Whole-Blood Gene Expression Profile After Hypoxic-Ischemic Encephalopathy.

Importance: Induced hypothermia, the standard treatment for hypoxic-ischemic encephalopathy (HIE) in high-income countries (HICs), is less effective in the low-income populations in South Asia, who have the highest disease burden. Objective: To investigate the differences in blood genome expression profiles of neonates with HIE from an HIC vs neonates with HIE from South Asia. Design, Setting, and Participants: This case-control study analyzed data from (1) a prospective observational study involving neonates with moderate or severe HIE who underwent whole-body hypothermia between January 2017 and June 2019 and age-matched term healthy controls in Italy and (2) a randomized clinical trial involving neonates with moderate or severe HIE in India, Sri Lanka, and Bangladesh recruited between August 2015 and February 2019. Data were analyzed between October 2020 and August 2023. Exposure: Whole-blood RNA that underwent next-generation sequencing. Main Outcome and Measures: The primary outcomes were whole-blood genome expression profile at birth associated with adverse outcome (death or disability at 18 months) after HIE in the HIC and South Asia cohorts and changes in whole-genome expression profile during the first 72 hours after birth in neonates with HIE and healthy controls from the HIC cohort. Blood samples for RNA extraction were collected before whole-body hypothermia at 4 time points (6, 24, 48, and 72 hours after birth) for the HIC cohort. Only 1 blood sample was drawn within 6 hours after birth for the South Asia cohort. Results: The HIC cohort was composed of 35 neonates (21 females [60.0%]) with a median (IQR) birth weight of 3.3 (3.0-3.6) kg and gestational age of 40.0 (39.0-40.6) weeks. The South Asia cohort consisted of 99 neonates (57 males [57.6%]) with a median (IQR) birth weight of 2.9 (2.7-3.3) kg and gestational age of 39.0 (38.0-40.0) weeks. Healthy controls included 14 neonates (9 females [64.3%]) with a median (IQR) birth weight of 3.4 (3.2-3.7) kg and gestational age of 39.2 (38.9-40.4) weeks. A total of 1793 significant genes in the HIC cohort and 99 significant genes in the South Asia cohort were associated with adverse outcome (false discovery rate <0.05). Only 11 of these genes were in common, and all had opposite direction in fold change. The most significant pathways associated with adverse outcome were downregulation of eukaryotic translation initiation factor 2 signaling in the HIC cohort (z score = -4.56; P < .001) and aldosterone signaling in epithelial cells in the South Asia cohort (z score = null; P < .001). The genome expression profile of neonates with HIE (n = 35) at birth, 24 hours, 48 hours, and 72 hours remained significantly different from that of age-matched healthy controls in the HIC cohort (n = 14). Conclusions and Relevance: This case-control study found that disease mechanisms underlying HIE were primarily associated with acute hypoxia in the HIC cohort and nonacute hypoxia in the South Asia cohort. This finding might explain the lack of hypothermic neuroprotection.

Duration of birth depression and neurodevelopmental outcomes after whole-body hypothermia for hypoxic ischemic encephalopathy in India, Sri Lanka and Bangladesh - an exploratory analysis of the HELIX trial.

Background: Effect of duration of birth depression on neurodevelopmental outcomes in low- and middle-income countries (LMICs) is not known. We examined the association of birth depression with brain injury, neurodevelopmental outcomes, and hypothermia after hypoxic ischemic encephalopathy (HIE) in south Asia. Methods: We compared cerebral magnetic resonance (MR) at 2 weeks, and adverse outcomes (death or moderate or severe disability) at 18 months in 408 babies with moderate or severe HIE who had long birth depression (positive pressure ventilation (PPV) >10 min or Apgar score<6 at 10 min or cord pH < 7.0) and short birth depression (PPV for 5-10 min or Apgar score<6 at 5 min, but ≥6 at 10 min). Findings: Long depression group (n = 201) had more severe HIE (32.8% versus 6.8%), mortality (47.5% versus 26.4%), death or disability at 18 months (62.2% versus 35.4%) (all p < 0.001), MR injury (Odds ratio; 95% CI) to basal ganglia (2.4 (1.3, 4.1); p = 0.003), posterior limb of internal capsule (2.3 (1.3, 4.3); p < 0.001) and white matter (1.7 (1.1, 2.7); p = 0.021), and lower thalamic N-acetylaspartate levels (7.69 ± 1.84 versus 8.29 ± 1.60); p = 0.031) than short depression group (n = 207). Three babies had no heartbeat at 5 min, of which 1 died and 2 survived with severe disability. No significant interaction between the duration of birth depression and whole-body hypothermia was seen for any of the MR biomarker or clinical outcomes. Interpretation: Long birth depression was associated with more brain injury and adverse outcomes than short depression. Effect of hypothermia was not modified by duration of birth depression. Funding: National Institute for Health Research.

Telehealth services for children with neuro-developmental disabilities in the Asia-Pacific region: A systematic review.

BACKGROUND: In recent years telehealth became a popular and a rational health service delivery approach, especially amidst multiple challenges posed while providing health care interventions during the COVID-19 pandemic. AIM: We synthesized available evidence on telehealth for managing children with NDDs in the Asia-Pacific region with the aim of identifying successful methods. METHODOLOGY: We systematically reviewed six electronic databases: MEDLINE, AMED, EMBASE, PsychInfo, Web of Science, and (CINAHL plus) using the keywords and database-specific subject headings from their inception to 25th August 2021. Review findings were synthesized narratively, and harvest plots were used to demonstrate the effect of interventions. The protocol and reporting the findings of this review adhered to PRISMA 2020 guidelines. PROSPERO registration: CRD 340690. RESULTS: We harvested 30,823 records; 17,563 duplicates were removed, and 196 full-text articles were assessed for eligibility. 16 studies with multiple research designs were included in the review. Eight were from the Pacific region and eight represented Asia. The interventions targeted families and children with a variety of NDDs (autism spectrum disorder, Down syndrome, cleft lip and palate, hearing impairment, cerebral palsy etc.) via telehealth. Telehealth packages consisted of direct and indirect methods of synchronous, asynchronous, and hybrid approaches. All studies used parent-led intervention strategies. Telehealth reported a positive effect in 7/16 studies while five showed a neutral effect. CONCLUSIONS: According to published evidence telehealth for children with NDDs is an evolving, evidence-based service facilitation modality in the Asia-Pacific region, with only a few published randomized controlled trials. The systematic review shows promising telehealth practices emerging across the region despite the diversity in NDDs studied.

A short report on a preliminary interventional study to evaluate play-mediated interaction skills in caregivers of children with autism spectrum disorder from Sri Lanka.

LAY ABSTRACT: Most children with autism spectrum disorder live in low- and middle-income countries. Most of them do not have access to timely and culturally acceptable interventions. Research from high-income countries and low- and middle-income countries, such as Sri Lanka, show that parent-mediated intervention programmes improve functional outcomes, highlighting the importance of parents as partners. We undertook a preliminary study to evaluate how play-based parent coaching will enhance the parent interaction skills to promote social-emotional, cognitive and language skills in children with autism spectrum disorder aged 2-4 years. We evaluated how parents acquire interaction skills to engage with children using a caregiver skills assessment checklist adapted from freely accessible resources. Before and after training, all parent-child dyads participated in a 10-min video-recorded play session with a set of toys of their choice. Over the course of 2 weeks, all parents spent 2 h/day playing and interacting with the child to harness the desired skills. The results showed that the parental training had a positive effect on all 30 caregivers in gaining skills, with a significant improvement in all three domains with the highest impact on skills for social-emotional development. Overall, parents reported high levels of satisfaction on the training. The significant improvement in parent interaction skills was promising. However, further studies to look at the sustainability of the skills and the impact on children's overall development need to be looked into using larger and more generalised studies.

Whole-Body Hypothermia, Cerebral Magnetic Resonance Biomarkers, and Outcomes in Neonates With Moderate or Severe Hypoxic-Ischemic Encephalopathy Born at Tertiary Care Centers vs Other Facilities: A Nested Study Within a Randomized Clinical Trial.

Importance: The association between place of birth and hypothermic neuroprotection after hypoxic-ischemic encephalopathy (HIE) in low- and middle-income countries (LMICs) is unknown. Objective: To ascertain the association between place of birth and the efficacy of whole-body hypothermia for protection against brain injury measured by magnetic resonance (MR) biomarkers among neonates born at a tertiary care center (inborn) or other facilities (outborn). Design, Setting, and Participants: This nested cohort study within a randomized clinical trial involved neonates at 7 tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh between August 15, 2015, and February 15, 2019. A total of 408 neonates born at or after 36 weeks' gestation with moderate or severe HIE were randomized to receive whole-body hypothermia (reduction of rectal temperatures to between 33.0 °C and 34.0 °C; hypothermia group) for 72 hours or no whole-body hypothermia (rectal temperatures maintained between 36.0 °C and 37.0 °C; control group) within 6 hours of birth, with follow-up until September 27, 2020. Exposure: 3T MR imaging, MR spectroscopy, and diffusion tensor imaging. Main Outcomes and Measures: Thalamic N-acetyl aspartate (NAA) mmol/kg wet weight, thalamic lactate to NAA peak area ratios, brain injury scores, and white matter fractional anisotropy at 1 to 2 weeks and death or moderate or severe disability at 18 to 22 months. Results: Among 408 neonates, the mean (SD) gestational age was 38.7 (1.3) weeks; 267 (65.4%) were male. A total of 123 neonates were inborn and 285 were outborn. Inborn neonates were smaller (mean [SD], 2.8 [0.5] kg vs 2.9 [0.4] kg; P = .02), more likely to have instrumental or cesarean deliveries (43.1% vs 24.7%; P = .01), and more likely to be intubated at birth (78.9% vs 29.1%; P = .001) than outborn neonates, although the rate of severe HIE was not different (23.6% vs 17.9%; P = .22). Magnetic resonance data from 267 neonates (80 inborn and 187 outborn) were analyzed. In the hypothermia vs control groups, the mean (SD) thalamic NAA levels were 8.04 (1.98) vs 8.31 (1.13) among inborn neonates (odds ratio [OR], -0.28; 95% CI, -1.62 to 1.07; P = .68) and 8.03 (1.89) vs 7.99 (1.72) among outborn neonates (OR, 0.05; 95% CI, -0.62 to 0.71; P = .89); the median (IQR) thalamic lactate to NAA peak area ratios were 0.13 (0.10-0.20) vs 0.12 (0.09-0.18) among inborn neonates (OR, 1.02; 95% CI, 0.96-1.08; P = .59) and 0.14 (0.11-0.20) vs 0.14 (0.10-0.17) among outborn neonates (OR, 1.03; 95% CI, 0.98-1.09; P = .18). There was no difference in brain injury scores or white matter fractional anisotropy between the hypothermia and control groups among inborn or outborn neonates. Whole-body hypothermia was not associated with reductions in death or disability, either among 123 inborn neonates (hypothermia vs control group: 34 neonates [58.6%] vs 34 [56.7%]; risk ratio, 1.03; 95% CI, 0.76-1.41), or 285 outborn neonates (hypothermia vs control group: 64 neonates [46.7%] vs 60 [43.2%]; risk ratio, 1.08; 95% CI, 0.83-1.41). Conclusions and Relevance: In this nested cohort study, whole-body hypothermia was not associated with reductions in brain injury after HIE among neonates in South Asia, irrespective of place of birth. These findings do not support the use of whole-body hypothermia for HIE among neonates in LMICs. Trial Registration: ClinicalTrials.gov Identifier: NCT02387385.

Availability of rehabilitation services for communication disorders in Sri Lanka: a cross-sectional survey.

OBJECTIVES: To describe the rehabilitation services available for communication disorders in Sri Lanka and to estimate the adequacy of the services in provinces and districts of the country. SETTING: The study considered government and private institutions, which provide rehabilitation services for communication disorders in Sri Lanka. PARTICIPANTS: Institutions providing services of speech-language pathologists, audiologists and audiology technicians in Sri Lanka. PRIMARY AND SECONDARY OUTCOME MEASURES: We investigated the number of government hospitals and private institutions, which provide speech-language pathology and audiology services in Sri Lanka as the primary outcome measure. A number of speech-language pathologists, audiologists and audiology technicians working in the institutions were obtained from records and institution-based inquiries to identify the adequacy of the services in the country as the secondary outcome measure. RESULTS: Of the 647 government hospitals that provide free healthcare services in the country, 45 and 33 hospitals had speech and language therapy and audiology units, respectively. Government hospitals do not have audiologists but only have audiology technicians. The number of speech and language therapists and audiology technicians in the government sector per 100 000 population in the country was 0.44 and 0.18, respectively. There were wide variations in specialist to population ratio between districts. 77 private centres provide speech therapy services in 15 out of the 25 districts; 36 private centres provide audiological evaluations in 9 districts. CONCLUSIONS: The number of specialist speech and language therapists and audiologists is not sufficient to provide adequate rehabilitation services for communications disorder for the Sri Lankan population. Not recruiting audiologists to the government sector affects the management of hearing impairment in the affected.

Stakeholders' perspectives on the provision of vocational training for youth with disabilities in Sri Lanka: protocol for a mixed-methods study.

INTRODUCTION: The quality and the range of vocational training (VT) courses offered to youth with disabilities (YwD) in low-middle-income countries are underexplored. This protocol describes a study designed to gather perceptions of a range of stakeholders related to the quality and relevance of VT programmes conducted by the Department of Social Services in Sri Lanka. The purpose of this study is to communicate with authorities the ways in which they can improve their services by paying close attention to the needs and recommendations of all stakeholders. METHODS AND ANALYSIS: A parallel mixed-methods study will be conducted at eight vocational training institutes (VTIs). A survey will be conducted with five participant groups; YwD presently enrolled in VTIs (n=358) and their caregivers (n=358), YwD who completed the VT (n=45) and their caregivers (n=45) and educators at VTIs (n=47). The qualitative component includes semi-structured interviews and focus group discussions. The three groups of participants include: educators, caregivers of potential YwD for future VT (6-10 per group) and key informants from state, corporate and non-governmental sectors (a total of 20). Quantitative and qualitative data will be analysed using descriptive and inferential statistics and cross-thematic analysis, respectively. ETHICS AND DISSEMINATION: This study received ethical clearance from the Ethics Review Committee, Faculty of Medicine, University of Kelaniya (Ref. No: P/15/02/2021). All data collection processes will abide by health and safety measures required by the national government. Written informed consent will be obtained from all participants. Results from this research will be disseminated, to local stakeholders and participants, via local and international conferences and publications in peer-reviewed journals.

Early Interventions for Infants at Risk for Developmental Impairment: The South Asian Perspective.

Majority of under-five children with developmental disabilities live in low- and middle-income countries (LMIC). A considerable proportion of disabilities results from perinatal adversities. The neonatal and infant mortality rates in India, Bangladesh, and Sri Lanka have improved over the last two decades, implying survival of infants at risk for developmental impairments. The need to thrive beyond survival is a well-recognized concept and it is imperative to establish high-risk infant follow-up (HRIF) programmes to capture these infants within the first 1000 d of life. Many challenges are present within the LMICs to identify infants at risk and to ensure early intervention (EI) during the window of optimal neural plasticity. However, it is essential to acknowledge the strengths within such systems to understand the impact of these programmes and packages on the activity and participation of these infants and their families. The International Classification of Functioning, Health and Disability for Children and Youth (ICF-CY) version is a holistic framework that will enable the families, clinicians, and policymakers to measure the impact of these interventions. Though all three countries have national policies to reach for high-risk infants, there is lack of published evidence on the successful implementation of such strategies. Therefore, it is timely to establish universally accessible, culturally appropriate and sustainable HRIF programmes. It is also recommended to measure the outcomes of such programmes based on the ICF-CY to understand the impact on the activity and participation of children in South Asia.

Parental and professional perceptions of informed consent and participation in a time-critical neonatal trial: a mixed-methods study in India, Sri Lanka and Bangladesh.

INTRODUCTION: Time-critical neonatal trials in low-and-middle-income countries (LMICs) raise several ethical issues. Using a qualitative-dominant mixed-methods design, we explored informed consent process in Hypothermia for encephalopathy in low and middle-income countries (HELIX) trial conducted in India, Sri Lanka and Bangladesh. METHODS: Term infants with neonatal encephalopathy, aged less than 6 hours, were randomly allocated to cooling therapy or usual care, following informed parental consent. The consenting process was audio-video (A-V) recorded in all cases. We analysed A-V records of the consent process using a 5-point Likert scale on three parameters-empathy, information and autonomy. In addition, we used exploratory observation method to capture relevant aspects of consent process and discussions between parents and professionals. Finally, we conducted in-depth interviews with a subgroup of 20 parents and 15 healthcare professionals. A thematic analysis was performed on the observations of A-V records and on the interview transcripts. RESULTS: A total of 294 A-V records of the HELIX trial were analysed. Median (IQR) score for empathy, information and autonomy was 5 (0), 5 (1) and 5 (1), respectively. However, thematic analysis suggested that the consenting was a ceremonial process; and parental decision to participate was based on unreserved trust in the treating doctors, therapeutic misconception and access to an expensive treatment free of cost. Most parents did not understand the concept of a clinical trial nor the nature of the intervention. Professionals showed a strong bias towards cooling therapy and reported time constraints and explaining to multiple family members as key challenges. CONCLUSION: Despite rigorous research governance and consent process, parental decisions were heavily influenced by situational incapacity and a trust in doctors to make the right decision on their behalf. Further research is required to identify culturally and context-appropriate strategies for informed trial participation.

Effect of intramuscular ACTH versus oral prednisolone on the developmental trajectories of children with West syndrome over 24 months: A randomised control study.

OBJECTIVE: To assess the developmental progression and compare the developmental attainments of children treated with two hormonal therapies for infantile spasms (IS) over two years (seizure and EEG outcomes of this RCT published previously). METHODS: Newly diagnosed infants with IS were randomised to receive adrenocorticotrophin (ACTH) or prednisolone for 14 days. All underwent Bayley III Infant and Toddler Assessments in cognitive (Cog), receptive (RC) and expressive (EC) communication, fine (FM) and gross (GM) motor developmental subsets at baseline (T0), one-year (T1) and two-years (T2). RESULTS: 95 infants randomised to prednisolone (n = 48) and ACTH (n = 47) groups were eligible for developmental assessments. Mean age at initial assessment was 8.75 months (SD = 6.37, range 1.46-34.4 months). 48 children presented for all three assessments. Mean composite scores of each developmental domain improved across the three time points; but the progression was significant only in relation to motor development (p = 0.04). When comparing the treatment outcomes at 2-years, mean composite scores of children treated with ACTH were significantly lower in motor domain (p = 0.023). As for developmental delay, the ACTH group (n = 32) showed significant delay in expressive communication (adjusted OR 5.46, 95% CI: 1.1, 28.57; p = 0.04) and fine motor (adjusted OR 9.4, 95% CI: 1.1, 83.3; p = 0.04) at T2 compared to the prednisolone (n = 30) in a regression analysis. CONCLUSION: The number of children with delay at the 2 year follow up were significantly higher in two domains in the ACTH group compared to the prednisolone group. Overall results do not show a significant advantage of ACTH over prednisolone for developmental outcomes at two years, but further comparative studies over longer periods are required for more definitive conclusions.

Protocol for the Sri Lankan Cerebral Palsy Register pilot study.

INTRODUCTION: Cerebral palsy (CP) describes a heterogeneous group of motor disorders resulting from disturbance in the developing brain. CP occurs in approximately 2.1 per 1000 live births in high-income countries, but in low- and middle-income countries (LMICs) the prevalence and severity of CP may be greater and aetiological risk factors different. In Sri Lanka, a LMIC, there have been no epidemiological studies of CP to date. Systematically collected data are required to identify opportunities for primary and secondary prevention, to plan and establish services to support children and adults with CP and their families and to act as a sampling frame for new research. Here we describe a pilot study protocol for a CP register in Sri Lanka. METHODS AND ANALYSIS: The aim of this study is to establish a CP register in Sri Lanka. We will use different surveillance methodologies in two provinces of Sri Lanka: hospital and community surveillance in the Western Province and community surveillance in the Eastern Province. A common record form will collect demographic, clinical and service data for children with CP <18 years living in these two provinces. Data will be transferred to a secure online data repository and used to describe the epidemiology of CP in these regions. We will describe the strengths and challenges of the surveillance mechanisms and estimate the resources required for ongoing hospital and community based surveillance in the Western and Eastern provinces and to include additional provinces across the country. ETHICS AND DISSEMINATION: This study has ethical clearance from The University of Kelaniya, National Health Research Council, the Institutional Ethics Review Committee of the Lady Ridgeway Hospital, Colombo South Teaching Hospital and the Director of the North Colombo Teaching Hospital. Results from this research will be disseminated through local and international conferences and through publications in peer-reviewed journals.

Developmental profile at initial presentation in children with infantile spasms.

AIM: To describe the baseline developmental profile and influence of clinical and demographic factors on the developmental skills of infants diagnosed with infantile spasms. METHOD: Ninety-five infants (55 males, 40 females) newly diagnosed with infantile spasms were recruited for a cross-sectional, longitudinal study. All infants underwent Bayley Scales of Infant and Toddler Development assessments in the cognitive, receptive communication, expressive communication, and fine and gross motor developmental domains; they also underwent visual, auditory, and social behaviour assessments. Infants were categorized as 'early' (<6mo) or 'late' (≥6mo) presenters; if presented within 28 days, this was considered as 'early presentation', whereas a delay greater than 28 days was considered as a 'delay in presentation'. Antenatal, perinatal, and postnatal risk factors were identified. RESULTS: Over 90% of infants showed impairment in all domains, with the majority having severe delay; 99% showed cognitive impairment. Delayed presentation was significantly associated with receptive communication delay (odds ratio [OR]=5.35; 95% confidence interval [CI]=1.05-27.32). Onset at 6 months or less influenced auditory (OR=2.8; 95% CI=1.16-6.8) and visual (OR=3.03; 95% CI=1.22-7.57) behaviours. Neonatal infections impacted both receptive (OR=1.12; 95% CI=1.04-1.2) and expressive communication (OR=1.08; 95% CI=1.02-1.14) delay. Neonatal seizures significantly influenced visual, auditory, and social impairments. Expressive communication and gross motor development shared common perinatal risk factors. INTERPRETATION: Adverse developmental status at presentation, associated with delayed presentation and neonatal risk factors should alert clinicians to the surveillance of at-risk infants and seek out timely interventions. WHAT THIS PAPER ADDS: Ninety per cent of infants showed impaired cognitive, communication, and motor skills at presentation. Visual, auditory, and social behaviour impairments were significantly associated with perinatal risks. Visual, auditory, and social behaviour impairments were significantly associated with neonatal seizures.

PERFIL DE DESARROLLO DURANTE LA PRESENTACIÓN INICIAL DE LOS ESPASMOS INFANTILES EN NIÑOS: OBJETIVO: Describir el perfil de desarrollo basal y la influencia de factores clínicos y demográficos sobre las habilidades de desarrollo en niños diagnosticados con espasmos infantiles. METODO: Se reclutaron 95 niños recientemente diagnosticados con espasmos infantiles en una corte transversal, de un estudio longitudinal. Se realizaron Escalas de Bayley (Bayley Scales of Infant and Toddler Development) para el desarrollo de lactantes y preescolares a todos los niños, evaluando cognición, comunicación receptiva, comunicación expresiva, y los dominios del desarrollo motor, grueso y fino; también se sometieron a evaluaciones visuales, auditivas y de comportamiento social. Los niños fueron clasificados como presentación Temprana'(< 6 meses) o Tardía (≥ 6 meses); si los espasmos se presentaron dentro de los primeros 28 días, se consideró como presentación temprana, mientras que un retraso mayor de 28 días fue considerado como un retraso en la presentación. Se identificaron los factores de riesgo prenatales, perinatales y postnatales. RESULTADOS: Más del 90% de los lactantes mostró discapacidad en todos los dominios, la mayoría con retraso severo; 99% mostró deterioro cognitivo. El retraso en la presentación está significativamente asociado con retraso en la comunicación receptiva (razón de probabilidades [OR]= 5,35; 95% intervalo de confianza [CI]= 1,05-27,32). El inicio a los 6 meses o menos influenció en el comportamiento auditivo (OR = 2,8; 95% CI = 1,16-6,8) y visual (OR = 3,03; 95% CI = 1,22-7,57). Las infecciones neonatales impactaron tanto en el retraso de la comunicación receptiva (OR = 1,12; 95% CI=1,04-1,2) como en la expresiva (OR =1,08; 95% CI = 1,02-1,14). Las convulsiones neonatales influenciaron significativamente en discapacidades visuales, auditivas, y sociales. La comunicación expresiva y el desarrollo motor grueso tuvieron factores de riesgo perinatales comunes. INTERPRETACIÓN: Un estado de desarrollo adverso al momento de la presentación de espasmos infantiles, asociado con un retraso en la presentación y los factores de riesgo neonatal deben alertar a los clínicos a la vigilancia de niños en riesgo y buscar intervenciones oportunas.

PERFIL DE DESENVOLVIMENTO NA APRESENTAÇÃO INICIAL EM CRIANÇAS COM ESPASMOS INFANTIS: Xxx. OBJETIVO: Descrever o perfil de desenvolvimento inicial e a influência de fatores clínicos e demográficos nas habilidades do desenvolvimento de crianças diagnosticadas com espasmos infantis. MÉTODO: Noventa e cinco lactentes diagnosticados com espasmos infantis foram recrutados para um estudo transversal longitudinal. Todas as crianças foram submetidas a avaliações pela Escala Bayley de Desenvolvimento para bebes e crianças nos domínios Cognitivo, comunicação receptiva e expressiva, e desenvolvimento motor fino e grosso; eles também foram submetidos a avaliações: visual, auditivo e comportamento social. Os bebês foram categorizados como "precoces" (<6 m) ou "atrasados" (≥6 m); se apresentada no prazo de 28 dias, foi considerado como "precoces", enquanto que superior a 28 dias foi considerado como "atrasados". Fatores de risco pré-natais, perinatais e pós-natais foram identificados. RESULTADOS: Mais de 90% dos lactentes apresentaram comprometimento em todos os domínios, sendo a maioria com atraso grave; 99% apresentaram comprometimento cognitivo. A apresentação tardia foi significativamente associada ao atraso na comunicação receptiva (odds ratio [OR] = 5,35; intervalo de confiança de 95% [IC] = 1,05-27,32). O início aos 6 meses ou menos influenciou os comportamentos auditivos (OR = 2,8; 95% IC = 1,16-6,8) e visuais (OR = 3,03; IC95% = 1,22-7,57). As infecções neonatais impactaram no atraso na comunicação receptiva (OR = 1,12; 95% IC = 1,04-1,2) e expressiva (OR = 1,08; 95% IC = 1,02-1,14). As convulsões neonatais comprometeram significativamente as áreas: visual, auditiva e social. Comunicação expressiva e desenvolvimento motor grosso ambos demostraram fatores de risco perinatais comuns. INTERPRETAÇÃO: O estado de desenvolvimento adverso, associado à atraso na apresentação e fatores de risco neonatais devem alertar os clínicos para a vigilância de bebês de risco e buscar intervenções oportunas.

Randomized, Single-Blind, Parallel Clinical Trial on Efficacy of Oral Prednisolone Versus Intramuscular Corticotropin: A 12-Month Assessment of Spasm Control in West Syndrome.

OBJECTIVE: We earlier completed a single-blind, parallel-group, randomized clinical trial to test the null hypothesis that adrenocorticotropic hormone (ACTH) is not superior to high-dose prednisolone for short-term control of West syndrome. We now present long-term follow-up data for spasm control for individuals who completed this earlier trial. METHODS: Infants with untreated West syndrome were randomized to receive 14 days of prednisolone (40 to 60 mg/day) or intramuscular long-acting ACTH (40 to 60 IU every other day). They were evaluated at three, six, and 12 months to evaluate long-term spasm control. RESULTS: The total number of infants treated was 97 (48 prednisolone; 49 ACTH). All completed the treatment course. Eighty-five, 82, and 76 children were available for follow-up at three, six, and 12 months. The number lost to follow-up at each interval was not statistically different. Likelihood of spasm freedom at three months was significantly higher for prednisolone (64.6%) than for ACTH (38.8%) (P = 0.01; odds ratio = 2.9; 95% confidence interval = 1.3 to 6.6). At six months (P = 0.19) and twelve months (P = 0.13), the control of spasms was not statistically different, although a trend in favor of prednisolone was documented at both of these time points (58.3% versus 44.9% for ACTH at six months and 56.2% versus 40.8% with ACTH at 12 months). After initial remission by day 14 (n = 46), the likelihood of a relapse within the next 12 months was not statistically different between the two treatment groups (P = 0.1). CONCLUSIONS: Control of spasms at three months was significantly better if initially treated with prednisolone. Control of spasms at six and 12 months was not significantly different despite a trend favoring prednisolone. Risk of relapse following initial remission was similar in the two groups.

The efficacy of moderate-to-high dose oral prednisolone versus low-to-moderate dose intramuscular corticotropin for improvement of hypsarrhythmia in West syndrome: a randomized, single-blind, parallel clinical trial.

BACKGROUND: The role of therapy on improvement of hypsarrhythmia has not been systematically assessed. This study was performed to assess the efficacy of oral prednisolone and intramuscular adrenocorticotrophin hormone in improving hypsarrhythmia in West syndrome. METHOD: Children (2 months-2 years), with previously untreated West syndrome, were randomized to receive 40-60 IU every other day of intramuscular adrenocorticotrophin hormone or 40-60 mg/day of oral prednisolone for 14 days. Children with tuberous sclerosis were excluded. Improvement of hypsarrhythmia was assessed blindly using a hypsarrhythmia severity scale before and after completion of therapy. Adverse effects were assessed on day 14 using symptom diary. (Clinical trial registry identifier: SLCTR/2010/010.) RESULTS: From 92 newly diagnosed West syndrome infants, 48 were randomized to receive prednisolone and 44 to receive adrenocorticotrophin hormone. Eighty infants completed the posttreatment evaluation according to specifications. The hypsarrhythmia severity score, significantly improved with hormonal therapy for 2 weeks (10.45 ± 2.65 vs 3.45 ± 2.67); P < 0.01. When individual treatment arms were compared using mean differences in the improvement of scores, improvement in prednisolone arm (7.95 ± 2.76) was significantly greater than that in the adrenocorticotrophin hormone arm (6.00 ± 2.61); P < 0.01. Both forms of therapy were tolerated well. Frequent crying, irritability, weight gain, increased appetite, and abdominal distension were more common (but not statistically significant) with prednisolone. CONCLUSIONS: Hypsarrhythmia severity score improved significantly with both hormonal therapies, but this improvement was significantly better with oral prednisolone than intramuscular adrenocorticotrophin hormone. This is the first ever documentation of a superior therapeutic role of oral steroids in West syndrome.

Clinical examination in paediatrics at final MBBS: views of children and their parents.

INTRODUCTION: The final examination in paediatrics for medical undergraduates in Sri Lanka consists of a written and a clinical component. Each candidate at the clinical component sees one long case and two short cases. OBJECTIVES: To assess the views of the bystanders regarding their sick children participating at a clinical examination, and to evaluate the children's perceptions of the clinical component. METHODS: An interviewer-administered questionnaire was discussed separately with the participating children and their bystanders at the final year examination in paediatrics of the Faculty of Medicine, Colombo, in 1999. RESULTS: 116 patients participated at the clinical examination in paediatrics. 107 (92%) of the bystanders were the children's mothers. Informed consent had not been obtained for use in the examination from 59 (51%) of the children's mothers. Seven (6%) were not satisfied with the way their children were handled by the candidates, and 25 (21.5%) showed concern about the number of candidates examining their child. Bystanders who participated at the long cases were inconvenience more than those in the short cases. 34 children above the age of 5 years were also interviewed. An explanation regarding the examination had not been given to 31 (92%) of them. Six children (17%) said they were examined for too long. A majority of the bystanders welcomed the payments received and all of them were satisfied with the medical students' conduct and politeness. All of them agreed that this form of clinical examination was a good method of evaluating a student's professional competence. CONCLUSIONS: Several aspects of the clinical component of the final examination in paediatrics for medical undergraduates need to be improved to minimise the inconvenience experienced by the children and their parents.