Pediatric Department Effects of Maternal Hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani Senior Pediatric Consultant Head of Pediatric Department Khorfakkan Hospital Sharjah, UAE

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani Pediatric Department Effects of Maternal Hyperglycemia on the fetus 2

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 3 Pediatric Department Congenital Anomalies A major threat to IDMs is the possibility of a life- threatening structural anomaly. In the normoglycemic pregnancy, the risk of a major birth defect is 1% to 2%. Among women with pregestational diabetes, the risk of a fetal structural anomaly is fourfold to eightfold higher.

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 4 Pediatric Department Cont. Major congenital anomalies occurred in 4.6% overall with :  4.8% for type 1 diabetes mellitus.  4.3% for type 2 diabetes mellitus. Neural tube defects in IDM were increased 4.2-fold. Congenital heart disease were increased 3.4-fold.

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 5 Pediatric Department

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 6 Pediatric Department Cont. There is no increase in birth defects among offspring of:  Diabetic fathers  Nondiabetic women  Women in whom gestational diabetes develops after the first trimester. Adverse outcome was significantly higher in the poor control group (HbA1c ≥7.5) than in the fair control group (HbA1c <7.5), with a nine fold increase in the congenital malformation rate (2)

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 7 Pediatric Department Prevention Because the critical period for teratogenesis is the first 3 to 6 weeks after conception, normal glycemic control must be instituted before pregnancy to prevent these birth defects. Any elevation of the HbA1c above normal increases the risk of teratogenesis proportionately.

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 8 Pediatric Department Macrosomia Fetal overgrowth is a major problem in pregnancies complicated by diabetes, leading to:  Unnecessary cesarean sections  Potentially avoidable birth injuries

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 9 Pediatric Department

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 10 Pediatric Department Definition Macrosomia is defined variously as birth weight above the 90th percentile for gestational age or birth weight greater than 4000 g. It occurs in 15% to 45% of diabetic pregnancies.

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 11 Pediatric Department Adverse effects Excessive fetal size contributes to a greater frequency of:  Intrapartum injuries:  Shoulder dystocia  Brachial plexus palsy  Asphyxia

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 12 Pediatric Department Lateral traction to the head occurs when the baby’s head is pulled sideways in an attempt to dislodge the trapped shoulder. Once the dystocia occurs, no lateral traction should be applied to the baby’s head.

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 13 Pediatric Department

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 14 Pediatric Department Prevention Measures that promote consistent maternal euglycemia may prevent macrosomia Strict maternal glycemic control using insulin and dietary therapy and fastidious blood glucose monitoring can reduce the incidence of macrosomia

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 15 Pediatric Department Fetal Hypoxic Stress Episodic maternal hyperglycemia promotes a fetal catabolic state in which oxygen depletion occurs. Profound episodic hyperglycemia in the third trimester causing severe fetal hypoxic stress

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 16 Pediatric Department Perinatal Complications of Diabetes During Pregnancy

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 17 Pediatric Department Perinatal Mortality Perinatal mortality rates among women with diabetes remain approximately twice those observed in nondiabetic women Most perinatal deaths in contemporary diabetic pregnancy are due to:  Congenital malformations  RDS  Extreme prematurity

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 18 Pediatric Department Birth Injury Birth injury, including shoulder dystocia and brachial plexus trauma, is more common among IDMs, and macrosomic fetuses are at the highest risk Shoulder dystocia occurs in 0.3% to 0.5% of vaginal deliveries among normal pregnant women; the incidence is twofold to fourfold higher in women with diabetes.

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 19 Pediatric Department Polycythemia and Hyperviscosity Polycythemia (defined as central venous hemoglobin concentration >20 g/dL or hematocrit >65%) is not uncommon in IDMs and is apparently related to glycemic control. Hyperglycemia is a powerful stimulus to fetal erythropoietin production, probably mediated by decreased fetal oxygen tension

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 20 Pediatric Department Cont. Neonatal polycythemia may promote:  Vascular sludging  Ischemia  Infarction of vital tissues, including the kidneys and central nervous system.

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 21 Pediatric Department Neonatal Hypoglycemia Approximately 15% to 25% of neonates delivered from women with diabetes during gestation will develop hypoglycemia during the immediate newborn period It is usually much milder and less common in the infant of a woman:  Whose insulin-dependent diabetes is well controlled throughout the entire pregnancy  Who exhibits euglycemia during labor and delivery.

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 22 Pediatric Department Cont. Unrecognized postnatal hypoglycemia can lead to:  Neonatal seizures  Coma  Brain damage it is imperative that the nurseries receiving IDMs have a protocol for frequent monitoring of the infant’s blood glucose level until metabolic stability is ensured.

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 23 Pediatric Department Hyperbilirubinemia The risk of hyperbilirubinemia is higher in IDMs than in normal infants. There are multiple causes of hyperbilirubinemia in IDMs, but prematurity and polycythemia are the primary contributing factors.

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 24 Pediatric Department Cont. Increased destruction of red blood cells contributes to the risks of jaundice and kernicterus. This complication is usually managed using phototherapy, but exchange transfusions may be necessary for marked bilirubin elevations.

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 25 Pediatric Department Infant with acute advanced bilirubin encephalopathy

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 26 Pediatric Department Hypertrophic and Congestive Cardiomyopathy IDMs with cardiomegaly may have either congestive or hypertrophic cardiomyopathy Echocardiograms show a hypercontractile, thickened myocardium, often with septal hypertrophy disproportionate to the ventricular free walls.

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 27 Pediatric Department

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 28 Pediatric Department Cont. Maternal insulin-like growth factor-1 (IGF-1) is significantly elevated among neonates with asymmetrical septal hypertrophy (1) B-type natriuretic peptide, a marker for congestive cardiac failure, is elevated in neonates whose mothers had poor glycemic control during the third trimester.(2) 1.Hayati A.R., Cheah F.C., Tan A.E., et al: Insulin-like growth factor-1 receptor expression in the placentae of diabetic and normal pregnancies. Early Hum Dev 2007; 83: pp Halse K.G., Lindegaard M.L., Goetze J.P., et al: Increased plasma pro-B-type natriuretic peptide in infants of women with type 1 diabetes. Clin Chem 2005; 51: pp

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 29 Pediatric Department Cont. IDMs can also have congestive cardiomyopathy without hypertrophy. Echocardiography shows the myocardium to be overstretched and poorly contractile This condition is often rapidly reversible with correction of neonatal hypoglycemia, hypocalcemia, and polycythemia; it responds to digoxin, diuretics, or both.* * Jaeggi E.T., Fouron J.C., and Proulx F.: Fetal cardiac performance in uncomplicated and well-controlled maternal type I diabetes. Ultrasound Obstet Gynecol 2001; 17: pp

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 30 Pediatric Department Cont. Treatment of hypertrophic cardiomyopathy with an inotropic or diuretic agent tends to further decrease the size of the ventricular chambers and leads to obstruction of blood flow. Routine fetal echocardiogram in diabetics has not been proved to be cost-effective or to improve outcomes* *Bernard L.S., Ramos G.A., Fines V., et al: Reducing the cost of detection of congenital heart disease in fetuses of women with pregestational diabetes mellitus. J Ultrasound Obstet Gynecol 2009; 33: pp

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 31 Pediatric Department Respiratory Distress Syndrome Respiratory dysfunction in the newborn IDM continues to be a common complication of diabetic pregnancy In a diabetic pregnancy, however, it is unwise to assume that the risk of respiratory distress has passed until after 38.5 weeks’ gestation* *Moore T.R.: A comparison of amniotic fluid fetal pulmonary phospholipids in normal and diabetic pregnancy. Am J Obstet Gynecol 2002; 186: pp

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 32 Pediatric Department

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 33 Pediatric Department Cont. Any delivery contemplated before 38.5 weeks’ gestation for other than the most urgent fetal and maternal indications should be preceded by documentation of pulmonary maturity through amniocentesis.

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 34 Pediatric Department References Macintosh M.C., Fleming K.M., Bailey J.A., et al: Perinatal mortality and congenital anomalies in babies of women with type 1 or type 2 diabetes in England, Wales, and Northern Ireland: population based study. BMJ 2006; 333: pp. 177 Temple R., Aldridge V., Greenwood R., et al: Association between outcome of pregnancy and glycaemic control in early pregnancy in type 1 diabetes: population based study. BMJ 2002; 325: pp Athukorala C., Crowther C.A., and Willson K.: Women with gestational diabetes mellitus in the ACHOIS trial: risk factors for shoulder dystocia. Aust N Z J Obstet Gynaecol 2007; 47: pp Alam M., Raza S.J., Sherali A.R., et al: Neonatal complications in infants born to diabetic mothers. J Coll Physicians Surg Pak 2006; 16: pp Hayati A.R., Cheah F.C., Tan A.E., et al: Insulin-like growth factor-1 receptor expression in the placentae of diabetic and normal pregnancies. Early Hum Dev 2007; 83: pp Halse K.G., Lindegaard M.L., Goetze J.P., et al: Increased plasma pro-B-type natriuretic peptide in infants of women with type 1 diabetes. Clin Chem 2005; 51: pp Jaeggi E.T., Fouron J.C., and Proulx F.: Fetal cardiac performance in uncomplicated and well-controlled maternal type I diabetes. Ultrasound Obstet Gynecol 2001; 17: pp Bernard L.S., Ramos G.A., Fines V., et al: Reducing the cost of detection of congenital heart disease in fetuses of women with pregestational diabetes mellitus. J Ultrasound Obstet Gynecol 2009; 33: pp

9/25/2017 Effect of maternal hyperglycemia on the fetus and neonate Prof. Dr. Saad S Al Ani 35 Pediatric Department Presenter Media