Intrauterine growth restriction: impact on cardiovascular development and function throughout infancy

Abstract

Intrauterine growth restriction (IUGR) refers to the situation where a fetus does not grow according to its genetic growth potential. One of the main causes of IUGR is uteroplacental vascular insufficiency. Under these circumstances of chronic oxygen and nutrient deprivation, the growth-restricted fetus often displays typical circulatory changes, which in part represent adaptations to the suboptimal intrauterine environment. These fetal adaptations aim to preserve oxygen and nutrient supply to vital organs such as the brain, the heart, and the adrenals. These prenatal circulatory adaptations are thought to lead to an altered development of the cardiovascular system and "program" the fetus for life long cardiovascular morbidities. In this review, we discuss the alterations to cardiovascular structure, function, and control that have been observed in growth-restricted fetuses, neonates, and infants following uteroplacental vascular insufficiency. We also discuss the current knowledge on early life surveillance and interventions to prevent progression into chronic disease. Intrauterine growth restriction (IUGR) refers to the situation where a fetus does not grow according to its genetic growth potential. The main cause of IUGR in developed countries is uteroplacental vascular insufficiency (1), which drives the fetus to redistribute its cardiac output to preserve oxygen and nutrient supply to the brain, heart, and adrenals. Although these adaptive circulatory changes are beneficial during intrauterine life, they are thought to cause dysfunctional development of the cardiovascular system and "program" the fetus for life long cardiovascular morbidities (2). This is also known as the Developmental Origins of Health and Disease hypothesis, which postulates that insults during intrauterine and early postnatal development can permanently change the body's structure, function, and metabolism and influence susceptibility to adult noncommunicable diseases (2). Despite their increased risk of cardiovascular disease, infants born growth restricted usually do not receive long-term cardiovascular follow-up. Depending on the definition used, IUGR can occur in up to 10% of pregnancies, and as cardiovascular disease is the number one cause of death worldwide (3), early identification of cardiovascular risk factors and targeted interventions in this high-risk population are of major clinical importance. In this review, we discuss the alterations of cardiovascular structure, function, and control that have been observed in infants born growth restricted and their implications for surveillance and intervention to prevent progression into chronic disease. CHALLENGES IN IDENTIFYING IUGRThe current literature uses many different definitions of IUGR, which may explain some of the contradicting findings discussed in this review. Traditionally, and most commonly, IUGR is defined as a birth weight below the 10th percentile for gestational age on the normative population growth curve (4). This definition, however, merely describes those who ...

Pravastatin therapy during preeclampsia prevents long-term adverse health effects in mice

“…In addition, intrauterine growth restriction, observed in the PE model, might also have a direct effect on organ development, such as the kidney and the heart, contributing to the increased cardiovascular risk observed in the offspring exposed to PE (36).…”

Altered feto-placental vascularization, feto-placental malperfusion, and fetal growth restriction in mice with Egfl7 loss-of-function

“…Uteroplacental vascular insufficiency, the main cause of IUGR, results in chronic oxygen and nutrient deprivation. Fetal circulatory adaptations compensate for growth restriction, but also program the fetus for increased risk of hypertension, cardiovascular disease and type 2 diabetes later in life (Osmond and Barker, 2000;Cohen et al, 2016). It would be of interest to determine whether the IUGR observed in Egfl7 −/− embryos is linked to morbidities in the adult.…”

Reduction in Cerebral Oxygenation due to Patent Ductus Arteriosus Is Pronounced in Small-for-Gestational-Age Neonates

“…IUGR is associated with systemic vascular remodelling [18]. Histological changes of the ductus arteriosus have also been reported [19].…”