Group B streptococcus (GBS) was identified as the leading cause of neonatal morbidity and mortality in the United States in the 1970s. In the decades that followed, trials have demonstrated that intrapartum antibiotics administered to laboring patients reduced the rates of neonatal disease associated with GBS. Despite current screening and intrapartum management recommendations, early-onset GBS remains a leading cause of neonatal morbidity and mortality with an incidence of 0.3–0.4 cases per 1,000 live births and a case-fatality rate of 4 to 6%. Early-onset GBS is associated with maternal GBS colonization, preterm delivery, prolonged rupture of membranes, chorioamnionitis, age, race, and a history of a prior neonate with early-onset GBS sepsis.1
Early-onset GBS is defined as onset of infection occurring within the first week of life.1 Typically, neonates with early-onset GBS present with bacteremia, respiratory compromise, and meningitis.1–4 Ninety percent of early-onset GBS sepsis cases have clinical signs of infection within the first 24 hours of life, and greater than 95% of cases are symptomatic or confirmed within the first 72 hours of life.3–6 Diagnosis of early-onset GBS sepsis within 72 hours is most consistent with acquisition of GBS disease during the peripartum period.6 Previous investigations at Parkland Health & Hospital Systems demonstrate that 94% of neonates with early-onset GBS infection received a diagnosis within 4 hours after birth by having either a blood culture performed that was positive for GBS or had clinical signs of infection.4 We sought to estimate if neonates with early-onset GBS sepsis have signs of infection during labor or at the time of delivery.
MATERIALS AND METHODS
Parkland Hospital is a publicly funded hospital that serves primarily the uninsured residents of Dallas County. The institutional review board at Parkland Hospital and the University of Texas Southwestern approved this analysis.
The medical records of all neonates born between January 1, 2000, and December 31, 2008, that were diagnosed with early-onset GBS sepsis were obtained and studied. Disease was defined by the isolation of GBS from blood or cerebrospinal fluid from the neonate within 72 hours of life and by disease-specific International Classification of Diseases, 9th Revision codes.
Antepartum GBS cultures were not performed. At our institution, a risk-based approach is used for intrapartum antibiotic administration. All term neonates born to women who do not receive intrapartum antibiotic prophylaxis are administered intramuscular penicillin after delivery.
An obstetric operations database with maternal and neonate information is collected for each delivery performed at this institution. All neonates were identified from this database and maternal data obtained from this source. The maternal–neonate pairs were also identified by the Pediatric Infectious Control Group at Parkland Hospital and this information was used to verify the cohort. Maternal, neonatal, labor, and delivery information for this cohort was compared with all neonates delivered within this time period.
Student t test and Pearson's χ2 test were used to examine the association between early-onset GBS sepsis and obstetric, delivery, and neonatal outcomes. Logistic regression was used to adjust for effect modifiers including nulliparity and chorioamnionitis. A P value of <.05 was significant.
There were 143,384 live births and 94 cases of early-onset GBS sepsis at Parkland Hospital during the 9-year study period. Maternal characteristics are presented in Table 1. Mothers of neonates with early-onset GBS sepsis were significantly more likely to be younger, nulliparous, and African American when compared with our general population. Of the 94 cases of early-onset GBS, 74 had maternal risk factors for which intrapartum antibiotics should have been administered. Sixty-two (84%) received antibiotics based on risk factors during the intrapartum period. There were 12 patients who did not receive antibiotics during the labor period. Twenty (21.2%) did not have risk factors for intrapartum antibiotic administration. Nineteen neonates presented with symptoms of early-onset GBS at birth and did not receive intramuscular penicillin but had intravenous antibiotics started.
Ninety-three neonates were diagnosed with early-onset GBS sepsis by symptoms with blood and cerebrospinal fluid cultures or both symptoms and blood and cerebrospinal fluid cultures within the first hour of life (Table 2). One neonate was diagnosed on day 3 of life after development of respiratory distress. Respiratory distress was the most common clinical presentation, occurring in 42 of the 50 neonates with clinical symptoms. Four neonates underwent lumbar puncture, and none were diagnosed with GBS meningitis. There was one death in the cohort; this neonate was 25 weeks of gestation, 610 g, and had ruptured membranes for more than 4 weeks; the mother went into labor with chorioamnionitis. The median length (25th percentile, 75th percentile) of stay was 8 days (7, 8).
The labor characteristics of all neonates delivered in the study period are shown in Table 3. Neonates diagnosed with early-onset GBS were significantly more likely to be delivered before 33 weeks of gestation and through cesarean delivery for fetal distress as the surgical indication. There were five cases of early-onset GBS that were delivered by a repeat cesarean delivery; four had rupture of membranes before surgery. The Apgar scores at 1 and 5 minutes were also significantly lower in neonates with early-onset GBS; 19% were assigned a 1-minute score and 3% a 5-minute score of less than or equal to 3. Neonates with early-onset GBS also had lower umbilical cord pH and a larger base deficit compared with the other neonates.
Nulliparity and chorioamnionitis were strongly associated with early-onset GBS sepsis. The data were adjusted for nulliparity because an association was noted with longer intrapartum delivery time and increased rates of chorioamnionitis. Table 4 details selected outcomes after adjustment for these two variables. All outcomes remained significant except for the 5-minute Apgar score.
In this review of more than 140,000 patients who were delivered at Parkland Hospital, we found evidence that neonates diagnosed with early-onset GBS manifest signs of sepsis during the peripartum period. There was an increase in cesarean delivery for fetal distress, lower umbilical cord pH, and larger base deficits in those with early-onset disease. The majority of neonates with early-onset GBS were diagnosed within 1 hour of birth, which supports the idea of early-onset GBS as a spectrum of infection that often precedes delivery. There were no neonatal deaths in our study cohort attributed to early-onset sepsis, which unfortunately is not always the case with this disease. Our other findings were consistent with those of previous investigations: neonates diagnosed with early-onset sepsis were more likely to be of term gestation, born to African American mothers, present with respiratory distress, and be diagnosed with bacteremia or sepsis.1–5,7
After adjustment for two confounders, nulliparity and chorioamnionitis, neonates with early-onset GBS were more likely to have umbilical cord gas values reflective of metabolic acidosis. According to the American College of Obstetricians and Gynecologists, metabolic acidosis is defined as an umbilical cord blood pH of less than 7 and a base deficit of larger than or equal to 12 mmol/L. At this level of base deficit, there are numerous neurological complications that can manifest.8 The results of umbilical cord gas pH and base deficit have not been largely reported in the literature with GBS sepsis. Montgomery and colleagues found that an arterial pH less than 7.18 with either an arterial carbon dioxide pressure less than 59 mm Hg or a bicarbonate level less than 19 mEq/L indicated an increased risk of early-onset GBS disease.9 Although a small study of 4,483 live births with 11 neonates diagnosed with GBS sepsis, it does support our findings that metabolic acidosis with a significant base deficit at delivery is a predictor of early-onset GBS sepsis. This holds true even in patients with pregnancies complicated by chorioamnionitis who received intrapartum antibiotics.
Operative vaginal delivery and fetal distress resulting in a cesarean delivery are also markers for intrapartum fetal compromise. We propose that acquisition of GBS disease in utero results in fetal acid-base abnormalities, leading to nonreassuring fetal heart rate tracings requiring rapid delivery. Our study found a significant increase in both operative vaginal delivery and cesarean delivery for fetal distress in the women delivering neonates with early-onset GBS.
Our data confirm previously described findings on timing of diagnosis of early-onset disease. As previously mentioned, early-onset GBS is defined as disease manifesting within the first week of life. Prior studies demonstrate that 95–100% of all cases are diagnosed within the first 72 hours of life with 89–100% within the first 24 hours.3,4,6,10 Classically 3 days of life has been suggested to be most indicative of infection acquired in the immediate peripartum period.6 Our findings confirm this with 100% of neonates with early-onset GBS having symptoms of disease within the first hour after delivery and the diagnosis of early-onset GBS confirmed within the first hour of life in 98%.
Our study suggests that there are signs of early-onset GBS sepsis during the labor process. This could be valuable information for health care providers taking care of patients who are carriers of GBS as well as those with negative screening cultures, preterm labor before obtaining the results of cultures, and those attending to the newborn. Although intrapartum prophylaxis has decreased rates of early-onset GBS, previous investigations have demonstrated that 61–82% of mothers who had term neonates with early-onset GBS had screening cultures that were negative.3,5,11 Adding intrapartum factors associated with GBS sepsis could facilitate early diagnosis and treatment, even in those that appear well at delivery.
1. Verani JR, McGee L, Schrag SJ; Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC). Prevention of perinatal group B streptococcal disease—revised guidelines from CDC, 2010. MMWR Recomm Rep 2010; 59: 1–36.
2. Phares CR, Lynfield R, Farley MM, Mohle-Boetani J, Harrison LH, Petit S, et al.. Epidemiology of invasive group B streptococcal disease in the United States 1999–2005. JAMA 2008; 299: 2056–65.
3. Pulver LS, Hopfenbeck MM, Young PC, Stoddard GJ, Korgenski K, Daly J, et al.. Continued early onset group B streptococcal infections in the era of intrapartum prophylaxis. J Perinatol 2009; 29: 20–5.
4. Velaphi S, Siegel JD, Wendel GD Jr, Cushion N, Eld WM, Sánchez PJ. Early-onset group B streptococcal infection after a combined maternal and neonatal group B streptococcal chemoprophylaxis strategy. Pediatrics 2003; 111: 541–7.
5. Puopolo KM, Madoff LC, Eichenwald EC. Early-onset group B streptococcal disease in the era of maternal screening. Pediatrics 2005; 115: 1240–6.
6. Siegel JD, Cushion NB. Prevention of early-onset Group B streptococcal disease: another look at single-dose penicillin at birth. Obstet Gynecol 1996; 87: 692–8.
7. Eberly MD, Rajnik M. The effect of universal maternal screening on the incidence of neonatal early-onset group B streptococcal disease. Clin Pediatr (Phila) 2009; 48: 369–75.
8. Umbilical cord blood gas and acid-base analysis. ACOG Committee Opinion No. 348. American College of Obstetricians and Gynecologists. Obstet Gynecol 2006; 108: 1319–22.
9. Montgomery DM, Stedman CM, Robichaux AG III, Joyner JC, Scariano SM. Cord blood gas patterns identifying newborns at increased risk of group B streptococcal sepsis. Obstet Gynecol 1991; 78: 774–7.
10. Verani JR, Schrag SJ. Group B streptococcal disease in infants: progress in prevention and continued challenges. Clin Perinatol 2010; 37: 375–92.
11. Van Dyke MK, Phares CR, Lynfield R, Thomas AR, Arnold KE, Craig AS, et al.. Evaluation of universal antenatal screening for group B streptococcus. N Engl J Med 2009; 360: 2626–36.