Blood Pressure and Angiogenic Markers in Pregnancy: Contributors to Pregnancy-Induced Hypertension and Offspring Cardiovascular Risk

Hypertension. 2020 Sep;76(3):901-909. doi: 10.1161/HYPERTENSIONAHA.119.13966. Epub 2020 Jun 8.


Pregnancy-induced hypertension is a severe pregnancy complication, increasing risk of long-term cardiovascular disease in mothers and offspring. We hypothesized that maternal blood pressure in pregnancy associated with offspring blood pressure; that the associations were sex-specific; and that maternal circulating placental angiogenic markers (PlGF [placental growth factor] and sFlt-1 [soluble fms-like tyrosine kinase-1]) mediated this relationship. We analyzed data from 2434 women and 2217 children from the Odense Child Cohort, a prospective Danish cohort study. Offspring blood pressure trajectory from 4 months to 5 years was highly associated to maternal first, second, and third trimester blood pressure, and mean blood pressure in pregnancy, independent of maternal and offspring covariates. There were offspring sex-specific associations: Girls from mothers in the highest quartile of first and third trimester blood pressure had significantly higher systolic blood pressure at 5 years than the rest of the cohort (mean difference±SEM: 1.81±0.59 and 2.11±0.59 mm Hg, respectively, all P<0.01); whereas boys had significantly higher diastolic blood pressure at 5 years (mean difference±SEM: 1.11±0.45 and 1.03±0.45, respectively, all P<0.05). Concentrations of PlGF at gestational week 28 correlated inversely to maternal gestational blood pressure trajectory, independent of the diagnosis of pregnancy-induced hypertension, adjusted β coefficients (95% CI) for predicting systolic blood pressure (SBP): -3.18 (-4.66 to -1.70) mm Hg, for predicting diastolic blood pressure (DBP): -2.48 (-3.57 to -1.40) mm Hg. In conclusion, maternal gestational blood pressure predicted offspring blood pressure trajectory until 5 years in a sex-differential manner. Furthermore, subtle alterations in blood pressure in early pregnancy preceded hypertension or preeclampsia, and PlGF was a mediator of cardiovascular health in pregnancy.

Keywords: blood pressure; hypertension, pregnancy-induced; placenta; pre-eclampsia; pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / metabolism
  • Blood Pressure / physiology
  • Blood Pressure Determination / statistics & numerical data*
  • Child, Preschool
  • Correlation of Data
  • Denmark / epidemiology
  • Female
  • Gestational Age
  • Humans
  • Hypertension, Pregnancy-Induced* / blood
  • Hypertension, Pregnancy-Induced* / diagnosis
  • Hypertension, Pregnancy-Induced* / epidemiology
  • Infant
  • Male
  • Placenta Growth Factor / blood*
  • Pre-Eclampsia* / blood
  • Pre-Eclampsia* / diagnosis
  • Pre-Eclampsia* / epidemiology
  • Pregnancy
  • Prenatal Exposure Delayed Effects* / diagnosis
  • Prenatal Exposure Delayed Effects* / epidemiology
  • Risk Assessment
  • Sex Factors
  • Vascular Endothelial Growth Factor Receptor-1 / blood*


  • Biomarkers
  • PGF protein, human
  • Placenta Growth Factor
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1