Published online before print July 9, 2007, doi: 10.1161/HYPERTENSIONAHA.107.094029
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(Hypertension. 2007;50:465.)
© 2007 American Heart Association, Inc.
Editorial Commentaries |
Divergent Origins of Slow Fetal Growth
Relevance to Adult Cardiovascular Disease
From the Department of Physiology, University of Mississippi Medical Center, Jackson.
Correspondence to Barbara T. Alexander, PhD, Department of Physiology, University of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216-4505. E-mail balexander{at}physiology.umsmed.edu
Barker and Osmond hypothesized nearly 20 years ago that fetal undernutrition leads to permanent alterations in the body’s structure and physiology and increases susceptibility to cardiovascular disease in adult life.1,2 Furthermore, they suggested that high blood pressure may be a link between an adverse intrauterine environment and the risk for cardiovascular disease.2 Since then, numerous epidemiologic studies have assessed the inverse relation between birth weight and blood pressure.3 Furthermore, experimental studies have supported this inverse association and have demonstrated that the timing, length, and degree of in utero insult, as well as postnatal influences, determine the adult phenotype.4–6
In humans, postnatal influences may also have an important impact on later development of cardiovascular disease in babies who are born small.2,7 Accordingly, Barker and colleagues7 recently suggested that 2 different pathways of childhood growth may precede development of hypertension and adult cardiovascular disease. Early development of more severe hypertension associated with obesity and insulin resistance is more common in individuals who are born small but who experience rapid catch-up growth during childhood. Individuals who are born short and maintain slow growth during childhood and therefore remain short and thin before puberty develop hypertension at a later age. However, these individuals also have a greater risk for stroke as adults.7,8
Interestingly, the increased risk for stroke is more common in individuals with mothers who have a "flat" bony pelvis.8 Because a flat pelvis is associated with malnutrition during the first year of life, Barker and colleagues8 proposed that malnutrition during infancy increases the risk for stroke in the next generation. Previous reports also suggest that reduced growth in the female fetus due to undernutrition results in increased blood pressure in the next generation.9 Thus, findings from these studies suggest that subtle variations in the timing of undernutrition in the mother, whether in utero or during infancy, contributes to cardiovascular disease, including hypertension and/or stroke, in the next generation.
In this issue of Hypertension, Barker and colleagues10 examined influences that affect prenatal and postnatal growth and the development of hypertension in individuals with divergent postnatal patterns of growth. Hypertension that is severe and/or diagnosed early was associated with being small at birth followed by rapid catch-up growth (Figure). This pattern of fetal and childhood growth was likely due to fetal undernutrition, as indicated by a strong association with decreased placental size, and was associated with poor living conditions after birth, suggesting increased vulnerability to postnatal stress.10 However, newly diagnosed hypertension and risk of stroke were associated with slow growth in utero and throughout childhood. This pattern of fetal and childhood growth was more strongly associated with mothers who had small pelvic bones, a likely consequence of vitamin D deficiency and rickets during their infancy. Thus, these findings suggest that the reduced fetal and childhood growth observed in these individuals originates from influences that occur early in the lives of their mothers.10 Thus, slow fetal growth, whether occurring as a result of malnutrition during fetal development or occurring as a result of malnutrition of the mother during her infancy, is associated with adult cardiovascular disease.
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In conclusion, fetal undernutrition leads to permanent alterations in the regulatory systems involved in the long-term control of arterial pressure. The severity of hypertension can be exacerbated by postnatal insults. Current studies are beginning to elucidate the role of prenatal and postnatal undernutrition and adverse effects that persist from the previous generation on adult cardiovascular disease. Although undernutrition in the female fetus may lead to development of hypertension in the next generation,9 as reported by Barker et al10 in this issue of Hypertension, deficiency during infancy of an essential nutrient, such as vitamin D, leads to permanent alterations in the metabolism of the mother that slow fetal and childhood growth and increase the risk for stroke in the next generation. The obvious implication is that proper nutrition during fetal life and childhood may be critical for the cardiovascular health of the individual and her offspring.
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Acknowledgments |
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Sources of Funding
B.T.A. is supported by grants from the National Institutes of Health, HL074927 and HL51971.
Disclosures
None.
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Footnotes |
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The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.
This paper was sent to Norman M. Kaplan, consulting editor, for review by expert referees, editorial decision, and final disposition.
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References |
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 Top References |
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1. Barker DJ, Osmond C. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet. 1986; 1: 1077–1081.[Medline] [Order article via Infotrieve]
2. Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ. 1989; 298: 564–567.
3. Law CM, Shiell AW. Is blood pressure inversely related to birth weight? the strength of evidence from a systematic review of the literature. J Hypertens. 1996; 14: 935–941.[Medline] [Order article via Infotrieve]
4. Barker DJ, Bagby SP, Hanson MA. Mechanisms of disease: in utero programming in the pathogenesis of hypertension. Nat Clin Pract Nephrol. 2006; 2: 700–707.[CrossRef][Medline] [Order article via Infotrieve]
5. Zandi-Nejad K, Luyckx VA, Brenner BM. Adult hypertension and kidney disease: the role of fetal programming. Hypertension. 2006; 47: 502–508.
6. Alexander BT. Fetal programming of hypertension. Am J Physiol Regul Integr Comp Physiol. 2006; 290: R1–R10.
7. Eriksson JG, Forsén TJ, Kajantie E, Osmond C, Barker DJ. Childhood growth and hypertension in later life. Hypertension. 2007; 49: 1415–1421.
8. Osmond C, Kajantie E, Forsén TJ, Eriksson JG, Barker DJP. Infant growth and stroke in adult life: the Helsinki birth cohort study. Stroke. 2007; 38: 264–270.
9. Barker DJ, Shiell AW, Barker ME, Law CM. Growth in utero and blood pressure levels in the next generation. J Hypertens. 2000; 18: 843–846.[CrossRef][Medline] [Order article via Infotrieve]
10. Barker DJP, Osmond C, Forsen TJ, Kajantie E, Eriksson JG. Maternal and social origins of hypertension. Hypertension. 2007; 50: 565–571.
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Hypertension 2007 50: 565-571.
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