Using the Norwegian Mother and Child Cohort Study to determine risk factors for delayed development and neuropsychiatric

Abstract

Introduction: Antiepileptic drug (AED) teratogenicity is suspected to be the main cause of impaired development in children of women with epilepsy. However, many factors may confound the reported risks. The purpose of this review is to characterize the epilepsy cohort in the Norwegian Mother and Child Cohort Study (MoBa) and show how it can be used to detangle various risk factors for adverse outcome in children of mothers with epilepsy. Methods: MoBa is a large, long-term prospective, family-based cohort study. The database is linked to the Medical Birth Registry of Norway. The epilepsy cohort consists of mothers and their children representing more than 700 pregnancies. Blood samples were obtained from the mother during pregnancy and from the umbilical cord after delivery, and AED concentrations were measured. Validated screening tools determined the frequency of maternal confounding risk factors and adverse offspring outcomes. Risk estimates were reported as adjusted odds ratios with confidence intervals using the remaining MoBa cohort as a reference (n=107,597). Outcome in offspring of women with epilepsy without AED treatment in pregnancy and of fathers with epilepsy were used to separate the effect of epilepsy from the effect of in utero exposure to AEDs. Results: Socioeconomic and psychiatric risk factors for adverse offspring outcomes were more frequent in mothers with epilepsy. The frequency of adverse offspring outcome was increased at 6, 18 and 36 months for verbal, motor and social development. Children of women with epilepsy without AED treatment and of fathers with epilepsy were generally similar to children of women without epilepsy. Conclusion: Children of mothers with epilepsy are at risk of adverse outcomes. AED exposure emerges as the most important risk factor.

Overweight in epilepsy as a risk factor for pregnancy and delivery complications

“…The participation rate of 41% at first assessment is as expected for population-based studies. 10,11 There was no significant difference in the prevalence estimates of epilepsy in the MoBa cohort and the total population. However, this is not expected to influence or bias effect measures.…”

The treatment of epilepsy in pregnancy: The neurodevelopmental risks associated with exposure to antiepileptic drugs

“…Longitudinal studies following the children from birth are limited to just a few studies (33,34,36,37,48,49,51,84,88) but provide critical and in depth information about the neurodevelopment of children exposed to AEDs. Thus the area has evolved however more research is needed and a lack of evidence of risk to neurodevelopment should not be taken as evidence of safety.…”

“…5075ETS 14 few such investigations. A further line of investigation is when the father has epilepsy and there has been a failure to find an increased rate of neurodevelopment difficulties for children born to fathers with epilepsy (83,84). An association between child verbal IQ levels and exposure to seizures was reported by a UK retrospective study (47) and in the study by Shallcross and colleagues (57), however, this finding has not been supported by the majority of prospective studies (33,35,48,49,72) or Pregnancy Register based studies (40,42).…”

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

“…Antiepileptic drug use and plasma AED concentrations Information on type of AED use during the pregnancy was obtained from Q1 and Q2, and from MBRN data [13]. Plasma concentrations of valproate, lamotrigine, carbamazepine, oxcarbazepine monohydroxyderivative metabolite, levetiracetam and topiramate were analysed in 226 maternal blood samples (gestational week [17][18][19] and 198 umbilical cord samples for altogether 254 AEDexposed children (73%) [14,16]. The reported AED was detected in samples from 237 of the 254 children (93%) (Appendix S1: Methods S1).…”