Meta-analysis of Major Congenital Anomaly Outcomes Following Prenatal Exposure to Monotherapy Antiseizure Medications.
Abstract number :
2.448
Submission category :
4. Clinical Epilepsy / 4E. Women's Issues
Year :
2022
Submission ID :
2233006
Source :
www.aesnet.org
Presentation date :
12/4/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:29 AM
Authors :
Rebecca Bromley, PhD – University of Manchester; Naghme Adab, MD – Consultant Neurologist, Neurology, University Hospitals Coventry and Warwickshire NHS Trust, UK; Matthew Bluett-Duncan, PhD – Post Doctoral Research Associate, Division of Neuroscience, University of Manchester, Manchester, UK; Jakob Christensen, MD – Consultant Neurologist, Department of Neurology, Aarhus University Hospital, Aarhus, Denmark; Jill Clayton-Smith, MD – Consultant Clinical Geneticist, Manchester Rare Disease Centre, University of Manchester, Manchester, UK; Katherine Edwards, BSc – Systematic Reviewer, Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK; Janette Greenhalgh, PhD – Systematic Reviewer, Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK; Ruaraidh Hill, PhD – Lecturer, Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK; Cerian Jackson, DClinPsy – Department of Pharmacology and Therapeutics – University of Liverpool, Liverpool, UK; Sonia Khanom, PhD – Post Doctoral Research Associate, Division of Neuroscience, University of Manchester, Manchester, UK; Ronan McGinty, MD – Specialist Registrar, Department of Neurology, Walton Centre for Neurology and Neurosurgery; Catrin Tudur-Smith, PhD – Professor of Biostatistics, Department of Health Data Science, University of Liverpool, Liverpool, UK; Jennifer Weston, PhD – Information Scientist, Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK; Marson Anthony, MD – Professor of Neurology, Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK
This is a Late Breaking abstract
Rationale: A Cochrane systematic review was undertaken to investigate major congenital anomaly (MCA) outcomes following prenatal exposure to antiseizure medications (ASMs).
Methods: Searches were undertaken in MEDLINE (Ovid), EMBASE, and the Cochrane Central Register of Controlled Trials (May 2022). Predetermined inclusion criteria were defined by population, ASM type and control group. Both prospective cohort studies and studies using routine health record data were included. Data were analysed in RevManWeb using fixed effect risk-ratios. The evidence for lamotrigine (LTG) and levetiracetam (LEV) is presented here.
Results: Fifteen cohort studies and eight studies using routine health record data were identified to include pregnancies exposed to LTG, with eleven cohort studies and one routine health record data study identified for LEV. There was no significant difference in MCA risk between LEV or LTG exposure from either cohort study data (n=1223 vs. 4389, RR 0.97, 95% CI 0.58 to 1.63, p=0.91) or routine health record studies (n=130 vs. 1235, RR 1.01, 95% CI 0.41 to 2.50, p=0.98). The MCA risk was significantly higher for exposure to carbamazepine (CBZ) in comparison to LTG from cohort studies (n=4018 vs. 4550, RR 1.37, 95% CI 1.06 to 1.77, p=0.02), but not from routine health record studies (n=1755 vs. 1906, RR 1.31, 95% CI 0.91 to 1.88, p=0.14). The MCA risk was significantly higher for CBZ exposure in comparison to LEV exposure from cohort studies (n=3814 vs. 1242, RR 1.51, 95% CI 1.01 to 2.26, p=0.04), with data from routine health record studies limited to one study (n=315 vs. 130, RR 1.73, 95% CI 0.67 to 4.50, p=0.26). Exposure to LTG had a lower MCA risk in comparison to topiramate (TPM) in cohort study data (n=4275 vs 505, RR 0.59, 95% CI 0.36 to 0.96, p=0.03), but data was limited for routine health record studies. The MCA risk was not significantly different for LEV exposure in comparison to TPM exposure (n=1124 vs. 505, RR 0.57, 95% CI 0.32 to 1.04, p=0.07). However, both LTG and LEV exposures were associated with lower rates of skeletal and limb anomalies in comparison to TPM exposure. There was no significant difference between the MCA risk for LTG exposure in comparison to oxcarbazepine (OXC) for cohort study data (n=2208 vs. 333, RR 0.73, 95% CI 0.33 to 1.62, p=0.44) or routine health record studies (n=1325 vs. 320, RR 1.16, 95% CI 0.61 to 2.23, p= 0.65). Similarly, there was no significant difference between LEV exposure in comparison to OXC exposure for cohort studies (n=833 vs. 333, RR 1.04, 95% CI 0.51 to 2.09, p=0.92) or for routine health record studies (n=130 vs. 316, RR 1.22, 95% CI 0.42 to 3.49, p=0.72). Comparisons to other second or third generation ASMs were limited by available data.
Conclusions: Overall pooled data demonstrated that LTG and LEV exposure were associated with comparable MCA risks and tended to have a lower risk than CBZ and TPM exposures. Data were more limited in comparison to OXC exposure.
Funding: This review was supported by the National Institute for Health Research and Epilepsy Research UK.
Clinical Epilepsy