Neurodevelopmental problems in children with febrile seizures followed to young school age: A prospective longitudinal community‐based study in Sweden

Nilsson, Gill; Lundström, Staffan; Fernell, Elisabeth; Gillberg, Christopher

doi:10.1111/apa.16171

Cited by 5 publications

(4 citation statements)

References 23 publications

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“…8,11 Iron is an essential nutrient for brain maturation and overall body growth with unprecedented indispensability during "critical periods" of accelerated brain development spanning ages 6 to 24 months. [13][14][15][16] Within this time, the brain is prone to structural and functional alterations that may manifest immediately or arise later in life in the form of epilepsy, 17,18 neurodevelopmental problems such as memory problems, learning de cit, poor attention span, intellectual disability, behavioral disturbance, 16,18,19 or even as various psychiatric disorders. 6,19,20 Although the peak onset of FS is concurrent with this time period, 8 the impact of altered blood iron status on brain iron status, and consequently on brain structure and function, is unclear.…”

Section: Discussionmentioning

confidence: 99%

Multivariate models for the prediction of febrile seizure risk and recurrence: a prospective case-control study

Papež

Labounek

Jabandžiev

et al. 2023

Preprint

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Our goal was to identify highly accurate empirical models for the prediction of the risk of febrile seizure (FS) and FS recurrence. In a prospective, three-arm, case-control study, we enrolled 162 children (age 25.8±17.1 months old, 71 females). Participants formed one case group (patients with FS) and two control groups (febrile patients without seizures and healthy controls). The impact of blood iron status, peak body temperature, and participants’ demographics on FS risk and recurrence was investigated with univariate and multivariate statistics. Serum iron concentration, iron saturation, and unsaturated iron-binding capacity differed between the three investigated groups (pFWE<0.05). These serum analytes were key variables in the design of novel multivariate linear mixture models. The models classified FS risk with higher accuracy than univariate approaches. The designed bi-linear classifier achieved a sensitivity/specificity of 83%/89% and was closest to the gold-standard classifier. A multivariate model assessing FS recurrence provided a difference (pFWE<0.05) with a separating sensitivity/specificity of 79%/69%. Iron deficiency, height percentile, and age were significant FS risk factors. In addition, height percentile and hemoglobin concentration were linked to FS recurrence. Novel multivariate models utilizing blood iron status and demographic variables predicted FS risk and recurrence among infants and young children with fever.

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Section: Discussionmentioning

confidence: 99%

Multivariate models for the prediction of febrile seizure risk and recurrence: a prospective case-control study

Papež

Labounek

Jabandžiev

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Iron is an essential nutrient for brain maturation and overall body growth with unprecedented indispensability during “critical periods” of accelerated brain development spanning ages 6 to 24 months 15 – 17 . Within this time, the brain is prone to structural and functional alterations that may manifest immediately or arise later in life in the form of epilepsy 18 , 19 , neurodevelopmental problems such as memory problems, learning deficit, poor attention span, intellectual disability, behavioral disturbance 15 , 19 , 20 , or even as various psychiatric disorders 6 , 20 , 21 . Although the peak onset of FS is concurrent with this time period 8 , the impact of altered blood iron status on brain iron status, and consequently on brain structure and function, is unclear.…”

Section: Discussionmentioning

confidence: 99%

“…In analogy, the male sex represents a risk factor for ID or ID anemia in infants and young children 23 , 24 , 26 , 28 . Moreover, sex may determine seizure susceptibility and type, as demonstrated in the animal model 20 , 21 . The sex difference or male overrepresentation in FS human studies is well documented 1 , 2 , 6 , 11 .…”

Section: Discussionmentioning

confidence: 99%

Multivariate linear mixture models for the prediction of febrile seizure risk and recurrence: a prospective case–control study

Papež,

Labounek,

Jabandžiev

et al. 2023

Sci Rep

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Our goal was to identify highly accurate empirical models for the prediction of the risk of febrile seizure (FS) and FS recurrence. In a prospective, three-arm, case–control study, we enrolled 162 children (age 25.8 ± 17.1 months old, 71 females). Participants formed one case group (patients with FS) and two control groups (febrile patients without seizures and healthy controls). The impact of blood iron status, peak body temperature, and participants’ demographics on FS risk and recurrence was investigated with univariate and multivariate statistics. Serum iron concentration, iron saturation, and unsaturated iron-binding capacity differed between the three investigated groups (pFWE < 0.05). These serum analytes were key variables in the design of novel multivariate linear mixture models. The models classified FS risk with higher accuracy than univariate approaches. The designed bi-linear classifier achieved a sensitivity/specificity of 82%/89% and was closest to the gold-standard classifier. A multivariate model assessing FS recurrence provided a difference (pFWE < 0.05) with a separating sensitivity/specificity of 72%/69%. Iron deficiency, height percentile, and age were significant FS risk factors. In addition, height percentile and hemoglobin concentration were linked to FS recurrence. Novel multivariate models utilizing blood iron status and demographic variables predicted FS risk and recurrence among infants and young children with fever.

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“…Febrile seizures (FS), characterized as convulsive episodes in association with fever, are distinct from seizures caused by intracranial pathologies, metabolic imbalances, or acute neurological insults [ 8 ]. Previous studies indicated that FS is related to a range of developmental and behavioral problems [ 9 – 12 ]. According to a nationally representative sample of twins, FS is associated with increased ASD prevalence [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Additive interaction between birth asphyxia and febrile seizures on autism spectrum disorder: a population-based study

Mao,

Lin,

et al. 2024

Molecular Autism

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Background Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder that can significantly impact an individual’s ability to socially integrate and adapt. It’s crucial to identify key factors associated with ASD. Recent studies link both birth asphyxia (BA) and febrile seizures (FS) separately to higher ASD prevalence. However, investigations into the interplay of BA and FS and its relationship with ASD are yet to be conducted. The present study mainly focuses on exploring the interactive effect between BA and FS in the context of ASD. Methods Utilizing a multi-stage stratified cluster sampling, we initially recruited 84,934 Shanghai children aged 3–12 years old from June 2014 to June 2015, ultimately including 74,251 post-exclusion criteria. A logistic regression model was conducted to estimate the interaction effect after controlling for pertinent covariates. The attributable proportion (AP), the relative excess risk due to interaction (RERI), the synergy index (SI), and multiplicative-scale interaction were computed to determine the interaction effect. Results Among a total of 74,251 children, 192 (0.26%) were diagnosed with ASD. The adjusted odds ratio for ASD in children with BA alone was 3.82 (95% confidence interval [CI] 2.42–6.02), for FS alone 3.06 (95%CI 1.48–6.31), and for comorbid BA and FS 21.18 (95%CI 9.10–49.30), versus children without BA or FS. The additive interaction between BA and FS showed statistical significance (P < 0.001), whereas the multiplicative interaction was statistically insignificant (P > 0.05). Limitations This study can only demonstrate the relationship between the interaction of BA and FS with ASD but cannot prove causation. Animal brain experimentation is necessary to unravel its neural mechanisms. A larger sample size, ongoing monitoring, and detailed FS classification are needed for confirming BA-FS interaction in ASD. Conclusion In this extensive cross-sectional study, both BA and FS were significantly linked to ASD. The coexistence of these factors was associated with an additive increase in ASD prevalence, surpassing the cumulative risk of each individual factor.

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Neurodevelopmental problems in children with febrile seizures followed to young school age: A prospective longitudinal community‐based study in Sweden

Cited by 5 publications

References 23 publications

Multivariate models for the prediction of febrile seizure risk and recurrence: a prospective case-control study

Multivariate models for the prediction of febrile seizure risk and recurrence: a prospective case-control study

Multivariate linear mixture models for the prediction of febrile seizure risk and recurrence: a prospective case–control study

Additive interaction between birth asphyxia and febrile seizures on autism spectrum disorder: a population-based study

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