STUDY QUESTION Are children conceived by ART or born to subfertile parents more susceptible to upper or lower respiratory tract infections (URTI, LRTI)? SUMMARY ANSWER ART-conceived children had a higher frequency of and risk of hospitalization for respiratory infections up to age 3, which was only partly explained by parental subfertility. WHAT IS KNOWN ALREADY Some studies report 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 Norwegian Mother, Father and Child Cohort Study (MoBa) born between 1999 and 2009. Mothers reported time-to-pregnancy at recruitment and child history of, frequency of and hospitalization for, respiratory infections when the child was 6, 18 and 36 months old by questionnaires. Subfertility was defined as having taken 12 or more months to conceive. The Medical Birth Registry of Norway (MBRN) provided information on ART. 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% CI of any respiratory tract infection and hospitalization, and negative-binomial regression to calculate incidence rate ratios (IRR) and 95% CI for number of infections. We compared children conceived by ART, and naturally conceived children of subfertile parents, to children of fertile parents (<12 months to conceive) while adjusting for maternal age, education, BMI and smoking during pregnancy and previous livebirths. We accounted for dependency between 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%) were conceived by ART. Between age 0 and 36 months, 41 609 (49.5%) of children experienced any URTI, 15 542 (18.5%) any LRTI and 4134 (4.9%) were hospitalized due to LRTI. Up to age 3, children conceived by ART had higher frequencies of URTI (adjusted IRR (aIRR) 1.16; 95% CI 1.05–1.28) and hospitalizations due to LRTI (adjusted RR (aRR) 1.25; 95% CI 1.02–1.53), which was not seen for children of subfertile parents. Children conceived by ART were not at higher risks of respiratory infections up to age 18 months; only at age 19–36 months, they had increased risk of any LRTI (aRR 1.16; 95% CI 1.01–1.33), increased frequency of LRTIs (IRR 1.22; 95% CI 1.02–1.47) and a higher risk of hospitalization for LRTI (aRR 1.35; 95% CI 1.01–1.80). They also had an increased frequency of URTIs (aIRR; 1.19; 95% CI 1.07–1.33). Children of subfertile parents only had a higher risk of LRTIs (aRR 1.09; 95% CI 1.01–1.17) at age 19–36 months. LIMITATIONS, REASONS FOR CAUTION Self-reported time-to-pregnancy and respiratory tract infections by parents could lead to misclassification. Both the initial participation rate and loss to follow up in the MoBa limits generalizability to the general Norwegian population. 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 underlying parental subfertility. Exactly what aspects related to the ART procedure might be reflected in these associations need to be further investigated. STUDY FUNDING/COMPETING INTEREST(S) Funding was received from the Swiss National Science Foundation (P2BEP3_191798), the Research Council of Norway (no. 262700), and the European Research Council (no. 947684). All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

中文翻译：

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通过辅助生殖技术根据父母不育和受孕的儿童早期呼吸道感染

研究问题 通过 ART 怀孕或由不育父母所生的孩子是否更容易感染上呼吸道或下呼吸道感染（URTI、LRTI）？总结 回答 ART 受孕的儿童在 3 岁之前因呼吸道感染而住院的频率和风险更高，这仅部分由父母生育能力低下所致。已知情况 一些研究报告称，接受 ART 的儿童感染风险增加。URTIs 和 LRTIs 的结果尚无定论，潜在的父母生育能力低下的贡献仍不清楚。研究设计、规模、持续时间 我们纳入了 1999 年至 2009 年间出生的挪威母亲、父亲和儿童队列研究 (MoBa) 的 84 102 名单身人士。通过问卷调查，孩子 6、18 和 36 个月大时的呼吸道感染情况。不孕症被定义为需要 12 个月或更长时间才能怀孕。挪威医学出生登记处 (MBRN) 提供了有关 ART 的信息。URTI 包括喉咙和耳朵感染，而 LRTI 包括支气管炎、细支气管炎、呼吸道合胞病毒和肺炎。参与者/材料、设置、方法感染人数。我们比较了通过 ART 和自然受孕的父母生育能力低下的孩子与生育能力父母的孩子（小于 12 个月受孕），同时调整了母亲的年龄、教育程度、怀孕期间和以前的活产期间的体重指数和吸烟。我们考虑了同一个母亲所生孩子之间的依赖关系。主要结果和机会的作用 共有 7334 名 (8.7%) 单胎由不育父母自然受孕，1901 名 (2.3%) 由 ART 受孕。在 0 到 36 个月之间，41 609 名 (49.5%) 的儿童经历了任何 URTI，15 542 名 (18.5%) 的任何 LRTI 和 4134 名 (4.9%) 因 LRTI 住院。直到 3 岁，接受 ART 的儿童发生 URTI（调整后的 IRR (aIRR) 1.16；95% CI 1.05–1.28）和因 LRTI 住院（调整后的 RR (aRR) 1.25；95% CI 1.02–1.53）的频率更高，对于不育父母的孩子来说，这是看不到的。接受抗逆转录病毒治疗的孩子在 18 个月之前没有更高的呼吸道感染风险；仅在 19-36 个月大时，他们发生任何 LRTI 的风险增加（aRR 1.16；95% CI 1.01–1.33），LRTI 的频率增加（IRR 1.22；95% CI 1.02–1.47）和 LRTI 住院风险更高（aRR 1.35；95% CI 1.01–1.80）。他们的 URTI 频率也增加了（aIRR；1.19；95% CI 1.07–1.33）。不育父母的孩子仅在 19-36 个月时发生 LRTI 的风险较高（aRR 1.09；95% CI 1.01-1.17）。限制、谨慎的原因 父母自我报告的怀孕时间和呼吸道感染可能导致错误分类。MoBa 的初始参与率和后续损失都限制了对挪威普通人群的推广。研究结果的更广泛意义 ART 受孕的儿童在儿童早期可能更容易受到呼吸道感染。这似乎只能部分地由潜在的父母生育能力低下来解释。这些关联中可能反映了与 ART 程序相关的具体哪些方面需要进一步调查。研究资金/竞争利益 资金来自瑞士国家科学基金会 (P2BEP3_191798)、挪威研究委员会 (no. 262700) 和欧洲研究委员会 (no. 947684)。所有作者声明没有利益冲突。试用注册号 不适用。