Angiogenic factors during pregnancy in Asian women with elevated blood pressure in early pregnancy and the risk of preeclampsia: a longitudinal cohort study

OBJECTIVE: It remains unclear what roles placenta-originated angiogenic factors play in the pathogenesis of preeclampsia among hypertensive women. We compared maternal soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) levels throughout pregnancy in women with normal blood pressure (BP), elevated BP and hypertension in early pregnancy and their risks of developing preeclampsia. DESIGN: A prospective cohort study. SETTING: KK Women’s and Children’s Hospital, Singapore. PARTICIPANTS: 923 women with singleton pregnancy <14 weeks of gestation were included in the prospective Neonatal and Obstetrics Risks Assessment cohort between September 2010 and October 2014. Systolic, diastolic, mean arterial blood pressure (MAP) were measured at 11–14 weeks. PRIMARY AND SECONDARY OUTCOMES: Maternal serum sFlt-1, PlGF and sFlt-1/PlGF ratio were tested at 11–14, 18–22, 28–32 and 34 weeks onwards of gestation. Preeclampsia was main pregnancy outcome. RESULTS: Women were divided based on their BP in early pregnancy: normal (n=750), elevated BP (n=98) and hypertension (n=75). Maternal sFlt-1 levels and sFlt-1/PlGF ratios were higher in hypertensive women throughout pregnancy, but maternal PlGF levels were not significantly lower. Rise in maternal systolic, diastolic BP and MAP at 11–14 weeks were significantly associated with higher sFlt-1/PlGF ratios during pregnancy. A 10 mm Hg increase in MAP was associated with a 5.6-fold increase in risk of preterm preeclampsia and a 3.3-fold increase in risk of term preeclampsia, respectively. CONCLUSION: Women with elevated BP in early pregnancy already had a higher sFlt-1/PlGF ratio in early gestation and throughout pregnancy, and an increased risk of preeclampsia. In contrast, PlGF levels in these women remained normal.