Antimicrobial resistance heterogeneity among multidrug-resistant Gram-negative pathogens: Phenotypic, genotypic, and proteomic analysis.

Microbes evolve rapidly by modifying their genomes through mutations or through the horizontal acquisition of mobile genetic elements (MGEs) linked with fitness traits such as antimicrobial resistance (AMR), virulence, and metabolic functions. We conducted a multicentric study in India and collected different clinical samples for decoding the genome sequences of bacterial pathogens associated with sepsis, urinary tract infections, and respiratory infections to understand the functional potency associated with AMR and its dynamics. Genomic analysis identified several acquired AMR genes (ARGs) that have a pathogen-specific signature. We observed that blaCTX-M-15, blaCMY-42, blaNDM-5, and aadA(2) were prevalent in Escherichia coli, and blaTEM-1B, blaOXA-232, blaNDM-1, rmtB, and rmtC were dominant in Klebsiella pneumoniae. In contrast, Pseudomonas aeruginosa and Acinetobacter baumannii harbored blaVEB, blaVIM-2, aph(3'), strA/B, blaOXA-23, aph(3') variants, and amrA, respectively. Regardless of the type of ARG, the MGEs linked with ARGs were also pathogen-specific. The sequence type of these pathogens was identified as high-risk international clones, with only a few lineages being predominant and region-specific. Whole-cell proteome analysis of extensively drug-resistant K. pneumoniae, A. baumannii, E. coli, and P. aeruginosa strains revealed differential abundances of resistance-associated proteins in the presence and absence of different classes of antibiotics. The pathogen-specific resistance signatures and differential abundance of AMR-associated proteins identified in this study should add value to AMR diagnostics and the choice of appropriate drug combinations for successful antimicrobial therapy.

Body composition from birth to 6 months in term small for gestational age Indian infants: Effect of catch-up growth.

The objective of this prospective observational study was to assess the growth and body composition of term small for gestational age (SGA) infants from birth to 6 months and evaluate the effect of catch-up growth (CUG) on body composition. Term SGA newborns were recruited at birth. Anthropometry and body composition were evaluated at 3 days, 6, 10 and 14 weeks, and 6 months. Fat and fat-free mass (FM and FFM) were compared between infants with and without CUG (increase in weight Z-score by >0.67) by air displacement plethysmography. Factors that could affect body composition and CUG, including parents' BMI and stature, infants' weight, gender and feeding were evaluated. 143 SGA newborns (66 boys) with birth weight of 2336 ± 214 g were enrolled; 109 were followed-up till 6 months. Median weight Z-score increased from -2.3 at birth to -1.3 at 6 months, with 51.9% of infants showing CUG. Infants with CUG had higher FM (1796 ± 491g vs. 1196 ± 474 g, p<0.001) but similar FFM (4969 ± 508g vs. 4870 ± 622g, p=0.380); and consequently higher FM% (26.5 ± 5.8 vs. 19.7 ± 6.9, p<0.001), compared to those without CUG. Lower birth weight, exclusive breastfeeding and higher parental stature were positively associated with CUG. In conclusion, CUG in term SGA infants in first 6 months of life was almost entirely attributable to greater gain in fat mass. Follow-up of this cohort will provide insight into the long-term effect of disproportionate gain in FM in early infancy in SGA babies.

Research on Assimilation of Unmanned Aerial Vehicle Remote Sensing Data and AquaCrop Model.

Taking the AquaCrop crop model as the research object, considering the complexity and uncertainty of the crop growth process, the crop model can only achieve more accurate simulation on a single point scale. In order to improve the application scale of the crop model, this study inverted the canopy coverage of a tea garden based on UAV multispectral technology, adopted the particle swarm optimization algorithm to assimilate the canopy coverage and crop model, constructed the AquaCrop-PSO assimilation model, and compared the canopy coverage and yield simulation results with the localized model simulation results. It is found that there is a significant regression relationship between all vegetation indices and canopy coverage. Among the single vegetation index regression models, the logarithmic model constructed by OSAVI has the highest inversion accuracy, with an R2 of 0.855 and RMSE of 5.75. The tea yield was simulated by the AquaCrop-PSO model and the measured values of R2 and RMSE were 0.927 and 0.12, respectively. The canopy coverage R2 of each simulated growth period basically exceeded 0.9, and the accuracy of the simulation results was improved by about 19.8% compared with that of the localized model. The results show that the accuracy of crop model simulation can be improved effectively by retrieving crop parameters and assimilating crop models through UAV remote sensing.

Patterns of antibiotic use, pathogens, and prediction of mortality in hospitalized neonates and young infants with sepsis: A global neonatal sepsis observational cohort study (NeoOBS).

BACKGROUND: There is limited data on antibiotic treatment in hospitalized neonates in low- and middle-income countries (LMICs). We aimed to describe patterns of antibiotic use, pathogens, and clinical outcomes, and to develop a severity score predicting mortality in neonatal sepsis to inform future clinical trial design. METHODS AND FINDINGS: Hospitalized infants <60 days with clinical sepsis were enrolled during 2018 to 2020 by 19 sites in 11 countries (mainly Asia and Africa). Prospective daily observational data was collected on clinical signs, supportive care, antibiotic treatment, microbiology, and 28-day mortality. Two prediction models were developed for (1) 28-day mortality from baseline variables (baseline NeoSep Severity Score); and (2) daily risk of death on IV antibiotics from daily updated assessments (NeoSep Recovery Score). Multivariable Cox regression models included a randomly selected 85% of infants, with 15% for validation. A total of 3,204 infants were enrolled, with median birth weight of 2,500 g (IQR 1,400 to 3,000) and postnatal age of 5 days (IQR 1 to 15). 206 different empiric antibiotic combinations were started in 3,141 infants, which were structured into 5 groups based on the World Health Organization (WHO) AWaRe classification. Approximately 25.9% (n = 814) of infants started WHO first line regimens (Group 1-Access) and 13.8% (n = 432) started WHO second-line cephalosporins (cefotaxime/ceftriaxone) (Group 2-"Low" Watch). The largest group (34.0%, n = 1,068) started a regimen providing partial extended-spectrum beta-lactamase (ESBL)/pseudomonal coverage (piperacillin-tazobactam, ceftazidime, or fluoroquinolone-based) (Group 3-"Medium" Watch), 18.0% (n = 566) started a carbapenem (Group 4-"High" Watch), and 1.8% (n = 57) a Reserve antibiotic (Group 5, largely colistin-based), and 728/2,880 (25.3%) of initial regimens in Groups 1 to 4 were escalated, mainly to carbapenems, usually for clinical deterioration (n = 480; 65.9%). A total of 564/3,195 infants (17.7%) were blood culture pathogen positive, of whom 62.9% (n = 355) had a gram-negative organism, predominantly Klebsiella pneumoniae (n = 132) or Acinetobacter spp. (n = 72). Both were commonly resistant to WHO-recommended regimens and to carbapenems in 43 (32.6%) and 50 (71.4%) of cases, respectively. MRSA accounted for 33 (61.1%) of 54 Staphylococcus aureus isolates. Overall, 350/3,204 infants died (11.3%; 95% CI 10.2% to 12.5%), 17.7% if blood cultures were positive for pathogens (95% CI 14.7% to 21.1%, n = 99/564). A baseline NeoSep Severity Score had a C-index of 0.76 (0.69 to 0.82) in the validation sample, with mortality of 1.6% (3/189; 95% CI: 0.5% to 4.6%), 11.0% (27/245; 7.7% to 15.6%), and 27.3% (12/44; 16.3% to 41.8%) in low (score 0 to 4), medium (5 to 8), and high (9 to 16) risk groups, respectively, with similar performance across subgroups. A related NeoSep Recovery Score had an area under the receiver operating curve for predicting death the next day between 0.8 and 0.9 over the first week. There was significant variation in outcomes between sites and external validation would strengthen score applicability. CONCLUSION: Antibiotic regimens used in neonatal sepsis commonly diverge from WHO guidelines, and trials of novel empiric regimens are urgently needed in the context of increasing antimicrobial resistance (AMR). The baseline NeoSep Severity Score identifies high mortality risk criteria for trial entry, while the NeoSep Recovery Score can help guide decisions on regimen change. NeoOBS data informed the NeoSep1 antibiotic trial (ISRCTN48721236), which aims to identify novel first- and second-line empiric antibiotic regimens for neonatal sepsis. TRIAL REGISTRATION: ClinicalTrials.gov, (NCT03721302).

Government-led initiative increased the effective use of Kangaroo Mother Care in a region of North India.

AIM: To learn how to achieve high-quality, effective coverage of Kangaroo Mother Care (KMC), defined as 8 hours or more of skin-to-skin contact per day and exclusive breastfeeding in district Sonipat in North India, and to develop and evaluate an implementation model. METHODS: We conducted implementation research using a mixed-methods approach, including formative research, followed by repeated, rapid cycles of implementation, evaluation and refinement until a model with the potential for high and effective coverage was reached. Evaluation of this model was conducted over a 12-month period. RESULTS: Formative research findings informed the final implementation model. Programme learning was critical to achieve high coverage. The model included improving the identification of small babies, creating KMC wards, modification in hospitalisation criteria, private sector engagement and in-built programme learning to refine implementation progress. KMC was initiated in 87% of eligible babies. At discharge, 85% received skin-to-skin contact care, 60% effective KMC and 80% were exclusively breastfed. At home, 7-day post discharge, 81% received skin-to-skin care and 79% were exclusively breastfed in the previous 24 hours. CONCLUSION: Achieving high KMC coverage is feasible in the study setting using a model responsive to the local context and led by the Government.

Antibiotics needed to treat multidrug-resistant infections in neonates.

Infections remain a leading cause of death in neonates. The sparse antibiotic development pipeline and challenges in conducting neonatal research have resulted in few effective antibiotics being adequately studied to treat multidrug-resistant (MDR) infections in neonates, despite the increasing global mortality burden caused by antimicrobial resistance. Of 40 antibiotics approved for use in adults since 2000, only four have included dosing information for neonates in their labelling. Currently, 43 adult antibiotic clinical trials are recruiting patients, compared with only six trials recruiting neonates. We review the World Health Organization (WHO) priority pathogens list relevant to neonatal sepsis and propose a WHO multiexpert stakeholder meeting to promote the development of a neonatal priority antibiotic development list. The goal is to develop international, interdisciplinary consensus for an accelerated neonatal antibiotic development programme. This programme would enable focused research on identified priority antibiotics for neonates to reduce the excess morbidity and mortality caused by MDR infections in this vulnerable population.

Les infections demeurent l'une des principales causes de décès chez les nouveau-nés. Les rares projets de développement d'antibiotiques et les défis posés par la recherche néonatale ont entraîné une pénurie d'antibiotiques efficaces spécialement étudiés pour traiter les infections multirésistantes (MR) chez les nouveau-nés, en dépit d'une mortalité galopante due à une résistance accrue aux antimicrobiens. Sur 40 antibiotiques autorisés pour les adultes depuis 2000, quatre à peine sont munis d'un étiquetage indiquant la posologie adaptée aux nouveau-nés. Actuellement, 43 essais cliniques portant sur des antibiotiques recrutent des patients du côté des adultes, contre six seulement du côté des nouveau-nés. Dans le présent document, nous passons en revue la liste prioritaire d'agents pathogènes établie par l'Organisation mondiale de la Santé (OMS) pour soigner la septicémie néonatale et proposons de réunir, sous l'égide de l'OMS, des parties prenantes issues de plusieurs domaines d'expertise afin de promouvoir la création d'une liste prioritaire de développement d'antibiotiques destinés aux nouveau-nés. Objectif: parvenir à un consensus international et interdisciplinaire visant à accélérer le programme de mise au point d'antibiotiques à usage néonatal. Ce programme permettrait d'orienter les recherches vers des antibiotiques identifiés comme prioritaires pour les nouveau-nés, en vue de faire baisser les taux de morbidité et de mortalité excessifs qu'engendrent les infections MR au sein de cette population vulnérable.

Las infecciones siguen siendo una de las principales causas de muerte en los recién nacidos. Debido al escaso desarrollo de los antibióticos y a las dificultades para llevar a cabo la investigación neonatal, son pocos los antibióticos eficaces que se estudian de manera adecuada para tratar las infecciones multirresistentes (MR) en los recién nacidos, a pesar de la creciente carga de mortalidad mundial causada por la resistencia a los antimicrobianos. De los 40 antibióticos aprobados para su uso en adultos desde el 2000, solo cuatro han incluido información sobre la dosis para recién nacidos en su etiquetado. En la actualidad, 43 ensayos clínicos con antibióticos para adultos están reclutando pacientes, en comparación con solo seis ensayos que reclutan recién nacidos. Se revisa la lista de patógenos prioritarios de la Organización Mundial de la Salud (OMS) relevantes para la sepsis neonatal y se propone una reunión de la OMS con múltiples expertos para promover el desarrollo de una lista de antibióticos prioritarios para los recién nacidos. El objetivo es desarrollar un consenso internacional e interdisciplinario para establecer un programa acelerado de desarrollo de antibióticos neonatales. Este programa permitiría centrar la investigación en los antibióticos prioritarios identificados para los recién nacidos con el fin de reducir el exceso de morbilidad y mortalidad causado por las infecciones MR en esta población vulnerable.

'Lip-to-Tip' study: comparison of three methods to determine optimal insertion length of endotracheal tube in neonates.

The aim of this prospective observational study was to compare the incidence of endotracheal tube (ETT) malposition using weight-based (Tochen), gestation-based (Kempley), and nasotragal length (NTL) methods in deceased neonates and fresh stillbirths. We enrolled deceased neonates and fresh stillbirths within 2 ± 1 h of death or delivery, respectively; without hydrops, tracheostomy or major congenital anomalies affecting face, neck, or thorax. Each enrolled subject was intubated orotracheally, with lip-to-tip distance determined by three methods in random succession. Chest X-ray was acquired after each insertion. The primary outcome was proportion of malpositioned ETTs on chest X-ray (defined as ETT tip not lying between upper border of T1 and lower border of T2 vertebrae), assessed by two experts masked to the methods used. The proportion of malpositioned tubes was not significantly different with any of the three methods: (weight 27/50 (54%), gestation 35/50 (70%), and NTL 35/50 (70%), p value 0.055). The malpositioned tubes were too far in (87/150; 58%) than too far out (10/150; 6.7%).Conclusions: None of the currently recommended methods accurately predicts optimal ETT length in neonates. There is an urgent need for newer bedside modalities for estimating ETT position in neonates. What is known? • NRP guidelines recommend gestation-based and nasotragal length (NTL) methods to estimate initial ETT depth in neonates. Weight-based (Tochen) method is still widely used in neonatal units for ETT depth estimation. Evidence till date has not proven superiority of one method over the other. What is new? • All three methods for ETT depth estimation (Tochen, gestation-based, and NTL) resulted in high rates of ETT malposition in neonates. Formulae, devised from this study based on linear regression models, did not perform well for estimation of optimal ETT position.

Utility of fetal whole exome sequencing in the etiological evaluation and outcome of nonimmune hydrops fetalis.

INTRODUCTION: Nonimmune hydrops fetalis (NIHF) has varied etiology. We assessed the etiological spectrum and evaluated the utility of fetal whole exome sequencing (fWES) for the diagnosis of NIHF. METHODS: In this prospective cohort study, we evaluated antenatally diagnosed fetuses with NIHF between July 2018 and December 2019 according to the routine diagnostic algorithm. Fetuses that remained undiagnosed after routine NIHF workup were subjected to fetal chromosomal microarray and/or WES. Pregnancies were followed up for clinical outcomes. RESULTS: Of the 45 fetuses, consanguinity and recurrent hydrops fetalis were observed in 13.3% (6/45) and 28.8% (13/45), respectively. Overall, an etiological diagnosis was possible in 75.5% (34/45) of fetuses, while the cause remained unknown in 24.4% (11/45). A genetic etiology was identified in 46.6% (21/45): aneuploidy and monogenic disorders in 28.8% (13/45) and 17.8% (8/45), respectively. fWES on 19 fetuses detected disease-causing variants in 42.1% (8/19). Nine novel variants were detected in RAPSN, ASCC1, NEB, PKD1L1, GUSB, and PIEZO1. Only 8.8% (4/45) of the cohort survived without morbidity. CONCLUSIONS: This study describes the etiological spectrum and the disease-causing variants in an Indian cohort of hydropic fetuses.

Bed sharing versus no bed sharing for healthy term neonates.

BACKGROUND: There is great global variation in the sleeping arrangements for healthy newborn infants. Bed sharing is a type of sleeping practice in which the sleeping surface (e.g. bed, couch or armchair, or some other sleeping surface) is shared between the infant and another person. The possible physiological benefits include better oxygen and cardiopulmonary stability, fewer crying episodes, less risk of hypothermia, and a longer duration of breastfeeding. On the other hand, the most important harmful effect of bed sharing is that it may increase the risk of sudden infant death syndrome (SIDS). Studies have found conflicting evidence regarding the safety and efficacy of bed sharing during infancy. OBJECTIVES: To evaluate the efficacy and safety of bed sharing, started during the neonatal period, on breastfeeding status (exclusive and total duration of breastfeeding), incidence of SIDS, rates of hypothermia, neonatal and infant mortality, and long-term neurodevelopmental outcomes. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 7) in the Cochrane Library; MEDLINE via PubMed (1966 to 23 July 2020), CINAHL (1982 to 23 July 2020), and LILACS (1980 to 23 July 2020). We also searched clinical trials databases, and the reference lists of retrieved articles, for randomised controlled trials (RCTs) and quasi-RCTS. SELECTION CRITERIA: We planned to include RCTs or quasi-RCTs (including cluster-randomised trials) that included term neonates initiated on bed sharing within 24 hours of birth (and continuing to bed share with the mother in the first four weeks of life, followed by a variable time period thereafter), and compared them to a 'no bed sharing' group. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as recommended by Cochrane. We planned to use the GRADE approach to assess the certainty of evidence. MAIN RESULTS: Our search strategy yielded 6231 records. After removal of duplicate records, we screened 2745 records by title and abstract. We excluded 2739 records that did not match our inclusion criteria. We obtained six full-text studies for assessment. These six studies did not meet the eligibility criteria and were excluded. AUTHORS' CONCLUSIONS: We did not find any studies that met our inclusion criteria. There is a need for RCTs on bed sharing in healthy term neonates that directly assess efficacy (i.e. studies in a controlled setting, like hospital) or effectiveness (i.e. studies conducted in community or home settings) and safety. Future studies should assess outcomes such as breastfeeding status and risk of SIDS. They should also include neonates from high-income countries and low- and middle-income countries, especially those countries where bed sharing is more prevalent because of cultural practices (e.g. Asian countries).

Low dose fentanyl infusion versus 24% oral sucrose for pain management during laser treatment for retinopathy of prematurity-an open label randomized clinical trial.

To compare the efficacy of low dose fentanyl infusion and 24% oral sucrose in providing optimal pain relief during laser for retinopathy of prematurity (ROP), we enrolled fifty-eight spontaneously breathing preterm infants undergoing laser. The preterm infants were randomized to either fentanyl infusion (1 mcg/kg/hr) or 24% oral sucrose (2 ml). We evaluated and compared the proportion of time spent crying during the procedure, salivary cortisol before and after the procedure, premature infant pain profile- revised (PIPP-R) scores during the procedure, apnoea during and after the procedure, need for mechanical ventilation, and feed intolerance and urinary retention 24 h after the procedure between the two groups. We found that the proportion of time spent crying during the procedure was significantly less in the fentanyl group [62.5% (50.7-74.2) vs 73.8% (55.6-83.4); P = 0.02]. Average PIPP-R score during the procedure was significantly less in the fentanyl group [7.2 vs 9.0; (mean difference of - 1.8; P = 0.01)]. There was no difference in other outcomes between the two groups.Conclusion: During laser for ROP, low dose fentanyl infusion was found to be efficacious in reducing pain as compared with 24% sucrose.What is Known:• Preterm infants undergoing laser photocoagulation for ROP suffer significant amount of pain.• Standard of care for pain relief in infants undergoing laser therapy in developed countries is general anesthesia (GA) or combination of sedation, analgesia, and paralysis (SAP).What is New:• During laser photocoagulation for ROP, fentanyl infusion at low dose (1 mcg/kg/hr) is efficacious in reducing pain as compared to 24% oral sucrose.

Delayed cord clamping in Rh-alloimmunised infants: a randomised controlled trial.

Despite advancement in medical care, Rh alloimmunisation remains a major cause of neonatal hyperbilirubinaemia, neuro-morbidity, and late-onset anaemia. Delayed cord clamping (DCC), a standard care now-a-days, is yet not performed in Rh-alloimmunised infants due to paucity of evidence. Hence, we randomised these infants of 28- to 41-week gestation to delayed cord clamping (N = 36) or early cord clamping (N = 34) groups. The primary outcome variable was venous packed cell volume (PCV) at 2 h of birth. The secondary outcomes were incidence of double volume exchange transfusion (DVET) and partial exchange transfusion (PET), duration of phototherapy (PT), functional echocardiography (parameters measured: superior vena cava flow, M-mode fractional shortening, left ventricular output, myocardial perfusion index, and inferior vena cava collapsibility) during hospital stay, and blood transfusion (BT) until 14 weeks of life. Neonates were managed as per unit protocol. The baseline characteristics of enrolled infants were comparable between the groups. The median (IQR) gestation and mean (SD) birth weight of enrolled infants were 35 (33-37) weeks and 2440 (542) g, respectively. The DCC group had a higher mean PCV at 2 h of life (48.4 ± 9.2 vs. 43.5 ± 8.7, mean difference 4.9% (95% CI 0.6-9.1), p = 0.03). However, incidence of DVET and PET, duration of PT, echocardiography parameters, and BT until 14 weeks of postnatal age were similar between the groups.Conclusion: DCC in Rh-alloimmunised infants improved PCV at 2 h of age without significant adverse effects.Trial registration: Clinical Trial Registry of India (CTRI), Ref/2016/11/012572 http://ctri.nic.in/Clinicaltrials, date of trial registration 19.12.2016, date of first patient enrolment 1 January 2017.What is Known:•Delayed cord clamping improves haematocrit, results in better haemodynamic stability, and decreases the need of transfusion in early infancy.•However, due to lack of evidence, potential risk of hyperbilirubinaemia, and exacerbation of anaemia (following delayed cord clamping), early cord clamping is the usual norm in Rh-alloimmunised infantsinfants.What is New:•Delayed cord clamping in Rh-alloimmunised infants improves haematocrit at 2 h of life without any increase in incidence of serious adverse effects.

Nasal masks or binasal prongs for delivering continuous positive airway pressure in preterm neonates-a randomised trial.

The objective of this study was to compare the efficacy and safety of continuous positive airway pressure (CPAP) delivered using nasal masks with binasal prongs. We randomly allocated 72 neonates between 26 and 32 weeks gestation to receive bubble CPAP by either nasal mask (n = 37) or short binasal prongs (n = 35). Primary outcome was mean FiO2 requirement at 6, 12 and 24 h of CPAP initiation and the area under curve (AUC) of FiO2 against time during the first 24 h (FiO2 AUC0-24). Secondary outcomes were the incidence of CPAP failure and nasal trauma. FiO2 requirement at 6, 12 and 24 h (mean (SD); 25 (5.8) vs. 27.9 (8); 23.8 (4.5) vs. 25.4 (6.8) and 22.6 (6.8) vs. 22.7 (3.3)) as well as FiO2 AUC0-24 (584.0 (117.8) vs. 610.6 (123.6)) were similar between the groups. There was no difference in the incidence of CPAP failure (14 vs. 20%; relative risk 0.67; 95% confidence interval 0.24-1.93). Incidence of severe nasal trauma was lower with the use of nasal masks (0 vs. 31%; p < .001). CONCLUSIONS: Nasal masks appear to be as efficacious as binasal prongs in providing CPAP. Masks are associated with lower risk of severe nasal trauma. TRIAL REGISTRATION: CTRI2012/08/002868 What is Known? • Binasal prongs are better than single nasal and nasopharyngeal prongs for delivering continuous positive airway pressure (CPAP) in preventing need for re-intubation. • It is unclear if they are superior to newer generation nasal masks in preterm neonates requiring CPAP. What is New? • Oxygen requirement during the first 24 h of CPAP delivery is comparable with use of nasal masks and binasal prongs. • Use of nasal masks is, however, associated with significantly lower risk of severe grades of nasal injury.

Reduction of Neonatal Mortality Requires Strengthening of the Health System: A Situational Analysis of Neonatal Care Services in Ballabgarh.

Background: Planning a comprehensive program addressing neonatal mortality will require a detailed situational analysis of available neonatal-specific health infrastructure. Methods: We identified facilities providing essential and sick neonatal care (ENC, SNC) by a snowballing technique in Ballabgarh Block. These were assessed for infrastructure, human resource and equipment along with self-rated competency of the staff and compared with facility-based or population-based norms. Results: A total of 35 facilities providing ENC and 10 facilities for SNC were identified. ENC services were largely in the public-sector domain (68.5% of births) and were well distributed in the block. SNC burden was largely being borne by the private sector (66% of admissions), which was urban-based. The private sector and nurses reported lower competency especially for SNC. Only 53.9% of government facilities and 17.5% of private facilities had a fully equipped newborn care corner. Conclusions: Serious efforts to reduce neonatal mortality would require major capacity strengthening of the health system, including that of the private sector.

Feasibility study of a novel intraosseous device in adult human cadavers.

BACKGROUND & OBJECTIVES: Intraosseous (IO) access is an alternative to difficult intravenous (iv) access during emergency clinical situations. Existing IO solutions are expensive, require power supply and trained manpower; limiting their use in resource constrained settings. To address these limitations, a novel IO device has been developed. The objectives of this study were to evaluate functionality and safety of this device in adult human cadavers. METHODS: The ability of the IO device to penetrate the proximal and/or distal tibia was evaluated in three adult cadavers. Subjective parameters of loss of resistance, stable needle hold, easy needle withdrawal and any damage to the device were evaluated during the study. The insertion time was the objective parameter measured. Four sets of radiographs per insertion confirmed the position of the needle and identified complications. RESULTS: A single physician performed 12 IO access procedures using the same device. Penetration of proximal and/or distal tibia was achieved in all instances. It was successful in the first attempt in eight (66.7%) and during second attempt in the remaining. The mean time to insertion was 4.1 ± 3.1 sec. Appropriate insertion of needle in the intra-medullary space of bone was confirmed with radiological examination in 10 (83.3%) insertions. In two occasions after penetrating the cortical layer of bone, the device overshot the intra-medullary space, as detected by radiological examination. Device got bent during insertion in one instance. There was no evidence of needle breakage or bone fracture. The needle could be withdrawn effortlessly in all instances. INTERPRETATION & CONCLUSIONS: The novel IO device could successfully penetrate the adult cadaver bones in most cases. Further studies are needed to confirm these results on a large sample.

Changes in Myocardial Contractility and Electromechanical Interval During the First Month of Life in Healthy Neonates.

This study aims at documenting the changes in ventricular tissue velocities, longitudinal strain and electromechanical coupling during the first month of life. During the neonatal period, when the ventricular myocardium is not yet fully maturated, the heart is subjected to significant hemodynamic changes. We studied the ventricular performance of 16 healthy neonates at three time points over the first month of life: on days 2 (IQR [2;2]), 13 [12;14] and 27 [25;29]. We found that systolic and diastolic tissue velocities increased significantly in both left and right ventricle (by 1.2-1.7 times, p < 0.001). Congruently, we found that peak systolic longitudinal strain of the right and left ventricles increased significantly. However, no significant changes in longitudinal strain rate were observed. Finally, QS-intervals shortened during the neonatal period: being measured at 12 points throughout the left ventricle, time to peak systolic velocity decreased on average to 89 % in the second and to 80 % in the fourth week of life (22.3 ± 0.2 vs. 19.8 ± 0.3 vs. 17.8 ± 0.5 ms, r = -0.564, p < 0.001). When comparing opposing walls of the left ventricle, no dyssynchrony in left ventricular contraction was found. In addition to increasing systolic and diastolic tissue velocities during the first month of life, the time to peak systolic contraction shortens in the neonatal heart, which may reflect an increasing efficiency of the excitation-contraction coupling in the maturing myocardium. While there appears to be no dyssynchrony in ventricular contraction, these findings may extend our appreciation of the immature neonatal heart and certain disease states.

Perinatal survival and procedure-related complications after intrauterine transfusion for red cell alloimmunization.

OBJECTIVES: To study the perinatal survival and procedure-related (PR)complications after intrauterine transfusions in red cell alloimmunization. METHODS: Prospective data of 102 women with Rh-alloimmunized pregnancy undergoing intrauterine intravascular transfusion for fetal anemia, from January 2011 to October 2014 were analyzed. Main outcome measures were perinatal survival and procedure-related (PR) complications. RESULTS: A total of 303 intrauterine transfusions were performed in 102 women. Of 102 fetuses, 22 were hydropic at first transfusion. The mean period of gestation and hematocrit at first transfusion was 26.9 ± 3.3 weeks (range 19.7-33.8 weeks) and 17 ± 7.82 % (range 5.7-30 %), respectively. Average number of transfusions was 2.97 (range 1-7) per patient. Overall survival was 93 % and mean period of gestation at delivery was 34.5 ± 1.94 (range 28.3-37.4) weeks. Mean hematocrit at delivery was 36.9 ± 8.77 % (range 10-66 %). Fetal death occurred in four cases (3PR), neonatal death occurred in three cases (2PR). Emergency cesarean delivery after transfusion was performed in four pregnancies. The total PR complication rate was 2.97 %, resulting in overall PR loss in 1.65 % per procedure. CONCLUSION: Our results compare favorably with other studies published in the literature. Intravascular transfusion is a safe procedure improving perinatal survival in fetuses with anemia due to Rh-alloimmunization.

Efficacy and acceptability of an "App on sick newborn care" in physicians from newborn units.

BACKGROUND: There has been an increased emphasis on institutional births, and thus an increasing clinical work load for health care professionals in the recent past. Hence, continuing education, training, ongoing supervision, and mentorship of health care professionals working in these health facilities with easy access to guidelines in a cost effective manner has become a challenging task. With the increased emphasis on institutional births, and an increasing clinical work load, continuing education and training of health care professional managing these health facilities, their ongoing supervision, mentorship, with ready availability of guidelines in a cost effective manner becomes imperative and is a challenging task. Training opportunities can be linked to mobile electronic devices and 'Apps' to improve the care of seriously ill newborn. The aim of this study was to evaluate the efficacy of an innovative point of care tool- Android based App- 'AIIMS-WHO CC STPs' on the knowledge, skill scores, and satisfaction among Special Newborn Care Unit (SNCU) physicians managing sick neonates. METHODS: The baseline knowledge and skill scores of pediatricians working in SNCUs in the state of Tamil Nadu, India (n = 32) were assessed by 25 multiple choice questions (MCQs) and by five Objective Structured Clinical Examination (OSCE) skill stations. The training was conducted in a single-day workshop using the app on four modules followed by post-training assessment of knowledge and skill scores after 3 weeks using the same. The satisfaction was assessed by mixed method approach using Likert's scale and focus group discussion (FGD) after 3 weeks. RESULTS: The mean knowledge scores [19.4 (2.6) vs. 10.7 (3.2); maximum marks (MM) 25, mean difference 8.7 (95 % CI 7.6 to 9.9)], and the composite mean skill scores [55.2 (5.8) and 42 (6.2), MM 75, mean difference 13.2 (95 % CI 10.4 to 15.9)] improved after training. The median (IQR) satisfaction score with the course was 4 (4 to 5) (Likert's scale). Focus group discussion revealed that the physicians were overall satisfied using the device. They expressed overall satisfaction on the teaching methodology using wall charts, simulators, and device. CONCLUSION: Training SNCU physicians on Android based App- 'AIIMS-WHO CC STPs' improved their knowledge and skills. This app may have a potential role as a supplement to other modalities in training doctors for improving newborn care.

Description and Validation of a Novel Method of Measuring Pharyngeal Pressure in New-born.

Study background: Measurement of delivered pharyngeal pressure during continuous positive airway pressure (CPAP) therapy is not in routine practice due to lack of a simple and affordable technique of intrapharyngeal pressure measurement. To overcome the lack of the gold standard solid-state catheter-tip pressure measurement technology in our set up, we improvised a novel method of pressure measurement and tested its validity in a simulated pharynx. METHODS: A low-cost pressure transducer was improvised by attaching an orogastric tube to its one end. The other end of the orogastric tube was sealed into an artificial pharynx - a 20 ml syringe. The pressure transducer readings were compared with that obtained by a digital manometer attached to the tip of the syringe. Bland-Altman statistic was used to quantify the measurement reliability of the novel method against the digital manometer. Effect of tube length on the measurement agreement was also studied. The developed technique was applied in new-borns. RESULTS & CONCLUSION: Pressures measured by this technique were in good agreement with that obtained using a digital manometer. This technique has the potential to be used as an alternative to catheter-tip pressure transducers for bedside pharyngeal pressure measurement in new-born babies, especially in under-resourced setups.

Oral zinc for the prevention of hyperbilirubinaemia in neonates.

BACKGROUND: Between 6% and 15% of neonates develop hyperbilirubinaemia requiring treatment. Successful management of neonatal hyperbilirubinaemia relies on prevention and early treatment, with phototherapy being the mainstay of treatment. Oral zinc has been reported to decrease the serum total bilirubin (STB), presumably by decreasing the enterohepatic circulation. OBJECTIVES: To determine the effect of oral zinc supplementation compared to placebo or no treatment on the incidence of hyperbilirubinaemia in neonates during the first week of life and to assess the safety of oral zinc in enrolled neonates. SEARCH METHODS: We searched CENTRAL (The Cochrane Library 2014, Issue 1), MEDLINE (1966 to November 30, 2014), and EMBASE (1990 to November 30, 2014). SELECTION CRITERIA: Randomised controlled trials were eligible for inclusion if they enrolled neonates (term and preterm) to whom oral zinc, in a dose of 10 to 20 mg/day, was initiated within the first 96 hours of life, for any duration until day seven, compared with no treatment or placebo. DATA COLLECTION AND ANALYSIS: We used the standard methods of The Cochrane Collaboration and its Neonatal Review Group for data collection and analysis. MAIN RESULTS: Only one study met the criteria of inclusion in the review. This study compared oral zinc with placebo. Oral zinc was administered in a dose of 5 mL twice daily from day 2 to day 7 postpartum. The drug was administered into the mouth of the infant by the plastic measure provided with the bottle or with a spoon. Incidence of hyperbilirubinaemia, defined as serum total bilirubin (STB) ≥ 15 mg/dL, was similar between groups (N = 286; risk ratio (RR) 0.94, 95% confidence interval (CI) 0.58 to 1.52). Mean STB levels, mg/dL, at 72 ± 12 hours were comparable in both the groups (N = 286; mean difference (MD) -0.20; 95% CI -1.03 to 0.63). Although the duration of phototherapy in the zinc group was significantly shorter compared to the placebo group (N = 286; MD -12.80, 95% CI -16.93 to -8.67), the incidence of need for phototherapy was comparable across both the groups (N = 286; RR 1.20; 95% CI 0.66 to 2.18). Incidences of side effects like vomiting (N = 286; RR 0.65, 95% CI 0.19 to 2.25), diarrhoea (N = 286; RR 2.92, 95% CI 0.31 to 27.71), and rash (N = 286; RR 2.92, 95% CI 0.12 to 71.03) were found to be rare and statistically comparable between groups. AUTHORS' CONCLUSIONS: The limited evidence available has not shown that oral zinc supplementation given to infants up to one week old reduces the incidence of hyperbilirubinaemia or need for phototherapy.

Topical Oil Application and Trans-Epidermal Water Loss in Preterm Very Low Birth Weight Infants-A Randomized Trial.

OBJECTIVE: Topical emollient application reduces trans-epidermal water loss (TEWL) in preterm neonates. Coconut oil used traditionally for infant massage in India has not been evaluated for the same. PATIENTS AND METHODS: Very low birth weight (VLBW) neonates were randomized at 12 h of age to Oil (n = 37) or Control (n = 37) groups. Oil group neonates received twice-daily coconut oil application without massage, and Control group received standard care. TEWL was measured every 12 h using an evaporimeter till Day 7 when skin swabs were obtained for bacterial growth and skin condition was assessed using a validated score. RESULTS: Birth weight (g; mean ± SD: 1213 + 214 vs. 1164 + 208, p = 0.31), gestation [week; median (interquartile range): 32 (31-33) vs. 32 (29-33), p = 0.10] and other baseline variables were comparable. TEWL was significantly reduced (g/m(2)/h, mean difference: -6.80, 95% confidence interval: -3.48, -10.15; p < 0.01) with better skin condition and lower bacterial growth in the Oil group (20% vs. 60%, p < 0.01). CONCLUSION: Coconut oil application reduced TEWL without increasing skin colonization in VLBW neonates. CLINICAL TRIALS REGISTRATION: NCT01758068.