Asthma in children born after infertility treatment: findings from the UK Millennium Cohort Study
Asthma in children born after infertility treatment: findings from the UK Millennium Cohort Study
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DOI：
10.1093/humrep/des398
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发表时间：
2013-02-01
影响因子：
6.1
通讯作者：
Quigley, M. A.
中科院分区：
文献类型：
--
作者：
Carson, C.;Sacker, A.;Quigley, M. A.
哮喘在低生育能力和辅助生殖技术（ART）后出生的儿童中更常见吗？是。去年的哮喘、喘息和抗哮喘药物在怀孕较长时间后出生的孩子中都更常见。这主要是由于抗逆转录病毒治疗后出生的儿童增加所致。很少有研究调查抗逆转录病毒治疗与随后儿童哮喘之间的关系，迄今为止的研究结果好坏参半。一项基于登记的大型研究发现，在接受抗逆转录病毒治疗的儿童中，哮喘药物的使用有所增加，但潜在的不孕症是假定的危险因素。人们对意外怀孕或不合时宜受孕后的儿童哮喘知之甚少。千禧年队列研究是一项全英国范围的前瞻性研究，招募了18818名9个月大的儿童。后续工作正在进行中。本研究分析了5岁和7岁随访调查的数据（应答率分别为79和70）。包括生母提供随访数据的独生子女。母亲们报告了她们的怀孕是否在计划之中；规划者提供TTC和ART的详细信息。将人群分为“计划外”（计划外但不快乐）、“计划外”（计划外但快乐）、“计划外”（计划，TTC 12个月）、未治疗的低生育力”（计划，TTC 12个月）、促排卵（接受克罗米芬）和oART（体外受精或ICSI）。初步分析以计划生育儿童为对照组；二次分析比较了治疗组和未治疗的低生育能力父母所生的孩子。结果是5岁和7岁时哮喘和喘息的父母报告，来自国际儿童哮喘和过敏研究的验证问题，加上使用抗哮喘药物。共有13 041（72）名儿童在5岁时被纳入哮喘和混杂因素的完整数据，11 585（64）名儿童在7岁时被纳入。与计划生育的孩子相比，低生育能力父母所生的孩子在5岁时患哮喘、喘息和服用抗哮喘药物的可能性显著增加[调整优势比（OR）： 1.39(95可信区间（CI）： 1.07, 1.80), OR: 1.27（1.00, 1.63）和OR: 1.90(1.32,2.74)]。这种关联主要与ART后出生的儿童患病率增加有关(哮喘、喘息和服用抗哮喘药物分别校正OR: 2.65（1.48, 4.76）、OR: 1.97（1.10, 3.53）和OR: 4.67（2.20, 9.94）。这种关联在7岁时也存在，但有所减弱。抗逆转录病毒治疗后出生的单胎数量相对较少（104例），因此研究结果应谨慎解释。然而，关于各种可能的混淆和中介因素的数据是可用的，并进行了分析。对无反应的数据进行加权，以尽量减少选择偏差。越来越多的证据表明，儿童生育能力低下、抗逆转录病毒治疗和哮喘之间存在关联，这些发现进一步证明了这一点。需要进一步的工作来确定因果关系并阐明潜在的机制。这些发现只适用于单例，需要对多例进行进一步的研究。这项研究由医学研究委员会项目拨款资助。没有竞争利益。
Is asthma more common in children born after subfertility and assisted reproduction technologies (ART)?Yes. Asthma, wheezing in the last year and anti-asthmatic medication were all more common in children born after a prolonged time to conception (TTC). This was driven specifically by an increase in children born after ART.Few studies have investigated any association between ART and asthma in subsequent children, and findings to date have been mixed. A large registry-based study found an increase in asthma medication in ART children but suggests underlying infertility is the putative risk factor. Little is known about asthma in children after unplanned or mistimed conceptions.The Millennium Cohort Study is a UK-wide, prospective study of 18 818 children recruited at 9 months of age. Follow-up is ongoing. This study analyses data from follow-up surveys at 5 and 7 years of age (response rates of 79 and 70, respectively).Singleton children whose natural mothers provided follow-up data were included. Mothers reported whether their pregnancy was planned; planners provided TTC and details of any ART. The population was divided into ounplanned' (unplanned and unhappy), omistimed' (unplanned but happy), oplanned' (planned, TTC 12 months), ountreated subfertile' (planned, TTC 12 months), oovulation induced' (received clomiphene citrate) and oART' (IVF or ICSI). The primary analysis used the planned children as the comparison group; secondary analysis compared the treatment groups to the children born to untreated subfertile parents. Outcomes were parent report of asthma and wheezing at 5 and 7 years, derived from validated questions in the International Study of Asthma and Allergies in Childhood, plus use of anti-asthmatic medications. A total of 13 041 (72) children with full data on asthma and confounders were included at 5 years of age, and 11 585 (64) at 7 years.Compared with planned children, those born to subfertile parents were significantly more likely to experience asthma, wheezing and to be taking anti-asthmatics at 5 years of age [adjusted odds ratio (OR): 1.39 (95 confidence interval (CI): 1.07, 1.80), OR: 1.27 (1.00, 1.63) and OR: 1.90 (1.32,2.74), respectively]. This association was mainly related to an increase among children born after ART (adjusted OR: 2.65 (1.48, 4.76), OR: 1.97, (1.10, 3.53) and OR: 4.67 (2.20, 9.94) for asthma, wheezing and taking anti-asthmatics, respectively). The association was also present, though reduced, at the age of 7 years.The number of singletons born after ART was relatively small (n 104), and as such the findings should be interpreted with caution. However, data on a wide range of possible confounding and mediating factors were available and analysed. The data were weighted for non-response to minimize selection bias.The findings add to the growing body of evidence suggesting an association between subfertility, ART and asthma in children. Further work is needed to establish causality and elucidate the underlying mechanism. These findings are generalizable to singletons only, and further work on multiples is needed.This study was funded by a Medical Research Council project grant. No competing interests.