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

2023

98-104.e6

05/2023

1097-6833

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.

10.1016/j.jpeds.2022.12.007

J Pediatr

36529283

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

2023

e13035

04/2023

2047-6310

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/m , caesarean 0.40 kg/m ).

10.1111/ijpo.13035

Pediatr Obes

37026509

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

2023

02/2023

1098-4275

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.

10.1542/peds.2022-059595

Pediatrics

36995183

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

2023

02/2023

1538-3598

10.1001/jama.2023.0166

JAMA

36735270

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

2022

e2245826

12/2022

2574-3805

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.

10.1001/jamanetworkopen.2022.45826

JAMA Netw Open

36480199

Diagnostic performance and patient outcomes with C-reactive protein use in early-onset sepsis evaluations.

2022

12/2022

1097-6833

OBJECTIVES: To determine performance of C-reactive protein (CRP) in diagnosis of early-onset sepsis (EOS), and to assess patient outcomes with and without routine use of CRP.

STUDY DESIGN: Retrospective cohort study of infants admitted to two neonatal intensive care units. CRP was routinely used in EOS evaluations during 2009-2014; this period was utilized to determine CRP performance at a cut-off of ≥10 mg/L in diagnosis of culture-confirmed EOS. Routine CRP use was discontinued during 2018-2020; outcomes among infants admitted during this period were compared with those in 2012-2014.

RESULTS: From 2009-2014, 10,134 infants were admitted; 9,103 (89.8%) had CRP and 7,549 (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 EOS. 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=4,977) and without (n=5,135) routine use of CRP, we observed lower rates of EOS evaluation (74.5% vs. 50.5%), antibiotic initiation (65.0% vs. 50.8%), and antibiotic prolongation in the absence of EOS (17.3% vs. 7.2%) in the later period. Rate and timing of EOS detection, transfer to a higher level of care, and in-hospital mortality were not different between periods.

CONCLUSIONS: CRP diagnostic performance was not sufficient to guide decision-making in EOS. Discontinuation of routine CRP use was not associated with differences in patient outcomes despite lower rates of antibiotic administration.

10.1016/j.jpeds.2022.12.007

J Pediatr

36529283

Late-Onset Sepsis Among Very Preterm Infants.

2022

11/2022

1098-4275

 

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.

10.1542/peds.2022-058813

Pediatrics

36366916

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

2022

e2240993

11/2022

2574-3805

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.

10.1001/jamanetworkopen.2022.40993

JAMA Netw Open

36350652

Neonatal Early-Onset Sepsis.

2022

756-770

11/2022

1526-9906

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.

10.1542/neo.23-10-e756

Neoreviews

36316253

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

2022

1405-1415

10/2022

1537-6591

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.

10.1093/cid/ciac222

Clin Infect Dis

35323895