Infant of a diabetic mother
- Arieh Riskin, MD, MHA
Arieh Riskin, MD, MHA
- Department of Neonatology
- Bnai Zion Medical Center, Israel
- Clinical Associate Professor
- Rappaport Faculty of Medicine, Technion, Israel
- Joseph A Garcia-Prats, MD
Joseph A Garcia-Prats, MD
- Section Editor — Neonatology
- Professor of Pediatrics
- Baylor College of Medicine
- Section Editors
- Leonard E Weisman, MD
Leonard E Weisman, MD
- Section Editor — Neonatology
- Professor of Pediatrics
- Baylor College of Medicine
- Joseph I Wolfsdorf, MB, BCh
Joseph I Wolfsdorf, MB, BCh
- Section Editor — Pediatric Endocrinology
- Professor of Pediatrics
- Harvard Medical School
Diabetes in pregnancy is associated with an increased risk of fetal, neonatal, and long-term complications in the offspring. Maternal diabetes may be pregestational (ie, type 1 or type 2 diabetes diagnosed before pregnancy with a prevalence rate of about 1.8 percent) or gestational (ie, diabetes diagnosed during pregnancy with a prevalence rate of about 7.5 percent). The outcome is generally related to the onset and duration of glucose intolerance during pregnancy and severity of the mother's diabetes. (See "Pregestational diabetes: Preconception counseling, evaluation, and management".)
This topic will review the complications seen in the offspring of mothers with diabetes and the management of affected neonates. The prenatal management of pregestational and gestational diabetic mothers is discussed in separate topic reviews. (See "Diabetes mellitus in pregnancy: Screening and diagnosis" and "Pregestational diabetes mellitus: Obstetrical issues and management" and "Gestational diabetes mellitus: Obstetrical issues and management" and "Gestational diabetes mellitus: Glycemic control and maternal prognosis" and "Pregestational diabetes: Preconception counseling, evaluation, and management".)
Poor glycemic control in pregnant diabetic women leads to deleterious fetal effects throughout pregnancy, as follows :
●In the first trimester and time of conception, maternal hyperglycemia can cause diabetic embryopathy resulting in major birth defects and spontaneous abortions. This primarily occurs in pregnancies with pregestational diabetes. The risk for congenital malformations is only slightly increased with gestational diabetes mellitus (GDM) compared with the general population (odds ratio [OR] 1.1-1.3). The risk of malformations increases as maternal fasting blood glucose levels and body mass index (BMI) increases when GDM is diagnosed early in pregnancy. These findings suggest that some of these mothers are probably undiagnosed women with type 2 diabetes [2,3]. (See 'Congenital anomalies' below and "Pregestational diabetes: Preconception counseling, evaluation, and management".)
●Diabetic fetopathy occurs in the second and third trimesters, resulting in fetal hyperglycemia, hyperinsulinemia, and macrosomia.
- Buchanan TA, Kitzmiller JL. Metabolic interactions of diabetes and pregnancy. Annu Rev Med 1994; 45:245.
- Mitanchez D, Burguet A, Simeoni U. Infants born to mothers with gestational diabetes mellitus: mild neonatal effects, a long-term threat to global health. J Pediatr 2014; 164:445.
- Mitanchez D, Yzydorczyk C, Siddeek B, et al. The offspring of the diabetic mother--short- and long-term implications. Best Pract Res Clin Obstet Gynaecol 2015; 29:256.
- Philips AF, Dubin JW, Matty PJ, Raye JR. Arterial hypoxemia and hyperinsulinemia in the chronically hyperglycemic fetal lamb. Pediatr Res 1982; 16:653.
- Nold JL, Georgieff MK. Infants of diabetic mothers. Pediatr Clin North Am 2004; 51:619.
- Widness JA, Teramo KA, Clemons GK, et al. Temporal response of immunoreactive erythropoietin to acute hypoxemia in fetal sheep. Pediatr Res 1986; 20:15.
- Widness JA, Teramo KA, Clemons GK, et al. Direct relationship of antepartum glucose control and fetal erythropoietin in human type 1 (insulin-dependent) diabetic pregnancy. Diabetologia 1990; 33:378.
- Kitzmiller JL. Sweet success with diabetes. The development of insulin therapy and glycemic control for pregnancy. Diabetes Care 1993; 16 Suppl 3:107.
- Sarikabadayi YU, Aydemir O, Aydemir C, et al. Umbilical cord oxidative stress in infants of diabetic mothers and its relation to maternal hyperglycemia. J Pediatr Endocrinol Metab 2011; 24:671.
- Lappas M, Hiden U, Desoye G, et al. The role of oxidative stress in the pathophysiology of gestational diabetes mellitus. Antioxid Redox Signal 2011; 15:3061.
- Topcuoglu S, Karatekin G, Yavuz T, et al. The relationship between the oxidative stress and the cardiac hypertrophy in infants of diabetic mothers. Diabetes Res Clin Pract 2015; 109:104.
- Escobar J, Teramo K, Stefanovic V, et al. Amniotic fluid oxidative and nitrosative stress biomarkers correlate with fetal chronic hypoxia in diabetic pregnancies. Neonatology 2013; 103:193.
- Cordero L, Treuer SH, Landon MB, Gabbe SG. Management of infants of diabetic mothers. Arch Pediatr Adolesc Med 1998; 152:249.
- Michael Weindling A. Offspring of diabetic pregnancy: short-term outcomes. Semin Fetal Neonatal Med 2009; 14:111.
- Yang J, Cummings EA, O'connell C, Jangaard K. Fetal and neonatal outcomes of diabetic pregnancies. Obstet Gynecol 2006; 108:644.
- Kapoor N, Sankaran S, Hyer S, Shehata H. Diabetes in pregnancy: a review of current evidence. Curr Opin Obstet Gynecol 2007; 19:586.
- Boghossian NS, Hansen NI, Bell EF, et al. Outcomes of Extremely Preterm Infants Born to Insulin-Dependent Diabetic Mothers. Pediatrics 2016; 137.
- Becerra JE, Khoury MJ, Cordero JF, Erickson JD. Diabetes mellitus during pregnancy and the risks for specific birth defects: a population-based case-control study. Pediatrics 1990; 85:1.
- Correa A, Gilboa SM, Besser LM, et al. Diabetes mellitus and birth defects. Am J Obstet Gynecol 2008; 199:237.e1.
- Weintrob N, Karp M, Hod M. Short- and long-range complications in offspring of diabetic mothers. J Diabetes Complications 1996; 10:294.
- Wren C, Birrell G, Hawthorne G. Cardiovascular malformations in infants of diabetic mothers. Heart 2003; 89:1217.
- Ellis H, Kumar R, Kostyrka B. Neonatal small left colon syndrome in the offspring of diabetic mothers-an analysis of 105 children. J Pediatr Surg 2009; 44:2343.
- Khoury MJ, Becerra JE, Cordero JF, Erickson JD. Clinical-epidemiologic assessment of pattern of birth defects associated with human teratogens: application to diabetic embryopathy. Pediatrics 1989; 84:658.
- Mills JL. Malformations in infants of diabetic mothers. Teratology 1982; 25:385.
- Mimouni F, Miodovnik M, Siddiqi TA, et al. Perinatal asphyxia in infants of insulin-dependent diabetic mothers. J Pediatr 1988; 113:345.
- Persson M, Pasupathy D, Hanson U, Norman M. Birth size distribution in 3,705 infants born to mothers with type 1 diabetes: a population-based study. Diabetes Care 2011; 34:1145.
- Persson M, Fadl H, Hanson U, Pasupathy D. Disproportionate body composition and neonatal outcome in offspring of mothers with and without gestational diabetes mellitus. Diabetes Care 2013; 36:3543.
- Esakoff TF, Cheng YW, Sparks TN, Caughey AB. The association between birthweight 4000 g or greater and perinatal outcomes in patients with and without gestational diabetes mellitus. Am J Obstet Gynecol 2009; 200:672.e1.
- Ballard JL, Rosenn B, Khoury JC, Miodovnik M. Diabetic fetal macrosomia: significance of disproportionate growth. J Pediatr 1993; 122:115.
- McFarland MB, Trylovich CG, Langer O. Anthropometric differences in macrosomic infants of diabetic and nondiabetic mothers. J Matern Fetal Med 1998; 7:292.
- Acker DB, Sachs BP, Friedman EA. Risk factors for shoulder dystocia in the average-weight infant. Obstet Gynecol 1986; 67:614.
- Gregory KD, Henry OA, Ramicone E, et al. Maternal and infant complications in high and normal weight infants by method of delivery. Obstet Gynecol 1998; 92:507.
- Nesbitt TS, Gilbert WM, Herrchen B. Shoulder dystocia and associated risk factors with macrosomic infants born in California. Am J Obstet Gynecol 1998; 179:476.
- Robert MF, Neff RK, Hubbell JP, et al. Association between maternal diabetes and the respiratory-distress syndrome in the newborn. N Engl J Med 1976; 294:357.
- Bourbon JR, Farrell PM. Fetal lung development in the diabetic pregnancy. Pediatr Res 1985; 19:253.
- Gewolb IH, O'Brien J. Surfactant secretion by type II pneumocytes is inhibited by high glucose concentrations. Exp Lung Res 1997; 23:245.
- Gewolb IH. Effect of high glucose on fetal lung maturation at different times in gestation. Exp Lung Res 1996; 22:201.
- Bental Y, Reichman B, Shiff Y, et al. Impact of maternal diabetes mellitus on mortality and morbidity of preterm infants (24-33 weeks' gestation). Pediatrics 2011; 128:e848.
- Piper JM. Lung maturation in diabetes in pregnancy: if and when to test. Semin Perinatol 2002; 26:206.
- Persson B, Hanson U. Neonatal morbidities in gestational diabetes mellitus. Diabetes Care 1998; 21 Suppl 2:B79.
- Pinter E, Peyman JA, Snow K, et al. Effects of maternal diabetes on fetal rat lung ion transport. Contribution of alveolar and bronchiolar epithelial cells to Na+,K(+)-ATPase expression. J Clin Invest 1991; 87:821.
- Das S, Irigoyen M, Patterson MB, et al. Neonatal outcomes of macrosomic births in diabetic and non-diabetic women. Arch Dis Child Fetal Neonatal Ed 2009; 94:F419.
- HAPO Study Cooperative Research Group, Metzger BE, Lowe LP, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008; 358:1991.
- Metzger BE, Persson B, Lowe LP, et al. Hyperglycemia and adverse pregnancy outcome study: neonatal glycemia. Pediatrics 2010; 126:e1545.
- Cowett RM, Susa JB, Giletti B, et al. Glucose kinetics in infants of diabetic mothers. Am J Obstet Gynecol 1983; 146:781.
- Aucott SW, Williams TG, Hertz RH, Kalhan SC. Rigorous management of insulin-dependent diabetes mellitus during pregnancy. Acta Diabetol 1994; 31:126.
- Kalhan SC, Savin SM, Adam PA. Attenuated glucose production rate in newborn infants of insulin-dependent diabetic mothers. N Engl J Med 1977; 296:375.
- Demarini S, Mimouni F, Tsang RC, et al. Impact of metabolic control of diabetes during pregnancy on neonatal hypocalcemia: a randomized study. Obstet Gynecol 1994; 83:918.
- Rosenn B, Miodovnik M, Tsang R. Common clinical manifestations of maternal diabetes in newborn infants: implications for the practicing pediatrician. Pediatr Ann 1996; 25:215.
- Tsang RC, Strub R, Brown DR, et al. Hypomagnesemia in infants of diabetic mothers: perinatal studies. J Pediatr 1976; 89:115.
- Tyrala EE. The infant of the diabetic mother. Obstet Gynecol Clin North Am 1996; 23:221.
- Freitag JJ, Martin KJ, Conrades MB, et al. Evidence for skeletal resistance to parathyroid hormone in magnesium deficiency. Studies in isolated perfused bone. J Clin Invest 1979; 64:1238.
- Banerjee S, Mimouni FB, Mehta R, et al. Lower whole blood ionized magnesium concentrations in hypocalcemic infants of gestational diabetic mothers. Magnes Res 2003; 16:127.
- O W, Omori K, Emmanouilides GC, Phelps DL. Placenta to lamb fetus transfusion in utero during acute hypoxia. Am J Obstet Gynecol 1975; 122:316.
- Kuhle S, Massicotte P, Chan A, Mitchell L. A case series of 72 neonates with renal vein thrombosis. Data from the 1-800-NO-CLOTS Registry. Thromb Haemost 2004; 92:729.
- Georgieff MK, Landon MB, Mills MM, et al. Abnormal iron distribution in infants of diabetic mothers: spectrum and maternal antecedents. J Pediatr 1990; 117:455.
- Peevy KJ, Landaw SA, Gross SJ. Hyperbilirubinemia in infants of diabetic mothers. Pediatrics 1980; 66:417.
- Ullmo S, Vial Y, Di Bernardo S, et al. Pathologic ventricular hypertrophy in the offspring of diabetic mothers: a retrospective study. Eur Heart J 2007; 28:1319.
- Veille JC, Sivakoff M, Hanson R, Fanaroff AA. Interventricular septal thickness in fetuses of diabetic mothers. Obstet Gynecol 1992; 79:51.
- Way GL, Wolfe RR, Eshaghpour E, et al. The natural history of hypertrophic cardiomyopathy in infants of diabetic mothers. J Pediatr 1979; 95:1020.
- Denfield SW, Gajarski RJ, Towbin JA. Cardiomyopathies. In: The science and practice of pediatric cardiology, Garson AG, Bricker JT, Fisher DJ, Neish SR (Eds), Williams and Wilkins, Baltimore 1998. p.1851.
- Mace S, Hirschfield SS, Riggs T, et al. Echocardiographic abnormalities in infants of diabetic mothers. J Pediatr 1979; 95:1013.
- Heart Disease: A Textbook of Cardiovascular Medicine, Braunwald E (Ed), Saunders, Philadelphia 1997.
- Weber HS, Copel JA, Reece EA, et al. Cardiac growth in fetuses of diabetic mothers with good metabolic control. J Pediatr 1991; 118:103.
- Hornberger LK. Maternal diabetes and the fetal heart. Heart 2006; 92:1019.
- Elmekkawi SF, Mansour GM, Elsafty MS, et al. Prediction of Fetal Hypertrophic Cardiomyopathy in Diabetic Pregnancies Compared with Postnatal Outcome. Clin Med Insights Womens Health 2015; 8:39.
- Committee on Fetus and Newborn, Adamkin DH. Postnatal glucose homeostasis in late-preterm and term infants. Pediatrics 2011; 127:575.
- Rizzo TA, Dooley SL, Metzger BE, et al. Prenatal and perinatal influences on long-term psychomotor development in offspring of diabetic mothers. Am J Obstet Gynecol 1995; 173:1753.
- Ornoy A. Growth and neurodevelopmental outcome of children born to mothers with pregestational and gestational diabetes. Pediatr Endocrinol Rev 2005; 3:104.
- Ornoy A, Wolf A, Ratzon N, et al. Neurodevelopmental outcome at early school age of children born to mothers with gestational diabetes. Arch Dis Child Fetal Neonatal Ed 1999; 81:F10.
- Riggins T, Miller NC, Bauer PJ, et al. Consequences of low neonatal iron status due to maternal diabetes mellitus on explicit memory performance in childhood. Dev Neuropsychol 2009; 34:762.
- Reece EA, Homko CJ. Infant of the diabetic mother. Semin Perinatol 1994; 18:459.
- Redondo MJ, Jeffrey J, Fain PR, et al. Concordance for islet autoimmunity among monozygotic twins. N Engl J Med 2008; 359:2849.
- Pettitt DJ, Aleck KA, Baird HR, et al. Congenital susceptibility to NIDDM. Role of intrauterine environment. Diabetes 1988; 37:622.
- Dabelea D, Hanson RL, Bennett PH, et al. Increasing prevalence of Type II diabetes in American Indian children. Diabetologia 1998; 41:904.
- Dabelea D, Knowler WC, Pettitt DJ. Effect of diabetes in pregnancy on offspring: follow-up research in the Pima Indians. J Matern Fetal Med 2000; 9:83.
- 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.
- Mughal MZ, Eelloo J, Roberts SA, et al. Body composition and bone status of children born to mothers with type 1 diabetes mellitus. Arch Dis Child 2010; 95:281.
- Sobngwi E, Boudou P, Mauvais-Jarvis F, et al. Effect of a diabetic environment in utero on predisposition to type 2 diabetes. Lancet 2003; 361:1861.
- Touger L, Looker HC, Krakoff J, et al. Early growth in offspring of diabetic mothers. Diabetes Care 2005; 28:585.
- Vääräsmäki M, Pouta A, Elliot P, et al. Adolescent manifestations of metabolic syndrome among children born to women with gestational diabetes in a general-population birth cohort. Am J Epidemiol 2009; 169:1209.
- Vohr BR, McGarvey ST, Tucker R. Effects of maternal gestational diabetes on offspring adiposity at 4-7 years of age. Diabetes Care 1999; 22:1284.
- Clausen TD, Mathiesen ER, Hansen T, et al. Overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus or type 1 diabetes. J Clin Endocrinol Metab 2009; 94:2464.
- Page KA, Romero A, Buchanan TA, Xiang AH. Gestational diabetes mellitus, maternal obesity, and adiposity in offspring. J Pediatr 2014; 164:807.
- Logan KM, Gale C, Hyde MJ, et al. Diabetes in pregnancy and infant adiposity: systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2017; 102:F65.
- Lawlor DA, Lichtenstein P, Långström 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.
- Adane AA, Mishra GD, Tooth LR. Diabetes in Pregnancy and Childhood Cognitive Development: A Systematic Review. Pediatrics 2016; 137.
- Bytoft B, Knorr S, Vlachova Z, et al. Long-term Cognitive Implications of Intrauterine Hyperglycemia in Adolescent Offspring of Women With Type 1 Diabetes (the EPICOM Study). Diabetes Care 2016; 39:1356.
- Sells CJ, Robinson NM, Brown Z, Knopp RH. Long-term developmental follow-up of infants of diabetic mothers. J Pediatr 1994; 125:S9.
- FETAL EFFECTS
- NEONATAL EFFECTS
- Congenital anomalies
- Preterm delivery
- Perinatal asphyxia
- - Birth injury
- Respiratory distress
- - Respiratory distress syndrome
- - Other causes of respiratory distress
- Metabolic complications
- - Hypoglycemia
- - Hypocalcemia
- - Hypomagnesemia
- Polycythemia and hyperviscosity syndrome
- Low iron stores
- NEONATAL MANAGEMENT
- LONG-TERM OUTCOME
- Metabolic risks
- - Diabetes
- - Obesity and glucose metabolism
- Neurodevelopmental outcome
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS