Investigation of the effects of phenytoin on pregnancy in neonatal malformations (Systematic review)

Investigation of the effects of phenytoin on pregnancy in neonatal malformations (Systematic review)
Shiva Sharifzadeh ,¹ Elham Safari ,² Farzaneh Pardeh Shenas ,³ Elahe safari ,^4,*
1. Member of Omid research group
2. Member of Omid research group
3. Member of Omid research group
Introduction: Epilepsy is the most common neurological disorder in women of reproductive age. Phenytoin (PHT) is one of the antiepileptic drugs, which is frequently prescribed for epilepsy. Within the pregnancy, women experience physiological changes that have consequences for the pharmacokinetics and pharmacodynamics of the medications they take. Also, PHT can go through the placenta and concentrates on placental tissue. However, most women with epilepsy have normal pregnancy outcomes, but fetal anomalies and pregnancy complications are related to epilepsy and PHT use, therefore the current review aims to investigate the effect of PHT on pregnancy in neonatal malformations disorders.
Methods: This review was collected by searching within articles published at PubMed, ScienceDirect, Google Scholar, Scopus, Cochrane database systematic reviews from 1985 to 2020. The keywords were seizures, Phenytoin, neonatal, pregnancy. By searching this database, 57 articles were found, 11 of them were not related to investigating, and by reading abstracts were removed. All articles were chosen from English and Persian articles.
Results: Finally, 46 articles were included in the study. Waters et al. expressed most abnormal outcomes were reported with PHT and phenobarbital [1]. In terms of abnormal outcome (death and anomalies), phenobarbital was associated with the highest relative risk, PHT with intermediate relative risk. High third-trimester PHT levels may have a significant impact on newborn Sucking reflexes, development motor skills, malformations of the hands and feet, and the talipes deformity [2]. In other studies, the rate of fetal death and anomalies had a higher in the Offspring of women with epilepsy who were exposed to PHT [3, 4].
Conclusion: The basic spectrum of birth defects was confirmed and expanded upon by subsequent investigations into the teratogenicity of PHT include tracheoesophageal fistulas, cutaneous hemorrhages, and neural tube defects (NTDs). There is no safe dose that will supply therapeutic efficacy without the potential risk of inducing developmental or structural defects in the exposed infant. Based on the assumption, seizures should be adequately controlled during pregnancy. Therefore polytherapy must be avoided, in the management of women of reproductive age and whenever that is at risk of getting pregnant.
Keywords: Epilepsy, Phenytoin, Neonatal, Pregnancy