Sterile water moisturizer of the skin of extremely low birth weight infants.

OBJECTIVE: To assess the feasibility of sterile water application to the skin of the extremely low birth weight (ELBW) newborns in the first week of life and examine its effects on their skin integrity and outcomes. DESIGN: Pilot randomized controlled trial. SETTING: Open-bay, 18 bed Level III NICU in the Eastern United States. PARTICIPANTS: Twenty-eight ELBW neonates. Two newborns expired, sixteen newborns remained in the intervention group and twelve newborns in the control group. METHODS: ELBW neonates were either assigned to receive frequent sterile water wash to skin or not during care for the first week of life. Using the Neonatal Skin Condition Scale (NSCS), assessments were performed twice a day during the first week. Fluid intake, serum electrolytes, culture proven sepsis and other morbidities, and length of stay (LOS) were compared while controlling for confounding variables using multiple regression analysis. RESULTS: There was no difference in the demographic or clinical characteristics between both groups. Sterile water wash application to skin was not associated with differences in skin health indices or fluid intake. However, it was associated with higher median sodium level and with early regression of bilirubin level when compared to controls. CONCLUSION: Frequent skin washes with sterile water are feasible and safe. However, they may not be associated with improved skin integrity or fluid intake.

Bedside and laboratory neuromonitoring in neonatal encephalopathy.

Several bedside and laboratory neuromonitoring tools are currently used in neonatal encephalopathy (NE) to assess 1) brain function [amplitude-integrated electroencephalogram (aEEG) and EEG], 2) cerebral oxygenation delivery and consumption [near-infrared spectroscopy (NIRS)] and 3) blood and cerebrospinal fluid biomarkers. The aim of the review is to provide the role of neuromonitoring in understanding the development of brain injury in these newborns and better predict their long-term outcome. Simultaneous use of these monitoring modalities may improve our ability to provide meaningful prognostic information regarding ongoing treatments. Evidence will be summarized in this review for each of these modalities, by describing (1) the methods, (2) the clinical evidence in context of NE both before and with hypothermia, and (3) the research and future directions.

Interobserver Reliability of an MR Imaging Scoring System in Infants with Hypoxic-Ischemic Encephalopathy.

BACKGROUND AND PURPOSE: MR imaging has a key role in predicting neurodevelopmental outcomes following neonatal hypoxic-ischemic encephalopathy (HIE). A novel MR imaging scoring system for hypoxic-ischemic brain injury was used in our patient population with the aim of assessing interobserver variability and developing subcategories for the severity of brain injury. MATERIALS AND METHODS: We evaluated brain MR images of 252 infants who underwent hypothermia for HIE between 2014 and 2019. First, 40 infants were selected randomly to test interobserver variability. Discrepancies were identified during the assessment of the first 20 MR images. The remaining 20 MR images were scored after adjusting the scoring system. Second, we determined cutoff values for the severity of injury that were based on the percentiles of the total scores in the full cohort. RESULTS: The interobserver reliability showed excellent agreement for the total score both before (intraclass correlation coefficient = 0.96; 95% CI 0.89-0.99) and after the adjustment (intraclass correlation coefficient = 0.96; 95% CI, 0.89-0.98). The average of the differences and the agreement interval between the 2 readers decreased after the adjustment. Subcategories of brain injury were the following: We considered a total score of ≤4 (≤75%) as normal, 5-10 (76%-90%) as mild, 11-15 (91%-95%) as moderate, and >15 (>95%) as severe brain injury. The agreement on the classification of brain injury improved in the second epoch (weighted κ = 0.723 versus 0.887). CONCLUSIONS: The adjusted scoring system may lead to a higher degree of interrater agreement. The presented cutoff values may be used to determine the severity of brain injury in future clinical studies including infants with mild hypoxia-ischemia.

Early exit from neonatal therapeutic hypothermia: A single institution experience using MRI to guide decision-making.

BACKGROUND: To evaluate the feasibility of a protocol using combined magnetic resonance imaging (MRI), clinical data, and electroencephalogram (EEG) to identify neonates with mild neonatal encephalopathy (NE) treated with therapeutic hypothermia (TH) who are eligible for "early exit". METHODS: Retrospective chart review of TH cases at a single Level III NICU over a 5-year period was used to describe the demographic, clinical, and outcome data in neonates that received early exit in contrast to 72 hour TH treatment. RESULTS: Two hundred and eight TH cases, including 18 early exit cases (9%) and 9 cases (4%) evaluated for early exit with MRI but continued on 72 hours of TH, were identified. Early exit and 72 hour treatment groups did not differ in demographics or cord gas measures, although early exit neonates had a shorter length of stay (p < 0.05). Consistent with the early exit protocol, no early exit infants had evidence of moderate or severe encephalopathy on EEG or evidence of hypoxic ischemic injury on MRI at 24 hours of life. Neurology follow up between age 1 and 18 months was available for 10 early exit infants, 8 of whom had a normal examination. CONCLUSIONS: Early MRI at 24 hours of age, alongside clinical and EEG criteria, is feasible as part of a protocol to identify neonates eligible for early exit from therapeutic hypothermia.

Patent ductus arteriosus in premature infants: to treat or not to treat?

OBJECTIVE: Closing patent ductus arteriosus (PDA) is a widely accepted approach in the management of very low birth weight (VLBW) infants. Our objective is to test the hypothesis that conservative management (no treatment) of PDA will not affect survival without chronic lung diseases (CLD). STUDY DESIGN: This retrospective study utilizes a prospectively collected database to compare two cohorts of VLBW infants. Infants in the first group (2001 to 2009) had their PDA treated with pharmacological and if necessary with surgical ligation. PDA in the second group (2010 to 2014) was not treated with medical or surgical intervention. The primary outcome was survival without oxygen requirement at 36 weeks. Pulmonary and non-pulmonary morbidities were also compared. Logistic regression analyses were performed to control for confounders. RESULTS: This study included 643 VLBW infants, of them 415 infants in the Treat group and 228 in the No-Treat group. The rate of survival without CLD did not differ between Treat and No-Treat groups (78.4% vs 83.9%, respectively; adjusted odds ratio (aOR)=1.72, confidence interval (CI): 0.92 to 3.23, P=0.09). Mortality declined in No-Treat group (15.2% vs 10.5%, aOR=0.51, CI: 0.25 to 0.99, P=0.049), but the two groups did not differ in the incidence of CLD among survivors (5.8% vs 5.0%,=P0.47). Pulmonary complications and non-pulmonary morbidities did not differ between groups. CONCLUSIONS: Conservative management (no treatment) of PDA may not compromise survival without CLD and is not associated with increased morbidities in VLBW infants. Prospective physiological studies are needed to determine the sector of VLBW infants, if any, who could benefit from PDA treatment.

EEG maturation and stability of cerebral oxygen extraction in very low birth weight infants.

OBJECTIVE: Fractional cerebral tissue oxygen extraction (FTOE) can be continuously monitored by simultaneous near-infrared spectroscopy (NIRS) and pulse oximetry. The objective of this study is to test the hypothesis that in very low birth weight (VLBW) infants, the more mature EEG activity is, the less variable FTOE is. STUDY DESIGN: A prospective study was conducted on VLBW infants (< 1500 g and ⩽ 34 weeks gestation) without significant brain injury. Simultaneous continuous two-channel electroencephalography (EEG), NIRS and pulse oximetry were recorded. Absolute and relative powers of EEG in the delta, theta, alpha, beta and total frequency bands have been calculated. FTOE variability was calculated on two scales: short scales (3 to 20 s) and long scales (20 to 150 s). FTOE variability was examined against changes in relative spectral power of different EEG bands. RESULT: We evaluated 67 studies performed on 46 VLBW infants. Average study duration was 21.3 ± 5.5 h. Relative power of delta band positively correlated with FTOE short- and long-scale variability (r=0.45, P<0.001; r=0.44, P<0.001, respectively). Relative power of alpha bands negatively correlated with FTOE short- and long-scale variability (r=-0.38, P=0.002; r=-0.42, P<0.001, respectively). These correlations continued to be significant when controlling for sex, small for gestational age, postmenstrual age, being on respiratory support, hemoglobin concentration, systemic oxygen saturation and transcutaneous carbon dioxide tension. CONCLUSION: Increased maturation of EEG activity is associated with decreased variability in cerebral oxygen extraction. The implications of increased variability in FTOE on brain injury in premature infants need further exploration.

Maternal juvenile rheumatoid arthritis may be associated with preterm birth but not poor fetal growth.

OBJECTIVE: Adverse pregnancy outcomes in mothers with juvenile rheumatoid arthritis (JRA) are not known. The objective of this study was to examine the risk of preterm birth and restricted fetal growth in pregnant mothers diagnosed with JRA, and to examine the impact of race/ethnicity and maternal age on this association. STUDY DESIGN: Hospital discharge records for mothers who gave birth in 2011 and 2012 were examined in the National Inpatient Sample (NIS) database. JRA, preterm birth (<37 weeks of gestation), birth weight that is small for gestational age (SGA) and other demographic and clinical variables were identified using ICD-9 (International Classification of Disease--9th revision) diagnostic codes. The associations of JRA with preterm birth and restricted fetal growth were examined controlling for confounding variables. RESULT: The sample included 8,273,987 birthing mothers, of these 1236 (0.01%) had JRA. The prevalence of preterm birth and SGA was 6.08% and 2.34%, respectively. Preterm birth in mothers with JRA was 12.9% compared with 6.1% in mothers without JRA with an adjusted odds ratio (OR) of 2.1 (confidence interval (CI): 1.74 to 2.42, P<0.001). The incidence of SGA in infants born to mothers with JRA was 3.34% compared with 2.34% in non-JRA mothers, which was not statistically significant. Adjusted OR for preterm birth in association with JRA among White mothers was 1.78 (CI: 1.41 to 2.24, P<0.001). However, Hispanic mothers with JRA (12%) were the ethnicity to suffer the most from preterm birth with an adjusted OR of 4.43 (CI: 2.97 to 6.62, P<0.001). Preterm birth among advanced maternal age (AMA) mothers with JRA was 25% compared with 7% in those without JRA with an adjusted OR of 5.42 (CI: 3.51 to 8.35, P<0.001). CONCLUSION: JRA is associated with preterm birth but not with SGA. This association is significantly influenced by race/ethnicity and maternal age. More studies are needed to examine these findings in relation to medications used, severity of the disease and exacerbation during pregnancy to understand the genetic/socioeconomic factors behind these racial/ethnic differences.

Melatonin use for neuroprotection in perinatal asphyxia: a randomized controlled pilot study.

OBJECTIVE: Melatonin has been shown to be neuroprotective in animal models. The objective of this study is to examine the effect of melatonin on clinical, biochemical, neurophysiological and radiological outcomes of neonates with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: We conducted a prospective trial on 45 newborns, 30 with HIE and 15 healthy controls. HIE infants were randomized into: hypothermia group (N=15; received 72-h whole-body cooling) and melatonin/hypothermia group (N=15; received hypothermia and five daily enteral doses of melatonin 10 mg kg(-1)). Serum melatonin, plasma superoxide dismutase (SOD) and serum nitric oxide (NO) were measured at enrollment for all infants (N=45) and at 5 days for the HIE groups (N=30). In addition to electroencephalography (EEG) at enrollment, all surviving HIE infants were studied with brain magnetic resonance imaging (MRI) and repeated EEG at 2 weeks of life. Neurologic evaluations and Denver Developmental Screening Test II were performed at 6 months. RESULT: Compared with healthy neonates, the two HIE groups had increased melatonin, SOD and NO. At enrollment, the two HIE groups did not differ in clinical, laboratory or EEG findings. At 5 days, the melatonin/hypothermia group had greater increase in melatonin (P<0.001) and decline in NO (P<0.001), but less decline in SOD (P=0.004). The melatonin/hypothermia group had fewer seizures on follow-up EEG and less white matter abnormalities on MRI. At 6 months, the melatonin/hypothermia group had improved survival without neurological or developmental abnormalities (P<0.001). CONCLUSION: Early administration of melatonin to asphyxiated term neonates is feasible and may ameliorate brain injury.

A prospective study on hyperglycemia and retinopathy of prematurity.

OBJECTIVE: Retinopathy of prematurity (ROP) constitutes a significant morbidity in premature infants that can lead to blindness. Multiple retrospective studies have identified neonatal hyperglycemia as a risk for developing ROP. However, in the absence of any reported prospective study, it is not clear whether hyperglycemia is associated with ROP independent of the commonly associated comorbidities. The objective of this study was to investigate whether hyperglycemia in premature infants is independently associated with ROP. STUDY DESIGN: Premature infants (<1500 g or⩽32 weeks gestational age) were enrolled in a prospective longitudinal cohort study. All demographic, clinical and laboratory data were collected. Bedside whole-blood glucose concentration was measured every 8 h daily for 7 days. For any glucose reading<50 or>150 mg dl(-1), serum sample was sent to the laboratory for confirmation. Hyperglycemia was defined as any blood glucose level⩾150 mg dl(-1). ROP patients were compared with non-ROP patients in a bivariate analysis. Variables significantly associated with ROP were studied in a logistic regression model. RESULT: A total of 65 patients were enrolled with gestational age 31.1±1.2 weeks and birth weight 1385±226 g. Thirty-one patients (48%) were identified with hyperglycemia. On eye examination, 19 cases (29.2%) had ROP (13 with stage 1, 4 with stage 2 and 2 with stage 3). There were more cases of ROP in the hyperglycemia group compared with the euglycemia group (45% vs 15%, P=0.007). Patients who developed ROP had significantly higher maximum and average glucose concentrations when compared with non-ROP patients. Multiple factors have been associated with ROP on bivariate analysis, including gestational age, exposure to oxygen, respiratory support and poor weight gain. However, in a logistic regression model including all significant variables, average blood glucose in the first week of life was the factor independently associated with ROP with an odds ratio of: 1.77 (95% confidence interval: 1.08 to 2.86), P=0.024. CONCLUSION: In a cohort of premature infants, elevated average blood glucose concentrations in the first week of life is independently associated with the development of ROP.

Neurobehavioral assessment as a predictor of neurodevelopmental outcome in preterm infants.

OBJECTIVE: Preterm infants are at risk for neurodevelopmental impairment. The Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) is a standardized assessment for the neurobehavioral integrity of the newborn. The use of NNNS as a prognostic tool is still emerging. We hypothesized that the NNNS examination performed at term equivalent can detect neurobehavioral alterations in very low birth weight infants and can help in predicting their neurodevelopmental outcome at 18 months corrected age (CA). STUDY DESIGN: This is a prospective study that included preterm infants with birth weight <1500 g and gestational age ≤ 34 weeks. They were evaluated with NNNS at term-equivalent and 12 summary scores were assigned. Infants who had 2 or more NNNS summary scores that were 2 s.d. beyond the mean of the study group were categorized as having abnormal NNNS. Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) of Bayley Scales of Infant Development (BSID-II) were determined at 18 months CA. Multiple linear regression models were used to examine the predictivity of the NNNS summary scores for both MDI and PDI. RESULT: A total of 41 infants were evaluated at term and at 18 months CA. The average MDI was 78±15 and the average PDI was 80 ± 14. Significant neurodevelopmental delay was observed in 50% and 31% of infants with abnormal and normal NNNS, respectively. Using multiple linear regression, NNNS was predictive for both MDI (P=0.011, adjusted R (2)=0.295) and PDI (P=0.002, adjusted R (2)=0.441). Lower MDI was associated with less regulation and more nonoptimal reflexes, whereas lower PDI was associated with less regulation, more nonoptimal reflexes, hypertonicity and handling. CONCLUSION: NNNS at term-equivalent age can detect neurobehavioral alterations in very low birth weight infants. Individual summary scores showed significant correlation with both the MDI and PDI at 18 months CA.

Red blood cell transfusion, feeding and necrotizing enterocolitis in preterm infants.

OBJECTIVE: Preliminary studies suggested an association between red blood cell (RBC) transfusion and necrotizing enterocolitis (NEC) in premature neonates. An advantageous effect of withholding feeds during transfusion has never been studied. We aimed, first, to determine whether preterm infants who developed NEC were more likely to be transfused in the 48 to 72 h before the diagnosis of NEC; second, to test if a strict policy of withholding feeds during transfusion would decrease the incidence of transfusion-associated NEC. STUDY DESIGN: The study was conducted in two phases. Phase 1: a retrospective case-control study of premature low-birth weight (<32 weeks and <2500 g) infants who developed NEC over a 6-year period. Phase 2: a comparison study of the incidence of NEC during the 18-months preceding, and the 18 months following the change of practice to withholding feeds during RBC transfusion. RESULT: In the case-control study (25 infants with NEC and 25 controls), more infants in the NEC group received transfusions in the 48 and 72 h preceding diagnosis (56 vs 20% within 48 h, P=0.019; and 64 vs 24% within 72 h, P=0.01). The total number of transfusions and age of RBCs were not different between the two groups. Implementing the policy of withholding feeds during transfusion was associated with a decrease in the incidence of NEC from 5.3 to 1.3% (P=0.047). CONCLUSION: Infants who developed NEC frequently received RBC transfusions in the 48 and 72 h preceding presentation of NEC. A strict policy of withholding feeds during transfusion may have a protective effect from NEC.

Ascorbic acid combined with ibuprofen in hypoxic ischemic encephalopathy: a randomized controlled trial.

OBJECTIVE: Free oxygen radicals and proinflammatory cytokines are important causes for brain injury in neonates with hypoxic ischemic encephalopathy (HIE). Our objectives were to test the hypothesis that a combination of antioxidants (ascorbic acid) and anti-inflammatory agents (ibuprofen) can ameliorate the brain injury in HIE and improve neurodevelopmental outcomes when given to term infants immediately after birth. STUDY DESIGN: In a prospective, randomized, double-blinded controlled trial, 60 asphyxiated term infants were assigned to one of two groups, intervention and control. The intervention group (n=30) received intravenous ascorbic acid and oral ibuprofen for 3 days; and the control group (n=30) received similar volumes of a placebo. We measured a panel of cytokines at enrollment and administered the treatment drugs within 2 h after birth. Neurological evaluations and developmental screenings were performed for all survivors at 6 months of age. RESULT: The Intervention and Control groups did not differ in the severity of HIE at enrollment, the concentrations of IL-1 beta and IL-6, the incidence of mortality (37 vs 33%), the incidence of neurological abnormalities at hospital discharge (47 vs 55%) and the incidence of developmental delay at 6 months of age (32 vs 40%), respectively. None of the observed complications were related to intervention. Serum interleukin (IL)-1 beta and IL-6 concentrations correlated positively with the severity of HIE at birth (P<0.01), whereas only serum IL-6 correlated with neurodevelopmental outcome at 6 months (P<0.001). CONCLUSION: Early administration of ascorbic acid and ibuprofen did not affect outcomes in infants with perinatal asphyxia. This study does not explain whether our intervention was not effective in blocking free radicals and inflammatory cytokines, if the dosing and route of administration were inadequate, or if other mediators existed that could have a more powerful role in brain injury during hypoxia-ischemia.

Fuel oil effect on the population growth, species diversity and chlorophyll (a) content of freshwater microalgae.

Fresh water algae were subjected to different concentrations (0.03, 0.07, 0.12, 0.25 and 0.5 g x l(-1)) of aqueous extract of reference fuel oil (EPA, USA, API Oil No. 2, 38% aromatic, 1274). Significant decrease in Chlorophyll. (a) was observed as the concentration of fuel oil was increased. The EC50 value of fuel oil after 7 days was 0.29 g x l(-1). Total algal counts and growth rate decreased in response to the studied fuel oil. High diversity values in diatoms were observed in all treated aqueous cultures. High concentrations of fuel oil significantly decreased carbohydrate and protein contents of algal cells.

Color removal via adsorption on wood shaving.

Factors affecting the adsorption capacity of dyes on wood shavings, such as the mesh size of the adsorbent, wood dosages, contact time, and the structure of the adsorbant, were studied. Adsorption of dye on wood follows the classical Freundlich's isotherm. Available results indicated that wood shaving is a good adsorbent. Its capacity varies according to the structure of the dye and mesh size. Powdered activated carbon was used as a reference adsorbent for the same dyes under investigation.