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03-25-2014 | Pregnancy | Review | Article

Long-Term Health Outcomes in Offspring Born to Women with Diabetes in Pregnancy

Journal: Current Diabetes Reports

Authors: Abigail Fraser, Debbie A. Lawlor

Abstract

In this review, we critically assess recent evidence from human studies regarding the potential implications of exposure to maternal diabetes in-utero for long-term adiposity, cardiometabolic outcomes, and cognitive ability of the offspring. Evidence supports a direct causal role for exposure to maternal diabetes in utero in determining offspring long-term greater adiposity and adverse cardiometabolic health. Although a majority of observational studies report associations of exposure to maternal pregnancy diabetes with lower cognitive ability, there is also evidence supporting an opposite ‘protective’ intrauterine effect of exposure to maternal pregnancy diabetes on offspring cognitive ability. Epigenetic modification has been suggested as a mediator on the pathways from maternal pregnancy diabetes to long-term offspring outcomes and several recent studies that are reviewed here lend some support to this notion, but research in this area is still too novel to be conclusive.

Bell R, Bailey K, Cresswell T, Hawthorne G, Critchley J, et al. Trends in prevalence and outcomes of pregnancy in women with pre-existing type I and type II diabetes. BJOG. 2008;115:445–52.PubMedCrossRef

de Andrés AL, Jiménez-García R, Carrasco-Garrido P. Trends in pregestational diabetes among women delivering in Spain, 2001–2008. Int J Gynecol Obstet. 2012;117:182–3.CrossRef

Rajab KE, Issa AA, Hasan ZA, Rajab E, Jaradat AA. Incidence of gestational diabetes mellitus in Bahrain from 2002 to 2010. Int J Gynecol Obstet. 2012;117:74–7.CrossRef

Buckley BS, Harreiter J, Damm P, Corcoy R, Chico A, et al. Gestational diabetes mellitus in Europe: prevalence, current screening practice and barriers to screening. A review. Diabet Med. 2012;29:844–54.PubMedCrossRef

Albrecht SS, Kuklina EV, Bansil P, Jamieson DJ, Whiteman MK, et al. Diabetes trends among delivery hospitalizations in the U.S., 1994–2004. Diabetes Care. 2010;33:768–73.PubMedCentralPubMedCrossRef

National Institute for Health and Clinical Excellence. NICE clinical guideline 63: diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. London: NICE; 2008.

National Institute of Health. National Institutes of Health Consensus Development Conference on Diagnosing Gestational Diabetes Mellitus: Final Statement; 2013.

Xiang AH, Li BH, Black MH, Sacks DA, Buchanan TA, et al. Racial and ethnic disparities in diabetes risk after gestational diabetes mellitus. Diabetologia. 2011;54:3016–21.PubMedCrossRef

Association AD. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2011;34:S62–9.CrossRef

10.

Ogata ES. Problems of the infant of the diabetic mother. NeoReviews. 2010;11:e627–31.CrossRef

11.

Hay Jr W. Care of the infant of the diabetic mother. Curr Diabet Rep. 2012;12:4–15.CrossRef

12.••

The HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008;358:1991–2002. This large multi-center study demonstrated the continuous association between maternal glucose levels across the entire distribution and birthweight. CrossRef

13.

HAPO Study Cooperative Research Group. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. Diabetes. 2009;58:453–9.CrossRef

14.•

Lawlor DA, The Society for Social Medicine John Pemberton lecture 2011. Developmental overnutrition—an old hypothesis with new importance? Int J Epidemiol. 2013;42:7–29. This reference provides an overview of the developmental overnutrition hypothesis, its evolvement over time, and the supporting evidence. PubMedCrossRef

15.

Wood E. Sugar content of mother’s blood after fasting: its relation to the birth weight of infants. Am J Dis Child. 1936;51:297–301.CrossRef

16.

Whie PHH. Pregnancy complicating diabetes: a report of clinical results. J Clin Endocrinol Metab. 1942;3:500–11.

17.

Sridhar SB, Ferrara A, Ehrlich SF, Brown SD, Hedderson MM. Risk of large-for-gestational-age newborns in women with gestational diabetes by race and ethnicity and body mass index categories. Obstet Gynecol. 2013;121:1255–62.PubMedCrossRef

18.•

Lawlor DA, Relton C, Sattar N, Nelson SM. Maternal adiposity—a determinant of perinatal and offspring outcomes? Nat Rev Endocrinol. 2012;8:679–88. This is a comprehensive review of the evidence supporting a causal role for maternal obesity in its association with offspring outcomes. PubMedCrossRef

19.

Patel S, Fraser A, Davey Smith G, Lindsay RS, Sattar N, et al. Associations of gestational diabetes, existing diabetes, and glycosuria with offspring obesity and cardiometabolic outcomes. Diabetes Care. 2012;35:63–71.PubMedCentralPubMedCrossRef

20.

Gillman MW, Rifas-Shiman S, Berkey CS, Field AE, Colditz GA. Maternal gestational diabetes, birth weight, and adolescent obesity. Pediatrics. 2003;111:e221–6.PubMedCrossRef

21.

Kim SY, England JL, Sharma JA, Njoroge T. Gestational diabetes mellitus and risk of childhood overweight and obesity in offspring: a systematic review. Exp Diabetes Res. 2011;2011:9.CrossRef

22.

Philipps LH, Santhakumaran S, Gale C, Prior E, Logan KM, et al. The diabetic pregnancy and offspring BMI in childhood: a systematic review and meta-analysis. Diabetologia. 2011;54:1957–66.PubMedCrossRef

23.•

Snell-Bergeon J, Dabelea D. The infant of the diabetic mother: metabolic imprinting. In: Tsatsoulis A, Wyckoff J, Brown FM, editors. Diabetes in women. NYC, NY: Humana Press; 2010; p. 359–75. This is a thorough review of the long- term metabolic effects of exposure to pregnancy diabetes in utero and of studies in the Pima Indians in particular.

24.

Pettitt DJ, Nelson RG, Saad MF, Bennett PH, Knowler WC. Diabetes and obesity in the offspring of Pima Indian women with diabetes during pregnancy. Diabetes Care. 1993;16:310–4.PubMedCrossRef

25.

Dabelea D. Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. Diabetes. 2000;49:2208–11.PubMedCrossRef

26.

Lawlor DA, Lichtenstein P, Langstrom N. Association of maternal diabetes mellitus in pregnancy with offspring adiposity into early adulthood: sibling study in a prospective cohort of 280,866 men from 248,293 families. Circulation. 2011;123:258–65.PubMedCrossRef

27.

Rizzo TA, Dooley SL, Metzger BE, Cho NH, Ogata ES, et al. Prenatal and perinatal influences on long-term psychomotor development in offspring of diabetic mothers. Am J Obstet Gynecol. 1995;173:1753–8.PubMedCrossRef

28.

Nelson CA, Wewerka S, Thomas KM, Tribby-Walbridge S, deRegnier R, et al. Neurocognitive sequelae of infants of diabetic mothers. Behav Neurosci. 2000;114:950–6.PubMedCrossRef

29.

Gin H, Vambergue A, Vasseur C, Rigalleau V, Dufour P, et al. Blood ketone monitoring: a comparison between gestational diabetes and nondiabetic pregnant women. Diabet Metab. 2006;32:592–7.CrossRef

30.

Ornoy A, Wolf A, Ratzon N, Greenbaum C, Dulitzky M. Neurodevelopmental outcome at early school age of children born to mothers with gestational diabetes. Arch Dis Child Fetal Neonatal. 1999;81:F10–4.CrossRef

31.

Ornoy A, Ratzon N, Greenbaum C, Peretz E, Soriano D, et al. Neurobehaviour of school age children born to diabetic mothers. Arch Dis Child Fetal Neonatal. 1998;79:F94–9.CrossRef

32.

Ornoy A, Ratzon N, Greenbaum C, Wolf A, Dulitzky M. School-age children born to diabetic mothers and to mothers with gestational diabetes exhibit a high rate of inattention and fine and gross motor impairment. J Pediatr Endocrinol Metab. 2001;14 Suppl 1:681–9.PubMed

33.

Nielsen GL, Dethlefsen C, Sørensen HT, Pedersen JF, Molsted-Pedersen L. Cognitive function and army rejection rate in young adult male offspring of women with diabetes: a Danish population-based cohort study. Diabetes Care. 2007;30:2827–31.PubMedCrossRef

34.

Nomura Y, Marks DJ, Grossman B, Yoon M, Loudon H, Stone J, Halperin JM. Exposure to gestational diabetes mellitus and low socioeconomic status: effects on neurocognitive development and risk of attention-deficit/hyperactivity disorder in offspring. Arch Pediatr Adolesc Med. 2012;166:337–43.PubMedCrossRef

35.

Temple RC, Hardiman M, Pellegrini M, Horrocks L, Martinez-Cengotitabengoa MT. Cognitive function in 6- to 12-year-old offspring of women with Type 1 diabetes. Diabet Med. 2011;28:845–8.PubMedCrossRef

36.

Clausen TD, Mortensen EL, Schmidt L, Mathiesen ER, Hansen T, et al. Cognitive function in adult offspring of women with Type-á1 diabetes. Diabet Med. 2011;28:838–44.PubMedCrossRef

37.

Clausen TD, Mortensen EL, Schmidt L, Mathiesen ER, Hansen T, et al. Cognitive function in adult offspring of women with gestational diabetes–the role of glucose and other factors. PLoS One. 2013;8:e67107.PubMedCentralPubMedCrossRef

38.

Dahlquist G, Kallen B. School marks for Swedish children whose mothers had diabetes during pregnancy: a population-based study. Diabetologia. 2007;50:1826–31.PubMedCrossRef

39.

Fraser A, Nelson SM, Macdonald-Wallis C, Lawlor DA. Associations of existing diabetes, gestational diabetes, and glycosuria with offspring IQ and educational attainment: the Avon Longitudinal Study of Parents and Children. Exp Diabetes Res. 2012;2012:7.CrossRef

40.

Veena SR, Krishnaveni GV, Srinivasan K, Kurpad AV, Muthayya S, et al. Childhood cognitive ability: relationship to gestational diabetes mellitus in India. Diabetologia. 2010;53:2134–8.PubMedCentralPubMedCrossRef

41.

Rizzo T, Metzger BE, Burns WJ, Burns K. Correlations between antepartum maternal metabolism and intelligence of offspring. N Engl J Med. 1991;325:911–6.PubMedCrossRef

42.

Nielsen GL, Dethlefsen C, Sorensen HT, Pedersen JF, Molsted-Pedersen L. Cognitive function and Army rejection rate in young adult male offspring of women with diabetes. Diabetes Care. 2007;30:2827–31.PubMedCrossRef

43.

Nielsen GL, Andersen E, Lundbye-Christensen S. Maternal blood glucose in diabetic pregnancies and cognitive performance in offspring in young adulthood: a Danish cohort study. Diabet Med. 2010;27:786–90.PubMedCrossRef

44.

Davey Smith G, Ebrahim S. Mendelian randomization: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003;32:1–22.CrossRef

45.

Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey SG. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008;27:1133–63.PubMedCrossRef

46.

Bonilla C, Lawlor D, Ben-Shlomo Y, Ness A, Gunnell D, et al. Maternal and offspring fasting glucose and type 2 diabetes-associated genetic variants and cognitive function at age 8: a Mendelian randomization study in the Avon Longitudinal Study of Parents and Children. BMC Med Genet. 2012;13:90.PubMedCentralPubMedCrossRef

47.

Fraser A, Almqvist C, Larsson H, Långström N, Lawlor D. Maternal diabetes in pregnancy and offspring cognitive ability: sibling study with 723,775 men from 579,857 families. Diabetologia. 2014;57:102–9.

48.

Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 2003;33(Suppl):245–54.PubMedCrossRef

49.

Wong CC, Caspi A, Williams B, Craig IW, Houts R, et al. A longitudinal study of epigenetic variation in twins. Epigenetics. 2010;5:516–26.PubMedCentralPubMedCrossRef

50.

Day JJ, Sweatt JD. Epigenetic treatments for cognitive impairments. Neuropsychopharmacology. 2012;37:247–60.PubMedCentralPubMedCrossRef

51.

Bouchard L. Leptin gene epigenetic adaptation to impaired glucose metabolism during pregnancy. Diabetes Care. 2010;33:2436–41.PubMedCentralPubMedCrossRef

52.

Bouchard L, Hivert MF, Guay SP, St-Pierre J, Perron P, et al. Placental adiponectin gene DNA methylation levels are associated with mothers’ blood glucose concentration. Diabetes. 2012;61:1272–80.PubMedCentralPubMedCrossRef

53.

Ruchat SM, Houde AA, Voisin G, St-Pierre J, Perron P, et al. Gestational diabetes mellitus epigenetically affects genes predominantly involved in metabolic diseases. Epigenetics. 2013;8:935–43.PubMedCrossRef

54.

El Hajj N, Pliushch G, Schneider E, Dittrich M, Müller T, et al. Metabolic programming of MEST DNA methylation by intrauterine exposure to gestational diabetes mellitus. Diabetes. 2013;62:1320–8.PubMedCentralPubMedCrossRef

55.

Godfrey KM, Sheppard A, Gluckman PD, Lillycrop KA, Burdge GC, et al. Epigenetic gene promoter methylation at birth is associated with child’s later adiposity. Diabetes. 2011;60:1528–34.PubMedCentralPubMedCrossRef

56.

Relton CL, Groom A, St. Pourcain B, Sayers AE, Swan DC, et al. DNA methylation patterns in cord blood DNA and body size in childhood. PLoS One. 2012;7:e31821.PubMedCentralPubMedCrossRef

57.

Kuehnen P, Mischke M, Wiegand S, Sers C, Horsthemke B, et al. An Alu element-associated hypermethylation variant of the POMC gene is associated with childhood obesity. PLoS Genet. 2012;8:e1002543.PubMedCentralPubMedCrossRef

58.

Relton CL, Davey Smith G. Two-step epigenetic Mendelian randomization: a strategy for establishing the causal role of epigenetic processes in pathways to disease. Int J Epidemiol. 2012;41:161–76.PubMedCentralPubMedCrossRef

59.

Relton CL, Davey Smith G. Epigenetic epidemiology of common complex disease: prospects for prediction, prevention, and treatment. PLoS Med. 2010;7:e1000356.PubMedCentralPubMedCrossRef

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