Risks of congenital malformations in offspring exposed to valproic acid in utero: A systematic review and cumulative meta‐analysis

@article{Tanoshima2015RisksOC,
  title={Risks of congenital malformations in offspring exposed to valproic acid in utero: A systematic review and cumulative meta‐analysis},
  author={Mina Tanoshima and T. Kobayashi and Reo Tanoshima and Joseph Beyene and Gideon Koren and Shinya Ito},
  journal={Clinical Pharmacology \& Therapeutics},
  year={2015},
  volume={98}
}
Despite extensive research efforts over decades, the teratogenic profile of valproic acid (VPA) remains obscure. We performed cumulative and conventional meta‐analyses of cohort studies to determine the time profiles of signal emergence of VPA‐associated congenital malformations (CMs) and to define risk estimates of each of the CMs. Fifty‐nine studies were identified and analyzed. We found that the significant risk signals began to emerge over the last 10–20 years even before large‐scale… 

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References

SHOWING 1-10 OF 42 REFERENCES

Increased rate of major malformations in offspring exposed to valproate during pregnancy

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.

Major malformations in infants exposed to antiepileptic drugs in utero, with emphasis on carbamazepine and valproic acid: a nation‐wide, population‐based register study

The teratogenic effect of valproic acid (VPA) and carbamazepine (CBZ) in monotherapy and the number of therapeutic abortions, or the different types of epilepsy or drug dosage in the two treatment groups, is compared.

Major malformations in offspring of women with epilepsy

Major malformations in the offspring of mothers with epilepsy are associated with use of AED during early pregnancy, and also with low serum folate concentrations and a low level of education.

Major malformations with valproic acid.

There is compelling evidence that the risk of teratogenic risks is dose dependent and the risks appear to begin increasing at doses of 600 mg/d and to become more prominent at doses above 1000mg/d.

Folic acid use and major congenital malformations in offspring of women with epilepsy: a prospective study from the UK Epilepsy and Pregnancy Register

The study supports the view that extrapolation from studies carried out in the general population to groups of women with epilepsy may be questionable and it may be that the increased risk of MCM recorded in this group occurs through mechanisms other than that of folic acid metabolism.

Final results from 18 years of the International Lamotrigine Pregnancy Registry

With over 1,500 first-trimester monotherapy exposures, the Registry was powered to detect major teratogenicity and failed to observe an increased MCM frequency with increasing lamotrigine dose.

Malformation risks of antiepileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register

Only 4.2% of live births to women with epilepsy had an MCM, and polytherapy exposure was greater than for monotherapy exposure, and carbamazepine was associated with the lowest risk of MCM.

MALFORMATION RISKS OF ANTIEPILEPTIC DRUG MONOTHERAPIES IN PREGNANCY

AED exposure during pregnancy increases the risk of MCM in the infants of women with epilepsy and suggests that either lamotrigine or levetiracetam should be used as drugs of choice over valproate, even at low dose, in women of childbearing age with epilepsy.