Outline Case presentation Discussion Screening and Management of neonatal glucose hemostasis Neonatal effect of infant of a diabetic mother (IDM)

Patient profile Name:許O敏之子 Chart number: 1775xxxx Age: 1 d/o Gender: male Admission date: 105/8/25 17759904

Chief complaint Short of breath soon after delivery 17759904

Present illness 1-day-old boy infant Born to a 38 year-old mother, G2P2, GA 38+4 weeks, NSD Mother had DM type II (baseline sugar 130 mg/dL), HTN before pregnancy, with medication controlled Prenatal was uneventful Level II ultrasound showed no congenital anomaly Did not have amniocentesis test Perinatal Apgar 7-9 SpO2 82% Suction: medium amount

Physical examination T/P/R: 36.2/162/40 BP: 79/41 (54) O2: room air Abundant lanugo (forehead) T/P/R: 36.2/162/40 BP: 79/41 (54) O2: room air SpO2:88-100 % BH: 51.2cm(75-90%) BW: 3760gm (>90 %) Ponderal index 2.8 (50-90%) Chest: Symmetrical expansion Bilateral diffused crackles breathing sounds Suprasternal/ subcostal retraction Negative findings: No tremor/ jitteriness/seizure/apnea/cyanosis No irritable/ high peach crying No shoulder dystocia/ neurological defect No specific heart murmur No hepatosplenomegaly Large for gestational age

Apgar 7-9 T/P/R: 32.6/162/40 BP: 79/41 (54) O2: room air SpO2:88-100 % BH: 51.2cm(75-90%) BW: 3760gm (>90 %) Ponderal index 2.8 Chest: Symmetrical expansion Bilateral diffused crackles breathi Suprasternal/ subcostal retraction Abundant lanugo (forhead)

Lab (8/25 10:30) Peripheral artery Micro gas Micro dextrose 33mg/dl CK (4-8 HR) 214-1175 CK isoenzymes (MB) 1.7-7.9 WBC 9100-34000 Hct 腳跟 70 周邊65 實驗室 55 (coulter counter) Hct 60.4%(8/26)→58.7%(8/27) micro K 5.34, micro Ca 0.991

 CXR: patch in right lower lung -->TTNB

Impression and plan LGA Infant with diabetic mother  Hypoglycemia & Polycythemia Closely monitor sugar and hematocrit level Sufficient IV hydration and nutrition support Monitor breathing pattern Further check electrolyte, esp. Ca, Mg Dyspnea, r/o Pneumonitis, r/o TTNB On NPO with fluid support Blood work including CBC/DC, CRP, B/C Empirical antibiotics with ampicillin and gentamycin Closely monitor vital signs

GIR 5.54 mg/kg/min check dex Q4H-Q6H check dex Q8H-QD After delivery 10:30 D10W 12.5 ml/hr (80 ml/kg/day) 10:30 (report at 14:05) Sugar(random) 9 mg/dl 11:15 Micro dextrose 33mg/dl 11:15 D10W 7.4ml IVP in 3min GIR 5.54 mg/kg/min 11:45 Micro dextrose 57 mg/dl This calculation is a simple conversion of units (into mg/kg/min): GIR = [IV Rate (mL/hr) * Dextrose Conc (g/dL) * 1000 (mg/g)] / [Weight (kg) * 60 (min/hr) * 100 (mL/dL) ] where the dextrose concentration is expressed as a whole number, e.g. 5 or 10. A GIR of 5-8 mg/kg/min is typical. Infants who are not feeding should not be allowed a rate less than 5 mg/kg/min for any significant period of time. The GIR needed to optimize nutrition in neonates is 14 mg/kg/min. check dex Q4H-Q6H 19:53 80 mg/dl 23:25 81 mg/dl check dex Q8H-QD

14:00 micro Hct: 69% 16:00 micro Hct: 67% 20:00 65% 23:25 58% D10W 12.5 ml/hr (80 ml/kg/day) After delivery Artery Hct : 58% (10:30 sample) (13:40 report) 14:00 micro Hct: 69% D10W 15.7 ml/hr (100 ml/kg/day) 16:00 micro Hct: 67% Q4H check Hct 20:00 65% 23:25 58%

Calcium level since day 2 8/26 Micro K 5.18 mg/dl (3.2-5.5) Micro Ca 1.00 mg/dl (1.07-1.27) 8/27 Micro K 5.34 mg/dl Micro Ca 1.00mg/dl 8/28 Micro Ca 1.057 mg/dl

Hospital course Glucose level and Hematocrit level was within normal value after management No further complication was noted The patient was discharged on 8/30

Discussion Screening and Management of neonatal glucose hemostasis

Discussion The neonatal effect of Infant of a diabetic mother

INTRODUCTION Diabetes in pregnancy is associated with an 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

NEONATAL EFFECTS IDMs are at increased risk for mortality and morbidity compared with neonates born to a nondiabetic mother

NEONATAL EFFECTS Overview Neonatal complications in offspring of diabetic mothers include: Congenital anomalies Prematurity Perinatal asphyxia Macrosomia Metabolic complications (hypoglycemia and hypocalcemia) Low iron stores Hyperbilirubinemia Cardiomyopathy Respiratory distress Hematologic complications (polycythemia and hyperviscosity)

NEONATAL EFFECTS Congenital anomalies IDMs are at significant risk for major congenital anomalies due to maternal hyperglycemia at the time of conception and during early gestation Congenital malformations account for half of the perinatal deaths in IDMs In a study of 13,030 infants with congenital anomalies and 4895 without birth defects, when compared with a reference group of nondiabetic control mothers, the risk of isolated and multiple congenital anomalies was highest in infants of mothers with pregestational diabetes followed by infants born to mothers with gestational diabetes Congenital malformations account for half of the perinatal deaths in IDMs  The Risk can be reduced by strict glycemic control during the pre- and periconceptual (first eight weeks of pregnancy) periods.

NEONATAL EFFECTS Congenital anomalies 2/3 of the anomalies in IDMs involve the cardiovascular system or central nervous system (CNS) Cardiovascular malformations occur in 9 % of diabetic pregnancies  TGA, VSD, PDA, truncus arteriosus, and tricuspid atresia Central nervous system occur in 5.3 % of diabetic pregnancies  Anencephaly and spinal bifida are 20 times more frequent among IDMs

NEONATAL EFFECTS Perinatal asphyxia Fetal heart rate abnormalities during labor, low Apgar scores & intrauterine death   IDMs are at increased risk for intrauterine or perinatal asphyxia due to macrosomia (failure to progress and shoulder dystocia) and cardiomyopathy (fetal heart rate abnormalities) Perinatal asphyxia defined here as fetal heart rate abnormalities during labor, low Apgar scores, and intrauterine death   IDMs are at increased risk for intrauterine or perinatal asphyxia due to macrosomia (failure to progress and shoulder dystocia) and cardiomyopathy (fetal heart rate abnormalities) In a study of 162 IDMs, for example, 27 percent had perinatal asphyxia. Perinatal asphyxia correlated with hyperglycemia in labor, prematurity, and nephropathy. Maternal vascular disease, manifested by nephropathy, may contribute to the development of fetal hypoxia and subsequent perinatal asphyxia

NEONATAL EFFECTS Macrosomia BBW > 90th percentile or BBW above 4000 gm A common complication in IDMs The incidence is greater in infants born to mothers with pregestational diabetes IDMs with macrosomia are more likely than those who are not macrosomic to have hyperbilirubinemia, hypoglycemia, acidosis, respiratory distress, shoulder dystocia, and brachial plexus injury In a population-based study using the Swedish Medical Birth Registry (MBR) of 3705 infants born to mothers with type 1 diabetes between 1998 and 2007, 47 percent of the infants were LGA, defined as BW greater than 90th percentile. In another Swedish study based on all births from the Swedish MBR from 1998 to 2007, infants born to mothers with gestational diabetes were 2.5 times more likely to be LGA than infants born to nondiabetic mothers (26 versus 11 percent)

NEONATAL EFFECTS Respiratory distress syndrome RDS due to surfactant deficiency occurs more frequently in IDMs: IDMs are more likely to be delivered prematurely Neonatal hyperinsulinemia interferes with the induction of lung maturation by glucocorticoids RDS due to surfactant deficiency occurs more frequently in IDMs for the following two reasons: IDMs are more likely to be delivered prematurely than infants born to nondiabetic mothers. At a given gestational age, IDMs are more likely to develop RDS because maternal hyperglycemia appears to delay surfactant synthesis. The proposed underlying mechanism is neonatal hyperinsulinemia, which interferes with the induction of lung maturation by glucocorticoids. The risk of RDS in preterm infants of mothers whose diabetes is well-controlled approaches that of infants born to nondiabetic mothers at a similar gestational age. The clinical manifestations, diagnosis, prevention, and management of RDS are discussed separately

NEONATAL EFFECTS Other causes of respiratory distress Transient tachypnea of the newborn (TTNB) & Cardiomyopathy TTNB occurs 3 times in IDMs than in normal infants Reduced fluid clearance in the diabetic fetal lung In infants born to mothers with GDM, the risk for respiratory distress increases for those with BBW >4000 g Transient tachypnea of the newborn (TTNB) and cardiomyopathy. TTN occurs two to three times more commonly in IDMs than in normal infants. The mechanism may be related to reduced fluid clearance in the diabetic fetal lung. Cesarean delivery, which is more frequently performed in diabetic versus nondiabetic pregnancies, may be a contributing factor In infants born to mothers with gestational diabetes mellitus (GDM), the risk for respiratory distress increases for those with BW >4000 g

NEONATAL EFFECTS Hypoglycemia Blood glucose levels below 40 mg/dL in the first 24 hours Occurs frequently in IDMs (27 %) likely caused by persistent hyperinsulinemia in the newborn after interruption of the intrauterine glucose supply from the mother The onset typically occurs within the first few hours after birth The hyperinsulinemic state typically lasts 2 - 4 days Blood glucose levels below 40 mg/dL in the first 24 hours, occurs frequently in IDMs (27 %) The onset of hypoglycemia typically occurs within the first few hours after birth. Thus, IDMs require close blood glucose monitoring after delivery and frequently need glucose supplementation, including parental glucose infusion. In our experience, the hyperinsulinemic state typically lasts two to four days. In neonates requiring glucose supplementation, the maintenance of normal plasma glucose levels while supplemental glucose is being weaned is evidence of resolving hyperinsulinism. Further testing should be undertaken to define the cause of persistent hypoglycemia in infants who continue to require glucose infusions at rates exceeding 8 to 10 mg/kg per minute to maintain normal plasma glucose levels beyond the first week of life.

NEONATAL EFFECTS Hypoglycemia Macrosomic IDMs are more likely to develop hyperinsulinemia and hypoglycemia Further testing should be undertaken to define the cause of persistent hypoglycemia in infants who continue to require GIR > 8 mg/kg/min to maintain normal glucose levels in the first week Strict glycemic control during pregnancy decreases, but does not abolish, the risk of neonatal hypoglycemia

NEONATAL EFFECTS Hypocalcemia Total serum Ca < 7 mg/dL (1.8 mmol/L) or An ionized Ca < 4 mg/dL (1 mmol/L) or An ionized Ca < 3.2 mg/dL (0.8 mmol/L) in ELBW infant At least 5 percent of IDMs

NEONATAL EFFECTS Hypocalcemia The lowest serum Ca concentration occurs between 24 & 72 hours after birth Hypocalcemia in term IDMs usually is asymptomatic and resolves without treatment  Routine screening is not recommended Should be measured in infants with jitteriness, lethargy, apnea, tachypnea, or seizures, and in those with prematurity, asphyxia, respiratory distress, or suspected infection

NEONATAL EFFECTS Polycythemia Central venous Hct > 65 percent Pathogenesis : Chronic fetal hypoxemia Increased erythropoietin concentrations More likely in IDMs Higher Hb and Hct values are associated with fetal exposure to oxidative stress

NEONATAL EFFECTS Polycythemia and hyperviscosity syndrome Polycythemia may lead to hyperviscosity syndrome, including vascular sludging, ischemia, and infarction of vital organs To detect polycythemia, the Hct should be measured within 12 hours of birth

NEONATAL EFFECTS Cardiomyopathy IDMs are at increased risk for transient hypertrophic cardiomyopathy The most prominent change is thickening of the interventricular septum with reduction in the size of the ventricular chambers, resulting in obstructed left ventricular outflow

NEONATAL EFFECTS Cardiomyopathy Infants often are asymptomatic 10 % have respiratory distress or signs of poor cardiac output or heart failure Cardiomyopathy is transient and resolves as plasma insulin concentrations normalize Symptomatic infants typically recover after 3 weeks of supportive care, and echocardiographic findings resolve within 6 to 12 months Supportive care includes increased IV fluid administration and propranolol Inotropic agents are contraindicated because they may decrease ventricular size and further obstruct cardiac outflow.