Prolonged duration of early antibiotic therapy in extremely premature infants.

BackgroundProlonged 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.MethodsCohort 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.ResultsA 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.ConclusionsThe 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

Postnatal Cytomegalovirus Infection and the Risk for Bronchopulmonary Dysplasia

Postnatally acquired cytomegalovirus (CMV) is typically benign in term infants but, in very low birth weight (VLBW) infants, can cause pneumonitis and sepsis-like illness. Whether postnatal CMV infection results in long-term pulmonary sequelae in these infants is unknown

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

Early-Onset Neonatal Sepsis 2015 to 2017, the Rise of Escherichia coli, and the Need for Novel Prevention Strategies

Importance: Early-onset sepsis (EOS) remains a potentially fatal newborn condition. Ongoing surveillance is critical to optimize prevention and treatment strategies. Objective: To describe the current incidence, microbiology, morbidity, and mortality of EOS among a cohort of term and preterm infants. Design, setting, and participants: This prospective surveillance study included a cohort of infants born at a gestational age (GA) of at least 22 weeks and birth weight of greater than 400 g from 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from April 1, 2015, to March 31, 2017. Data were analyzed from June 14, 2019, to January 28, 2020. Main outcomes and measures: Early-onset sepsis defined by isolation of pathogenic species from blood or cerebrospinal fluid culture within 72 hours of birth and antibiotic treatment for at least 5 days or until death. Results: A total of 235 EOS cases (127 male [54.0%]) were identified among 217 480 newborns (1.08 [95% CI, 0.95-1.23] cases per 1000 live births). Incidence varied significantly by GA and was highest among infants with a GA of 22 to 28 weeks (18.47 [95% CI, 14.57-23.38] cases per 1000). No significant differences in EOS incidence were observed by sex, race, or ethnicity. The most frequent pathogens were Escherichia coli (86 [36.6%]) and group B streptococcus (GBS; 71 [30.2%]). E coli disease primarily occurred among preterm infants (68 of 131 [51.9%]); GBS disease primarily occurred among term infants (54 of 104 [51.9%]), with 24 of 45 GBS cases (53.3%) seen in infants born to mothers with negative GBS screening test results. Intrapartum antibiotics were administered to 162 mothers (68.9%; 110 of 131 [84.0%] preterm and 52 of 104 [50.0%] term), most commonly for suspected chorioamnionitis. Neonatal empirical antibiotic treatment most frequently included ampicillin and gentamicin. All GBS isolates were tested, but only 18 of 81 (22.2%) E coli isolates tested were susceptible to ampicillin; 6 of 77 E coli isolates (7.8%) were resistant to both ampicillin and gentamicin. Nearly all newborns with EOS (220 of 235 [93.6%]) displayed signs of illness within 72 hours of birth. Death occurred in 38 of 131 infected infants with GA of less than 37 weeks (29.0%); no term infants died. Compared with earlier surveillance (2006-2009), the rate of E coli infection increased among very low-birth-weight (401-1500 g) infants (8.68 [95% CI, 6.50-11.60] vs 5.07 [95% CI, 3.93-6.53] per 1000 live births; P = .008). Conclusions and relevance: In this study, EOS incidence and associated mortality disproportionately occurred in preterm infants. Contemporary cases have demonstrated the limitations of current GBS prevention strategies. The increase in E coli infections among very low-birth-weight infants warrants continued study. Ampicillin and gentamicin remained effective antibiotics in most cases, but ongoing surveillance should monitor antibiotic susceptibilities of EOS pathogens

Combining Immature and Total Neutrophil Counts to Predict Early Onset Sepsis in Term and Late Preterm Newborns

BackgroundThe absolute neutrophil count and the immature/total neutrophil ratio (I/T) provide information about the risk of early onset sepsis in newborns. However, it is not clear how to combine their potentially overlapping information into a single likelihood ratio.MethodsWe obtained electronic records of blood cultures and of complete blood counts with manual differentials drawn &lt;1 hour apart on 66,846 infants ≥ 34 weeks gestation and &lt;72 hours of age born at Kaiser Permanente Northern California and Brigham and Women's Hospitals. We hypothesized that dividing the immature neutrophil count (I) by the total neutrophil count (T) squared (I/T) would provide a useful summary of the risk of infection. We evaluated the ability of the I/T to discriminate newborns with pathogenic bacteremia from other newborns tested using the area under the receiver operating characteristic curve (c).ResultsDiscrimination of the I/T (c = 0.79; 95% confidence interval: 0.76-0.82) was similar to that of logistic models with indicator variables for each of 24 combinations of the absolute neutrophil count and the proportion of immature neutrophils (c = 0.80, 95% confidence interval: 0.77-0.83). Discrimination of the I/T improved with age, from 0.70 at &lt;1 hour to 0.87 at ≥ 4 hours. However, 60% of I/T had likelihood ratios of 0.44-1.3, thus only minimally altering the pretest odds of disease.ConclusionsCalculating the I/T could enhance prediction of early onset sepsis, but the complete blood counts will remain helpful mainly when done at &gt;4 hours of age and when the pretest probability of infection is close to the treatment threshold

Postnatal Cytomegalovirus Infection and the Risk for Bronchopulmonary Dysplasia

Postnatally acquired cytomegalovirus (CMV) is typically benign in term infants but, in very low birth weight (VLBW) infants, can cause pneumonitis and sepsis-like illness. Whether postnatal CMV infection results in long-term pulmonary sequelae in these infants is unknown

Stratification of Risk of Early-Onset Sepsis in Newborns ≥34 Weeks’ Gestation

ObjectiveTo define a quantitative stratification algorithm for the risk of early-onset sepsis (EOS) in newborns ≥ 34 weeks' gestation.MethodsWe conducted a retrospective nested case-control study that used split validation. Data collected on each infant included sepsis risk at birth based on objective maternal factors, demographics, specific clinical milestones, and vital signs during the first 24 hours after birth. Using a combination of recursive partitioning and logistic regression, we developed a risk classification scheme for EOS on the derivation dataset. This scheme was then applied to the validation dataset.ResultsUsing a base population of 608,014 live births ≥ 34 weeks' gestation at 14 hospitals between 1993 and 2007, we identified all 350 EOS cases &lt;72 hours of age and frequency matched them by hospital and year of birth to 1063 controls. Using maternal and neonatal data, we defined a risk stratification scheme that divided the neonatal population into 3 groups: treat empirically (4.1% of all live births, 60.8% of all EOS cases, sepsis incidence of 8.4/1000 live births), observe and evaluate (11.1% of births, 23.4% of cases, 1.2/1000), and continued observation (84.8% of births, 15.7% of cases, incidence 0.11/1000).ConclusionsIt is possible to combine objective maternal data with evolving objective neonatal clinical findings to define more efficient strategies for the evaluation and treatment of EOS in term and late preterm infants. Judicious application of our scheme could result in decreased antibiotic treatment in 80,000 to 240,000 US newborns each year

Stratification of Risk of Early-Onset Sepsis in Newborns ≥34 Weeks’ Gestation

OBJECTIVE: To define a quantitative stratification algorithm for the risk of early-onset sepsis (EOS) in newborns ≥34 weeks’ gestation. METHODS: We conducted a retrospective nested case-control study that used split validation. Data collected on each infant included sepsis risk at birth based on objective maternal factors, demographics, specific clinical milestones, and vital signs during the first 24 hours after birth. Using a combination of recursive partitioning and logistic regression, we developed a risk classification scheme for EOS on the derivation dataset. This scheme was then applied to the validation dataset. RESULTS: Using a base population of 608 014 live births ≥34 weeks’ gestation at 14 hospitals between 1993 and 2007, we identified all 350 EOS cases <72 hours of age and frequency matched them by hospital and year of birth to 1063 controls. Using maternal and neonatal data, we defined a risk stratification scheme that divided the neonatal population into 3 groups: treat empirically (4.1% of all live births, 60.8% of all EOS cases, sepsis incidence of 8.4/1000 live births), observe and evaluate (11.1% of births, 23.4% of cases, 1.2/1000), and continued observation (84.8% of births, 15.7% of cases, incidence 0.11/1000). CONCLUSIONS: It is possible to combine objective maternal data with evolving objective neonatal clinical findings to define more efficient strategies for the evaluation and treatment of EOS in term and late preterm infants. Judicious application of our scheme could result in decreased antibiotic treatment in 80 000 to 240 000 US newborns each year