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

doi:10.1016/j.ajog.2010.10.911

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 journal › Article › Academic › peer-review

Abstract

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 language	English
Pages (from-to)	236.e1-8
Journal	American Journal of Obstetrics and Gynecology
Volume	204
Issue number	3
DOIs	https://doi.org/10.1016/j.ajog.2010.10.911
Publication status	Published - Mar 2011
Externally published	Yes

Keywords

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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10.1016/j.ajog.2010.10.911

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Obermann-Borst, S. A., Isaacs, A., Younes, Z., van Schaik, R. H. N., van der Heiden, I. P., van Duyn, C. M., Steegers, E. A. P., & Steegers-Theunissen, R. P. M. (2011). General maternal medication use, folic acid, the MDR1 C3435T polymorphism, and the risk of a child with a congenital heart defect. American Journal of Obstetrics and Gynecology, 204(3), 236.e1-8. https://doi.org/10.1016/j.ajog.2010.10.911

@article{ea88786566d841c8beb86fdcc78b2211,

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

abstract = "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.",

keywords = "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",

author = "Obermann-Borst, {Sylvia A} and Aaron Isaacs and Zobia Younes and {van Schaik}, {Ron H N} and {van der Heiden}, {Ilse P} and {van Duyn}, {Cornelia M} and Steegers, {Eric A P} and Steegers-Theunissen, {R{\'e}gine P M}",

year = "2011",

month = mar,

doi = "10.1016/j.ajog.2010.10.911",

language = "English",

volume = "204",

pages = "236.e1--8",

journal = "American Journal of Obstetrics and Gynecology",

issn = "0002-9378",

publisher = "MOSBY-ELSEVIER",

number = "3",

}

Obermann-Borst, SA, Isaacs, A, Younes, Z, van Schaik, RHN, van der Heiden, IP, van Duyn, CM, Steegers, EAP & Steegers-Theunissen, RPM 2011, 'General maternal medication use, folic acid, the MDR1 C3435T polymorphism, and the risk of a child with a congenital heart defect', American Journal of Obstetrics and Gynecology, vol. 204, no. 3, pp. 236.e1-8. https://doi.org/10.1016/j.ajog.2010.10.911

TY - JOUR

T1 - General maternal medication use, folic acid, the MDR1 C3435T polymorphism, and the risk of a child with a congenital heart defect

AU - Obermann-Borst, Sylvia A

AU - Isaacs, Aaron

AU - Younes, Zobia

AU - van Schaik, Ron H N

AU - van der Heiden, Ilse P

AU - van Duyn, Cornelia M

AU - Steegers, Eric A P

AU - Steegers-Theunissen, Régine P M

PY - 2011/3

Y1 - 2011/3

N2 - 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.

AB - 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.

KW - ATP Binding Cassette Transporter, Subfamily B

KW - ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics

KW - Adult

KW - Drug-Related Side Effects and Adverse Reactions

KW - Female

KW - Folic Acid/therapeutic use

KW - Genetic Predisposition to Disease

KW - Heart Defects, Congenital/etiology

KW - Humans

KW - Infant

KW - Maternal Exposure

KW - Polymorphism, Genetic

KW - Pregnancy

KW - Prenatal Exposure Delayed Effects/etiology

KW - Risk Factors

KW - Surveys and Questionnaires

KW - Vitamin B Complex/therapeutic use

U2 - 10.1016/j.ajog.2010.10.911

DO - 10.1016/j.ajog.2010.10.911

M3 - Article

C2 - 21183151

SN - 0002-9378

VL - 204

SP - 236.e1-8

JO - American Journal of Obstetrics and Gynecology

JF - American Journal of Obstetrics and Gynecology

IS - 3

ER -

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

Abstract

Keywords

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