Maternal Paracetamol And Ondansetron Use During Pregnancy And Risk Of Autism Spectrum Disorder In Offspring

Abstract

Background: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition influenced by genetic, prenatal, perinatal, and environmental factors. Paracetamol and ondansetron are commonly used during pregnancy, but evidence regarding their association with later ASD remains limited and inconsistent.

Objective: To evaluate the association between maternal paracetamol and ondansetron use during pregnancy and ASD in offspring, while considering relevant maternal, obstetric, neonatal, familial, and environmental factors.

Methods: A hospital-based matched case–control study was conducted at the Antenatal Care Clinic and Labor Ward of the Department of Obstetrics and Gynecology, Tikrit Teaching Hospital, Salah Al-Din Governorate, Iraq. Ninety mother–child pairs were included: 45 mothers of children with confirmed ASD and 45 mothers of children without ASD or another major neurodevelopmental disorder. Prenatal medication exposure was assessed by structured maternal interview and review of available medical, antenatal, obstetric, and prescription records. Exposure was classified according to medication, timing, frequency, duration, indication, and combined use. Associations were evaluated using crude odds ratios and multivariable logistic regression with 95% confidence intervals.

Results: Paracetamol exposure was more frequent among ASD cases than controls (68.89% vs. 42.22%, P=0.01; OR=3.00, 95% CI 1.27–7.09). Frequent/prolonged paracetamol use was also more common among cases (29.03% vs. 10.53%, P=0.04), with longer mean exposure duration (13.70±8.50 vs. 8.10±5.20 days, P=0.01). Ondansetron exposure was more frequent among cases (40.00% vs. 20.00%, P=0.04; OR=2.67, 95% CI 1.04–6.84), but was not independently associated after adjustment. Combined paracetamol and ondansetron exposure was associated with approximately fivefold higher crude odds of ASD (OR=5.23, 95% CI 1.63–16.77, P=0.005). In multivariable analysis, frequent/prolonged paracetamol use (AOR=3.86, 95% CI 1.08–13.79, P=0.04), combined exposure (AOR=4.12, 95% CI 1.17–14.52, P=0.03), and family history of ASD (AOR=5.63, 95% CI 1.08–29.41, P=0.04) remained independently associated with ASD.

Conclusion: In this study, frequent/prolonged maternal paracetamol use and combined prenatal exposure to paracetamol and ondansetron were independently associated with ASD in offspring, whereas exposure to either drug alone was not independently significant after adjustment. These findings indicate association rather than causation and should be interpreted in light of the small sample, retrospective exposure assessment, and possible residual confounding. Larger prospective studies using objective exposure measures are warranted.