Jareen Meinzen-Derr

Role of human milk in extremely low birth weight infants’ risk of necrotizing enterocolitis or death

Objective:To determine the association between human milk (HM) intake and risk of necrotizing enterocolitis (NEC) or death among infants 401 to 1000 g birth weight.Study Design:Analysis of 1272 infants in the National Institute of Child Health and Human Development Neonatal Network Glutamine Trial was performed to determine if increasing HM intake was associated with decreased risk of NEC or death. HM intake was defined as the proportion of HM to total intake, to enteral intake and total volume over the first 14 days. Known NEC risk factors were included as covariates in Cox proportional hazard analyses for duration of survival time free of NEC.Result:Among study infants, 13.6% died or developed NEC after 14 days. The likelihood of NEC or death after 14 days was decreased by a factor of 0.83 (95% confidence interval, CI 0.72, 0.96) for each 10% increase in the proportion of total intake as HM. Each 100 ml kg−1 increase in HM intake during the first 14 days was associated with decreased risk of NEC or death (hazard ratio, HR 0.87 (95% CI 0.77, 0.97)). There appeared to be a trend towards a decreased risk of NEC or death among infants who received 100% HM as a proportion to total enteral intake (HM plus formula), although this finding was not statistically significant (HR 0.85 (95% CI 0.60, 1.19)).Conclusion:These data suggest a dose-related association of HM feeding with a reduction of risk of NEC or death after the first 2 weeks of life among extremely low birth weight infants.

Elevated cytokine levels in children with autism spectrum disorder

UNLABELLED This study compared production of IL-2, IFN-gamma, IL-4, IL-13, IL-5 and IL-10 in peripheral blood mononuclear cells from 20 children with autism spectrum disorder to those from matched controls. Levels of all Th2 cytokines were significantly higher in cases after incubation in media alone, but the IFN-gamma/IL-13 ratio was not significantly different between cases and controls. Cases had significantly higher IL-13/IL-10 and IFN-gamma/IL-10 than controls. CONCLUSION Children with ASD had increased activation of both Th2 and Th1 arms of the adaptive immune response, with a Th2 predominance, and without the compensatory increase in the regulatory cytokine IL-10.

Prolonged initial empirical antibiotic treatment is associated with adverse outcomes in premature infants.

OBJECTIVE To investigate the outcomes after prolonged empirical antibiotic administration to premature infants in the first week of life, and concluding subsequent late onset sepsis (LOS), necrotizing enterocolitis (NEC), and death. STUDY DESIGN Study infants were ≤ 32 weeks gestational age and ≤ 1500 g birth weight who survived free of sepsis and NEC for 7 days. Multivariable logistic regression was conducted to determine independent relationships between prolonged initial empirical antibiotic therapy (≥ 5 days) and study outcomes that control for birth weight, gestational age, race, prolonged premature rupture of membranes, days on high-frequency ventilation in 7 days, and the amount of breast milk received in the first 14 days of life. RESULTS Of the 365 premature infants who survived 7 days free of sepsis or NEC, 36% received prolonged initial empirical antibiotics, which was independently associated with subsequent outcomes: LOS (OR, 2.45 [95% CI, 1.28-4.67]) and the combination of LOS, NEC, or death (OR, 2.66 [95% CI, 1.12-6.3]). CONCLUSIONS Prolonged administration of empirical antibiotics to premature infants with sterile cultures in the first week of life is associated with subsequent severe outcomes. Judicious restriction of antibiotic use should be investigated as a strategy to reduce severe outcomes for premature infants.

Amplitude-Integrated EEG Is Useful in Predicting Neurodevelopmental Outcome in Full-Term Infants With Hypoxic-Ischemic Encephalopathy: A Meta-Analysis

Hypoxic ischemic encephalopathy is a common cause of neurological complications resulting in chronic handicapping conditions, such as cerebral palsy. Amplitude-integrated electroencephalography (EEG) has been used in many European countries for more than a decade in the evaluation of infants with hypoxic ischemic encephalopathy but has not been widely used in the United States. The objective of this study was to evaluate the evidence supporting use of amplitude-integrated EEG as a quantitative predictor of neurodevelopmental outcome in full-term infants with hypoxic ischemic encephalopathy. To assess efficacy, the authors performed a meta-analysis of the literature evaluating the use of the amplitude-integrated EEG or cerebral function monitor in full-term infants with hypoxic ischemic encephalopathy and their neurodevelopmental outcome. A total of 8 studies were eligible for the primary meta-analysis. There was an overall sensitivity of 91% (95% CI 87-95) and a negative likelihood ratio of 0.09 (95% CI .06-.15) for amplitude-integrated EEG tracings to accurately predict poor outcome. Amplitude-integrated EEG is a valuable bedside tool for predicting long-term neurodevelopmental outcome in term infants with hypoxic ischemic encephalopathy. This information is useful in structuring communication and care plans for physicians and parents. Early assessment techniques such as amplitude-integrated EEG provide objective means for determining inclusion in clinical studies evaluating therapies for hypoxic ischemic encephalopathy and for predicting which patients are most likely to respond to treatment.

Vernix Caseosa in Neonatal Adaptation

OBJECTIVES:To characterize vernix caseosa in newborn infants with respect to factors that influence vernix distribution on the skin surface, vernix effects on thermal stability, skin hydration, acid mantle development, and vernix antioxidant properties.STUDY DESIGN:Vernix distribution was determined for 430 infants. Thermal stability was assessed in parallel groups following vernix retention (n=66) and removal (n=64). The effects of vernix retention on skin hydration, pH, erythema, and dryness/scaling were determined. Samples were analyzed for vitamin E before and after UV exposure.RESULTS:Vernix distribution depended upon gestational age, delivery mode, gender, race, and meconium exposure. Retention had no effect on axillary temperatures. Skin hydration was significantly higher for vernix-retained skin. Skin pH and erythema were significantly lower with retention. Vitamin E levels were decreased by ultraviolet radiation.CONCLUSIONS:Vernix is a naturally occurring barrier cream with multiple salubrious effects, which support its retention on the skin surface at birth.

Urinary NGAL in Premature Infants

Premature infants are at unique risk for developing acute kidney injury (AKI) due to incomplete nephrogenesis, early exposure to nephrotoxic medications, and coexisting conditions such as patent ductus arteriosus (PDA) and respiratory distress syndrome (RDS). Unfortunately, laboratory testing for the diagnosis of AKI in this population is problematic because of the physiology of both the placenta and the extra-uterine premature kidney. Recent research has led to the development of promising biomarkers for the early detection of AKI in children but there are no published reports in neonates. Our goal was to determine whether urine neutrophil gelatinase-associated lipocalin (NGAL) was detectable in premature infants and to correlate levels with gestational age, birth weight (BW), or indomethacin exposure. We enrolled 20 infants in four BW groups: 500–750, 751–1000, 1001–1250, and 1251–1500 g. Urine was collected every day for the first 14 d of life. Neonates born at earlier gestational ages and lower BWs had higher urine NGAL levels (p < 0.01). We conclude that urine NGAL is easily obtained in premature infants and that it correlates significantly with both BW and gestational age. The use of urinary NGAL as a biomarker of AKI in premature infants warrants further investigation.

Fucosyltransferase 2 Non-Secretor and Low Secretor Status Predicts Severe Outcomes in Premature Infants

OBJECTIVE To investigate secretor gene fucosyltransferase 2 (FUT2) polymorphism and secretor phenotype in relation to outcomes of prematurity. STUDY DESIGN Study infants were ≤32 weeks gestational age. Secretor genotype was determined from salivary DNA. Secretor phenotype was measured with H antigen, the carbohydrate produced by secretor gene enzymes, in saliva samples collected on day 9 ± 5. The optimal predictive cutoff point in salivary H values was identified with Classification and Regression Tree analysis. Study outcomes were death, necrotizing enterocolitis (NEC, Bells stage II/III), and confirmed sepsis. RESULTS There were 410 study infants, 26 deaths, 30 cases of NEC, and 96 cases of sepsis. Analyzed by genotype, 13% of 95 infants who were non-secretors, 5% of 203 infants who were heterozygotes, and 2% of 96 infants who were secretor dominant died (P = .01). Analyzed by phenotype, 15% of 135 infants with low secretor phenotype died, compared with 2% of 248 infants with high secretor phenotype (predictive value = 76%, P < .001). Low secretor phenotype was associated (P < .05) with NEC, and non-secretor genotype was associated (P = .05) with gram negative sepsis. Secretor status remained significant after controlling for multiple clinical factors. CONCLUSIONS Secretor genotype and phenotype may provide strong predictive biomarkers of adverse outcomes in premature infants.

Alterations in the host defense properties of human milk following prolonged storage or pasteurization.

Objectives: Preterm infants are often fed pasteurized donor milk or mothers milk that has been stored frozen for up to 4 weeks. Our objectives were to assess the impact of pasteurization or prolonged storage at −20°C on the immunologic components of human milk and the capability of the different forms of human milk to support bacterial proliferation. Materials and Methods: The concentrations and activities of major host defense proteins in the whey fractions of mothers milk stored for 4 weeks at −20°C or pasteurized human donor milk were compared with freshly expressed human milk. Proliferation of bacteria incubated in the 3 forms of human milk was assessed. Results: Relative to freshly expressed human milk, the concentrations of lysozyme, lactoferrin, lactoperoxidase, and secretory immunoglobulin A were reduced 50% to 82% in pasteurized donor milk and the activities of lysozyme and lactoperoxidase were 74% to 88% lower (P < 0.01). Proliferation of bacterial pathogens in pasteurized donor milk was enhanced 1.8- to 4.6-fold compared with fresh or frozen human milk (P < 0.01). Conclusions: The immunomodulatory proteins in human milk are reduced by pasteurization and, to a lesser extent, by frozen storage, resulting in decreased antibacterial capability. Stringent procedure to minimize bacterial contamination is essential during handling of pasteurized milk.

The large vestibular aqueduct: A new definition based on audiologic and computed tomography correlation:

Objective The study goal was to determine the prevalence and clinical significance of a large vestibular aqueduct (LVA) in children with sensorineural hearing loss (SNHL). Study Design and Setting We conducted a retrospective review of a pediatric SNHL database. One hundred seven children with SNHL were selected and their radiographic and audiometric studies were evaluated. Radiographic comparisons were made to a group of children without SNHL. Results A vestibular aqueduct (VA) larger than the 95th percentile of controls was present in 32% of children with SNHL. Progressive SNHL was more likely to occur in ears with an LVA and the rate of progressive hearing loss was greater than in ears without an LVA. The risk of progressive SNHL increased with increasing VA size as determined by logistic regression analysis. Conclusions An LVA is defined as one that is ≥2mm at the operculum and/or ≥1 mm at the midpoint in children with nonsyndromic SNHL. An LVA appears to be more common than previously reported in children with SNHL. A linear relationship is observed between VA width and progressive SNHL. Significance The finding of an LVA in children with SNHL provides diagnostic as well as prognostic information.

A multicenter cohort study of treatments and hospital outcomes in neonatal abstinence syndrome.

OBJECTIVES: To compare pharmacologic treatment strategies for neonatal abstinence syndrome (NAS) with respect to total duration of opioid treatment and length of inpatient hospital stay. METHODS: We conducted a cohort analysis of late preterm and term neonates who received inpatient pharmacologic treatment of NAS at one of 20 hospitals throughout 6 Ohio regions from January 2012 through July 2013. Physicians managed NAS using 1 of 6 regionally based strategies. RESULTS: Among 547 pharmacologically treated infants, we documented 417 infants managed using an established NAS weaning protocol and 130 patients managed without protocol-driven weaning. Regardless of the treatment opioid chosen, when we accounted for hospital variation, infants receiving protocol-based weans experienced a significantly shorter duration of opioid treatment (17.7 vs 32.1 days, P < .0001) and shorter hospital stay (22.7 vs 32.1 days, P = .004). Among infants receiving protocol-based weaning, there was no difference in the duration of opioid treatment or length of stay when we compared those treated with morphine with those treated with methadone. Additionally, infants treated with phenobarbital were treated with the drug for a longer duration among those following a morphine-based compared with methadone-based weaning protocol. (P ≤ .002). CONCLUSIONS: Use of a stringent protocol to treat NAS, regardless of the initial opioid chosen, reduces the duration of opioid exposure and length of hospital stay. Because the major driver of cost is length of hospitalization, the implications for a reduction in cost of care for NAS management could be substantial.