You are in: eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology Hemochromatosis, NeonatalArticle Last Updated: Mar 6, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Roland L Boyd, DO, FAAP, FACOP, Neonatologist, Section of Neonatology, Neonatal Services Limited Roland L Boyd is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, and American College of Osteopathic Pediatricians Coauthor(s): Jatinder Bhatia, MBBS, Professor of Pediatrics, Chief, Section of Neonatology, Department of Pediatrics, Medical College of Georgia; Joseph H Clark, MD, Professor, Department of Pediatric, Division of Gastroenterology, Medical College of Georgia Editors: Hisham Nazer, MBBCh, FRCP, Professor of Pediatrics, Consultant in Pediatric Gastroenterology, Hepatology and Clinical Nutrition, Bushnaq Medical Centre, University of Jordan; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; David Piccoli, MD, Chief, Division of Gastroenterology and Nutrition, Department of Pediatrics, The Children's Hospital of Philadelphia; Professor, University of Pennsylvania School of Medicine; Steven M Schwarz, MD, FAAP, FACN, AGAF, Professor of Pediatrics, State University of New York, Downstate Medical Center College of Medicine; Distinguished Lecturer, New York Medical College, School of Public Health; Carmen Cuffari, MD, Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine Author and Editor Disclosure Synonyms and related 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 INTRODUCTIONSection 2 of 10
  BackgroundNeonatal hemochromatosis is a syndrome in which severe liver disease of fetal or perinatal onset is associated with deposition of stainable iron in extrahepatic sites.1 The distribution of extrahepatic iron mimics that observed in hepatic iron (HFE) disease, the most common form of hemochromatosis known in Europe and the Americas, and liver disease is common in late-stage HFE disease. Nonetheless, neonatal hemochromatosis is not a manifestation of HFE disease. Neonatal hemochromatosis is not a single disorder but is a syndrome with an unclear etiology. Neonatal hemochromatosis represents disordered iron handling due to injury to the perinatal liver.2 Neonatal hemochromatosis can be thought of as a form of fulminant hepatic failure. Four pieces of evidence suggest that neonatal hemochromatosis may be due to an acquired and persistent maternal factor. (1) Neonatal hemochromatosis recurs within sibships at a rate higher than expected for disorders transmitted in an autosomal recessive manner. (2) Several kindreds are known in which mothers have given birth to children with neonatal hemochromatosis who were fathered by different men. (3) Several kindreds are known in which parents of children with neonatal hemochromatosis had histories of exposure to blood with or without clinical hepatitis. (4) Anecdotal evidence suggests that administering intravenous immunoglobulin during pregnancy in a woman who has already had an infant with neonatal hemochromatosis leads to a relatively favorable outcome. This data suggest mitochondrial disease; transplacental transmission of an infective, possibly viral, agent; or transplacental transmission of an antibody as a cause of at least some instances of neonatal hemochromatosis. Because neonatal hemochromatosis is a syndrome, any of these possibilities may be correct in a given family, and all of them must be considered. Treatment after birth requires supportive care with or without administration of an iron-chelating cocktail and several antioxidants. Liver transplantation has saved some babies. Liver disease ascribed to siderosis has not recurred in survivors to date. PathophysiologyIn hemochromatosis, hepatocytes are the first site of iron deposition. This then extends to involve the hepatic lobule and the pancreatic parenchyma. The myocardial and endocrine systems may also be involved, which can lead to failure of both. The effects can be observed antenatally with involvement of the placenta, causing placental edema and oligohydramnios. These infants may be stillborn, premature, or have intrauterine growth retardation (IUGR). FrequencyUnited StatesNeonatal hemochromatosis is rare.3 To date, no rates of this disease are reported. Studies suggest a genetic prevalence of 0.03-0.038 or a heterozygosity prevalence of 6-7%. Mortality/MorbidityThe prognosis is extremely poor. Some infants recover with supportive care, but this rarely occurs. Survival is documented in patients who have received liver transplantation. RaceNeonatal hemochromatosis has been documented in Filipino, African American, Hong Kong Chinese, and Caucasian infants. No reported increase rates in any race are noted to date. SexNo sex predilection is known. AgeNeonatal hemochromatosis is thought to occur with damage to the liver at 16-30 weeks' gestation. CLINICALSection 3 of 10
HistoryClues that the patient has or does not have neonatal hemochromatosis may not be present. Clues in pregnancy may indicate the diagnosis of neonatal hemochromatosis, but they are nonspecific.
Physical
CausesThe exact cause of neonatal hemochromatosis remains a mystery. The following are two schools of thought:
DIFFERENTIALSSection 4 of 10
Galactose-1-Phosphate Uridyltransferase Deficiency (Galactosemia)
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| Drug Name | Deferoxamine (Desferal mesylate) |
|---|---|
| Description | 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 Dose | 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 Dose | 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 |
| Contraindications | Documented hypersensitivity; severe renal disease and anuria (dose reduction after the loading dose should be considered in these circumstances) |
| Interactions | Concomitant administration with prochlorperazine can cause transient loss of consciousness |
| 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 |
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.
| Drug Name | N-Acetylcysteine (Mucomyst) |
|---|---|
| Description | 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. |
| Pediatric Dose | 200 mg/kg/d PO divided q8h for 17-21 doses |
| Contraindications | Documented hypersensitivity |
| Interactions | None reported |
| 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 |
| Drug Name | Alpha-tocopherol (Liquid E TPGS) |
|---|---|
| Description | 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. |
| Pediatric Dose | 20-25 IU/kg/d PO divided bid |
| Contraindications | Documented hypersensitivity |
| Interactions | Mineral oil decreases absorption of vitamin E; vitamin E delays absorption of iron and increases effects of anticoagulants |
| 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 |
| Drug Name | Selenium |
|---|---|
| Description | Essential trace element part of enzyme glutathione peroxidase. Protects cell components from oxidative damage due to peroxides produced in cellular metabolism. |
| Pediatric Dose | 2-3 mcg/kg/d PO/IV |
| Contraindications | Documented hypersensitivity |
| Interactions | None reported |
| 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) |
These agents elicit cryoprotective effect.
| Drug Name | Prostaglandin E1 (Alprostadil) |
|---|---|
| Description | 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. |
| Pediatric Dose | 0.4 mcg/kg/d IV initially, increase to 0.6 mcg/kg/d IV for 3-4 wk |
| Contraindications | Documented hypersensitivity |
| Interactions | 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 |
| 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 |
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.
| Drug Name | Beractant (Survanta) |
|---|---|
| Description | 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. |
| Pediatric Dose | 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 |
| Contraindications | None known |
| Interactions | None reported |
| 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 |
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.
| Drug Name | Dopamine (Intropin) |
|---|---|
| Description | 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 Dose | 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 Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity; hypersensitivity to sulfites; ventricular fibrillation; pheochromocytoma |
| Interactions | Phenytoin, alpha- and beta-adrenergic blockers, general anesthesia, and MAOIs increase and prolong effects of dopamine |
| 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 |
| Drug Name | Dobutamine (Dobutrex) |
|---|---|
| Description | 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 Dose | 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 Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity; IHSS; hypertension; recent MI; arrhythmia; hypovolemia |
| Interactions | Beta-adrenergic blockers antagonize effects of dobutamine; general anesthetics may increase toxicity |
| 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 |
Hemochromatosis, Neonatal excerpt
Article Last Updated: Mar 6, 2008
