Early onset neonatal sepsis and its associatited factors: a cross sectional study.

BACKGROUND: Sepsis is the 3rd leading cause of neonatal mortality in Ethiopia contributing to 16% of neonatal death. In a hospital study, neonatal sepsis was the leading diagnosis at admission and the second leading cause of neonatal death at the neonatal intensive care unit. Among other factors repeated vaginal examination during labor is known to contribute to sepsis in low-income settings. However, there is limited evidence in the Ethiopian setting. OBJECTIVE: The objective of this study was to examine the association between early-onset neonatal sepsis and repeated vaginal examinations. METHODS: The study was conducted at Gandhi Memorial Hospital, a public maternity and newborn care hospital. We followed 672 mother-newborn pairs by phone until 7 days of age to detect clinical sepsis. Data were analyzed using SPSS version 20 software. Adjusted odds ratio risk (AOR) with a corresponding 95% confidence interval (CI) was used to show the strength of associations and variables with p-value < 0.05 were considered to be statistically significant. RESULTS: The incidence of early-onset neonatal sepsis was found to be 20.83% (95% CI 17.60, 24.00). Having a frequent vaginal examination (four or more times) during labor and delivery, prolonged rupture of membranes, induced labor and gestational age < 37 weeks were strongly associated with the development of early-onset neonatal sepsis, (AOR 2. 69;95 CI: 1.08, 6.70) AOR 5.12(95% CI 1.31, 20.00), AOR of 5.24 (95% CI 1.72, AOR4.34 (95% CI 1.20, 15.68), 16.00), respectively. CONCLUSION: Frequent digital vaginal examination prolonged rupture of membranes, induced labor and gestational age < 37 weeks significantly increases the risk of early onset neonatal sepsis. We also recommend further study using neonatal blood culture to better diagnose early onset neonatal sepsis objectively.

Reducing intravenous antibiotics in neonates born ≥35 weeks' gestation: A quality improvement study.

AIM: To assess the impact of the Early Onset Sepsis (EOS) calculator, implemented as a quality improvement study, to reduce the rate of unnecessary antibiotics in neonates born ≥35 weeks' gestation. METHODS: An audit of routinely collected hospital data from January 2008 to March 2014 (retrospective) and from January 2018 to September 2019 (prospective) determined baseline incidence of EOS intravenous antibiotic use in neonates born ≥35 weeks' gestation in a tertiary level perinatal centre. Plan-do-study-act (PDSA) cycles were applied to implement the EOS calculator. Statistical process control methodology and time series analysis assessments were used to assess the potential impact of the PDSA cycles on the rate of intravenous antibiotics, blood culture collection, EOS, length of stay and health care costs (not adjusted for potential confounders). RESULTS: In the study population, from January 2008 to March 2014, the baseline incidence of intravenous antibiotic use was 10.49% (2970/28290), whilst only 0.067% (19/28290) neonates had culture proven EOS. From January 2018 to October 2019, prior to implementation of the EOS calculator, 13.3% (1119/8411) neonates were treated with intravenous antibiotic and the use decreased to 8.3% (61/734) post-implementation. The rate of blood culture collection decreased from 14.4% (1211/8411) to 11.9% (87/734). There were no cases of missed EOS. Length of stay decreased from 2.68 to 2.39 days, with an estimated cost saving of $366 per patient per admission. CONCLUSION: Implementing the EOS calculator in a tertiary hospital setting reduced invasive investigations for EOS and intravenous antibiotic use among neonates ≥35 weeks' gestation. This can result in reduced length of neonatal hospital stays, and associated health care cost savings and may reduce separation of mother and baby.

Vaginal and neonatal microbiota in pregnant women with preterm premature rupture of membranes and consecutive early onset neonatal sepsis.

BACKGROUND: Preterm premature rupture of membranes (PPROM), which is associated with vaginal dysbiosis, is responsible for up to one-third of all preterm births. Consecutive ascending colonization, infection, and inflammation may lead to relevant neonatal morbidity including early-onset neonatal sepsis (EONS). The present study aims to assess the vaginal microbial composition of PPROM patients and its development under standard antibiotic therapy and to evaluate the usefulness of the vaginal microbiota for the prediction of EONS. It moreover aims to decipher neonatal microbiota at birth as possible mirror of the in utero microbiota. METHODS: As part of the PEONS prospective multicenter cohort study, 78 women with PPROM and their 89 neonates were recruited. Maternal vaginal and neonatal pharyngeal, rectal, umbilical cord blood, and meconium microbiota were analyzed by 16S rRNA gene sequencing. Significant differences between the sample groups were evaluated using permutational multivariate analysis of variance and differently distributed taxa by the Mann-Whitney test. Potential biomarkers for the prediction of EONS were analyzed using the MetaboAnalyst platform. RESULTS: Vaginal microbiota at admission after PPROM were dominated by Lactobacillus spp. Standard antibiotic treatment triggers significant changes in microbial community (relative depletion of Lactobacillus spp. and relative enrichment of Ureaplasma parvum) accompanied by an increase in bacterial diversity, evenness and richness. The neonatal microbiota showed a heterogeneous microbial composition where meconium samples were characterized by specific taxa enriched in this niche. The vaginal microbiota at birth was shown to have the potential to predict EONS with Escherichia/Shigella and Facklamia as risk taxa and Anaerococcus obesiensis and Campylobacter ureolyticus as protective taxa. EONS cases could also be predicted at a reasonable rate from neonatal meconium communities with the protective taxa Bifidobacterium longum, Agathobacter rectale, and S. epidermidis as features. CONCLUSIONS: Vaginal and neonatal microbiota analysis by 16S rRNA gene sequencing after PPROM may form the basis of individualized risk assessment for consecutive EONS. Further studies on extended cohorts are necessary to evaluate how far this technique may in future close a diagnostic gap to optimize and personalize the clinical management of PPROM patients. TRIAL REGISTRATION: NCT03819192, ClinicalTrials.gov. Registered on January 28, 2019.

Antibiotic treatment of women with isolated intrapartum fever vs clinical chorioamnionitis: maternal and neonatal outcomes.

BACKGROUND: Clinical chorioamnionitis refers to the presence of maternal fever (≥38°C) and at least 2 clinical signs: (1) maternal tachycardia (>100 bpm), (2) fetal tachycardia (>160 bpm), (3) maternal leukocytosis >15,000/mm2, (4) purulent vaginal discharge, and (5) uterine tenderness. Few data exist to guide the appropriate management of women with isolated intrapartum fever in the absence of other clinical signs suggesting chorioamnionitis. OBJECTIVE: This study compared maternal and neonatal infectious outcomes and microbiological outcomes between women with isolated intrapartum fever and women with clinical chorioamnionitis. STUDY DESIGN: This 10-year retrospective study included all the laboring women at our institution, at ≥34 weeks of gestation, with a singleton pregnancy and body temperature of ≥38.0°C, with or without other evidences of infection. According to our department protocol, women with isolated intrapartum fever received intravenous ampicillin, whereas women with clinical chorioamnionitis received intravenous ampicillin plus gentamicin. The primary outcome was puerperal endometritis, compared between women with isolated intrapartum fever (treated with ampicillin) and women with clinical chorioamnionitis (treated with ampicillin plus gentamicin). The secondary maternal outcomes consisted of (1) maternal clinical outcomes, such as cesarean delivery, surgical site infection, postpartum hemorrhage, and postpartum length of stay, and (2) microbiological studies, including positive chorioamniotic membrane swabs and blood culture. Among the secondary neonatal outcomes were early-onset sepsis, neonatal intensive care unit admission, and length of stay. Of note, 2 multivariate logistic regression models were created. A model aimed to predict puerperal endometritis controlled for gestational age of >41 weeks, diabetes mellitus, obesity, positive group B streptococcus status, rupture of membrane ≥18 hours, meconium staining, positive chorioamniotic membrane swabs, cesarean delivery, and empiric postdelivery antibiotic administration. A model aimed to predict neonatal early-onset sepsis controlled for gestational age of 34 to 37 weeks, positive group B streptococcus status, rupture of membrane ≥18 hours, and positive chorioamniotic membrane swabs. RESULTS: Overall, 458 women met the inclusion criteria. Compared with women with clinical chorioamnionitis (n=231), women with isolated intrapartum fever (n=227) had higher rates of puerperal endometritis (3.9% vs 8.8%; P=.03), early-onset sepsis (0.4% vs 4.4%; P=.005), positive chorioamniotic membrane swabs (46.3% vs 63.9%; P<.001), and ampicillin-resistant Escherichia coli (35.5% vs 48.9%; P=.033). The rate of group B streptococcus-positive chorioamniotic membrane swabs was similar between the groups. In a subanalysis of women with negative or unknown group B streptococcus status, the puerperal endometritis and neonatal early-onset sepsis rates were higher among women with isolated intrapartum fever than women with suspected chorioamnionitis (8.7% vs 3.3% [P=.041] and 4.1% vs 0% [P<.001], respectively). In 2 multivariate analysis models, among women with isolated intrapartum fever treated with ampicillin compared with those with clinical chorioamnionitis treated with ampicillin and gentamicin, the odds ratio of antibiotic treatment of endometritis was 2.65 (95% confidence interval, 1.06-6.62; P=.036), and the odds ratio of neonatal early-onset sepsis was 8.33 (95% confidence interval, 1.04-60.60; P=.045). CONCLUSION: Women with intrapartum fever, with or without other signs of infection, were at increased risk of maternal and neonatal complications. The use of ampicillin as a sole agent in isolated intrapartum fever might promote ampicillin-resistant E coli growth in the chorioamniotic membranes and consequently lead to puerperal endometritis and early-onset sepsis. In this context, a broad-range antibiotic should be considered.

Performance of the HiberGene Group B Streptococcus kit, a loop-mediated isothermal amplification-based assay for GBS screening during pregnancy.

Timely and accurate detection of Group B Streptococcus (GBS) carriage in pregnant women allows for targeted peripartum prophylaxis. Replacing culture-based screening by molecular biology assays enables faster results obtention, better targeted antibiotic prophylaxis, and reduces the laboratory workload. Here, we present a comparative analysis between a Loop Mediated Isothermal Amplification assay (HiberGene GBS kit) and culture (gold-standard). The HiberGene GBS kit showed a sensitivity of 97.9% and a specificity of 96.8% compared with culture. The limit of detection was estimated at 103 cfu/ml and results were obtained within 30 min. HiberGene GBS assay can be used for peripartum GBS screening and targeted antibiotic prophylaxis provided sample processing can be swiftly performed around the clock.

Congenital cerebral malaria: a masquerader in a neonate.

BACKGROUND: Congenital malaria, which is caused by vertical transmission of malaria parasites, is a potentially fatal condition. Despite Africa's high malaria burden, congenital malaria is not routinely screened for, and thus may go undiagnosed. Malaria, if not treated promptly, can quickly progress to severe forms and result in death. Severe congenital malaria is believed to be uncommon in neonates due to maternal antibodies, fetal haemoglobin, and the placenta's sieving effect. The majority of reported cases were classified as having severe anaemia. Following a thorough review of the literature, only one case of congenital cerebral malaria (CCM) has been reported, and it was misdiagnosed. CASE PRESENTATION: A 5-day-old Nigerian neonate born to an apparently healthy mother initially displayed characteristics consistent with neonatal sepsis and severe neonatal hyperbilirubinaemia. He quickly developed characteristics consistent with meningitis. Surprisingly, the peripheral blood film revealed evidence of malaria parasites, which was immediately confirmed by Giemsa-stained thick and thin blood film microscopy for malaria. The patient was diagnosed with congenital cerebral malaria. The medication was modified to parenteral artesunate followed by oral artemisinin combination therapy. The neonate recovered fully and had no neurological deficits on follow up. CONCLUSION: Because CCM and infant meningitis have similar clinical presentations, CCM could be misdiagnosed and lead to death if there isn't a high index of suspicion.

Management of neonates with 35 weeks of gestational age or more with infectious risk factors at birth: opportunities for improvement.

OBJECTIVES: The Northern California Kaiser-Permanente Neonatal Sepsis Risk Calculator (SRC) has proved to be safe and effective in reducing laboratory tests, hospital admissions, and administration of antibiotics to patients at risk of early-onset neonatal sepsis (EONS). Many studies have focused on maternal chorioamnionitis as the principal risk factor for EONS. We wanted to know if the use of the SRC could be equally efficient in the context of several other infectious risk factors (IRF), in addition to chorioamnionitis, such as intrapartum maternal fever, GBS colonization and/or prolonged rupture of membranes (PROM). METHODS: Systematic study of neonates with ≥35 weeks gestational age (GA), born in our tertiary university hospital during a period of 18 months. Patients were retrospectively assessed with the SRC and its recommendations were compared with the actual management. A bivariate analysis of perinatal interventions, and outcomes was performed. RESULTS: A total of 5,885 newborns were born during the study period and 1783 mothers (31%) had at least one IRF. The incidence of culture-proven EONS was 0.5‰. The use of the SRC would have reduced laboratory evaluations (CBC and CRP) from 56.2 to 23.3%, and blood cultures, hospital admissions and antibiotic therapy from 22.9 to 15.5%, 17.8 and 7.6%, respectively. The management based on patients' symptoms would have shown a reduction to 7.5% in all the outcomes of interest. CONCLUSIONS: Both, the SRC and the management based on clinical findings, are safe and efficient to reduce the number of analytical studies, hospital admissions and administration of antibiotics to neonates with IRF.

Prevalence of Group B Streptococcus in pregnant women in Kerala and relation to neonatal outcomes: a prospective cross-sectional study.

BACKGROUND AND OBJECTIVES: Early onset sepsis (EOS) in neonates is a scourge that contributes to morbidity and mortality. Prominent stakeholders recommend universal screening of antenatal women for Group B Streptococcus (GBS) and intrapartum antibiotic prophylaxis (IAP) for those who are carriers. However, there are controversies. Other guidelines allow region-specific protocols due to sociodemographic, geographical and ethnic differences. We planned to analyze the prevalence of GBS rectovaginal carriage at 36-37 weeks gestation and its effect on early neonatal status. METHODS: This prospective multidisciplinary study (Obstetrics, Perinatology, Neonatology, Microbiology and Infectious diseases) was conducted in our tertiary care center between February 2020 and May 2021. RESULTS: In our study group which included 966 mothers who delivered at the hospital, 4.8% of mothers who were screened by genito-rectal swabs were positive for GBS at 36-37 weeks gestation. All these mothers were given IAP as per protocol. Other organisms detected on screening mothers were Candida and Gram-negative bacteria. None of the neonates born to these mothers required any intensive care unit admission or therapy for systemic illness. There was no difference in clinically relevant outcomes between neonates who were born to GBS-positive mothers as compared to those born to negative screen result mothers. CONCLUSIONS: GBS prevalence in our cohort was lower than most scientific reports. The neonates born to carrier mothers did not present with signs of early-onset sepsis.

Universal screening versus risk-based protocols for antibiotic prophylaxis during childbirth to prevent early-onset group B streptococcal disease: a systematic review and meta-analysis.

BACKGROUND: Early-onset group B streptococcal (EOGBS) disease (including sepsis, meningitis, and pneumonia) causes significant morbidity and mortality in newborn infants worldwide. Antibiotic prophylaxis can prevent vertical streptococcal transmission, yet no uniform criteria exist to identify eligible women for prophylaxis. Some guidelines recommend universal GBS screening to pregnant women in their third trimester (screening-based protocol), whereas others employ risk-based protocols. OBJECTIVES: To compare the effectiveness of screening-based versus risk-based protocols in preventing EOGBS disease. SEARCH STRATEGY: Key words for the database searches included GBS, Streptococcus agalactiae, pregnancy, screening, culture-based, risk-based. SELECTION CRITERIA: Studies were included if they investigated EOGBS disease incidence in newborn infants and compared screening or risk-based protocols with each other or with controls. DATA COLLECTION AND ANALYSIS: Risk ratios (RR) and 95% confidence intervals (CI) were determined using Mantel-Haenszel analyses with random effects. MAIN RESULTS: Seventeen eligible studies were included. In this meta-analysis, screening was associated with a reduced risk for EOGBS disease compared either with risk-based protocols (ten studies, RR 0.43, 95% CI 0.32-0.56) or with no policy (four studies, RR 0.31, 95% CI 0.11-0.84). Meta-analysis could not demonstrate a significant effect of risk-based protocols versus no policy (seven studies, RR 0.86, 95% CI 0.61-1.20). In studies reporting on the use of antibiotics, screening was not associated with higher antibiotic administration rates (31 versus 29%). CONCLUSIONS: Screening-based protocols were associated with lower incidences of EOGBS disease compared with risk-based protocols, while not clearly overexposing women to antibiotics. This information is of relevance for future policymaking. TWEETABLE ABSTRACT: Meta-analysis: general screening is associated with lower rates of early-onset group B strep. neonatal sepsis compared with risk-based protocols.

Time to positive blood culture in early onset neonatal sepsis: A retrospective clinical study and review of the literature.

AIM: Neonatal early onset sepsis (EOS) is a low-incidence, high-risk disease which has prompted significant overtreatment with antibiotics for the standard duration of 48 h. The aims of this study were to determine whether blood cultures collected from term and late preterm neonates for EOS would return a positive result for pathogenic bacteria within 24 h and to review the literature to supplement the results. METHODS: This is a retrospective observational study of time to positive blood culture in the BACTEC culture system from neonates ≥34 weeks in a single referral centre between 1999 and 2018. A literature review was conducted through PubMed, MEDLINE and Embase using search terms of 'neonatal sepsis' AND 'blood culture'. Studies were included if they reported time to positive blood culture in EOS. RESULTS: Forty positive cultures were included in this report, with 39 (98%) showing bacterial growth within 24 h. One culture, obtained after commencement of antibiotics, became positive at 3 days. Sixteen papers were included in our literature review and six presented data for an EOS cohort; a median of 96.5% of pathogenic EOS blood cultures become positive within 24 h. CONCLUSIONS: All pathogenic blood cultures collected pre-therapy from neonates ≥34 weeks suspected of EOS returned a positive result within 24 h of incubation. Similar studies have found that 92-100% of cultures are positive by 24 h. This data could contribute to re-evaluation of the current standard duration of antibiotic use in term and late preterm neonates with suspected EOS.

Predictors of Early Onset Neonatal Sepsis among Neonates in Dodoma, Tanzania: A Case Control Study.

OBJECTIVE: To assess the predictors of early onset neonatal sepsis (EONS) among neonates in Dodoma Tanzania. METHODS: A hospital-based case-control study of randomly selected 105 cases and 217 controls in three hospitals in Dodoma region. Cases were neonates diagnosed with neonatal sepsis. Controls were matched to the cases by mother's age and parity at a ratio of 1 case to 2 controls. A semi-structured questionnaire was used to collect data on the potential mother, neonate and interventional predictors of EONS. Both descriptive and inferential statistical analysis were employed to test for independent association. RESULTS: Most (92.5%) of neonates were born at term (≥37 weeks) and 84% had normal birth weight of ≥3 kg. After adjusting for confounders, the maternal factors which showed significant association with EONS were maternal history of chorioamnionitis [adjusted odds ratios (AOR) = 1.910, p = 0.042, 95% confidence interval (CI): 1.0223.56], HIV status (AOR = 2.909, p = 0.012, 95% CI: 1.020-8.296), prolonged rupture of membrane (AOR = 2.857, p = 0.014, 95% CI: 1.233-6.619) and multiple digital vaginal examinations during labor (AOR = 5.178, p = 0.026, 95% CI: 1.220-21.986). The neonatal history of perinatal asphyxia was observed to have a significant association with EONS (AOR = 6.781, p = 0.006, 95% CI: 1.725-26.652). CONCLUSION: Both maternal and neonatal predictors had significant contribution to EONS. Results shed light on critical factors for consideration to prevent this disease and poor outcomes.

CLINICAL PREDICTION OF EARLY ONSET SEPSIS IN PRETERM NEONATES.

OBJECTIVE: The aim of the study was to analyze and identify risk factors for the development of early onset sepsis in preterm neonates and to develop a clinical prognostic model. PATIENTS AND METHODS: Materials and methods: A retrospective cohort study included 152 newborns with birth weight from 1000 to 2500 g, who were treated in the neonatal intensive care units of medical institutions in the Poltava region. Among 152 children, 121 had clinical and laboratory symptoms of infection, which were regarded as manifestations of early onset sepsis, the rest of the children (n = 31) had no manifestations of infection. RESULTS: Results: According to the results of multiple stepwise logistic regression analysis, the predictive model has been developed. It included gestational age, visual changes of placenta, Apgar score at the 1st minute, the level of monocytes more than 6.5%, the history of abortions and premature rupture of membranes. The diagnostic characteristics of the developed model had high: sensitivity - 82.2%, specificity - 93.55%, positive predictive value - 97.98%, negative predictive value - 58%. CONCLUSION: Conclusions: The prognostic model developed by us, which showed high diagnostic characteristics, includes information on maternal risk factors, the state of the newborn immediately after birth, and biomarkers of infection (C-reactive protein and monocyte count). Therefore, we believe that when interpreting biomarkers, the decision to prescribe antibiotics should be based on the presence of maternal risk factors and clinical symptoms of infection in the prematurely born child, which may be nonspecific.

Nationwide epidemiology of early-onset sepsis in Israel 2010-2015, time to re-evaluate empiric treatment.

AIM: Early-onset neonatal sepsis (EOS) may lead to significant morbidity and mortality, yet the recommended antimicrobials have not changed for many years. We aimed to optimise EOS treatment by examining EOS pathogens, resistance rates and resistance risk factors. METHODS: A retrospective, nationwide cohort study analysing 2010-2015 EOS data in Israel. RESULTS: The 21 participating centres constitute 92% of the total birth cohort (around 180 000 live births/year). Of 549 EOS neonates (0.57/1000 live births), 306 (56%) and 243 (44%) were full-term and preterm, respectively (0.35 vs. 2.94 per/1000 live births). Gram-negative pathogens predominated, especially in preterms. Escherichia coli and Streptococcus agalactiae were most common pathogens (0.2 and 0.19 per 1000 live births, respectively). In 277 Gram-negatives, 16%, 14%, 8% and 3% were gentamicin-resistant, extended-spectrum beta-lactamase (ESBL)-positive, gentamicin-resistant and ESBL-positive, and amikacin-resistant, respectively; preterms had higher resistance rates. No risk factors for antimicrobial resistance were identified. Mortality was reported in 21% of Gram-negative EOS versus 7% of Gram-positive EOS [OR 3.4 (95% CI 1.8-6.2), p < 0.01]. CONCLUSION: In this nationwide study, EOS was caused predominantly by Gram-negatives, with high gentamicin resistance and ESBL phenotype rates, without identifiable resistance risk factors. As EOS is life-threatening, modification of empiric therapy for amikacin-based regimens should be considered, mainly in preterms.

Presepsin as a predictor of early onset neonatal sepsis in the umbilical cord blood of premature infants with premature rupture of membranes.

BACKGROUND: The aim of this study was to investigate whether presepsin level in umbilical cord blood can be used as a predictor of early onset neonatal sepsis (EONS) in preterm labor with premature rupture of membranes (PROM), allowing rational use of antibiotics. METHODS: All preterm infants between 24 + 0 and 36 + 6 weeks of gestation born to pregnant women with PROM were enrolled in the study. Blood samples were obtained from clamped umbilical cords after delivery of the neonate and prior to the delivery of the placenta for C-reactive protein and presepsin measurement. A diagnosis or suspicion of EONS was based on clinical symptoms or laboratory results in the absence of positive blood culture. RESULTS: A total of 288 women were included in the study and delivered at 31 + 4 weeks (range, 25-36 + 5 weeks). Microbial invasion of the amniotic cavity was identified in 62 women (81.6%) with EONS and in 31 (14.6%) without (P = 0.004). The prevalence of EONS was 26.4% (76/288). Median umbilical cord presepsin was significantly higher in neonates with EONS than in those without: 2,231 pg/mL (range, 1,442-3,988 pg/mL) versus 275 pg/mL (range, 116-326 pg/mL; P < 0.000). On logistic regression analysis the only independent predictor of EONS was umbilical cord blood presepsin (OR, 12.6; 95% CI: 2.5-28.1, P = 0.000). CONCLUSIONS: Umbilical cord blood presepsin is a predictor for EONS in preterm infants with PROM and may help to reduce the unnecessary use of antibiotics.

Management of early-onset neonatal sepsis differs in the north and south of Scandinavia.

AIM: This study compared the management and outcomes of early-onset neonatal sepsis (EONS) in two tertiary neonatal units in Denmark and Norway. METHODS: We retrospectively studied all infants diagnosed with EONS between April 2010 and March 2013 and managed at Odense University Hospital, Denmark, and the University Hospital of North Norway, Norway. Clinical and laboratory data were collected from patient records. RESULTS: We identified 137 EONS cases in Denmark and 101 in Norway. There were 35 culture-confirmed EONS cases: 16% of the Danish cases and 13% of the Norwegian cases. Staphylococcus aureus was the most frequently detected pathogen in 11 cases (31%), followed by Group B streptococci in nine (26%) and Escherichia coli in six (17%). In 85% of the 238 cases, the empiric therapy comprised gentamicin and a beta-lactam, namely ampicillin in Denmark and benzylpenicillin in Norway. Patients with positive blood cultures had higher C-reactive protein levels than patients with negative blood cultures and higher sepsis-attributable mortality. Lumbar punctures were performed more frequently in Denmark. CONCLUSION: There were marginal differences in the management of EONS between units in Denmark and Norway, mainly in their choice of antibiotics and the use of lumbar punctures. Staphylococcus aureus was the most common pathogen.

The utility of maternal mean platelet volume levels for early onset neonatal sepsis prediction of term infants.

OBJECTIVES: This study is aimed to evaluate the role of maternal mean platelet volume (MPV) levels for antenatal prediction marker of early onset neonatal sepsis in term infants born to mothers who have low infection risk. MATERIAL AND METHODS: A total of 62 pregnant women who gave birth in our hospital and whose neonates were admitted to a third level Neonatal Intensive Care Unit due to confirmed neonatal sepsis between January 2010 and May 2016 were selected as a study group. Within the same period, 68 women who gave birth to healthy neonates were enrolled as a control group. We compared maternal MPV values which were evaluated before delivery. The receiver operating characteristic (ROC) curves were drawn to evaluate the values maternal MPV in the diagnosis of neonatal sepsis. RESULTS: MPV levels were detected statistically higher in the study group than the control group (8.27 ± 1.85 vs. 8.98 ± 1.16) (p = 0.001). CONCLUSION: The maternal serum MPV level is a clinically useful, non-invasive and reliable marker in antenatal prediction of EOS.

Increased Risk Of Early-Onset Neonatal Sepsis After Laser Surgery For Twin-to-Twin Transfusion Syndrome.

OBJECTIVE: To investigate the occurrence of early-onset neonatal sepsis (EOS) in twin-twin transfusion syndrome (TTTS) managed with laser surgery. STUDY DESIGN: We performed a prospective cohort study of all consecutive TTTS cases treated with laser surgery (TTTS group) delivered at the Leiden University Medical Center. We recorded the occurrence of EOS, defined as a positive blood culture ≤72 hours postpartum (proven sepsis) or administration of a full course of antibiotics due to risk factors or signs of sepsis, in the absence of a positive blood culture (suspected sepsis). Perinatal variables in the TTTS group were compared with uncomplicated monochorionic twins (no-TTTS group). A multivariate model was generated, examining the association between EOS and gestational age at birth, interval between laser surgery and birth, anterior placenta, laser period (first study period: 2002-2008; second study period: 2009-2015), and preterm premature rupture of membranes (PPROM). RESULTS: The rates of combined suspected and proven EOS in the TTTS group and no-TTTS group were 16% (68/416) and 10% (55/542), respectively (relative ratio [RR] 1.74, 95% confidence interval [CI] 1.19-2.55). Multivariate analysis showed that EOS in the TTTS group was independently associated with lower gestational age at birth (odds ratio [OR] 0.75, 95% CI 0.63-0.88), first study period (OR 2.25, 95% CI 1.08-4.67) and PPROM (OR 2.47, 95% CI 1.28-4.75). CONCLUSION: The rate of EOS in the TTTS group is low, but increased compared to the no-TTTS group. EOS in TTTS is independently associated with premature delivery, earlier laser period, and PPROM.

Assessment of interleukin-17A, C5a and RANTES for early diagnosis of neonatal sepsis - a preliminary study.

The aim of the present study was to investigate serum levels of novel markers: interleukin 17A (IL-17A), anaphylatoxin C5a and chemokine regulated upon activation normal T-cell expressed and secreted (RANTES) in neonates with clinically suspected early-onset neonatal sepsis (EONS), and to compare their values with those of non-infected neonates. Eighteen neonates with clinical signs and symptoms of EONS were enrolled in this study. Fifty healthy, non-infected neonates served as the control group. In all neonates serum levels of IL-17A, C5a and RANTES were measured by solid-phase sandwich enzyme-linked immunosorbent assay (ELISA). At the time of investigation serum levels of anaphylatoxin C5a were significantly higher in neonates with clinical symptoms of EONS than in non-infected neonates (median 65.35 vs. 50.4 ng/ml, p = 0.034), whereas levels of RANTES were similar and levels of IL-17A were under detection limit of the method. Based on these preliminary results, serum levels of C5a may be a useful marker of inflammation in early onset neonatal sepsis. Because traditional methods of microbiological diagnostics in EONS are frequently unsuccessful, the search for an alternative laboratory biomarkers is of great clinical importance. Thus, there is a strong need for further studies evaluating usefulness of this anaphylatoxin in EONS diagnosis on a larger group of patients.

Fetal and early neonatal interleukin-6 response.

In 1998, a systemic fetal cytokine response, defined as a plasma interleukin-6 (IL-6) value above 11 pg/mL, was reported to be a major independent risk factor for the subsequent development of neonatal morbid events even after adjustments for gestational age and other confounders. Since then, the body of literature investigating the use of blood concentrations of IL-6 as a hallmark of the fetal inflammatory response syndrome (FIRS), a diagnostic marker of early-onset neonatal sepsis (EONS) and a risk predictor of white matter injury (WMI), has grown rapidly. In this article, we critically review: IL-6 biological functions; current evidence on the association between IL-6, preterm birth, FIRS and EONS; IL-6 reference intervals and dynamics in the early neonatal period; IL-6 response during the immediate postnatal period and perinatal confounders; accuracy and completeness of IL-6 diagnostic studies for EONS (according to the Standards for Reporting of Diagnostic Accuracy statement); and recent breakthroughs in the association between fetal blood IL-6, EONS, and WMI.

[Group B streptococcal early-onset neonatal sepsis in the area of Barcelona (2004-2010). Analysis of missed opportunities for prevention]. / Evolución de la sepsis neonatal precoz por Streptococcus agalactiae en el área de Barcelona (2004-2010). Análisis de los fallos del cumplimiento del protocolo de prevención.

OBJECTIVES: To study the evolution of the incidence of early-onset neonatal sepsis (EOS) by Streptococcus agalactiae in the area of Barcelona and to analyze failure of compliance with the prevention protocol. METHODS: A retrospective review was carried out on EOS cases in 8 Health-Care Centers in the Barcelona area between 2004 and 2010. RESULTS: Forty-nine newborns from 48 mothers were diagnosed with EOS. The incidence was 0.29‰ living newborns (0.18-0.47‰), with no significant differences in the fluctuations along the 7 years. The mortality rate was 8.16%. In 68.5% cases the maternal colonization studies were negative, and in 21% these studies were not performed. No risk factors were detected in 58.3% of pregnant women, and 22.9% of births were premature. In 58% of cases intra-partum antibiotic prophylaxis was not administered because it was not indicated, and in 42% due to failure to follow the protocol (3 strains were resistant to erythromycin). Resistance to clindamycin was 33.3%. The Streptococcus agalactiae serotypes more frequently isolated were iii, v, and ia. CONCLUSIONS: No significant changes were detected in the incidence of Streptococcus agalactiae EOS in the 7 years of the study. The increased sensitivity of screening methods with the use of molecular techniques, the performance of susceptibility testing of strains isolated from pregnant women, and the improvement of communication between Health-Care Centers, can contribute to a better implementation of the protocol, as well as to reduce the incidence of EOS.