Neonatal Outcomes Worse in Babies Exposed to Antipsychotics

NICU admission also occurred in seven babies who were exposed to quetiapine (16%), one exposed to olanzapine (19%), three exposed to clozapine (50%), two exposed to Consta (66%), and one exposed to flupenthixol (50%).

Large-for-gestational-age babies (greater than the 90% percentile) occurred in eight who were exposed to quetiapine (19%), one exposed to olanzapine (7%), one exposed to aripiprazole (25%), one exposed to haloperidol (25%), and in the single baby exposed to ziprasidone.

Five infants were born with congenital anomalies. One infant who was exposed to clozapine had craniosynostosis and hypertelorism; the mother took 350-750 m/day throughout the pregnancy. The baby’s skull deformity had a partial surgical correction and resulted in a developmental delay at 12 months.

The second infant had gastroschisis and a horseshoe kidney. The mother took 400 mg of clozapine daily throughout pregnancy. The gastroschisis had a surgical correction, whereas the kidney is being managed conservatively and the baby is progressing well.

Congenital malformations occurred in 2 of the 14 babies who were exposed to quetiapine. One baby had an atrial-septal defect; the mother took 1,110 mg/day of quetiapine throughout pregnancy as well as 1,000 mg/day of zuclopenthixol. The defect was resolving spontaneously by 12 months with conservative management.

The second baby who was exposed to quetiapine had a cleft lip and palate, as well as hydrocephalus. The mother took 600 mg/day well throughout the pregnancy. The clefts were surgically repaired and excess cephalic fluid was drained. The baby is progressing and being monitored.

[Sidebar: Removing Antipsychotic Medications in Pregnancy: A Case in Point]

One anomaly occurred in a baby exposed to risperidone: This infant had an abnormal renal collecting tubule and bilateral talipes. The mother took 2 mg/day risperidone up to 36 weeks’ gestation. The abnormal collecting tubule is functioning well, and the talipes underwent surgical repair and braces, with a good result.

Gestational diabetes accounted for most of the maternal complications. "We are seeing a lot of gestational diabetes in the moms – higher than the general population. Maybe this is because they were already overweight, or the drugs contributed to weight gain and insulin intolerance. But clinicians should be aware of this heightened risk, look diligently for signs of it, and give this information to their patients."

The disorder occurred in 16 of the 100 women, including 6 who were taking quetiapine (14%), 4 taking olanzapine (28%), 1 taking risperidone (17%), 4 taking clozapine (67%), and 1 taking Consta (33%). Preeclampsia occurred in one patient who was taking quetiapine (2%).

The registry also tracked smoking, as well as alcohol and substance abuse, but did not control for these factors in any multivariate analysis. Antenatally, smoking was noted in 31% of registry women, compared with 16% of the general population. But antenatal alcohol consumption among registry participants was lower than that in the general population (12% vs. 60%). Substance abuse incidence was about 12% in the registry participants, compared with 7% in the general population. "We have lots of stories from women who smoked a lot of cigarettes and drank a lot, and decreased this during pregnancy. That protective instinct of the mother for the fetus is alive and well, and kicked in among these women."

Managing antipsychotic medications during pregnancy is a new concept to most clinicians in Australia, who continue to assume that the drugs will tip the risk:benefit ratio to the pit of endangering the developing baby, Dr. Kulkarni said. This has led to many recommendations that women with serious mental disorders avoid ever bearing children. She has even received calls from physicians who are angry that the registry seems to support childbearing in this group, "asking me why I’m allowing the gene pool to be polluted."

In her daily work, Dr. Kulkarni deals with significant regrets from women who were told that their mental illness and medication should preclude any childbearing. "I see a number of women in their 50s, approaching menopause, who were given the advice many years back never to have children because of the drug dangers," she said. "Now, they are grieving and experiencing depression over what could have been. The medical profession does not play God. We can only provide information and advice, but not take the role of driving the decision about having children or not."

Dr. Kulkarni said that the registry’s results are interesting, but until many more women are enrolled, it’s difficult to use it as a clinical guideline about what drug is safest for both mother and baby. "We need to accumulate a lot more data, and in the future, we hope to expand the program to sites all over the world."