Persistence of Cardiac Remodeling in Preadolescents With Fetal Growth Restriction

Abstract

Background— Fetal growth restriction (FGR) affects 5% to 10% of newborns and is associated with increased cardiovascular mortality in adulthood. We evaluated whether prenatal cardiovascular changes previously demonstrated in FGR persist into preadolescence. Methods and Results— A cohort study of 58 FGR (defined as birth weight below 10th centile) and 94 normally grown fetuses identified in utero and followed-up into preadolescence (8–12 years of age) by echocardiography and 3-dimensional shape computational analysis. Compared with controls, FGR preadolescents had a different cardiac shape, with more spherical and smaller hearts. Left ventricular ejection fraction was similar among groups, whereas FGR had decreased longitudinal motion (decreased mitral annular systolic peak velocities: control median, 0.11 m/s [interquartile range, 0.09–0.12] versus FGR median 0.09 m/s [interquartile range, 0.09–0.10]; P <0.01) and impaired relaxation (isovolumic relaxation time: control, 0.21 ms [interquartile range, 0.12–0.35] versus FGR, 0.35 ms [interquartile range, 0.20–0.46]; P =0.04). Global longitudinal strain was decreased (control mean, −22.4% [SD, 1.37] versus FGR mean, −21.5% [SD, 1.16]; P <0.001) compensated by an increased circumferential strain and with a higher prevalence of postsystolic shortening in FGR as compared with controls. These differences persisted after adjustment for parental ethnicity and smoking, prenatal glucocorticoid administration, preeclampsia, gestational age at delivery, days in intensive care unit, sex, age, and body surface area at evaluation. Conclusions— This study provides evidence that cardiac remodeling induced by FGR persists until preadolescence with findings similar to those reported in their prenatal life and childhood. The findings support the hypothesis of primary cardiac programming in FGR for explaining the association between low birth weight and cardiovascular risk in adulthood.

Main Patterns of Fetal Cardiac Remodeling

“…However, while postnatal cardiac remodeling reverts after treating the cause, cardiac remodeling occurring in utero might persist postnatally even after the trigger has disappeared. Actually, postnatal persistence of fetal cardiac remodeling has been demonstrated in several conditions such as fetal growth restriction, maternal diabetes, exposure to antiretroviral drugs, prematurity, or assisted reproductive technologies [9,10,16,[34][35][36][37][38]. This phenomenon is explained by the fetal programming hypothesis that proposes a prenatal origin for some adult cardiovascular diseases.…”

The Transitional Heart: From Early Embryonic and Fetal Development to Neonatal Life

“…It is likely that these early changes are of long-term clinical significance, given that epidemiologic studies have consistently shown an association between IUGR and an increased rate of cardiovascular mortality in adulthood [99]. In line with this, it has been demonstrated that many of the cardiovascular changes that first emerge during fetal life, including cardiac morphological changes, subclinical myocardial dysfunction, arterial remodeling, and impaired endothelial function, persist long-term [94]. DOI: 10.1159/000501906 Preeclampsia Preeclampsia is a common hypertension-related pregnancy complication that is characterized by proteinuria and maternal organ dysfunction (such as renal insufficiency, liver, and placental dysfunction) post 20 weeks' gestation, affecting over 8% of pregnancies worldwide [9,100].…”

“…IUGR offspring demonstrate early cardiac changes that emerge during fetal life and persist into neonatal life, including a relatively hypertrophied ventricular septum, LV dilatation, decreased myocardial reserve, a more globular cardiac morphology, and abnormal early postnatal hemodynamic adaptations [8,[93][94][95]. Furthermore, IUGR neonates exhibit an increase in left myocardial performance index (a marker of ventricular dysfunction), an inability to increase LV stroke volume, as well as reduced heart rate in the first week of postnatal life when compared with appropriate-for-gestational-age controls [8,96].…”

Transgenerational transmission of small‐for‐gestational age

“…It affects about 5-10% of all pregnancies, and is one of the main causes of perinatal morbidity and mortality worldwide 3 . Apart from perinatal complications, individuals born small present long-term consequences, with an increased risk for cardiovascular and metabolic disease in adulthood [4][5][6][7][8] .…”