The Long-Term Effects of Prenatal Development on Growth and Metabolism

ABSTRACT

People who were small at birth and had poor infant growth have an increased risk of adult cardiovascular disease, osteoporosis, and type 2 diabetes, particularly if their restricted early growth was followed by increased childhood weight gain. These relations extend across the normal range of birth size in a graded manner, so reduced size is not a prerequisite. In addition, larger birth size is associated with risks of obesity and type 2 diabetes. The associations appear to reflect developmental plastic responses made by the fetus and infant based on cues about the environment, influenced by maternal characteristics including diet, body composition, stress, and exercise levels. These responses involve epigenetic processes that modify the offspring's phenotype. Vulnerability to ill health results if the environment in infancy, childhood, and later life is mismatched to the phenotype induced in development, informed by the developmental cues. This mismatch may arise through unbalanced diet or body composition of the mother or a change in lifestyle factors between generations. These insights offer new possibilities for the early diagnosis and prevention of chronic disease.

KEYWORDS

Nutrition - fetal growth - metabolic disease - epigenetics

REFERENCES

• 1 Ramachandran A, Ma R C, Snehalatha C. Diabetes in Asia.  Lancet. 2010;  375 (9712) 408-418
• 2 Godfrey K M, Gluckman P D, Hanson M A. Developmental origins of metabolic disease: life course and intergenerational perspectives.  Trends Endocrinol Metab. 2010;  21 (4) 199-205
• 3 Dörner G. Die mögliche Bedeutung der prä- und/oder perinatalen Ernährung für die Pathogenese der Obesitas.  Acta Biol Med Ger. 1973;  30 19-22
• 4 Forsdahl A. Living conditions in childhood and subsequent development of risk factors for arteriosclerotic heart disease. The cardiovascular survey in Finnmark 1974-75.  J Epidemiol Community Health. 1978;  32 (1) 34-37
• 5 Barker D J, Osmond C. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales.  Lancet. 1986;  1 (8489) 1077-1081
• 6 Osmond C, Barker D JP, Winter P D, Fall C HD, Simmonds S J. Early growth and death from cardiovascular disease in women.  BMJ. 1993;  307 (6918) 1519-1524
• 7 Godfrey K M, Barker D JP. Fetal nutrition and adult disease.  Am J Clin Nutr. 2000;  71 (5, Suppl) 1344S-1352S
• 8 Pike K C, Hanson M A, Godfrey K M. Developmental mismatch: consequences for later cardiorespiratory health.  BJOG. 2008;  115 (2) 149-157
• 9 Cooper C, Javaid M K, Taylor P, Walker-Bone K, Dennison E, Arden N. The fetal origins of osteoporotic fracture.  Calcif Tissue Int. 2002;  70 (5) 391-394
• 10 Gluckman P D, Hanson M A, Cooper C, Thornburg K L. Effect of in utero and early-life conditions on adult health and disease.  N Engl J Med. 2008;  359 (1) 61-73
• 11 Gale C R, Jiang B, Robinson S M, Godfrey K M, Law C M, Martyn C N. Maternal diet during pregnancy and carotid intima-media thickness in children.  Arterioscler Thromb Vasc Biol. 2006;  26 (8) 1877-1882
• 12 Crozier S R, Inskip H M, Godfrey K M Southampton Women's Survey Study Group et al. Weight gain in pregnancy and childhood body composition: findings from the Southampton Women's Survey.  Am J Clin Nutr. 2010;  91 (6) 1745-1751
• 13 Johnsen S L, Wilsgaard T, Rasmussen S, Hanson M A, Godfrey K M, Kiserud T. Fetal size in the second trimester is associated with the duration of pregnancy, small fetuses having longer pregnancies.  BMC Pregnancy Childbirth. 2008;  8 25
• 14 Hanson M A, Godfrey K M. Commentary: Maternal constraint is a pre-eminent regulator of fetal growth.  Int J Epidemiol. 2008;  37 (2) 252-254
• 15 Waddington C H. Canalization of development and the inheritance of acquired characters.  Nature. 1942;  150 563-565
• 16 Pener M P, Yerushalmi Y. The physiology of locust phase polymorphism: an update.  J Insect Physiol. 1998;  44 (5–6) 365-377
• 17 Lee T M, Zucker I. Vole infant development is influenced perinatally by maternal photoperiodic history.  Am J Physiol. 1988;  255 (5 Pt 2) R831-R838
• 18 Waddington C H. Canalization of development and genetic assimilation of acquired characters.  Nature. 1959;  183 (4676) 1654-1655
• 19 Bateson P, Barker D, Clutton-Brock T et al.. Developmental plasticity and human health.  Nature. 2004;  430 (6998) 419-421
• 20 Gluckman P D, Hanson M A, Spencer H G, Bateson P. Environmental influences during development and their later consequences for health and disease: implications for the interpretation of empirical studies.  Proc Biol Sci. 2005;  272 (1564) 671-677
• 21 Uller T. Developmental plasticity and the evolution of parental effects.  Trends Ecol Evol. 2008;  23 (8) 432-438
• 22 Kuzawa C W. Developmental perspectives on the origin of obesity. In: Fantuzzi G, Mazzone T, eds. Adipose Tissue and Adipokines in Health and Disease. Totowa, NJ: Humana Press; 2007: 207-219
• 23 Gluckman P D, Hanson M A. Evolution, development and timing of puberty.  Trends Endocrinol Metab. 2006;  17 (1) 7-12
• 24 Sloboda D M, Howie G J, Pleasants A, Gluckman P D, Vickers M H. Pre- and postnatal nutritional histories influence reproductive maturation and ovarian function in the rat.  PLoS ONE. 2009;  4 (8) e6744
• 25 Gluckman P D, Hanson M A, Spencer H G. Predictive adaptive responses and human evolution.  Trends Ecol Evol. 2005;  20 (10) 527-533
• 26 Sloboda D M, Hart R, Doherty D A, Pennell C E, Hickey M. Age at menarche: influences of prenatal and postnatal growth.  J Clin Endocrinol Metab. 2007;  92 (1) 46-50
• 27 Jablonka E, Raz G. Transgenerational epigenetic inheritance: prevalence, mechanisms, and implications for the study of heredity and evolution.  Q Rev Biol. 2009;  84 (2) 131-176
• 28 West-Eberhard M J. Developmental Plasticity and Evolution. Oxford, United Kingdom: Oxford University Press; 2003
• 29 Gluckman P D, Hanson M A, Beedle A S. Early life events and their consequences for later disease: a life history and evolutionary perspective.  Am J Hum Biol. 2007;  19 (1) 1-19
• 30 Gluckman P D, Hanson M A. The Fetal Matrix: Evolution, Development, and Disease. Cambridge, United Kingdom: Cambridge University Press; 2005
• 31 Hollingsworth J W, Maruoka S, Boon K et al.. In utero supplementation with methyl donors enhances allergic airway disease in mice.  J Clin Invest. 2008;  118 (10) 3462-3469
• 32 Hoppe C C, Evans R G, Moritz K M et al.. Combined prenatal and postnatal protein restriction influences adult kidney structure, function, and arterial pressure.  Am J Physiol Regul Integr Comp Physiol. 2007;  292 (1) R462-R469
• 33 Sellayah D, Sek K, Anthony F W et al.. Appetite regulatory mechanisms and food intake in mice are sensitive to mismatch in diets between pregnancy and postnatal periods.  Brain Res. 2008;  1237 146-152
• 34 Vickers M H, Gluckman P D, Coveny A H et al.. Neonatal leptin treatment reverses developmental programming.  Endocrinology. 2005;  146 (10) 4211-4216
• 35 Cleal J K, Poore K R, Boullin J P et al.. Mismatched pre- and postnatal nutrition leads to cardiovascular dysfunction and altered renal function in adulthood.  Proc Natl Acad Sci U S A. 2007;  104 (22) 9529-9533
• 36 Khan I, Dekou V, Hanson M, Poston L, Taylor P. Predictive adaptive responses to maternal high-fat diet prevent endothelial dysfunction but not hypertension in adult rat offspring.  Circulation. 2004;  110 (9) 1097-1102
• 37 Gluckman P D, Hanson M A. Mismatch; How Our World No Longer Fits Our Bodies. Oxford, United Kingdom: Oxford University Press; 2006
• 38 Leon D A, Lithell H O, Vâgerö D et al.. 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.  BMJ. 1998;  317 (7153) 241-245
• 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
• 40 Torrens C, Snelling T H, Chau R et al.. Effects of pre- and periconceptional undernutrition on arterial function in adult female sheep are vascular bed dependent.  Exp Physiol. 2009;  94 (9) 1024-1033
• 41 Gardner D S, Van Bon B W, Dandrea J et al.. Effect of periconceptional undernutrition and gender on hypothalamic-pituitary-adrenal axis function in young adult sheep.  J Endocrinol. 2006;  190 (2) 203-212
• 42 Kwong W Y, Wild A E, Roberts P, Willis A C, Fleming T P. Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension.  Development. 2000;  127 (19) 4195-4202
• 43 Watkins A J, Ursell E, Panton R et al.. Adaptive responses by mouse early embryos to maternal diet protect fetal growth but predispose to adult onset disease.  Biol Reprod. 2008;  78 (2) 299-306
• 44 Stettler N, Stallings V A, Troxel A B et al.. Weight gain in the first week of life and overweight in adulthood: a cohort study of European American subjects fed infant formula.  Circulation. 2005;  111 (15) 1897-1903
• 45 Eriksson J G, Forsén T J, Kajantie E, Osmond C, Barker D J. Childhood growth and hypertension in later life.  Hypertension. 2007;  49 (6) 1415-1421
• 46 Ylihärsilä H, Kajantie E, Osmond C, Forsén T, Barker D J, Eriksson J G. Body mass index during childhood and adult body composition in men and women aged 56-70 y.  Am J Clin Nutr. 2008;  87 (6) 1769-1775
• 47 Osmond C, Kajantie E, Forsén T J, Eriksson J G, Barker D J. Infant growth and stroke in adult life: the Helsinki birth cohort study.  Stroke. 2007;  38 (2) 264-270
• 48 Kajantie E, Barker D J, Osmond C, Forsén T, Eriksson J G. Growth before 2 years of age and serum lipids 60 years later: the Helsinki Birth Cohort study.  Int J Epidemiol. 2008;  37 (2) 280-289
• 49 Godfrey K M. The “Developmental Origins” hypothesis: epidemiology. In: Hanson M A, Gluckman P D, eds. Developmental Origins of Health and Disease – A Biomedical Perspective. Cambridge, United Kingdom: Cambridge University Press; 2006: 6-32
• 50 Hawkins P, Hanson M A, Matthews S G. Maternal undernutrition in early gestation alters molecular regulation of the hypothalamic-pituitary-adrenal axis in the ovine fetus.  J Neuroendocrinol. 2001;  13 (10) 855-861
• 51 Gluckman P D, Lillycrop K A, Vickers M H et al.. Metabolic plasticity during mammalian development is directionally dependent on early nutritional status.  Proc Natl Acad Sci U S A. 2007;  104 (31) 12796-12800
• 52 Reik W, Dean W, Walter J. Epigenetic reprogramming in mammalian development.  Science. 2001;  293 (5532) 1089-1093
• 53 Burdge G C, Hanson M A, Slater-Jefferies J L, Lillycrop K A. Epigenetic regulation of transcription: a mechanism for inducing variations in phenotype (fetal programming) by differences in nutrition during early life?.  Br J Nutr. 2007;  97 (6) 1036-1046
• 54 Brawley L, Torrens C, Anthony F W et al.. Glycine rectifies vascular dysfunction induced by dietary protein imbalance during pregnancy.  J Physiol. 2004;  554 (Pt 2) 497-504
• 55 Lillycrop K A, Phillips E S, Jackson A A, Hanson M A, Burdge G C. Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring.  J Nutr. 2005;  135 (6) 1382-1386
• 56 Burdge G C, Phillips E S, Dunn R L, Jackson A A, Lillycrop K A. Effect of reduced maternal protein consumption during pregnancy in the rat on plasma lipid concentrations and expression of peroxisomal proliferator-activated receptors in the liver and adipose tissue of the offspring.  Nutr Res. 2004;  24 639-646
• 57 Watkins A J, Platt D, Papenbrock T et al.. Mouse embryo culture induces changes in postnatal phenotype including raised systolic blood pressure.  Proc Natl Acad Sci U S A. 2007;  104 (13) 5449-5454
• 58 Gopalakrishnan G S, Gardner D S, Rhind S M et al.. Programming of adult cardiovascular function after early maternal undernutrition in sheep.  Am J Physiol Regul Integr Comp Physiol. 2004;  287 (1) R12-R20
• 59 Edwards L J, McMillen I C. Periconceptional nutrition programs development of the cardiovascular system in the fetal sheep.  Am J Physiol Regul Integr Comp Physiol. 2002;  283 (3) R669-R679
• 60 Wisløff U, Najjar S M, Ellingsen O et al.. Cardiovascular risk factors emerge after artificial selection for low aerobic capacity.  Science. 2005;  307 (5708) 418-420
• 61 Taylor P D, McConnell J, Khan I Y et al.. Impaired glucose homeostasis and mitochondrial abnormalities in offspring of rats fed a fat-rich diet in pregnancy.  Am J Physiol Regul Integr Comp Physiol. 2005;  288 (1) R134-R139
• 62 Bruce K D, Cagampang F R, Argenton M et al.. Maternal high-fat feeding primes steatohepatitis in adult mice offspring, involving mitochondrial dysfunction and altered lipogenesis gene expression.  Hepatology. 2009;  50 (6) 1796-1808
• 63 Jensen A, Roman C, Rudolph A M. Effects of reducing uterine blood flow on fetal blood flow distribution and oxygen delivery.  J Dev Physiol. 1991;  15 (6) 309-323
• 64 Jones A, Beda A, Osmond C, Godfrey K M, Simpson D M, Phillips D I. Sex-specific programming of cardiovascular physiology in children.  Eur Heart J. 2008;  29 (17) 2164-2170
• 65 Johnstone J F, Zelsman M, Crozier S et al.. The relationship between placental 11ßHSD-2 and maternal body composition, age and dieting status.  J Soc Gynecol Investig. 2005;  12 453
• 66 Edwards L J, Coulter C L, Symonds M E, McMillen I C. Prenatal undernutrition, glucocorticoids and the programming of adult hypertension.  Clin Exp Pharmacol Physiol. 2001;  28 (11) 938-941
• 67 Phillips D I, Walker B R, Reynolds R M et al.. Low birth weight predicts elevated plasma cortisol concentrations in adults from 3 populations.  Hypertension. 2000;  35 (6) 1301-1306
• 68 Jones A, Godfrey K M, Wood P, Osmond C, Goulden P, Phillips D IW. Fetal growth and the adrenocortical response to psychological stress.  J Clin Endocrinol Metab. 2006;  91 (5) 1868-1871
• 69 Reynolds R M, Godfrey K M, Barker M, Osmond C, Phillips D I. Stress responsiveness in adult life: influence of mother's diet in late pregnancy.  J Clin Endocrinol Metab. 2007;  92 (6) 2208-2210
• 70 Yehuda R, Engel S M, Brand S R, Seckl J, Marcus S M, Berkowitz G S. Transgenerational effects of posttraumatic stress disorder in babies of mothers exposed to the World Trade Center attacks during pregnancy.  J Clin Endocrinol Metab. 2005;  90 (7) 4115-4118
• 71 Phillips D I, Barker D J. 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 (8) 673-677
• 72 McMillen I C, MacLaughlin S M, Muhlhausler B S, Gentili S, Duffield J L, Morrison J L. Developmental origins of adult health and disease: the role of periconceptional and foetal nutrition.  Basic Clin Pharmacol Toxicol. 2008;  102 (2) 82-89