Pregnancy, Infant, Newborn, Humans, Female, Cohort Studies, *Population Surveillance, Isotretinoin -- ADVERSE EFFECTS -- ADMINISTRATION & DOSAGE, Maternal Exposure -- ADVERSE EFFECTS, Abortion, Spontaneous -- CHEMICALLY INDUCED, and Abnormalities, Drug-Induced -- ETIOLOGY
Background: Although isotretinoin has been on the market formore than 20 years, no population-based data exists on the incidence of pregnancy and birth defects while on the drug. Given the fact that women decide to terminate pregnancies based on the available data, such estimates are needed. Objectives: (1) Estimate the population-based incidence rates of pregnancy and birth defects associated with isotretinoin use, and (2) determine predictors of becoming pregnant while on isotretinoin. The impact of the Pregnancy Prevention Program (PPP-1988) was also studied. Methods: Using the RAMQ (medical and Rx data), MEDECHO (hospitalisations) and ISQ (births/deaths) databases for 1984�2002, a cohort of 8609 women between 13�45 years of age and with a first prescription of isotretinoin (date of entry in the cohort: DE) was identified. Women were eligible if they had no Rx for isotretinoin in the year prior to their DE and were insured by RAMQ for their Rx at least 12 months before DE and until the end of their isotretinoin treatment. Descriptive statistics and multivariate logistic regression models were used to determine predictors of pregnancy while on the drug. Time series modelling was used to determine trends in pregnancy rates over time. Results: Of the 8609 women included, 90 became pregnant (32.7/1000 person-year of treatment (95%CI: 26.6, 40.1)); no significant effect of the PPP was detected. Of the 90 women who became pregnant while on the drug, 76 terminated the pregnancy (84%), 3 had a miscarriage (4%), 2 had trauma during delivery resulting in neonatal deaths (2%), and 9 had a live born (10%). Among the live births, only 1 had a congenital anomaly of the face and neck (11%), the remaining had no birth defects. Adjusting for maternal age, OC use, place of residence, being treated by a dermatologist, and health care utilisation before DE, predictors of becoming pregnant while on isotretinoin were lower socioeconomic level (welfare recipients (yes/no) RR: 1.93, 95%CI: 1.03, 3.61), >=1-MD visits while on isotretinoin treatment (other than for acne, RR: 9.51, 95%CI: 5.06, 17.80), >=1 emergency department visit while on treatment (RR: 2.44, 95%CI: 1.28, 4.66), and 1 hospitalisations while on treatment (RR: 32.0, 95%CI: 17.5, 58.6); taking other medications (other than isotretinoin and OC) had a preventive effect (RR: 0.36, 95%CI: 0.21, 0.62). Conclusions: Although this first non-interventional study generated incidence rates of pregnancy while on isotretinoin four times greater than what is available in the literature thus far, the incidence of birth defects was 2/3 smaller.