Correspondence
Varicella Infection in Pregnancy
N Engl J Med 1994; 331:482August 18, 1994
- Article
To the Editor:
Pastuszak and her colleagues (March 31 issue)1 report embryopathy in 1 of 49 infants born alive after first-trimester maternal varicella. In the meta-analysis of their own results and those of four comparable published studies, they calculate a 2.2 percent aggregate mean rate of congenital varicella embryopathy among such live-born infants. Their Table 4 shows the fetal risk for the congenital varicella syndrome in each study. However, according to the references cited, only 1 of 145 cases in the table involved defects typical of the syndrome. The authors' case may be added, but it is not clear whether the distribution of skin lesions in that case corresponded to dermatomes. Although the syndrome has been variously named,2-4 the diagnostic criteria seem well established.
The authors quote a report by Siegel5 as the source of data on two cases listed in the table, but he wrote of “the single case” in his study “with findings suggesting a causal relationship to a specific disease.” The infant in question had a cataract in one eye, detected in the second year of life, but no other defect. As with the authors' own case, there was no reported laboratory evidence to establish a diagnosis of varicella embryopathy. Such evidence is needed in any unusual form of embryopathy if a causal role for the virus is to be demonstrated. Hence, Table 4 includes at the most three cases or, at the least, one case of varicella embryopathy, the one case being typical of the congenital varicella syndrome.
5 ReferencesD.C.J. Bassett, M.B., B.S., F.R.C.Path.
Chinese University of Hong Kong, Shatin, New Territories, Hong Kong1
Pastuszak AL ,Levy M ,Schick B , et al. Outcome after maternal varicella infection in the first 20 weeks of pregnancy. N Engl J Med 1994;330:901-905
Full Text | Web of Science | Medline2
Srabstein JC ,Morris N ,Larke RPB ,DeSa DJ ,Castelino BB ,Sum E . Is there a congenital varicella syndrome? J Pediatr 1974;84:239-243
CrossRef | Web of Science | Medline3
Higa K ,Dan K ,Manabe H . Varicella-zoster virus infections during pregnancy: hypothesis concerning the mechanisms of congenital malformations. Obstet Gynecol 1987;69:214-222
Web of Science | Medline4
Alkalay AL ,Pomerance JJ ,Rimoin DL . Fetal varicella syndrome. J Pediatr 1987;111:320-323
CrossRef | Web of Science | Medline5
Siegel M . Congenital malformations following chickenpox, measles, mumps, and hepatitis: results of a cohort study. JAMA 1973;226:1521-1524
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Dr. Bassett suggests that, of the infants born to varicella-infected mothers included in our meta-analysis, only the infant described by Paryani and Arvin had classic varicella embryopathy1. He questions the inclusion of the two infants described by Siegel2 and the infant in our study in the calculation of aggregate fetal risk. Confirmation of an in utero infection in atypical cases requires isolation of the virus from tissue. Although this was not done, ascitic fluid from the infant in our study was positive for specific antibody to the virus, and the clinical examination confirmed scarring. It is true that the two defects reported by Siegel2 were relatively mild (microcephaly and cataract); however, ocular manifestations may be isolated or occur in association with other findings. Both abnormalities have been observed in infants with more definitive signs of infection in utero.
The mildest manifestations of prenatal infection are unknown, but the spectrum of possibilities is widening. In a recent cohort study, Jones et al.3 checked for 170 physical signs in every infant exposed to varicella in utero and in 146 live-born infants whose mothers were infected during weeks 0 to 20. One infant had mild cutaneous scarring, Horner's syndrome, and retinal scarring (maternal infection at 17 weeks), and one had horizontal nystagmus (maternal infection at 7 weeks).
We now have follow-up data on one additional, prospectively ascertained case of embryopathy after maternal infection at 15 weeks. At 42 weeks' gestation, a 3890-g baby was delivered vaginally. Clinical examination revealed mild scoliosis, Horner's syndrome, a severely hypoplastic right arm, and zoster vesicles (located at C4 to C5-6, C7-8, and T1). An electromyelogram at 8.5 months revealed denervation, with some evidence of reinnervation of the distal muscles of the right arm and triceps; the right biceps and deltoid muscle were spared. Evoked-potential testing revealed no definite response on the right side and normal responses on the left. The child's neurobehavioral development at four years is normal. This case was among the 119 for which we could not obtain data at the time of our report.
We believe that the inclusion of these four cases is appropriate and that, if anything, our estimate of the aggregate risk is overly cautious at 2.2 percent. Careful follow-up, including an ophthalmologic examination, is required to identify infants who may have minor manifestations of in utero varicella infection.
3 ReferencesAnne L. Pastuszak, M.Sc.
Gideon Koren, M.D.
Hospital for Sick Children, Toronto, ON M5G 1X8, Canada1
Paryani SG ,Arvin AM . Intrauterine infection with varicella-zoster virus after maternal varicella. N Engl J Med 1986;314:1542-1546
Full Text | Web of Science | Medline2
Siegel M . Congenital malformations following chickenpox, measles, mumps, and hepatitis: results of a cohort study. JAMA 1973;226:1521-1524
CrossRef | Web of Science | Medline3
Jones KL ,Johnson KA ,Chambers CD . Offspring of women infected with varicella during pregnancy: a prospective study. Teratology 1994;49:29-32
CrossRef | Medline
