Efficacy of different doses of daily prophylactic iron supplementation in pregnant women: A systematic review and meta-analysis.

INTRODUCTION: Several randomized controlled trials (RCT) have been conducted in the past to determine the optimum dose of iron supplementation during pregnancy, but there is a lack of consensus among different guidelines regarding the appropriate dosage of iron for prophylaxis during pregnancy. METHODS: Relevant electronic databases were searched to identify publications describing RCTs comparing different daily dosages of iron supplementation during pregnancy. Meta-analysis for various efficacy and safety outcomes such as changes in blood hemoglobin, serum ferritin, serum iron, and serum transferrin saturation, as well as the frequency of adverse effects, was performed using random and fixed effect models suitably depending on the degree of heterogeneity. Two groups were compared: those receiving 60 mg elemental iron or less and those receiving more than 60 mg elemental iron per day. Additionally, the efficacy of those receiving 30 mg elemental iron per day and those receiving 60 mg elemental iron per day were also compared. RESULTS: A to total of 15 RCTs comprising 2726 participants were included in the meta-analysis. Change in blood hemoglobin levels was comparable between the ≤60 mg/day and >60 mg/day group (pooled estimate for mean difference, 0.01 [-0.11, 0.09], p=0.86, I2=96%), but serum ferritin, iron level, and serum transferrin saturation change were higher in the >60 mg group (p<0.0001, 0.008, and 0.02, respectively). Change in blood hemoglobin level was better in the 60 mg/day group compared to the 30 mg/day group (pooled estimate for mean difference, -0.11 [-0.21, 0.00], p=0.04, I2=90%), as well as changes in serum ferritin and serum transferrin saturations (p=0.004 and 0.0004, respectively). CONCLUSION: Daily supplementation of 60 mg elemental iron is more efficacious than daily supplementation of 30 mg elemental iron for the prophylaxis of anemia in pregnant women (certainty of evidence-moderate), and daily supplementation of ≤60 mg elemental iron is equally efficacious compared to daily supplementation of >60 mg elemental iron for the prophylaxis of anemia in pregnant women (certainty of evidence-moderate). PROESPERO REGISTRATION NO: CRD42023455485.

Efficacy of oral folinic acid supplementation in children with autism spectrum disorder: a randomized double-blind, placebo-controlled trial.

Oral folinic acid has shown potential to improve symptoms in children with autism spectrum disorder (ASD). However, randomized controlled trials (RCTs) are limited. This double-blind, placebo-controlled RCT aimed to compare changes in Childhood Autism Rating Scale (CARS) scores in children with ASD aged 2-10 years, among folinic acid (2 mg/kg/day, maximum of 50 mg/day) and placebo groups at 24 weeks, in comparison with baseline. Both the groups received standard care (ABA and sensory integration therapy). Secondary objectives included changes in behavioral problems measured by the Child Behavior Checklist (CBCL) and serum levels of anti-folate receptor autoantibodies and folic acid, correlated with changes in autism symptom severity. Out of the 40 participants recruited in each group, 39 and 38 participants completed the 24-week follow-up in the folinic acid and placebo groups, respectively. The change in CARS score was higher in the folinic acid group (3.6 ± 0.8) compared to the placebo group (2.4 ± 0.7, p < 0.001). Changes in CBCL total score and CBCL internalizing score were also better in the folinic acid group (19.7 ± 9.5 vs. 12.6 ± 8.4 and 15.4 ± 7.8 vs. 8.5 ± 5.7, p < 0.001 for both). High-titer anti-folate receptor autoantibodies were positive in 32/40 and 33/40 cases in the folinic acid and placebo groups, respectively (p = 0.78). In the placebo group, improvement in CARS score was comparable regardless of autoantibody status (p = 0.11), but in the folinic acid group, improvement was more pronounced in the high-titer autoantibody group (p = 0.03). No adverse reactions were reported in either group. CONCLUSIONS: Oral folinic acid supplementation is effective and safe in improving ASD symptoms, with more pronounced benefits in children with high titers of folate receptor autoantibodies. TRIAL REGISTRATION:  CTRI/2021/07/034901, dated 15-07-2021. WHAT IS KNOWN: • Folate receptor autoantibodies are more prevalent in children with autism spectrum disorder (ASD) compared to typically developing children. • Folate receptor autoantibodies play a significant role in the neuropathogenesis of autism spectrum disorder. WHAT IS NEW: • Add-on oral folinic acid supplementation is safe and effective in reducing the severity of symptoms in children with ASD. • The clinical benefits are more pronounced in children with high titers of folate receptor autoantibodies.

Association Between Clinical Severity, Neuroimaging, and Electroencephalographic Findings in Children with Subacute Sclerosing Panencephalitis.

BACKGROUND: Children diagnosed with subacute sclerosing panencephalitis (SSPE) display a range of neuroimaging abnormalities during different stages of the disease, but their exact clinical significance remains unclear. METHODS: In this retrospective cohort study, our objective was to examine magnetic resonance imaging (MRI) abnormalities in the brains of patients aged 18 years or younger with subacute sclerosing panencephalitis. We aimed to correlate these MRI abnormalities with clinical severity, sociodemographic variables, electroencephalographic (EEG) abnormalities, and cerebrospinal anti-measles antibody titers. RESULTS: The study included 112 cases of subacute sclerosing panencephalitis (mean age at onset: 8.9 ± 2.6 years). MRI analysis at the time of presentation revealed the following abnormalities: subcortical white matter signal changes (n = 95), periventricular white matter signal changes (n = 76), splenium of corpus callosum involvement (n = 39), diffuse corpus callosum involvement (n = 27), cerebral atrophy (n = 35), basal ganglia involvement (n = 10), and brain stem involvement (n = 2). Notably, subcortical white matter involvement, periventricular white matter involvement, diffuse corpus callosum involvement, and basal ganglia involvement were more prevalent in patients with stage III and IV subacute sclerosing panencephalitis (P < .05 for all). Cerebral atrophy was also significantly more common in patients with stage III compared to those with stage IV subacute sclerosing panencephalitis (P < .0001). However, no substantial positive or negative associations were found between MRI findings and EEG abnormalities, other sociodemographic/clinical variables, and cerebrospinal fluid measles-specific antibody titers (P > .05). CONCLUSION: Early in the disease progression of subacute sclerosing panencephalitis, the temporoparietal and parietooccipital regions of the subcortical white matter are affected. Neuroimaging abnormalities exhibit a stronger association with Jabbour's clinical staging, but do not show significant associations with other clinical, sociodemographic, and EEG features.

Efficacy of oral sodium chloride in reducing the incidence of hyponatremia in children with epilepsy receiving oxcarbazepine monotherapy: A randomized controlled trial (SCHO Trial).

INTRODUCTION: Hyponatremia is a well-documented adverse effect of oxcarbazepine treatment, but no clinical trial has yet been conducted to explore any intervention for reducing the incidence of hyponatremia. MATERIALS AND METHODS: This open-label trial evaluated the efficacy of add-on daily oral sodium chloride supplementation of 1-2 g/day for 12 weeks in reducing the incidence of hyponatremia in children receiving oxcarbazepine monotherapy aged 1-18 years. Apart from comparing the incidence of symptomatic and severe hyponatremia, serum and urine sodium levels, serum and urine osmolality, changes in behavior and cognition, and the number of participants with recurrence of seizures and requiring additional antiseizure medication (ASM) were also compared. RESULTS: A total of 120 children (60 in each group) were enrolled. The serum sodium level at 12 weeks in the intervention group was higher than that of the control group (136.5 ± 2.6 vs 135.4 ± 2.5 mEq/L, p = 0.01). The number of patients with hyponatremia was significantly lower in the intervention group (4/60vs14/60, p = 0.01). However, the incidence of symptomatic and severe hyponatremia (0/60vs1/60, p = 0.67 for both), changes in social quotient and child behavior checklist total score (0.6 ± 0.8 vs 0.7 ± 0.5, p = 0.41 and 0.9 ± 1.2 vs 1.1 ± 0.9, p = 0.30 respectively), the number of patients with breakthrough seizures (9/60vs10/60, p = 0.89), and the number of patients requiring additional ASMs (8/60vs10/60, p = 0.79) were comparable in both groups. CONCLUSIONS: Daily oral sodium chloride supplementation is safe and efficacious in reducing the incidence of hyponatremia in children with epilepsy receiving oxcarbazepine monotherapy. However, sodium chloride supplementation does not significantly reduce more clinically meaningful outcome measures like symptomatic and severe hyponatremia. Trial registry No. CTRI/2021/12/038388.

Efficacy of Oral Trihexyphenidyl Plus Clonazepam Versus Trihexyphenidyl for the Treatment of Dystonia in Children With Dystonic Cerebral Palsy: An Open-Label Randomized Controlled Trial.

BACKGROUND: Trihexyphenidyl and clonazepam are commonly used to treat dystonia in children with cerebral palsy (CP). However, there is a notable gap in the literature when it comes to studies that combine these first-line agents for the management of dystonia. METHODS: This open-label, randomized controlled trial aimed to compare the efficacy of adding oral clonazepam to trihexyphenidyl (THP + CLZ) versus using trihexyphenidyl alone (THP) in reducing the severity of dystonia, as measured by the Barry-Albright Dystonia (BAD) score. The study was conducted over a 12-week therapy period in children with dystonic CP aged two to 14 years. RESULTS: Each group enrolled 51 participants. The THP + CLZ group showed significantly better improvement in dystonia severity at 12 weeks compared with the THP group alone (-4.5 ± 2.9 vs -3.4 ± 1.7, P = 0.02). Furthermore, the THP + CLZ group exhibited superior improvement in the severity of choreoathetosis, upper limb function, pain perception by the child, and quality of life, with P values of 0.02, 0.009, 0.01, and 0.01, respectively. The number of participants experiencing treatment-emergent adverse events was comparable in both groups (P = 0.67). Importantly, none of the participants in any of the groups reported any serious adverse events. CONCLUSION: A combination of oral THP + CLZ proves to be more efficacious than using THP alone for the treatment of dystonic CP in children aged two to 14 years in terms of reducing the severity of dystonia.

Effectiveness of IMPUTE ADT-1 mobile application in children with autism spectrum disorder: An interim analysis of an ongoing randomized controlled trial.

Objectives: IMPUTE Inc., a software firm dedicated to healthcare technology, has developed a mobile medical application known as IMPUTE ADT-1 for children with autism spectrum disorder (ASD) based on the principle of applied behavior analysis. Materials and Methods: The primary objective of this trial was to compare the efficacy of add-on treatment with IMPUTE ADT-1 in children with ASD aged two to six years as compared to standard care alone for 12 weeks (in terms of change in Autism Diagnostic Observation Schedule [ADOS-2] scores). The secondary objective of the study was to assess the compliance with IMPUTE ADT-1 among participants and also to evaluate the feedback of parents regarding IMPUTE ADT-1 at the end of 12 weeks. The application provides personalized programs tailored to each user's needs, and the program evolves based on the user's progress. It also utilizes face tracking, eye tracking, and body tracking to gather behavior-related information for each child and apply it in reinforcement learning employing artificial intelligence-based algorithms. Results: Till the time of interim analysis, 37 and 33 children had completed 12-week follow-up in IMPUTE ADT-1 and control arm. At 12 weeks, as compared to baseline, change in social affect domain, repetitive ritualistic behavior domain, total ADOS-2 score, and ADOS-2 comparison score was better in the intervention group as compared to the control group (P < 0.001 for all). A total of 30 (81%), 28 (75%), and 29 (78%) caregivers in the IMPUTE ADT-1 group believed that the ADT-1 app improved their child's verbal skills, social skills, and reduced repetitive behavior, respectively. Conclusion: IMPUTE ADT-1 mobile application has the efficacy to improve the severity of autism symptoms in children. Parents of these children also feel that the application is beneficial for improving the socialization and verbal communication of their children.

Efficacy of verbal suggestion, verbal suggestion with a tuning fork, and verbal suggestion with a cotton swab for inducing the paroxysmal event during video-EEG recording in children with suspected psychogenic nonepileptic seizures.

INTRODUCTION: Video-electroencephalogram (EEG) with suggestion is widely considered the gold standard for diagnosing psychogenic nonepileptic seizures (PNES). However, ethical concerns and uncertainties persist regarding the most minimally invasive and least deceptive suggestion approach. MATERIALS AND METHODS: In an open-label randomized controlled trial, we evaluated the effectiveness of three suggestion methods (verbal suggestion, verbal suggestion with a tuning fork, and verbal suggestion with a cotton swab) during short-term video-EEG (STVEEG) recordings to induce PNES in children aged 5-18 years. If the paroxysmal event couldn't be elicited with the assigned method, alternative techniques were employed. RESULTS: Out of 97 initially screened children, 75 were enrolled, with 25 in each group. The efficacy of all three suggestion methods was comparable in reproducing paroxysmal events (success rate of 16/25, 17/25 and 17/25 in verbal suggestion only, verbal suggestion with tuning fork and sterile cotton swab group respectively, p = 0.83) and the time required for induction (median of 2, 3 and 3 min respectively, p = 0.21). After trying alternative methods, 20 %, 12 %, and 12 % more patients in these three groups, respectively, were able to reproduce the paroxysmal event, with the differences not reaching statistical significance (p = 0.74). The assigned induction method or the success/failure of event reproduction did not significantly impact clinical outcomes at 12 weeks, and none of the patients in whom PNES could not be reproduced during STVEEG were later found to have an organic cause. Only the presence of psychiatric comorbidity independently predicted successful event reproduction during STVEEG, with statistical significance even after adjusting for other variables (p = 0.03). CONCLUSION: The efficacy of verbal suggestion alone in inducing paroxysmal nonepileptic seizures is on par with using a tuning fork or cotton swab in conjunction with verbal suggestion during STVEEG.

Efficacy and safety of phenytoin and levetiracetam for acute symptomatic seizures in children with acute encephalitis syndrome: an open label, randomised controlled trial.

INTRODUCTION: Seizures represent a significant comorbidity in children with acute encephalitis syndrome (AES). Despite this, there is a notable absence of randomized controlled trials (RCTs) directly comparing antiseizure medications (ASMs) in children with AES. MATERIALS AND METHODS: This RCT aimed to assess the efficacy and safety of phenytoin and levetiracetam in controlling seizures among children with AES. Both ASMs were administered with a loading followed by maintenance dose. After a 12-week period, children exhibiting a normal electroencephalogram and no seizure recurrence underwent tapering and discontinuation of ASM. Clinical follow-up occurred daily for the first week, and subsequently at 4, 12, and 24 weeks, evaluating seizure recurrence, incidence of status epilepticus, cognition, behavior, functional status, ASM acquisition cost, and adverse effects. RESULTS: A total of 100 children (50 in each group) were enrolled. Within the first week, 5 and 3 children in the phenytoin and levetiracetam groups expired. Up to 1 week or death (whichever occurred earliest), 46 (92 %) and 44 (88 %) children remained seizure-free. Intention-to-treat analysis for both best and worst-case scenarios showed insignificant differences (p=0.52 and 1.0). No children experienced seizure recurrence after 1 week in either group. The number of patients with breakthrough status epilepticus, need for mechanical ventilation, duration of hospital stay, presence of epileptiform abnormalities in repeat electroencephalogram at 12 weeks, functional outcomes at 1, 12, and 24 weeks, as well as cognition and behavioral profiles at 24 weeks, were comparable in both groups (p>0.05 for all). However, the incidence of treatment-emergent adverse events (TEAEs) causally related to study medications was significantly higher in the phenytoin group (p=0.04). CONCLUSION: Levetiracetam and phenytoin are comparable in efficacy in terms of achieving clinical seizure control in children with acute encephalitis syndrome, although levetiracetam group demonstrated fewer adverse effects.

Early versus late switch over of antiseizure medications from intravenous to the oral route in children with seizures: Single-blinded, randomized controlled trial (ELAIO trial).

INTRODUCTION: Early switch-over of anti-seizure medications (ASMs) from intravenous to oral route may reduce the duration of hospitalization, drug acquisition costs, and behavioral upset in hospitalized children with seizures. OBJECTIVE: The primary objective was to compare short-term seizure recurrence within 1 week in hospitalized children aged 1 month to 18 years with new-onset/breakthrough seizures after an early versus late switch-over from intravenous to the oral route of ASMs. Secondary objectives were to compare the incidence of status epilepticus, duration of hospital stay, drug acquisition costs, and caregiver-reported satisfaction scores in both groups. METHODS: In this single-blind randomized controlled trial, patients with seizures were categorized based on the number of ASMs required and the history of status epilepticus. Patients in each category were randomized in a 1:1 ratio into either early or late switch-over (ES or LS) groups. In the ES groups, ASMs were tapered one-by-one between 0 and 24 hours of seizure freedom, while in the LS groups, they were tapered one-by-one between 24 and 48 hours of seizure freedom. RESULTS: A total of 112 children were enrolled in the study, with 56 in each arm. Seizure recurrence at 1 week and 12 weeks was comparable in ES and LS groups (3/55 vs. 1/54 at 1 week, p=0.61; 7/49 vs. 6/49 at 12 weeks, p=0.98). Drug acquisition costs were significantly lower in the ES group (393±274 vs. 658±568 INR, p=0.002). Thrombophlebitis and dysphoria were significantly more common in the LS group (p=0.008 and 0.03, respectively). CONCLUSION: The early switch-over of ASMs from intravenous to oral route is safe without any significant increased risk of short-term seizure recurrence and also associated with a reduction in the incidence of thrombophlebitis and ASM acquisition costs. TRIAL REGISTRATION NO: CTRI/2021/03/032145.

An atypical case of bilateral optic neuritis after strabismus surgery under general anesthesia.

INTRODUCTION: Strabismus surgery under general anesthesia is a common procedure with rare complications in the form of hemorrhage, infection, slipped muscle, lost muscle, scleral perforation, and anterior segment ischemia. We report a unique case of bilateral optic neuritis following squint surgery under general anesthesia in a 15-year-old girl. METHODS: A 15-year-old girl presented with accommodative esotropia with V pattern. She underwent uneventful bilateral inferior oblique recession surgery under general anesthesia with Propofol 60 mg, Atracurium 30 mg, and Fentanyl 70 mcg. On the first post-operative day, the patient had an acute onset of temporal headache which was non-radiating. She responded to supportive treatment and was discharged. However, on the 7th postoperative day, she presented with a constant severe headache in the bitemporal region (left > right) for 3 days. She also experienced a painless diminution of vision for 2 days. There was no vomiting, fever, loose stools, diplopia, difficulty in breathing, peripheral sensation loss, generalized weakness, or bowel/bladder incontinence. RESULTS: The best corrected visual acuity was 6/9 in right eye, and 6/9p in left eye with a relative afferent pupillary defect (RAPD) in the left eye. Both optic discs appeared hyperemic with blurred margins. Magnetic resonance imaging (MRI) of the brain and orbit showed hyperintensity along the intraorbital and intracanalicular parts of bilateral optic nerves on T2 weighted image suggesting bilateral optic neuritis. She received intravenous methylprednisolone pulse therapy followed by oral steroids and responded to the medical treatment with improvement in vision but developed steroid-induced glaucoma requiring medical management over several weeks. DISCUSSION: Neuro-ophthalmic complication in the form of non-arteritic ischemic optic neuropathy has been reported after various ophthalmic surgeries, but bilateral optic neuritis has not been reported to date. This possibility should be kept in mind if any patient presents with similar symptoms. This report also highlights IOP monitoring in pediatric patients receiving systemic steroids to prevent loss of vision due to steroid-induced glaucoma.