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. 2024 Nov 18;184(1):24.
doi: 10.1007/s00431-024-05883-y.

In vitro fertilization and long-term child health and development: nationwide birth cohort study in Japan

Naomi Matsumoto  1 , Takashi Mitsui  2 , Tomoka Kadowaki  3 , Toshiharu Mitsuhashi  4 , Tomoya Hirota  5 , Hisashi Masuyama  2 , Takashi Yorifuji  6
Affiliations

In vitro fertilization and long-term child health and development: nationwide birth cohort study in Japan

Naomi Matsumoto et al. Eur J Pediatr. .

Abstract

The aim of this study is to compare long-term health outcomes between IVF-conceived children and non-IVF-conceived children in Japan, in the context of strong recommendation for single embryo transfer. Using data from a nationwide birth cohort linked with perinatal database, this study analyzed 2140 children born in Japan in May 2010. It compared child health and development outcomes up to 9 years of age between IVF-conceived and non-IVF-conceived children (binary exposure). A Poisson regression with robust variance to estimate the risk ratios for the association between IVF and various long-term child health and developmental outcomes. After adjusting for confounding factors, no significant differences were observed between IVF-conceived and naturally conceived children for most outcomes, including hospitalization, obesity, and developmental milestones. IVF-conceived children showed a slightly lower risk of attention problems at 8 years (adjusted Risk Ratio [aRR]: 0.73, 95% CI: 0.53-1.00). In subgroup analyses, IVF-conceived term children and singletons demonstrated reduced risk of cognitive delays at 5.5 years (aRR: 0.31, 95% CI: 0.10-0.96 and aRR: 0.37, 95% CI: 0.14-0.98, respectively).Conclusion: In this Japanese cohort, IVF conception was not associated with adverse long-term health or developmental outcomes. These findings provide reassurance about the safety of IVF, particularly in the context of single embryo transfer policies. Further research is needed to explore specific IVF protocols and subgroups.

Keywords: Assisted reproductive technology (ART); Development; In vitro fertilization (IVF); Long-term outcome.

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Conflict of interest statement

Declarations Ethics approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Review Board of the Graduate School of Biomedical Sciences, Okayama University (No. 2310–018), and the Clinical Research Management and Review Committee of the Japan Society of Obstetrics and Gynecology (No. 150). Consent to participate Patient consent was waived for this study as it utilized secondary data from national surveys and databases managed by relevant authorities and obstetrics and gynecology societies. All data used were anonymized and collected in accordance with applicable ethical guidelines and regulations. Competing interests The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of the participants. Numbers in boxes represent the number of children with available follow-up data for each outcome, not the number of children who experienced the outcome. More detailed outcome data are presented in Table 2
Fig. 2
Fig. 2
Associations of IVF on child health outcomes (adjusted model). The complete case analysis model was adjusted for maternal age at delivery, maternal underlying diseases, pregnancy complications, maternal smoking during pregnancy, maternal alcohol consumption during pregnancy, maternal education, paternal age, paternal education, and place of residence at birth. In the obesity outcome model, maternal pre-pregnancy body mass index was also adjusted for. NA: not applicable
Fig. 3
Fig. 3
Associations of IVF on child developmental outcomes (adjusted model). The model was adjusted for maternal age at delivery, maternal underlying diseases, pregnancy complications, maternal smoking during pregnancy, maternal alcohol consumption during pregnancy, maternal education, paternal age, paternal education, and place of residence at birth. NA: not applicable
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