Treating Center Volume and Congenital Diaphragmatic Hernia Outcomes in California.

OBJECTIVE: To examined outcomes for infants born with congenital diaphragmatic hernias (CDH), according to specific treatment center volume indicators. STUDY DESIGN: A population-based retrospective cohort study was conducted involving neonatal intensive care units in California. Multivariable analysis was used to examine the outcomes of infants with CDH including mortality, total days on ventilation, and respiratory support at discharge. Significant covariables of interest included treatment center surgical and overall neonatal intensive care unit volumes. RESULTS: There were 728 infants in the overall CDH cohort, and 541 infants (74%) in the lower risk subcohort according to a severity-weighted congenital malformation score and never requiring extracorporeal membrane oxygenation. The overall cohort mortality was 28.3% (n = 206), and 19.8% (n = 107) for the subcohort. For the lower risk subcohort, the adjusted odds of mortality were significantly lower at treatment centers with higher CDH repair volume (OR, 0.41; 95% CI, 0.23-0.75; P = .003), ventilator days were significantly lower at centers with higher thoracic surgery volume (OR, 0.56; 9 5% CI, 0.33-0.95; P = .03), and respiratory support at discharge trended lower at centers with higher neonatal intensive care unit admission volumes (OR, 0.51; 9 5% CI, 0.26-1.02; P = .06). CONCLUSIONS: Overall and surgery-specific institutional experience significantly contribute to optimized outcomes for infants with CDH. These data and follow-on studies may help inform the ongoing debate over the optimal care setting and relevant quality indicators for newborn infants with major surgical anomalies.

Point-of-Care Fecal Calprotectin Monitoring in Preterm Infants at Risk for Necrotizing Enterocolitis.

OBJECTIVE: To establish baseline trends in fecal calprotectin, a protein excreted into the stool when there is neutrophilic inflammation in the bowel, in infants at risk for necrotizing enterocolitis (NEC). STUDY DESIGN: We performed a prospective observational cohort study in infants with a birth weight of <1500 g without existing bowel disease at a level IV neonatal intensive care unit from October 2015 to September 2016. Stools were collected once daily for 30 days or until 32 weeks postmenstrual age and processed using the Fecal Calprotectin High Range Quantitative Quantum Blue assay. RESULTS: In 64 preterm infants, during the first week after birth, 62% of infants had an initial stool sample with high baseline calprotectin levels (≥200 µg/g). In assessment of maternal and neonatal risk factors, maternal etiology for preterm birth (ie, eclamplsia or preeclampsia) was the only significant factor associated with high baseline calprotectin level. Two patients in the cohort developed NEC. Calprotectin levels for the entire cohort fluctuated during the observed period but generally increased in the third and fourth weeks after birth. CONCLUSIONS: At-risk infants had highly variable fecal calprotectin levels, with maternal causes for preterm birth associated with higher baseline levels. More longitudinal data in infants with NEC are necessary to determine whether acute rises in fecal calprotectin levels prior to clinical diagnosis can be confirmed as a diagnostic or prognostic biomarker.

The Effect of Level of Care on Gastroschisis Outcomes.

OBJECTIVE: To examine the relationship between level of care in neonatal intensive care units (NICUs) and outcomes for newborns with gastroschisis. STUDY DESIGN: A retrospective cohort study was conducted at 130 California Perinatal Quality Care Collaborative NICUs from 2008 to 2014. All gastroschisis births were examined according to American Academy of Pediatrics NICU level of care at the birth hospital. Multivariate analyses examined odds of mortality, duration of mechanical ventilation, and duration of stay. RESULTS: For 1588 newborns with gastroschisis, the adjusted odds of death were higher for those born into a center with a level IIA/B NICU (OR, 6.66; P = .004), a level IIIA NICU (OR, 5.95; P = .008), or a level IIIB NICU (OR, 5.85; P = .002), when compared with level IIIC centers. The odds of having more days on ventilation were significantly higher for births at IIA/B and IIIB centers (OR, 2.05 [P < .001] and OR, 1.91 [P < .001], respectively). The odds of having longer duration of stay were significantly higher at IIA/B and IIIB centers (OR, 1.71 [P < .004]; OR, 1.77 [P < .001]). CONCLUSIONS: NICU level of care was associated with significant disparities in odds of mortality for newborns with gastroschisis.

Acylcarnitine Profiles Reflect Metabolic Vulnerability for Necrotizing Enterocolitis in Newborns Born Premature.

OBJECTIVE: To evaluate the association between newborn acylcarnitine profiles and the subsequent development of necrotizing enterocolitis (NEC) with the use of routinely collected newborn screening data in infants born preterm. STUDY DESIGN: A retrospective cohort study was conducted with the use of discharge records for infants born preterm admitted to neonatal intensive care units in California from 2005 to 2009 who had linked state newborn screening results. A model-development cohort of 94 110 preterm births from 2005 to 2008 was used to develop a risk-stratification model that was then applied to a validation cohort of 22 992 births from 2009. RESULTS: Fourteen acylcarnitine levels and acylcarnitine ratios were associated with increased risk of developing NEC. Each log unit increase in C5 and free carnitine /(C16 + 18:1) was associated with a 78% and a 76% increased risk for developing NEC, respectively (OR 1.78, 95% CI 1.53-2.02, and OR 1.76, 95% CI 1.51-2.06). Six acylcarnitine levels, along with birth weight and total parenteral nutrition, identified 89.8% of newborns with NEC in the model-development cohort (area under the curve 0.898, 95% CI 0.889-0.907) and 90.8% of the newborns with NEC in the validation cohort (area under the curve 0.908, 95% CI 0.901-0.930). CONCLUSIONS: Abnormal fatty acid metabolism was associated with prematurity and the development of NEC. Metabolic profiling through newborn screening may serve as an objective biologic surrogate of risk for the development of disease and thus facilitate disease-prevention strategies.

Urine protein biomarkers for the diagnosis and prognosis of necrotizing enterocolitis in infants.

OBJECTIVES: To test the hypothesis that an exploratory proteomics analysis of urine proteins with subsequent development of validated urine biomarker panels would produce molecular classifiers for both the diagnosis and prognosis of infants with necrotizing enterocolitis (NEC). STUDY DESIGN: Urine samples were collected from 119 premature infants (85 NEC, 17 sepsis, 17 control) at the time of initial clinical concern for disease. The urine from 59 infants was used for candidate biomarker discovery by liquid chromatography/mass spectrometry. The remaining 60 samples were subject to enzyme-linked immunosorbent assay for quantitative biomarker validation. RESULTS: A panel of 7 biomarkers (alpha-2-macroglobulin-like protein 1, cluster of differentiation protein 14, cystatin 3, fibrinogen alpha chain, pigment epithelium-derived factor, retinol binding protein 4, and vasolin) was identified by liquid chromatography/mass spectrometry and subsequently validated by enzyme-linked immunosorbent assay. These proteins were consistently found to be either up- or down-regulated depending on the presence, absence, or severity of disease. Biomarker panel validation resulted in a receiver-operator characteristic area under the curve of 98.2% for NEC vs sepsis and an area under the curve of 98.4% for medical NEC vs surgical NEC. CONCLUSIONS: We identified 7 urine proteins capable of providing highly accurate diagnostic and prognostic information for infants with suspected NEC. This work represents a novel approach to improving the efficiency with which we diagnose early NEC and identify those at risk for developing severe, or surgical, disease.

Cytokine levels and profiles in children related to sickle cell disease and asthma status.

Atopic asthma in patients with sickle cell disease (SCD) is associated with an increased risk of acute chest syndrome (ACS). Cytokine-mediated inflammation might explain this association. Studies of cytokine profiles in patients with SCD have yielded conflicting data, but the possible influence of asthma status has not been examined. Our aim was to test the hypothesis that cytokine levels and profiles in SCD children reflected their asthma status. Samples from 155 Jamaican children (80 had SCD) and 64 British children (53 had SCD) who had their asthma status documented were analyzed for the presence and levels of interleukin 4 (IL-4) and interferon (IFN)-γ; they were also classified by their T helper cell (Th) cytokine profile. Jamaican children with SCD, when compared with Jamaican controls, were more likely to be diagnosed with asthma (P=0.001), more likely to be IL-4 positive (P<0.001), and more likely to be classified as having a Th-2 pattern (<0.001). In contrast, British children with SCD, when compared with the British controls, were less likely to have been diagnosed with asthma (P=0.04) and less likely to be classified as having a Th-2 pattern (P=0.006). Regression analysis demonstrated that amongst Jamaican children, SCD status, but not asthma status, ACS history, or gender, was predictive of IL-4 positivity and Th-2 status (P<0.001). In British children, none of those variables were significant predictors of IL-4 positivity or Th status. Cytokine profiles differed between Jamaican and British children. In the Jamaican children they reflected SCD, but not asthma or ACS status.

Risk factors for intestinal failure in infants with necrotizing enterocolitis: a Glaser Pediatric Research Network study.

OBJECTIVE: To determine risk factors for intestinal failure (IF) in infants undergoing surgery for necrotizing enterocolitis (NEC). STUDY DESIGN: Infants were enrolled in a multicenter prospective cohort study. IF was defined as the requirement for parenteral nutrition for >or= 90 days. Logistic regression was used to identify predictors of IF. RESULTS: Among 473 patients enrolled, 129 had surgery and had adequate follow-up data, and of these patients, 54 (42%) developed IF. Of the 265 patients who did not require surgery, 6 (2%) developed IF (OR 31.1, 95% CI, 12.9 - 75.1, P < .001). Multivariate analysis identified the following risk factors for IF: use of parenteral antibiotics on the day of NEC diagnosis (OR = 16.61, P = .022); birth weight < 750 grams, (OR = 9.09, P < .001); requirement for mechanical ventilation on the day of NEC diagnosis (OR = 6.16, P = .009); exposure to enteral feeding before NEC diagnosis (OR=4.05, P = .048); and percentage of small bowel resected (OR = 1.85 per 10 percentage point greater resection, P = .031). CONCLUSION: The incidence of IF among infants undergoing surgical treatment for NEC is high. Variables characteristic of severe NEC (low birth weight, antibiotic use, ventilator use, and greater extent of bowel resection) were associated with the development of IF.

Impact of acute chest syndrome on lung function of children with sickle cell disease.

OBJECTIVE: To test the hypothesis that children with sickle cell disease (SCD) who experienced an acute chest syndrome (ACS) hospitalization episode would have worse lung function than children with SCD without ACS episodes. STUDY DESIGN: Forced expiratory volume in 1 second (FEV(1)); forced vital capacity (FVC); FEV(1)/FVC ratio; peak expiratory flow (PEF); forced expiratory flow at 25% (FEF(25)), 50% (FEF(50)), and 75% (FEF(75)) of FVC; airway resistance (Raw); and lung volumes were compared in 20 children with ACS and 20 aged-matched children without ACS (median age, 11 years; range, 6 to 16 years). Fourteen age-matched pairs were assessed before and after bronchodilator use. RESULTS: The mean Raw (P = .03), TLC (P = .01), and RV (P = .003) were significantly higher in the group with ACS than in the group without ACS. There were no significant differences in the changes in lung function test results in response to bronchodilator administration between the 2 groups, but the children with ACS had a lower FEF(25) (P = .04) and FEF(75) (P = .03) pre-bronchodilator use and a lower mean FEV(1)/FVC ratio (P = .03) and FEF(75) (P = .03) post-bronchodilator use. CONCLUSIONS: Children with SCD who experienced an ACS hospitalization episode had significant differences in lung function compared with those who did not experience ACS episodes. Our results are compatible with the hypothesis that ACS episodes predispose children to increased airway obstruction.

Lung volumes in healthy Afro-Caribbean children aged 4-17 years.

Lung volumes in healthy children differ according to their ethnic origin. We wished to determine if any differences in the lung volumes of Afro-Caribbean (AC) children from those predicted by Caucasian reference values disappeared if the results were related to sitting height or to 90% or 77% of lung volumes predicted for height from Caucasian reference values based on standing height. We took, as our working hypothesis, that it is inappropriate to use Caucasian reference values to interpret data from Afro-Caribbean children, and that ethnic-specific reference values are required. This was a prospective, observational study. Subjects included 80 AC children with a median age of 9 (range, 4.3-17.8) years. Standing and sitting height were measured. Lung volumes were measured by body plethysmography (total lung capacity, TLC(pleth); functional residual capacity, FRC(pleth); and vital capacity, VC(pleth)), helium gas dilution (functional residual capacity, (FRC(He)), spirometry (forced expiratory volume in 1 sec, FEV(1)), and forced vital capacity (FVC). The lung volumes of AC children correlated significantly with standing height, but differed significantly from values predicted from Caucasian reference values based on standing height (P < 0.05). Significant differences remained for TLC(pleth), FRC(pleth), FRC(He), RV(pleth), VC(pleth), FEV(1), and FVC when the results were related to sitting height or 90% or 77% of values predicted from Caucasian reference values based on height (P < 0.05). Lung volumes in Afro-Caribbean children should be compared to ethnic-specific reference values.