Showing papers by "Barbara J. Stoll published in 2013"
TL;DR: Recent trends in epidemiology are reviewed and an update on risk factors, diagnostic methods, and management of neonatal sepsis is provided.
393 citations
TL;DR: In this paper, the incidence of late-onset sepsis and demographic and clinical characteristics associated with LOS in very low birth weight (VLBW) infants from singleton and multiple births, and examined the heritability of susceptibility to LOS among VLBW twins by comparing same-sex and unlike-sex twin pairs.
196 citations
TL;DR: Prophylactic fluconazole administration to very low-birth-weight neonates during the first 6 weeks of life prevents invasive candidiasis in neonatal intensive care units (NICU) with high rates of fungal infections.
Abstract: Identifying neonates with sepsis is complicated by variability in clinical presentation. The incidence of early onset sepsis (EOS) resulting from invasive group B streptococcal (GBS) infections has been notably reduced by the widespread delivery of intrapartum antibiotic prophylaxis. Rates of EOS attributable to non-GBS etiologies have remained constant, and ampicillin-resistant Escherichia coli has become more prevalent. Late-onset sepsis (LOS) attributable to gram-positive organisms including coagulase-negative Staphylococci and Staphylococcus aureus is associated with increased morbidity and mortality among premature infants. Invasive candidiasis is an emerging cause of LOS, especially among infants who receive broad-spectrum antimicrobial agents. Prophylactic fluconazole administration to very low-birth-weight (VLBW) neonates during the first 6 weeks of life prevents invasive candidiasis in neonatal intensive care units (NICU) with high rates of fungal infections. Targeted fluconazole prophylaxis may be beneficial in VLBW neonates who receive care in NICUs with lower rates of invasive fungal infections. Assessment of immune function, neutrophil markers, acute phase reactants, and utilization of sepsis screening scores may contribute to the management of sepsis. Maternal decolonization, antimicrobial stewardship, early enteral feeding, and optimal infection control practices are potential practical strategies for reducing the burden of neonatal sepsis.
132 citations
TL;DR: Data are lacking for impairment after neonatal sepsis and pneumonia, especially among those of >32 wk gestation, and improved recognition and treatment of pSBI will reduce neonatal mortality.
Abstract: Background : Survivors of neonatal infections are at risk of neurodevelopmental impairment (NDI), a burden not previously systematically quantified and yet important for program priority setting. Systematic reviews and meta-analyses were undertaken and applied in a three-step compartmental model to estimate NDI cases after severe neonatal bacterial infection in South Asia, sub-Saharan Africa, and Latin America in neonates of >32 wk gestation (or >1,500 g). Methods: We estimated cases of sepsis, meningitis, pneumonia, or no severe bacterial infection from among estimated cases of possible severe bacterial infection ((pSBI) step 1). We applied respective case fatality risks ((CFRs) step 2) and the NDI risk among survivors (step 3). For neonatal tetanus, incidence estimates were based on the estimated deaths, CFRs, and risk of subsequent NDI. results: For 2010, we estimated 1.7 million (uncertainty range: 1.1–2.4 million) cases of neonatal sepsis, 200,000 (21,000–350,000) cases of meningitis, 510,000 cases (150,000– 930,000) of pneumonia, and 79,000 cases (70,000–930,000) of tetanus in neonates >32 wk gestation (or >1,500 g). Among the survivors, we estimated moderate to severe NDI after neonatal meningitis in 23% (95% confidence interval: 19–26%) of survivors, 18,000 (2,700–35,000) cases, and after neonatal tetanus in 16% (6–27%), 4,700 cases (1,700–8,900). conclusion: Data are lacking for impairment after neonatal sepsis and pneumonia, especially among those of >32 wk gestation. Improved recognition and treatment of pSBI will reduce neonatal mortality. Lack of follow-up data for survivors of severe bacterial infections, particularly sepsis, was striking. Given the high incidence of sepsis, even minor NDI would be of major public health importance. Prevention of neonatal infection, improved case management, and support for children with NDI are all important strategies, currently receiving limited policy attention.
131 citations
Southern Illinois University Carbondale1, Case Western Reserve University2, University of New Mexico3, University of Utah4, University of North Carolina at Chapel Hill5, Stanford University6, University of Alabama at Birmingham7, Indiana University8, University of Iowa9, University of Texas Southwestern Medical Center10, Yale University11, Duke University12, Brown University13, University of Texas Health Science Center at Houston14, Tufts University15, Wayne State University16, University of Cincinnati17, National Institutes of Health18
TL;DR: Infant outcomes were not improved with antihypotensive therapy for any of the 15 definitions of low BP investigated, and factors other than BP contributed to the decision to use antiHypotensive therapies.
Abstract: OBJECTIVE: To investigate the relationships among blood pressure (BP) values, antihypotensive therapies, and in-hospital outcomes to identify a BP threshold below which antihypotensive therapies may be beneficial. METHODS: Prospective observational study of infants 230/7 to 266/7 weeks’ gestational age. Hourly BP values and antihypotensive therapy use in the first 24 hours were recorded. Low BP was investigated by using 15 definitions. Outcomes were examined by using regression analysis controlling for gestational age, the number of low BP values, and illness severity. RESULTS: Of 367 infants enrolled, 203 (55%) received at least 1 antihypotensive therapy. Treated infants were more likely to have low BP by any definition (P CONCLUSIONS: Factors other than BP contributed to the decision to use antihypotensive therapies. Infant outcomes were not improved with antihypotensive therapy for any of the 15 definitions of low BP investigated.
98 citations
TL;DR: In this paper, small for gestational age (SGA) infants were found to have higher mortality and were more likely to have postnatal growth failure, prolonged mechanical ventilation, and postnatal steroid use.
96 citations
TL;DR: This article evaluated the relationship between abnormal feeding patterns and language performance on the Bayley Scales of Infant Development-Third Edition at 18-22 months adjusted age among a cohort of extremely premature infants.
92 citations
Emory University1, United States Environmental Protection Agency2, RTI International3, Duke University4, Case Western Reserve University5, University of Texas Southwestern Medical Center6, National Institutes of Health7, Wayne State University8, University of New Mexico9, University of Miami10, University of Alabama at Birmingham11, University of Cincinnati12, Stanford University13, University of Texas Health Science Center at Houston14, University of Iowa15, University of Rochester16, Brown University17, University of California, San Diego18, Yale University19, Tufts University20, Wake Forest University21
TL;DR: Infants with Candida sepsis and/or meningitis had an increased risk of death and were more likely to have the composite outcome of deathand/or NDI compared with uninfected infants in adjusted analysis.
88 citations
TL;DR: The data support consideration of testing for antiphospholipid antibodies in cases of otherwise unexplained stillbirth, and Elevated levels of anticardiolipin and anti-&bgr;2-glycoprotein-I antibodies were associated with a threefold to fivefold increased odds of stillbirth.
77 citations
TL;DR: It is suggested that deaths may be prevented by standardizing care for very early GA infants, especially for infants born at <25 weeks’ GA, and for infants with GA ≥25 weeks these differences account for only a small part of the variation in mortality.
Abstract: OBJECTIVE: To examine factors affecting center differences in mortality for extremely low birth weight (ELBW) infants. METHODS: We analyzed data for 5418 ELBW infants born at 16 Neonatal Research Network centers during 2006–2009. The primary outcomes of early mortality (≤12 hours after birth) and in-hospital mortality were assessed by using multilevel hierarchical models. Models were developed to investigate associations of center rates of selected interventions with mortality while adjusting for patient-level risk factors. These analyses were performed for all gestational ages (GAs) and separately for GAs RESULTS: Early and in-hospital mortality rates among centers were 5% to 36% and 11% to 53% for all GAs, 13% to 73% and 28% to 90% for GAs CONCLUSIONS: Center intervention rates explain a portion of the center variation in mortality, especially for infants born at
70 citations
TL;DR: Indometacin used for IVH prophylaxis and ANS were not associated with the occurrence of SIP in ELBW infants, but indometacIn used for treatment of symptomatic PDA was however associated with an increased risk of Sip.
Abstract: Background Spontaneous intestinal perforation (SIP) is associated with the use of postnatal glucocorticoids and indometacin in extremely low birth weight (ELBW) infants. The authors hypothesised: 1) an association of SIP with the use of antenatal steroids (ANS) and indometacin either as prophylaxis for intraventricular hemorrhage (IVH) (P Indo) or for treatment of PDA (Indo/PDA) and 2) an increased risk of death or abnormal neurodevelopmental outcomes in infants with SIP at 18–22 months corrected age. Design/Methods The authors retrospectively identified ELBW infants with SIP in the Neonatal Research Network9s generic database. Unadjusted analysis identified the differences in maternal, neonatal and clinical variables between infants with and without SIP. Logistic regression analysis identified the adjusted OR for SIP with reference to ANS, P Indo and Indo/PDA. Neurodevelopmental outcomes were assessed among survivors at 18–22 months corrected age. Results Indo/PDA was associated with an increased risk of SIP (adjusted OR 1.61; 95% CI 1.25 to 2.08), while P Indo and ANS were not. SIP was independently associated with an increased risk of death or neurodevelopmental impairment (NDI) (adjusted OR 1.85; 95% CI 1.32 to 2.60) and NDI among survivors (adjusted OR 1.75, 95% CI 1.20 to 2.55). Conclusion Indometacin used for IVH prophylaxis and ANS were not associated with the occurrence of SIP in ELBW infants. Indometacin used for treatment of symptomatic PDA was however associated with an increased risk of SIP. ELBW infants with SIP have an increased risk of poor neurodevelopmental outcomes.
TL;DR: Effective ameliorative interventions could have a substantial public health impact, since there is at least a 50% increased risk of stillbirth for the approximately 21% of all women and 32% of non-Hispanic black women who experience 3 or more SLE factors during the year prior to delivery.
Abstract: Stillbirths (fetal deaths occurring at ≥20 weeks' gestation) are approximately equal in number to infant deaths in the United States and are twice as likely among non-Hispanic black births as among non-Hispanic white births. The causes of racial disparity in stillbirth remain poorly understood. A population-based case-control study conducted by the Stillbirth Collaborative Research Network in 5 US catchment areas from March 2006 to September 2008 identified characteristics associated with racial/ethnic disparity and interpersonal and environmental stressors, including a list of 13 significant life events (SLEs). The adjusted odds ratio for stillbirth among women reporting all 4 SLE factors (financial, emotional, traumatic, and partner-related) was 2.22 (95% confidence interval: 1.43, 3.46). This association was robust after additional control for the correlated variables of family income, marital status, and health insurance type. There was no interaction between race/ethnicity and other variables. Effective ameliorative interventions could have a substantial public health impact, since there is at least a 50% increased risk of stillbirth for the approximately 21% of all women and 32% of non-Hispanic black women who experience 3 or more SLE factors during the year prior to delivery.
TL;DR: Surgical NEC is a profoundly more proinflammatory disease than SIP and the cytokine profiles of patients with SIP are closer to those of a nonseptic surgical neonate.
Abstract: Objectives The purpose of this study is to characterize the cytokine response of preterm newborns with surgical necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP) before surgical treatment and to relate these finding to intestinal disease (NEC vs. SIP). Study Design The study was a 14-month prospective, cohort study of neonates undergoing surgery or drainage for NEC or SIP or surgical ligation of patent ductus arteriosus (PDA). Multiplex cytokine detection technology was used to analyze six inflammatory markers: interleukin-2, interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 β (IL-1β), interferon-gamma, and tumor necrosis factor-α (TNF-α). Results Patients with NEC had much higher median preoperative levels of IL-6 (NEC: 8,381 pg/mL; SIP: 36 pg/mL; PDA: 25 pg/mL, p Conclusion Surgical NEC is a profoundly more proinflammatory disease than SIP. The cytokine profiles of patients with SIP are closer to those of a nonseptic surgical neonate.
TL;DR: It is suggested that changes in amino acid and nitrogen metabolism resulting from antibiotic- or probiotic-induced shifts in the microbiota are localized to the gut and liver and have limited impact on whole body growth and anabolism in neonatal piglets.
Abstract: We examined whether changes in the gut microbiota induced by clinically relevant interventions would impact the bioavailability of dietary amino acids in neonates. We tested the hypothesis that modulation of the gut microbiota in neonatal pigs receiving no treatment (control), intravenously administered antibiotics, or probiotics affects whole body nitrogen and amino acid turnover. We quantified whole body urea kinetics, threonine fluxes, and threonine disposal into protein, oxidation, and tissue protein synthesis with stable isotope techniques. Compared with controls, antibiotics reduced the number and diversity of bacterial species in the distal small intestine (SI) and colon. Antibiotics decreased plasma urea concentrations via decreased urea synthesis. Antibiotics elevated threonine plasma concentrations and turnover, as well as whole body protein synthesis and proteolysis. Antibiotics decreased protein synthesis rate in the proximal SI and liver but did not affect the distal SI, colon, or muscle. Probiotics induced a bifidogenic microbiota and decreased plasma urea concentrations but did not affect whole body threonine or protein metabolism. Probiotics decreased protein synthesis in the proximal SI but not in other tissues. In conclusion, modulation of the gut microbiota by antibiotics and probiotics reduced hepatic ureagenesis and intestinal protein synthesis, but neither altered whole body net threonine balance. These findings suggest that changes in amino acid and nitrogen metabolism resulting from antibiotic- or probiotic-induced shifts in the microbiota are localized to the gut and liver and have limited impact on whole body growth and anabolism in neonatal piglets.
TL;DR: Precise assignment of GA at death, defined as reliable dating criteria and a short interval during which fetal death was known to have occurred, was possible in 46.6% of cases.
Abstract: Investigation of the factors leading to stillbirth, defined as fetal death ≥ 20 weeks of gestation, should employ the best possible assessment of gestational age (GA) at the time of fetal death. Precise estimation of GA at fetal death requires accuracy of two key pieces of information: the timing of fetal death and the estimated due date (EDD). Unfortunately, precise data are often lacking, particularly regarding timing of fetal death. Some investigators have equated timing of fetal death with the time of delivery1 or have estimated timing of death from pathologic findings in the fetus or placenta2–4. Because there may be a prolonged period between fetal death and delivery, the estimated GA at time of fetal death may be overestimated, particularly when the date of delivery is used as the basis to determine the date of death. The accuracy of vital statistics data and clinicopathologic correlations are impacted when gestational age information is unreliable5,6.
We describe a set of rules (the “algorithm”) developed by the Stillbirth Collaborative Research Network (SCRN) to estimate gestational age at fetal death in cases of singleton stillbirth, incorporating clinical and pathologic data. We report the results obtained by applying the algorithm and evaluate the performance of a key component using a well-dated subset of cases in which both estimated due date and timing of death were known with precision.
TL;DR: Surprisingly, risk of LOS following EOS appeared to be reduced in the smallest, most premature infants, underscoring the need for age-specific analyses of immune function.
Emory University1, United States Environmental Protection Agency2, Wayne State University3, University of Iowa4, Brown University5, Case Western Reserve University6, University of Alabama at Birmingham7, University of Texas Southwestern Medical Center8, Stanford University9, RTI International10, National Institutes of Health11
TL;DR: The prevalence of birth defects in a cohort of very low birth weight infants cared for at the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers over a 10-year period increased and the relationship between anomalies, neonatal outcomes, and surgical care was examined.
Abstract: OBJECTIVE: Birth defects (BDs) are an important cause of infant mortality and disproportionately occur among low birth weight infants. We determined the prevalence of BDs in a cohort of very low birth weight (VLBW) infants cared for at the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) centers over a 10-year period and examined the relationship between anomalies, neonatal outcomes, and surgical care. METHODS: Infant and maternal data were collected prospectively for infants weighing 401 to 1500 g at NRN sites between January 1, 1998, and December 31, 2007. Poisson regression models were used to compare risk of outcomes for infants with versus without BDs while adjusting for gestational age and other characteristics. RESULTS: A BD was present in 1776 (4.8%) of the 37 262 infants in our VLBW cohort. Yearly prevalence of BDs increased from 4.0% of infants born in 1998 to 5.6% in 2007, P P 3 days, more infants with BDs underwent major surgery (48% vs 13%, P CONCLUSIONS: Prevalence of BDs increased during the 10 years studied. BDs remain an important cause of neonatal morbidity and mortality among VLBW infants.
TL;DR: Clinicians must have a clear understanding of the epidemiology and risk factors associated with neonatal infection to ensure prompt diagnostic evaluation and appropriate treatment to decrease infection-related mortality during the neonatal period.
TL;DR: This year is the 125th anniversary of the American Pediatric Society (APS), a time to reflect on the past 125 years of child health and child health research, and consider the health of America’s children in a social and global context.
Abstract: This year is the 125th anniversary of the American Pediatric Society (APS), a time to reflect on the past 125 years of child health and child health research, a time to consider the health of America’s children in a social and global context, and a time to consider the future. This paper is a combination of pediatric and APS history and personal story.
TL;DR: For measurable and sustainable gains in child health, pediatric research should be informed by the changing epidemiology of childhood illness, the need to monitor both survival and long-term outcomes, and the increasing recognition of pediatric origins of adult chronic disease and social determinants of health.
Abstract: DESPITE A REMARKABLE RECORD OF ACCOMPLISHments, the pediatric research community faces mounting evidence that the nature and scope of current research are inadequate. The Editorial “Challenges to Excellence in Child Health Research,” by Zylke et al, casts this paradox in sharp relief by summarizing a series of articles suggesting that the quality and number of pediatric research studies lag behind research focused on adults. For measurable and sustainable gains in child health, pediatric research should be informed by the changing epidemiology of childhood illness, the need to monitor both survival and long-term outcomes, and the increasing recognition of pediatric origins of adult chronic disease and social determinants of health. Recent advances in genetics, imaging, and bioinformatics provide new venues for productive research. Moreover, the status of children in society must be elevated and the political will necessary to provide adequate financial support for research enhanced. A variety of technical challenges specific to child health research have been identified. Of central concern is the relative rarity of serious child health problems, which reflects the success of prior research and public health interventions to reduce traditional threats of acute, infectious diseases. Moreover, improved medical and surgical therapies have transformed important conditions that were once fatal in early childhood into more manageable chronic conditions. However, for many chronic childhood illnesses, etiology is still unclear and therapies are suboptimal. The increased survival of very low-birth-weight, preterm infants has cast attention beyond survival to long-term health and neurodevelopmental outcomes. More broadly, improvements in early outcomes may be fundamental to defining later child and adult health. In addition, injuries are the leading cause of death for children in the United States, demanding increased attention to evidence-based prevention. The shift in the epidemiology of childhood illness away from acute infectious diseases to chronic illness and acute injury highlights the need to develop novel research strategies. Currently funded pediatric research networks could provide a strong foundation for expanded collaborative protocols. For example, the National Institute of Child Health and Human Development Neonatal Research Network could be enhanced by expansion of clinical sites and longer-term outcome studies. The impressive improvement in survival from pediatric cancers has been directly linked to a culture of participation in clinical trials developed by the Children’s Oncology Group. Yet support to bring the group’s successes and innovations to other arenas has been limited. The development of the Standards for Research in (StaR) Child Health, an international network dedicated to improving collaborative pediatric research, has highlighted the technical requirements of high-quality child health research. Although this technical guidance is helpful, the true promise of this effort will be its ability to generate functioning, international collaborations and the financial support such initiatives require. Moreover, the expansion of electronic health records and the development of bioinformatics to integrate health information and biologic specimens create an environment in which every patient is a potential research participant and each can benefit from the contributions of others. At the same time, a continual pipeline of young basic, clinical, and public health scientists interested in advancing child health is needed. Financial support of trainees and young faculty is particularly challenging in pediatrics. The funding model for pediatric care leaves many academic departments, especially in safety-net settings, with limited reserves for research and training. For departments in large children’s hospitals or well-endowed universities, institutional support for research and training should be expanded. Moreover, pediatric leaders need to garner increased public support to make long-term funding for pediatric research training a national priority. Excellent examples of successful public and private programs that should be expanded include the National Institutes of Health (NIH) Pediatric Scientist Development Program, the Robert Wood Johnson Clinical Scholars Program, and training programs associated with the NIH Clinical and Translational Science Awards. These programs ensure rigorous, high-quality research training, providing young faculty with strong foun-
TL;DR: BSI was not associated with reduced odds of World Health Organization-defined protective PCV7 responses in VLBWs, and serotype antibodies were compared between infants with or without a history of BSI.
Abstract: Blood stream infection is associated with altered heptavalent pneumococcal conjugate vaccine immune responses in very low birth weight infants
TL;DR: As postneonatal mortality has declined, an increasing proportion of under-5 deaths are occurring in the neonatal period, underscoring the importance of prevention of neonatal mortality to overall infant and under- 5 mortality.
Abstract: Efforts by developing countries, backed by international support, are helping achieve a steady decline in under-5 mortality. Recent estimates suggest that under-5 deaths fell from 9.6 million to 6.9 million between 2000 and 2011, with the under-5 mortality rate falling from 73 to 51 per 1000 live births.1 This progress, though slower than hoped in some countries, nevertheless gives cause for optimism. Of note, as postneonatal mortality has declined, an increasing proportion of under-5 deaths are occurring in the neonatal period, underscoring the importance of prevention of neonatal mortality to overall infant and under-5 mortality. Research must focus on the design of innovative solutions that are both efficacious and effective for preventing neonatal deaths.
Prematurity and clinical infections are major causes of neonatal deaths. Neonatal infections, including pneumonia, sepsis and meningitis, are estimated to cause over 700,000 deaths each year.2 Until recently, neonatal deaths associated with clinical infections were considered difficult to address, but several advances are paving the way for the design of a concrete strategy and action plan to address infectious causes of neonatal mortality.
TL;DR: It is suggested that blood spot TGF-β alone is unlikely to be a reliable biomarker of a clinically significant PDA or its responsiveness to treatment.
Abstract: Permanent ductal closure involves anatomic remodeling, in which transforming growth factor (TGF)-β appears to play a role. Our objective was to evaluate the relationship, if any, between blood spot TGF-β on day 3 and day 7 of life and patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants. Prospective observational study involving ELBW infants (n = 968) in the National Institute of Child Health and Human Development Neonatal Research Network who had TGF-β measured on filter paper spot blood samples using a Luminex assay. Infants with a PDA (n = 493) were significantly more immature, had lower birth weights, and had higher rates of respiratory distress syndrome than those without PDA (n = 475). TGF-β on days 3 and 7 of life, respectively, were significantly lower among neonates with PDA (median 1,177 pg/ml [range 642–1,896]; median 1,386 pg/ml [range 868–1,913]) compared with others without PDA (median 1,334 pg/ml [range 760–2,064]; median 1,712 pg/ml [range 1,014–2,518 pg/ml]). The significant difference persisted when death or PDA was considered a composite outcome. TGF-β levels were not significantly different among subgroups of infants with PDA who were not treated (n = 51) versus those who were treated medically (n = 283) or by surgical ligation (n = 159). TGF-β was not a significant predictor of death or PDA (day 3 odds ratio [OR] 0.99, 95 % confidence interval [CI] 0.83–1.17; day 7 OR 0.88, 95 % CI 0.74–1.04) on adjusted analyses. Our results suggest that blood spot TGF-β alone is unlikely to be a reliable biomarker of a clinically significant PDA or its responsiveness to treatment.
University of Rochester1, United States Environmental Protection Agency2, University of Texas Southwestern Medical Center3, Wake Forest University4, Oregon Health & Science University5, Wayne State University6, University of Miami7, Duke University8, Emory University9, Stanford University10, Brown University11, University of Alabama at Birmingham12, Rochester General Health System13, RTI International14, National Institutes of Health15
01 Jan 2013
TL;DR: This article cites€27 articles, 15 of which you can access for free at: http://ajpgi.physiology.org/content/279/6/G1249#ref-list-1, which have been cited by€37 other HighWire-hosted articles.
Abstract: You might find this additional info useful...This article cites€27 articles, 15 of which you can access for free at: http://ajpgi.physiology.org/content/279/6/G1249.full#ref-list-1This article has been cited by€37 other HighWire-hosted articles: http://ajpgi.physiology.org/content/279/6/G1249#cited-by Updated information and services including high resolution figures, can be found at: http://ajpgi.physiology.org/content/279/6/G1249.fullAdditional material and information about AJP - Gastrointestinal and Liver Physiology can be found at:http://www.the-aps.org/publications/ajpgiThis information is current as of July 25, 2013.