Isotretinoin exposure during pregnancy: a population-based study in The Netherlands.
OBJECTIVE
To estimate isotretinoin exposure in Dutch pregnant women despite the implemented pregnancy prevention programme (PPP) and second, to analyse the occurrence of adverse fetal or neonatal outcomes in these isotretinoin exposed pregnancies.


METHODS
Population-based study.


METHODS
The Netherlands.


METHODS
A cohort of 203,962 pregnancies with onset between 1 January 1999 and 1 September 2007 consisting of 208,161 fetuses or neonates.


METHODS
Isotretinoin exposure in the 30 days before or during pregnancy. Proportions of adverse fetal or neonatal outcomes, defined as intrauterine deaths ≥16 week of gestation and neonates with major congenital anomalies. ORs with 95% CIs adjusted for maternal age were calculated to estimate the risk of adverse fetal or neonatal outcome after maternal isotretinoin exposure.


RESULTS
51 pregnancies, 2.5 (95% CI 1.9 to 3.3) per 10,000 pregnancies, were exposed to isotretinoin despite the pregnancy prevention programme. Forty-five of these pregnancies, 2.2 (95% CI 1.6 to 2.9) per 10,000 pregnancies, were exposed to isotretinoin during pregnancy and six additional women became pregnant within 30 days after isotretinoin discontinuation. In 60% of isotretinoin exposed pregnancies, women started isotretinoin while already pregnant. In five out of the 51 isotretinoin exposed pregnancies (53 fetuses), 9.4% (95% CI 1.3% to 17.6%), had an adverse fetal or neonatal outcome. The OR for adverse fetal or neonatal outcomes after isotretinoin exposure in 30 days before or during pregnancy was 2.3 (95% CI 0.9 to 5.7) after adjustment for maternal age.


CONCLUSIONS
Although a PPP was already implemented in 1988, we showed that isotretinoin exposed pregnancies and adverse fetal and neonatal events potentially related to the exposure still occur. These findings from the Netherlands add to the evidence that there is no full compliance to the isotretinoin PPP in many Western countries. Given the limited success of iPLEDGE, the question is which further measures are able to improve compliance.
Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands Department of pharmacovigilance, Dutch Medicines Evaluation Board, Utrecht, The Netherlands.
Ingeborg M
IM
Zomerdijk
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands Department of Internal Medicine, Groene Hart Hospital, Gouda, The Netherlands.
Rikje
R
Ruiter
PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands.
Leanne M A
LM
Houweling
PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands.
Ron M C
RM
Herings
Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Miriam C J M
MC
Sturkenboom
Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands Department of pharmacovigilance, Dutch Medicines Evaluation Board, Utrecht, The Netherlands.
Sabine M J M
SM
Straus
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands Drug Safety Unit, Inspectorate of Health Care, The Hague, The Netherlands.
Bruno H
BH
Stricker
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000328:Adult; D003879:Dermatologic Agents / Q000009:adverse effects*; D005260:Female; D005313:Fetal Death / Q000209:etiology*; D006801:Humans; D007231:Infant, Newborn; D015474:Isotretinoin / Q000009:adverse effects*; D009426:Netherlands; D011247:Pregnancy; D055815:Young Adult
D003879:Dermatologic Agents; D015474:Isotretinoin
EPIDEMIOLOGY; isotretinoin; pregnancy prevention programme