Abstract
Introduction:
Preterm birth affects 8–12% of live births and is associated with the development of elevated arterial blood pressure and aortic narrowing in later life; this suggests that preterm birth may alter the development of arteries. Our objective was to determine the effects of preterm birth, accompanied by antenatal corticosteroid administration, on the structure of the aorta and pulmonary artery, which experience different alterations in pressure flow at birth.
Results:
At 11 wk, preterm lambs had significantly thicker aortic walls and a smaller lumen, whereas the morphometry of the pulmonary artery was unaffected. Elastin deposition was markedly increased in the aorta and pulmonary artery and smooth muscle content was reduced in the aorta only. In preterm lambs we found injury in the aorta only; controls were unaffected.
Discussion:
We conclude that moderate preterm birth after antenatal betamethasone can cause injury and persistent alterations in the structure and composition of the aorta, with lesser effects in the pulmonary artery. Our findings suggest that preterm birth may increase the risk of atherosclerosis and aortic aneurysms in later life.
Methods:
Using an established ovine model of preterm birth, lambs were born at 0.9 of gestation and underwent necropsy at 11 wk after birth; controls were born at term.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Costeloe K, Hennessy E, Gibson AT, Marlow N, Wilkinson AR . The EPICure study: outcomes to discharge from hospital for infants born at the threshold of viability. Pediatrics 2000;106:659–71.
Johansson S, Iliadou A, Bergvall N, Tuvemo T, Norman M, Cnattingius S . Risk of high blood pressure among young men increases with the degree of immaturity at birth. Circulation 2005;112:3430–6.
Leon DA, Johansson M, Rasmussen F . Gestational age and growth rate of fetal mass are inversely associated with systolic blood pressure in young adults: an epidemiologic study of 165,136 Swedish men aged 18 years. Am J Epidemiol 2000;152:597–604.
Dalziel SR, Parag V, Rodgers A, Harding JE . Cardiovascular risk factors at age 30 following pre-term birth. Int J Epidemiol 2007;36:907–15.
Siewert-Delle A, Ljungman S . The impact of birth weight and gestational age on blood pressure in adult life: a population-based study of 49-year-old men. Am J Hypertens 1998;11(8 Pt 1):946–53.
Cooper R, Atherton K, Power C . Gestational age and risk factors for cardiovascular disease: evidence from the 1958 British birth cohort followed to mid-life. Int J Epidemiol 2009;38:235–44.
Edstedt Bonamy AK, Bengtsson J, Nagy Z, De Keyzer H, Norman M . Preterm birth and maternal smoking in pregnancy are strong risk factors for aortic narrowing in adolescence. Acta Paediatr 2008;97:1080–5.
Bonamy AK, Martin H, Jörneskog G, Norman M . Lower skin capillary density, normal endothelial function and higher blood pressure in children born preterm. J Intern Med 2007;262:635–42.
Bonamy AK, Bendito A, Martin H, Andolf E, Sedin G, Norman M . Preterm birth contributes to increased vascular resistance and higher blood pressure in adolescent girls. Pediatr Res 2005;58:845–9.
Cook NR, Cohen J, Hebert PR, Taylor JO, Hennekens CH . Implications of small reductions in diastolic blood pressure for primary prevention. Arch Intern Med 1995;155:701–9.
Burke GL, Evans GW, Riley WA, et al. Arterial wall thickness is associated with prevalent cardiovascular disease in middle-aged adults. The Atherosclerosis Risk in Communities (ARIC) Study. Stroke 1995;26:386–91.
Bensley JG, Stacy VK, De Matteo R, Harding R, Black MJ . Cardiac remodelling as a result of pre-term birth: implications for future cardiovascular disease. Eur Heart J 2010;31:2058–66.
Kelleher CM, McLean SE, Mecham RP . Vascular extracellular matrix and aortic development. Curr Top Dev Biol 2004;62:153–88.
Labella FS, Lindsay WG . The structure of human aortic elastin as influenced by age. J Gerontol 1963;18:111–8.
Struijk PC, Mathews VJ, Loupas T, et al. Blood pressure estimation in the human fetal descending aorta. Ultrasound Obstet Gynecol 2008;32:673–81.
Rudolph AM . Fetal and neonatal pulmonary circulation. Annu Rev Physiol 1979;41:383–95.
Berry CL, Looker T, Germain J . Nucleic acid and scleroprotein content of the developing human aorta. J Pathol 1972;108:265–74.
Emmanouilides GC, Moss AJ, Duffie ER Jr, Adams FH . Pulmonary arterial pressure changes in human newborn infants from birth to 3 days of age. J Pediatr 1964;65:327–33.
Pinson CW, Morton MJ, Thornburg KL . An anatomic basis for fetal right ventricular dominance and arterial pressure sensitivity. J Dev Physiol 1987;9:253–69.
McQuillan BM, Picard MH, Leavitt M, Weyman AE . Clinical correlates and reference intervals for pulmonary artery systolic pressure among echocardiographically normal subjects. Circulation 2001;104:2797–802.
Polyakov A, Cohen S, Baum M, Trickey D, Jolley D, Wallace EM . Patterns of antenatal corticosteroid prescribing 1998-2004. Aust N Z J Obstet Gynaecol 2007;47:42–5.
Karmonik C, Bismuth JX, Davies MG, Lumsden AB . Computational hemodynamics in the human aorta: a computational fluid dynamics study of three cases with patient-specific geometries and inflow rates. Technol Health Care 2008;16:343–54.
Pekkan K, Dasi LP, Nourparvar P, et al. In vitro hemodynamic investigation of the embryonic aortic arch at late gestation. J Biomech 2008;41:1697–706.
Svensson J, Gårdhagen R, Heiberg E, et al. Feasibility of patient specific aortic blood flow CFD simulation. Med Image Comput Comput Assist Interv 2006;9(Pt 1):257–63.
Rudolph AM . The changes in the circulation after birth. Their importance in congenital heart disease. Circulation 1970;41:343–59.
Rudolph AM . Fetal and neonatal pulmonary circulation. Am Rev Respir Dis 1977;115(6 Pt 2):11–8.
Louey S, Cock ML, Harding R . Postnatal development of arterial pressure: influence of the intrauterine environment. Arch Physiol Biochem 2003;111:53–60.
Guyton JR, Klemp KF . Transitional features in human atherosclerosis. Intimal thickening, cholesterol clefts, and cell loss in human aortic fatty streaks. Am J Pathol 1993;143:1444–57.
Bendeck MP, Keeley FW, Langille BL . Perinatal accumulation of arterial wall constituents: relation to hemodynamic changes at birth. Am J Physiol 1994;267(6 Pt 2):H2268–79.
Shapiro SD, Endicott SK, Province MA, Pierce JA, Campbell EJ . Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon. J Clin Invest 1991;87:1828–34.
Cooper R, Atherton K, Power C . Gestational age and risk factors for cardiovascular disease: evidence from the 1958 British birth cohort followed to mid-life. Int. J. Epidemiol 2009;38:235–244.
Roghair RD, Segar JL, Kilpatrick RA, Segar EM, Scholz TD, Lamb FS . Murine aortic reactivity is programmed equally by maternal low protein diet or late gestation dexamethasone. J Matern Fetal Neonatal Med 2007;20:833–41.
Pulgar VM, Figueroa JP . Antenatal betamethasone administration has a dual effect on adult sheep vascular reactivity. Pediatr Res 2006;60:705–10.
Newnham JP, Moss TJ, Nitsos I, Sloboda DM . Antenatal corticosteroids: the good, the bad and the unknown. Curr Opin Obstet Gynecol 2002;14:607–12.
De Matteo R, Blasch N, Stokes V, Davis P, Harding R . Induced preterm birth in sheep: a suitable model for studying the developmental effects of moderately preterm birth. Reprod Sci 2010;17:724–33.
Verhoeff FH . Some new staining methods of wide applicability. Including a rapid differential stain for elastic tissue. JAMA 1908;L:876–877.
Acknowledgements
The authors thank Victoria Stacy, Natasha Blasch, Ian Boundy, and Stefania Tombs for their assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bensley, J., De Matteo, R., Harding, R. et al. Preterm birth with antenatal corticosteroid administration has injurious and persistent effects on the structure and composition of the aorta and pulmonary artery. Pediatr Res 71, 150–155 (2012). https://doi.org/10.1038/pr.2011.29
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/pr.2011.29
This article is cited by
-
Dexamethasone induces an imbalanced fetal-placental-maternal bile acid circulation: involvement of placental transporters
BMC Medicine (2021)
-
Is late-preterm birth a risk factor for hypertension in childhood?
European Journal of Pediatrics (2014)
