General maternal medication use, folic acid, the MDR1 C3435T polymorphism, and the risk of a child with a congenital heart defect

Sylvia A Obermann-Borst*, Aaron Isaacs, Zobia Younes, Ron H N van Schaik, Ilse P van der Heiden, Cornelia M van Duyn, Eric A P Steegers, Régine P M Steegers-Theunissen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


OBJECTIVE: We sought to investigate maternal and child functional MDR1 C3435T polymorphism, periconception medication, folic acid use, and the risk of a congenital heart defect (CHD) in the offspring.

STUDY DESIGN: MDR1 3435C>T genotyping was performed in 283 case triads (mother, father, child) and 308 control triads. Information on periconception medication and folic acid use was obtained through questionnaires.

RESULTS: Mothers with MDR1 3435CT/TT genotype and using medication showed a significant association with the risk of a child with CHD (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.3-4.3) compared to mothers with MDR1 3435CC genotype not using medication. This risk increased without folic acid use (OR, 2.8; 95% CI, 1.2-6.4), and decreased in folic acid users (OR, 1.7; 95% CI, 0.8-3.7). Children carrying the MDR1 3435CT/TT genotype and periconceptionally exposed to medication without folic acid did not show significant risks.

CONCLUSION: Mothers carrying the MDR1 3435T allele, using medication without folic acid, are at nearly 3-fold increased risk for CHD in the offspring.

Original languageEnglish
Pages (from-to)236.e1-8
JournalAmerican Journal of Obstetrics and Gynecology
Issue number3
Publication statusPublished - Mar 2011
Externally publishedYes


  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics
  • Adult
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Folic Acid/therapeutic use
  • Genetic Predisposition to Disease
  • Heart Defects, Congenital/etiology
  • Humans
  • Infant
  • Maternal Exposure
  • Polymorphism, Genetic
  • Pregnancy
  • Prenatal Exposure Delayed Effects/etiology
  • Risk Factors
  • Surveys and Questionnaires
  • Vitamin B Complex/therapeutic use

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