Effect of Atypical Antipsychotics on Fetal Growth: Is the Placenta Involved?

Abstract

There is currently considerable uncertainty regarding prescribing practices for pregnant women with severe and persistent psychiatric disorders. The physician and the mother have to balance the risks of untreated psychiatric illness against the potential fetal toxicity associated with pharmacological exposure. This is especially true for women taking atypical antipsychotics. Although these drugs have limited evidence for teratological risk, there are reports of altered fetal growth, both increased and decreased, with maternal atypical antipsychotic use. These effects may be mediated through changes in the maternal metabolism which in turn impacts placental function. However, the presence of receptors targeted by atypical antipsychotics in cell lineages present in the placenta suggests that these drugs can also have direct effects on placental function and development. The signaling pathways involved in linking the effects of atypical antipsychotics to placental dysfunction, ultimately resulting in altered fetal growth, remain elusive. This paper focuses on some possible pathways which may link atypical antipsychotics to placental dysfunction.

Antipsychotic use in pregnancy

“…Although it is known that all psychotropic medications cross the placenta [34], there is uncertainty regarding the teratogenic effects of antipsychotics on pregnancy [37]. One of the reasons for this is the previous lack of high-quality evidence.…”

“…The exposure of these medications in utero has been reported to result in an increased incidence of both low and high birth weight compared to the general population. However, this association remains unclear due to conflicting results in a number of observational studies [37]. Newham et al [40] prospectively examined newborns exposed to either classes of antipsychotics and observed that newborns exposed to atypical antipsychotics had a significantly higher risk of being large for gestational age (LGA) and presented a higher birth weight mean than those exposed to typical antipsychotics.…”

“…Hence, this data begins to fill a much needed gap in the literature regarding the use of atypical antipsychotic agents in particular. By collecting data of pregnancy outcomes from mothers and infants who were exposed to antipsychotics, it is expected that greater knowledge in this information scarce area will eventuate and culminate in the provision of detailed, evidence-based treatment options, which will hopefully improve the quality of life for mothers with mental illnesses and their children [37].…”

Effect of in utero exposure to the atypical anti‐psychotic risperidone on histopathological features of the rat placenta

“…The only report is one review article (Raha et al . ). Hence, this laboratory is a pioneer in reporting placental and foetal toxicity and their correlation when AAPDs like RIS was administered to pregnant rats.…”

“…Maternal exposure to drugs or chemicals may induce placental injuries and subsequently lead to placental dystrophy, reproductive toxicity, impaired foetal growth and development as well as congenital malformations depending upon the drug doses and exposure period (Raha et al . ; Furukawa et al . ,b).…”