Lamotrigine use in pregnancy not linked with risk of orofacial clefts

Researchers say babies with orofacial cleft were no more likely to have been exposed to lamotrigine in the womb than babies with other defects.

New born baby with a cleft palate

Using antiepileptic drug lamotrigine during pregnancy does not significantly increase the risk of orofacial cleft in babies, a new study shows. 

Researchers found that babies with orofacial cleft were no more likely to have been exposed to lamotrigine in the first trimester of pregnancy than babies with other non-genetic birth defects. 

Reporting their findings in Neurology
 (online, 6 April 2016), the researchers used data from EUROCAT, a network of population-based congenital anomaly registries that includes live births, stillbirths and terminations for fetal anomaly. The study involved 226,806 babies with congenital anomalies who were added to the registry between 1995 and 2011. 

The team, led by Helen Dolk, head of the centre for maternal, fetal and infant research at the Institute for Nursing Research at the University of Ulster, Northern Ireland, found that exposure to any antiepileptic drug in the first trimester was associated with a 34% increased risk of orofacial cleft and a 97% increased risk of cleft palate specifically, compared with other congenital anomalies. 

But when they analysed only those exposed to lamotrigine, researchers found no significantly increased risk for orofacial cleft or cleft palate. Overall, they estimate that lamotrigine exposure would result in orofacial cleft in fewer than one in every 550 babies. 

The same team previously identified a potential increased risk of club foot with lamotrigine from 1995–2005 data from the EUROCAT registries, but they did not replicate this finding in longer term data. 

Concerns about the use of lamotrigine in pregnancy were raised after a North American registry detected a signal indicating a six-fold increased risk of orofacial cleft. But the researchers of the current study say that the baseline risk of orofacial cleft was probably underestimated in the North American cohort. No study since then has supported its findings and the current study is the biggest population examined to date. 

In its patient information leaflet, the Medicines and Healthcare products Regulatory Agency (MHRA) mentions “a moderate increase in the risk” of orofacial clefts if lamotrigine is used during pregnancy. 

Dolk suggests that they should update the information in light of her team’s findings. “The MHRA should make it clear that the excess risk of orofacial clefts, if present at all with average doses, is less than an estimated one in every 550 babies, so that clinicians and women can weigh the risks and benefits of different medication options appropriately prior to conception,” she says. 

“Clinicians and pharmacists should also be aware that women with epilepsy and other women taking antiepileptics should be given preconception care to consider which antiepileptics have the best benefit-risk profile for them in pregnancy, in the light of the most up-to-date evidence available, as any change of medication needs to occur before pregnancy,” she advises. 

Simon Wigglesworth, deputy chief executive of UK charity Epilepsy, says that the study results are reassuring and consistent with what is already known about the risks of the drug during pregnancy. 

“Most women with epilepsy have healthy pregnancies and give birth to healthy babies,” he says. “There has been a clear change in prescribing epilepsy medicines for many women of child-bearing years. However, more information still needs to be made available. It is important to weigh up the risk of increased seizures with the risks involved with antiepilepsy medicines.” 

But he adds that as many women find their dosage needs to be increased during pregnancy, more research is needed into the risks of lamotrigine exposure at higher doses. “We would welcome the MHRA to review all the available data before revising its advice on the use of lamotrigine during pregnancy,” he says. 


[1] Dolk H, Wang H, Loane M et al. Lamotrigine use in pregnancy and risk of orofacial cleft and other congenital anomalies. Neurology 2016. doi: 10.1212/WNL.0000000000002540

Last updated
The Pharmaceutical Journal, Lamotrigine use in pregnancy not linked with risk of orofacial clefts;Online:DOI:10.1211/PJ.2016.20200977

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