title: Pregnancy outcome after TNF-α inhibitor therapy during the first trimester: a prospective multicentre cohort study.
abstract: OBJECTIVE
  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.
authors: Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und Toxikologie, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors: Corinna
authors: C
authors: Weber-Schoendorfer
authors: Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und Toxikologie, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors: Marc
authors: M
authors: Oppermann
authors: Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und Toxikologie, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors: Evelin
authors: E
authors: Wacker
authors: Centre Régional de Pharmacovigilance, Hospices Civils de Lyon, Lyon, France.
authors: Nathalie
authors: N
authors: Bernard
authors: Centre de Référence sur les Agents Tératogènes (CRAT), Hôpitaux Universitaires Est Parisien (APHP), Paris, France.
authors: Delphine
authors: D
authors: Beghin
authors: Teratology Information Service, MH 's-Hertogenbosch, Netherlands.
authors: Benedikte
authors: B
authors: Cuppers-Maarschalkerweerd
authors: UK Teratology Information Service, Newcastle upon Tyne Hospitals NHS Foundation Trust & Newcastle University, Newcastle upon Tyne, United Kingdom.
authors: Jonathan L
authors: JL
authors: Richardson
authors: Swiss Teratogen Information Service (STIS) and Division of Clinical Pharmacology, University Hospital, Lausanne, Switzerland.
authors: Laura E
authors: LE
authors: Rothuizen
authors: Centro di Riferimento Regionale di Tossicologia Perinatale, Azienda Ospedaliero Universitaria Careggi, Firenze, Italy.
authors: Alessandra
authors: A
authors: Pistelli
authors: Teratology Information Service, HUSLAB and Helsinki University Central Hospital, Helsinki, Finland.
authors: Heli
authors: H
authors: Malm
authors: Poison Control Centre and Teratology Information Service, Hospital Papa Giovanni XXIII, Bergamo, Italy.
authors: Georgios
authors: G
authors: Eleftheriou
authors: Mothersafe, Royal Hospital for Women, Randwick, Australia.
authors: Debra
authors: D
authors: Kennedy
authors: Department of Pharmacology, Karadeniz Technical University, Trabzon, Turkey.
authors: Mine
authors: M
authors: Kadioglu Duman
authors: Department of Mathematics, Beuth Hochschule für Technik Berlin (University of Applied Sciences), Berlin, Germany.
authors: Reinhard
authors: R
authors: Meister
authors: Pharmakovigilanzzentrum Embryonaltoxikologie, Institut für Klinische Pharmakologie und Toxikologie, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors: Christof
authors: C
authors: Schaefer
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology*; D000022:Abortion, Spontaneous / Q000453:epidemiology*; D000068879:Adalimumab / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D001724:Birth Weight / Q000187:drug effects*; D016022:Case-Control Studies; D000068582:Certolizumab Pegol / Q000009:adverse effects; D000068800:Etanercept / Q000009:adverse effects; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D000069285:Infliximab / Q000009:adverse effects; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000453:epidemiology*; D011261:Pregnancy Trimester, First; D047928:Premature Birth / Q000453:epidemiology*; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; C529000:golimumab; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept; D000068582:Certolizumab Pegol
keywords: TNF-α inhibitors; birth defects; birth weight; malformations; pregnancy outcome