Clinical Risk Factors Associated With Late-Onset Invasive Group B Streptococcal Disease: Systematic Review and Meta-Analyses.

BACKGROUND: Group B streptococcal (GBS) infection remains one of the most significant causes of late-onset sepsis and meningitis (LOGBS) among young infants. However, transmission routes and risk factors for LOGBS are not yet fully understood. METHODS: We conducted systematic reviews on clinical risk factors previously reported in the literature (prematurity, low birth weight [<2500 g], antenatal colonization, multiple-gestation pregnancy, maternal age <20 years, male infant sex, intrapartum fever, prolonged rupture of membranes) and meta-analyses to determine pooled estimates of risk. RESULTS: We included 27 articles, reporting 5315 cases. Prematurity (odds ratio [OR] 5.66; 95% confidence interval [CI]: 4.43-7.22), low birth weight (OR 6.73; 95% CI: 4.68-9.67), maternal colonization (2.67; [2.07-3.45]), and multiple-gestation pregnancies (OR 8.01; 95% CI: 5.19-12.38) were associated with an increased risk of LOGBS. CONCLUSIONS: Prematurity/low birth weight and maternal colonization are major risk factors for LOGBS. Future GBS vaccine studies should try to establish the optimal time for vaccination during pregnancy to protect preterm infants.

Incidence of invasive Group B Streptococcal infection and the risk of infant death and cerebral palsy: a Norwegian Cohort Study.

BACKGROUND: Group B Streptococcus (GBS) is the leading cause of invasive neonatal infection worldwide. In high-income countries mortality rates are 4-10%, and among survivors of GBS meningitis 30-50% have neurodevelopmental impairments. We hypothesized that invasive GBS infection was associated with increased risk of infant mortality and cerebral palsy (CP). METHODS: All children born alive in Norway during 1996-2012 were included. Data were collected from three national registers. Invasive GBS infection during infancy was categorized into early-onset disease (EOD), late-onset disease (LOD), and very late-onset disease (VLOD). Primary outcomes were infant mortality and CP. RESULTS: Invasive GBS infection was diagnosed in 625 children (incidence: 0.62 per 1000 live births; 95% confidence interval (CI): 0.57-0.67). The incidence of EOD was 0.41 (0.37-0.45), of LOD 0.20 (0.17-0.23), and of VLOD 0.012 (0.007-0.021). The annual incidence of LOD increased slightly. Among infected infants, 44 (7%) died (odds ratio (OR): 24.5; 95% CI: 18.0-33.3 compared with the background population). Among survivors, 24 (4.1%) children were later diagnosed with CP, compared with 1887 (0.19%) in the background population (OR: 22.9; 95% CI: 15.1-34.5). CONCLUSION: Despite a relatively low incidence of invasive GBS infection in Norway, the risk of death and CP remains high. Improvements in prevention strategies are needed. IMPACT: During the first decade of the twenty-first century, invasive GBS disease in infancy is still associated with high mortality. Despite the overall low incidence of invasive GBS disease, the incidence of LOD increased during the study period. The finding that invasive GBS infection in the neonatal period or during infancy is associated with an excess risk of CP, comparable to the risk following moderate preterm birth and moderate low Apgar scores, adds to the existing literature. The results of this study emphasize the importance of adhering to guidelines and the need for better prevention strategies.

Prelabor rupture of membranes and the association with cerebral palsy in term born children: a national registry-based cohort study.

BACKGROUND: Guidelines regarding management of prelabor rupture of membranes (PROM) at term vary between immediate induction and expectant management. A long interval between PROM and delivery increases the risk for perinatal infections. Severe perinatal infections are associated with excess risk for cerebral palsy (CP) and perinatal death. We investigated if increasing intervals between PROM and delivery were associated with perinatal death or CP. METHODS: Eligible to participate in this population-based cohort-study were term born singletons without congenital malformations born in Norway during 1999-2009. Data was retrieved from the Medical Birth Registry of Norway (MBRN) and the Cerebral Palsy Register of Norway. In line with the registration in the MBRN, intervals between PROM and delivery of more than 24 h was defined as 'prolonged' and intervals between 12 and 24 h as 'intermediate'. Outcomes were stillbirth, death during delivery, neonatal mortality and CP. Logistic regression was used to calculate odds ratio (OR) with 95% confidence intervals (CI) for adverse outcomes in children born after prolonged and intermediate intervals, compared with a reference group comprising all children born less than 12 h after PROM or without PROM. RESULTS: Among 559,972 births, 34,759 children were born after intermediate and 30,332 were born after prolonged intervals. There was no association between increasing intervals and death during delivery or in the neonatal period, while the prevalence of stillbirths decreased with increasing intervals. Among children born after intermediate intervals 38 (0.11%) had CP, while among those born after prolonged intervals 46 (0.15%) had CP. Compared with the reference group, the OR for CP was 1.16 (CI; 0.83 to 1.61) after intermediate and 1.61 (CI; 1.19 to 2.18) after prolonged intervals. Adjusting for antenatal factors did not affect these associations. Among children with CP the proportion with diffuse cortical injury and basal ganglia pathology on cerebral MRI, consistent with hypoxic-ischemic injuries, increased with increasing intervals. CONCLUSION: Intervals between PROM and delivery of more than 24 h were associated with CP, but not with neonatal mortality or death during delivery. The inverse association with stillbirth is probably due to reverse causality.