Maternal medication use in pregnancy and offspring ASD risk: A prescription-wide, target-informed study.

This large Israeli study looked at whether medications taken during pregnancy might affect autism risk in children. Researchers compared nearly 1,400 children with autism to over 94,000 children without autism. They found that five medications appeared to increase autism risk while two seemed protective. The medications that showed increased risk included certain hormones and steroids.

Iron supplements appeared protective. The study used advanced methods to account for why medications were prescribed, but more research is needed to confirm these findings.

This Israeli case-cohort study examined associations between maternal prescription drug use during pregnancy and autism spectrum disorder (ASD) risk in offspring. Among 1,400 individuals with ASD and 94,713 without, researchers found five medications significantly associated with increased ASD risk (including cyproterone and prednisolone) and two with decreased risk (ferrous sulfate and lynestrenol). The study employed sophisticated methodology including indication proxy adjustment and pharmacological target analysis to address confounding by indication. Four shared pharmacological targets were identified, with enrichment analysis suggesting involvement of cholinergic and serotonergic signaling pathways.

While the study design aimed to minimize confounding, the authors acknowledge limitations and call for further research to establish causality.

Results suggest certain medications during pregnancy may influence ASD risk, but findings require replication before clinical practice changes. Healthcare providers should continue evidence-based prescribing while considering individual risk-benefit ratios. Further research needed to establish causality and inform pregnancy medication guidelines.

Single study design limits generalizability. Causal inference remains challenging despite methodological adjustments for confounding by indication. Ethical constraints prevent randomized controlled trials. Sample from single country may not apply to other populations. Further replication studies needed.

Certain prescription drugs used during pregnancy are associated with offspring autism spectrum disorder (ASD). Nonetheless, ASD risk following prenatal exposure to most drugs remains unknown. Furthermore, methodological challenges and ethical concerns hinder the scope for causal inference. We used a case-cohort study design of a nationally representative sample from Israel to examine the associations between maternal prescription drug use during pregnancy and offspring ASD.

To scrutinize these associations, the analyses were (a) adjusted for indication proxy (level 2 Anatomical Therapeutic Chemical (ATC) codes), (b) repeated using shared pharmacological targets as exposures, and (c) inspected further through target-enrichment analysis. The sample included 1,400 individuals with and 94,713 without an ASD diagnosis. Among all drugs prescribed during pregnancy, five were statistically significantly associated with increased offspring ASD risk after adjustment for indication proxy (e.g., hazard ratio [95% confidence interval] cyproterone = 2.71 [1.17-6.25] and prednisolone = 2.10 [1.27-3.49]), and two with decreased risk (ferrous sulfate = 0.82 [0.68, 0.99] and lynestrenol = 0.43 [0.2, 0.93]). Further analysis revealed four pharmacological targets shared by these drugs, which were themselves associated with ASD (e.g., neuronal acetylcholine receptor α4β4 = 1.45 [1.05-1.99] and serotonin 2b receptor = 1.31 [1.04-1.61]).

Enrichment analysis suggested the association between ASD and medications affecting cholinergic and serotonergic signaling. Increased ASD risk followed prenatal exposure to five prescription drugs, and decreased risk followed exposure to two. Subsequent analyses suggested no confounding by indication in these associations, but further studies are warranted.