Sagori Mukhopadhyay

Risk Assessment in Neonatal Early Onset Sepsis

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.

Neonatal early-onset sepsis evaluations among well-appearing infants: projected impact of changes in CDC GBS guidelines

Objective:To determine (a) the proportion of asymptomatic infants born at ⩾35 weeks gestation evaluated for early-onset sepsis (EOS) and exposed to postnatal antibiotics; (b) reasons for and outcomes of the evaluations, and (c) anticipated changes when applying the Centers for Disease Control and Prevention (CDC) 2010 guidelines to this study population.Study Design:Retrospective cohort study of infants born at ⩾35 weeks gestation in 2008–2009 in a large maternity center.Result:Out of the 7226 infants that met the study criteria: 1062 (14.7%) were evaluated for EOS and half of those evaluated, received empiric antibiotics. 70.4% of evaluations were performed owing to maternal intrapartum fever, but 23% were prompted by inadequate Group B Streptococcus (GBS) prophylaxis alone. Three cases of blood culture-proven infection were identified.Conclusion:Improved approaches are needed to identify asymptomatic infants who are at risk for EOS to decrease unnecessary evaluations and antibiotic exposure. Transition to the 2010 CDC GBS guidelines may eliminate a quarter of EOS evaluations among these infants.

2010 Perinatal GBS Prevention Guideline and Resource Utilization

OBJECTIVES: To quantify differences in early-onset sepsis (EOS) evaluations, evaluation-associated resource utilization, and EOS cases detected, when comparing time periods before and after the implementation of an EOS algorithm based on the Centers for Disease Control and Prevention (CDC) 2010 guidelines for prevention of perinatal Group B Streptococcus (GBS) disease. METHODS: Retrospective cohort study of infants born at ≥36 weeks’ gestation from 2009 to 2012 in a single tertiary care center. One 12-month period during which EOS evaluations were based on the CDC 2002 guideline was compared with a second 12-month period during which EOS evaluations were based on the CDC 2010 guideline. A cost minimization analysis was performed to determine the EOS evaluation-associated costs and resources during each time period. RESULTS: During the study periods, among well-appearing infants ≥36 weeks’ gestation, EOS evaluations for inadequate GBS prophylaxis decreased from 32/1000 to <1/1000 live births; EOS evaluation-associated costs decreased by

Effect of Early-Onset Sepsis Evaluations on In-Hospital Breastfeeding Practices Among Asymptomatic Term Neonates

6994 per 1000 live births; and EOS evaluation-associated work hours decreased by 29 per 1000 live births. We found no increase in EOS evaluations for other indications, total NICU admissions, frequency of infants evaluated for symptoms before hospital discharge, or incidence of EOS during the 2 study periods. CONCLUSIONS: Implementation of an EOS algorithm based on CDC 2010 GBS guidelines resulted in a 25% decrease in EOS evaluations performed among well-appearing infants ≥36 weeks’ gestation, attributable to decreased evaluation of infants born in the setting of inadequate indicated GBS prophylaxis. This resulted in significant changes in EOS evaluation-associated resource expenditures.

Variation in sepsis evaluation across a national network of nurseries

OBJECTIVE To examine the effect of separation for early-onset sepsis (EOS) evaluations due to perinatal risk factors on breastfeeding practices among asymptomatic term newborns. METHODS This observational study included 692 nulliparous women with term, singleton uncomplicated pregnancies who intended to breastfeed and whose infants were well appearing at birth. We examined the rate of early breastfeeding initiation (within 2 hours of birth) and formula supplementation (in the first 24 hours) among this mother-infant cohort. RESULTS Asymptomatic infants separated for EOS evaluation within 2 hours of birth were more likely to have delayed initiation of breastfeeding (46.5% vs 12.5%; P<.001). This association remained significant when adjusted for potential confounders (adjusted odds ratio [aOR]: 5.5 [95% confidence interval (CI): 3.4-8.9]; P<.001). Among infants separated for EOS evaluation, mother-infant time together of ≤0.5 hour in the first 2 hours of life significantly delayed initiation (aOR: 8.9 [95% CI: 1.5-53.7]; P=.02) compared with infants spending >1.5 hours with their mothers. In bivariate analysis, both separation and initiation were associated with formula supplementation. After adjusting for confounders, only delayed initiation remained significantly associated with supplementation (aOR: 1.9 [95% CI: 1.1-3.5]; P=.03). CONCLUSIONS Early separation of asymptomatic infants from their mothers for EOS evaluation was significantly associated with delayed initiation of breastfeeding, which in turn was associated with increased formula supplementation in the first day of life. This unintended consequence of EOS evaluations among asymptomatic infants may be minimized by delaying early separation for performance of the evaluation, attempting breastfeeding initiation before separation, and/or applying more efficient criteria for identifying infants requiring evaluation.

The effect of obstetric practice change to reduce early term delivery on perinatal outcome.

Variation exists in risk assessment of early onset sepsis that impacts the level of medical intervention and frequency of mother-infant separation among well-appearing term newborns. BACKGROUND AND OBJECTIVES: The extent to which clinicians use currently available guidelines for early-onset sepsis (EOS) screening has not been described. The Better Outcomes through Research for Newborns network represents 97 nurseries in 34 states across the United States. The objective of this study was to describe EOS risk management strategies across a national sample of newborn nurseries. METHODS: A Web-based survey was sent to each Better Outcomes through Research for Newborns network nursery site representative. Nineteen questions addressed specific practices for assessing and managing well-appearing term newborns identified at risk for EOS. RESULTS: Responses were received from 81 (83%) of 97 nurseries located in 33 states. Obstetric diagnosis of chorioamnionitis was the most common factor used to identify risk for EOS (79 of 81). Among well-appearing term infants with concern for maternal chorioamnionitis, 51 of 79 sites used American Academy of Pediatrics or Centers for Disease Control and Prevention guidelines to inform clinical care; 11 used a published sepsis risk calculator; and 2 used clinical observation alone. Complete blood cell count (94.8%) and C-reactive protein (36.4%) were the most common laboratory tests obtained and influenced duration of empirical antibiotics at 13% of the sites. Some degree of mother–infant separation was required for EOS evaluation at 95% of centers, and separation for the entire duration of antibiotic therapy was required in 40% of the sites. CONCLUSIONS: Substantial variation exists in newborn EOS risk assessment, affecting the definition of risk, the level of medical intervention, and ultimately mother–infant separation. Identification of the optimal approach to EOS risk assessment and standardized implementation of such an approach could affect care of a large proportion of newborns.

Clinical and Microbiologic Characteristics of Early-onset Sepsis Among Very Low Birth Weight Infants: Opportunities for Antibiotic Stewardship

Objective:To investigate whether the national emphasis on attaining ⩾39 weeks gestation has altered obstetric practice, and if so whether this has affected perinatal morbidity.Study Design:We examined trends in gestational age, neonatal morbidity, maternal complications and stillbirth for a retrospective cohort of singleton, live births between 37+0 and 39+6 weeks of gestation over a 5-year period at a single tertiary care center.Result:There were 21 343 eligible deliveries. The proportion of deliveries in the early term (<39 weeks) decreased from 47.8 to 40.2% (P<0.01). The reduction was most pronounced for elective inductions (27.5 to 8.0%; P<0.01) and scheduled cesareans (56.9 to 24.9%; P<0.01), although a similar trend was seen for nonelective inductions (51.2 to 47.9%; P=0.03). In multivariable analysis, there was a 10% decreased odds of early term delivery per year (P<0.01). There were no changes in the rates of neonatal intensive care unit (NICU) evaluation (29.8 to 28.1%; P=0.11), pre-eclampsia (7.6 to 8.5%; P=0.06) or stillbirth (11.5 to 14.4 per 10 000; P=0.55).Conclusion:A 10% annual decline in the odds of early term delivery was not accompanied by significant changes in perinatal morbidity.

Identification of extremely premature infants at low risk for early-onset sepsis

Background: Most very low birth weight (VLBW, birth weight <1500 g) infants receive empiric antibiotics for risk of early-onset sepsis (EOS). The objective of this study was to determine the characteristics of VLBW infants with culture-confirmed EOS at a single center during 25 years and to identify opportunities for antibiotic stewardship. Methods: Retrospective cohort study includes VLBW infants admitted from 1990 to 2015. EOS was defined as isolation of a pathogen in blood or cerebrospinal fluid culture obtained at <72 hours of age. Clinical and microbiologic characteristics of EOS case infants were obtained by review of medical, laboratory and administrative records. Blood culture, antibiotic initiation and maternal discharge code data were available for all VLBW infants born between 1999 and 2013. Result: One-hundred nine EOS cases (20.5/1000 VLBW births) occurred during the study period. Preterm labor, preterm rupture of membranes and/or the obstetrical diagnosis of chorioamnionitis were present in 106/109 cases (97%). Obligate anaerobic organisms accounted for 16% of cases. Time to culture positivity was 36 hours for 88% and 48 hours for 98% of cases. From 1999 to 2013, 97% of VLBW infants were evaluated for EOS and 90% administered empiric antibiotics; 22% of these infants were born by cesarean section to mothers with preeclampsia and without preterm labor or chorioamnionitis and had a 12-fold lower incidence of EOS compared with the remaining infants. Conclusion: Decisions to initiate and discontinue empiric antibiotics among VLBW infants can be informed by the delivery characteristics of infected infants and by local microbiologic data.BACKGROUND Most very-low birth weight (birth weight <1500 grams, VLBW) infants receive empiric antibiotics for risk of early-onset sepsis (EOS). The objective of this study was to determine the characteristics of VLBW infants with culture-confirmed EOS at a single center during 25 years, to identify opportunities for antibiotic stewardship. METHODS Retrospective cohort study including VLBW infants admitted from 1990-2015. EOS was defined as isolation of a pathogen in blood or cerebrospinal fluid culture obtained < 72 hours of age. Clinical and microbiologic characteristics of EOS case infants were obtained by review of medical, laboratory and administrative records. Blood culture, antibiotic initiation, and maternal discharge code data was available for all VLBW infants born 1999-2013. RESULT 109 EOS cases (20.5/1000 VLBW births) occurred during the study period. Preterm labor, preterm rupture of membranes and/or the obstetrical diagnosis of chorioamnionitis were present in 106/109 cases (97%). Obligate anaerobic organisms accounted for 16% of cases. Time to culture positivity was 36 hours for 88% and 48 hours for 98% of cases. From 1999-2013, 97% of VLBW infants were evaluated for EOS and 90% administered empiric antibiotics; 22% of these infants were born by Cesarean section to mothers with pre-eclampsia and without preterm labor or chorioamnionitis and had a 12-fold lower incidence of EOS compared to the remaining infants. CONCLUSION Decisions to initiate and discontinue empiric antibiotics among VLBW infants can be informed by the delivery characteristics of infected infants, and by local microbiologic data.

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

Delivery characteristics of infants born at 22 to 28 weeks’ gestation can be used to identify those with significantly lower risk of EOS. BACKGROUND: Premature infants are at high risk of early-onset sepsis (EOS) relative to term infants, and most are administered empirical antibiotics after birth. We aimed to determine if factors evident at birth could be used to identify premature infants at lower risk of EOS. METHODS: Study infants were born at 22 to 28 weeks’ gestation in Neonatal Research Network centers from 2006 to 2014. EOS was defined by isolation of pathogenic species from blood or cerebrospinal fluid culture at ≤72 hours age. Infants were hypothesized as “low risk” for EOS when delivered via cesarean delivery, with membrane rupture at delivery, and absence of clinical chorioamnionitis. Frequency of prolonged antibiotics (≥5 days) was compared between low-risk infants and all others. Risks of mortality, EOS, and other morbidities were assessed by using regression models adjusted for center, race, antenatal steroid use, multiple birth, sex, gestation, and birth weight. RESULTS: Of 15 433 infants, 5759 (37%) met low-risk criteria. EOS incidence among infants surviving >12 hours was 29 out of 5640 (0.5%) in the low-risk group versus 209 out of 8422 (2.5%) in the comparison group (adjusted relative risk = 0.24 [95% confidence interval, 0.16–0.36]). Low-risk infants also had significantly lower combined risk of EOS or death ≤12 hours. Prolonged antibiotics were administered to 34% of low-risk infants versus 47% of comparison infants without EOS. CONCLUSIONS: Delivery characteristics of extremely preterm infants can be used to identify those with significantly lower incidence of EOS. Recognition of differential risk may help guide decisions to limit early antibiotic use among approximately one-third of these infants.

Temporal Trends and Center Variation in Early Antibiotic Use Among Premature Infants

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.