Prostaglandin E1 for maintaining ductal patency in neonates with ductal-dependent cardiac lesions.

BACKGROUND: Prostaglandin E1 (PGE1) is used to keep the ductus arteriosus patent and can be life-saving in neonates with ductal-dependent cardiac lesions. PGE1 is used to promote mixing of pulmonary and systemic blood flow or improve pulmonary or systemic circulations, prior to balloon atrial septostomy or surgery. PGE1 therapy may cause several short-term and long-term adverse effects. The efficacy and safety of PGE1 in neonates with ductal-dependent cardiac lesions has not been systematically reviewed. OBJECTIVES: To determine the efficacy and safety of both short-term (< 120 hours) and long-term (≥120 hours) PGE1 therapy in maintaining patency of the ductus arteriosus and decreasing mortality in ductal-dependent cardiac lesions. SEARCH METHODS: We searched the literature in October 2017, using the search strategy recommended by Cochrane Neonatal. We searched electronic databases (CENTRAL (in the Cochrane Library), MEDLINE, CINAHL, Embase); abstracts of the Pediatric Academic Societies; websites for registered trials at www.clinicaltrials.gov and www.controlled-trials.com; and in the reference list of identified articles. SELECTION CRITERIA: Randomized or quasi-randomized trials using PGE1 at any dose or duration to maintain ductal patency in term or late preterm (≥ 34 weeks' gestation) infants with ductal-dependent cardiac lesions and which reported effectiveness and safety in the short term or long term. DATA COLLECTION AND ANALYSIS: We followed the standard Cochrane methods for conducting a systematic review. Two review authors (SA and MP) independently assessed the titles and abstracts of studies identified by the search strategy to determine eligibility for inclusion. We obtained the full-text version if eligibility could not be done reliably by title and abstract. We resolved any differences by discussion. We designed electronic forms for trial inclusion/exclusion, data extraction, and for requesting additional published information from authors of the original reports. MAIN RESULTS: Our search did not identify any completed or ongoing trials that met our inclusion criteria. AUTHORS' CONCLUSIONS: There is insufficient evidence from randomized controlled trials to determine the safety and efficacy of PGE1 in neonates with ductal-dependent cardiac lesions. Evidence from observational trials have informed clinical practice on the use of PGE, which is now considered the standard of care for ductal-dependent cardiac lesions. It is unlikely that randomized controlled studies will be performed for this indication but comparative efficacy of newer formulations of PGE1, different doses of PGE1 and studies comparing PGE with PDA stents or other measures to keep the ductus open may be ethical and necessary.

Age-based difference in activation markers of coagulation and fibrinolysis in extracorporeal membrane oxygenation.

OBJECTIVE: Coagulation system activation in extracorporeal membrane oxygenation results in hemostatic derangements. Thrombin generation markers like prothrombin fragment 1+2 and thrombin-antithrombin complex are sensitive markers of hypercoagulability. Plasmin-antiplasmin complex is a sensitive marker for fibrinolysis. D-dimers reflect thrombin generation and fibrinolysis. The aim was to identify the extent of hemostasis activation during extracorporeal membrane oxygenation by measuring thrombin-antithrombin complex, prothrombin fragment 1+2, plasmin-antiplasmin complex, and D-dimer. DESIGN: Prospective cohort study. SETTING: Tertiary care academic center. PATIENTS: Children placed on extracorporeal membrane oxygenation from April 2011 to January 2013. INTERVENTIONS: Prothrombin fragment 1+2, thrombin-antithrombin complex, plasmin-antiplasmin complex, and D-dimer were measured on days 1 and 5 of extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Data presented as median (interquartile range); nonparametric tests were done using SPSS. Twenty-nine children (52% < 30 d old [neonates], median extracorporeal membrane oxygenation length 151 hr) were studied. Complications included thrombosis in 14%, bleeding in 45%, and thrombosis and bleeding together in 10%. Thrombin-antithrombin complex, prothrombin fragment 1+2, plasmin-antiplasmin complex, and D-dimer levels were high on day 1 and remained increased on extracorporeal membrane oxygenation. In neonates, all levels were higher on day 5 compared with day 1: thrombin-antithrombin complex (55.6 µg/L [30.7-76.0] vs 18.7 µg/L [10.9-34.6]; p = 0.03), prothrombin fragment 1+2 (2,038 pmol/L [1,093-4,018.5] vs 377.5 pmol/L [334.3-1,103.0]; p = 0.00), plasmin-antiplasmin complex (2,160 µg/L [786-3,090] vs 398 µg/L [296.8-990.8]; p = 0.00), and D-dimer (3.0 µg/mL [1.9-11.5] vs 1.5 µg/mL [0.6-2.9]; p = 0.01). Thrombin-antithrombin complex, prothrombin fragment 1+2, plasmin-antiplasmin complex, and D-dimer levels did not correlate with anti-Xa activity or heparin dose. In bleeders older than 30 days, plasmin-antiplasmin complex stayed elevated on day 5, but in patients with no bleeding complications, plasmin-antiplasmin level showed a declining trend. In neonates, plasmin-antiplasmin levels increased over the course of extracorporeal membrane oxygenation irrespective of bleeding. CONCLUSION: Despite our best efforts at adequate anticoagulation with unfractionated heparin, neonates showed persistent increase in coagulation activation on extracorporeal membrane oxygenation. Fibrinolysis activation may contribute to bleeding in patients older than 30 days. Different anticoagulation protocols should be individualized based on age.

Bone mass in Rett syndrome: association with clinical parameters and MECP2 mutations.

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutations in the MECP2 gene. In 49 female RTT children, aged 1.9-17 y, bone mass was assessed and correlated with clinical parameters and mutations involving the MECP2 gene. We also studied five adult females, aged 20-33 y, and one male child, aged 6 y. Lumbar spine bone mineral content (BMC) and bone mineral density (BMD) were correlated with weight, height, BMI, clinical severity, degree of scoliosis, use of anticonvulsants, and ambulatory status. L1-L4 BMD and BMC showed that 48.9% of them had BMD values >2 SD below age-related norms. BMD values were in the osteoporotic range in the five adult females with RTT. Eleven percent of the children and adults with RTT experienced fractures. Low bone mass was correlated with marginal significance to clinical severity and ambulation but not to scoliosis or anticonvulsant use. Lowest bone mass occurred in patients with T158M or R270X mutations but without statistical significance. Studies in a murine model of RTT confirmed low bone mass as an inherent component of this syndrome. MECP2 mutations and clinical parameters impact bone mass in RTT, but an association with a specific mutation was not demonstrable.

Efficacy and safety of mitoxantrone, as an initial therapy, in multiple sclerosis: experience in an Indian tertiary care setting.

BACKGROUND AND PURPOSE: Mitoxantrone is an approved disease modifying agent for treatment of multiple sclerosis (MS). The aim of the study was to assess its efficacy and safety in Indian MS patients. MATERIALS AND METHODS: A total of 23 patients with clinically definite MS (Poser criteria) were enrolled in an open label study. Of which, 21 satisfied the McDonald's criteria for MS and two satisfied the diagnostic criteria of neuromyelitis optica (NMO). The numbers of relapses and expanded disability status scale (EDSS) score were used as primary and secondary outcome measures. The patients were monitored for the adverse effects. RESULTS: In 17 (15 MS and two NMO) patients who completed one year of therapy, there was significant difference in the mean annual relapse rates [before 0.879+/-0.58; on mitoxantrone 0.091+/-0.17, (P=0.003)]. Of the 17 patients, ten (MS 9 and NMO 1) completed therapy for two years. Annual relapse rates [before (1.024+/-0.59), on therapy (0.155+/-0.21), (P=0.0054)] and EDSS score [before start of therapy 5.3, at the end of therapy 2.4, (P=0.001)] showed significant benefit in the ten patients who completed two years therapy. This benefit persisted during the mean follow-up period of two and a half years after completion of therapy. The adverse events noted in the entire cohort were leucopenia in four patients and asymptomatic reversible decrease in cardiac ejection fraction in one patient. Leucopenia was severe in two patients requiring discontinuation of the therapy and mitoxantrone was also discontinued in the patient with cardiotoxicity. CONCLUSIONS: Mitoxantrone, as an initial therapy, decreases clinical exacerbations and disability progression, and has a reasonable safety profile in Indian patients with MS and NMO.

Development and validation of a simple algorithm for initiation of CPAP in neonates with respiratory distress in Malawi.

BACKGROUND: Low-cost bubble continuous positive airway pressure (bCPAP) systems have been shown to improve survival in neonates with respiratory distress, in developing countries including Malawi. District hospitals in Malawi implementing CPAP requested simple and reliable guidelines to enable healthcare workers with basic skills and minimal training to determine when treatment with CPAP is necessary. We developed and validated TRY (T: Tone is good, R: Respiratory Distress and Y=Yes) CPAP, a simple algorithm to identify neonates with respiratory distress who would benefit from CPAP. OBJECTIVE: To validate the TRY CPAP algorithm for neonates with respiratory distress in a low-resource setting. METHODS: We constructed an algorithm using a combination of vital signs, tone and birth weight to determine the need for CPAP in neonates with respiratory distress. Neonates admitted to the neonatal ward of Queen Elizabeth Central Hospital, in Blantyre, Malawi, were assessed in a prospective, cross-sectional study. Nurses and paediatricians-in-training assessed neonates to determine whether they required CPAP using the TRY CPAP algorithm. To establish the accuracy of the TRY CPAP algorithm in evaluating the need for CPAP, their assessment was compared with the decision of a neonatologist blinded to the TRY CPAP algorithm findings. RESULTS: 325 neonates were evaluated over a 2-month period; 13% were deemed to require CPAP by the neonatologist. The inter-rater reliability with the algorithm was 0.90 for nurses and 0.97 for paediatricians-in-training using the neonatologist's assessment as the reference standard. CONCLUSIONS: The TRY CPAP algorithm has the potential to be a simple and reliable tool to assist nurses and clinicians in identifying neonates who require treatment with CPAP in low-resource settings.

The influence of free hemoglobin and bilirubin on heparin monitoring by activated partial thromboplastin time and anti-Xa assay.

CONTEXT: Elevated free hemoglobin (Hb) and bilirubinemia complicate extracorporeal membrane oxygenation and could affect unfractionated heparin (UH) therapy monitoring by anti-Xa assay and activated partial thromboplastin time (aPTT). OBJECTIVES: To compare in vitro response of anti-Xa and aPTT assays to UH in samples with artificial hyperbilirubinemia and hyperhemoglobinemia and to estimate if this interference is also observed in vivo in pediatric extracorporeal membrane oxygenation. DESIGN: Measurement of aPTT and anti-Xa activity in plasma spiked with UH and increased concentration of free Hb and/or conjugated bilirubin. All samples with anti-Xa activity, antithrombin, free Hb, and bilirubin determination and infused dose of UH from inpatients on extracorporeal membrane oxygenation were extracted from the clinical patient database and analyzed. RESULTS: Each increment of free Hb by 100 mg/dL significantly shortened aPTT, whereas an increment of bilirubin by 6 mg/dL caused significant prolongation of aPTT and stepwise increase of free Hb and/or bilirubin in plasma decreased anti-Xa activity by 0.03 to 0.05 IU/mL. Extracorporeal membrane oxygenation samples with free Hb 50 mg/dL or greater had significantly lower anti-Xa activity compared with normal ones: 0.33 (0.25-0.42) versus 0.4 (0.31-0.48) IU/mL (P = .01), despite the identical UH infusion and similar antithrombin activity. Moderate increase of free Hb by 59 mg/dL was associated with absolute decrease of anti-Xa activity by 0.07 IU/mL. CONCLUSIONS: Activated partial thromboplastin time and anti-Xa assay are affected by elevated level of free Hb and/or bilirubin in the presence of UH, and lower anti-Xa activity is noted in extracorporeal membrane oxygenation patients with elevated free Hb. Severe hemolysis and/or hyperbilirubinemia could compromise UH monitoring based on these assays.

Invasive fungal infections in newborns and current management strategies.

Invasive fungal infections due to Candida are the third most common late-onset infection in infants born with birth weight <1500 g. Invasive candidiasis in infants born with birth weight <1000 g is associated with a 30% mortality and with neurodevelopmental impairment in more than half the survivors. A high degree of suspicion and a thorough multisystem evaluation is necessary for diagnosis of invasive fungal infections and to detect complications or sequalae. Amphotericin B deoxycholate is the mainstay in the treatment of invasive fungal infections in newborns. Early initiation of enteral feeds with human milk, decreasing dependence on catheters and avoidance of antacids, steroids and broad-spectrum antibiotics are the recommended preventive measures. Fluconazole prophylaxis should be targeted towards neonates born with <1000 g in neonatal units where baseline rates of invasive candidiasis are more than 5%.

Breastfeeding among inner-city women: from intention before delivery to breastfeeding at hospital discharge.

OBJECTIVE: This study assessed the degree to which women's intention to breastfeed prior to delivery translates to actual breastfeeding at hospital discharge and to investigate predictors of breastfeeding in a minority inner-city population. STUDY DESIGN AND METHODS: We conducted a retrospective cohort study of consecutive mother-infant dyads born July-September 2010 and discharged from the nursery at an academic community hospital in Philadelphia. RESULTS: The demographics of the 578 women who participated included a mean age of 25.3 years (SD 6.1), 61% African American and 18% Latina, 85% covered by Medicaid, and a mean postpartum hospital stay of 2.3 days. Overall, 60% expressed an intention to breastfeed prior to delivery (exclusively or with formula), but only 50% were breastfeeding at discharge. Of those who intended to breastfeed (exclusively or with formula), 75% were breastfeeding at discharge. Of those who intended to breastfeed exclusively, 40% were doing so at discharge. Of those who intended to bottle feed, 11% were breastfeeding at discharge. In multivariable analysis, older mothers and those with lower parity were more likely to breastfeed at discharge and also to breastfeed exclusively, controlling for ethnicity, parity, insurance, pregravida body mass index, score on the Edinburgh Postpartum Depression Scale, type of delivery, infant birth weight and gestational age. CONCLUSIONS: In a minority inner-city population, only three in four women who intended to breastfeed prior to delivery were breastfeeding at hospital discharge. However, one in 10 women previously not intending to breastfeed did so. Strategies are needed to promote and strengthen women's intention to breastfeed and to help women's breastfeeding outcomes meet their intentions.

Hour-specific bilirubin nomogram in infants with ABO incompatibility and direct Coombs-positive results.

OBJECTIVE: To determine the usefulness of the hour-specific Bhutani et al bilirubin nomogram when applied to infants with Coombs-positive test results. DESIGN: Retrospective chart review. SETTING: Term nursery and neonatal intensive care unit of a university-affiliated hospital. PATIENTS: All infants with A+ or B+ blood type born in our center from September 1, 2006, through August 31, 2008, to mothers with O+ blood. OUTCOMES: Proportion of infants with Coombs-positive results from the nomogram zones who required phototherapy and comparison of the percentage of infants with Coombs-positive results in each zone with the percentage of those with Coombs-negative results in each zone. RESULTS: A total of 240 infants with Coombs-positive and 460 with Coombs-negative results having a gestational age of 35 weeks or older were evaluated. Sensitivity and specificity of data for infants with direct Coombs-positive results in zone 4 (high risk; 74.2% and 97.1%) and those for infants in zones 3 (high-intermediate risk) and 4 combined (96.7% and 83.7%) compared favorably with the data from the Bhutani et al cohort, which had direct Coombs-negative results (54.0% and 96.2% for zone 4; 90.5% and 84.7% for zones 3 and 4 combined). The likelihood ratio for infants with direct Coombs-positive results in zone 4, 25.8 (95% confidence interval, 11.4-58.4), was twice that of the Bhutani et al cohort, 14.1 (11.0-18.1). The nomogram performed well in directing the timing of bilirubin level follow-up. All infants in zones 3 and 4 with Coombs-positive results were followed up after hospital discharge. None required an exchange transfusion or developed bilirubin encephalopathy. CONCLUSIONS: The Bhutani et al bilirubin nomogram reliably identified infants at gestational age of older than 35 weeks with direct Coombs-positive results who were at risk for significant hyperbilirubinemia and directed the timing of follow-up for these infants. This finding has direct clinical applicability to the health care professional practicing in the newborn nursery.