AUTHOR INFORMATION

Section 1 of 12

Authored by Charles F Potter, MD, Assistant Professor, Department of Pediatrics, Division of Neonatology, Southern Illinois University School of Medicine; Director of Neonatology, Newborn Medicine, Memorial Medical Center, St. John's Hospital

Coauthored by Stephen D Kicklighter, MD, Clinical Assistant Professor, Department of Pediatrics, Division of Neonatology, University of North Carolina at Raleigh and Wake Medical Center

Charles F Potter, MD, is a member of the following medical societies: American Academy of Pediatrics, and American Medical Association

Edited by George Cassady, MD, Clinical Professor, Department of Pediatrics, Stanford University School of Medicine; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Brian S Carter, MD, FAAP, Associate Professor, Associate Director, Department of Pediatrics, Division of Neonatology, Vanderbilt University Medical Center; Consulting Staff, New Beginnings Family Birth Center, Gateway Medical Center; Carol L Wagner, MD, Professor of Pediatrics, Medical University of South Carolina; and Ted Rosenkrantz, MD, Head, Division of Neonatal-Perinatal Medicine, Professor, Departments of Pediatrics and Obstetrics/Gynecology, University of Connecticut School of Medicine

Author's Email:	Charles F Potter, MD
Editor's Email:	George Cassady, MD

eMedicine Journal, December 20 2006, VOLUME 7, Number 12

INTRODUCTION

Section 2 of 12

Background: Diabetes has long been associated with maternal and perinatal morbidity and mortality. Before the discovery of insulin in 1921, diabetic women rarely reached reproductive age or survived pregnancy. In fact, pregnancy termination was recommended routinely for pregnant diabetic patients because of high mortality rates.

Fetal and neonatal mortality rates were as high as 65% before the development of specialized maternal, fetal, and neonatal care. Since then, infants of diabetic mothers (IDMs) have experienced a nearly 30-fold decrease in morbidity and mortality rates. Today, 3-10% of pregnancies are affected by abnormal glucose regulation and control. Of these, 80% are related to abnormal glucose control of pregnancy or gestational diabetes mellitus.

Infants born to mothers with glucose intolerance are at an increased risk of morbidity and mortality related to the following:

• Respiratory distress

• Growth abnormalities (large for gestational age [LGA], small for gestational age [SGA])

• Hyperviscosity secondary to polycythemia

• Hypoglycemia

• Congenital malformations

• Hypocalcemia, hypomagnesemia, and iron abnormalities

These infants are likely to be born by cesarean section for many reasons, among which are such complications as shoulder dystocia with potential brachial plexus injury related to the infant's large size. It is important for these mothers to be monitored closely throughout pregnancy. If optimal care is provided, the perinatal mortality rate, excluding congenital malformations, is nearly equivalent to that observed in normal pregnancies.

Pathophysiology: It is necessary to understand the physiology of fetal glucose control to appreciate the causes of the associated complications. Increased levels of both estrogen and progesterone affect glucose homeostasis as counter-regulatory hormones in the mother early in pregnancy. As a result, beta-cell hyperplasia occurs in the pancreas, stimulating an increased release of insulin.

Increased insulin levels stimulate glycogen deposition and decrease hepatic glucose production. It is not uncommon to recognize a decreased need for insulin in the diabetic patient in early pregnancy. Furthermore, amino acids decrease and fatty acid triglycerides and ketones both increase with increased fatty acid deposition. As a result, increased protein catabolism and accelerated renal gluconeogenesis occurs.

As pregnancy progresses, human placental lactogen is released by the syncytiotrophoblast, leading to lipolysis in the mother. The subsequent release of glycerol and fatty acids reduces maternal use of glucose and amino acid, thus preserving these substrates for the fetus.

The release of increasing amounts of contrainsulin factors as placental growth continues causes up to a 30% increase in maternal insulin needs as pregnancy progresses. Mothers with previous borderline glucose control, obesity, or frank diabetes may require initiation of or increase in their insulin requirements to maintain glucose homeostasis.

Glucose and amino acids traverse the placental membrane. On the other hand, insulin is unable to cross from maternal to fetal circulations. Using a carrier-mediated facilitated diffusion mechanism, fetal glucose levels are maintained at a level that is 20-30 mg/dL lower than those of the mother.

The fetus is subjected to high levels of glucose during times of maternal hyperglycemia. Before 20 weeks' gestation, fetal islet cells are incapable of responding, subjecting the fetus to unchecked hyperglycemia and decreased fetal growth. Poor growth is especially noted in mothers with diabetic vascular disease. After 20 weeks' gestation, the fetus responds to hyperglycemia with pancreatic beta-cell hyperplasia and increased insulin levels.

Proinsulin (insulinlike growth factor-1 [IGF-1], insulinlike growth factor–binding protein-3 [IGFBP-3]) also acts as a growth factor that, in the presence of increased fetal amino acids, results in fetal macrosomia. Fetal growth acceleration can be noted on ultrasound by 24 weeks' gestation, especially with fluctuating maternal glucose levels. The combination of hyperglycemia and insulin increases fat and glycogen stores, resulting in weight increases marked by hepatosplenomegaly and cardiomegaly without an increase in head circumference.

Chronic fetal hyperglycemia and hyperinsulinemia increase the fetal basal metabolic rate and oxygen consumption, leading to a relative hypoxic state. The fetus responds by increasing oxygen-carrying capacity through increased erythropoieten production, possibly leading to polycythemia. The fetus redistributes iron from developing organs, including the heart and brain, to support this expanded blood mass, leaving these organs iron deficient and with possible long-term functional consequences.

Prior to birth, elevated insulin levels may inhibit the maturational effect of cortisol on the lung, including the production of surfactant from type 2 pneumocytes. This puts the fetus at risk for developing respiratory distress syndrome after birth.

Frequency:

• In the US: The 1988 National Maternal and Infant Health Survey reported that diabetes complicated 4% of pregnancies resulting in live births. Of these, 88% were the result of gestational diabetes mellitus, 8% were the result of non–insulin-dependent diabetes, and 4% were from insulin-dependent diabetes mellitus. Given recent estimates of 0.2-0.3% of pregnancies complicated by preexisting diabetes and a further 1-5% complicated by gestational diabetes mellitus, approximately 50,000-150,000 infants are born to diabetic mothers every year.

• Internationally: Women of Asian, Indian, or Middle-Eastern descent are at a higher risk than the general population.

Mortality/Morbidity:

• Birth defects in infants of diabetic mothers have risen from 1-2% to 8-15% as a consequence of increased perinatal survival. Major congenital malformations are found in 5-9% of affected infants and account for 30-50% of perinatal deaths of infants of mothers with gestational diabetes.

• In mothers with insulin-dependent diabetes, the stillbirth and perinatal mortality rate is 5 times the rate in the general population, and neonatal and infant mortality rates are 15 and 3 times the rate in the general population, respectively. These infants are 3 times more likely to be born by cesarean delivery, twice as likely to suffer serious birth injury, and 4 times as likely to be admitted to a neonatal intensive care unit.

• Major causes of morbidity include the following:
  • LGA or SGA infants

  • Hypoglycemia

  • Prematurity

  • Respiratory distress syndrome

  • Intrapartum asphyxia

Race: Incidence is higher in Latinos and African-Americans than in whites. Diabetes occurs more frequently in persons of American Indian descent, particularly among the Pimas of the southwestern United States.

Sex: Frequency of involvement in boy and girl IDMs is equal.

Age: Generally, the first 1-3 hours after birth are the most critical for the development of hypoglycemia.

CLINICAL

Section 3 of 12

History:

• Fetal congenital malformations are most common when maternal glucose control has been poor during the first trimester of pregnancy. Given that many pregnancies are unplanned, the need for preconceptional glycemic control in diabetic women cannot be overstated.



• Maternal hyperglycemia during late gestation is more likely to lead to fetal macrosomia, neonatal electrolyte abnormalities, or cardiomegaly with outflow tract obstruction.



• Fetal macrosomia


• • Quality of fetal growth is determined by plotting birthweight against gestational age on standard growth curves. Infants whose weight exceeds the 90th percentile for gestational age are classified as large for gestational age. Maternal hyperglycemia during late pregnancy is commonly followed by excessive fetal growth.
  
  
  
  • LGA infants should be routinely screened for potential hypoglycemia. This is particularly important if the mother has received large amounts of glucose-containing fluids during her labor.
  
  
  
  • Fetal macrosomia is observed in 26% of IDMs and in 10% (by definition) of infants of nondiabetic women. While most common as a consequence of maternal hyperglycemia and hyperinsulinemia, fetal macrosomia may occur despite maternal euglycemia.
  
  
  
• Impaired fetal growth


• • Infants whose birthweight is below the 10th percentile, when plotted against gestational age on a standard growth curve, are considered small for gestational age.

  • Impaired fetal growth may occur in as many as 20% of diabetic pregnancies, compared to a 10% incidence (by definition) for infants born to nondiabetic mothers. Maternal renovascular disease is the common cause of impaired fetal growth in pregnancies complicated by maternal diabetes.
  
  
  
• Pulmonary disease


• • These infants are at an increased risk of respiratory distress syndrome and may present within the first few hours after birth with tachypnea, nasal or intercostal retractions, and hypoxia. Operative delivery due to macrosomia also increases the risk for transient tachypnea of the newborn, while polycythemia predisposes the infant for persistent pulmonary hypertension of the newborn.
  
  
  
  • Initially, the differential diagnosis might include transient tachypnea of the newborn, respiratory distress syndrome, pneumonia, or persistent pulmonary hypertension.
  
  
  
• Metabolic and electrolyte abnormalities
  • Hypoglycemia may present within the first few hours of life, with such symptoms as jitteriness, irritability, apathy, poor feeding, high pitched or weak cry, hypotonia, or frank seizure activity. This hypoglycemia may persist for as long as one week. More commonly, the neonate is asymptomatic.

  • Hypoglycemia is caused by hyperinsulinemia due to hyperplasia of fetal pancreatic beta cells consequent to maternal-fetal hyperglycemia. Because the continuous supply of glucose is stopped after birth, the neonate develops hypoglycemia because of insufficient substrate. Stimulation of fetal insulin release by maternal hyperglycemia during labor significantly increases the risk of early hypoglycemia in these infants. Perinatal stress may have an additive effect on hypoglycemia due to catecholamine release and glycogen depletion.

  • The overall risk of hypoglycemia is anywhere from 25-40%, with LGA and preterm infants at highest risk.

  • Hypocalcemia or hypomagnesemia also may be apparent in the first few hours after birth; symptoms may include jitteriness or seizure activity. Hypocalcemia (levels <7 mg/dL) is believed to be associated with a delay in parathyroid hormone synthesis after birth.

  • Sixty-five percent of all IDMs demonstrate abnormalities of iron metabolism at birth. Iron deficiency increases an infant's risk for neurodevelopmental abnormalities. Iron is redistributed to the iron-deficient tissues after birth, as the RBC mass is postnatally broken down.



• Hematologic problems: Polycythemia, caused by increased erythropoiesis triggered by chronic fetal hypoxia, may present as a clinically "ruddy" appearance, sluggish capillary refill, or respiratory distress. Hyperviscosity due to polycythemia increases the IDM's risk for stroke, seizure, necrotizing enterocolitis, and renal vein thrombosis.

• Thrombocytopenia: Thrombopoiesis may be inhibited because of an excess of red blood cell precursors within the bone marrow as a result of chronic in utero asphyxia.

• Hyperbilirubinemia: This is common, especially in association with polycythemia. Excessive red cell hemolysis, caused by vascular sludging, leads to elevated bilirubin levels.



• Cardiovascular anomalies


• • Cardiomyopathy with intraventricular hypertrophy and outflow tract obstruction may occur in as many as 30% of these infants. The cardiomyopathy may be caused by congestive failure with a weakly functioning myocardium or to a hypertrophic myocardium with significant septal hypertrophy and outflow tract obstruction. When cardiomegaly or poor perfusion and hypotension are present, it is important to obtain an echocardiogram to differentiate between these processes.

  • These infants also are at an increased risk of congenital heart defects, including (most commonly) ventricular septal defect (VSD) and transposition of the great arteries (TGA).
  
  
  
• Congenital malformations


• • Central nervous malformations are 16 times more likely in these infants. In particular, the risk of anencephaly is 13 times higher, while the risk of spina bifida is 20 times higher. The risk of caudal dysplasia is up to 600 times higher in these infants. Neurologic immaturity, demonstrated by immature sucking patterns, has been found in infants born to insulin managed mothers with diabetes.
  
  
  
  • Renal (eg, hydronephrosis, renal agenesis, ureteral duplication), ear, cardiovascular (eg, single umbilical artery, VSDs, atrial septal defects, TGA, coarctation of the aorta, cardiomegaly), and gastrointestinal (eg, duodenal or anorectal atresia, small left colon syndrome) anomalies are more frequent in these infants.
  
  
  

Physical:

• Fetal macrosomia (>90th percentile for gestational age or >4000 g in the term infant) occurs in 15-45% of diabetic pregnancies. When present, the infant appears puffy, fat, ruddy, and often mildly limp.



• Impaired fetal growth, secondary to poor placental blood flow, is a consequence of severe maternal diabetics with diabetic nephropathy. Perinatal asphyxia, more common in such infants, may be anticipated by prenatal history, thus stressing the importance of communication between obstetrician and pediatrician.

Causes:

• HbA1C levels


• • Complications caused by maternal hyperglycemia during pregnancy are reflected by elevated HbA1C levels, particularly during the first trimester of pregnancy.
  
  
  
  • Because HbA1C is a direct measure of glucose control in the mother, higher levels are predictive of increased risks for congenital complications. Thus, the incidence of complications has been reported as 3.4% with HbA1C levels lower than 8.5% and 22.4% with levels higher than 8.5%.

  • There is speculation that birth defects in IDMs may be related to reduced arachidonic acid and myoinositol levels and elevated sorbitol and trace metal levels in the fetus.
  
  
  
  • Others speculate about the role of excess oxygen radicals and hydroperoxides in the mitochondria of susceptible fetal tissues because these prostacyclin inhibitors may cause disruption in the vascularization of developing tissues.
  
  
  
  • A past history of LGA infants, diabetes, stillbirth, hypertension, gestational diabetes, obesity, or glycosuria, or a current history of excessive weight gain in the present pregnancy or low socioeconomic class place the mother at an increased risk of poor glucose control during pregnancy and increase her risk of delivering an infant with subsequent complications.
  
  
  
• Fetal macrosomia


• • IDMs experience higher levels of glucose during gestation, resulting in pancreatic beta cell hyperplasia with increased secretion of insulin and proinsulin factors (IGF-1, IGFBP-3). Amino acid availability also is increased. All of these factors are involved in the excessive growth observed in the infants of diabetic mothers.
  
  
  
  • All organ systems, aside from the kidney and brain, are sensitive to the increased glucose and amino acid pools. Increased insulin levels result in an increase in cell number and cell size.
  
  
  
• Impaired fetal growth


• • The major cause of impaired fetal growth is maternal diabetic nephropathy. Maternal vascular disease compromises uteroplacental blood flow and impairs fetal nutrient supply.
  
  
  
  • IDMs are at increased risk of preterm labor, stillbirth, neonatal death, birth injury, and perinatal asphyxia.
  
  
  
• Pulmonary disease
  • These infants are at increased risk for respiratory distress syndrome, transient tachypnea of the newborn, and persistent pulmonary hypertension.

  • Insulin restricts substrate availability for surfactant biosynthesis and interferes with the normal timing of glucocorticoid-induced biosynthesis.

  • Insulin also blocks cortisol action at the fibroblast level by reducing production of fibroblast-pneumocyte factor, which normally would stimulate type II cells to produce surfactant.

  • Several studies agree that the risk of respiratory distress syndrome in well-managed diabetic women delivered at term is no higher than in the general population.



• Electrolyte abnormalities
  • These infants are at high risk for hypoglycemia, especially within the early hours after birth.

  • High levels of fetal insulin with cessation of continued maternal glucose supply take place after birth. The neonatal shift to gluconeogenesis with fatty acid use may provide an insufficient supply of substrate, and, thus, the infant may experience hypoglycemia (<20-40 mg/dL), which may be asymptomatic. Alternatively, the infant may display such symptoms as jitteriness, irritability, lethargy, poor feeding tolerance, and seizures. With hypoglycemia, the body responds with increased counterregulatory hormones and production of ketones for use as an energy source. With continued hyperinsulinemia, this production of ketones is inhibited, thus lowering the source of energy for these infants even further.

  • Hypocalcemia, with or without hypomagnesemia, also may be present and is believed to be secondary to parathyroid hormone suppression.

  • Postnatal parathormone response of IDMs is decreased compared to their gestationally matched controls. The associated hypomagnesemia has been speculated to be secondary to increased urinary losses associated with a more severe diabetic state. This maternal hypomagnesemia is reflected in the fetus also.



• Cardiovascular anomalies


• • Cardiac hypertrophy may be observed in as many as 30% of IDMs.
  
  
  
  • Fetal growth is regulated by insulin binding to cell receptors. Compared to the adult, the fetus has an increased number of receptors. Because the fetal heart is particularly rich in receptors, this may lead to increased myocardial protein, glycogen, and fat synthesis with hyperplasia and hypertrophy of myocardial cells.
  
  
  
• Congenital malformations


• • Some speculate that many of the congenital anomalies in IDMs may arise from an insult to the developing somite mesoderm and cephalic neural crest cells.
  
  
  
  • Metabolic disturbances, such as hyperglycemia, hypoglycemia, hyperketonemia, and hypoxia, also may be involved.
  
  
  
  • Glucose-induced free radicals of oxygen also have been implicated.
  
  
  

DIFFERENTIALS

Section 4 of 12

Beckwith-Wiedemann Syndrome

WORKUP

Section 5 of 12

Lab Studies:

• Complete blood cell count


• • Polycythemia, commonly defined as a central hematocrit higher than 65% or hemoglobin concentration higher than 20 g/dL, is a potential concern.
  
  
  
  • Maternal-fetal hyperglycemia is a strong stimulus for fetal erythropoietin production and subsequent increase in fetal hemoglobin concentration secondary to chronic in utero hypoxia, which can be associated with the infant of a diabetic mother. Fetal hyperviscosity, intravascular sludging, regional ischemia, and hypoxemia are all potential complications. Thrombocytopenia may occur because of impaired thrombopoiesis due to "crowding-out" of thrombocytes by the excess of erythroid precursors in the bone marrow.
  
  
  
• Glucose concentration (serum or whole-blood)


• • Seizures, coma, and long-term brain damage may occur if neonatal hypoglycemia is unrecognized and untreated.
  
  
  
  • Most centers recognize levels lower than 20-40 mg/dL within the first 24 hours after birth as abnormal, but the precise level remains controversial. A policy to screen IDMs for hypoglycemia should be in place in every hospital. A recent suggestion of operational thresholds was proposed by Cornblath et al. Their suggestion in an infant with compromised metabolic adaptation (ie, IDMs) should include blood glucose measurements (1) as soon as possible after birth, (2) within 2-3 hours after birth and before feeding, and (3) at any time abnormal clinical signs are observed.
  
  
  
• Magnesium concentration (serum)


• • Hypomagnesemia is related to younger maternal age, severity of maternal diabetes, and prematurity. Neonatal magnesium levels are also related to maternal serum magnesium, neonatal calcium and phosphorus levels, and neonatal parathyroid function.

  • The clinical significance of low magnesium levels in these infants remains controversial and uncertain.
  
  
  
• Calcium concentration (serum, ionized or total levels): Low serum calcium levels in IDMs are common. They are speculated to be caused by a functional hypoparathyroidism; however, their clinical relevance remains uncertain and controversial.



• Bilirubin level (serum, total and unconjugated): Hyperbilirubinemia is notably more common than in the general population of neonates. Causative factors include prematurity, hepatic enzyme immaturity, polycythemia with hyperviscosity and "sludging," and reduced red blood cell half-life.



• Arterial blood gas: Assessing oxygenation and ventilation is essential in infants with clinical evidence of respiratory distress. Although noninvasive methods (eg, transcutaneous oxygen and carbon dioxide electrodes, oximeters) have gained wide acceptance at many centers, comparison of results with those from arterial blood is intermittently required.

Imaging Studies:

• Chest radiograph


• • Clinical evidences of cardiopulmonary distress require a detailed evaluation, which always should include a chest radiograph.
  
  
  
  • Adequacy of lung expansion, evidences of focal or diffuse atelectasis, presence of interstitial fluid, signs of free air in pleural or interstitial spaces, as well as findings of pneumonia should be looked for carefully. The possibility of pulmonary malformations also should be considered. In the macrosomic infant with a history of shoulder dystocia, examination of the clavicles may be indicated.
  
  
  
  • Cardiac size, shape, and great vessel/outflow tract should be examined carefully.
  
  
  
• Cardiac echocardiogram


• • A thickened myocardium and significant septal hypertrophy may be present in as many as 1 in 3 IDMs. Evidence of hypercontractile, thickened myocardium, often with septal hypertrophy disproportionate to the size of the ventricular free walls, may be noted on examination. Myocardial contractility also should be evaluated because the myocardium is overstretched and poorly contractile with congenital cardiomyopathies. Evidence of anatomical malformation must be searched for carefully because cardiac malformations are significantly more common in IDMs, including a VSD and a TGA.
  
  
  
• Abdominal, pelvic, or lower extremity radiographs


• • When caudal dysplasia is present, anatomic details must be evaluated. Orthopedic anomalies may include fusion of the legs, hypoplastic femur, defects of the tibia and the fibula, flexion contractures of the knee and hip, or clubfoot. Sacral agenesis also is described.

  • Lower extremity congenital malformations require radiographic evaluation to determine the exact skeletal defect or defects present.
  
  
  
• Barium enema


• • Infants with feeding intolerance, abdominal distention, nonbilious emesis, or poor passage of meconium may require a barium enema. Congenital anomalies of the gastrointestinal tract are more common in IDMs. These infants may have "small left colon syndrome," also known as "lazy colon."
  
  
  
  • Clinical features of the small left colon syndrome may mimic those of Hirschsprung disease and distal tapering of the colon is a radiologic feature of both disorders. The 2 disorders can be distinguished using a biopsy because normal ganglionic cells are present in lazy colon and absent in Hirschsprung disease.
  
  
  

Procedures:

• Nasal or endotracheal continuous positive airway pressure, endotracheal intubation, and mechanical ventilation


• • Nasal continuous positive airway pressure (NCPAP) or endotracheal intubation with CPAP and/or intermittent mandatory or synchronized positive pressure ventilation (IMV, SIMV) may be employed for management of severe respiratory distress.
  
  
  
  • Common criteria for such interventions include inspired oxygen requirements (FiO₂) of 60-100% to maintain arterial PO₂ of 50-80 mm Hg, arterial PCO₂ levels higher than 60-80 mm Hg or rising 10 or more mm Hg/h, and apnea. The specific criteria for using these modes of assisted ventilation may vary considerably among neonatologists or across institutions.
  
  
  
• Indwelling vascular lines (peripheral, umbilical, or central)


• • Noninvasive blood gas monitoring using transcutaneous electrodes (PaO₂ and PaCO₂) and oximeters (O₂% saturation) has greatly reduced the need for invasive indwelling catheters. However, indwelling lines often are needed early in the course of cardiorespiratory disease. In some instances, the need for continuous arterial blood pressure monitoring may warrant placement of a peripheral or umbilical arterial line. Once again, use of these invasive methods varies.
  
  
  
  • Placement of an umbilical venous or a central venous catheter often is employed when the infant requires hyperosmolar intravenous fluids or when peripheral access is limited or exhausted.
  
  
  

TREATMENT

Section 6 of 12

Medical Care:

• Communication between members of the perinatal team is of crucial importance to identify infants who are at highest risk of complications from maternal diabetes. A cost-effective screening policy for hypoglycemia during the hours after birth is necessary to detect hypoglycemia.



• Hypoglycemic management
  • It is generally agreed that serum or whole blood glucose levels less than 20-40 mg/dL within the first 24 hours after birth are significantly low. Cornblath et al’s recent suggestions for approach at treatment suggest that measurement of the blood glucose level should be determined, as follows:
    1. As soon as possible after birth

    2. Within 2-3 hours after birth and before feeding

    3. At any time abnormal clinical signs are observed

  • Guidelines based on glucose level
    • Level less than 36 mg/dL (2 mmol/L): Close surveillance of glucose levels with intervention is needed if plasma glucose remains below this level, if it does not increase after a feeding, or if the infant develops symptoms of hypoglycemia.

    • Level less than 20-25 mg/dL (1.1-1.4 mmol/L): Intravenous glucose should be administered, with the target glucose level of more than 45 mg/dL (2.5 mmol/L). This goal of 45 mg/dL is accentuated as a margin of safety. Should the infant be significantly symptomatic with profound, recurrent, or persistent hyperinsulinemic hypoglycemia, then a goal of more than 60 mg/dL (3.3 mmol/L) may be more appropriate.

• It is difficult to determine which infants require the highest dextrose administration to maintain euglycemia. The following suggestions represent a guideline for glucose administration to a hypoglycemic, clinically symptomatic, infant.
  • Immediate intravenous therapy with 2-mL/kg infusion of dextrose 10% (D10 provides 100 mg/mL of dextrose, starting dose is 200 mg/kg of dextrose) is required in any symptomatic hypoglycemic infant. Administration over 5-10 minutes usually is recommended because of the high osmolarity. This is especially true for immature infants younger than 32 weeks’ gestational age who are at some risk for intracranial hemorrhage. This procedure originally was described as a 2-minute infusion, and it accomplishes a filling of the glucose space analogous to the volume of distribution of glucose.

  • Maintenance of a continuous infusion of dextrose at an infusion rate of 6-8 mg/kg/min of dextrose is necessary once bolus therapy is complete. Failure to do so may result in rebound hypoglycemia as a result of heightened pancreatic insulin release triggered by the glucose infusion.

  • Frequent serum or whole blood glucose analyses are important to properly titrate the dextrose infusion. Should follow-up glucose levels remain less than 40 mg/dL, the dextrose infusion may be increased by 2 mg/kg/min until euglycemia is achieved.

  • If the infant requires a dextrose concentration more than D12.5 through a peripheral vein at 80-100 mL/kg/d, placement of a central venous catheter may be considered to avoid venous sclerosis. Continued enteral feedings hasten improvement in glucose control because of the presence of protein and fat in the formula.

  • Once the infant’s glucose levels have been stable for 12 hours, intravenous glucose may be tapered by 1-2 mg/kg/min, depending on maintenance of preprandial glucose levels higher than 40 mg/dL.



• Electrolyte management
  • Hypocalcemia and hypomagnesemia may complicate the clinical course.

  • Because low serum calcium levels cannot be corrected in the presence of hypomagnesemia, correction of low magnesium levels is an initial step in the treatment of hypocalcemia.

  • In IDMs, calcium and magnesium levels are commonly measured within the first hours after birth. Ideally, ionized levels of these electrolytes should be obtained and employed to properly manage these electrolyte disturbances.

  • True symptomatic hypocalcemia is extremely rare in these infants. In most cases, symptoms interpreted to be caused by low calcium or magnesium levels are due to low glucose levels associated with perinatal asphyxia or associated with a variety of central nervous system problems.

  • When these low levels are treated, an infusion of 10% calcium gluconate at 2 mL/kg often is administered over 5 minutes (18 mg/kg of elemental calcium). This treatment has particular hazards because the hyperosmolal mixture may cause serious tissue necrosis and sclerosis; also, serious cardiac arrhythmias may occur during the infusion. It is routine in many centers to monitor the infant's ECG during infusion.



• Respiratory management
  • Pulmonary management is tailored to the individual infant's signs and symptoms.

  • Increased ambient oxygen concentrations may be required to maintain oxygen saturations higher than 90%, transcutaneous oxygen tensions at 40-70 mm Hg, or arterial oxygen tensions at 50-90 mm Hg.

  • When an inspired oxygen concentration (FiO₂) higher than 40% is required, the most important task is to determine a precise diagnosis of the cause for the hypoxemia. Principals of management, which are generally agreed on, are based on monitoring of blood levels of oxygen and carbon dioxide, as well as their maintenance within physiologic ranges using the least invasive techniques that are successful.



• Cardiac management
  • If signs of congestive heart failure or cardiomyopathy with cardiomegaly, hypotension, or significant cardiac murmur are observed, echocardiographic evaluation is essential to distinguish among cardiac anomalies, septal hypertrophy, and/or cardiomyopathy.

  • Once a precise diagnosis is available, management of the cardiac disorder is no different for the IDM than for any other newborn with a similar cardiac condition. It is imperative to be extremely careful in the use of cardiotonic agents in the presence of any hypertrophic cardiomyopathy or significant septal hypertrophy. These infants are at risk of actual decreased left ventricular output resulting from this form of therapy. Beta-blockers such as propranolol may be used to relieve the outflow obstruction that is seen with septal hypertrophy.



• Congenital anomalies: A precise and complete diagnosis is an essential prerequisite to proper care.

Consultations: Because of the frequency with which cardiac problems occur in these infants, early consultation with a pediatric cardiologist often is necessary. Because malformations in several organ systems are more common in IDMs, consultation with appropriate subspecialists often is required.

MEDICATION

Section 7 of 12

Several drugs may be used in the treatment of these infants. Metabolic and electrolyte stabilization (dextrose, calcium, magnesium), cardiotropic support (digitalis, dopamine, or dobutamine in the presence of poor cardiac function and propranolol for symptomatic hypertrophic obstructive cardiomyopathy), and the use of sedation (infants with pulmonary hypertension or on mechanical ventilation) are commonly employed. In addition, infants with hyaline membrane disease may require surfactant administration.

Drug Category: Minerals -- IV calcium or magnesium is indicated for acute treatment to correct symptomatic low serum levels.

Drug Name	Calcium gluconate (Kalcinate) -- Employed by some clinicians to correct hypocalcemia (serum ionized calcium level <4 mg/dL or serum total calcium level <8 mg/dL). The 10% IV solution provides 100 mg/mL of calcium gluconate that equals 9 mg/mL (0.46 mEq/mL) of elemental calcium.
Pediatric Dose	Initial: 100-200 mg/kg (1-2 mL/kg, equivalent to 10-20 mg/kg elemental calcium) IV Maintenance: 200-800 mg/kg (2-8 mL/kg) PO/IV
Contraindications	Documented hypersensitivity; renal calculi, hypercalcemia, hypophosphatemia, renal or cardiac disease, and digitalis toxicity
Interactions	May decrease effects of tetracyclines, atenolol, salicylates, iron salts, and fluoroquinolones; antagonizes effects of verapamil; large intakes of dietary fiber may decrease calcium absorption and levels; incompatible with clindamycin, fluconazole, esmolol, amphotericin B, indomethacin, methylprednisolone, metoclopramide, sodium bicarbonate, and phosphate and magnesium salts
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Use extravasation precautions; may cause severe sclerosing of peripheral veins, administer via central line if possible; administer slowly over at least 5 min; monitor ECG for bradycardia or dysrhythmia; caution in digitalized patients, respiratory failure, acidosis, or severe hyperphosphatemia; calcium chloride is more irritating; calcium gluconate provides less predictable increases in plasma calcium levels

Drug Name	Calcium chloride -- Rarely used in pediatric patients due to vascular irritation and extravasation risk. Employed by some clinicians to correct hypocalcemia (serum ionized calcium level <4 mg/dL or serum total calcium level <8 mg/dL). The 10% IV solution provides 100 mg/mL of calcium chloride that equals 27.2 mg/mL (1.4 mEq/mL) of elemental calcium.
Pediatric Dose	Initial: 35-70 mg/kg (0.35-0.7 mL/kg, equivalent to 10-20 mg/kg elemental calcium) IV Maintenance: 75-300 mg/kg (0.75-3 mL/kg) IV
Contraindications	Ventricular fibrillation not associated with hyperkalemia; digitalis toxicity, hypercalcemia, renal insufficiency, cardiac disease
Interactions	Coadministration with digoxin may cause arrhythmias; coadministration with thiazides, may induce hypercalcemia; may antagonize effects of calcium channel blockers, atenolol, and sodium polystyrene sulfonate; incompatible with amphotericin B, methylprednisolone, metoclopramide, sodium bicarbonate, and phosphate and magnesium salts when mixed directly.
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Use extravasation precautions; may severely sclerose peripheral veins, administer via central line if possible; administer slowly over at least 5 min; monitor ECG for bradycardia or dysrhythmia; caution in digitalized patients, respiratory failure, acidosis, or severe hyperphosphatemia

Drug Name	Magnesium sulfate -- Used to correct low levels of serum ionized or total magnesium. Cofactor in enzyme systems involved in neurochemical transmission and muscular excitability. Magnesium sulfate 1 g equals 98 mg elemental magnesium (8.12 mEq or 4.06 mmol elemental magnesium).
Pediatric Dose	Hypomagnesemia or hypocalcemia: 25-50 mg/kg/dose IV q4-6h for 3-4 doses; repeat prn Maintenance: 30-60 mg/kg IV q24h; not to exceed 1 g/d
Contraindications	Documented hypersensitivity; heart block, Addison disease, myocardial damage, or severe hepatitis
Interactions	Concurrent use with nifedipine may cause hypotension and neuromuscular blockade; may increase neuromuscular blockade observed with aminoglycosides and potentiate neuromuscular blockade produced by tubocurarine, vecuronium, and succinylcholine; may increase CNS effects and toxicity of CNS depressants, betamethasone, and cardiotoxicity of ritodrine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	May alter cardiac conduction leading to heart block in digitalized patients; respiratory rate, deep tendon reflex, and renal function should be monitored when electrolyte is administered parenterally; caution when administering magnesium dose because may produce significant hypertension or asystole; in overdose, calcium gluconate, 10-20 mL IV of 10% solution, can be given as antidote for clinically significant hypermagnesemia

Drug Category: Dextrose -- Emergent blood glucose elevation requires IV dextrose.

Drug Name	Dextrose -- Parenterally injected dextrose is used in patients unable to sustain adequate oral intake. Direct oral absorption results in a rapid increase in blood glucose concentrations. Dextrose is effective in small doses and there is no evidence that may cause toxicity. Concentrated dextrose infusions provide higher amounts of glucose and increased caloric intake in a small volume of fluid.
Pediatric Dose	Glucose level <20-25 mg/dL (1.1-1.4 mmol/L): Administer IV dextrose to maintain blood glucose at 45-60 mg/dL (2.5-3.3 mmol/L) Clinically symptomatic infant: 200 mg/kg (2 mL/kg) IV of D10 over 5-10 min initially; followed by 6-8 mg/kg/min IV continuous infusion; may increase by 2 mg/kg/min prn to achieve euglycemia
Contraindications	Do not administer to a patient in diabetic coma if blood sugar levels are extremely high; avoid in severely dehydrated patients
Interactions	Caution when administering parenteral fluids to patients receiving corticosteroids or corticotropin, especially if the solution contains sodium ions
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	May cause nausea, which also may occur with hypoglycemia; IV dextrose solutions may result in dilution of serum electrolyte concentrations, or overhydration when fluid overload is present; caution in patients with congestion or pulmonary edema; hypertonic dextrose given peripherally may cause thrombosis (administer instead through central venous catheter); caution in subclinical diabetes mellitus or carbohydrate intolerance; risk of inducing significant hyperglycemia or hyperosmolar syndrome is increased if solution is administered rapidly, especially in patients with chronic uremia or carbohydrate intolerance; concentrated solutions should not be administered SC or IM; rates of dextrose infusion higher than 0.5 g/kg/h may produce glycosuria; at infusion rates of 0.8 g/kg/h, the incidence of glycosuria is 5%; monitor fluid balance, electrolyte concentrations, and acid-base balance closely; dextrose administration may produce vitamin B-complex deficiency

Drug Category: Cardiotropic agents -- These agents are used to improve poor cardiac output.

Drug Name	Dopamine (Intropin) -- Stimulates both adrenergic and dopaminergic receptors. Hemodynamic effect is dependent on the dose. Lower doses predominantly stimulate dopaminergic receptors that, in turn, produce renal and mesenteric vasodilation. Cardiac stimulation and renal vasodilation produced by higher doses. After initiating therapy, increase dose by 1-4 mcg/kg/min q10-30min until optimal response obtained. More than 50% of patients are satisfactorily treated on doses <20 mcg/kg/min.
Adult Dose	1-5 mcg/kg/min IV; not to exceed 20 mcg/kg/min
Pediatric Dose	Administer as in adults; premature infants may respond to very small doses
Contraindications	Documented hypersensitivity; pheochromocytoma or ventricular fibrillation
Interactions	Phenytoin, alpha- and beta-adrenergic blockers, general anesthesia, and MAOIs increase and prolong dopamine effects; incompatible with acyclovir, amphotericin B, furosemide, indomethacin, insulin, and sodium bicarbonate
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Continuous heart rate and intraarterial blood pressure monitoring preferred; tachycardia and arrhythmia; may increase pulmonary artery pressure; tissue sloughing with IV infiltration; correct hypovolemia before infusion; caution if evidence of hypertrophic cardiomyopathy exists in infant due to increased risk of decreased left ventricular output resulting from inotropic use

Drug Name	Dobutamine (Dobutrex) -- Used to improve cardiac output. It is a synthetic catecholamine with primarily beta1-adrenergic activity. Increases myocardial contractility, cardiac index, oxygen delivery, and oxygen consumption and is more effective on cardiac contractility than dopamine.
Adult Dose	0.5 mcg/kg/min IV initially, titrate until desired therapeutic effect attained, typically up to 20 mcg/kg/min
Pediatric Dose	Administer as in adults; premature infants may respond to very small doses
Contraindications	Documented hypersensitivity; idiopathic hypertrophic subaortic stenosis and atrial fibrillation or flutter
Interactions	Beta-adrenergic blockers antagonize effects of dobutamine; general anesthetics may increase toxicity Incompatible with acyclovir, aminophylline, bumetanide, diazepam, digoxin, furosemide, indomethacin, phenytoin, and sodium bicarbonate
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Continuous heart rate and intraarterial blood pressure monitoring preferred; watch for extravasation associated with infiltration; correct hypovolemia before infusion; caution if evidence of hypertrophic cardiomyopathy exists in infant due to increased risk of decreased left ventricular output resulting from inotropic use

Drug Name	Digoxin (Lanoxin) -- Cardiac glycoside with direct inotropic effects in addition to indirect effects on the cardiovascular system. Acts directly on cardiac muscle, increasing myocardial systolic contractions. Its indirect actions result in increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure.
Adult Dose	0.125-0.375 mg PO qd
Pediatric Dose	Total digitalizing dose: 5-10 years: 20-35 mcg/kg PO divided in 3 doses q6h >10 years: 10-15 mcg/kg PO divided in 3 doses q6h Maintenance dose: Use 25-35% of PO loading dose
Contraindications	Documented hypersensitivity; beriberi heart disease, idiopathic hypertrophic subaortic stenosis, constrictive pericarditis, and carotid sinus syndrome
Interactions	Medications that may increase digoxin levels include alprazolam, benzodiazepines, bepridil, captopril, cyclosporine, propafenone, propantheline, quinidine, diltiazem, aminoglycosides, oral amiodarone, anticholinergics, diphenoxylate, erythromycin, felodipine, flecainide, hydroxychloroquine, itraconazole, nifedipine, omeprazole, quinine, ibuprofen, indomethacin, esmolol, tetracycline, tolbutamide, and verapamil Medications that may decrease serum digoxin levels include aminoglutethimide, antihistamines, cholestyramine, neomycin, penicillamine, aminoglycosides, oral colestipol, hydantoins, hypoglycemic agents, antineoplastic treatment combinations (eg, carmustine, bleomycin, methotrexate, cytarabine, doxorubicin, cyclophosphamide, vincristine, procarbazine), aluminum or magnesium antacids, rifampin, sucralfate, sulfasalazine, barbiturates, kaolin/pectin, and aminosalicylic acid
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Hypokalemia may reduce positive inotropic effect of digitalis; IV calcium may produce arrhythmias in digitalized patients; hypercalcemia predisposes patient to digitalis toxicity, and hypocalcemia can make digoxin ineffective until serum calcium levels are normal; magnesium replacement therapy must be instituted in patients with hypomagnesemia to prevent digitalis toxicity; patients diagnosed with incomplete AV block may progress to complete block when treated with digoxin; exercise caution in hypothyroidism, hypoxia, and acute myocarditis; in the infant of a diabetic mother, caution must be used with these agents if evidence of hypertrophic cardiomyopathy exists; these infants are at increased risk of decreased left ventricular output resulting from the use of these agents

Drug Name	Propranolol (Inderal) -- Nonselective beta-adrenergic–receptor blocker decreases the degree of outflow obstruction caused by septal hypertrophy.
Adult Dose	Hypertension, angina, or tremor: 120-320 mg/d PO in divided doses Tachyarrythmia, anxiety, or hyperthyroidism: 10-40 mg PO tid/qid
Pediatric Dose	Oral: 0.25 mg/kg/dose PO q6h initially; may increase as needed, not to exceed 3.5 mg/kg/dose q6h IV: 0.01 mg/kg/dose IV q6h infused over 10 min, if needed, increase dose, not to exceed 0.15 mg/kg/dose q6h
Contraindications	Documented hypersensitivity; reactive airway disease; diminished myocardial contractility
Interactions	Coadministration with aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease propranolol effects; calcium channel blockers, cimetidine, loop diuretics, and MAOIs may increase toxicity of propranolol; toxicity of hydralazine, haloperidol, benzodiazepines, lidocaine, quinidine, and phenothiazines may increase with administration; coadministration with epinephrine may result in severe hypertensive response; abrupt withdrawal of clonidine while taking beta-blockers may exaggerate hypertensive rebound due to excessive alpha stimulation; coadministration with ergot alkaloids may result in excess vasoconstriction
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Beta-adrenergic blockade may decrease signs of acute hypoglycemia and hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; withdraw drug slowly and monitor closely; may cause bradycardia, bronchospasm, or hypotension; continuous monitoring required with IV administration

FOLLOW-UP

Section 8 of 12

Further Outpatient Care:

• Basic outpatient care should consist of routine well-baby care provided by the infant’s general pediatrician. Additional follow-up by consultant subspecialists depends on the neonatal clinical problems and their resolution.

Transfer:

• Infants of diabetic mothers having congenital anomalies, heart disease, or significant respiratory illness may require transfer to a tertiary care neonatal intensive care unit (NICU) for continued care and access to subspecialists.

Deterrence/Prevention:

• The best prevention is preconceptional diabetes care. Pregnancy planning and accessing early prenatal care with meticulous attention to glycemic control and good obstetric management throughout pregnancy aids in optimizing pregnancy outcome. The consideration of maternal-fetal medicine consultation may be appropriate in many cases of established diabetes. With excellent glycemic control throughout pregnancy and regularly scheduled prenatal visits, the overall mortality rate approaches that of the general population. This should be emphasized excessively, even before pregnancy, in the population at risk for or with a history of poor glycemic control during pregnancy. Furthermore, it should be part of all prenatal counseling.

Complications:

• All risks are directly proportional to the degree of maternal hyperglycemia in utero.



• Thompson and associates found that tight control of euglycemia in the patient with gestational diabetes led to normal perinatal outcomes. When comparing good glucose control (mean plasma glucose level <120 mg/dL) with poor glucose control (mean plasma glucose level >140 mg/dL), the hyperglycemic group was found to have more preeclampsia, maternal urinary tract infections, premature deliveries, cesarean deliveries, macrosomia, respiratory distress, neonatal hypoglycemia, congenital malformations, and perinatal mortality.



• Congenital anomalies: The overall risk is 8-15%, with 30-50% of perinatal fatalities related to major congenital malformations. Poor glycemic control early in pregnancy directly correlates with a higher incidence of congenital malformations.



• Perinatal mortality


• • In the past, 10-30% of pregnancies terminated with sudden and unexplained stillbirth. This is believed to have been secondary to chronic fetal hypoxia with subsequent polycythemia and vascular sludging. A higher incidence was noted in pregnancies further complicated by maternal vascular disease.
  
  
  
  • A considerable proportion of perinatal problems are a consequence of fetal macrosomia. Macrosomia is associated with protracted labor, perinatal asphyxia, shoulder dystocia and brachial plexus injury, other skeletal and nerve injuries, and an elevated rate of operative deliveries.
  
  
  

Prognosis:

• Prognosis is very good when appropriate care is provided during the perinatal period.



• As many as 50% of mothers with gestational diabetes develop insulin-dependent diabetes within 15 years of their pregnancy.



• Neurodevelopmental outcome


• • Overall findings from multiple studies indicate that infants of mothers with poor glucose control during pregnancy are at highest risk for neurodevelopmental deficits.

  • In 2005, DeBoer et al demonstrated deficits in mnemonic behavior in IDMs aged one year, suggesting a connection between the prenatal environment of the fetus and subsequent memory development.

  • In 1991, Rizzo et al published a study that included 223 pregnant women and their singleton offspring. Of these mothers, 89 had diabetes before pregnancy, 99 had gestational diabetes, and 35 had normal carbohydrate metabolism. The children were examined at ages 2, 3, 4, and 5 years.
    • Mental developmental index scores at 2 years correlated inversely with the mother's third-trimester plasma beta-hydroxybutyrate levels, after correcting for socioeconomic status, race, and ethnicity.

    • Stanford-Binet Intelligence scores at ages 3, 4, and 5 years were inversely correlated with the third-trimester plasma beta-hydroxybutyrate and free fatty acid levels of the mothers.

    • No correlation was found between perinatal complications and cognitive development in the same group of infants. Thus, it appears that the metabolic milieu that the fetus is exposed to in utero may very well affect long-term neurodevelopmental outcome.
  
  
  
  • In another study by the same group, 139 women with diabetes in pregnancy and their singleton offspring were followed.
    • After statistically controlling for other influences, Wechsler Intelligence Scale for Children-Revised (WISC-R) verbal, performance, and full scale IQ scores, and Bannatyne indices of verbal conceptualization ability, acquired knowledge, spatial ability, and sequencing ability were inversely correlated with measures of maternal lipid and glucose metabolism in the second and third trimesters.

    • When looking at the neurodevelopmental outcome at early school-aged children born to mothers with gestational diabetes, Ornoy and associates followed 32 school-aged children born to 32 mothers with well-controlled gestational diabetes and 57 control children. They determined that gestational diabetes induces long-term minor neurological deficits that are more pronounced in younger children, with differences tending to disappear with age.
  
  
  
  • Concerning episodes of hypoglycemia and overall prognosis, a recent article examining the long-term effects of neonatal hypoglycemia on brain growth and psychomotor development in SGA preterm infants was published by Duvanel et al.
    • They systematically detected hypoglycemia of less than 47 mg/dL in 85 SGA preterm infants. Through prospective serial evaluations of physical growth and psychomotor development, they determined that those infants with repeated episodes of hypoglycemia had significantly reduced head circumferences at ages 18 months and 3 1/2 years. Furthermore, those with recurrent episodes were noted to have lower scores of psychometric tests at ages 3 1/2 and 5 years.

    • Although this article was looking specifically at those infants who were SGA and, therefore, might be at risk for developmental delays and small head size caused by other factors, the fact that those with multiple episodes of hypoglycemia had poorer development and smaller head circumference measurements may be a concern for IDMs with multiple episodes of hypoglycemia.
  
  
  
• Growth


• • Some evidence indicates that IDMs will have obesity as they get older.
  
  
  
  • Silverman and associates followed physical growth from birth to age 8. At birth, 50% of the infants weighed more than the 90th percentile. At 12 months, length and weight were both normal. At age 7 years, height was slightly higher than average. In comparison to infants born to mothers without diabetes, IDMs were noted to have an increase in weight after age 5 years, resulting in weights higher than the 90th percentile in 50% of those infants by the age of 8 years.

  • In 2005, Boney et al demonstrated that LGA offspring of diabetic or obese mothers were at significant risk of developing metabolic syndrome (obesity, hypertension, dyslipidemia, glucose intolerance) in childhood. Given the relationship of obesity and gestational diabetes, this finding has significant implications for future generations.
  
  
  

MISCELLANEOUS

Section 9 of 12

Medical/Legal Pitfalls:

• Failure to recognize and appropriately treat the infant with hypoglycemia can be devastating from a medicolegal standpoint.

TEST QUESTIONS

Section 10 of 12

CME Question 1: A term infant is born to a woman who has received no prenatal care. Following a spontaneous vaginal delivery, Apgar scores at 1 and 5 minutes were 7 and 9, respectively. The infant is large for gestational age and has an apneic spell associated with jitteriness within 1 hour of birth. Which of the following is the most appropriate next step?

A: Administer 20 mg/kg of phenobarbital immediately.
B: Secure the infant's airway, assure adequate ventilation, and then initiate intravenous glucose.
C: Assess the baby for adequate air exchange and check serum glucose level.
D: Tell the nurse to feed the infant formula and to call you if the infant has another spell.
E: Reassure the nurse that the infant is fine, and continue routine newborn care.

The correct answer is C: This infant is macrosomic and shows symptoms consistent with hypoglycemia within an hour of birth. It is likely the mother had impaired carbohydrate metabolism during her unsupervised pregnancy. An initial assessment of air exchange and measurement of serum or whole blood glucose level would be appropriate.

CME Question 2: A term infant presents who is small for gestational age (SGA). The mother is known to have diabetes with renal complications, and the infant had a glucose level of 20 mg/dL 1 hour after birth. The infant is responsive to examination, is not jittery, and is mildly hypotonic. What should be the treatment for this infant?

A: Give 10 mL/kg IV of dextrose 15% in water (D15W) over 5 minutes.
B: Initiate intravenous fluids of dextrose 10% in water (D10W) at 80 mL/kg/d and continue to feed as needed. Follow glucose levels every 30 minutes until stable.
C: Increase frequency of feedings to 2 per hour.
D: Reassure the nurse that no treatment is necessary because the infant is asymptomatic.
E: Give 2 mL/kg IV of D10W over 5 minutes, then initiate intravenous fluids of D10W at 80 mL/kg/d and follow glucose levels every 30 minutes until stable.

The correct answer is E: Impaired fetal growth is an anticipated complication when the mother has renal disease or chronic hypertension. Treatment of the asymptomatic infant with hypoglycemia includes correction of hypoglycemia with 2 mL/kg IV dextrose 10% in water (D10W), followed by maintenance of euglycemia with intravenous IV dextrose and serial measurement of serum or blood glucose levels until stable. It is important to maintain a continuous infusion of glucose following bolus correction of hypoglycemia to avoid rebound hypoglycemia secondary to increased release of neonatal insulin.

Pearl Question 1 (T/F): Sacral dysgenesis (ie, caudal regression syndrome), a congenital anomaly affecting the CNS and lower extremities, is most often seen in infants of diabetic mothers.

The correct answer is True: Caudal regression syndrome, or sacral dysgenesis, occurs up to 600 times more frequently in infants of diabetic mothers than in the general population.

Pearl Question 2 (T/F): Infants of diabetic mothers (IDMs) are at an increased risk of having a small for gestational age (SGA) infant.

The correct answer is False: IDMs are more commonly macrosomic (large for gestational age [LGA]) status and, thus, at particular risk for shoulder dystocia or brachial plexus injury. Severe maternal diabetes with renovascular disease may impair fetal growth but this is less common.

Pearl Question 3 (T/F): An infant with symptomatic hypoglycemia should be treated by first administering a 2-mL/kg bolus of dextrose 10% (D10) followed by an IV dextrose infusion.

The correct answer is True: Administering 2 mL/kg IV D10 provides approximately 3.3 mg glucose per kg/min to the infant. Continued intravenous dextrose is necessary to avoid rebound hypoglycemia.

Pearl Question 4 (T/F): An infant of a diabetic mother is jittery with a normal glucose value of 73 mg/dL. The jitteriness is probably secondary to seizure activity.

The correct answer is False: Calcium and magnesium levels should be assessed immediately, and the infant should be treated accordingly.

PICTURES

Section 11 of 12

Caption: Picture 1. An increase in the number and size of the islets is commonly seen in the pancreas of infants born to diabetic mothers.
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BIBLIOGRAPHY

Section 12 of 12

• Al-Najashi SS: Control of gestational diabetes. Int J Gynaecol Obstet 1995; 49: 131-5[Medline].
• Boney CM, Verma A, Tucker R, Vohr BR: Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 2005 Mar; 115(3): e290-6[Medline][Full Text].
• Bromiker R, Rachamim A, Hammerman C: Immature Sucking Patterns in Infants of Mothers with Diabetes. Journal of Pediatrics 2006; 149: 640-643.
• Cordero L, Landon MB: Infant of the diabetic mother. Clin Perinatol 1993; 20: 635-48[Medline].
• Cornblath M, Hawdon JM, Williams AF, et al: Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds. Pediatrics 2000 May; 105(5): 1141-5[Medline][Full Text].
• Cowett RM, Schwartz R: The infant of the diabetic mother. Pediatr Clin North Am 1982; 29: 1213-31[Medline].
• DeBoer T, Wewerka S, Bauer PJ, et al: Explicit memory performance in infants of diabetic mothers at 1 year of age. Dev Med Child Neurol 2005 Aug; 47(8): 525-31[Medline].
• Duvanel CB, Fawer CL, Cotting J, et al: Long-term effects of neonatal hypoglycemia on brain growth and psychomotor development in small-for-gestational-age preterm infants. J Pediatr 1999 Apr; 134(4): 492-8[Medline].
• Engelgau MM, Herman WH, Smith PJ, et al: The epidemiology of diabetes and pregnancy in the U.S., 1988. Diabetes Care 1995; 18: 1029-33[Medline].
• Greco P, Vimercati A, Scioscia M, et al: Timing of fetal growth acceleration in women with insulin-dependent diabetes. Fetal Diagn Ther 2003 Nov-Dec; 18(6): 437-41[Medline].
• Hod M, Levy-Shiff R, Lerman M, et al: Developmental outcome of offspring of pregestational diabetic mothers. J Pediatr Endocrinol Metab 1999; 12: 867-72[Medline].
• Landon MB, Gabbe SG: Diabetes Mellitus and Pregnancy. Obstetrics and Gynecology Clinics of North America 1992; 19: 633-53[Medline].
• Nold JL, Georgieff MK: Infant of diabetic mothers. Pediatric Clinics of North America 2004; 51: 619-637.
• 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-F14[Medline].
• Rizzo T, Metzger BE, Burns WJ, Burns K: Correlations between antepartum maternal metabolism and child intelligence. New Eng J Med 1991; 26: 911-6[Medline].
• Rizzo TA, Ogata ES, Dooley SL, et al: Perinatal complications and cognitive development in 2- to 5-year-old children of diabetic mothers. Am J Obsted Gynecol 1994; 171: 706-13[Medline].
• Rizzo TA, Dooley SL, Metzger BE: Prenatal and perinatal influences on long-term psychomotor development in offspring of diabetic mothers. Am J Obstet Gynecol 1995; 173: 1753-8[Medline].
• Rizzo TA, Metzger BE, Dooley SL: Early malnutrition and child neurobehavioral development: insights from the study of children of diabetic mothers. Child Dev 1997; 68: 26-38[Medline].
• Siddiqui F, James D: Fetal monitoring in type 1 diabetic pregnancies. Early Human Development 2003; 72: 1-13.
• Silverman BL, Rizzo T, Green OC, et al: Long-term prospective evaluation of offspring of diabetic mothers. Diabetes 1991; 40: 121-5[Medline].
• Suevo DM: The infant of the diabetic mother. Neonatal Netw 1997; 16: 25-33[Medline].
• Thompson DM, Dansereau J, Creed M, Ridell L: Tight glucose control results in normal perinatal outcome in 150 patients with gestational diabetes. Obstet Gynecol 1994; 83: 362-6[Medline].
• Tyrala E: The infant of the diabetic mother. Obstetrics and Gynecology Clinics of North America 1996; 23: 221-41[Medline].
• Weintrob N, Karp M, Hod M: Short- and long-range complications in offspring of diabetic mothers. J Diabetes Complications 1996 Sep-Oct; 10(5): 294-301[Medline].

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