Munish Gupta

Cord blood biomarkers of the fetal inflammatory response

Objective. In current, neonatal practice, clinical signs of intrauterine infection (IUI) are often non-specific. From a large panel of immune biomarkers, we seek to identify cord blood markers that are most strongly associated with the fetal inflammatory response (FIR), a specific placental lesion associated with serious neonatal complications. Methods. We used multiplex immunoassay to measure 27 biomarkers, selected as part of an NIH-funded study of preterm birth, according to gestational age (GA) and extent of placental inflammation: involvement of chorion, amnion, decidua (maternal inflammatory response, MIR); extension to umbilical cord or chorionic plate (FIR). We used false-discovery rate (FDR < 5%, P < 0.001) to account for multiple comparisons. Results. Among 506 births (GA 23–42 weeks), IL-1β increased with FIR among preterm subgroups (P = 0.0001 for <32 weeks; P = 0.0009 for 33–36 weeks). IL-6 and IL-8 increased with FIR among preterm and full-term infants (P < 0.0001). P-trend for IL-6 and IL-8 with MIR versus FIR was <0.0001. Comparison with respect to clinical IUI yielded persistent elevation with FIR even when clinical signs were absent. The remaining 24 markers were not significantly associated. Conclusion. We conclude that among 27 cord blood biomarkers, IL-1β, IL-6 and IL-8 are selectively associated with FIR. These markers may be clinically useful indicators of extensive IUI associated with poor neonatal outcome.

Impact of clinical and histologic correlates of maternal and fetal inflammatory response on gestational age in preterm births

Objective.u2003To evaluate the impact of clinical and histopathologic correlates related to maternal and fetal inflammatory responses (MIR and FIR) on degree of preterm birth. Methods.u2003Pathology reports and clinical data from 577 singleton preterm births (<37 weeks of gestation) that took place between 1998 and 2004 were analyzed according to decreasing gestational age (≥33 weeks, 29–32 weeks, and <29 weeks). MIR was defined by presence of subchorionitis, chorioamnionitis, deciduitis, or free membranitis; FIR was defined by presence of funisitis or chorionic plate vasculitis. The associations between MIR alone and MIR with FIR and gestational age subgroups were assessed using logistic regression. Results.u2003The presence of FIR in addition to MIR was more strongly associated with degree of prematurity than the presence of MIR alone, especially for those born at <29 weeks (OR = 10.1 (95% CI 4.3–23.7) and OR = 5.3 (95% CI 2.3–12.5), respectively). These associations remained significant after adjusting for maternal race, clinical signs of chorioamnionitis, medically indicated birth, and intrapartum corticosteroid, tocolysis and antibiotic use, and after stratification by clinical signs of chorioamnionitis and medically indicated birth. Conclusions.u2003The combined presence of MIR and FIR is associated with a higher risk of extreme preterm birth (<29 weeks) than MIR alone, suggesting a contributory role of FIR in the pathophysiology of preterm birth.

Improving Care for Neonatal Abstinence Syndrome

BACKGROUND AND OBJECTIVE: Care for neonatal abstinence syndrome (NAS), a postnatal drug withdrawal syndrome, remains variable. We designed and implemented a multicenter quality improvement collaborative for infants with NAS. Our objective was to determine if the collaborative was effective in standardizing hospital policies and improving patient outcomes. METHODS: From 2012 to 2014, data were collected through serial cross-sectional audits of participating centers. Hospitals assessed institutional policies and patient-level data for infants with NAS requiring pharmacotherapy, including length of pharmacologic treatment and length of hospital stay (LOS). Models were fit, clustered according to hospital, to evaluate changes in patient outcomes over time. RESULTS: Among 199 participating centers, the mean number of NAS-focused guidelines increased from 3.7 to 5.1 of a possible 6 (P < .001), with improvements noted in all measured domains. Among infants cared for at participating centers, decreases occurred in median (interquartile range) length of pharmacologic treatment, from 16 days (10 to 27 days) to 15 days (10 to 24 days; P = .02), and LOS from 21 days (14 to 33 days) to 19 days (15 to 28 days; P = .002). In addition, there was a statistically significant decrease in the proportion of infants discharged on medication for NAS, from 39.7% to 26.5% (P = .02). After adjusting for potential confounders, standardized NAS scoring process was associated with shorter LOS (–3.3 days,95% confidence interval, –4.9 to –1.4). CONCLUSIONS: Involvement in a multicenter, multistate quality improvement collaborative focused on infants requiring pharmacologic treatment for NAS was associated with increases in standardizing hospital patient care policies and decreases in health care utilization.

Evaluation of a rapid, real-time intrapartum group B streptococcus assay.

OBJECTIVEnWe sought to evaluate an intrapartum nucleic acid amplification test (NAAT) for group B streptococcus (GBS).nnnSTUDY DESIGNnThis was a prospective cohort study of 559 women comparing intrapartum GBS culture with antepartum culture and intrapartum NAAT.nnnRESULTSnGBS prevalence was 19.5% by antepartum culture and 23.8% by intrapartum culture. Compared with intrapartum culture, antepartum culture had 69.2% sensitivity (60.6-76.9%) and 96.0% specificity (93.7-97.7%). The NAAT demonstrated sensitivity of 90.8% (84.6-95.2%), specificity of 97.6% (95.6-98.8%), and predictive values >92%. The incidence of discordant cultures was 10.4%. Of the women with negative antepartum and positive intrapartum cultures, only 1 (2.4%) received intrapartum antibiotics. Compared with white women, black (P = .02) and Hispanic (P = .02) women were more likely to have discordant cultures.nnnCONCLUSIONnThis intrapartum NAAT has excellent characteristics. It may be superior to antepartum culture for detecting intrapartum GBS-allowing more accurate management of laboring mothers and reducing neonatal GBS sepsis.

Donation after cardiac death: the potential contribution of an infant organ donor population.

OBJECTIVEnTo determine the percentage of deaths in level III neonatal intensive care unit (NICU) settings that theoretically would have been eligible for donation after cardiac death (DCD), as well as the percentage of these who would have been potential DCD candidates based on warm ischemic time.nnnSTUDY DESIGNnWe conducted a retrospective study of all deaths in 3 Harvard Program in Neonatology NICUs between 2005 and 2007. Eligible donors were identified based on criteria developed with our transplantation surgeons and our local organ procurement organization. Potential candidates for DCD were then identified based on an acceptable warm ischemic time.nnnRESULTSnOf the 192 deaths that occurred during the study period, 161 were excluded, leaving 31 theoretically eligible donors. Of these, 16 patients had a warm ischemic time of <1 hour and were potential candidates for DCD of 14 livers and 18 kidneys, and 14 patients had a warm ischemic time of <30 minutes and were potential candidates for DCD of 10 hearts.nnnCONCLUSIONSnEight percent of NICU mortalities were potential candidates for DCD. Based on the size of the potential donor pool, establishing an infant DCD protocol for level III NICUs should be considered.

Effect of Catheter Dwell Time on Risk of Central Line–Associated Bloodstream Infection in Infants

BACKGROUND AND OBJECTIVE: Central venous catheters in the NICU are associated with significant morbidity and mortality because of the risk of central line–associated bloodstream infections (CLABSIs). The purpose of this study was to determine the effect of catheter dwell time on risk of CLABSI. METHODS: Retrospective cohort study of 13u2009327 infants with 15u2009567 catheters (93% peripherally inserted central catheters [PICCs], 7% tunneled catheters) and 256u2009088 catheter days cared for in 141 NICUs. CLABSI was defined using National Health Surveillance Network criteria. We defined dwell time as the number of days from line insertion until either line removal or day of CLABSI. We generated survival curves for each week of dwell time and estimated hazard ratios for CLABSI at each week by using a Cox proportional hazards frailty model. We controlled for postmenstrual age and year, included facility as a random effect, and generated separate models by line type. RESULTS: Median postmenstrual age was 29 weeks (interquartile range 26–33). The overall incidence of CLABSI was 0.93 per 1000 catheter days. Increased dwell time was not associated with increased risk of CLABSI for PICCs. For tunneled catheters, infection incidence was significantly higher in weeks 7 and 9 compared with week 1. CONCLUSIONS: Clinicians should not routinely replace uninfected PICCs for fear of infection but should consider removing tunneled catheters before week 7 if no longer needed. Additional studies are needed to determine what daily maintenance practices may be associated with decreased risk of infection, especially for tunneled catheters.

Is Zero Central Line–Associated Bloodstream Infection Rate Sustainable? A 5-Year Perspective

BACKGROUND AND OBJECTIVE: Adoption and implementation of evidence-based measures for catheter care leads to reductions in central line–associated bloodstream infection (CLABSI) rates in the NICU. The purpose of this study is to evaluate whether this rate reduction is sustainable for at least 1 year and to identify key determinants of this sustainability at the NICU of the Floating Hospital for Children at Tufts Medical Center. METHODS: We reviewed the incidence of CLABSIs in the NICU temporally to the implementation of new practice policies and procedures, from July 2008 to December 2013. RESULTS: Adoption of standardized care practices, including bundles and checklists, was associated with a significant reduction of the CLABSI rate to zero for >370 consecutive days in our NICU in 2012. Overall, our CLABSI rates decreased from 4.1 per 1000 line days in 2009 (13 infections; 3163 line days) to 0.94 in 2013 (2 infections; 2115 line days), which represents a 77% reduction over a 5-year period. In the first quarter of 2013, there was a brief increase in CLABSI rate to 3.3 per 1000 line days; after a series of interventions, the CLABSI rate was maintained at zero for >600 days. Ongoing training, surveillance, and vigilance with catheter insertion and maintenance practices and improved documentation were identified as key drivers for success. CONCLUSIONS: High-quality training, strict compliance with evidence-based guidelines, and thorough documentation is associated with significant reductions in CLABSIs. Mindful organizing may lead to a better understanding of what goes into a unit’s ability to handle peak demands and sustain extraordinary performance in the long-term.

Low Urine Vascular Endothelial Growth Factor Levels Are Associated with Mechanical Ventilation, Bronchopulmonary Dysplasia and Retinopathy of Prematurity

Background: Organ-specific vascular endothelial growth factor (VEGF) expression is decreased during the pathogenesis of bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) several weeks before either disease can be diagnosed. Early measurement of organ-specific tissue VEGF levels might allow identification of infants at high risk for these diseases, but is not clinically feasible. Urine VEGF is easily measured and useful in early diagnosis of several diseases. Objectives: Our aims were to assess the correlation of urine VEGF levels measured in the first postnatal month with subsequent BPD or ROP diagnosis and to determine whether various infant characteristics influence urine VEGF levels. Methods: 106 subjects born at <29 weeks gestation and surviving to 36 weeks postmenstrual age were selected from an existing database and biorepository. Urine VEGF and total protein were measured in 2-3 samples per subject. Results: Urine VEGF/protein levels increased by 72% per week (p < 0.0001) during the first postnatal month. In multivariable analysis controlling for postnatal age, lower VEGF/protein was associated with higher levels of mechanical respiratory support (p = 0.006), male gender (p = 0.001) and early sepsis (p = 0.003) but not with fraction of inspired oxygen. Lower urine VEGF/protein and mechanical ventilation were each associated with BPD and ROP. In analyses adjusted for respiratory support, lower urine VEGF/protein and ROP remained associated but urine VEGF/protein and BPD did not. Conclusions: Low urine VEGF/protein levels in the first postnatal month are associated with mechanical ventilation, BPD, and ROP.

Developing a Quality and Safety Curriculum for Fellows: Lessons Learned From a Neonatology Fellowship Program

Formal training in health care quality and safety has become an important component of medical education at all levels, and quality and safety are core concepts within the practice-based learning and system-based practice medical education competencies. Residency and fellowship programs are rapidly attempting to incorporate quality and safety curriculum into their training programs but have encountered numerous challenges and barriers. Many program directors have questioned the feasibility and utility of quality and safety education during this stage of training. In 2010, we adopted a quality and safety educational module in our neonatal fellowship program that sought to provide a robust and practical introduction to quality improvement and patient safety through a combination of didactic and experiential activities. Our module has been successfully integrated into the fellowship programs curriculum and has been beneficial to trainees, faculty, and our clinical services, and our experience suggests that fellowship may be particularly well suited to incorporation of quality and safety training. We describe our module and share tools and lessons learned during our experience; we believe these resources will be useful to other fellowship programs seeking to improve the quality and safety education of their trainees.

A survey of infection control practices for influenza in mother and newborn units in US hospitals

The purpose of this study was to describe infection control practices for influenza in mother and newborn units in United States hospitals in the context of the 2009 H1N1 pandemic. We conducted surveys of neonatal intensive care unit directors in February and November 2010 and requested information on infection control practices during the 2009 and 2010 influenza seasons. We received 111 responses to the initial survey and 48 to the follow-up survey. In 2009, 58% of respondents restricted breastfeeding by mothers with influenza-like illness; 42% did not. Ninety percent of the respondents maintained physical separation between an ill mother and her newborn infant, although the approaches to this separation varied. Eighty percent of postpartum units and 89% of neonatal intensive care units restricted access by children. In 2010, fewer hospitals restricted mother-infant contact and children visitation compared with 2009. Infection control practices for influenza in mother and newborn units vary considerably in US hospitals, particularly regarding contact between an ill mother and her newborn infant. The identification of this variation may inform best practices in this area, as well as future investigations and future guideline development.