First name
Karen
Middle name
M
Last name
Puopolo

Title

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

Year of Publication

2022

Number of Pages

e2245826

Date Published

12/2022

ISSN Number

2574-3805

Abstract

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.

DOI

10.1001/jamanetworkopen.2022.45826

Alternate Title

JAMA Netw Open

PMID

36480199

Title

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

Year of Publication

2022

Date Published

12/2022

ISSN Number

1097-6833

Abstract

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.

DOI

10.1016/j.jpeds.2022.12.007

Alternate Title

J Pediatr

PMID

36529283

Title

Late-Onset Sepsis Among Very Preterm Infants.

Year of Publication

2022

Date Published

11/2022

ISSN Number

1098-4275

Abstract

 

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.

DOI

10.1542/peds.2022-058813

Alternate Title

Pediatrics

PMID

36366916

Title

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

Year of Publication

2022

Number of Pages

e2240993

Date Published

11/2022

ISSN Number

2574-3805

Abstract

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.

DOI

10.1001/jamanetworkopen.2022.40993

Alternate Title

JAMA Netw Open

PMID

36350652

Title

Neonatal Early-Onset Sepsis.

Year of Publication

2022

Number of Pages

756-770

Date Published

11/2022

ISSN Number

1526-9906

Abstract

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.

DOI

10.1542/neo.23-10-e756

Alternate Title

Neoreviews

PMID

36316253

Title

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

Year of Publication

2022

Number of Pages

1405-1415

Date Published

10/2022

ISSN Number

1537-6591

Abstract

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.

DOI

10.1093/cid/ciac222

Alternate Title

Clin Infect Dis

PMID

35323895

Title

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

Year of Publication

2022

Number of Pages

904-910

Date Published

11/2022

ISSN Number

1532-0987

Abstract

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.

DOI

10.1097/INF.0000000000003671

Alternate Title

Pediatr Infect Dis J

PMID

36102681

Title

Time to positivity of blood cultures in neonatal late-onset bacteraemia.

Year of Publication

2022

Number of Pages

583-588

Date Published

11/2022

ISSN Number

1468-2052

Abstract

OBJECTIVE: To determine the time to positivity (TTP) of blood cultures among infants with late-onset bacteraemia and predictors of TTP >36 hours.

DESIGN: Retrospective cohort study.

SETTING: 16 birth centres in two healthcare systems.

PATIENTS: Infants with positive blood cultures obtained >72 hours after birth.

OUTCOME: The main outcome was TTP, defined as the time interval from specimen collection to when a neonatal provider was notified of culture growth. TTP analysis was restricted to the first positive culture per infant. Patient-specific and infection-specific factors were analysed for association with TTP >36 hours.

RESULTS: Of 10 235 blood cultures obtained from 3808 infants, 1082 (10.6%) were positive. Restricting to bacterial pathogens and the first positive culture, the median TTP (25th-75th percentile) for 428 cultures was 23.5 hours (18.4-29.9); 364 (85.0%) resulted in 36 hours. Excluding coagulase-negative staphylococci (CoNS), 275 of 294 (93.5%) cultures were flagged positive by 36 hours. In a multivariable model, CoNS isolation and antibiotic pretreatment were significantly associated with increased odds of TTP >36 hours. Projecting a 36-hour empiric duration at one site and assuming that all negative evaluations were associated with an empiric course of antibiotics, we estimated that 1164 doses of antibiotics would be avoided in 629 infants over 10 years, while delaying a subsequent antibiotic dose in 13 infants with bacteraemia.

CONCLUSIONS: Empiric antibiotic administration in late-onset infection evaluations (not targeting CoNS) can be stopped at 36 hours. Longer durations (48 hours) should be considered when there is pretreatment or antibiotic therapy is directed at CoNS.

DOI

10.1136/archdischild-2021-323416

Alternate Title

Arch Dis Child Fetal Neonatal Ed

PMID

35273079

Title

Neighborhood Characteristics and Racial Disparities in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Seropositivity in Pregnancy.

Year of Publication

2022

Number of Pages

1018-1026

Date Published

06/2022

ISSN Number

1873-233X

Abstract

OBJECTIVE: To quantify the extent to which neighborhood characteristics contribute to racial and ethnic disparities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity in pregnancy.

METHODS: This cohort study included pregnant patients who presented for childbirth at two hospitals in Philadelphia, Pennsylvania from April 13 to December 31, 2020. Seropositivity for SARS-CoV-2 was determined by measuring immunoglobulin G and immunoglobulin M antibodies by enzyme-linked immunosorbent assay in discarded maternal serum samples obtained for clinical purposes. Race and ethnicity were self-reported and abstracted from medical records. Patients' residential addresses were geocoded to obtain three Census tract variables: community deprivation, racial segregation (Index of Concentration at the Extremes), and crowding. Multivariable mixed effects logistic regression models and causal mediation analyses were used to quantify the extent to which neighborhood variables may explain racial and ethnic disparities in seropositivity.

RESULTS: Among 5,991 pregnant patients, 562 (9.4%) were seropositive for SARS-CoV-2. Higher seropositivity rates were observed among Hispanic (19.3%, 104/538) and Black (14.0%, 373/2,658) patients, compared with Asian (3.2%, 13/406) patients, White (2.7%, 57/2,133) patients, and patients of another race or ethnicity (5.9%, 15/256) (P<.001). In adjusted models, per SD increase, deprivation (adjusted odds ratio [aOR] 1.16, 95% CI 1.02-1.32) and crowding (aOR 1.15, 95% CI 1.05-1.26) were associated with seropositivity, but segregation was not (aOR 0.90, 95% CI 0.78-1.04). Mediation analyses revealed that crowded housing may explain 6.7% (95% CI 2.0-14.7%) of the Hispanic-White disparity and that neighborhood deprivation may explain 10.2% (95% CI 0.5-21.1%) of the Black-White disparity.

CONCLUSION: Neighborhood deprivation and crowding were associated with SARS-CoV-2 seropositivity in pregnancy in the prevaccination era and may partially explain high rates of SARS-CoV-2 seropositivity among Black and Hispanic patients. Investing in structural neighborhood improvements may reduce inequities in viral transmission.

DOI

10.1097/AOG.0000000000004791

Alternate Title

Obstet Gynecol

PMID

35675599

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