ADHD Risk Not Related With Prenatal Benzodiazepine or Z-Hypnotic Exposure

Prenatal exposure to benzodiazepines or z-hypnotics likely has little impact on childhood attention-deficit/hyperactivity disorder (ADHD) risk, according to results of a study published in JAMA Network Open.

Investigators from the University of Oslo and the Norwegian Institute of Public Health sourced data for this prospective cohort study from the population-based Mother, Father and Child Cohort Study (MoBa) which pooled data from linked Norwegian registries. Pregnant women and their families were recruited for MoBa between 1999 and 2008. Mother-offspring dyads (n=82,201) were evaluated for the effect of prenatal exposure to benzodiazepines and z-hypnotics during early (gestational weeks 0-16), middle (gestational weeks 17-28), or late (gestational week 29-delivery) pregnancy and the risk for ADHD diagnosed during childhood.

Among pregnancies, 0.8% were exposed and 99.2% were unexposed to the study drugs. The women in the cohorts had a mean ages of 31.2 (SD, 4.8) and 30.2 (SD, 4.5) years, 52.3% and 54.2% were primiparous, 16.4% and 7.5% smoked during pregnancy, 22.8% and 11.6% consumed alcohol during pregnancy, 71.7% and 82.0% of pregnancies were planned, and the obstetric comorbidity indexes were 0.8 (SD, 1.2) and 0.5 (SD, 1.0), respectively.

Among the exposed group, more used benzodiazepine-anxiolytics (n=332) than z-hypnotics (n=225) and 25 women used both. Exposure was higher in early (n=435) rather than middle and/or late (n=374) pregnancy.

During an average follow-up period of 11.3 years, 2.7% of offspring were diagnosed with ADHD. Children were diagnosed with ADHD at an average age of 8.5 (SD, 2.0) years and filled their first ADHD prescription at 9.2 (SD, 2.1) years.

The rate of ADHD (3.3%) was higher among children born to the subset of women (n=19,585) who reported anxiety, depression, or sleeping problems in the 6 months prior to pregnancy.

No association between ADHD and exposure to benzodiazepines and/or z-hypnotics was observed in early pregnancy (weighted hazard ratio [wHR], 0.74; 95% CI, 0.39-1.94) or middle/late pregnancy (wHR, 0.76; 95% CI, 0.35-1.61) compared with no exposure or for exposure in multiple periods compared with a single 4-week period (wHR, 1.48; 95% CI, 0.63-3.45). Results were similar among the cohort with prepregnancy mental health symptoms.

The findings of this study may have been limited by the reliance on self-reported medication use during pregnancy which could have been subject to recall or willingness to divulge.

“This cohort study found no association between use of benzodiazepines and z-hypnotics during pregnancy and childhood ADHD in their offspring according to timing of exposure and number of exposed intervals. The study results provide reassurance for pregnant patients in need of benzodiazepines and z-hypnotics; however, these findings need to be interpreted with caution due to low study power in some of the analyses,” concluded the study authors.