Exposure to Antiseizure medicines via breastfeeding doesn't affect child's cognitive level: MONEAD study

Breastfeeding is known to have many beneficial effects, but it also provides a vehicle for transfer of medication from mother to child. Until the NEAD study, there had been no investigations of the potential risks of AED exposure via breastfeeding on child cognitive outcomes.

Use of antiseizure medications while breastfeeding is not associated with differences in child cognitive outcomes at age 3, according to new results from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs, MONEAD study. Additionally, no significant differences were seen between AED drug groups. Taken together, these findings suggest that, for those AEDs that were studied, there was no adverse effect of exposure via breastfeeding on cognitive function in children already exposed in utero.

The MONEAD study included women from 20 different sites, with 145 participating investigators. The researchers compared outcomes in 284 women with epilepsy and 87 healthy women. The maternal mean IQ was 98 among women with epilepsy (95% confidence interval [CI], 96-99), and 105 (95% CI, 102-107) among healthy women. Seventy-six percent of women with epilepsy breastfed, versus 89% of controls. Among the study cohort, 79% of women with epilepsy were on monotherapy, and 21% were on polytherapy. Thirty-five percent received lamotrigine, 28% levetiracetam, 16% were on another monotherapy, 10% received a combination of lamotrigine and levetiracetam, and 11% received a different combination.

• The researchers found no association between third trimester antiseizure medication blood levels and verbal index score after adjustment (–2.9; P = .149), with the exception of levetiracetam (–9.0; P = .033).

• overall the children on levetiracetam did well, but that of teratogens act in an exposure dependent manner, so there is a balancing act of trying to make sure you get enough medication on board to stop the seizures and protect the mother and the child, and at the same time, by increasing the risk of teratogenicity in the child.

• At age 3, there was no association between the verbal index score of the child and whether the mother had epilepsy or not (difference, 0.4; P = .770).

• The researchers did find associations with the mother's IQ (0.3; P < .001), male versus female child sex (–4.9; P < .001), Hispanic or Latino ethnicity (vs. Non-Hispanic, –5.5; P < .001), mother without college degree (–7.0; P < .001), average Beck Anxiety Inventory score after birth (–0.4; P < .001), and weeks of gestational age at enrollment.

Researchers concluded that "Breastfeeding has health benefits for both mothers and children, including reduced risk of respiratory tract infections, and diabetes in children, and reduced risk of diabetes, cancer and postpartum depression in mothers. Despite those benefits, concerns about harms from exposure to antiepileptic drugs may prompt some women to avoid breastfeeding."

References

Meador KJ, Baker GA, Browning N, Clayton-Smith J, Combs-Cantrell DT, Cohen M, Kalayjian LA, Kanner A, Liporace JD, Pennell PB, Privitera M, and Loring DW for the NEAD Study Group. Cognitive Function at 3 Years of Age after Fetal Exposure to Antiepileptic Drugs. New England Journal of Medicine. 2009;360(16):1597-1605. NIHMSID134109/PMID19369666/PMCID2737185

Meador KJ, Baker GA, Browning N, Clayton-Smith J, Combs-Cantrell DT, Cohen M, Kalayjian LA, Kanner A, Liporace JD, Pennell PB, Privitera M, and Loring DW for the NEAD Study Group. Effects of breastfeeding in children of women on antiepileptic drugs. Neurology. 2010;75:1954-1960 NIHMSID327817/PMID21106960/PMCID3014232

Meador KJ, Baker GA, Browning N, Cohen MJ, Clayton-Smith J, Kalayjian LA, Kanner A, Liporace JD, Pennell PB, Privitera M, and Loring DW for the NEAD Study Group. Foetal antiepileptic drug exposure and verbal vs non-verbal abilities at three years of age. BRAIN. 2011;396-404. PMID21224309/PMCID3030767

Meador KJ, Baker GA, Browning N, Cohen MJ, Bromley RL, Clayton-Smith J, Kalayjian LA, Kanner A, Liporace JD, Pennell PB, Privitera M, and Loring DW. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD Study): a prospective observational study. Lancet Neurology. 2013, March;12(3): 244-252. NIHMS461834/PMCID23352199

Pennell PB, Klein AM, Browning N, Baker GA, Clayton-Smith J, Kalayjian LA, Liporace JD, Privitera M, Crawford T, Loring DW, Meador KJ. Differential Effects of Antiepileptic Drugs on Neonatal Outcomes. Epilepsy and Behavior. 2012;24(4):449-456 PMID22749607/PMCID3483041