmacol. 2015 Oct.

Abstract

Aims: TNF-α inhibitors are considered relatively safe in pregnancy but experience is still limited. The aim of this study was to evaluate the risk of major birth defects, spontaneous abortion, preterm birth and reduced birth weight after first trimester exposure to TNF-α inhibitors.

Methods: Pregnancy outcomes of women on adalimumab, infliximab, etanercept, certolizumab pegol or golimumab were evaluated in a prospective observational cohort study and compared with outcomes of a non-exposed random sample. The samples were drawn from pregnancies identified by institutes collaborating in the European Network of Teratology Information Services.

Results: In total, 495 exposed and 1532 comparison pregnancies were contributed from nine countries. The risk of major birth defects was increased in the exposed (5.0%) compared with the non-exposed group (1.5%; adjusted odds ratio (ORadj ) 2.2, 95% CI 1.0, 4.8). The risk of preterm birth was increased (17.6%; ORadj 1.69, 95% CI 1.1, 2.5), but not the risk of spontaneous abortion (16.2%; adjusted hazard ratio [HRadj ] 1.06, 95% CI 0.7, 1.7). Birth weights adjusted for gestational age and sex were significantly lower in the exposed group compared to the non-exposed cohort (P = 0.02). As a diseased comparison group was not possible to ascertain, the influence of disease and treatment on birth weight and preterm birth could not be differentiated.

Conclusions: TNF-α inhibitors may carry a risk of adverse pregnancy outcome of moderate clinical relevance. Considering the impact of insufficiently controlled autoimmune disease on the mother and the unborn child, TNF-α inhibitors may nevertheless be a treatment option in women with severe disease refractory to established immunomodulatory drugs.

Keywords: TNF-α inhibitors; birth defects; birth weight; malformations; pregnancy outcome.

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Figures

Figure 1
Figure 1
Cumulative incidence rates of fetal loss and live births by cohort. Cumulative incidences of pregnancy outcomes of the TNF-α inhibitor cohort (A) and of the comparison cohort (B) are plotted one above the other. Cumulative incidences for live births are drawn in blue, for spontaneous abortions in red, for elective terminations in black and for stillbirth in pink (y-axis labelling on the right). Of note, the final cumulative incidences add up to 1 covering all possible outcomes. The dotted line represents the number at risk over time (y-axis labelling on the left)
Figure 2
Figure 2
Birth weights according to centile categories and sex by cohort. Coloured bars give the proportions of singletons of both study cohorts according to centile categories. Grey bars represent the proportion of new-borns from the German perinatal survey . (The differences in numbers of infants compared with Table4 are due to missing values in the gestational week at delivery, sex of the infant or birth weight)
Figure 3
Figure 3
Duration of prenatal ADA, IFX or ETA exposure in live-born infants. Each pregnancy is represented by a single line, showing assumed fetal exposure times, i.e. treatment duration plus 1 dosing interval. The differences in exposure times among the three TNF-α-inhibitors are obvious
See this image and copyright information in PMC

References

    1. Nielsen OH, Loftus EV, Jr, Jess T. Safety of TNF-α inhibitors during IBD pregnancy: a systematic review. BMC Med. 2013;11:174. . doi: 10.1186/1741-7015-11-174. - DOI - PMC - PubMed
    1. Shivananda S, Lennard-Jones J, Logan R, Fear N, Price A, Carpenter L, van Blankenstein M. Incidence of inflammatory bowel disease across Europe: is there a difference between north and south? Results of the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD) Gut. 1996;39:690–7. - PMC - PubMed
    1. Narula N, Al-Dabbagh R, Dhillon A, Sands BE, Marshall JK. Anti-TNFalpha therapies are safe during pregnancy in women with inflammatory bowel disease: a systematic review and meta-analysis. Inflamm Bowel Dis. 2014;20:1862–9. - PubMed
    1. Cheent K, Nolan J, Shariq S, Kiho L, Pal A, Arnold J. Case Report: Fatal case of disseminated BCG infection in an infant born to a mother taking infliximab for Crohn’s disease. J Crohns Colitis. 2010;4:603–5. - PubMed
    1. Chambers CD, Johnson DL. Emerging data on the use of anti-tumor necrosis factor-alpha medications in pregnancy. Birth Defects Res A Clin Mol Teratol. 2012;94:607–11. - PubMed

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