Infant of diabetic mother

Infant of diabetic mother

1. INFANT OF DIABETIC MOTHER

2. INTRODUCTION Diabetes is the most common metabolic disorder to affect pregnancy. Associated with increased maternal morbidity as well increased risk of fetal , neonatal, and long-term complications in the offspring. The outcome is generally related to the onset and duration of glucose intolerance during pregnancy and severity of the mother's diabetes. 

3. EPIDEMIOLOGY The International Diabetes Federation estimated that 223 million women worldwide had DM in 2019. The Federation predicts that, this number will rise to 343 million  by 2045 (both T1DM and T2DM). In developed countries, it is estimated that T2DM makes up 85% to 95% of all cases of DM. Approximately  half of women with a history of GDM go on to  develop type 2 diabetes  within  five to ten years after delivery .

4. CLASSIFICATION OF DIABETES IN PREGNANCY Maternal diabetes ---- Pregestational Gestational (T1DM , T2DM , Monogenic-MODY )

5. Type 1 diabetes is characterized by insulin deficiency resulting from autoimmune destruction of pancreatic insulin-producing beta cells Type 2 diabetes is characterized by insulin resistance and is therefore more significantly associated with obesity. MODY - affecting beta-cell development, function, or regulation.

6. MODY AD inheritance , most commonly affected genes are glucokinase ( GCK ) and hepatocyte nuclear factor ( HNF1A, HNF4A ). Women with GCK mutations usually have a stable, mild hyperglycemia with elevated fasting glucose levels most prominent. HNF mutations represent the most common cause of monogenic diabetes Treatment ( HNF1A, HNF4A ) – more responsive to sulfonylureas (e.g., glyburide) than to biguanides (metformin).

7. GESTATIONAL DIABETES Incidence of Diabetes in pregnancy is 6-7% , 85-90% are GDM. Definition - Carbohydrate intolerance of variable severity , resulting from insulin resistance arising for the first time during pregnancy. Increasing rates of GDM are due to - increasing rates of obesity , older maternal ages at delivery, physical inactivity, smoking, and diets high in saturated fats

8. GDM represents – maternal system failing to adapt to normal pregnancy physiology . In early gestation --- Maternal fat stores FFA concentration As the gestation advances – insulin sensitivity decreases in liver and peripheral tissues .

9. PATHOPHYSIOLOGY In GDM , inadequate Insulin Secretion hyperglycemia in pregnancy Usually diagnosed b/w – 24-28 weeks of GA .

10. Pregestational versus gestational diabetes   Infants born to pregestational diabetic mothers - have a higher risk of mortality and morbidity compared with offspring from mothers with gestational DM. These infants are more likely to be macrosomic , preterm, and have congenital anomalies and respiratory distress . For infants born to mothers with gestational DM, the risk of adverse neonatal effects modestly increases when mothers require insulin treatment during pregnancy compared with infants whose mothers are managed by diet alone [ 20 ]. Strict glycemic control preconception and during pregnancy is associated with lower perinatal mortality and morbidity. 

11. IMPACT OF DIABETES IN PREGNANCY ON THE NEONATE DEPENDS ON : Time of onset of DM Degree of maternal hyperglycemia /hyperinsulinemia Length of fetal exposure to hyperglycemia (GDM resulting in a shorter exposure than pregestational DM) Severity of maternal disease, because comorbidities (cardiac and renal) have significant neonatal and obstetric effects

12. DIABETIC EMBRYOPATHY In women with pregestational diabetes, poor periconceptional glycemic control has increased risk of embryopathy . The reported incidence of major congenital anomalies is approximately threefold higher at 6%–12%. in DM( Cardiac – 40-50 % > CNS > SKELETAL ) Leading cause of perinatal mortality No anomaly that is pathognomic to maternal DM . Sacral agenesis or caudal dysplasia should prompt evaluation for maternal DM .

13. DIABETIC FETOPATHY - FETAL GROWTH & MACROSOMIA Poor glycemic control in pregnant diabetic women leads to deleterious fetal effects throughout pregnancy.(2 nd &3 rd trimester ) Fetal hyperglycemia , hyperinsulinemia and macrosomia , neonatal hypoglycaemia

14. Chronic fetal hyperinsulinemia elevated metabolic rates increased oxygen consumption placenta - unable to meet the increased metabolic demands FETAL HYPOXEMIA increased mortality, metabolic acidosis, alterations in fetal iron distribution, and increased erythropoiesis , POLYCYTHEMIA OXIDATIVE STRESS abnormal cardiac remodeling hypertrophic cardiomyopathy  storage of glycogen in the liver , increased hepatic enzymes activity involved in lipid synthesis accumulation of fat in adipose tissue. long-term metabolic complications

15. NEONATAL COMPLICATIONS

16. Macrosomia   ACOG Defines macrosomia as Birth weight larger than 4000 to 4500 grams (or 9 to 10 pounds). Shoulder dystocia represents an obstetric emergency because of the risk of hypoxia, hypoperfusion, and birth injury. Brachial plexus injury is the most common, followed by clavicle or humerus fracture and cephalhematoma .

17. COMPLICATIONS ASSOCIATED WITH MACROSOMIA Maternal : Protracted or arrested labor Assisted vaginal birth Cesarean birth Genital tract lacerations Postpartum hemorrhage Uterine rupture FETAL : Shoulder dystocia leading to birth trauma (brachial plexus injury, fracture) or asphyxia.  Neonatal -- Hypoglycemia , Respiratory problems , Polycythemia , Minor congenital anomalies , Increased frequency of admission and prolonged admission to a neonatal intensive care unit Childhood  -- Obesity , Metabolic syndrome , cardiac remodelling

18. Fetal Growth Restriction Women with T1DM or long-standing T2DM complicated by vascular disease or renal disease are at high risk for fetal growth restriction (asymmetrical FGR) . Diabetic ketoacidosis (DKA), maternal hypertension, pre- eclampsia, and structural anomalies, all of which are more common in women with T1DM and T2DM--- at risk for FGR

19. PERINATAL ASPHYXIA Intrauterine or perinatal asphyxia in IDM is due to macrosomia (failure to progress and shoulder dystocia) and cardiomyopathy. Maternal vascular disease, manifested by nephropathy, may contribute to the development of fetal hypoxia and subsequent perinatal asphyxia.

20. Respiratory Distress RDS due to surfactant deficiency -- - Infants of mothers with diabetes are more likely to be delivered prematurely - maternal hyperglycemia appears to delay surfactant synthesis. - Neonatal hyperinsulinemia, which interferes with the induction of lung maturation by glucocorticoids. TTN occurs two to three times more commonly in infants of mothers with diabetes than in normal infants

21. ASSESSMENT OF FETAL LUNG MATURITY – By amniocentesis .

22. METABOLIC COMPLICATIONS : HYPOGLYCEMIA  —   Hypoglycemia , defined as blood glucose levels below 40 mg/ dL (2.2 mmol/L) in the first 24 hours of life . Hypoglycemia is likely caused by persistent hyperinsulinemia in the newborn after interruption of the intrauterine glucose supply from the mother. IDM s with neonatal hypoglycemia have elevated cord blood C-PEPTIDE and S.INSULIN levels at birth .  

23. Strict glycemic control during last trimester and intrapartum decreases, but does not abolish, the risk of neonatal hypoglycaemia ACOG – recommends maintaining maternal glucose levels between 70 &110 mg/ dL . Postpartum management – early initiation of breast feeding ,prevents hypoglycemia .

24. HYPOCALCEMIA : S.Ca – 7 mg/ dL , i.Ca - <4.4 mg/ dL Mostly asymptomatic , resolves spontaneously . Result from a delayed transition from fetal to neonatal parathyroid action in calcium metabolism as fetal parathyroid glands are relatively inactive until after delivery . Risk increases with hypoxia, and preterm birth .

25. HYPOMAGNESEMIA S.Mg < 1.5 mg/ dL . Relevant in the context of significant hypocalcemia , as concurrent hypomagnesemia makes the treatment of hypocalcemia more difficult. Some hypothesize that - fetal hypomagnesemia may result from lower maternal magnesium levels with diabetes from increased maternal urinary losses or renal dysfunction

26. HYPERTROPHIC CARDIOMYOPATHY The prominent change is thickening of the interventricular septum (IVS) with reduction in the size of the ventricular chambers, resulting in potential obstruction of left ventricular outflow. Outflow obstruction occasionally is aggravated by anterior systolic motion of the mitral valve. Cardiomyopathy is transient and resolves as plasma insulin concentrations normalize. Symptomatic infants typically recover after 2-3 weeks of supportive care, and echocardiographic findings resolve within 6 to 12 months

27. Prenatal echocardiographic measurements (at 35 weeks or more) IVS thickness ≥4.5 mm IVS/left myocardial wall thickness (LMWT) ratio ≤1.18 Predictive of hypertrophic cardiomyopathy & increased risk for intrauterine and perinatal mortality 

28. POLYCYTHEMIA Due to increased erythropoietin concentrations caused by chronic fetal hypoxemia Polycythemia may lead to hyperviscosity syndrome, including vascular sludging, ischemia, and infarction of vital organs. Hyperviscosity is thought to contribute to the increased incidence of renal vein thrombosis 

29. HYPERBILIRUBINEMIA Hyperbilirubinemia occurs in 25% of infants of mothers with diabetes, especially in preterm & macrosomic infants . RISK – due to polycythemia (larger source of bilirubin to be conjugated by the liver prior to excretion), - ineffective erythropoiesis with an increased red blood cell turnover - to immaturity of hepatic bilirubin conjugation and excretion.

30. STILL BIRTH Before the use of insulin -(IUFD) or stillbirth occurred in up to 30% . Chronic intrauterine hypoxia – main cause . Greatest risk is among women with vascular disease, hypoglycemia , DKA, macrosomia, polyhydramnios, and preeclampsia.

31. BREASTFEEDING Intrauterine exposure to maternal diabetes and/or obesity appears to be associated with an increased risk of childhood obesity; successful breastfeeding of durations greater than or equal to 6 months may mitigate some of this risk. During lactation, women with diabetes have a significant decrease in insulin or oral hypoglycemic medication requirements

32. LONG TERM OUTCOMES Increases the risk of postnatal metabolic complications ( eg , diabetes, increased body mass index [BMI], and impaired glucose metabolism) and may also negatively impact neurodevelopmental outcome.

33. MATERNAL MONITORING TO LIMIT NEONATAL EFFECTS Antenatal Care - should ideally begin before pregnancy. Given the elevated risk of neural tube defects in diabetic pregnancies, folic acid supplementation should be initiated before conception. The US Preventive Services Task Force has recommended the use of low-dose aspirin in women at elevated risk of developing preeclampsia including women with pregestational diabetes (type 1 or type 2) .

34. SCREENING Women with risk factors for GDM should undergo early glucose screening around 16 weeks’ gestation . All other women undergo universal GDM screening at 24 to 28 weeks of gestation. ACOG - Two step” method consisting of a 50-g, 1-hour glucose challenge test (GCT) and a 100-g, 3-hour oral glucose tolerance test (OGTT) for a definitive diagnosis

35. The International Association of Diabetes in Pregnancy Study Group recommended in 2007 a simplified “one step” - 75-g, 2-hour glucose tolerance test. Fetal Surveillance - assessment of fetal well-being and growth as well as screening for congenital anomalies, is recommended.

36. Diagnostic Glucose Values for Gestational Diabetes Treatment Targets for Gestational Diabetes Mellitus

37. The results of this trial point to a linear correlation between increasing maternal glucose levels and increasing birth weight, primary cesarean delivery, fetal C-peptide levels, and neonatal hypoglycemia .

38. PHARMACOTHERAPY Good glycemic control is a primary goal of the management of diabetes in pregnancy. First-line therapy for women with gestational diabetes is nutritional and lifestyle modification . Pharmacotherapy is indicated when nutritional control is inadequate. Both the American Diabetes Association and ACOG recommend a threshold of 140 mg/ dL (7.7 mmol/L) at 1 hour or 120 mg/ dL at 2 hours after meals.

39. Medical management of maternal hyperglycemia in women with pregestational diabetes – s/c INSULIN . Women with GDM or mild type 2 diabetes may be treated with oral medications such as metformin or glyburide instead of insulin. Metformin - decreases hepatic glucose production, decreasing intestinal absorption of glucose, and by improving insulin sensitivity in peripheral tissues. Metformin has a low risk of producing hypo- glycemia. Glyburide acts on the pancreas to promote and increase insulin secretion

40. TIMING OF DELIVERY For pregestational diabetics and gestational diabetics requiring medication management, timed early delivery has been considered in an attempt to reduce perinatal morbidity and mortality.

41. TAKE HOME POINTS The incidence of diabetes in pregnancy is steadily rising, likely in parallel with the rising incidence of obesity among women of reproductive age. Women with diabetes are at increased risk for fetal complications (such as congenital malformations, fetal growth abnormalities, and stillbirth) and perinatal/neonatal complications Good maternal glycemic control achieved preconception and maintained throughout pregnancy is key to optimizing fetal and neonatal outcomes. Breastfeeding should be strongly encouraged and supported as it may reduce some of the possible adverse effects of intrauterine programming in the context of maternal diabetes.