Impact of the Vulnerable Preterm Heart and Circulation on Adult Cardiovascular Disease Risk

Abstract

Preterm birth accounts for over 15 million global births per year. Perinatal interventions introduced since the early 1980s, such as antenatal glucocorticoids, surfactant, and invasive ventilation strategies, have dramatically improved survival of even the smallest, most vulnerable neonates. As a result, a new generation of preterm-born individuals has now reached early adulthood, and they are at increased risk of cardiovascular diseases. To better understand the sequelae of preterm birth, cardiovascular follow-up studies in adolescents and young adults born preterm have focused on characterizing changes in cardiac, vascular, and pulmonary structure and function. Being born preterm associates with a reduced cardiac reserve and smaller left and right ventricular volumes, as well as decreased vascularity, increased vascular stiffness, and higher pressure of both the pulmonary and systemic vasculature. The purpose of this review is to present major epidemiological evidence linking preterm birth with cardiovascular disease; to discuss findings from clinical studies showing a long-term impact of preterm birth on cardiac remodeling, as well as the systemic and pulmonary vascular systems; to discuss differences across gestational ages; and to consider possible driving mechanisms and therapeutic approaches for reducing cardiovascular burden in individuals born preterm.

Keywords: cardiovascular diseases; hypertension; hypertension, pulmonary; premature birth; vascular stiffness.

Figure 1.

Summary of long-term cardiovascular sequelae of preterm birth. RAS indicates renin-angiotensin system.

Figure 2.

Gestational age categories. Cardiovascular disease risk determined from large population-based studies increases with the degree of prematurity.

Figure 3.

Examples of short-axis end-diastolic cardiac images acquired using cardiovascular magnetic resonance from 3 young adult men born at different gestational ages. A 27-y-old man born at 26⁺¹ weeks’ gestation (extremely preterm; A); a 27-y-old man born at 32⁺⁵ weeks’ gestation (moderately preterm; B); and a 28-y-old man born at 40⁺⁰ weeks’ gestation (term; C). The extremely preterm–born young adult man (A) has the smallest left ventricular (LV) end-diastolic volume index and the lowest LV mass index. Wall thickness is greatest in the moderately preterm–born young adult man (B), with visible relative hypertrophy. The young adult man born at term (C) has a higher LV end-diastolic volume index than both individuals born preterm, with an LV mass between the two.

Figure 4.

Examples of axial cardiovascular magnetic resonance images at the level of the pulmonary artery (PA) bifurcation from 2 young adult women born at different gestational ages demonstrating increased PA to aorta (Ao) after preterm birth. A 28-y-old woman born at 27⁺⁶ weeks’ gestation (extremely preterm; PA:Ao is 1.03; A) and a 28-y-old woman born at 40⁺² weeks’ gestation (term; PA:Ao is 0.79; B).

Figure 5.

Screening considerations for adults born preterm. DLCO indicates diffusing capacity of the lungs for carbon monoxide; and PFT, pulmonary function test.