eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology

Hemochromatosis, Neonatal

Roland L Boyd, DO, FAAP, FACOP, Neonatologist, Section of Neonatology, Neonatal Services Limited
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

Updated: Mar 6, 2008

Introduction

Background

Neonatal 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.

Pathophysiology

In 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).

Frequency

United States

Neonatal 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/Morbidity

The prognosis is extremely poor. Some infants recover with supportive care, but this rarely occurs. Survival is documented in patients who have received liver transplantation.

Race

Neonatal 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.

Sex

No sex predilection is known.

Age

Neonatal hemochromatosis is thought to occur with damage to the liver at 16-30 weeks' gestation.

Clinical

History

Clues 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.

• Oligohydramnios is frequently observed.
• Polyhydramnios is less commonly observed.
• Suspect neonatal hemochromatosis if the infant develops liver disease and all other metabolic, infectious, and hemorrhagic causes are eliminated.
• Decreased fetal movement has been reported.
• Forty percent of infants born with neonatal hemochromatosis are premature.
• IUGR occurs in 25% of infants with neonatal hemochromatosis.

Physical

• The physical examination in the neonatal period is of little help but may reveal the following:
  • Placental edema
  • IUGR
  • Edema without ascites
  • Oliguria
  • Disseminated intravascular coagulation
  • Jaundice in the first few days after birth
  • Splenomegaly
• Postmortem examination reveals the following:
  • The liver is small, and the bile is stained. Contours may be irregular, and the stroma may be collapsed.
  • Microscopic examination of the liver reveals that the hepatocytes have giant cell transformation with bile plugs or that the hepatocytes may not be present at all. Also, the hepatocytes may show siderosis. Scarring from macrophages, which contain high levels of stainable iron, may be present.
  • Bile duct is proliferated.
  • The spleen, lymph nodes, and bone marrow contain minimal levels of stainable iron.
• Splenomegaly
  • Pancreatic islet cell hyperplasia
  • Absence of proximal renal tubules

Causes

The exact cause of neonatal hemochromatosis remains a mystery. The following are two schools of thought:

• The first hypothesizes that injury to the liver causes abnormal handling of iron by the liver.
• The other hypothesizes that the abnormal handling of iron by the liver leads to liver injury and failure.

Differential Diagnoses

Galactose-1-Phosphate Uridyltransferase Deficiency (Galactosemia)

Other Problems to Be Considered

Adenovirus
Coxsackie virus
Echovirus
Herpes virus
Alpha1-antitrypsin (A1At) deficiency
Maternofetal blood group incompatibility
Hemophagocytic syndrome
Hepatic infarct
Maternal systemic lupus erythematosus
Mitochondrial disease with hepatic predominance
Not hepatitis viruses
Ischemia/abnormal perfusion
Maternal shock
Placentitis
Fetal heart disease
Myelodysplasia
Congenital leukemia
Hemangiomatosis

Workup

Laboratory Studies

• When liver failure is diagnosed in the first 1-2 days of life, neonatal hemochromatosis is by far the most common diagnosis. Afterward, many other conditions can manifest and must be excluded. They include all other causes of hepatic failure, including infective, metabolic, and hemorrhagic causes. The following are other causes of liver failure in the newborn:
  • Antenatal infection with adenovirus
  • Coxsackie virus
  • Cytomegalovirus
  • Echovirus
  • Herpesvirus
  • Hepatitis A, B, or C
  • Parvovirus B19
  • Rubella
  • Syphilis
  • Toxoplasmosis
  • A1At deficiency
  • Galactosemia
  • Hereditary fructose intolerance
  • Tyrosinemia
  • Maternofetal blood group incompatibility
  • Hemoglobinopathy
  • Hemophagocytic syndrome
  • Inborn defects in erythrocyte membrane or enzymes
  • Sepsis
  • Ischemia or abnormal perfusion
  • Extrahepatic biliary atresia
  • Hepatic infarct
  • Congenital leukemia
• Relevant laboratory tests and findings include the following:
  • CBC count with differential - To check for anemia and thrombocytopenia
  • Total and direct bilirubin levels - Elevated
  • Reticulocyte count - To check for any signs of hemolysis
  • Glucose level - Because infants with neonatal hemochromatosis can present with hypoglycemia
  • Albumin level - Because it may be low, which accounts for the infants' edema
  • Urinalysis - To check for causes of oliguria and any renal involvement
  • BUN and creatinine levels - To evaluate renal function
  • Prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrin split products - To rule out any hemorrhagic causes
  • Transferrin level (one of the most common findings) - Low but hypersaturated
  • Serum ferritin levels - Elevated
  • Total iron-binding capacity - Low
  • Cytoferrin level - Markedly elevated
  • Lactic acid dehydrogenase (LDH) level - Markedly elevated
  • Aminotransferases level - Mildly elevated
  • Iron levels - Usually in the reference range

Imaging Studies

• MRI is the most helpful study in the diagnosis of neonatal hemochromatosis.⁴
  • MRI can be used to detect increased levels of iron in the liver compared with levels in normal tissues.
  • MRI can be used to document any areas of siderosis of the pancreas and myocardium. Absence of siderosis of the spleen may also be observed.
  • MRI of infants in utero has not demonstrated any siderosis or signs of neonatal hemochromatosis.
• Ultrasonography demonstrates patency of the ductus venosum; this is because of liver injury and, thus, portocaval shunting occurs.

Procedures

• Biopsy
  • Liver biopsy is not easily performed in these infants because of the increased tendency of bleeding, but it is helpful in aiding in the diagnosis.
  • Another option is to perform a punch biopsy of the oral mucosa. This area is used secondary to the small salivary glands. Punch biopsy is performed by using 3-mm punch biopsy of the mucosa of the lower lip, and bleeding can be controlled. Salivary glands are siderotic if neonatal hemochromatosis is present.

Histologic Findings

Microscopic examination of the liver reveals that the hepatocytes have giant-cell transformation or pseudoacinar transformation with bile plugs, or no hepatocytes are present at all. Also, the hepatocytes may show siderosis, while Kupffer cells are spared. Scarring may be present from macrophages, which contain high levels of stainable iron. Bile duct is proliferated. The spleen, lymph nodes, and bone marrow contain a small amount of stainable iron. The placenta is not siderotic, and villitis has not been reported.

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.

Dosing

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

Interactions

Concomitant administration with prochlorperazine can cause transient loss of consciousness

Contraindications

Documented hypersensitivity; severe renal disease and anuria (dose reduction after the loading dose should be considered in these circumstances)

Precautions

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.

Dosing

Adult

Pediatric

200 mg/kg/d PO divided q8h for 17-21 doses

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

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.

Dosing

Adult

Pediatric

20-25 IU/kg/d PO divided bid

Interactions

Mineral oil decreases absorption of vitamin E; vitamin E delays absorption of iron and increases effects of anticoagulants

Contraindications

Documented hypersensitivity

Precautions

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.

Dosing

Adult

Pediatric

2-3 mcg/kg/d PO/IV

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

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.

Dosing

Adult

Pediatric

0.4 mcg/kg/d IV initially, increase to 0.6 mcg/kg/d IV for 3-4 wk

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

Contraindications

Documented hypersensitivity

Precautions

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.

Dosing

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

Interactions

None reported

Contraindications

None known

Precautions

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.

Dosing

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

Interactions

Phenytoin, alpha- and beta-adrenergic blockers, general anesthesia, and MAOIs increase and prolong effects of dopamine

Contraindications

Documented hypersensitivity; hypersensitivity to sulfites; ventricular fibrillation; pheochromocytoma

Precautions

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.

Dosing

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

Interactions

Beta-adrenergic blockers antagonize effects of dobutamine; general anesthetics may increase toxicity

Contraindications

Documented hypersensitivity; IHSS; hypertension; recent MI; arrhythmia; hypovolemia

Precautions

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

Follow-up

Transfer

• If an infant with neonatal hemochromatosis is born outside of a tertiary care setting, transfer the patient to a level IV neonatal intensive care unit (NICU) or to a center that regularly performs neonatal liver transplantation.

Complications

• Liver failure
• Cardiac failure
• Respiratory failure
• Disseminated intravascular coagulation

Prognosis

• Prognosis is extremely poor because, without liver transplantation, most, if not all, infants die. The average age at death is 1.1 months; some patients are stillborn, and some live up to 5 months.

Patient Education

• Suggest genetic counseling if the parents of a child with neonatal hemochromatosis desire to have another child.

Miscellaneous

Medicolegal Pitfalls

• All infants with a diagnosis of liver failure should undergo testing until a final diagnosis is reached.
• Failure to diagnose neonatal hemochromatosis, resulting in the family having subsequent children with the same diagnosis, could result in legal actions against the physician.

References

1. Adams PC, Searle J. Neonatal hemochromatosis: a case and review of the literature. Am J Gastroenterol. Apr 1988;83(4):422-5. [Medline].

2. 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].

3. Colletti RB, Clemmons JJ. Familial neonatal hemochromatosis with survival. J Pediatr Gastroenterol Nutr. Jan-Feb 1988;7(1):39-45. [Medline].

4. Liet JM, Urtin-Hostein C, Joubert M, et al. Neonatal hemochromatosis [in French]. Arch Pediatr. Jan 2000;7(1):40-4. [Medline].

5. Sigurdsson L, Reyes J, Kocoshis SA, et al. Neonatal hemochromatosis: outcomes of pharmacologic and surgical therapies. J Pediatr Gastroenterol Nutr. Jan 1998;26(1):85-9. [Medline].

6. Whitington PF, Hibbard JU. High-dose immunoglobulin during pregnancy for recurrent neonatal haemochromatosis. Lancet. Nov 6-12 2004;364(9446):1690-8. [Medline].

7. 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].

8. Neonatal gastroenterology. In: Neu J, ed. Clinical Perinatology. Vol 23. Philadelphia, PA: WB Saunders; 1996:327-8.

9. Gracey M, Burke V. Metabolic disorders. In: Pediatric Gastroenterology and Hepatology. 3^rd ed. Boston, MA: Blackwell Scientific; 1991:611.

10. Knisely AS. Neonatal hemochromatosis. Adv Pediatr. 1992;39:383-403. [Medline].

11. Lebenthal E. Inherited metabolic liver disorders. In: Textbook of Gastroenterology and Nutrition in Infancy. 2^nd ed. New York, NY: Raven; 1990:981-2.

12. 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].

13. Rodrigues FM, Kallas M, Nash R. Neonatal hemochromatosis in eleven families: pattern of presentation and outcome [abstr]. Hepatol. 1999;9:1882-5.

14. United States Pharmacopeial Convention Inc. Drug Information for the Health Care Professional. Vol 1. 1997:18-21, 51-3, 1145-8, 2589-90.

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

Contributor Information and Disclosures

Author

Roland L Boyd, DO, FAAP, FACOP, Neonatologist, Section of Neonatology, Neonatal Services Limited
Roland L Boyd, DO, FAAP, FACOP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, and American College of Osteopathic Pediatricians
Disclosure: Nothing to disclose.

Coauthor(s)

Jatinder Bhatia, MBBS, Professor of Pediatrics, Chief, Section of Neonatology, Department of Pediatrics, Medical College of Georgia
Jatinder Bhatia, MBBS is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American Dietetic Association, American Federation for Clinical Research, American Pediatric Society, American Society for Clinical Nutrition, American Society for Parenteral and Enteral Nutrition, New York Academy of Sciences, Society for Pediatric Research, and Southern Society for Pediatric Research
Disclosure: Mead Johnson Consulting fee Consulting; Mead Johnson Honoraria Speaking and teaching; Dey LP Consulting fee Consulting; Dey LP Honoraria Speaking and teaching; Wyeth Grant/research funds Other; Med Immune Grant/research funds Other; Ovation  None

Joseph H Clark, MD, Professor, Department of Pediatric, Division of Gastroenterology, Medical College of Georgia
Joseph H Clark, MD is a member of the following medical societies: American Academy of Pediatrics, American Gastroenterological Association, American Society for Parenteral and Enteral Nutrition, North American Society for Pediatric Gastroenterology and Nutrition, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Hisham Nazer, MBBCh, FRCP, Professor of Pediatrics, Consultant in Pediatric Gastroenterology, Hepatology and Clinical Nutrition, Bushnaq Medical Centre, University of Jordan
Hisham Nazer, MBBCh, FRCP is a member of the following medical societies: Royal College of Paediatrics and Child Health and Royal College of Physicians
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

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
David Piccoli, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition
Disclosure: Nothing to disclose.

CME Editor

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
Steven M Schwarz, MD, FAAP, FACN, AGAF is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American College of Physician Executives, American Gastroenterological Association, American Pediatric Society, Gastroenterology Research Group, New York Academy of Medicine, North American Society for Pediatric Gastroenterology and Nutrition, and Society for Pediatric Research
Disclosure: TAP Pharmaceuticals Honoraria Speaking and teaching; Curemark, LLC Consulting fee Board membership

Chief Editor

Carmen Cuffari, MD, Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine
Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

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