In Utero Origins of Hypertension: Mechanisms and Targets for Therapy

Abstract

The developmental origins of health and disease theory is based on evidence that a suboptimal environment during fetal and neonatal development can significantly impact the evolution of adult-onset disease. Abundant evidence exists that a compromised prenatal (and early postnatal) environment leads to an increased risk of hypertension later in life. Hypertension is a silent, chronic, and progressive disease defined by elevated blood pressure (>140/90 mmHg) and is strongly correlated with cardiovascular morbidity/mortality. The pathophysiological mechanisms, however, are complex and poorly understood, and hypertension continues to be one of the most resilient health problems in modern society. Research into the programming of hypertension has proposed pharmacological treatment strategies to reverse and/or prevent disease. In addition, modifications to the lifestyle of pregnant women might impart far-reaching benefits to the health of their children. As more information is discovered, more successful management of hypertension can be expected to follow; however, while pregnancy complications such as fetal growth restriction, preeclampsia, preterm birth, etc., continue to occur, their offspring will be at increased risk for hypertension. This article reviews the current knowledge surrounding the developmental origins of hypertension, with a focus on mechanistic pathways and targets for therapeutic and pharmacologic interventions.

Race and Sex Differences of Long-Term Blood Pressure Profiles From Childhood and Adult Hypertension

“…The concept has been widely accepted that roots of chronic diseases, including hypertension, extend back into early life (5–8,14–16). The theory of developmental origins of hypertension is supported by evidence from a large number of longitudinal epidemiological studies showing that childhood BP levels are significantly and positively associated with adult BP levels (18–21).…”

“…The black-white and gender differences in BP even occur in childhood (5–8), with black children showing higher levels and faster rate of change than white children (5,6). A large body of evidence suggests that socioeconomic, psychologic, physiologic, metabolic and genetic mechanisms underlying the development of hypertension are different between races and genders in human populations (4,8–14). …”

“…Prenatal and early postnatal growth is thought to cause persisting impairment in many physiologic and metabolic pathways that affect hypertension susceptibility in later life (14–17). The case for childhood origins of hypertension is supported by numerous publications from large-scale population-based cohorts of cardiovascular risk factors followed since childhood (18–22).…”

In Development—A New Paradigm for Understanding Vascular Disease

“…Epidemiological studies by Barker and others demonstrated that compared to infants born ‘appropriate for gestational age’ (AGA), those born ‘small for gestational age’ (SGA) are at increased risk for developing cardiovascular and metabolic diseases (168–170). This led to the ‘Barker hypothesis’: that a suboptimal environment or poor nutrition during fetal or neonatal development predisposes an individual to develop cardiovascular and metabolic diseases later in life.…”

Developmental Programming of Hypertension

“…Recent reviews highlight a role for numerous factors in the pathogenesis of the developmental programming of hypertension including epigenetic processes, glucocorticoids, reduced nephron number, activation of the sympathetic nervous system and the renin angiotensin system ( RAS ) and endothelial dysfunction (4, 5, 6, 7). Studies published in Hypertension and other journals highlight the complexity of cardiovascular ( CV ) risk that has its origins in fetal life.…”