Assessment of hemodynamic dysfunction in septic newborns by functional echocardiography: a systematic review.

BACKGROUND: Neonatal sepsis remains a leading cause of mortality in neonatal units. Neonatologist-performed echocardiography (NPE) offers the potential for early detection of sepsis-associated cardiovascular dysfunction. This review examines available echocardiographic findings in septic neonates. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically reviewed prospective observational, cross-sectional, case control, and cohort studies on septic newborns with echocardiographic assessments from PubMed, Scopus and Embase. Quality assessment employed the Newcastle-Ottawa Scale, with results analyzed descriptively. RESULTS: From an initial pool of 1663 papers, 12 studies met inclusion criteria after relevance screening and eliminating duplicates/excluded studies. The review encompassed 438 septic newborns and 232 controls. Septic neonates exhibited either increased risk of pulmonary hypertension or left ventricular diastolic dysfunction, and a warm shock physiology characterized by higher cardiac outputs. DISCUSSION: The included studies exhibited heterogeneity in sepsis definitions, sepsis severity scores, echocardiographic evaluations, and demographic data of newborns. Limited sample sizes compromised analytical interpretability. Nonetheless, this work establishes a foundation for future high-quality echocardiographic studies. CONCLUSION: Our review confirms that septic neonates show significant hemodynamic changes that can be identified using NPE. These findings underscore the need for wider NPE use to tailor hemodynamics-based strategies within this population. IMPACT: 1. Our study emphasizes the value of neonatologist-performed echocardiography (NPE) as a feasible tool for identifying significant hemodynamic changes in septic neonates. 2. Our study underscores the importance of standardized echocardiographic protocols and frequent monitoring of cardiac function in septic neonates. 3. The impact of the study lies in its potential to increase researchers' awareness for the need for more high-quality echocardiographic data in future studies. By promoting wider use of NPE, neonatologists can more accurately assess the hemodynamic status of septic newborns and tailor treatment approaches, potentially improving patient outcomes.

Hemodynamic dysfunction in neonatal sepsis.

Cardiovascular disturbances are a frequent occurrence in neonatal sepsis. Preterm and term infants are particularly vulnerable due to the unique features of their cardiovascular function and reserve, compared to older children and adults. The clinical manifestations of neonatal sepsis are a product of the variable inflammatory pathways involved (warm vs. cold shock physiology), developmental state of the cardiovascular system, and hormonal responses. Targeted neonatal echocardiography has played an important role in advancing our knowledge, may help delineate specific hemodynamic phenotypes in real-time, and supports an individualized physiology-based management of sepsis-associated cardiovascular dysfunction. IMPACT: Cardiovascular dysfunction is a common sequela of sepsis. This review aims to highlight the pathophysiological mechanisms involved in hemodynamic disturbance in neonatal sepsis, provide insights from targeted neonatal echocardiography-based clinical studies, and suggest its potential incorporation in day-to-day management.

Vital signs as physiomarkers of neonatal sepsis.

Neonatal sepsis accounts for significant morbidity and mortality, particularly among premature infants in the Neonatal Intensive Care Unit. Abnormal vital sign patterns serve as physiomarkers of sepsis and provide early warning of illness before overt clinical decompensation. The systemic inflammatory response to pathogens signals the autonomic nervous system, leading to changes in temperature, respiratory rate, heart rate, and blood pressure. In infants with comorbidities of prematurity, vital sign abnormalities often occur in the absence of infection, which confounds sepsis diagnosis. This review will cover the mechanisms of vital sign changes in neonatal sepsis, including the cholinergic anti-inflammatory pathway mediated by the vagus nerve, which is critical to the host response to infectious and inflammatory insults. We will also review the clinical implications of vital sign changes in neonatal sepsis, including their use in early warning scores and systems to direct clinicians to the bedside of infants with physiologic changes that might be due to sepsis. IMPACT: This manuscript summarizes and reviews the relevant literature on the physiological manifestations of neonatal sepsis and how we monitor and analyze these through vital signs and advanced analytics.

Knowledge gaps in late-onset neonatal sepsis in preterm neonates: a roadmap for future research.

Late-onset neonatal sepsis (LONS) remains an important threat to the health of preterm neonates in the neonatal intensive care unit. Strategies to optimize care for preterm neonates with LONS are likely to improve survival and long-term neurocognitive outcomes. However, many important questions on how to improve the prevention, early detection, and therapy for LONS in preterm neonates remain unanswered. This review identifies important knowledge gaps in the management of LONS and describe possible methods and technologies that can be used to resolve these knowledge gaps. The availability of computational medicine and hypothesis-free-omics approaches give way to building bedside feedback tools to guide clinicians in personalized management of LONS. Despite advances in technology, implementation in clinical practice is largely lacking although such tools would help clinicians to optimize many aspects of the management of LONS. We outline which steps are needed to get possible research findings implemented on the neonatal intensive care unit and provide a roadmap for future research initiatives. IMPACT: This review identifies knowledge gaps in prevention, early detection, antibiotic, and additional therapy of late-onset neonatal sepsis in preterm neonates and provides a roadmap for future research efforts. Research opportunities are addressed, which could provide the means to fill knowledge gaps and the steps that need to be made before possible clinical use. Methods to personalize medicine and technologies feasible for bedside clinical use are described.

Diagnosis of neonatal sepsis: the past, present and future.

Sepsis remains a significant cause of neonatal mortality and morbidity, especially in low- and middle-income countries. Neonatal sepsis presents with nonspecific signs and symptoms that necessitate tests to confirm the diagnosis. Early and accurate diagnosis of infection will improve clinical outcomes and decrease the overuse of antibiotics. Current diagnostic methods rely on conventional culture methods, which is time-consuming, and may delay critical therapeutic decisions. Nonculture-based techniques including molecular methods and mass spectrometry may overcome some of the limitations seen with culture-based techniques. Biomarkers including hematological indices, cell adhesion molecules, interleukins, and acute-phase reactants have been used for the diagnosis of neonatal sepsis. In this review, we examine past and current microbiological techniques, hematological indices, and inflammatory biomarkers that may aid sepsis diagnosis. The search for an ideal biomarker that has adequate diagnostic accuracy early in sepsis is still ongoing. We discuss promising strategies for the future that are being developed and tested that may help us diagnose sepsis early and improve clinical outcomes. IMPACT: Reviews the clinical relevance of currently available diagnostic tests for sepsis. Summarizes the diagnostic accuracy of novel biomarkers for neonatal sepsis. Outlines future strategies including the use of omics technology, personalized medicine, and point of care tests.

Probiotics Reduce Mortality and Morbidity in Preterm, Low-Birth-Weight Infants: A Systematic Review and Network Meta-analysis of Randomized Trials.

BACKGROUND & AIMS: We aimed to compare the effectiveness of single- vs multiple-strain probiotics in a network meta-analysis of randomized trials. METHODS: We searched MEDLINE, Embase, Science Citation Index Expanded, CINAHL, Scopus, Cochrane CENTRAL, BIOSIS Previews, and Google Scholar through January 1, 2019, for studies of single-strain and multistrain probiotic formulations on the outcomes of preterm, low-birth-weight neonates. We used a frequentist approach for network meta-analysis and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence. Primary outcomes included all-cause mortality, severe necrotizing enterocolitis (NEC) (Bell stage II or more), and culture-proven sepsis. RESULTS: We analyzed data from 63 trials involving 15,712 preterm infants. Compared with placebo, a combination of 1 or more Lactobacillus species (spp) and 1 or more Bifidobacterium spp was the only intervention with moderate- or high-quality evidence of reduced all-cause mortality (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.39-0.80). Among interventions with moderate- or high-quality evidence for efficacy compared with placebo, combinations of 1 or more Lactobacillus spp and 1 or more Bifidobacterium spp, Bifidobacterium animalis subspecies lactis, Lactobacillus reuteri, or Lactobacillus rhamnosus significantly reduced severe NEC (OR, 0.35 [95% CI, 0.20-0.59]; OR, 0.31 [95% CI, 0.13-0.74]; OR, 0.55 [95% CI, 0.34-0.91]; and OR, 0.44 [95% CI, 0.21-0.90], respectively). There was moderate- or high-quality evidence that combinations of 1 or more Lactobacillus spp and 1 or more Bifidobacterium spp and Saccharomyces boulardii reduced the number of days to reach full feeding (mean reduction of 3.30 days [95% CI, reduction of 5.91-0.69 days]). There was moderate- or high-quality evidence that, compared with placebo, the single-species product B animalis subsp lactis or L reuteri significantly reduced duration of hospitalization (mean reduction of 13.00 days [95% CI, reduction of 22.71-3.29 days] and mean reduction of 7.89 days [95% CI, reduction of 11.60-4.17 days], respectively). CONCLUSIONS: In a systematic review and network meta-analysis of studies to determine the effects of single-strain and multistrain probiotic formulations on outcomes of preterm, low-birth-weight neonates, we found moderate to high evidence for the superiority of combinations of 1 or more Lactobacillus spp and 1 or more Bifidobacterium spp vs single- and other multiple-strain probiotic treatments. The combinations of Bacillus spp and Enterococcus spp, and 1 or more Bifidobacterium spp and Streptococcus salivarius subsp thermophilus, might produce the largest reduction in NEC development. Further trials are needed.

Utility of volatile organic compounds as a diagnostic tool in preterm infants.

BACKGROUND: Volatile organic compounds (VOCs) are hydrocarbons that originate within different healthy and diseased tissues. VOCs can be secreted into the circulation and then excreted in the urine and faeces. In the lungs, VOCs are locally produced and can be detected in exhaled breath. VOCs can be identified using non-invasive techniques, which make their use in preterm infants safe and desirable. METHODS: A systematic search of the literature in PubMed, Embase and Web of Science was conducted looking for VOCs techniques and diagnostic performance in preterm infants. A total of 50 articles identified with only seven papers were included in the final analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: VOCs could diagnose necrotising enterocolitis up to 4 days before a clinical diagnosis; for late onset sepsis, up to 3 days before; and for bronchopulmonary dysplasia, up to 2 weeks before. In addition to these diagnostic uses, VOCs analysis could also distinguish breastfed from formula-fed preterm neonates in the first month of life. CONCLUSION: VOCs analysis is a non-invasive tool that makes the use in preterm infants of preference. VOCs analytic techniques require more research and consensus between researchers to overcome their limitations. IMPACT: Volatile organic compounds are hydrocarbons that can separate between healthy and diseased states in preterm infants. Biomarker panels developed from volatile organic compounds are potential diagnostic tools. The non-invasive nature of acquiring volatile organic compounds markers make it desirable in the paediatric patients. Research into exact chemical components of the volatile organic compounds can inform about the pathophysiology of disease in preterm infants. More robust longitudinal studies with repeated experiments are required before volatile organic compounds can be applied in clinical practice.

A neonatal sequential organ failure assessment score predicts mortality to late-onset sepsis in preterm very low birth weight infants.

BACKGROUND: An operational definition of organ dysfunction applicable to neonates that predicts mortality in the setting of infection is lacking. We determined the utility of an objective, electronic health record (EHR)-automated, neonatal sequential organ failure assessment (nSOFA) score to predict mortality from late-onset sepsis (LOS) in premature, very low birth weight (VLBW) infants. METHODS: Retrospective, single-center study of bacteremic preterm VLBW newborns admitted between 2012 and 2016. nSOFA scores were derived for patients with LOS at multiple time points surrounding the sepsis evaluation. RESULTS: nSOFA scores at evaluation and at all points measured after evaluation were different between survivors and non-survivors. Among patients with an nSOFA score of >4, mortality was higher at evaluation (13% vs 67%, p < 0.001), +6 h (15% vs 64%, p = 0.002), and +12 h (7% vs 71%, p < 0.001) as compared to patients with a score of ≤4. Receiver operating characteristics area under the curve was 0.77 at evaluation (95% CI 0.62-0.92; p = 0.001), 0.78 at +6 h (0.66-0.92; p < 0.001), and 0.93 at +12 h (0.86-0.997; p < 0.001). CONCLUSIONS: The nSOFA scoring system predicted mortality in VLBW infants with LOS and this automated system was integrated into our EHR. Prediction of LOS mortality is a critical step toward improvements in neonatal sepsis outcomes.

Low vasopressin and progression of neonatal sepsis to septic shock: a prospective cohort study.

The study objective was to analyze the association between low plasma vasopressin and progression of sepsis to septic shock in neonates < 34 weeks gestation. Septic neonates of < 34 weeks gestation were consecutively enrolled; moribund neonates and those with major malformations were excluded. Subjects were monitored for progression of sepsis to septic shock over the first 7 days from enrolment. Plasma vasopressin levels and inducible nitric oxide synthase levels were measured at the onset of sepsis (T0), severe sepsis (T1), and septic shock (T2). Primary outcome was plasma vasopressin levels at the point of sepsis in those who progressed to septic shock in comparison with matched nested controls in the non-progression group. Forty-nine (47%) enrolled subjects developed severe sepsis or septic shock. Plasma vasopressin levels (pg/ml) at the onset of sepsis were significantly low in those who progressed to septic shock (median (IQR), 31 (2.5-80) versus 100 (12-156); p = 0.02). After adjusting for confounders, vasopressin levels were independently associated with progression to septic shock (adjusted OR (95% CI), 0.97 (0.96, 0.99); p = 0.01).Conclusion: Preterm septic neonates who progressed to septic shock had suppressed vasopressin levels before the onset of shock. Low vasopressin levels were independently associated with progression to septic shock.What is known:• In animal sepsis models and adult septic patients, exuberant production of nitric oxide metabolites and low vasopressin levels have been reportedly associated with progression to septic shock.• Vasopressin levels have been variably reported as low as well as elevated in children with septic shock.What is New:• Preterm neonates who progressed from sepsis to septic shock had significantly lower levels of vasopressin before the onset of shock in comparison with those who did not progress.• Low vasopressin levels independently predicted the progression from sepsis to septic shock in this population.

C-reactive protein as a predictor of meningitis in early onset neonatal sepsis: a single unit experience.

Objectives To determine whether there is a cut off value of serum C-reactive protein (CRP) associated with a higher risk of meningitis in suspected early onset sepsis (EOS) (onset birth to 7 days of life). Methods A retrospective cohort study on neonates admitted in neonatal intensive care unit at McMaster Children's Hospital from January 2010 to 2017 and had lumbar puncture (LP) and CRP for workup of EOS. Included subjects had either (a) non-traumatic LP or (b) traumatic LP with cerebral spinal fluid (CSF) polymerase chain reaction or gram stain or culture-positive or had received antimicrobials for 21 days. Excluded were CSF done for metabolic errors, before cytomegalovirus (CMV) treatment; from ventriculo-peritoneal (VP) shunts; missing data and contamination. Neonates were classified into definite and probable meningitis and on the range of CRP. We calculated sensitivity, specificity, and likelihood ratios for CRP values; and area under the receiver operating characteristic (AUROC) curve. Results Out of 609 CSF samples, 184 were eligible (28 cases of definite or probable meningitis and 156 controls). Sensitivity, specificity, predictive values, likelihood ratios, and AUROC were too low to be of clinical significance to predict meningitis in EOS. Conclusions Serum CRP values have poor discriminatory power to distinguish between subjects with and without meningitis, in symptomatic EOS.

Implementation of the Neonatal Sepsis Calculator in Early-Onset Sepsis and Maternal Chorioamnionitis.

BACKGROUND: Utilization of the neonatal sepsis calculator published by Kaiser Permanente is rapidly increasing. This freely available online tool can be used in assessment of early-onset sepsis (EOS) in newborns 34 weeks' gestation or more based on maternal risk factors and neonatal examination. However, many hospitals lack standard guidelines for its use, leading to provider discomfort with practice change. PURPOSE: The goal of this project was to study the antibiotic use rate for EOS at a level III neonatal intensive care unit and create standardized guidelines and staff education for using the sepsis calculator. Our ultimate goal was to decrease antibiotic use for EOS in newborns 34 weeks' gestation or more. METHODS: A standard quality improvement Plan-Do-Study-Act (PDSA) model was utilized with a plan to study the problem, implement the intervention, and test again for improvement. The primary outcome of interest was a decrease in the use of antibiotics for EOS in neonates 34 weeks' gestation or more. RESULTS: Over a 4-month period, prior to sepsis calculator implementation, antibiotic use for suspected EOS was 11% and blood culture was done on 14.8% of live births. After implementation of the sepsis calculator and completion of the PDSA cycle, sepsis calculator use was greater than 95%, antibiotic use dropped significantly to 5% (P = .00069), and blood culture use dropped to 7.6% (P = .00046). IMPLICATIONS FOR PRACTICE: Staff education and systematic intervention using a PDSA model can significantly impact patient care, decreasing the administration of antibiotics to infants at risk for sepsis. IMPLICATIONS FOR RESEARCH: Future research is needed to decrease antibiotic use in premature infants less than 34 weeks' gestation with similar risk factors and clinical features.Video Abstract available at https://journals.na.lww.com/advancesinneonatalcare/Pages/videogallery.aspx?videoId=34&autoPlay=true.

Clinical Characteristic and Pathogen Spectrum of Neonatal Sepsis in Guangzhou City from June 2011 to June 2017.

BACKGROUND Preterm and low birth weight (birth weight <2500 g) neonates are vulnerable to sepsis, and the causative pathogens vary in different regions and times. The objective of this study was to identify common organisms leading to neonatal sepsis and identify the characteristic of patients infected with different bacteria, which may help in the selection of antibiotics for empirical treatment. MATERIAL AND METHODS We retrospectively collected the clinical and microbiological data of neonates with culture-proven sepsis in our clinical setting from June 2011 to June 2017. The demography, composition, and distribution of the pathogens and the clinical characteristic of the cases infected with different bacteria were analyzed. RESULTS Of a total of 1048 bacteria that were isolated from patient samples, detailed clinical and microbiological data of 297 cases were available. Escherichia coli, Klebsiella pneumoniae, and coagulase-negative Staphylococcus (co-NS) were the top 3 isolated pathogens. Streptococcus agalactiae predominantly led to early-onset sepsis, while K. pneumoniae and Staphylococcus aureus mainly led to late-onset sepsis. K. pneumoniae was mainly acquired in the hospital. Leukopenia was more commonly seen than leukocytosis in our study, and patients infected with K. pneumoniae and Candida spp encountered more thrombocytopenia. CONCLUSIONS The results of our study revealed the composition of the pathogens of neonatal sepsis in our region and the clinical characteristic of sepsis caused by different bacteria; these data may help in the selection of antibiotics for empirical treatment of neonates with high risk of sepsis.

The combination of procalcitonin and C-reactive protein or presepsin alone improves the accuracy of diagnosis of neonatal sepsis: a meta-analysis and systematic review.

BACKGROUND: Sepsis is an important cause of neonatal morbidity and mortality; therefore, the early diagnosis of neonatal sepsis is essential. METHOD: Our aim was to compare the diagnostic accuracy of procalcitonin (PCT), C-reactive protein (CRP), procalcitonin combined with C-reactive protein (PCT + CRP) and presepsin in the diagnosis of neonatal sepsis. We searched seven databases to identify studies that met the inclusion criteria. Two independent reviewers performed data extraction. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under curve (AUC), and corresponding 95% credible interval (95% CI) were calculated by true positive (TP), false positive (FP), false negative (FN), and true negative (TN) classification using a bivariate regression model in STATA 14.0 software. The pooled sensitivity, specificity, PLR, NLR, DOR, AUC, and corresponding 95% CI were the primary outcomes. Secondary outcomes included the sensitivity and specificity in multiple subgroup analyses. RESULTS: A total of 28 studies enrolling 2661 patients were included in our meta-analysis. The pooled sensitivity of CRP (0.71 (0.63, 0.78)) was weaker than that of PCT (0.85 (0.79, 0.89)), PCT + CRP (0.91 (0.84, 0.95)) and presepsin (0.94 (0.80, 0.99)) and the pooled NLR of presepsin (0.06 (0.02, 0.23)) and PCT + CRP (0.10 (0.05, 0.19)) were less than CRP (0.33 (0.26, 0.42)), and the AUC for presepsin (0.99 (0.98, 1.00)) was greater than PCT + CRP (0.96 (0.93, 0.97)), CRP (0.85 (0.82, 0.88)) and PCT (0.91 (0.89, 0.94)). The results of the subgroup analysis showed that 0.5-2 ng/mL may be the appropriate cutoff interval for PCT. A cut-off value > 10 mg/L for CRP had high sensitivity and specificity. CONCLUSIONS: The combination of PCT and CRP or presepsin alone improves the accuracy of diagnosis of neonatal sepsis. However, further studies are required to confirm these findings.

Potential biomarkers for effective screening of neonatal sepsis infections: An overview.

Neonatal sepsis, a clinical disorder developed by bacterial blood stream infections (BSI) in neonates, is one of the serious global public health problems that must be addressed. More than one million of the estimated global newborn deaths per year are occurred due to severe infections. The genesis of the infection is divided into early-onset sepsis (EOS) and late-onset sepsis (LOS) of the disease. The clinical complications of neonatal sepsis may be associated with bronchopulmonary dysplasia, ductus arteriosus and necrotizing enterocolitis. The clinical diagnosis and treatment of neonatal sepsis is highly complicated. Over the past few years distinct biomarkers have been identified. Most widely used biomarkers are C-reactive protein, Procalcitonin (PCT) and Serum amyloid A (SAA). Until recently, many potential biomarkers including Cell Surface antigens and Bacterial surface antigens and genetic biomarkers are being investigated. Protein biomarkers, cytokines and chemokines are getting much interest for identification of neonatal sepsis infection.

Early-onset neonatal sepsis is associated with a high heart rate during automatically selected stationary periods.

AIM: This study examined the heart rate variability characteristics associated with early-onset neonatal sepsis in a prospective, observational controlled study. METHODS: Eligible patients were full-term neonates hospitalised with clinical signs that suggested early-onset sepsis and a C-reactive protein of >10 mg/L. Sepsis was considered proven in cases of symptomatic septicaemia, meningitis, pneumonia or enterocolitis. Heart rate variability parameters (n = 16) were assessed from five-, 15- and 30-minute stationary sequences automatically selected from electrocardiographic recordings performed at admission and compared with a control group using the U-test with post hoc Benjamini-Yekutieli correction. Stationary sequences corresponded to the periods with the lowest changes of heart rate variability over time. RESULTS: A total of 40 full-term infants were enrolled, including 14 with proven sepsis. The mean duration of the cardiac cycle length was lower in the proven sepsis group than in the control group (n = 11), without other significant changes in heart rate variability parameters. These durations, measured in five-minute stationary periods, were 406 (367-433) ms in proven sepsis group versus 507 (463-522) ms in the control group (p < 0.05). CONCLUSION: Early-onset neonatal sepsis was associated with a high mean heart rate measured during automatically selected stationary periods.

Intraamniotic Infection and the Term Neonate.

Intraamniotic infection (IAI) may occur when the amniotic membranes are ruptured >18 hours prior to birth. The term neonate is at risk for early onset sepsis. This article describes the pathophysiology of IAI and the role of the mother-baby nurse during the anticipated birth and the ongoing assessment of the neonate.

Increased Risk Of Early-Onset Neonatal Sepsis After Laser Surgery For Twin-to-Twin Transfusion Syndrome.

OBJECTIVE: To investigate the occurrence of early-onset neonatal sepsis (EOS) in twin-twin transfusion syndrome (TTTS) managed with laser surgery. STUDY DESIGN: We performed a prospective cohort study of all consecutive TTTS cases treated with laser surgery (TTTS group) delivered at the Leiden University Medical Center. We recorded the occurrence of EOS, defined as a positive blood culture ≤72 hours postpartum (proven sepsis) or administration of a full course of antibiotics due to risk factors or signs of sepsis, in the absence of a positive blood culture (suspected sepsis). Perinatal variables in the TTTS group were compared with uncomplicated monochorionic twins (no-TTTS group). A multivariate model was generated, examining the association between EOS and gestational age at birth, interval between laser surgery and birth, anterior placenta, laser period (first study period: 2002-2008; second study period: 2009-2015), and preterm premature rupture of membranes (PPROM). RESULTS: The rates of combined suspected and proven EOS in the TTTS group and no-TTTS group were 16% (68/416) and 10% (55/542), respectively (relative ratio [RR] 1.74, 95% confidence interval [CI] 1.19-2.55). Multivariate analysis showed that EOS in the TTTS group was independently associated with lower gestational age at birth (odds ratio [OR] 0.75, 95% CI 0.63-0.88), first study period (OR 2.25, 95% CI 1.08-4.67) and PPROM (OR 2.47, 95% CI 1.28-4.75). CONCLUSION: The rate of EOS in the TTTS group is low, but increased compared to the no-TTTS group. EOS in TTTS is independently associated with premature delivery, earlier laser period, and PPROM.

Clinical Indicators of Late-Onset Sepsis Workup in Very Low-Birth-Weight Infants in the Neonatal Intensive Care Unit.

Background Late-onset sepsis (LOS) in very low-birth-weight (VLBW) infants is associated with significant morbidity and mortality. Objectives To determine the incidence of LOS workup, association, and predictive value of clinical indicators leading to culture-positive versus culture-negative sepsis workup. Methods All sepsis workups performed after 7 days of life, in neonates with birth weight of < 1,500 g were included. Each case (culture-positive workup) was matched with a control (culture-negative workup) for gestational age (GA), birth weight, corrected gestational age, and chronological age, at the time of workup. The clinical indicators leading to the performance of sepsis workup were compared between cases and controls. Results The incidence of culture-positive workup was 87/345 (25.2%) and that of LOS was 84/279 (30.1%). Among various clinical indicators, hypothermia and apnea were significantly associated with culture-positive sepsis workup (p = 0.015 and 0.004, respectively), with a positive predictive value of 81.2 and 71.4%, respectively. Conclusion In VLBW infants, one-fourth of sepsis workups resulted in a positive culture. Apnea and hypothermia were the most significant predictors of culture-positive workup after matching for GA, birth weight, chronological age, and corrected GA at the time of the workup.