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Infant of the Diabetic Mother

Infant of the Diabetic Mother. Sunhwa Kim, MD Loma Linda University Children Hospital. Diabetes … Obesity. Not every high blood sugar is Diabetes. Diabetes. Obesity. Obesity…Diabetes. Metabolic abnormalities associated with obesity

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Infant of the Diabetic Mother

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  1. Infant of the Diabetic Mother Sunhwa Kim, MD Loma Linda University Children Hospital

  2. Diabetes … Obesity Not every high blood sugar is Diabetes Diabetes Obesity

  3. Obesity…Diabetes • Metabolic abnormalities associated with obesity • Hyperglycemia, dyslipidemia, alterations in growth factors, hyperinsulinism etc. • Excessive abdominal fat independently associated with diseases: cardiovascular, cancer, osteoarthritis, gall bladder, diabetes, etc • Excess body fat leads to type 2 diabetes within 20 years • Undiagnosed diabetes

  4. Obesity… Pregnancy Complications Adjusted* Odds Ratios for Pregnancy Complications by Maternal BMI *Adjusted for maternal age, smoking, education, marital status, trimester prenatal care began, payer, and weight gain during pregnancy; BMI<20.0 (lean) reference group. Baeten et al., Am J Public Health 91;436, 2001

  5. Maternal Complications of Diabetes • Unstable maternal BG • Cardiovascular conditions • Sepsis • Birth Difficulties • PP recovery issues • Psychosocial issues • Delivering an affected infant

  6. Infant of the Diabetic Mother • First described: 1880 • Insulin isolated in 1921 maternal mortality decreased from 50 to 9 % • Stillbirhts decreased from >20% to 2% in the 1980’s • Perinatal mortality decreased after 1970NICU is still higher than controls (17 vs. 6/1000 in Europe 22 vs. 10/1000 in CA) • Congenital malformations remain high

  7. IDM - Definitions • Any offspring of a gestational or insulin dependent diabetic woman • Type 1-insulin dependent • Type 2 • Gestation Diabetes Mellitus • Impaired Glucose Tolerance

  8. Diabetes complicating Pregnancy • 0.5-1.0% of all pregnancies are complicated by pre-existing diabetes • 0.1 % are insulin dependent diabetes • 1-5% gestational diabetes

  9. IDM -Incidence • 50-150,000 IDMs born annually • Perinatal mortality: 20/1000 total births • 5% of all NICU admissions

  10. IDM - Outcome • Outcome is largely dependent on consistent blood glucose control from the preconception period through embryonic and fetal life. • Lack of control in early or late pregnancy leads to different problems in the offspring

  11. IDM -Early PregnancyDiabetic Embryopathy • Poor early control (Hyperglycemic embryo)  Risk for Congenital Malformations

  12. Glucose Control and Malformations MALFORMATION RATES BY LEVEL Of MATERNAL HEMOGLOBIN A1c 6.9 or less 0 % 7.0-8.5 5.1 % 8.6 or greater 22.4 % Miller et al. N Engl J Med 304:1331-1333, 1988 • Ylinen et al [89] • 7.9 or less • 3.2 • 8.0-9.9 • 8.1 • 10 or greater • 23.5

  13. Glucose Control and Malformations HbA1c*% Malformations RR (95% CI) <6 3.0% 1.0 6.1-9.0 5.2% 1.7 (0.4-1.7) 9.1-12.0 4.3% 1.4 (0.3-8.3) 12.1-15.0 38.9% 12.8 (4.7-35.0) >15.0 40.0% 13.2 (4.3-40.4) *1st trimester HbA1c in 303 insulin-requiring diabetics (Green et al. Teratology 39:224-231, 1989)

  14. EmbryopathyGestational Diabetic Women’s Risk • Becerra JE et al., 1990 • Relative risk for major malformations among IDM was 7.9 compared to infants of non-diabetic mothers • Gestational diabetics who require insulin in 3rd trimester were 20.6 times more likely to have a child with a cardiovascular defect • Kouseff BG, 1999 • 152 infants of women with gestational DM, 87 had anomalies compatible with diabetic embryopathy

  15. Embryopathy Gestational Diabetic Women’s Risk • Schaefer-Graf et al., Am J Obstet Gynecol 182:313-320, 2000 • 4,180 consecutive pregnancies complicated by gestational diabetes (3,764) or type 2 diabetes (416) diagnosed after 20 weeks gestation (County USC). • Initial fasting glucose < 120 mg/dL 2.1% malfs • Initial fasting glucose 121-200 mg/dL 5.9% malfs • Initial fasting glucose > 200 mg/dL 12.9% malfs • Watkins et al., Pediatrics 111:1152-1158, 2003 • Prepregnancy obesity (with no known diabetes) associated with increased risks for spina bifida, omphalocele, heart defects, and multiple anomalies.

  16. Diabetic Embryopathy -Incidence • 2 to 4-fold Increased Risk for Malformations (4-8%) • 7 to 10-fold Increased Risk for Major Anomalies that are fatal or require surgery • Central nervous system • Cardiac malformations • Renal / urinary and GI tract anomalies • Skeletal anomalies

  17. Diabetic Embryopathy -CNS anomalies • Central nervous system • Neural tube defects • Anencephaly • Meningomyelocele • Hydrocephaly • Holoprosencephaly

  18. Diabetic Embryopathy • Midline facial defects • Facial microsomia and microtia/anotia: Diabetes in 10.3% of 155 case mothers versus 1.4% of 854 control mothers Multivariate-adjusted odds ratios (CI): Diabetes 6.3 (2.7 -1 4.9) (Werler et al., Birth Defects Research 70:258, 2004)

  19. Diabetic Embryopathy – Cardiac anomalies • Transposition of great vessels • Coarctation of the aorta • Atrial & Ventricular septal defects • Dextrocardia • Single ventricle, hypoplastic right heart • Patent ductus arteriosus • Pulmonary hypoplasia / atresia • DiGeorge sequence

  20. Diabetic Embryopathy, GI anomalies • GI: Small Left Colon Syndrome • Bowel atresia • Bowel dysmotility (feeding intolerance)

  21. Diabetic Embryopathy – Skeletal Anomalies • Caudal Dysplasia or Regression SD • Rare disorder (1/25000) • The most specific malformation related to diabetes 200-400 times more often in IDMs • Sacral agenesis with hypoplastic pelvis and spinopelvic instability • Usually with other malformations like: femoral hypoplasia, extrophy of the bladder, and club foot

  22. Diabetic Embryopathy -Pathophysiology • Hyperglycemia + Genetic background • Teratogenic period (3-6 weeks) • Disturbances in maternal-fetal circulatory transport systems • Concentrations of metabolites • Hyperglycemia • Hyperketonemia • Elevated intracellular levels of free oxygen radicals • Disturbances in arachadonic acid and prostaglandin/prostacyclin metabolism affecting intracellular signaling and circulation • Somatomedin inhibitors • Genotoxicity as a result of aberrant fuels (Reece et al., Teratology 54:171-182, 1997)

  23. Diabetic Embryopathy PREVENTION • PREVENTION BEFORE CONCEPTION • Good Glycemic control • Folic Acid/ Vitamin intake PREVENTION PREVENTION

  24. IDM - Late PregnancyFetal and Neonatal Complications • Poor late control (Hyperglycemic fetus)  Risk for Hyperinsulinemia (growth factor)

  25. IDM -Late Pregnancy • Fetal and Neonatal Complications of Hyperinsulinemia • Macrosomia growth of insulin-sensitive tissues plus glycogen and fat deposition • Hypoglycemia • Polycythemia/hyperbilirubinemia • Renal vein thrombosis • Cardiomyopathy • RDS

  26. Fetal & Neonatal Complications Macrosomia • LGA • Birth weight > 4 kg or above the 90thpercentile for gestational age • Occurs in 20-60% IDM • Physical findings • Increased adipose tissue • Disproportionate head/shoulder ratio • Plethoric • Large placenta & cord IDM may also be SGA in advanced diabetes complicated with renal and cardiac disease

  27. Fetal & Neonatal Complications Macrosomia Complications associated with delivery • Birth trauma • Shoulder dystocia • Brachial plexus injury • Fractured clavicle • Visceral hemorrhage • CPD • Risks associated with C/Section and operative vaginal deliveries (vacuum extraction, forceps, etc.) • Fetal distress • Meconium aspiration • Birth Asphyxia

  28. Hypoglycemia Symptoms • Jitteriness 81% • Seizures 58% • Apnea/cyanosis 47% • Irritability 41 % • Hypotonia 26% • Poor feeding • Hypothermia • None Defintition: Blood glucose <40 mg/dL Usually presents at ½-2 hours of life Incidence: up to 40% of IDM

  29. Hypoglycemia Treatment • If stable give early feedings • If not able to feed: • D10%W 2mL/kg (slow IVP) plus • Continuous IV infusion of D10%W at 80-100 mL/kg/day • Use glucagon in extreme cases • Follow blood glucose with frequent Chemstrips

  30. Hyperbilirubinemia • Definitions: Elevated indirect (unconjugated) bilirubin >10mg/dL in term infant, lower levels for preterms Incidence in IDM 20-40% • Pathophysiology • Increased bilirubin production • Polycythemia • Heme turnover (ineffective erythropoeitin. and trauma) • Decrease in bilirubin binding and excretion • Liver immaturity

  31. Hyperbilirubinemia • Prevention • Early, adequate breastfeeding • Good hydration and stooling • Diagnosis • Transcutaneous or serum bilirubin at 24 hours of age, and at signs of increasing jaundice • Treatment: • Adequate hydration and nutrition • Phototherapy • Exchange transfusion • Medications (agar) • Family teaching • Appropriate follow-up after discharge

  32. Polycythemia • Due to bone marrow stimulation (high erythropoietin levels) • Elevated venous hematocrit of > 65% • Caused by chronic hypoxia and increased O2 requirements in utero • Placental insufficiency during fetal life • May be worsened by placental transfusion at birth • Incidence in IDM 35% • Signs and symptoms • Plethora • Jitteriness • Tachypnea • Cyanosis (general or circumoral) • Oliguria • Poor feeding • Lethargy/seizures • Screening: obtain hematocrit at 24 hrs of life or if symptoms noted

  33. Polycythemia • Treatment • Treat underlying symptoms • Hydration • Hyperbilirubinemia treatment • Partial exchange transfusion • Common complications • Respiratory Distress • Hyperbilirubinemia • Respiratory distress • Renal vein thrombosis • Hypertension

  34. IDM -Cardiomyopathy • Cardiomegaly present in 30% • Septal hypertrophy • Myocardial dysfunction • Glycogen stores • Hypoxia • CHF in 5% • Treatment: supportive therapy and beta blockers

  35. Other Fetal & Neonatal Complications • Perinatal hypoxia/asphyxia • Respiratory Distress • Metabolic abnormalities: • Hypocalcemia • Hypomagnesemia • Small left colon Syn. • Neurologic dysfunction

  36. Perinatal Hypoxia • May lead to fetal demise or neonatal asphyxia • May result from complicated labor and delivery • Placental insufficiency (vascular disease, pre eclampsia) • Maternal ketoacidosis • CPD/ Prolonged labor due to Macrosomia • Meconium Aspiration • Intra-abdominal hematoma/hemorrhage • Polycythemia • Increased oxygen utilization from hyperinsulinism and increased metabolism • TTNB (delayed lung fluid clearance)

  37. Respiratory Distress • Transient Tachypnea of Newborn (delayed lung fluid clearance) • Aspiration of meconium or amniotic fluid • Prematurity Diagnosis • Tachypnea/Retractions • Grunting • Cyanosis • Apnea • Hypoxemia • Chest X-Ray

  38. Respiratory Distress Syndrome • RDS (delayed lung maturity), higher risk than non IDMs.

  39. Respiratory Distress Syndrome • surfactant from decreased steroids due to insulin • Prevention: Check for lung maturity with presence of PG and L:S ratio >2 • Treatment: • Surfactant • Assisted support and ventilation • Supplemental oxygen

  40. Hypocalcemia/Hypomagnesemia • Incidence: 25% • Secondary to hypoparathyroid function due to maternal-fetal hypomagnesemia • Related to severity of maternal diabetes • Develops in first 3 days

  41. Hypocalcemia/Hypomagnesemia • Symptoms: • Irritability • Jitteriness • Apnea • Lip smacking • Tongue thrusting • Laboratory Tests • Calcium • Ionized CA • Magnesium • Treatment • Transfer to Neonatal Intensive Care Unit • Calcium gluconate • Magnesium sulfate

  42. Jitteriness Irritability Increased or Decreased tone Seizures Due to: Chronic and/or acute hypoxia Immaturity Hypoglycemia Hypocalcemia Polycythemia/strokes Delivery trauma Iron deficiency IDM - Neurologic Dysfunction

  43. Oral Feedings • Significant feeding difficulties Severe uncoordination • Assess oral-motor coordination • Assess adequacy of feeding • Monitor pre feeding blood glucose

  44. IDM and Breastfeeding • Offer breast as soon as possible within 1 hour of delivery • Encourage feedings whenever oral cues noted or at least every 3 hours • Formulas: only when medically indicated or mother has given informed consent • Keep mother and infant together continuously • Support mothers to nurse often (10-12 times per day)

  45. IDM- Long Term Prognosis • Metabolic Syndrome • (identifiable early precursor to adult chronic diseases including diabetes, heart disease, • certain cancers, and others) • Obesity • Glucose Intolerance • Dyslipidemia • Hypertension • Predisposing factors • . Infant of a diabetic mother • . Infant of an obese mother • . Large for gestational age infant

  46. Long Term Prognosis • Growth / Development • Childhood obesity • (50%, 5 fold higher at adolescence) • Risk of Developing Insulin Dependent DM • . Diabetic mother 2% • . Diabetic father 7% • Risk for delayed motor and cognitive development • Neurological development indefinite

  47. IDM Neurodevelopmental Outcome

  48. The IDM needs to be supported since conception

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