2026-04-17T04:17:42Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/120322025-10-24T10:29:16Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Onken, Marlies author Lohse, Lukas author Coulm, Bénédicte author Beghin, Delphine author Richardson, Jonathan author BERMEJO-SANCHEZ, EVA author Bosch Ferrer, Montserrat author Aguilera, Cristina author 2024-10-08T06:18:35Z 2024-10-08T06:18:35Z 2024-11 Modafinil; Fetal development; Teratology Modafinilo; Desarrollo fetal; Teratología Modafinil; Desenvolupament fetal; Teratologia Objective In recent years, safety concerns about modafinil exposure during pregnancy have emerged. In particular, increased risks for major congenital anomalies (MCA) and impaired fetal growth were reported, although study results were conflicting. Our investigation aims to examine previously reported safety signals. Method Multicenter case series based on data from 18 Teratology Information Services from 12 countries. Modafinil exposed pregnancies with an estimated date of birth before August 2019 were included in this study. For prospectively ascertained pregnancies, cumulative incidences of pregnancy outcomes, rate of nonchromosomal MCA in first trimester exposed pregnancies and percentiles of neonatal/infant weight and head circumference (HC) were calculated. Potential dose-dependent effects on fetal growth were explored by linear regression models. Retrospectively ascertained cases were screened for pattern of MCA and other adverse events. Results One hundred and seventy-five prospectively ascertained cases were included, of which 173 were exposed at least during the first trimester. Cumulative incidences for live birth, spontaneous abortion and elective termination of pregnancy were 76.9% (95% CI, 68.0%–84.8%), 9.3% (95% CI, 5.0%–16.9%), and 13.9% (95% CI, 8.1%–23.1%), respectively. Nonchromosomal MCA was present in 3/150 live births, corresponding to an MCA rate of 2.0% (95%CI, 0.6%–6.1%), none were reported in pregnancy losses. Compared to reference standards, birth weight (BW) tended to be lower and neonatal HC to be smaller in exposed newborns (data available for 144 and 73 of 153 live births, respectively). In nonadjusted linear regression models, each 100 mg increase of average dosage per pregnancy day was associated with a decrease in standard deviation score (SDS) of −0.28 SDS (95% CI, −0.45 to −0.10) for BW and of −0.28 SDS (95% CI, −0.56 to 0.01) for HC. Screening of 22 retrospectively reported cases did not reveal any specific pattern of MCA or other adverse outcomes. Conclusion The results do not indicate an increased risk of MCA after in utero exposure to modafinil, but a tendency toward lower BW and reduced neonatal HC. However, these findings should be regarded as preliminary. Until further studies allow for a definite conclusion, modafinil should not be used during pregnancy. The Berlin Embryotox Center of Clinical Teratology and Drug Safety in Pregnancy is financially supported by the German Federal Institute for Drugs and Medical Devices (BfArM); included German study cases were obtained from the Embryotox cohort. The UK Teratology Information Service is funded by the UK Health Security Agency. The Dutch Teratology Information Service is funded by the Ministerie van Volksgezondheid, Welzijn en Sport Research Unit on Congenital Anomalies-UIAC & Spanish Teratology Information Services SITTE and SITE are financially supported by Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, of Spain. http://hdl.handle.net/11351/12032 Embaràs Malalties congènites Fetus - Trastorns del creixement Neurofarmacologia Medicaments - Efectes secundaris DISEASES::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Congenital Abnormalities PHENOMENA AND PROCESSES::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproduction::Pregnancy PHENOMENA AND PROCESSES::Physiological Phenomena::Growth and Development CHEMICALS AND DRUGS::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Benzhydryl Compounds::Modafinil Other subheadings::Other subheadings::Other subheadings::/adverse effects ENFERMEDADES::enfermedades y anomalías neonatales congénitas y hereditarias::anomalías congénitas FENÓMENOS Y PROCESOS::fenómenos fisiológicos reproductivos y urinarios::fenómenos fisiológicos de la reproducción::reproducción::embarazo FENÓMENOS Y PROCESOS::fenómenos fisiológicos::crecimiento y desarrollo COMPUESTOS QUÍMICOS Y DROGAS::compuestos orgánicos::hidrocarburos::hidrocarburos cíclicos::hidrocarburos aromáticos::derivados del benceno::compuestos de bencidrilo::modafinilo Otros calificadores::Otros calificadores::Otros calificadores::/efectos adversos Effects of maternal modafinil treatment on fetal development and neonatal growth parameters — a multicenter case series of the European Network of Teratology Information Services (ENTIS)