Context-Prenatal folic acid supplements reduce the risk of neural tube defects and may have beneficial effects on other aspects of neurodevelopment.Objective-To examine associations between mothers' use of prenatal folic acid supplements and risk of severe language delay in their children at age 3 years. Online-Only Material: The 9 eTables and eFigure are available at http://www.jama.com.Additional Contributions: Caroline Relton, PhD (Institute of Genetic Medicine, Newcastle University), provided critical comments to the manuscript and Eivind Ystrøm, PhD (Department of Adult Mental Health, Norwegian Institute of Public Health), provided assistance with the breastfeeding data. Neither received any compensation from a funding sponsor for their contributions. The donations of questionnaire data and biological material from MoBa participants are gratefully acknowledged. We thank investigators at Columbia University, the National Institute of Neurological Disorders and Stroke, and the Norwegian Institute of Public Health for access to data from the Autism Birth Cohort Study (NS-U01NS047537).
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Methods
Study PopulationMoBa is a prospective pregnancy cohort that has been described in detail elsewhere. 10 Pregnant women from Norway were recruited to the study through a postal invitation in connection with the routine ultrasound examination offered to all pregnant women at their local hospital around gestational week17.During the period of recruitment between 1999 and December 2008, 108 841 pregnant women enrolled in the study, with a participation rate of 38.5% (http://www.fhi.no/moba-en). Written informed consent was obtained from each participant and the study was approved by the Regional Committee for Medical Research and the Norwegian Data Inspectorate.The data collection during pregnancy and at birth included self-report questionnaires and biological samples from the mother, father, and child. Follow-up after birth is ongoing and designed to be long term. Up to age 3 years, follow-up included questionnaires periodically sent to mothers for the entire sample. We used the quality ensured Data Version 5 released by MoBa in 2010. Included in this study were 44 220 children born before 2008 for whom the age 3 years questionnaire had been returned by the mother by June 16, 2010, and
Measure of Severe Language DelayThe present analysis of age 3 years outcomes focuses on severe language delay. Although a rare outcome, it has clinical significance and is associated with a range of neurodevelopmental disorders. 11 In a corollary analysis, we also examined moderate language delay at age 3 years, an outcome that is less readily interpretable, because many children with moderate language delay will later catch up with their peers. 12On a language grammar rating scale 13 in the age 3 years questionnaire, the mother was asked to choose 1 of 6 categories, ranging from no word production to full sentences with complete grammatical markings. Children whose mothers reported minimal expressive language (only ...