Asthma and allergies in offspring conceived by ART: a systematic review and meta-analysis

Currently, 1 in 25 children born in Australia are conceived through ARTs such as IVF and ICSI. Worldwide over 8 million children have been born after ART. There is evidence that these children are at an increased risk of congenital malformations, preterm birth, low birth weight and neonatal morbidity. However, studies on long-term health outcomes of offspring conceived after ART are lacking. Atopic disorders, such as asthma, atopic dermatitis and various allergies are increasingly common within society, and concerns have been raised that ART increases the risk of atopy amongst offspring.

The aim of this study was to systematically summarise and quantify the risk of atopic disorders in offspring conceived with ART compared to those conceived without ART.

A systematic review was conducted according to the PRISMA guidelines. Several systematic searches were performed in the following international databases: Medline, Embase, Cinahl, PsychINFO, AMED, Global Health and ISI Web of Science. Search terms utilised were all terms pertaining to ART, IVF, ICSI, asthma, atopic dermatitis and allergies. The search period was 1978-2021. Included observational studies stated a primary outcome of asthma or allergies in offspring conceived after ART, with a comparison group conceived without ART. Individual studies were scored on quality and risk of bias, using the Newcastle-Ottawa scale (NOS).

There were 26 studies which met the inclusion criteria; of these, 24 studies investigated asthma in offspring conceived after ART. While 10 studies, including the two largest population-based studies, reported a significantly increased risk of asthma in offspring conceived after ART (adjusted odds ratio (aOR) range: 1.20-2.38), 14 smaller cohort studies found no difference (aOR range 0.70-1.27). In the meta-analysis of the 14 highest-quality studies (NOS ≥ 7), a modest yet significantly increased risk of asthma was demonstrated in offspring conceived after ART [risk ratio (RR) 1.28 (1.08-1.51)]. Although heterogeneity in these 14 studies was high (I2 = 85%), the removal of outliers and high weight studies significantly reduced heterogeneity (I2 = 0% and I2 = 34% respectively) while still demonstrating a significantly increased risk [RR 1.19 (1.10-1.28) and RR 1.31 (1.03-1.65), respectively]. The increased asthma risk was also observed in most subgroup and sensitivity analyses. The allergy rates were not increased in offspring conceived after ART in 9 of 12 studies (aOR range 0.60-1.30). In summary, the findings of this systematic review and meta-analysis suggest a trend towards a significantly increased risk of asthma, but not allergies, in offspring conceived after ART. There was no evidence of publication bias in the asthma studies and minimal evidence of publication bias in the allergy studies (both P > 0.05).

Asthma brings considerable burden to the quality of life of individuals and to society. Hence, it is of great importance to untangle potential causal pathways. Although ART use is common, knowledge about its long-term health effects is required to provide evidence-based advice to couples considering ART, and to be vigilant for any potential adverse health effects on offspring conceived after ART.