eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology
Hemochromatosis, Neonatal: Treatment & Medication
Updated: Mar 6, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Current care is basically supportive. No definitive or curative care has been identified as of this publication; however, experience with treatment is very limited. Some limited use of deferoxamine and multiple antioxidants has occurred and is discussed in Medication.5
Whitington and Hibbard conducted a recent study at the Feinberg School of Medicine of Northwestern University; 15 women whose most recent pregnancy ended in documented neonatal hemochromatosis were treated with intravenous immunoglobulin 1 g/kg/wk from 18 week's gestation until end of gestation.6 Twelve infants had evidence of neonatal hemochromatosis, but all survived with or without medical treatment and were healthy at the time of the report. However, this is a small study, and further trials are needed.
- ABCs: The first order of treatment in infants with neonatal hemochromatosis is to establish the ABCs because the infants are usually born very ill or deteriorate shortly thereafter. Therefore, intubate infants with neonatal hemochromatosis shortly after birth to establish a patent airway. Also, if any cardiovascular support is needed, such as volume replacement or inotropic therapy, add it accordingly.
- Respiratory system: Intubation is usually warranted because infants with neonatal hemochromatosis are born prematurely and possibly require surfactant to improve their lung function. These infants can also have pneumonia and, in severe cases, pleural effusions.
- Cardiovascular system: These infants usually require some sort of pressor support because of poor contractility and the deposition of iron in the myocardium. Also, these infants are born with heart failure and require much cardiac support.
- GI system: General support care of nutrition and replacement of hematologic factors, such as fresh-frozen plasma (FFP), platelets, cryoprecipitate, and packed red blood cells (PRBCs), are necessary.
Surgical Care
At present, the only surgical option is liver transplantation. This is the only known curative treatment. Studies have shown that iron does not redeposit after transplantation.
Consultations
Consult a pediatric gastroenterologist and pediatric surgeon if transplantation may be needed.
- Because of the rarity of this disease process, a pediatric gastroenterologist can provide recent updates in research and experimental therapy.
- Consult a pediatric surgeon for possible transplantation and need for possible biopsy for accurate diagnosis.
- Social services are offered mainly for family and financial support.
Medication
Few drugs are available for treating neonatal hemochromatosis. Infants with neonatal hemochromatosis have been treated with a combination of antioxidants, cryoprotective agents, and chelation. Three antioxidants are used throughout the course of therapy: N -acetylcysteine, alpha-tocopherol polyethylene glycol succinate (TPGS), and selenium. These are used in combination with prostaglandin E and deferoxamine, which have a cryoprotective effect and which chelate iron, respectively. The few infants who received this combination therapy had normalization of liver function, improved clotting factors, and decrease in serum ammonia levels.
A suggested cocktail is the following: N -Acetylcysteine 200 mg/kg/d PO divided tid for 17–21 doses, alpha-TPGS 25 IU/kg/d PO divided bid for 6 wk, deferoxamine 30 mg/kg/d IV infused over 8 h until the serum ferritin level is less than 500 mcg/L, selenium 3 mcg/kg/d IV continuous infusion for the length of hospitalization, and prostaglandin E1 0.4 mcg/kg/h IV increased to 0.6 mcg/kg/h over 3-4 h. The infusion is maintained for 10 d.7
Chelating agents
These agents inhibit toxin by reacting with it to form less active or inactive complex. The complex is then excreted from the body.
Deferoxamine (Desferal mesylate)
Freely soluble in water. Approximately 8 mg of iron bound by 100 mg. Excreted in urine and bile and produces red discoloration of urine. Readily chelates iron from ferritin and hemosiderin but not transferrin. Most effective with continuous infusion. May be administered IM, SC, or slow IV infusion. Does not effectively chelate other trace metals of nutritional importance. Vials contain 500 mg of lyophilized sterile drug; add 2 mL sterile water for injection to each vial, bringing concentration to 250 mg/mL. For IV use, may be diluted in 0.9% sterile saline, dextrose 5% in water (D5W), or Ringer solution.
IM preferred except in patients with hypotension and cardiovascular collapse, in whom IV should be considered.
Controversial in treatment of neonatal hemochromatosis, for which experience is limited; therefore, use with caution.
Adult
90 mg/kg IM initially, then 45 mg/kg; not to exceed 1 g/dose q4-12h, 6 g/d
15 mg/kg/h IV: not to exceed 90 mg/kg q8h or 6 g/d
Pediatric
30 mg/kg IV infused over minimum 2h, may repeat until serum ferritin <500 mcg/L
10-15 mg/kg/h IV; not to exceed 20 mg/kg/h
Concomitant administration with prochlorperazine can cause transient loss of consciousness
Documented hypersensitivity; severe renal disease and anuria (dose reduction after the loading dose should be considered in these circumstances)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Limited data in human pregnancy (use only if potential benefit justifies potential risk to fetus); long term and high doses may cause auditory and ocular toxicity; tachycardia, hypotension, and shock may occur with long-term therapy and can add to cardiovascular collapse due to iron toxicity; GI adverse effects include abdominal discomfort, nausea, vomiting, and diarrhea, which may add to the symptoms of acute iron toxicity; flushing and fever reported
Antioxidants
These agents protect sensitive tissues throughout the body from oxidizing substances known as free radicals. Although antioxidants protect most cell membranes, vitamin E is particularly important in preventing damage to the linings of blood vessels and maintaining good circulation.
N-Acetylcysteine (Mucomyst)
Derivative of amino acid cysteine and scavenger of oxygen free radicals. Also glutathione precursor and used to replenish depleted intracellular glutathione. Therefore, theoretically augments antioxidant defenses.
Adult
Pediatric
200 mg/kg/d PO divided q8h for 17-21 doses
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
GI distress may occur
Alpha-tocopherol (Liquid E TPGS)
Vitamin E particularly important in preventing damage to linings of blood vessels and maintaining good circulation. Acts as antioxidant in cell membranes to prevent propagated oxidation of unsaturated fatty acids. Also known to impair hematologic response to iron.
Adult
Pediatric
20-25 IU/kg/d PO divided bid
Mineral oil decreases absorption of vitamin E; vitamin E delays absorption of iron and increases effects of anticoagulants
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Pregnancy category C if dose above RDA; vitamin E may induce vitamin K deficiency; necrotizing enterocolitis may occur when large doses of vitamin E administered
Selenium
Essential trace element part of enzyme glutathione peroxidase. Protects cell components from oxidative damage due to peroxides produced in cellular metabolism.
Adult
Pediatric
2-3 mcg/kg/d PO/IV
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
High doses of selenium cause adverse embryologic effects in chickens; do not use injection that contains benzyl alcohol in neonates because associated with fatal toxic syndrome (ie, metabolic acidosis, CNS, respiratory, circulatory, renal function impairment)
Prostaglandins
These agents elicit cryoprotective effect.
Prostaglandin E1 (Alprostadil)
Used primarily to keep patency of ductus arteriosus but also has mild pulmonary vasodilatory effect. Reported to inhibit macrophage activation, neutrophil chemotaxis, and release of oxygen radicals and lysosomal enzymes. Affects coagulation by inhibiting platelet aggregation and possibly by inhibiting activation of factor X. May promote fibrinolysis by stimulating production of tissue plasminogen activator.
Adult
Pediatric
0.4 mcg/kg/d IV initially, increase to 0.6 mcg/kg/d IV for 3-4 wk
Limited data; caution with concurrent use of antiplatelet drugs, anticoagulants, thrombolytic agents, and other drugs that affect bleeding (eg, cefamandole, cefoperazone, cefotetan, moxalactam); vasodilators may cause additive effect; sympathomimetics may counteract effect
Documented hypersensitivity
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Adverse effects and toxicity include apnea, seizures, fever, hypotension, leukocytosis, fever, and pulmonary overcirculation; neonates may require intubation because of potential risk of apnea (10-12%); prolonged use may be associated with third spacing of fluid; monitor blood oxygenation and arterial pressure
Surfactants
Exogenous surfactant can be helpful in treatment of airspace disease (eg, respiratory distress syndrome [RDS]). After inhaled administration, surface tension is reduced and alveoli are stabilized, decreasing the work of breathing and increasing lung compliance.
Beractant (Survanta)
Mimics surface tension–lowering properties of natural lung surfactant. Contains colfosceril palmitate, cetyl alcohol, and tyloxapol. Used for prophylaxis of RDS in premature infants with birthweight <1350 g or RDS in premature infants with birthweight >1350 g who have evidence of pulmonary immaturity. Also used for rescue treatment of infants who develop RDS.
Adult
Pediatric
100 mg (ie, 4 mL)/kg/dose intratracheally divided in 4 aliquots administered at least 6 h apart
Prophylaxis: Administer as soon as possible after delivery; repeat at 12 and 24 h
Rescue: Usually 2 doses administered 12 h apart
None reported
None known
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Increased episodes of pulmonary hemorrhage in infants <700 g were reported in the clinical trials; must be warmed to room temperature; administer only under carefully supervised conditions because of risk of acute airway obstruction
Inotropic agents
Positive inotropic agents increase the force of contraction of the myocardium and are used to treat acute and chronic congestive heart failure (CHF). Some may also increase or decrease the heart rate (ie, positive or negative chronotropic agents), provide vasodilatation, or improve myocardial relaxation. These additional properties influence the choice of drug for specific circumstances.
Dopamine (Intropin)
Used to treat hypotension not secondary to hypovolemia. Has preferential sparing effect on renal circulation. Often used with dobutamine. Stimulates adrenergic and dopaminergic receptors. Hemodynamic effect depends on dose. Low doses predominantly stimulate dopaminergic receptors that in turn produce renal and mesenteric vasodilation. High doses produce cardiac stimulation and renal vasodilation.
Mechanism of action in neonates controversial because of variations in endogenous norepinephrine stores, receptor function, and ability to increase stroke volume.
Low dose (<2 mcg/kg/min) provides dopaminergic stimulation and increases urine output, fractional excretion of sodium, and creatinine clearance.
Intermediate dose (2-10 mcg/kg/min) increases cardiac contractility and blood pressure at low doses and increases heart rate at high doses. Inotropic response varies with gestational age and baseline stroke volume.
High dose (>20 mcg/kg/min) predominantly increases systemic and pulmonary vascular resistance. Use with caution in patients with PPHN.
Adult
2-20 mcg/kg/min IV
Blood pressure support: 5-10 mcg/kg/min IV initially, titrate to effect
Renal perfusion: 2-3 mcg/kg/min IV
Example infusion: 10 mg in 25 mL D5W = 400 mcg/mL infused at 0.3-3 mL/kg/h IV (equivalent to 2-20 mcg/kg/min)
Pediatric
Administer as in adults
Phenytoin, alpha- and beta-adrenergic blockers, general anesthesia, and MAOIs increase and prolong effects of dopamine
Documented hypersensitivity; hypersensitivity to sulfites; ventricular fibrillation; pheochromocytoma
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Tachycardia and arrhythmias may occur; may increase pulmonary artery pressure
Dobutamine (Dobutrex)
Inotropic support in patients with shock and hypotension. Not a pressor. Used for demonstrated or suspected decreased cardiac contractility. Often used in concert with dopamine. Echocardiography is useful in evaluating need (eg, contractility, ventricular dilation, ejection fraction).
Produces vasodilation and increases inotropic state. At high dosages may increase heart rate. Onset of action 1-2 min, peak effect in 10 min. Administer as continuous IV infusion because half-life is several minutes. Metabolized in liver. Action synthetic catecholamine with primarily beta1-adrenergic activity. Increases myocardial contractility, cardiac index, oxygen delivery, and oxygen consumption. Decreases systemic and pulmonary vascular resistance in adults.
Adult
2-20 mcg/kg/min IV initially, increased doses may be required; not to exceed maximum rate of 40 mcg/kg/min
Initial dose: 10 mcg/kg/min IV with 5-10 mcg/kg/min IV dopamine
Pediatric
Administer as in adults
Beta-adrenergic blockers antagonize effects of dobutamine; general anesthetics may increase toxicity
Documented hypersensitivity; IHSS; hypertension; recent MI; arrhythmia; hypovolemia
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
May cause hypotension in hypovolemia; preliminary volume loading may be necessary; tachycardia at high dosage; arrhythmias; hypertension; cutaneous vasodilation; increases myocardial oxygen consumption; tissue ischemia occurs with infiltration
More on Hemochromatosis, Neonatal |
| Overview: Hemochromatosis, Neonatal |
| Differential Diagnoses & Workup: Hemochromatosis, Neonatal |
 Treatment & Medication: Hemochromatosis, Neonatal |
| Follow-up: Hemochromatosis, Neonatal |
| References |
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References
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Muller-Berghaus J, Knisely AS, Zaum R, et al. Neonatal haemochromatosis: report of a patient with favourable outcome. Eur J Pediatr. Apr 1997;156(4):296-8. [Medline].
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Whitington PF, Kelly S, Ekong UD. Neonatal hemochromatosis: fetal liver disease leading to liver failure in the fetus and newborn. Pediatr Transplant. Oct 2005;9(5):640-5. [Medline].
Neonatal gastroenterology. In: Neu J, ed. Clinical Perinatology. Vol 23. Philadelphia, PA: WB Saunders; 1996:327-8.
Gracey M, Burke V. Metabolic disorders. In: Pediatric Gastroenterology and Hepatology. 3rd ed. Boston, MA: Blackwell Scientific; 1991:611.
Knisely AS. Neonatal hemochromatosis. Adv Pediatr. 1992;39:383-403. [Medline].
Lebenthal E. Inherited metabolic liver disorders. In: Textbook of Gastroenterology and Nutrition in Infancy. 2nd ed. New York, NY: Raven; 1990:981-2.
Rand EB, McClenathan DT, Whitington PF. Neonatal hemochromatosis: report of successful orthotopic liver transplantation. J Pediatr Gastroenterol Nutr. Oct 1992;15(3):325-9. [Medline].
Rodrigues FM, Kallas M, Nash R. Neonatal hemochromatosis in eleven families: pattern of presentation and outcome [abstr]. Hepatol. 1999;9:1882-5.
United States Pharmacopeial Convention Inc. Drug Information for the Health Care Professional. Vol 1. 1997:18-21, 51-3, 1145-8, 2589-90.
Further Reading
Keywords
neonatal hemochromatosis, NH, neonatal iron storage disease, neonatal iron storage disorder, perinatal hemochromatosis fulminant, hepatic failure in utero, hepatic iron disease, HFE disease, siderosis, liver disease, placental edema, oligohydramnios, intrauterine growth retardation, IUGR, polyhydramnios, hyperpigmented skin, hepatomegaly, diabetes mellitus, oligoria, splenomegaly
