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不孕治疗与儿童哮喘和特应性相关。

Infertility treatment associated with childhood asthma and atopy.

机构信息

Epidemiology Branch, Division of Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA.

Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA.

出版信息

Hum Reprod. 2022 Jun 30;37(7):1609-1618. doi: 10.1093/humrep/deac070.

Abstract

STUDY QUESTION

Are children who were conceived with infertility treatment at an increased risk of developing asthma and atopic conditions?

SUMMARY ANSWER

Infertility treatment is associated with an elevated risk of asthma and atopic conditions in early and middle childhood, even after adjustment for parental asthma and atopy.

WHAT IS KNOWN ALREADY

Asthma and atopic conditions are prevalent in childhood. The development of these conditions may be linked to early life exposures, including the use of infertility treatments.

STUDY DESIGN, SIZE, DURATION: Upstate KIDS is a prospective cohort study of singletons and multiples born between 2008 and 2010. A total of 5034 mothers and 6171 children were enrolled and followed up until 2019, and 2056 children participated in the middle childhood follow-up.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Women reported the fertility agents used to become pregnant on a baseline questionnaire. Treatment was categorized as ART (∼22%) use, ovulation induction via oral/injectable medications with or without IUI (OI/IUI, ∼20%), or no treatment (∼58%). Outcomes were assessed by maternal report on questionnaires in early (up to age 3 years, prevalence 9-28%) and middle (7-9 years, prevalence 10-16%) childhood. Weighted Poisson regression models with robust standard errors were used to analyze the risk of atopic outcomes in relation to infertility treatment exposure.

MAIN RESULTS AND THE ROLE OF CHANCE

Compared to children conceived without treatment, children conceived with any infertility treatment were at an increased risk of persistent wheeze by age 3 years (relative risk (RR): 1.66; 95% CI: 1.17, 2.33) with adjustments for parental atopy among other risk factors. Around 7-9 years, children conceived with treatment were more likely to have current asthma (RR: 1.30; 95% CI: 0.98, 1.71), eczema (RR: 1.77; 95% CI: 1.25, 2.49) or be prescribed allergy-related medications (RR: 1.45; 95% CI: 1.06, 1.99). Similar effect sizes were found when examining associations by treatment type (i.e. ART versus OI/IUI).

LIMITATIONS, REASONS FOR CAUTION: Childhood outcomes were based on maternal report and are subject to potential misclassification. There was attrition in this study, which limits the precision of our measures of association.

WIDER IMPLICATIONS OF THE FINDINGS

Though future research is needed to clarify the mechanisms involved, our findings support that both ART and OI/IUI influences the development of asthma and atopic conditions in the offspring from an early age.

STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Institutes of Health's Intramural Research Program at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; contracts #HHSN275201200005C, #HHSN267200700019C, #HHSN275201400013C, #HHSN275201300026I/27500004, #HHSN275201300023I/27500017). The authors have no relevant conflicts of interest to disclose.

TRIAL REGISTRATION NUMBER

N/A.

摘要

研究问题

接受不孕治疗后受孕的儿童患哮喘和特应性疾病的风险是否会增加?

总结答案

即使在调整了父母哮喘和特应性的情况下,不孕治疗与儿童早期和中期哮喘和特应性疾病的风险升高有关。

已知情况

哮喘和特应性疾病在儿童中很常见。这些疾病的发展可能与包括使用不孕治疗在内的早期生活暴露有关。

研究设计、规模、持续时间:Upstate KIDS 是一项针对 2008 年至 2010 年间单胎和多胎出生的前瞻性队列研究。共有 5034 名母亲和 6171 名儿童入组并随访至 2019 年,其中 2056 名儿童参加了中期随访。

参与者/材料、设置、方法:女性在基线问卷中报告了用于怀孕的生育药物。治疗分为 ART(约 22%)使用、口服/注射药物诱导排卵(OI/IUI,约 20%)或无治疗(约 58%)。通过母亲在早期(最多 3 岁,患病率 9-28%)和中期(7-9 岁,患病率 10-16%)儿童期的问卷调查评估结果。使用加权泊松回归模型和稳健标准差分析不孕治疗暴露与特应性结局风险的关系。

主要结果及其机遇作用

与未经治疗受孕的儿童相比,接受任何不孕治疗受孕的儿童在 3 岁时持续性喘息的风险增加(相对风险 (RR):1.66;95%CI:1.17,2.33),在其他风险因素之外还调整了父母特应性。大约在 7-9 岁时,接受治疗的儿童更有可能患有当前哮喘(RR:1.30;95%CI:0.98,1.71)、湿疹(RR:1.77;95%CI:1.25,2.49)或接受过敏相关药物治疗(RR:1.45;95%CI:1.06,1.99)。当按治疗类型(即 ART 与 OI/IUI)检查关联时,也发现了类似的效应大小。

局限性、谨慎的原因:儿童期结局基于母亲报告,可能存在潜在的分类错误。该研究存在失访,限制了我们关联测量的精度。

研究结果的更广泛意义

尽管需要进一步研究来阐明所涉及的机制,但我们的研究结果表明,ART 和 OI/IUI 都会影响后代从早期开始哮喘和特应性疾病的发展。

研究资金/利益冲突:这项工作得到了美国国立卫生研究院儿科学国家研究所(NICHD)内部研究计划的支持(合同 #HHSN275201200005C、#HHSN267200700019C、#HHSN275201400013C、#HHSN275201300026I/27500004、#HHSN275201300023I/27500017)。作者没有相关的利益冲突需要披露。

试验注册编号

无。

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