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Transplacental passage of acyclovir
1 64
E d i t o r i a l correspondence
instrument, and the patient under general anesthesia allows a more leisurely examination. In the reported study, rigid bronchoscopy was done in all patients with severe stenosis and in five of six patients with moderate stenosis. In all but one instance, the rigid endoscopic findings confirmed the findings by flexible endoscopy. In that one exception, a patient with moderate stenosis by FFB was thought at rigid endoscopy to have only mild stenosis, but 2 months had elapsed between examinations. Vocal cords may fail to move because they are paralyzed or because their motion is limited mechanically. The subglottic stenosis in these patients was sufficient to "tether" the cords and inhibit movement, even passively. This finding was confirmed by rigid endoscopy. James M. Sherman, M.D. Assistant Professor Section o f Pulmonary Diseases University o f South Florida Medical Center College o f Medicine Department o f Pediatrics Box 15 12901 N. 30th St. Tampa, FL 33612-4799
Transplacental passage of acyclovir To the Editor: We wish to add some data and a comment to the paper by Greffe et al. (J PEDIATR 1986;108:1020-1). Transplacental passage of acyclovir certainly occurs. Kingsley~ has reported the outcome of 95 pregnancies in which acyclovir was prescribed during the first, second, or third trimester. Eleven of the firsttrimester pregnancies ended in elective abortion, and two others in the spontaneous abort!on. Of the 82 healthy babies, 16 had early problems but not related to acyclovir administration. Neither fatal side effects nor teratogenicity was assessed. After birth, in 13 cases the acyclovir level in cord blood ranged from <0.5 to 2.5
See related article, p. 151. #mol/L; amniotic fluid samples contained <0.5 to 5.5/xmol/L. In our unit, an acyclovir concentration of 2.95 ttmol/L was observed in cord blood obtained from a baby born to a woman with genital herpes, 13 hours after a maternal dose of 5 mg/kg. The baby was healthy and showed no treatment side effects. Inasmuch as in vitro IDs0 for herpes simplex viruses 1 and 2 (HSV, HSV2) and varicella zoster virus ( v z v ) ranged fom 0.1 to 3 #mol/L, 2 it is quite likely that levels noted above may be effective for in utero inhibition of viral replication. Berger et al: have described the failure of aeyelovir to prevent neonatal herpes in a gravid woman with HSV2 encephalitis; in this case the fetus had been infected before maternal acyclovir therapy and his disease was mild. Although HSV hematogenous contamination is rare, transplaeental passage of VZV is more frequent. In an
The Journal o f Pediatrics January 1987
attempt to prevent this occurence, in utero inhibition of viral replication may be sought even if efficacy is not well documented. In our opinion, the preliminary data are not sufficient tO warrant routine use of acyelovir during gestation, but it seems wise to resort to it in high-risk situations. However, prophylactic acyclovir therapy seems advisable in the newborn infant in more circumstances: infants born to mothers with varice!la Occurring from 4 days before up to 2 days after delivery, 4 or with genital herpes, and in dubious cases where a presumptive diagnosis of herpes may be suspected. J. Haddad, M.D. U. Simeoni, M.D. J. Messer, M.D. D. Willard, M.D. Neonatal Service Hbpital de Hautepierre 67098 Strasbourg Cedex, France
REFERENCES 1.
Kingsley S. Fetal and neonatal exposure to acyclovir [Abstract]. Second World Congress on Sexually Transmitted Diseases, Paris, June 1986. 2. Crumpacker CS, Schnipper LE, Zaia JA, Levin MJ. Growth inhibition by acycloguanosine of herpes viruses isolated from human ifnections. Antimicrob Agents Chemother 1979; 15:642-5. 3. Berger SA, Weinberg M, Treves T, et al. Herpes encephalitis during pregnancy: failure of acyclovir and adenine arabinoside to prevent neonatal herpes. Isr J Med Sci 1986; 22/1:41-4. 4. Haddad J, Simeoni U, Messer J, Willard D. Perinatal varicella. Lancet 1986;1:1494-5.
To the Editor." Greffe et al. (J PEDIATR1986;108:1020-1) reported the intravenous administration of acyclovir to a gravida 5 woman for presumed herpes encephalitis. Their results indicate that acyclovir was transported across the placenta without adversely affecting the infant. Although aeyclovir, when administered alone, is apparently not teratogenic and has limited mutagenie capacity, the authors caution that the potential side effects of acyclovir therapy in early gestation are unevaluated. In this respect, females who potentially harbor a concurrent cytomegalovirus (CMV) infection woul d appear to constitute one group to which aeyclovir therapy should be cautiously applied. There is accumulating evidence that tumorigenesis is a multistep phenomenon involving the collaboration of two independent genetic events) In CMV infected patients, the action of an otherwise latent CMV-encoded oncogene2 might be complemented by the DNA chain terminating action of acyclovir. Although the dose required to induce a cellular mutation suggests that aeyclovirinduced cellular DNA chain termination is rare, aeyclovir therapy in conjunction with a subclinical CMV infection could constitute a potent combination in the rapidly dividing and differentiating cells of the developing fetus. In view of the capacity for the concurrent reactivation of several herpesviruses and the prevalence of subclinical in utero CMV
E d i t o r i a l correspondence
instrument, and the patient under general anesthesia allows a more leisurely examination. In the reported study, rigid bronchoscopy was done in all patients with severe stenosis and in five of six patients with moderate stenosis. In all but one instance, the rigid endoscopic findings confirmed the findings by flexible endoscopy. In that one exception, a patient with moderate stenosis by FFB was thought at rigid endoscopy to have only mild stenosis, but 2 months had elapsed between examinations. Vocal cords may fail to move because they are paralyzed or because their motion is limited mechanically. The subglottic stenosis in these patients was sufficient to "tether" the cords and inhibit movement, even passively. This finding was confirmed by rigid endoscopy. James M. Sherman, M.D. Assistant Professor Section o f Pulmonary Diseases University o f South Florida Medical Center College o f Medicine Department o f Pediatrics Box 15 12901 N. 30th St. Tampa, FL 33612-4799
Transplacental passage of acyclovir To the Editor: We wish to add some data and a comment to the paper by Greffe et al. (J PEDIATR 1986;108:1020-1). Transplacental passage of acyclovir certainly occurs. Kingsley~ has reported the outcome of 95 pregnancies in which acyclovir was prescribed during the first, second, or third trimester. Eleven of the firsttrimester pregnancies ended in elective abortion, and two others in the spontaneous abort!on. Of the 82 healthy babies, 16 had early problems but not related to acyclovir administration. Neither fatal side effects nor teratogenicity was assessed. After birth, in 13 cases the acyclovir level in cord blood ranged from <0.5 to 2.5
See related article, p. 151. #mol/L; amniotic fluid samples contained <0.5 to 5.5/xmol/L. In our unit, an acyclovir concentration of 2.95 ttmol/L was observed in cord blood obtained from a baby born to a woman with genital herpes, 13 hours after a maternal dose of 5 mg/kg. The baby was healthy and showed no treatment side effects. Inasmuch as in vitro IDs0 for herpes simplex viruses 1 and 2 (HSV, HSV2) and varicella zoster virus ( v z v ) ranged fom 0.1 to 3 #mol/L, 2 it is quite likely that levels noted above may be effective for in utero inhibition of viral replication. Berger et al: have described the failure of aeyelovir to prevent neonatal herpes in a gravid woman with HSV2 encephalitis; in this case the fetus had been infected before maternal acyclovir therapy and his disease was mild. Although HSV hematogenous contamination is rare, transplaeental passage of VZV is more frequent. In an
The Journal o f Pediatrics January 1987
attempt to prevent this occurence, in utero inhibition of viral replication may be sought even if efficacy is not well documented. In our opinion, the preliminary data are not sufficient tO warrant routine use of acyelovir during gestation, but it seems wise to resort to it in high-risk situations. However, prophylactic acyclovir therapy seems advisable in the newborn infant in more circumstances: infants born to mothers with varice!la Occurring from 4 days before up to 2 days after delivery, 4 or with genital herpes, and in dubious cases where a presumptive diagnosis of herpes may be suspected. J. Haddad, M.D. U. Simeoni, M.D. J. Messer, M.D. D. Willard, M.D. Neonatal Service Hbpital de Hautepierre 67098 Strasbourg Cedex, France
REFERENCES 1.
Kingsley S. Fetal and neonatal exposure to acyclovir [Abstract]. Second World Congress on Sexually Transmitted Diseases, Paris, June 1986. 2. Crumpacker CS, Schnipper LE, Zaia JA, Levin MJ. Growth inhibition by acycloguanosine of herpes viruses isolated from human ifnections. Antimicrob Agents Chemother 1979; 15:642-5. 3. Berger SA, Weinberg M, Treves T, et al. Herpes encephalitis during pregnancy: failure of acyclovir and adenine arabinoside to prevent neonatal herpes. Isr J Med Sci 1986; 22/1:41-4. 4. Haddad J, Simeoni U, Messer J, Willard D. Perinatal varicella. Lancet 1986;1:1494-5.
To the Editor." Greffe et al. (J PEDIATR1986;108:1020-1) reported the intravenous administration of acyclovir to a gravida 5 woman for presumed herpes encephalitis. Their results indicate that acyclovir was transported across the placenta without adversely affecting the infant. Although aeyclovir, when administered alone, is apparently not teratogenic and has limited mutagenie capacity, the authors caution that the potential side effects of acyclovir therapy in early gestation are unevaluated. In this respect, females who potentially harbor a concurrent cytomegalovirus (CMV) infection woul d appear to constitute one group to which aeyclovir therapy should be cautiously applied. There is accumulating evidence that tumorigenesis is a multistep phenomenon involving the collaboration of two independent genetic events) In CMV infected patients, the action of an otherwise latent CMV-encoded oncogene2 might be complemented by the DNA chain terminating action of acyclovir. Although the dose required to induce a cellular mutation suggests that aeyclovirinduced cellular DNA chain termination is rare, aeyclovir therapy in conjunction with a subclinical CMV infection could constitute a potent combination in the rapidly dividing and differentiating cells of the developing fetus. In view of the capacity for the concurrent reactivation of several herpesviruses and the prevalence of subclinical in utero CMV