Maternal administration of valaciclovir in symptomatic intrauterine cytomegalovirus infection.
OBJECTIVE
To report early experience with treatment of intrauterine cytomegalovirus (CMV) infection using maternal oral administration of valaciclovir (VACV).


METHODS
Observational study of fetuses infected with CMV with or without treatment with valaciclovir.


METHODS
Pregnancies with confirmed fetal CMV infection were treated with oral VACV (8 g/day).


METHODS
Fetal viral load and drug concentration were monitored in amniotic fluid and in fetal blood. Data on the course and outcome of a group of untreated symptomatic fetuses infected with CMV are also reported.


RESULTS
Therapeutic concentrations were achieved in maternal and fetal bloods. The viral load in the fetal blood (VLFB) decreased significantly after 1-12 weeks of treatment (Wilcoxon paired test P = 0.02). Twenty pregnancies including 21 fetuses were treated at 28 weeks (median, range: 22-34) for 7 weeks (median, range: 1-12). Ten infants were developing normally at between 1 and 5 years of age. Two infants (both aged 2 years) had severe isolated unilateral deafness. One neonate presented with microcephaly and severe deafness but was also diagnosed with incontinentia pigmenti. Six out of seven cases that eventually required termination of pregnancy (TOP) had evidence of in utero progression of the disease with worsening cerebral lesions. One fetus died in utero. The outcome of 14/24 (58.3%) untreated symptomatic infected fetuses was poor with either TOP, intrauterine fetal demise or severe congenital infection disease of the neonate; the remaining ten infants were healthy at follow up.


CONCLUSIONS
Maternal oral administration of VACV leads to therapeutic concentrations in the maternal and fetal compartments, with a decrease in VLFB. Our results suggest that in cases where TOP is declined, a randomised controlled trial to study this treatment option further is indicated.
Jacquemard
F
F
Service de Médecine foetale, Institut de Puériculture de Paris, Paris, France.
Yamamoto
M
M
Costa
J-M
JM
Romand
S
S
Jaqz-Aigrain
E
E
Dejean
A
A
Daffos
F
F
Ville
Y
Y
D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000284:Administration, Oral; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003586:Cytomegalovirus Infections / Q000097:blood / Q000188:drug therapy*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D005315:Fetal Diseases / Q000097:blood / Q000821:virology*; D006801:Humans; D010865:Pilot Projects; D010976:Platelet Count; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood / Q000188:drug therapy*; D012646:Self Administration; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019562:Viral Load
D000998:Antiviral Agents; D004279:DNA, Viral; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir