Congenital varicella syndrome: the evidence for secondary prevention with varicella-zoster immune globulin

• Published in: Canadian Medical Association journal (CMAJ) Vol. 183; no. 2; pp. 204 - 208
• Main Authors: Cohen, Arlan, Moschopoulos, Panagis, Maschopoulos, Panagis, Stiehm, Richard E, Koren, Gideon
• Format: Journal Article
• Language: English
• Published: Canada CMA Joule Inc 08-02-2011; CMA Impact, Inc; Canadian Medical Association
• Subjects: Adult; Chicken pox; Chickenpox; Chickenpox - congenital; Chickenpox - prevention & control; Chickenpox vaccine; Complications and side effects; Drug therapy; Evidence-Based Medicine; Female; Health aspects; Humans; Immune Sera - administration & dosage; Immune Sera - immunology; Immunization; Immunoglobulin G; Infant, Newborn; Infectious Disease Transmission, Vertical - prevention & control; Patients; Post-Exposure Prophylaxis; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Infectious; Pregnancy, Complications of; Prevention; Review; Syndrome; United States; United States
• ISSN: 0820-3946; 1488-2329
• DOI: 10.1503/cmaj.100615

To identify all articles examining the evidence related to whether varicella-zoster immune globulin prevents congenital varicella syndrome, we completed a computerized search of Medline, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane library from inception to July 1, 2010. We supplemented the search by investigating relevant references from published reviews. There were no exclusionary criteria by language of publication. Search terms included "pregnancy and chickenpox" or "varicella zoster," and "congenital varicella syndrome" or "VZIG." We included all original research involving humans and related to prevention of congenital varicella syndrome by varicella-zoster immune globulin. A number of studies, which date back half a century, have shown that the administration of varicella- zoster immune globulin is effective in decreasing rates of contraction of clinically evident chicken pox in exposed immunocompetent patients by 40%-50% or more and in attenuating the severity of varicella infection in those who contract it, whether they are immunocompetent or immunocompromised.7-13 Varicella-zoster immune globulin neutralizes free virus and is effective even at very low levels in antibodydependent cellular cytotoxicity.8 [McGregor JA] and colleagues,9 for example, found that 80% of seronegative pregnant women with exposure who received varicella-zoster immune globulin remained symptom-free, whereas 89% of untreated control patients developed clinical illness. However, the sample size of the study and the size of each study arm were not reported. Brunell and colleagues,7 in a study done over 40 years ago, found that all of six immunocompetent children exposed to varicella virus who did not receive varicella-zoster immune globulin contracted varicella, whereas none of the six treated with varicella-zoster immune globulin developed the disease or antibodies against the disease. Using the grading scheme of the Canadian Task Force on Preventive Health Care,4 we graded the existing evidence supporting the use of varicella-zoster immune globulin in protecting the mother from varicella as Level I (i.e., one or more properly randomized controlled trial). In the first study, Enders and colleagues reported that the incidence of congenital varicella syndrome among babies treated with varicella- zoster immune globulin whose mothers contracted varicella during the thirteenth to twentieth week of pregnancy was 0/97. In contrast, the incidence of congenital varicella syndrome among babies of women who contracted varicella during the same time period, but who did not receive varicella-zoster immune globulin, was 7/351 (1.99%) (p < 0.01).3 Enders subsequently extended this study with data derived from her Stuttgart site, collected from 1994 to 1999.11 An additional 11 pregnant women with varicella during pregnancy who had received varicella-zoster immune globulin were followed; none of the babies developed congenital varicella syndrome. By contrast, another 82 patients were followed who contracted varicella during weeks 13-20 but were not given varicella- zoster immune globulin; four instances of congenital varicella syndrome occurred.