Neonatology pp 717-730 | Cite as

Infants of Diabetic Mothers

  • Erin A. Osterholm
  • Jane E. Barthell
  • Michael K. GeorgieffEmail author
Reference work entry


Ten per cent of all pregnancies are complicated by gestational diabetes mellitus or preconceptional diabetes and, given the increased prevalence of obesity, this percentage is expected to rise over the next few years. While advances in maternal and neonatal medical care continue to improve the outcomes for infants born to mothers with glucose intolerance during pregnancy, the risks for spontaneous abortion, stillbirth, congenital malformations, and perinatal mortality still exist. Pregnancies of mothers with diabetes are given increased surveillance, as the multifaceted metabolic changes that occur in the mother affect fetal growth, glucose and iron metabolism, cardiac anatomy and function, transition to extrauterine life, placing the infant at risk for periconceptional, fetal, neonatal, and long-term morbidities. This chapter gives a perspective on the risks of glucose intolerance during pregnancies, neonatal complications, and long-term health sequelae of infants of diabetic mothers.


  1. Abuhamad AZ for the ACOG Practice Committee (2009) Ultrasonography in pregnancy. Obstet Gynecol 113:451–461, PMID: 19155920CrossRefGoogle Scholar
  2. Amarnath UM, Ophoven JJ, Mills MM (1989) The relationship between decreased iron stores, serum iron and neonatal hypoglycemia in large-for-date newborn infants. Acta Paediatr Scand 78:538–543CrossRefGoogle Scholar
  3. American College of Obstetricians and Gynecologists (2014) Safe prevention of the primary cesarean delivery. Obstet Gynecol 123:693–711CrossRefGoogle Scholar
  4. Bard H, Prosmanne J (1987) Relative rates of fetal hemoglobin and adult hemoglobin synthesis in cord blood of infants of insulin-dependent diabetic mothers. Pediatrics 75:1143–1147Google Scholar
  5. Beard J (2003) Neonatal iron deficiency results in irreversible changes in dopamine function in rats. J Nutr 133:1174–1179CrossRefGoogle Scholar
  6. Bennett SE, McPeake J, McCance DR, Manderson JG, Johnston P, McGalliard R, McGinty A (2014) Maternal vitamin D status in Type 1 diabetic pregnancy: impact on neonatal vitamin D status and association with maternal glycaemic control. Pregnancy Hypertens 4:235–236, PMID: 26104623CrossRefGoogle Scholar
  7. Boney CM, Verma A, Tucker R, Vohr BR (2005) Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 115:e290–e296CrossRefGoogle Scholar
  8. Brand PL, Molenaar NL, Kaaijk C, Wierenga WS (2005) Neurodevelopmental outcome of hypoglycaemia in healthy, large for gestational age, term newborns. Arch Dis Child 90:78–81CrossRefGoogle Scholar
  9. Burns CM, Rutherford MA, Boardman JP, Cowan FM (2008) Patterns of cerebral injury and neurodevelopmental outcomes after symptomatic neonatal hypoglycemia. Pediatrics 122:65–74CrossRefGoogle Scholar
  10. Carlton Johnnny J, Anuratha N (2016) Study of lipid status in the euglycemic offsrpin of diabetic parents with sex, age matched controls among South India population. Diabetes Metab Syndr 16 pii: S1871 – 4021. PMID: 27012159Google Scholar
  11. Catalano PM, Thomas A, Huston-Presley L, Amini SB (2003) Increased fetal adiposity: a very sensitive marker of abnormal in utero development. Am J Obstet Gynecol 189:1698–1704CrossRefGoogle Scholar
  12. Chockalingam UM, Murphy E, Ophoven JC et al (1987) Cord transferrin and ferritin values in newborn infants at risk for prenatal uteroplacental insufficiency and chronic hypoxia. J Pediatr 111:283–286CrossRefGoogle Scholar
  13. Connor JR, Menzies SL (1996) Relationship of iron to oligodendrocytes and myelination. Glia 17:89–93, CrossRefCrossRefGoogle Scholar
  14. Correa A, Gilboa SM, Besser LM et al (2008) Diabetes mellitus and birth defects. Am J Obstet Gynecol 199(237):e1–e9Google Scholar
  15. de Regnier RA, Nelson CA, Thomas KM et al (2000) Neurophysiologic evaluation of auditory recognition memory in healthy newborn infants and infants of diabetic mothers. J Pediatr 137:777–784, CrossRefCrossRefGoogle Scholar
  16. de Regnier RA, Long JD, Georgieff MK, Nelson CA (2007) Using event-related potentials to study perinatal nutrition and brain development in infants of diabetic mothers. Dev Neuropsychol 31:379–396, CrossRefCrossRefGoogle Scholar
  17. de Ungria M, Rao R, Wobken JD et al (2000) Perinatal iron deficiency decreases cytochrome c oxidase (cytox) activity in selected regions of neonatal rat brain. Pediatr Res 48:169–176, CrossRefCrossRefGoogle Scholar
  18. DeBoer T, Wewerka S, Bauer PJ (2005) Explicit memory performance in infants of diabetic mothers at 1 year of age. Dev Med Child Neurol 47:525–531CrossRefGoogle Scholar
  19. Deinard AS, List A, Lindgren B et al (1986) Cognitive deficits in iron-deficient and iron-deficient anemic children. J Pediatr 108(5 Part 1):681–689CrossRefGoogle Scholar
  20. Fahrenkrog S, Harder T, Stolaczyk E et al (2004) Cross-fostering to diabetic rat dams affects early development of mediobasal hypothalamic nuclei regulating food intake, body weight, and metabolism. J Nutr 134:648–654CrossRefGoogle Scholar
  21. Fuhrmann K, Reiher H, Semmler K et al (1983) Prevention of congenital malformations in infants of insulin-dependent diabetic mothers. Diabetes Care 6:219–223CrossRefGoogle Scholar
  22. Galindo A, Burguillo AG, Azriel S, Fuente Pde L (2006) Outcome of fetuses in women with pregestational diabetes mellitus. J Perinat Med 34:323–331CrossRefGoogle Scholar
  23. Gao Q, Gao YM (2007) Hyperglycemic condition disturbs the proliferation and cell death of neural progenitors in mouse embryonic spinal cord. Int J Dev Neurosci 25:349–357CrossRefGoogle Scholar
  24. Georgieff MK (1995) Therapy of infants of diabetic mothers. In: Burg FD, Ingelfinger JR, Wald ER, Polin RA (eds) Current pediatric therapy, 15th edn. WB Saunders, Philadelphia, pp 793–803Google Scholar
  25. Georgieff MK (2006) The effect of maternal diabetes during pregnancy on the neurodevelopment of offspring. Minn Med 89:44–47PubMedGoogle Scholar
  26. Georgieff MK, Sasanow SR, Chockalingam UM, Pereira GR (1988) A comparison of the mid-arm circumference/head circumference ratio and ponderal index for the evaluation of newborn infants after abnormal intrauterine growth. Acta Paediatr Scand 77:214–219CrossRefGoogle Scholar
  27. Georgieff MK, Widness JA, Mills MM, Stonestreet BS (1989) The effect of prolonged intrauterine hyperinsulinemia on iron utilization in fetal sheep. Pediatr Res 26:467–469CrossRefGoogle Scholar
  28. Georgieff MK, Landon MB, Mills MM et al (1990) Abnormal iron distribution in infants of diabetic mothers: spectrum and maternal antecedents. J Pediatr 117:455–461CrossRefGoogle Scholar
  29. Georgieff MK, Petry CD, Mills MM (1997) Increased N-glycosylation and reduced transferrin binding capacity of transferrin receptor isolated from placentas of diabetic mothers. Placenta 18:563–568CrossRefGoogle Scholar
  30. Gomella TL, Cunningham MD, Eyal FG, Zenk KE (2004) Neonatology: management, procedures, on-call problems, diseases, and drugs, 5th edn. McGraw-Hill, New York, pp 418–433Google Scholar
  31. Green DW, Khoury J, Mimouni F (1992) Neonatal hematocrit and maternal glycemic control in insulin-dependent diabetic mothers. J Pediatr 12:302–305CrossRefGoogle Scholar
  32. Hami J, Shojae F, Vafaee-Nezhad S, Lotfi N, Kheradmand H, Haghir H (2015) Some of the experimental and clinical aspects of the effects of the maternal diabetes on the developing hippocampus. World J Diabetes 15:412–422, PMID: 25897352CrossRefGoogle Scholar
  33. Herranz L, Pallardo LF, Hillman N et al (2007) Maternal third trimester hyperglycaemic excursions predict large-for-gestationalage infants in type 1 diabetic pregnancy. Diabetes Res Clin Pract 75:42–46CrossRefGoogle Scholar
  34. Herrera E, Desoye G (2015) Maternal and fetal lipid metabolism under normal and gestational diabetic conditions. Horm Mol Biol Clin Invest 23:1868–1883, PMID: 26351960Google Scholar
  35. Herrera E, Ortega-Senovilla H (2014) Lipid metabolism during pregnancy and its implications for fetal growth. Curr Pharm Biotechnol 15:24–31, PMID: 247201597CrossRefGoogle Scholar
  36. Inder T (2008) How low can I go? The impact of hypoglycemia on the immature brain. Pediatrics 122:440–441CrossRefGoogle Scholar
  37. Jain A, Agarwal R, Sankar MJ (2008) Hypocalcemia in the newborn. Indian J Pediatr 75:165–169CrossRefGoogle Scholar
  38. Kalhan SC, Parimi PS (2006) Diabetes in pregnancy: the infant of a diabetic mother. In: Martin RJ, Fanaroff AA, Walsh MC (eds) Neonatal-perinatal medicine, 8th edn. Elsevier Mosby, Philadelphia, pp 1473–1478Google Scholar
  39. 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 30:34, CrossRefCrossRefGoogle Scholar
  40. Langer O, Berkus MD, Huff RW, Samueloff A (1991) Shoulder dystocia: should the fetus weighing greater than or equal to 4000 grams be delivered by cesarean section? Am J Obstet Gynecol 165(4 Pt 1):831–837CrossRefGoogle Scholar
  41. Lucas MJ (2001) Medical complications of pregnancy: diabetes complicating pregnancy. Obstet Gynecol Clin N Am 28:513–536CrossRefGoogle Scholar
  42. Matias SL, Dewey KG, Quesenberry CP, Gunderson EP (2014) Maternal prepregnancy obesity and insulin treatment during pregnancy are independently associated with delayed lactogenesis in women with recent gestational diabetes mellitus. Am J Clin Nutr 99:115–121, PMID: 24196401CrossRefGoogle Scholar
  43. Moore TR (1999) Diabetes in pregnancy. In: Creasy RK, Resnik R (eds) Maternal-fetal medicine. WB Saunders, Philadelphia, pp 964–995Google Scholar
  44. 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 82:453–463CrossRefGoogle Scholar
  45. 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 142:575–582CrossRefGoogle Scholar
  46. Nold JL, Georgieff MK (2004) Infants of diabetic mothers. Pediatr Clin N Am 51:619–637, CrossRefCrossRefGoogle Scholar
  47. Ornoy A (2005) Growth and neurodevelopmental outcome of children born to mothers with pregestational and gestational diabetes. Pediatr Endocrinol Rev 3:104–113PubMedGoogle Scholar
  48. Panagos PG, Vishwanathan R, Penfield-Cyr A, Matthan NR, Shivappa N, Wirth MD, Herbert JR, Sen S (2016) Breastmilk from obese mothers has pro-inflamatory properties and decreased neuroprotective factors. J Perinatol 36:284–290, PMID: 26741571CrossRefGoogle Scholar
  49. Petry CD, Eaton MA, Wobken JA et al (1992) Liver, heart, and brain iron deficiency in newborn infants of diabetic mothers. J Pediatr 121:109–114CrossRefGoogle Scholar
  50. Petry CD, Wobken JD, McKay H et al (1994) Placental transferrin receptor in diabetic pregnancies with increased fetal iron demand. Am J Physiol 267:E507–E514CrossRefGoogle Scholar
  51. Plagemann A (2005) Perinatal programming and functional teratogenesis: impact on body weight regulation and obesity. Physiol Behav 86:661–668CrossRefGoogle Scholar
  52. Radder JK, van Roosmalen J (2005) HbA1c in healthy, pregnant women. Neth J Med 63:256–259PubMedGoogle Scholar
  53. Rajdl D, Racek J, Steinerová A et al (2005) Markers of oxidative stress in diabetic mothers and their infants during delivery. Physiol Res 54:429–436PubMedGoogle Scholar
  54. Riggins T, Miller NC, Bauer PJ et al (2009) Consequences of low neonatal iron status due to maternal diabetes mellitus on explicit memory performance in childhood. Dev Neuropsychol 34:762–779CrossRefGoogle Scholar
  55. Rizzo TA, Metzger BE, Dooley SL, Cho NH (1997) Early malnutrition and child neurobehavioral development: insights from the study of children of diabetic mothers. Child Dev 68:26–38CrossRefGoogle Scholar
  56. Russell NE, Holloway P, Quinn S et al (2008) Cardiomyopathy and cardiomegaly in stillborn infants of diabetic mothers. Pediatr Dev Pathol 11:10–14CrossRefGoogle Scholar
  57. Savona-Ventura C, Gatt M (2004) Embryonal risks in gestational diabetes mellitus. Early Hum Dev 79:59–63CrossRefGoogle Scholar
  58. Schaefer-Graf UM, Kleinwechter H (2006) Diagnosis and new approaches in the therapy of gestational diabetes mellitus. Curr Diabetes Rev 2:343–352CrossRefGoogle Scholar
  59. Schmidt AT, Waldow KJ, Salinas JA, Georgieff MK (2004) The long-term behavioral effects of fetal/neonatal iron deficiency on a hippocampally dependent learning task in the rat. Pediatr Res 55:279AGoogle Scholar
  60. Schushan-Eisen I, Cohen M, Leibovitch L, Maayan-Metzger A, Strauss T (2015) Bone density among infants of gestational diabetic mothers and macrosomic neonates. Matern Child Health J 19:578–582, PMID: 25138627CrossRefGoogle Scholar
  61. Schwartz RP (1997) Neonatal hypoglycemia: how low is too low? J Pediatr 131:171–173CrossRefGoogle Scholar
  62. Siddappa AM, Georgieff MK, Wewerka S et al (2004) Iron deficiency alters auditory recognition memory in newborn infants of diabetic mothers. Pediatr Res 55:1034–1041CrossRefGoogle Scholar
  63. Smilowitz JT, Totten SM, Huang J, Grapov D, Durham HA, Lammi-Keefe CJ, Lebrilla C, German JB (2013) Human milk secretory immunoglobulin a and lactoferrin N-glycans are altered in women with gestational diabetes mellitus. J Nutr 143:1906–1912, PMID 24047700CrossRefGoogle Scholar
  64. Stonestreet BS, Goldenstein M, Oh W, Widness JA (1989) Effect of prolonged hyperinsulinemia on erythropoiesis in fetal sheep. Am J Physiol 257:R1199–R1204PubMedGoogle Scholar
  65. Torres-Espinola FJ, Berglund SK, Garcia-Valdes LM, Segura MT, Jerez A, Campos D, Moreno-Torres R, Rueda R, Catena A, Perez-Garcia M, Campoy C, PREOBE Team (2015) Maternal obesity, overweight, and gestational diabetes affect the offspring neurodevelopment at 6 and 18 months of age- a follow up from the PREOBE cohort. PLoS One 10:e0133010, PMID: 26208217CrossRefGoogle Scholar
  66. Touger L, Looker HC, Krakoff J et al (2005) Early growth in offspring of diabetic mothers. Diabetes Care 28:585–589CrossRefGoogle Scholar
  67. Vohr BR, Boney CM (2008) Gestational diabetes: the forerunner for the development of maternal and childhood obesity and metabolic syndrome? J Matern Fetal Neonatal Med 21:149–157CrossRefGoogle Scholar
  68. Volpe JJ (2001) Neonatal seizures. In: Volpe JJ (ed) Neurology of the newborn, 4th edn. WB Saunders, Philadelphia, pp 178–216Google Scholar
  69. Weber HS, Copel JA, Reece EA et al (1991) Cardiac growth in fetuses of diabetic mothers with good metabolic control. J Pediatr 118:103–107CrossRefGoogle Scholar
  70. Widness JA (1989) Fetal risks and neonatal complications of diabetes mellitus and metabolic and endocrine disorders. In: Brody SA, Ueland K (eds) Endocrine disorders in pregnancy. Appleton-Lang, Norwalk, pp 273–297Google Scholar
  71. Widness JA, Susa JB, Garcia JF et al (1981) Increased erythropoiesis and elevated erythropoietin in infants born to diabetic mothers and in hyperinsulinemic rhesus fetuses. J Clin Invest 67:637–642CrossRefGoogle Scholar
  72. Wong SF, Lee-Tannock A, Amaraddio D et al (2006) Fetal growth patterns in fetuses of women with pregestational diabetes mellitus. Ultrasound Obstet Gynecol 28:934–938CrossRefGoogle Scholar
  73. Zhao Z, Reece EA (2005) Experimental mechanisms of diabetic embryopathy and strategies for developing therapeutic interventions. J Soc Gynecol Investig 12:549–557CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Erin A. Osterholm
    • 1
  • Jane E. Barthell
    • 2
  • Michael K. Georgieff
    • 1
    Email author
  1. 1.Division of Neonatology, Department of Pediatrics Center for Neurobehavioral DevelopmentUniversity of MinnesotaMinneapolisUSA
  2. 2.Children’s Hospitals and Clinics of MinnesotaMinneapolisUSA

Personalised recommendations