The rare genetic disease research landscape in India.

I am delighted to see this special issue on 'The Rare Genetic Disease Research Landscape in India'' by the Journal of Biosciences, published by the Indian Academy of Sciences in collaboration with Springer Nature. It is the first time that a mainstream biology journal has decided to publish a whole issue on rare genetic disorders. I congratulate the editorial board of the Journal of Biosciences for their timely support to encourage research in this area. I also believe that this issue will increase awareness about rare genetic diseases research and encourage many in India to enter the field.

Serum Trace Elements in Children with Well-Controlled and Drug Refractory Epilepsy Compared to Controls: An Observational Study.

Background: Trace elements have been implicated in pathogenesis of epilepsy. Studies till date have shown altered levels of serum trace elements in children with epilepsy. Objective: The objective of the current was to estimate serum levels of trace elements in children with well-controlled and drug refractory epilepsy and compare it with controls. Methodology: In a tertiary care teaching hospital of North India, serum selenium, copper, zinc, and iron were estimated in well-controlled and drug refractory epileptic children aged 2-12 years and compared with age and gender matched controls. Results: A total of 106 children with epilepsy (55 drug refractory and 51 well controlled) and 52 age and gender matched controls were included in the study. Serum selenium and copper were significantly decreased in cases compared to controls. After classifying epilepsy into well-controlled and drug refractory cases, only in the latter the significant difference for serum selenium and copper levels remained compared to controls. Additionally, in the drug refractory cases, serum iron levels were significantly reduced compared to controls. Conclusions: Serum trace elements are altered in children with epilepsy (more so in the drug refractory group) compared to controls. Monitoring of serum trace elements in children with epilepsy should be considered. Up to one-third of epilepsy is drug refractory of which only another third are amenable to surgery. It is worth investigating the therapeutic potential of altered micronutrient status in these patients.

Short-term neurodevelopment and growth outcomes of very and moderate preterm Indian infants.

OBJECTIVE: To study the growth and neurodevelopmental outcome of very and moderate preterm infants (VMPT) compared to term appropriate-for-age (term AGA) infants at 18-months corrected age. METHODS: This prospective cohort study enrolled consecutively born 212 VMPT infants and 250 term AGA controls delivered during study period. OUTCOME MEASURES: Major neurodevelopmental impairment (NDI) defined as any one of cerebral palsy, motor (MoDQ) or mental developmental quotient (MoDQ) <70 on Developmental Assessment Scale for Indian infants, visual or hearing impairment, or epilepsy, and growth outcomes. RESULTS: Among 195 VMPT and 240 term AGA infants who completed follow-up, the frequency of major NDI was 12.8% and 2.5% respectively (RR 5.1; 95% CI [2.13-12.19]). Major NDI was higher among infants <28 weeks gestation (39%) and birthweight <1000 grams (27%). A quarter of VMPT infants exhibited wasting and 18% stunting than 7% each among controls. CONCLUSION: VMPT infants had a higher frequency of major NDI and growth failure at 18-months.

Neurocognitive Outcomes and Their Diffusion Tensor Imaging Correlates in Children With Mild Traumatic Brain Injury.

This study aimed to assess the neurocognitive outcomes and their diffusion tensor imaging correlates in children (aged 6-16 years) with mild traumatic brain injury. This prospective analysis included 74 children with mild traumatic brain injury (52 boys; mean age: 9.5 [±2.7] years). Wechsler Intelligence Scale for Children-Indian adaptation (WISC-IV), Child Behavior Checklist, and Children's Sleep Habits Questionnaire were administered for 57 cases (at 3 months postinjury) and 51 controls of similar age. The findings of diffusion tensor imaging (done within 7 days of injury) were correlated with various WISC-IV indices. The presenting features at the time of injury were loss of consciousness (53%), confusion or disorientation (47%), and post-traumatic amnesia (10%). Other features in the acute phase included drowsiness (86%), headache (78%), balance problems (62%), nausea (47%), fatigue (45%), vomiting (35%), nasal or ear bleed (12%), sensitivity to sound and light (12%), etc. At 3 months postinjury, the children with mild traumatic brain injury performed poorly in terms of Intelligence Quotient, perceptual reasoning index, and processing speed index as compared to controls. Based on the Child Behavior Checklist, 17% of children with mild traumatic brain injury had internalizing behavioral problems in comparison with 4% of controls. Prevalence of poor sleepers in the mild traumatic brain injury cohort and controls was 12.3% and 2% respectively. Headache, reduced attention span, and fatigue were common postconcussion symptoms. There was a positive correlation between right uncinate fasciculus fractional anisotropy and verbal comprehension index (r = 0.32; P < .05).

Effect of home-based newborn care on neonatal and infant mortality: a cluster randomised trial in India.

BACKGROUND: Home-based newborn care has been found to reduce neonatal mortality in rural areas. Study evaluated effectiveness of home-based care delivered by specially recruited newborn care workers- Shishu Rakshak (SR) and existing workers- anganwadi workers (AWW) in reducing neonatal and infant mortality rates. METHODS: This three-arm, community-based, cluster randomised trial was conducted in five districts in India. Intervention package consisted of pregnancy surveillance, health education, care at birth, care of normal/low birthweight neonates, identification and treatment of sick neonates and young infants using oral and injectable antibiotics and community mobilisation. The package was similar in both intervention arms-SR and AWW; difference being healthcare provider. The control arm received routine health services from the existing health system. Primary outcomes were neonatal and young infant mortality rates at 'endline' period (2008-2009) assessed by an independent team from January to April 2010 in the study clusters. FINDINGS: A total of 6623, 6852 and 5898 births occurred in the SR, AWW and control arms, respectively, during the endline period; the proportion of facility births were 69.0%, 64.4% and 70.6% in the three arms. Baseline mortality rates were comparable in three arms. During the endline period, the risk of neonatal mortality was 25% lower in the SR arm (adjusted OR 0.75, 95% CI 0.57 to 0.99); the risks of early neonatal mortality, young infant mortality and infant mortality were also lower by 32%, 27%, and 33%, respectively. The risks of neonatal, early neonatal, young infant, infant mortality in the AWW arm were not different from that of the control arm. INTERPRETATION: Home-based care is effective in reducing neonatal and infant mortality rates, when delivered by a dedicated worker, even in settings with high rates of facility births. TRIAL REGISTRATION NUMBER: The study was registered with Clinical Trial Registry of India (CTRI/2011/12/002181).

Efficacy of Ketogenic Diet, Modified Atkins Diet, and Low Glycemic Index Therapy Diet Among Children With Drug-Resistant Epilepsy: A Randomized Clinical Trial.

Importance: The ketogenic diet (KD) has been used successfully to treat children with drug-resistant epilepsy. Data assessing the efficacy of the modified Atkins diet (MAD) and low glycemic index therapy (LGIT) diet compared with the KD are scarce. Objective: To determine whether the MAD and LGIT diet are noninferior to the KD among children with drug-resistant epilepsy. Design, Setting, and Participants: One hundred seventy children aged between 1 and 15 years who had 4 or more seizures per month, had not responded to 2 or more antiseizure drugs, and had not been treated previously with the KD, MAD, or LGIT diet were enrolled between April 1, 2016, and August 20, 2017, at a tertiary care referral center in India. Exposures: Children were randomly assigned to receive the KD, MAD, or LGIT diet as additions to ongoing therapy with antiseizure drugs. Main Outcomes and Measures: Primary outcome was percentage change in seizure frequency after 24 weeks of dietary therapy in the MAD cohort compared with the KD cohort and in the LGIT diet cohort compared with the KD cohort. The trial was powered to assess noninferiority of the MAD and LGIT diet compared with the KD with a predefined, noninferiority margin of -15 percentage points. Intention-to-treat analysis was used. Results: One hundred fifty-eight children completed the trial: KD (n = 52), MAD (n = 52), and LGIT diet (n = 54). Intention-to-treat analysis showed that, after 24 weeks of intervention, the median (interquartile range [IQR]) change in seizure frequency (KD: -66%; IQR, -85% to -38%; MAD: -45%; IQR, -91% to -7%; and LGIT diet: -54%; IQR, -92% to -19%) was similar among the 3 arms (P = .39). The median difference, per intention-to-treat analysis, in seizure reduction between the KD and MAD arms was -21 percentage points (95% CI, -29 to -3 percentage points) and between the KD and LGIT arms was -12 percentage points (95% CI, -21 to 7 percentage points), with both breaching the noninferiority margin of -15 percentage points. Treatment-related adverse events were similar between the KD (31 of 55 [56.4%]) and MAD (33 of 58 [56.9%]) arms but were significantly less in the LGIT diet arm (19 of 57 [33.3%]). Conclusions and Relevance: Neither the MAD nor the LGIT diet met the noninferiority criteria. However, the results of this study for the LGIT diet showed a balance between seizure reduction and relatively fewer adverse events compared with the KD and MAD. These potential benefits suggest that the risk-benefit decision with regard to the 3 diet interventions needs to be individualized. Trial Registration: ClinicalTrials.gov Identifier: NCT02708030.

The Development and Validation of DSM 5-Based AIIMS-Modified INDT ADHD Tool for Diagnosis of ADHD: A Diagnostic Test Evaluation Study.

BACKGROUND: The current study was planned at a tertiary centre in northern India to develop and validate a Diagnostic and Statistical Manual-5 (DSM-5)-based diagnostic tool and design a severity score for attention deficit hyperactivity disorder (ADHD) in children aged 6-18 years. An existing DSM-IV-based tool, INDT (International Clinical Epidemiology Network [INCLEN] diagnostic tool) for ADHD has been modified and named All India Institute of Medical Sciences (AIIMS)-modified INDT ADHD tool. METHOD: The first phase was development of the tool and the second phase was validation of the same against the gold standard of diagnosis by the DSM-5. A severity score was developed for ADHD in concordance with the Conners rating scale. RESULTS: The tool was validated in 66 children with a sensitivity and specificity of 100 per cent and 90 per cent, respectively. A cut-off score of 12 was decided for labelling severity of ADHD, which corresponded to 63 in the Conners rating scale. CONCLUSION: This diagnostic tool for ADHD based on DSM-5 has acceptable psychometric properties. The severity score will be useful for prognostication, monitoring treatment response, and designing intervention trials.

Outcome of extremely low birth weight (ELBW) infants from a birth cohort (2013-2018) in a tertiary care unit in North India.

OBJECTIVE: To evaluate mortality and short-term morbidities in extremely low birth weight (ELBW) infants (<1000 g) in a birth cohort in North India. METHODS: In-hospital data of 231 ELBW infants (Jan 2013 to Sept 2018) were collected from a prospectively maintained electronic database by using standard definitions. RESULTS: The mean (SD) gestation and birth weight were 27.9 (2.2) weeks and 783 (133) g, respectively. Major morbidities included respiratory distress syndrome (n = 132, 57%), moderate-to-severe bronchopulmonary dysplasia (n = 62, 26.8%), hemodynamically significant patent ductus arteriosus (n = 65, 28%), intracranial hemorrhage ≥ grade II (n = 38, 16%), and culture-positive sepsis (n = 44, 19%). Median (IQR) duration of hospital stay (survivors) was 50 (17-79) days. The overall survival was 62%. On logistic regression, severe birth asphyxia, gestation ≤26 weeks, and respiratory distress syndrome were major predictors of mortality. CONCLUSION: In the current ELBW cohort, nearly two-thirds survived until discharge, who had considerable morbidities needing prolonged hospital stay. This study can be utilized for counseling and planning of care of ELBW infants in similar settings.

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.

Goat lung surfactant for treatment of respiratory distress syndrome among preterm neonates: a multi-site randomized non-inferiority trial.

OBJECTIVE: To investigate the safety and efficacy of goat lung surfactant extract (GLSE) compared with bovine surfactant extract (beractant; Survanta®, AbbVie, USA) for the treatment of neonatal respiratory distress syndrome (RDS). STUDY DESIGN: We conducted a double-blind, non-inferiority, randomized trial in seven Indian centers between June 22, 2016 and January 11, 2018. Preterm neonates of 26 to 32 weeks gestation with clinical diagnosis of RDS were randomized to receive either GLSE or beractant. Repeat dose, if required, was open-label beractant in both the groups. The primary outcome was a composite of death or bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age (PMA). Interim analyses were done by an independent data and safety monitoring board (DSMB). RESULT: After the first interim analyses on 5% enrolment, the "need for repeat dose(s) of surfactant" was added as an additional primary outcome and enrolment restricted to intramural births at five of the seven participating centers. Following second interim analysis after 98 (10% of 900 planned) neonates were enroled, DSMB recommended closure of study in view of inferior efficacy of GLSE in comparison to beractant. There was no significant difference in the primary outcome of death or BPD between GLSE group (n = 52) and beractant group (n = 46) (50.0 vs. 39.1%; OR 1.5; 95% CI 0.7-3.5; p = 0.28). The need for repeat dose of surfactant was significantly higher in GLSE group (65.4 vs. 17.4%; OR 9.0; 95% CI 3.5-23.3; p < 0.001). CONCLUSIONS: Goat lung surfactant was less efficacious than beractant (Survanta®) for treatment of RDS in preterm infants. Reasons to ascertain inferior efficacy of goat lung surfactant requires investigation and possible mitigating strategies in order to develop a low-cost and effective surfactant.

Causes of death in preterm neonates (<33 weeks) born in tertiary care hospitals in India: analysis of three large prospective multicentric cohorts.

OBJECTIVE: To estimate the direct causes of mortality among preterm neonates <33 weeks' gestation by examining three large multisite, hospital-based datasets in India. METHOD: Three prospective hospital-based datasets: the National Neonatal Perinatal Database (NNPD) of India, the Delhi Neonatal Infection Study (DeNIS) cohort, and the Goat Lung Surfactant Extract (GLSE)-Plus cohort were analyzed to study the causes of death among preterm neonates of less than 33 weeks' gestation admitted to the participating tertiary care hospitals in India. RESULTS: A total of 8024 preterm neonates were admitted in the three cohorts with 2691 deaths. Prematurity-related complications and sepsis contributed to 53.5% and 19.8% of deaths in the NNPD cohort, 51.0% and 25.0% in the DeNIS cohort, and 39.7% and 40.9% in GLSE-Plus cohort, respectively. CONCLUSIONS: Nearly a quarter (20-40%) of preterm neonates less than 33 weeks' gestation admitted to Indian NICUs died of sepsis. The study results have implications for health policies targeted to reduce the neonatal mortality rate in India.

Development and validation of DSM-5 based diagnostic tool for children with Autism Spectrum Disorder.

Diagnostic and Statistical Manual of mental disorder-IV (DSM-IV) TR based INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD) is an established instrument for the diagnosis of ASD in Indian subcontinent and low-middle income countries (LMIC). The introduction of DSM-5 necessitated revision of existing INDT-ASD tool to incorporate the DSM-5 related changes. This study was undertaken to develop and validate the DSM-5 based All India Institute of Medical Sciences (AIIMS)-Modified-INDT-ASD Tool. The modifications were done using Delphi method and included: (a) rearrangement of questions from the previous tool; and (b) addition of new questions on sensory symptoms. The modified tool was validated against DSM-5 diagnostic criteria. In addition, receiver operating characteristic (ROC) curves were used to determine the cut-off for total score as compared to Childhood Autism Rating Scale (CARS) score to grade the severity of ASD. Two-hundred-twenty-five children (159 boys, median age = 47months) were enrolled. The modified tool demonstrated sensitivity of 98.4% and specificity of 91.7% to diagnose ASD. A score ≥14 on the tool was suggestive of severe ASD (CARS>36.5) with a sensitivity and specificity of 80% and 80.7% respectively [Area under the curve = 0.89]. AIIMS-Modified-INDT-ASD Tool is a simple and structured instrument based on DSM-5 criteria which can facilitate diagnosis of ASD with acceptable diagnostic accuracy.

Does ultrasound guidance for peripherally inserted central catheter (PICC) insertion reduce the incidence of tip malposition? - a randomized trial.

OBJECTIVE: The aim of the study was to evaluate the incidence of peripheral inserted central catheter (PICC) tip malposition when the catheter is inserted under real-time ultrasound (RTUS) guidance when compared with conventional landmark (CL) technique in neonates. Additional objectives were to evaluate the PICC longevity and central line associated blood stream infections (CLABSI). STUDY DESIGN: In this randomised controlled trial, neonates were randomised to 'RTUS' (n = 40) or 'CL' (n = 40) groups. PICC tip was placed under ultrasound guidance in lower third of superior vena cava in the RTUS group. In 'CL' group, PICC was inserted as calculated by anatomical landmarks. RESULTS: The birth weight (1286 (926, 1662) vs. 1061 (889, 1636) g) and gestation (31.12 (3.1) vs. 31.4 (3.6) wks) were comparable among the groups. RTUS guidance during PICC insertion reduced incidence of tip malposition by 52% (67.5 vs. 32.5%; RR: 0.48; 95% CI: 0.29-0.79). The longevity of PICC and episodes of CLABSI were however similar in the two groups. CONCLUSIONS: Real-time ultrasound guidance during PICC placement reduces the incidence of tip malposition.

Postnatal Maturation of Amplitude Integrated Electroencephalography (aEEG) in Preterm Small for Gestational Age Neonates.

OBJECTIVE: The primary objective was to evaluate the postnatal maturation pattern on aEEG during first two weeks of life in clinically stable and neurologically normal preterm small for gestational age (PSGA) and gestation matched (1 week) preterm appropriate for gestational age (PAGA) neonates born between 300/7 and 346/7 weeks of gestation. METHODS: Serial aEEG tracings were recorded on 3rd, 7th and 14th day of life. The primary outcome was total aEEG maturation score. Three blinded assessors assigned the scores. RESULTS: We analyzed a total of 117 aEEG recordings in 40 (19 PSGA and 21 PAGA) neonates. The baseline characteristics were comparable except for birthweight [1186 (263) vs 1666(230) g]. There was no difference in the mean (SD) total scores on day 3 (9.0 (1.8) vs. 9.5 (1.1), P=0.32) and day 14 of life, but was lower in PSGA infants on day 7 (8.6 (2.4) vs. 10.1 (1.1), P=0.02). On multivariate analysis, maturation of PSGA neonates was found to be significantly delayed at any point of life from day 3 to day 14 (mean difference, -0.8, 95% CI: -1.6 to -0.02, P=0.04). CONCLUSIONS: Lower aEEG maturation score on day 7 possibly indicates delayed maturation in PSGA neonates in the first week of life.

Target Oxygen Saturation Among Preterm Neonates on Supplemental Oxygen Therapy: A Quality Improvement Study.

OBJECTIVE: To avoid excessive oxygen exposure and achieve target oxygen saturation (SpO2) within intended range of 88%-95% among preterm neonates on oxygen therapy. METHODS: 20 preterm neonates receiving supplemental oxygen in the first week of life were enrolled. The percentage of time per epoch (a consecutive time interval of 10 hours/day) spent by them within the target SpO2 range was measured in phase 1 followed by implementation of a unit policy on oxygen administration and targeting in phase 2. In phase 3, oxygen saturation histograms constructed from pulse-oximeter data were used as daily feedback to nurses and compliance with oxygen-targeting was measured again. RESULTS: 48 epochs in phase 1 and 69 in phase 3 were analyzed. The mean (SD) percent time spent within target SpO2 range increased from 65.9% (21.4) to 76.5% (12.6) (P=0.001). CONCLUSION: Effective implementation of oxygen targeting policy and feedback using oxygen saturation histograms may improve compliance with oxygen targeting.

Assisted Physical Exercise and Stress in Preterm Neonates.

OBJECTIVE: To evaluate the markers of stress before and after a session of assisted physical exercise in infants born before 35 weeks' gestation. METHODS: 25 infants born at 280/7 to 346/7 weeks were subjected to assisted physical exercise daily for about 10-15 min at one week of postnatal age or 33 weeks of post menstrual age, whichever was later. Primary outcome was salivary cortisol and secondary outcome was Premature infant pain profile (PIPP) score. Outcomes were measured, on day 5 (±1) of exercise. RESULTS: There was no difference in salivary cortisol between baseline and immediately after (P=0.16), at 90 min (P=0.6) or 120 min (P=0.7) after exercise. Salivary cortisol was lower at 30 min after exercise as compared to baseline (mean difference -0.08 µg/dL; 95% CI -0.16 to -0.002; P=0.04). The median (IQR) PIPP score was significantly higher at 5 min into exercise (4 (3-6) vs 4 (3-5); P=0.04) and at completion of exercise 6 (4-8) vs 4 (3-5); P<0.01), as compared to baseline. CONCLUSION: Assisted physical exercise does not seem to result in stress in premature infants.

Alarming rates of antimicrobial resistance and fungal sepsis in outborn neonates in North India.

BACKGROUND: There is a paucity of data on the epidemiology of sepsis in outborn neonates being referred to level-3 units in low- and middle-income countries (LMIC). The objective of the present study was to evaluate the prevalence of sepsis and outcomes of outborn neonates with sepsis, and to characterize the pathogen profile and antimicrobial resistance (AMR) patterns of common isolates in them. METHODS: In this prospective observational cohort study (2011-2015), a dedicated research team enrolled all neonates admitted to an outborn level-3 neonatal unit and followed them until discharge/death. Sepsis work-up including blood culture(s) was performed upon suspicion of sepsis. All the isolates were identified and tested for antimicrobial susceptibility. Gram-negative pathogens resistant to any three of the five antibiotic classes (extended-spectrum cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and piperacillin-tazobactam) were labeled multi-drug resistant. RESULTS: Of the total of 2588 neonates enrolled, culture positive sepsis and total sepsis-i.e. culture positive and/or culture negative sepsis-was diagnosed in 13.1% (95% CI 11.8% to 14.5%) and 54.7% (95% CI 52.8% to 56.6%), respectively. The case fatality rates were 23.4% and 11.0% in culture-positive and total sepsis, respectively. Sepsis accounted for two-thirds of total neonatal deaths (153/235, 63.0%). Bacterial isolates caused about three-fourths (296/401; 73.8%) of the infections. The two common pathogens-Klebsiella pneumoniae (n = 50, 12.5%) and Acinetobacter baumannii (n = 46, 11.5%)-showed high degree of multi-drug resistance (78.0% and 91.3%, respectively) and carbapenem resistance (84.0% and 91.3%, respectively). About a quarter of infections were caused by Candida spp. (n = 91; 22.7%); almost three-fourths (73.7%) of these infections occurred in neonates born at or after 32 weeks' gestation and about two-thirds (62.1%) in those weighing 1500 g or more at birth. CONCLUSIONS: In this large outborn cohort, we report high burden of sepsis, high prevalence of systemic fungal infections, and alarming rates of antimicrobial resistance among bacterial pathogens.

Assisted Physical Exercise for Improving Bone Strength in Preterm Infants Less than 35 Weeks Gestation: A Randomized Controlled Trial.

OBJECTIVE: To compare the efficacy of daily assisted physical exercise (starting from one week of postnatal age) on bone strength at 40 weeks of post menstrual age to no intervention in infants born between 27 and 34 weeks of gestation. DESIGN: Open-label randomized controlled trial. SETTING: Tertiary-care teaching hospital in northern India from 16 May, 2013 to 21 November, 2013. PARTICIPANTS: 50 preterm neonates randomized to Exercise group (n=26) or Control group (n=24). INTERVENTION: Neonates in Exercise group underwent one session of physical exercise daily from one week of age, which included range-of-motion exercises with gentle compression, flexion and extension of all the extremities with movements at each joint done five times, for a total of 10-15 min. Infants in Control group underwent routine care and were not subjected to any massage or exercise. MAIN OUTCOME MEASURES: Primary: Bone speed of sound of left tibia measured by quantitative ultrasound at 40 weeks post menstrual age. Secondary: Anthropometry (weight length and head circumference) and biochemical parameters (calcium, phosphorus, alkaline phosphatase) at 40 weeks post menstrual age. RESULTS: The tibial bone speed of sound was comparable between the two groups [2858 (142) m/s vs. 2791 (122) m/s; mean difference 67.6 m/s; 95% CI - 11 to 146 m/s; P=0.38]. There was no difference in anthropometry or biochemical parameters. CONCLUSIONS: Daily assisted physical exercise does not affect the bone strength, anthropometry or biochemical parameters in preterm (27 to 34 weeks) infants.

Development of All India Institute of Medical Sciences-Modified International Clinical Epidemiology Network Diagnostic Instrument for Neuromotor Impairments in Children Aged 1 Month to 18 Years.

INTRODUCTION: There is shortage of specialists for the diagnosis of children with neuromotor impairments (NMIs), especially in resource limited settings. Existing International Clinical Epidemiology Network (INCLEN) instrument for diagnosing NMI have been validated for children aged 2-9 years. The current study modified the same including wider symptomatology and age group (1 month to 18 years). METHODS: The Modified INCLEN diagnostic tool (INDT) was developed by a team of experts by modifying the existing tool to widen the age range (1 month to 18 years) and include broader symptomatology (inclusion of milestones from the first 2 years of life and better elucidation of cerebellar and extrapyramidal features) in a tertiary care teaching hospital of North India between January and April 2015. A trained medical graduate applied the candidate tool, which was followed by gold standard evaluation by a Pediatric Neurologist (both blinded to each other). RESULTS: A total of 197 children (102 with NMI and 95 without NMI) were enrolled for the study. The sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratio of the modified NMI tool were 90.4% (82.6-95.5), 95.5% (88.7-98.7), 95.5% (88.9-98.7), 90.3% (82.4-95.5), 19.9 (12.1-32.6), and 0.13 (0.08-0.12), respectively. CONCLUSION: The All India Institute of Medical Sciences modified INDT NMI tool is a simple and structured instrument covering a wider symptomatology in the 1 month to 18 years age group with acceptable diagnostic accuracy.