Influence of Maternal Obesity on the Long-Term Health of Offspring

  • Emma C. Johns
  • David Q. Stoye
  • Liu Yang
  • Rebecca M. ReynoldsEmail author
Part of the Healthy Ageing and Longevity book series (HAL, volume 9)


Maternal obesity is a growing public health problem across the world. In many high-income countries, more than 1 in 5 pregnant women are now categorised as obese. Compared to offspring born to normal weight women, babies born to obese mothers have a greater risk of adverse health outcomes across their lifespan, including obesity, cardiovascular disease and premature mortality in adulthood. The mechanisms through which maternal obesity elicits this long-term influence on offspring health is believed to represent a ‘programming’ effect of the obesogenic in utero environment. Alterations in maternal glucose and insulin sensitivity and hypothalamic-pituitary-adrenal axis regulation have been described in association with maternal obesity and may contribute to fetal programming. In addition, epigenetic modifications in maternal adipose and feto-placental tissues have been described, although their clinical significance remains uncertain. Lifestyle and medical interventions have shown limited success in attenuating the impact of maternal obesity on offspring growth and body composition during infancy, although longer-term follow-up is required.


In utero environment Fetal programming Epigenetic modification Maternal obesity Long-term health outcome Lifespan 


  1. Acosta O et al (2015) Increased glucose and placental GLUT-1 in large infants of obese nondiabetic mothers. Am J Obstet Gynecol 212(227):e1–227.e7Google Scholar
  2. Aron-Wisnewsky J et al (2011) Effect of bariatric surgery-induced weight loss on SR-BI-, ABCG1-, and ABCA1-mediated cellular cholesterol efflux in obese women. J Clin Endocrinol Metab 96:1151–1159PubMedCrossRefPubMedCentralGoogle Scholar
  3. Aubuchon-Endsley NL, Bublitz MH, Stroud LR (2014) Pre-pregnancy obesity and maternal circadian cortisol regulation: moderation by gestational weight gain. Biol Psychol 102:38–43PubMedCrossRefPubMedCentralGoogle Scholar
  4. Baibazarova E et al (2013) Influence of prenatal maternal stress, maternal plasma cortisol and cortisol in the amniotic fluid on birth outcomes and child temperament at 3 months. Psychoneuroendocrinology 38:907–915PubMedCrossRefPubMedCentralGoogle Scholar
  5. Barker DJP (2004) The developmental origins of adult disease. J Am Coll Nutr 23:588S–595SPubMedCrossRefPubMedCentralGoogle Scholar
  6. Bashiri A et al (2014) Pregnancy complicated by obesity induces global transcript expression alterations in visceral and subcutaneous fat. Mol Genet Genomics 289:695–705PubMedPubMedCentralCrossRefGoogle Scholar
  7. Beaujean N et al (2004) Non-conservation of mammalian preimplantation methylation dynamics. Curr Biol 14:R266–R267PubMedCrossRefPubMedCentralGoogle Scholar
  8. Benediktsson R, Calder AA, Edwards CRW, Seckl JR (1997) Placental 11β-hydroxysteroid dehydrogenase: a key regulator of fetal glucocorticoid exposure. Clin Endocrinol (Oxf) 46:161–166CrossRefGoogle Scholar
  9. Berglund SK et al (2016) Maternal, fetal and perinatal alterations associated with obesity, overweight and gestational diabetes: an observational cohort study (PREOBE). BMC Public Health 16:207PubMedPubMedCentralCrossRefGoogle Scholar
  10. Bianco-Miotto T, Craig JM, Gasser YP, van Dijk SJ, Ozanne SE (2017) Epigenetics and DOHaD: from basics to birth and beyond. J Dev Orig Health Dis 8:513–519PubMedCrossRefPubMedCentralGoogle Scholar
  11. Bleker LS, Roseboom TJ, Vrijkotte TG, Reynolds RM, de Rooij SR (2017) Determinants of cortisol during pregnancy—the ABCD cohort. Psychoneuroendocrinology 83:172–181PubMedCrossRefPubMedCentralGoogle Scholar
  12. Brelje TC et al (1993) Effect of homologous placental lactogens, prolactins, and growth hormones on islet b-cell division and insulin secretion in rat, mouse, and human islets: implication for placental lactogen regulation of islet function during pregnancy. Endocrinology 132:879–887PubMedCrossRefPubMedCentralGoogle Scholar
  13. Brennecke J, Stark A, Russell RB, Cohen SM (2005) Principles of MicroRNA–target recognition. PLoS Biol 3:e85–e85PubMedPubMedCentralCrossRefGoogle Scholar
  14. Brightling CE et al (2014) Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study. Lancet Respir Med 2:891–901PubMedPubMedCentralCrossRefGoogle Scholar
  15. Burris HH et al (2015) Offspring DNA methylation of the aryl-hydrocarbon receptor repressor gene is associated with maternal BMI, gestational age, and birth weight. Epigenetics 10:913–921PubMedPubMedCentralCrossRefGoogle Scholar
  16. Buss C et al (2012) Maternal cortisol over the course of pregnancy and subsequent child amygdala and hippocampus volumes and affective problems. Proc Natl Acad Sci 109:E1312–E1319PubMedCrossRefPubMedCentralGoogle Scholar
  17. Catalano PM (2014) Trying to understand gestational diabetes. Diabet Med 31:273–281PubMedPubMedCentralCrossRefGoogle Scholar
  18. Catalano PM, Tyzbir ED, Roman NM, Amini SB, Sims EAH (1991) Longitudinal changes in insulin release and insulin resistance in nonobese pregnant women. Am J Obstet Gynecol 165:1667–1672PubMedCrossRefPubMedCentralGoogle Scholar
  19. Catalano PM et al (1992) Longitudinal changes in basal hepatic glucose production and suppression during insulin infusion in normal pregnant women. Am J Obstet Gynecol 167:913–919PubMedCrossRefPubMedCentralGoogle Scholar
  20. Catalano PM, Presley L, Minium J, de Mouzon SH (2009) Fetuses of obese mothers develop insulin resistance in utero. Diabetes Care 32:1076–1080PubMedPubMedCentralCrossRefGoogle Scholar
  21. Chen C, Xu X, Yan Y (2018) Estimated global overweight and obesity burden in pregnant women based on panel data model. PLoS ONE 13:e0202183PubMedPubMedCentralCrossRefGoogle Scholar
  22. Cherak SJ, Giesbrecht GF, Metcalfe A, Ronksley PE, Malebranche ME (2018) The effect of gestational period on the association between maternal prenatal salivary cortisol and birth weight: a systematic review and meta-analysis. Psychoneuroendocrinology 94:49–62PubMedCrossRefPubMedCentralGoogle Scholar
  23. Chiswick C et al (2015) Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 3:778–786PubMedPubMedCentralCrossRefGoogle Scholar
  24. Chu S et al (2007) Maternal obesity and risk of gestational diabetes mellitus. Diabetes Care 30:2070–2076PubMedCrossRefPubMedCentralGoogle Scholar
  25. Clausen TD et al (2008) High prevalence of type 2 diabetes and pre-diabetes in adult offspring of women with gestational diabetes mellitus or type 1 diabetes: the role of intrauterine hyperglycemia. Diabetes Care 31:340–346PubMedCrossRefPubMedCentralGoogle Scholar
  26. Clausen TD et al (2009) Overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus or type 1 diabetes. J Clin Endocrinol Metab 94:2464–2470PubMedCrossRefPubMedCentralGoogle Scholar
  27. Cnop M et al (2002) The concurrent accumulation of intra-abdominal and subcutaneous fat explains the association between insulin resistance and plasma leptin concentrations: distinct metabolic effects of two fat compartments. Diabetes 51:1005–1015PubMedCrossRefPubMedCentralGoogle Scholar
  28. Colomiere M, Permezel M, Riley C, Desoye G, Lappas M (2009) Defective insulin signaling in placenta from pregnancies complicated by gestational diabetes mellitus. Eur J Endocrinol 160:567–578PubMedCrossRefPubMedCentralGoogle Scholar
  29. Contu L, Hawkes CA (2017) A review of the impact of maternal obesity on the cognitive function and mental health of the offspring. Int J Mol Sc 18Google Scholar
  30. Cora’ D, Re A, Caselle M, Bussolino F (2017) MicroRNA-mediated regulatory circuits: outlook and perspectives. Phys Biol 14:45001PubMedCrossRefPubMedCentralGoogle Scholar
  31. Costa-Font J, Mas N (2016) ‘Globesity’? The effects of globalization on obesity and caloric intake. Food Policy 64:121–132CrossRefGoogle Scholar
  32. Côté S et al (2016) PPARGC1α gene DNA methylation variations in human placenta mediate the link between maternal hyperglycemia and leptin levels in newborns. Clin Epigenetics 8:72PubMedPubMedCentralCrossRefGoogle Scholar
  33. Cottrell EC, Seckl JR (2009) Prenatal stress, glucocorticoids and the programming of adult disease. Front Behav Neurosci 3:19PubMedPubMedCentralCrossRefGoogle Scholar
  34. Cottrell EC, Seckl JR, Holmes MC, Wyrwoll CS (2014) Foetal and placental 11β-HSD2: a hub for developmental programming. Acta Physiol 210:288–295CrossRefGoogle Scholar
  35. Dalziel SR et al (2005) Cardiovascular risk factors after antenatal exposure to betamethasone: 30-Year follow-up of a randomised controlled trial. Lancet 365:1856–1862PubMedCrossRefPubMedCentralGoogle Scholar
  36. Davis EP, Sandman CA (2010) The timing of prenatal exposure to maternal cortisol and psychosocial stress is associated with human infant cognitive development. Child Dev 81:131–148PubMedPubMedCentralCrossRefGoogle Scholar
  37. Devlieger R et al (2016) Maternal obesity in Europe: where do we stand and how to move forward?: A scientific paper commissioned by the European Board and College of Obstetrics and Gynaecology (EBCOG). Eur J Obstet Gynecol Reprod Biol 201:203–208PubMedCrossRefGoogle Scholar
  38. Diego MA et al (2009) Prenatal depression restricts fetal growth. Early Hum Dev 85:65–70PubMedCrossRefGoogle Scholar
  39. DiPietro JA, Costigan KA, Kivlighan KT, Chen P, Laudenslager ML (2011) Maternal salivary cortisol differs by fetal sex during the second half of pregnancy. Psychoneuroendocrinology 36:588–591PubMedPubMedCentralCrossRefGoogle Scholar
  40. Dodd JM (2014) Antenatal lifestyle advice for women who are overweight or obese: LIMIT randomised trial OPEN ACCESS. BMJ 348:g1285PubMedPubMedCentralCrossRefGoogle Scholar
  41. Dodd JM et al (2018) Effects of an antenatal dietary intervention in overweight and obese women on 6 month infant outcomes: follow-up from the LIMIT randomised trial. Int J Obes 42:1326–1335CrossRefGoogle Scholar
  42. Doyle LW, Ford GW, Davis NM, Callanan C (2000) Antenatal corticosteroid therapy and blood pressure at 14 years of age in preterm children. Clin Sci (Lond) 98:137–142CrossRefGoogle Scholar
  43. Ericsson A, Hamark B, Powell TL, Jansson T (2005) Glucose transporter isoform 4 is expressed in the syncytiotrophoblast of first trimester human placenta. Hum Reprod 20:521–530PubMedCrossRefPubMedCentralGoogle Scholar
  44. Eriksson J, Forsén T, Osmond C, Barker D (2003) Obesity from cradle to grave. Int J Obes 27:722–727CrossRefGoogle Scholar
  45. Eriksson JG, Sandboge S, Salonen MK, Kajantie E, Osmond C (2014) Long-term consequences of maternal overweight in pregnancy on offspring later health: findings from the Helsinki Birth Cohort Study. Ann Med 46:434–438PubMedCrossRefPubMedCentralGoogle Scholar
  46. Ferrara A (2007a) Increasing prevalence of gestational diabetes mellitus: a public health perspective. Diabetes Care 30:S141–S146PubMedCrossRefPubMedCentralGoogle Scholar
  47. Ferrara A (2007b) Increasing prevalence of gestational diabetes mellitus: a public health perspective. Diabetes Care 30(Suppl 2):S141–S146PubMedCrossRefPubMedCentralGoogle Scholar
  48. Ford N, Narayan KMV, Patel S (2017) Obesity in low- and middle-income countries: burden, drivers, and emerging challenges. SSRN 38PubMedCrossRefPubMedCentralGoogle Scholar
  49. Forno E, Young OM, Kumar R, Simhan H, Celedon JC (2014) Maternal obesity in pregnancy, gestational weight gain, and risk of childhood asthma. Pediatrics 134:e535–e546PubMedPubMedCentralCrossRefGoogle Scholar
  50. Forsén T et al (1997) Mother’s weight in pregnancy and coronary heart disease in a cohort of Finnish men: follow up study. BMJ 315:837–840PubMedPubMedCentralCrossRefGoogle Scholar
  51. Fowden AL, Li J, Forhead AJ (1998) Glucocorticoids and the preparation for life after birth: are there long-term consequences of the life insurance? Proc Nutr Soc 57:113–122PubMedCrossRefPubMedCentralGoogle Scholar
  52. Gaillard R et al (2014) Childhood cardiometabolic outcomes of maternal obesity during pregnancy: the Generation R Study. Hypertension 63:683–691PubMedCrossRefPubMedCentralGoogle Scholar
  53. Gemma C et al (2009) Maternal pregestational BMI is associated with methylation of the PPARGC1A promoter in newborns. Obesity 17:3–10PubMedCrossRefPubMedCentralGoogle Scholar
  54. Gentilini D et al (2013) Role of epigenetics in human aging and longevity: genome-wide DNA methylation profile in centenarians and centenarians’ offspring. Age (Omaha) 35:1961–1973CrossRefGoogle Scholar
  55. Ghosh S, Bouchard C (2017) Convergence between biological, behavioural and genetic determinants of obesity. Nat Rev Genet 18:731–748PubMedCrossRefPubMedCentralGoogle Scholar
  56. Gifford RM, Reynolds RM (2017) Sex differences in early-life programming of the hypothalamic–pituitary–adrenal axis in humans. Early Hum Dev 114:7–10PubMedCrossRefPubMedCentralGoogle Scholar
  57. Gitau R, Cameron A, Fisk NM, Glover V (1998) Fetal exposure to maternal cortisol. Lancet 352:707–708PubMedCrossRefPubMedCentralGoogle Scholar
  58. Godfrey KM, Costello PM, Lillycrop KA (2015) The developmental environment, epigenetic biomarkers and long-term health. J Dev Orig Health Dis 6:399–406PubMedPubMedCentralCrossRefGoogle Scholar
  59. Godfrey KM et al (2017) Influence of maternal obesity on the long-term health of offspring. Lancet Diabetes Endocrinol 5:53–64PubMedCrossRefPubMedCentralGoogle Scholar
  60. Goedhart G et al (2010) Maternal cortisol and offspring birthweight: Results from a large prospective cohort study. Psychoneuroendocrinology 35:644–652PubMedCrossRefPubMedCentralGoogle Scholar
  61. Goland RS, Jozak S, Conwell I (1994) Placental corticotropin-releasing hormone and the hypercortisolism of pregnancy. Am J Obstet Gynecol 171:1287–1291PubMedCrossRefPubMedCentralGoogle Scholar
  62. Gorski JN (2006) Postnatal environment overrides genetic and prenatal factors influencing offspring obesity and insulin resistance. AJP Regul Integr Comp Physiol 291:R768–R778CrossRefGoogle Scholar
  63. Graham AM et al (2018) Maternal cortisol concentrations during pregnancy and sex specific associations with neonatal amygdala connectivity and emerging internalizing behaviors. Biol Psychiatry. Scholar
  64. Hammoud NM et al (2018) Long-term BMI and growth profiles in offspring of women with gestational diabetes. Diabetologia 61:1037–1045PubMedPubMedCentralCrossRefGoogle Scholar
  65. Harris T, North M (2010) The genetics of obesity. Curr Opin Genet Dev 10:398–404Google Scholar
  66. Heslehurst N et al (2007) Trends in maternal obesity incidence rates, demographic predictors, and health inequalities in 36,821 women over a 15-year period. BJOG Int J Obstet Gynaecol 114:187–194CrossRefGoogle Scholar
  67. Heslehurst N, Rankin J, Wilkinson JR, Summerbell CD (2010) A nationally representative study of maternal obesity in England, UK: trends in incidence and demographic inequalities in 619 323 births, 1989–2007. Int J Obes 34:420–428CrossRefGoogle Scholar
  68. Hidalgo B et al (2014) Epigenome-wide association study of fasting measures of glucose, insulin, and HOMA-IR in the genetics of lipid lowering drugs and diet network study. Diabetes 63:801–807PubMedPubMedCentralCrossRefGoogle Scholar
  69. Hoyo C et al (2012) Association of cord blood methylation fractions at imprinted insulin-like growth factor 2 (IGF2), plasma IGF2, and birth weight. Cancer Causes Control 23:635–645PubMedPubMedCentralCrossRefGoogle Scholar
  70. Hussen HI, Persson M, Moradi T (2015) Maternal overweight and obesity are associated with increased risk of type 1 diabetes in offspring of parents without diabetes regardless of ethnicity. Diabetologia 58:1464–1473PubMedCrossRefGoogle Scholar
  71. Illsley NP (2000) Glucose transporters in the human placenta. Placenta 21:14–22PubMedCrossRefGoogle Scholar
  72. Incollingo Rodriguez AC et al (2015) Hypothalamic-pituitary-adrenal axis dysregulation and cortisol activity in obesity: a systematic review. Psychoneuroendocrinology 62:301–318PubMedCrossRefGoogle Scholar
  73. International Diabetes Federation (2017) IDF diabetes atlas 2017Google Scholar
  74. Jablonka E, Lamb MJ (2006) Book review evolution in four dimensions. J Hered 97Google Scholar
  75. Johansson LE et al (2012) Differential gene expression in adipose tissue from obese human subjects during weight loss and weight maintenance. Am J Clin Nutr 96:196–207PubMedCrossRefGoogle Scholar
  76. Johansson K, Stephansson O, Neovius M (2015) Outcomes of pregnancy after bariatric surgery. N Engl J Med 372:2266–2268Google Scholar
  77. Jones PA, Takai D (2001) The role of DNA methylation in mammalian epigenetics. Science 293:1068–1070PubMedCrossRefPubMedCentralGoogle Scholar
  78. Joubert BR et al (2012) 450 K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy. Environ Health Perspect 120:1425–1431PubMedPubMedCentralCrossRefGoogle Scholar
  79. Jung C et al (2011) A longitudinal study of plasma and urinary cortisol in pregnancy and postpartum. J Clin Endocrinol Metab 96:1533–1540PubMedCrossRefPubMedCentralGoogle Scholar
  80. Kahn BB, Flier JS (2000) Obesity and insulin resistance. J Clin Investig 106:473–481PubMedCrossRefPubMedCentralGoogle Scholar
  81. Kalafatakis K et al (2018) Ultradian rhythmicity of plasma cortisol is necessary for normal emotional and cognitive responses in man. Proc Natl Acad Sci 115:201714239CrossRefGoogle Scholar
  82. Kanagalingam MG, Forouhi NG, Greer IA, Sattar N (2005) Changes in booking body mass index over a decade: retrospective analysis from a Glasgow Maternity Hospital. BJOG Int J Obstet Gynaecol 112:1431–1433CrossRefGoogle Scholar
  83. Karin M, Ben-Neriah Y (2000) Phosphorylation meets ubiquitination: the control of NF-κB activity. Annu Rev Immunol 18:621–663PubMedCrossRefPubMedCentralGoogle Scholar
  84. Kelstrup L et al (2013) Insulin resistance and impaired pancreatic β-cell function in adult offspring of women with diabetes in pregnancy. J Clin Endocrinol Metab 98:3793–3801PubMedPubMedCentralCrossRefGoogle Scholar
  85. Kim SY et al (2010) Percentage of gestational diabetes mellitus attributable to overweight and obesity. Am J Public Health 100:1047–1052PubMedPubMedCentralCrossRefGoogle Scholar
  86. King BR, Smith R, Nicholson RC (2001) The regulation of human corticotrophin-releasing hormone gene expression in the placenta. Peptides 22:795–801PubMedCrossRefPubMedCentralGoogle Scholar
  87. Konstantakou P, Mastorakos G, Vrachnis N, Tomlinson JW, Valsamakis G (2017) Dysregulation of 11beta-hydroxysteroid dehydrogenases: implications during pregnancy and beyond. J Matern Fetal Neonatal Med 30:284–293PubMedCrossRefPubMedCentralGoogle Scholar
  88. Krishnaveni GV et al (2010) Intrauterine exposure to maternal diabetes is associated with higher adiposity and insulin resistance and clustering of cardiovascular risk markers in Indian children. Diabetes Care 33:402–404PubMedCrossRefPubMedCentralGoogle Scholar
  89. Lager S, Powell TL (2012) Regulation of nutrient transport across the placenta. J Pregnancy 2012:179827PubMedPubMedCentralCrossRefGoogle Scholar
  90. Lindsay JR, Nieman LK (2005) The hypothalamic-pituitary-adrenal axis in pregnancy: challenges in disease detection and treatment. Endocr Reviews 26:775–799CrossRefGoogle Scholar
  91. Liu KH et al (2003) Sonographic measurement of mesenteric fat thickness is a good correlate with cardiovascular risk factors: comparison with subcutaneous and preperitoneal fat thickness, magnetic resonance imaging and anthropometric indexes. Int J Obes 27:1267–1273CrossRefGoogle Scholar
  92. Lowe WL et al (2018) Association of gestational diabetes with maternal disorders of glucose metabolism and childhood adiposity. JAMA, J Am Med Assoc 320:1005–1016CrossRefGoogle Scholar
  93. Luiza JW, Gallaher MJ, Powers RW (2015) Urinary cortisol and depression in early pregnancy: role of adiposity and race. BMC Pregnancy Childbirth 15:30PubMedPubMedCentralCrossRefGoogle Scholar
  94. Moisiadis VG, Matthews SG (2014) Glucocorticoids and fetal programming part 1: outcomes. Nat Rev Endocrinol 10:391–402PubMedCrossRefPubMedCentralGoogle Scholar
  95. Mook-Kanamori DO et al (2009) Abdominal fat in children measured by ultrasound and computed tomography. Ultrasound Med Biol 35:1938–1946PubMedCrossRefPubMedCentralGoogle Scholar
  96. NCD Risk Factor Collaboration (NCD-RisC) (2017) Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet (London, England) 390:2627–2642Google Scholar
  97. Ogden CL, Carroll MD, Kit BK, Flegal KM (2012) Prevalence of obesity and trends in body mass index among US children and adolescents, 1999–2010. JAMA, J Am Med Assoc 307:483–490CrossRefGoogle Scholar
  98. Ogden CL, Carroll MD, Kit BK, Flegal KM (2014) Prevalence of childhood and adult obesity in the United States, 2011–2012. JAMA, J Am Med Assoc 311:806–814CrossRefGoogle Scholar
  99. Ohgane J, Yagi S, Shiota K (2008) Epigenetics: the DNA methylation profile of tissue-dependent and differentially methylated regions in cells. Placenta 29:29–35CrossRefGoogle Scholar
  100. Oster H et al (2017) The functional and clinical significance of the 24-hour rhythm of circulating glucocorticoids. Endocrine Rev 38:3–45CrossRefGoogle Scholar
  101. Owens LA et al (2010) ATLANTIC DIP: the impact of obesity on pregnancy outcome in glucose-tolerant women. Diabetes Care 33:577–579PubMedPubMedCentralCrossRefGoogle Scholar
  102. Patel N et al (2017) Infant adiposity following a randomised controlled trial of a behavioural intervention in obese pregnancy. Int J Obes 41:1018–1026CrossRefGoogle Scholar
  103. Polat TB, Urganci N, Caliskan KC, Akyildiz B (2008) Correlation of abdominal fat accumulation and stiffness of the abdominal aorta in obese children. J Pediatr Endocrinol Metab 21:1031–1040PubMedCrossRefPubMedCentralGoogle Scholar
  104. Popkin BM, Adair LS, Ng SW (2012) Global nutrition transition and the pandemic of obesity in developing countries. Nutr Rev 70:3–21PubMedPubMedCentralCrossRefGoogle Scholar
  105. Poston L et al (2015) Effect of a behavioural intervention in obese pregnant women (the UPBEAT study): a multicentre, randomised controlled trial. Lancet Diabetes Endocrinol 3:767–777PubMedCrossRefPubMedCentralGoogle Scholar
  106. Qureshi AC et al (2007) The influence of the route of oestrogen administration on serum levels of cortisol-binding globulin and total cortisol. Clin Endocrinol (Oxf) 66:632–635CrossRefGoogle Scholar
  107. Reynolds RM (2013) Glucocorticoid excess and the developmental origins of disease: two decades of testing the hypothesis—2012 Curt Richter Award Winner. Psychoneuroendocrinology 38:1–11PubMedCrossRefPubMedCentralGoogle Scholar
  108. Reynolds RM et al (2013) Maternal obesity during pregnancy and premature mortality from cardiovascular event in adult offspring: follow-up of 1 323 275 person years. BMJ 347:f4539PubMedPubMedCentralCrossRefGoogle Scholar
  109. Rowan JA, Hague WM, Gao W, Battin MR, Moore MP (2008) Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med 358:2003–2015PubMedCrossRefPubMedCentralGoogle Scholar
  110. Rowan JA et al (2011) Metformin in gestational diabetes: the offspring follow-up (MiG TOFU)—body composition at 2 years of age. Diabetes Care 34:2279–2284PubMedPubMedCentralCrossRefGoogle Scholar
  111. Rowan JA et al (2018) Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition and metabolic outcomes at 7–9 years of age. BMJ Open Diabetes Res Care 6:e000456PubMedPubMedCentralCrossRefGoogle Scholar
  112. Ryan EA, O’Sullivan MJ, Skyler JS (1985) Insulin action during pregnancy: studies with the euglycemic clamp technique. Diabetes 34:380–389PubMedCrossRefGoogle Scholar
  113. Sandman CA et al (2006) Elevated maternal cortisol early in pregnancy predicts third trimester levels of placental corticotropin releasing hormone (CRH): priming the placental clock. Peptides 27:1457–1463PubMedCrossRefGoogle Scholar
  114. Santos F, Hendrich B, Reik W, Dean W (2002) Dynamic reprogramming of DNA methylation in the early mouse embryo. Dev Biol 241:172–182PubMedCrossRefGoogle Scholar
  115. Sarkar P, Bergman K, Fisk NM, O’Connor TG, Glover V (2007) Ontogeny of foetal exposure to maternal cortisol using midtrimester amniotic fluid as a biomarker. Clin Endocrinol (Oxf) 66:636–640CrossRefGoogle Scholar
  116. Sebire NJ et al (2001) Maternal obesity and pregnancy outcome: a study of 287 213 pregnancies in London. Int J Obes 25:1175–1182CrossRefGoogle Scholar
  117. Sharp GC et al (2015) Maternal pre-pregnancy BMI and gestational weight gain, offspring DNA methylation and later offspring adiposity: findings from the Avon Longitudinal Study of Parents and Children. Int J Epidemiol 44:1288–1304PubMedPubMedCentralCrossRefGoogle Scholar
  118. Singh RR, Cuffe JS, Moritz KM (2012) Short- and long-term effects of exposure to natural and synthetic glucocorticoids during development. Clin Exp Pharmacol Physiol 39:979–989PubMedCrossRefPubMedCentralGoogle Scholar
  119. Sloboda D, Challis J, Moss T, Newnham J (2005) Synthetic glucocorticoids: antenatal administration and long-term implications. Curr Pharm Des 11:1459–1472PubMedCrossRefGoogle Scholar
  120. Sorenson RL, Brelje TC (2009) Prolactin receptors are critical to the adaptation of islets to pregnancy. Endocrinology 150:1566–1569PubMedCrossRefPubMedCentralGoogle Scholar
  121. Stinson LJ et al (2015) Prospective evaluation of associations between prenatal cortisol and adulthood coronary heart disease risk: the New England family study. Psychosom Med 77:237–245PubMedPubMedCentralCrossRefGoogle Scholar
  122. Stirrat LI et al (2016) Decreased maternal hypothalamic-pituitary-adrenal axis activity in very severely obese pregnancy: associations with birthweight and gestation at delivery. Psychoneuroendocrinology 63:135–143PubMedCrossRefPubMedCentralGoogle Scholar
  123. Stirrat LI et al (2017) Glucocorticoids are lower at delivery in maternal, but not cord blood of obese pregnancies. Sci Rep 7:10263PubMedPubMedCentralCrossRefGoogle Scholar
  124. Stirrat LI et al (2018) Pulsatility of glucocorticoid hormones in pregnancy: changes with gestation and obesity. Clin Endocrinol (Oxf) 88:592–600CrossRefGoogle Scholar
  125. Susa JB et al (1984) Chronic hyperinsulinemia in the fetal rhesus monkey. Effects of physiologic hyperinsulinemia on fetal growth and composition. Diabetes 33:656–660PubMedCrossRefPubMedCentralGoogle Scholar
  126. Syngelaki A et al (2016) Metformin versus placebo in obese pregnant women without diabetes. N Engl J Med 374:2501CrossRefGoogle Scholar
  127. Tadokoro N et al (2000) Preperitoneal fat thickness determined by ultrasonography is correlated with coronary stenosis and lipid disorders in non-obese male subjects. Int J Obes 24:502–507CrossRefGoogle Scholar
  128. Talge NM, Neal C, Glover V (2007) Antenatal maternal stress and long-term effects on child neurodevelopment: how and why? J Child Psychol Psychiatry Allied Discipl 48:245–261CrossRefGoogle Scholar
  129. Tamura A, Mori T, Hara Y, Komiyama A (2000) Preperitoneal fat thickness in childhood obesity: association with serum insulin concentration. Pediatr Int 42:155–159PubMedCrossRefPubMedCentralGoogle Scholar
  130. Tessarz P, Kouzarides T (2014) Histone core modifications regulating nucleosome structure and dynamics. Nat Rev Mol Cell Biol 15:703–708PubMedCrossRefPubMedCentralGoogle Scholar
  131. The GBD 2015 Obesity Collaborators (2017) Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med 377:13–27Google Scholar
  132. The HAPO Study Cooperative Research Group (2008) Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 358:1991–2002CrossRefGoogle Scholar
  133. The International Weight Management in Pregnancy (i-WIP) Collaborative Group (2017) Effect of diet and physical activity based interventions in pregnancy on gestational weight gain and pregnancy outcomes: meta-analysis of individual participant data from randomised trials. BMJ 358:j3119Google Scholar
  134. Tottenham N (2009) A review of adversity, the amygdala and the hippocampus: a consideration of developmental timing. Front Hum Neurosci 3:68PubMedPubMedCentralGoogle Scholar
  135. Uebel K et al (2014) Effect of maternal obesity with and without gestational diabetes on offspring subcutaneous and preperitoneal adipose tissue development from birth up to year-1. BMC Pregnancy Childbirth 14:138PubMedPubMedCentralCrossRefGoogle Scholar
  136. van Dijk SJ, Tellam RL, Morrison JL, Muhlhausler BS, Molloy PL (2015) Recent developments on the role of epigenetics in obesity and metabolic disease. Clin Epigenetics 7:66PubMedPubMedCentralCrossRefGoogle Scholar
  137. Waddington CH (1956) Embryology, epigenetics and biogenetics. Nature 177:1241CrossRefGoogle Scholar
  138. Wahl S et al (2017) Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity. Nature 541:81–86PubMedCrossRefPubMedCentralGoogle Scholar
  139. Waterland RA et al (2004) Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases. Nutrition 20:63–68PubMedCrossRefPubMedCentralGoogle Scholar
  140. World Health Organization (1999) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus. World Health OrganizationGoogle Scholar
  141. World Health Organization (2016) Fact sheet: obesity and overweight. WHO. Accessed 11 Oct 2018
  142. Yu Z et al (2013) Pre-pregnancy body mass index in relation to infant birth weight and offspring overweight/obesity: a systematic review and meta-analysis. PLoS ONE 8:e61627PubMedPubMedCentralCrossRefGoogle Scholar
  143. Zhang T, Cooper S, Brockdorff N (2015) The interplay of histone modifications—writers that read. EMBO Rep 16:1467–1481PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Emma C. Johns
    • 1
  • David Q. Stoye
    • 1
  • Liu Yang
    • 2
  • Rebecca M. Reynolds
    • 1
    • 2
    Email author
  1. 1.MRC Centre for Reproductive Health, Queen’s Medical Research Institute, University of EdinburghEdinburghUK
  2. 2.BHF/University Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of EdinburghEdinburghUK

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