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

Kristiina Rönö*, Essi Rissanen, Christina Bergh, Ulla Britt Wennerholm, Signe Opdahl, Liv Bente Romundstad, Anna Karina Aaris Henningsen, Anne Lærke Spangmose, Anja Pinborg, Mika Gissler, Aila Tiitinen

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

12 Citationer (Scopus)

Abstract

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.

OriginalsprogEngelsk
TidsskriftFertility and Sterility
Vol/bind117
Udgave nummer5
Sider (fra-til)1026-1037
Antal sider12
ISSN0015-0282
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
K.R. has nothing to disclose. E.R. has nothing to disclose. C.B. reports receiving a grant from ALF (grants from Swedish state under the agreement on medical education and clinical research between the Swedish government and the county councils) 70940 for the submitted work, payments for lectures from Ferring Pharmaceuticals and Merck, and a grant from ALF 70940 outside the submitted work. U.-B.W. has nothing to disclose. S.O. has nothing to disclose. L.B.R. has nothing to disclose. A.-K.A.H. has nothing to disclose. A.L.S. reports receiving a Ph.D. research grant from the Research Fund of Rigshospitalet, Copenhagen University Hospital, for the submitted work. A.P. reports receiving grants from Gedeon Richter, Ferring Pharmaceuticals, and Merck A/S; consulting fees from Preglem and Novo Nordisk; payment for lectures from Gedeon Richter, Ferring Pharmaceuticals, Merck A/S, and Theramex; travel support from Gedeon Richter; payment for advisory board service from Preglem; and nonfinancial support from Gedeon Richter outside the submitted work. M.G. has nothing to disclose. A.T. has nothing to disclose.

Funding Information:
The Committee of Nordic Assisted Reproductive Technology and Safety has been supported by the Nordic Trial Alliance: a pilot project jointly funded by the Nordic Council of Ministers and NordForsk, Oslo Norway (grant number: 71450), the Central Norway Regional Health Authorities , Stjørdal, Norway (grant number: 46045000 ), the Nordic Federation of Obstetrics and Gynaecology, Helsinki, Finland (grant numbers: NF13041, NF15058, NF16026, and NF17043), the Interreg Öresund-Kattegat-Skagerrak European Regional Development Fund, Copenhagen, Denmark (ReproUnion project), and the Research Council of Norway’s Centre of Excellence funding scheme, Oslo, Norway (grant number: 262700 ). The funding sources had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

Funding Information:
The Committee of Nordic Assisted Reproductive Technology and Safety has been supported by the Nordic Trial Alliance: a pilot project jointly funded by the Nordic Council of Ministers and NordForsk, Oslo Norway (grant number: 71450), the Central Norway Regional Health Authorities, Stjørdal, Norway (grant number: 46045000), the Nordic Federation of Obstetrics and Gynaecology, Helsinki, Finland (grant numbers: NF13041, NF15058, NF16026, and NF17043), the Interreg Öresund-Kattegat-Skagerrak European Regional Development Fund, Copenhagen, Denmark (ReproUnion project), and the Research Council of Norway's Centre of Excellence funding scheme, Oslo, Norway (grant number: 262700). The funding sources had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. K.R. has nothing to disclose. E.R. has nothing to disclose. C.B. reports receiving a grant from ALF (grants from Swedish state under the agreement on medical education and clinical research between the Swedish government and the county councils) 70940 for the submitted work, payments for lectures from Ferring Pharmaceuticals and Merck, and a grant from ALF 70940 outside the submitted work. U.-B.W. has nothing to disclose. S.O. has nothing to disclose. L.B.R. has nothing to disclose. A.-K.A.H. has nothing to disclose. A.L.S. reports receiving a Ph.D. research grant from the Research Fund of Rigshospitalet, Copenhagen University Hospital, for the submitted work. A.P. reports receiving grants from Gedeon Richter, Ferring Pharmaceuticals, and Merck A/S; consulting fees from Preglem and Novo Nordisk; payment for lectures from Gedeon Richter, Ferring Pharmaceuticals, Merck A/S, and Theramex; travel support from Gedeon Richter; payment for advisory board service from Preglem; and nonfinancial support from Gedeon Richter outside the submitted work. M.G. has nothing to disclose. A.T. has nothing to disclose.

Publisher Copyright:
© 2022 American Society for Reproductive Medicine

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