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Arch Pediatr Adolesc Med. 2009;163(5):482. doi:10.1001/archpediatrics.2009.41-b.
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DENOUEMENT AND COMMENT: NEONATAL VARICELLA INFECTION

The mother was diagnosed 2 days after delivery as having varicella. She did not have a prior history of varicella or documented immunization. The newborn received a varicella-zoster immunoglobulin preparation (VariZIG; Cangene Corporation, Winnipeg, Manitoba, Canada) on her third day of life just before discharge from the hospital. When the newborn returned for evaluation of the rash, varicella-zoster virus DNA was detected in the blood and the bloody cerebrospinal fluid by polymerase chain reaction. She was treated with intravenous acyclovir for 10 days.

Congenital varicella infections occur when pregnant mothers are infected during the first 2 trimesters of pregnancy. Clinical manifestations include cicatricial skin lesions in a dermatomal distribution, which are often depressed and pigmented. Neurologic defects, such as intellectual disability and seizures, may also occur. Ocular and skeletal defects are also present in half of cases.1Neonatal varicella may be caused by maternal varicella infection during the last 3 weeks of pregnancy or postnatal infection of the infant. Because of the incubation period of the virus, intrauterine-acquired infections present within the first 12 days of life, whereas postnatal infections typically present later in life. Either may have a variable clinical course, ranging from mild to severe.

Late congenital and neonatal varicella infections are often serious, with a mortality rate of up to 30%. Infants can acquire the virus through transplacental infection, exposure in the birth canal, or postpartum exposure. The risks of neonatal infection, adverse outcomes, and subsequent fatality are highest when maternal infection manifests less than 5 days before and 2 days after delivery.2This increased risk is attributed to the lack of maternal IgG development and the failure to passively transfer protective antibodies to the neonate. Therefore, exogenous immunoglobulin is often administered to neonates whose delivery occurs in this time frame in an attempt to attenuate the disease course.

Varicella-zoster immunoglobulin (VZIG) production was discontinued in 2004. The product is a purified human immunoglobulin preparation made from plasma that contains high levels of antivaricella antibodies; it is available under an investigational new drug application submitted to the Food and Drug Administration. Unlike VZIG, this product is lyophilized and requires reconstitution. It is indicated for the same uses as VZIG and can be obtained through an expanded access protocol.3It should be administered within the first 96 hours of life at a dose of 125 U per 10 kg of body weight, with minimum and maximum dosages of 125 and 625 U/kg, respectively. If VZIG cannot be administered within the first 96 hours, administration of intravenous immunoglobulin (IVIG) should be considered. Limited data regarding IVIG's efficacy are available, and antivaricella antibody titers may vary. Within the same line of reasoning, breastfeeding may also be encouraged because antibodies present in breast milk may be protective.3One small study4also suggested that preventive care with a combination of acyclovir and IVIG may also be efficacious.

If, despite attempts at prevention, an exposed infant manifests signs of infection, he or she may be treated with acyclovir intravenously. Acyclovir decreases the number of days of fever and the number of lesions in children aged 2 to 12 years, with no delineable impact on disease complications, such as bacterial skin infections and encephalitis.5However, there is a paucity of data on the treatment of perinatal varicella infection with acyclovir. Case reports suggest that this treatment may attenuate the disease severity,6,7but randomized controlled trials have not been conducted in this population. New studies are needed to examine this treatment because neonatal varicella is a serious infection and has led to fatality despite the use of VZIG and acyclovir.8,9

Infection may also lead to other complications. Population-based studies have shown that bacterial skin superinfection and pneumonia are among the most common complications of varicella infection in children younger than 5 years.10Encephalitis is more common in children 5 years or older, but varicella encephalitis has previously been reported in children as young as 8 months.11

Return to Quiz Case.

Correspondence:Riva Kamat, MD, Inova Fairfax Hospital for Children, 3300 Gallows Rd, Falls Church, VA 22042 (Riva_prasad@yahoo.com).

Accepted for Publication: November 30, 2008.

Author Contributions:Study concept and design: Click and Robinson. Acquisition of data: Robinson. Analysis and interpretation of data: Robinson and Kamat. Drafting of the manuscript: Click and Robinson. Critical revision of the manuscript for important intellectual content: Kamat. Administrative, technical, and material support: Robinson. Study supervision: Click.

Financial Disclosure:None reported.

Meyers  JD Congenital varicella in term infants: risk considered. J Infect Dis 1974;129 (2) 215- 217
PubMed Link to Article
Ogilvie  MM Antiviral prophylaxis and treatment in chickenpox. J Infect 1998;36 ((suppl 1)) 31- 38
PubMed Link to Article
Grumach  ASCarmona  RCLazarotti  D  et al.  Immunological factors in milk from Brazilian mothers delivering small-for-date term neonates. Acta Paediatr 1993;82 (3) 284- 290
PubMed Link to Article
Dunkle  LMArvin  AMWhitley  RJ  et al.  A controlled trial of acyclovir for chickenpox in normal children. N Engl J Med 1991;325 (22) 1539- 1544
PubMed Link to Article
Kavaliotis  J Acyclovir therapy in neonates [letter to editor]. J Pediatr 1992;119655
PubMed
Williams  HLatif  AMorgan  JAnsari  BM Acyclovir in treatment of neonatal varicella. J Infect 1987;15 (1) 65- 67
PubMed Link to Article
Huang  YCLin  TYLin  YJLien  RIChou  YH Prophylaxis of intravenous immunoglobulin and acyclovir in perinatal varicella. Eur J Pediatr 2001;160 (2) 91- 94
PubMed Link to Article
Holland  PIsaacs  DMoxon  ER Fatal neonatal varicella infection. Lancet 1986;2 (8516) 1156
PubMed Link to Article
King  SMGorensek  MFord-Jones  ELRead  SE Fatal varicella-zoster infection in a newborn treated with varicella-zoster immunoglobulin. Pediatr Infect Dis 1986;5 (5) 588- 589
PubMed Link to Article
Guess  HABroughton  DDMelton  LJ  IIIKurland  LT Population-based studies of varicella complications. Pediatrics 1986;78 (4, pt 2) 723- 727
PubMed
Preblud  SR Age-specific risks of varicella complications. Pediatrics 1981;6814- 17
PubMed

Figures

Tables

References

Meyers  JD Congenital varicella in term infants: risk considered. J Infect Dis 1974;129 (2) 215- 217
PubMed Link to Article
Ogilvie  MM Antiviral prophylaxis and treatment in chickenpox. J Infect 1998;36 ((suppl 1)) 31- 38
PubMed Link to Article
Grumach  ASCarmona  RCLazarotti  D  et al.  Immunological factors in milk from Brazilian mothers delivering small-for-date term neonates. Acta Paediatr 1993;82 (3) 284- 290
PubMed Link to Article
Dunkle  LMArvin  AMWhitley  RJ  et al.  A controlled trial of acyclovir for chickenpox in normal children. N Engl J Med 1991;325 (22) 1539- 1544
PubMed Link to Article
Kavaliotis  J Acyclovir therapy in neonates [letter to editor]. J Pediatr 1992;119655
PubMed
Williams  HLatif  AMorgan  JAnsari  BM Acyclovir in treatment of neonatal varicella. J Infect 1987;15 (1) 65- 67
PubMed Link to Article
Huang  YCLin  TYLin  YJLien  RIChou  YH Prophylaxis of intravenous immunoglobulin and acyclovir in perinatal varicella. Eur J Pediatr 2001;160 (2) 91- 94
PubMed Link to Article
Holland  PIsaacs  DMoxon  ER Fatal neonatal varicella infection. Lancet 1986;2 (8516) 1156
PubMed Link to Article
King  SMGorensek  MFord-Jones  ELRead  SE Fatal varicella-zoster infection in a newborn treated with varicella-zoster immunoglobulin. Pediatr Infect Dis 1986;5 (5) 588- 589
PubMed Link to Article
Guess  HABroughton  DDMelton  LJ  IIIKurland  LT Population-based studies of varicella complications. Pediatrics 1986;78 (4, pt 2) 723- 727
PubMed
Preblud  SR Age-specific risks of varicella complications. Pediatrics 1981;6814- 17
PubMed

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