CAREFOL-HT - Clinical Antenatal Randomised study to CharactErise key roles of TetrahydroFOLate in HyperTensive Pregnancies
CAREFOL-HT is investigating whether the circulating molecule tetrahydropbiopterin (BH4), plays a role in pre-eclampsia and if its levels are associated with changes in the structure and function of the heart and blood vessels in mothers and babies.
High blood pressure during pregnancy is a worldwide health problem that can be dangerous to mothers and commonly causes premature birth and small babies. There is also growing evidence that mothers who suffer from high blood pressure in pregnancy, and their babies, have a higher risk of high blood pressure and cardiovascular disease later in life. Previous studies have revealed detrimental changes in the structure and function of the heart and blood vessels of mothers, and their babies, who experience this common complication. These changes may explain their increased risk of later disease. We have also learned through previous studies that tetrahydrobiopterin (BH4), a molecule that has a role in blood vessel health, plays an important role in stabilising blood vessel function. Lower levels of BH4 are evident in both the placenta and the umbilical cord from mothers with high blood pressure. We, therefore, want to investigate how closely BH4 levels are related to clinical features of pre-eclampsia and whether altering levels of BH4, using a nutritional supplement, improves features of the disease such as blood vessel function. To do this, we need to compare the levels of BH4 between mothers with pre-eclampsia, those taking the supplement and those without pre-eclampsia. We also compare how the heart and blood vessels look and function in these groups using ultrasound methods, including echocardiography and fetal sonography.
CAREFOL-HT will assess how levels of BH4 differ in pregnant women with high blood pressure and if this is reflected in functional changes in the heart and blood vessels of these women. We will also determine whether changing levels of BH4, using a tetrahydrofolate supplement (5-MTHF), changes blood vessel function.
We are asking females aged > 18 up to 45 years of age, with and without the diagnosis of pre-eclampsia (at less than 34 weeks of gestation), to take part.
There are three study visits. The first two visits last up to 2 hours and take place at Women’s Centre in the John Radcliffe Hospital in Oxford. Visit 1 and 2 include maternal echocardiography, blood tests, blood vessel ultrasound (flow-mediated dilation), and a fetal ultrasound scan. We will also record blood pressure during this visit and collect demographic and anthropometric data. Visit three will occur after delivery and involve collection of the placenta and umbilical cord collection. After this, your participation in our study will finish.
Support for the study is provided by research funding from the British Heart Foundation with additional support from a Medical Research Council programme grant and the NIHR Oxford Biomedical Research Centre. The 5-MTHF supplement and placebo supplement is provided by Merck & Cie.
All research in the NHS is looked at by an independent group of people called a Research Ethics Committee, to protect your safety, rights, wellbeing and dignity. This study has been reviewed by Wales Research Ethics Committee 6, (Reference 21/WA/1069).
The CAREFOL-HT Study team