Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-78c5997874-s2hrs Total loading time: 0 Render date: 2024-11-18T04:29:16.813Z Has data issue: false hasContentIssue false

Chapter 2 - A Fetal Origin of Adult Disease

from Section 1: - General Principles

Published online by Cambridge University Press:  21 October 2019

By
Mark Hanson  and
Lucy Green
Edited by
Mark D. Kilby ,
Anthony Johnson  and
Dick Oepkes
Mark D. Kilby
Affiliation:
University of Birmingham
Anthony Johnson
Affiliation:
University of Texas Medical School at Houston
Dick Oepkes
Affiliation:
Leids Universitair Medisch Centrum
Get access

Summary

There is a worldwide epidemic of non-communicable diseases (NCDs), including cardiovascular disease (CVD), type 2 diabetes, chronic lung disease, and some forms of cancer; predisposition to these is linked to obesity. This is despite efforts by individuals to modify their diet and lifestyle, and government and global programs aimed at promoting healthy eating or increased physical activity. Some initiatives have begun to target childhood eating and activity. But a strong and international body of scientific and epidemiological data suggests that health interventions should be focused on a much earlier period of development: pregnancy. Expectant couples are often focused on the immediate result of their pregnancy – a viable baby. It may come as a surprise to many of them to hear that the finer details of building a baby are in fact the foundation of lifelong health.

Type
Chapter
Information
Fetal Therapy
Scientific Basis and Critical Appraisal of Clinical Benefits
 , pp. 8 - 19
Publisher: Cambridge University Press
Print publication year: 2020

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Hanson, MA, Gluckman, PD. Early developmental conditioning of later health and disease: physiology or pathophysiology? Physiol Rev. 2014; 94: 1027–76.Google Scholar
World Health Organization (2017). Cardiovascular Diseases (CVDs). https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds).Google Scholar
World Health Organization (2018).Diabetes. https://www.who.int/news-room/fact-sheets/detail/diabetes.Google Scholar
Godfrey, KM, Barker, D J. Fetal programming and adult health. Public Health Nutr. 2001; 4: 611–24.Google Scholar
Barker, D J, Osmond, C, Forsen, T J, Kajantie, E, Eriksson, JG. Trajectories of growth among children who have coronary events as adults. New Engl J Med. 2005; 353: 1802–9.Google Scholar
Gluckman, PD, Hanson, MA, Spencer, HG, 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: 671–7.Google ScholarPubMed
Godfrey, KM. The ‘developmental origins’ hypothesis: epidemiology. In Gluckman, PD and Hanson, M, eds., Developmental Origins of Health and Disease. Cambridge, UK: Cambridge University Press, 2006, pp. 6–32.CrossRefGoogle Scholar
Roseboom, T J, van der Meulen, JH, Osmond, C, Barker, DJ, Ravelli, AC, Schroeder-Tanka, JM, et al. Coronary heart disease after prenatal exposure to the Dutch famine, 1944-45. Heart. 2000; 84: 595–8.Google Scholar
National Institute for Health and Care Excellence (NICE). Public health guideline: dietary interventions and physical activity interventions for weight management before, during and after pregnancy. London, 2010.Google Scholar
Crozier, SR, Inskip, HM, Godfrey, KM, Cooper, C, Harvey, NC, Cole, ZA, Robinson, SM, Southampton Women’s Survey Study Group: weight gain in pregnancy and childhood body composition: findings from the Southampton Women’s Survey. Am J Clin Nutr. 2010; 91: 1745–51.CrossRefGoogle ScholarPubMed
Fraser, A, Tilling, K, Macdonald-Wallis, C, Sattar, N, Brion, MJ, Benfield, L, et al. Association of maternal weight gain in pregnancy with offspring obesity and metabolic and vascular traits in childhood. Circulation. 2010; 121: 2557–64.Google Scholar
Mamun, AA, O’Callaghan, M, Callaway, L, Williams, G, Najman, J, Lawlor, DA. Associations of gestational weight gain with offspring body mass index and blood pressure at 21 Years of age: evidence from a birth cohort study. Circulation. 2009; 199: 1720–7.Google Scholar
Forsen, T, Eriksson, JG, Tuomilehto, J, Teramo, K, Osmond, C, Barker, DJ. Mother’s weight in pregnancy and coronary heart disease in a cohort of Finnish men: follow up study. BMJ. 1997; 315: 837–40.Google Scholar
Stein, CE, Fall, CH, Kumaran, K, Osmond, C, Cox, V, Barker, DJ. Fetal growth and coronary heart disease in south India. Lancet. 1996; 348: 1269–73.CrossRefGoogle ScholarPubMed
Poore, KR, Cleal, JK, Newman, JP, Boullin, JP, Noakes, DE, Hanson, MA, Green, LR. Nutritional challenges during development induce sex-specific changes in glucose homeostasis in the adult sheep. Am J Physiol. 2007; 292: E32–9.Google Scholar
Vickers, MH, Breier, BH, Cutfield, WS, Hofman, PL, Gluckman, PD. Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition. Am J Physiol Endocrinol Metab. 2000; 279: E83–7.Google Scholar
Sellayah, D, Sek, K, Anthony, FW, Watkins, AJ, Osmond, C, Fleming, TP, Hanson, MA, Cagampang, FR. Appetite regulatory mechanisms and food intake in mice are sensitive to mismatch in diets between pregnancy and postnatal periods. Brain Res. 2008; 1237: 146–52.Google Scholar
Brawley, L, Itoh, S, Torrens, C, Barker, A, Bertram, C, Poston, L, Hanson, M. Dietary protein restriction in pregnancy induces hypertension and vascular defects in rat male offspring. Pediatr Res. 2003; 54: 83–90.CrossRefGoogle ScholarPubMed
Gopalakrishnan, GS, Gardner, DS, Rhind, SM, Rae, MT, Kyle, CE, Brooks, AN, et al. Programming of adult cardiovascular function after early maternal undernutrition in sheep. Am J Physiol Regul Integr Comp Physiol. 2004; 287: R12–R20.CrossRefGoogle ScholarPubMed
Hawkins, P, Steyn, C, McGarrigle, HH, Calder, NA, Saito, T, Stratford, LL, et al. Cardiovascular and hypothalamic-pituitary-adrenal axis development in late gestation fetal sheep and young lambs following modest maternal nutrient restriction in early gestation. Reprod Fertil Dev. 2000; 12: 443–56.CrossRefGoogle Scholar
Hawkins, P, Steyn, C, Ozaki, T, Saito, T, Noakes, DE, Hanson, MA. Effect of maternal undernutrition in early gestation on ovine fetal blood pressure and cardiovascular reflexes. Am J Physiol. 2000; 279: R340–8.Google Scholar
Langley-Evans, SC, Welham, SJ, Jackson, AA. Fetal exposure to a maternal low protein diet impairs nephrogenesis and promotes hypertension in the rat. Life Sci. 1999; 64: 965–74.Google Scholar
Cleal, JK, Poore, KR, Boullin, JP, Khan, O, Chau, R, Hambidge, O, 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: 9529–33.Google Scholar
Bertram, C, Khan, O, Ohri, S, Phillips, DI, Matthews, SG, Hanson, MA. Transgenerational effects of prenatal nutrient restriction on cardiovascular and hypothalamic-pituitary-adrenal function. J Physiol. 2008; 586: 2217–29.Google Scholar
Cleal, JK, Poore, KR, Newman, JP, Noakes, DE, Hanson, MA, Green, LR. The effect of maternal undernutrition in early gestation on gestation length and fetal and postnatal growth in sheep. Pediatr Res. 2007; 62: 422–7.CrossRefGoogle ScholarPubMed
Gardner, DS, Tingey, K, Van Bon, BW, Ozanne, SE, Wilson, V, Dandrea, J, et al. Programming of glucose-insulin metabolism in adult sheep after maternal undernutrition. Am J Physiol Regul Integr Comp Physiol. 2005; 289: R947–54.CrossRefGoogle ScholarPubMed
Hawkins, P, Hanson, MA, Matthews, SG. Maternal undernutrition in early gestation alters molecular regulation of the hypothalamic-pituitary-adrenal axis in the ovine fetus. J Neuroendocrinol. 2001; 13: 855–61.CrossRefGoogle ScholarPubMed
Poore, KR, Boullin, JP, Cleal, JK, Newman, JP, Noakes, DE, Hanson, MA, Green, LR. Sex- and age-specific effects of nutrition in early gestation and early postnatal life on hypothalamo-pituitary-adrenal axis and sympathoadrenal function in adult sheep. J Physiol. 2010; 588: 2219–37.CrossRefGoogle ScholarPubMed
Torrens, C, Poston, L, Hanson, MA. Transmission of raised blood pressure and endothelial dysfunction to the F2 generation induced by maternal protein restriction in the F0, in the absence of dietary challenge in the F1 generation. Br J Nutr. 2008; 100: 760–6.Google Scholar
Shasa, DR, Odhiambo, JF, Long, NM, Tuersunjiang, N, Nathanielsz, PW, Ford, SP. Multigenerational impact of maternal overnutrition/obesity in the sheep on the neonatal leptin surge in granddaughters. Int J Obes. 2015; 39: 695–701.Google Scholar
Torrens, C, Snelling, TH, Chau, R, Shanmuganathan, M, Cleal, JK, Poore, KR, et al. Effects of pre- and periconceptional undernutrition on arterial function in adult female sheep are vascular bed dependent. Exp Physiol. 2009; 94: 1024–33.Google Scholar
Gopalakrishnan, GS, Gardner, DS, Dandrea, J, Langley-Evans, SC, Pearce, S, Kurlak, LO, et al. Influence of maternal pre-pregnancy body composition and diet during early-mid pregnancy on cardiovascular function and nephron number in juvenile sheep. Br J Nutr. 2005; 94: 938–47.CrossRefGoogle ScholarPubMed
Costello, PM, Hollis, LJ, Cripps, RL, Bearpark, N, Patel, HP, Sayer, AA, et al. Lower maternal body condition during pregnancy affects skeletal muscle structure and glut-4 protein levels but not glucose tolerance in mature adult sheep. Reprod Sci. 2013; 20: 1144–55.Google Scholar
Fainberg, HP, Sharkey, D, Sebert, S, Wilson, V, Pope, M, Budge, H, Symonds, ME. Suboptimal maternal nutrition during early fetal kidney development specifically promotes renal lipid accumulation following juvenile obesity in the offspring. Reprod Fertil Dev. 2013; 25: 728–36.CrossRefGoogle ScholarPubMed
Nielsen, MO, Kongsted, AH, Thygesen, MP, Strathe, AB, Caddy, S, Quistorff, B, et al. Late gestation undernutrition can predispose for visceral adiposity by altering fat distribution patterns and increasing the preference for a high-fat diet in early postnatal life. Br J Nutr. 2013; 109: 2098–110.CrossRefGoogle ScholarPubMed
Khanal, P, Johnsen, L, Axel, AM, Hansen, PW, Kongsted, AH, Lyckegaard, NB, Nielsen, MO. Long-term impacts of foetal malnutrition followed by early postnatal obesity on fat distribution pattern and metabolic adaptability in adult sheep. PLoS One. 2016; 11: e0156700.Google Scholar
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: 1097–102.Google Scholar
Desai, M, Byrne, CD, Meeran, K, Martenz, ND, Bloom, SR, Hales, CN. Regulation of hepatic enzymes and insulin levels in offspring of rat dams fed a reduced-protein diet. Am J Physiol. 1997; 273: G899–904.Google ScholarPubMed
Ozanne, SE, Hales, CN. Lifespan: catch-up growth and obesity in male mice. Nature. 2004; 427: 411–12.Google Scholar
Norman, JF, LeVeen, RF. Maternal atherogenic diet in swine is protective against early atherosclerosis development in offspring consuming an atherogenic diet post-natally. Atherosclerosis. 2001; 157: 41–7.Google Scholar
Halvorsen, CP, Andolf, E, Hu, J, Pilo, C, Winbladh, B, Norman, M. Discordant twin growth in utero and differences in blood pressure and endothelial function at 8 years of age. J Intern Med. 2006; 259: 155–63.Google Scholar
Jiang, BY, Godfrey, KM, Martyn, CN, Gale, CR. Birth weight and cardiac structure in children. Pediatrics. 2006; 117: E257–61.Google Scholar
Torrance, HL, Bloemen, MC, Mulder, EJ, Nikkels, PG, Derks, JB, de Vries, LS, Visser, GH. Predictors of outcome at 2 years of age after early intrauterine growth restriction. Ultrasound Obs. 2010; 36: 171–7.Google ScholarPubMed
Burrage, DM, Braddick, L, Cleal, JK, Costello, P, Noakes, DE, Hanson, MA, Green, LR. The late gestation fetal cardiovascular response to hypoglycaemia is modified by prior peri-implantation undernutrition in sheep. J Physiol. 2009; 587: 611–24.Google Scholar
Aberdeen, GW, Baschat, AA, Harman, CR, Weiner, CP, Langenberg, PW, Pepe, GJ, Albrecht, ED. Uterine and fetal blood flow indexes and fetal growth assessment after chronic estrogen suppression in the second half of baboon pregnancy. Am J Physiol Heart Circ Physiol. 2010; 298: H881–9.CrossRefGoogle ScholarPubMed
Burrage, D, Green, LR, Moss, TJ, Sloboda, DM, Nitsos, I, Newnham, JP, Hanson, MA. The carotid bodies influence growth responses to moderate maternal undernutrition in late-gestation fetal sheep. BJOG. 2008; 115: 261–8.Google Scholar
Cleal, JK, Bagby, S, Hanson, MA, Gardiner, HM, Green, LR. The effect of late gestation foetal hypoglycaemia on cardiovascular and endocrine function in sheep. J Dev Orig Health Dis. 2010; 1: 42–9.CrossRefGoogle ScholarPubMed
Haugen, G, Hanson, M, Kiserud, T, Crozier, S, Inskip, H, Godfrey, KM. Fetal liver-sparing cardiovascular adaptations linked to mother’s slimness and diet. Circ Res. 2005; 96: 12–14.Google Scholar
Kessler, J, Rasmussen, S, Godfrey, K, Hanson, M, Kiserud, T. Longitudinal study of umbilical and portal venous blood flow to the fetal liver: low pregnancy weight gain is associated with preferential supply to the fetal left liver lobe. Pediatr Res. 2008; 63: 315–20.Google Scholar
Nishina, H, Green, LR, McGarrigle, HH, Noakes, DE, Poston, L, Hanson, MA. Effect of nutritional restriction in early pregnancy on isolated femoral artery function in mid-gestation fetal sheep. J Physiol. 2003; 553: 637–47.Google Scholar
Ozaki, T, Hawkins, P, Nishina, H, Steyn, C, Poston, L, Hanson, MA. Effects of undernutrition in early pregnancy on systemic small artery function in late-gestation fetal sheep. Am J Obstet Gynecol. 2000; 183: 1301–7.Google Scholar
Edwards, L, McMillen, I. Maternal undernutrition increases arterial blood pressure in the sheep fetus during late gestation. J Physiol. 2001; 533: 561–70.Google Scholar
Vasak, B, Koenen, SV, Koster, MP, Hukkelhoven, CW, Franx, A, Hanson, MA, Visser, GH. Human fetal growth is constrained below optimal for perinatal survival. Ultrasound Obstet Gynecol. 2015; 45: 162–7.Google Scholar
Kiserud, T, Piaggio, G, Carroli, G, Widmer, M, Carvalho, J, Neerup Jensen, L, et al. The World Health Organization Fetal Growth Charts: A Multinational Longitudinal Study of Ultrasound Biometric Measurements and Estimated Fetal Weight. PLOS Med. 2017; 14: e1002220.Google Scholar
Oliver, MH, Hawkins, P, Harding, JE. Periconceptional undernutrition alters growth trajectory and metabolic and endocrine responses to fasting in late-gestation fetal sheep. Pediatr Res. 2005; 57: 591–8.Google Scholar
Costello, PM, Rowlerson, A, Astaman, NA, Anthony, FE, Sayer, AA, Cooper, C, Hanson, MA, Green, LR. Peri-implantation and late gestation maternal undernutrition differentially affect fetal sheep skeletal muscle development. J Physiol. 2008; 586: 2371–9.Google Scholar
Shukla, P, Ghatta, S, Dubey, N, Lemley, CO, Johnson, ML, Modgil, A, et al. Maternal nutrient restriction during pregnancy impairs an endothelium-derived hyperpolarizing factor-like pathway in sheep fetal coronary arteries. Am J Physiol Heart Circ Physiol. 2014; 307: H134–42.Google Scholar
Lie, S, Sim, SM, McMillen, IC, Williams-Wyss, O, MacLaughlin, SM, Kleemann, DO, et al. Maternal undernutrition around the time of conception and embryo number each impact on the abundance of key regulators of cardiac growth and metabolism in the fetal sheep heart. J Dev Orig Health Dis. 2013; 4: 377–90.Google Scholar
Han, H-C, Austin, KJ, Nathanielsz, PW, Ford, SP, Nijland, MJ, Hansen, TR. Maternal nutrient restriction alters gene expression in the ovine fetal heart. J Physiol. 2004; 558: 111–21.Google Scholar
Vonnahme, KA, Hess, BW, Hansen, TR, McCormick, RJ, Rule, DC, Moss, GE, et al. Maternal undernutrition from early- to mid-gestation leads to growth retardation, cardiac ventricular hypertrophy, and increased liver weight in the fetal sheep. Biol Reprod. 2003; 69: 133–40.CrossRefGoogle ScholarPubMed
Dong, F, Ford, SP, Fang, CX, Nijland, MJ, Nathanielsz, PW, Ren, J. Maternal nutrient restriction during early to mid gestation up-regulates cardiac insulin-like growth factor (IGF) receptors associated with enlarged ventricular size in fetal sheep. Growth Horm IGF Res. 2005; 15: 291–9.Google Scholar
Wang, J, Ma, H, Tong, C, Zhang, H, Lawlis, GB, Li, Y, et al. Overnutrition and maternal obesity in sheep pregnancy alter the JNK-IRS-1 signaling cascades and cardiac function in the fetal heart. FASEB J. 2010; 24: 2066–76.Google Scholar
Paradis, F, Wood, KM, Swanson, KC, Miller, SP, McBride, BW, Fitzsimmons, C. Maternal nutrient restriction in mid-to-late gestation influences fetal mRNA expression in muscle tissues in beef cattle. BMC Genomics. 2017; 18: 632.Google Scholar
Lie, S, Morrison, JL. Impact of periconceptional and preimplantation undernutrition on factors regulating myogenesis and protein synthesis in muscle of singleton and twin fetal sheep. Physiol Rep. 2015; 3: e12495.Google Scholar
Lie, S, Morrison, JL, Williams-Wyss, O, Suter, CM, Humphreys, DT, Ozanne, SE, et al. Periconceptional undernutrition programs changes in insulin-signaling molecules and microRNAs in skeletal muscle in singleton and twin fetal sheep. Biol Reprod. 2014; 90: 5.Google Scholar
Green, LR, Hester, RL (eds). Parental Obesity: Intergenerational Programming and Consequences. New York: Springer-Verlag, 2016.Google Scholar
Hellmuth, C, Uhl, O, Kirchberg, FF, Harder, U, Peissner, W, Koletzko, B, Nathanielsz, PW. Influence of moderate maternal nutrition restriction on the fetal baboon metabolome at 0.5 and 0.9 gestation. Nutr Metab Cardiovasc Dis. 2016; 26: 786–96.Google Scholar
Lie, S, Morrison, JL, Williams-Wyss, O, Ozanne, SE, Zhang, S, Walker, SK, et al. Impact of embryo number and periconceptional undernutrition on factors regulating adipogenesis, lipogenesis, and metabolism in adipose tissue in the sheep fetus. Am J Physiol Endocrinol Metab. 2013; 305: E931–41.Google Scholar
Nicholas, LM, Rattanatray, L, MacLaughlin, SM, Ozanne, SE, Kleemann, DO, Walker, SK, et al. Differential effects of maternal obesity and weight loss in the periconceptional period on the epigenetic regulation of hepatic insulin-signaling pathways in the offspring. FASEB J. 2013; 27: 3786–96.Google Scholar
Poore, KR, Hollis, LJ, Murray, RJ, Warlow, A, Brewin, A, Fulford, L, et al. Differential pathways to adult metabolic dysfunction following poor nutrition at two critical developmental periods in sheep. PLoS One. 2014; 9: e90994.Google Scholar
Bloomfield, FH, Oliver, MH, Hawkins, P, Campbell, M, Phillips, DJ, Gluckman, PD, Challis, JR, Harding, JE. A periconceptional nutritional origin for noninfectious preterm birth. Science. 2003; 300: 606.Google Scholar
Pardal, R, Lopez-Barneo, J. Low glucose-sensing cells in the carotid body. Nat. Neurosci. 2002; 5: 197–8.Google Scholar
Ahokas, RA, Reynolds, SL, Anderson, GD, Lipshitz, J. Maternal organ distribution of cardiac output in the diet-restricted pregnant rat. J Nutr. 1984; 114: 2262–8.Google Scholar
Itoh, S, Brawley, L, Wheeler, T, Anthony, FW, Poston, L, Hanson, MA. Vasodilation to vascular endothelial growth factor in the uterine artery of the pregnant rat is blunted by low dietary protein intake. Pediatr Res. 2002; 51: 485–91.Google Scholar
Lemley, CO, Meyer, AM, Camacho, LE, Neville, TL, Newman, DJ, Caton, JS, Vonnahme, KA. Melatonin supplementation alters uteroplacental hemodynamics and fetal development in an ovine model of intrauterine growth restriction. Am J Physiol Integr Comp Physiol. 2012; 302: R454–67.Google Scholar
Torrens, C, Brawley, L, Anthony, FW, Dance, CS, Dunn, R, Jackson, AA, Poston, L, Hanson, MA. Folate supplementation during pregnancy improves offspring cardiovascular dysfunction induced by protein restriction. Hypertension. 2006; 47: 982–7.CrossRefGoogle ScholarPubMed
Fleming, TP, Watkins, AJ, Velazquez, MA, Mathers, JC, Prentice, AM, Stephenson, J, et al. Origins of lifetime health around the time of conception: causes and consequences. Lancet. 2018; 391: 1842–52.Google Scholar
Lewis, RM, Cleal, JK, Hanson, MA. Review: Placenta, evolution and lifelong health. Placenta. 2012; 33 (Suppl.): S28–S32.CrossRefGoogle ScholarPubMed
Roberts, VHJ, Lo, JO, Lewandowski, KS, Blundell, P, Grove, KL, Kroenke, CD, Sullivan, EL, Roberts, CT Jr., Frias, AE. Adverse placental perfusion and pregnancy outcomes in a new nonhuman primate model of gestational protein restriction. Reprod Sci. 2018; 25: 110–19.Google Scholar
Cleal, JK, Day, PE, Simner, CL, Barton, SJ, Mahon, PA, Inskip, HM, et al. Placental amino acid transport may be regulated by maternal vitamin D and vitamin D-binding protein: results from the Southampton Women’s Survey. Br J Nutr. 2015; 113: 1903–10.Google Scholar
Sferruzzi-Perri, AN, López-Tello, J, Fowden, AL, Constancia, M. Maternal and fetal genomes interplay through phosphoinositol 3-kinase(PI3K)-p110α signaling to modify placental resource allocation. Proc Natl Acad Sci. 2016; 113: 11255–60.Google Scholar
Lewis, RM, Greenwood, SL, Cleal, JK, Crozier, SR, Verrall, L, Inskip, HM, et al. Maternal muscle mass may influence system A activity in human placenta. Placenta. 2010; 31: 418–22.Google Scholar
Sinclair, KD, Allegrucci, C, Singh, R, Gardner, DS, Sebastian, S, Bispham, J, et al. DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proc Natl Acad Sci U.S.A. 2007; 104: 19351–6.CrossRefGoogle ScholarPubMed
Burdge, GC, Hanson, MA, Slater-Jefferies, JL, Lillycrop, KA. 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: 1036–46.Google Scholar
Begum, G, Stevens, A, Smith, EB, Connor, K, Challis, JR, Bloomfield, F, White, A. Epigenetic changes in fetal hypothalamic energy regulating pathways are associated with maternal undernutrition and twinning. FASEB J. 2012; 26: 1694–1703.Google Scholar
Nijland, MJ, Mitsuya, K, Li, C, Ford, S, McDonald, TJ, Nathanielsz, PW, Cox, LA. Epigenetic modification of fetal baboon hepatic phosphoenolpyruvate carboxykinase following exposure to moderately reduced nutrient availability. J Physiol. 2010; 588: 1349–59.Google Scholar
Murray, R, Bryant, J, Titcombe, P, Barton, SJ, Inskip, H, Harvey, NC, et al. DNA methylation at birth within the promoter of ANRIL predicts markers of cardiovascular risk at 9 years. Clin. Epigenetics. 2016; 8: 90.Google Scholar
Curtis, EM, Murray, R, Titcombe, P, Cook, E, Clarke-Harris, R, Costello, P, et al. Perinatal DNA methylation at CDKN2A is associated with offspring bone mass: findings from the Southampton women’s survey. J Bone Miner Res. 2017; 32: 2030–40.Google Scholar
Carr, DJ, Wallace, JM, Aitken, RP, Milne, JS, Martin, JF, Zachary, IC, Peebles, DM, David, AL. Peri- and postnatal effects of prenatal adenoviral VEGF gene therapy in growth-restricted sheep. Biol Reprod. 2016; 94: 1–12.CrossRefGoogle ScholarPubMed
Patel, N, Godfrey, KM, Pasupathy, D, Levin, J, Flynn, AC, Hayes, L, et al. Infant adiposity following a randomised controlled trial of a behavioural intervention in obese pregnancy. Int J Obes. 2017; 41: 1018–26.Google Scholar
Kermack, AJ, Calder, PC, Houghton, FD, Godfrey, KM, Macklon, NS. A randomised controlled trial of a preconceptional dietary intervention in women undergoing IVF treatment (PREPARE trial). BMC Womens Health. 2014; 14: 130.Google Scholar
Barker, M, Dombrowski, SU, Colbourn, T, Fall, CHD, Kriznik, NM, Lawrence, WT, et al. Intervention strategies to improve nutrition and health behaviours before conception. Lancet. 2018; 391: 1853–64.Google Scholar
Woods-Townsend, K, Bagust, L, Barker, M, Christodoulou, A, Davey, H, Godfrey, K, et al. Engaging teenagers in improving their health behaviours and increasing their interest in science (Evaluation of LifeLab Southampton): study protocol for a cluster randomized controlled trial. Trials. 2015; 16: 372.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×