Abstract

Abstract Study question Are children conceived by assisted reproductive technologies (ART) or born to subfertile parents more susceptible for upper- or lower respiratory infections (URTI, LRTI)? Summary answer ART-conceived children had higher frequency and risk of hospitalization for respiratory infections up to age 3, which can only partly be explained by parental subfertility. What is known already Some studies report higher health care use, health care costs and increased risks of infections in children conceived by ART. Results for URTIs and LRTIs are inconclusive, and the contribution of underlying parental subfertility remains unclear. Study design, size, duration We included 84 102 singletons of the prospective Norwegian Mother, Father and Child Cohort Study (MoBa) born between 1999-2008. Mothers reported time-to-pregnancy at recruitment and respiratory infections, frequency, and hospitalisation by questionnaires when the child was 6, 18 and 36 months old. The birth registry provided information on ART and subfertility was defined ≥ 12 months to conception. URTI included throat and ear infections, while LRTI included bronchitis, bronchiolitis, respiratory syncytial virus, and pneumonia. Participants/materials, setting, methods We used log-binomial regression to estimate risk ratios (RR) and 95% confidence intervals (CI) of any infection and hospitalisation. We used negative-binomial regression receiving incidence rate ratios (IRR) and 95% CI for number of infections. We compared children conceived by ART and naturally conceived by subfertile parents to children of fertile parents (reference) while adjusting for maternal age, education, body-mass-index and smoking during pregnancy and previous livebirths. We clustered children born to the same mother. Main results and the role of chance A total of 7334 (8.7%) singletons were naturally conceived by subfertile parents and 1901 (2.3%) by ART. Between age 0-36 months, 41 639 (49.5%) of children experienced any URTI, 15 542 (18.5%) any LRTI, and 4134 (4.9%) were hospitalized due to LRTI. Over the first three years of life, the risk for higher frequency of URTI (aIRR 1.16; 95% CI 1.05-1.28) and any hospitalisation due to LRTI (aRR 1.25; 95% CI 1.02-1.53) was increased for children conceived by ART but not for children of subfertile parents. Risks of respiratory infections were not increased at age 0-6 or 7-18 months. Only at age 19-36 months, children of subfertile parents had higher risk of LRTIs (adjusted relative risk (aRR) 1.09, 95%CI 1.01-1.17). Children conceived by ART had an increased risk of any LRTI (aRR 1.16, 95% CI 1.01-1.33), increased frequency of LRTI’s (IRR 1.26; 95%CI 1.04- 1.51) and higher risk of hospitalisation for LRTI (aRR 1.38; 95% CI 1.03-1.84) at 19-36 months as well as an increased frequency of URTI’s (aIRR 1.20; 95% CI 1.08-1.34). Limitations, reasons for caution Use of self-reported time-to-pregnancy and respiratory tract infections by parents could lead to misclassification. Selection bias makes the MoBa Cohort somewhat different from the general Norwegian population and lost to follow-up is not at random. Wider implications of the findings ART-conceived children might be more susceptible to respiratory tract infections in early childhood. This appears to be only partly explained by factors related to underlying parental subfertility. The immune response in children might be affected by parental subfertility or through ART technology and this should be further investigated. Trial registration number not applicable

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