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Pregnancy Complications and the Risk of Metabolic Syndrome for the Offspring

  • Women and Heart Disease (J Robinson, Section Editor)
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Abstract

Metabolic syndrome is a growing problem globally, and is a contributor to non-communicable diseases such as type II diabetes and cardiovascular disease. The risk of developing specific components of the metabolic syndrome such as obesity, hyperlipidemia, hypertension, and elevated fasting blood sugar has been largely attributed to environmental stressors including poor nutrition, lack of exercise, and smoking. However, large epidemiologic cohorts and experimental animal models support the “developmental origins of adult disease” hypothesis, which posits that a significant portion of the risk for adult metabolic conditions is determined by exposures occurring in the perinatal period. Maternal obesity and the rate of complications during pregnancy such as preterm birth, preeclampsia, and gestational diabetes continue to rise. As our ability to reduce perinatal morbidity and mortality improves the long-term metabolic consequences remain uncertain, pointing to the need for further research in this area.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Povel CM, Beulens JW, van der Schouw YT, et al. Metabolic Syndrome Model definitions predicting type 2 diabetes and cardiovascular disease. Diabetes Care. 2013;36:362–8.

    Google Scholar 

  2. Barker DJ. The developmental origins of adult disease. J Am Coll Nutr. 2004;23:588S–95.

    PubMed  CAS  Google Scholar 

  3. Barker DJ. The developmental origins of chronic adult disease. Acta Paediatr Suppl. 2004;93:26–33.

    Article  PubMed  CAS  Google Scholar 

  4. de Boo HA, Harding JE. The developmental origins of adult disease (Barker) hypothesis. Aust N Z J Obstet Gynaecol. 2006;46:4–14.

    Article  PubMed  Google Scholar 

  5. Hattersley AT, Tooke JE. The fetal insulin hypothesis: an alternative explanation of the association of low birthweight with diabetes and vascular disease. Lancet. 1999;353:1789–92.

    Article  PubMed  CAS  Google Scholar 

  6. • Roseboom TJ, Watson ED. The next generation of disease risk: are the effects of prenatal nutrition transmitted across generations? Evidence from animal and human studies. Placenta. 2012;33 Suppl 2:e40–4. This article focuses on existing animal and human evidence for intergenerational and transgenerational transmission of disease. Potential mechanisms for transmission of disease between generations are discussed.

    Article  PubMed  Google Scholar 

  7. Gluckman PD, Hanson MA, Cooper C, Thornburg KL. Effect of in utero and early-life conditions on adult health and disease. N Engl J Med. 2008;359:61–73.

    Article  PubMed  CAS  Google Scholar 

  8. Skinner MK. What is an epigenetic transgenerational phenotype? F3 or F2. Reprod Toxicol. 2008;25:2–6.

    Article  PubMed  CAS  Google Scholar 

  9. Peixoto-Silva N, Frantz ED, Mandarim-de-Lacerda CA, Pinheiro-Mulder A. Maternal protein restriction in mice causes adverse metabolic and hypothalamic effects in the F1 and F2 generations. Br J Nutr. 2011;106:1364–73.

    Article  PubMed  CAS  Google Scholar 

  10. Zambrano E, Martinez-Samayoa PM, Bautista CJ, et al. Sex differences in transgenerational alterations of growth and metabolism in progeny (F2) of female offspring (F1) of rats fed a low protein diet during pregnancy and lactation. J Physiol. 2005;566:225–36.

    Article  PubMed  CAS  Google Scholar 

  11. Silveira VM, Horta BL. Birth weight and metabolic syndrome in adults: meta-analysis. Rev Saude Publica. 2008;42:10–8.

    Article  PubMed  Google Scholar 

  12. Harder T, Rodekamp E, Schellong K, et al. Birth weight and subsequent risk of type 2 diabetes: a meta-analysis. Am J Epidemiol. 2007;165:849–57.

    Article  PubMed  Google Scholar 

  13. Whincup PH, Kaye SJ, Owen CG, et al. Birth weight and risk of type 2 diabetes: a systematic review. JAMA. 2008;300:2886–97.

    Article  PubMed  CAS  Google Scholar 

  14. Mu M, Wang SF, Sheng J, et al. Birth weight and subsequent blood pressure: a meta-analysis. Arch Cardiovasc Dis. 2012;105:99–113.

    Article  PubMed  Google Scholar 

  15. de Jong F, Monuteaux MC, van Elburg RM, et al. Systematic review and meta-analysis of preterm birth and later systolic blood pressure. Hypertension. 2012;59:226–34.

    Article  PubMed  Google Scholar 

  16. Gamborg M, Byberg L, Rasmussen F, et al. Birth weight and systolic blood pressure in adolescence and adulthood: meta-regression analysis of sex- and age-specific results from 20 Nordic studies. Am J Epidemiol. 2007;166:634–45.

    Article  PubMed  Google Scholar 

  17. Zhao Y, Wang SF, Mu M, Sheng J. Birth weight and overweight/obesity in adults: a meta-analysis. Eur J Pediatr. 2012;171:1737–46.

    Article  PubMed  Google Scholar 

  18. Yu ZB, Han SP, Zhu GZ, et al. Birth weight and subsequent risk of obesity: a systematic review and meta-analysis. Obes Rev. 2011;12:525–42.

    Article  PubMed  CAS  Google Scholar 

  19. Owen CG, Whincup PH, Odoki K, et al. Birth weight and blood cholesterol level: a study in adolescents and systematic review. Pediatrics. 2003;111:1081–9.

    Article  PubMed  Google Scholar 

  20. Xu X, Dailey AB, Peoples-Sheps M, et al. Birth weight as a risk factor for breast cancer: a meta-analysis of 18 epidemiological studies. J Womens Health. 2009;18:1169–78.

    Article  Google Scholar 

  21. Baird J, Kurshid MA, Kim M, et al. Does birthweight predict bone mass in adulthood? A systematic review and meta-analysis. Osteoporos Int. 2011;22:1323–34.

    Article  PubMed  CAS  Google Scholar 

  22. Andersen LG, Angquist L, Gamborg M, et al. Birth weight in relation to leisure time physical activity in adolescence and adulthood: meta-analysis of results from 13 Nordic cohorts. PLoS One. 2009;4:e8192.

    Article  PubMed  Google Scholar 

  23. Cardwell CR, Stene LC, Joner G, et al. Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data. Diabetologia. 2010;53:641–51.

    Article  PubMed  CAS  Google Scholar 

  24. Caughey RW, Michels KB. Birth weight and childhood leukemia: a meta-analysis and review of the current evidence. Int J Cancer. 2009;124:2658–70.

    Article  PubMed  CAS  Google Scholar 

  25. Cook MB, Akre O, Forman D, et al. A systematic review and meta-analysis of perinatal variables in relation to the risk of testicular cancer—experiences of the son. Int J Epidemiol. 2010;39:1605–18.

    Article  PubMed  Google Scholar 

  26. Flaherman V, Rutherford GW. A meta-analysis of the effect of high weight on asthma. Arch Dis Child. 2006;91:334–9.

    Article  PubMed  CAS  Google Scholar 

  27. Lawlor DA, Ebrahim S, Davey Smith G. Association of birth weight with adult lung function: findings from the British Women's Heart and Health Study and a meta-analysis. Thorax. 2005;60:851–8.

    Article  PubMed  CAS  Google Scholar 

  28. White SL, Perkovic V, Cass A, et al. Is low birth weight an antecedent of CKD in later life? A systematic review of observational studies. Am J Kidney Dis. 2009;54:248–61.

    Article  PubMed  Google Scholar 

  29. •• Neitzke U, Harder T, Plagemann A. Intrauterine growth restriction and developmental programming of the metabolic syndrome: a critical appraisal. Microcirculation. 2011;18:304–11. This review summarizes the current literature on low birth weight, intrauterine growth restriction, and the risk for adult metabolic syndrome. Both systematic reviews and meta-analysis of human data as well as animal models are discussed. The authors conclude that low birth weight, IUGR, and/or SGA are not independent risk factors for metabolic syndrome in adulthood but rather neonatal overfeeding and rapid neonatal weight gain increase the lifetime risks for metabolic syndrome.

    Article  PubMed  Google Scholar 

  30. Silverman BL, Rizzo TA, Cho NH, Metzger BE. Long-term effects of the intrauterine environment. The Northwestern University Diabetes in Pregnancy Center. Diabetes Care. 1998;21 Suppl 2:B142–9.

    PubMed  Google Scholar 

  31. Kajantie E, Eriksson JG, Osmond C, et al. Pre-eclampsia is associated with increased risk of stroke in the adult offspring: the Helsinki birth cohort study. Stroke. 2009;40:1176–80.

    Article  PubMed  Google Scholar 

  32. World Health Organization. Obesity: Preventing and managing the global epidemic. Available at http://libdoc.who.int/trs/WHO_TRS_894.pdf. Accessed December 2012.

  33. Ogden C, Carroll M. Prevalence of obesity among children and adolescents: United States, trends 1963–1965 through 2007–2008. National Center for Health Statistics 2010; Available at: http://www.cdc.gov/nchs/data/hestat/obesity_child_07_08/obesity_child_07_08.htm. Accessed December 2012.

  34. Armitage JA, Poston L, Taylor PD. Developmental origins of obesity and the metabolic syndrome: the role of maternal obesity. Front Horm Res. 2008;36:73–84.

    Article  PubMed  Google Scholar 

  35. Gunatilake RP, Perlow JH. Obesity and pregnancy: clinical management of the obese gravida. Am J Obstet Gynecol. 2011;204:106–19.

    Article  PubMed  Google Scholar 

  36. Reece EA. Perspectives on obesity, pregnancy, and birth outcomes in the United States: the scope of the problem. Am J Obstet Gynecol. 2008;198:23–7.

    Article  PubMed  Google Scholar 

  37. Yogev Y, Catalano PM. Pregnancy and obesity. Obstet Gynecol Clin North Am. 2009;36:285–300. viii.

    Article  PubMed  Google Scholar 

  38. Langer O. Management of obesity in GDM: old habits die hard. J Matern Fetal Neonatal Med. 2008;21:165–71.

    Article  PubMed  Google Scholar 

  39. Oken E, Rifas-Shiman SL, Field AE, et al. Maternal gestational weight gain and offspring weight in adolescence. Obstet Gynecol. 2008;112:999–1006.

    Article  PubMed  Google Scholar 

  40. Boney CM, Verma A, Tucker R, Vohr BR. Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics. 2005;115:e290–6.

    Article  PubMed  Google Scholar 

  41. Djelantik AA, Kunst AE, van der Wal MF, et al. Contribution of overweight and obesity to the occurrence of adverse pregnancy outcomes in a multi-ethnic cohort: population attributive fractions for Amsterdam. BJOG. 2012;119:283–90.

    Article  PubMed  CAS  Google Scholar 

  42. • Desai M, Beall M, Ross MG. Developmental origins of obesity: programmed adipogenesis. Curr Diab Rep. 2013;13:27–33. This report summarizes human epidemiological and animal model studies focused on the contribution of maternal obesity, with or without gestational diabetes, to the offspring's risk for childhood and adult obesity. The effects of postnatal catch-up growth and fat accrual are discussed, as well as potential causative mechanisms including epigenetic programming, altered organ development, and cellular signaling.

  43. Harder T, Schellong K, Stupin J, et al. Where is the evidence that low birthweight leads to obesity? Lancet. 2007;369:1859.

    Article  PubMed  Google Scholar 

  44. Hull HR, Thornton JC, Ji Y, et al. Higher infant body fat with excessive gestational weight gain in overweight women. Am J Obstet Gynecol. 2011;205:211.e1–7.

    Google Scholar 

  45. Gluckman PD, Hanson MA, Morton SM, Pinal CS. Life-long echoes—a critical analysis of the developmental origins of adult disease model. Biol Neonate. 2005;87:127–39.

    Article  PubMed  Google Scholar 

  46. Schack-Nielsen L, Michaelsen KF, Gamborg M, et al. Gestational weight gain in relation to offspring body mass index and obesity from infancy through adulthood. Int J Obes. 2010;34:67–74.

    Article  CAS  Google Scholar 

  47. Centers for Disease Control and Prevention. National diabetes fact sheet: National estimates and general information on diabetes and prediabetes in the United States, 2011. Available at: http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. Accessed December 2012.

  48. Coustan DR, Lowe LP, Metzger BE, et al. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: paving the way for new diagnostic criteria for gestational diabetes mellitus. Am J Obstet Gynecol. 2010;202:654.e1–6.

    Google Scholar 

  49. Yogev Y, Visser GH. Obesity, gestational diabetes, and pregnancy outcome. Semin Fetal Neonatal Med. 2009;14:77–84.

    Article  PubMed  Google Scholar 

  50. • Ornoy A. Prenatal origin of obesity and their complications: gestational diabetes, maternal overweight, and the paradoxical effects of fetal growth restriction and macrosomia. Reprod Toxicol. 2011;32:205–12. This article reviews the literature on the effects of gestational diabetes, maternal obesity, and fetal growth restriction on the offspring's risk for metabolic syndrome. The roles of insulin resistance, leptin, hypothalamic programming, and epigenetics are also discussed.

    Article  PubMed  CAS  Google Scholar 

  51. Gillman MW, Rifas-Shiman S, Berkey CS, et al. Maternal gestational diabetes, birth weight, and adolescent obesity. Pediatrics. 2003;111:e221–6.

    Article  PubMed  Google Scholar 

  52. Cho NH, Silverman BL, Rizzo TA, Metzger BE. Correlations between the intrauterine metabolic environment and blood pressure in adolescent offspring of diabetic mothers. J Pediatr. 2000;136:587–92.

    Article  PubMed  CAS  Google Scholar 

  53. Damm P. Future risk of diabetes in mother and child after gestational diabetes mellitus. Int J Gynaecol Obstet. 2009;104 Suppl 1:S25–6.

    Article  PubMed  Google Scholar 

  54. Osungbade KO, Ige OK. Public health perspectives of preeclampsia in developing countries: implication for health system strengthening. J Pregnancy. 2011;2011:481095.

    PubMed  Google Scholar 

  55. Anderson UD, Olsson MG, Kristensen KH, et al. Review: biochemical markers to predict preeclampsia. Placenta. 2012;33(Suppl):S42–7.

    Article  PubMed  Google Scholar 

  56. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ. 2007;335:974.

    Article  PubMed  Google Scholar 

  57. •• Davis EF, Lazdam M, Lewandowski AJ, et al. Cardiovascular risk factors in children and young adults born to preeclamptic pregnancies: a systematic review. Pediatrics. 2012;129:e1552–61. This systematic review and meta-analysis demonstrates that in utero exposure to preeclampsia is associated with higher childhood and adulthood blood pressure in the offspring. The role of preeclampsia and offspring BMI, cholesterol levels, and glucose metabolism are also reviewed.

    Article  PubMed  Google Scholar 

  58. •• Yaghootkar H, Freathy RM. Genetic origins of low birth weight. Curr Opin Clin Nutr Metab Care. 2012;15:258–64. This article reviews current literature on common genetic variants that are associated with both birth weight and type 2 diabetes. To-date there are 6 genetic loci that show strong evidence for association with birth weight; of these 5 are also associated with type II diabetes indicating a genetic mechanism for the relationship between low birth weight and the development of adult diabetes.

    Article  PubMed  Google Scholar 

  59. Dupuis J, Langenberg C, Prokopenko I, et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet. 2010;42:105–16.

    Article  PubMed  CAS  Google Scholar 

  60. Saxena R, Hivert MF, Langenberg C, et al. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet. 2010;42:142–8.

    Article  PubMed  CAS  Google Scholar 

  61. Saxena R, Elbers CC, Guo Y, et al. Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci. Am J Hum Genet. 2012;90:410–25.

    Article  PubMed  CAS  Google Scholar 

  62. Freathy RM, Hayes MG, Urbanek M, et al. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: common genetic variants in GCK and TCF7L2 are associated with fasting and postchallenge glucose levels in pregnancy and with the new consensus definition of gestational diabetes mellitus from the International Association of Diabetes and Pregnancy Study Groups. Diabetes. 2010;59:2682–9.

    Article  PubMed  CAS  Google Scholar 

  63. Freathy RM, Mook-Kanamori DO, Sovio U, et al. Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight. Nat Genet. 2010;42:430–5.

    Article  PubMed  CAS  Google Scholar 

  64. Andersson EA, Pilgaard K, Pisinger C, et al. Type 2 diabetes risk alleles near ADCY5, CDKAL1, and HHEX-IDE are associated with reduced birthweight. Diabetologia. 2010;53:1908–16.

    Article  PubMed  CAS  Google Scholar 

  65. HAPO Study Cooperative Research Group, Metzger BE, Lowe LP, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008;358:1991–2002.

    Article  PubMed  Google Scholar 

  66. Li X, Li Y, Song B, et al. Hematopoietically-expressed homeobox gene three widely-evaluated polymorphisms and risk for diabetes: a meta-analysis. PLoS One. 2012;7:e49917.

    Article  PubMed  CAS  Google Scholar 

  67. ••Godfrey KM, Gluckman PD, Hanson MA. Developmental origins of metabolic disease: life course and intergenerational perspectives. Trends Endocrinol Metab. 2010;21:199–205. This article reviews the existing literature and evidence for the developmental origins of metabolic disease. Epigenetic mechanisms are discussed and the existing literature on this topic is nicely reviewed.

    Article  PubMed  CAS  Google Scholar 

  68. Godfrey KM, Sheppard A, Gluckman PD, et al. Epigenetic gene promoter methylation at birth is associated with child's later adiposity. Diabetes. 2011;60:1528–34.

    Article  PubMed  CAS  Google Scholar 

  69. Jablonka E, Raz G. Transgenerational epigenetic inheritance: prevalence, mechanisms, and implications for the study of heredity and evolution. Q Rev Biol. 2009;84:131–76.

    Article  PubMed  Google Scholar 

  70. Lillycrop KA, Burdge GC. The effect of nutrition during early life on the epigenetic regulation of transcription and implications for human diseases. J Nutrigenet Nutrigenomics. 2011;4:248–60.

    Article  PubMed  CAS  Google Scholar 

  71. Hanson M, Godfrey KM, Lillycrop KA, et al. Developmental plasticity and developmental origins of non-communicable disease: theoretical considerations and epigenetic mechanisms. Prog Biophys Mol Biol. 2011;106:272–80.

    Article  PubMed  Google Scholar 

  72. Lillycrop KA, Burdge GC. Epigenetic mechanisms linking early nutrition to long term health. Best Pract Res Clin Endocrinol Metab. 2012;26:667–76.

    Article  PubMed  Google Scholar 

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Conflict of Interest

Kelli K. Ryckman declares that she has no conflict of interest.

Kristi S. Borowski declares that she has no conflict of interest.

Nisha I. Parikh declares that she has no conflict of interest.

Audrey F. Saftlas declares that she has no conflict of interest.

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Authors and Affiliations

  1. Department of Epidemiology, University of Iowa, 105 River St, Iowa City, IA, 52242, USA

    Kelli K. Ryckman & Audrey F. Saftlas

  2. Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, USA

    Kristi S. Borowski

  3. Cardiovascular Division, The Queens Medical Center, Honolulu, HI, 96813, USA

    Nisha I. Parikh

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  1. Kelli K. Ryckman
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  2. Kristi S. Borowski
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Correspondence to Kelli K. Ryckman.

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Ryckman, K.K., Borowski, K.S., Parikh, N.I. et al. Pregnancy Complications and the Risk of Metabolic Syndrome for the Offspring. Curr Cardiovasc Risk Rep 7, 217–223 (2013). https://doi.org/10.1007/s12170-013-0308-y

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