Association between Neonatal Intakes and Hyperglycemia, and Left Heart and Aortic Dimensions at 6.5 Years of Age in Children Born Extremely Preterm

Abstract

Survivors of extremely preterm birth (gestational age < 27 weeks) have been reported to exhibit an altered cardiovascular phenotype in childhood. The mechanisms are unknown. We investigated associations between postnatal nutritional intakes and hyperglycemia, and left heart and aortic dimensions in children born extremely preterm. Postnatal nutritional data and echocardiographic dimensions at 6.5 years of age were extracted from a sub-cohort of the Extremely Preterm Infants in Sweden Study (EXPRESS; children born extremely preterm between 2004–2007, n = 171, mean (SD) birth weight = 784 (165) grams). Associations between macronutrient intakes or number of days with hyperglycemia (blood glucose > 8 mmol/L) in the neonatal period (exposure) and left heart and aortic dimensions at follow-up (outcome) were investigated. Neonatal protein intake was not associated with the outcomes, whereas higher lipid intake was significantly associated with larger aortic root diameter (B = 0.040, p = 0.009). Higher neonatal carbohydrate intake was associated with smaller aorta annulus diameter (B = −0.016, p = 0.008). Longer exposure to neonatal hyperglycemia was associated with increased thickness of the left ventricular posterior wall (B = 0.004, p = 0.008) and interventricular septum (B = 0.004, p = 0.010). The findings in this study indicate that postnatal nutrition and hyperglycemia may play a role in some but not all long-lasting developmental adaptations of the cardiovascular system in children born extremely preterm.

Physiological response to fetal intravenous lipid emulsion

“…Much less is known about the relationship between lipids and myocardial health in the immature heart. Even brief exposure to high lipid levels in infancy is associated with increased aortic root diameter, aortic stiffness, and decreased peak systolic circumferential strain in later life [ 5 , 6 ]. Although there was normal Oil Red O staining in the left ventricular myocardium of the sheep in the present study, further investigation is warranted to determine the mechanisms contributing to cardiovascular pathology in individuals that received lipid emulsion PN.…”

“…Preterm neonates that receive lipid emulsion parenteral nutrition (PN) sometimes develop morbidities, including fat accumulation in the lung [ 4 ], cardiac pathologies [ 5 , 6 ], and PN-associated liver disease (PNALD) [ 7–9 ]. A clear understanding of the pathophysiological response to high circulating lipids in the preterm newborn is complicated by the other simultaneous physiological challenges of preterm birth.…”

Understanding the preterm human heart: What do we know so far?

“…Preterm‐born neonates are often unable to maintain similar intrauterine growth rates after birth, resulting in a higher need for nutrients during the neonatal period (Hamayun et al, 2021; Hay Jr., 2018; Horbar et al, 2015). This causes undernutrition and nutritional imbalances such as hyperglycemia to be common in preterm newborns admitted to the neonatal intensive care unit, suggesting that nutritional factors play a key role in their development (Hamayun et al, 2021; Hay Jr., 2018; Zamir et al, 2018). Different studies support this notion.…”

“…For example, in a cohort of prematurely born individuals followed up since birth, neonatal intravenous lipid exposure caused a subsequent rise in cholesterol, which was associated with aberrant aortic and myocardial function in adulthood (Lewandowski et al, 2011). Furthermore, in a cohort of extremely preterm‐born children born at <27 weeks of gestation, differences in lipid and protein intake during the first four postnatal weeks were linked to altered LV outflow tract dimensions at 6.5 years after birth (Hamayun et al, 2021). In addition to this, children who were exposed to a significant period of neonatal hyperglycemia demonstrated increased LV wall thickness, as well as higher blood pressures (Hamayun et al, 2021; Zamir et al, 2019).…”

“…Furthermore, in a cohort of extremely preterm‐born children born at <27 weeks of gestation, differences in lipid and protein intake during the first four postnatal weeks were linked to altered LV outflow tract dimensions at 6.5 years after birth (Hamayun et al, 2021). In addition to this, children who were exposed to a significant period of neonatal hyperglycemia demonstrated increased LV wall thickness, as well as higher blood pressures (Hamayun et al, 2021; Zamir et al, 2019).…”