Reduced brain volumes in children of women with epilepsy: A neuropsychological and voxel based morphometric analysis in pre-adolescent children

Sreedharan, Ruma Madhu; Raghavan, Subharekha; Anila, K.M.; Kesavadas, Chandrasekharan; Thomas, Sanjeev V

doi:10.1016/j.neurad.2018.02.005

Cited by 7 publications

(6 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our findings suggest a possible long-term AED-associated effect on language abilities in offspring after foetal AED exposure. Reduced total brain volume and grey matter volume compared to healthy children have been reported in valproate-exposed children aged 10 years with low IQ and language dysfunction [25]. Similarly, adults aged 23 years with antenatal exposure to mainly valproate, carbamazepine, phenytoin or primidone in monotherapy or polytherapy had reduced grey matter volume compared to healthy controls, and particularly in the left hemisphere controlling language [26].…”

Section: But Othermentioning

confidence: 88%

Language impairment in children aged 5 and 8 years after antiepileptic drug exposure in utero – the Norwegian Mother and Child Cohort Study

Husebye

Gilhus

Spigset

et al. 2019

Euro J of Neurology

View full text Add to dashboard Cite

Background and purpose The purpose was to examine the consequences of antiepileptic drug (AED) exposure during pregnancy on language abilities in children aged 5 and 8 years of mothers with epilepsy. Methods The study population included children of mothers with and without epilepsy enrolled in the Norwegian Mother and Child Cohort Study 1999–2008. Mothers prospectively provided information on epilepsy diagnosis, AED use during pregnancy and the child’s language abilities at age 5 and 8 years, in questionnaires with validated language screening tools. AED concentrations in gestation week 17–19 and in the umbilical cord were measured. Results The study population included 346 AED‐exposed and 388 AED‐unexposed children of mothers with epilepsy, and 113 674 children of mothers without epilepsy. Mothers of 117 and 121 AED‐exposed children responded to the questionnaires at age 5 and 8 years, respectively. For AED‐exposed children, the adjusted odds ratio for language impairment was 1.6 [confidence interval (CI) 1.1–2.5, P = 0.03] at age 5 years and 2.0 (CI 1.4–3.0, P < 0.001) at age 8 years, compared to children of mothers without epilepsy. Children exposed to carbamazepine monotherapy had a significantly increased risk of language impairment compared to control children at age 8 years (adjusted odds ratio 3.8, CI 1.6–9.0, P = 0.002). Higher maternal valproate concentrations correlated with language impairment at age 5 years. Periconceptional folic acid supplement use protected against AED‐associated language impairment. Conclusion Foetal AED exposure in utero is associated with an increased risk of language impairment in children aged 5 and 8 years of mothers with epilepsy. Periconceptional folic acid use had a protective effect on AED‐associated language impairment.

show abstract

Section: But Othermentioning

confidence: 88%

Language impairment in children aged 5 and 8 years after antiepileptic drug exposure in utero – the Norwegian Mother and Child Cohort Study

Husebye

Gilhus

Spigset

et al. 2019

Euro J of Neurology

View full text Add to dashboard Cite

show abstract

“…[179]20184patients18.9660.00reportedFSIQWASI: voc, mr820.30Sreedharan et al . [180]20184patients10.8066.00reportedFSIQWISC (Malayalam translation)300.00Takeuchi et al . [181]20184healthy20.8058.00reportedFSIQTanaka B Intelligence Scale13190.07Tozer et al .…”

Section: Methodsmentioning

confidence: 99%

Of differing methods, disputed estimates and discordant interpretations: the meta-analytical multiverse of brain volume and IQ associations

et al. 2022

View full text Add to dashboard Cite

Brain size and IQ are positively correlated. However, multiple meta-analyses have led to considerable differences in summary effect estimations, thus failing to provide a plausible effect estimate. Here we aim at resolving this issue by providing the largest meta-analysis and systematic review so far of the brain volume and IQ association (86 studies; 454 effect sizes from k = 194 independent samples; N = 26 000+) in three cognitive ability domains (full-scale, verbal, performance IQ). By means of competing meta-analytical approaches as well as combinatorial and specification curve analyses, we show that most reasonable estimates for the brain size and IQ link yield r -values in the mid-0.20s, with the most extreme specifications yielding r s of 0.10 and 0.37. Summary effects appeared to be somewhat inflated due to selective reporting, and cross-temporally decreasing effect sizes indicated a confounding decline effect, with three quarters of the summary effect estimations according to any reasonable specification not exceeding r = 0.26, thus contrasting effect sizes were observed in some prior related, but individual, meta-analytical specifications. Brain size and IQ associations yielded r = 0.24, with the strongest effects observed for more g -loaded tests and in healthy samples that generalize across participant sex and age bands.

show abstract

“…The persistence of language deficit in the second decade of life as observed in our study raises the possibility of an enduring anatomical or functional disturbance in these children. A voxel‐based morphometric study from our group reported earlier that children with intrauterine exposure to AEDs and impaired language functions have reduced total brain volume and gray matter volume when compared to healthy children 31 . Furthermore, children with intrauterine exposure to AEDs and impaired language functions can have an abnormal functional network connectivity, particularly involving language‐related areas of the brain 32 .…”

Section: Discussionmentioning

confidence: 96%

“…A voxel-based morphometric study from our group reported earlier that children with intrauterine exposure to AEDs and impaired language functions have reduced total brain volume and gray matter volume when compared to healthy children. 31 Furthermore, children with intrauterine exposure to AEDs and impaired language functions can have an abnormal functional network connectivity, particularly involving language-related areas of the brain. 32 The reduced gray matter volume in adults with language dysfunction and history of exposure to AEDs in utero may be attributable to premature neuronal loss.…”

Section: How Does Our Data Fit In With the Broad Neurobiology Of Lamentioning

confidence: 99%

Enduring language deficits in children of women with epilepsy and the potential role of intrauterine exposure to antiepileptic drugs

Unnikrishnan¹,

Jacob²,

Salim³

et al. 2020

Epilepsia

View full text Add to dashboard Cite

Objective: Exposure to certain intrauterine antiepileptic drugs (AEDs) can negatively influence the language skills and intelligence of young children. It remains unanswered whether these deficits are transient or persist as children grow up. This study aims to evaluate the language function of children of women with epilepsy (CWE) aged 9-13 years in comparison with their peers, and its relationship with intrauterine AED exposure. Methods: We included 191 CWE in our study from the Kerala Registry of Epilepsy and Pregnancy. Children in the same age group (n = 144) and without maternal epilepsy or antenatal AED exposure served as controls. We used Clinical Examination for Language Function version IV to assess language in both groups. Relevant data related to maternal epilepsy and AED use were obtained from the registry records. Results: The average Core Language Scaled Score (CLSS) was significantly lower in CWE as compared to controls (83.19 vs 90.18, P = .001). Similarly, the mean scaled scores in other language parameters were also significantly lower in CWE. In the multivariate analysis, compared to control children, the average CLSS in CWE was 4.5 units lower (95% confidence interval [CI] = −8.8 to −0.2, P = .04) with AED monotherapy exposure and 7.3 units lower with exposure to AED polytherapy (95% CI = −13.8 to −0.8, P = .03). Intrauterine exposure to phenobarbitone (n = 61) and valproate (n = 55) as either monotherapy or polytherapy showed a negative effect on CLSS in CWE as compared to control children. However, carbamazepine (n = 75) and phenytoin (n = 37) use was not associated with significant variation of CLSS. In head-to-head comparisons between AED monotherapies in CWE, phenobarbitone showed a negative effect on CLSS (−14.7, 95% CI = −23.1 to −6.4, P = .001) as compared to carbamazepine. Significance: Intrauterine exposure to phenobarbitone and valproate impairs language development in CWE, with effects persisting into the second decade.

show abstract

Reduced brain volumes in children of women with epilepsy: A neuropsychological and voxel based morphometric analysis in pre-adolescent children

Cited by 7 publications

References 22 publications

Language impairment in children aged 5 and 8 years after antiepileptic drug exposure in utero – the Norwegian Mother and Child Cohort Study

Language impairment in children aged 5 and 8 years after antiepileptic drug exposure in utero – the Norwegian Mother and Child Cohort Study

Of differing methods, disputed estimates and discordant interpretations: the meta-analytical multiverse of brain volume and IQ associations

Enduring language deficits in children of women with epilepsy and the potential role of intrauterine exposure to antiepileptic drugs

Contact Info

Product

Resources

About