- Email: [email protected]
Varicella zoster virus antibody titers before and after administration of zoster immune globulin to neonates in an intensive care nursery
Volume 103 Number 1
Clinical and laboratory observations
113
Clinical and laboratory observations
Varicella zoster virus antibody titers before and after administration o f zoster immune globulin to neonates in an intensive care nursery Elaine E. L. Wang, M.D., Charles G. Prober, M.D., and Ann M. Arvin, M.D. Toronto, Ont., Canada, a n d S t a n f o r d , Calif.
VARICELLA ZOSTER VIRUS rarely causes infection in young infants; the healthy term infant is probably protected after exposure to VZV by antibody that is passively transferred from the mother? Premature infants may not receive as much antibody transplacentally as term infants2 and may be at increased risk of severe VZV infection after exposure, as are older immunocompromised children? In a previous report, none of 31 infants in a neonatal intensive care unit developed varicella after exposure to a nurse with VZV infection.4 Infants in our intensive care nursery who were inadvertently exposed to a nurse with VZV infection were given zoster immune globulin, and VZV serum antibody titers were measured before and after ZIG administration to determine the number of patients with preexisting VZV antibody and whether a detectable antibody rise occurred after ZIG prophylaxis.
MATERIALS AND METHODS Thirty-two infants in our intensive care nursery who were exposed to VZV were given 1 ml ZIG (mean dose 0.6 ml/kg) intramuscularly within 72 hours after exposur e. All infants were less than 2 months of age. Their gestational ages ranged from 25 to 40 weeks, with a mean of 33.8 weeks, and their birth weights ranged from 750 to 4790 gm, with a mean of 2278 gm. ZIG, which was obtained from the Canadian Red Cross, was produced by the Massachusetts Public Health Laboratory. A blood sample was obtained by venipuncture from
From Division of Infectious Diseases, Department of Pediatrics, The Hospital for Sick Children, University of Toronto; and Department of Pediatrics, Stanford University Medical Center. Reprint requests: Charles G. Prober, M. D., Division of lnfectious Diseases, The Hospital for Sick Children, 555 University Ave., Toronto, Ont., Canada M5G lX8.
each infant just before prophylaxis was given. Repeat samples were obtained 72 hours and/or six weeks after ZIG administration. The serum fraction was separated and stored at 4 ~ C until radioimmunoassay for VZV antibody was performed? The assays of sera from each patient were performed in parallel. The antibody titer in most VZVimmune adults is >_1 : 16,384 (4.2 log~0) when measured by radioimmunoassay. The volume and frequency of red blood cell and freshfrozen plasma transfusions were noted. The patients were monitored for the development of clinical varicella for six weeks after exposure.
RESULTS No clinical cases of varicella were detected during the six-week study period. Thirty-one of 32 (97%) patients had detectable VZV antibody before ZIG administration (Table). The lowest mean VZV antibody titer was observed in infants whose
VZV ZIG
Varicella zoster virus Zoster immune globulin
gestational age was 25 weeks or less. Infants of 26 to 30 weeks' gestation had VZV antibody equivalent to those in the infants of more than 30 weeks' gestation. One infant in each birth weight group had a low initial antibody titer, defined as a titer <1:4,096 (3.6 log~0). The mothers of these three infants all recalled having childhood varicella. One of these patients was a 6-day-old, 600 gm infant of 30 weeks' gestation who lacked any detectable antibody. The infants weighing 1000 gm or less tended to have lower VZV antibody titers than infants of higher birth weight. The mean VZV antibody titer was not significantly differ-
1 14
Clinical and laboratory observations
The Journal of Pediatrics July 1983
Table. Varicella zoster virus antibody titers in relation to gestational age, birth weight, and postnatal age Number o~ patients Gestational age (wk) _<_25 2 26 to 30 6 31 to 35 7 36 17 Birth weight (gin) ~<1000 5 >1000 27 Postnatal age (too) _< 1 24 >1 8
Mean serum VZV antibodytiter
Log _+SE
1 : 16,384 1:64,565 1:81,283 1:50,118
4.2_+0 4.81 _+ 0.89 4.91 _+ 59 4.7 _+ 0.26
1:6,918 1:91,700
3.84 _+ 0.7 4.96 _+ 0,23
1 : 39,810 1 : 128,824
4.60 -+ 0.3 5.11 -+ 0.48
ent in infants whose postnatal age was less than 1 month compared with those who were 1 to 2 months of age. Fifteen infants who were tested after red blood cell transfusions had the same mean VZV titer of 1:50,200 (4.7 logj0) as untransfused infants. Seven infants who had been given fresh-frozen plasma had a mean VZV titer of 1:251,000 (5.4 logt0); the difference from values in the untransfused patients did not reach statistical significance. Serum was obtained at 72 hours after Z I G administration from 13 infants and at six weeks after Z I G from 27 infants. A fourfold or greater rise in titer was observed in five patients (38%) at 72 hours and in eight patients (29%) at six weeks. Patients with an initial VZV antibody titer of 1 : 16,384 or less demonstrated an antibody rise at 72 hours significantly more frequently than patients with a pre-ZIG titer above 1 : 16,384 (five of seven vs none of six; P 0.02, Fisher exact test). The mean VZV antibody titer at 72 hours was 1 : 112,000 (5.05 log~o). The mean VZV antibody titer among infants tested at six weeks was 1:77,000 (4.88 log~o) compared with an initial mean titer of 1:55,000 (4.74 log~o) in these infants.
DISCUSSION The data from our study and from the report of Raker et al. 4 suggest that it is not necessary to administer VZV antibody to all premature or sick infants who are inadvertently exposed to VZV. Our results indicate that infants with birth weights of 1000 gm or less or gestational ages less than 25 weeks may have tow or undetectable antibody to VZV. Infants who have received red blood cell or fresh-frozen plasma transfusions may be expected to have VZV antibody concentrations within the range found in immune adults. If exposure to VZV occurs in a nursery, infants of very low birth weight and gestational age should be screened for VZV antibody. If antibody screening is not feasible, Z I G a.dministration may be limited to t h i s group. The administration of Z I G in the standard dosage produces a significant increase in antibody titers among infants whose initial VZV antibody titers are low.
REFERENCES 1. Gershon AA, Raker R, Steinberg S, Topf-Olstein B, Drusin LM: Antibody to varicella-zoster virus in parturient women and their offspring during the first year of life. Pediatrics 58:692, 1976. 2. Gitlin D: Development and metabolism of the immune globulins. In Kagan BM, Stiehm ER, editors: Immunologic incompetence. Chicago, 197 l, Year Book Medical Publishers, pp 3-13. 3. Feldman S, Hughes WT, Daniel CB: Varicella in children with cancer: Seventy-seven cases. Pediatrics 56:388, 1975, 4. Raker RK, Steinberg S, Drusin LM, Gershon A: Antibody to varicella zoster virus in low-birth-weight newborn infants. J PEDIATR 93:505, 1978. 5. Arvin AM, Koropchak CM: lmmunoglobulins M and G to varicella-zoster virus measured by solid-phase radioimmunoassay: Antibody responses to varicella and herpes zoster infections. J Clin Microbiol 12:367, 1980.
Spontaneous elevation in arterial blood pressure during the first hours of life in the very-low-birth-weight infant Pedro Moscoso, M.D., Ronald N. Goldberg, M.D., Shnine Jamieson, and Eduardo Bancalari, M.D. Miami, Fla. From the Division of Neonatology and the Department of Pediatrics, University of Miami School of Medicine. Supported in part by Grant 1 ROIHD14940-02, the National Institute of Child Health and Human Development, and by Grant 6-303, March of Dimes/Birth Defects Foundation.
Reprint requests: Ronald 3/. Goldberg, M.D., Department of Pediatrics (R-t31), University of Miami School of Medicine, P.O. Box 016960, Miami, FL 33101.
Clinical and laboratory observations
113
Clinical and laboratory observations
Varicella zoster virus antibody titers before and after administration o f zoster immune globulin to neonates in an intensive care nursery Elaine E. L. Wang, M.D., Charles G. Prober, M.D., and Ann M. Arvin, M.D. Toronto, Ont., Canada, a n d S t a n f o r d , Calif.
VARICELLA ZOSTER VIRUS rarely causes infection in young infants; the healthy term infant is probably protected after exposure to VZV by antibody that is passively transferred from the mother? Premature infants may not receive as much antibody transplacentally as term infants2 and may be at increased risk of severe VZV infection after exposure, as are older immunocompromised children? In a previous report, none of 31 infants in a neonatal intensive care unit developed varicella after exposure to a nurse with VZV infection.4 Infants in our intensive care nursery who were inadvertently exposed to a nurse with VZV infection were given zoster immune globulin, and VZV serum antibody titers were measured before and after ZIG administration to determine the number of patients with preexisting VZV antibody and whether a detectable antibody rise occurred after ZIG prophylaxis.
MATERIALS AND METHODS Thirty-two infants in our intensive care nursery who were exposed to VZV were given 1 ml ZIG (mean dose 0.6 ml/kg) intramuscularly within 72 hours after exposur e. All infants were less than 2 months of age. Their gestational ages ranged from 25 to 40 weeks, with a mean of 33.8 weeks, and their birth weights ranged from 750 to 4790 gm, with a mean of 2278 gm. ZIG, which was obtained from the Canadian Red Cross, was produced by the Massachusetts Public Health Laboratory. A blood sample was obtained by venipuncture from
From Division of Infectious Diseases, Department of Pediatrics, The Hospital for Sick Children, University of Toronto; and Department of Pediatrics, Stanford University Medical Center. Reprint requests: Charles G. Prober, M. D., Division of lnfectious Diseases, The Hospital for Sick Children, 555 University Ave., Toronto, Ont., Canada M5G lX8.
each infant just before prophylaxis was given. Repeat samples were obtained 72 hours and/or six weeks after ZIG administration. The serum fraction was separated and stored at 4 ~ C until radioimmunoassay for VZV antibody was performed? The assays of sera from each patient were performed in parallel. The antibody titer in most VZVimmune adults is >_1 : 16,384 (4.2 log~0) when measured by radioimmunoassay. The volume and frequency of red blood cell and freshfrozen plasma transfusions were noted. The patients were monitored for the development of clinical varicella for six weeks after exposure.
RESULTS No clinical cases of varicella were detected during the six-week study period. Thirty-one of 32 (97%) patients had detectable VZV antibody before ZIG administration (Table). The lowest mean VZV antibody titer was observed in infants whose
VZV ZIG
Varicella zoster virus Zoster immune globulin
gestational age was 25 weeks or less. Infants of 26 to 30 weeks' gestation had VZV antibody equivalent to those in the infants of more than 30 weeks' gestation. One infant in each birth weight group had a low initial antibody titer, defined as a titer <1:4,096 (3.6 log~0). The mothers of these three infants all recalled having childhood varicella. One of these patients was a 6-day-old, 600 gm infant of 30 weeks' gestation who lacked any detectable antibody. The infants weighing 1000 gm or less tended to have lower VZV antibody titers than infants of higher birth weight. The mean VZV antibody titer was not significantly differ-
1 14
Clinical and laboratory observations
The Journal of Pediatrics July 1983
Table. Varicella zoster virus antibody titers in relation to gestational age, birth weight, and postnatal age Number o~ patients Gestational age (wk) _<_25 2 26 to 30 6 31 to 35 7 36 17 Birth weight (gin) ~<1000 5 >1000 27 Postnatal age (too) _< 1 24 >1 8
Mean serum VZV antibodytiter
Log _+SE
1 : 16,384 1:64,565 1:81,283 1:50,118
4.2_+0 4.81 _+ 0.89 4.91 _+ 59 4.7 _+ 0.26
1:6,918 1:91,700
3.84 _+ 0.7 4.96 _+ 0,23
1 : 39,810 1 : 128,824
4.60 -+ 0.3 5.11 -+ 0.48
ent in infants whose postnatal age was less than 1 month compared with those who were 1 to 2 months of age. Fifteen infants who were tested after red blood cell transfusions had the same mean VZV titer of 1:50,200 (4.7 logj0) as untransfused infants. Seven infants who had been given fresh-frozen plasma had a mean VZV titer of 1:251,000 (5.4 logt0); the difference from values in the untransfused patients did not reach statistical significance. Serum was obtained at 72 hours after Z I G administration from 13 infants and at six weeks after Z I G from 27 infants. A fourfold or greater rise in titer was observed in five patients (38%) at 72 hours and in eight patients (29%) at six weeks. Patients with an initial VZV antibody titer of 1 : 16,384 or less demonstrated an antibody rise at 72 hours significantly more frequently than patients with a pre-ZIG titer above 1 : 16,384 (five of seven vs none of six; P 0.02, Fisher exact test). The mean VZV antibody titer at 72 hours was 1 : 112,000 (5.05 log~o). The mean VZV antibody titer among infants tested at six weeks was 1:77,000 (4.88 log~o) compared with an initial mean titer of 1:55,000 (4.74 log~o) in these infants.
DISCUSSION The data from our study and from the report of Raker et al. 4 suggest that it is not necessary to administer VZV antibody to all premature or sick infants who are inadvertently exposed to VZV. Our results indicate that infants with birth weights of 1000 gm or less or gestational ages less than 25 weeks may have tow or undetectable antibody to VZV. Infants who have received red blood cell or fresh-frozen plasma transfusions may be expected to have VZV antibody concentrations within the range found in immune adults. If exposure to VZV occurs in a nursery, infants of very low birth weight and gestational age should be screened for VZV antibody. If antibody screening is not feasible, Z I G a.dministration may be limited to t h i s group. The administration of Z I G in the standard dosage produces a significant increase in antibody titers among infants whose initial VZV antibody titers are low.
REFERENCES 1. Gershon AA, Raker R, Steinberg S, Topf-Olstein B, Drusin LM: Antibody to varicella-zoster virus in parturient women and their offspring during the first year of life. Pediatrics 58:692, 1976. 2. Gitlin D: Development and metabolism of the immune globulins. In Kagan BM, Stiehm ER, editors: Immunologic incompetence. Chicago, 197 l, Year Book Medical Publishers, pp 3-13. 3. Feldman S, Hughes WT, Daniel CB: Varicella in children with cancer: Seventy-seven cases. Pediatrics 56:388, 1975, 4. Raker RK, Steinberg S, Drusin LM, Gershon A: Antibody to varicella zoster virus in low-birth-weight newborn infants. J PEDIATR 93:505, 1978. 5. Arvin AM, Koropchak CM: lmmunoglobulins M and G to varicella-zoster virus measured by solid-phase radioimmunoassay: Antibody responses to varicella and herpes zoster infections. J Clin Microbiol 12:367, 1980.
Spontaneous elevation in arterial blood pressure during the first hours of life in the very-low-birth-weight infant Pedro Moscoso, M.D., Ronald N. Goldberg, M.D., Shnine Jamieson, and Eduardo Bancalari, M.D. Miami, Fla. From the Division of Neonatology and the Department of Pediatrics, University of Miami School of Medicine. Supported in part by Grant 1 ROIHD14940-02, the National Institute of Child Health and Human Development, and by Grant 6-303, March of Dimes/Birth Defects Foundation.
Reprint requests: Ronald 3/. Goldberg, M.D., Department of Pediatrics (R-t31), University of Miami School of Medicine, P.O. Box 016960, Miami, FL 33101.