Presented at the Neonatal Society 2011 Autumn Meeting.
Lewandowski AJ1,2, Davis EF1,2, Lazdam M1,2, Diesch J1, Francis J2, Lucas A3, Singhal A3, Neubauer S2, Wilkinson AR4, McCormick K4, Kelly B5, Leeson P1,2
1 Oxford Cardiovascular Clinical Research Facility, Oxford, UK
2 University of Oxford Centre for Clinical Magnetic Resonance Research, Department of Cardiovascular Medicine, University of Oxford, Oxford, UK
3 MRC Childhood Nutrition Research Centre, Institute of Child Health, London, UK
4 Department of Paediatrics, John Radcliffe Hospital, Oxford. UK
5 Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Oxford. UK
Background: The postnatal period in very premature infants corresponds with a key developmental stage that normally occurs during the last trimester in utero. Animal studies suggest targeted interventions in this critical window have a long term cardiovascular impact. We determined whether, in humans, interventions during this period modify cardiovascular phenotype.
Methods: The Early Vascular Study is a longitudinal study of over 200 subjects now in young adulthood (23 – 28 years) that includes very preterm-born subjects (gestational age 30.4 ± 2.7 weeks; birthweight 1312 ± 334 g) and controls born term to uncomplicated pregnancies. Subjects undergo detailed cardiovascular phenotyping and have perinatal-related data. We studied the overall impact of prematurity on cardiovascular risk and then explored how perinatal glucocorticoid and lipid exposure in humans modifies phenotype.
Results: Preterm-born young adults have significantly increased blood pressure with changes in arterial stiffness, as well as left ventricular mass (P < 0.01). Interventions during their perinatal period had specific, long term effects. Intravenous lipids associate with an elevation in circulating lipids during administration and then greater aortic stiffness in young adulthood (r=0.616, P < 0.0001), particularly in the abdominal aorta (P = 0.012) (1), as well as reduced left ventricular systolic circumferential strain (P = 0.006). In contrast, antenatal glucocorticords lead to a selective increase in aortic arch stiffness (P < 0.01) characteristic of accelerated vascular ageing, and abnormalities in glucose metabolism in young adulthood.
Conclusion: Adults born preterm have an adverse cardiovascular risk profile. Furthermore, we demonstrate for the first time in humans that glucocorticoid or lipid exposure during critical developmental periods is associated with selective changes in cardiovascular structure, function and metabolism.
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1. Lewandowski AJ, Lazdam M, Davis E, Kylintireas I, Diesch J, Francis J, Neubauer S, Singhal A, Lucas A, Kelly B, Leeson P. Short-Term Exposure to Exogenous Lipids in Premature Infants and Long-Term Changes in Aortic and Cardiac Function. Arteriosclerosis, Thrombosis, and Vascular Biology. 2011;31(9):2125-2135.