Long term health outcomes for women and their children after assisted reproductive technologies: a data linkage study for England

每7对夫妇中就有1对不孕不育，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20万名儿童因抗逆转录病毒治疗而出生，现在每年约占新生儿总数的1%-2%。大多数试管婴儿的出生都是健康的，但有很好的证据表明，试管婴儿的围产期结局不良(早产、低出生体重、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更高。认知、发展和行为问题也已被发现，尽管证据有限，研究结果不那么令人信服--部分原因是这一领域的研究很难进行，有时还存在缺陷。其他不良后果的发生率也较高，如哮喘和自闭症，但同样，证据很少。对抗逆转录病毒治疗后出生的儿童的健康和发展结果的研究往往只关注儿童早期，因此对抗逆转录病毒治疗儿童的长期健康和发展研究仍然相对不足。在接受抗逆转录病毒治疗时，妇女也有公认的风险，治疗失败对妇女及其伴侣的负面影响已有记录。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、被认为是高危怀孕以及对分娩的焦虑都可能产生持久的影响。接受抗逆转录病毒治疗后，产后抑郁症的发生率更高，患者似乎更容易受到后来的抑郁发作的影响。对接受治疗的女性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产妇身心健康和卫生服务使用的长期影响的问题仍然没有得到回答。这项研究旨在解决这些问题，并为抗逆转录病毒治疗母亲及其子女的健康和福祉提供长期证据。该项目使用了不孕不育诊所(代表人类受精和胚胎学管理局)收集的1991年以来英国所有抗逆转录病毒治疗的数据，并将其与临床实践研究数据链接母婴数据集中持有的妇女及其孩子的全科医生医疗记录联系起来。预计将有超过28万对母婴，其中约4000对将在接受人工授精后出生。年龄最大的孩子将接受20多年的跟踪调查。我们将使用医生或护士在他们看医生的手术时记录的信息来探索儿童及其母亲的健康状况，例如医疗状况的诊断、药物处方和专科治疗的转介。还将评估抗逆转录病毒母婴配对中增加使用卫生服务的情况。目前，HFEA寻求所有接受ART的夫妇的同意，允许科学家在研究中使用他们的数据，但只有不到一半的人同意。该项目的另一个方面将是评估低参与率对使用HFEA数据的研究结果的影响，并探索如何减少或消除缺失数据的影响。这些项目都使用常规数据，但我们还将进行一项研究，招募接受治疗的夫妇，并探索他们为什么选择同意或拒绝进行研究。这部分研究的目的是提供信息，以尝试并帮助提高未来的同意率。这项研究将由牛津大学国家围产期流行病学部的流行病学家克莱尔·卡森领导，他将与围产期和孕产妇流行病学(詹妮弗·库林祖克、玛丽亚·奎格利、阿利斯泰尔·萨特克里夫)、定性研究方法(丽莎·辛顿)、卫生经济学(奥利弗·里维埃拉-阿里亚斯)和丢失数据管理(迈克·肯沃德)的专家合作。

Infertility affects 1 in 7 couples, and the number of babies using Assisted Reproductive Technologies (ART) such as IVF is increasing. Since 1991 over 200,000 children have been born in the UK as a result of ART, which now accounts for about 1-2% 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 research seeks to address these issues, 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 280,000 mother-baby pairs will be included, of whom about 4,000 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. Currently the HFEA seeks consent from all couples undergoing ART to allow scientists to use their data in research, but less than half agree. Another aspect of this project will be to assess the effect of this low participation rate on the results of research using the HFEA data, and to explore ways that the effects of missing data can be reduced or removed. These projects all use routine data, but we will also be conducting a study that recruits couples undergoing treatment and explores why they choose to give, or to refuse, consent for research. The aim of this part of the study is to provide information to try and help increase consent rates in the future. The research will be led by Claire Carson, an epidemiologist at the National Perinatal Epidemiology Unit, University of Oxford, who will be working with specialists in perinatal and maternal epidemiology (Jennifer Kurinczuk, Maria Quigley, Alistair Sutcliffe), qualitative research methods (Lisa Hinton), health economics (Oliver Riviera-Arias) and the management of missing data (Mike Kenward).