4.7 Article

The neurodevelopmental morbidity of children born after assisted reproductive technology: a Nordic register study from the Committee of Nordic Assisted Reproductive Technology and Safety group

Journal

FERTILITY AND STERILITY
Volume 117, Issue 5, Pages 1026-1037

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.fertnstert.2022.01.010

Keywords

Assisted reproduction; attention-deficit and hyperactivity disorder; autism spectrum disorder; learning and motor functioning disorder; tic disorder

Funding

  1. Nordic Trial Alliance: a pilot project - Nordic Council of Ministers [71450]
  2. Nordic Trial Alliance: a pilot project - NordForsk, Oslo Norway [71450]
  3. Central Norway Regional Health Authorities, Stjordal, Norway [46045000]
  4. Nordic Federation of Obstetrics and Gynaecology, Helsinki, Finland [NF13041, NF15058, NF16026, NF17043]
  5. Interreg Oresund-Kattegat-Skagerrak European Regional Development Fund, Copenhagen, Denmark (ReproUnion project)
  6. Research Council of Norway's Centre of Excellence funding scheme, Oslo, Norway [262700]

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This study assessed the risk of neurodevelopmental disorders in singletons born after the use of assisted reproductive technology (ART) compared with those born without ART. The findings showed that there were only small differences in neurodevelopment between ART and non-ART singletons, and the overall risk was low.
Objective: To assess the risk of neurodevelopmental disorders in singletons born after the use of assisted reproductive technology (ART) compared with singletons born without the use of ART. Design: Nordic register-based study. Setting: Cross-linked data from Medical Birth Registers and National ART and Patient Registers; liveborn singletons in 1995-2014 in Denmark and Finland, 2005-2015 in Norway, and 1995-2015 in Sweden with follow-up to 2014 (Denmark and Finland) or 2015 (Norway and Sweden). Patients: A total of 5,076,444 singletons: 116,909 (2.3%) born with and 4,959,535 (97.7%) born without the use of ART (non-ART). Interventions: In vitro fertilization, intracytoplasmic sperm injection, and fresh and frozen embryo transfer. Main Outcome Measures: The primary outcomes (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes) were learning and motor functioning disorders (F80-F83), autism spectrum disorder (F84), attention-deficit/hyperactivity disorder and conduct disorders (F90-F92), and tic disorders (F95). Crude hazard ratios (HRs) and adjusted hazard ratios (aHRs) with 95% confidence intervals were calculated. Results: Singletons in the ART cohort had a higher adjusted risk of learning and motor functioning disorders (HR, 1.01 [0.96-1.07]; aHR, 1.17 [1.11-1.24]) and a tendency toward a higher risk of autism spectrum disorder (HR, 1.12 [1.04-1.21]; aHR, 1.07 [0.98-1.16]) and attention-deficit/hyperactivity disorder and conduct disorders (HR, 0.82 [0.77-0.86]; aHR, 1.17 [0.99-1.12]) but not of tic disorders (HR, 1.21 [1.06-1.38]; aHR, 1.17 [0.96-1.27]). No differences in risk were found between children born after in vitro fertilization and intracytoplasmic sperm injection or after fresh and frozen embryo transfer. Conclusions: Our findings of only small differences in neurodevelopment between ART and non-ART singletons are reassuring and in line with previous studies. (C) 2022 by American Society for Reproductive Medicine.

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