Globally, a lot of focus has been placed on assessing mental health as part of antenatal maternal health assessments1. With this focus has come the increasing identification and diagnoses of psychiatric illnesses among pregnant and postpartum women. Consequently, there is now a growing use of antipsychotic medications during pregnancy, most of which are atypical antipsychotics 2. However, despite the widespread and increasing use of antipsychotics during pregnancy, most doctors continue to remain ill-informed about the potential dangers these drugs pose on the developing foetus3.

Compounding the problem is that studies conducted to evaluate the association between use of anti-psychotic during pregnancy and risk of congenital malformations have not only been inconsistent in their findings, but also inadequately represented owing to their small sample sizes4. Two of the largest epidemiologic studies conducted to date, with 570 and 561 participants respectively, reported a 1.5- to 2-fold increase in the risk for congenital malformations, contrasting previous smaller studies that reported no risk of congenital malformations with the intake of antipsychotics.5 So what are we to make of all this information, and how should we translate this into directions for patients?

Atypical antipsychotics more likely to increase risk of congenital malformations

In September 2016, JAMA Psychiatry published a large-scale study where the researchers sought to determine whether an association exists between antipsychotic use during the first trimester of pregnancy and the risk for congenital malformations. The cohort study6 was conducted by researchers from the Brigham Women’s Hospital using data from a national database of more than one million Medicaid-insured women in the United States of America, for pregnant women who sought treatment from January 2000 until December 2010.

In this database, 9258 women (0.69%) filled a prescription for an atypical antipsychotic during the first trimester, and 733 women (0.05%) filled a prescription for a typical antipsychotic. The rate of congenital malformations was then compared between those who took antipsychotics and those who did not.

Results showed that on average, 38% of the births by mothers who had taken typical antipsychotics during the first trimester of pregnancy had congenital malformations, while 44% of the births by those who took atypical antipsychotics had congenital malformations. Though the association between use of antipsychotic and risk of congenital malformations was weaker when the researchers controlled for the underlying psychiatric condition as well as other variables including race and age, the study concluded that the risk for malformations was small, it remained significantly increased for atypical antipsychotics, which is something that should be considered for all doctors who need to prescribe such medications.

Single-most large-scale study on association between antipsychotics and development of congenital anomalies

Thus far, this is the single-most large-scale study that gives credible evidence on the minimal association between intake of antipsychotics and development of congenital anomalies, an association which hitherto had been unclear. It is considered to be a well-designed one.

The findings of this study6 suggest that use of atypical antipsychotics does not significantly increase the risk for congenital malformation except for risperidone, which the researchers thought would benefit from additional studies.

As the most common cause of pregnancy loss in the first trimester is congenital abnormalities, the association between antipsychotics and the risk of congenital anomalies definitely still need to be studied in more detail, as findings could eventually help to reduce pregnancy loss. But for now, in light of the strong evidence presented, it is advisable for doctors to take all these factors into consideration if required to prescribe such medications. MIMS

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1. Satyanarayana, V. A., Lukose, A. & Srinivasan, K. Maternal mental health in pregnancy and child behavior. Indian J. Psychiatry 53, 351–61 (2011).
2. Toh, S. et al. Prevalence and trends in the use of antipsychotic medications during pregnancy in the U.S., 2001–2007: a population-based study of 585,615 deliveries. Arch. Womens. Ment. Health 16, 149–157 (2013).
3. Johnson, M. et al. Measuring perinatal mental health risk. Arch. Womens. Ment. Health 15, 375–86 (2012).
4. Galbally, M., Snellen, M. & Power, J. Antipsychotic drugs in pregnancy: a review of their maternal and fetal effects. Ther. Adv. drug Saf. 5, 100–9 (2014).
5. Iqbal, M. M. et al. The potential risks of commonly prescribed antipsychotics: during pregnancy and lactation. Psychiatry (Edgmont). 2, 36–44 (2005).
6. Huybrechts, K. F. et al. Antipsychotic Use in Pregnancy and the Risk for Congenital Malformations. JAMA Psychiatry 73, 938 (2016).