Lisa M. Hollier

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 χ2 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.

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.

Valacyclovir prophylaxis to prevent recurrent herpes at delivery: A randomized clinical trial

OBJECTIVE: To measure the efficacy of valacyclovir suppression in late pregnancy to reduce the incidence of recurrent genital herpes in labor and subsequent cesarean delivery. METHODS: A total of 350 pregnant women with a history of genital herpes were assigned randomly to oral valacyclovir 500 mg twice a day or an identical placebo from 36 weeks of gestation until delivery. In labor, vulvovaginal herpes simplex virus (HSV) culture and polymerase chain reaction (PCR) specimens were collected. Vaginal delivery was permitted if no clinical recurrence or prodromal symptoms were present. Neonatal HSV cultures and laboratory tests were obtained, and infants were followed up for 1 month after delivery. Data were analyzed using &khgr;2 and Student t tests. RESULTS: One hundred seventy women treated with valacyclovir and 168 women treated with placebo were evaluated. Eighty-two percent of the women had recurrent genital herpes; 12% had first episode, nonprimary genital herpes; and 6% had first episode, primary genital herpes. At delivery, 28 women (8%) had recurrent genital herpes requiring cesarean delivery: 4% in the valacyclovir group and 13% in the placebo group (P = .009). Herpes simplex virus was detected by culture in 2% of the valacyclovir group and 24% of the placebo group (P =.02). No infants were diagnosed with neonatal HSV, and there were no significant differences in neonatal complications. There were no significant differences in maternal or obstetric complications in either group. CONCLUSION: Valacyclovir suppression after 36 weeks of gestation significantly reduces HSV shedding and recurrent genital herpes requiring cesarean delivery. LEVEL OF EVIDENCE: I

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.

Treatment of Syphilis in Pregnancy and Prevention of Congenital Syphilis

Studies about the management of syphilis during pregnancy were reviewed. They lacked uniformity in diagnostic criteria and study design. Currently recommended doses of benzathine penicillin G are effective in preventing congenital syphilis in most settings, although studies are needed regarding increased dosing regimens. Azithromycin and ceftriaxone offer potential alternatives for penicillin-allergic women, but insufficient data on efficacy limit their use in pregnancy. Ultrasonography provides a noninvasive means to examine pregnant women for signs of fetal syphilis, and abnormal findings indicate a risk for obstetric complications and fetal treatment failure. Ultrasonography should precede antepartum treatment during the latter half of pregnancy to gauge severity of fetal infection. However, optimal management of the affected fetus has not been established; collaborative management with a specialist is recommended. Antepartum screening remains a critical component of congenital syphilis prevention, even in the era of syphilis elimination.

Cost-effectiveness of Universal Influenza Vaccination in a Pregnant Population

OBJECTIVE: The purpose of this study was to estimate whether universal influenza vaccination of pregnant women was cost-effective in the management of influenza-like illness during influenza season. METHODS: A decision analysis model was developed to investigate the cost-effectiveness of providing inactivated trivalent influenza vaccine to all pregnant women. This scenario was compared with providing supportive care only on a case-by-case basis to the unvaccinated pregnant population. RESULTS: Vaccination of 100% of pregnant women would save approximately

The clinical content of preconception care: infectious diseases in preconception care.

50 per woman, resulting in a net gain of approximately 45 quality-adjusted hours relative to providing supportive care only. CONCLUSION: Universal vaccination with inactivated trivalent influenza vaccine is cost-saving relative to providing supportive care alone in the pregnant population. LEVEL OF EVIDENCE: III

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

A number of infectious diseases should be considered for inclusion as part of clinical preconception care. Those infections strongly recommended for health promotion messages and risk assessment or for the initiation of interventions include Chlamydia infection, syphilis, and HIV. For selected populations, the inclusion of interventions for tuberculosis, gonorrheal infection, and herpes simplex virus are recommended. No clear evidence exists for the specific inclusion in preconception care of hepatitis C, toxoplasmosis, cytomegalovirus, listeriosis, malaria, periodontal disease, and bacterial vaginosis (in those with a previous preterm birth). Some infections that have important consequences during pregnancy, such as bacterial vaginosis (in those with no history of preterm birth), asymptomatic bacteriuria, parvovirus, and group B streptococcus infection, most likely would not be improved through intervention in the preconception time frame.

State laws regarding prenatal syphilis screening in the United States

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. NeonatalHSV 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.

Preventing preterm birth: What works, what doesn't

OBJECTIVE The purpose of this study was to assess the frequency and pattern of state laws or regulations regarding prenatal syphilis serologic screening in the United States in 2001. STUDY DESIGN We surveyed the United States for existing laws and regulations regarding serologic screening for syphilis during pregnancy. Testing was compared with 2000 state rates of syphilis in women and newborn infants, with states that had syphilis high morbidity areas, and with national 2000 and 2010 objectives for rates of syphilis. RESULTS Forty-six of the 50 states (90%) and the District of Columbia have laws regarding antenatal syphilis screening. Thirty-four of the 46 statutes (76%) mandate one prenatal test, usually at the first prenatal visit or early in pregnancy. Twelve laws (26%) include third-trimester testing for all or high-risk women. The presence of high morbidity areas, incidence of early syphilis in women, and rates of congenital syphilis are associated with increasing frequency of legislated antepartum screening. CONCLUSION Only 90% of states have statutes that require antepartum syphilis screening, and there is variation in the content of the statutes about the number and timing of tests. States with a heavy burden of infectious syphilis in women tend to require more prenatal testing.