First trimester exposure to paroxetine and risk of cardiac .... etc

[Guest guest]

Original Article

First trimester exposure to paroxetine and risk of cardiac

malformations in infants: the importance of dosage

http://www3.interscience.wiley.com/cgi-bin/abstract/113493580/ABSTRACT

Anick Bérard 1 2 *, Élodie Ramos 1 2, Évelyne Rey 2 3, Lucie Blais 1,

St.-André 4, Driss Oraichi 2

1Faculty of Pharmacy, University of Montreal, Montreal, Québec, Canada

2CHU Sainte-e, Research Center, Montreal, Québec, Canada

3Department of Obstetrics and Gynaecology, Faculty of Medicine,

University of Montreal, Montreal, Québec, Canada

4Department of Psychiatry, CHU Sainte-e, Montreal, Québec,

Canada

email: Anick Bérard (anick.berard@...)

*Correspondence to Anick Bérard, CHU Sainte-e, Research Center,

3175, Chemin de la Côte-Ste-, Montréal, Québec H3T 1C5

Funded by:

Les Fonds de la Recherche en Santé du Québec (FRSQ)

Le Réseau Québécois de Recherche sur l'Usage des Médicaments (RQRUM)

Le Réseau FRSQ for the Wellbeing of Children

Keywords

paroxetine • pregnancy • major congenital malformations • major

cardiac malformations • dosage • pregnancy registry

Abstract

BACKGROUND: Conflicting findings with regard to the teratogenic risks

of first trimester use of paroxetine have prompted the FDA, Health

Canada, and the manufacturer of the drug to issue warnings against

its use during pregnancy. Given that untreated depression during

pregnancy can lead to deleterious effect on the mother and her unborn

fetus, data on the relationship between the dose and the range of

malformations is warranted. This study attempts to quantify the

association between first trimester exposure to paroxetine and

congenital cardiac malformations, adjusting for possible confounders,

and to quantify the dose-response relationship between paroxetine use

and cardiac defects. METHODS: The Medication and Pregnancy registry

was used. This population-based registry was built by linking three

administrative databases (RAMQ, Med-Écho, and ISQ), and includes all

pregnancies in Quebec between 01/01/1997 and 06/30/2003. Date of

entry in the registry is the date of the first day of the last

menstrual period. To be eligible for this study, women had to: 1) be

15-45 years of age at entry; 2) be covered by the RAMQ drug plan 12

months before and during pregnancy; 3) be using only one type of

antidepressant during the first trimester; and 4) have a live birth.

Two nested case-control studies were carried out comparing the

prevalence of paroxetine use in the first trimester of pregnancy to

the prevalence of other antidepressant exposures during the same time

period. Cases were defined as: 1) any major malformations; or 2) any

cardiac malformations diagnosed in the first year of life; controls

were defined as no major or minor malformations. Multivariate

logistic regression techniques were used to analyze data. RESULTS:

Among the 1,403 women meeting inclusion criteria, 101 infants with

major congenital malformations were identified; 24 had cardiac

malformations. Adjusting for possible confounders, the use of

paroxetine (odds ratio [OR] = 1.38, 95% confidence interval [CI] =

0.49-3.92), and the use of other SSRIs (OR = 0.89, 95% CI = 0.28-

2.84) during the first trimester of pregnancy did not increase the

risk of congenital cardiac malformations compared with the use of non-

SSRI antidepressants. When considering the dose, however, a dose-

response relationship was observed, thus women exposed to >25 mg/day

of paroxetine during the first trimester of pregnancy were at

increased risk of having an infant with major congenital

malformations (adjusted [adj] OR = 2.23, 95% CI = 1.19, 4.17), or

major cardiac malformations (adj OR = 3.07, 95% CI = 1.00, 9.42).

CONCLUSIONS: Gestational exposure to paroxetine is associated with

major congenital malformations and major cardiac malformations for

only first trimester exposure above 25 mg/day. Birth Defects Res

(Part . © 2006 Wiley-Liss, Inc.

----------------------------------------------------------------------

----------

Received: 26 July 2006; Accepted: 12 October 2006

Digital Object Identifier (DOI)

10.1002/bdrb.20099 About DOI

[Guest guest]

Original Article

First trimester exposure to paroxetine and risk of cardiac

malformations in infants: the importance of dosage

http://www3.interscience.wiley.com/cgi-bin/abstract/113493580/ABSTRACT

Anick Bérard 1 2 *, Élodie Ramos 1 2, Évelyne Rey 2 3, Lucie Blais 1,

St.-André 4, Driss Oraichi 2

1Faculty of Pharmacy, University of Montreal, Montreal, Québec, Canada

2CHU Sainte-e, Research Center, Montreal, Québec, Canada

3Department of Obstetrics and Gynaecology, Faculty of Medicine,

University of Montreal, Montreal, Québec, Canada

4Department of Psychiatry, CHU Sainte-e, Montreal, Québec,

Canada

email: Anick Bérard (anick.berard@...)

*Correspondence to Anick Bérard, CHU Sainte-e, Research Center,

3175, Chemin de la Côte-Ste-, Montréal, Québec H3T 1C5

Funded by:

Les Fonds de la Recherche en Santé du Québec (FRSQ)

Le Réseau Québécois de Recherche sur l'Usage des Médicaments (RQRUM)

Le Réseau FRSQ for the Wellbeing of Children

Keywords

paroxetine • pregnancy • major congenital malformations • major

cardiac malformations • dosage • pregnancy registry

Abstract

BACKGROUND: Conflicting findings with regard to the teratogenic risks

of first trimester use of paroxetine have prompted the FDA, Health

Canada, and the manufacturer of the drug to issue warnings against

its use during pregnancy. Given that untreated depression during

pregnancy can lead to deleterious effect on the mother and her unborn

fetus, data on the relationship between the dose and the range of

malformations is warranted. This study attempts to quantify the

association between first trimester exposure to paroxetine and

congenital cardiac malformations, adjusting for possible confounders,

and to quantify the dose-response relationship between paroxetine use

and cardiac defects. METHODS: The Medication and Pregnancy registry

was used. This population-based registry was built by linking three

administrative databases (RAMQ, Med-Écho, and ISQ), and includes all

pregnancies in Quebec between 01/01/1997 and 06/30/2003. Date of

entry in the registry is the date of the first day of the last

menstrual period. To be eligible for this study, women had to: 1) be

15-45 years of age at entry; 2) be covered by the RAMQ drug plan 12

months before and during pregnancy; 3) be using only one type of

antidepressant during the first trimester; and 4) have a live birth.

Two nested case-control studies were carried out comparing the

prevalence of paroxetine use in the first trimester of pregnancy to

the prevalence of other antidepressant exposures during the same time

period. Cases were defined as: 1) any major malformations; or 2) any

cardiac malformations diagnosed in the first year of life; controls

were defined as no major or minor malformations. Multivariate

logistic regression techniques were used to analyze data. RESULTS:

Among the 1,403 women meeting inclusion criteria, 101 infants with

major congenital malformations were identified; 24 had cardiac

malformations. Adjusting for possible confounders, the use of

paroxetine (odds ratio [OR] = 1.38, 95% confidence interval [CI] =

0.49-3.92), and the use of other SSRIs (OR = 0.89, 95% CI = 0.28-

2.84) during the first trimester of pregnancy did not increase the

risk of congenital cardiac malformations compared with the use of non-

SSRI antidepressants. When considering the dose, however, a dose-

response relationship was observed, thus women exposed to >25 mg/day

of paroxetine during the first trimester of pregnancy were at

increased risk of having an infant with major congenital

malformations (adjusted [adj] OR = 2.23, 95% CI = 1.19, 4.17), or

major cardiac malformations (adj OR = 3.07, 95% CI = 1.00, 9.42).

CONCLUSIONS: Gestational exposure to paroxetine is associated with

major congenital malformations and major cardiac malformations for

only first trimester exposure above 25 mg/day. Birth Defects Res

(Part . © 2006 Wiley-Liss, Inc.

----------------------------------------------------------------------

----------

Received: 26 July 2006; Accepted: 12 October 2006

Digital Object Identifier (DOI)

10.1002/bdrb.20099 About DOI

[Guest guest]

Original Article

First trimester exposure to paroxetine and risk of cardiac

malformations in infants: the importance of dosage

http://www3.interscience.wiley.com/cgi-bin/abstract/113493580/ABSTRACT

Anick Bérard 1 2 *, Élodie Ramos 1 2, Évelyne Rey 2 3, Lucie Blais 1,

St.-André 4, Driss Oraichi 2

1Faculty of Pharmacy, University of Montreal, Montreal, Québec, Canada

2CHU Sainte-e, Research Center, Montreal, Québec, Canada

3Department of Obstetrics and Gynaecology, Faculty of Medicine,

University of Montreal, Montreal, Québec, Canada

4Department of Psychiatry, CHU Sainte-e, Montreal, Québec,

Canada

email: Anick Bérard (anick.berard@...)

*Correspondence to Anick Bérard, CHU Sainte-e, Research Center,

3175, Chemin de la Côte-Ste-, Montréal, Québec H3T 1C5

Funded by:

Les Fonds de la Recherche en Santé du Québec (FRSQ)

Le Réseau Québécois de Recherche sur l'Usage des Médicaments (RQRUM)

Le Réseau FRSQ for the Wellbeing of Children

Keywords

paroxetine • pregnancy • major congenital malformations • major

cardiac malformations • dosage • pregnancy registry

Abstract

BACKGROUND: Conflicting findings with regard to the teratogenic risks

of first trimester use of paroxetine have prompted the FDA, Health

Canada, and the manufacturer of the drug to issue warnings against

its use during pregnancy. Given that untreated depression during

pregnancy can lead to deleterious effect on the mother and her unborn

fetus, data on the relationship between the dose and the range of

malformations is warranted. This study attempts to quantify the

association between first trimester exposure to paroxetine and

congenital cardiac malformations, adjusting for possible confounders,

and to quantify the dose-response relationship between paroxetine use

and cardiac defects. METHODS: The Medication and Pregnancy registry

was used. This population-based registry was built by linking three

administrative databases (RAMQ, Med-Écho, and ISQ), and includes all

pregnancies in Quebec between 01/01/1997 and 06/30/2003. Date of

entry in the registry is the date of the first day of the last

menstrual period. To be eligible for this study, women had to: 1) be

15-45 years of age at entry; 2) be covered by the RAMQ drug plan 12

months before and during pregnancy; 3) be using only one type of

antidepressant during the first trimester; and 4) have a live birth.

Two nested case-control studies were carried out comparing the

prevalence of paroxetine use in the first trimester of pregnancy to

the prevalence of other antidepressant exposures during the same time

period. Cases were defined as: 1) any major malformations; or 2) any

cardiac malformations diagnosed in the first year of life; controls

were defined as no major or minor malformations. Multivariate

logistic regression techniques were used to analyze data. RESULTS:

Among the 1,403 women meeting inclusion criteria, 101 infants with

major congenital malformations were identified; 24 had cardiac

malformations. Adjusting for possible confounders, the use of

paroxetine (odds ratio [OR] = 1.38, 95% confidence interval [CI] =

0.49-3.92), and the use of other SSRIs (OR = 0.89, 95% CI = 0.28-

2.84) during the first trimester of pregnancy did not increase the

risk of congenital cardiac malformations compared with the use of non-

SSRI antidepressants. When considering the dose, however, a dose-

response relationship was observed, thus women exposed to >25 mg/day

of paroxetine during the first trimester of pregnancy were at

increased risk of having an infant with major congenital

malformations (adjusted [adj] OR = 2.23, 95% CI = 1.19, 4.17), or

major cardiac malformations (adj OR = 3.07, 95% CI = 1.00, 9.42).

CONCLUSIONS: Gestational exposure to paroxetine is associated with

major congenital malformations and major cardiac malformations for

only first trimester exposure above 25 mg/day. Birth Defects Res

(Part . © 2006 Wiley-Liss, Inc.

----------------------------------------------------------------------

----------

Received: 26 July 2006; Accepted: 12 October 2006

Digital Object Identifier (DOI)

10.1002/bdrb.20099 About DOI

[Guest guest]

Original Article

First trimester exposure to paroxetine and risk of cardiac

malformations in infants: the importance of dosage

http://www3.interscience.wiley.com/cgi-bin/abstract/113493580/ABSTRACT

Anick Bérard 1 2 *, Élodie Ramos 1 2, Évelyne Rey 2 3, Lucie Blais 1,

St.-André 4, Driss Oraichi 2

1Faculty of Pharmacy, University of Montreal, Montreal, Québec, Canada

2CHU Sainte-e, Research Center, Montreal, Québec, Canada

3Department of Obstetrics and Gynaecology, Faculty of Medicine,

University of Montreal, Montreal, Québec, Canada

4Department of Psychiatry, CHU Sainte-e, Montreal, Québec,

Canada

email: Anick Bérard (anick.berard@...)

*Correspondence to Anick Bérard, CHU Sainte-e, Research Center,

3175, Chemin de la Côte-Ste-, Montréal, Québec H3T 1C5

Funded by:

Les Fonds de la Recherche en Santé du Québec (FRSQ)

Le Réseau Québécois de Recherche sur l'Usage des Médicaments (RQRUM)

Le Réseau FRSQ for the Wellbeing of Children

Keywords

paroxetine • pregnancy • major congenital malformations • major

cardiac malformations • dosage • pregnancy registry

Abstract

BACKGROUND: Conflicting findings with regard to the teratogenic risks

of first trimester use of paroxetine have prompted the FDA, Health

Canada, and the manufacturer of the drug to issue warnings against

its use during pregnancy. Given that untreated depression during

pregnancy can lead to deleterious effect on the mother and her unborn

fetus, data on the relationship between the dose and the range of

malformations is warranted. This study attempts to quantify the

association between first trimester exposure to paroxetine and

congenital cardiac malformations, adjusting for possible confounders,

and to quantify the dose-response relationship between paroxetine use

and cardiac defects. METHODS: The Medication and Pregnancy registry

was used. This population-based registry was built by linking three

administrative databases (RAMQ, Med-Écho, and ISQ), and includes all

pregnancies in Quebec between 01/01/1997 and 06/30/2003. Date of

entry in the registry is the date of the first day of the last

menstrual period. To be eligible for this study, women had to: 1) be

15-45 years of age at entry; 2) be covered by the RAMQ drug plan 12

months before and during pregnancy; 3) be using only one type of

antidepressant during the first trimester; and 4) have a live birth.

Two nested case-control studies were carried out comparing the

prevalence of paroxetine use in the first trimester of pregnancy to

the prevalence of other antidepressant exposures during the same time

period. Cases were defined as: 1) any major malformations; or 2) any

cardiac malformations diagnosed in the first year of life; controls

were defined as no major or minor malformations. Multivariate

logistic regression techniques were used to analyze data. RESULTS:

Among the 1,403 women meeting inclusion criteria, 101 infants with

major congenital malformations were identified; 24 had cardiac

malformations. Adjusting for possible confounders, the use of

paroxetine (odds ratio [OR] = 1.38, 95% confidence interval [CI] =

0.49-3.92), and the use of other SSRIs (OR = 0.89, 95% CI = 0.28-

2.84) during the first trimester of pregnancy did not increase the

risk of congenital cardiac malformations compared with the use of non-

SSRI antidepressants. When considering the dose, however, a dose-

response relationship was observed, thus women exposed to >25 mg/day

of paroxetine during the first trimester of pregnancy were at

increased risk of having an infant with major congenital

malformations (adjusted [adj] OR = 2.23, 95% CI = 1.19, 4.17), or

major cardiac malformations (adj OR = 3.07, 95% CI = 1.00, 9.42).

CONCLUSIONS: Gestational exposure to paroxetine is associated with

major congenital malformations and major cardiac malformations for

only first trimester exposure above 25 mg/day. Birth Defects Res

(Part . © 2006 Wiley-Liss, Inc.

----------------------------------------------------------------------

----------

Received: 26 July 2006; Accepted: 12 October 2006

Digital Object Identifier (DOI)

10.1002/bdrb.20099 About DOI