Third trimester antiviral prophylaxis for preventing maternal genital herpes simplex virus (HSV) recurrences and neonatal infection.

BACKGROUND: Genital herpes simplex virus (HSV) infection is one of the most common viral sexually transmitted infections. The majority of women with genital herpes will have a recurrence during pregnancy. Transmission of the virus from mother to fetus typically occurs by direct contact with virus in the genital tract during birth. OBJECTIVES: To assess the effectiveness of antenatal antiviral prophylaxis for recurrent genital herpes on neonatal herpes and maternal recurrences at delivery. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 4), MEDLINE (January 1966 to February 2007) and EMBASE (January 1974 to February 2007; handsearched conference proceedings; reviewed bibliographies of all relevant articles for further references; and contacted experts in the field. SELECTION CRITERIA: Randomized controlled trials which assessed the effectiveness of antivirals compared to placebo or no therapy, on neonatal herpes and maternal disease endpoints among pregnant women with genital herpes. DATA COLLECTION AND ANALYSIS: Two authors independently applied study selection criteria and extracted data. MAIN RESULTS: Seven randomized controlled trials (1249 participants) which met our inclusion criteria compared acyclovir to placebo or no treatment (five trials) and valacyclovir to placebo (two trials). The effect of antepartum antiviral prophylaxis on neonatal herpes could not be estimated. There were no cases of symptomatic neonatal herpes in the included studies in either the treatment or placebo groups. Women who received antiviral prophylaxis were significantly less likely to have a recurrence of genital herpes at delivery (relative risk (RR) 0.28, 95% confidence interval (CI) 0.18 to 0.43, I(2 )= 0%). Women who received antiviral prophylaxis were also significantly less likely to have a cesarean delivery for genital herpes (RR 0.30, 95% CI 0.20 to 0.45, I(2) = 27.3%). Women who received antiviral prophylaxis were significantly less likely to have HSV detected at delivery (RR 0.14, 95% CI 0.05 to 0.39, I(2) = 0%). AUTHORS' CONCLUSIONS: Women with recurrent genital herpes simplex virus should be informed that the risk of neonatal herpes is low. There is insufficient evidence to determine if antiviral prophylaxis reduces the incidence of neonatal herpes. Antenatal antiviral prophylaxis reduces viral shedding and recurrences at delivery and reduces the need for cesarean delivery for genital herpes. Limited information exists regarding the neonatal safety of prophylaxis. The risks, benefits, and alternatives to antenatal prophylaxis should be discussed with women who have a history and prophylaxis initiated for women who desire intervention.

Viral infections in pregnancy.

Viral infections are a common complication of pregnancy and in some cases, can have profound effects for the unborn fetus. The human herpesvirus family is composed of large, enveloped DNA viruses that have close structural similarity. The family includes the herpes simplex viruses types 1 and 2, varicella zoster virus, Epstein Barr virus, cytomegalovirus (CMV), and human herpes viruses types 6, 7 and 8. These viruses all share the ability to establish latency and reactivate at a later time. Structural fetal abnormalities can result from intrauterine infection and transmission of the infection during the pregnancy or at the time of delivery can result in important neonatal disease. Human parvovirus B19 is a DNA virus with strong tropism for erythroid precursors and infection during pregnancy can result in fetal hydrops and stillbirth. The causative agents of hepatitis are hepatotropic viruses termed hepatitis A, B, C, D (deltavirus) and E. All except hepatitis B virus are RNA viruses. Vertical transmission of maternal infection with hepatitis B and C can result in significant long term sequelae.

Acyclovir suppression to prevent recurrent genital herpes at delivery.

OBJECTIVE: To determine if suppressive acyclovir near term decreased the frequency of clinical recurrences at delivery in women with recurrent genital herpes simplex virus (HSV) infection. METHODS: We conducted a prospective, double-blind, randomized trial in 234 women with recurrent genital herpes. Women with genital infection of any frequency were enrolled. Patients received either suppressive oral acyclovir 400 mg three times daily or an identical placebo after 36 weeks' gestation. Clinical lesions were identified, and HSV cultures were obtained at delivery. The frequencies of clinical and subclinical HSV recurrences at delivery were evaluated. RESULTS: Six percent of patients treated with acyclovir, and 14% of patients treated with placebo had clinical HSV at delivery (p = 0.046). No patients in the acyclovir group had positive HSV cultures, compared with 6% of placebo-treated patients (p = 0.029). There was no significant difference in subclinical HSV shedding in the acyclovir group (0%) compared with the placebo-treated group (3%) (p = 0.102). CONCLUSIONS: Suppressive acyclovir therapy significantly decreased the incidence of clinical genital herpes and the overall incidence of HSV excretion at delivery in patients with previous herpes infection.

Acyclovir suppression to prevent clinical recurrences at delivery after first episode genital herpes in pregnancy: an open-label trial.

OBJECTIVE: To continue evaluation of the use of acyclovir suppression in late pregnancy after first episode genital herpes simplex virus (HSV) infection, using an open-label study design. METHODS: Ninety-six women diagnosed with genital herpes for the first time in the index pregnancy were prescribed suppressive acyclovir 400 mg orally three times daily from 36 weeks until delivery in an open-label fashion. Herpes cultures were obtained when patients presented for delivery. Vaginal delivery was permitted if no clinical recurrence was present; otherwise a Cesarean delivery was performed. Neonatal HSV cultures were obtained and infants were followed clinically. Rates of clinical and asymptomatic genital herpes recurrences and Cesarean delivery for genital herpes were measured, and 95% confidence intervals were calculated. RESULTS: In 82 patients (85%) compliant with therapy, only 1% had clinical HSV recurrences at delivery. In an intent to treat analysis of the entire cohort, 4% had clinical recurrences (compared with 18-37% in historical controls). Asymptomatic shedding occurred in 1% of women without lesions at delivery. Two of the four clinical recurrences were HSV-culture positive. No significant maternal or fetal side-effects were observed. CONCLUSIONS: In clinical practice the majority of patients are compliant with acyclovir suppression at term. The therapy appears to be effective at reducing clinical recurrences after a first episode of genital herpes complicating a pregnancy.

Fetal syphilis: clinical and laboratory characteristics.

OBJECTIVE: To examine the pathophysiology of fetal syphilis and correlate hematologic, immunologic, and sonographic findings. METHODS: Twenty-four women with untreated syphilis during pregnancy were prospectively identified. Sonography with amniocentesis and percutaneous umbilical blood sampling were performed. Darkfield examination, rabbit infectivity testing, and polymerase chain reaction for detection of Treponema pallidum were performed on amniotic fluid. Hematologic and chemical testing of fetal blood was performed using standard techniques. Fetal antitreponemal IgM was detected by Western blot assay. Maternal syphilis was treated with 2.4 to 4.8 million units of benzathine penicillin G intramuscularly. Neonatal outcomes and signs of congenital syphilis were recorded. RESULTS: Six women had primary, 12 had secondary, and six had early latent syphilis. Sixty-six percent of fetuses (95% confidence interval [CI] 47%, 82%) had either congenital syphilis or detection of Treponema pallidum in amniotic fluid. Sixty-six percent had hepatomegaly, including three fetuses (12.5%, 95% CI 4%, 31%) with ascites. Fetal antitreponemal IgM was detected in three cases. Abnormal liver transaminases were found in 88% (CI 69%, 96%), anemia in 26% (CI 13%, 47%), and thrombocytopenia in 35% (CI 19%, 55%). Maternal treatment was successful in 83% (CI 64%, 93%). Risk of treatment failure was significantly increased when hepatomegaly and ascites were present (P =.01). CONCLUSION: Findings with fetal syphilis are similar to those of neonatal syphilis. We hypothesize that fetal transaminase elevation occurs early in the course of infection; hematologic abnormalities and hydrops occur later. Severity of disease may be associated with risk of treatment failure.

Seasonality in conception of births and influence on late initiation of prenatal care.

OBJECTIVE: To determine whether there is a summer peak in conception of births to adolescents (up to 17 years) compared with older teenagers (18-19 years) and adults (20-29 years), and to assess the influence of season of conception on late initiation of prenatal care. METHODS: We analyzed 1,178,607 singleton births to women aged 29 years and younger in Texas between 1994 and 1998. Dates of conception were estimated using last menstrual period and clinical estimates of gestation. Proportions of births conceived per month were assessed for seasonal patterns. Proportions of births with late initiation of prenatal care were also compared by month of conception. The outcomes were further stratified by sociodemographic variables. RESULTS: There was a consistent summer trough (7.5% in August) and year-end peak (9.1% in December) in conception of births to adolescents (P <.001), a pattern similar to that of older teenagers and adults. Among the adolescents, students and non-Hispanic women giving birth presented a secondary early summer peak (8.8% each in May and June) in their conceptions. There was a modest bimodal effect of season of conception on initiation of prenatal care in all age groups. Adolescent conceptions in April-May and September-October were 14-18% and 6% significantly more likely to have late prenatal care compared with other months, respectively. CONCLUSION: Adolescents giving birth in Texas were not more likely to conceive in the summer. They did present seasonal patterns of conception and late initiation of prenatal care similar to older women.

Maternal age and malformations in singleton births.

OBJECTIVE: To examine the effect of maternal age on incidence of nonchromosomal fetal malformations. METHODS: Malformations detected at birth or in the newborn nursery were catalogued prospectively for 102,728 pregnancies, including abortions, stillbirths, and live births, from January 1, 1988 to December 31, 1994. Maternal age was divided into seven epochs. Relative risks (RRs) were used to compare demographic variables and specific malformations. The Mantel-Haenszel chi(2) statistic was used to compare age-specific anomalies. Multiple logistic regression analysis was used to adjust for parity. RESULTS: Abnormal karyotypes were significantly more frequent in older women. After excluding infants with chromosomal abnormalities, the incidence of structurally malformed infants also was increased significantly and progressively in women 25 years of age or older. The additional age-related risk of nonchromosomal malformations was approximately 1% in women 35 years of age or older. The odds ratio for cardiac defects was 3.95 in infants of women 40 years of age or older (95% CI 1.70, 9.17) compared with women aged 20-24 years. The risks of clubfoot and diaphragmatic hernia also increased as maternal age increased. CONCLUSION: Advanced maternal age beyond 25 years was associated with significantly increased risk of fetuses having congenital malformations not caused by aneuploidy.

Can neurological injury be timed?

Our knowledge about the cause of cerebral palsy continues to expand and prenatal events are thought to play an important role. This article reviews laboratory tests, imaging studies and pathologic findings that have been used to identify the timing of neurological injury. Limitations exist for all modalities, however, imaging studies, electroencephalograms and pathologic examination provide the most useful information. Improvements in our ability to time neurological injury will better direct our efforts to prevent cerebral palsy.

Outcome of twin pregnancies according to intrapair birth weight differences.

OBJECTIVE: To assess the clinical significance of twin intrapair birth weight differences. METHODS: This was a retrospective study of twin pregnancy outcomes. Intrapair birth weight differences were stratified into the following six groups: 14% or less, 15-20%, 21-25%, 26-30%, 31-40%, and 41% or more using the larger infant as the growth standard. Statistical analysis was done using the Mantel-Haenzel chi2 test. RESULTS: We studied 1370 consecutive women who delivered at Parkland Hospital, Dallas, Texas, between January 1, 1988, and December 31, 1996, and had twin gestations and live births or fetal deaths within 7 days of delivery. Greater birth weight discordance was significantly associated with preterm delivery due to intervention (P<.001). Noncephalic-cephalic presentations and cesarean delivery were also associated with greater discordance (P = .001 and .02, respectively). Neonatal morbidities, including low birth weight, intensive care admission, and respiratory distress, were all associated with higher birth weight discordance. Fetal abnormalities were more common with increased discordance (P<.001). Greater birth weight discordance was also associated with intrauterine fetal death. There were no differences in outcome for the smaller compared with the larger twin of the twin pair. CONCLUSION: Twin birth weight discordance is problematic because severe divergent fetal growth increases the risk of fetal death and leads to obstetric intervention and consequent neonatal morbidity due to prematurity.

Syphilis.

Syphilis was first recognized as a distinct syndrome in Europe in the fifteenth century. Despite knowledge of congenital infection for more than 450 years and the existence of adequate therapy for 55 years, congenital infection remains a problem for the practicing clinician. Syphilis is caused by Treponema pallidum. Infection may be transmitted horizontally by sexual contact and vertically as a result of hematogenous dissemination across the placenta. Syphilis is classified as primary, secondary, latent, and tertiary. The diagnosis may be established by darkfield examination of clinical lesions and by serological assays. The drug of choice for syphilis is penicillin. This agent is the only antibiotic of proven value for the treatment of congenital syphilis. Accordingly, infected pregnant women who are allergic to beta-lactam antibiotics must be desensitized and then treated with penicillin.

Postpartum endometritis caused by herpes simplex virus.

BACKGROUND: Herpes simplex virus (HSV) is rarely the causative agent of endometritis and is usually found in association with pelvic inflammatory disease. Only one case of postpartum HSV endometritis has been reported. CASES: We describe two cases of herpes simplex postpartum endometritis. Neither patient had genital HSV lesions noted at the time of delivery. The first case developed after a preterm cesarean delivery in an 18-year-old primipara. She had persistent puerperal fever despite broad-spectrum anti-microbial treatment. The second case was a 16-year-old primipara whose vaginal delivery was complicated by severe postpartum endometritis. Vulvar and endometrial cultures were positive for HSV alone in both patients. Both infants died from disseminated HSV infection. CONCLUSION: Herpes simplex virus can cause clinical postpartum endometritis.

Perinatal herpesvirus infections. Herpes simplex, varicella, and cytomegalovirus.

The herpesvirus infections (herpes simplex, varicella, and cytomegalovirus) create many dilemmas when encountered during pregnancy. This article reviews the epidemiologic diagnosis and management of perinatal herpesvirus infections. A review of possible future trends is also included.

Malaria in pregnancy.

This review summarizes the epidemiology, clinical course, and diagnosis of malaria. The influence of infection during pregnancy upon maternal and neonatal anemia, stillbirth, preterm labor, low birth weight, and congenital malaria is discussed. Options for treatment and prophylaxis during pregnancy are presented.