MRC Transition Support Award: Long-term health outcomes for women & their children after assisted reproductive technologies: a data linkage study

七分之一的夫妇患有不孕症，使用体外受精等辅助生殖技术（ART）的婴儿数量正在增加。自1991年以来，英国有超过39万名儿童因抗逆转录病毒治疗而出生，目前每年约占新生儿总数的2%。大多数试管婴儿出生的孩子都是健康的，但有充分的证据表明，试管婴儿怀孕的围产期结局不佳（早产、出生体重低、剖腹产发生率较高）、先天性畸形和一些罕见的表观遗传综合征的风险较高。认知、发育和行为问题也被发现，尽管证据有限，结果也不那么令人信服——部分原因是这一领域的研究很难进行，有时还存在缺陷。其他不良后果，如哮喘和自闭症，也有报道，但证据也很少。对抗逆转录病毒治疗后出生的儿童的健康和发育结果的研究往往只关注幼儿期，因此对抗逆转录病毒治疗儿童的长期健康和发育的研究仍然相对不足。在接受抗逆转录病毒治疗时，妇女也面临公认的风险，治疗失败对妇女及其伴侣的负面影响已被记录在案。然而，当治疗成功时，对母亲的长期影响往往被忽视。怀孕的困难、被认为是高风险的怀孕以及对分娩的焦虑都可能产生持久的影响。抗逆转录病毒治疗后，产后抑郁症的发病率更高，患者似乎更容易出现后来的抑郁发作。对接受治疗的妇女患癌症风险增加的担忧似乎是没有根据的，但关于抗逆转录病毒治疗对孕产妇身心健康和卫生服务使用的长期影响的问题仍未得到解答。该过渡支持奖旨在巩固由牛津大学国家围产期流行病学部门的流行病学家克莱尔·卡森博士主持的现有职业发展奖中概述的研究。该研究旨在解决上述问题，并为抗逆转录病毒治疗母亲及其子女的长期健康和福祉提供证据。该项目使用了自1991年以来英国不孕不育诊所（代表人类受精和胚胎学管理局）收集的关于所有ART治疗的数据，并将其与临床实践研究数据链母婴数据集中保存的妇女及其子女的全科医生医疗记录联系起来。预计将包括40多万对母婴，其中约8000人是在抗逆转录病毒治疗后出生的。年龄最大的孩子将被跟踪调查20多年。我们将利用医生或执业护士在儿童及其母亲就诊时记录的信息，如疾病诊断、药物处方和专科治疗转诊，来探索儿童及其母亲的健康状况。还将评估抗逆转录病毒疗法母婴对中卫生服务使用率的增加（如果有的话）。

Infertility affects 1 in 7 couples, and the number of babies using Assisted Reproductive Technologies (ART) such as IVF is increasing. Since 1991 over 390,000 children have been born in the UK as a result of ART, which now accounts for about 2% of births each year. Most IVF births result in healthy children, but there is good evidence that IVF pregnancies are at higher risk of poor perinatal outcomes (prematurity, low birth weight, a higher incidence of caesarean section), congenital malformations and some rare epigenetic syndromes. Cognitive, developmental and behavioural problems have also been identified, though the evidence is limited and findings are less convincing - in part, because studies in this area are difficult to conduct and sometimes flawed. Higher rates of other adverse outcomes, such as asthma and autism, have also been reported but, again, the evidence is sparse. Studies of health and developmental outcomes of children born after ART tend to focus only on early childhood, so that the long term health and development of ART children is still relatively under-researched. There are also well-recognised risks to the woman at the time of ART treatment, and the negative impact of unsuccessful treatment on women and their partners has been documented. However, when treatment is successful the longer-term implications for the mother are often overlooked. The difficulty of becoming pregnant, perceived high-risk pregnancies and anxiety about birth can all have a lasting impact. The incidence of postnatal depression is higher after ART, and sufferers appear to be more vulnerable to later depressive episodes. Fears about increased cancer risks in women who have undergone treatment appear unfounded, but there remain unanswered questions regarding long-term impacts of ART on maternal physical and mental health, and use of health services. This Transition Support Award seeks to consolidate the research outlined in an existing Career Development Award held by Dr Claire Carson, an epidemiologist at the National Perinatal Epidemiology Unit, University of Oxford. The research seeks to address the issues outlined above, and provide evidence for the health and wellbeing of ART mothers and their children in the longer term. The project uses data that is collected by infertility clinics (on behalf of the Human Fertilisation and Embryology Authority) on all ART treatments in the UK since 1991, and links it to GP medical records for the women and their children held in the Clinical Practice Research Datalink mother-baby dataset. It is anticipated that over 400,000 mother-baby pairs will be included, of whom about 8,000 will have been born after ART. The oldest children will have been followed up for over 20 years. We will be exploring the health of children and their mothers using information that is recorded by the doctor or nurse practitioner when they visit their doctor's surgery, such as diagnoses of medical conditions, prescriptions for medication and referrals for specialist treatment. The increased use of health services, if any, among ART mother-baby pairs will also be assessed.