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Semin Vasc Med 2002; 2(1): 033-044
DOI: 10.1055/s-2002-23094
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Intrauterine Growth, the Vascular System, and the Metabolic Syndrome

Richard I.G. Holt1 , Christopher D. Byrne2
  • 1Endocrinology and Metabolism Sub-Division, Fetal Origins of Adult Disease Division, School of Medicine, Southampton University, Southampton General Hospital, Southampton, England
  • 2Wellcome Trust Clinical Research Facility, Southampton, England
Further Information

Publication History

Publication Date:
25 March 2002 (online)

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ABSTRACT

There is substantial evidence linking birth size with the risk of developing cardiovascular disease and its major biological risk factors in adulthood. The fetal origins hypothesis proposes that these diseases originate through adaptations, which the fetus makes when it is undernourished. These adaptations may be cardiovascular, metabolic, or endocrine. They permanently change the structure and function of the body. Prevention of the diseases may depend on prevention of imbalances in fetal growth or imbalances between prenatal and postnatal growth, or imbalances in nutrient supply to the fetus.

The purpose of this article is to examine some of the more recent epidemiological associations between low birth weight and adult atherosclerotic vascular disease and its risk factors. We will also discuss mechanisms that might explain these associations.

KEYWORD

Cardiovascular diseases - type 2 diabetes - hypertension - metabolic syndrome - birth weight

REFERENCES

  • 1 Barker D J. Fetal origins of cardiovascular disease.  Ann Med . 1999;  31 (suppl 1) 3-6
    PubMedSearch in Google Scholar
  • 2 Hales C N, Barker D J. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis.  Diabetologia . 1992;  35(7) 595-601
    CrossrefPubMedSearch in Google Scholar
  • 3 Barker D J, Osmond C. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales.  Lancet . 1986;  1(8489) 1077-1081
    PubMedSearch in Google Scholar
  • 4 Osmond C, Barker D J, Winter P D, Fall C H, Simmonds S J. Early growth and death from cardiovascular disease in women.  Br Med J . 1993;  307(6918) 1519-1524
    CrossrefPubMedSearch in Google Scholar
  • 5 Frankel S, Elwood P, Sweetnam P, Yarnell J, Smith G D. Birthweight, body-mass index in middle age, and incident coronary heart disease.  Lancet . 1996;  348(9040) 1478-1480
    CrossrefPubMedSearch in Google Scholar
  • 6 Rich-Edwards J W, Stampfer M J, Manson J E. Birth weight and risk of cardiovascular disease in a cohort of women followed up since 1976.  Br Med J . 1997;  315(7105) 396-400
    PubMedSearch in Google Scholar
  • 7 Forsen T, Eriksson J G, Tuomilehto J, Teramo K, Osmond C, Barker D J. Mother's weight in pregnancy and coronary heart disease in a cohort of Finnish men: follow-up study.  Br Med J . 1997;  315(7112) 837-840
    PubMedSearch in Google Scholar
  • 8 Leon D A, Lithell H O, Vagero D. Reduced fetal growth rate and increased risk of death from ischaemic heart disease: cohort study of 15,000 Swedish men and women born 1915-29.  Br Med J . 1998;  317(7153) 241-245
    PubMedSearch in Google Scholar
  • 9 Stein C E, Fall C H, Kumaran K, Osmond C, Cox V, Barker D J. Fetal growth and coronary heart disease in south India.  Lancet . 1996;  348(9037) 1269-1273
    CrossrefPubMedSearch in Google Scholar
  • 10 Martyn C N, Gale C R, Jespersen S, Sherriff S B. Impaired fetal growth and atherosclerosis of carotid and peripheral arteries.  Lancet . 1998;  352(9123) 173-178
    CrossrefPubMedSearch in Google Scholar
  • 11 Lucas A, Fewtrell M S, Cole T J. Fetal origins of adult disease-the hypothesis revisited.  Br Med J . 1999;  319(7204) 245-249
    PubMedSearch in Google Scholar
  • 12 Martyn C N, Barker D J, Osmond C. Mother's pelvic size, fetal growth, and death from stroke and coronary heart disease in men in the UK.  Lancet . 1996;  348(9037) 1264-1268
    CrossrefPubMedSearch in Google Scholar
  • 13 Koupilova I, Leon D A, McKeigue P M, Lithell H O. Is the effect of low birth weight on cardiovascular mortality mediated through high blood pressure?.  J Hypertens . 1999;  17(1) 19-25
    PubMedSearch in Google Scholar
  • 14 Eriksson J G, Forsen T, Tuomilehto J, Osmond C, Barker D J. Early growth, adult income, and risk of stroke.  Stroke . 2000;  31(4) 869-874
    PubMedSearch in Google Scholar
  • 15 Reaven G M. Role of insulin resistance in human disease. Banting Lecture 1988.  Diabetes . 1988;  37(12) 1595-1607
    CrossrefPubMedSearch in Google Scholar
  • 16 Mi J, Law C, Zhang K L, Osmond C, Stein C, Barker D. Effects of infant birth weight and maternal body mass index in pregnancy on components of the insulin resistance syndrome in China.  Ann Intern Med . 2000;  132(4) 253-260
    PubMedSearch in Google Scholar
  • 17 Barker D J, Hales C N, Fall C H, Osmond C, Phipps K, Clark P M. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth.  Diabetologia . 1993;  36(1) 62-67
    CrossrefPubMedSearch in Google Scholar
  • 18 Yarbrough D E, Barrett-Connor E, Kritz-Silverstein D, Wingard D L. Birth weight, adult weight, and girth as predictors of the metabolic syndrome in postmenopausal women: the Rancho Bernardo Study.  Diabetes Care . 1998;  21(10) 1652-1658
    PubMedSearch in Google Scholar
  • 19 Byberg L, McKeigue P M, Zethelius B, Lithell H O. Birth weight and the insulin resistance syndrome: association of low birth weight with truncal obesity and raised plasminogen activator inhibitor-1 but not with abdominal obesity or plasma lipid disturbances.  Diabetologia . 2000;  43(1) 54-60
    CrossrefPubMedSearch in Google Scholar
  • 20 Bavdekar A, Yajnik C S, Fall C H. Insulin resistance syndrome in 8-year-old Indian children: small at birth, big at 8 years, or both?.  Diabetes . 1999;  48(12) 2422-2429
    CrossrefPubMedSearch in Google Scholar
  • 21 Vanhala M J, Vanhala P T, Keinanen-Kiukaanniemi S M, Kumpusalo E A, Takala J K. Relative weight gain and obesity as a child predict metabolic syndrome as an adult.  Int J Obes Rel Metab Dis . 1999;  23(6) 656-659
    PubMedSearch in Google Scholar
  • 22 Huxley R R, Shiell A, Law C. The role of size at birth and postnatal catch-up growth in determining systolic blood pressure: a systematic review of the literature.  J Hypertens . 2000;  18 815-831
    CrossrefPubMedSearch in Google Scholar
  • 23 Law C, Shiell A, Syddall H E, The Brompton Adult Blood Pressure Study Steering Group. Growth in utero, infancy and childhood: which influences adult blood pressure?.  Pediatr Res . 2001;  50(Suppl) FC4/2
    PubMedSearch in Google Scholar
  • 24 Law C, Fall C, Newsome C, Shiell A, Phillips D, Shier R. Is birth weight related to glucose and insulin metabolism?.  <~>A systematic review. Pediatr Res . 2001;  50(Suppl) FC17/4
    PubMedSearch in Google Scholar
  • 25 Hales C N, Barker D J, Clark P M. Fetal and infant growth and impaired glucose tolerance at age 64.  Br Med J . 1991;  303(6809) 1019-1022
    CrossrefPubMedSearch in Google Scholar
  • 26 Phillips D I, Barker D J, Hales C N, Hirst S, Osmond C. Thinness at birth and insulin resistance in adult life.  Diabetologia . 1994;  37(2) 150-154
    CrossrefPubMedSearch in Google Scholar
  • 27 Law C M, Gordon G S, Shiell A W, Barker D J, Hales C N. Thinness at birth and glucose tolerance in seven-year-old children.  Diabet Med . 1995;  12(1) 24-29
    CrossrefPubMedSearch in Google Scholar
  • 28 Fall C H, Osmond C, Barker D J. Fetal and infant growth and cardiovascular risk factors in women.  Br Med J . 1995;  310(6977) 428-432
    PubMedSearch in Google Scholar
  • 29 Antal M, Agfalvi R, Nagy K. Lipid status in adolescents born with low birth weight.  Z Ernahrungswiss . 1998;  37 (suppl 1) 131-133
    PubMedSearch in Google Scholar
  • 30 Phillips D I, McLeish R, Osmond C, Hales C N. Fetal growth and insulin resistance in adult life: role of plasma triglyceride and non-esterified fatty acids.  Diabet Med . 1995;  12(9) 796-801
    PubMedSearch in Google Scholar
  • 31 Curhan G C, Chertow G M, Willett W C. Birth weight and adult hypertension and obesity in women.  Circulation . 1996;  94(6) 1310-1315
    CrossrefPubMedSearch in Google Scholar
  • 32 Phillips D I, Young J B. Birth weight, climate at birth and the risk of obesity in adult life.  Int J Obes Rel Metab Dis . 2000;  24(3) 281-287
    PubMedSearch in Google Scholar
  • 33 Kahn H S, Narayan K M, Williamson D F, Valdez R. Relation of birth weight to lean and fat thigh tissue in young men.  Int J Obes Rel Metab Dis . 2000;  24(6) 667-672
    PubMedSearch in Google Scholar
  • 34 Law C M, Barker D J, Osmond C, Fall C H, Simmonds S J. Early growth and abdominal fatness in adult life.  J Epidemiol Comm Health . 1992;  46(3) 184-186
    PubMedSearch in Google Scholar
  • 35 Choi C S, Kim C, Lee W J. Association between birth weight and insulin sensitivity in healthy young men in Korea: role of visceral adiposity.  Diabetes Res Clin Pract . 2000;  49(1) 53-59
    CrossrefPubMedSearch in Google Scholar
  • 36 Barker D J, Meade T W, Fall C H. Relation of fetal and infant growth to plasma fibrinogen and factor VII concentrations in adult life.  Br Med J . 1992;  304(6820) 148-152
    PubMedSearch in Google Scholar
  • 37 van der Salm P, Ubachs H M, van Wersch W J. Fibrinogen and factor VII in male neonates.  Thromb Res . 1994;  73(3-4) 239-245
    CrossrefPubMedSearch in Google Scholar
  • 38 Cook D G, Whincup P H, Miller G. Fibrinogen and factor VII levels are related to adiposity but not to fetal growth or social class in children aged 10-11 years.  Am J Epidemiol . 1999;  150(7) 727-736
    PubMedSearch in Google Scholar
  • 39 McKeigue P M, Lithell H O, Leon D A. Glucose tolerance and resistance to insulin-stimulated glucose uptake in men aged 70 years in relation to size at birth.  Diabetologia . 1998;  41(10) 1133-1138
    CrossrefPubMedSearch in Google Scholar
  • 40 Flanagan D E, Moore V M, Godsland I F, Cockington R A, Robinson J S, Phillips D I. Fetal growth and the physiological control of glucose tolerance in adults: a minimal model analysis.  Am J Physiol Endocrinol Metab . 2000;  278(4) E700-706
    PubMedSearch in Google Scholar
  • 41 Hofman P L, Cutfield W S, Robinson E M. Insulin resistance in short children with intrauterine growth retardation.  J Clin Endocrinol Metab . 1997;  82(2) 402-406
    CrossrefPubMedSearch in Google Scholar
  • 42 Hattersley A T, Beards F, Ballantyne E, Appleton M, Harvey R, Ellard S. Mutations in the glucokinase gene of the fetus result in reduced birth weight.  Nat Genet . 1998;  19(3) 268-270
    CrossrefPubMedSearch in Google Scholar
  • 43 Wright N M, Metzger D L, Borowitz S M, Clarke W L. Permanent neonatal diabetes mellitus and pancreatic exocrine insufficiency resulting from congenital pancreatic agenesis [letter].  Am J Dis Child . 1993;  147(6) 607-609
    PubMedSearch in Google Scholar
  • 44 Temple I K, Gardner R J, Mackay D J, Barber J C, Robinson D O, Shield J P. Transient neonatal diabetes: widening the understanding of the etiopathogenesis of diabetes.  Diabetes . 2000;  49(8) 1359-1366
    CrossrefPubMedSearch in Google Scholar
  • 45 Cresto J C, Abdenur J P, Bergada I, Martino R. Long-term follow up of persistent hyperinsulinaemic hypoglycaemia of infancy.  Arch Dis Child . 1998;  79(5) 440-444
    PubMedSearch in Google Scholar
  • 46 McCance D R, Pettitt D J, Hanson R L, Jacobsson L T, Knowler W C, Bennett P H. Birth weight and non-insulin dependent diabetes: thrifty genotype, thrifty phenotype, or surviving small baby genotype?.  Br Med J . 1994;  308(6934) 942-945
    PubMedSearch in Google Scholar
  • 47 Morton N E. The inheritance of human birth weight.  Ann Hum Genet . 1955;  19 262-268
    PubMedSearch in Google Scholar
  • 48 Penrose L S. Data on genetics of birth weight.  Ann Eugenics . 1952;  16 378-381
    PubMedSearch in Google Scholar
  • 49 Poulsen P, Vaag A A, Kyvik K O, Moller Jensen D, Beck-Nielsen H. Low birth weight is associated with NIDDM in discordant monozygotic and dizygotic twin pairs.  Diabetologia . 1997;  40(4) 439-446
    CrossrefPubMedSearch in Google Scholar
  • 50 Baird J, Osmond C, MacGregor A, Snieder H, Hales C N, Phillips D I. Testing the fetal origins hypothesis in twins: the Birmingham twin study.  Diabetologia . 2001;  44(1) 33-39
    CrossrefPubMedSearch in Google Scholar
  • 51 Spalding D A. Instinct with original observation on young animals.  Br J Animal Behav . 1954;  2 2-11
    PubMedSearch in Google Scholar
  • 52 McCance R A. Food, growth and time.  Lancet . 1962;  2 271-272
    PubMedSearch in Google Scholar
  • 53 Ravelli A C, van der Meulen H J, Michels R P. Glucose tolerance in adults after prenatal exposure to famine.  Lancet . 1998;  351(9097) 173-177
    CrossrefPubMedSearch in Google Scholar
  • 54 Stanner S A, Bulmer K, Andres C. Does malnutrition in utero determine diabetes and coronary heart disease in adulthood?.  <~>Results from the Leningrad siege study, a cross-sectional study. Br Med J . 1997;  315(7119) 1342-1348
    PubMedSearch in Google Scholar
  • 55 Godfrey K, Robinson S, Barker D J, Osmond C, Cox V. Maternal nutrition in early and late pregnancy in relation to placental and fetal growth.  Br Med J . 1996;  312(7028) 410-414
    PubMedSearch in Google Scholar
  • 56 Campbell D M, Hall M H, Barker D J, Cross J, Shiell A W, Godfrey K M. Diet in pregnancy and the offspring's blood pressure 40 years later.  Br J Obstet Gynaecol . 1996;  103(3) 273-280
    PubMedSearch in Google Scholar
  • 57 Haselden S, Shiell A, Campbell-Brown M, Robinson S, Godfrey K, Barker D. A high meat, low carbohydrate diet in pregnancy: relation to the offspring's blood pressure and glucose-insulin metabolism at age 30.  Pediatr Res . 2001;  50(Suppl) FC7/5
    PubMedSearch in Google Scholar
  • 58 Godfrey K M, Barker D J. Fetal nutrition and adult disease.  Am J Clin Nutr . 2000;  50 (suppl) 1344S-1352S
    PubMedSearch in Google Scholar
  • 59 Barker D J, Bull A R, Osmond C, Simmonds S J. Fetal and placental size and risk of hypertension in adult life.  Br Med J . 1990;  301(6746) 259-262
    CrossrefPubMedSearch in Google Scholar
  • 60 Laurin J, Lingman G, Marsal K, Persson P H. Fetal blood flow in pregnancies complicated by intrauterine growth retardation.  Obstet Gynecol . 1987;  69(6) 895-902
    PubMedSearch in Google Scholar
  • 61 Clark P M, Hindmarsh P C, Shiell A W, Law C M, Honour J W, Barker D J. Size at birth and adrenocortical function in childhood.  Clin Endocrinol . 1996;  45(6) 721-726
    CrossrefPubMedSearch in Google Scholar
  • 62 Ramsay D S, Lewis M. The effects of birth condition on infants' cortisol response to stress.  Pediatrics . 1995;  95(4) 546-549
    PubMedSearch in Google Scholar
  • 63 Phillips D I, Walker B R, Reynolds R M. Low birth weight predicts elevated plasma cortisol concentrations in adults from 3 populations.  Hypertension . 2000;  35(6) 1301-1306
    CrossrefPubMedSearch in Google Scholar
  • 64 Phillips D I, Barker D J, Fall C H. Elevated plasma cortisol concentrations: a link between low birth weight and the insulin resistance syndrome?.  J Clin Endocrinol Metab . 1998;  83(3) 757-760
    CrossrefPubMedSearch in Google Scholar
  • 65 Reynolds R M, Walker B R, Syddall H E. Altered control of cortisol secretion in adult men with low birth weight and cardiovascular risk factors.  J Clin Endocrinol Metab . 2001;  86(1) 245-250
    PubMedSearch in Google Scholar
  • 66 Barbazanges A, Piazza P V, Le Moal M, Maccari S. Maternal glucocorticoid secretion mediates long-term effects of prenatal stress.  J Neurosci . 1996;  16(12) 3943-3949
    PubMedSearch in Google Scholar
  • 67 Reul J M, Stec I, Wiegers G J. Prenatal immune challenge alters the hypothalamic-pituitary-adrenocortical axis in adult rats.  J Clin Invest . 1994;  93(6) 2600-2607
    PubMedSearch in Google Scholar
  • 68 Langley-Evans S C. Intrauterine programming of hypertension by glucocorticoids.  Life Sci . 1997;  60(15) 1213-1221
    CrossrefPubMedSearch in Google Scholar
  • 69 Seckl J R, Cleasby M, Nyirenda M J. Glucocorticoids, 11beta-hydroxysteroid dehydrogenase, and fetal programming.  Kidney Int . 2000;  57(4) 1412-1417
    CrossrefPubMedSearch in Google Scholar
  • 70 Lindsay R S, Lindsay R M, Edwards C R, Seckl J R. Inhibition of 11-beta-hydroxysteroid dehydrogenase in pregnant rats and the programming of blood pressure in the offspring.  Hypertension . 1996;  27(6) 1200-1204
    PubMedSearch in Google Scholar
  • 71 Cianfarani S, Germani D, Rossi P. Intrauterine growth retardation: evidence for the activation of the insulin-like growth factor (IGF)-related growth-promoting machinery and the presence of a cation-independent IGF binding protein-3 proteolytic activity by two months of life.  Pediatr Res . 1998;  44(3) 374-380
    CrossrefPubMedSearch in Google Scholar
  • 72 Langford K, Blum W, Nicolaides K, Jones J, McGregor A, Miell J. The pathophysiology of the insulin-like growth factor axis in fetal growth failure: a basis for programming by undernutrition?.  Eur J Clin Invest . 1994;  24(12) 851-856
    PubMedSearch in Google Scholar
  • 73 Fall C H, Pandit A N, Law C M. Size at birth and plasma insulin-like growth factor-1 concentrations.  Arch Dis Child . 1995;  73(4) 287-293
    PubMedSearch in Google Scholar
  • 74 Ben-Shlomo Y, Holly J M, McCarthy A. The association of birth weight, post-natal growth and adult height with insulin-like growth factor: results from the Barry Caerphilly Growth (BCG) study.  Pediatr Res . 2001;  50(Suppl) FC11/4
    PubMedSearch in Google Scholar
  • 75 Flanagan D E, Moore V M, Godsland I F, Cockington R A, Robinson J S, Phillips D I. Reduced foetal growth and growth hormone secretion in adult life.  Clin Endocrinol . 1999;  50(6) 735-740
    CrossrefPubMedSearch in Google Scholar
  • 76 Flanagan D E, Holt R IG, Moore V M, Owens P C, Robinson J S, Phillips D I. The association between birth weight and IGF-I activity in young adults.  Pediatr Res . 2001;  50(Suppl) POS11/10
    PubMedSearch in Google Scholar
  • 77 Martyn C N, Lever A F, Morton J J. Plasma concentrations of inactive renin in adult life are related to indicators of foetal growth.  J Hypertension . 1996;  14(7) 881-886
    PubMedSearch in Google Scholar
  • 78 Trowern A R, Bertram C, Whorwood C B. The intra-uterine environment programmes hypertension in later life through increased expression of renal type 1 angiotensin II receptor.  Pediatr Res . 2001;  50(Suppl) FC12/2
    PubMedSearch in Google Scholar
  • 79 Taylor D J, Thompson C H, Kemp G J. A relationship between impaired fetal growth and reduced muscle glycolysis revealed by 31P magnetic resonance spectroscopy.  Diabetologia . 1995;  38(10) 1205-1212
    PubMedSearch in Google Scholar
  • 80 Wootton S A, Murphy J L, Wilson F, Phillips D IW. Energy expenditure and substrate metabolism after carbohydrate ingestion in relation to fetal growth in women born in Preston.  Proc Nutr Soc . 1994;  53 174A
    PubMedSearch in Google Scholar
  • 81 Barbera A, Giraud G D, Reller M D, Maylie J, Morton M J, Thornburg K L. Right ventricular systolic pressure load alters myocyte maturation in fetal sheep.  Am J Physiol Regul Integr Comp Physiol . 2000;  279(4) R1157-1164
    PubMedSearch in Google Scholar
  • 82 Martyn C N, Barker D J, Jespersen S, Greenwald S, Osmond C, Berry C. Growth in utero, adult blood pressure, and arterial compliance.  Br Heart J . 1995;  73(2) 116-121
    PubMedSearch in Google Scholar
  • 83 Tooke J E. The association between insulin resistance and endotheliopathy.  Diabetes Obes Metab . 1999;  73(2) S17-22
    PubMedSearch in Google Scholar
  • 84 Manalich R, Reyes L, Herrera M, Melendi C, Fundora I. Relationship between weight at birth and the number and size of renal glomeruli in humans: a histomorphometric study.  Kidney Int . 2000;  58(2) 770-773
    CrossrefPubMedSearch in Google Scholar