Fetal Programming Elevated Blood Pressure in Offspring Born Premature to Hypertensive Pregnancy Is Endothelial Dysfunction the Underlying Vascular Mechanism?

Offspring born to mothers with hypertensive pregnancy have higher childhood blood pressure. We hypothesized this relates to prenatally programmed differences in the underlying vascular pathophysiology of the offspring and that these would be most apparent in those born preterm because of severe hypertension. We carried out a 20-year follow-up study of 71 subjects born preterm, 19 to a hypertensive pregnancy and 52 to a normotensive pregnancy. Findings were compared with 38 subjects born at term to uncomplicated pregnancies. Peripheral and central blood pressures were measured, and then central arterial stiffness was assessed by carotid-femoral pulse wave velocity using applanation tonometry. Ultrasound was used to assess flow-mediated endothelial-dependent and independent brachial artery responses and common carotid artery intima-media thickness. Offspring born preterm to either hypertensive or normotensive pregnancy had higher peripheral and central blood pressure compared with full-term born offspring (central mean arterial pressure after preterm hypertensive pregnancy: 84.92 7.0 mm Hg; preterm normotensive pregnancy: 84.13 8.9 mm Hg; full-term pregnancy: 76.24 7.96 mm Hg; P 0.0009). However, underlying vascular phenotype differed. Preterm offspring of normotensive pregnancy had greater arterial stiffness than offspring of hypertensive pregnancy (5.92 0.84 versus 5.42 0.73 m/s; P 0.039), whereas offspring of hypertensive pregnancy had greater carotid intima-media thickness (0.52 0.04 versus 0.48 0.06 mm; P 0.013) and 30% lower flow-mediated dilatation (4.25 4.02% versus 6.79 4.38%; P 0.05). Prematurity is associated with elevated blood pressure in later life. However, predominant underlying vascular phenotype depends on maternal pathology. Targeting endothelial function may be particularly important for primary prevention after hypertension in pregnancy. (Hypertension. 2010; 56:159-165.)