Prakeshkumar S Shah

Nasal continuous positive airway pressure from high flow cannula versus Infant Flow for preterm infants

Objective:To compare the feasibility of continuous positive airway pressure (CPAP) support generated by high flow nasal cannula with conventional CPAP for prevention of reintubation among preterm infants with a birth weight of ⩽1250 g.Study Design:Preterm infants were randomized to CPAP generated via high flow cannula or the Infant Flow Nasal CPAP System (VIASYS, Conshohocken, PA, USA) at extubation. Primary outcome was incidence of reintubation within 7 days. Secondary outcomes included change in oxygen use and frequency of apnea and bradycardias postextubation.Results:Forty neonates were randomized. Twelve of 20 infants randomized to high flow cannula CPAP were reintubated compared to three of 20 using Infant Flow (P=0.003). The high flow cannula group had increased oxygen use and more apneas and bradycardias postextubation.Conclusions:CPAP delivered by high flow nasal cannula failed to maintain extubation status among preterm infants ⩽1250 g as effectively as Infant Flow CPAP.

Periventricular/Intraventricular Hemorrhage and Neurodevelopmental Outcomes: A Meta-analysis.

CONTEXT: Periventricular/intraventricular hemorrhage (PIVH) is a common short-term morbidity in preterm infants, but its long-term neurodevelopmental impact, particularly with mild PIVH, remains unclear. OBJECTIVE: To systematically review and meta-analyze the neurodevelopmental outcomes of preterm infants ≤34 weeks’ gestation with mild and severe PIVH, compared with no PIVH. DATA SOURCES: Medline, Embase, CINAHL, and PsychINFO databases from January 2000 through June 2014. STUDY SELECTION: Studies reporting long-term neurodevelopmental outcomes based on severity of PIVH were included. DATA EXTRACTION: Study characteristics, inclusion/exclusion criteria, exposures, and outcome assessment data extracted independently by 2 coauthors. RESULTS: The pooled unadjusted odds ratios of the primary outcome of death or moderate-severe neurodevelopmental impairment (NDI) were higher with both mild (1.48, 95% CI 1.26–1.73; 2 studies) and severe PIVH (4.72, 4.21–5.31; 3 studies); no studies reported adjusted odds ratios. Among survivors, odds of moderate-severe NDI were higher with mild and severe PIVH in both unadjusted (1.75, 1.40–2.20; 3 studies; 3.36, 3.06–3.68; 5 studies) and adjusted (1.39, 1.09–1.77; 3 studies; 2.44, 1.73–3.42; 2 studies) pooled analyses. Adjusted odds of cerebral palsy and cognitive delay were higher with severe but not mild PIVH. LIMITATIONS: Only observational studies were included. Fifteen of 21 included studies had a moderate-high risk of bias. CONCLUSIONS: Mild and severe PIVH are associated with progressively higher odds of death or moderate-severe NDI compared with no PIVH, but no studies adjusted for confounders. Among survivors, mild PIVH was associated with higher odds of moderate-severe NDI compared with no PIVH.

Early-onset neonatal sepsis: rate and organism pattern between 2003 and 2008

Objective:Organisms causing early-onset neonatal sepsis (EONS) have consistently changed over time. The distribution of organisms in EONS helps to influence the appropriate type of antibiotic prophylaxis strategy during labor and the antibiotics used in neonates with suspected sepsis.Study Design:To compare the organisms distribution for EONS between 2003 and 2008 for infants admitted to neonatal intensive care units (NICUs) in Canada. Data were retrieved from infants with a positive bacterial blood or cerebrospinal fluid culture in the first 72 h after birth who were admitted to NICUs participating in the Canadian Neonatal Network from 2003 to 2008. Comparisons of incidence rate, demographics and causative organisms were carried out between earlier cohort (2003 to 2005) and later cohort (2006 to 2008).Result:A total of 405 infants had positive blood and/or cerebral spinal fluid cultures over the study period. The EONS rate was 6.8/1000 admissions (n=24969) in the earlier cohort compared with 6.2/1000 admissions (n=37484) in the later cohort (P=0.36). Rate of clinical chorioamnionitis was higher in the later cohort (38 vs 26%; P=0.02). For term infants, coagulase-negative Staphylococcus (CONS) (2.4/1000) followed by group B Streptococcus (GBS) (1.9/1000) were the most common organisms identified. For preterm infants, CONS (2.5/1000) followed by Escherichia coli (2.6/1000) were the most common organisms identified. There was a significant reduction in GBS EONS over time (P<0.01) and a trend toward an increase in other organisms.Conclusion:Although the rate of EONS among neonates admitted to NICUs has not changed, the pattern of infection has changed over the past 6 years. With the increased use of prophylactic antibiotics to mothers, careful surveillance of the changing trend of bacterial organisms among neonates is warranted.

Hepatotoxicity caused by methotrexate therapy in children with inflammatory bowel disease: a systematic review and meta-analysis.

Background:Methotrexate (MTX) is an immunomodulator used in pediatric inflammatory bowel disease (IBD) maintenance regimens. However, MTX use is associated with liver toxicity. We aimed to systematically review and meta-analyze the incidence of hepatotoxicity with MTX use among children with IBD. Methods:We searched MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases from 1946 to April 2013 for cohort studies and collected information about the study design, IBD treatment results, and hepatotoxicity. Pooled proportions of toxicity with 95% confidence interval (CI) were estimated using a random-effects model. Results:Twelve high-quality studies were included in this review. Fifty-seven of 457 patients treated with MTX developed varied degrees of abnormal liver biochemistry. The pooled proportion of patients with abnormal liver biochemistry was 10.2% (95% CI 5.4%–18.5%) across all studies included in the meta-analysis. Due to hepatotoxicity, dose reductions were required in 6.4% (95% CI 4.3%–9.5%), whereas 4.5% (95% CI 2.8%–7.2%) of patients required discontinuation. Conclusions:Hepatotoxicity after the use of MTX among IBD patients was a relatively common event. Monitoring for hepatotoxicity is strongly recommended, as discontinuation of MTX may be necessary in a significant proportion of children.

Prediction of Neonatal Outcomes in Extremely Preterm Neonates

OBJECTIVE: To develop and validate a statistical prediction model spanning the severity range of neonatal outcomes in infants born at ≤30 weeks’ gestation. METHODS: A national cohort of infants, born at 23 to 30 weeks’ gestation and admitted to level III NICUs in Canada in 2010–2011, was identified from the Canadian Neonatal Network database. A multinomial logistic regression model was developed to predict survival without morbidities, mild morbidities, severe morbidities, or mortality, using maternal, obstetric, and infant characteristics available within the first day of NICU admission. Discrimination and calibration were assessed using a concordance C-statistic and the Cg goodness-of-fit test, respectively. Internal validation was performed using a bootstrap approach. RESULTS: Of 6106 eligible infants, 2280 (37%) survived without morbidities, 1964 (32%) and 1251 (21%) survived with mild and severe morbidities, respectively, and 611 (10%) died. Predictors in the model were gestational age, small (<10th percentile) for gestational age, gender, Score for Neonatal Acute Physiology version II >20, outborn status, use of antenatal corticosteroids, and receipt of surfactant and mechanical ventilation on the first day of admission. High model discrimination was confirmed by internal bootstrap validation (bias-corrected C-statistic = 0.899, 95% confidence interval = 0.894–0.903). Predicted probabilities were consistent with the observed outcomes (Cg P value = .96). CONCLUSIONS: Neonatal outcomes ranging from mortality to survival without morbidity in extremely preterm infants can be predicted on their first day in the NICU by using a multinomial model with good discrimination and calibration. The prediction model requires additional external validation.

Neonatal outcomes among multiple births ≤ 32 weeks gestational age: Does mode of conception have an impact? A Cohort Study

BackgroundStudies comparing perinatal outcomes in multiples conceived following the use of artificial reproductive technologies (ART) vs. spontaneous conception (SC) have reported conflicting results in terms of mortality and morbidity. Therefore, the objective of our study was to compare composite outcome of mortality and severe neonatal morbidities amongst preterm multiple births ≤ 32 weeks gestation infant born following ART vs. SC.MethodsWe conducted a single center cohort study at Mount Sinai Hospital, Toronto, Ontario, Canada. Data on all preterm multiple births (≤ 32 weeks GA) discharged between July 2005 and June 2008 were retrospectively collected from a prospective database at our centre. Details regarding mode of conception were collected retrospectively from maternal health records. Preterm multiple births were categorized into those born following ART vs. SC. Composite outcome was defined as combination of death or any of the three neonatal morbidities (grade 3/4 intraventricular hemorrhage or periventricular leukomalacia; retinopathy of prematurity > stage 2 or chronic lung disease). Univariate and multivariate regression analysis were preformed after adjustment of confounders (maternal age, parity, triplets, gestational age, sex, and small for gestational age).ResultsOne hundred and thirty seven neonates were born following use of ART and 233 following SC. The unadjusted composite outcome rate was significantly higher in preterm multiples born following ART vs. SC [43.1% vs. 26.6%, p = 0.001; OR 1.98 (95% CI 1.13, 3.45)]; however, when adjusted for confounders the difference between groups was not statistically significant [OR 1.39, 95% CI 0.67, 2.89].ConclusionIn our population of preterm multiple births, the mode of conception had no detectable effect on the adjusted composite neonatal outcome of mortality and/or three neonatal morbidities.

Association of unit size, resource utilization and occupancy with outcomes of preterm infants

Objective:Assess association of NICU size, and occupancy rate and resource utilization at admission with neonatal outcome.Study Design:Retrospective cohort study of 9978 infants born at 23–32 weeks gestation and admitted to 23 tertiary-level Canadian NICUs during 2010–2012. Adjusted odds ratios (AOR) were estimated for a composite outcome of mortality/any major morbidity with respect to NICU size, occupancy rate and intensity of resource utilization at admission.Results:A total of 2889 (29%) infants developed the composite outcome, the odds of which were higher for 16–29, 30–36 and >36-bed NICUs compared with <16-bed NICUs (AOR (95% CI): 1.47 (1.25–1.73); 1.49 (1.25–1.78); 1.55 (1.29–1.87), respectively) and for NICUs with higher resource utilization at admission (AOR: 1.30 (1.08–1.56), Q4 vs Q1) but not different according to NICU occupancy.Conclusion:Larger NICUs and more intense resource utilization at admission are associated with higher odds of a composite adverse outcome in very preterm infants.

Incorporation of femur length leads to underestimation of fetal weight in asymmetric preterm growth restriction

To review the performance of a variety of biometry formulae for estimated fetal weight (EFW) in the management of severely growth restricted fetuses with abnormal umbilical artery Doppler at a single perinatal institution.

Quality of randomized clinical trials in juvenile idiopathic arthritis

OBJECTIVES We evaluated the quality of randomized clinical trials (RCTs) of therapy for juvenile idiopathic arthritis (JIA) using an individual component approach and assessed temporal changes. METHODS A systematic review of the literature was performed to identify all RCTs involving exclusively JIA patients. Two investigators independently assessed the identified articles for six quality indicators: generation of allocation sequence, allocation concealment, masking, intention-to-treat (ITT) analysis, dropout rates and clearly stated primary outcome. RESULTS Fifty-two RCTs involving JIA patients were assessed. Generation of allocation sequence was unclear in 79% of the studies. Reporting of allocation concealment was adequate in only one-third of the studies. Masking was adequate in 73%, inadequate in 19% and unclear in 8% of the reports. ITT analysis was employed in 37% of the reports. Per-protocol analysis was used in 40% and in 23% the method was unclear. Most of the reports (67%) had dropout rates < or = 20%. About half of the reports (n = 25) failed to show a significant effect of the experimental treatment. No significant associations were found between the study results and quality indicators. With the exception of adequate masking and dropout rate, all quality indicators showed a trend of improvement over the decades. CONCLUSIONS The quality of RCTs in JIA based on the selected indicators was poor. Although there were some positive changes over time, the reporting and methodological quality of trials should be improved. New, more powerful and acceptable RCT designs should be developed in this patient population.

Short-term and long-term outcomes of preterm neonates with acute severe pulmonary hypertension following rescue treatment with inhaled nitric oxide.

Objective To describe short-term and long-term outcomes of preterm neonates with severe acute pulmonary hypertension (aPHT) in relation to response to rescue inhaled nitric oxide (iNO) therapy. Design Retrospective cohort studyover a 6 year period. Setting Tertiary neonatal intensive care unit. Patients 89 neonates <35 weeks gestational age (GA) who received rescue iNO for aPHT, including 62 treated at ≤3 days of age (early aPHT). Interventions iNO ≥ 1 hour. Main outcome measures Positive responders (reduction in fraction of inspired oxygen (FiO2) ≥0.20 within 1 hour of iNO) were compared with non-responders. Primary outcome was survival without moderate-to-severe disability at 18 months of age. Results Mean (SD) GA and birth weight was 27.7 (3.0) weeks and 1077 (473) gm, respectively. Median (IQR) pre-iNO FiO2 was 1.0 (1.0, 1.0). Positive response rate to iNO was 46%. Responders showed improved survival without disability (51% vs 15%; p<0.01), lower mortality (34% vs 71%; p<0.01) and disability among survivors (17% vs 50%; p=0.06). Higher GA (adjusted OR: 1.44 (95% CI 1.10 to 1.89)), aPHT in context of preterm prolonged rupture of membranes (6.26 (95% CI 1.44 to 27.20)) and positive response to rescue iNO (5.81 (95% CI 1.29 to, 26.18)) were independently associated with the primary outcome. Compared with late cases (>3 days of age), early aPHT had a higher response rate to iNO (61% vs 11%; p<0.01) and lower mortality (43% vs 78%; p<0.01). Conclusion A positive response to rescue iNO in preterm infants with aPHT is associated with survival benefit, which is not offset by long-term disability.