Maternal colonization with Group B Streptococcus (GBS) is a risk factor for neonatal sepsis, as vertical transmission in utero or during labor can result in a life-threatening early-onset sepsis (EOS) in the newborn infant [1]. In the United States, GBS colonization is therefore extensively determined among pregnant women, with screening rates at 85% or higher [2]. This universal routine-based screening strategy contrasts with the heterogeneous practice worldwide. For example, in Europe various guidelines advocate risk-based GBS screening depending on obstetric history, whereas in Korea guidelines for the screening of pregnant women for GBS still need to be established [3-7]. A recent study found a GBS colonization rate of 11.6% among pregnant Korean women and recommended GBS screening and the administration of intrapartum antibiotic prophylaxis (IAP) in pregnant Korean women [4]. The status of maternal vaginal or rectal GBS colonization needs to be available in labor to allow timely administration of IAP to prevent EOS [3]. Partly attributed to IAP, a decline in the incidence of EOS to less than 0.5 in 1,000 live births has been observed among term infants [8]. However, the reported number of infants receiving empiric antibiotic therapy for suspected EOS is much higher [9].

To improve the accuracy of empirical antibiotic administration in newborn infants at risk for EOS, the neonatal EOS calculator was designed and validated in the United States. It has proven to be effective in limiting antibiotic treatment in suspected EOS in term and near-term infants without apparent adverse effects [10-15]. The sepsis calculator uses maternal GBS status at birth as 1 of 5 maternal risk factors. The EOS calculator allows ‘positive,’ ‘negative,’ and ‘unknown’ as input for maternal GBS status in the algorithm. In contrast to a routine-based GBS screening, risk-based GBS screening carries the possibility that maternal GBS colonization information is unavailable at time of birth. Often, the GBS culture results become later available after birth. As the EOS calculator is being evaluated for implementation in European and Asian practice, it is important to know whether implementation is compatible with risk-based GBS screening.

The aim of this study was to evaluate to what extent a risk-based GBS screening influences management recommendations by the EOS calculator. If our results indicate that antibiotic recommendations are not influenced by this strategy than the sepsis calculator may also be implemented in countries with a risk-based GBS screening policy.

As use of the EOS calculator spreads to areas without universal screening for GBS, it is important to consider how use of other screening strategies may impact recommendations by the EOS calculator. In particular, it is important to address whether the lack of universal GBS screening may lead to fewer recommendations of antibiotic therapy. We found that in 97% of newborn infants at risk for EOS in a single Dutch center, the EOS calculator recommendation remained unchanged after we recalculated the EOS risk using the definitive GBS results, which were not yet available at birth. Median EOS risk was slightly lower after recalculation using the definitive GBS screening results. Most importantly, additional knowledge on the GBS status did not increase the total number of recommendations for antibiotic treatment in newborn infants with a GBS-positive mother. In other words, the risk-based screening method did not withhold antibiotic treatment in infants at risk for EOS. These observations together indicate that use of a risk-based screening method only marginally influences EOS calculator management recommendations.

These findings correspond with the modest contribution of the GBS status as a risk factor to the total predictive value in the multivariate EOS calculator model [18]. They are further explained by the finding that definitive GBS results were mostly negative, thus decreasing EOS risk. In our study population, GBS status was available at birth in only few cases, whereas a definitive GBS status was determined in the vast majority of cases. This indicates that GBS screening shortly prior to birth is common with a risk-based screening strategy, limiting the opportunity to timely administer IAP. A definitive GBS status was not determined in the remaining fifth of our study population, most likely because of absence of indications for testing in obstetric history. Importantly, a substantial part of GBS-related EOS disease occurs despite negative GBS status [19], reflecting that other factors and clinical signs should be taken into account at all times.

Maternal GBS status can mediate the calculated EOS risk and management guided by the EOS calculator indirectly through IAP, which is widely used to decrease GBS-related EOS [20]. Notable differences across guidelines and in practice exist [5,21], but Dutch guidelines recommend IAP in case of a positive urine culture [5]. We found that in our population only 6% of tested mothers qualified for IAP as a result of a GBS-positive urine culture. Only half of these mothers received adequate intrapartum antibiotics, possibly due to late availability of results of maternal GBS screening.

As use of the EOS calculator spreads to areas with various approaches regarding prevention of GBS neonatal sepsis, this development should be accompanied with thoughtful evaluation of GBS screening strategies. Our findings indicate that use of risk-based GBS screening only marginally impacts EOS calculator antibiotic management recommendation in the newborn infant. However, GBS screening strategies may be most – if not only – helpful when results are provided timely enough for administration of IAP and for use in the EOS calculator. The new generation of rapid intrapartum tests based on polymerase-chain-reactions is a promising opportunity in this matter [22,23]. Rapid availability of results will be more suitable for guiding decisions on timely IAP and for direct use in the EOS calculator at birth.

Among the strengths of our study is its thorough data collection on maternal GBS status. Also, to our knowledge, this is the first study to evaluate the important difference in GBS screening strategies in the context of the increasingly adopted EOS calculator. Limitations include the single-center study design, which means that results may be different in settings with different risk-based screening strategies. It was conducted in a high-risk population subset with limited sample size, selected on presence of maternal EOS risk factors or neonatal clinical EOS symptoms. The results therefore cannot be generalized to the general newborn infant population without precautions. However, the remaining population of the newborn infants in our hospital had no known EOS risk factors or clinical EOS symptoms. It is therefore at low risk for EOS, and thus unlikely to receive an EOS calculator recommendation for empiric antibiotic therapy, irrespective of maternal GBS status. Hence, we are confident that our design included the vast majority of relevant births where GBS status could have a significant role in decisions regarding empiric antibiotic therapy, making the results indicative for the larger population. Finally, although these results are supportive of the applicability of the EOS calculator in settings with a risk-based screening strategy, this study does not validate the EOS calculator itself for such settings.

In conclusion, our results indicate that use of risk-based GBS screening is compatible with use of the EOS calculator. Larger studies are needed to address the best way of combining GBS screening with use of the EOS calculator.