isotretinoin and Fetal-Death

Rosacea fulminans (RF) is a rare facial dermatosis characterized by the sudden onset of severe facial inflammation consisting of numerous pustules, cystic swellings and coalescing sinuses. The standard treatment is the retinoid drug isotretinoin in combination with systemic corticosteroids or with high-dose oral tetracycline antibiotics. We report three recent cases of RF in pregnancy with differing obstetric outcomes: an intrauterine death, a termination of pregnancy, and a normal vaginal delivery. The pathogenesis of RF is considered and therapeutic options in pregnancy are reviewed.

Topics: Abortion, Induced; Acne Vulgaris; Adult; Anti-Bacterial Agents; Dermatologic Agents; Diabetes, Gestational; Drug Therapy, Combination; Erythromycin; Facial Dermatoses; Female; Fetal Death; Glucocorticoids; Humans; Isotretinoin; Oligohydramnios; Prednisolone; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Rosacea; Treatment Outcome

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.. Population-based study.. The Netherlands.. A cohort of 203,962 pregnancies with onset between 1 January 1999 and 1 September 2007 consisting of 208,161 fetuses or neonates.. 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.. 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.. 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.

Topics: Abnormalities, Drug-Induced; Adult; Dermatologic Agents; Female; Fetal Death; Humans; Infant, Newborn; Isotretinoin; Netherlands; Pregnancy; Young Adult

Retinoic acid, an analogue of vitamin A, is known to be teratogenic in laboratory animals and has recently been implicated in a few clinical case reports. To study the human teratogenicity of this agent, we investigated 154 human pregnancies with fetal exposure to isotretinoin, a retinoid prescribed for severe recalcitrant cystic acne. The outcomes were 95 elective abortions, 26 infants without major malformations, 12 spontaneous abortions, and 21 malformed infants. A subset of 36 of the 154 pregnancies was observed prospectively. The outcomes in this cohort were 8 spontaneous abortions, 23 normal infants, and 5 malformed infants. Exposure to isotretinoin was associated with an unusually high relative risk for a group of selected major malformations (relative risk = 25.6; 95 per cent confidence interval, 11.4 to 57.5). Among the 21 malformed infants we found a characteristic pattern of malformation involving craniofacial, cardiac, thymic, and central nervous system structures. The malformations included microtia/anotia (15 infants), micrognathia (6), cleft palate (3), conotruncal heart defects and aortic-arch abnormalities (8), thymic defects (7), retinal or optic-nerve abnormalities (4), and central nervous system malformations (18). The pattern of malformation closely resembled that produced in animal studies of retinoid teratogenesis. It is possible that a major mechanism of isotretinoin teratogenesis is a deleterious effect on cephalic neural-crest cell activity that results in the observed craniofacial, cardiac, and thymic malformations.

Topics: Abnormalities, Drug-Induced; Abortion, Spontaneous; Acne Vulgaris; Adolescent; Adult; Female; Fetal Death; Heart Defects, Congenital; Humans; Infant, Newborn; Isotretinoin; Male; Pregnancy; Pregnancy Trimester, First; Prospective Studies; Retrospective Studies; Risk; Tretinoin