Prenatal fever and autism risk.

Some studies suggest that prenatal infection increases risk of autism spectrum disorders (ASDs). This study was undertaken in a prospective cohort in Norway to examine whether we could find evidence to support an association of the prenatal occurrence of fever, a common manifestation of infection, with ASD risk. Prospective questionnaires provided maternal exposure data; case status was established from clinical assessments and registry linkages. In a large, prospectively ascertained cohort of pregnant mothers and their offspring, we examined infants born ⩾32 weeks for associations between fever exposure in each trimester and ASD risk using logistic regression. Maternal exposure to second-trimester fever was associated with increased ASD risk, adjusting for presence of fever in other trimesters and confounders (adjusted odds ratio (aOR), 1.40; 95% confidence interval, 1.09-1.79), with a similar, but nonsignificant, point estimate in the first trimester. Risk increased markedly with exposure to three or more fever episodes after 12 weeks' gestation (aOR, 3.12; 1.28-7.63). ASD risk appears to increase with maternal fever, particularly in the second trimester. Risk magnified dose dependently with exposure to multiple fevers after 12 weeks' gestation. Our findings support a role for gestational maternal infection and innate immune responses to infection in the pathogenesis of at least some cases of ASD.

Co-occurring development of early childhood communication and motor skills: results from a population-based longitudinal study.

BACKGROUND: Communicative and motor development is frequently found to be associated. In the current study we investigate to what extent communication and motor skills at 1½ years predict skills in the same domains at 3 years of age. METHODS: This study is based on the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Heath. Data stem from 62,944 children and their mothers. Mothers completed questionnaires on their child's communication and motor skills at ages 1½ and 3. Associations between communication and motor skills were estimated in a cross-lagged model with latent variables. RESULTS: Early communication skills were correlated with early motor skills (0.72). Stability was high (0.81) across time points for motor skills and somewhat lower (0.40) for communication skills. Early motor skills predicted later communication skills (0.38) whereas early communication skills negatively predicted later motor skills (-0.14). CONCLUSION: Our findings provide support for the hypothesis that these two difficulties are not symptoms of separate disorders, but might rather be different manifestations of a common underlying neurodevelopmental weakness. However, there also seem to be specific developmental pathways for each domain. Besides theoretical interest, more knowledge about the relationship between these early skills might shed light upon early intervention strategies and preventive efforts commonly used with children with problems in these areas. Our findings suggest that the relationship between language and motor skills is not likely to be simple and directional but rather to be complex and multifaceted.

The Autism Birth Cohort: a paradigm for gene-environment-timing research.

The reported prevalence of autism spectrum disorders (ASDs) has increased by 5- to 10-fold over the past 20 years. Whether ASDs are truly more frequent is controversial; nonetheless, the burden is profound in human and economic terms. Although autism is among the most heritable of mental disorders, its pathogenesis remains obscure. Environmental factors are proposed; however, none is implicated. Furthermore, there are no biomarkers to screen for ASD or risk of ASD. The Autism Birth Cohort (ABC) was initiated to analyze gene x environment x timing interactions and enable early diagnosis. It uses a large, unselected birth cohort in which cases are prospectively ascertained through population screening. Samples collected serially through pregnancy and childhood include parental blood, maternal urine, cord blood, milk teeth and rectal swabs. More than 107,000 children are continuously screened through questionnaires, referral, and a national registry. Cases are compared with a control group from the same cohort in a 'nested case-control' design. Early screening and diagnostic assessments and re-assessments are designed to provide a rich view of longitudinal trajectory. Genetic, proteomic, immunologic, metagenomic and microbiological tools will be used to exploit unique biological samples. The ABC is a paradigm for analyzing the role of genetic and environmental factors in complex disorders.

Maternal dietary exposure to dioxins and polychlorinated biphenyls (PCBs) is associated with language delay in 3year old Norwegian children.

BACKGROUND: Prenatal exposure to dioxins and PCBs is potentially harmful to the developing fetus and may increase the risk of delayed or impaired neurodevelopment. Several studies have reported negative associations between prenatal exposure to these compounds and aspects of cognition related to language in early childhood. OBJECTIVES: The aim was to examine the association between maternal low level dietary exposure to dioxins and PCB during pregnancy and language development in 3year old children in a large group of mother-child pairs participating in the Norwegian Mother and Child Cohort Study (MoBa). METHODS: This study includes 44,092 children of women who were recruited to the Norwegian Mother and Child Cohort Study (MoBa) during the years 2002-2009. Maternal dietary exposure to dioxins and PCBs was estimated based on a validated food frequency questionnaire (FFQ) answered mid-pregnancy and a database of dioxin and PCB concentrations in Norwegian foods. Exposure to dioxins and dioxin-like PCBs (dl-compounds) was expressed in total toxic equivalents (TEQ), and PCB-153 was used as marker for non-dioxin-like PCBs (ndlPCBs). Children's language skills at age 3 were assessed by parental report including a Dale and Bishop grammar rating and questions about communication skills from the Ages and Stages Questionnaire (ASQ). Logistic regression models adjusted for confounders were used to examine the association between maternal dietary exposure to dl-compounds or PCB-153 and language development in children. RESULTS: The maternal dietary exposure to dl-compounds and PCB-153 was generally low, and 98% of women had intakes of dl-compounds ≤14pg TEQ/kg bw/week, which is the tolerable weekly intake set by EU's Scientific Committee for Food (SCF). High maternal exposure (>14pg TEQ/kg bw/week of dl-compounds (median 2.6pg/kg bw/day, range 2-16) or >97.5-percentile intake of PCB-153 (median 11ng/kg bw/day, range 5-28) was associated with higher odds of incomplete grammar (in boys and girls, adjusted ORs 1.1 to 1.3) and severe language delay in girls, adjusted ORs 2.8 [95% CI 1.1, 7.1] for PCB-153 and 2.9 [95% CI 1.4, 5.9] for dl-compounds. Furthermore, high exposure to dl-compounds was associated with moderate language delay 1.4 [95% CI 1.0, 2.0] and lower communication score (ASQ), adjusted OR 1.4 [95% CI 1.1, 1.9] in girls. CONCLUSIONS: The main findings of this study were: 1) Girls born to mothers who exceeded the tolerable weekly intake for dl-compounds or had a PCB-153 intake above the 97.5 percentile in early pregnancy may have increased risk of language delay at age 3years. 2) Negative associations with maternal exposure to dl-compounds or PCB-153 were observed for both boys and girls having incomplete grammar, which is a subtle reduction in language skills. This interesting finding should not be considered as deviant at this age.