Indian Journal of Pediatrics最新文献

Advancement in genetic testing has become increasingly important in diagnosing and managing developmental and epileptic encephalopathies (DEEs), a group of rare neurodevelopmental disorders characterized by early-onset seizures, developmental delay, and electroencephalographic (EEG) abnormalities. These early epileptic encephalopathies are often described as various syndromes as per their clearly defined, relatively uniform, and distinct clinical phenotypes with consistent EEG and/or neuroimaging findings. Finding the underlying molecular mechanisms can cause a definitive change in the management strategy. With the evolving overlapping phenotypes, advent of technologies, and discovery of new genes, it is exceedingly becoming challenging to correctly characterise these disorders and plan subsequent evidence-based management. Cytogenetic microarray (CMA) and next generation sequencing (NGS) with improved data analysis pipe-lines and algorithms have revamped the diagnostic yield dramatically. However, as of now, there is a big lacuna in step-wise evaluation guideline or consensus on integration of genetic testing results with management plan. Understanding the genetic etiologies of such syndromes timely has three major implications: (1) Knowing the outcome of such a syndrome, (2) Therapeutic implications including licensing of drugs for certain forms (e.g. genetic syndromes involving ion channels) and (3) Genetic counseling, prenatal testing and choosing reproductive options in future pregnancies in such families. The focus of this review is to provide an understanding of different types of causative variants and their step-wise genetic testing approach; the most pressing clinical need and to develop an optimal diagnostic pathway for this group of patients.

Objectives: To review whether levetiracetam is non-inferior to phenobarbitone as the first-choice antiseizure medication (ASM).

Methods: The authors searched Medline, Embase, Web of Science, Scopus, and Cochrane Library for randomized controlled trials (RCTs) published until May 31, 2023. RCTs comparing the efficacy and safety of levetiracetam and phenobarbitone as first-line ASM in neonatal seizures were included. Random effects meta-analysis was performed, and the Risk of Bias version 2 tool was used for quality assessment.

Results: Eleven RCTs enrolling 821 neonates [mostly term, with hypoxic-ischemic encephalopathy (HIE)] were included. There was no significant difference in seizure control between levetiracetam and phenobarbitone (10 RCTs, 786 participants; relative risk RR: 1.11; 95% CI: 0.79, 1.54; I²- 88%). Neonates in the levetiracetam group had a significantly lower incidence of hypotension (RR: 0.28; 95% CI: 0.09, 0.86), respiratory depression (RR: 0.36, 95% CI: 0.19, 0.66), and depressed sensorium (RR: 0.52, 95% CI: 0.27, 1.00). Three studies compared neurodevelopmental outcomes; however two of them were cross-over trials where infants received both drugs. Only one RCT enrolled pure cohorts and showed better neurodevelopment in the levetiracetam group at one month of age.

Conclusions: With the limitation of very-low certainty evidence, the results of this systematic review suggest that levetiracetam may be non-inferior to phenobarbitone for managing neonatal seizures. Considering a better safety profile and marginally better neurodevelopment in the short term, levetiracetam may be considered an initial choice for managing neonatal seizures.

Registration number: PROSPERO (CRD42023438018).

Febrile seizures account for 2 to 14% of all childhood seizures, and one-third of febrile seizures are complex febrile seizures. Despite this, there is a lack of clinical equipoise in the diagnosis and management of complex febrile seizures and this results in significant practice variability amongst physicians. Although febrile seizures are generally noted to be benign phenomenon, complex febrile seizures carry the risk of subsequent epilepsy. Furthermore, long-term neurodevelopmental sequelae have been observed in some cohorts. The presence of both simple and complex febrile seizures have also been documented in sudden unexpected death in childhood cohorts, and there may be similarities in the underlying pathophysiology to sudden unexpected death in epilepsy. Finally, in some cases the presence of complex febrile seizures may herald the onset of a devastating developmental and epileptic encephalopathy (i.e., Dravet syndrome) or Febrile-Infection Related Epilepsy Syndrome (FIRES). In this narrative review the authors explore the current state of management of complex febrile seizures, their neurological sequelae and morbidity as well as rare epilepsy syndromes and conditions associated with them.

Objectives: To assess the impact of restricted vs. usual/liberal maintenance fluid strategy on fluid overload (FO) among mechanically ventilated children.

Methods: This open-label randomized controlled trial was conducted over a period of 1 y (October 2020-September 2021) in a Pediatric intensive care unit (PICU) in North India. Hemodynamically stable mechanically ventilated children were randomized to 40% (restricted group, n = 50) and 70-80% (usual/liberal group, n = 50) of maintenance fluids. The primary outcome was cumulative fluid overload percentage (FO%) on day 7. Secondary outcomes were FO% >10%; vasoactive inotropic score, sequential organ failure assessment score, pediatric logistic organ dysfunction score and oxygenation index from day 1-7; ventilation free days (VFDs) and PICU free days (PFDs) through day 28; and mortality.

Results: The restricted group had statistically non-significant trend towards lower cumulative FO% at day 7 [7.6 vs. 9.5, p = 0.40]; and proportion of children with FO% >10% (12% vs. 26%, p = 0.21) as compared to usual/liberal group. The increase in FO% from day 1-7 was significant in usual/liberal group as compared to restricted group (p <0.001 and p = 0.134, respectively). Restricted group received significantly lower amount of fluid in the first 5 d; had significantly higher VFDs (23 vs. 17 d, p = 0.008) and PFDs (19 vs. 15 d, p = 0.007); and trend towards lower mortality (8% vs. 16%, p = 0.21).

Conclusions: Restricted as compared to usual/liberal maintenance fluid strategy among mechanically ventilated children was associated with a trend towards lower rate and severity of FO and mortality; and significantly lower fluid volume received, and higher VFDs and PFDs.