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Senior Resident Department of Pediatrics and Neonatology St. Stephen's Hospital Tis Hazari, 110054 Delhi, India fax 00-91-11-25819143 vikasbhambhani{at}hotmail.com
Senior Consultant Department of Pediatrics and Neonatology St. Stephen's Hospital
Head Department of Pediatrics and Neonatology St. Stephen's Hospital
Published Online, November 30, 2004. www.theannals.com, DOI 10.1345/aph.1E311
Case Report.
Male twins (gestational age 33 wk), weighing 2.05 and 2.45 kg (diamniotic, dichorionic placenta), were born to a primigravida mother who had developed varicella zoster 5 days previously. Both had respiratory distress soon after birth, needing continuous positive-airway pressure ventilation. X-ray at 2 hours was suggestive of wet lungs. Both infants received vitamin K (menaphthone sodium bisulphate, 1 mg intramuscularly).
In the presence of maternal varicella, they were prescribed injectable acyclovir 10 mg/kg/dose every 8 hours, diluted in distilled water and given over 30 minutes, starting at 4 hours of life. Additionally, both babies were administered 125 units (5 mL) of intravenous VZIG (Varitect CP, Biotest Pharma Gmbh, D-63303 Dreieich, Germany, Lot 155011) starting at 8 hours of life. The VZIG was diluted in 10 mL of distilled water (total volume 15 mL), and 0.2 mL of this solution was given over 10 minutes (sensitization dose). Subsequently, in accordance with the product manual information, as their vital signs, heart rate, respiratory rate, and oxygen saturation were stable, the infusion rate was increased to 5 mL/h. The infusion continued for 3 hours, and the infants' vital signs recorded on the saturation monitor were normal throughout infusion. However, 15 minutes later, the first of the twins started gasping. Heart sounds were not audible. On intubation, fresh blood was seen pouring out of the airway. Five minutes later, the second twin also had cardiorespiratory arrest and pulmonary hemorrhage. Neither baby could be revived.
Discussion.
The Naranjo probability scale suggests that intravenous VZIG was the possible cause of death of the twins.3 The same adverse reaction occurring in twins exposed to a drug is in some ways akin to the recurrence of symptoms in an individual on rechallenge with the drug. The Naranjo scoring system does not anticipate this possibility, and no additional points on the scale have been allotted for this rare occurrence.
The manufacturer confirmed that there have been no previous reports of similar problems. As of November 17, 2004, our report is arguably the first of fatal adverse effects from the intravenous preparation.
Anaphylactoid reactions, immunoglobulin (Ig) A–mediated antibody reaction in IgA-deficient twins, or toxin-related alveolar damage could have been responsible for their deaths. In the absence of adverse effects in other patients who had used VZIG from the same lot, toxin contamination is unlikely. IgA sensitization and an anaphylactoid reaction seem unlikely at this age.
Transfusion-related acute lung injury (TRALI) is another possibility. It is due to a reaction between donor leukoagglutinating or human leukocyte antigen–specific antibodies and the recipient's white blood cells, causing damage to pulmonary vasculature.4 Many blood products are implicated in TRALI. It has been reported in a neonate receiving granulocyte transfusion4 and in an adult following administration of IVIG.5 While newborns seldom develop anaphylactoid reactions to blood products, transfusion-related lung reactions may occur.
Footnotes
We acknowledge help received from Leslie G Holness MD, Food and Drug Administration, in reviewing the literature.
References
This article has been cited by other articles:
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  R. Pabst and C. Dehnicke Comment: death of twins after intravenous varicella zoster immunoglobulin Ann. Pharmacother., December 1, 2005; 39(12): 2140 - 2140. [Full Text] [PDF]
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