Abstract
Low birthweight is associated with increased rates of coronary heart disease, stroke, hypertension and non-insulin-dependent diabetes during adult life. This is thought to be the consequence of a ‘programming’, whereby a stimulus or insult at a critical, sensitive period of early life has permanent effects on structure, physiology and metabolism. Programming of the fetus may, hence, result from adaptations to a condition where placental nutrient supply fails to match fetal demand. Recently, compensatory feto-placental up-regulation of the nitric oxide system during fetal growth restriction (FGR) was shown. Particularly, restricted hypoxic fetuses present an elevation of nitrites and a reduction of asymmetric dimethylarginine. S-nitrosohemoglobin is consumed under hypoxic conditions. These events are followed by nitric oxide pathway down-regulation postnatally, increasing susceptibility to cardiovascular disorders later in life. The relative hyperoxia would favor any such occurrence through depletion of tetrahydrobiopterin secondary to oxygen radical formation. This concept may lead to new therapeutic strategies, based on tetrahydrobiopterin supplementation, free-radical scavenging, l-arginine administration and/or inhaled NO therapy in FGR hypoxic newborns, to improve their postnatal adaptation and to reduce the risk of metabolic pathologies in adult age.
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References
Brar HS, Rutherford SE (1988) Classification of intrauterine growth retardation. Semin Perinatol 12(1):2–10
Hack M, Fanaroff AA (2000) Outcomes of children of extremely low birthweight and gestational age in the 1990s. Semin Neonatol 5(2):89–106
Phipps K, Barker DJ et al (1993) Fetal growth and impaired glucose tolerance in men and women. Diabetologia 36(3):225–228
Skilton MR, Evans N et al (2005) Aortic wall thickness in newborns with intrauterine growth restriction. Lancet 365(9469):1484–1486
Hossain MA, Islam MN et al (2006) Serum triglyceride level in IUGR babies and its comparison with preterm AGA and term normal babies. Mymensingh Med J 15(2):180–182
Barker DJ, Eriksson JG et al (2002) Fetal origins of adult disease: strength of effects and biological basis. Int J Epidemiol 31(6):1235–1239
Barker DJ (2004) The developmental origins of chronic adult disease. Acta Paediatr Suppl 93(446):26–33
Pisaneschi S, Strigini FA et al (2012) Compensatory feto-placental upregulation of the nitric oxide system during fetal growth restriction. PLoS One 7(9):e45294
Pettersson A, Hedner T et al (1998) Increased circulating concentrations of asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, in preeclampsia. Acta Obstet Gynecol Scand 77(8):808–813
Achan V, Broadhead M et al (2003) Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylaminohydrolase. Arterioscler Thromb Vasc Biol 23(8):1455–1459
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Pisaneschi, S., Boldrini, A., Genazzani, A.R. et al. Feto-placental vascular dysfunction as a prenatal determinant of adult cardiovascular disease. Intern Emerg Med 8 (Suppl 1), 41–45 (2013). https://doi.org/10.1007/s11739-013-0925-y
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DOI: https://doi.org/10.1007/s11739-013-0925-y