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

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.

Prenatal methylmercury exposure and language delay at three years of age in the Norwegian Mother and Child Cohort Study.

Prenatal methylmercury (MeHg) exposure and its possible neurodevelopmental effects in susceptible children are of concern. Studies of MeHg exposure and negative health outcomes have shown conflicting results and it has been suggested that co-exposure to other contaminants and/or nutrients in fish may confound the effect of MeHg. Our objective was to examine the association between prenatal exposure to MeHg and language and communication development at three years, adjusting for intake of fish, n-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs) and co-exposure to dioxins and dioxin like polychlorinated biphenyls (dl-PCBs). We used data from the Norwegian Mother and Child Cohort Study (MoBa) collected between 2002 and 2008. The study sample consisted of 46,750 mother-child pairs. MeHg exposure was calculated from reported fish intake during pregnancy by a FFQ in mid-pregnancy. Children's language and communication skills were measured by maternal report on the Dale and Bishop grammar rating and the Ages and Stages communication scale (ASQ). We estimated odds ratios (OR) and 95% confidence intervals (CI) using logistic regressions. Median MeHg exposure was 1.3µg/day, corresponding to 0.14µg/kgbw/week. An exposure level above the 90th percentile (>2.6µg/day, >0.29µg/kgbw/week) was defined as the high MeHg exposure. Results indicated an association between high MeHg exposure and unintelligible speech with an adjusted OR 2.22 (1.31, 3.72). High MeHg exposure was also associated with weaker communication skills adjusted OR 1.33 (1.03, 1.70). Additional adjustment for fish intake strengthened the associations, while adjusting for PCBs and n-3 LCPUFA from diet or from supplements had minor impact. In conclusion, significant associations were found between prenatal MeHg exposure above the 90th percentile and delayed language and communication skills in a generally low exposed population.

Valproic acid: long-term effects on children exposed in utero.

(1) Numerous follow-up studies of pregnancies in women with epilepsy show that valproic acid is more teratogenic than other antiepileptics. The risk of malformations increases with doses above 1000 mg/day; (2) Malformations associated with valproic acid include neural tube defects in 1-2% of exposed children, as well as urogenital, craniofacial and digital abnormalities. Cardiac disorders and limb defects have also been reported; (3) Convergent results of several cohort studies show that exposure to valproic acid in utero has detrimental effects on intelligence, language and behavior, which appear in school-age children; (4) In practice, the use of valproic acid should be avoided throughout pregnancy, as well as by women of childbearing age not using effective contraception. If a woman is planning pregnancy, the choice of valproic acid should be reassessed with the patient. If valproic acid therapy is maintained, the minimum effective daily dose should be determined and folic acid supplementation initiated.

The impact of maternal smoking on fast auditory brainstem responses.

Deficits in auditory processing have been posited as one of the underlying neurodevelopmental consequences of maternal smoking during pregnancy that leads to later language and reading deficits. Fast auditory brainstem responses were used to assess differences in the sensory processing of auditory stimuli among infants with varying degrees of prenatal cigarette exposure. Maternal report of consumption of cigarettes and blood samples were collected in the hospital to assess exposure levels and participants were then seen at 6-months. To participate in the study, all infants had to pass the newborn hearing exam or a clinically administered ABR and have no known health problems. After controlling for participant age, maternal smoking during pregnancy was negatively related to latency of auditory brainstem responses. Of several potential covariates, only perinatal complications and maternal alcohol use were also related to latency of the ABR responses and maternal smoking level accounted for significant unique variance after controlling for these factors. These results suggest that the relationship between maternal smoking may lead to disruption in the sensory encoding of auditory stimuli.