The risk of Type 1 diabetes in children born after ART: a Nordic cohort study from the CoNARTaS group
Authors: Kyhl Frederik , Spangmose Anne Lærke , Gissler Mika , Rönö Kristiina , Westvik-Johari Kjersti , Henningsen Anna-Karina Aaris , Bergh Christina , Wennerholm Ulla-Britt , Opdahl Signe , Forman Julie , Svensson Jannet , Clausen Tine , Vassard Ditte , Pinborg Anja 
Published: April 2024

Abstract

STUDY QUESTION
Do children born after ART have a higher risk of developing Type 1 diabetes (DM1) than children conceived without ART?

SUMMARY ANSWER
The risk of DM1 was similar for children conceived with and without ART, and there were no clear differences in risk according to method of fertility treatment.

WHAT IS KNOWN ALREADY
ART is associated with a higher risk of adverse perinatal outcomes, and the risk depends on the method of ART. The Developmental Origins of Health and Disease theory proposes that prenatal stress can provoke changes in endocrine processes which impact health later in life.

STUDY DESIGN, SIZE, DURATION
A Nordic register-based cohort study was carried out, including all children born in Denmark (birth years 1994–2014), Finland (1990–2014), and Norway (1984–2015). The study included 76 184 liveborn singletons born after ART and 4 403 419 born without ART. Median follow-up was 8.3 and 13.7 years in the ART and non-ART group, respectively.

PARTICIPANTS/MATERIALS, SETTING, METHODS
The cohort, initiated by the Committee of Nordic Assisted Reproductive Technology and Safety (CoNARTaS), was established by linking national registry data from the medical birth registries and national patient registries available in the Nordic countries. We performed multivariable logistic regression analyses for the birth year intervals 1984–1990, 1991–1995, 1996–2000, 2001–2005, 2006–2010, and 2011–2015, while adjusting for year of birth within each interval, sex of the child, parity, maternal age, maternal diabetes, and maternal smoking during pregnancy as potential confounders.

MAIN RESULTS AND THE ROLE OF CHANCE
During follow-up, 259 (3.4‰) children born after ART were diagnosed with DM1, while this was the case for 22 209 (5.0‰) born without ART, corresponding to an adjusted odds ratio of 0.98 (95% CI: 0.861.11). Within the different birth year intervals, no significant difference in risk of DM1 between the two groups was found, except for the youngest cohort of children born 2011–2015 where ART was associated with a higher risk of DM1. We found no significant differences in risk of DM1 when comparing children born after IVF versus ICSI or fresh versus frozen embryo transfer, but with only few cases in each group.

LIMITATIONS, REASONS FOR CAUTION
The main limitation of the study is the relatively short follow-up time. The incidence rate of DM1 peaks during ages 10–14 years, hence a longer follow-up would benefit all analyses and, in particular, the subgroup analyses.

WIDER IMPLICATIONS OF THE FINDINGS
Overall, our findings are reassuring especially considering the concomitantly increasing number of children born from ART and the increasing incidence of DM1 globally.

STUDY FUNDING/COMPETING INTEREST(S)
This Nordic registry study has been supported by the Nordic Trial Alliance/NORDFORSK and Rigshospitalets Research Foundation. 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. None of the authors has any conflicts of interest to declare regarding this study.

TRIAL REGISTRATION NUMBER
ISRCTN11780826.