Causes of Disease Through the Life Course

Collaborative studies have been developed in the national 1946 and 1958 birth cohorts and in the British Regional Heart Study cohort, which in combination have allowed us to investigate ill-health associations throughout the life course. Recent studies have investigated the relationships of cardiovascular risk with obesity and weight gain at different ages, and with socioeconomic position in childhood and adult life.

The recent Zika virus epidemic and the association of first trimester exposure with microcephaly and other brain anomalies in foetuses has highlighted the necessity of having a good surveillance network for congenital anomalies across Latin America. We are helping establish such a network, RELAMC. We are also working with the member registries of RELAMC to investigate the prevalence of microcephaly and other anomalies associated with maternal infections across Latin America from 2010 to 2017 (before, during and after the Zika virus epidemic).

Electronic databases of consultations in UK primary care have been used to quantify the risks of different types of infectious disease among people living with diabetes (both types 1 and types 2), as well the risks of adverse events (hospitalisation, mortality) due to infections. We have further quantified the role of poor diabetes control as well as changes or fluctuations in control on infection risk. 

Through systematic reviews, we previously evaluated the influence of birth weight and infant feeding on markers of cardiovascular risk in middle-age. The relationship between birth weight and measures of obesity and risk of diabetes in childhood has been a recent focus in the CHASE study of mainly local children from different ethnic groups.

Through a large number of international collaborations, genetic data from the British 1958 birth cohort has been collated and analysed in our institute. This data has contributed to many genome-wide association studies over the last decade. Interactions have been explored between genetic variants and non-genetic exposures such as smoking and environmental agents, with particular emphasis on respiratory and allergic disease outcomes.

Exposure to prescription and over-the-counter medication during pregnancy is common. Despite this, information on the safety of medicines in human pregnancy is lacking, particularly for new products; a key reason is that pregnant women are usually exempt from pre-marketing medication safety studies. In addition, the ability to predict risks of congenital anomalies (CAs) in humans from evidence of animal reproductive toxicity is limited. As such, post-marketing studies and the continued surveillance of medication use in pregnancy are essential in order to detect new teratogens. EUROmediCAT is a network of European congenital anomaly registries which collect information on first trimester medication exposures. We are continuing to develop a systematic signal detection method to identify medications potentially associated with an increased risk of specific CAs.