Maternal group B Streptococcus-related stillbirth: a systematic review.

BACKGROUND: Limited epidemiological data on the association between maternal rectovaginal group B Streptococcus (GBS) colonisation and stillbirth makes assessment of antenatal interventions for GBS stillbirth difficult. OBJECTIVES: To systematically review the existing literature and evaluate the incidence of GBS-related stillbirth by region up to March 2015. SEARCH STRATEGY: A systematic review of the published literature was completed using PubMed/MEDLINE, EMBASE, LILACS, and Cochrane Library, with Medical Subject Headings (MeSH) and search terms based upon the Centers for Disease Control and Prevention's (CDC) Active Bacterial Core Surveillance (ABCs) GBS-related stillbirth definition and chorioamnionitis. SELECTION CRITERIA: Studies reporting original data on GBS-related stillbirth occurring ≥20 weeks of gestation, with GBS confirmed by autopsy or by culture from the placenta, amniotic fluid, or other normally sterile site samples from the stillborn. DATA COLLECTION AND ANALYSIS: Descriptive analyses were performed with the absolute GBS-related stillbirth rates and proportion of stillbirths attributed to GBS calculated per study where possible. Differences in stillbirth definitions did not allow for pooled estimates to be calculated. MAIN RESULTS: Seventeen studies reported GBS-related stillbirth rates varying from 0.04 to 0.9 per 1000 births, with the proportion of stillbirths associated with GBS ranging from 0 to 12.1%. Most studies reported data from before the year 2000 and from high-income countries. CONCLUSIONS: The sparsely available epidemiological evidence was not reported consistently, emphasising the importance of standardised stillbirth definitions and diagnostic methods to optimally assess the effectiveness of any future antenatal interventions. Timing of stillbirth, GBS serotype, and global diversity were gaps in the current evidence. TWEETABLE ABSTRACT: Systematic review finds Group B Streptococcus causes up to 12.1% of stillbirths, but more research is needed.

Final results from 18 years of the International Lamotrigine Pregnancy Registry.

OBJECTIVE: To monitor for a signal for major teratogenicity following in utero lamotrigine exposure. METHODS: Health care providers reported lamotrigine exposure during pregnancy, and subsequent outcomes, on a voluntary basis. Prospective reporting early in pregnancy was encouraged. Major congenital malformations (MCMs) were classified according to the Centers for Disease Control and Prevention (CDC) criteria and were reviewed by a pediatrician on the Registry's Scientific Advisory Committee. The proportion of infants with MCMs was calculated by trimester and therapy type and descriptively compared to population-based reference estimates. RESULTS: Over an 18-year period, 35 infants with MCMs were observed among 1,558 first-trimester monotherapy exposures: 2.2%(95% confidence interval [CI] 1.6%-3.1%). This was similar to estimates from general population-based cohorts. The observed proportion of infants with MCMs among 150 lamotrigine/valproate polytherapy exposures was 10.7% (95% CI 6.4%-17.0%) and was 2.8% (95% CI 1.5%-5.0%) among 430 infants exposed to lamotrigine polytherapy without valproate. No consistent pattern of malformation type, or malformation frequency by dose, was observed. DISCUSSION: The Registry did not detect an appreciable increase in MCM frequency following first-trimester lamotrigine monotherapy exposure. With over 1,500 first-trimester monotherapy exposures, the Registry was powered to detect major teratogenicity. The proportion of infants with MCMs following lamotrigine/valproate polytherapy exposure was high, but similar to that previously reported with valproate monotherapy. The Registry failed to observe an increased MCM frequency with increasing lamotrigine dose. Monitoring of specific malformations among lamotrigine-exposed pregnancies will continue through case-control surveillance in the European Congenital Anomalies and Twins Registers network.

Nonadherence to antiepileptic drugs and increased mortality: findings from the RANSOM Study.

OBJECTIVES: The primary objective was to investigate whether nonadherence to antiepileptic drugs (AEDs) is associated with increased mortality and the secondary objective to examine whether nonadherence increases the risk of serious clinical events, including emergency department (ED) visits, hospitalizations, motor vehicle accident (MVA) injuries, fractures, and head injuries. METHODS: A retrospective open-cohort design was employed using Medicaid claims data from Florida, Iowa, and New Jersey from January 1997 through June 2006. Patients aged > or =18 years with > or =1 diagnosis of epilepsy by a neurologist and > or =2 AED pharmacy dispensings were selected. Medication possession ratio (MPR) was used to evaluate AED adherence on a quarterly basis with MPR > or =0.80 considered adherent and <0.80 nonadherent. The association of nonadherence with mortality was assessed using a time-varying Cox regression model adjusting for demographic and clinical confounders. Incidence rates for serious clinical events were compared between adherent and nonadherent quarters using incidence rate ratios (IRRs) with 95% CIs calculated based on the Poisson distribution. RESULTS: The 33,658 study patients contributed 388,564 AED-treated quarters (26% nonadherent). Nonadherence was associated with an over threefold increased risk of mortality compared to adherence (hazard ratio = 3.32, 95% CI = 3.11-3.54) after multivariate adjustments. Time periods of nonadherence were also associated with a significantly higher incidence of ED visits (IRR = 1.50, 95% CI = 1.49-1.52), hospital admissions (IRR = 1.86, 95% CI = 1.84-1.88), MVA injuries (IRR = 2.08, 95% CI = 1.81-2.39), and fractures (IRR = 1.21, 95% CI = 1.18-1.23) than periods of adherence. CONCLUSION: These findings suggest that nonadherence to antiepileptic drugs can have serious or fatal consequences for patients with epilepsy.

A population-based seroprevalence study of hepatitis A virus using oral fluid in England and Wales.

Population-based seroprevalence studies provide important data on susceptible groups and the potential for future outbreaks. However, the invasive nature of serum collection has limited studies. This paper describes the first postal population-based survey using noninvasive oral fluid technology to collect antibody prevalence data in conjunction with extensive risk factor data to assess the distribution of immunity to common viral infections in England and Wales. These results pertain to hepatitis A virus (HAV). Approximately 5,500 oral fluid samples were collected between August 2001 and May 2002, as well as individual risk factor data through a questionnaire, from persons aged less than 45 years randomly sampled from general practices countrywide. Samples were tested for immunoglobulin G-specific antibody marking a past infection or immunity to HAV using an antibody-capture enzyme-linked immunosorbent assay. The age-specific HAV seroprevalences indicated a low incidence of infection (overall seroprevalence of 18.9% (95% confidence interval: 17.0, 20.9) and of 9.2% (95% confidence interval: 7.1, 11.3) after the exclusion of vaccinees). Vaccination proved the most important determinant of seropositivity. Ethnic minority groups were underrepresented, and adjustment increased the overall prevalence to 20.1% and to 12.1% in unvaccinated individuals. The availability of comprehensive risk factor data allowed the description of two risk profiles related to natural infection and vaccination.

A novel method of oral fluid collection to monitor immunity to common viral infections.

Serological surveys among representative population samples have proved rare given their reliance on invasive sample collection. We therefore completed the first population-based postal survey of immunity in England and Wales using new oral fluid technology. This paper examines the feasibility of this new methodological approach. Nearly 5500 oral fluid samples were collected, with individual demographic and social data via a questionnaire, from persons under 45 years of age recruited through general practices. Instructions were accurately followed with only 1% of samples returned without risk-factor data. The overall response rate was 40%. Response was independently associated with age, sex and location. Response was highest in children aged 5-14 years, adult females and in rural locations. This approach allowed the successful collection of comprehensive individual risk data, but response rates in adults must be improved if oral fluid surveys are to routinely complement serological surveillance.