Risk of hypertension following perinatal adversity: IUGR and prematurity

Abstract

Consistent with the paradigm shifting observations of David Barker and colleagues that revealed a powerful relationship between decreased weight through 2 years of age and adult disease, intrauterine growth restriction (IUGR) and preterm birth are independent risk factors for the development of subsequent hypertension. Animal models have been indispensable in defining the mechanisms responsible for these associations and the potential targets for therapeutic intervention. Among the modifiable risk factors, micronutrient deficiency, physical immobility, exaggerated stress hormone exposure and deficient trophic hormone production are leading candidates for targeted therapies. With the strong inverse relationship seen between gestational age at delivery and the risk of hypertension in adulthood trumping all other major cardiovascular risk factors, improvements in neonatal care are required. Unfortunately, therapeutic breakthroughs have not kept pace with rapidly improving perinatal survival, and groundbreaking bench-to-bedside studies are urgently needed to mitigate and ultimately prevent the tsunami of prematurity-related adult cardiovascular disease that may be on the horizon. This review highlights our current understanding of the developmental origins of hypertension and draws attention to the importance of increasing the availability of lactation consultants, nutritionists, pharmacists and physical therapists as critical allies in the battle that IUGR or premature infants are waging not just for survival but also for their future cardiometabolic health.

Keywords: developmental origins; insulin; leptin; multidisciplinary; preterm; therapy.

Figure 1.

Perinatal factors converge to establish the risk of hypertension. Acting upon genetic susceptibility, maternal health and placental function powerfully influence fetal growth and development. The subsequent hormonal and nutritional milieu impact gene expression and organ morphology, two key determinants of the pathway conceptualized as fetal programming; at times, this adverse intrauterine environment manifests as intrauterine growth restriction or prematurity. Following delivery, the early life environment and postnatal growth continue to reset disease propensity through key regulatory systems, including leptin and insulin signaling pathways, as well as nephron endowment. Over the life course, central leptin resistance, reduced kidney function, and insulin resistance can increase the propensity towards hypertension and other components of the metabolic syndrome, including diabetes and obesity.