Occurrence of pregnancy and pregnancy outcomes during isotretinoin therapy.
BACKGROUND
Isotretinoin, a teratogen, is widely used to treat cystic acne. Although the risks of pregnancy during isotretinoin therapy are well recognized, there are doubts about the level of adherence with the pregnancy prevention program in Canada. Our objective was to evaluate the effectiveness of the Canadian pregnancy prevention program in 4 provinces: British Columbia, Saskatchewan, Manitoba and Ontario.


METHODS
Using administrative data, we identified 4 historical cohorts of female users of isotretinoin (aged 12-48 yr) for the period 1996 to 2011. We defined pregnancy using International Statistical Classification of Diseases and billing codes. One definition included only cases with documented pregnancy outcomes (high-specificity definition); the other definition also included individuals recorded as receiving prenatal care (high-sensitivity definition). We studied new courses of isotretinoin and detected pregnancies in 2 time windows: during isotretinoin treatment only and up to 42 weeks after treatment. Live births were followed for 1 year to identify congenital malformations.


RESULTS
A total of 59 271 female patients received 102 308 courses of isotretinoin. Between 24.3% and 32.9% of participants received prescriptions for oral contraceptives while they were taking isotretinoin, compared with 28.3% to 35.9% in the 12 months before isotretinoin was started. According to the high-specificity definition of pregnancy, there were 186 pregnancies during isotretinoin treatment (3.1/1000 isotretinoin users), compared with 367 (6.2/1000 users) according to the high-sensitivity definition. By 42 weeks after treatment, there were 1473 pregnancies (24.9/1000 users), according to the high-specificity definition. Of these, 1331 (90.4%) terminated spontaneously or were terminated by medical intervention. Among the 118 live births were 11 (9.3%) cases of congenital malformation. Pregnancy rates during isotretinoin treatment remained constant between 1996 and 2011.


CONCLUSIONS
Adherence to the isotretinoin pregnancy prevention program in Canada was poor during the 15-year period of this study.
Institute for Clinical Evaluative Sciences (Henry, Lévesque, Paterson), Toronto, Ont.; Institute of Health Policy, Management and Evaluation (Henry), University of Toronto, Toronto, Ont.; Faculty of Medicine (Dormuth, Carney), University of British Columbia, Vancouver, BC; Saskatchewan Health Quality Council (Winquist, Teare), Saskatoon, Sask.; College of Pharmacy (Bugden), Faculty of Health Sciences, University of Manitoba, Winnipeg, Man.; Centre for Health Services and Policy Research (Lévesque), Queen's University, Kingston, Ont.; Faculté de pharmacie (Bérard), Université de Montréal, Montréal, Qué.; Department of Family Medicine (Paterson), McMaster University, Hamilton, Ont.; Departments of Epidemiology and Biostatistics and of Pediatrics (Platt), McGill University, Montréal, Que. david.henry@ices.on.ca.
David
D
Henry
Institute for Clinical Evaluative Sciences (Henry, Lévesque, Paterson), Toronto, Ont.; Institute of Health Policy, Management and Evaluation (Henry), University of Toronto, Toronto, Ont.; Faculty of Medicine (Dormuth, Carney), University of British Columbia, Vancouver, BC; Saskatchewan Health Quality Council (Winquist, Teare), Saskatoon, Sask.; College of Pharmacy (Bugden), Faculty of Health Sciences, University of Manitoba, Winnipeg, Man.; Centre for Health Services and Policy Research (Lévesque), Queen's University, Kingston, Ont.; Faculté de pharmacie (Bérard), Université de Montréal, Montréal, Qué.; Department of Family Medicine (Paterson), McMaster University, Hamilton, Ont.; Departments of Epidemiology and Biostatistics and of Pediatrics (Platt), McGill University, Montréal, Que.
Colin
C
Dormuth
Institute for Clinical Evaluative Sciences (Henry, Lévesque, Paterson), Toronto, Ont.; Institute of Health Policy, Management and Evaluation (Henry), University of Toronto, Toronto, Ont.; Faculty of Medicine (Dormuth, Carney), University of British Columbia, Vancouver, BC; Saskatchewan Health Quality Council (Winquist, Teare), Saskatoon, Sask.; College of Pharmacy (Bugden), Faculty of Health Sciences, University of Manitoba, Winnipeg, Man.; Centre for Health Services and Policy Research (Lévesque), Queen's University, Kingston, Ont.; Faculté de pharmacie (Bérard), Université de Montréal, Montréal, Qué.; Department of Family Medicine (Paterson), McMaster University, Hamilton, Ont.; Departments of Epidemiology and Biostatistics and of Pediatrics (Platt), McGill University, Montréal, Que.
Brandace
B
Winquist
Institute for Clinical Evaluative Sciences (Henry, Lévesque, Paterson), Toronto, Ont.; Institute of Health Policy, Management and Evaluation (Henry), University of Toronto, Toronto, Ont.; Faculty of Medicine (Dormuth, Carney), University of British Columbia, Vancouver, BC; Saskatchewan Health Quality Council (Winquist, Teare), Saskatoon, Sask.; College of Pharmacy (Bugden), Faculty of Health Sciences, University of Manitoba, Winnipeg, Man.; Centre for Health Services and Policy Research (Lévesque), Queen's University, Kingston, Ont.; Faculté de pharmacie (Bérard), Université de Montréal, Montréal, Qué.; Department of Family Medicine (Paterson), McMaster University, Hamilton, Ont.; Departments of Epidemiology and Biostatistics and of Pediatrics (Platt), McGill University, Montréal, Que.
Greg
G
Carney
Institute for Clinical Evaluative Sciences (Henry, Lévesque, Paterson), Toronto, Ont.; Institute of Health Policy, Management and Evaluation (Henry), University of Toronto, Toronto, Ont.; Faculty of Medicine (Dormuth, Carney), University of British Columbia, Vancouver, BC; Saskatchewan Health Quality Council (Winquist, Teare), Saskatoon, Sask.; College of Pharmacy (Bugden), Faculty of Health Sciences, University of Manitoba, Winnipeg, Man.; Centre for Health Services and Policy Research (Lévesque), Queen's University, Kingston, Ont.; Faculté de pharmacie (Bérard), Université de Montréal, Montréal, Qué.; Department of Family Medicine (Paterson), McMaster University, Hamilton, Ont.; Departments of Epidemiology and Biostatistics and of Pediatrics (Platt), McGill University, Montréal, Que.
Shawn
S
Bugden
Institute for Clinical Evaluative Sciences (Henry, Lévesque, Paterson), Toronto, Ont.; Institute of Health Policy, Management and Evaluation (Henry), University of Toronto, Toronto, Ont.; Faculty of Medicine (Dormuth, Carney), University of British Columbia, Vancouver, BC; Saskatchewan Health Quality Council (Winquist, Teare), Saskatoon, Sask.; College of Pharmacy (Bugden), Faculty of Health Sciences, University of Manitoba, Winnipeg, Man.; Centre for Health Services and Policy Research (Lévesque), Queen's University, Kingston, Ont.; Faculté de pharmacie (Bérard), Université de Montréal, Montréal, Qué.; Department of Family Medicine (Paterson), McMaster University, Hamilton, Ont.; Departments of Epidemiology and Biostatistics and of Pediatrics (Platt), McGill University, Montréal, Que.
Gary
G
Teare
Institute for Clinical Evaluative Sciences (Henry, Lévesque, Paterson), Toronto, Ont.; Institute of Health Policy, Management and Evaluation (Henry), University of Toronto, Toronto, Ont.; Faculty of Medicine (Dormuth, Carney), University of British Columbia, Vancouver, BC; Saskatchewan Health Quality Council (Winquist, Teare), Saskatoon, Sask.; College of Pharmacy (Bugden), Faculty of Health Sciences, University of Manitoba, Winnipeg, Man.; Centre for Health Services and Policy Research (Lévesque), Queen's University, Kingston, Ont.; Faculté de pharmacie (Bérard), Université de Montréal, Montréal, Qué.; Department of Family Medicine (Paterson), McMaster University, Hamilton, Ont.; Departments of Epidemiology and Biostatistics and of Pediatrics (Platt), McGill University, Montréal, Que.
Linda E
LE
Lévesque
Institute for Clinical Evaluative Sciences (Henry, Lévesque, Paterson), Toronto, Ont.; Institute of Health Policy, Management and Evaluation (Henry), University of Toronto, Toronto, Ont.; Faculty of Medicine (Dormuth, Carney), University of British Columbia, Vancouver, BC; Saskatchewan Health Quality Council (Winquist, Teare), Saskatoon, Sask.; College of Pharmacy (Bugden), Faculty of Health Sciences, University of Manitoba, Winnipeg, Man.; Centre for Health Services and Policy Research (Lévesque), Queen's University, Kingston, Ont.; Faculté de pharmacie (Bérard), Université de Montréal, Montréal, Qué.; Department of Family Medicine (Paterson), McMaster University, Hamilton, Ont.; Departments of Epidemiology and Biostatistics and of Pediatrics (Platt), McGill University, Montréal, Que.
Anick
A
Bérard
Institute for Clinical Evaluative Sciences (Henry, Lévesque, Paterson), Toronto, Ont.; Institute of Health Policy, Management and Evaluation (Henry), University of Toronto, Toronto, Ont.; Faculty of Medicine (Dormuth, Carney), University of British Columbia, Vancouver, BC; Saskatchewan Health Quality Council (Winquist, Teare), Saskatoon, Sask.; College of Pharmacy (Bugden), Faculty of Health Sciences, University of Manitoba, Winnipeg, Man.; Centre for Health Services and Policy Research (Lévesque), Queen's University, Kingston, Ont.; Faculté de pharmacie (Bérard), Université de Montréal, Montréal, Qué.; Department of Family Medicine (Paterson), McMaster University, Hamilton, Ont.; Departments of Epidemiology and Biostatistics and of Pediatrics (Platt), McGill University, Montréal, Que.
J Michael
JM
Paterson
Institute for Clinical Evaluative Sciences (Henry, Lévesque, Paterson), Toronto, Ont.; Institute of Health Policy, Management and Evaluation (Henry), University of Toronto, Toronto, Ont.; Faculty of Medicine (Dormuth, Carney), University of British Columbia, Vancouver, BC; Saskatchewan Health Quality Council (Winquist, Teare), Saskatoon, Sask.; College of Pharmacy (Bugden), Faculty of Health Sciences, University of Manitoba, Winnipeg, Man.; Centre for Health Services and Policy Research (Lévesque), Queen's University, Kingston, Ont.; Faculté de pharmacie (Bérard), Université de Montréal, Montréal, Qué.; Department of Family Medicine (Paterson), McMaster University, Hamilton, Ont.; Departments of Epidemiology and Biostatistics and of Pediatrics (Platt), McGill University, Montréal, Que.
Robert W
RW
Platt
D000014:Abnormalities, Drug-Induced / Q000453:epidemiology* / Q000517:prevention & control; D000152:Acne Vulgaris / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D002170:Canada; D002648:Child; D003267:Contraception / Q000706:statistics & numerical data*; D003879:Dermatologic Agents / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015474:Isotretinoin / Q000009:adverse effects*; D050498:Live Birth / Q000453:epidemiology; D008875:Middle Aged; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000453:epidemiology*; D012189:Retrospective Studies; D055815:Young Adult
D003879:Dermatologic Agents; D015474:Isotretinoin