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.).

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.

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.

Group B Streptococcus Infection in Extremely Preterm Neonates and Neurodevelopmental Outcomes at 2 Years.

BACKGROUND: This study was performed to determine the incidence of group B Streptococcus (GBS) disease among extremely preterm infants and assess to risk of death or neurodevelopmental impairment (NDI) at a corrected age of 18-26 months. METHODS: In this observational cohort study of infants enrolled in a multicenter registry, the incidence of GBS disease was assessed in infants born in 1998-2016 at 22-28 weeks' gestation and surviving for >12 hours. The composite outcome, death or NDI, was assessed in infants born in 1998-2014 at 22-26 weeks' gestation. Infection was defined as GBS isolation in blood or cerebrospinal fluid culture at ≤72 hours (early-onset disease [EOD]) or >72 hours (late-onset disease [LOD]) after birth. Using Poisson regression models, the outcome was compared in infants with GBS disease, infants infected with other pathogens, and uninfected infants. RESULTS: The incidence of GBS EOD (2.70/1000 births [95% confidence interval (CI), 2.15-3.36]) and LOD (8.47/1000 infants [7.45-9.59]) did not change significantly over time. The adjusted relative risk of death/NDI was higher among infants with GBS EOD than in those with other infections (adjusted relative risk, 1.22 [95% CI, 1.02-1.45]) and uninfected infants (1.44 [1.23-1.69]). Risk of death/NDI did not differ between infants with GBS LOD and comparator groups. GBS LOD occurred at a significantly later age than non-GBS late-onset infection. Among infants surviving >30 days, the risk of death was higher with GBS LOD (adjusted relative risk, 1.90 [95% CI, 1.36-2.67]), compared with uninfected infants. CONCLUSIONS: In a cohort of extremely preterm infants, the incidence of GBS disease did not change during the study period. The increased risk of death or NDI with GBS EOD, and of death among some infants with GBS LOD, supports the need for novel preventive strategies for disease reduction. CLINICAL TRIALS REGISTRATION: NCT00063063.

Neonatal multidrug-resistant gram-negative infection: epidemiology, mechanisms of resistance, and management.

Infants admitted to the neonatal intensive care unit, particularly those born preterm, are at high risk for infection due to the combination of an immature immune system, prolonged hospitalization, and frequent use of invasive devices. Emerging evidence suggests that multidrug-resistant gram-negative (MDR-GN) infections are increasing in neonatal settings, which directly threatens recent and ongoing advances in contemporary neonatal care. A rising prevalence of antibiotic resistance among common neonatal pathogens compounds the challenge of optimal management of suspected and confirmed neonatal infection. We review the epidemiology of MDR-GN infections in neonates in the United States and internationally, with a focus on extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales and carbapenem-resistant Enterobacterales (CRE). We include published single-center studies, neonatal collaborative reports, and national surveillance data. Risk factors for and mechanisms of resistance are discussed. In addition, we discuss current recommendations for empiric antibiotic therapy for suspected infections, as well as definitive treatment options for key MDR organisms. Finally, we review best practices for prevention and identify current knowledge gaps and areas for future research. IMPACT: Surveillance and prevention of MDR-GN infections is a pediatric research priority. A rising prevalence of MDR-GN neonatal infections, specifically ESBL-producing Enterobacterales and CRE, compounds the challenge of optimal management of suspected and confirmed neonatal infection. Future studies are needed to understand the impacts of MDR-GN infection on neonatal morbidity and mortality, and studies of current and novel antibiotic therapies should include a focus on the pharmacokinetics of such agents among neonates.

Intrapartum Antibiotic Exposure and Body Mass Index in Children.

BACKGROUND: Intrapartum antibiotic prophylaxis (IAP) reduces a newborn's risk of group B streptococcal infection (GBS) but may lead to an increased childhood body mass index (BMI). METHODS: This was a retrospective cohort study of infants (n = 223 431) born 2007-2015 in an integrated healthcare system. For vaginal delivery, we compared children exposed to GBS-IAP and to any other type or duration of intrapartum antibiotics to no antibiotic exposure. For cesarean delivery, we compared children exposed to GBS-IAP to those exposed to all other intrapartum antibiotics, including surgical prophylaxis. BMI over 5 years was compared using nonlinear multivariate models with B-spline functions, stratified by delivery mode and adjusted for demographics, maternal factors, breastfeeding, and childhood antibiotic exposure. RESULTS: In vaginal deliveries, GBS-IAP was associated with higher BMI from 0.5 to 5.0 years of age compared to no antibiotics (P < .0001 for all time points, ΔBMI at age 5 years 0.12 kg/m2, 95% confidence interval [CI]: .07-.16 kg/m2). Other antibiotics were associated with higher BMI from 0.3 to 5.0 years of age. In cesarean deliveries, GBS-IAP was associated with increased BMI from 0.7 years to 5.0 years of age (P < .05 for 0.7-0.8 years, P < .0001 for all other time points) compared to other antibiotics (ΔBMI at age 5 years 0.24 kg/m2, 95% CI: .14-.34 kg/m2). Breastfeeding did not modify these associations. CONCLUSIONS: GBS-IAP was associated with a small but sustained increase in BMI starting at very early age. This association highlights the need to better understand the effects of perinatal antibiotic exposure on childhood health.

Neonatal blood culture inoculant volume: feasibility and challenges.

BACKGROUND: Clinicians often express concerns about poor sensitivity of blood cultures in neonates resulting from inadequate inoculant volumes. Our objective was to determine the inoculant volume sent for neonatal sepsis evaluations and identify areas of improvement. METHODS: Single-center prospective observational study of infants undergoing sepsis evaluation. Blood volume was determined by clinician documentation over 21 months, and additionally by weighing culture bottles during 12 months. Adequate volume was defined as ≥1 mL total inoculant per evaluation. For first-time evaluations, local guidelines recommend sending an aerobic-anaerobic pair with 1 mL inoculant in each. RESULTS: There were 987 evaluations in 788 infants. Clinicians reported ≥1 mL total inoculant in 96.9% evaluations. Among 544 evaluations where bottles were weighed, 93.4% had ≥1 mL total inoculant. Very low birth weight infants undergoing evaluations >7 days after birth had the highest proportion of inadequate inoculants (14.4%). Only 3/544 evaluations and 26/1011 bottles had total inoculant <0.5 mL. Ninety evaluations had <1 mL in both aerobic and anaerobic bottles despite a total inoculant volume that allowed inoculation of ≥1 mL in one of the bottles. CONCLUSIONS: Obtaining recommended inoculant volumes is feasible in majority of neonates. Measuring inoculant volumes can focus improvement efforts and improve test reliability. IMPACT: Clinicians express concern about the unreliability of neonatal blood cultures because of inadequate inoculant volume. We investigated over 900 evaluations and found >90% of evaluations have ≥1 mL inoculant. Monitoring adequacy of blood culture technique can identify areas of improvement and may allay concerns about blood culture reliability. Current recommendations for adequate inoculant volume for blood cultures are met in a majority of neonates. Areas of improvement include preterm late-onset sepsis evaluations and distribution techniques during inoculation.

Perinatal COVID-19: guideline development, implementation, and challenges.

PURPOSE OF REVIEW: The aim of this review was to describe the process of and challenges in developing national guidance for management of infants born to mothers with COVID-19. RECENT FINDINGS: Beginning in January 2020, infection with the novel coronavirus SARS-CoV-2 spread across the USA, causing the illness COVID-19. As pregnant women began to present for delivery while sick with COVID-19, the American Academy of Pediatrics (AAP) convened a writing group in March 2020 to develop guidance for the management of their newborns. The initial guidance was developed emergently and was forced to rely on extremely limited data from China. The initial guidance advocated for a conservative approach that included temporary physical separation of infected mother and newborn. To address the knowledge deficit, the AAP sponsored a volunteer registry to collect data on perinatal infection and management. As data have emerged informing the natural history of COVID-19, the performance of PCR-based diagnostics, the value of infection control measures and the risk of infant disease, AAP has issued serial updates to newborn guidance. SUMMARY: Evolving knowledge on the epidemiology of perinatal COVID-19 has informed newborn guidance. The most recent guidance focuses on the use of infection control measures to support maternal-newborn contact and breastfeeding.

Impact of Early-Onset Sepsis and Antibiotic Use on Death or Survival with Neurodevelopmental Impairment at 2 Years of Age among Extremely Preterm Infants.

OBJECTIVE: To evaluate the hypothesis that early-onset sepsis increases risk of death or neurodevelopmental impairment (NDI) among preterm infants; and that among infants without early-onset sepsis, prolonged early antibiotics alters risk of death/NDI. STUDY DESIGN: Retrospective cohort study of infants born at the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers (2006-2014) at 22-26 weeks of gestation and birth weight 401-1000 g. Early-onset sepsis defined as growth of a pathogen from blood or cerebrospinal fluid culture ≤72 hours after birth. Prolonged early antibiotics was defined as antibiotics initiated ≤72 hours and continued ≥5 days without culture-confirmed infection, necrotizing enterocolitis, or spontaneous perforation. Primary outcome was death before follow-up or NDI assessed at 18-26 months corrected age. Poisson regression was used to estimate adjusted relative risk (aRR) and CI for early-onset sepsis outcomes. A propensity score for receiving prolonged antibiotics was derived from early clinical factors and used to match infants (1:1) with and without prolonged antibiotic exposure. Log binomial models were used to estimate aRR for outcomes in matched infants. RESULTS: Among 6565 infants, those with early-onset sepsis had higher aRR (95% CI) for death/NDI compared with infants managed with prolonged antibiotics (1.18 [1.06-1.32]) and to infants without prolonged antibiotics (1.23 [1.10-1.37]). Propensity score matching was achieved for 4362 infants. No significant difference in death/NDI (1.04 [0.98-1.11]) was observed with or without prolonged antibiotics among the matched cohort. CONCLUSIONS: Early-onset sepsis was associated with increased risk of death/NDI among extremely preterm infants. Among matched infants without culture-confirmed infection, prolonged early antibiotic administration was not associated with death/NDI.

Weaning of Moderately Preterm Infants from the Incubator to the Crib: A Randomized Clinical Trial.

OBJECTIVE: To assess whether length of hospital stay is decreased among moderately preterm infants weaned from incubator to crib at a lower vs higher weight. STUDY DESIGN: This trial was conducted in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants with gestational ages 29-33 weeks, birthweight <1600 g, and in an incubator were randomly assigned to a weaning weight of 1600 or 1800 g. Within 60 to 100 g of weaning weight, the incubator temperature was decreased by 1.0°C to 1.5°C every 24 hours until 28.0°C. The infants were weaned to the crib following stable temperature at 36.5°C to 37.4°C for 8 to 12 hours. Clothing and bedcoverings were standardized. The primary outcome was length of hospital stay from birth to discharge; secondary outcomes included length of stay and growth velocity from weaning to discharge. Adverse events were monitored. RESULTS: Of 1565 infants screened, 885 were eligible, and 366 enrolled-187 to the 1600-g and 179 to the 1800-g group. Maternal and neonatal characteristics did not differ among weight groups. Length of hospital stay was a median of 43 days in the lower and 41 days in the higher weight group (P = .12). Growth velocity from completion of weaning to discharge was higher in the lower weight group, 13.7 g/kg/day vs 12.8 g/kg/day (P = .005). Groups did not differ in adverse events. CONCLUSIONS: Among moderately preterm neonates, weaning from incubator to crib at a lower weight did not decrease length of stay, but was safe and was accompanied by higher weight gain after weaning. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02160002.

Prolonged duration of early antibiotic therapy in extremely premature infants.

BACKGROUND: Prolonged early antibiotics in extremely premature infants may have negative effects. We aimed to assess prevalence and outcomes of provision of prolonged early antibiotics to extremely premature infants in the absence of culture-confirmed infection or NEC. METHODS: Cohort study of infants from 13 centers born without a major birth defect from 2008-2014 who were 401-1000 grams birth weight, 22-28 weeks gestation, and survived ≥5 days without culture-confirmed infection, NEC, or spontaneous intestinal perforation. We determined the proportion of infants who received prolonged early antibiotics, defined as ≥5 days of antibiotic therapy started at ≤72 h of age, by center and over time. Associations between prolonged early antibiotics and adverse outcomes were assessed using multivariable logistic regression. RESULTS: A total of 5730 infants were included. The proportion of infants receiving prolonged early antibiotics varied from 30-69% among centers and declined from 49% in 2008 to 35% in 2014. Prolonged early antibiotics was not significantly associated with death (adjusted odds ratio 1.17 [95% CI: 0.99-1.40], p = 0.07) and was not associated with NEC. CONCLUSIONS: The proportion of extremely premature infants receiving prolonged early antibiotics decreased, but significant center variation persists. Prolonged early antibiotics were not significantly associated with increased odds of death or NEC.

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.

Symptomatic Postnatal Cytomegalovirus Testing among Very Low-Birth-Weight Infants: Indications and Outcomes.

Objective The objective of this study was to describe the indications for postnatal cytomegalovirus (CMV) testing among very low-birth-weight (VLBW, birth weight [BW] < 1,500 g) infants, clinical characteristics of infected infants, and adverse outcomes associated with CMV infection. Study Design This is a single-center, retrospective study of 2,132 VLBW infants from 1999 to 2013. Results In this study, 145 (6.8%) infants out of 2,132 were evaluated for postnatal CMV infection and 27 (18.6%) infants out of 145 were infected. CMV-tested infants were of significantly lower gestational age and BW compared with untested VLBW infants (p < 0.001). Respiratory decompensation and thrombocytopenia were the findings most commonly associated with infection. CMV-infected infants had significantly more exposure to mechanical ventilation and longer duration of hospitalization. Adjusting for multiple predictors of respiratory morbidity, the incidence of bronchopulmonary dysplasia (BPD) was significantly elevated among infants diagnosed with postnatal CMV infection (odds ratio, 4.0 [95% confidence interval, 1.3-12.4); p, 0.02.) Conclusion Symptomatic postnatal CMV infection was diagnosed in 1.3% of VLBW infants, most commonly among infants with BW < 1,000 g with respiratory instability and thrombocytopenia. Similar to late-onset bacterial infection, symptomatic postnatal CMV infection may be an independent contributor to the development of BPD. This possibility should be addressed in a prospective study of extremely low BW infants.

Accuracy of ICD-9-CM coding to identify small for gestational age newborns.

PURPOSE: This study aimed to evaluate the accuracy of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code for small for gestational age (SGA) recorded in administrative healthcare records using birthweight and gestational age information recorded in electronic medical records. METHODS: We used billing and medical records from women aged 13-55 years who delivered at a tertiary care center in the USA between 2004 and 2011. Information on birthweight, gestational age at birth, and ICD-9-CM code for SGA, 656.5x, was abstracted from the database. Each infant's birthweight percentile for gestational age was calculated on the basis of published US references; infants below the 10th percentile were classified as SGA. The performance characteristics of SGA ICD-9-CM diagnosis code against SGA classification based on birthweight and gestational age were calculated, for all deliveries and by strata of demographic and delivery characteristics. RESULTS: We identified 51 292 singleton live birth deliveries. The prevalence of SGA infants calculated from birthweight and gestational age at birth was higher (13%) than the prevalence based on ICD-9-CM code (2%). Sensitivity of the SGA ICD-9-CM code was 14.2%, specificity was 99.7%, positive predictive value was 86.8%, and negative predictive value was 88.4%. Stratification by demographic and delivery characteristics yielded similar results. CONCLUSIONS: Identification of SGA infants using ICD-9-CM code, 656.5x, from administrative healthcare records has low sensitivity but high specificity; the accuracy did not differ across demographic and delivery characteristics. Thus, although this source of information would underestimate the prevalence of SGA, it could produce valid relative risk estimates.

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.

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.

The two-component response regulator LiaR regulates cell wall stress responses, pili expression and virulence in group B Streptococcus.

Group B Streptococcus (GBS) remains the leading cause of early onset sepsis among term infants. Evasion of innate immune defences is critical to neonatal GBS disease pathogenesis. Effectors of innate immunity, as well as numerous antibiotics, frequently target the peptidoglycan layer of the Gram-positive bacterial cell wall. The intramembrane-sensing histidine kinase (IM-HK) class of two-component regulatory systems has been identified as important to the Gram-positive response to cell wall stress. We have characterized the GBS homologue of LiaR, the response regulator component of the Lia system, to determine its role in GBS pathogenesis. LiaR is expressed as part of a three-gene operon (liaFSR) with a promoter located upstream of liaF. A LiaR deletion mutant is more susceptible to cell wall-active antibiotics (vancomycin and bacitracin) as well as antimicrobial peptides (polymixin B, colistin, and nisin) compared to isogenic wild-type GBS. LiaR mutant GBS are significantly attenuated in mouse models of both GBS sepsis and pneumonia. Transcriptional profiling with DNA microarray and Northern blot demonstrated that LiaR regulates expression of genes involved in microbial defence against host antimicrobial systems including genes functioning in cell wall synthesis, pili formation and cell membrane modification. We conclude that the LiaFSR system, the first member of the IM-HK regulatory systems to be studied in GBS, is involved in sensing perturbations in the integrity of the cell wall and activates a transcriptional response that is important to the pathogenesis of GBS infection.