Perinatal Risk Factors for Neonatal Early-onset Group B Streptococcal Sepsis after Initiation of Risk-based Maternal Intrapartum Antibiotic Prophylaxis—A Case Control Study

Perinatal Risk Factors for Neonatal Early-onset Group B Streptococcal Sepsis after Initiation of... Abstract Objectives To identify the perinatal risk factors for early-onset Group B Streptococcus (EOGBS) sepsis in neonates after inception of a risk-based maternal intrapartum antibiotic prophylaxis strategy in 2004. Design Case control study. Methods All newborn with early onset GBS sepsis (born between 2004 and 2013) were deemed to be “cases” and controls were selected in a 1:4 ratio. Results More than three per vaginal (PV) examinations [odds ratio (OR) 8.57, 95% confidence interval (CI) 3.10–23.6] was a significant risk factors. Peripartum fever (OR 3.54, 95% CI 1.3–9.67), urinary tract infection (OR 2.88, 95% CI 1.08–7.63), meconium-stained amniotic fluid (MSAF) (OR 2.52, 95% CI 1.18–5.37) and caesarean section (OR 1.99, 95% CI 1.16–3.43) were also found to be associated with EOGBS sepsis. Conclusion Multiple vaginal examinations are the strongest risk factors for peripartum Group B Streptococcal (GBS) sepsis. The association of MSAF and caesarean section indicates that foetal distress is an early symptom of perinatal GBS infection. Group B Streptococcus, infant, newborn, factors, risk, India, neonatal sepsis INTRODUCTION Group B Streptococcus is a Gram-positive coccus known to be one of the main causative agents of early-onset sepsis (EOS) in neonates. The reservoir of Group B Streptococcus is usually the gastrointestinal tract of the mother; hence, rectovaginal colonization of mothers results in vertical transmission at the time of delivery [1]. Intrapartum antibiotic prophylaxis (IAP) is given to reduce this transmission [2]. The Centre for Diseases Control (CDC) recommends universal screening of mothers between 35 and 37 weeks of gestation to identify colonized mothers and to provide antibiotics to all those who are colonized [3]. Another approach is to use a risk-based strategy and to provide IAP to those mothers who have certain risk factors. The incidence of Group B Streptococcal (GBS) sepsis in neonates was 0.17/1000 live births in our institution over a 10-year period (1988–97) [4]. At that time, intrapartum antibiotic (ampicillin) was only given to pregnant women with chorioamnionitis or GBS urinary tract infection (UTI). As the incidence of EOS with GBS appeared to be rising over the next 5 years, a case-control study was done in 2003 to identify the risk factors for EOS [5]. Following this study, the policy of IAP was revised in 2004, and it has since been given in the presence of the following risk factors: maternal chorioamnionitis, GBS UTI, spontaneous preterm labour, preterm premature rupture of membranes (PPROM), peripartum fever (≥38°C) and prolonged rupture of membranes (PROM) >18 h. The incidence of EOGBS decreased with this strategy from 0.68/1000 live births (1998–2003) to 0.55/1000 live births (2004–10) [6]. All newborns born to mothers with these risk factors also have a sepsis screen done. A study in our institution in 2012 showed rectovaginal colonization in 7.6% of pregnant women screened at 35–37 weeks gestation [7]. Since then, some obstetricians offer women an option of having a rectovaginal screening at 35–37 weeks with IAP given if screen is positive. More than 30 000 women attend the obstetric outpatient department per year, and therefore, universal screening is not feasible either at clinic or laboratory levels. Hence, few obstetricians offer screening to their patients. Therefore, <1% women undergo screening. As there was a reduction in incidence of EOS with GBS after introduction of IAP, but the incidence remained higher than most high-middle-income countries, this study was undertaken to identify any additional risk factors for EOGBS. This case-control study was done to identify the risk factors for EOGBS sepsis after initiation of risk-based IAP. To our knowledge, no study has reported on risk factors after providing IAP. Identification of persisting and new risk factors may help us modify the current risk-based IAP policy. METHODS Christian Medical College is a tertiary-level perinatal centre, which is a private, patient-paid/charitable hospital catering to three districts in South India. As this is the only referral centre for a large population, >50% of deliveries are high-risk deliveries. All babies admitted in the neonatology unit from 1 January 2004 to 31 December 2014 who were found to have invasive GBS infection within 72 h of birth were identified as the ‘cases’. Invasive disease was described as isolation of the organism from any sterile site (blood/cerebrospinal fluid). The two babies born just before and the two babies born after the ‘cases’ were deemed to be the controls. The records of the mother–baby dyad were retrieved from the Medical Records Department. Data on maternal risk factors and neonatal outcome were collected in a predesigned questionnaire. Data from the pre-IAP era (1998–2003) were also re-analysed using the same methodology and the results were compared between the two epochs. However, data from only three controls per ‘case’ could be obtained from the earlier era. Sample size In a previous study by Benitz et al. [8], the risk factors, which were most significant for the development of EOS in newborns, were intrapartum fever [odds ratio (OR) 4.05] and chorioamnionitis with an OR of 6.43. Therefore, with an estimated 10% of controls having intrapartum fever and 1:4 case:control ratio, we needed a minimum of 54 cases and 216 controls. Descriptive statistics were reported using frequency and percentage for categorical variables. Association between the outcome and categorical variables was analysed using chi-square/Fisher’s exact test. Maternal risk factors associated with neonatal GBS infection were analysed by binary logistic regression using stepwise method with 25% significance for unadjusted analysis and 5% level of significance for adjusted analysis. The values were reported using OR and 95% confidence interval (CI). SPSS 16.0 was used for statistical analysis. The study was conducted with approval from the institutional review board. RESULTS In the period 2004–14, after the initiation of a risk-based intrapartum antibiotic policy, 71 babies were found to have an EOGBS sepsis. On analysing the risk factors associated with developing EOGBS sepsis, more than three per vaginal (PV) examinations after rupture of membranes was found to be a significant factor associated with EOGBS, with an adjusted OR of 8.57 (3.10–23.6) (Table 1). Peripartum fever with OR of 3.54 (95% CI 1.30–9.67) and UTI with OR of 2.88 (95% CI 1.08–7.63) were both significantly associated with EOGBS sepsis. The risk factors for EOGBS sepsis before 2003 are also represented in Table 1 for comparison. Factors like preterm pre-labour rupture of membranes (PPROM) and PROM >18 or 24 h, that were significant risk factors before 2003, were not found to be significant after initiating IAP. In both the eras, there was a trend of babies with EOGBS infection being born by caesarean section (20.1 and 27.3% versus 42.6 and 42.9%). Table 1 Perinatal risk factors for early onset GBS sepsis after and before intrapartum antibiotics Risk factors Pre IAP era (1998–2003) Post IAP era (2004–2015) Cases Controls Unadjusted OR Adjusted OR Cases Controls Unadjusted OR Adjusted OR N = 47 N = 144 OR (95% CI) OR (95% CI) N = 71 N = 284 OR (95% CI) OR (95% CI) n (%) n (%) n (%) n (%) Prematurity<37 wks 9 (19.1%) 11 (7.6%) 2.91 (1.12–7.57) – 10 (14.3%) 42 (14.9%) 0.95 (0.45–2.01) – Low birth weight <2500 gm 8 (17%) 22 (15.3%) 1.16 (0.48–2.8) – 22 (31.9%) 59 (20.8%) 1.78 (0.9–3.19) – Chorioamnionitis 4 (8.5%) 0 5.53 – 0 6 (2.1%) – – Prolonged rupture of membranes >18 hours 14 (29.8%) 14 (9.7%) 3.93 (1.71–9.06) – 2 (2.8%) 17 (5.9%) 2.197 (0.4–9.7) – Prolonged rupture of membranes >24 hours 10 (21.3%) 7 (4.9%) 5.29 (1.88–14.84) 5.09 (1.44–17.93) 2 (2.8%) 8 (2.8%) 1.0 (0.2–4.8) – Prelabour rupture of membranes 11 (23.4%) 28 (19.4%) 1.26 (0.57–2.79) – 10 (14.1%) 54 (19%) 1.4 (0.6–2.9) – Peripartum fever 17 (36.2%) 21 (14.6%) 3.62 (1.69–7.78) 2.23 (0.57–5.73) 9 (14.5%) 12 (4.3%) 3.77 (1.5–9.41) 3.54 (1.30–9.67) More than 3 per vaginal examination after rupture of membranes 16 (34%) 5 (3.5%) 17.7 (5.9–52.9) 11.22 (3.38–37.22) 11 (16.7%) 8 (2.8%) 6.9 (2.65–17.94) 8.57 (3.10–23.6) Meconium stained amniotic fluid 10 (21.3%) 25 (17.4%) 1.36 (0.59–3.10) – 15 (23.8%) 33 (11.8%) 2.33 (1.180–4.63) 2.52 (1.18–5.37) Urinary tract infection 3 (6.4%) 0 – – 9 (13.4%) 16 (5.7%) 2.57 (1.08–6.10) 2.88 (1.08–7.63) Primigravida 26 (55.3%) 68 (47.2%) 1.45 (0.74–2.83) – 43 (61%) 145 (51.4%) 1.50 (0.88–2.56) – Caesarean 20 (42.6%) 29 (20.1%) 3.05 (1.49–6.21) 1.43 (0.55–3.71) 30 (42.9%) 77 (27.3%) 1.99 (1.16–3.43) – Risk factors Pre IAP era (1998–2003) Post IAP era (2004–2015) Cases Controls Unadjusted OR Adjusted OR Cases Controls Unadjusted OR Adjusted OR N = 47 N = 144 OR (95% CI) OR (95% CI) N = 71 N = 284 OR (95% CI) OR (95% CI) n (%) n (%) n (%) n (%) Prematurity<37 wks 9 (19.1%) 11 (7.6%) 2.91 (1.12–7.57) – 10 (14.3%) 42 (14.9%) 0.95 (0.45–2.01) – Low birth weight <2500 gm 8 (17%) 22 (15.3%) 1.16 (0.48–2.8) – 22 (31.9%) 59 (20.8%) 1.78 (0.9–3.19) – Chorioamnionitis 4 (8.5%) 0 5.53 – 0 6 (2.1%) – – Prolonged rupture of membranes >18 hours 14 (29.8%) 14 (9.7%) 3.93 (1.71–9.06) – 2 (2.8%) 17 (5.9%) 2.197 (0.4–9.7) – Prolonged rupture of membranes >24 hours 10 (21.3%) 7 (4.9%) 5.29 (1.88–14.84) 5.09 (1.44–17.93) 2 (2.8%) 8 (2.8%) 1.0 (0.2–4.8) – Prelabour rupture of membranes 11 (23.4%) 28 (19.4%) 1.26 (0.57–2.79) – 10 (14.1%) 54 (19%) 1.4 (0.6–2.9) – Peripartum fever 17 (36.2%) 21 (14.6%) 3.62 (1.69–7.78) 2.23 (0.57–5.73) 9 (14.5%) 12 (4.3%) 3.77 (1.5–9.41) 3.54 (1.30–9.67) More than 3 per vaginal examination after rupture of membranes 16 (34%) 5 (3.5%) 17.7 (5.9–52.9) 11.22 (3.38–37.22) 11 (16.7%) 8 (2.8%) 6.9 (2.65–17.94) 8.57 (3.10–23.6) Meconium stained amniotic fluid 10 (21.3%) 25 (17.4%) 1.36 (0.59–3.10) – 15 (23.8%) 33 (11.8%) 2.33 (1.180–4.63) 2.52 (1.18–5.37) Urinary tract infection 3 (6.4%) 0 – – 9 (13.4%) 16 (5.7%) 2.57 (1.08–6.10) 2.88 (1.08–7.63) Primigravida 26 (55.3%) 68 (47.2%) 1.45 (0.74–2.83) – 43 (61%) 145 (51.4%) 1.50 (0.88–2.56) – Caesarean 20 (42.6%) 29 (20.1%) 3.05 (1.49–6.21) 1.43 (0.55–3.71) 30 (42.9%) 77 (27.3%) 1.99 (1.16–3.43) – Table 1 Perinatal risk factors for early onset GBS sepsis after and before intrapartum antibiotics Risk factors Pre IAP era (1998–2003) Post IAP era (2004–2015) Cases Controls Unadjusted OR Adjusted OR Cases Controls Unadjusted OR Adjusted OR N = 47 N = 144 OR (95% CI) OR (95% CI) N = 71 N = 284 OR (95% CI) OR (95% CI) n (%) n (%) n (%) n (%) Prematurity<37 wks 9 (19.1%) 11 (7.6%) 2.91 (1.12–7.57) – 10 (14.3%) 42 (14.9%) 0.95 (0.45–2.01) – Low birth weight <2500 gm 8 (17%) 22 (15.3%) 1.16 (0.48–2.8) – 22 (31.9%) 59 (20.8%) 1.78 (0.9–3.19) – Chorioamnionitis 4 (8.5%) 0 5.53 – 0 6 (2.1%) – – Prolonged rupture of membranes >18 hours 14 (29.8%) 14 (9.7%) 3.93 (1.71–9.06) – 2 (2.8%) 17 (5.9%) 2.197 (0.4–9.7) – Prolonged rupture of membranes >24 hours 10 (21.3%) 7 (4.9%) 5.29 (1.88–14.84) 5.09 (1.44–17.93) 2 (2.8%) 8 (2.8%) 1.0 (0.2–4.8) – Prelabour rupture of membranes 11 (23.4%) 28 (19.4%) 1.26 (0.57–2.79) – 10 (14.1%) 54 (19%) 1.4 (0.6–2.9) – Peripartum fever 17 (36.2%) 21 (14.6%) 3.62 (1.69–7.78) 2.23 (0.57–5.73) 9 (14.5%) 12 (4.3%) 3.77 (1.5–9.41) 3.54 (1.30–9.67) More than 3 per vaginal examination after rupture of membranes 16 (34%) 5 (3.5%) 17.7 (5.9–52.9) 11.22 (3.38–37.22) 11 (16.7%) 8 (2.8%) 6.9 (2.65–17.94) 8.57 (3.10–23.6) Meconium stained amniotic fluid 10 (21.3%) 25 (17.4%) 1.36 (0.59–3.10) – 15 (23.8%) 33 (11.8%) 2.33 (1.180–4.63) 2.52 (1.18–5.37) Urinary tract infection 3 (6.4%) 0 – – 9 (13.4%) 16 (5.7%) 2.57 (1.08–6.10) 2.88 (1.08–7.63) Primigravida 26 (55.3%) 68 (47.2%) 1.45 (0.74–2.83) – 43 (61%) 145 (51.4%) 1.50 (0.88–2.56) – Caesarean 20 (42.6%) 29 (20.1%) 3.05 (1.49–6.21) 1.43 (0.55–3.71) 30 (42.9%) 77 (27.3%) 1.99 (1.16–3.43) – Risk factors Pre IAP era (1998–2003) Post IAP era (2004–2015) Cases Controls Unadjusted OR Adjusted OR Cases Controls Unadjusted OR Adjusted OR N = 47 N = 144 OR (95% CI) OR (95% CI) N = 71 N = 284 OR (95% CI) OR (95% CI) n (%) n (%) n (%) n (%) Prematurity<37 wks 9 (19.1%) 11 (7.6%) 2.91 (1.12–7.57) – 10 (14.3%) 42 (14.9%) 0.95 (0.45–2.01) – Low birth weight <2500 gm 8 (17%) 22 (15.3%) 1.16 (0.48–2.8) – 22 (31.9%) 59 (20.8%) 1.78 (0.9–3.19) – Chorioamnionitis 4 (8.5%) 0 5.53 – 0 6 (2.1%) – – Prolonged rupture of membranes >18 hours 14 (29.8%) 14 (9.7%) 3.93 (1.71–9.06) – 2 (2.8%) 17 (5.9%) 2.197 (0.4–9.7) – Prolonged rupture of membranes >24 hours 10 (21.3%) 7 (4.9%) 5.29 (1.88–14.84) 5.09 (1.44–17.93) 2 (2.8%) 8 (2.8%) 1.0 (0.2–4.8) – Prelabour rupture of membranes 11 (23.4%) 28 (19.4%) 1.26 (0.57–2.79) – 10 (14.1%) 54 (19%) 1.4 (0.6–2.9) – Peripartum fever 17 (36.2%) 21 (14.6%) 3.62 (1.69–7.78) 2.23 (0.57–5.73) 9 (14.5%) 12 (4.3%) 3.77 (1.5–9.41) 3.54 (1.30–9.67) More than 3 per vaginal examination after rupture of membranes 16 (34%) 5 (3.5%) 17.7 (5.9–52.9) 11.22 (3.38–37.22) 11 (16.7%) 8 (2.8%) 6.9 (2.65–17.94) 8.57 (3.10–23.6) Meconium stained amniotic fluid 10 (21.3%) 25 (17.4%) 1.36 (0.59–3.10) – 15 (23.8%) 33 (11.8%) 2.33 (1.180–4.63) 2.52 (1.18–5.37) Urinary tract infection 3 (6.4%) 0 – – 9 (13.4%) 16 (5.7%) 2.57 (1.08–6.10) 2.88 (1.08–7.63) Primigravida 26 (55.3%) 68 (47.2%) 1.45 (0.74–2.83) – 43 (61%) 145 (51.4%) 1.50 (0.88–2.56) – Caesarean 20 (42.6%) 29 (20.1%) 3.05 (1.49–6.21) 1.43 (0.55–3.71) 30 (42.9%) 77 (27.3%) 1.99 (1.16–3.43) – An increased number of cases were born through meconium-stained amniotic fluid (MSAF) [OR 2.52 (95% 1.18–5.37)]. As compared with the controls, a significant number of babies with sepsis had abnormal cardiotocogram (CTG) before delivery [33.8%, OR 2.17 (1.22–3.86)]. Abnormal CTG was defined as Category II or Category III CTG. There was also an increased need for resuscitation at birth—23 versus 3.5%, OR 2.58 (1.12–5.9) (Table 2). Table 2 Association of CTG abnormalities and resuscitation with GBS sepsis Variable Cases (N, %) Controls (N, %) OR (95% CI) Resuscitation 17 (23) 10 (3.5) 2.58 (1.12–5.90) Non-reassuring foetal status on CTG 24 (33.8) 54 (19) 2.17 (1.22–3.86) Variable Cases (N, %) Controls (N, %) OR (95% CI) Resuscitation 17 (23) 10 (3.5) 2.58 (1.12–5.90) Non-reassuring foetal status on CTG 24 (33.8) 54 (19) 2.17 (1.22–3.86) Table 2 Association of CTG abnormalities and resuscitation with GBS sepsis Variable Cases (N, %) Controls (N, %) OR (95% CI) Resuscitation 17 (23) 10 (3.5) 2.58 (1.12–5.90) Non-reassuring foetal status on CTG 24 (33.8) 54 (19) 2.17 (1.22–3.86) Variable Cases (N, %) Controls (N, %) OR (95% CI) Resuscitation 17 (23) 10 (3.5) 2.58 (1.12–5.90) Non-reassuring foetal status on CTG 24 (33.8) 54 (19) 2.17 (1.22–3.86) DISCUSSION Prevention of vertical transmission of Group B Streptococci from a colonized mother to her newborn has been one of the successful strategies adopted to reduce early-onset infection in newborn. This is ideally done by screening pregnant women in late pregnancy and giving intrapartum antibiotics to those found colonized. Alternatively, antibiotics can be given in labour to pregnant women who have certain risk factors, which predispose their newborn to EOGBS infection. Universal screening has been found to be cost-effective only when the incidence of EOGBS is >1.2/1000 live births [9]. This strategy might also be cost prohibitive and technically not feasible in most mid-low-income countries. Hence, many institutions use a risk-based intrapartum antibiotic policy. After a case-control study in 2003, we adopted a risk-based IAP policy since 2004. This study looks at the risk factors for EOGBS infections when an IAP policy is in place. This was done to identify any new risk factors and to assess the effect of IAP on existing risk factors. Prematurity (<37 weeks) was a risk factor in the pre-IAP epoch. This was similar to previous similar studies [8, 10, 11]. In the post-IAP epoch, it was not significantly associated with GBS infection. This is attributed to the successful IAP coverage of mothers who present with preterm labour or PPROM since 2004. Similarly, PROM >18 h has been identified to be significantly associated with GBS sepsis in many studies [8, 10]. A similar association was found in our pre-IAP epoch, which was no longer seen after initiating IAP. This again is probably because of IAP given in this setting. Peripartum fever continued to be a risk factor, despite a policy of IAP for women in labour having fever >38°C. A previous study by Al-Kadri et al. [12] also found an association between peripartum fever and EOGBS (OR 7.10, 2.50–20.71). Though we are not able to account for this continuing association, a possible explanation could be that the obstetricians’ compliance with giving IAP in fever is lower (compared with other risk factors), especially if they felt that fever could be attributed to another aetiology. We do not have data on overall compliance with the overall IAP policy and in individual risk factors throughout the period under study. Observationally, the compliance seems to be between 50 and 60%. It is logical to assume that improvement in compliance to IAP closer to 100% in mothers with risk factors would further reduce neonatal EOGBS incidence in the institution. More than three vaginal examinations after ROM showed the strongest association with EOGBS disease in both the pre- and post-IAP epochs. This indirectly points to a high colonization rate in our population. However, a study in 2012 showed maternal colonization rate of only 7.6%, which is much lower than most high-middle-income countries. We are hence unable to account for this discrepancy. Previous studies have not reported the magnitude of association of multiple PVs and EOGBS sepsis in neonates, though this is known to be associated with chorioamnionitis [13]. Hence, we would strongly encourage IAP to unscreened mothers who had multiple vaginal examinations in labour. Alternatively, this could be considered a major risk factor for EOGBS sepsis necessitating sepsis workup in the newborns. This could go a long way in reducing EOGBS sepsis in developing countries. Our data show that babies with GBS sepsis were more likely to be born through MSAF, have an abnormal CTG, be delivered by caesarean section and require resuscitation at birth. Studies have shown that GBS-colonized women had more foetal distress when compared with GBS-negative women [13]. It has been hypothesized that EOGBS sepsis is a spectrum of infection that also involves the foetus, which seems to be borne out by our data. Over the past few years, babies who have unexplained foetal distress and are asphyxiated/have respiratory depression at birth have had sepsis workup in our hospital and been covered with penicillin and gentamicin. The study proves that IAP definitely helps in the settings of preterm labour/PPROM as well as PROM in reducing EOGBS sepsis. It highlights the strong association of multiple vaginal examinations with GBS invasive disease. Where universal screening of mothers is not practised, this should be a guide to obstetricians to reduce unwanted vaginal examinations and also be the single most important risk factor to do a sepsis screen in symptomatic newborns. Our study thus can serve as a template for risk-based intrapartum treatment of mothers and newborn evaluation for EOS, especially in middle-low-income countries. Further studies are needed to evaluate the effect of infection in causing foetal distress/asphyxia in the developing world. References 1 Dillon HC , Gray E , Pass MA , et al. Anorectal and vaginal carriage of group B streptococci during pregnancy . J Infect Dis 1982 ; 145 : 794 – 9 . Google Scholar CrossRef Search ADS PubMed 2 Ohlsson A , Shah VS. Intrapartum antibiotics for known maternal Group B Streptococcal colonization . Cochrane Database Syst Rev 2014 ; 10 : CD007467 . 3 Verani JR , McGee L , Schrag SJ. Centers for Disease Control and Prevention: Prevention of perinatal group B streptococcal disease–revised guidelines from CDC, 2010. Morb Mortal Wkly Rep 2010; 59 : 1 – 36 . 4 Kuruvilla KA , Thomas N , Jesudasan MV , et al. Neonatal Group B Streptococcal bacteraemia in India: ten years’ experience . Acta Paediatr 1999 ; 88 : 1031 – 2 . Google Scholar CrossRef Search ADS PubMed 5 Sridhar S , Jolly C , Niranjan T , et al. Neonatal Group B Streptococcal infection in India—myth or reality? Poster presented at The XXIII annual convention of the National Neonatology Forum, Hyderabad. December 19–21, 2003 . 6 Sridhar S , Grace R , Nithya PJ , et al. Group B Streptococcal infection in a tertiary hospital in India—1998–2010 . Pediatr Infect Dis J 2014 ; 33 : 1091 – 2 . Google Scholar CrossRef Search ADS PubMed 7 Santhanam S , Jose R , Sahni RD , et al. Prevalence of Group B Streptococcal colonization among pregnant women and neonates in a tertiary hospital in India . J Turk Ger Gynecol Assoc 2017 ; (In press). doi: 10.4274/jtgga.2017.0032. 8 Benitz WE , Gould JB , Druzin ML. Risk factors for early-onset group streptococcal sepsis: estimation of odds ratios by critical literature review . Pediatrics 1999 ; 103 : e77 . Google Scholar CrossRef Search ADS PubMed 9 Mohle-Boetani JC , Schuchat A , Plikaytis BD , et al. Comparison of prevention strategies for neonatal Group B Streptococcal infection: a population-based economic analysis . JAMA 1993 ; 270 : 1442 – 8 . Google Scholar CrossRef Search ADS PubMed 10 Oddie S , Embleton ND. Risk factors for early onset neonatal Group B Streptococcal sepsis: case-control study . BMJ 2002 ; 325 : 308 . Google Scholar CrossRef Search ADS PubMed 11 Adair CE , Kowalsky L , Quon H , et al. Risk factors for early-onset Group B Streptococcal disease in neonates: a population-based case-control study . CMAJ Can Med Assoc J J Assoc Medicale Can 2003 ; 169 : 198 – 203 . 12 Al-Kadri HM , Bamuhair SS , Johani SMA , et al. Maternal and neonatal risk factors for early-onset Group B Streptococcal disease: a case control study . Int J Womens Health 2013 ; 5 : 729 – 35 . Google Scholar CrossRef Search ADS PubMed 13 Shi C , Qu S , Yang L , et al. Detection of maternal colonization of group B streptococcus in late pregnancy by real-time polymerase chain reaction and its effect on perinatal outcome . Zhonghua Fu Chan Ke Za Zhi 2010 ; 45 : 12 – 6 . Google Scholar PubMed © The Author [2017]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Tropical Pediatrics Oxford University Press

Perinatal Risk Factors for Neonatal Early-onset Group B Streptococcal Sepsis after Initiation of Risk-based Maternal Intrapartum Antibiotic Prophylaxis—A Case Control Study

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Oxford University Press
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© The Author [2017]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com
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0142-6338
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Abstract

Abstract Objectives To identify the perinatal risk factors for early-onset Group B Streptococcus (EOGBS) sepsis in neonates after inception of a risk-based maternal intrapartum antibiotic prophylaxis strategy in 2004. Design Case control study. Methods All newborn with early onset GBS sepsis (born between 2004 and 2013) were deemed to be “cases” and controls were selected in a 1:4 ratio. Results More than three per vaginal (PV) examinations [odds ratio (OR) 8.57, 95% confidence interval (CI) 3.10–23.6] was a significant risk factors. Peripartum fever (OR 3.54, 95% CI 1.3–9.67), urinary tract infection (OR 2.88, 95% CI 1.08–7.63), meconium-stained amniotic fluid (MSAF) (OR 2.52, 95% CI 1.18–5.37) and caesarean section (OR 1.99, 95% CI 1.16–3.43) were also found to be associated with EOGBS sepsis. Conclusion Multiple vaginal examinations are the strongest risk factors for peripartum Group B Streptococcal (GBS) sepsis. The association of MSAF and caesarean section indicates that foetal distress is an early symptom of perinatal GBS infection. Group B Streptococcus, infant, newborn, factors, risk, India, neonatal sepsis INTRODUCTION Group B Streptococcus is a Gram-positive coccus known to be one of the main causative agents of early-onset sepsis (EOS) in neonates. The reservoir of Group B Streptococcus is usually the gastrointestinal tract of the mother; hence, rectovaginal colonization of mothers results in vertical transmission at the time of delivery [1]. Intrapartum antibiotic prophylaxis (IAP) is given to reduce this transmission [2]. The Centre for Diseases Control (CDC) recommends universal screening of mothers between 35 and 37 weeks of gestation to identify colonized mothers and to provide antibiotics to all those who are colonized [3]. Another approach is to use a risk-based strategy and to provide IAP to those mothers who have certain risk factors. The incidence of Group B Streptococcal (GBS) sepsis in neonates was 0.17/1000 live births in our institution over a 10-year period (1988–97) [4]. At that time, intrapartum antibiotic (ampicillin) was only given to pregnant women with chorioamnionitis or GBS urinary tract infection (UTI). As the incidence of EOS with GBS appeared to be rising over the next 5 years, a case-control study was done in 2003 to identify the risk factors for EOS [5]. Following this study, the policy of IAP was revised in 2004, and it has since been given in the presence of the following risk factors: maternal chorioamnionitis, GBS UTI, spontaneous preterm labour, preterm premature rupture of membranes (PPROM), peripartum fever (≥38°C) and prolonged rupture of membranes (PROM) >18 h. The incidence of EOGBS decreased with this strategy from 0.68/1000 live births (1998–2003) to 0.55/1000 live births (2004–10) [6]. All newborns born to mothers with these risk factors also have a sepsis screen done. A study in our institution in 2012 showed rectovaginal colonization in 7.6% of pregnant women screened at 35–37 weeks gestation [7]. Since then, some obstetricians offer women an option of having a rectovaginal screening at 35–37 weeks with IAP given if screen is positive. More than 30 000 women attend the obstetric outpatient department per year, and therefore, universal screening is not feasible either at clinic or laboratory levels. Hence, few obstetricians offer screening to their patients. Therefore, <1% women undergo screening. As there was a reduction in incidence of EOS with GBS after introduction of IAP, but the incidence remained higher than most high-middle-income countries, this study was undertaken to identify any additional risk factors for EOGBS. This case-control study was done to identify the risk factors for EOGBS sepsis after initiation of risk-based IAP. To our knowledge, no study has reported on risk factors after providing IAP. Identification of persisting and new risk factors may help us modify the current risk-based IAP policy. METHODS Christian Medical College is a tertiary-level perinatal centre, which is a private, patient-paid/charitable hospital catering to three districts in South India. As this is the only referral centre for a large population, >50% of deliveries are high-risk deliveries. All babies admitted in the neonatology unit from 1 January 2004 to 31 December 2014 who were found to have invasive GBS infection within 72 h of birth were identified as the ‘cases’. Invasive disease was described as isolation of the organism from any sterile site (blood/cerebrospinal fluid). The two babies born just before and the two babies born after the ‘cases’ were deemed to be the controls. The records of the mother–baby dyad were retrieved from the Medical Records Department. Data on maternal risk factors and neonatal outcome were collected in a predesigned questionnaire. Data from the pre-IAP era (1998–2003) were also re-analysed using the same methodology and the results were compared between the two epochs. However, data from only three controls per ‘case’ could be obtained from the earlier era. Sample size In a previous study by Benitz et al. [8], the risk factors, which were most significant for the development of EOS in newborns, were intrapartum fever [odds ratio (OR) 4.05] and chorioamnionitis with an OR of 6.43. Therefore, with an estimated 10% of controls having intrapartum fever and 1:4 case:control ratio, we needed a minimum of 54 cases and 216 controls. Descriptive statistics were reported using frequency and percentage for categorical variables. Association between the outcome and categorical variables was analysed using chi-square/Fisher’s exact test. Maternal risk factors associated with neonatal GBS infection were analysed by binary logistic regression using stepwise method with 25% significance for unadjusted analysis and 5% level of significance for adjusted analysis. The values were reported using OR and 95% confidence interval (CI). SPSS 16.0 was used for statistical analysis. The study was conducted with approval from the institutional review board. RESULTS In the period 2004–14, after the initiation of a risk-based intrapartum antibiotic policy, 71 babies were found to have an EOGBS sepsis. On analysing the risk factors associated with developing EOGBS sepsis, more than three per vaginal (PV) examinations after rupture of membranes was found to be a significant factor associated with EOGBS, with an adjusted OR of 8.57 (3.10–23.6) (Table 1). Peripartum fever with OR of 3.54 (95% CI 1.30–9.67) and UTI with OR of 2.88 (95% CI 1.08–7.63) were both significantly associated with EOGBS sepsis. The risk factors for EOGBS sepsis before 2003 are also represented in Table 1 for comparison. Factors like preterm pre-labour rupture of membranes (PPROM) and PROM >18 or 24 h, that were significant risk factors before 2003, were not found to be significant after initiating IAP. In both the eras, there was a trend of babies with EOGBS infection being born by caesarean section (20.1 and 27.3% versus 42.6 and 42.9%). Table 1 Perinatal risk factors for early onset GBS sepsis after and before intrapartum antibiotics Risk factors Pre IAP era (1998–2003) Post IAP era (2004–2015) Cases Controls Unadjusted OR Adjusted OR Cases Controls Unadjusted OR Adjusted OR N = 47 N = 144 OR (95% CI) OR (95% CI) N = 71 N = 284 OR (95% CI) OR (95% CI) n (%) n (%) n (%) n (%) Prematurity<37 wks 9 (19.1%) 11 (7.6%) 2.91 (1.12–7.57) – 10 (14.3%) 42 (14.9%) 0.95 (0.45–2.01) – Low birth weight <2500 gm 8 (17%) 22 (15.3%) 1.16 (0.48–2.8) – 22 (31.9%) 59 (20.8%) 1.78 (0.9–3.19) – Chorioamnionitis 4 (8.5%) 0 5.53 – 0 6 (2.1%) – – Prolonged rupture of membranes >18 hours 14 (29.8%) 14 (9.7%) 3.93 (1.71–9.06) – 2 (2.8%) 17 (5.9%) 2.197 (0.4–9.7) – Prolonged rupture of membranes >24 hours 10 (21.3%) 7 (4.9%) 5.29 (1.88–14.84) 5.09 (1.44–17.93) 2 (2.8%) 8 (2.8%) 1.0 (0.2–4.8) – Prelabour rupture of membranes 11 (23.4%) 28 (19.4%) 1.26 (0.57–2.79) – 10 (14.1%) 54 (19%) 1.4 (0.6–2.9) – Peripartum fever 17 (36.2%) 21 (14.6%) 3.62 (1.69–7.78) 2.23 (0.57–5.73) 9 (14.5%) 12 (4.3%) 3.77 (1.5–9.41) 3.54 (1.30–9.67) More than 3 per vaginal examination after rupture of membranes 16 (34%) 5 (3.5%) 17.7 (5.9–52.9) 11.22 (3.38–37.22) 11 (16.7%) 8 (2.8%) 6.9 (2.65–17.94) 8.57 (3.10–23.6) Meconium stained amniotic fluid 10 (21.3%) 25 (17.4%) 1.36 (0.59–3.10) – 15 (23.8%) 33 (11.8%) 2.33 (1.180–4.63) 2.52 (1.18–5.37) Urinary tract infection 3 (6.4%) 0 – – 9 (13.4%) 16 (5.7%) 2.57 (1.08–6.10) 2.88 (1.08–7.63) Primigravida 26 (55.3%) 68 (47.2%) 1.45 (0.74–2.83) – 43 (61%) 145 (51.4%) 1.50 (0.88–2.56) – Caesarean 20 (42.6%) 29 (20.1%) 3.05 (1.49–6.21) 1.43 (0.55–3.71) 30 (42.9%) 77 (27.3%) 1.99 (1.16–3.43) – Risk factors Pre IAP era (1998–2003) Post IAP era (2004–2015) Cases Controls Unadjusted OR Adjusted OR Cases Controls Unadjusted OR Adjusted OR N = 47 N = 144 OR (95% CI) OR (95% CI) N = 71 N = 284 OR (95% CI) OR (95% CI) n (%) n (%) n (%) n (%) Prematurity<37 wks 9 (19.1%) 11 (7.6%) 2.91 (1.12–7.57) – 10 (14.3%) 42 (14.9%) 0.95 (0.45–2.01) – Low birth weight <2500 gm 8 (17%) 22 (15.3%) 1.16 (0.48–2.8) – 22 (31.9%) 59 (20.8%) 1.78 (0.9–3.19) – Chorioamnionitis 4 (8.5%) 0 5.53 – 0 6 (2.1%) – – Prolonged rupture of membranes >18 hours 14 (29.8%) 14 (9.7%) 3.93 (1.71–9.06) – 2 (2.8%) 17 (5.9%) 2.197 (0.4–9.7) – Prolonged rupture of membranes >24 hours 10 (21.3%) 7 (4.9%) 5.29 (1.88–14.84) 5.09 (1.44–17.93) 2 (2.8%) 8 (2.8%) 1.0 (0.2–4.8) – Prelabour rupture of membranes 11 (23.4%) 28 (19.4%) 1.26 (0.57–2.79) – 10 (14.1%) 54 (19%) 1.4 (0.6–2.9) – Peripartum fever 17 (36.2%) 21 (14.6%) 3.62 (1.69–7.78) 2.23 (0.57–5.73) 9 (14.5%) 12 (4.3%) 3.77 (1.5–9.41) 3.54 (1.30–9.67) More than 3 per vaginal examination after rupture of membranes 16 (34%) 5 (3.5%) 17.7 (5.9–52.9) 11.22 (3.38–37.22) 11 (16.7%) 8 (2.8%) 6.9 (2.65–17.94) 8.57 (3.10–23.6) Meconium stained amniotic fluid 10 (21.3%) 25 (17.4%) 1.36 (0.59–3.10) – 15 (23.8%) 33 (11.8%) 2.33 (1.180–4.63) 2.52 (1.18–5.37) Urinary tract infection 3 (6.4%) 0 – – 9 (13.4%) 16 (5.7%) 2.57 (1.08–6.10) 2.88 (1.08–7.63) Primigravida 26 (55.3%) 68 (47.2%) 1.45 (0.74–2.83) – 43 (61%) 145 (51.4%) 1.50 (0.88–2.56) – Caesarean 20 (42.6%) 29 (20.1%) 3.05 (1.49–6.21) 1.43 (0.55–3.71) 30 (42.9%) 77 (27.3%) 1.99 (1.16–3.43) – Table 1 Perinatal risk factors for early onset GBS sepsis after and before intrapartum antibiotics Risk factors Pre IAP era (1998–2003) Post IAP era (2004–2015) Cases Controls Unadjusted OR Adjusted OR Cases Controls Unadjusted OR Adjusted OR N = 47 N = 144 OR (95% CI) OR (95% CI) N = 71 N = 284 OR (95% CI) OR (95% CI) n (%) n (%) n (%) n (%) Prematurity<37 wks 9 (19.1%) 11 (7.6%) 2.91 (1.12–7.57) – 10 (14.3%) 42 (14.9%) 0.95 (0.45–2.01) – Low birth weight <2500 gm 8 (17%) 22 (15.3%) 1.16 (0.48–2.8) – 22 (31.9%) 59 (20.8%) 1.78 (0.9–3.19) – Chorioamnionitis 4 (8.5%) 0 5.53 – 0 6 (2.1%) – – Prolonged rupture of membranes >18 hours 14 (29.8%) 14 (9.7%) 3.93 (1.71–9.06) – 2 (2.8%) 17 (5.9%) 2.197 (0.4–9.7) – Prolonged rupture of membranes >24 hours 10 (21.3%) 7 (4.9%) 5.29 (1.88–14.84) 5.09 (1.44–17.93) 2 (2.8%) 8 (2.8%) 1.0 (0.2–4.8) – Prelabour rupture of membranes 11 (23.4%) 28 (19.4%) 1.26 (0.57–2.79) – 10 (14.1%) 54 (19%) 1.4 (0.6–2.9) – Peripartum fever 17 (36.2%) 21 (14.6%) 3.62 (1.69–7.78) 2.23 (0.57–5.73) 9 (14.5%) 12 (4.3%) 3.77 (1.5–9.41) 3.54 (1.30–9.67) More than 3 per vaginal examination after rupture of membranes 16 (34%) 5 (3.5%) 17.7 (5.9–52.9) 11.22 (3.38–37.22) 11 (16.7%) 8 (2.8%) 6.9 (2.65–17.94) 8.57 (3.10–23.6) Meconium stained amniotic fluid 10 (21.3%) 25 (17.4%) 1.36 (0.59–3.10) – 15 (23.8%) 33 (11.8%) 2.33 (1.180–4.63) 2.52 (1.18–5.37) Urinary tract infection 3 (6.4%) 0 – – 9 (13.4%) 16 (5.7%) 2.57 (1.08–6.10) 2.88 (1.08–7.63) Primigravida 26 (55.3%) 68 (47.2%) 1.45 (0.74–2.83) – 43 (61%) 145 (51.4%) 1.50 (0.88–2.56) – Caesarean 20 (42.6%) 29 (20.1%) 3.05 (1.49–6.21) 1.43 (0.55–3.71) 30 (42.9%) 77 (27.3%) 1.99 (1.16–3.43) – Risk factors Pre IAP era (1998–2003) Post IAP era (2004–2015) Cases Controls Unadjusted OR Adjusted OR Cases Controls Unadjusted OR Adjusted OR N = 47 N = 144 OR (95% CI) OR (95% CI) N = 71 N = 284 OR (95% CI) OR (95% CI) n (%) n (%) n (%) n (%) Prematurity<37 wks 9 (19.1%) 11 (7.6%) 2.91 (1.12–7.57) – 10 (14.3%) 42 (14.9%) 0.95 (0.45–2.01) – Low birth weight <2500 gm 8 (17%) 22 (15.3%) 1.16 (0.48–2.8) – 22 (31.9%) 59 (20.8%) 1.78 (0.9–3.19) – Chorioamnionitis 4 (8.5%) 0 5.53 – 0 6 (2.1%) – – Prolonged rupture of membranes >18 hours 14 (29.8%) 14 (9.7%) 3.93 (1.71–9.06) – 2 (2.8%) 17 (5.9%) 2.197 (0.4–9.7) – Prolonged rupture of membranes >24 hours 10 (21.3%) 7 (4.9%) 5.29 (1.88–14.84) 5.09 (1.44–17.93) 2 (2.8%) 8 (2.8%) 1.0 (0.2–4.8) – Prelabour rupture of membranes 11 (23.4%) 28 (19.4%) 1.26 (0.57–2.79) – 10 (14.1%) 54 (19%) 1.4 (0.6–2.9) – Peripartum fever 17 (36.2%) 21 (14.6%) 3.62 (1.69–7.78) 2.23 (0.57–5.73) 9 (14.5%) 12 (4.3%) 3.77 (1.5–9.41) 3.54 (1.30–9.67) More than 3 per vaginal examination after rupture of membranes 16 (34%) 5 (3.5%) 17.7 (5.9–52.9) 11.22 (3.38–37.22) 11 (16.7%) 8 (2.8%) 6.9 (2.65–17.94) 8.57 (3.10–23.6) Meconium stained amniotic fluid 10 (21.3%) 25 (17.4%) 1.36 (0.59–3.10) – 15 (23.8%) 33 (11.8%) 2.33 (1.180–4.63) 2.52 (1.18–5.37) Urinary tract infection 3 (6.4%) 0 – – 9 (13.4%) 16 (5.7%) 2.57 (1.08–6.10) 2.88 (1.08–7.63) Primigravida 26 (55.3%) 68 (47.2%) 1.45 (0.74–2.83) – 43 (61%) 145 (51.4%) 1.50 (0.88–2.56) – Caesarean 20 (42.6%) 29 (20.1%) 3.05 (1.49–6.21) 1.43 (0.55–3.71) 30 (42.9%) 77 (27.3%) 1.99 (1.16–3.43) – An increased number of cases were born through meconium-stained amniotic fluid (MSAF) [OR 2.52 (95% 1.18–5.37)]. As compared with the controls, a significant number of babies with sepsis had abnormal cardiotocogram (CTG) before delivery [33.8%, OR 2.17 (1.22–3.86)]. Abnormal CTG was defined as Category II or Category III CTG. There was also an increased need for resuscitation at birth—23 versus 3.5%, OR 2.58 (1.12–5.9) (Table 2). Table 2 Association of CTG abnormalities and resuscitation with GBS sepsis Variable Cases (N, %) Controls (N, %) OR (95% CI) Resuscitation 17 (23) 10 (3.5) 2.58 (1.12–5.90) Non-reassuring foetal status on CTG 24 (33.8) 54 (19) 2.17 (1.22–3.86) Variable Cases (N, %) Controls (N, %) OR (95% CI) Resuscitation 17 (23) 10 (3.5) 2.58 (1.12–5.90) Non-reassuring foetal status on CTG 24 (33.8) 54 (19) 2.17 (1.22–3.86) Table 2 Association of CTG abnormalities and resuscitation with GBS sepsis Variable Cases (N, %) Controls (N, %) OR (95% CI) Resuscitation 17 (23) 10 (3.5) 2.58 (1.12–5.90) Non-reassuring foetal status on CTG 24 (33.8) 54 (19) 2.17 (1.22–3.86) Variable Cases (N, %) Controls (N, %) OR (95% CI) Resuscitation 17 (23) 10 (3.5) 2.58 (1.12–5.90) Non-reassuring foetal status on CTG 24 (33.8) 54 (19) 2.17 (1.22–3.86) DISCUSSION Prevention of vertical transmission of Group B Streptococci from a colonized mother to her newborn has been one of the successful strategies adopted to reduce early-onset infection in newborn. This is ideally done by screening pregnant women in late pregnancy and giving intrapartum antibiotics to those found colonized. Alternatively, antibiotics can be given in labour to pregnant women who have certain risk factors, which predispose their newborn to EOGBS infection. Universal screening has been found to be cost-effective only when the incidence of EOGBS is >1.2/1000 live births [9]. This strategy might also be cost prohibitive and technically not feasible in most mid-low-income countries. Hence, many institutions use a risk-based intrapartum antibiotic policy. After a case-control study in 2003, we adopted a risk-based IAP policy since 2004. This study looks at the risk factors for EOGBS infections when an IAP policy is in place. This was done to identify any new risk factors and to assess the effect of IAP on existing risk factors. Prematurity (<37 weeks) was a risk factor in the pre-IAP epoch. This was similar to previous similar studies [8, 10, 11]. In the post-IAP epoch, it was not significantly associated with GBS infection. This is attributed to the successful IAP coverage of mothers who present with preterm labour or PPROM since 2004. Similarly, PROM >18 h has been identified to be significantly associated with GBS sepsis in many studies [8, 10]. A similar association was found in our pre-IAP epoch, which was no longer seen after initiating IAP. This again is probably because of IAP given in this setting. Peripartum fever continued to be a risk factor, despite a policy of IAP for women in labour having fever >38°C. A previous study by Al-Kadri et al. [12] also found an association between peripartum fever and EOGBS (OR 7.10, 2.50–20.71). Though we are not able to account for this continuing association, a possible explanation could be that the obstetricians’ compliance with giving IAP in fever is lower (compared with other risk factors), especially if they felt that fever could be attributed to another aetiology. We do not have data on overall compliance with the overall IAP policy and in individual risk factors throughout the period under study. Observationally, the compliance seems to be between 50 and 60%. It is logical to assume that improvement in compliance to IAP closer to 100% in mothers with risk factors would further reduce neonatal EOGBS incidence in the institution. More than three vaginal examinations after ROM showed the strongest association with EOGBS disease in both the pre- and post-IAP epochs. This indirectly points to a high colonization rate in our population. However, a study in 2012 showed maternal colonization rate of only 7.6%, which is much lower than most high-middle-income countries. We are hence unable to account for this discrepancy. Previous studies have not reported the magnitude of association of multiple PVs and EOGBS sepsis in neonates, though this is known to be associated with chorioamnionitis [13]. Hence, we would strongly encourage IAP to unscreened mothers who had multiple vaginal examinations in labour. Alternatively, this could be considered a major risk factor for EOGBS sepsis necessitating sepsis workup in the newborns. This could go a long way in reducing EOGBS sepsis in developing countries. Our data show that babies with GBS sepsis were more likely to be born through MSAF, have an abnormal CTG, be delivered by caesarean section and require resuscitation at birth. Studies have shown that GBS-colonized women had more foetal distress when compared with GBS-negative women [13]. It has been hypothesized that EOGBS sepsis is a spectrum of infection that also involves the foetus, which seems to be borne out by our data. Over the past few years, babies who have unexplained foetal distress and are asphyxiated/have respiratory depression at birth have had sepsis workup in our hospital and been covered with penicillin and gentamicin. The study proves that IAP definitely helps in the settings of preterm labour/PPROM as well as PROM in reducing EOGBS sepsis. It highlights the strong association of multiple vaginal examinations with GBS invasive disease. Where universal screening of mothers is not practised, this should be a guide to obstetricians to reduce unwanted vaginal examinations and also be the single most important risk factor to do a sepsis screen in symptomatic newborns. Our study thus can serve as a template for risk-based intrapartum treatment of mothers and newborn evaluation for EOS, especially in middle-low-income countries. Further studies are needed to evaluate the effect of infection in causing foetal distress/asphyxia in the developing world. References 1 Dillon HC , Gray E , Pass MA , et al. Anorectal and vaginal carriage of group B streptococci during pregnancy . J Infect Dis 1982 ; 145 : 794 – 9 . Google Scholar CrossRef Search ADS PubMed 2 Ohlsson A , Shah VS. Intrapartum antibiotics for known maternal Group B Streptococcal colonization . Cochrane Database Syst Rev 2014 ; 10 : CD007467 . 3 Verani JR , McGee L , Schrag SJ. Centers for Disease Control and Prevention: Prevention of perinatal group B streptococcal disease–revised guidelines from CDC, 2010. Morb Mortal Wkly Rep 2010; 59 : 1 – 36 . 4 Kuruvilla KA , Thomas N , Jesudasan MV , et al. Neonatal Group B Streptococcal bacteraemia in India: ten years’ experience . Acta Paediatr 1999 ; 88 : 1031 – 2 . Google Scholar CrossRef Search ADS PubMed 5 Sridhar S , Jolly C , Niranjan T , et al. Neonatal Group B Streptococcal infection in India—myth or reality? Poster presented at The XXIII annual convention of the National Neonatology Forum, Hyderabad. December 19–21, 2003 . 6 Sridhar S , Grace R , Nithya PJ , et al. Group B Streptococcal infection in a tertiary hospital in India—1998–2010 . Pediatr Infect Dis J 2014 ; 33 : 1091 – 2 . Google Scholar CrossRef Search ADS PubMed 7 Santhanam S , Jose R , Sahni RD , et al. Prevalence of Group B Streptococcal colonization among pregnant women and neonates in a tertiary hospital in India . J Turk Ger Gynecol Assoc 2017 ; (In press). doi: 10.4274/jtgga.2017.0032. 8 Benitz WE , Gould JB , Druzin ML. Risk factors for early-onset group streptococcal sepsis: estimation of odds ratios by critical literature review . Pediatrics 1999 ; 103 : e77 . Google Scholar CrossRef Search ADS PubMed 9 Mohle-Boetani JC , Schuchat A , Plikaytis BD , et al. Comparison of prevention strategies for neonatal Group B Streptococcal infection: a population-based economic analysis . JAMA 1993 ; 270 : 1442 – 8 . Google Scholar CrossRef Search ADS PubMed 10 Oddie S , Embleton ND. Risk factors for early onset neonatal Group B Streptococcal sepsis: case-control study . BMJ 2002 ; 325 : 308 . Google Scholar CrossRef Search ADS PubMed 11 Adair CE , Kowalsky L , Quon H , et al. Risk factors for early-onset Group B Streptococcal disease in neonates: a population-based case-control study . CMAJ Can Med Assoc J J Assoc Medicale Can 2003 ; 169 : 198 – 203 . 12 Al-Kadri HM , Bamuhair SS , Johani SMA , et al. Maternal and neonatal risk factors for early-onset Group B Streptococcal disease: a case control study . Int J Womens Health 2013 ; 5 : 729 – 35 . Google Scholar CrossRef Search ADS PubMed 13 Shi C , Qu S , Yang L , et al. Detection of maternal colonization of group B streptococcus in late pregnancy by real-time polymerase chain reaction and its effect on perinatal outcome . Zhonghua Fu Chan Ke Za Zhi 2010 ; 45 : 12 – 6 . Google Scholar PubMed © The Author [2017]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

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Journal of Tropical PediatricsOxford University Press

Published: Aug 1, 2018

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