INTRODUCTION
Neonatal herpes infection is a devastating illness with a mortality of 50% if untreated1. Optimal treatment with acyclovir can reduce this to 30%, but there are substantial numbers of children left alive with severe neurological sequelae2. The majority of cases of neonatal herpes infection are acquired through contact with herpes simplex virus at the time of delivery from the mother's birth canal. Other routes of infection, such as from birth attendants and relatives, have been described but are assumed to be relatively infrequent3.
In order to prevent neonatal herpes infection in women with recurrent genital herpes infection it has been recommended that the baby is delivered by caesarean section if there is evidence of active herpes lesions at the time of delivery4,5. However, although the consequences of neonatal herpes infection are very severe, the risk of acquiring neonatal herpes infection following vaginal delivery in a woman with active recurrent lesions at delivery is small. The opinion of obstetricians in the field suggests that the risk is < 5% and estimates of the risk in a study of 34 women has suggested a theoretical maximum of 8%6. Therefore, at least 12 women will undergo caesarean section to prevent each case of neonatal herpes. If the risk of transmission is < 8% the number of women undergoing caesarean section to prevent one case of neonatal herpes will be even higher.
Acyclovir is a drug which inhibits herpes simplex virus replication and has been used extensively in individuals with herpes infections, regardless of the site of infection7. It has been shown to be effective in the long term suppression of recurrences in adults with frequently recurring genital herpes8 and has been used parenterally in high doses for neonatal herpes infection2. There have been no reports of serious short term toxicity associated with oral administration or with intravenous infusion as long as there is adequate hydration9. There is also no evidence of teratogenicity of acyclovir given in pregnancy10.
The objectives of this trial were: 1. to evaluate the efficacy of a suppressive course of acyclovir in late pregnancy in women with a history of recurrent genital herpes infection in terms of the number of women undergoing delivery by caesarean section, the number of episodes of clinical herpes recurrences and the number of episodes of asymptomatic virus shedding during treatment; and 2. to evaluate the safety and tolerance of suppressive acyclovir in the woman and her infant.
The main outcome measure was the risk of delivery by caesarean section because of recurrent herpes infection. The decision to perform a caesarean section was left to the discretion of the obstetrician caring for the woman, In London, obstetricians recommended delivery by caesarean section for recurrent genital herpes infection at the time of labour or induction of labour. In Shefield, the obstetricians recommended delivery by caesarean section if there was either recurrent genital herpes infection at the onset of labour or if there was a clinical recurrence at ≥ 38 weeks of gestation, in which case delivery was by elective caesarean section.