Authors :
Presenting Author: Barbara Mostacci, MD, PhD – IRCCS Istituto delle Scienze Neurologiche di Bologna
Lidia Di Vito, MD, PhD – IRCCS Istituto delle Scienze Neurologiche di Bologna; laura Maria Beatrice Belotti, MSC – IRCCS Istituto delle Scienze Neurologiche di Bologna; Corrado Zenesini, MSC – IRCCS Istituto delle Scienze Neurologiche di Bologna; Elisabetta Poluzzi, MD, PhD – Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italia; Stefania Mazzoni, MSC – IRCCS Istituto delle Scienze Neurologiche di Bologna; Elisa Baldin, MD, PhD – IRCCS Istituto delle Scienze Neurologiche di Bologna; Elisa Ballardini, MD – Registro IMER (Registro Emilia Romagna dei Difetti Congeniti), Dipartimento di Scienze Mediche, Università di Ferrara, Ferrara, Italia; Amanda Julie Neville, MSC – Registro IMER (Registro Emilia Romagna dei Difetti Congeniti), Dipartimento di Scienze Mediche, Università di Ferrara, Ferrara, Italia; Paolo Tinuper, MD – Università di Bologna- Bologna, Italy; Francesca Bisulli, MD, PhD – IRCCS Istituto delle Scienze Neurologiche di Bologna
Rationale:
Most of the available knowledge on fetal risks due to intrauterine exposure to anti-seizure medications (ASMs) results from clinical registries with voluntary enrolment. A few population-based studies are available on the topic, most conducted in Northern Europe. With our population-based study, we aimed to assess the relative risk of fetal adverse events after intrauterine exposure to ASMs in the Emilia Romagna Region (ERR), Italy (approximately 4,400,000 inhabitants).
Methods:
We identified all deliveries and spontaneous abortions in ERR in the period 2010–2020. Exposure to ASMs during pregnancy, major congenital anomalies (MCAs) detected during the first year of life, Apgar scores, stillbirth, and cases of small for gestational age (SGA) were identified from regional registries covering all the residents. The presence of fetal distress or one or more of the aforementioned outcomes was considered a “composite adverse outcome” (CAO). Logistic regression models were used to evaluate the association between ASMs exposure and outcome. The OR were then adjusted for maternal age, other known teratogens, diabetes, hypertension, eclampsia and pre-eclampsia, genetic disorders, presumed fetal lesion from viral or other kind of maternal disease and multiple births.
Results:
We identified 359,136 deliveries (365,276 birth) and 55,982 spontaneous abortions. Exposure to ASMs concerned 0.42% of pregnancies (1716 birth/abortions), of whom 12% were exposed to polytherapy. Exposure to ASMs was associated with increased risk of spontaneous abortion (OR 1.36; 95%CI
1.20-1.54) and CAO (OR 1.24; 95%CI
1.11-1.38). Polytherapy increased these risks and was a risk factor for MCAs ( OR 2.18; 95%CI
1.07-4.48). Valproate (VPA), gabapentinoids, levetiracetam and zonisamide (ZNS) were associated with abortion. Clonazepam (CNZ), VPA, gabapentinoids and ZNS were associated with CAO. CNZ was associated with SGA. Carbamazepine was associated with MCAs (OR 2.32; 95%CI
1.32-4.05) and so was Lacosamide (OR 11.6; 95%CI
2.4-56.1).
Conclusions:
The prevalence of ASMs exposure in pregnancy in ERR was 0.42%, comparable with previous European studies. Exposure to ASMs was associated to increased risk of spontaneous abortion and composite adverse outcome. Carbamazepine and polytherapy were associated with increased risk of MCAs. Though lacosamide and zonisamide were associated with adverse outcomes, exposures are few, and caution is needed in interpreting the results.
Funding:
This project was funded by Fondazione LICE