Antiseizure drugs in pregnancy: polytherapy and topiramate were associated with the poorest fetal growth

Design

Prospective international registry cohort, multivariable adjusted

Population

15,893 singleton births exposed to antiseizure medication (EURAP, 1999–2023)

Primary outcome

Birthweight centile; small for gestational age

Effect

Polytherapy vs monotherapy SGA OR 1.48 (1.29 to 1.70); topiramate vs lamotrigine centile −11.9 (−16.7 to −7.2)

EURAP is an international prospective registry of pregnancies in women with epilepsy. This analysis included 15,893 exposed births from 1999 to 2023 and adjusted for a wide range of maternal and clinical factors.

Compared with monotherapy, polytherapy was associated with a lower birthweight centile and about 50% higher odds of small for gestational age (OR 1.48), severe small for gestational age (1.49) and low birthweight (1.50). Risk rose with each added drug. Against lamotrigine, birthweight centile was lower with topiramate (−11.9 centile points), phenobarbital (−8.1), oxcarbazepine (−5.1), carbamazepine (−3.2), valproate (−2.5) and levetiracetam (−2.5). Lamotrigine combined with levetiracetam or valproate did not differ from lamotrigine alone.

Fetal growth now belongs alongside malformations and neurodevelopment in preconception counselling. The planning that matters happens before conception: simplify to the fewest drugs that control seizures, and favour lamotrigine or levetiracetam where suitable. Phenobarbital, still common in India, carried one of the larger deficits.

• Review every woman with epilepsy of childbearing potential before pregnancy
• Aim for the lowest effective number of antiseizure drugs
• Avoid topiramate, phenobarbital and valproate where alternatives control seizures
• Arrange fetal growth scans in pregnancies exposed to polytherapy or topiramate
• Never stop antiseizure drugs abruptly on discovering a pregnancy

Why it matters

Poor fetal growth is a separate harm of prenatal exposure that counselling has so far overlooked.

Don't overread it

This was observational; women on polytherapy or older drugs may have more severe epilepsy, which adjustment cannot fully remove.

The statistics, in plain English

A birthweight centile coefficient of −11.9 for topiramate means babies were on average about 12 centile places lower than those exposed to lamotrigine, after adjustment. An odds ratio of 1.48 for small for gestational age with polytherapy, with an interval of 1.29 to 1.70, is a precise estimate from a large sample. Small drug groups, such as the 48 on four drugs, give wide intervals and should be read as direction only.

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