120. A study to investigate calcium mechanisms in women at high risk of pre-eclampsia through analysis of putative protein markers. A sub-study of the calcium and pre-eclampsia (CAP) study (a WHO collaboration)

Abstract

Introduction The mechanisms by which calcium reduces the severity of preeclampsia are currently not established. Objective/hypothesis Blood samples were studied from participants in CAP, a recent study of the efficacy of giving calcium prior to pregnancy to reduce preeclampsia. The aim was to characterize blood biomarkers in order to identify potential mechanisms by which calcium might exert an effect on preventing preeclampsia. Identifying these mechanisms could guide additional interventions. Methods Women with previous preeclampsia were randomised to calcium 500 mg/day or placebo prior to pregnancy. From 20 weeks’ gestation both groups received 1500 mg/day Ca as recommended by WHO. Blood samples were obtained pre-pregnancy and at 8, 20 and 32 weeks’ gestation with biomarkers chosen to assess placental, angiogenic, vasoconstrictor/dilator, endothelial and immune function. Results Altogether 111 women were included in this sub-study. Eleven women (20%) in the placebo group and nine (16%) in the calcium group developed preeclampsia. Biomarker comparisons (calcium vs placebo) Most biomarkers increased over time with similar increases observed across calcium and placebo groups. AT1-AA and Endothelin were relatively constant over time, Copeptin values were higher in the calcium group (pre-pregnancy through to week 8). Biomarker comparisons (preeclamptic vs non-preeclamptic women) Biomarkers levels were similar, on average, between women who went on to develop preeclampsia and those who did not. Slight differences were observed for some biomarkers with directionality of results similar to reported values (e.g. PIGF lower and Activin-A, s-ENG and PIGF higher in women who developed pre-eclampsia). Copeptin values were higher in the preeclamptic women prior to pregnancy and at weeks 8 and 20. Discussion/conclusion This small study did not demonstrate any obvious difference in analytes assessing relevant pathophysiological pathways for preeclampsia with calcium treatment. This exploratory study was not powered to detect or exclude relevant effects with certainty.