Birth Outcomes in Children Fathered by Men Treated with Anti-TNF-α Agents Before Conception.
The safety of paternal use of anti-tumor necrosis factor-α (TNF-α) agents immediately prior to conception is practically unknown. On the basis of nationwide data from Danish health registries, we examined the association between paternal use of anti-TNF-α agents within 3 months before conception and adverse birth outcomes.



This nationwide cohort study is based on data from all women who had a live born singleton child in Denmark from 1 January 2007 through 2013. Children fathered by men treated with anti-TNF-α agents within three months before conception constituted the exposed cohort (N=372), and children fathered by men not treated before conception constituted the unexposed cohort (N=399,498). The outcomes were congenital abnormalities (CAs), preterm birth, and small for gestational age (SGA). We adjusted for multiple covariates, and considered paternal underlying disease and concomitant medication.



The adjusted risks of CAs and preterm birth were close to unity, and the adjusted odds ratio (OR) for SGA was 1.70 (95% confidence interval (CI): 0.94-3.09). Restricting our analysis to fathers with inflammatory bowel disease, we found no increased risk of CAs or SGA, and the adjusted OR for pretem birth was 1.42 (95% CI: 0.52-3.86). Restricting our analysis to fathers with rheumatologic/dermatological diseases, we found no increased risk of CAs or preterm birth, and the adjusted OR for SGA was 1.70 (95% CI: 0.74-3.89).



Our results are overall reassuring regarding the safety of paternal preconceptional use of anti-TNF-α agents. The result regarding SGA should, however, be interpreted with caution as we found an increased risk, although not significantly increased.
Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark.
Michael Due
MD
Larsen
Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark.|Center for Crohn's and Colitis, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Sonia
S
Friedman
Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark.
Bjarne
B
Magnussen
Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark.|Center for Crohn's and Colitis, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Bente Mertz
BM
Nørgård
D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000453:epidemiology*; D003718:Denmark; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008297:Male; D016017:Odds Ratio; D018812:Paternal Exposure / Q000706:statistics & numerical data*; D011247:Pregnancy; D047928:Premature Birth / Q000453:epidemiology*; D012042:Registries; D012216:Rheumatic Diseases / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha