Do antipsychotics increase risk of congenital malformations?

August 31, 2016

A study looks at the potential link between antipsychotic medication and congenital malformations. Also, are current prenatal screening standards as good as expanded carrier screening? Plus: How much do overweight and obesity increase the risk of certain cancers.

Analysis of a nationwide sample of pregnant women provides reassurance about use of antipsychotic medication in the first trimester while raising concern about a potential link between one particular drug in this class and congenital malformations. The findings, published inJAMA Psychiatry, represent outcomes from more than 1.3 million pregnancies.

The data reviewed were from 1,341,715 women who were represented in the Medicaid Analytic Extract database from January 1, 2000 to December 31, 2010. The participants had been enrolled in Medicaid from 3 months before their last menstrual period until at least 1 month after delivery of a live-born infant. To estimate the relative risk of congenital malformations associated with use of antipsychotic medication, the authors used generalized linear models with fine stratification on the propensity score to control for underlying psychiatric disorders and other confounders.

During the first trimester, 9258 (0.69%) of the women filled at least 1 prescription for an atypical antipsychotic medication and 733 (0.05%) filled at least 1 prescription for a typical antipsychotic medication. Congenital malformations were reported in 32.7 per 1000 births that were not exposed to the drugs versus 44.5 per 1000 births exposed to atypical antipsychotic medications and 38.2 per 1000 births exposed to typical antipsychotic medications.

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Risk of malformations was increased by exposure to the atypical drugs (relative risk [RR], 1.36; 95% CI, 1.24-1.50) but not by exposure to the typical antipsychotic agents. After adjustment for confounding, the RR fell to 1.05 (95% CI, 0.96-1.16) for the atypical agents and 0.90 (95% CI, 0.62-1.31) for the typical antipsychotic drugs. Similar findings were reported for cardiac malformations.

Looking at individual antipsychotic agents, the authors found that risperidone was associated with a small increased risk of overall malformations (RR, 1.26; 95% CI, 1.02-1.56) and of cardiac malformations (RR, 1.26; 95% CI, 0.88-1.81), which was not statistically significant. Both were independent of the confounders measured.

The researchers concluded that use of antipsychotic drugs in the first trimester “does not meaningfully increase the risk of congenital malformations overall or cardiac malformations in particular.” They also said that additional study was required of the association seen between risperidone and increased risk of malformations.  

NEXT: Is the current standard for prenatal carrier screening too limited?


Is the current standard for prenatal carrier screening too limited?

Results of a new study published in JAMA suggest that expanded carrier screening may increase detection of more potentially serious genetic conditions than are accounted for in current professional guidelines, which focus on a limited number of single-gene conditions.

The findings are from a retrospective modeling analysis of results with expanded carrier screening between January 2012 and July 2015. The testing was done on 346,790 reproductive-aged individuals, mostly from the United States, who did not have any known indications for specific genetic testing and was offered by doctors providing reproductive care. For the purpose of the analysis, risk was defined as the probability that a hypothetical fetus created by a random pairing of individuals (within or across 15 self-reported racial/ethnic categories; there were 11 categories with >5000 samples) would be either homozygous or compound heterozygous for 2 mutations that were presumed to cause intellectual disability or a significantly shortened lifespan. Profound conditions were those that caused both.

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Among major US racial/ethnic groups, the calculated frequency of fetuses affected by either a profound or severe condition ranged from 94.5 per 100,000 (95% confidence interval [CI], 82.4-108.3 per 100,000) for Hispanic couples to 392.2 per 100,000 (95% CI, 366.3-420.2 per 100,000) for Ashkenazi Jewish couples. In most of the categories, expanded carrier screening modeled more hypothetical fetuses at risk of severe or profound conditions than screening based on current screening guidelines (Mann-Whitney P < .001). Among Northern European couples, the 2 professional guidelines-based screening panels modeled 55.2 hypothetical fetuses affected per 100,000 (95% CI, 51.3-59.3 per 100 000), while expanded carrier screening modeled 159.2 fetuses per 100,000 (95% CI, 150.4-168.6 per 100,000). When compared to expanded carrier screening, guideline-based screening ranged in the identification of hypothetical fetuses from 6% (95% CI, 4%-8%) among East Asian couples to 87% (95% CI, 84%-90%) for African or African-American couples.

The researchers concluded that expanded carrier screening may increase the detection of carrier status for more potentially serious genetic conditions than are represented in current recommendations from professional societies. They believe, however, that prospective studies in at-risk populations should be done before expanded screening is adopted.

NEXT: How overweight and obesity may increase risk of some cancers


How overweight and obesity may increase risk of some cancers

Data from the Women’s Health Initiative (WHI) suggest that the longer a woman is overweight or obese and the greater the degree of overweight, the higher her risk of certain cancers-particularly endometrial cancer. The findings, published in PLOS Medicine, are from an observational study of WHI.

Included in the analysis were data on 73,913 women from whom the investigators had body mass index (BMI) information from at least 3 occasions during follow-up, who were free of cancer at the study’s baseline, and for whom complete covariate information was available. A quadratic growth model was used to estimate BMI across ages. Overweight duration (BMI ≥ 25 kg/m2), obesity duration (BMI ≥ 30 kg/m2), and weighted cumulative overweight and obese years were calculated using predicted BMIs. Cox proportional hazard models were used to determine cancer risks associated with overweight and obesity duration. Through secondary analyses, the importance of effect modifiers and confounders like smoking status and ethnicity were assessed.

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The data showed that a longer duration of overweight was significantly linked to incidence of all obesity-related cancers (hazard ratio per 10-year increment: 1.07, 95% confidence interval 1.06–1.09). For postmenopausal breast and endometrial cancer, every 10-year increase in adulthood duration of overweight was tied to a 5% and 17% increase in risk, respectively. After adjusting for the intensity of overweight, those figures rose to 8% and 37%, respectively. The risks of both of those cancers was far more pronounced in women who had never used postmenopausal hormones.

Some of the limitations of the study included that some of the anthropometric information was obtained through retrospective self-reports. In addition, some data were missing from various time points, as often happens with longitudinal studies with long periods of follow-up. However, the researchers said this was overcome partially by using growth curve models.

Investigators concluded that longer durations of overweight and obesity are associated with an increased risk of developing certain cancers. The degree of overweight also appears to play a major role in that risk, especially with endometrial cancer.