Routine culture based screening versus risk based management for the prevention of early onset group B streptococcus disease in the neonate: a systematic review protocol

Review objective To determine the effectiveness of routine culture based screening and risk based management in the prevention of early onset group B streptococcus disease (EOGBSD) and group B streptococcus (GBS) morbidity and mortality in the neonate as well as compare rates of intrapartum antibiotic prophylaxis (IAP) in both groups. Background Early onset group B streptococcus disease (EOGBSD), defined as the systemic infection of the newborn between birth and the first seven days of life due to the microorganism group B streptococcus, is recognised as the most common cause of all early onset neonatal sepsis in developed countries.1 Although neonatal sepsis is uncommon, it is responsible for gross morbidity that can impact greatly on the life of the infant who survives EOGBSD as well as their family and in some cases is fatal.2, 3 Group B streptococcus (GBS), the microorganism responsible for EOGBSD, is carried as a commensal in the maternal intestinal tract.4 Maternal GBS colonisation increases the risk of preterm birth and is thought to be one of the several bacteria that increase the risk of premature rupture of membranes.5 It is also a leading cause of chorioamnionitis.5 Premature (< 37 weeks gestation) and low birth weight infants (<2500 grams) are more susceptible to colonisation and infection of GBS. Neonatal infection is the result of the ascending spread of GBS from the maternal rectum and perineum throughout the vagina and, in some cases, to the amniotic fluid. It is also possible for babies to acquire GBS during their passage through the birth canal or via aspiration of infected amniotic fluid.5, 6 The Australian maternal GBS carriage rate is reported at 20 to 24 per cent.7, 8 Up to 70%of infants born to colonised women will become colonised with GBS.9 A GBS infection occurs in one per cent of colonised infants.9 In the United Kingdom (UK), where the carriage rate is similar to that of Australia at 21%, Brocklehurst and Kenyon3 calculate that every woman who carries GBS in the lower genital tract during pregnancy has a three per 10,000 chance of losing their baby to EOGBSD. The risk of a preterm infant developing EOGBSD is greater, as preterm infants are immunologically more prone to sepsis. Prophylaxis The two main methods employed in the prevention of EOGBSD are culture based screening and risk‐based management. In both methods, EOGBSD prophylaxis focuses on interrupting the spread of the micro‐organism from mother to neonate by administering prophylactic intravenous antibiotics to the mother in the intrapartum.15,16,17 Maternal antibiotic therapy, however, may affect the community negatively because of the propensity for maternal allergic reactions, increase in drug resistant organisms, the exposure of neonates to antibiotics and the medicalization of birth required in the antibiotic therapy treatment process.2,18,12 Other treatment options such as antenatal antibiotic therapy for GBS carriers or management of neonates after birth are not in use as they have been found ineffective3 compared with IAP. Screening While future treatment options such as GBS vaccination and rapid bedside testing for maternal GBS colonisation are being explored as more effective EOGBSD strategies of prevention, the current mainstay of management is based on two main screening methods. These aim to identify women suitable for IAP; however neither has been evaluated in randomized controlled trials. The screening methods are: 1. Identifying women as at risk of GBS colonisation in labour through the clinical signs (risk factors) of: preterm labour at less than 37 weeks gestation, prolonged rupture of membranes, maternal pyrexia during labour equal to or more than 38 degrees Celsius, previous EOGBSD affected infant, and bacteriuria in the index pregnancy. These women are offered IAP.15 This strategy is referred to in this review as risk based management or protocol. 2. Culturing a swab from the vagina and rectum of all women at 35‐37 weeks gestation and offering IAP to those women whose swabs culture positive for GBS.13‐15 In a perfect application of this protocol, women who screen negative receive IAP for the development of any of the above mentioned risk factors. Women with an unknown GBS status in labour are treated as per risk based protocol.14, 15 This strategy is referred to in this review as routine culture based screening or protocol. Maniatis et al.10 identified that women may carry GBS persistently, intermittently or not at all. The transient colonisation of the vagina by GBS stems from the fact that the vaginal environment fluctuates and hence does not always provide ideal living conditions for the microorganism.11 The status of a woman's GBS colonisation may change throughout her pregnancy, a situation that is problematic from a culture based screening perspective.8,12 The best time to perform a culture‐based screening is 35 to 37 weeks as the GBS status of only four percent of women changes from negative to positive between this gestation until time of birth.13, 14 The transient nature of colonisation means that treatment based on culture based screening can therefore cause the over or under treatment of women with IAP. Although geographic, ethnic and socioeconomic factors may influence the carriage rates, Maniatis et al10 suggest that the true carriage rate of GBS may be obfuscated by lack of consistency and technique of culturing. The implementation of routine culture based versus risk based protocol is country and region specific. In 1996, the Centers for Disease Control and Prevention (CDC)15 in the United States of America (USA) released guidelines recommending either risk based or culture based screening for IAP in EOGBSD prevention. Research undertaken in 2002 by Schrag et al.19 reshaped CDC guidelines. The routine culture based protocol was found to be more efficacious as a) it prevented disease in infants of women colonised with GBS who were presented without GBS risk factors, and b) the adherence to IAP protocol by maternity care provider was higher with culture based screening.19,20 Accordingly, the CDC now endorses routine culture based screening over the risk based protocol.14 United Kingdom guidelines do not recommend culture based screening on the basis that, at this point, it is still unclear as to whether this strategy does more good than harm.3,21 Globally, countries are divided as to EOGBSD prevention management and are influenced by the policy and guidelines in place in the USA and the UK. The evaluation of the screening strategies is based on observational studies.22,23 Whilst the incidence of EOGBSD in the UK is approximately 0.5 per 1000 live births in the absence of routine culture based screening, observational studies from the USA in 1996 suggest that the introduction of a national screening program for antenatal GBS carriage resulted in a substantial fall in the incidence of EOGBSD.2, 24‐26 Between 1996 and 2000 CDC guidelines supported the implementation of either culture based or risk based protocol. This period saw a fall in EOGBSD incidence from 1.5 per 1000 live births to 0.5 live births. The incidence fell further to 0.35 per 1000 births in 2005 following the implementation of routine culture based protocol only from the year 2000.24‐26 A 2005 Australian retrospective cohort study estimated EOGBSD incidence at 0.84 per 1000 live births with risk based management and 0 per 1000 live births with routine culture based management.8 One systematic review with meta‐analysis has been published on this topic.27 The inclusion criteria of this review are unclear and accordingly it is feasible to suggest that relevant studies may have been excluded with less relevant studies included. This second systematic review looks to offer a clearer picture of the evidence. It will aim to do this via tighter inclusion and exclusion definition, including studies of observational and experimental design as well as providing an updated overview of the evidence and the original review including studies published prior to January 2010.