Introduction
Assisted reproductive technology has transformed fertility treatment, allowing many couples to conceive when natural conception is challenging. With techniques such as in vitro fertilization and intracytoplasmic sperm injection, the prevalence of ART-conceived children is rising globally, particularly in high-income countries. While ART provides new opportunities, concerns remain regarding the long-term health outcomes for children conceived through these methods, including the risk of atopic diseases such as asthma, allergic rhinitis, and atopic dermatitis.
A comprehensive study published in JAMA Network Open in December 2025 used Taiwan's nationwide health databases to examine whether ART-conceived children have a higher risk of developing atopic diseases compared to naturally conceived children. This article explores the study's findings, methodology, and clinical implications.
Study Overview
This population-based retrospective cohort study included 69,785 children born between 2004 and 2014. Data were obtained from Taiwan's National Health Insurance Research Database, the Assisted Reproduction Database, and the Maternal and Child Health Database. The ART group consisted of 13,957 children, and the control group included 55,828 naturally conceived children, matched by maternal age, neonatal sex, and birth month.
The primary outcome was the development of atopic diseases, specifically asthma, allergic rhinitis, and atopic dermatitis. Diagnoses were confirmed using inpatient admissions or multiple outpatient encounters. The study adjusted for confounders including parental history of atopic diseases, pregnancy complications, mode of delivery, neonatal sex, birth weight, gestational age, urbanization, and family income.
Key Findings
Children conceived via ART had a significantly higher risk of atopic diseases compared to those conceived naturally. After adjustment, the hazard ratios were:
Subgroup analyses revealed that intracytoplasmic sperm injection (ICSI) did not increase atopic risk, but fresh embryo transfers were associated with a higher risk of allergic rhinitis compared to frozen embryos. No significant differences were observed for asthma or atopic dermatitis based on embryo type.
Cohort Characteristics Table
| Characteristic | Natural Conception (Control, n=55,828) | ART (n=13,957) | P value |
|---|---|---|---|
| Maternal age ≥35 | 26,388 (47.3%) | 6,597 (47.3%) | >0.99 |
| Family income >42,000 $ | 12,702 (22.8%) | 4,542 (32.5%) | <0.001 |
| Urban residence | 37,107 (66.5%) | 9,428 (67.6%) | 0.05 |
| Paternal allergic rhinitis | 12,461 (22.3%) | 3,691 (26.4%) | <0.001 |
| Maternal allergic rhinitis | 16,256 (29.1%) | 4,497 (32.2%) | <0.001 |
| Cesarean delivery | 23,421 (42.0%) | 9,151 (65.6%) | <0.001 |
| Multiple births | 1,135 (2.0%) | 4,252 (30.5%) | <0.001 |
| Birth weight <2500 g | 4,431 (7.9%) | 3,828 (27.4%) | <0.001 |
| Preterm birth (<37 weeks) | 5,750 (10.9%) | 4,946 (29.0%) | <0.001 |
Understanding Atopic Diseases
Asthma, allergic rhinitis, and atopic dermatitis are immune-mediated conditions influenced by genetic and environmental factors. Asthma is a leading chronic disease in children, affecting school attendance, sleep, and overall wellbeing. Allergic rhinitis and atopic dermatitis also impact daily activities, sleep quality, and quality of life. Recognizing early risk factors, including conception methods, can improve early diagnosis and intervention.
ART and Immune System Development
ART involves hormonal stimulation and embryo manipulation, which may influence fetal development and immune system programming. The developmental origins of health and disease theory suggests that early life exposures, including prenatal factors, can cause permanent changes in organ and tissue development, affecting long-term health.
Animal studies support this theory. ART-conceived mice have shown altered immune responses, including increased Th2 activity, which is associated with atopic disease. Human studies suggest ART-conceived children may have altered cytokine levels, including higher interleukin-4 and altered interferon-gamma ratios, supporting the potential for immune modulation.
Clinical Implications
Healthcare providers should be aware of the increased risk of atopic diseases in ART-conceived children. Close monitoring for asthma, allergic rhinitis, and atopic dermatitis can enable early interventions and improve outcomes. Additionally, findings about fresh embryo transfers may inform counseling and decision-making for parents considering ART.
Limitations
Limitations include the use of claims data without genetic or laboratory information. Environmental and lifestyle factors, disease severity, recurrence, and medication use were not included. Residual confounding is possible despite statistical adjustments.
Conclusion
This nationwide cohort study indicates that children conceived via ART have a higher risk of developing atopic diseases. Families and healthcare providers should consider proactive monitoring and preventive strategies. Further research is needed to clarify the underlying biological mechanisms.
References
Hsieh YC, Lin CH, Lin MC, et al. Atopic Disease Development in Offspring Conceived via Assisted Reproductive Technology. JAMA Netw Open. 2025;8(12):e2551690. doi:10.1001/jamanetworkopen.2025.51690.
Disclaimer
This blog is for informational purposes only and is based on a published research article. It is not a substitute for professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider with any questions regarding medical conditions or treatment options.
