Assisted Reproduction · Safety and Risks

Congenital heart defects in children born after assisted reproductive technology: a CoNARTaS study

Sargisian N, Petzold M, Furenäs E, Gissler M, Spangmose AL, Malchau Lauesgaard S, Opdahl S, Pinborg A, Henningsen AA, Westvik-Johari K, Rönö K, Bergh C, Wennerholm UB

Published December 2024 European heart journal
DOI 10.1093/eurheartj/ehae572 PMID 39326528 PMC PMC11638113

RRM Academy Synopsis

Congenital heart defects were more common in children born after ART

Major heart defects were more common after ART than after spontaneous conception, about 18 against 12 out of 1,000, in a Nordic registry cohort of 7 747 637 liveborn children. The cohort included 171 735 children born after ART. Risk was highest in multiples, however they were conceived.

Key Findings

  • Major congenital heart defects occurred in 3159 children born after ART (1.84%) and 86 824 born after spontaneous conception (1.15%); adjusted odds ratio 1.36 (95% CI 1.31–1.41).
  • Severe congenital heart defects occurred in 594 children born after ART (0.35%) and 19 375 children born after spontaneous conception (0.26%); adjusted odds ratio 1.30 (95% CI 1.20–1.42).
  • Among singletons, major defects occurred in 1.62% born after ART and 1.11% born after spontaneous conception (adjusted odds ratio 1.19; 95% CI 1.14–1.24).
  • Among multiples, major defects occurred in 2.47% born after ART and 2.41% born after spontaneous conception, with no significant difference (adjusted odds ratio 0.94; 95% CI 0.88–1.01).
  • In ART singletons, major defects occurred in 1.67% after ICSI and 1.51% after IVF (adjusted odds ratio 1.07; 95% CI 0.97–1.18), and 1.82% after frozen and 1.54% after fresh transfer (1.04; 0.91–1.18).

Interpretation

The study is an observational registry cohort and reports an association between ART and heart defects. The authors adjusted for birth year, country, maternal age, parity, smoking, diabetes and maternal heart defects, and note that unmeasured factors may remain. The study had no information on causes of infertility. Stillbirths were excluded, and data on terminations for birth defects were unavailable. Children conceived with ovulation induction or intrauterine insemination counted as spontaneous conceptions. Follow-up ended at birth in Norway and at 1 year elsewhere. Data on ICSI, IVF and embryo transfer type came from Denmark, Norway and Sweden. The authors describe the absolute risks as modest.

RRM Context

ART bypasses the reproductive system and leaves unanswered why conception has not occurred. The study had no information on causes of infertility. According to a recent Australian study the authors cite, reduced fertility in the parents could partly explain the higher rate of birth defects after ART. Multiples made up 25.9% of ART births and 2.6% of spontaneous births, and the authors describe the risks as partly associated with multiple pregnancies. Restorative reproductive medicine evaluates both partners for the underlying cause of infertility.

Abstract

Children born after assisted reproductive technology (ART) have worse perinatal outcomes compared with spontaneously conceived children. This study investigates whether children conceived after ART have a higher risk of congenital heart defects (CHDs) compared with children born after spontaneous conception (SC). All 7 747 637 liveborn children in Denmark (1994-2014), Finland (1990-2014), Norway (1984-2015), and Sweden (1987-2015), where 171 735 children were conceived after ART, were included. National ART and medical birth registry data were cross-linked with data from other health and population registries. Outcomes were major CHDs, severe CHDs, 6 hierarchical CHD lesion groups, and 10 selected major CHDs, diagnosed prenatally or up to 1 year of age (Denmark, Finland, and Sweden) and prenatally or at birth (Norway). The association between ART and CHDs was assessed with multivariable logistic regression analysis, with adjustment for available confounders. Major CHDs were detected in 3159 children born after ART (1.84%) and in 86 824 children born after SC [1.15%; adjusted odds ratio (AOR) 1.36; 95% confidence interval (CI) 1.31-1.41]. Risk was highest in multiples, regardless of conception method. Severe CHDs were detected in 594 children born after ART (0.35%) and in 19 375 children born after SC (0.26%; AOR 1.30; 95% CI 1.20-1.42). Risk was similar between ICSI and IVF and between frozen and fresh embryo transfer. Assisted reproductive technology-conceived children have a higher prevalence of major CHDs, being rare, but severe conditions. The absolute risks are, however, modest and partly associated with multiple pregnancies, more prevalent in ART.

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Assisted Reproduction › Safety and Risks › Birth Defects
Nona Sargisian, Max Petzold, Eva Furenäs, Mika Gissler, Anne Lærke Spangmose, Sara Malchau Lauesgaard, Signe Opdahl, Anja Pinborg, Anna-Karina A Henningsen, Kjersti Westvik-Johari, Kristiina Rönö, Christina Bergh, Ulla-Britt Wennerholm
N Sargisian, M Petzold, E Furenäs, M Gissler, A Spangmose, S Lauesgaard, S Opdahl, A Pinborg, A Henningsen, K Westvik-Johari, K Rönö, C Bergh, U Wennerholm
PMID 39326528 39326528 DOI 10.1093/eurheartj/ehae572 10.1093/eurheartj/ehae572 Sargisian et al. 2024, Sargisian 2024