Premature rupture of membranes (PROM) refers to the spontaneous rupture of the amniotic membrane before the onset of labor at or before term 1. If rupture occurs before 37 weeks of gestation, it is referred to as preterm PROM (PPROM) 2. Preterm labor is the main expected consequence of PPROM with latency between rupture and delivery inversely proportional to gestational age 3. PPROM is an independent predictor of perinatal complications, and pregnancies complicated by PPROM are associated with a higher incidence of severe neonatal morbidity than those with preterm labor with intact membranes 4.
Group B streptococcus (GBS) infection has been associated with adverse pregnancy outcomes. The presence of heavy colonization with GBS has been associated with preterm labor and PROM 5. GBS infection also represents a very significant cause of neonatal morbidity and mortality. Neonatal GBS disease can be classified as early or late onset. Early-onset disease occurs less than 7 days after birth and comprises 80% of the disease in infants, and the mortality rate ranges from 5 to 20% 6.
The US Centers for Disease Control and Prevention (CDC) now recommend that all pregnant women undergo bacteriological screening with vaginal and rectal swabs for GBS culture at 35–37 weeks of gestation 7. A CDC surveillance study estimated that the use of intrapartum chemoprophylaxis has prevented 4500 cases per year of GBS sepsis and 225 deaths per year 8.
This study was carried out to examine the association between maternal colonization by GBS in pregnant women with PROM and early-onset neonatal GBS disease and to evaluate the role of intrapartum antibiotic prophylaxis.
Patients and methods
This prospective clinical trial was conducted in the Obstetric Unit of Kasr El-Aini and El-Galaa Teaching Hospitals (Cairo, Egypt) during the period from January 2011 to September 2011. The study protocol was reviewed and approved by the Scientific Research Committee. Sixty pregnant women at 35–37 weeks’ gestation were included in the study after obtaining their informed consent.
The study population was allocated to two main groups:
- Group I: PROM group (n=40), which was further subdivided into
- Group Ia: high-risk group (n=20); prolonged PROM (>18 h) and/or preterm labor.
- Group Ib: low-risk group (n=20); PROM less than 18 h and not in labor.
- Group II: control group (n=20); intact membranes and not in labor.
All women were subjected to the following:
- Assessment of history: especially obstetric history for the determination of gestational age, and also history of sudden gush of fluid and its duration.
- General examination for maternal pulse and temperature (fever and tachycardia may be signs of chorioamnionitis) as well as blood pressure.
- Abdominal examination for uterine tenderness (sign of chorioamnionitis), clinical assessment of amount of liquor, uterine contractions, and FHS (fetal tachycardia may be a sign of intrauterine infection).
- Vaginal examination (only a sterile speculum examination was allowed) to inspect draining fluid and to assess cervical dilatation.
- High vaginal swab and rectal swab were taken at 35 to 37 weeks and sent for culture and bacteriological examination for GBS.
- Complete blood picture was determined for patients with rupture of membranes for detection of leukocytosis.
- Prophylactic antibiotic: ampicillin/sulbactam 3 gm intravenous was administered for women with PROM and then 1.5 gm was administered every 4 h until delivery.
- Spontaneous or induced vaginal delivery, or cesarean section (if indicated).
- Neonatal assessment: neonatal sepsis in the first 24 h after delivery was diagnosed according to the following criteria 10: (a) body temperature changes, (b) breathing problems, (c) diarrhea, (d) low blood sugar, (e) reduced movements, (f) reduced sucking, (g) seizures, (h) slow heart rate, (i) swollen belly area, (j) vomiting, (k) jaundice, and (l) laboratory tests (blood culture, C-reactive protein, WBCs count).
Continuous data were expressed as mean±SD and were compared using the ANOVA test. Categorical data were expressed as number and percentage and were compared using the χ 2-test or Fisher’s exact test, as appropriate. A P-value of less than 0.05 was considered to be statistically significant. The Statistical Package for the Social Sciences (SPSS Inc., Chicago, Illinois, USA) for MS Windows was used for data analysis.
A total of 40 pregnant women with PROM were recruited into the study (group I), along with 20 pregnant women with intact membranes as a control (group II). Group I was further subdivided into a high-risk group (n=20) and a low-risk group (n=20).
Table 1 shows the clinical data of the study groups. There were no significant differences between the three groups in age, parity, and gestational age. All women of group Ia had PROM of more than an 18-h duration; six (30%) between 18 and 24 h, eight (40%) between 24 and 48 h, and six (30%) more than 48 h before recruitment. The incidence of chorioamnionitis was significantly higher in group Ia compared with groups Ib and II.
The differences in the prevalence of positive vaginal and rectal swabs for GBS between the groups were not statistically significant (Table 1). There was also an insignificant agreement (κ coefficient) between the results of vaginal and rectal swabs for GBS in all the included women (κ=0.118; P=0.355) as well as in different groups (group Ia: κ=0.136; P=0.494, group Ib: κ=0.255; P=0.251, group II: κ=0.192; P=0.391).
All the included women in groups Ia and Ib received antibiotics (3 g ampicillin/sulbactam, either a single dose [11 (55%) and 14 (70%), respectively] or two or more doses [9 (45%) and 6 (30%), respectively]. However, only 13 (65%) women in group II, who had PROM after recruitment, received prophylactic antibiotics either as a single dose [6 (30%)] or two or more doses [7 (35%)]. These figures were significantly lower compared with the corresponding figures of groups Ia and Ib (Table 1).
Of the 20 neonates of group Ia, seven (35%) had neonatal sepsis, one (5%) had meningitis, and three (15%) had pneumonia. Of the 20 neonates of group Ib, only one (5%) had neonatal sepsis and none had neonatal meningitis or pneumonia. None of the neonates of group II had GBS-related neonatal infection. Group Ia had a significantly higher incidence of neonatal sepsis (P=0.002) and pneumonia (P=0.043) compared with groups Ib and II (Table 2).
Among all the included women, there were no significant associations between a positive vaginal swab for GBS and each of neonatal sepsis (P=0.095), meningitis (P=0.865), and pneumonia (P=0.764). Analysis of group Ia indicated a significant association between a positive vaginal swab for GBS with an almost four-fold higher risk of neonatal sepsis [relative risk (RR)=3.75; 95% confidence interval (CI), 1.09–14.92; P=0.035]; however, there was no significant association between a positive vaginal swab for GBS and each of neonatal meningitis or pneumonia (Table 3). In group Ib, there was no significant association between positive vaginal swabs for GBS and neonatal sepsis (P=0.834).
Among all the included women, there were no significant associations between a positive rectal swab for GBS and each of neonatal sepsis (P=0.893), meningitis (P=0.999), and pneumonia (P=0.999). There was also no significant association between a positive rectal swab and neonatal sepsis, meningitis, and pneumonia in group Ia (Table 4). In group Ib, there was no significant association between a positive rectal swab for GBS and neonatal sepsis (P=0.747).
There was no significant association between the duration of PROM (whether >18 h or <18 h) and positive vaginal (P=0.853) or rectal (P=0.208) swabs for GBS. There was also no significant association between chorioamnionitis and each of neonatal sepsis (P=0.503), meningitis (P=0.209), and pneumonia (P=0.306) in group Ia.
The administration of two or more doses of antibiotics in women of group Ia was associated with a significantly five-fold lower risk of neonatal sepsis (RR=0.2; 95% CI, 0.03–0.98; P=0.043); however, it was not significantly associated with a lower risk of neonatal meningitis or pneumonia (Table 5).
Among women with a positive vaginal swab for GBS in group Ia, administration of two or more doses of antibiotics significantly reduced the risk of neonatal sepsis almost three-fold (RR=0.3; 95% CI, 0.04–0.82; P=0.042), but had no significant impact on neonatal meningitis or pneumonia (Table 6).
The study included 60 pregnant women. High vaginal swab and rectal swab were taken for the detection of GBS. Pregnant women were administered intrapartum antibiotics and their neonates were followed up after birth for early GBS sepsis.
In the present study, the prevalence of a positive vaginal swab for GBS was 41% in all cases, 40% in the high-risk group, 40% in the low-risk group, and 45% in the control group. The prevalence of a positive rectal swab for GBS was 33% in all cases, 20% in the high-risk group, 35% in the low-risk group, and 45% in the control group (Table 1).
Nomura et al. 11 examined the prevalence of maternal colonization by GBS in vaginal and rectal swabs for 203 pregnant women pregnant women with premature labor and/or PROM. They found that the prevalence of maternal GBS colonization was 27.6% (56 cases). The colonization rates according to gestational complications were 30% for PROM, 25.2% for premature labor, and 17.8% for premature labor+PROM.
Jones et al. 12 examined asymptomatic vaginorectal carriage of GBS in women in the final trimester of pregnancy; 21.3% had GBS colonization vaginorectally. Risk factors for neonatal GBS disease (maternal fever, prolonged rupture of membranes, and preterm delivery) were present in 34 of 167 women (20.4%), and the presence of these factors correlated poorly with GBS carriage.
Garland et al. 13 screened all public patients antenatally for genital carriage of GBS by collection of a low vaginal swab at 28–32 weeks. All patients with GBS colonization antenatally are administered penicillin as intrapartum chemoprophylaxis. They found that the maternal GBS colonization rate was 12.9% (580 of 4495 patients), and the association between antepartum GBS colonization and preterm labor and preterm rupture of membranes was not significant.
Chaaya et al. 14 examined the carriage rate of GBS in vaginal swab for 166 pregnant women with a gestational age of 32 to 42 weeks. The recovery rate of GBS was found to be 7.8% (13/166). Twelve of the 13 (92%) mothers with GBS colonization had term newborns as compared with 141 of 153 (92.1%) mothers without GBS colonization (P=0.72). Three of 13 (23%) mothers with GBS colonization had PROM compared with 38 of 153 (25.1%) mothers without GBS colonization (P=0.58).
In the present study, of the neonates of the high-risk group, 35% had neonatal sepsis, 5% had meningitis, and 15% had pneumonia. Of the neonates of the low-risk group, only 5% had neonatal sepsis and none had neonatal meningitis or pneumonia. None of the neonates of the control group had GBS-related neonatal infection (Table 2).
In the high-risk group, there was a significant association between positive vaginal swabs for GBS with an almost four-fold higher risk of neonatal sepsis (Table 3). However, there were no significant associations between a positive rectal swab for GBS and neonatal infections (Table 4).
Nomura et al. 11 found that the neonatal colonization rate was 3.1%. Two cases of early sepsis by GBS occurred in the sample, with a prevalence of 10.8 cases/1000 live births and a mortality rate of 50%. Chaaya et al. 14 found that two of the 13 (15.4%) newborn infants born to mothers with GBS colonization had an early neonatal infection: one had pneumonia and had a favorable outcome, and the other one developed sepsis and meningitis and died on day 3.
Davies et al. 8 identified 168 cases of invasive neonatal GBS infections including stillbirths among 262 398 total births. The average annual incidence was 0.64 of 1000 total births/year. Of these, 95 (57%) had early-onset disease and 15 (9%) were still births. The most common clinical presentation was bacteremia without focus (74%), followed by meningitis (14%) and pneumonia (12%). Twenty-five percent of cases occur in preterm infants (<37 weeks).
In the present study, the administration of two or more doses of antibiotics was associated with a significantly five-fold lower risk of neonatal sepsis in women of the high-risk group (Table 5) and an almost three-fold risk reduction among women with a positive vaginal swab for GBS in the high-risk group (Table 6).
Boyer and Gotoff 15 concluded that intrapartum ampicillin prophylaxis in women with positive prenatal cultures for group GBS who have certain perinatal risk factors can prevent early-onset neonatal GBS disease. Rosenstein and Schuchat 16 found that the estimated preventable portion of early-onset GBS cases was 78% for the screening-based approach compared with 41% for the risk-based approach. Schrag et al. 10 also concluded that routine screening for GBS during pregnancy prevents more cases of early-onset disease than the risk-based approach.
Verani et al. 17 concluded that in the absence of a licensed GBS vaccine, universal screening at 35–37 weeks’ gestation for maternal GBS colonization and intrapartum antibiotic prophylaxis continue to be the cornerstones of prevention of early-onset GBS disease. Alós Cortés et al. 18 also recommended monitoring of all pregnant women at 35–37 weeks’ gestation to determine whether they have GBS colonization and to administer intrapartum antibiotic prophylaxis to all mothers with GBS colonization.
In high-risk patients with prolonged PROM and/or preterm labor, there is an association between a positive vaginal swab for GBS with an almost four-fold higher risk of neonatal sepsis, and administration of two or more doses of intrapartum antibiotics is associated with an almost three-fold reduction in risk. Bacteriological screening for maternal GBS colonization is recommended for all pregnant women at 35–37 weeks’ gestation, and intrapartum antibiotic prophylaxis should be offered to women with GBS colonization, especially those who have risk factors for early-onset neonatal GBS disease.
Conflicts of interest
There are no conflicts of interest.
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