Whereas now we have a physique of literature analyzing the danger of main malformations in youngsters uncovered to benzodiazepines throughout being pregnant (which is basically reassuring), there may be significantly much less data on the results of this class of medicines on long-term neurodevelopmental outcomes. Earlier this yr, a scientific overview from Wang and colleagues pulled collectively the restricted data on neurodevelopmental outcomes in youngsters with in utero publicity to benzodiazepines.
The overview from Wang and colleagues famous that whereas there was not a robust sign to point threat of worse neurodevelopmental outcomes in benzodiazepine-exposed youngsters, the info concerning long run neurodevelopmental outcomes was, as much as that time, very restricted.
New Information from Taiwan Well being Insurance coverage Database
In a research printed final week, researchers used linked information from beginning certificates and the Taiwan Nationwide Well being Insurance coverage Analysis Database (2004-2017) to look at the prevalence of autism spectrum dysfunction and attention-deficit/hyperactivity dysfunction in youngsters with and with out benzodiazepine publicity. The cohort research included 1,138,732 moms with a complete of 1,516,846 reside births.
Pharmacy dispensation information had been used to establish uncovered pregnancies. ICD-9 and 10 codes within the medical file had been used to establish youngsters with ASD and ADHD. The imply (SD) follow-up time for the total little one pattern was 8.5 (SD 3.2) years.
About 5.0% of the kids (n = 76,411) had been uncovered to a benzodiazepine throughout being pregnant. Benzodiazepine publicity throughout being pregnant was related to a small however statistically important improve in threat of ADHD; trimester of publicity didn’t have an effect on threat (first trimester publicity: unadjusted hazard ratio [HR], 1.24 [95% CI, 1.20-1.28]; second trimester: HR, 1.27 [95% CI, 1.21-1.34]; third trimester: HR, 1.25 [95% CI, 1.14-1.37]).
The danger of ASD was additionally barely elevated in youngsters with benzodiazepine publicity (first trimester publicity: HR, 1.13 [95% CI, 1.05-1.21]; second trimester: HR, 1.10 [95% CI, 0.98-1.22]; third trimester: HR, 1.21 [95% CI, 1.00-1.47]).
Adjusted Analyses Present No Improve in Threat of ADHD or ASD
Earlier research analyzing little one outcomes have documented the numerous challenges in calculating threat in uncovered versus unexposed youngsters. Estimates of threat are by necessity derived from non-randomized research, by which there are vital variations between the ladies who elect to take a specific medicine throughout being pregnant and the ladies who don’t use the medicine. Most clearly the 2 teams differ when it comes to the explanation (or indication) for taking a specific medicine. Confounding by indication is a crucial consideration, and now we have seen in lots of research observing that, after adjusting for potential confounding components, many dangers attributed to medicine publicity are now not important.
Within the present research, the researchers had been capable of modify for a lot of completely different potential confounding components, together with yr of beginning, gestational age, maternal and paternal age, maternal and paternal historical past of psychiatric sickness, maternal smoking, and maternal use of opioids. After adjustment, there was now not a distinction between uncovered and unexposed youngsters when it comes to threat for ASD or ADHD.
As well as, the researchers had been capable of management maternal genetic and environmental components by evaluating threat in uncovered versus unexposed siblings. They noticed no variations between the 2 teams when it comes to threat for ADHD or ASD.
That is the most important research thus far analyzing neurodevelopmental outcomes in youngsters uncovered to benzodiazepines throughout being pregnant, together with over 76,000 youngsters. It’s also the research with the longest follow-up. Whereas these are appreciable strengths, there are some limitations. This research doesn’t embody data concerning frequency of dosing or dosage. Relying on the dysfunction being handled, benzodiazepines are prescribed throughout a variety of dosages and could also be used repeatedly or intermittently. Neurodevelopmental outcomes could differ relying on the dose and sort of benzodiazepine used.
Whereas this research can’t utterly rule out the likelihood that prenatal publicity to benzodiazepines could have an effect on neurodevelopmental outcomes, this research, mixed with earlier smaller research, supplies reassuring data to ladies with questions concerning the usage of benzodiazepines throughout being pregnant.
So what can we inform our sufferers? The present research and former systematic critiques don’t present a robust sign indicating threat of worse neurodevelopmental outcomes in youngsters with prenatal publicity to benzodiazepines.
Ruta Nonacs, MD PhD
Chen VC, Wu SI, Lin CF, Lu ML, Chen YL, Stewart R. Association of Prenatal Exposure to Benzodiazepines With Development of Autism Spectrum and Attention-Deficit/Hyperactivity Disorders. JAMA Netw Open. 2022 Nov 1;5(11):e2243282.
Wang X, Zhang T, Ekheden I, et al. Prenatal exposure to benzodiazepines and Z-drugs in humans and risk of adverse neurodevelopmental outcomes in offspring: a systematic review. Neurosci Biobehav Rev. 2022 Jun; 137:104647.
