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Fetal programming and adult health

  • Keith M Godfrey (a1) and David JP Barker (a1)
Abstract
Abstract

Low birthweight is now known to be associated with increased rates of coronary heart disease and the related disorders stroke, hypertension and non-insulin dependent diabetes. These associations have been extensively replicated in studies in different countries and are not the result of confounding variables. They extend across the normal range of birthweight and depend on lower birthweights in relation to the duration of gestation rather than the effects of premature birth. The associations are thought to be consequences of ‘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 result from adaptations invoked when the materno-placental nutrient supply fails to match the fetal nutrient demand. Although the influences that impair fetal development and programme adult cardiovascular disease remain to be defined, there are strong pointers to the importance of maternal body composition and dietary balance during pregnancy.

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Corresponding author
*Corresponding author: Email kmg@mrc.soton.ac.uk
References
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1Barker DJP. Mothers, babies and health in later life. 2nd ed. Edinburgh: Churchill Livingstone, 1998.
2McCance RA, Widdowson EM. The determinants of growth and form. Proc. R. Soc. Lond B 1974; 185: 117.
3Lucas A.Role of nutritional programming in determining adult morbidity. Arch Dis. Child 1994; 71: 288–90.
4Langley-Evans SC, Jackson AA. Increased systolic blood pressure in adult rats induced by fetal exposure to maternal low protein diets. Clin. Sci. 1994; 86: 217–22.
5Desai M, Crowther NJ, Ozanne SE, Lucas A, Hales CN. Adult glucose and lipid metabolism may be programmed during fetal life. Biochem. Soc. Trans. 1995; 23: 331–5.
6Osmond C, Barker DJP, Winter PD, Fall CHD, Simmonds SJ. Early growth and death from cardiovascular disease in women. BMJ 1993; 307: 1519–24.
7Barker DJP, Osmond C, Simmonds SJ, Wield GA. The relation of small head circumference and thinness at birth to death from cardiovascular disease in adult life. BMJ 1993; 306: 422–6.
8Frankel S, Elwood P, Sweetnam P, Yarnell J, Davey Smith G.Birthweight, body-mass index in middle age, and incident coronary heart disease. Lancet 1996; 348: 1478–80.
9Rich-Edwards JW, Stampfer MJ, Manson JE, Rosner B, Hankinson SE, Colditz GA, Willett WC, Hennekens CH. Birth weight and risk of cardiovascular disease in a cohort of women followed up since 1976. BMJ 1997; 315: 396400.
10Stein CE, Fall CHD, Kumaran K, Osmond C, Cox V, Barker DJP. Fetal growth and coronary heart disease in South India. Lancet 1996; 348: 1269–73.
11Martyn CN, Barker DJP, Osmond C.Mothers' pelvic size, fetal growth, and death from stroke and coronary heart disease in men in the UK. Lancet 1996; 348: 1264–8.
12Forsen T, Eriksson JG, Tuomilehto J, Teramo K, Osmond C, Barker DJP. Mother's weight in pregnancy and coronary heart disease in a cohort of Finnish men: follow up study. BMJ 1997; 315: 837–40.
13Leon DA, Lithell H, Vagero D, et al. Biological and social influences on mortality in a cohort of 15 000 Swedes followed from birth to old age. J. Epidemiol. Community Health 1997; 51: 594 [Abstract].
14Hales CN, Barker DJP, Clark PMS, Cox LJ, Fall C, Osmond C, Winter PD. Fetal and infant growth and impaired glucose tolerance at age 64. BMJ 1991; 303: 1019–22.
15Law 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: 935–41.
16Barker DJP, Godfrey KM, Osmond C, Bull A.The relation of fetal length, ponderal index and head circumference to blood pressure and the risk of hypertension in adult life. Paediatr. Perinat. Epidemiol. 1992; 6: 3544.
17Moore VM, Cockington RA, Ryan P, Robinson JS. The relationship between birth weight and blood pressure amplifies from childhood to adulthood. J. Hypertens 1999; 17: 883–8.
18Law CM, Barker DJP, Bull AR, Osmond C.Maternal and fetal influences on blood pressure. Arch. Dis. Child 1991; 66: 1291–5.
19Campbell DM, Hall MH, Barker DJP, Cross J, Shiell AW, Godfrey KM. Diet in pregnancy and the offspring's blood pressure 40 years later. Br. J. Obstet. Gynaecol. 1996; 103: 273–80.
20Robinson JS, Owens JA, de Barro T, et al. Maternal nutrition and fetal growth. In: Ward RHT, Smith SK, Donnai D, eds. Early fetal growth and development. London: Royal College of Obstetricians and Gynaecologists, 1994; 317–34.
21Martyn CN, Barker DJP, Jespersen S, Greenwald S, Osmond C, Berry C.Growth in utero, adult blood pressure, and arterial compliance. Br. Heart J. 1995; 73: 116–21.
22Lever AF, Harrap SB. Essential hypertension: a disorder of growth with origins in childhood? J. Hypertens 1992; 10: 101–20.
23Martyn CN, Lever AF, Morton JJ. Plasma concentrations of inactive renin in adult life are related to indicators of foetal growth. J. Hypertens 1996; 14: 881–6.
24Mackenzie HS, Brenner BM. Fewer nephrons at birth: a missing link in the etiology of essential hypertension? Am. J. Kidney Dis. 1995; 26: 91–8.
25Konje JC, Bell SC, Morton JJ, de Chazal R, Taylor DJ. Human fetal kidney morphometry during gestation and the relation-ship between weight, kidney morphometry and plasma active renin concentration at birth. Clin. Sci. 1996; 91: 169–75.
26Edwards CRW, Benediktsson R, Lindsay RS, Seckl JR. Dysfunction of placental glucocorticoid barrier: link between fetal environment and adult hypertension? Lancet 1993; 341: 355–7.
27Phillips DI, Barker DJ, Fall CH, Seckl JR, Whorwood CB, Wood PJ, Walker BR. Elevated plasma cortisol concentrations: a link between low birth weight and the insulin resistance syndrome? J. Clin. Endocrinol Metab. 1998; 83: 757–60.
28Martyn CN, Greenwald SE. Impaired synthesis of elastin in walls of aorta and large conduit arteries during early development as an initiating event in pathogenesis of systemic hypertension. Lancet 1997; 350: 953–5.
29Al-Ghazali W, Chita SK, Chapman MG, Allan LD. Evidence of redistribution of cardiac output in asymmetrical growth retardation. Br. J. Obstet Gynaecol 1989; 96: 697704.
30Leeson CPM, Whincup PH, Cook DG, Donald AE, Papacosta O, Lucas A, Deanfield JE. Flow-mediated dilation in 9- to 11-year old children. The influence of intrauterine and childhood factors. Circulation 1997; 96: 2233–8.
31Phillips DIW, Barker DJP. Association between low birthweight and high resting pulse in adult life: is the sympathetic nervous system involved in programming the insulin resistance syndrome?. Diabet. Med. 1997; 14: 673–7.
32Lithell HO, McKeigue PM, Berglund L, Mohsen R, Lithell UB, Leon DA. Relation of size at birth to non-insulin dependent diabetes and insulin concentrations in men aged 50–60 years. BMJ 1996; 312: 406–10.
33Curhan GC, Willett WC, Rimm EB, et al. Birth weight and adult hypertension and diabetes mellitus in US men. Am. J. Hypertens 1996; 9: 11A [Abstract].
34McCance DR, Pettitt DJ, Hanson RL, Jacobsson LTH, Knowler WC, Bennett PH. Birth weight and non-insulin dependent diabetes: thrifty genotype, thrifty phenotype, or surviving small baby genotype? BMJ 1994; 308: 942–5.
35Barker DJP, Hales CN, Fall CHD, Osmond C, Phipps K, Clark PMS. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 1993; 36: 62–7.
36Phillips DIW, Hirst S, Clark PMS, Hales CN, Osmond C.Fetal growth and insulin secretion in adult life. Diabetologia 1994; 37: 592–6.
37Valdez R, Athens MA, Thompson GH, Bradshaw BS, Stern MP. Birthweight and adult health outcomes in a biethnic population in the USA. Diabetologia 1994; 37: 624–31.
38Leger J, Levy-Marchal C, Bloch J, Pinet A, Chevenne D, Porquet D, Collin D, Czernichow P.Reduced final height and indications for insulin resistance in 20 year olds born small for gestational age: regional cohort study. BMJ 1997; 315: 341–7.
39Ravelli ACJ, van der Meulen JHP, Michels RPJ, Osmond C, Barker DJP, Hales CN, Bleker OP. Glucose tolerance in adults after prenatal exposure to famine. Lancet 1998; 351: 173–7.
40Law CM, Gordon GS, Shiell AW, Barker DJP, Hales CN. Thinness at birth and glucose tolerance in seven year old children. Diabet. Med. 1995; 12: 24–9.
41Whincup PH, Cook DG, Adshead F, Taylor SJC, Walker M, Papacosta O, Alberti KGMM. Childhood size is more strongly related than size at birth to glucose and insulin levels in 10–11-year-old children. Diabetologia 1997; 40: 319–26.
42Taylor DJ, Thompson CH, Kemp GJ, Barnes PRJ, Sanderson AL, Radda GK, Phillips DIW. A relationship between impaired fetal growth and reduced muscle glycolysis revealed by 31P magnetic resonance spectroscopy. Diabetologia 1995; 38: 1205–12.
43Bjorntorp P.Insulin resistance: the consequence of a neuroendocrine disturbance? Int. J. Obesity 1995; 19(suppl 1): S6–10.
44Hales CN, Barker DJP. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 1992; 35: 595601.
45Phillips DIW, Barker DJP, Hales CN, Hirst S, Osmond C.Thinness at birth and insulin resistance in adult life. Diabetologia 1994; 37: 150–4.
46Alvarsson M, Efendic S, Grill VE. Insulin responses to glucose in healthy males are associated with adult height but not with birth weight. J. Intern. Med. 1994; 236: 275–9.
47Robinson S, Walton RJ, Clark PM, Barker DJP, Hales CN, Osmond C.The relation of fetal growth to plasma glucose in young men. Diabetologia 1992; 35: 444–6.
48Wills J, Watson JM, Hales CN, Phillips DIW. The relation of fetal growth to insulin secretion in young men. Diabet. Med. 1996; 13: 773–4.
49Leger J, Levy-Marchal C, Block J, et al. Evidence for insulin-resistance developing in young adults with intra-uterine growth retardation. Diabetologia 1997; 40: A53 [Abstract].
50Fall CHD, Stein CE, Kumaran K, Cox V, Osmond C, Barker DJP, Hales CN. Size at birth, maternal weight, and type 2 diabetes in South India. Diabet. Med. 1998; 15: 220–7.
51Farmer G, Russell G, Hamilton-Nicol DR, Ogenbede HO, Ross IS, Pearson DWM, Thom H, Kerridge DF, Sutherland HW. The influence of maternal glucose metabolism on fetal growth, development and morbidity in 917 singleton pregnancies in nondiabetic women. Diabetologia 1988; 31: 134–41.
52Snow MHL. Effects of genome on fetal size at birth. In: Sharp F, Fraser RB, Milner RDG, eds. Fetal growth. Proceedings of the 20th Study Group. London: Royal College of Obstetricians and Gynaecologists, 1989; 111.
53Morton NE. The inheritance of human birth weight. Ann. Hum. Genet. 1955; 20: 123–34.
54Brooks AA, Johnson MR, Steer PJ, Pawson ME, Abdalla HI. Birth weight: nature or nurture? Early Hum. Dev. 1995; 42: 2935.
55Stein Z, Susser M, Saenger G, et al. Famine and human development: The Dutch Hunger Winter of 1944/45.New York: Oxford University Press, 1975.
56Godfrey KM, Barker DJP, Robinson S, Osmond C.Maternal birthweight and diet in pregnancy in relation to the infant's thinness at birth. Br. J. Obstet. Gynaecol. 1997; 104: 663–7.
57Kramer MS. Effects of energy and protein intakes on pregnancy outcome: an overview of the research evidence from controlled clinical trials. Am. J. Clin. Nutr. 1993; 58: 627–35.
58Harding JE, Liu L, Evans P, Oliver M, Gluckman P.Intrauterine feeding of the growth-retarded fetus: can we help? Early Hum. Dev. 1992; 29: 193–7.
59Walker SK, Hartwich KM, Seamark RF. The production of unusually large offspring following embryo manipulation: concepts and challenges. Theriogenology 1996; 45: 111–20.
60Stewart RJC, Sheppard H, Preece R, Waterlow JC. The effect of rehabilitation at different stages of development of rats marginally malnourished for ten to twelve generations. Br. J. Nutr. 1980; 43: 403–12.
61Emanuel I, Filakti H, Alberman E, Evans SJW. Intergenerational studies of human birthweight from the 1958 birth cohort. I. Evidence for a multigenerational effect. Br. J. Obstet. Gynaecol. 1992; 99: 6774.
62Godfrey K, Robinson S, Barker DJP, Osmond C, Cox V.Maternal nutrition in early and late pregnancy in relation to placental and fetal growth. BMJ 1996; 312: 410–4.
63Lumey LH. Compensatory placental growth after restricted maternal nutrition in early pregnancy. Placenta 1998; 19: 105–11.
64Robinson JS, Chidzanja S, Kind K, Lok F, Owens P, Owens JA. Placental control of fetal growth. Reprod. Fertil. Dev. 1995; 7: 333–44.
65Kind KL, Clifton PM, Katsman AI, Tsiounis M, Robinson JS, Owens JA. Restricted fetal growth and the response to dietary cholesterol in the guinea pig. Am. J. Physiol. 1999; 277: R1675–82.
66Belizan JM, Villar J, Bergel E, del Pino A, Di Fulvio S, Galliano SV, Kattan C.Long term effect of calcium supplementation during pregnancy on the blood pressure of offspring: follow up of a randomised controlled trial. BMJ 1997; 315: 281–5.
67Rush D. Effects of changes in maternal energy and protein intake during pregnancy, with special reference to fetal growth. In: Sharp F, Fraser RB, Milner RDG, eds. Fetal Growth. London: Royal College of Obstetricians and Gynaecologists, 1989; 203–33.
68Godfrey KM, Forrester T, Barker DJP, Jackson AA, Landman JP, Hall JStE, Cox V, Osmond C.Maternal nutritional status in pregnancy and blood pressure in childhood. Br. J. Obstet. Gynaecol. 1994; 101: 398403.
69Clark PM, Atton C, Law CM, Shiell A, Godfrey K, Barker DJP. Weight gain in pregnancy, triceps skinfold thickness and blood pressure in the offspring. Obstet. Gynaecol. 1998; 91: 103–7.
70Independent Inquiry into Inequalities in Health. Report of the Independent Inquiry into Inequalities in Health. London: The Stationery Office, 1998.
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