Antiseizure Medications in Pregnancy: What Every Clinician Needs to Know
Clinical Practice Update — Teratogenesis Risk, Neurodevelopmental Outcomes, and Safer Drug Selection for People with Epilepsy of Childbearing Potential
This is an original clinical education article informed by current guidelines and evidence. See References below for source documents.
- Clinical Focus
- Teratogenesis risk stratification, neurodevelopmental safety, drug selection, dose optimisation, and folic acid supplementation for antiseizure medications in pregnancy
- Target Audience
- Neurologists, obstetricians, maternal-fetal medicine specialists, primary care physicians, pharmacists, paediatric neurologists, residents
- Setting
- Outpatient neurology, obstetric clinics, preconception counselling, inpatient obstetrics, paediatric follow-up
- Source Evidence
- •AAN/AES/SMFM Practice Guideline — Teratogenesis, Perinatal, and Neurodevelopmental Outcomes (2024)
- •EURAP International Registry — Comparative MCM Risk With 8 ASMs (Tomson et al., Lancet Neurol 2018; Battino et al., JAMA Neurol 2024)
- •NEAD/MONEAD Studies — Neurodevelopmental Outcomes at Ages 3 and 6 (Meador et al., Lancet Neurol 2013; Lancet Neurol 2023; JAMA Neurol 2025)
- •SCAN-AED Nordic Register Study — Prenatal ASM Exposure and Neurodevelopmental Disorders (Björk et al., JAMA Neurol 2022)
- •EMA/MHRA/FDA Topiramate Safety Communications (2023–2024)
Key Clinical Takeaways
The most important actionable points from this Practice Update on antiseizure medications in pregnancy. Each links to the detailed discussion below.
- 1Optimise antiseizure medication choice before conception whenever possible — do not wait until pregnancy is confirmed → Preconception Planning
- 2Lamotrigine, levetiracetam, and oxcarbazepine carry the lowest structural malformation risk of the well-studied antiseizure medications → Choosing a Safer ASM
- 3Valproate poses the greatest teratogenic and neurodevelopmental threat — avoid in all people of childbearing potential unless no alternative exists → Valproate Risk
- 4Topiramate is now restricted or contraindicated in pregnancy in many jurisdictions due to cleft palate risk, fetal growth restriction, and emerging neurodevelopmental concerns → Topiramate Warnings
- 5Malformation risk is dose-dependent for valproate, carbamazepine, and phenobarbital — use the lowest effective dose → Dose Matters
- 6Prescribe folic acid at least 0.4 mg daily to all people with epilepsy of childbearing potential, starting before conception → Folic Acid
- 7The MONEAD study provides reassurance that lamotrigine and levetiracetam do not impair cognitive outcomes at age 6 → Neurodevelopmental Outcomes
- 8Monitor ASM blood levels each trimester — pregnancy alters clearance significantly for lamotrigine and levetiracetam → Monitoring During Pregnancy
- 9Seizure control must be maintained — convulsive seizures during pregnancy carry serious risks to both the parent and foetus → Balancing Risks
- 10Do not abruptly stop an ASM upon discovering pregnancy — counsel and plan changes with the treating neurologist → Already Pregnant
Should You Adjust the ASM Before Pregnancy?
The most critical window for preventing antiseizure medication-related birth defects is before conception. Roughly half of pregnancies are unplanned, which makes proactive counselling of every person with epilepsy of childbearing potential essential — not just those actively planning pregnancy.
Counsel all people with epilepsy of childbearing potential about the reproductive risks of their current antiseizure medication at every clinical encounter — not only when pregnancy is raised by the patient.
Strong Rec Moderate Evidence AAN/AES/SMFM 2024Start the transition to a lower-risk ASM before conception whenever clinically feasible. Allow enough time to confirm seizure control on the new regimen before pregnancy.
Strong Rec High Evidence AAN/AES/SMFM 2024Prescribe folic acid at a minimum of 0.4 mg daily to all people with epilepsy of childbearing potential, regardless of whether pregnancy is planned. Start supplementation well before conception.
Strong Rec Moderate Evidence AAN/AES/SMFM 2024 MONEAD 2025Do not abruptly discontinue an effective ASM when pregnancy is discovered. Uncontrolled convulsive seizures during pregnancy carry serious risks including trauma, hypoxia, and foetal loss.
Strong Rec Moderate Evidence AAN/AES/SMFM 2024Ensure effective contraception is in place for any person of childbearing potential taking valproate or topiramate. Document that the patient understands the reproductive risks at each visit.
Strong Rec High Evidence EMA 2023 MHRA 2024Which Antiseizure Medications Are Safest in Pregnancy?
Registry data spanning tens of thousands of pregnancies now allow reasonably precise estimates of the risk of major congenital malformations (MCMs) for the most commonly used ASMs. Three medications consistently show the lowest structural malformation rates — comparable to the background population rate of roughly 2–3%.
Consider levetiracetam as a preferred ASM in people of childbearing potential when clinically appropriate, given its favourable malformation profile and neurodevelopmental safety data.
Moderate Rec High Evidence AAN/AES/SMFM 2024 EURAP 2018Consider lamotrigine as a preferred ASM in people of childbearing potential, particularly for focal epilepsy, given its low MCM rate and strong neurodevelopmental safety profile from NEAD and MONEAD data.
Moderate Rec High Evidence AAN/AES/SMFM 2024 MONEAD 2025Do not prescribe valproate to people of childbearing potential unless no alternative ASM provides adequate seizure control. If valproate is the only option, use the lowest effective dose and ensure informed consent and effective contraception.
Strong Rec High Evidence AAN/AES/SMFM 2024 EMA 2018Avoid topiramate in people of childbearing potential if clinically feasible, due to increased risk of oral clefts, small-for-gestational-age birth weight, and emerging signals of neurodevelopmental harm.
Strong Rec High Evidence AAN/AES/SMFM 2024 EMA 2023 MHRA 2024Avoid routine use of phenobarbital in people of childbearing potential given its elevated malformation rate and cardiac-specific risk. Transition to a safer alternative preconceptionally when possible.
Strong Rec High Evidence EURAP 2018ASM Safety in Pregnancy: A Drug-by-Drug Overview
| Drug | MCM Rate (Registry Data) | Dose-Dependent Risk? | Key Malformation Patterns | Practical Considerations |
|---|---|---|---|---|
| Lamotrigine | ~2–3% | Weak signal at highest doses | No consistent pattern identified | Clearance increases up to 2× in pregnancy — monitor levels and adjust dose. Preferred for focal epilepsies. |
| Levetiracetam | ~2–3% | Not established | No consistent pattern identified | Clearance also increases during pregnancy. Broad-spectrum efficacy makes it useful for generalised epilepsy. |
| Oxcarbazepine | ~3% | Not established | Limited data; no clear pattern | Less data than lamotrigine or levetiracetam. May interact with hormonal contraceptives. |
| Carbamazepine | ~3–6% | Yes | Neural tube defects, cardiac malformations | Moderate risk. Use lowest effective dose. Interacts with many drugs. Enzyme inducer affects hormonal contraception. |
| Topiramate | ~4–9% | Yes (likely) | Oral clefts, SGA (~18%) | Restricted in pregnancy by EMA/MHRA (contraindicated for migraine/weight; for epilepsy, only if no alternative). Pregnancy prevention programme required. Emerging NDD signals. |
| Phenobarbital | ~6% | Yes | Cardiac malformations (~4.4%), oral clefts | Still widely used in low-resource settings. Transition to safer alternative if available. |
| Valproate | ~6–10% (up to 25% at high doses) | Yes (strongly) | Neural tube defects, cardiac, urogenital, skeletal, facial | Highest teratogenic risk. Also impairs IQ and increases autism/ADHD risk. Avoid unless no alternative. |
- MCM rates are approximate pooled estimates from major registries (EURAP, NAAPR, UK Epilepsy and Pregnancy Register). Individual patient risk depends on dose, polytherapy, genetics, and comorbidities.
- Background MCM rate in the general population is approximately 2–3%. The rate in untreated people with epilepsy is roughly similar.
What Do We Know About Long-Term Cognitive Effects?
Structural malformations are only part of the picture. The neurodevelopmental impact of in utero ASM exposure — effects on IQ, language, behaviour, and risk of autism or ADHD — is increasingly recognised as equally important. The NEAD and MONEAD studies, along with large Nordic register data, have substantially clarified this landscape.
Counsel patients that in utero valproate exposure is associated with reduced IQ (approximately 7–10 points lower than other ASMs at age 6) and increased risk of autism spectrum disorder. This effect is dose-dependent.
Strong Rec High Evidence NEAD 2013 SCAN-AED 2022Reassure patients that lamotrigine and levetiracetam exposure during pregnancy has not been associated with impaired cognitive outcomes at age 3 or age 6 in the MONEAD study, compared to children of healthy women without epilepsy.
Strong Rec High Evidence MONEAD 2023/2025Advise patients that topiramate exposure during pregnancy may carry a two- to three-fold increased risk of neurodevelopmental disorders including autism spectrum disorder, intellectual disability, and ADHD, based on Nordic register data. This risk is still being clarified.
Conditional Rec Low Evidence SCAN-AED 2022 EMA 2023Monitor children who were exposed to higher-risk ASMs (valproate, topiramate, phenobarbital) in utero with developmental screening at standard paediatric milestones, and refer early for neurodevelopmental assessment if any concerns arise.
Moderate Rec Low Evidence AAN/AES/SMFM 2024Clinical Decision Pathway
A practical, question-based approach to antiseizure medication management in people of childbearing potential. Follow the questions in order.
Monitoring ASM Levels and Foetal Health During Pregnancy
Monitor ASM blood levels at least once per trimester for all people with epilepsy during pregnancy. For lamotrigine and levetiracetam, more frequent monitoring (monthly) is recommended due to significant clearance changes.
Strong Rec Moderate Evidence AAN/AES/SMFM 2024Perform a detailed foetal anomaly ultrasound at 18–20 weeks for all pregnancies exposed to ASMs. Consider additional early imaging for pregnancies exposed to high-risk ASMs (valproate, topiramate, phenobarbital).
Strong Rec Moderate Evidence AAN/AES/SMFM 2024Reassess and taper any pregnancy-related dose increases in the first two weeks postpartum to avoid ASM toxicity as drug clearance returns to pre-pregnancy levels.
Strong Rec Moderate Evidence AAN/AES/SMFM 2024Pregnancy Monitoring Schedule by ASM and Timepoint
| Timepoint | What to Check | Why It Matters | Common Pitfalls |
|---|---|---|---|
| Preconception | Baseline ASM blood level, folate status, epilepsy syndrome review | Establishes target blood level to maintain during pregnancy | Forgetting to establish baseline before pregnancy — you lose the reference point |
| Each trimester | ASM blood level, seizure frequency, side effects | Lamotrigine clearance may double; levetiracetam rises 50–60% | Only checking once during whole pregnancy — rapid changes are missed |
| 18–20 weeks | Detailed foetal anomaly scan | Detects major structural malformations in time for counselling and planning | Not requesting detailed cardiac views for phenobarbital-exposed pregnancies |
| Third trimester | Foetal growth assessment (especially if on topiramate), ASM level | Topiramate carries ~18% SGA rate; early detection allows planning | Assuming growth is fine because the anomaly scan was normal |
| First 2 weeks postpartum | ASM blood level, plan for dose taper | Clearance normalises rapidly; toxicity can occur if dose not reduced | Leaving the pregnancy dose unchanged — lamotrigine toxicity (diplopia, ataxia) is common |
Evidence in Context
What the evidence shows, where the regulatory bodies align, and what remains uncertain.
Where All Guidelines and Registries Agree
There is now strong consensus across the AAN/AES/SMFM 2024 guideline, the EURAP registry, and regulatory bodies (EMA, FDA, MHRA) on several core points: valproate is the single highest-risk ASM for both structural and neurodevelopmental harm; lamotrigine and levetiracetam are the safest well-studied options; dose matters — higher doses of valproate, carbamazepine, and phenobarbital carry higher malformation rates; preconception planning is essential; folic acid supplementation should be universal; and ASM blood level monitoring during pregnancy is necessary to maintain seizure control.
The Topiramate Controversy: Where AAN and EMA Diverge
The EMA (2023) and MHRA (2024) have implemented pregnancy prevention programmes for topiramate, citing both structural malformation risk and emerging neurodevelopmental disorder signals from the SCAN-AED study. The AAN/AES/SMFM 2024 guideline also recommends against topiramate in pregnancy but concluded — based on their evidence classification methodology — that the neurodevelopmental data for topiramate were less definitive than for valproate. Some authors have noted this may reflect how the SCAN-AED study was classified in the guideline process, and have urged re-evaluation. In practice, most experts now recommend avoiding topiramate in people of childbearing potential unless no other option exists.
The MONEAD Study: What Changed Our Understanding
The MONEAD study is a long-running, prospective, NIH-funded multicentre study enrolling women from 2012 onwards — a period when lamotrigine and levetiracetam had become the dominant ASMs. At age 3, children exposed to these newer ASMs showed verbal and cognitive scores equivalent to children of healthy women without epilepsy. At age 6, these findings were confirmed and extended. The study also found that folate supplementation in the first trimester was associated with improved cognitive and behavioural outcomes, even at doses above 4 mg daily, providing reassurance against earlier concerns about high-dose folic acid.
Folic Acid: What Dose, and Does It Actually Help?
The AAN/AES/SMFM 2024 guideline recommends at least 0.4 mg daily, which is the standard general population dose. There has been considerable debate about whether higher doses (4–5 mg) are needed for people taking enzyme-inducing ASMs or valproate. The MONEAD data suggest that higher doses may be beneficial and do not appear harmful. However, one Nordic study raised concern about a possible association between very high folic acid doses and childhood cancer risk. The guideline authors discussed this extensively and ultimately recommended the standard dose as a minimum, leaving higher-dose supplementation to clinical judgement.
What We Still Don't Know
References
- 1.Pack AM, Oskoui M, Williams Roberson S, et al. Teratogenesis, Perinatal, and Neurodevelopmental Outcomes After In Utero Exposure to Antiseizure Medication: Practice Guideline From the AAN, AES, and SMFM. Neurology. 2024;102(11):e209279. doi:10.1212/WNL.0000000000209279
- 2.Tomson T, Battino D, Bonizzoni E, et al. Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry. Lancet Neurol. 2018;17(6):530–538. doi:10.1016/S1474-4422(18)30107-8
- 3.Meador KJ, Baker GA, Browning N, et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurol. 2013;12(3):244–252. doi:10.1016/S1474-4422(12)70323-X
- 4.Meador KJ, Cohen MJ, Loring DW, et al. Cognitive outcomes at age 3 years in children with fetal exposure to antiseizure medications (MONEAD study): a prospective, observational cohort study. Lancet Neurol. 2023;22(8):712–722. doi:10.1016/S1474-4422(23)00199-0
- 5.Björk MH, Zoega H, Leinonen MK, et al. Association of Prenatal Exposure to Antiseizure Medication With Risk of Autism and Intellectual Disability. JAMA Neurol. 2022;79(7):672–681. doi:10.1001/jamaneurol.2022.1269
- 6.Battino D, Tomson T, Bonizzoni E, et al. Risk of Major Congenital Malformations and Exposure to Antiseizure Medication Monotherapy. JAMA Neurol. 2024;81(5):481–489. doi:10.1001/jamaneurol.2024.0258
- 7.European Medicines Agency. PRAC recommends new measures to avoid topiramate exposure in pregnancy. September 2023. ema.europa.eu
- 8.Meador KJ, Cohen MJ, Loring DW, et al. Neuropsychological Outcomes in 6-Year-Old Children of Women With Epilepsy: A Prospective Nonrandomized Clinical Trial. JAMA Neurol. 2025;82(1):30–39. doi:10.1001/jamaneurol.2024.3982
How to Read the Evidence Tags
Every recommendation in this article carries two tags indicating how strong the recommendation is and how robust the supporting evidence is. These are Medaptly's own simplified interpretations for educational clarity.
Recommendation Strength
| Tag | What It Means | In Practice |
|---|---|---|
| Strong Rec | High-quality evidence broadly supports this action. Benefits clearly outweigh risks for most patients. | This should be standard practice for most patients meeting the criteria. |
| Moderate Rec | The weight of evidence favours this action, though some uncertainty remains. | Most patients should receive this, but clinical context may lead to a different decision. |
| Conditional Rec | Benefit is less certain. The right choice depends on individual circumstances. | Discuss with the patient. Use shared decision-making. |
| Against | Evidence shows no benefit, or risks outweigh potential benefits. | Avoid this intervention. Document reasoning if used in unusual circumstances. |
Evidence Quality
| Tag | What It Means | How Confident Can You Be? |
|---|---|---|
| High Evidence | Based on multiple large prospective registries, well-designed cohort studies, or meta-analyses. | Very confident. Future research is unlikely to change the direction of this recommendation. |
| Moderate Evidence | Based on a single large study or multiple smaller observational studies. | Reasonably confident. The direction is likely correct, but the magnitude may be refined. |
| Low Evidence | Based on expert consensus, small studies, or extrapolated from related evidence. | Less certain. This is the best available guidance, but it may change as better evidence emerges. |
These are Medaptly's simplified interpretations for educational clarity. For the full classification systems used by each source guideline, consult the original documents listed in References.