Effect of maternal diabetes on the embryo, fetus, and children: Congenital anomalies, genetic and epigenetic changes and developmental outcomes

Birth Defects Research Part C - Embryo Today: Reviews

Volumn 105, Issue 1, 2015, Pages 53-72

  Ornoy, Asher ^a   Reece, E Albert ^b   Pavlinkova, Gabriela ^c   Kappen, Claudia ^d   Miller, Richard Kermit ^e  

^a HEBREW UNIVERSITY   (Israel)

^b UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^c INSTITUTE OF BIOTECHNOLOGY   (Czech Republic)

^d PENNINGTON BIOMEDICAL RESEARCH CENTER   (United States)

^e UNIVERSITY OF ROCHESTER SCHOOL OF MEDICINE AND DENTISTRY   (United States)

Author keywords

Congenital anomalies; Developmental disorders; Diabetic embryopathy; Epigenetics; GDM; PGDM

Indexed keywords

ADIPONECTIN; GHRELIN; GLUCOSE; LEPTIN;

ACRANIA; ANENCEPHALUS; APOPTOSIS; ARRHINENCEPHALY; ARTICLE; ATTENTION DEFICIT DISORDER; AUTISM; BRAIN MALFORMATION; BREAST FEEDING; CARDIOVASCULAR DISEASE; CATARACT; CHROMATIN ASSEMBLY AND DISASSEMBLY; CLEFT LIP; CLEFT PALATE; COGNITIVE DEFECT; CONGENITAL MALFORMATION; CRANIOFACIAL MALFORMATION; EMBRYOPATHY; EPIGENETICS; EXENCEPHALY; FALLOT TETRALOGY; FETUS GROWTH; FOLLOW UP; FRONTAL NASAL DYSPLASIA; GENE EXPRESSION; GREAT VESSELS TRANSPOSITION; GROWTH DISORDER; HEART LEFT VENTRICLE DOUBLE OUTLET; HEART RIGHT VENTRICLE DOUBLE OUTLET; HEMIFACIAL MICROSOMIA; HEREDITY; HOLOPROSENCEPHALY; HUMAN; HYPERGLYCEMIA; HYPOPLASTIC LEFT HEART SYNDROME; HYPOXIA; INTRAUTERINE GROWTH RETARDATION; LEARNING DISORDER; LOW BIRTH WEIGHT; MACROSOMIA; MATERNAL DIABETES MELLITUS; MENINGOMYELOCELE; METABOLIC DISORDER; MICROCEPHALY; MICROGNATHIA; MICROOPHTHALMIA; MICROTIA; MITRAL VALVE ATRESIA; MOTOR DYSFUNCTION; NEURAL TUBE DEFECT; NEUROLOGIC DISEASE; NUTRITION; OXIDATIVE STRESS; PERINATAL MORTALITY; POSTNATAL GROWTH; PREECLAMPSIA; PREGNANCY COMPLICATION; PREGNANCY OUTCOME; PREMATURE LABOR; PREVENTION; PRIORITY JOURNAL; SPINAL DYSRAPHISM; TRANSCRIPTION REGULATION; TRICUSPID VALVE ATRESIA; CONGENITAL ABNORMALITIES; DIABETES MELLITUS; EMBRYO DEVELOPMENT; FEMALE; FETAL DISEASES; GENETIC EPIGENESIS; PATHOPHYSIOLOGY; PHYSIOLOGY; PREGNANCY; PREGNANCY DIABETES MELLITUS; PRENATAL EXPOSURE;

ANIMALIA;

CONGENITAL ABNORMALITIES; DIABETES COMPLICATIONS; EMBRYONIC DEVELOPMENT; EPIGENESIS, GENETIC; FEMALE; FETAL DISEASES; HUMANS; PREGNANCY; PREGNANCY IN DIABETICS; PREGNANCY OUTCOME; PRENATAL EXPOSURE DELAYED EFFECTS;

EID: 84925400339     PISSN: 1542975X     EISSN: 15429768     Source Type: Journal    
DOI: 10.1002/bdrc.21090     Document Type: Article

References (189)

1. Atkinson MA, Leiter EH. 1999. The NOD mouse model of type 1 diabetes: as good as it gets? Nat Med 5:601-604.
2. Barker DJ. 1997. Maternal nutrition, fetal nutrition and disease in later life. Nutrition 13:807-813.
3. Best RM, Chakravarthy U. 1997. Diabetic retinopathy in pregnancy. Br J Ophthalmol 81:249-251.
4. Biesenbach G, Grafinger P, Zazgornik J, Stoger H.2000. Perinatal complications and three year follow up of infants of diabetic mothers with diabetic nephropathy stage IV. Renal Failure 22:573-580.
5. Bird A. 2007. Perceptions of epigenetics. Nature 24;447:396-398.
6. Bloch-Petersen M. 1989. Status at 4-5 years in 90 children of insulin-dependent diabetic mothers. In: Stowers, Sutherland HW, editor. Carbohydrate metabolism in pregnancy and the newborn. NY: Springer. pp. 354-361.
7. Bohuslavova R, Skvorova L, Sedmera D, Semenza GL, Pavlinkova G, 2013. Increased susceptibility of HIF-1alpha heterozygous-null mice to cardiovascular malformations associated with maternal diabetes. J Mol and Cel Cardiology 60:129-141.
8. Bohuslavova R, Skvorova L, Sedmera D, Semenza GL, Pavlinkova G. 2013. Increased susceptibility of HIF-1alpha heterozygous-null mice to cardiovascular malformations associated with maternal diabetes. J Mol. and Cell. Cardiology 60:129-141.
9. Cao Y, Zhao Z, Eckert RL, Reece EA. 2012. The essential role of protein kinase Cdelta in diabetes-induced neural tube defects. J Matern Fetal Neonatal Med 25:2020-2024.
10. Carpenter MW, Canick JA, Hogan JW, et al. 2001. Amniotic fluid insulin at 14-20 weeks gestation: association with later maternal glucose intolerance and birth macrosomia. Diabetes Care 24:1259-1263.
11. Cederberg J, Siman CM, Eriksson UJ. 2001. Combined treatment with vitamin E and vitamin C decreases oxidative stress and improves fetal outcome in experimental diabetic pregnancy. Pediatr Res 49:755-762.
12. Chew EY, Mills JL, Metzger BE, et al. 1995. Metabolic control and progression of retinopathy. The Diabetes in Early Pregnancy Study. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study. Diabetes care 18:631-637.
13. Christianson A HC, Modell B. 2006. March of dimes global report on birth defects: the hidden toll of dying and disabled children. NY: White Plains. p. 76.
14. Churchill JA, Berendes HW, Nemore J 1969. Neuropsychological deficits in children of diabetic mothers: a report from the collaborative study of cerebral palsy. Am J Obstet Gynecol 105:257.
15. Corbetta S, Bulfamante G, Cortelazzi D, et al. 2005. Adiponectin expression in human fetal tissues during mid-and late gestation. J Clin Endocrinol Metab 90:2397-2402.
16. Correa A, Botto L, Liu Y, et al. 2003. Do multivitamin supplements attenuate the risk for diabetes-associated birth defects? Pediatrics 111(5 Pt 2):1146-1151.
17. Correa A, Gilboa SM, Besser LM, et al. 2008. Diabetes mellitus and birth defects. Am J Obstet Gynecol 199:237.e231-e239.
18. Correa A, Gilboa SM, Botto LD, et al., 2012. Lack of periconceptional vitamins or supplements that contain folic acid and diabetes mellitus-associated birth defects. Am J Obstet Gynecol 206:218 e211-e213.
19. Corrigan N, Brazil DP, McAuliffe F 2009. Fetal cardiac effects of maternal hyperglycemia during pregnancy. Birth Defect Res Part A, Clin Mol Teratol 85:523-530.
20. Cropley JE, Suter CM, Beckman KB, Martin DI. 2006. Germ-line epigenetic modification of the murine A vy allele by nutritional supplementation. Proc Natl Acad Sciences U S A 103:17308-17312.
21. Cummins M, Norrish M. 1980. Follow-up of children of diabetic mothers. Arch Dis Child 55:259-264.
22. Danaei G, Finucane MM, Lu Y, et al. 2011. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet 378:31-40.
23. Darias R, Herranz L, Garcia-Ingelmo MT, Pallardo LF. 2001. Pregnancy in a patient with type 1 diabetes mellitus and prior ischaemic heart disease. Eur J Endocrinol 144:309-310.
24. de Groote ML, Verschure PJ, Rots MG. 2012. Epigenetic editing: targeted rewriting of epigenetic marks to modulate expression of selected target genes. Nucleic acids Res 40:10596-10613.
25. Dhanasekaran N, Wu YK, Reece EA. 1999. Signaling pathways and diabetic embryopathy. Semin Reprod Endocrinol 17:167-174.
26. Dorner G, Plagemann A 1994. Perinatal hyperinsulinism as possible predisposing factor for diabetes mellitus, obesity and enhanced cardiovascular risk in later life. Hormone Metab Res 26:213-221.
27. Eriksson JG, Forsen T, Tuomilehto J, et al. 2000. Fetal and childhood growth and hypertension in adult. Hypertension 36:790-794.
28. Ergaz Z, Dror D, Zangen S, et al. 2012. The role of copper deficiency in diabetes-induced fetal growth restriction in the cohen diabetic rat model. Toxicol Appl Pharmacol 265:209-220.
29. Ergaz Z, Claire G, Neeman-Azulay M, et al. 2014. Placental oxidative stress and decreased global DNA methylation are corrected by copper in the Cohen Diabetic Rat. Toxicol Appl Pharmacol 276:220-230.
30. Fahed AC, Gelb BD, Seidman JG, Seidman CE 2013. Genetics of congenital heart disease: the glass half empty. Circ Res 112:707-720.
31. Farquar J, Heman M, Wong ACK, et al. 2003. Elevated umbilical cord ghrelin concentrations in small for gestational age neonates. J Clin Endocrin Metab 88:4324-4327.
32. Fine EL, Horal M, Chang TI, Fortin G, Loeken MR. 1999. Evidence that elevated glucose causes altered gene expression, apoptosis, and neural tube defects in a mouse model of diabetic pregnancy. Diabetes 48:2454-2462.
33. Fox DA, Grandjean P, de Groot D, Paule MG. 2012. Developmental origins of adult diseases and neurotoxicity: epidemiological and experimental studies. Neurotoxicology 33:810-816.
34. Fischer MJ. 2007. Chronic kidney disease and pregnancy: maternal and fetal outcomes. Adv Chronic Kidney Dis 14:132-145.
35. Fujiki R, Chikanishi T, Hashiba W, et al. 2009. GlcNAcylation of a histone methyltransferase in retinoic-acid-induced granulopoiesis. Nature 459:455-459.
36. Gardener H, Spiegelman D, Buka SL. 2009. Prenatal risk factors for autism: comprehensive meta-analysis. Br J Psych 195:7-14.
37. Gareskog M, Eriksson UJ, Wentzel P. 2006. Combined supplementation of folic acid and vitamin E diminishes diabetes-induced embryotoxicity in rats. Birth Defects Res A Clin Mol Teratol 76:483-490.
38. Greene MF, Hare JW, Cloherty JP, et al. 1989. First-trimester hemoglobin A1 and risk for major malformation and spontaneous abortion in diabetic pregnancy. Teratology 39:225-231.
39. Greene MF. Diabetic embryopathy 2001: moving beyond the "diabetic milieu." Teratology 63:116-118.
40. Greco P, Vimercati A, Scioscia M, et al. 2003. Timing of fetal growth acceleration in women with insulin dependent diabetes. Fetal Diagn Therap 18:437-441.
41. Gutierrez JC, Hrubec TC, Prater MR, et al. 2007. Aortic and ventricular dilation and myocardial reduction in gestation day 17 ICR mouse fetuses of diabetic mothers. Birth Defects Res A Clin Mol Teratol 79:459-464.
42. Harris MJ, Juriloff DM. 2007. Mouse mutants with neural tube closure defects and their role in understanding human neural tube defects. Birth Defect Res Part A Clin Mol Teratol 79:187-210.
43. Hawthorne G. 2011. Maternal complications in diabetic pregnancy. Best Pract Res Clin Obstet Gynaecol 25:77-90.
44. Hayslett JP, Reece EA. 1987a. Effect of diabetic nephropathy on pregnancy. Am J Kidney Dis 9:344-349.
45. Hayslett JP, Reece EA. 1987b. Managing diabetic patients with nephropathy and other vascular complications. Bailliere's Clin Obstet Gynaecol 1:939-954.
46. Higa R, White V, Martinez N, et al. 2010. Safflower and olive oil dietary treatments rescue aberrant embryonic arachidonic acid and nitric oxide metabolism and prevent diabetic embryopathy in rats. Mol Hum Reprod 16:286-295.
47. Hehir MP, Laursen H, Higgins MF, et al. 2013. Ghrelin concentrations in maternal and cord blood from Type 1 diabetic and non-diabetic pregnancies at term. Endocrine, 43:233-235.
48. Hod M, Levy-Shiff R, Lerman M, et al. 2001. Developmental outcome of offspring of pregestational diabetc women. J Pediatr Endocrinol Metab 14 Suppl 1:695-696.
49. Holman RR, Paul SK, Bethel MA, et al. 2008. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 359:1577-1589.
50. Honein MA, Paulozzi LJ, Mathews TJ, et al. 2001. Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects. J Am Med Assoc 285:2981-2986.
51. Horosz E, Bomba-Opon DA, Szymanska M, Wielgos M. 2011. Third trimester plasma adiponectin and leptin in gestational diabetes and normal pregnancies. Diabetes Res Clin Pract 93:350-356.
52. Hytinantti TK, Juntunen M, Kiostinen HA, et al. 2001. Postnatal changes in concentrations of free and bound leptin. Arch Dis Child Fetal Neonatal Ed 5:F123-F126.
53. Jawerbaum A, White V. 2010. Animal models in diabetes and pregnancy. Endocr Rev 31:680-701.
54. Jiang B, Kumar SD, Loh WT, et al. 2008. Global gene expression analysis of cranial neural tubes in embryos of diabetic mice. J Neurosci Res 86:3481-3493.
55. Jirtle RL, Skinner MK: 2007. Environmental epigenomics and disease susceptibility. Nat Rev Genet 8:253-262.
56. Kappen C, Kruger C, MacGowan J, Salbaum JM. 2011. Maternal diet modulates the risk for neural tube defects in a mouse model of diabetic pregnancy. Reprod Toxicol 31:41-49.
57. Kappen C. 2013. Modeling anterior development in mice: diet as modulator of risk for neural tube defects. Am J Med Genet C Semin Med Genet 163C:333-356.
58. Kappen C, Salbaum JM. 2014. Gene expression in teratogenic exposures: a new approach to understanding individual risk. ReprodToxicol 45:94-104.
59. Kimmerle R, Zab RP, Cupisti S, et al. 1995. Pregnancies in women with diabetic nephropathy: long-term outcome for mother and child. Diabetologia 38:227-235.
60. King P, Peacock I, Donnelly R. 1999. The UK Prospective Diabetes Study (UKPDS): clinical and therapeutic implications for type 2 diabetes. Br J Clin Pharmacol 48:643-648.
61. Kitzmiller JL, Combs CA. 1996. Diabetic nephropathy and pregnancy. Obstet Gynecol Clin North Am 23:173-203.
62. Knowler WC, Barrett-Connor E, Fowler SE, et al. 2002. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393-403.
63. Krakowiak P, Walker CK, Bremer AA, et al. 2012. Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics 129:1121-1128.
64. Kumar SD, Dheen ST, Tay SS. 2007. Maternal diabetes induces congenital heart defects in mice by altering the expression of genes involved in cardiovascular development. Cardiovasc Diabetol 6:34.
65. Kuroda A, Rauch TA, Todorov I, et al. 2009. Insulin gene expression is regulated by DNA methylation. PloS One 4:e6953.
66. Lage K, Greenway SC, Rosenfeld JA, et al. 2012. Genetic and environmental risk factors in congenital heart disease functionally converge in protein networks driving heart development. Proc Natl Acad Sci U S A 109:14035-14040.
67. Lampl M, Jeanty P. 2004. Exposure to maternal diabetes is associated with altered fetal growth patterns: a hypothesis regarding metabolic allocation to growth under hyperglycemic-hypoxemic conditions. Am J Hum Biol 16:237-263.
68. Langer O, Levy J, Brustman L, et al. 1989. Glycemic control in gestational diabetes mellitus-how tight is tight enough: small for gestational age versus large for gestational age. Am J Obstet Gynecol 161:646-653.
69. Lau C, Rogers JM. 2004. Embryonic and fetal programming of physiological disorders in adulthood. Birth Defects Res C Embryo Today 2004;72:300-312.
70. Leguizamon G, Reece EA. 2000. Effect of medical therapy on progressive nephropathy: influence of pregnancy, diabetes and hypertension. J Matern Fetal Med 9:70-78.
71. Lepercq J, Taupin P, Dubois-Laforgue D, et al. 2001. Heterogeneity of fetal growth in type 1 diabetic pregnancy. Diabetes Metab 27:339-344.
72. Leiter EH. 1989. The genetics of diabetes susceptibility in mice. FASEB J 3:2231-2241.
73. Leventakou V, Roumeliotaki T, Koutra K, et al. 2014. Breastfeeding duration and cognitive, language and motor development at 18 months of age: rhea mother-child cohort in Crete, Greece. J Epidemiol Community Health 68.
74. Liao DM, Ng YK, Tay SS, Ling EA, Dheen ST. 2004. Altered gene expression with abnormal patterning of the telencephalon in embryos of diabetic Albino Swiss mice. Diabetologia 47:523-531.
75. Lindsay SR, Walker JD, Havel PJ, et al. 2003. Adiponectin is present in cord blood but is unrelated to birth weight. Diabetes Care 26:2244-2249.
76. Lindstrom J, Louheranta A, Mannelin M, et al. 2003. The Finnish Diabetes Prevention Study (DPS): lifestyle intervention and 3-year results on diet and physical activity. Diabetes Care 26:3230-3236.
77. Lyall K, Pauls DL, Spiegelmam D, et al. 2012. Pregnancy complications and obstetric suboptimality in association with autism spectrum disorder in children of the Nurses Health Study II. Autism Res 5:21-30.
78. Mali P, Cheng L. 2012. Concise review: human cell engineering: cellular reprogramming and genome editing. Stem Cells 30:75-81.
79. Manderson JG, Mullan B, Patterson CC, et al. 2002. Cardiovascular and metabolic abnormalities in the offspring of diabetic pregnancy. Diabetologia 45:991-996.
80. Martinez-Frias ML. 1994. Epidemiological analysis of outcomes of pregnancy in diabetic mothers: identification of the most characteristic and most frequent congenital anomalies. Am J Med Genet 51:108-113.
81. McCarthy MI. 2010. Dorothy Hodgkin Lecture: from hype to hope? A journey through the genetics of Type 2 diabetes. Diabet Med 28:132-140.
82. Mendenhall EM, Williamson KE, Reyon D, et al. 2013. Locus-specific editing of histone modifications at endogenous enhancers. Nat Biotechnol 31:1133-1136.
83. Metzger BE, Silverman B, Freinkel N, et al. 1990. Amniotic fluid insulin as a predictor of obesity. Arch Dis Child 65:1050-1052.
84. Mikulandra F, Gryuric J, Banovic I, et al. 2000. The effect of high birth weight (400 g or more) on the weight and height of adult men and women. Coll Antropol 24:133-136.
85. Morgan SC, Relaix F, Sandell LL, Loeken MR. 2008. Oxidative stress during diabetic pregnancy disrupts cardiac neural crest migration and causes outflow tract defects. Birth Defects Res A Clin Mol Teratol 82:453-463.
86. Murphy SL XJ, Kochanek KD. 2013. Death: final Data for 2010. p 168.
87. Nathan DM, Bayless M, Cleary P, et al., for the DCCT/EDIC Research Group* 2013. Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study at 30 Years: advances and Contributions. Diabetes 62:3976-3986.
88. National Diabetes Fact Sheet 2011. National estimates and general information on diabetes and prediabetes in the United States, 2011. In: Services USDoHaH, editor. Atlanta, GA: Centers for Disease Control and Prevention.
89. Nelson CA, Wewerka SS, Borscheid AJ, et al. 2003. Electrophysiologic evidence of impaired cross-modal recognition memory in 8-month-old infants of diabetic mothers. J Pediatr 142:575-582.
90. Ng PC, Lee CH, Lam CWK, et al. 2004. Plasma ghrelin and resistin concentrations are suppressed in infants of insulin-dependent diabetic mothers. J Clin Endocrinol Metab 89:5563-5568.
91. Nomura Y, Marks DJ, Grossman B, et al. 2012. Exposure to gestational diabetes mellitus and low socio-economic status: effects on neurocognitive development and risk of attention-deficit hyperactivity disorder in offspring. Arch Pediatr Adolesc Med 166:337-343.
92. Ornoy A, Zaken V, Abir R, Yaffe P, Raz I. 1995. Serum from women with gestational diabetes is teratogenic to rat embryos in culture. Toxicol In Vitro 9:643-651.
93. Ornoy A, Ratzon N, Greenbaum C, et al. 1998. Neurobehaviour of school age children born to diabetic mothers. Arch Dis Child 79:F94-F99.
94. Ornoy A, Wolf A, Ratzon N, et al. 1999a. Neurodevelopmental outcome at early school age of children born to mothers with gestational diabetes. Arch Dis Child 81:F10-F14.
95. Ornoy A, Zaken V, Kohen R. 1999b The role of reactive oxygen species (ROS) in the diabetes-induced anomalies, in rat embryos in vitro: a reduction in antioxidant enzymes and low molecular weight antioxidants (LMWA) may be a causative factor for increased anomalies. Teratology 60:376-386.
96. Ornoy A, Ratzon N, Greenbaum C, et al. 2001. School-age children born to mothers with pregestational or gestational diabetes exhibit a high rate of inattention and fine and gross motor impairment. J Pediatr Endocrinol Metab 14:681-690.
97. Ornoy A. 2003. The impact of intrauterine exposure versus postnatal environment in neurodevelopment toxicity: long term neurobehavioral studies in children at risk for developmental disorders. Toxicol Lett 140/141:171-181.
98. Ornoy A, Avgil-Tsadok M, Yaffe P, Zangen WS. 2009. The Cohen diabetic rat as a model for fetal growth restriction: vitamins C and E reduce fetal oxidative stress but do not restore normal growth. Reprod Toxicol 28:521-529.
99. Ornoy A, Rand SB, Bischitz N. 2010. Hyperglycemia and hypoxia are interrelated in their teratogenic mechanism: studies on cultured rat embryos. Birth Defects Res Part B Dev Reprod Toxicol 89:106-115.
100. Ornoy A. 2011a. Prenatal origin of obesity and their complications: gestational diabetes, maternal overweight and the paradoxical effects of fetal growth restriction and macrosomia. Reprod Toxicol 32:205-212.
101. Ornoy A, Livshitz A, Ergaz A, et al. 2011b. Hyperglycemia, hypoxia and their combination exert oxidative stress and changes in antioxidant gene expression: studies on cultured rat embryos. Birth Defects Res Part B 92:231-219.
102. Otani H, Tanaka O, Tatewaki R, et al. 1991. Diabetic environment and genetic predisposition as causes of congenital malformations in NOD mouse embryos. Diabetes 40:1245-1250.
103. Oyama K, Sugimura Y, Murase T, et al. 2009. Folic acid prevents congenital malformations in the offspring of diabetic mice. Endocr J 56:29-37.
104. Pani L, Horal M, Loeken MR. 2002. Polymorphic susceptibility to the molecular causes of neural tube defects during diabetic embryopathy. Diabetes 51:2871-2874.
105. Park JH, Stoffers DA, Nicholls RD, Simmons RA. 2008. Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1. J Clin Invest 118:2316-2324.
106. Pavlinkova G, Salbaum JM, Kappen C. 2009. Maternal diabetes alters transcriptional programs in the developing embryo. BMC Genom 10:274.
107. Pearson B, Gentz J. 1984. Follow-up of children of insulin-dependent and gestational diabetes mothers. Acta Pediatr Scan 73:349-358.
108. Pedersen J. 1967. The pregnant diabetic and her newborn: problems and management. Baltimore, Phelan SA: The Williams & Wilkins Company.
109. Petersen BM, Pedersen SA, Greisen G, et al. 1988. Early growth delay in diabetic pregnancy: relation to psychomotor development at age 4. Br Med J 296:598-600.
110. Phelan SA, Ito M, Loeken MR. 1997. Neural tube defects in embryos of diabetic mice: role of the Pax-3 gene and apoptosis. Diabetes 46:1189-1197.
111. Pierpont ME, Basson CT, Benson DW, et al. 2007. Genetic basis for congenital heart defects: current knowledge: a scientific statement from the American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics. Circulation 115:3015-3038.
112. Pinter E, Reece EA, Leranth CZ, et al. 1986. Yolk sac failure in embryopathy due to hyperglycemia: ultrastructural analysis of yolk sac differentiation associated with embryopathy in rat conceptuses under hyperglycemic conditions. Teratology 33:73-84.
113. Plagemann A, Harder T 2005. Breast feeding and the risk of obesity and related metabolic diseases in the child. Metab Syndr Relat Disord 3:222-232.
114. Pociot F, Akolkar B, Concannon P, et al. 2010. Genetics of type 1 diabetes: what's next? 59:1561-1571.
115. Polak JF, Backlund JY, Cleary PA, et al. DCCT/EDIC Research Group. 2011. Progression of carotid artery intima-media thickness during 12 years in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. Diabetes 60:607-613.
116. Pombar X, Strassner HT, Fenner PC. 1995. Pregnancy in a woman with class H diabetes mellitus and previous coronary artery bypass graft: a case report and review of the literature. Obstet Gynecol 85:825-829.
117. Porta M, Maldari P, Mazzaglia F. 2011. New approaches to the treatment of diabetic retinopathy. Diab Obes Metab 13:784-790.
118. Rahman W, Rahman FZ, Yassin S, et al. 2007. Progression of retinopathy during pregnancy in type 1 diabetes mellitus. Clin Exp Ophthalmol 35:231-236.
119. Ramachandran A, Snehalatha C, Mary S, et al. 2006. The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). Diabetologia 49:289-297.
120. Reece EA, Pinter E, Leranth CZ, et al. 1985. Ultrastructural analysis of malformations of the embryonic neural axis induced by in vitro hyperglycemic conditions. Teratology 32:363-373.
121. Reece EA, Gabrielli S, Abdalla M. 1988. The prevention of diabetes-associated birth defects. Semin Perinatol 12:292-301.
122. Reece EA, Assimakopoulos E, Zheng XZ, et al. 1990a. The safety of obstetric ultrasonography: concern for the fetus. Obstet Gynecol 76:139-146.
123. Reece EA, Winn HN, Hayslett JP, et al. 1990b. Does pregnancy alter the rate of progression of diabetic nephropathy? Am J Perinatol 7:193-197.
124. Reece EA, Homko CJ, Wu YK. 1996a. Multifactorial basis of the syndrome of diabetic embryopathy. Teratology 54:171-182.
125. Reece EA, Wu YK, Wiznitzer A, et al. 1996b. Dietary polyunsaturated fatty acid prevents malformations in offspring of diabetic rats. Am J Obstet Gynecol 175(4 Pt 1):818-823.
126. Reece EA, Wu YK. 1997. Prevention of diabetic embryopathy in offspring of diabetic rats with use of a cocktail of deficient substrates and an antioxidant. Am J Obstet Gynecol 176:790-797; discussion 797-798.
127. Reece EA, Homko CJ, Wu YK, Wiznitzer A. 1998a. The role of free radicals and membrane lipids in diabetes-induced congenital malformations. J Soc Gynecol Invest 5:178-187.
128. Reece EA, Leguizamon G, Homko C. 1998b. Pregnancy performance and outcomes associated with diabetic nephropathy. Am J Perinatol 15:413-421.
129. Reece EA, Leguizamon G, Homko C. 1998c. Stringent controls in diabetic nephropathy associated with optimization of pregnancy outcomes. J Matern Fetal Med 7:213-216.
130. Reece EA, Ma XD, Wu YK, Dhanasekaran D. 2002. Aberrant patterns of cellular communication in diabetes-induced embryopathy. I. Membrane signalling. J Matern Fetal Neonatal Med 11:249-253.
131. Reece EA, Wu YK, Zhao Z, Dhanasekaran D. 2006a. Dietary vitamin and lipid therapy rescues aberrant signaling and apoptosis and prevents hyperglycemia-induced diabetic embryopathy in rats. Am J Obstet Gynecol 194:580-585.
132. Reece EA, Ji I, Wu YK, Zhao Z. 2006b. Characterization of differential gene expression profiles in diabetic embryopathy using DNA microarray analysis. Am J Obstet Gynecol 195:1075-1080.
133. Reece EA, Homko CJ. 2007. Prepregnancy care and the prevention of fetal malformations in the pregnancy complicated by diabetes. Clin Obstet Gynecol 50:990-997.
134. Reece EA. 2012. Diabetes-induced birth defects: what do we know? What can we do? Curr Diab Rep 12:24-32.
135. Rizzo TA, Dooley SL, Metzger BE, et al. 1995. Prenatal and perinatal influences on long-term psychomotor development in offspring of diabetic mothers. Am J Obstet Gynecol 173:1753-1758.
136. Romon M, Nuttens MC, Vambergue A, et al. 2001. Higher carbohydrate intake is associated with decreased incidence of newborn macrosomia in women with gestational diabetes. J Am Diet Assoc 101:897-902.
137. Rossing K, Jacobsen P, Hommel E, et al. 2002. Pregnancy and progression of diabetic nephropathy. Diabetologia 45:36-41.
138. Sabin LR, Delas MJ, Hannon GJ. 2013. Dogma derailed: the many influences of RNA on the genome. Mol Cell 49:783-794.
139. Salbaum JM, Kappen C. 2010. Neural tube defect genes and maternal diabetes during pregnancy. Birth Defects Res A Clin Mol Teratol 88:601-611.
140. Salbaum JM, Kappen C. 2011. Diabetic embryopathy: a role for the epigenome? Birth Defects Res A Clin Mol Teratol 91: 770-780.
141. Salbaum JM, Kappen C. 2012. Responses of the embryonic epigenome to maternal diabetes. Birth Defect Res Part A, Clin Mol Teratol 94:770-781.
142. Salbaum JM, Kruger C, Zhang X, et al. 2011. Altered gene expression and spongiotrophoblast differentiation in placenta from a mouse model of diabetes in pregnancy. Diabetologia 54:1909-1920.
143. Sandovici I, Smith NH, Nitert MD, et al. 2011. Maternal diet and aging alter the epigenetic control of a promoter-enhancer interaction at the Hnf4a gene in rat pancreatic islets. Proc Natl Acad Sci U S A 108:5449-5454.
144. Schaffer-Graf UM, Pawliczak J, Passow D, et al. 2005. Birth weight and parental BMI predict overweight in children from mothers with gestational diabetes. Diabetes Care 28:1745-1750.
145. Schlotz W, Phillips DIW 2009. Fetal origin of mental health: evidence and mechanism. Brain Behav Immun 23:905-916.
146. Scholl TO, Sowers MF, Chen X, Lenders C 2001. Maternal glucose concentration influences fetal growth, gestation, and pregnancy complications. Am J Epidemiol 154:514-520.
147. Schneider S, Bock C, Wetzel M, et al. 2012. The prevalence of gestational diabetes in advanced economies. J Perinat Med 40:511-520.
148. Sells CJ, Robinson NM, Brown Z, Knopp RH. 1994. Long-term developmental follow-up of infants of diabetic mothers. J Pediatr 125:S9-S17.
149. Shantikunar S, Caporali A, Emanuali C. 2012. Role of microRNAs in diabetes and its cardivascular complications. Cardiovasc Res 93:583-593.
150. Shen H, Laird PW. 2013. Interplay between the cancer genome and epigenome. Cell 153:38-55.
151. Silverman BL, Landsberg L, Metzger BE 1993. Fetal hyperinsulinism in offspring of diabetic mothers. Ann N Y Acad Sci 699:36-45.
152. Siman CM, Eriksson UJ. 1997. Vitamin E decreases the occurrence of malformations in the offspring of diabetic rats. Diabetes 46:1054-1061.
153. Sivan E, Reece EA, Wu YK, et al. 1996. Dietary vitamin E prophylaxis and diabetic embryopathy: morphologic and biochemical analysis. Am J Obstet Gynecol 175(4 Pt 1):793-799.
154. Stehbens JA, Baker GL, Kitchell M.1977. Outcome at age 1, 3 and 5 years of children born to diabetic women. Am J Obst Gynecol 127:408-415.
155. Stevenin C, Collet C, White C, Marre M. 2001. Management of diabetic nephropathy before and during pregnancy. Diab Metab 27(4 Pt 2):S42-S47.
156. Stodgell CJ, Miller RK, Glazko G, Salamone A, Ornoy A. 2011. Gene expression in a rat model of Type II diabetes mellitus: Effects of Environmental and gene influences on fetal development. Repro Tox 31:266.
157. Symonds ME, Sebert SP, Hyatt MA, Budge H. 2009. Nutritional programming of the metabolic syndrome. Nat Rev Endocrinol 5:604-610.
158. Tanne JH. 2012. Maternal obesity and diabetes are linked to children's autism and similar disorders. BMJ 17;344:e2768.
159. Toriello HV. 2005. Folic acid and neural tube defects. Genet Med 7:283-284.
160. Vijaya M, Manikandan J, Parakalan R, et al. 2013. Differential gene expression profiles during embryonic heart development in diabetic mice pregnancy. Gene 516:218-227.
161. Vitoratos N, Christodoulacos G, Salamalekis E, Kassano D, Kouskouni E, Creatsas G. Fetoplacental leptin levels and their relation to birth weight and insulin in gestational diabetic pregnant women. J Obstet Gynecol 2002;22:29-33.
162. Vohr BR, McGarvey ST. 1997. Growth patterns of large-for-gestational-age and appropriate-for-gestational-age infants of gestational diabetic mothers and control mothers at age 1 year. Diabetes Care 20:1066-1072.
163. Vohr BR, McGarvey ST, Tucker R. 1999. Effects of maternal gestational diabetes on offspring adiposity at 4-7 years of age. Diabetes Care 22:1284-1289.
164. Voigt P, Reinberg D. 2013. Epigenome editing. Nat Biotechnol 31:1097-1099.
165. Wallingford JB, Niswander LA, Shaw GM, Finnell RH. 2013. The continuing challenge of understanding, preventing, and treating neural tube defects. Science 339:1222002.
166. Wang Q, Ratchford AM, Chi MM, et al. 2009. Maternal diabetes causes mitochondrial dysfunction and meiotic defects in murine oocytes. Mol Endocrinol (Baltimore, MD) 23:1603-1612.
167. Walsh LM, McAuliffe FM. 2012 Prediction and prevention of the macrosomic fetus. Eur J Obstet Gynecol Reprod Biol 162:125-130.
168. Wei D, Loeken MR. 2014. Increased DNA methyltransferase 3b (Dnmt3b)-mediated CpG Island methylation stimulated by oxidative stress inhibits expression of a gene required for neural tube and neural crest development in diabetic pregnancy. Diabetes 63:3512-3522.
169. Weksler-Zangen S. Yaffe P, Ornoy A. 2003. Reduced SOD activity and increased neural tube defects in embryos of the sensitive but not of the resistant Cohen diabetic rats cultured under diabetic conditions. Birth Defects Res A Clin Mol Teratol 67:429-437.
170. Weksler-Zangen S, Seonghun R, Ornoy A. 2006. The role of antioxidant enzymes and transcription factor NF-kappa B in diabetic embryopathy in the cohen diabetic rat model. Birth Defect Res Part A Clin Mol Teratol 76:107-114.
171. Wellen KE, Hatzivassiliou G, Sachdeva UM, et al. 2009. ATP-citrate lyase links cellular metabolism to histone acetylation. Science 324:1076-1080.
172. Wellen KE, Lu C, Mancuso A, et al. 2010 The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism. Genes Dev 24:2784-2799.
173. Wentzel P, Eriksson UJ. 1998. Antioxidants diminish developmental damage induced by high glucose and cyclooxygenase inhibitors in rat embryos in vitro. Diabetes 47:677-684.
174. Wentzel P, Eriksson UJ. 2005a. A diabetes-like environment increases malformation rate and diminishes prostaglandin E(2) in rat embryos: reversal by administration of vitamin E and folic acid. Birth Defects Res A Clin Mol Teratol 73:506-511.
175. Wentzel P, Gareskog M, Eriksson UJ. 2005b. Folic acid supplementation diminishes diabetes- and glucose-induced dysmorphogenesis in rat embryos in vivo and in vitro. Diabetes 54:546-553.
176. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, et al. 2001. Hypoadiponectimia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86:1930-1935.
177. Wiznitzer A, Ayalon N, Hershkovitz R, et al. 1999. Lipoic acid prevention of neural tube defects in offspring of rats with streptozocin-induced diabetes. Am J Obstet Gynecol 180(1 Pt 1):188-193.
178. Wiznitzer A, Furman B, Zuili I, et al. 2000. Cord leptin levels and fetal macrosomia. Obstet Gynecol 96:707-713.
179. Worda C, Leipold H, Gruber C, et al. 2004. Decreased plasma adiponectin concentrations in women with gestational diabetes mellitus. Am J Obstet Gynecol 191:2120-2124.
180. Wu Y, Viana M, Thirumangalathu S, Loeken MR. 2012. AMP-activated protein kinase mediates effects of oxidative stress on embryo gene expression in a mouse model of diabetic embryopathy. Diabetologia 55:245-254.
181. Yamashita Y, Kawano Y, Kuriya N, et al. 1996. Intellectual development of offspring of diabetic mothers. Acta Paediatr 85:1192-1196.
182. Yang P, Zhao Z, Reece EA. 2007. Involvement of c-Jun N-terminal kinases activation in diabetic embryopathy. Biochem Biophys Res Commun 357:749-754.
183. Yang P, Zhao Z, Reece EA. 2008. Activation of oxidative stress signaling that is implicated in apoptosis with a mouse model of diabetic embryopathy. Am J Obstet Gynecol 198:130 e131-e137.
184. Yang P, Reece EA. 2011. Role of HIF-1alpha in maternal hyperglycemia-induced embryonic vasculopathy. Am J Obstet Gynecol 204:332.e331-e337.
185. Zaken V, Kohen R, Ornoy A. 2001. Vitamins C and E improve rat embryonic antioxidant defense mechanism in diabetic culture medium. Teratology 64:33-44.
186. Zhao Z, Yang P, Eckert RL, Reece EA. 2009. Caspase-8: a key role in the pathogenesis of diabetic embryopathy. Birth Defect Res Part B, Dev Reprod Toxicol 86:72-77.
187. Zhao Z, Eckert RL, Reece EA. 2012. Reduction in embryonic malformations and alleviation of endoplasmic reticulum stress by nitric oxide synthase inhibition in diabetic embryopathy. Reprod Sciences (Thousand Oaks, CA) 19:823-831.
188. Zusman I, Yaffe P, Ornoy A. 1987. The effects of high sucrose diet and maternal diabetes on the ultrastructure of the visceral yolk sac endoderm in rat embryos developing in vivo and in vitro. Acta Anat 128:11-19.
189. Xu G, Jing J, Bowers K, Liu B, Bao W. 2014. Maternal diabetes and the risk of autism spectrum disorders in the offspring: a systematic review and meta-analysis. J Autism Dev Disorder 44:766-775.