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Global emphasis has shifted beyond reducing child survival rates to improving health and developmental trajectories in childhood. Optimum early childhood experience is believed to allow children to benefit fully from educational opportunities resulting in improved human capital. Investment in early childhood initiatives in low-income and middle-income countries (LMICs) is increasing. These initiatives use early childhood developmental assessment tools (CDATs) as outcome measures. CDATs are also key measures in the evaluation of programmatic health initiatives in LMICs, influencing public health policy. Interpretation of CDAT outcomes requires understanding of their structure and psychometric properties. This article reviews the structure and main methods of CDAT development with specific considerations when applied in LMICs.

BackgroundPreterm infants are at risk of neurodevelopmental delay, but data on long-term outcomes in low-income and middle-income countries remain scarce.ObjectivesTo examine neurodevelopment using Bayley Scales of Infant and Toddler Development-3rd edition (Bayley-III) and neurological findings in 2-year-old preterm infants, and to compare with healthy Vietnamese infants. Further, to assess factors associated with neurodevelopmental impairment.Design and settingCohort study to follow up preterm infants discharged from a neonatal intensive care unit (NICU) of a tertiary children’s hospital in Vietnam.ParticipantsInfants born at <37 weeks of gestational age.Main outcomesBayley-III assessment and neurological examination at 2-year corrected age (CA) compared with healthy Vietnamese infants.ResultsOf 294 NICU preterm infants, Bayley-III scores of all 184/243 (76%) survivors at 2 years CA were significantly lower than those of healthy Vietnamese peers in all three domains: cognition (mean (SD): 84.5 (8.6) vs 91.4 (7.5), p<0.001), language (mean (SD): 88.7 (12.5) vs 95.9 (11.9), p<0.001) and motor (mean (SD): 93.1 (9.0) vs 96.8 (9.3), p=0.003). The mean differences in Bayley-III scores between preterm and healthy Vietnamese infants were −6.9 (−9.1 to −4.7), −7.2 (−10.5 to −3.8) and −3.7 (−6.1 to −1.2) for cognitive, language and motor scores, respectively. The prevalence of neurodevelopmental impairment was 17% for cognitive, 8% for language and 4% for motor performance. In total, 7% were diagnosed with cerebral palsy. Higher maternal education was positively associated with infant neurodevelopment (OR 0.32, 95% CI 0.11 to 0.94).ConclusionsVietnamese preterm infants in need of neonatal intensive care showed poor neurodevelopment at 2 years. Higher maternal education was positively associated with infant neurodevelopment. Standard follow-up programmes for preterm infants should be considered in low-resource settings.

Hand, foot and mouth disease (HFMD) is a common infectious disease in western Asia area and the full range of the long-term sequelae of HFMD remains poorly described. We conducted a retrospective hospital-based cohort study of HFMD patients with central nervous system (CNS) complications caused by EV-A71 or CV-A16 between 2010 and 2016. Patients were classified into three groups, including CNS only, autonomic nervous system (ANS) dysregulation, and cardiorespiratory failure. Neurologic examination, neurodevelopmental assessments, Magnetic Resonance Imaging (MRI) and lung function, were performed at follow up. Of the 176 patients followed up, 24 suffered CNS only, 133 ANS dysregulation, and 19 cardiorespiratory failure. Median follow-up period was 4.3 years (range [1.4-8.3]). The rate of neurological abnormalities was 25% (43 of 171) at discharge and 10% (17 of 171) at follow-up. The rates of poor outcome were significantly different between the three groups of complications in motor (28%, 38%, 71%) domain (p=0.020), but not for cognitive (20%, 24%, 35%), language (25%, 36%, 41%) and adaptive (24%, 16%, 26%) domains (p = 0.537, p = 0.551, p = 0.403). For children with ventilated during hospitalization, 41% patients (14 of 34) had an obstructive ventilatory defect, and one patient with scoliosis had mixed ventilatory dysfunction. Persistent abnormalities on brain MRI were 0% (0 of 7), 9% (2 of 23) and 57% (4 of 7) in CNS, ANS and cardiorespiratory failure group separately. Patients with HFMD may have abnormalities in neurological, motor, language, cognition, adaptive behaviour and respiratory function. Long-term follow-up programmes for children's neurodevelopmental and respiratory function may be warranted.

Objectives To describe the clinical presentation, investigations, management, and disease course in pediatric autoimmune limbic encephalitis (LE). Methods In this retrospective observational study, from the UK Childhood Neuroinflammatory Disease network, we identified children from six tertiary centers with LE <18 years old between 2008 and 2021. Clinical and paraclinical data were retrieved from medical records. Results Twenty‐five children fulfilling LE criteria were identified, with median age of 11 years (IQR 8, 14) and median follow‐up of 24 months (IQR 18, 48). All children presented with seizures; 15/25 (60%) were admitted to intensive care. Neuroimaging demonstrated asymmetric mesial temporal changes in 8/25 (32%), and extra‐limbic changes with claustrum involvement in 9/25 (38%). None were positive for LGI1/CASPR2 antibodies (Abs), 2/25 were positive for serum anti‐NMDAR Abs, and 2/15 positive for anti‐Hu Abs; one died from relapsing neuroblastoma. Two children had serum and CSF anti‐GAD antibodies. Initial immune therapy included steroids in 23/25 (92%), intravenous immunoglobulin (IVIg) in 14/25 (56%), and plasma exchange in 7/25 (28%). The commonest second‐line treatment was rituximab in 15/25 (60%). Median duration of hospital admission was 21 days (IQR 11, 30). At last follow‐up, 13/25 (52%) had refractory seizures and 16/25 (64%) had memory impairment. Six children (24%) had modified Rankin Scale (mRS) scores ≥3. There was no significant difference in mRS, or long‐term cognitive and epilepsy outcomes in those who received rituximab versus those who did not. Interpretation A diagnosis of autoimmune LE was associated with significant morbidity and adverse outcomes in this pediatric cohort.

Background Brainstem encephalitis is a serious complication of hand foot and mouth disease (HFMD) in children. Autonomic nervous system (ANS) dysregulation and hypertension may occur, sometimes progressing to cardiopulmonary failure and death. Vietnamese national guidelines recommend use of milrinone if ANS dysregulation with Stage 2 hypertension develops. We wished to investigate whether magnesium sulfate (MgSO 4 ) improved outcomes in children with HFMD if used earlier in the evolution of the ANS dysregulation (Stage 1 hypertension). Methods During a regional epidemic we conducted a randomized, double-blind, placebo-controlled trial of MgSO 4 in children with HFMD, ANS dysregulation and Stage 1 hypertension, at the Hospital for Tropical Diseases in Ho Chi Minh city. Study participants received an infusion of MgSO 4 or matched placebo for 72 h. We also reviewed data from non-trial HFMD patients in whom milrinone failed to control hypertension, some of whom received MgSO 4 as second line therapy. The primary outcome for both analyses was a composite of disease progression within 72 h - addition of milrinone (trial participants only), need for ventilation, shock, or death. Results Between June 2014 and September 2016, 14 and 12 participants received MgSO 4 or placebo respectively, before the trial was stopped due to futility. Among 45 non-trial cases with poorly controlled hypertension despite high-dose milrinone, 33 received MgSO 4 while 12 did not. There were no statistically significant differences in the composite outcome between the MgSO 4 and the placebo/control groups in either study (adjusted relative risk (95%CI) of [6/14 (43%) vs. 6/12 (50%)], 0.84 (0.37, 1.92), p  = 0.682 in the trial and [1/33 (3%) vs. 2/12 (17%)], 0.16 (0.01, 1.79), p  = 0.132 in the observational cohort). The incidence of adverse events was similar between the groups. Potentially toxic magnesium levels occurred very rarely with the infusion regime used. Conclusion Although we could not demonstrate efficacy in these studies, there were no safety signals associated with use of 30-50 mg/kg/hr. MgSO 4 in severe HFMD. Intermittent outbreaks of HFMD are likely to continue across the region, and an adequately powered trial is still needed to evaluate use of MgSO 4 in controlling hypertension in severe HFMD, potentially involving a higher dose regimen. Trial registration ClinicalTrials.gov Identifier: NCT01940250 (Registered 22 AUG 2013). Trial sponsor : University of Oxford

Background Neonatal tetanus continues to occur in many resource-limited settings but there are few data regarding long-term neurological outcome from the disease, especially in settings with critical care facilities. Methods We assessed long-term outcome following neonatal tetanus in infants treated in a pediatric intensive care unit in southern Vietnam. Neurological and neurodevelopmental testing was performed in 17 survivors of neonatal tetanus and 18 control children from the same communities using tools previously validated in Vietnamese children. Results The median age of children assessed was 36 months. Eight neonatal tetanus survivors and 9 community control cases aged < 42 months were tested using the Bayley III Scales of Infant and Toddler Development (Bayley III-VN) and 8 neonatal tetanus survivors and 9 community controls aged ≥42 months were tested using the Movement Assessment Battery for Children. No significant reductions in growth indices or neurodevelopmental scores were shown in survivors of neonatal tetanus compared to controls although there was a trend towards lower scores in neonatal tetanus survivors. Neurological examination was normal in all children except for two neonatal tetanus survivors with perceptive deafness and one child with mild gross motor abnormality. Neonatal tetanus survivors who had expienced severe disease (Ablett grade ≥ 3) had lower total Bayley III-VN scores than those with mild disease (15 (IQR 14–18) vs 24 (IQR 19–27), p  = 0.05) with a significantly lower cognitive domain score (3 (IQR 2–6) severe disease vs 7 (IQR 7–8) mild disease, p  = 0.02). Conclusions Neonatal tetanus is associated with long-term sequelae in those with severe disease. In view of these findings, prevention of neonatal tetanus should remain a priority.

BACKGROUND: Hand foot and mouth disease (HFMD) is a disease of public health importance across the Asia-Pacific region. The disease is caused by enteroviruses (EVs), in particular enterovirus A71 (EV-A71). In EV-A71-associated HFMD, the infection is sometimes associated with severe manifestations including neurological involvement and fatal outcome. The availability of a robust diagnostic assay to distinguish EV-A71 from other EVs is important for patient management and outbreak response. METHODS: We developed and validated an internally controlled one-step single-tube real-time RT-PCR in terms of sensitivity, linearity, precision, and specificity for simultaneous detection of EVs and EV-A71. Subsequently, the assay was then applied on throat and rectal swabs sampled from 434 HFMD patients. RESULTS: The assay was evaluated using both plasmid DNA and viral RNA and has shown to be reproducible with a maximum assay variation of 4.41 % and sensitive with a limit of detection less than 10 copies of target template per reaction, while cross-reactivity with other EV serotypes was not observed. When compared against a published VP1 nested RT-PCR using 112 diagnostic throat and rectal swabs from 112 children with a clinical diagnosis of HFMD during 2014, the multiplex assay had a higher sensitivity and 100 % concordance with sequencing results which showed EVs in 77/112 (68.8 %) and EV-A71 in 7/112 (6.3 %). When applied to clinical diagnostics for 322 children, the assay detected EVs in throat swabs of 257/322 (79.8 %) of which EV-A71 was detected in 36/322 (11.2 %) children. The detection rate increased to 93.5 % (301/322) and 13.4 % (43/322) for EVs and EV-A71, respectively, when rectal swabs from 65 throat-negative children were further analyzed. CONCLUSION: We have successfully developed and validated a sensitive internally controlled multiplex assay for rapid detection of EVs and EV-A71, which is useful for clinical management and outbreak control of HFMD.

Background: There are limited psychometric reports of construct validity following adaptation of the Bayley Scales of Infant and Toddler Development 3 rd edition (Bayley III). This paper aims to demonstrate a process of assessing reliability, validity, and gender equivalence of the adapted tool for Vietnamese children. Methods: We evaluated cognitive, fine motor, gross motor, expressive communication and receptive communication subtests of the adapted tool in 267 healthy urban Vietnamese children. Subsets of participants were used to evaluate inter-observer and test-retest reliability. Confirmatory factor analysis (CFA) was carried out to evaluate construct validity and measurement invariance between genders. Results: The adaptation demonstrated good inter-observer and test-retest reliability. CFA indicated that a construct representing a single underlying factor showed the best fit, although relationships between the observed scores and the latent traits underlying the scores varied between age groups. Within age groups, relationships between observed scores and these factors were not significantly influenced by gender. Conclusions: The Vietnamese Bayley III demonstrated good internal consistency and reliability. A latent structure with one general factor and additional residual correlations that change with age is supported by the theoretical understanding of child development. This is the first study to demonstrate gender invariance by age group. This adaptation is suitable for further research studies in urban Vietnamese children, but further work is needed to extend its applicability more broadly across Vietnam.

[...]dissemination of EVs to the reticuloendothelial system (liver, spleen, bone marrow and lymph nodes), skin and mucous membranes coincides with the onset of clinical symptoms. MRI of the brain suggests typical involvement of the medulla oblongata, pons, midbrain and spinal cord, that resolves within 2 months in most cases. 6 A prospective study of 730 children admitted with HFMD in Sarawak found high fever, fever for more than 3 days and lethargy as risk factors for central nervous system involvement. 11 However the positive predictive values for these risk factors were relatively low, resulting in high numbers of hospitalisations for relatively mild disease.