Psychopharmacologic Therapy in Pregnancy: Effects on Newborns

Antiepileptic drugs (AEDs)

A mother's use of AEDs is linked to the immediate withdrawal effects of the newborn and to long-term neurologic dysfunctions. Valproate(Drug information on valproate) was shown to be associated with immediate NWS symptoms, such as hyperexcitability, causing neurologic deficits, seizures, and jitteriness.^32,33 Furthermore, in a retrospective study based on hospital records, Dean and associates³⁴ found significant NWS symptoms, including jitteriness, hypotonia, seizures, apneic episodes, hypoglycemia, and feeding disorder, after exposure in utero to valproate, phenytoin(Drug information on phenytoin), or combination therapy.

Long-term effects of AEDs have also been demonstrated. In the study by Koch and associates,³² when children were examined 6 years later, they continued to have long-term neurologic dysfunctions, which are more congruent with drug toxicity than withdrawal effects. Similar results are reported in the study by Moore and associates³³ of 57 children prenatally exposed to AEDs: 77% had learning difficulties, 81% had speech delay, 60% had gross motor delay, and 42% had fine motor delay. Eighty percent of these children had prenatal exposure to valproate alone or in combination with another AED. Seventy-four percent of school-aged children were enrolled in special education classes or were receiving learning support, and 81% had some type of behavioral dysfunction; of these, 60% had some autistic features and 39% had hyperactivity, but autism or Asperger syndrome had actually been diagnosed in only a few. The developmental effects seem to be associated not only with valproate but also with carbamazepine(Drug information on carbamazepine), phenytoin, and polypharmacy.³⁴ Although these investigators did not find a link between NWS and cognitive dysfunction, this is a topic in which further research is badly needed.

Conclusions

Pregnant women with psychiatric conditions must be adequately treated. Pharmacologic treatment should be initiated or maintained when the disorder is severe and the efficacy of the psychopharmacologic approach has been demonstrated, giving attention to nonpharmacologic alternatives in order to prevent the relapse of the disease in the mother. Psychiatric clinical practice shows that most pregnant women with psychiatric conditions are treated with polypharmacy,³⁵ making it even more complex to identify the effects of these drugs on the newborn. Psychopharmacologic agents can induce direct effects on the newborn, as well as withdrawal symptoms associated with their suppression. The clinical picture of both cases is often similar and confounding. Nevertheless, NWS has clearly been associated with TCAs, SSRIs, and AEDs. However, with the exception of AEDs, the clinical picture for most of these drugs appears to be self-limited and moderate, most frequently needing only supportive therapy.

Dr Sanz is associate professor in clinical pharmacology at the University of La Laguna in Tenerife, Canary Islands, Spain, and a member of the Review Panel of Experts of the WHO Collaborating Centre for International Drug Monitoring. He reports that he has no conflicts of interest concerning the subject matter of this article.

Dr De las Cuevas is associate professor of psychiatry at the University of La Laguna in Tenerife, Canary Islands, Spain, a specialist in psychiatry with clinical responsibilities, and a senior member of the Educational Liaisons Network of the World Psychiatric Association. He reports that he has no conflicts of interest concerning the subject matter of this article.