Metabolic: NICU Handbook

John A. Widness, MD
Peer Review Status: Internally Peer Reviewed

Definition:

plasma ionized calcium concentration < 3 mg/dL (0.75 mmol/L).

Infants at risk:

• premature infants
• infants of diabetic mother
• infants with birth asphyxia infants with certain congenital, genetic and hormonal disorders

Categorization by age of onset:

• Early: In pre-term infants who has received sodium bicarbonate for the treatment of metabolic acidosis, the risk is greatest at 12 to 24 hours of life. Most hypocalcemic neonates without symptoms will normalize their serum calcium levels by 72 hours of age with or without treatment.
• Late: after 7 days infants receiving formulas with low calcium and high phosphorus contents (rare today).
• Very late osteopenia of prematurity: see section on neonatal nutrition.

Symptoms:

extreme jitteriness, seizures (including apnea), bleeding and/or decreased myocardial contractility.

Treatment:

Treatment of infants whose symptoms are thought to be due to hypocalcemia should be begun as soon as possible. Treatment of asymptomatic infants is controversial since in the vast majority of infants the condition is currently thought to have no short or long terms effects. Nevertheless, some authorities recommend treatment of low calcium levels.

• Once a decision to treat has been made, initial treatment should be 100 to 200 mg/kg of 10% calcium gluconate by slow i.v. "push", i.e., over at least 30 minutes, followed by a continuous i.v. infusion of 400 mg/kg/day calcium gluconate. Alternatively, calcium may be administered as a slow infusion (over 30 to 60 minutes), given at a dose of 100 mg/kg every 6 hours. If other calcium salts are used, e.g. calcium chloride, the dose will be different. Calcium gluconate should be infused through a peripheral venous line and not given with sodium bicarbonate, dioxin, or antibiotics. If there is a question as to compatibility of calcium with other drugs, contact the Hospital Pharmacy (6-1849).
• In treated infants plasma ionized calcium level should be monitored every 12 to 24 hours. Once the calcium level has normalized, and parenteral and/or enteral sources of calcium intake have been begun, the infusion of calcium should be decreased by 50% after 24 hours, and then discontinued after an additional 24 hours if follow-up plasma calcium levels remain normal and the patient is asymptomatic.
• To prevent the very late osteopenia occurring most commonly in sickest and least mature premature infants, optimal enteral and parenteral calcium nutritional support on a long term basis are needed (see sections on neonatal nutrition and feeding).

Reference:

Salle BL, Delvin E, Glorieux F, David L. Human neonatal hypocalcemia. Biol Neonate 1990;58:1:22-31.

John A. Widness, MD
Peer Review Status: Internally Peer Reviewed

Hypoglycemia

Definition:

Plasma glucose < 40 mg/dL in both term or preterm infants.

Incidence:

The definition of neonatal hypoglycemia has been based on statistical criteria.2 The incidence of this condition in term AGA infants is approximately 2%.

Infants at risk immediately following birth:

IDMs, IGDMs (especially those whose mothers received oral hypoglycemic agents), LGA (>90%ile), SGA (IUGR <10%ile), post-asphyxiated, APGAR < 5 at five minutes, polycythemic, immune hemolytic disease, suspected sepsis, hypothermia (rectal temperature <35¾C), congenital anomalies, Beckwith-Wiedman syndrome, infants ≤ 36 wks gestation, infants ≥42 wks gestation, & those whose mothers received large amounts of i.v. glucose prior to delivery.

Signs:

Non-specific, including tremulousness, twitching, jitteriness, irritability, exaggerated Moro reflex, high pitched cry, seizures, apnea, limpness, poor feeding, cyanosis, temperature instability, and coma.

Screening of infants at risk (see table at end of this section):

Screen by plasma glucose measurements at 1, 2, 4, 8 and 24 hours of age if not receiving glucose containing i.v. fluids, or when symptomatic.

Diagnosis:

By plasma glucose measurements only. For diagnostic purposes it is imperative that plasma glucose be measured in the NICU or Hospital laboratory by quantitative chemical analysis and NOT by a semi-quantitative reagent strip method (e.g., Chemstrip bG®). Although use of reagent strips is widespread, their use, even for glucose screening purposes, is controversial1. This is because of their inaccuracy and imprecision relative to accepted laboratory determined glucose values. Treatment decisions in infants without signs ("asymptomatic") of hypoglycemia should not be based on Chemstrip data.

Treatment:

Symptomatic infants:

Guidelines for monitoring plasma glucose in hypoglycemic infants

In hypoglycemic infants, plasma glucose values should be repeated 1-2 hours after initiation of treatment if the infant remains asymptomatic, or every 20-30 minutes if symptomatic (see table at end of this section). If signs of hypoglycemia persist or recur, or if plasma plasma glucose concentration as determined by the neonatal or hospital laboratory remains below 40 mg/dL, increase glucose infusion rate to 10 to 12 mg/kg/min. If further hypoglycemia persists, IMMEDIATELY notify staff neonatologist for consideration of further treatment and diagnosis.

After the plasma glucose has been normal for 24 hours, and enteral feedings have been started, taper i.v. glucose infusion rate by 1-2 mg/kg/min every 4 to 8 hours as tolerated. (This may necessitate a reduction in the concentration of dextrose in the i.v. fluid being used.) Intravenous glucose intake usually cannot be reduced below 4-6 mg/kg/min until enteral feedings are begun.

Hyperglycemia

Definition:

Unknown and controversial, although the neonatal staff has suggested a definition of plasma glucose as >200 mg/dL.2 Hyperglycemia almost always occurs in the first hours to days of life.

Incidence:

Unknown.

Infants at risk:

Infants with birth weights > 1 kg receiving intravenous fluids at high dextrose infusion rates >8mg/kg/min); VLBW infants < 1 kg at moderate glucose infusion rates (4-8 mg/kg/min); infants with congenital diabetes mellitus (rare); infants receiving, or whose mothers received, selected drugs, e.g. diazoxide.

Signs:

Polyuria due to glycosuria (rare if blood glucose < 250 mg/dL); intracranial hemorrhage if hyperglycemia occurs rapidly as a result of an abrupt increase in plasma glucose concentration, e.g., following an i.v. D25W or D50W glucose bolus. As noted above, use of either of these high concentration glucose solutions is to be avoided.

Diagnosis:

Same as hypoglycemia, i.e., plasma glucose measurement is needed--NOT Chemstrip.

Treatment:

If plasma glucose > 200 mg/dL.

Reduce glucose infusion rate.

IV insulin administration (0.1 U/kg/hr) if reducing the rate of glucose infusion is not effective, or is not possible. This treatment should not be undertaken without first consulting the staff neonatologist.

Guidelines for monitoring plasma glucose in hyperglycemic infants:

Plasma glucose measurements should be determined every 1 to 4 hours depending on the degree of hyperglycemia, with therapy adjusted according to plasma plasma glucose results. Glucose determinations should be done on capillary blood from an extremity, or from a non-glucose-containing indwelling catheter.

Normoglycemia

Definition:

Plasma glucose 50-100 mg/dL in infants not receiving i.v. fluids.

Guidelines for monitoring plasma and urine glucose in infants receiving I.V. fluids:

Blood glucose monitoring (see table at end of this section):

Monitoring of plasma glucose concentrations in sick and premature infants receiving parenteral fluids is indicated. When clinically feasible, try to do this at times when other blood work is being done. This will reduce the number of heelsticks.

Urine should be tested by the nursing staff once a shift for glucosuria. Some infants, especially those <1,000g, may not be able to fully utilize high glucose infusion rates, and will spill glucose in their urine. Although glucose-induced osmotic diuresis is rare in neonates, it should be looked for once glucosuria is present. The presence of glucosuria is an indication to perform a chemical determination of plasma glucose for the purpose of defining an individual infant's renal glucose threshold. If glycosuria is present and the plasma glucose is <200 mg/dL, it is NOT necessary to decrease the glucose infusion rate.

In the management of extremely small infants weighing <700 g, it may be advisable to perform less frequent plasma glucose monitoring (once daily), and to rely more on the results of urine glucose testing. In these situations, if plasma glucose testing documents the absence of hypoglycemia, urine glucose testing may be substituted for blood glucose testing for the purpose of avoiding hyperglycemia. Infants whose blood glucose values are within the normal range, and whose urine glucoses are negative, may have their glucose infusion rate increased to increase energy intake if deemed appropriate.

Newly admitted infants without risk factors for hypoglycemia should have a plasma glucose value measured between 1 and 4 hours after birth and again between 8-16 hr unless clinical circumstances mandate earlier glucose testing.

Subsequently, infants at high risk who are receiving only i.v. fluids, should have plasma glucose determinations done every shift for 3 days and once a day for days 4-7 after birth. In infants not at high risk, consider monitoring plasma glucose levels once or twice a day in the first week of life.

In infants who have been on i.v. fluids for over 1 week, and whose plasma glucose values have been within the normal range monitoring of plasma plasma glucose, may be decreased to twice a week.
Use of blood glucose screening using semi-quantitative reagent strips, i.e. Chemstrips, is to be discouraged.2 In addition, do not use blood from arterial lines for glucose determination.

Infants whose plasma glucose values are < 200 mg/dL may have their infusion rate of glucose (and lipid) increased to provide additional energy if their caloric intake is deemed suboptimal (< 90 kcal/kg/dL). It is prudent to increase glucose infusion rate slowly (1-3 mg/kg/min) with change made once/day. For infants receiving long-term i.v. fluids, the upper limit of the glucose infusion rate used may be defined by the infant's plasma glucose values.

An infant whose glucose has been stable on plain IV fluids may show hyperglycemia with the addition of lipids. Conversely, the addition of protein (NVN) may require an increase in the role of dextrose administration.

Urine:

References:

Cornblath M, Schwartz R, Aynsley-Green A, Lloyd JK. Hypoglycemia in infancy: the need for a rational definition. Pediatrics 1990;85:834-837.

Cornblath M, Schwartz R. Disorders of Carbohydrate Metabolism in Infancy. 3rd ed. Philadelphia: W.B. Saunders, 1991, pp. 87-124, 225-246.

This graph may be used in your management of neonates as an aid for determining:

1. the i.v. rate needed to achieve a desired glucose infusion rate, i.e., in mg/kg/min as is needed for writing orders; or
2. determining the glucose infusion rate of an existing i.v. to determine an infant's caloric intake.

As an example, a 2.5 kg infant whom you would like to have receive 6 mg/kg/min of glucose should be receiving 9.5 cc/hr of D10W (equivalent to 90 cc/kg of i.v. fluid).

John A. Widness, MD
Peer Review Status: Internally Peer Reviewed

Maternal factors

The degree of illness in the IDM has been associated with the duration, severity and control of the mother's diabetes. Hence, essential points in the maternal history are:

• White's Class of diabetes (increasing from "Classes" A->R),
• Therapy (diet, insulin, oral hypoglycemic drugs, etc.),
• Time of the last insulin injection prior to delivery since this affects maternal glucose,
• Amount and type of IV fluids given during labor and delivery,
• Estimated gestational age , and
• Degree of chronic glucose control during pregnancy by HgbA1c and/or by maternal outpatient glucose "home" monitoring.

Congenital anomalies

Because the incidence of congenital anomalies is increased in IDM's, a thorough physical examination is essential. In particular, the incidence of congenital heart disease and anomalies of the nervous system, e.g., anencephaly, spina bifida, microcephaly, caudal regression syndrome, are higher in IDM's. (This knowledge also has important implications in counseling diabetics who have delivered and adolescent girls who have diabetes.)

RDS

The IDM is at greater risk for RDS than most non-IDM infants of comparable gestational age. During the first hours of life, all IDMs should be observed carefully for this morbidity and treated promptly.

Hypoglycemia

The incidence of hypoglycemia in IDM’s has been reported as high as 50% in some studies. Optimally, cord blood obtained at delivery should be sent to STAT for a true plasma glucose level. The higher the cord plasma glucose value, the greater the likelihood the infant will develop hypoglycemia within the first hours of life.

The incidence of hypoglycemia is highest at 1-4 hours of age after the fall in plasma glucose following the cessation of maternal glucose infusion (see Figure). In the asymptomatic infant, true plasma glucose should be monitored at 1,2,4,6,9,12, and 24 hours. Because of their inaccuracy, Chemstrips® are not recommended for this purpose. The hypoglycemia in IDM’s is usually transient and easily treated. (See section on hypoglycemia for therapeutic approach.)

All IDM's without respiratory distress should be fed by nipple or gavage by 2 hours of age. If the clinical condition is such that s/he cannot tolerate enteral feedings by 2 hours of age, an IV infusion of D10W should be considered.

Hypocalcemia

The infant should be monitored for hypocalcemia frequently occurring in the first 24 hours (see section on "Hypocalcemia").

Polycythemia

A screening capillary hematocrit should be obtained at 4 to 6 hours of life since the incidence of hyperviscosity is higher in IDM's. Values > 65% should be repeated immediately by a peripheral venous ("central") hematocrit. (see section on "Polycythemia/Hyperviscosity").

References

Cornblath M & Schwartz R. Disorders of Carbohydrate Metabolism in Infancy. (3rd Ed.). Philadelphia:W. B. Saunders, 1991.

Widness JA . Fetal risks and neonatal complications of diabetes mellitus. In Brody SA, Ueland K and Kase N. Endocrine Disorders in Pregnancy. Norwalk, CN: Appleton & Lange,1989:273-297.

John A. Widness, MD
Peer Review Status: Internally Peer Reviewed

† Infants at risk include: IDMs, IGDMs (especially those whose mothers received oral hypogylcemic agents), LGA (>90%ile), SGA ("IGUR": <10%ile>, post-asphyxiated, APGAR <5 at five minutes, polycythemic, immune hemolytic disease, suspected sepsis, hypothermia (rectal temperature >35°C), congenital anomalies, Beckwith-Weidman syndrome, infants < 36 wks gestation, infants > 42 wks gestation, & infants whose mothers received large amounts of i.v. glucose prior to delivery.

*In the "micropremie" with transparent skin which could break down, consider decreasing the number of plasma glucose determinations by monitoring urine "dipsticks" for the appearance of dextrose. Since these infants will invariably have parenteral glucose infusions running, hyperglycemia is often a more common clinical finding.

John A. Widness, MD
Peer Review Status: Internally Peer Reviewed

Figure: Serial Changes in the concentration of glucose in the blood of infants immediately following delivery. The group from mothers with gestational diabetes have abnormal intravenous glucose tolerance tests during pregnancy but received no insulin therapy. Note initially elevated levels in the mothers. (Adapted from McCann, et al, N Engl J Med. 1966; 275:1, with permission.)