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

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.

This Transition Support Award will allow the applicant to consolidate the research outlined in an existing Career Development Award.

The main aim of the project is to assess the long-term health outcomes of mothers and children after the use of assisted reproductive technologies (ART) in England. A linked dataset combining information from the Clinical Practice Research Datalink and the Human Fertilisation and Embryology Authority (HFEA) register has been created. Over 400,000 babies, born 1991-2018, and their mothers, who are registered at GP practices in England, will be included. Duration of follow-up varies from a few months to over 20 years, depending on date of delivery. The main 'exposure' is ART, which comprises IVF, ICSI, and ovulation induction; other techniques (e.g. cryopreservation) will be examined, where possible. Outcome data include all consultations, diagnoses, prescriptions and referrals recorded by GPs, supplemented by data on hospital episodes and mental health treatment. Key outcomes for children include growth, illness and infection, atopic and allergic conditions, behaviour and developmental outcomes; and for mothers, physical and mental health. Multivariable regression models will be used to estimate adjusted rate ratios and odds ratios as appropriate, comparing outcomes in the ART and non-ART groups. An economic analysis will compare differences in NHS expenditure on the long-term provision of care for ART and non-ART pairs, and model future costs.
Concern among researchers that low consent rates since 2009 adversely affect the representativeness of the HFEA dataset, means that the newest data are under-utilised. Methodological work to explore the impact of missingness, and to develop methods to reduce the potential bias, will be conducted.

This study will contribute to the evidence for the safety and costs of ART in England, and provide tools for future work using these rich data sources