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Pregnancy outcome after intrauterine exposure to triptans
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Abstracts / Reproductive Toxicology 57 (2015) 210–227
in reassuring women who were inadvertently exposed to topical retinoids during their pregnancy. However, it does not have the statistical power to justify the use of topical retinoids during the pregnancy. http://dx.doi.org/10.1016/j.reprotox.2015.06.007 Pregnancy outcome after intrauterine exposure to triptans Svetlana Shechtman 1 , Olga Tkach Brayman 2 , Orna Diav-Citrin 1,3 , Asher Ornoy 1,3 1 The Israeli Teratology Information Service Jerusalem, Israel Ministry of Health, Israel 2 The Division of Clinical Pharmacy, Israel 3 The Hebrew University Hadassah Medical School, Jerusalem, Israel
Introduction: Migraine is a common, chronic, multifactorial neurovascular disorder. The lifetime prevalence of migraine in women is 16–32%. The burden of migraine is highest in women of reproductive age. The main purpose of the present study was to prospectively evaluate the rate of major anomalies after pregnancy exposure to new triptans with relatively limited human data compared to disease matched (sumatriptan-exposed) and non-teratogenic exposures comparison groups (NTC). Secondary endpoints were pregnancy loss, gestational age at delivery, and birth weight. Methods: Pregnancies of women, who consulted the Israeli TIS during the years 2005–2011 in regard to triptan or known nonteratogenic exposure in pregnancy, were prospectively followed up after the expected date of delivery. Results: Follow up data was collected on 169 pregnancies of women who used one of the new triptans drugs during gestation: 92 – eletriptan, 53 – rizatriptan, 23 – zolmitriptan, and 1 naratriptan. In 139 (82%) cases the exposure was at least during the first trimester. The sumatriptan group included 106 pregnancies with 1st trimester exposure. NTC consisted of 675 pregnant women. The rate of major congenital anomalies after 1st trimester exposure was similar in both newer triptan 9/129 (7.0%) and sumatriptan 6/84 (7.1%) groups but significantly higher than the NTC 17/656 (2.6%), p = 0.011. We further analyzed the rate of anomalies excluding genetic, cytogenetic and familial ones, and cardiovascular anomalies that spontaneously resolved in the first year, as well as anomalies not formed in the 1st trimester of pregnancy, or developmental problems diagnosed after 3 years from birth. No significant differences in the rate of congenital anomalies were observed [newer triptans – 2/129 (1.6%), sumatriptan – 4/84 (4.8%) vs. NTC – 12/656 (1.8%), p = 0.186]. The rate of miscarriages was similarly higher in both exposed groups compared to NTC after accounting for potential covariates (week at call, maternal age, history of miscarriages, smoking, and multiple pregnancies). Elective terminations of pregnancy were more frequent in the group exposed to newer triptans compared to the other groups. The gestational age at delivery, the rate of preterm deliveries, and birth weight did not significantly differ between the groups. Conclusions: The present study suggests that triptans, including newer medications, should not be considered major teratogens. However, further studies are still required to establish their pregnancy safety with special emphasis on the miscarriage risk. http://dx.doi.org/10.1016/j.reprotox.2015.06.008
First trimester use of second generation antipsychotics and major malformations Maria A. Ellfolk 1 , Anna-Maria Lahesmaa-Korpinen 2 , Heli Malm 1,3 , the Drugs and Pregnancy group 1 HUCH Teratology Information Service, HUCH Emergency Care, Helsinki, Finland 2 National Institute for health and Welfare (THL), Helsinki, Finland 3 Department of Clinical Pharmacology, Helsinki University and Helsinki University Central Hospital, Helsinki, Finland
Introduction: Second generation antipsychotics are used increasingly also during pregnancy, with 0.8% of pregnant women using them in Finland in 2012. Information on safety during pregnancy is limited. Objective: To determine if second generation antipsychotic use is associated with an increased risk of major congenital anomalies (MCA), taking into consideration maternal underlying illness. Design and setting: A prospective cohort study, based on national registers in Finland: the Medical Birth Register, the Register of Congenital Malformations, and the Drug Reimbursement Register. Participants: The total study population includes 937,543 women/offspring dyads (including all births and pregnancy terminations due to fetal major congenital anomaly, MCA) during January 1st 1996–December 31st 2011. Exposures: Prevalence of MCAs in offspring exposed to second generation antipsychotics in the first trimester (n = 1588) were compared to (i) offspring exposed only to first generation antipsychotics (n = 2298) and (ii) offspring unexposed to second and first generation antipsychotics, with five controls per each exposed, selected randomly and matched by year of pregnancy ending (Unexposed, n = 9570). Results: Compared to women with purchases of first generation antipsychotics, the rate of MCA was not increased (6.0% vs. 5.9%; crude OR 1.04, 95% CI 0.79–1.36) but was increased when compared to the Unexposed (6.0% vs. 4.2%; OR 1.48, 95% CI 1.18–1.87). Individual second generation antipsychotics were purchased as follows: clozapine, n = 77; olanzapine, n = 276; quetiapine, n = 986; risperidone, n = 176; and aripiprazole, n = 72. Olanzapine use was associated with an increased risk of MCA compared to offspring exposed to first generation antipsychotics (OR 1.60, 95% CI 1.02–2.49) and to Unexposed (OR 2.28, 95% CI 1.49–3.48). No increased risk was observed for any of the other second generation antipsychotics. Conclusions: Olanzapine use was associated with a marginally increased risk of MCA when controlling for maternal psychiatric disorder. Further adjusted analyses are needed to confirm this finding. http://dx.doi.org/10.1016/j.reprotox.2015.06.009
Abstracts / Reproductive Toxicology 57 (2015) 210–227
in reassuring women who were inadvertently exposed to topical retinoids during their pregnancy. However, it does not have the statistical power to justify the use of topical retinoids during the pregnancy. http://dx.doi.org/10.1016/j.reprotox.2015.06.007 Pregnancy outcome after intrauterine exposure to triptans Svetlana Shechtman 1 , Olga Tkach Brayman 2 , Orna Diav-Citrin 1,3 , Asher Ornoy 1,3 1 The Israeli Teratology Information Service Jerusalem, Israel Ministry of Health, Israel 2 The Division of Clinical Pharmacy, Israel 3 The Hebrew University Hadassah Medical School, Jerusalem, Israel
Introduction: Migraine is a common, chronic, multifactorial neurovascular disorder. The lifetime prevalence of migraine in women is 16–32%. The burden of migraine is highest in women of reproductive age. The main purpose of the present study was to prospectively evaluate the rate of major anomalies after pregnancy exposure to new triptans with relatively limited human data compared to disease matched (sumatriptan-exposed) and non-teratogenic exposures comparison groups (NTC). Secondary endpoints were pregnancy loss, gestational age at delivery, and birth weight. Methods: Pregnancies of women, who consulted the Israeli TIS during the years 2005–2011 in regard to triptan or known nonteratogenic exposure in pregnancy, were prospectively followed up after the expected date of delivery. Results: Follow up data was collected on 169 pregnancies of women who used one of the new triptans drugs during gestation: 92 – eletriptan, 53 – rizatriptan, 23 – zolmitriptan, and 1 naratriptan. In 139 (82%) cases the exposure was at least during the first trimester. The sumatriptan group included 106 pregnancies with 1st trimester exposure. NTC consisted of 675 pregnant women. The rate of major congenital anomalies after 1st trimester exposure was similar in both newer triptan 9/129 (7.0%) and sumatriptan 6/84 (7.1%) groups but significantly higher than the NTC 17/656 (2.6%), p = 0.011. We further analyzed the rate of anomalies excluding genetic, cytogenetic and familial ones, and cardiovascular anomalies that spontaneously resolved in the first year, as well as anomalies not formed in the 1st trimester of pregnancy, or developmental problems diagnosed after 3 years from birth. No significant differences in the rate of congenital anomalies were observed [newer triptans – 2/129 (1.6%), sumatriptan – 4/84 (4.8%) vs. NTC – 12/656 (1.8%), p = 0.186]. The rate of miscarriages was similarly higher in both exposed groups compared to NTC after accounting for potential covariates (week at call, maternal age, history of miscarriages, smoking, and multiple pregnancies). Elective terminations of pregnancy were more frequent in the group exposed to newer triptans compared to the other groups. The gestational age at delivery, the rate of preterm deliveries, and birth weight did not significantly differ between the groups. Conclusions: The present study suggests that triptans, including newer medications, should not be considered major teratogens. However, further studies are still required to establish their pregnancy safety with special emphasis on the miscarriage risk. http://dx.doi.org/10.1016/j.reprotox.2015.06.008
First trimester use of second generation antipsychotics and major malformations Maria A. Ellfolk 1 , Anna-Maria Lahesmaa-Korpinen 2 , Heli Malm 1,3 , the Drugs and Pregnancy group 1 HUCH Teratology Information Service, HUCH Emergency Care, Helsinki, Finland 2 National Institute for health and Welfare (THL), Helsinki, Finland 3 Department of Clinical Pharmacology, Helsinki University and Helsinki University Central Hospital, Helsinki, Finland
Introduction: Second generation antipsychotics are used increasingly also during pregnancy, with 0.8% of pregnant women using them in Finland in 2012. Information on safety during pregnancy is limited. Objective: To determine if second generation antipsychotic use is associated with an increased risk of major congenital anomalies (MCA), taking into consideration maternal underlying illness. Design and setting: A prospective cohort study, based on national registers in Finland: the Medical Birth Register, the Register of Congenital Malformations, and the Drug Reimbursement Register. Participants: The total study population includes 937,543 women/offspring dyads (including all births and pregnancy terminations due to fetal major congenital anomaly, MCA) during January 1st 1996–December 31st 2011. Exposures: Prevalence of MCAs in offspring exposed to second generation antipsychotics in the first trimester (n = 1588) were compared to (i) offspring exposed only to first generation antipsychotics (n = 2298) and (ii) offspring unexposed to second and first generation antipsychotics, with five controls per each exposed, selected randomly and matched by year of pregnancy ending (Unexposed, n = 9570). Results: Compared to women with purchases of first generation antipsychotics, the rate of MCA was not increased (6.0% vs. 5.9%; crude OR 1.04, 95% CI 0.79–1.36) but was increased when compared to the Unexposed (6.0% vs. 4.2%; OR 1.48, 95% CI 1.18–1.87). Individual second generation antipsychotics were purchased as follows: clozapine, n = 77; olanzapine, n = 276; quetiapine, n = 986; risperidone, n = 176; and aripiprazole, n = 72. Olanzapine use was associated with an increased risk of MCA compared to offspring exposed to first generation antipsychotics (OR 1.60, 95% CI 1.02–2.49) and to Unexposed (OR 2.28, 95% CI 1.49–3.48). No increased risk was observed for any of the other second generation antipsychotics. Conclusions: Olanzapine use was associated with a marginally increased risk of MCA when controlling for maternal psychiatric disorder. Further adjusted analyses are needed to confirm this finding. http://dx.doi.org/10.1016/j.reprotox.2015.06.009