Neonatal Outcomes Worse in Babies Exposed to Antipsychotics
FROM THE WORLD CONFERENCE ON WOMEN'S MENTAL HEALTH
MADRID – Neonatal outcomes were generally worse among pregnant women who take antipsychotics than among those in the general population, but the rates of birth defects were not significantly altered, with an incidence of 5% compared with 4% in the general population.
Outcomes varied with the type of medication, Heather Gilbert, R.N., said at the World Conference on Women’s Mental Health.* The infants of women taking clozapine were most at risk, with two of the six babies born to these mothers (33%) exhibiting a congenital malformation. These infants also had a higher rate of neonatal complications, including premature birth, respiratory distress, and admission to the neonatal intensive care unit, according to Australia’s National Register of Antipsychotic Medications in Pregnancy. The incidence of gestational diabetes also was higher than among the general population (16% vs. 4%).
It was not surprising that clozapine proved particularly troublesome for babies exposed in utero, primary investigator Dr. Jayashri Kulkarni said in an interview. "The clozapine babies did have the worst outcomes, but this was not unexpected, because that is the most difficult medication to manage. But even in that worst group, the adverse issues were not catastrophic."
Thus, she said, the registry is "essentially a good-news story. "Most of the babies born were pretty healthy. We saw that the use of these medications did not lead to miscarriages and stillbirths," said Dr. Kulkarni, director of the Monash Alfred Psychiatry Research Centre in Melbourne. "What is important, from our standpoint, is that if a patient is doing well on a medication, it’s important to keep that medication going during pregnancy and not let her mental health deteriorate."
In fact, the tragic story of a patient who did stop her antipsychotic drugs during pregnancy inspired Dr. Kulkarni to begin the project.
The National Registry of Psychotic Medications in Pregnancy (NRAMP) obtained ethical approval from 42 boards across Australia before beginning to recruit patients. All women who register undergo a psychiatric evaluation at baseline, which includes the PANSS (Positive and Negative Syndrome Scale). Information about the pregnancy and outcomes is supplied by the clinicians attending the mother. The mother/infant pair is followed for 1 year, with six to eight postnatal interviews using the maternal assessment scales. The baby is assessed for developmental milestones at 6 and 12 weeks and at 6 and 12 months.
Because the registry is not a randomized controlled trial, Dr. Kulkarni has met with some skepticism from clinicians, who say that the data are not a reliable method of judging drug safety. "Ethically, a randomized trial is not something that we could do," she said. "We have to cope with people saying the data are messy," at least until the registry accumulates a much larger number of mother/infant pairs.
The participants’ mean age at recruitment was 32 years; the mean baseline PANSS score was 37. Diagnoses included bipolar affective disorder (40 patients), schizophrenia (28), schizoaffective disorder (8), unspecified psychotic disorder (8), depression (6), anxiety disorder (3), schizophreniform disorder (2), and borderline personality disorder (1). Diagnostic data were missing in four participants.
The largest proportion of the 100 women in the registry thus far took quetiapine during their pregnancy (43); the next most commonly used drug was olanzapine (14). Other medications were risperidone (6), clozapine (6), aripiprazole (4), haloperidol (4), long-acting injectable risperidone (Consta; 3), flupenthixol (2) and ziprasidone (1). In all, 12 women registered but did not receive antipsychotic treatment, and there are missing data on 5.
Pregnancy outcomes were somewhat better than those seen in the general population, with a 2% rate of stillbirth and miscarriage, compared with a 7% rate in the general population. There were two miscarriages (one exposed to quetiapine and one to clozapine) and one stillbirth (quetiapine).
Premature births occurred in 15% of the registry infants, compared with 8% of the general population. This occurred in nine infants exposed to quetiapine (21%), one exposed to risperidone (17%), one to flupenthixol (50%) and in the one exposed to ziprasidone.
Respiratory distress occurred in 27% of the registry infants, compared with 7% of the general population. It was seen in 14 babies exposed to quetiapine (32%), 5 exposed to olanzapine (36%), 1 exposed to risperidone (17%), 2 exposed to clozapine (33%), 1 exposed to haloperidol (24%), 2 exposed to Consta (66%) and in the single baby exposed to ziprasidone.
Medication withdrawal occurred in seven babies who were exposed to quetiapine (16%), and one exposed to olanzapine (7%).
Admission to the neonatal intensive care unit was highest among those exposed to clozapine (three patients; 50%) and flupenthixol (one; 50%). Birth weight below the 10th percentile occurred in babies exposed to quetiapine (four; 9%), olanzapine (one; 7%), risperidone (two; 33%), clozapine (one; 17%), and flupenthixol (one; 50%)
