The risk of asthma in singletons conceived by ART: a retrospective cohort study

Abstract

STUDY QUESTION Do singleton children conceived by ART have a higher asthma risk than naturally conceived (NC) singletons? SUMMARY ANSWER The asthma risk was similar for ART-conceived singletons and NC singletons, and there were no clear differences between the various types of ART. WHAT IS KNOWN ALREADY Whether ART increases asthma risk in offspring is questionable. The evidence is inconsistent and limited by ethnicity, geographic distribution, inadequate confounder adjustment, unsatisfactory control groups and specific methods of ART. Furthermore, the mediating effects of obstetric and neonatal outcomes on the association between ART and asthma remain unclear. STUDY DESIGN, SIZE, DURATION This observational, single-centre study was conducted at a reproductive centre of an affiliated university hospital, between September 2009 and April 2023. A total of 3227 singletons aged 3-6 years conceived by IVF versus ICSI or fresh versus frozen embryo transfer were retrospectively enrolled, and a total of 1206 NC singletons of the same age were subsequently recruited. PARTICIPANTS/MATERIALS, SETTING, METHODS Asthma was self-reported physician diagnosis or wheezing in the past 12 months. We performed multivariable logistic regression analyses for associations between asthma in offspring and ART use, with adjusting for parental characteristics (age, education level, occupation type, BMI, asthma), smoking exposure, residence type, child sex, child age and year of follow-up. Mediating effects were explored using longitudinal mediation structural equation modelling. MAIN RESULTS AND THE ROLE OF CHANCE Asthma was reported for 51 (4.2%) of the 1206 NC singletons (median [interquartile range, IQR] age 5 [4-5] years; 48.1% females) and 169 (5.2%) of the 3227 ART- conceived singletons (5 [5-5] years; 47.6% females). We found that risks of childhood asthma in singletons conceived by ART were, overall, similar to those of NC singletons, before (odds ratio [OR], 1.25 [95% CI, 0.92-1.74]; P = 0.170) and after adjustment (adjusted OR [aOR], 0.66 [95% CI, 0.44-1.03]; P = 0.126). Results were similar in multiple sensitivity analyses and there were no clear differences in asthma risks according to method of ART. Mediation analysis revealed a significant positive indirect effect of neonatal intensive care unit (NICU) admission (standard path coefficient, b = 0.025, P < 0.05) and a negative indirect effect of breastfeeding (b = -0.012, P < 0.05) on the association between ART and asthma in singleton offspring. LIMITATIONS, REASONS FOR CAUTION This study is limited to singletons only and cannot be generalized. The study is also limited by its retrospective observational single centre nature and sample size. Mediation analyses were exploratory. Therefore, the findings need to be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS These findings can help infertile couples undergoing ART be reassured about the risk of childhood asthma in singleton offspring. Breastfeeding is recommended as a potentially feasible intervention to reduce the asthma risks in ART-conceived children who are at increased potential risk of asthma, such as those with NICU admissions. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the Key Research and Development Program of Zhejiang Province (2021C03100), the National Key Research and Development Program of China (2021YFC2700603), and the Program for Key Subjects of Zhejiang Province in Medicine and Hygiene to Zhu, the Zhejiang Province Natural Science Foundation (No. LQ22H040006) and the National Natural Science Foundation of China (No.82101759) to Tang, and the National Natural Science Foundation of China (No. 82201860) to You. The authors declare no competing interests. TRIAL REGISTRATION NUMBER ChiCTR2300069906