Pregnancy outcome following gestational exposure to TNF-alpha-inhibitors: a prospective, comparative, observational study

Reprod Toxicol. 2014 Jan;43:78-84. doi: 10.1016/j.reprotox.2013.11.004. Epub 2013 Nov 24.

Abstract

Objective: To evaluate pregnancy safety of anti-TNF-α medications.

Design: Prospective, comparative, observational study done at the Israeli Teratology Information Service between 2002 and 2011.

Results: 83 anti-TNF-α-exposed-pregnancies (97.6% in the first trimester, T1) were followed-up and compared with 86 disease-matched (DM) and 341 non-teratogenic-exposed (NTE) pregnancies. The anti-TNF-α group consisted of 35 infliximab-, 25 etanercept-, and 23 adalimumab-exposed pregnancies. The rate of major congenital anomalies did not significantly differ between the three groups [3/65 (4.6%) (anti-TNF-α, T1), 5/79 (6.3%) (DM), 8/336 (2.4%) (NTE)], even after excluding genetic or cytogenetic anomalies [3/65 (4.6%) (anti-TNF-α, T1), 4/79 (5.1%) (DM), 6/336 (1.8%) (NTE)]. There were no cases of VATER/VACTERL association.

Conclusion: The present study suggests that anti-TNF-α treatment does not pose a major teratogenic risk in humans. This conclusion is based on relatively small numbers of exposed pregnancies and should be interpreted with caution. Larger studies are needed to establish anti-TNF-α pregnancy safety.

Keywords: Adalimumab; Anti-TNF-α; Autoimmune diseases; Congenital anomalies; Etanercept; Infliximab; Pregnancy.

MeSH terms

  • Adalimumab
  • Adult
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Arthritis / drug therapy
  • Behcet Syndrome / drug therapy
  • Colitis, Ulcerative / drug therapy
  • Crohn Disease / drug therapy
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / therapeutic use*
  • Infliximab
  • Maternal-Fetal Exchange
  • Pregnancy
  • Pregnancy Outcome*
  • Prospective Studies
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Spondylitis, Ankylosing / drug therapy
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab
  • Etanercept