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Necrotizing Enterocolitis in a Newborn Following Intravenous Immunoglobulin Treatment for Haemolytic Disease

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Necrotizing Enterocolitis in a Newborn Following Intravenous Immunoglobulin Treatment for Haemolytic Disease CASE REPORT Necrotizing Enterocolitis in a Newborn Following Intravenous Immunoglobulin Treatment for Haemolytic Disease Semra Kara1, Hulya Ulu-ozkan2, Yavuz Yilmaz2, Fatma Inci Arikan3, Ugur Dilmen4 and Yildiz Dallar Bilge3 ABSTRACT ABO iso-immunization is the most frequent haemolytic disease of the newborn. Treatment depends on the total serum bilirubin level, which may increase very rapidly in the first 48 hours of life in cases of haemolytic disease of the newborn. Phototherapy and, in severe cases, exchange transfusion are used to prevent hyperbilirubinaemic encephalopathy. Intravenous immunoglobulins (IVIG) are used to reduce exchange transfusion. Herein, we present a female newborn who was admitted to the NICU because of ABO immune haemolytic disease. After two courses of 1 g/kg of IVIG infusion, she developed necrotizing enterocolitis (NEC). Administration of IVIG to newborns with significant hyperbilirubinaemia due to ABO haemolytic disease should be cautiously administered and followed for complications. Key Words: Necrotizing enterocolitis. Hyperbilirubinaemia. Newborn. Intravenous immunoglobulins. Iso-immunization. INTRODUCTION important adverse reactions,6 one of which is described Blood group incompatibilities are most frequent and hereby. severe conditions causing hyperbilirubinaemia in the neonatal period.1 Phototherapy and in severe cases CASE REPORT exchange transfusion are used to prevent kernicterus A female newborn was admitted to our neonatal unit and reduce perinatal mortality. Exchange transfusion because of jaundice on the tenth hours after being born. is not free of severe complications such as thrombo- The baby was born by uncomplicated vaginal delivery to cytopenia, apnoea, pulmonary haemorrhage, haemodyna- a healthy 31-year-old mother who was fourth gravida mic instability, septicaemia and necrotizing enterocolitis and second para. Her body weight was 2,600 grams and (NEC).2 her gestational age was 40 weeks. Her Apgar score Intravenous immunoglobulin (IVIG) can also be used for were 8 and 9 for the first and fifth minute respectively. newborns with significant hyperbilirubinaemia and it The mother's past history was unremarkable. The first reduces the need for exchange transfusion.3 IVIG is a sibling were treated with phototherapy due to neonatal concentrated, purified solution of immunoglobulins hyperbilirubinaemia. At the time of admission, the derived from pooled plasma of the donor population. patient's physical examination was normal except IVIG is indicated for severe iso-immune thrombo- yellowish colour of skin. cytopenia and iso-immune haemolytic jaundice in The laboratory data indicated a haemoglobin value of 20 neonates with a dose of 500 – 1000 mg/kg infused over mg/dL, a reticulocyte count of 14.9% and moderate 2 to 6 hours.4 IVIG administration has been successfully anisocytosis and severe polychromasia in the peripheral employed to block circulating maternal antibodies and to blood smear. The seroanalysis showed a total bilirubin of reduce the need for exchange transfusion in iso-immune 8 mg/dL at 10 hours of life, a direct bilirubin of 0,6 mg/dL, haemolytic jaundice.5 Although studies performed blood urea nitrogen (BUN) value of 25 mg/dL, creatinine showed a significant reduction in the need for exchange level of 0.5 mg/dL, sodium level of 137 mEq/L, transfusion in those treated with IVIG, the applicability of potassium level at 4.1 mEq/L, chloride level of 102 the results is limited because the number of studies and mEq/L and a strong positive result (+++) on the direct infants included was small. IVIG may also cause Coombs test. Blood group was A +. The mother's blood group was O+. Double phototherapy was initiated; 1 Department of Neonatology / Paediatrics2, Ankara Training however, 4 hours later total bilirubin level rose to 10 and Research Hospital, Ankara, Turkey. mg/dL. 3 4 Department of Paediatric Surgery / Neonatology , Zekai Tahir After obtaining approval from the parents, administration Burak Training and Research Hospital, Turkey. of two courses of IVIG dose: 1 g ⁄ kg ⁄ dose/day at a slow Correspondence: Dr. Semra Kara, Department of rate (over 3 hours) was started. Breastfeeding was Neonatology, Ankara Training and Research Hospital, satisfactorily initiated. After second dose of IVIG, the Ankara, Turkey. patient developed vomiting followed by abdominal E-mail: [email protected] tenderness and distention. X-ray abdomen showed Received: February 28, 2012; Accepted: September 7, 2012. diffuse pneumatosis intestinalis (Figure 1). After 598 Journal of the College of Physicians and Surgeons Pakistan 2013, Vol. 23 (8): 598-600 Necrotizing enterocolitis following intravenous immunoglobulin treatment condition,9 thus implicating that HDN in itself is a risk factor for NEC in term infants. In this case, the patient was term and she has got ABO iso-immune haemolytic disease. There was no other risk factor for NEC. But it started abruptly with clinical symptoms of NEC immediately after receiving IVIG. The pathophysiologic process and clinical presentation of NEC in late-preterm infants or term newborns is different from standard NEC in more immature preterm infants because it is especially attributable to intestinal hypoxia-ischaemia (as a result of thrombosis) instead of infection.10 Hyperviscosity of the IVIG solutions may increase the risk for intestinal thrombosis. Because IVIG is administered during the first day of life, its prothrombotic effect may also increase the physiologic hypercoagulability of the fetus and newborn after birth. There was a possible combination of various factors such as HDN, intense phototherapy, IVIG infusion and the appearance of NEC symptoms shortly thereafter in this patient. Figure 1: Abdominal radiograph showing a dilation of intestinal loops and Alcock and Liley concluded that the role of IVIG remains pneumatosis intestinalis. uncertain, although its use reduces the need for diagnosis of NEC, feeding was stopped and intravenous exchange transfusion.4 IVIG may play a role in special antibiotics and total parenteral nutrition was started. The circumstances, such as parental refusal or unavailability patient's condition worsened and was suspected to be of blood components for exchange transfusion. In due to an intestinal perforation. Abdominal percutaneous contrast, Gottstein and Cooke showed that IVIG is an drainage was performed. After 5 days, drainage was effective treatment for neonatal haemolytic disease stopped and oral feeding was started and intravenous because it reduces the need for exchange transfusion, antibiotic therapy completed for 14 days with an duration of phototherapy, and length of hospital stay.5 adequate clinical response. Adverse events were mild and usually clinically irrelevant.5 DISCUSSION Figueras-Aloy et al. reported that the administration of Intravenous immunoglobulin can be used for newborns high-dose IVIG for severe iso-immune haemolytic with significant hyperbilirubinema.3 Adverse events that jaundice was associated with a higher incidence of NEC were reported after the use of IVIG include pyrogenic in late-preterm and term infants, female gender, low birth reactions, volume overload (with transient tachycardia or weight, and need for resuscitation maneuvers at the time hypertension), hypoglycemia, and hypotension that of delivery, in the presence of caesarean delivery and disappeared after stopping the infusion. Hemolysis can low Apgar score at 5 minutes. They also referred that the be an uncommon complication as well as acute renal infusion should be administered slowly (at least during 4 failure and NEC. NEC is the most common and severe hours) to reduce the effects of hyperviscosity.11 This gastrointestinal disease in newborns. The aetiology and patient was female, but there was no other risk factors pathophysiology of NEC remain unclear; however, both and infusion rate was 3 hours. The authors believe that intestinal immaturity and bacterial overgrowth are pre- a multicentre, randomized controlled trial is needed to requisites for its development. Moreover, pre-maturity examine the safety and efficacy of high-dose IVIG and low birth weight are risk factors consistently treatment to assess the incidence of adverse events, 7 associated with the development of NEC. In mature short-term results, and long-term neurodevelopmental newborns perinatal asphyxia, presence of umbilical outcomes. catheters, antecedent respiratory distress, poly- cythemia, and maternal pre-eclampsia are the risk REFERENCES factors for NEC. 1. Murray NA, Roberts IA. Haemolytic disease of the newborn. NEC episodes have been previously described after Arch Dis Child Fetal Neonatal Ed 2007; 92:83-8. intravenous IVIG infusion in patients with iso-immune 2. Steiner LA, Bizzarro MJ, Ehrenkranz RA, Gallagher PG. 8 thrombocytopenia. Moreover, it has also been reported A decline in the frequency of neonatal exchange transfusions in full term neonates with haemolytic disease of the and its effect on exchange-related morbidity and mortality. newborn (HDN), and after exchange transfusion for this Pediatrics 2007; 120:27-32. Journal of the College of Physicians and Surgeons Pakistan 2013, Vol. 23 (8): 598-600 599 Semra Kara, Hulya Ulu-ozkan, Yavuz Yilmaz, Fatma Inci Arikan, Ugur Dilmen and Yildiz Dallar Bilge 3. American Academy of Pediatrics Subcommittee on hyper- Development Neonatal Research Network. N Engl J Med bilirubinemia. Management of hyperbilirubinemia in the 1994; 330:1107-13. newborn infant 35 or more weeks of gestation [published
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