Transient Neonatal Liver Disease After Maternal Antenatal Intravenous Ig Infusions in Gestational Alloimmune Liver Disease Associated With Neonatal Haemochromatosis
Corresponding Author
Julien Baruteau
Pediatric Hepatology and Inborn Metabolic Diseases Unit, University Children's Hospital, Toulouse
Address correspondence and reprint requests to Julien Baruteau, Metabolic Medicine Department, Great Ormond Street Hospital, WC1N 3JH London, UK (e-mail: [email protected]).Search for more papers by this authorSophie Heissat
Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hopital Femme Mère Enfant, Bron
Search for more papers by this authorPierre Broué
Pediatric Hepatology and Inborn Metabolic Diseases Unit, University Children's Hospital, Toulouse
Search for more papers by this authorSophie Collardeau-Frachon
Pathology Department, Hopital Femme Mère Enfant, Bron
Search for more papers by this authorRaymonde Bouvier
Pathology Department, Hopital Femme Mère Enfant, Bron
Search for more papers by this authorMonique Fabre
Pathology Department, Institut Gustave Roussy, Paris
Search for more papers by this authorHannah Debiec
Sorbonne Universités, UPMC Univ Paris 06, Paris
Fetal Medicine, Saint Nicolas Hospital, Blaye
Search for more papers by this authorPierre Ronco
Sorbonne Universités, UPMC Univ Paris 06, Paris
Fetal Medicine, Saint Nicolas Hospital, Blaye
Search for more papers by this authorMartine Uzan
Internal Medicine Department, Poissy-Saint Germain en Laye Hospital, Poissy
Search for more papers by this authorPhilippe Narcy
Special Care Baby Unit, Poissy-Saint Germain en Laye Hospital, Poissy
Search for more papers by this authorMarie-Pierre Cordier
Clinical Genetics, Hopital Femme Mère Enfant, Bron
Search for more papers by this authorAlain Lachaux
Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hopital Femme Mère Enfant, Bron
Search for more papers by this authorThierry Lamireau
Pediatric Hepatology and Gastroenterology Unit, University Children's Hospital, Bordeaux
Search for more papers by this authorChristophe Elleau
Special Care Baby Unit, University Children's Hospital, Bordeaux
Search for more papers by this authorJean Philippe Filet
Sorbonne Universités, UPMC Univ Paris 06, Paris
Fetal Medicine, Saint Nicolas Hospital, Blaye
Search for more papers by this authorDelphine Mitanchez
Neonatal Intensive Care Unit, Armand Trousseau Hospital, Paris
Search for more papers by this authorMarie-Pierre Dupuy
Neonatal Intensive Care Unit, General Hospital, Saint-Brieuc
Search for more papers by this authorSylvie Odent
Clinical Genetics, University Hospital, Rennes, France
Search for more papers by this authorJames Davison
Metabolic Medicine Department, Great Ormond Street Hospital, London, UK
Search for more papers by this authorDominique Debray
Department of Pediatric Surgery, Hepatology, and Transplantation, Necker Enfants Malades Hospital, Paris
Search for more papers by this authorVincent Guigonis
Pediatrics, University Hospital, Limoges, France
Search for more papers by this authorCorresponding Author
Julien Baruteau
Pediatric Hepatology and Inborn Metabolic Diseases Unit, University Children's Hospital, Toulouse
Address correspondence and reprint requests to Julien Baruteau, Metabolic Medicine Department, Great Ormond Street Hospital, WC1N 3JH London, UK (e-mail: [email protected]).Search for more papers by this authorSophie Heissat
Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hopital Femme Mère Enfant, Bron
Search for more papers by this authorPierre Broué
Pediatric Hepatology and Inborn Metabolic Diseases Unit, University Children's Hospital, Toulouse
Search for more papers by this authorSophie Collardeau-Frachon
Pathology Department, Hopital Femme Mère Enfant, Bron
Search for more papers by this authorRaymonde Bouvier
Pathology Department, Hopital Femme Mère Enfant, Bron
Search for more papers by this authorMonique Fabre
Pathology Department, Institut Gustave Roussy, Paris
Search for more papers by this authorHannah Debiec
Sorbonne Universités, UPMC Univ Paris 06, Paris
Fetal Medicine, Saint Nicolas Hospital, Blaye
Search for more papers by this authorPierre Ronco
Sorbonne Universités, UPMC Univ Paris 06, Paris
Fetal Medicine, Saint Nicolas Hospital, Blaye
Search for more papers by this authorMartine Uzan
Internal Medicine Department, Poissy-Saint Germain en Laye Hospital, Poissy
Search for more papers by this authorPhilippe Narcy
Special Care Baby Unit, Poissy-Saint Germain en Laye Hospital, Poissy
Search for more papers by this authorMarie-Pierre Cordier
Clinical Genetics, Hopital Femme Mère Enfant, Bron
Search for more papers by this authorAlain Lachaux
Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hopital Femme Mère Enfant, Bron
Search for more papers by this authorThierry Lamireau
Pediatric Hepatology and Gastroenterology Unit, University Children's Hospital, Bordeaux
Search for more papers by this authorChristophe Elleau
Special Care Baby Unit, University Children's Hospital, Bordeaux
Search for more papers by this authorJean Philippe Filet
Sorbonne Universités, UPMC Univ Paris 06, Paris
Fetal Medicine, Saint Nicolas Hospital, Blaye
Search for more papers by this authorDelphine Mitanchez
Neonatal Intensive Care Unit, Armand Trousseau Hospital, Paris
Search for more papers by this authorMarie-Pierre Dupuy
Neonatal Intensive Care Unit, General Hospital, Saint-Brieuc
Search for more papers by this authorSylvie Odent
Clinical Genetics, University Hospital, Rennes, France
Search for more papers by this authorJames Davison
Metabolic Medicine Department, Great Ormond Street Hospital, London, UK
Search for more papers by this authorDominique Debray
Department of Pediatric Surgery, Hepatology, and Transplantation, Necker Enfants Malades Hospital, Paris
Search for more papers by this authorVincent Guigonis
Pediatrics, University Hospital, Limoges, France
Search for more papers by this authorThe authors report no conflicts of interest.
ABSTRACT
Objectives:
Neonatal haemochromatosis is a rare gestational disease that results in severe foetal liver disease with extrahepatic iron overload, sparing the reticuloendothelial system. Recurrence can be prevented with intravenous immunoglobulin (IVIG) infusions during pregnancy, supporting an alloimmune aetiology. The aim of the study was to assess the effect of antenatal treatment with IVIG infusion on the outcome of pregnancies in women with a history of documented neonatal haemochromatosis likely owing to gestational alloimmune disease and to analyse IVIG tolerance.
Methods:
From 2004 to 2012, 8 pregnant women were treated with IVIG at 1 g/kg body weight weekly from 18 weeks' gestation until birth in a prospective multicentre study.
Results:
All 8 neonates born to the treated women survived. Five developed mild neonatal liver disease with hepatomegaly (n = 1), hyperechogenic liver (n = 2), abnormal liver function tests (n = 1), raised serum ferritin (n = 3) and α-fetoprotein (n = 5) levels, or mild iron overload on liver magnetic resonance imaging (n = 1). Ferritin and α-fetoprotein levels normalised before 14 days and 2 months, respectively. A per-mother-basis analysis comparing outcomes of treated (n = 8) and untreated (n = 9) gestations showed a significant improvement in the survival of neonates with gestational IVIG therapy (survival 8/8 vs 0/9, P < 0.001). Adverse effects of IVIG infusion occurred in 5 mothers leading to discontinuation of treatment in 1 case. Preterm neonates born before 37 weeks' gestation had a decreased risk of neonatal liver disease (P = 0.04).
Conclusions:
Antenatal treatment with IVIG infusion in women at risk for gestational alloimmune disease recurrence improves the outcome of pregnancies despite mild signs of transient neonatal liver disease.
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