Correspondence

Cognitive Function after Fetal Exposure to Antiepileptic Drugs

N Engl J Med 2009; 361:629-630August 6, 2009

Article

To the Editor:

Meador et al. (April 16 issue)1 suggest that children who had been exposed to valproate in utero had significantly lower IQ scores than those who had been exposed to other antiepileptic drugs. However, the results of their study should be interpreted with caution. Many factors have a role in the neuropsychological development of children, apart from fetal exposure to antiepileptic drugs. We are not given details of the quality of the home environment, which has been recognized as a key environmental influence on child development.2 The Home Screening Questionnaire (HSQ) is a widely used tool to assess the qualities of the home environment that may influence the development of children,3 such as emotional and verbal responses of the mother and avoidance of restriction and punishment.

Although the study by Meador and colleagues included detailed monitoring of multiple potential confounding factors relating to child IQ, the HSQ may be helpful for obtaining more detailed and appropriate assessments of and conclusions about the children at the age of 6 years.

Yong-Hong Liu, M.D., Ph.D.
Xijing Hospital, Xi'an, China

Lian Wang, M.D., Ph.D.
Kunming General Hospital, Kunming, China

Yuan-Gui Huang, M.D.
Xijing Hospital, Xi'an, China
lianwang@fmmu.edu.cn

3 References

1. 1

   Meador KJ, Baker GA, Browning N, et al. Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs. N Engl J Med 2009;360:1597-1605
   Full Text | Web of Science | Medline

2. 2

   Zhou SJ, Baghurst P, Gibson RA, Makrides M. Home environment, not duration of breast-feeding, predicts intelligence quotient of children at four years. Nutrition 2007;23:236-241
   CrossRef | Web of Science | Medline

3. 3

   Frankenburg WK, Coons CE. Home Screening Questionnaire: its validity in assessing home environment. J Pediatr 1986;108:624-626
   CrossRef | Web of Science | Medline

Author/Editor Response

Liu et al. suggest that the results of our recent study should be interpreted with caution because of the lack of details on the home environment. In fact, we assessed home environment at 1 year of age using the Home Observation for Measurement of the Environment (HOME) scale, an established instrument with good psychometric properties.1-3 HOME results were not included, because most children in the United Kingdom were older than 1 year of age by the time of the merger with the U.S. study. Mean (±SD) scores on the HOME scale among the 187 children who underwent this assessment were: carbamazepine, 39.7±5.3; lamotrigine, 42.1±2.9; phenytoin, 39.6±4.2; and valproate, 40.1±4.0. HOME scale scores have a range of 0 to 45, with a higher score indicating a better home environment. When added to the statistical model that includes maternal IQ, drug group, dose, maternal age, gestational age, and folate, the score on the HOME scale was not a significant predictor of child IQ in this subgroup (P=0.55). The addition of HOME results (whether analyzed as imputed data for intention-to-treat analyses or completer data only, or categorized according to quartiles) does not change our conclusion about associations between maternal valproate use and childhood IQ.

Kimford J. Meador, M.D.
Emory University, Atlanta, GA
kimford.meador@emory.edu

Nancy Browning, Ph.D.
EMMES Corporation, Rockville, MD

David W. Loring, Ph.D.
Emory University, Atlanta, GA

3 References

1. 1

   Bradley RH, Caldwell BM. Home Observation for Measurement of the Environment: a validation study of screening efficiency. Am J Ment Defic 1977;81:417-420
   Medline

2. 2

   Bradley RH, Mundfrom DJ, Whiteside L, Casey PH, Barrett K. A factor analytic study of the infant-toddler and early childhood versions of the HOME Inventory administered to white, black, and Hispanic American parents of children born preterm. Child Dev 1994;65:880-888
   CrossRef | Web of Science | Medline

3. 3

   Bradley RH. The Home Inventory: review and reflections. Adv Child Dev Behav 1994;25:241-288
   CrossRef | Web of Science | Medline

Citing Articles (2)

Citing Articles

1. 1

   NAGHME ADAB, MICHAEL F O'DONOGHUE. (2010) ANTI-EPILEPTIC DRUGS AND BRAIN AND BEHAVIOURAL DEVELOPMENT IN ANIMAL MODELS AND HUMANS. Fetal and Maternal Medicine Review1-24
   CrossRef

2. 2

   (2010) Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiology and Drug Safety 19:2, i-xii
   CrossRef