Identification of normal and at-risk trajectories of blood pressure in pregnancy in relation to offspring perinatal health and childhood development

In normal pregnancy blood pressure decreases until mid-pregnancy and then rises until delivery. Women who experience high blood pressure during the second half of pregnancy are diagnosed with a hypertensive disorder of pregnancy; namely gestational hypertension or pre-eclampsia. These can cause the baby to be born early (preterm) or with a low birth weight and in extreme cases they can result in the death of the fetus or mother. This project aims to improve understanding of blood pressure changes during pregnancy, and allow women with unhealthy patterns of change to be identified earlier in pregnancy, so that it might be possible to prevent problems for the mother and her baby. I will do this by taking into account the different characteristics and blood pressure levels of women at the beginning of pregnancy, and developing charts to show how patterns of blood pressure vary by these characteristics. I will determine what the normal ranges of blood pressure over the course of pregnancy are for different women (for example for older women and younger women) so that doctors and midwives can use these to work out when someone is at risk of problems in later pregnancy. I will also investigate whether particular aspects of blood pressure change, for example, the time at which blood pressure begins to rise during pregnancy are related to the risk of problems in pregnancy.

As well as considering the risk of immediate health of the mother and her child, the project will investigate whether children whose mothers have unhealthy changes in blood pressure during pregnancy have higher blood pressure and higher levels of other heart disease risk factors in childhood and adolescence. The relationships of patterns of the mother's blood pressure change in pregnancy with how their child then grows will also be assessed, to find out whether children whose mothers had unhealthy changes in blood pressure have poor levels of growth or are more likely to become obese.

The project will use data from the Avon Longitudinal Study of Parents and Children, which includes around 14,000 women who were pregnant in 1991 and 1992, and also a number of other similar studies from the UK and from other countries, including European countries, Australia and the US.

Aim: To characterise patterns of blood pressure change in pregnancy which are associated with increased risk of adverse health outcomes in offspring.
Objectives:
1. To develop normograms for blood pressure change across pregnancy based on pre/early-pregnancy maternal risk factors, and to assess the predictive ability of deviations from these trajectories to identify women at risk of pre-eclampsia, preterm birth and small for gestational age offspring.
2. To investigate whether particular patterns of maternal blood pressure change are associated with offspring perinatal outcomes and cardiovascular risk factors, growth and changes in adiposity in childhood and adolescence.
3. To identify maternal and fetal genetic variants related to patterns of blood pressure change during pregnancy.
Methodology: The project will use antenatal blood pressure measurements (median 14 per woman) of ~13,000 women in the Avon Longitudinal Study of Parents and Children (ALSPAC). Early-pregnancy risk factors such as maternal body mass index, age, parity, smoking, previous hypertension, family history and markers of socio-economic position have been obtained via questionnaires. Genome wide SNP data is available for ~10000 mother-offspring pairs. The children have attended clinics between the ages of 7 and 18, in which cardiovascular risk factors and anthropometric measurements have been recorded. Statistical analysis will include multivariate multilevel models and Bayesian methods and validation, replication and pooling of results with a number of other similar pregnancy/birth cohorts will be undertaken.
Scientific and Medical Opportunities: Recent findings have highlighted the potential for rates of blood pressure change in addition to blood pressure thresholds to be used to indicate high risk pregnancies. The development of normograms for blood pressure change could enable the identification of women at risk of adverse offspring outcomes earlier than current monitoring allows.

The project's ultimate aim is to improve the monitoring and clinical management of all women undergoing routine antenatal care. The development of normograms for blood pressure change across pregnancy will provide general practitioners, midwives and obstetricians with greater information about their patients' risk of either requiring preterm induced delivery or spontaneously delivering preterm and about their risk of delivering a small for gestational age baby. This will enable more accurate and earlier identification of women requiring more frequent and detailed monitoring throughout their pregnancies. The normograms will be developed within the timeframe of the fellowship, and therefore this benefit of the research would be available by the end of the fellowship. Through my collaboration with Prof Scott Nelson, a nationally very highly regarded obstetrician I will discuss my findings with the Royal College of Obstetricians and Gynaecologists and other relevant bodies and seek ways to translate my research findings (as relevant) into clinical practice.

The research into offspring cardiovascular risk factors, growth and adiposity changes during childhood and adolescence would not have an immediate impact on population health, but it will contribute to our aetiological understanding. Thus it is hoped that information gained could be used to input into the development of interventions aimed at improving the health and development of children whose mothers experienced adverse blood pressure trajectories during their pregnancy. These interventions, if successful, would have potentially lifelong impact on the cardiovascular and musculo-skeletal health of these targeted individuals.

Identification of maternal and fetal genetic variants related to particular patterns of blood pressure change during pregnancy will provide information about the biological mechanisms behind these changes, and inform the development of treatments and interventions to prevent hypertensive disorders of pregnancy.