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Effects of maternal modafinil treatment on fetal development and neonatal growth parameters — a multicenter case series of the European Network of Teratology Information Services (ENITS)

Lookup NU author(s): Jonathon Richardson



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


© 2023 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.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.

Publication metadata

Author(s): Onken M, Lohse L, Coulm B, Beghin D, Richardson JL, Bermejo-Sanchez E, Aguilera C, Bosch M, Cassina M, Chouchana L, De Santis M, Duman MK, Goren MZ, Johnson D, Bera APJ, Kaplan YC, Kennedy D, Kwok S, Lacroix I, Lepelley M, Pistelli A, Schaefer C, Te Winkel B, Uysal N, Winterfeld U, Yakuwa N, Diav-Citrin O, Vial T, Dathe K

Publication type: Article

Publication status: Published

Journal: Acta Psychiatrica Scandinavica

Year: 2024

Pages: epub ahead of print

Online publication date: 18/12/2023

Acceptance date: 19/11/2023

Date deposited: 05/01/2024

ISSN (print): 0001-690X

ISSN (electronic): 1600-0447

Publisher: John Wiley and Sons Inc


DOI: 10.1111/acps.13643


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Funder referenceFunder name
German Federal Institute for Drugs and Medical Devices (BfArM)
Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación
Ministerie van Volksgezondheid, Welzijn en Sport
Projekt DEAL
UK Health Security Agency