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Research paper
Emilia-Romagna Study on Pregnancy and Exposure to Antiepileptic drugs (ESPEA): a population-based study on prescription patterns, pregnancy outcomes and fetal health
  1. Barbara Mostacci1,
  2. Francesca Bisulli1,2,
  3. Elisabetta Poluzzi3,
  4. Guido Cocchi3,4,
  5. Carlo Piccinni3,
  6. Alessandra Curti3,5,
  7. Giuliana Simonazzi3,5,
  8. Gianni Astolfi6,
  9. Nicola Rizzo3,5,
  10. Corrado Zenesini1,
  11. Roberto D’Alessandro1,
  12. Paolo Tinuper1,2
  13. and the ESPEA Study Group
    1. 1 Institute of Neurological Sciences of Bologna, Bologna, Italy
    2. 2 Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy
    3. 3 Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
    4. 4 Division of Neonatology, Sant’Orsola Malpighi Hospital, Bologna, Italy
    5. 5 Division of Prenatal Medicine, Sant’Orsola Malpighi Hospital, Bologna, Italy
    6. 6 IMER Registry (Emila Romagna Registry of Birth Defects)- Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Ferrara, Italy
    1. Correspondence to Dr Barbara Mostacci, IRCCS Institute of Neurological Sciences of Bologna, Bologna, 40124, Italy; bmostacci{at}gmail.com

    Abstract

    Objectives To assess the prevalence of antiepileptic drug (AED) exposure in pregnant women and the comparative risk of terminations of pregnancy (TOPs), spontaneous abortions, stillbirths, major birth defects (MBDs), neonatal distress and small for gestational age (SGA) infants following intrauterine AED exposure in the Emilia Romagna region, Italy (4 459 246 inhabitants on 31 December 2011).

    Methods We identified all deliveries and hospitalised abortions in Emilia Romagna in the period 2009–2011 from the certificate of delivery assistance registry (Certificato di Assistenza al Parto— CedAP) and the hospital discharge card registry, exposure to AEDs from the reimbursed drug prescription registries, MBDs from the regional registry of congenital malformations, and Apgar scores and cases of SGA from the CedAP. Records from different registries were linked.

    Results We identified 145 243 pregnancies: 111 284 deliveries, 16 408 spontaneous abortions and 17 551 TOPs. Six hundred and eleven pregnancies (0.42%; 95% Cl 0.39 to 0.46) were exposed to AEDs. In the AED-exposed group 21% of pregnancies ended in TOPs vs 12% in the non-exposed women (OR: 2.24; 95% CI 1.41 to 3.56). Rates of spontaneous abortions, stillbirths, neonatal distress and SGA were comparable. Three hundred and fifty-three babies (0.31%; 95% CI 0.28 to 0.35) were exposed to AEDs during the first trimester. MBD rates were 2.3% in the exposed vs 2.0% in the non-exposed pregnancies (OR: 1.12, 95% CI 0.55 to 2.55).

    Conclusion The Emilia Romagna prevalence of AED exposure in pregnancy was 0.42%, comparable with previous European studies. Rates of spontaneous abortions, stillbirths, neonatal distress, SGA and MBDs following AED exposure were not significantly increased. The rate of TOPs was significantly higher in the AED-exposed women.

    • epilepsy,anticonvulsants
    • clinical neurology
    • pharmacology
    • neuropharmacology

    This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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    Footnotes

    • Contributors BM contributed to the conception and design of the study, drafted the study protocol, coordinated the collection and analysis of data, and drafted the paper. FB contributed to the conception and design of the study and to the writing of the study protocol. EP contributed to the design and writing of the study protocol, and to the analysis of data on prescriptions. GC contributed to the writing of the study protocol and analysed data on fetal adverse outcomes. CP contributed to the analysis of data on prescriptions and to the database construction. AC and GS contributed to the analysis of data on abortions. GA linked data from the registries of birth defects to the other regional registries. NR contributed to the writing of the study protocol and to the analysis of data on abortions. CZ contributed to the statistical analysis. RDA contributed to the conception and design of the study, to the writing of the study protocol, and monitored the study methods and the statistical analysis. PT contributed to the conception, design and writing of the study protocol, coordinated the study group. All authors contributed to the interpretation of the results, revised the text of this article and approved it.

    • Funding This study was funded by the Italian Ministry of Health (RF 2010-2315893).

    • Competing interests BM and FB received a personal fee for an advisory board from EISAI.

    • Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.

    • Ethics approval Local ethical committee (AUSL of Bologna) and Hospital Management Executive.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Collaborators Gabriele Accetta (IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy), Gianni Astolfi (IMER Registry - Department of Biomedical and Specialty Surgical Sciences, University ofFerrara, Ferrara, Italy), Cosimo Ippazio Antonazzo(Department of Medical and Surgical Sciences DIMEC, University of Bologna, Bologna, Italy) Sergio Battaglia (Regione Emilia Romagna, SISePS, Italy), Francesca Bisulli (IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy; Department of Biomedical and Neuromotor Sciences DIBINEM, University of Bologna, Bologna, Italy), Guido Cocchi, Letizia Conti (Department of Medical and Surgical Sciences DIMEC, Division of Neonatology, St Orsola Malpighi Hospital, University of Bologna, Bologna, Italy), Alessandra Curti (Department of Medical and Surgical Sciences DIMEC, Division of Prenatal Medicine, St Orsola Malpighi Hospital, University of Bologna, Bologna, Italy), Roberto D’Alessandro (IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy), Laura Licchetta (IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy; Department of Biomedical and Neuromotor Sciences DIBINEM, University of Bologna, Bologna, Italy), Camilla Lupi (Regione Emilia Romagna, SISePS, Italy), Barbara Mostacci (IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy), Ilaria Naldi, Carlo Piccinni, Elisabetta Poluzzi (Department of Medical and Surgical Sciences DIMEC, University of Bologna, Bologna, Italy), Nicola Rizzo, Giuliana Simonazzi (Department of Medical and Surgical Sciences DIMEC, Division of Prenatal Medicine, St Orsola Malpighi Hospital, University of Bologna, Bologna, Italy), Paolo Tinuper (IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy; Department of Biomedical and Neuromotor Sciences DIBINEM, University of Bologna, Bologna, Italy), Corrado Zenesini (IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy).

    • Author note This work was part of BM’s PhD thesis in specialised medical sciences at Alma Mater Studiorum-University of Bologna.

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