Management issues for women with epilepsy—Focus on pregnancy (an evidence‐based review): III. Vitamin K, folic acid, blood levels, and breast‐feeding

@article{Harden2009ManagementIF,
  title={Management issues for women with epilepsy—Focus on pregnancy (an evidence‐based review): III. Vitamin K, folic acid, blood levels, and breast‐feeding},
  author={Cynthia Harden and Page B Pennell and Barbara S Koppel and Collin A. Hovinga and Barry E. Gidal and Kimford J. Meador and Jennifer L. Hopp and Tricia Y. Ting and Willard A Hauser and David J Thurman and Peter W. Kaplan and Julian N. Robinson and Jacqueline A. French and Samuel Wiebe and Andrew Wilner and Blanca Vazquez and Lewis E Holmes and A Krumholz and Richard H. Finnell and Patricia Osborne Shafer and Claire L. Le Guen},
  journal={Epilepsia},
  year={2009},
  volume={50}
}
A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid and prenatal vitamin K use and the clinical implications of placental and breast‐milk transfer of antiepileptic drugs (AEDs). The committee evaluated the available evidence based on a structured literature review and classification of relevant articles. Preconceptional folic acid supplementation is… 
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TLDR
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TLDR
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TLDR
The general strategy is to select the most appropriate AED for the individual woman taking efficacy as well as teratogenic potential into account and to try out the lowest effective dose, and to measure the serum concentration of the drug that will serve as a reference for drug concentrations obtained during pregnancy.
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Women with epilepsy (WWE) who choose to get pregnant must also consider the risk to their developing fetus of exposure to anticonvulsant therapy as birth defects occur more often in children born to WWE exposed to these agents.
Folic acid dose, valproate, and fetal malformations
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It would seem misguided to hope that a folic acid dose of 5 mg/day taken before and during pregnancy would protect against the occurrence of valproate-associated and other AED-associated fetal structural malformations.
High dose folic acid supplementation in women with epilepsy: Are we sure it is safe?
TLDR
Considering the potential significant drug-drug interactions between high doses of folic acid and some AEDs in patients with epilepsy and also with the emerging evidence from animal studies that high levels of folics acid throughout gestation may have adverse effects on fetal brain development, it is not suggested to advocate high dose folic Acid supplementation in women with epilepsy.
Is there Evidence for Vitamin K Prophylaxis in Pregnant Women taking Anticonvulsant Drugs?
Purpose: The objective of this study was to examine the need of vitamin K prophylaxis in women with epilepsy (WWE) taking anticonvulsant drugs (AED) during pregnancy to prevent neonatal bleeding.
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References

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Practice Parameter update: Management issues for women with epilepsy—Focus on pregnancy (an evidence-based review): Obstetrical complications and change in seizure frequency
TLDR
Women with epilepsy (WWE) should be counseled that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high rate (84%–92%) of remaining seizure-free during pregnancy (Level B), however, WWE who smoke should be Counseled that they possibly have a substantially increased risk of premature contractions and premature labor and delivery during pregnancy.
Quality of life, epilepsy advances, and the evolving role of anticonvulsants in women with epilepsy.
TLDR
The management of women with epilepsy (WWE) presents physicians with unique problems, ranging from the cosmetic consequences of some AEDs to the seizures of catamenial epilepsy (apparently related to a relative lack of progesterone during the luteal phase of the menstrual cycle).
Enzyme-inducing antiepileptic drugs in pregnancy and the risk of bleeding in the neonate
TLDR
These data do not support the hypothesis that maternal enzyme-inducing AED increase the risk for bleeding in the offspring, and antenatal administration of vitamin K to these mothers may still be needed in selected cases.
Epilepsy and Pregnancy: A Prospective Study of Seizure Control in Relation to Free and Total Plasma Concentrations of Carbamazepine and Phenytoin
TLDR
It is indicated that total plasma concentrations may be misleading and that monitoring of free concentrations, in particular of PHT concentrations, may be advantageous during pregnancy, as well as the small number of cases with an increased seizure frequency.
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TLDR
All women of childbearing age in the United States who are capable of becoming pregnant should consume 0.4 mg of folic acid per day for the purpose of reducing their risk of having a pregnancy affected with spina bifida or other NTDs.
Proactive pre-conception counselling for women with epilepsy—is it effective?
TLDR
An audit of the outcomes in the two groups suggests that re-investigation of women pre-conceptually is worthwhile and that foetal morbidity may be reduced by judicious rationalization of medication: folic acid taken before conception may also be protective for the foetus.
The Australian registry of anti-epileptic drugs in pregnancy: experience after 30 months
TLDR
The model for the Australian Pregnancy Register appears to be successful, with strong enrolment from all regions over the first 30 months, and analysis of the pregnancy outcomes to date may reveal early trends, but numbers are still to small for any definitive conclusions to be made regarding the relative risk in pregnancy of individual AEDs.
Critical relationship between sodium valproate dose and human teratogenicity: results of the Australian register of anti-epileptic drugs in pregnancy
TLDR
There is a dose-effect relationship for FM and exposure to VPA during the first trimester of pregnancy, with higher doses of VPA associated with a significantly greater risk than with lower doses or with other AEDs.
Controversies Concerning Vitamin K and the Newborn
TLDR
Late HDN, a syndrome defined as unexpected bleeding due to severe vitamin K deficiency in infants aged 2 to 12 weeks, occurs primarily in exclusively breast-fed infants who have received no or inadequate neonatal vitamin K prophylaxis.
Increased rate of major malformations in offspring exposed to valproate during pregnancy
TLDR
Maternal exposure to valproic acid during the first trimester of pregnancy significantly increased the risk of major malformations in infants whose mothers had taken the drug VPA as monotherapy and had enrolled in the North American Antiepileptic Drug Pregnancy Registry.
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