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Rationale Bronchopulmonary dysplasia (BPD) is associated with post-prematurity respiratory disease (PRD) in survivors of extreme preterm birth. Identifying early biomarkers that correlate with later development of BPD and PRD may provide insights for intervention. In a preterm baboon model, elevated gastrin-releasing peptide (GRP) is associated with BPD, and GRP inhibition mitigates BPD occurrence. Objective We performed a prospective cohort study to investigate whether urine GRP levels obtained in the first postnatal week were associated with BPD, PRD, and other urinary biomarkers of oxidative stress. Methods Extremely low gestational age infants (23-28 completed weeks) were enrolled in a US multicenter observational study, The Prematurity and Respiratory Outcomes Program (http://clinicaltrials.gov/ct2/show/NCT01435187). We used multivariable logistic regression to examine the association between urine GRP in the first postnatal week and multiple respiratory outcomes: BPD, defined as supplemental oxygen use at 36 + 0 weeks postmenstrual age, and post-PRD, defined by positive quarterly surveys for increased medical utilization over the first year (PRD score). Results A total of 109 of 257 (42%) infants had BPD, and 120 of 217 (55%) had PRD. On adjusted analysis, GRP level more than 80 was associated with BPD (adjusted odds ratio [aOR], 1.83; 95% confidence interval [CI], 1.03-3.25) and positive PRD score (aOR, 2.46; 95% CI, 1.35-4.48). Urine GRP levels correlated with duration of NICU ventilatory and oxygen support and with biomarkers of oxidative stress: allantoin and 8-hydroxydeoxyguanosine. Conclusions Urine GRP in the first postnatal week was associated with concurrent urine biomarkers of oxidative stress and with later diagnoses of BPD and PRD.

Background: The Neonatal Research Network (NRN) has used 3 definitions for bronchopulmonary dysplasia (BPD): 1) a clinical definition based on supplemental oxygen at 36 weeks postmenstrual age (PMA) (clinBPD), 2) a physiologic definition inclusive of a room air challenge (RAC) at 36 weeks (physBPD), and 3) a pragmatic definition based on any respiratory support at 36 weeks (pragBPD). PragBPD has been shown to be strongly correlated …

ObjectiveTo identify sociodemographic and clinical factors associated with withholding or withdrawing life-sustaining treatment (WWLST) for extremely low gestational age neonates.DesignObservational study of prospectively collected registry data from 19 National Institute of Child Health and Human Development Neonatal Research Network centres on neonates born at 22–28 weeks gestation who died >12 hours through 120 days of age during 2011–2016. Sociodemographic and clinical factors were compared between infants who died following WWLST and without WWLST.ResultsOf 1168 deaths, 67.1% occurred following WWLST. Withdrawal of assisted ventilation (97.4%) was the primary modality. WWLST rates were inversely proportional to gestational age. Life-sustaining treatment was withheld or withdrawn more often for non-Hispanic white infants than for non-Hispanic black infants (72.7% vs 60.4%; 95% CI 1.00 to 1.92) or Hispanic infants (72.7% vs 67.2%; 95% CI 1.32 to 3.72). WWLST rates varied across centres (38.6–92.6%; pConclusionsAmong infants who died, WWLST rates varied widely across centres and were associated with gestational age, race, ethnicity, necrotiing enterocolitis, and severe brain injury. Further exploration is needed into how race, centre, and approaches to care of infants with necrotiing enterocolitis and severe brain injury influence WWLST.

Infant delirium is an under-recognized clinical entity in neonatal intensive care, and earlier identification and treatment could minimize morbidities associated with this condition. We describe a case of a 6-month-old former 32 weeks gestation infant undergoing a prolonged mechanical ventilation course diagnosed with delirium related to the combination of his underlying illness and the use of multiple sedative and analgesic medications. Initiation of the atypical antipsychotic risperidone allowed for weaning from continuous infusions of benzodiazepines and opiods, and lower dosages of bolus-dosed sedation and analgesics. The patient experienced no adverse side effects from use of this neuroleptic.

Objective Determine whether antenatal exposure to magnesium is associated with spontaneous intestinal perforation in extremely low birth weight infants (≤1000 g). Study Design We identified all extremely low birth weight infants admitted to one of 323 neonatal intensive care units from 2007 to 2013. We used multivariable conditional logistic regression to compare outcomes in the first 21 days after birth between infants exposed and unexposed to magnesium in utero. Results Of the 28,035 infants, 11,789 (42%) were exposed to antenatal magnesium. There was no difference in the risk of spontaneous intestinal perforation, odds ratio=1.08 (95% confidence interval; 0.91–1.29), between infants exposed and unexposed to antenatal magnesium. Mortality in the first 21 days after birth was lower in the magnesium exposed infants, odds ratio=0.76 (0.70–0.83). Conclusion Antenatal magnesium exposure in extremely low birth weight infants was not associated with increased risk of spontaneous intestinal perforation.

Antibiotics have not only saved lives and improved outcomes, but they also influence the evolving microbiome. This review summarizes reports on neonatal infections and variation in antibiotic utilization, discusses the emergence of resistant organisms, and presents data from human neonates and animal models demonstrating the impact of antibiotics on the microbiome, and how microbiome alterations impact health. The importance of antibiotic stewardship is also discussed.Infections increase neonatal morbidity and mortality. Furthermore, the clinical presentation of infections can be subtle, prompting clinicians to empirically start antibiotics when infection is a possibility. Antibiotic-resistant infections are a growing problem. Cohort studies have identified extensive center variations in antibiotic usage and associations between antibiotic exposures and outcomes. Studies of antibiotic-induced microbiome alterations and downstream effects on the developing immune system have increased our understanding of the mechanisms underlying the associations between antibiotics and adverse outcomes. The emergence of resistant microorganisms and recent evidence linking antibiotic practice variations with health outcomes has led to the initiation of antibiotic stewardship programs.The review encourages practitioners to assess local antibiotic use with regard to local microbiology, and to adopt steps to reduce infections and use antibiotics wisely.

Background Necrotizing enterocolitis (NEC) is a gastrointestinal disease of premature, very low birth weight neonates resulting in sepsis and death. Loop diuretics are widely used in neonates as a treatment for pulmonary fluid retention. An association between diuretic use and NEC has not been explored. Methods The medical records of all neonates admitted to Duke Children's Hospital between 2007 and 2012 with a birth weight ≤1,500 grams were reviewed. Results Using multivariable logistic regression analysis, we found that loop diuretic administration was not a risk factor for the development of NEC. On subanalysis, 75% of medical NEC infants had prior exposure to loop diuretics, compared with 100% of surgical NEC infants ( P = .004). Conclusions Loop diuretics do not increase the risk of development of NEC in very low birth weight neonates. However, on diagnosis of NEC, administration of loop diuretics may be associated with the progression of NEC severity from medical NEC to surgical NEC.

Emerging data suggest intraventricular hemorrhage (IVH) of the preterm neonate is a complex disorder with contributions from both the environment and the genome. Environmental analyses suggest factors mediating both cerebral blood flow and angiogenesis contribute to IVH, while candidate gene studies report variants in angiogenesis, inflammation, and vascular pathways. Gene-by-environment interactions demonstrate the interaction between the environment and the genome, and a non-replicated genome-wide association study suggests that both environmental and genetic factors contribute to the risk for severe IVH in very low-birth weight preterm neonates.

Objective To analyze reasons for low enrollment in an RCT of the effect of hydrocortisone for cardiovascular insufficiency on survival without neurodevelopmental impairment (NDI) in term/late-preterm newborns. Study Design The original study was a multicenter RCT. Eligibility: ≥34 weeks’ gestation

Objective To compare the left ventricular eccentricity index (EI) and tricuspid valve systolic–diastolic (SD) ratio in infants at risk of bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH). Study Design Review of echocardiograms performed on infants born at ≤ 28 weeks' postmenstrual age, categorized into the following three cohorts: BPD and PH (n = 13); BPD only (n = 16); and controls (n = 59). EI was measured from a parasternal short axis 2D image. The SD ratio was measured from the continuous wave Doppler tracing. Groups were compared using Kruskal–Wallis and Wilcoxon rank sum tests. Result EI and SD ratios were successfully measured in all infants. There were no differences between controls and BPD cohort. In contrast, the BPD and PH cohort had increased systolic EI (1.46 vs. 1.00–1.01), diastolic EI (1.47 vs. 1.00), and SD ratio (1.12 vs. 0.97–1.00) compared with controls and BPD only cohort (p ≤ 0.01 for all). Conclusion The EI and SD ratio may be useful as a screening tool for PH in this population.

Evaluate spontaneous intestinal perforation (SIP)/death among extremely low birthweight (ELBW) infants before, during and after initiation of an antenatal magnesium for neuroprotection protocol (MgPro).We tested associations between SIP/death and magnesium exposure, gestational age (GA) and interactions with GA and magnesium exposure in a cohort of inborn ELBW infants before, during and after MgPro.One hundred and fifty-five ELBW infants were included, 81 before, 23 during and 51 after MgPro. ELBW infants (78.3%) were exposed to Mg during MgPro compared with 50.6% and 60.8% before and after, respectively. Incidence of SIP on protocol was 30.4% vs 12.9% off protocol (P=0.03). GA was strongly associated with SIP (P0.01). Antenatal Mg dose was also associated with SIP/death regardless of epoch (odds ratio 9.3 (1.04-104.6)), but increased SIP/death was limited to those25 weeks gestation.Higher Mg dose was associated with higher SIP and death risk among infants with the lowest birthweights. Validation of this observation in larger populations is warranted.

Objective Report clinical response to recombinant factor VIIa in a cohort of critically ill infants. Study Design We identified all infants who received factor VIIa in the Duke Neonatal Intensive Care Unit between January 2005 and July 2008. Hematologic data and volume of blood transfusions before and after factor VIIa treatment were compared. The precipitating diagnosis for each factor VIIa use and the ensuing clinical outcomes of bleeding, thrombosis, and mortality were noted. Result We identified 18 infants with median birth weight of 880 g and median gestational age of 26 weeks. One to six doses of factor VIIa (90 mcg/kg/dose) were administered, with 13 (72%) infants receiving a single dose. Hemostasis was achieved in 13 (72%) of the infants. Prothrombin time and activated partial thromboplastin time significantly decreased following treatment with factor VIIa. Volume of plasma transfusions significantly decreased following treatment with factor VIIa (p=0.02). Thrombosis occurred in 1 (11%) infant. Six (33%) infants died within 72 hours of treatment, and overall mortality was 10/18 (56%). Conclusion Treatment with factor VIIa at doses of 90 mcg/kg improved coagulation studies and decreased the need for plasma transfusions in a group of critically ill infants without significant risk. Factor VIIa may be an effective addition to current treatment modalities for refractory hemorrhage in infants.

Prevalence of renal anomalies after urinary tract infections in hospitalized infants less than 2 months of age

OBJECTIVE Our aim was to assess safety and efficacy of transpyloric tube feeding as a therapeutic option to reduce apnea and bradycardia in hospitalized very low birthweight infants with clinical signs suggestive of gastroesophageal reflux. PATIENTS AND METHODS This was a retrospective single center cohort study of VLBW infants hospitalized from 2001–2004 with signs of GER who received transpyloric enteral tube feedings. Apnea (>10 sec) and bradycardia (

Cerebrospinal fluid (CSF) findings are often used to diagnose meningitis in neonates given antibiotics before the lumbar puncture is performed. Traumatic lumbar punctures are common and complicate interpretation of CSF white blood cell counts. The purpose of this study is to evaluate the diagnostic utility of adjusting CSF white blood cell counts based on CSF and peripheral red blood cell counts.Cohort study of lumbar punctures performed between 1997 and 2004 at 150 neonatal intensive care units managed by the Pediatrix Medical group. Traumatic lumbar punctures were defined as CSF specimens withor =500 red blood cells/mm. CSF white blood cell counts were adjusted downward for traumatic lumbar punctures using several commonly used methods. We calculated sensitivity, specificity, likelihood ratios, and area under the receiver operating characteristic curve of unadjusted and adjusted CSF white blood cell counts for predicting meningitis in neonates with traumatic lumbar punctures.Of 6374 lumbar punctures, 2519 (39.5%) were traumatic. 114/6374 (1.8%) were positive for meningitis; 50 neonates with traumatic lumbar punctures had meningitis. The areas under the receiver operating characteristic curve for white blood cell count unadjusted and adjusted by all methods were similar.Adjustment of CSF white blood cell counts to account for increased red cells does not improve diagnostic utility. Adjustment can result in loss of sensitivity with marginal gain in specificity. Adjustment of WBC counts in the setting of a traumatic lumbar puncture does not aid in the diagnosis of bacterial and fungal meningitis in neonates.

Surgical closure of a patent ductus arteriosus (PDA) continues to be a frequent procedure among extremely preterm infants. Recent evidence indicates surgical closure is associated with worse outcomes than after medical closure. Left vocal fold paralysis is a known complication of this surgery, but there is little information available on the impact of this specific complication on long-term outcomes of these infants. In this case series, we describe the clinical course of three sets of multiple births, in which at least one infant underwent surgical closure of the PDA and subsequently developed feeding and/or breathing difficulties due to left vocal fold paralysis, and compare to their siblings who did not sustain this complication. The case series suggests that some long-term morbidities associated with surgical closure of the PDA may be attributable to this specific complication.

Sepsis is a major cause of neonatal morbidity and mortality, especially in vulnerable preterm populations. Immature immune defenses, and environmental and maternal factors contribute to this risk, with as many as a third of very preterm infants experiencing sepsis during their stay in the neonatal intensive care unit (NICU). Epidemiologic and twin studies have suggested that there is a genetic contribution to sepsis predilection. Several investigators have conducted candidate gene association studies on variants of specific interest and potential functional significance in neonatal sepsis. In this review, we describe details of studies that have evaluated genetic susceptibility in neonatal sepsis, and summarize findings from a review of candidate gene association studies.

Evaluate changes in end-of-life care following initiation of a palliative care program in a neonatal intensive care unit. Retrospective study comparing infant deaths before and after implementation of a Palliative Care Program comprised of medication guidelines, an individualized order set, a nursing care plan and staff education. Eighty-two infants died before (Era 1) and 68 infants died after implementation of the program (Era 2). Morphine use was similar (88% vs 81%; P =0.17), whereas benzodiazepines use increased in Era 2 (26% vs 43%; P=0.03). Withdrawal of life support (73% vs 63%; P=0.17) and do-not-resuscitate orders (46% vs 53%; P=0.42) were similar. Do-not-resuscitate orders and family meetings were more frequent among Era 2 infants with activated palliative care orders (n=21) compared with infants without activated orders (n=47). End-of-life family meetings and benzodiazepine use increased following implementation of our program, likely reflecting adherence to guidelines and improved communication.

Background: Hypoxic ischemic encephalopathy (HIE) is one of the most serious complications of full term birth that can lead to long-term neurological consequences or death. Parents and providers are faced with making complex decisions about which therapies to pursue within hours of birth. Purpose: The purpose of this study was to describe the decisions made for infants with HIE, who participated in the decision-making process, and what factors influenced the decision-making process. Design: A longitudinal, prospective, multiple case study design was used to study infant illness trajectories and parental responses (parental distress and hope) associated with caring for infants with HIE. Results: Two groups of parent decision-making emerged: standard care and experimental care. The decisionmaking groups appear to be dictated by the treatment the infants received within hours of birth. Parents within each group shared specific responses including similar hope and distress, which continued over the first 2 postnatal months. Conclusions: The results indicate that the type of medical therapy the infant receives determines the level of parental participation in decision-making. In the group of parents, in which providers obtained consent for study interventions parents had less hope for their infant even though the infant had a lower severity of illness compared to the infants receiving standard therapies. The reverse was true for parents of infants receiving standard therapy, parents were more hopeful even though their infants had a higher severity of illness.

Pulmonary artery thrombus is a rarely reported complication in premature neonates. The management of life-threatening thrombotic events in neonates is controversial, especially regarding the use of thrombolytics versus anticoagulation alone for treatment. We report a case of a premature neonate with symptomatic pulmonary artery thrombus treated with recombinant tissue plasminogen activator who survived without bleeding complications.

Candidemia is common in extremely low birth weight infants and is associated with substantial mortality and morbidity. Treatment options have traditionally been limited to amphotericin B deoxycholate or fluconazole. We present a case of a premature infant with persistent candidemia despite antifungal treatment that responded to therapy with caspofungin, an echinocandin antifungal. The infant's Candida isolate developed resistance to azoles during fluconazole administration and also suffered from severe hypercalcemia during the initiation of caspofungin therapy.

Sepsis in older children and adults modifies immune system function. We compared serotype-specific antibody responses to heptavalent pneumococcal conjugate vaccine (PCV7) in very low birth weight infants (1500 g,VLBWs) with and without blood stream infection (BSI) during their birth hospitalization.Retrospective analysis of prospectively collected data for the Neonatal Research Network study of PCV7 responses among VLBWs. Infants received PCV7 at 2, 4 and 6 months after birth with blood drawn 4 to 6 weeks after third dose. Serotype antibodies were compared between infants with or without a history of BSI. Regression models were constructed with BW groups and other confounding factors identified in the primary study.In all, 244 infants completed the vaccine series and had serum antibody available; 82 had BSI. After adjustment, BSI was not associated with reduced odds of serum antibody 0.35 μg ml(-1).BSI was not associated with reduced odds of World Health Organization-defined protective PCV7 responses in VLBWs.

To determine the effects of low-dose dopamine on urine output (UOP) in very low birth weight premature neonates.Retrospective cohort study of all low-dose (3-5 μg kg(-1) per min) dopamine infusions24-h duration in neonates 1500 g and 32 weeks gestation from August 2009 through September 2011. Linear regression was used to estimate the impact of covariates on UOP.We identified 91 episodes of low-dose dopamine use in 65 neonates. Increased UOP occurred in 64% of episodes. Low-dose dopamine use was associated with a 0.6 ml kg(-1) h(-1) increase in UOP (P0.001) and a 1.3 ml kg(-1)h(-1) increase when baseline UOP was1.5 ml kg(-1) h(-1) (P0.001). The improvement remained statistically significant after controlling for medications (diuretics and hydrocortisone) and fluid intake.Low-dose dopamine use was associated with increased UOP in very low birth weight neonates.

The purpose of this study is to examine the results of repeat lumbar puncture in infants with initial positive cerebrospinal fluid (CSF) cultures in order to determine the clinical characteristics and outcomes of infants with repeat positive cultures. Cohort study of infants with an initial positive CSF culture undergoing repeat lumbar puncture between 1997 and 2004 at 150 neonatal intensive care units managed by the Pediatrix Medical group. We compared the clinical outcomes of infants with repeat positive cultures and infants with repeat negative cultures. We identified 118 infants with repeat CSF cultures. Of these, 26 infants had repeat positive cultures. A higher proportion with repeat positive cultures died compared with those with repeat negative cultures, 6/23 (26%) vs. 6/81 (7%), respectively (P=0.02). Among infants with a positive CSF culture, a repeat positive CSF culture is common. The presence of a second positive culture is associated with increased mortality.

Intravenous immunoglobulin (IVIg) has been evaluated as an adjunctive therapy for neonatal sepsis with modest clinical success despite strong biological plausibility. Multiple factors contribute to this outcome, but perhaps none greater than the limited immune system function in newborns, especially in the very premature neonates. For very premature neonates (

Determine associations between left vocal cord paralysis (LVCP) and poor respiratory, feeding and/or developmental outcomes in extremely low birth weight (ELBW) infants following surgical closure of a patent ductus arteriosus (PDA). ELBW infants who underwent PDA ligation between January 2004 and December 2006 were identified. We compared infants with and without LVCP following ligation to determine relationships between LVCP and respiratory morbidities, feeding and growth difficulties and neurodevelopmental impairment at 18 to 22-month follow-up. Student's t-test, Fisher's exact test and multivariable regression analyses were used to determine associations. In all, 60 ELBW infants with a mean gestational age of 25 weeks and mean birth weight of 725 g had a PDA surgically closed. Twenty-two of 55 survivors (40%) were diagnosed with LVCP post-operatively. Infants with LVCP were significantly more likely to develop bronchopulmonary dysplasia (82 vs 39%, P=0.002), reactive airway disease (86 vs 33%, P

OBJECTIVES. Our goals were (1) to determine the use of medications to treat gastroesophageal reflux in extremely low birth weight infants (birth weight of METHODS. This retrospective cohort analysis included extremely low birth weight infants enrolled at National Institute of Child Health and Human Development Neonatal Research Network Centers between 2002 and 2003 who survived to follow-up evaluations at corrected ages of 18 to 22 months. Analyses were used to identify factors associated with discharge with antireflux medications and poor growth or neurodevelopmental impairment after discharge. RESULTS. A total of 1598 infants were included in the analyses; 24.8% were discharged from the hospital with medications to treat gastroesophageal reflux. A total of 19.3% of the 1287 infants discharged at postmenstrual age of ≤42 weeks were discharged with antireflux medications. For those infants, center, lower gestational age, and race had significant effects on the use of antireflux medications at discharge. A total of 47.6% of the 311 infants discharged at postmenstrual age of >42 weeks were discharged with antireflux medications. For those infants, no tested variables were associated with treatment with antireflux medications at discharge. Use of antireflux medications at discharge was not associated with either poor growth or neurodevelopmental impairment at corrected ages of 18 to 22 months. CONCLUSIONS. Use of antireflux medications at the time of discharge seems to be common for extremely low birth weight infants, especially those discharged at postmenstrual age of >42 weeks, but does not seem to have effects on growth or development at the time of follow-up evaluations.

Recent reports suggest that specific care strategies improve survival of infants with congenital diaphragmatic hernia (CDH). This review presents details of care from centers reporting high rates of survival among CDH infants. We conducted a MEDLINE search (1995 to 2006) and searched all citations in the Cochrane Central Register of Controlled Trials. Studies were included if they contained reports of >20 infants with symptomatic CDH, and >75% survival of isolated CDH. Thirteen reports from 11 centers met inclusion criteria. Overall survival, including infants with multiple anomalies, was 603/763 (79%; range: 69 to 93%). Survival for isolated CDH was 560/661 (85%; range: 78 to 96%). The frequency of extracorporeal membrane oxygenation (ECMO) use for isolated CDH varied widely among reporting centers 251/622 (40%; range: 11 to 61%), as did survival for infants with isolated CDH placed on ECMO: 149/206 (73%; range: 33 to 86%). There was no suggestion of benefit from use of antenatal glucocorticoids given after 34 weeks gestation or use of postnatal surfactant. Low mortality was frequently attributed to minimizing lung injury and adhering to center-specific criteria for ECMO. Use of strategies aimed at minimizing lung injury, tolerance of postductal acidosis and hypoxemia, and adhering to center-specific criteria for ECMO were strategies most consistently reported by successful centers. The literature lacks randomized clinical trials of these or other care strategies in this complex patient population; prospective studies of safety and long-term outcome are needed.

The purpose of this study was to examine the frequency of normal cerebrospinal fluid (CSF) parameters in Candida meningitis and the proportion of candidemia associated with Candida meningitis.We evaluated the initial lumbar puncture results from infants discharged from 150 Neonatal Intensive Care Units between 1997 and 2004. Candida meningitis was diagnosed by a positive CSF culture or positive Gram stain for yeast. We calculated two-tailed P-values using non-parametric testing, Mann-Whitney, Kruskal-Wallis or Fisher's exact tests where appropriate.Twenty infants had culture-positive Candida meningitis. Normal CSF parameters were found in 43% (3/7) of the infants with Candida meningitis and only 37% (7/19) of them had positive blood cultures for Candida.Normal CSF parameters do not exclude the diagnosis of neonatal Candida meningitis. The majority of infants in this cohort with Candida meningitis did not have evidence of candidemia at the time of diagnosis.

Intestinal malrotation is a relatively uncommon condition with diverse outcomes. Familiarity with variations in the presentation of malrotation is imperative as early diagnosis and prompt subsequent surgical intervention are essential to optimizing outcome. The most frequent clinical sign in the neonate is bile-stained emesis. We report three cases of unsuspected malrotation that were diagnosed in neonates with a history of nonbilious emesis who were assessed for presumed gastroesophageal reflux or aspiration. Gastroesophageal reflux is a common condition among newborns, and can be a subtle presentation of malrotation. Clinicians should consider malrotation as a possible cause of reflux, particularly in infants with unusually pathologic or persistent symptoms necessitating ongoing treatment for reflux.

Neonatal meningitis is an illness with potentially devastating consequences. Early identification of potential risk factors for Gram-negative rod (GNR) infections versus Gram-positive cocci (GPC) infection prior to obtaining final culture results is of value in order to appropriately guide expirical therapy. We sought to compare laboratory and clinical parameters of GNR and GPC meningitis in a cohort of term and premature infants. We evaluated lumbar punctures from neonates cared for at 150 neonatal intensive care units managed by the Pediatrix Medical Group Inc. We compared cerebrospinal fluid (CSF) parameters (white blood cell count, red blood cell count, glucose, and protein), demographics, and outcomes between infants with GNR and GPC meningitis. CSF cultures positive with coagulase-negative staphylococci were excluded. We identified 77 infants with GNR and 86 with GPC meningitis. There were no differences in gestational age, birth weight, infant sex, race, or rate of Caesarean section. GNR meningitis was more often diagnosed after the third postnatal day and was associated with higher white blood cell and red blood cell counts. GNR meningitis diagnosed in the first 3 days of life was associated with antepartum antibiotic exposure. No difference was noted in either CSF protein or glucose levels. After correcting for gestational age, there was no observed difference in mortality between infants infected with GNR or GPC. Compared to GPC meningitis, GNR meningitis was associated with several aspects of the clinical history and laboratory findings including older age of presentation, antepartum exposure to antibiotics, and elevated CSF white blood cell and red blood cell counts.

BACKGROUND: Neonatal nosocomial Gram-negative rod bacteremia (GNR-b) is considered ominous. DESIGN: Multi-center cohort study of premature infants (N=6172) who had a blood culture after day of life 3 and whose birthweight was ≤1250 g. RESULTS: A total of 437 neonates developed GNR-b; most commonly with Klebsiella (122/437; 28%), Enterobacter (97/437; 22%), Escherichia coli (90/437; 21%), Pseudomonas (63/437; 14%), and Serratia (49/437; 11%). Neonates infected with Pseudomonas were more likely to die (21/63; 33%) than infants infected with other GNR (50/374; 13%). In multivariable logistic regression, infection with Pseudomonas, mechanical ventilation, and race were associated with subsequent mortality. Postconception age (PCA) was most strongly associated with mortality. Using neonates with >34 weeks PCA at the time of the first blood culture as the reference category, mortality was higher in neonates

Commentary on: Terrin G, Passariello A, De Curtis M, et al. Ranitidine is associated with infections, necrotizing enterocolitis, and fatal outcome in newborns. Pediatrics 2012;129:e40–5.[OpenUrl][1][Abstract/FREE Full Text][2] Gastroesophageal reflux (GER) is the retrograde movement of stomach contents into the oesophagus. Pharmacotherapy aimed at reducing problems attributed to GER includes histamine receptor blockers (H2 blockers), such as ranitidine, which reduce stomach acidity. Extremely preterm infants often exhibit clinical signs consistent with GER,1 and GER medications are among the most commonly prescribed medications in neonatal intensive care units (NICUs).2 Approximately one third of extremely premature (