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An accurate diagnosis of early-onset sepsis (EOS) is challenging because of subtle symptoms and the lack of a good diagnostic tool, resulting in considerable antibiotic overtreatment. A biomarker, discriminating between infected and non-infected newborns at an early stage of the disease, could improve EOS prediction. Numerous biomarkers have been tested, but have never been compared directly. We aimed to provide a comprehensive overview of early biomarkers and their diagnostic value in maternal samples, umbilical cord blood, and neonatal serum. PubMed-Medline, EMBASE, The Cochrane Library, and Web of Science were searched up to 1 March 2023, without restrictions on publication date, population, or language. Articles describing the diagnostic value of at least one biomarker in the detection of EOS in neonates, independent of gestational age, were included. The QUADAS-2 tool was used to assess study quality. Three independent researchers assessed the articles using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Meta-analysis was performed with all manuscripts describing diagnostic accuracy using a random-effects model. Of 2296 identified articles, 171 reports were included in the systematic review and 69 in the meta-analysis. Literature showed mixed and inconsistent evidence for most biomarkers and sample types, because of a lack of a uniform EOS case definition, small sample sizes, and large heterogeneity between studies. Interesting markers were procalcitonin (pooled sensitivity 79%, 95% CI 71–84%; specificity 91%, 95% CI 83–96%, n = 11) and interleukin (IL)-6 (pooled sensitivity 83%, 95% CI 71–90%; specificity 87%, 95% CI 78–93%, n = 8) in umbilical cord blood and presepsin (pooled sensitivity 82%, 95% CI 62–93%; specificity 86%, 95% CI 73–93%, n = 3) and serum amyloid A (pooled sensitivity 92%, 95% CI 75–98%; specificity 96%, 95% CI 78–99%, n = 4) in neonatal serum. Studies on the combination of biomarkers were scarce. A biomarker stand-alone test is currently not reliable for direct antibiotic stewardship in newborns, although several biomarkers show promising initial results. Further research into biomarker combinations could lead to an improved EOS diagnosis, reduce antibiotic overtreatment, and prevent associated health-related problems. [ABSTRACT FROM AUTHOR]

Overuse of empirical intravenous antibiotics in neonates in high-income countries (HICs) is well documented. The Kaiser Permanente neonatal early-onset sepsis (EOS) calculator is an evidence-based sepsis risk assessment tool that has demonstrated potential to reduce antibiotic usage in this population. The incidence of early-onset sepsis in most HICs is 0.4–0.8 per 1000 live births. The objective was to evaluate the calculator's impact on antibiotic rates and length of stay in a regional level II Special Care Nursery. A single-centre retrospective cohort study compared antibiotic administration rates in the first 72 h in neonates ≥35 weeks gestation born during two 6-month periods in 2019 (pre-EOS calculator) and 2021 (post-EOS calculator). Electronic and paper case records were accessed to capture data. Continuous data were summarised using mean and standard deviation, and categorical data were summarized using frequency distributions. There were 951 (2019) and 1129 (2021) infants born during the study periods. Following implementation of the calculator, antibiotic exposure decreased from 13.7% to 4.7% of all neonates without reported negative outcomes. Mean length of stay for neonates born across the two periods decreased from 2.38 to 2.13 days. Indications for antibiotic use shifted more towards clinical condition and away from obstetric risk factors. There were no culture-proven cases of sepsis or readmissions with EOS in either period. Implementation of the EOS calculator significantly reduced exposure to antibiotics, without adverse outcomes. [ABSTRACT FROM AUTHOR]

Accidental rupture of membranes (acROM), an insertion-related complication of the balloon catheter for labor induction, may prolong the duration of ruptured membranes. Prolonged rupture of membranes is associated with an increased risk of intra-uterine infection with possibly neonatal infection as result. Little is known about safety profiles of different catheters regarding the occurrence of these complications. This study compares the incidence of neonatal early-onset sepsis (EOS) and acROM in women receiving either silicone or latex balloon catheters. A retrospective cohort study was performed including 2200 women (silicone balloon catheter, n = 1100 vs. latex balloon catheter, n = 1100). The primary outcomes were the incidence of acROM, and suspected and proven neonatal EOS. Secondary outcomes were: prolonged rupture of membranes, intrapartum fever, pre- or postnatal neonatal exposure to antibiotics, and perinatal outcomes. A subgroup analysis was performed between women with and without acROM. No statistically significant difference with regard to suspected or proven EOS was seen between the silicone and latex groups. The acROM rate was significantly higher in the silicone group compared to the latex group (2.9 % and 0.3 %, p < 0.01). Prolonged rupture of membranes was significantly more common in the silicone group compared to the latex group (5.0 % and 2.4 %, p < 0.01), as was the use of intrapartum antibiotics (12.7 % and 9.6 %, p = 0.02). Neonates were significantly more often exposed to pre- or postnatal antibiotics in the silicone group compared to the latex group (17.6 % and 13.6 %, p = 0.01). Subgroup analysis showed significantly more suspected and proven neonatal EOS when catheter-insertion was complicated with acROM (11.4 % and 20.0 %), compared to cases without acROM (3.8 % and 2.5 %), irrespective of the type of catheter used. The use of silicone balloon catheters for labor induction results in higher rates of acROM, prolonged rupture of membranes and use of intrapartum antibiotics, compared to latex balloon catheters. No statistically significant differences were found in the occurrence of suspected or proven neonatal EOS, however neonates from the silicone group were more often exposed to pre- or postnatal antibiotics. When acROM occurs, irrespective of type of catheter used, suspected and proven neonatal EOS was seen more often. [ABSTRACT FROM AUTHOR]

Two distinct defense strategies, disease resistance (DR) and disease tolerance (DT), enable a host to survive infectious diseases. Newborns, constrained by limited energy reserves, predominantly rely on DT to cope with infection. However, this approach may fail when pathogen levels surpass a critical threshold, prompting a shift to DR that can lead to dysregulated immune responses and sepsis. The mechanisms governing the interplay between DR and DT in newborns remain poorly understood. Here, we compare metabolic traits and defense strategies between survivors and non-survivors in Staphylococcus epidermidis (S. epidermidis)-infected preterm piglets, mimicking infection in preterm infants. Compared to non-survivors, survivors displayed elevated DR during the initial phase of infection, followed by stronger DT in later stages. In contrast, non-survivors showed clear signs of respiratory and metabolic acidosis and hyperglycemia, together with exaggerated inflammation and organ dysfunctions. Hepatic transcriptomics revealed a strong association between the DT phenotype and heightened oxidative phosphorylation in survivors, coupled with suppressed glycolysis and immune signaling. Plasma metabolomics confirmed the findings of metabolic regulations associated with DT phenotype in survivors. Our study suggests a significant association between the initial DR and subsequent DT, which collectively contributes to improved infection survival. The regulation of metabolic processes that optimize the timing and balance between DR and DT holds significant potential for developing novel therapeutic strategies for neonatal infection. • Newborn host defense strategies are critical to surviving infection. • Infected survivors show enhanced early disease resistance and later tolerance. • Hepatic transcriptome and plasma metabolome link disease tolerance and survival. • Disease tolerance is associated with reduced glycolysis but increased OXPHOS. [ABSTRACT FROM AUTHOR]

• Neonatal late onset sepsis (LOS) in a neonatal intensive care unit in Peru. • Neonatal sepsis contributes significantly to neonatal morbidity and mortality. • Coagulase-negative Staphylococcus is the most common pathogen in LOS in our series. • Pseudomonas aeruginosa and Candida spp. have very high fatality in neonatal LOS. Our study aimed to determine the incidence of late onset sepsis and the most frequent microorganisms causing it in the neonatal unit at Hospital Cayetano Heredia in Lima, Peru. Descriptive and retrospective study. We reviewed all positive blood cultures and cultures of cerebrospinal fluid drawn from inborn patients beyond 72 h of life, admitted to the neonatal unit from January 2015 to December 2019. The incidence of late onset sepsis was 7.4% of admitted patients and 10.04 per 1000 live births. During our study period, 234 episodes of late onset sepsis occurred in 204 patients. The incidence was higher in very low birth weight infants, reaching 36.2% and even higher in extremely low birth weight infants (40.7%). Coagulase-negative Staphylococcus and then Klebsiella spp. were the most frequent causative microorganisms. The most frequent cause of late onset sepsis in very low birth weight infants was gram-negative bacteria (Klebsiella spp., was the most frequent causative microorganism). Late onset neonatal sepsis is prevalent in our neonatal unit. It is important to know which are the most prevalent causative microorganisms to be able to choose adequate antibiotic coverage and to design strategies to prevent infection. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aimed to conduct a thorough and contemporary assessment of maternal and neonatal outcomes associated with water birth in comparison with land-based birth. We conducted a comprehensive search of PubMed, EMBASE, CINAHL, and gray literature sources, from inception to February 28, 2023. We included randomized and nonrandomized studies that assessed maternal and neonatal outcomes in patients who delivered either conventionally or while submerged in water. Pooled unadjusted odds ratios with 95% confidence intervals were calculated using a random-effects model (restricted maximum likelihood method). We assessed the 95% prediction intervals to estimate the likely range of future study results. To evaluate the robustness of the results, we calculated fragility indices. Maternal infection was designated as the primary outcome, whereas postpartum hemorrhage, perineal lacerations, obstetrical anal sphincter injury, umbilical cord avulsion, low Apgar scores, neonatal aspiration requiring resuscitation, neonatal infection, neonatal mortality within 30 days of birth, and neonatal intensive care unit admission were considered secondary outcomes. Of the 20,642 articles identified, 52 were included in the meta-analyses. Based on data from observational studies, water birth was not associated with increased probability of maternal infection compared with land birth (10 articles, 113,395 pregnancies; odds ratio, 0.93; 95% confidence interval, 0.76–1.14). Patients undergoing water birth had decreased odds of postpartum hemorrhage (21 articles, 149,732 pregnancies; odds ratio, 0.80; 95% confidence interval, 0.68–0.94). Neonates delivered while submerged in water had increased odds of cord avulsion (10 articles, 91,504 pregnancies; odds ratio, 1.75; 95% confidence interval, 1.38–2.24) and decreased odds of low Apgar scores (21 articles, 165,917 pregnancies; odds ratio, 0.69; 95% confidence interval, 0.58–0.82), neonatal infection (15 articles, 53,635 pregnancies; odds ratio, 0.64; 95% confidence interval, 0.42–0.97), neonatal aspiration requiring resuscitation (19 articles, 181,001 pregnancies; odds ratio, 0.60; 95% confidence interval, 0.43–0.84), and neonatal intensive care unit admission (30 articles, 287,698 pregnancies; odds ratio, 0.56; 95% confidence interval, 0.45–0.70). When compared with land birth, water birth does not appear to increase the risk of most maternal and neonatal complications. Like any other delivery method, water birth has its unique considerations and potential risks, which health care providers and expectant parents should evaluate thoroughly. However, with proper precautions in place, water birth can be a reasonable choice for mothers and newborns, in facilities equipped to conduct water births safely. [ABSTRACT FROM AUTHOR]

There is limited data regarding the safety of vaginal delivery in women infected with COVID-19. Our goal was to assess the safety of vaginal delivery in women infected with COVID-19 and the risk of neonatal infection. This was a single medical center cohort study. Data were collected about the outcome of twenty-one women with laboratory-confirmed COVID-19 infection who delivered between March 23, 2020, and May 8, 2020. Twenty-one gravidas were diagnosed with COVID-19 infection. None required admission to the intensive care unit (ICU) and there were no fatalities. Seventeen delivered vaginally and four by caesareans. Apgar scores of all neonates were 9 at 1 min and 10 at 5 min. One neonate was diagnosed with COVID-19 infection 24 h after birth. Vaginal delivery in women infected with COVID-19 is not associated with a significant risk of neonatal infection. [ABSTRACT FROM AUTHOR]

• The epidemiology and microbiology of late-onset sepsis was assessed in the largest contemporary cohort of preterm infants in China. • The incidence of culture-proven late-onset sepsis among infants <34 weeks' gestation was 4.4% with a case-fatality rate of 15.4% in Chinese NICUs. • Gram-negative bacteria were the most common pathogens (51.8%) causing late-onset sepsis in Chinese NICUs. • The proportion of fungal sepsis was alarmingly high (17.1%). • Gram-negative bacterial and fungal sepsis were associated with increased risk of adverse neonatal outcomes. To describe the incidence, case-fatality rate and pathogen distribution of late-onset sepsis (LOS) among preterm infants in China. To investigate risk factors and short-term outcomes associated with LOS caused by Gram-positive bacteria, Gram-negative bacteria and fungi. This cohort study included all infants born at <34 weeks' gestation and admitted to 25 tertiary hospitals in 19 provinces in China from May, 2015 to April, 2018. Infants were excluded who died or were discharged within 3 days of being born. A total of 1199 episodes of culture-positive LOS were identified in 1133 infants, with an incidence of 4.4% (1133/25,725). Overall, 15.4% (175/1133) of infants with LOS died and 10.0% (113/1133) of infants died within 7 days of LOS onset. Among 1214 isolated pathogens, Gram-negative bacteria were the most common (51.8%, 629/1214) and fungi accounted for 17.1% (207/1214). Use of central lines, longer duration of antibiotics and previous carbapenem exposure were related to increased risk of fungal LOS compared with Gram-positive bacteria. Gram-negative bacteria LOS was independently associated with increased risk of death, periventricular leukomalacia, bronchopulmonary dysplasia, and necrotizing enterocolitis. Fungal LOS was independently associated with increased risk of periventricular leukomalacia, bronchopulmonary dysplasia and necrotizing enterocolitis. Late-onset sepsis was a significant cause of morbidity and mortality in Chinese neonatal intensive care units, with a distinct pathogen distribution from industrial countries. Clinical guidelines on the prevention and treatment of LOS should be developed and tailored to these LOS characteristics in Chinese neonatal intensive care units. [ABSTRACT FROM AUTHOR]

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• First cost-effectiveness analysis of a potential hexavalent GBS vaccine in a low-resource setting. • A hexavalent GBS vaccine could avert 55% of Gambian cases and 768 disability adjusted life years per year. • Maximum cost-effective price per dose would be 12 US$ (2016 US$) • GBS incidence was the most influential parameter on the cost effectiveness ratio. To estimate neonatal health benefits and healthcare provider costs of a theoretical Group B streptococcal (GBS) hexavalent maternal vaccination programme in The Gambia, a low-income setting in West Africa. A static decision analytic cost-effectiveness model was developed from the healthcare provider perspective. Demographic data and acute care costs were available from studies in The Gambia undertaken in 2012–2015. Further model parameters were taken from United Nations and World Health Organisation sources, supplemented by data from a global systematic review of GBS and literature searches. As vaccine efficacy is not known, we simulated vaccine efficacy estimates of 50–90%. Costs are reported in US dollars. Cost-effectiveness thresholds of one (US$473, very cost effective) and three (US$1420, cost effective) times Gambian GDP were used. Vaccination with a hexavalent vaccine would avert 24 GBS disease cases (55%) and 768 disability adjusted life years compared to current standard of care (no interventions to prevent GBS disease). At vaccine efficacy of 70%, the programme is cost-effective at a maximum vaccine price per dose of 12 US$ (2016 US$), and very cost-effective at a maximum of $3/dose. The total costs of vaccination at $12 is $1,056,962 for one annual cohort of Gambian pregnant women. One-way sensitivity analysis showed that GBS incidence was the most influential parameter on the cost effectiveness ratio. The introduction of a hexavalent vaccine would considerably reduce the current burden of GBS disease in The Gambia but to be cost-effective, the vaccine price per dose would need to be $12/dose or less. [ABSTRACT FROM AUTHOR]

Objective: To compare the detection rates of vaginal-perineal cultures for group B streptococci (GBS) with the standard vaginal and rectal cultures and evaluate the diagnostic yield of vaginal-perineal vs. rectal swabs for extended spectrum β-lactamase producing Enterobacterales (ESBL-E) during the third trimester of pregnancy.Study Design: Vagino-perineal and rectal swabs were collected cross-sectionally from pregnant women between 35-37 weeks gestation and tested for the presence of GBS and ESBL-E. Accuracy of the vagino-perineal swab was compared to the combined vagino-perineal/rectal swab. Risk factors for ESBL carriage were examined. Degrees of pain, discomfort and stress related to the rectal swab were analyzed on visual analogue scales.Results: 48 out of 250 participants (19.2%) were GBS positive. The vagino-perineal swab was positive in 44 of 48 women (91.7%) yielding a negative predictive value of 98.1%. Agreement (kappa) between the two methods was 0.95. Six out of 190 women with additional ESBL-E screening (3.2%) tested positive by rectal swab. Of these, only two had also a positive vagino-perineal swab. The rectal swab caused overall little subjective discomfort, pain or stress, as indicated by low scores indicated on the visual scales.Conclusions: The GBS detection rate of the vagino-perineal swab was lower compared to the reference standard. However, agreement between the two screening methods was high and there were no cases of GBS neonatal sepsis in the recruited population, supporting this less invasive screening strategy. In contrast, the vaginal-perineal swab was inferior to the rectal swab for detecting ESBL-E, indicating that this less invasive method for detecting antibiotic resistant bacteria that may be potentially transferred to the neonate during labor and delivery would be inappropriate for ESBL-E screening in pregnant women. The low ESBL-E carriage rate among pregnant women likely reflects the prevalence in the general population. [ABSTRACT FROM AUTHOR]

Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and an important cause of maternal disease in many countries; however, no accurate population-based epidemiological data on GBS is yet available in mainland China. In this systematic literature review, we obtained published data regarding the maternal GBS colonization rate, incidence of invasive GBS disease in infants, clinical screening, and the associated GBS typing and clinical outcomes in China. The maternal GBS colonization rate in mainland China ranged from 3.7 to 14.52%, and the incidence of invasive GBS disease in infants was 0.55–1.79 per 1000 live births, with a case fatality risk ranging from 6.45 to 7.1%. Serotype III was the dominant serotype that was observed in GBS isolates. GBS detection and identification has become more commonplace, due to the availability of polymerase chain reaction and DNA microarray technologies. Immunizing pregnant women against GBS is an emerging approach through which newborns are protected from GBS. The available data suggest that five GBS serotypes (Ia, Ib, II, III, and V) account for the majority of the cases of GBS disease in mainland China. Furthermore, conjugate vaccines comprising some or all of these serotypes are of potential value in the prevention of GBS infection. [ABSTRACT FROM AUTHOR]

Highlights • Females have higher Iba-1 expression than males in the hippocampus and cerebellum. • Neonatal infection increases IL-6 expression in the neonatal female cerebellum. • Neonatal infection decreases BDNF expression in the neonatal male cerebellum. • Neonatal infection increases peripheral cytokines and chemokines in both sexes. Abstract Early-life infection has been shown to have profound effects on the brain and behavior across the lifespan, a phenomenon termed "early-life programming". Indeed, many neuropsychiatric disorders begin or have their origins early in life and have been linked to early-life immune activation (e.g. autism, ADHD, and schizophrenia). Furthermore, many of these disorders show a robust sex bias, with males having a higher risk of developing early-onset neurodevelopmental disorders. The concept of early-life programming is now well established, however, it is still unclear how such effects are initiated and then maintained across time to produce such a phenomenon. To begin to address this question, we examined changes in microglia, the immune cells of the brain, and peripheral immune cells in the hours immediately following early-life infection in male and female rats. We found that males showed a significant decrease in BDNF expression and females showed a significant increase in IL-6 expression in the cerebellum following E.coli infection on postnatal day 4; however, for most cytokines examined in the brain and in the periphery we were unable to identify any sex differences in the immune response, at least at the time points examined. Instead, neonatal infection with E.coli increased the expression of a number of cytokines in the brain of both males and females similarly including TNF-α, IL-1β, and CD11b (a marker of microglia activation) in the hippocampus and, in the spleen, TNF-α and IL-1β. We also found that protein levels of GRO-KC, MIP-1a, MCP1, IP-10, TNF-α, and IL-10 were elevated 8-hours postinfection, but this response was resolved by 24-hours. Lastly, we found that males have more thin microglia than females on P5, however, neonatal infection had no effect on any of the microglia morphologies we examined. These data show that sex differences in the acute immune response to neonatal infection are likely gene, region, and even time dependent. Future research should consider these factors in order to develop a comprehensive understanding of the immune response in males and females as these changes are likely the initiating agents that lead to the long-term, and often sex-specific, effects of early-life infection. [ABSTRACT FROM AUTHOR]

Abstract Objective To explore the expression and function of nucleotide-binding oligomerization domain (NOD) proteins NOD1 and NOD2 and provide guidance for prophylaxis and treatment of neonatal infection. Methods Peripheral blood samples were collected from preterm infants, term infants and, healthy adult volunteers. A portion of collected blood was used to examine the expression of NOD1 and NOD2 by real-time PCR. The remaining blood was stimulated in vitro with NOD2 agonist L-Ala-D-Glu- meso (Tri-DAP) or NOD1 agonist muramyl dipeptide (MurNAc-L-Ala-D-isoGln; MDP) for 4 h. Consequently, the levels of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) were quantified by enzyme-linked immunosorbent assay (ELISA). Results NOD1 expression was found to be decreased in preterm and term newborns compared with adults. NOD2 was significantly lower in preterm infants alone in comparison with adults. After treated by Tri-DAP or MDP, the levels of IL-6 and TNF-α in peripheral blood were significantly lower in preterm and term newborns when comparing to adults. Conclusion NOD1 and NOD2 expression and induced release of pro-inflammatory mediators were impaired in infants, contributing to the high susceptibility of infants to infection. Our results insisted on developing a new immunological approach for prophylaxis and treatment of neonatal infection. [ABSTRACT FROM AUTHOR]

Abstract Larval Baylisascaris nematodes (L3), resulting from transuterine infection and neural migration, were discovered in the cerebrum of sibling moose calves (Alces alces gigas) near 1–3 days in age from Alaska. We provide the first definitive identification, linking morphology, biogeography, and molecular phylogenetics, of Baylisascaris transfuga in naturally infected ungulates. Life history and involvement of paratenic hosts across a broader assemblage of mammals, from rodents to ungulates, in the transmission of B. transfuga remains undefined. Neural infections, debilitating young moose, may seasonally predispose calves to predation by brown bears, facilitating transmission to definitive hosts. Discovery of fatal neurological infections by L3 of B. transfuga in mammalian hosts serves to demonstrate the potential for zoonotic infection, as widely established for B. procyonis, in other regions and where raccoon definitive hosts are abundant. In zones of sympatry for multi-species assemblages of Baylisascaris across the Holarctic region presumptive identification of B. procyonis in cases of neurological larval migrans must be considered with caution. Diagnostics in neural and somatic larval migrans involving species of Baylisascaris in mammalian and other vertebrate hosts should include molecular-based and authoritative identification established in a phylogenetic context. Graphical abstract Image 1 Highlights • Larval Baylisascaris nematodes, demonstrating transuterine infection, were discovered in sibling moose calves from Alaska. • Baylisascaris transfuga was identified through morphology, biogeography and molecular phylogenetics. • Neural infections in ungulate paratenic hosts may predispose calves to predation by brown bears facilitating transmission. • Diagnostics for L3 Baylisascaris in zones of sympatry for multiple species should include molecular-based identification. [ABSTRACT FROM AUTHOR]

Objectives: The main aim of this exploratory study was to evaluate functional activity of antibodies elicited by a maternal Group B Streptococcus (GBS) investigational vaccine composed of capsular polysaccharides Ia, Ib, and III conjugated to genetically detoxified Diphtheria toxin CRM197. The second objective was to investigate the relationship between serotype-specific IgG concentrations and functional activity in maternal and cord sera.Methods: Maternal and cord sera collected at baseline and at delivery from vaccine and placebo recipients during a double-blind placebo-controlled Phase II study (www.clinicaltrials.gov, NCT01446289) were tested in an opsono-phagocytic bacterial killing assay. Cord sera from vaccine recipients were also passively transferred to newborn mice to investigate conferred protection against bacterial challenge.Results: Antibody-mediated GBS phagocytic killing was significantly increased in maternal serum at delivery and in cord sera from the investigational vaccine group as compared to the placebo group. Anti-capsular IgG concentrations above 1 µg/mL mediated in vitro killing against GBS strains belonging to all three serotypes and IgG levels correlated with functional titers. Passively administered cord sera elicited a dose-dependent protective response against all GBS serotypes in the in vivo model.Conclusions: The maternal vaccine elicited functional antibodies that were placentally transferred. Anti-capsular IgG concentrations in maternal and cord sera were predictive of functional activity and in vivo protection in the mouse model. [ABSTRACT FROM AUTHOR]

Nonpolio enteroviruses and parechoviruses are frequent causes of neonatal infection. Clinical manifestations of infection range from asymptomatic infection to mild infection without sequelae to septic shock with muiltiorgan failure. Neonates with clinically apparent infection typically have mothers and/or other contacts with recent symptoms consistent with a viral illness. Severe neonatal infection with nonpolio enterovirus or parechovirus cannot be differentiated clinically from serious bacterial infection. The preferred method for diagnosing neonatal nonpolio enterovirus or parechovirus infection is PCR as it is rapid, sensitive, specific, and commercially available for the detection of virus from various clinical specimens. Investigational agents such as the capsid inhibitors pleconaril and pocapavir show promise for treatment of neonatal enterovirus infections, and other investigational agents are being developed. This review focuses on the epidemiology, diagnosis, and treatment of neonatal nonpolio enterovirus and parechovirus infections. [ABSTRACT FROM AUTHOR]

Background: The goal of this study was to explore the association between neonatal infection and outcomes in children with cerebral palsy.Methods: We conducted a retrospective cohort study using the Canadian CP Registry. Neonatal infection was defined as meeting one of the following criteria: (1) septicemia, (2) septic shock, or (3) administration of antibiotics for ≥10 days. Phenotypic profiles of children with cerebral palsy with and without an antecedent neonatal infection were compared. Subgroup analysis was performed, stratified by gestational age (term versus preterm).Results: Of the 1229 registry participants, 505 (41.1%) were preterm, and 192 (15.6%) met the criteria for neonatal infection with 29% of preterm children having a neonatal infection compared with 6.5% in term-born children. Children with prior neonatal infection were more likely to have a white matter injury (odds ratio 2.2, 95% confidence interval 1.5 to 3.2), spastic diplegic neurological subtype (odds ratio 1.6, 95% confidence interval 1.1 to 2.3), and sensorineural auditory impairment (odds ratio 2.1, 95% confidence interval 1.4 to 3.3). Among preterm children, neonatal infection was not associated with a difference in phenotypic profile. Term-born children with neonatal infection were more likely to have spastic triplegia or quadriplegia (odds ratio 2.4, 95% confidence interval 1.3 to 4.3), concomitant white matter and cortical injury (odds ratio 4.1, 95% confidence interval 1.6 to 10.3), and more severe gross motor ability (Gross Motor Function Classification System IV to V) (odds ratio 2.6, 95% confidence interval 1.4 to 4.8) compared with preterm children.Conclusions: Findings suggest a role of systemic infection on the developing brain in term-born infants, and the possibility to develop targeted therapeutic and preventive strategies to reduce cerebral palsy morbidity. [ABSTRACT FROM AUTHOR]

Summary Objectives This study aimed to investigate the incidence of late-onset sepsis (LOS) in neonatal intensive care units (NICUs) in Arab states in the Gulf region and to describe the main causative organisms and their antibiotic resistance. Methods This observational prospective cohort study was conducted over a 2-year period in five NICUs in Kuwait, Saudi Arabia, and the United Arab Emirates. LOS was defined as the growth of a single potentially pathogenic organism from blood or cerebrospinal fluid in infants >3 days of age with clinical and laboratory findings consistent with infection. Results Seven hundred and eighty-five cases of LOS occurred among 67 474 live births. The overall incidence of LOS was 11.63 (95% confidence interval (CI) 10.84–12.47) per 1000 live births, or 56.14 (95% CI 52.38–60.08) per 1000 admissions. Coagulase-negative staphylococci and Klebsiella spp were the most common organisms, causing 272 (34.65%) and 179 (22.80%) of LOS cases, respectively. No evidence of a seasonal variation in the incidence of Klebsiella spp or in the incidence of all Gram-negative organisms was found. More than half of the Klebsiella spp were resistant to third-generation cephalosporins. Conclusion LOS poses a major burden in this area, which could be due to the increasing care of premature babies. Gram-negative organisms, particularly Klebsiella spp , are having an increasing role in LOS in this region, with high levels of resistance to third-generation cephalosporins. NICUs in the area should create a platform through which to share experience in reducing neonatal sepsis and contribute to a common antibiotic stewardship program. [ABSTRACT FROM AUTHOR]

Summary Objective To investigate the incidence and the pattern of causative organisms of culture-proven early-onset sepsis (EOS) in Arab states in the Gulf region. Methods Five neonatal care units participated in this 2-year prospective study in Kuwait, the United Arab Emirates, and Saudi Arabia. Data were collected prospectively using a standardized data collection form. EOS was defined as the growth of a single potentially pathogenic organism from blood or cerebrospinal fluid in infants within 72 h of birth, with clinical and laboratory findings consistent with infection. Results Out of 67 474 live births, 102 cases of EOS occurred. The overall incidence of EOS was 1.5 (95% confidence interval 1.2–1.8) per 1000 live-births, ranging from 2.64 per 1000 live-births in Kuwait to 0.40 per 1000 live-births in King Abdulaziz Hospital in Saudi Arabia. The most common causative organism of EOS was group B Streptococcus (GBS; 60.0%), followed by Escherichia coli (13%). The incidence of invasive GBS disease was 0.90 per 1000 live-births overall and ranged from 1.4 per 1000 live-births in Kuwait to 0.6 per 1000 live-births in Dubai Hospital. Conclusions The incidence of EOS and the patterns of the causative organisms in the Arab states in the Gulf region are similar to those in developed countries before the era of intrapartum antibiotic prophylaxis. Efforts should be made to improve intrapartum antibiotic prophylaxis in the Arab state setting, which could avert large numbers of GBS infections. [ABSTRACT FROM AUTHOR]

Neonatal mice are more susceptible than adults to mouse adenovirus type 1 (MAV1) respiratory infection. In adult mice, MAV-1 respiratory infection induces production of prostaglandin E 2 (PGE 2 ), a lipid mediator that exerts suppressive effects on a variety of host immune functions. We tested the hypothesis that exaggerated PGE 2 production in neonatal mice contributes to increased susceptibility to MAV-1. PGE 2 concentrations were lower in lungs of uninfected neonatal mice than in adults. PGE 2 production was induced by both MAV-1 and a nonspecific stimulus to a greater degree in neonatal mice than in adults, but only in adults was PGE 2 induced in a virus-specific manner. Lung viral loads were equivalent in PGE 2 -deficient neonatal mice and wild type controls, as was virus-induced expression of IFN-γ, IL-17A, and CCL5 in the lungs. PGE 2 deficiency had minimal effect on production of virus-specific IgG or establishment of protective immunity in neonatal mice. Collectively, our data indicate that lung PGE 2 production is exaggerated early in life, but this effect does not mediate increased susceptibility to MAV-1 infection. [ABSTRACT FROM AUTHOR]

Objectives: To determine risk factors for GBS colonisation in Gambian mothers and in their infants from birth to day 60-89 of age.Methods: Swabs and breastmilk from mothers/infant pairs were collected and cultured on selective agar. Negative samples were analysed for GBS DNA via real-time PCR. Positive isolates were serotyped using multiplex PCR and gel-agarose electrophoresis.Results: Seven hundred and fifty women/infant pairs were recruited. 253 women (33.7%) were GBS-colonised at delivery. The predominant serotypes were: V (55%), II (16%), III (10%), Ia (8%) and Ib (8%). 186 infants were colonised (24.8%) at birth, 181 (24.1%) at 6 days and 96 at day 60-89 (14%). Infants born before 34 weeks of gestation and to women with rectovaginal and breastmilk colonisation at delivery had increased odds of GBS colonisation at birth. Season of birth was associated with increased odds of persistent infant GBS colonisation (dry season vs. wet season AOR 2.9; 95% CI 1.6-5.2).Conclusion: GBS colonisation is common in Gambian women at delivery and in their infants to day 60-89 and is dominated by serotype V. In addition to maternal colonisation, breastmilk and season of birth are important risk factors for infant GBS colonisation. [ABSTRACT FROM AUTHOR]

Neonatal infection is associated with increased lifetime risk for neuropsychiatric disorders including anxiety and depression, with evidence showing that dysregulation of the hypothalamic–pituitary–adrenal-(HPA)-axis system may be partly responsible. Preclinical and clinical studies demonstrate that minocycline exhibits antidepressant effects through inhibition of microglial activation and anti-inflammatory actions, and of interest is that recent studies suggest that minocycline alleviates the behavioral abnormalities induced by early-life insults. The current study was designed to determine if developmental minocycline treatment attenuates the neonatal immune activation-induced anxiety- and depression-like symptoms and HPA-axis-dysregulation later in life. To this end , neonatal mice were treated to either lipopolysaccharide or saline on postnatal days (PND) 3–5, then dams during lactation (PND 6–20) and male offspring during adolescence (PND 21–40) received oral administration of minocycline or water via regular drinking bottles. Anxiety- and depression-like behaviors, HPA-axis-reactivity (corticosterone), and hippocampal inflammation (TNF-α and IL-1β) after exposure to stress were evaluated. The results indicated that neonatal immune activation resulted in increased anxiety and depression-like symptoms, HPA-axis-hyperactivity, and elevated the levels of TNF-α and IL-1β in the hippocampus in response to stress in adulthood. Interestingly, developmental minocycline treatment significantly reduced the abnormalities induced by neonatal inflammation in adult mice. In addition, minocycline, regardless of postnatal inflammation, did not have any detrimental effects on the above measured parameters. Considering that minocycline is currently under exploration as an alternative or adjunctive therapy for reducing the symptoms of neurological disorders, our findings suggest that minocycline during development can decrease the behavioral abnormalities induced by early life inflammation in adulthood. [ABSTRACT FROM AUTHOR]

Brazil has the highest SARS-CoV-2 case-fatality rate in pregnant women in the Americas. In this study, clinical and virological findings of five mildly symptomatic pregnant women and their infected fetuses/newborns treated at a referral hospital for COVID19-pregnant women in Midwestern Brazil are reported. Mother and fetal samples were tested by RT-qPCR, ECLIA and Illumina MiSeq sequencing. From the five cases, one resulted in spontaneous abortion, one was stillborn, two were preterm births and one full-term birth. Maternal and fetal placenta, newborn and stillborn secretions were SARS-CoV-2+; one neonate developed ground-glass opacities in his lungs. One neonate's umbilical cord was IgG+ and all were IgM negative upon hospital discharge. Genomes recovered from two placentas belong to the B.1.1.28 and B.1.1.33 lineages and present nonsynonymous mutations associated with virus fitness and infectivity; other not frequently reported mutations (B.1.1.33: NSP3 V2090G, M A2S and ORF3ab S253P and Y264N; B.1.1.28: NSP3 E995D, NSP12 R240K, NSP14H1897Y and in ORF7b V21F) were found in proteins involved in viral replication, viral induction of apoptosis, viral interference on interferon and on NF-Κβ pathways. Phylogeny indicates the south of Brazil as the possible origin of these lineages circulating in Mato Grosso State. These findings contribute to describe SARS-CoV-2 infection and outcomes in pregnant women and their fetuses, at any stage of gestation and even in mild symptomatic cases. [ABSTRACT FROM AUTHOR]

Highlights: [•] Neonatal TNF-α exposure decreases body weight in neonate mice. [•] Neonatal TNF-α exposure increases anxiety in adult male and female mice. [•] Neonatal TNF-α exposure increases depression in adult males, but not in females. [Copyright &y& Elsevier]

Abstract: Background: Maternal colonisation with group B streptococcus (GBS) is recognised as the most frequent cause of severe early onset infection in newborns. National and international guidelines outline two approaches to the prevention of early onset disease in the neonate: risk based management and antenatal culture-based screening. We undertook an analysis of existing national and international guidelines in relation to GBS in pregnancy using a standardised and validated instrument to highlight the different recommended approaches to care. Methods: English language guidelines on the screening and management of GBS colonisation in pregnant women and the prevention of early-onset group B streptococcal disease in newborns were sought. Results: Four guidelines met the inclusion criteria, one from the United States of America (USA), the United Kingdom (UK), Canada and New Zealand. All four were appraised as at a high standard in terms of development using the AGREE II tool. Both approaches were recommended in the guidelines with different regions of the world advocating different approaches often based on the same evidence. Guidelines from the USA recommend an antenatal culture-based approach while the UK guidelines recommend risk-based management. Conclusion: Based on an AGREE II analysis, the standard of the guidelines was high despite having disparate recommendations. Both approaches to the prevention of early onset GBS infection in neonates are recommended with the split being geographically-based. [Copyright &y& Elsevier]

Highlights: [•] We investigated for the first time effect of neonatal infection on anxiety in mice. [•] Neonatal immune activation increased anxiety levels in adult male and female mice. [•] The open field, elevated plus-maze and light–dark box were used in this study. [•] Adolescent fluoxetine reduced the effects of neonatal infection on anxiety in mice. [ABSTRACT FROM AUTHOR]

Abstract: Several reports have suggested that early neonatal immune activation adversely influences the hypothalamic–pituitary–adrenal (HPA) axis development in humans and animal models. In addition, there have been several studies indicating that early intervention with fluoxetine (FLX) can alter HPA axis development and function, and prevent occurrence of behavioral abnormalities induced by common early-life insults. The present study aims to investigate the effects of early intervention with FLX following early neonatal immune activation on depression-like behaviors and body weight in mice. Neonatal mice in their postnatal days (PNDs) 3 and 5 received either lipopolysaccharide (LPS; 50μg/kg, s.c.) or saline treatment, then male and female mice of both neonatal intervention groups received oral administration of FLX (5 and 10mg/kg/day) or water via regular drinking bottles during the periadolescent period (PNDs 35–65). The results showed that neonatal LPS exposure elevated depression-like behaviors accompanied by increasing corticosterone levels in adulthood and decreasing body weight during neonatal and adolescent periods. Furthermore, the periadolescent FLX treatment inhibited the depression-like behaviors induced by neonatal infection in both sexes. This study obtained some experimental evidence indicating the potential adverse impacts of the FLX on normal behavioral development in male control animals. In conclusion, our findings suggest that an early pharmacological intervention with FLX may prevent emergence of depression-like behaviors induced by neonatal immune challenge without any detrimental effect on health in a sex- and dose-dependent manner in mice. [Copyright &y& Elsevier]

Summary: Neonatal thrombocytopenia are common, they represent 20% of inpatients in neonatal units and intensive care. The causes are multiple; the main consequence of this condition is the risk of bleeding including intracranial hemorrhage. Objective: The objective of our work is to focus on the etiologic profile of thrombocytopenic hemorrhagic syndrome of origin and to emphasize the importance of having an accurate diagnostic approach to avoid late squealer or severe neurosensory deaths. Patients and methods: Our work is a retrospective study of 91 cases of infants with hemorrhagic syndrome of thrombotic origin, during a study period spanning 1st January 2009 to June 30, 2010. Results: During the study period, there were 91 cases of neonatal thrombocytopenic hemorrhagic syndrome, which represents 7.02% of hospitalized neonates. Premature infants had more thrombocytopenic hemorrhagic syndrome (68.13%) than in term newborns. The hypotrophy was encountered in 27 newborns (29.67%) including 17 of them were premature. Biologically, 37 cases or 40.65% had severe thrombocytopenia with a rate less than 13 cases or 30,000/mm3 and 14.28% had levels between 30,000/mm3 and 50,000/mm3. The etiologies of hemorrhagic syndrome of thrombotic origin were dominated by neonatal sepsis (74.72%) and périnatals asphyxia (13.18%). The outcome was favorable in 28 cases corresponding to 30.76% and 63 cases died or 69.23% in an array of severe hemorrhagic syndrome. Conclusion: We emphasize the interest of early treatment to prevent severe neurological squealer and mortality significant. [Copyright &y& Elsevier]

The incidence of neonatal early onset sepsis has declined with the widespread use of intrapartum antibiotic therapies, yet early onset sepsis remains a potentially fatal condition, particularly among very low birth-weight infants. Clinical signs of neonatal infection are nonspecific and may be absent in the immediate postnatal period. Maternal and infant clinical characteristics, as well as infant laboratory values, have been used to identify newborns at risk and to administer empiric antibiotic therapy to prevent progression to more severe illness. Such approaches result in the evaluation of approximately 15% of asymptomatic term and late preterm infants and of nearly all preterm infants. The development of multivariate predictive models may provide more accurate methods of identifying newborns at highest risk and allow for more limited newborn antibiotic exposures. [Copyright &y& Elsevier]

Summary: Background: Panton–Valentine leucocidin-positive meticillin-resistant Staphylococcus aureus (PVL-MRSA) has become a globally common cause of community-acquired infections. Aim: We report an outbreak of PVL-MRSA in a regional neonatal unit in the UK involving three babies and three staff members. Methods: Quinolone susceptibility was helpful in identifying potential PVL-MRSA but toxin gene profiling and sequence-based typing were required to distinguish between two PVL-MRSA strains present in the unit. Findings: All three symptomatic babies and two staff carriers, one of whom was symptomatic, were found to be carrying the South West Pacific (SWP) clone of PVL-MRSA (ST30). One of the staff carriers had recently visited the Philippines and was thought to be the source of the outbreak. Control was established using standard infection control procedures but one baby with relapsing MRSA colonization has required more than 100 days in isolation. Conclusion: This is the first reported neonatal outbreak associated with the SWP clone in the UK. Our study highlights the potential risk of further introductions of this organism by healthcare staff or patients epidemiologically linked with the Philippines. [ABSTRACT FROM AUTHOR]

Clin Microbiol Infect 2011; 17: 1294-1303 Abstract Streptococcus agalactiae, or group B streptococcus (GBS), remains the leading cause of neonatal sepsis and meningitis, as early-onset or late-onset diseases (EOD, LOD). Where consensus guidelines to detect and treat intrapartum women with GBS colonization have been widely adopted, incidence of neonatal EOD has dramatically declined. In response to both successful impacts on the incidence of GBS-EOD and analyses of missed opportunities, the first American guidelines for prevention issued in the 1990s have since been adapted in several stages to improve their efficacy. In some countries in Europe, nationwide guidelines, whether screening-based or risk-based, for the prevention of neonatal GBS diseases have also been issued and adopted, with the expected impact on incidence of GBS-EOD. In spite of universal screening, in spite of the great progress that has been made, GBS-EOD continues to occur and the GBS burden remains a significant public health issue. Continuous efforts to improve screening for GBS status continue to be important and may be able to take advantage of new rapid diagnostic technologies. The current screening-based strategy for prevention is highly effective but imperfect. Given the challenges, limitations and potential complications of maternal intrapartum prophylaxis, a new approach is still needed. Maternal immunization against GBS is an attractive alternative for the prevention of not only neonatal diseases but also stillbirths and maternal diseases. Vaccines against GBS may become the most effective and sustainable long-term preventive strategy. [ABSTRACT FROM AUTHOR]

Abstract: Premature rupture of membranes is a common situation in obstetrics that links the amniotic cavity and the bacterial cervicovaginal flora. The main risk in case of preterm premature rupture of membranes is the occurrence of an amniochorial infection, which increases neonatal morbidity and mortality. One main purpose in cases of preterm premature rupture of membranes is to identify infection early to adapt the clinical care. Among the marker used in practice, CRP has a sensitivity between 56% and 86% and specificity between 55% and 82% for predicting clinical chorioamnionitis. These values are respectively 21% to 56% and 76% to 95% for the prediction of early neonatal infection. The white blood cell count, also used in routine, has a poor predictive value of clinical chorioamnionitis although a high specificity when the threshold is of 16 giga/l. Among the pro-inflammatory cytokines, interleukin-6 has been the most studied. Its predictive value for chorioamnionitis or neonatal infection is higher but its clinical usefulness is limited by the various threshold used in the studies and the lack of routine measure. Procalcitonin appears to have low predictive values for detecting amniochorial infection but has finally been little studied. Ways to improve prediction of infection in cases of premature rupture of membranes are either looking for new markers or the analysis of local markers (vaginal secretions and amniotic fluid). [Copyright &y& Elsevier]

Each year 3.6 million infants are estimated to die in the first 4 weeks of life (neonatal period)—but the majority continue to die at home, uncounted. This article reviews progress for newborn health globally, with a focus on the countries in which most deaths occur—what data do we have to guide accelerated efforts? All regions are advancing, but the level of decrease in neonatal mortality differs by region, country, and within countries. Progress also differs by the main causes of neonatal death. Three major causes of neonatal deaths (infections, complications of preterm birth, and intrapartum-related neonatal deaths or “birth asphyxia”) account for more than 80% of all neonatal deaths globally. The most rapid reductions have been made in reducing neonatal tetanus, and there has been apparent progress towards reducing neonatal infections. Limited, if any, reduction has been made in reducing global deaths from preterm birth and for intrapartum-related neonatal deaths. High-impact, feasible interventions to address these 3 causes are summarized in this article, along with estimates of potential for lives saved. A major gap is reaching mothers and babies at birth and in the early postnatal period. There are promising community-based service delivery models that have been tested mainly in research studies in Asia that are now being adapted and evaluated at scale and also being tested through a network of African implementation research trials. To meet Millennium Development Goal 4, more can and must be done to address neonatal deaths. A critical step is improving the quantity, quality and use of data to select and implement the most effective interventions and strengthen existing programs, especially at district level. [Copyright &y& Elsevier]

Abstract: Maternal to child transmission of viral infections can have devastating outcomes on the developing fetus and the neonate. Effective prevention and screening programs for women of childbearing age are key factors in influencing the outcomes for the neonate. Furthermore, early identification of viral infections in neonates is critical to the success of the treatment plan. This article describes the mechanism of maternal to child transmission of viral infections and examines the general approach to the neonate with suspected viral infection. The diagnosis, treatment, and prevention of neonatal cytomegalovirus, herpes simplex virus, and human immunodeficiency virus infections are presented. Lastly, current challenges and controversies related to the management of viral infections in the neonate are discussed. [Copyright &y& Elsevier]

Abstract: Neonatal bacterial infection in rats alters the responses to a variety of subsequent challenges later in life. Here we explored the effects of neonatal bacterial infection on a subsequent drug challenge during adolescence, using administration of the psychostimulant amphetamine. Male rat pups were injected on postnatal day 4 (P4) with live Escherichia coli (E. coli) or PBS vehicle, and then received amphetamine (15mg/kg) or saline on P40. Quantitative RT-PCR was performed on micropunches taken from medial prefrontal cortex, nucleus accumbens, and the CA1 subfield of the hippocampus. mRNA for glial and neuronal activation markers as well as pro-inflammatory and anti-inflammatory cytokines were assessed. Amphetamine produced brain region specific increases in many of these genes in PBS controls, while these effects were blunted or absent in neonatal E. coli treated rats. In contrast to the potentiating effect of neonatal E. coli on glial and cytokine responses to an immune challenge previously observed, neonatal E. coli infection attenuates glial and cytokine responses to an amphetamine challenge. [Copyright &y& Elsevier]

Preterm premature rupture of membranes (PPROM) occurs in 3% of pregnancies and is responsible for 30% of preterm births. The management is discussed between active and expectant management. French recommendations let open both possibilities. The risks described in the case of PPROM are those of prematurity, maternofetal infection, acute procidence of the umbilical cord and abruptio placentae. Before 32 weeks of gestation (WG) and even 34 WG, a prolongation of one week of gestational age significantly decreases neonatal mortality and morbidity. Therefore, most of the authors choose expectant management in case of PPROM. Between 34 and 37 WG, the risk of rare severe morbidity associated with prematurity has to be balanced with risks of an acute maternofetal infection and of abruptio placentae. Further randomized trials are required to choose a type of management with a sufficient level of evidence. [Copyright &y& Elsevier]

Abstract: A variety of early life stressors have consistently been implicated in the development of psychopathology in adulthood. The current study investigates a rarely considered form of early life stress, bacterial infection, for its ability to induce psychopathology-like symptoms in adult rat. Specifically, neonatal rats were exposed to a simulated bacterial infection. In adulthood the acoustic startle response of these animals was evaluated both prior to and following exposure to restraint stress. Our results indicate that animals neonatally exposed to infection exhibit a significantly exaggerated acoustic startle response but only following exposure to stress. Additionally, we observed that adult animals neonatally exposed to infection, exhibited increased production of circulating corticosterone following stress, indicating potentiated hypothalamic pituitary adrenal axis activity as well as altered novelty seeking behaviour and locomotor activity. These results extend upon existing pre-clinical findings that indicate certain stressful early life events can predispose the adult animal to exhibit abnormal behaviour in adulthood. [Copyright &y& Elsevier]

Abstract: Breastfeeding has a major impact on HCMV epidemiology. The incidence of postnatal HCMV reactivation during lactation equals the maternal seroprevalence. Infectious virus, viral DNA and RNA can be isolated easily from cell and fat-free milk whey. Early onset of viral DNAlactia and virolactia as well as high viral load in milk whey are maternal risk factors for virus transmission. The dynamics of HCMV reactivation can be described by unimodal kinetics with interindividual variation. Virus reactivation during lactation is a self-limiting local process in the absence of systemic HCMV infection. Preterm infants below 1000g birthweight and a gestational age below 30 weeks may be at high risk of acquiring a symptomatic HCMV infection. Several recent studies described low transmission rates and mostly asymptomatically infected neonates using frozen milk. Despite different freeze-storing procedures, HCMV transmissions occurred, and severe HCMV infections were observed. Few data exist on the long-term outcome of postnatally acquired HCMV infection via breast milk. To substantiate the international debate on the use of native or inactivated milk for feeding of preterm infants, additional data are necessary for better identification of mother–infant-pairs at risk for viral transmission and symptomatic infection early after birth. [Copyright &y& Elsevier]

In the 1970s, group B streptococci emerged as the leading cause of neonatal infections. The incidence ranged between 1.5 and 2 cases per 1000 in the U.S. in the 1980s up to the early 1990s. In the 1980s, selective treatment with β-lactam antibiotics of mothers in labor turned out to be the most successful mode of prevention. In 1996, the CDC, American College of Obstetrics and Gynecology, and the American Academy of Pediatrics recommended the use of one of two prevention strategies: the culture-based strategy or a risk-based strategy for mothers who did not have prenatal cultures. In 2002, the guidelines were updated to recommend as preferable the culture-based method, which was found to result in superior prevention compared with the risk-based method. Subsequent to the 1996 recommendations, early-onset GBS infection has been reduced by greater than 70% and racial inequalities have been narrowed. Whether exposure of millions of mothers to penicillin or ampicillin will have an undesirable effect of causing more Escherichia coli infections in neonates or will result in more ampicillin-resistant organisms being responsible for early-onset neonatal infections remains unclear. [Copyright &y& Elsevier]

Abstract: Group B Streptococcus (GBS) is the leading infectious cause of neonatal morbidity and mortality. Although intrapartum antibiotic prophylaxis (IAP) strategies are effective in preventing GBS transmission from mothers to newborns, there are growing concerns about adverse effects, and the development of antibiotic resistance. GBS vaccines targeting the most virulent neonatal disease serotypes are currently under development and may be used during pregnancy. The objective of this study was to explore the key issues and concerns that would be associated with GBS vaccination during pregnancy from the perspectives of pregnant women and health care providers. Twenty-two women and 25 health care professionals in Alberta, Canada participated in 10 focus groups, each group ranging from 2 to 20 participants. Valuable information emerged from the focus groups about the factors that would affect acceptance of a maternal GBS vaccine. This information will be essential for health systems to consider in the introduction, promotion and delivery of such a vaccine. The data may help optimize education about GBS and a putative vaccine to pregnant women. [Copyright &y& Elsevier]

Abstract: Herpes simplex virus (HSV) type 1/2 and Epstein-Barr virus (EBV) belong to the human herpes viruses and are among the most ubiquitous viruses in the adult population. In spite of the fact that a large proportion of women at childbearing age are seropositive to these viruses, especially to HSV, primary or secondary infections with these viruses may occur during pregnancy. Genital HSV, especially in primary infections, may be dangerous to the neonate if infected during delivery, as it can cause a severe neonatal disease. Intrauterine infection causing abortion or stillbirth as well as skin scars (cutaneous manifestations), ophthalmologic findings (chorioretinitis, microphtalmia), and neurological involvement (causing brain damage) is also possible, but relatively rare. Primary infection with EBV during pregnancy with apparent transplacental transmission is rare and only few cases were reported. They main damage was in the heart, eyes and liver. The actual damage to the developing embryo and fetus from maternal HSV and EBV seems to be very small. It should be mentioned that both HSV and EBV seem to be able to cross the placenta and cause, as described by several investigators, placental infection manifested by deciduitis and villitis. These placental pathological changes may increase fetal damage. [Copyright &y& Elsevier]

Abstract: Strategies to reduce early-onset sepsis (EOS) with group B streptococcus (GBS) have relied on the administration of maternal intra-partum antibiotics (IPA) to mothers with identified risk factors. We studied the relationship between IPA, risk factors, and EOS for 14 years in our hospital, an inner-city, tertiary center serving primarily poor, high-risk, African-American mothers. Methods: For each birth from 1989 to 2002, we identified presence or absence of maternal risk factors (prolonged rupture of membranes [PROM], chorioamnionitis, prematurity [<37 weeks]) and IPA use. In addition, for identified cases of EOS (+blood culture <72 h for a recognized pathogen), we identified bacterial organism and prior maternal GBS culture status. During these years, our obstetricians used a combination of risk-factor-based and culture-based GBS prophylaxis strategies. Results: Data from ∼44,000 pregnancies were collected. The most common risk factor was prematurity (21% of deliveries). The percentage of mothers with any identified risk factor did not change significantly over the study period (∼33% of deliveries). From 1989 to 2002, IPA rose from 13% to 44% of all deliveries (p <0.001). For premature delivery, IPA rose from 27% to 69% (p <0.001); for PROM, IPA rose from 43% to 88% (p <0.001); for mothers with no identified risk factors of any kind, IPA rose from 7% to 27% (p <0.001). For babies with EOS, the frequency of known GBS culture results rose from ∼15% to ∼80% (p <0.001). Nonetheless, incidence of GBS EOS was unchanged (average of 2.0/1000 births); the incidence of non-GBS EOS was also unchanged (average of 2.1/1000 births). No maternal social demographic distinguished GBS from non-GBS EOS cases. Of the 57 infants with GBS EOS and risk factors, 35 (62%) received IPA; of the 85 infants with non-GBS EOS and risk factors, 62 (73%) received IPA (p <0.05). Conclusions: 1) IPA tripled between 1989 and 2002. 2) Yet EOS was unaffected—both GBS and non-GBS EOS persisted at ∼2/1000 live births. 3) We suggest that vaccination will eventually be needed to reduce GBS EOS in our institution. We have no good idea how to reduce non-GBS EOS cases. [Copyright &y& Elsevier]

Abstract: The incidence of postnatal human cytomegalovirus (HCMV) reactivation during lactation equals the maternal seroprevalence. Infectious virus, viral DNA and RNA can be isolated from cells and fat free milk whey. Early onset of viral DNAlactia and virolactia as well as high viral load in milk whey are maternal risk factors for virus transmission. Preterm infants below 1000 g birthweight and a gestational age below 30 weeks may be at high risk of acquiring a symptomatic HCMV infection. Several recent studies using frozen milk for feeding describe low transmission rates and mostly asymptomatically infected neonates. However despite different freeze-storing procedures HCMV transmission occurred and severe HCMV infections were observed. Only few data exist on the long-term outcome of postnatally acquired HCMV infection via breast milk. Additional long-term outcome studies are needed. The newly developed short-term pasteurisation may be a reliable alternative to freezing and Holder pasteurisation, since important milk constituents are conserved. [Copyright &y& Elsevier]

Summary: Despite the advent of antibiotics and improved diagnostic facilities, infectious diseases in pregnancy continue to be significant contributors to maternal and fetal morbidity and mortality. These are more common in the developing than the developed nations, where poverty, a lack of hygiene, a lack of medical resources and a lack of trained health-care workers are common. Although infectious diseases in pregnancy are not so common in the UK, there has been an increase in the incidence of syphilis, tuberculosis and HIV in pregnancy in inner-city areas. This has implications for health-care professionals, who require a knowledge of these conditions along with the other infectious diseases that are likely to influence maternal and/or fetal and neonatal health. This article discusses some of the significant infections encountered in practice and others that are not as common but require a higher index of suspicion and appropriate investigations to improve maternal and fetal outcomes. [Copyright &y& Elsevier]

Objective: The purpose of this study was to evaluate the diagnostic value of an interleukin-6 (IL-6) bedside test of vaginal secretions for neonatal infection in cases of preterm premature rupture of membranes. Study design: This prospective clinical study included 73 patients. Interleukin-6 protein in vaginal secretions was determined with an immunochromatographic bedside test in <20 minutes. Results: Elevated C-reactive protein level (>20 mg/dL; odds ratio, 5.1; 95% CI, 0.9-28.6) and positive interleukin-6 level (odds ratio, 4.6; 95% CI, 1.2-18.4) were both associated with neonatal infection. After adjustment, only interleukin-6 remained associated with neonatal infection (odds ratio, 4.5; 95% CI, 1.1-18.5). The sensitivity of interleukin-6 for the prediction of neonatal infection was 79% (95% CI, 65-92); its specificity was 56% (95% CI, 42-70); its positive predictive value was 30% (95% CI, 12-47), and its negative predictive value was 92% (95% CI, 84-99). Conclusion: Interleukin-6 protein determination by this new immunochromatographic test is a noninvasive prenatal vaginal marker of neonatal infection. [ABSTRACT FROM AUTHOR]

Objective: Neonatal cerebral white matter injury represents a major precursor for neurological impairment and cerebral palsy. Our objective was to identify risk factors associated with its development. Study Design: This retrospective case-control study of all births between 23 and 34 weeks gestation at a single university hospital between May 1994 and September 2001 identified 150 cases with white matter injury characterized by periventricular leukomalacia or ventricular dilatation from white matter atrophy that were chromosomally normal and did not have other congenital anomalies. Cases were matched to controls without brain injury by the next delivery within 7 days of their gestational age. Results: There were small differences between controls and cases in gestational age (27.5 +/- 2.7, 27.4 +/- 2.6 weeks, P = .01) and birth weight (1053 +/- 402, 966 +/- 285 g, P = .002) that were statistically but not clinically significant. There was no difference in the percentage of controls and cases delivered by cesarean (45%, 49%, P = .64). There were no differences between controls and cases in umbilical arterial pH (7.27 +/- 0.11, 7.25 +/- 0.15, P = .19), base excess (-2.1 +/- 2.7, -3.0 +/- 4.1 mmol/L, P = .28), pH less than 7.0 (2/122 [2%], 3/107 [3%], P = 1.0), or base excess less than -12 mmol/L (4/121 [3%], 6/106 [6%], P = .75). The cases had a significant increase in positive blood (19%, 29%, P = .036), cerebrospinal fluid (6%, 17%, P = .002), and tracheal (9%, 22%, P = .003) cultures during the neonatal period. Conditional logistic regression showed a significant association among multiple gestations ( P = .02), intraventricular hemorrhage ( P < .001), and positive tracheal cultures ( P = .02) with cerebral white matter injury. Conclusion: Culture-positive infection was associated with an increased risk of cerebral white matter injury in preterm neonates. Intrapartum hypoxia-ischemia as manifested by metabolic acidosis was rarely associated with white matter injury and was not different from the incidence in premature neonates without injury. [ABSTRACT FROM AUTHOR]

Objectives: To determine the significant predictors of clinical chorioamionitis and neonatal infection in patients with prelabor rupture of the membranes at term, and to apply this information to determination of optimal timing of labor induction. Study design: A retrospective case control series of women at ≥37 weeks’ with prelabor rupture of the membranes. The study group consisted of women with evidence of maternal or neonatal infection. Controls had no evidence of infection. Three types of management were compared. (1) Immediate induction of labor, (2) expectant management up to 24 h followed by induction of labor if still necessary, or (3) expectant management for over 24 h. Univariate and multivariate analyses were performed by stepwise logistic regression (SPSS software package). The size of the study and the control groups was calculated for a 90% power with two sided P value of 0.05 in order to demonstrate an odds ratio of 2 for expectant management (two groups: early and late) versus immediate induction of labor (132 and 279 women in the study and the control groups, respectively). Results: The rate of expectant management for over 24 h versus expectant management until 24 h followed by induction of labor when still necessary, was higher among cases than among controls (OR=1.84; P<0.017; 95% CI, 1.127–3.003). Conversely, the rate of immediate induction of labor versus expectant management until 24 h followed by induction of labor when still necessary, was also higher among cases (OR=2.66; P<0.001; 95% CI, 0.222–0.644). Conclusion: In women with prelabor rupture of the membranes at term, the best approach is to induce labor if spontaneous labor has not begun after 24 h. [Copyright &y& Elsevier]