The present study reports on the clinical and microbiological characteristics, as well as risk factors and outcome in 153 infant patients with invasive GBS disease from eight different European countries, a cohort collected within the framework of the EU-funded DEVANI project. Among the countries included in the DEVANI consortium, epidemiological and clinical data related to GBS neonatal disease were not equal, sometimes very poor or lacking.
Concordant with previous publications, GBS EOD presented shortly after birth with predominantly respiratory symptoms . The time point of infection was indicative of intrapartum or in-utero GBS transmission from the colonized mother. At the time of the study, a screening-based strategy was recommended in Belgium, Czech Republic, Germany, Italy and Spain; nevertheless, mothers of numerous EOD cases had not been screened accordingly in these five countries, partly due to preterm birth before reaching the recommended time point for screening. But among other reasons for the low reporting were likely lack of adherence to guidelines by health care providers, refused screening offers by pregnant women and incomplete data traceability. Indeed, poor adherence to existing recommendations has been identified as a factor limiting the effectiveness of antenatal screening . On the other hand, a risk-based strategy was applied in the UK, Bulgaria and Denmark, however, a lower number of EOD cases’ mothers had had antenatal screening. In summary, in our study, less than half of EOD cases’ mothers (33/77) had an antenatal swab taken and of those, 48.5% were identified GBS-positive, which is concordant with previous studies [37, 38]. Concerning the presence of risk factors, the rate was even lower with 33% of parturients (to EOD cases) presenting with at least one risk factor, a frequently described limitation to this strategy of prevention [39, 40]. Thus, both strategies were likely to miss opportunities for preventing neonatal invasive cases. In addition, even with the knowledge of an existing positive screening result, IAP was not administered timely in a significant number of cases, a finding concordant with other publications [5, 6, 36, 38]. The reasons for this non-compliance had not been systematically analyzed but were potentially due to the limited time period between arrival in the hospital and birth. These considerations reflected some important limitations of both prevention strategies. The low sensitivity of antenatal screening methods needed to be improved. And, as most cases occurred in situations where testing or treating for GBS in pregnant women was not done according to the standard of care, emphasizing the necessity to more stringently adhere to the existing recommendations in order to improve the overall quality of care. They also highlighted the need to harmonize recommendations for prevention throughout Europe and for an alternative approach, i.e., maternal GBS immunization.
GBS LOD cases differed substantially with regards to clinical presentation and microbiological characteristics. A high proportion of cases caused by GBS CC17 (71.4% of all sequence typable strains), known to be hypervirulent, was detected in our LOD cohort, however, at a rate lower than recently published findings from the USA , but similar to findings from France and China [41, 42]. More than half of the LOD cases showed neurological symptoms, confirming GBS LOD to be a neurotropic disease. The transmission route in GBS LOD remains controversial, though transmission via breast milk has been reported [6, 43]. Other routes include neonatal colonization during birth , nosocomial infection through health-care workers  and others [6, 43, 46]. Nine LOD cases (14.8%) of our cohort had not received breast milk before the onset of symptoms. The colonization rate in mothers of LOD cases was roughly 50%, a rate similar to previously published findings , much higher than the ~ 20% in the general population . Other than that, no information on the transmission route was available from our data. Known risk factors for LOD included prematurity and a positive antenatal GBS culture .
Adverse outcomes are still repeatedly reported with invasive GBS disease despite adequate treatment, and the preterm cohort is especially at risk . In our EOD cohort, this is mostly associated with cardiorespiratory failure. Death from LOD had occurred in only one case in our cohort, 3/20 cases with clinical meningitis (15%) had survived with neurological sequelae though such sequelae were more frequently reported after GBS meningitis, . However, no long-term follow-up data was available for our cohort. Overall, the mortality (5.7% in EOD and 1.6% in LOD) was lower than or similar to most published cohorts .
The study revealed relevant differences in clinical practice between the different participating countries such as the percentage of pregnancies with antenatal screening and general clinical practice such as performing an X-ray for neonates with invasive infections (data not shown). Antenatal GBS screening was recommended in many European countries between 35 + 0 and 37 + 0 weeks of gestation, but not always covered by health insurance resulting in difference of compliance and not generally recommended as in the UK, Bulgaria and in Denmark . Among these countries as well as in other European countries, during the last decade, guidelines have not evolved significantly even if attempts towards a European consensus has been done but not yet concluded . So, it seems imperative to harmonize the recommendations in order to improve the quality of care and to systematically assess effects of measures taken across Europe.
Microbiological characteristics showed a wide distribution between European countries, especially the frequency of isolates attributable to CC17 in LOD, which range from 40% in Spain to 86% in Italy. This is likely to impact on the disease course, e.g., the prevalence of meningitis in different countries.
Limitations of our study include the lack of information on the actual incidence, as no steps were implemented to guarantee that every case was reported. Furthermore, the observational period extends only during inpatient care, thus probably missing the detection of neurological sequelae that frequently become apparent only later in life . This study did not include a control group of healthy neonates, thus clinical characteristics cannot specifically be attributed to GBS disease and the specificity of maternal risk factors cannot be determined. The delay in reporting is attributable to difficulties in data management that were only recently resolved. However, the clinical findings in our cohort are still relevant for to the actual situation of invasive GBS infections in neonates and young infants and reflect the spectrum of GBS disease nowadays. Even if the epidemiology of GBS disease has changed over the last decade, knowledge about the low acceptance rate of GBS screening and the low rate of appropriate intrapartal antibiotic prophylaxis is an eye-opener to GBS policy makers in current days. Indeed, our study includes data from eight European countries for which no or very few more recent epidemiological data has been published and where recommendations for prevention of GBS neonatal disease has not much changed.