Hyperthermia in the Newborn

Elevations in temperature (38-39°C [100-103°F]) are occasionally noted on the 2nd or 3rd day of life in infants whose clinical course has been otherwise satisfactory. This disturbance is especially likely to occur in breast-fed infants whose intake of fluid has been particularly low or in infants who are overdressed or are exposed to high environmental temperatures, either in an incubator, in a bassinette near a radiator, or in the sun.

The infant may lose weight. A consistent relationship may not be seen between the fever and the extent of weight loss or inadequacy of fluid intake. Urinary output and the frequency of voiding diminish. The fontanel may be depressed. The infant takes fluids avidly, but the apparent vigor of the infant contrasts with the usual appearance of “being sick” from an infection. The rise in temperature may be associated with increases in serum levels of protein and sodium and in hematocrit. The possibility of local or systemic infection should be evaluated. Lowering the environmental temperature leads to prompt reduction of the fever and alleviation of symptoms. Oral hydration should be accomplished with additional nursing or formula and not with pure water, because of the risk of hyponatremia.

A more severe form of neonatal hyperthermia occurs in both newborn and older infants when they are warmly dressed. The diminished sweating capacity of newborn infants is a contributing factor. Warmly dressed infants left near stoves or radiators, traveling in well-heated automobiles, or left with bright sunlight shining directly on them through the windows of a closed room or automobile are likely to be victims. Body temperature may become as high as 41-44°C (106-111°F). The skin is hot and dry, and initially the infant usually appears flushed and apathetic. The extremities are warm. Tachypnea and irritability may be noted. This stage may be followed by stupor, grayish pallor, coma, and convulsions. Hypernatremia may contribute to the convulsions. Mortality and morbidity (brain damage) rates are high. Hyperthermia has been associated with sudden infant death, hemorrhagic shock, and encephalopathy syndrome (Chapter 64). The condition is prevented by dressing infants in clothing suitable for the temperature of the immediate environment. In newborn infants, exposure of the body to usual room temperature or immersion in tepid water usually suffices to bring the temperature back to normal levels. Older infants may require cooling for a longer time by repeated immersion. Attention to possible fluid and electrolyte disturbance is essential.

Hyperthermia a few days after birth can be due to infection, particularly herpes sepsis. Infants with infection appear ill with cold extremities, in contrast to those in whom hyperthermia is due to environmental causes.

Neonatal Cold Injury

Neonatal cold injury usually occurs in abandoned infants, infants in inadequately heated homes during cold spells when the outside temperature is in the freezing range, and in preterm infants (Chapter 69). The initial features are apathy, refusal of food, oliguria, and coldness to touch. The body temperature is usually between 29.5 and 35°C (85-95°F), and immobility, edema, and redness of the extremities, especially the hands and feet, and of the face are observed. Bradycardia and apnea may also occur. The facial erythema frequently gives a false impression of health and delays recognition that the infant is ill. Local hardening over areas of edema may lead to confusion with scleredema. Hypoglycemia and acidosis are common. Hemorrhagic manifestations are frequent; massive pulmonary hemorrhage is a common finding at autopsy. Hypothermia in preterm infants can be prevented with special plastic wraps that reduce evaporation and heat loss. Because of their high ratio of surface area to body mass, preterm infants are very vulnerable to evaporation heat loss. Infants at <28-30 wk should be placed inside a clear polyethylene bag without prior drying. Neonatal cold injury in preterm infants occurs in the developing world and can be prevented with skin-to-skin (kangaroo mother) care. Treatment consists of warming and paying scrupulous attention to recognition and correction of hypotension and metabolic imbalances, particularly hypoglycemia. Prevention consists of providing adequate environmental heat. The mortality rate is about 10%; about 10% of survivors have evidence of brain damage.

Edema

Generalized edema occurs in association with hydrops fetalis (Chapter 97.2) and in the offspring of diabetic mothers. In premature infants, edema is often a consequence of a decreased ability to excrete water or sodium, although some have considerable edema without identifiable cause. Infants with respiratory distress syndrome may become edematous without heart failure. Edema of the face and scalp may be caused by pressure from the umbilical cord around the neck, and transient localized swelling of the hands or feet may similarly be due to intrauterine pressure. Edema may be associated with heart failure. A lag in renal excretion of electrolytes and water may result in edema after a sudden large increase in intake of electrolytes, particularly with feeding of concentrated cow’s milk formulas. High-protein formulas may also cause edema as a result of the excessive renal solute load, particularly in premature infants. Rarely, idiopathic hypoproteinemia with edema lasting weeks or months is observed in term infants. The cause is unclear, and the disturbance is benign. Persistent edema of 1 or more extremities may represent congenital lymphedema (Milroy disease) or, in females, Turner syndrome. Generalized edema with hypoproteinemia may be seen in the neonatal period with congenital nephrosis and rarely with Hurler syndrome or after feeding hypoallergenic formulas to infants with cystic fibrosis of the pancreas. Sclerema is described in Chapter 639.

Hypocalcemia (Tetany) (Chapter 48)

Hypomagnesemia

Rarely, hypomagnesemia of unknown cause may occur in newborn infants, usually in association with hypocalcemia. It may also be associated with insufficient stores of skeletal magnesium secondary to deficient placental transfer, decreased intestinal absorption, neonatal hypoparathyroidism, hyperphosphatemia, renal loss (primary or secondary to drugs, e.g., amphotericin B), a defect in magnesium and calcium homeostasis, or iatrogenic deficiency caused by loss incurred during exchange transfusion or insufficient replacement during total intravenous alimentation. Infants of diabetic mothers may have lower than normal serum magnesium levels. The clinical manifestations of hypomagnesemia are indistinguishable from those of hypocalcemia and tetany and may, in fact, contribute to the accompanying hypocalcemia.

Hypomagnesemia occurs when serum magnesium levels fall below 1.5 mg/dL (0.62 mmol/L), although clinical signs do not usually develop until serum magnesium levels fall below 1.2 mg/dL. During exchange transfusion with citrated blood, which is low in magnesium because of binding by citrate, serum magnesium decreases about 0.5 mg/dL (0.2 mmol/L); approximately 10 days are required for return to normal. In non-iatrogenic hypomagnesemia, the serum magnesium level may be <0.5 mg/dL. Serum calcium in either instance is usually at levels noted in hypocalcemic tetany, but the serum phosphorus value is normal or high. Because the hypocalcemia accompanying hypomagnesemia is inadequately corrected by administration of calcium alone, hypomagnesemia should also be suspected in any patient with tetany not responding to calcium therapy.

Immediate treatment consists of intramuscular injection of magnesium sulfate. For newborn infants, 25-50 mg/kg/dose every 8 hr for 3-4 doses usually suffices. The accompanying hypocalcemia usually corrects itself as the hypomagnesemia resolves. The same daily dose can be given for oral maintenance therapy. Four to 5 times higher doses may be required in malabsorptive states. In most cases, the metabolic defect is transient, and treatment can be discontinued after 1-2 wk. A few patients appear to have a permanent form of the disease that requires continuous oral supplementation with magnesium to prevent recurrence of hypomagnesemia. No residual damage to the central nervous system is evident after prompt treatment.

Hypermagnesemia

Hypermagnesemia may occur in newborn infants of mothers treated with magnesium sulfate during labor. At high serum levels, the central nervous system is depressed and infants have respiratory depression that may require mechanical ventilation. Lower levels may result in hypoventilation, lethargy, flaccidity, hyporeflexia, and poor sucking. Hypermagnesemia may be associated with failure to pass meconium. The upper limit of normal magnesium is 2.8 mg/dL (1.15 mmol/L), but serious symptoms rarely occur at levels < 5 mg/dL (2.1 mmol/L). In most cases, no specific therapy (beyond supportive care and maintenance of respiratory support) is required. Intravenous calcium and diuresis will reduce the magnesium levels. In rare cases, exchange transfusion has been used for rapid removal of magnesium ion from the blood.

Substance Abuse and Neonatal Abstinence (Withdrawal)

Substance abuse during pregnancy is a serious problem for both the mother and her newborn. The mother may suffer adverse consequences of her addiction, including episodes of drug withdrawal during pregnancy and illnesses related to high-risk behavior. Effects on the fetus and newborn include chronic or intermittent drug exposure, poor maternal nutrition, acute withdrawal shortly after birth, and long-term effects on physical growth and neurodevelopment. Because infants with in utero drug exposure often have social and environmental risk factors and may have been exposed to multiple substances, it may be difficult to evaluate the effects of specific in utero drug exposure on long-term neurodevelopmental outcome.

Pregnancies in women who use illegal drugs or alcohol are high risk. Prenatal care is usually inadequate, and these women have a higher incidence of sexually transmitted infections, including syphilis, HIV, and hepatitis. In addition, the risk of preterm labor, intrauterine growth restriction, premature rupture of membranes, and perinatal morbidity and mortality is higher. Physiologic addiction to narcotics occurs in most infants born to actively addicted mothers because opiates cross the placenta. Withdrawal may manifest even before birth as increased activity of the fetus when the mother feels a need for the drug or withdrawal symptoms develop. Heroin and methadone are the drugs most frequently associated with withdrawal syndromes, but such syndromes may also occur with alcohol, nicotine, phenobarbital, pentazocine, codeine, propoxyphene, hydroxyzine, amphetamines, neuroleptics, antidepressants, and benzodiazepines.

Heroin addiction results in a 50% incidence of LBW infants, half of whom are small for gestational age. Chronic infections, maternal undernutrition, and a direct fetal growth–inhibiting effect are possible causes. The rate of stillbirths is increased, but not the incidence of congenital anomalies. Clinical manifestations of withdrawal occur in 50-75% of infants, usually beginning within the 1st 48 hr, depending on the daily maternal dose (<6 mg/24 hr is associated with no or mild symptoms), the duration of addiction (duration > 1 yr has a > 70% incidence of withdrawal), and the time of the last maternal dose (the incidence is higher if the last dose was taken within 24 hr of birth). Rarely, symptoms may appear as late as 4-6 wk of age. The incidence of respiratory distress syndrome and hyperbilirubinemia may be decreased in preterm infants of heroin users; accelerated production of pulmonary surfactant may explain the former, and enzyme induction of hepatic glucuronyl transferase the latter.

Tremors and hyperirritability are the most prominent symptoms. The tremors may be fine or jittery and indistinguishable from those of hypoglycemia, but they are more often coarse, “flapping,” and bilateral; the limbs are frequently rigid, hyperreflexic, and resistant to flexion and extension. Irritability and hyperactivity are generally marked and may lead to skin abrasions. Other signs include wakefulness, hyperacusis, hypertonicity, tachypnea, diarrhea, vomiting, high-pitched cry, fist sucking, poor feeding with weight loss (disorganized sucking), and fever. Sneezing, yawning, hiccups, myoclonic jerks, convulsions, abnormal sleep cycles, nasal stuffiness, apnea, flushing alternating rapidly with pallor, and lacrimation are less common. The Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) is a useful way to evaluate neonates exposed to opiates or other drugs (Table 100-1). The risk of sudden infant death syndrome is higher in such neonates. The diagnosis is generally established from the history and clinical findings. Examining the urine for opiates may reveal only low levels during withdrawal, but quinine, which is often mixed with heroin, may be present in higher concentrations. Meconium testing is more accurate than neonatal urine drug testing. Hypoglycemia and hypocalcemia should be excluded.

Table 100-1 NEUROBEHAVIORAL SCALE

CNS, central nervous system.

From Lester BM, Tronick EZ, Brazelton TB: The Neonatal Intensive Care Unit Network Neurobehavioral Scales procedures, Pediatrics 113:641–667, 2004.

Methadone addiction is associated with severe withdrawal symptoms, the incidence varying from 20 to 90%. Mothers taking methadone usually have better prenatal care than those taking heroin; these mothers have a high incidence of polysubstance abuse, including alcohol, barbiturates, and tranquilizers, and they are often heavy smokers. The incidence of congenital anomalies is not increased. The average birthweight of infants of mothers taking methadone is higher than that of infants of heroin-addicted mothers; the clinical manifestations are similar, except that the former group has a higher incidence of seizures (10-20%) and later onset (2-6 wk of age) of withdrawal. Women who continue to abuse heroin, even if they enter a methadone program, are more likely to have preterm and/or low birthweight infants than those born to women who stop using heroin. They are also more likely to suffer withdrawal and have a higher risk of neonatal mortality

Alcohol withdrawal is uncommon. Infants of women who have been drinking immediately before delivery may have alcohol on their breath for several hours because it rapidly crosses the placenta. Blood levels in the infant are similar to those in the mother. Hypoglycemia and metabolic acidosis may be present. Infants in whom withdrawal symptoms develop often become agitated and hyperactive, with marked tremors lasting 72 hr, followed by about 48 hr of lethargy before return to normal activity. Seizures may develop.

Phenobarbital withdrawal usually occurs in infants of mothers addicted to the drug. Symptoms begin at a median age of 7 days (range, 2-14 days). Infants may have a brief acute stage consisting of irritability, constant crying, sleeplessness, hiccups, and mouthing movements, followed by a subacute stage consisting of voracious appetite, frequent regurgitation and gagging, episodic irritability, hyperacusis, sweating, and a disturbed sleep pattern, all of which may last 2-4 mo.

Cocaine abuse in pregnant women is common, but withdrawal in their infants is unusual; the pregnancy may be complicated by premature labor, abruptio placentae, and fetal asphyxia. Infants may have intrauterine growth restriction and neurobehavioral deficits characterized by impaired state regulation, impaired auditory information processing, developmental delay, and learning disabilities. At 24 mo of age, they score lower on the mental portion of the Bayley Scales of Infant Development and are twice as likely to have developmental delay. Family disorganization, polysubstance abuse, sexually transmitted infections, and child abuse and neglect may also be present. At 4 yr of age, children exposed prenatally to cocaine demonstrate specific cognitive impairments (visual-spatial and math skills; general knowledge) and are less likely to have an IQ above the normative mean. With a more enriching home environment, IQ scores of cocaine-exposed children are similar to those of nonexposed children.