Management issues for women with epilepsy-Focus on pregnancy Teratogenesis and perinatal outcomes: Evidence-based Guideline

Recent estimates of the US population and the prevalence of epilepsy indicate that approximately one-half million women with epilepsy (WWE) are of childbearing age. It has also been estimated that three to five births per thousand will be to WWE. Epilepsy is defined by the presence of recurrent, unprovoked seizures, and the treatment is typically a daily, long-term antiepileptic drug (AED) regimen. The majority of people with epilepsy have well-controlled seizures, are otherwise healthy, and therefore expect to participate fully in life experiences, including childbearing.

American Academy of Neurology (AAN) has released guidelines of Evidence-based Guideline for Clinicians on Management issues for women with epilepsy-Focus on pregnancy Teratogenesis and perinatal outcomes in July 2009 and reaffirmed on October 22, 2022. Guideline being updated. The purpose of the guideline is to management and care of women with epilepsy (WWE) during pregnancy.

Following are its major recommendations:

1. If possible, avoidance of the use of VPA as part of polytherapy during the first trimester of pregnancy should be considered to decrease the risk of MCMs (Level B).

2. If possible, avoidance of the use of VPA monotherapy during the first trimester of pregnancy may be considered to decrease the risk of MCMs (Level C).

3. Although there is evidence that AEDs taken during the first trimester probably increase therisk of MCMs in the offspring of WWE, it cannot be determined if the increased risk is imparted from all AEDs or from only one or some AEDs. Therefore, no recommendation is made from this conclusion.

4. To reduce the risk of MCMs, the use of VPA during the first trimester of pregnancy should be avoided, if possible, compared to the use of CBZ (Level A).

5. To reduce the risk of MCMs, avoidance of the use of polytherapy with VPA during the first trimester of pregnancy, if possible, should be considered, compared to polytherapy without VPA (Level B).

6. To reduce the risk of MCMs, avoidance of the use of VPA during the first trimester of pregnancy, if possible, may be considered, compared to the use of PHT or LTG (Level C).

7. To reduce the risk of MCMs, avoidance of the use of AED polytherapy during the first trimester of pregnancy, if possible, compared to monotherapy should be considered (Level B).

8. Limiting the dosage of VPA or LTG during the first trimester, if possible, should be considered to lessen the risk of MCMs (Level B).

9. Avoidance of the use of VPA, if possible, should be considered to reduce the risk of neural tube defects and facial clefts (Level B) and may be considered to reduce the risk of hypospadias (Level C).

10. Avoidance of PHT, CBZ, and PB, if possible, may be considered to reduce the risk of specific MCMs: cleft palate for PHT use, posterior cleft palate for CBZ use, and cardiac malformations for PB use (Level C).

11. Counseling of WWE who are contemplating pregnancy should reflect that there is probably no increased risk of reduced cognition in the offspring of WWE not taking AEDs (Level B).

12. CBZ exposure probably does not produce cognitive impairment in offspring of WWE (Level B).

13. Avoiding VPA in WWE during pregnancy, if possible, should be considered to reduce the risk of poor cognitive outcomes (Level B).

14. Avoiding PHT in WWE during pregnancy, if possible, may be considered to reduce the risk of poor cognitive outcomes (Level C).

15. Avoiding PB in WWE during pregnancy, if possible, may be considered to reduce the risk of poor cognitive outcomes (Level C).

16. Monotherapy should be considered in place of polytherapy, if possible, for WWE who take AEDs during pregnancy to reduce the risk of poor cognitive outcomes (Level B).

17. For WWE who are pregnant, avoidance of VPA, if possible, should be considered compared to CBZ to reduce the risk of poor cognitive outcomes (Level B).

18. For WWE who are pregnant, avoidance of VPA, if possible, may be considered compared to PHT to reduce the risk of poor cognitive outcomes (Level C).

19. Pregnancy risk stratification should reflect that the offspring of WWE taking AEDs during pregnancy probably have an increased risk of SGA. Further, AED use in WWE during pregnancy.

20. Pregnancy risk stratification should reflect that neonates born to WWE probably do not have a substantially increased risk of perinatal death (Level B).

21. Pregnancy risk stratification should reflect that the offspring of WWE taking AEDs during pregnancy possibly have an increased risk of 1-minute Apgar scores of <7. Further, AED use in WWE during pregnancy may be considered in the differential diagnosis of a 1-minute Apgar score of <7 in their offspring (Level C).

Reference:

C. L. Harden, K. J. Meador, P. B. Pennell, W. A. Hauser, G. S. Gronseth, J. A. French, S. Wiebe, D. Thurman, B. S. Koppel, P. W. Kaplan, J. N. Robinson, J. Hopp, T. Y. Ting, B. Gidal, C. A. Hovinga, A. N. Wilner, B. Vazquez, L. Holmes, A. Krumholz, R. Finnell, D. Hirtz, C. Le Guen Neurology Jul 2009, 73 (2) 133-141; DOI: 10.1212/WNL.0b013e3181a6b312