Utility of Anaerobic Blood Cultures in Neonatal Sepsis Evaluation.

BACKGROUND: Clinicians variably obtain anaerobic blood cultures as part of sepsis evaluations in the neonatal intensive care unit (NICU). Our objective was to determine if anaerobic blood culture bottles yielded clinically relevant information by either recovering pathogens exclusively or more rapidly than the concurrently obtained aerobic culture bottle in the NICU. METHODS: A retrospective cohort study of blood cultures obtained from infants admitted to the NICU from 08/01/2015-08/31/2023. Standard practice was to inoculate 2 mL of blood divided equally between an aerobic and an anaerobic culture bottle. We analyzed positive blood cultures where both aerobic and anaerobic bottles were obtained and compared pathogen recovery and time to positivity between the bottles. RESULTS: During the study period, 4599 blood cultures were obtained from 3665 infants, and 265 (5.8%) were positive. Of these, 182 cultures were sent as aerobic-anaerobic pairs and recovered pathogenic organisms. Organisms were recovered exclusively from the anaerobic bottle in 32 (17.6%) cultures. Three organisms were obligate anaerobes; the rest were facultative anaerobes including Coagulase-negative staphylococci (40.6%), Escherichia coli (15.6%), and Staphylococcus aureus (15.6%). Cultures with exclusive recovery in the anaerobic bottle were more frequently obtained ≤3 days after birth, compared to other cultures (31.3% vs. 15.3%, p=0.03). When both bottles recovered the pathogen (n=113), the anaerobic bottle had a shorter time to positivity in 76 (67.3%) cultures. CONCLUSIONS: Including anaerobic culture bottles could lead to identification of pathogens not recovered in the aerobic bottle, as well as earlier identification of pathogens.

Perinatal COVID-19: Implications for care of the newborn.

The maternal/newborn dyad presents special challenges to infection management. Early in the COVID-19 pandemic, lack of information regarding SARS-CoV-2 transmission and virulence made it difficult to develop appropriate care guidance when pregnant persons had COVID-19 at the time of presentation for childbirth. We will review the considerations for the parturient, newborn, and care team, and describe the evolution of perinatal COVID management guidance.

Neonatal Group B Streptococcus Disease.

Group B Streptococcus (GBS) is an important cause of neonatal sepsis in term and preterm infants. Because GBS colonizes human genitourinary and gastrointestinal tracts, a significant focus of neonatal GBS disease prevention is to interrupt vertical transmission of GBS from mother to infant during parturition. Routine antepartum GBS screening in pregnant women, as well as widespread use of intrapartum antibiotic prophylaxis, have aided in overall reductions in neonatal GBS disease during the past 3 decades. However, neonatal GBS disease persists and may cause mortality and significant short- and long-term morbidity among survivors. Herein, we highlight contemporary epidemiology, microbial pathogenesis, and the clinical presentation spectrum associated with neonatal GBS disease. We summarize obstetric recommendations for antenatal GBS screening, indications for intrapartum antibiotic prophylaxis, and considerations for antibiotic selection. Finally, we review national guidelines for risk assessment and management of infants at risk for GBS disease.

Antibiotic Use Among Infants Admitted to Neonatal Intensive Care Units.

This cross-sectional study examines antibiotic exposure, days of therapy, types of antibiotics, and changes in use patterns among newborns in neonatal intensive care units (NICUs) across the US from 2009 to 2021.

Association of delivery risk phenotype with early-onset sepsis in preterm infants.

OBJECTIVE: To determine delivery risk phenotype-specific incidence of early-onset sepsis (EOS) among preterm infants. STUDY DESIGN: Retrospective cohort study of infants born <35 weeks' gestation at four perinatal centers during 2017-2021. Infants were classified into one of six delivery risk phenotypes incorporating delivery mode, presence of labor, and duration of rupture of membranes (ROM). The primary outcome was EOS incidence within the overall cohort and each risk phenotype. RESULTS: Among 2937 preterm infants, 21 had EOS (0.7%, or 7.1 cases/1000 preterm infants). The majority of EOS cases (13/21, 62%) occurred in the setting of prolonged ROM ≥ 18 h, with a phenotype incidence of 23.8 cases/1000 preterm infants. There were no EOS cases among infants born by cesarean section without ROM (with or without labor), nor via cesarean section with ROM < 18 h without labor. CONCLUSION: Delivery risk phenotyping may inform EOS risk stratification in preterm infants.

Early antibiotic exposure in very-low birth weight infants and infection risk at 3-7 days after birth.

OBJECTIVE: To determine rates of late-onset infection (LOI) during postnatal days 3-7 among preterm infants, based on antibiotic exposure during days 0-2. STUDY DESIGN: Retrospective cohort study of infants born <1500 grams and ≤30 weeks gestation, 2005-2018. We analyzed the incidence and microbiology of LOI at days 3-7 based on antibiotic exposure during postnatal days 0-2. RESULTS: The cohort included 88,574 infants, of whom 85% were antibiotic-exposed. Fewer antibiotic-exposed compared to unexposed infants developed LOI (1.5% vs. 2.1%; adjusted hazard ratio, 0.28, 95% CI 0.24-0.33). Among antibiotic-exposed compared to unexposed infants, Gram-negative (38% vs. 28%, p = 0.002) and fungal (11% vs. 1%, p < 0.001) species were more commonly isolated, and gram-positive organisms (49% vs. 70%, p < 0.001) were less commonly isolated. CONCLUSIONS: We observed low overall rates of LOI at days 3-7 after birth, but antibiotic exposure from birth was associated with lower rates, and with differing microbiology, compared to no exposure.

Eat, Sleep, Console Approach or Usual Care for Neonatal Opioid Withdrawal.

BACKGROUND: Although clinicians have traditionally used the Finnegan Neonatal Abstinence Scoring Tool to assess the severity of neonatal opioid withdrawal, a newer function-based approach - the Eat, Sleep, Console care approach - is increasing in use. Whether the new approach can safely reduce the time until infants are medically ready for discharge when it is applied broadly across diverse sites is unknown. METHODS: In this cluster-randomized, controlled trial at 26 U.S. hospitals, we enrolled infants with neonatal opioid withdrawal syndrome who had been born at 36 weeks' gestation or more. At a randomly assigned time, hospitals transitioned from usual care that used the Finnegan tool to the Eat, Sleep, Console approach. During a 3-month transition period, staff members at each hospital were trained to use the new approach. The primary outcome was the time from birth until medical readiness for discharge as defined by the trial. Composite safety outcomes that were assessed during the first 3 months of postnatal age included in-hospital safety, unscheduled health care visits, and nonaccidental trauma or death. RESULTS: A total of 1305 infants were enrolled. In an intention-to-treat analysis that included 837 infants who met the trial definition for medical readiness for discharge, the number of days from birth until readiness for hospital discharge was 8.2 in the Eat, Sleep, Console group and 14.9 in the usual-care group (adjusted mean difference, 6.7 days; 95% confidence interval [CI], 4.7 to 8.8), for a rate ratio of 0.55 (95% CI, 0.46 to 0.65; P<0.001). The incidence of adverse outcomes was similar in the two groups. CONCLUSIONS: As compared with usual care, use of the Eat, Sleep, Console care approach significantly decreased the number of days until infants with neonatal opioid withdrawal syndrome were medically ready for discharge, without increasing specified adverse outcomes. (Funded by the Helping End Addiction Long-term (HEAL) Initiative of the National Institutes of Health; ESC-NOW ClinicalTrials.gov number, NCT04057820.).

Higher body mass index after intrapartum antibiotic exposure in children persists over 10-years.

Exposure to intrapartum antibiotic prophylaxis to reduce perinatal group B streptococcal disease was associated with increased childhood body mass index (BMI) persisting to age 10 years compared to no exposure (Δ BMI at 10 years: vaginal delivery 0.14 kg/m2 , caesarean 0.40 kg/m2 ).

Maternal and Newborn Hospital Outcomes of Perinatal SARS-CoV-2 Infection: A National Registry.

OBJECTIVES: The American Academy of Pediatrics National Registry for the Surveillance and Epidemiology of Perinatal coronavirus disease 2019 (COVID-19) (NPC-19) was developed to provide information on the effects of perinatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: National Registry for the Surveillance and Epidemiology of Perinatal COVID-19 participating centers entered maternal and newborn data for pregnant persons who tested positive for SARS-CoV-2 infection between 14 days before and 10 days after delivery. Incidence of and morbidities associated with maternal and newborn SARS-CoV-2 infection were assessed. RESULTS: From April 6, 2020 to March 19, 2021, 242 centers in the United States centers reported data for 7524 pregnant persons; at the time of delivery, 78.1% of these persons were asymptomatic, 18.2% were symptomatic but not hospitalized specifically for COVID-19, 3.4% were hospitalized for COVID-19 treatment, and 18 (0.2%) died in the hospital of COVID-related complications. Among 7648 newborns, 6486 (84.8%) were tested for SARS-CoV-2, and 144 (2.2%) were positive; the highest rate of newborn infection was observed when mothers first tested positive in the immediate postpartum period (17 of 125, 13.6%). No newborn deaths were attributable to SARS-CoV-2 infection. Overall, 15.6% of newborns were preterm: among tested newborns, 30.1% of polymerase chain reaction-positive and 16.2% of polymerase chain reaction-negative were born preterm (P < .001). Need for mechanical ventilation did not differ by newborn SARS-CoV-2 test result, but those with positive tests were more likely to be admitted to a NICU. CONCLUSIONS: Early in the pandemic, SARS-CoV-2 infection was acquired by newborns at variable rates and without apparent short-term effects. During a period that preceded widespread availability of vaccines, we observed higher than expected numbers of preterm births and maternal in-hospital deaths.

Measles Serostatus Among Parturient Patients at 2 Philadelphia Hospitals in 2021.

This observational study explores whether rubella serostatus, which is routinely assessed during pregnancy, can serve as a proxy for measles serostatus in parturient persons.

Serratia Infection Epidemiology Among Very Preterm Infants in the Neonatal Intensive Care Unit.

BACKGROUND: Serratia spp. are opportunistic, multidrug resistant, Gram-negative pathogens, previously described among preterm infants in case reports or outbreaks of infection. We describe Serratia late-onset infection (LOI) in very preterm infants in a large, contemporary, nationally representative cohort. METHODS: In this secondary analysis of prospectively collected data of preterm infants born 401-1500 grams and/or 22-29 weeks gestational age from 2018 to 2020 at 774 Vermont Oxford Network members, LOI was defined as culture-confirmed blood and/or cerebrospinal fluid infection > 3 days after birth. The primary outcome was incidence of Serratia LOI. Secondary outcomes compared rates of survival and discharge morbidities between infants with Serratia and non-Serratia LOI. RESULTS: Among 119,565 infants, LOI occurred in 10,687 (8.9%). Serratia was isolated in 279 cases (2.6% of all LOI; 2.3 Serratia infections per 1000 infants). Of 774 hospitals, 161 (21%) reported at least one Serratia LOI; 170 of 271 (63%) cases occurred at hospitals reporting 1 or 2 Serratia infections, and 53 of 271 (20%) occurred at hospitals reporting ≥5 Serratia infections. Serratia LOI was associated with a lower rate of survival to discharge compared with those with non-Serratia LOI (adjusted relative risk 0.88, 95% CI: 0.82-0.95). Among survivors, infants with Serratia LOI had higher rates of tracheostomy, gastrostomy and home oxygen use compared with those with non-Serratia LOI. CONCLUSIONS: The incidence of Serratia LOI was 2.3 infections per 1000 very preterm infants in this cohort. Lower survival and significant morbidity among Serratia LOI survivors highlight the need for recognition and targeted prevention strategies for this opportunistic nosocomial infection.

Diagnostic Performance and Patient Outcomes With C-Reactive Protein Use in Early-Onset Sepsis Evaluations.

OBJECTIVES: To determine performance of C-reactive protein (CRP) in the diagnosis of early-onset sepsis, and to assess patient outcomes with and without routine use of CRP. STUDY DESIGN: This was a retrospective cohort study of infants admitted to 2 neonatal intensive care units. CRP was used routinely in early-onset sepsis evaluations during 2009-2014; this period was used to determine CRP performance at a cut-off of ≥10 mg/L in diagnosis of culture-confirmed early-onset sepsis. Routine CRP use was discontinued during 2018-2020; outcomes among infants admitted during this period were compared with those in 2012-2014. RESULTS: From 2009 to 2014, 10 134 infants were admitted; 9103 (89.8%) had CRP and 7549 (74.5%) had blood culture obtained within 3 days of birth. CRP obtained ±4 hours from blood culture had a sensitivity of 41.7%, specificity 89.9%, and positive likelihood ratio 4.12 in diagnosis of early-onset sepsis. When obtained 24-72 hours after blood culture, sensitivity of CRP increased (89.5%), but specificity (55.7%) and positive likelihood ratio (2.02) decreased. Comparing the periods with (n = 4977) and without (n = 5135) routine use of CRP, we observed lower rates of early-onset sepsis evaluation (74.5% vs 50.5%), antibiotic initiation (65.0% vs 50.8%), and antibiotic prolongation in the absence of early-onset sepsis (17.3% vs 7.2%) in the later period. Rate and timing of early-onset sepsis detection, transfer to a greater level of care, and in-hospital mortality were not different between periods. CONCLUSIONS: CRP diagnostic performance was not sufficient to guide decision-making in early-onset sepsis. Discontinuation of routine CRP use was not associated with differences in patient outcomes despite lower rates of antibiotic administration.

Incidence of and Neurodevelopmental Outcomes After Late-Onset Meningitis Among Children Born Extremely Preterm.

Importance: Late-onset meningitis (LOM) has been associated with adverse neurodevelopmental outcomes in children born extremely preterm. Objective: To report the incidence of LOM during birth hospitalization and neurodevelopmental outcomes at 18 to 26 months' corrected age. Design, Setting, and Participants: This cohort study is a secondary analysis of a multicenter prospective cohort of children born at 22 to 26 weeks' gestation between 2003 and 2017 with follow-up from 2004 to 2021. The study was conducted at 25 Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers. Exposures: Culture-confirmed LOM. Main Outcomes and Measures: Incidence and microbiology of LOM (2003-2017); lumbar puncture (LP) performance in late-onset sepsis (LOS) evaluations (2011-2017); composite outcome of death or neurodevelopmental impairment (NDI; 2004-2021). Results: Among 13 372 infants (median [IQR] gestational age, 25.4 [24.4-26.1] weeks; 6864 [51%] boys), LOM was diagnosed in 167 (1%); LOS without LOM in 4564 (34%); and neither LOS nor LOM in 8641 (65%). The observed incidence of LOM decreased from 2% (95% CI, 1%-3%) in 2003 to 0.4% (95% CI, 0.7%-1.0%) in 2017 (P < .001). LP performance in LOS evaluations decreased from 36% (95% CI, 33%-40%) in 2011 to 24% (95% CI, 21%-27%) in 2017 (P < .001). Among infants with culture-confirmed LOS, LP performance decreased from 58% (95% CI, 51%-65%) to 45% (95% CI, 38%-51%; P = .008). LP performance varied by center among all LOS evaluations (10%-59%, P < .001) and among those with culture-confirmed LOS (23%-79%, P < .001). LOM occurred in the absence of concurrent LOS in 27 of 167 cases (16%). The most common LOM isolates were coagulase-negative Staphylococcus (98 [59%]), Candida albicans (38 [23%]), and Escherichia coli (27 [16%]). Death or NDI occurred in 22 of 46 children (48%) with LOM due to coagulase-negative Staphylococcus, 43 of 67 (64%) due to all other bacterial pathogens, and 26 of 33 (79%) due to fungal pathogens. The adjusted relative risk of death or NDI was increased among children with LOM (aOR, 1.53; 95% CI, 1.04-2.25) and among those with LOS without LOM (aOR, 1.41; 95% CI, 1.29-1.54) compared with children with neither infection. Conclusions and Relevance: In this cohort study, LP was performed with decreasing frequency, and the observed incidence of LOM also decreased. Both LOM and LOS were associated with increased risk of death or NDI; risk varied by LOM pathogen. The full association of LOM with outcomes of children born extremely preterm may be underestimated by current diagnostic practices.

Comparison of Maternal and Neonatal Antibody Levels After COVID-19 Vaccination vs SARS-CoV-2 Infection.

Importance: Pregnant persons are at an increased risk of severe COVID-19 from SARS-CoV-2 infection, and COVID-19 vaccination is currently recommended during pregnancy. Objective: To ascertain the association of vaccine type, time from vaccination, gestational age at delivery, and pregnancy complications with placental transfer of antibodies to SARS-CoV-2. Design, Setting, and Participants: This cohort study was conducted in Pennsylvania Hospital in Philadelphia, Pennsylvania, and included births at the study site between August 9, 2020, and April 25, 2021. Maternal and cord blood serum samples were available for antibody level measurements for maternal-neonatal dyads. Exposures: SARS-CoV-2 infection vs COVID-19 vaccination. Main Outcomes and Measures: IgG antibodies to the receptor-binding domain of the SARS-CoV-2 spike protein were measured by quantitative enzyme-linked immunosorbent assay. Antibody concentrations and transplacental transfer ratios were measured after SARS-CoV-2 infection or receipt of COVID-19 vaccines. Results: A total of 585 maternal-newborn dyads (median [IQR] maternal age, 31 [26-35] years; median [IQR] gestational age, 39 [38-40] weeks) with maternal IgG antibodies to SARS-CoV-2 detected at the time of delivery were included. IgG was detected in cord blood from 557 of 585 newborns (95.2%). Among 169 vaccinated persons without SARS-CoV-2 infection, the interval from first dose of vaccine to delivery ranged from 12 to 122 days. The geometric mean IgG level among 169 vaccine recipients was significantly higher than that measured in 408 persons after infection (33.88 [95% CI, 27.64-41.53] arbitrary U/mL vs 2.80 [95% CI, 2.50-3.13] arbitrary U/mL). Geometric mean IgG levels were higher after vaccination with the mRNA-1273 (Moderna) vaccine compared with the BNT162b2 (Pfizer/BioNTech) vaccine (53.74 [95% CI, 40.49-71.33] arbitrary U/mL vs 25.45 [95% CI, 19.17-33.79] arbitrary U/mL; P < .001). Placental transfer ratios were lower after vaccination compared with after infection (0.80 [95% CI, 0.68-0.93] vs 1.06 [95% CI, 0.98-1.14]; P < .001) but were similar between the mRNA vaccines (mRNA-1273: 0.70 [95% CI, 0.55-0.90]; BNT162b2: 0.85 [95% CI, 0.69-1.06]; P = .25). Time from infection or vaccination to delivery was associated with transfer ratio in models that included gestational age at delivery and maternal hypertensive disorders, diabetes, and obesity. Placental antibody transfer was detectable as early as 26 weeks' gestation. Transfer ratio that was higher than 1.0 was present for 48 of 51 (94.1%) births at 36 weeks' gestation or later by 8 weeks after vaccination. Conclusions and Relevance: This study found that maternal and cord blood IgG antibody levels were higher after COVID-19 vaccination compared with after SARS-CoV-2 infection, with slightly lower placental transfer ratios after vaccination than after infection. The findings suggest that time from infection or vaccination to delivery was the most important factor in transfer efficiency.

Late-Onset Sepsis Among Very Preterm Infants.

OBJECTIVES: To determine the epidemiology, microbiology, and associated outcomes of late-onset sepsis among very preterm infants using a large and nationally representative cohort of NICUs across the United States. METHODS: Prospective observational study of very preterm infants born 401 to 1500 g and/or 22 to 29 weeks' gestational age (GA) from January 1, 2018, to December 31, 2020, who survived >3 days in 774 participating Vermont Oxford Network centers. Late-onset sepsis was defined as isolation of a pathogenic bacteria from blood and/or cerebrospinal fluid, or fungi from blood, obtained >3 days after birth. Demographics, clinical characteristics, and outcomes were compared between infants with and without late-onset sepsis. RESULTS: Of 118 650 infants, 10 501 (8.9%) had late-onset sepsis for an incidence rate of 88.5 per 1000 (99% confidence interval [CI] [86.4-90.7]). Incidence was highest for infants born ≤23 weeks GA (322.0 per 1000, 99% CI [306.3-338.1]). The most common pathogens were coagulase negative staphylococci (29.3%) and Staphylococcus aureus (23.0%), but 34 different pathogens were identified. Infected infants had lower survival (adjusted risk ratio [aRR] 0.89, 95% CI [0.87-0.90]) and increased risks of home oxygen (aRR 1.32, 95% CI [1.26-1.38]), tracheostomy (aRR 2.88, 95% CI [2.47-3.37]), and gastrostomy (aRR 2.09, 95% CI [1.93-2.57]) among survivors. CONCLUSIONS: A substantial proportion of very preterm infants continue to suffer late-onset sepsis, particularly those born at the lowest GAs. Infected infants had higher mortality, and survivors had increased risks of technology-dependent chronic morbidities. The persistent burden and diverse microbiology of late-onset sepsis among very preterm infants underscore the need for innovative and potentially organism-specific prevention strategies.

Neonatal Early-Onset Sepsis.

Early-onset sepsis (EOS) is a significant cause of morbidity and mortality among newborn infants, particularly among those born premature. The epidemiology of EOS is changing over time. Here, we highlight the most contemporary data informing the epidemiology of neonatal EOS, including incidence, microbiology, risk factors, and associated outcomes, with a focus on infants born in high-income countries during their birth hospitalization. We discuss approaches to risk assessment for EOS, summarizing national guidelines and comparing key differences between approaches for term and preterm infants. Lastly, we analyze contemporary antibiotic resistance data for EOS pathogens to inform optimal empiric treatment for EOS.

Breast Milk and Saliva for Postnatal Cyto†megalovirus Screening among Very Low Birth Weight Infants.

BACKGROUND: The optimal approach to managing postnatal cytomegalovirus disease (pCMV) among very low birth weight (VLBW) infants remains unknown. Methods to facilitate screening are needed. OBJECTIVE: Determine whether mother's milk and infant saliva can be used to reliably identify maternal cytomegalovirus (CMV) serostatus and detect infant pCMV acquisition. METHODS: This was a single-center, prospective cohort study of VLBW infants, and their mothers, born between 2017 and 2020. Maternal milk samples were tested for CMV immunoglobulin G (IgG) using a CMV glycoprotein B binding enzyme-linked immunosorbent assay and the results were compared with maternal serum CMV IgG results. Biweekly paired saliva and urine samples were collected from infants born to mothers with positive or unknown CMV serostatus. Saliva samples were tested for CMV DNA by quantitative real-time polymerase chain reaction (PCR) and compared with urine CMV qualitative PCR results obtained from a clinical laboratory. RESULTS: Among 108 infants without congenital CMV included in the study, 10 (9%) acquired pCMV. Both milk and blood CMV serology results were available for 70 mothers. Maternal milk antibody testing had a sensitivity of 97.2% (95% CI: 85.5-99.9%) and specificity of 91.2% (95% CI: 76.3-98.1%) in establishing CMV serostatus. Paired serially collected saliva and urine samples (n = 203) were available for 66 infants. Saliva PCR had a sensitivity of 30.0% (95% CI: 6.7-65.2%) and specificity of 92.7% (95% CI: 88.1-96.0%) in detecting pCMV acquisition. CONCLUSIONS: Maternal breast milk is a reliable alternative sample to determine CMV serostatus. Serial testing of infant saliva was not adequately sensitive for identifying pCMV acquisition in preterm infants.

Neonatal infections: Insights from a multicenter longitudinal research collaborative.

For more than 30 years, the Neonatal Research Network (NRN) has conducted studies addressing the epidemiology of neonatal infections, including incidence, microbiology, maternal and neonatal risk factors, associated clinical findings, and outcomes. These studies have provided clinicians and policymakers critical data needed to inform national guidance for infection risk assessment and support daily practice. Further, NRN studies have prompted research into optimal approaches to infection diagnosis, treatment, and antimicrobial stewardship. In this article, we summarize the key findings of NRN infection-related studies, with an emphasis on those published in 2000 or later.