METABOLIC DISORDERS IN NEWBORN

Some important metabolic problems in newborns are as follows:

Hypoglycemia is the commonest metabolic problem in newborn, generally defined as blood glucose (BG) values of lt;25 mg/dl during first 3 hours, lt;35 mg/dl between 3 and 24 hours and lt;45 mg/dl beyond the first day, irrespective of gestation or birth weight.

However, there is lack of consensus on cut-off BG value and current practice is based on operational thresholds for intervention, i.e. BG should be maintained gt;60 mg/dl in symptomatic neonates after 48 hrs of life. Etiology: Normal fetal glucose levels are ~2/3rd of maternal values, which drop further during first two hours before rising again to normalize by 3-4 hours of age. Poor fetal reserves in preterm/LBW babies and delayed feeding are two most common causes of neonatal hypoglycemia (Table 12.57).

TABLE 12.57: Risk-factors for neonatal hypoglycemia

• Preterms, low birth weight and IUGR

• Large for date or post-term newborns

• Infants of diabetic mother (IDM)

• Delayed or inadequate feeding

• Rh-incompatibility and exchange transfusion

• Critical illness: Polycythemia, sepsis, hypothermia

• Inborn errors of metabolism (rare)

Clinical manifestations of hypoglycemia not necessarily correlate with blood glucose level. Most cases present on 2^nd-3^rd day with:

• Abnormal movements, e.g. jitteriness, tremors or seizures,

• Abnormal behavior, e.g. apathy, limpness, refusal to feeds and coma,

• Autonomic disturbances, e.g. recurrent apnea, tachy­cardia, sudden pallor, sweating, etc.

Diagnosis rests low blood glucose levels, preferably from laboratory. Dextrostix, while adequate for screening, are not reliable at very low glucose levels.

Prevention of hypoglycemia includes: (a) early breast­feeding, (b) routine glucose monitoring in high-risk newborns at 2,6,12, 24, 48 and 72 hours, and (c) prevention/ treatment of precipitating factors, e.g.

Routine BG monitoring is recommended for all preterms lt; 35 weeks, LBW lt; 2000 gm, infant of diabetic mothers, large-for-date babies and sick newborns.

Management depends on the severity of hypoglycemia as follows:

• Symptomatic hypoglycemia or BG levels lt; 20 mg /dl irrespective of symptoms, need IV bolus of Dextrose 10%, followed by slow infusion of 6-12 mg/kg/ min to maintain BG levels gt;45 mg/dl for at least 24 hours before tapering slowly under monitoring and simultaneously ensuring oral feeds.

• Asymptomatic hypoglycemia with BG gt;20 mg/dl does not need urgent correction and treated with adequate feeding and additional sugar-fortified feeds, if necessary. However, BG must be reassessed after 30 minutes and must be treated with IV Dextrose 10%, if remains lt;40 mg/dl.

• Refractory hypoglycemia, defined as failure to maintain normal BG levels despite 12 mg/kg/ min of Dextrose 10% infusion for 48 hours must be investigated for endocrinal disorders, (e.g. adrenal insufficiency), hyperinsulinemic states, (e.g. Islet cell hyperplasia) and inborn errors of metabolism, (e.g. glycogen storage disorders). Some of them may benefit with IV hydrocortisone (5 mg/kg), IV Glucagon (300 mg/kg) or IV Diazoxide (25 mg/kg/d q8hr) therapy. Glucagon is more useful in high-insulin hypoglycemia, e.g. infants of diabetic mothers and hemolytic disease of newborn.

Outcome: Untreated symptomatic hypoglycemia may be fatal, though timely intervention ensures dramatic recovery. Persistent hypoglycemia in newborn may leave neurodevelopmental problems in 30-70% cases.

Hypocalcemia is second commonest metabolic dis­order in newborns, defined as S. calcium lt;7 mg/dl in preterms and lt;8 mg/dl in term newborns or ionic fraction lt; 4 mg/dl.

TABLE 12.58: Causes of neonatal hypocalcaemia

• Early-onset (with 24-72 hours)

- Preterms and VLBWs

- Infants of diabetic mothers

- Perinatal complications, e.g. prolonged labor

- Maternal medications, e.g.

• Late-onset (classic tetany)

- Formula-fed newborn (wrong Ca:P ratio)

- Iatrogenic—ET, rapid acidosis correction

- Maternal hyperparathyroidism

- Hypoparathyroidism, e.g. DiGeorge syndrome

ET: Exchange transfusion

Etiology of hypocalcemia differs with age of presentation (Table 12.58).

• Early-onset hypocalcemia (lt;72 hour) is common in preterms due to poor storage and immature renal functions to conserve calcium.

• Late-onset hypocalcemia is common in formula-fed newborns, due to high phosphorus content that prevents calcium absorption.

Clinical features of hypocalcemia include:

• Seizures, usually on 3rd day, in otherwise alert and active newborn,

• Neuromuscular irritability, e.g. jitteriness, sustained clonus and high-pitched cry. Well-defined tetany is uncommon in newborns.

Diagnosis depends on S. Calcium levels including ionic fraction, drawn before the therapy and therapeutic response to IV calcium infusion. Parathyroid studies are indicated in refractory hypocalcemia.

Management of hypocalcemia includes:

• Symptomatic cases should be treated by IV Calcium gluconate 10%, 2 ml/kg (half-diluted in DW 5%), infused slowly at the rate of lt;1 ml/min with cardiac monitoring for bradycardia. Maximum dose is 10 ml in term newborns and 5 ml in preterms. Post-bolus, a maintenance dose of 2 mg/kg 6-hrly must be continued for next 24-48 hours, before switch-over on oral maintenance. IV site should also be observed for extravasation.

• Asymptomatic hypocalcemia or symptomatic cases after initial therapy as above, should receive oral elemental calcium supplements as 40-80 mg/kg/d for next 3 days.

• Unresponsive hypocalcemia may be associated with hypomagnesemia, which needs to be corrected along with calcium therapy (as discussed below).

Outcome is excellent in hypocalcemic seizures, with no neurodevelopmental sequelae, unless due to primary cause.

Hypomagnesemia, defined as serum magnesium levels lt; 1.2 mEq/L, is relatively uncommon, usually seen along

with hypocalcemia in IUGR babies, infants of diabetic mothers and after diarrhea.

Clinically Hypomagnesemia per se rarely produces seizures, but in its presence, hypocalcemic seizures do not respond to calcium therapy.

Treatment includes IM magnesium sulphate 50% (0.2 ml/kg), two doses at 12-hour interval, followed by oral supplements (30 mg/d) for 3-5 days.

Late metabolic acidosis is common in top-fed preterms (5-10%), due to high solute load in formula milks and immature renal acidification.

Clinically, these cases present in 2^nd-3^rd week, with failure to thrive, tachypnea without lung signs, circumoral pallor and sluggish activity.

Diagnosis rests on blood gas analysis showing: (a) persistent metabolic acidosis, (b) increased anion gap, (c) normal/low pCO₂, and (d) base excess lt;5 mmol/L. Treatment includes oral NaHCO₃ therapy for 2 weeks or till 35 weeks of conceptional maturity, with suitable modifications in formula-feeds.

Infant of diabetic mother (IDM): Diabetes mellitus, including gestational diabetes, is the commonest metabolic disorder in pregnancy with significant effects of fetal outcome.

Pathological effect on fetus: Hyperglycemic state in mother leads to fetal hyperglycemia with compensatory rise in fetal insulin levels and islet cell hyperplasia. In presence of fetal hyperglycemia, insulin acts as an anabolic hormone-leading to macrosomia. Post-birth, with sudden cut-off of transplacental glucose supply, this high insulin-state may precipitate severe hypoglycaemia in early neonatal period.

Clinically IDMs present with:

• Typical physical features, i.e. macrosomia, moon facies, hypertrichosis and hairy pinna.

• Complications, e.g.

- Obstructed labor and birth trauma due to large size,

- Hypoglycemia and hypocalcemia (on 2^nd-3^rd day),

- Hyaline membrane disease (surfactant maturity),

- Polycythemia, leading to hyperbilirubinemia and renal vein thrombosis.

Congenital malformations, e.g. CHDs (specially asymmetric septal hypertrophy), neural tube defects and small left-colon syndrome, are also common in IDMs.

Management of IDMs include:

• Antenatal management: Oral hypoglycemic agents are contraindicated in pregnancy due to teratogenic effects and intractable hypoglycemia in newborn and near-normoglycemic state should be maintained with insulin. Periodic monitoring of amniotic fluid surfactant activity by L:S ratio is advised to ensure adequate maturity at birth.

• Obstetrical care: Planned delivery is preferable in most cases and those with large fetal size may be taken for elective caesarean section.

• Postnatal management includes: (a) early feeding within 30 minutes to prevent hypoglycemia, (b) glucose monitoring at 2, 6, 12, 24, 48 and 72 hours, (c) detection and treatment of hypoglycemia as well as other complications, e.g. HMD, polycythemia, hyperbilirubinemia and other metabolic disturbances, and (d) management of co-existing malformations, e.g. cardiac disease. All IDMs with respiratory dis­tress must undergo echocardiography to exclude asymmetric septal hypertrophy.

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