Paracetamol, also known as acetaminophen, is one of the most commonly used over-the-counter medications during pregnancy for the management of pain and fever (Zvanca et al., 2018).It remains the recommended first-line analgesic due to its long history of use and its perceived safety compared to other painkillers (ENTIS, 2025). However, a 2021 consensus statement by an international group of scientists and clinicians, alongside several observational studies, raised concerns about possible associations between prenatal paracetamol exposure and neurodevelopmental disorders in offspring, particularly autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) (Andrade, 2016; Afadassa et al., 2016). Despite ongoing debate, a definitive causal link has not been established, and many concerns arise from methodological limitations within existing research (Sheikh et al., 2025). Until clearer evidence is available, paracetamol remains the first-line analgesic for use during pregnancy when clinically indicated, guided by the lowest effective dose for the shortest possible duration (ENTIS, 2025). 

Estimates suggest that over 50% of pregnant women worldwide use paracetamol (Zvanca et al., 2018). Its widespread use is due to its effectiveness as both an analgesic and an antipyretic (fever reducer). Pregnant women commonly use paracetamol to manage headaches and fever, but it is also used for conditions such as infections, migraines, and pain associated with autoimmune diseases, where the immune system mistakenly attacks healthy cells (ENTIS, 2025). Untreated fever or severe pain during pregnancy can pose significant risks to both the mother and the foetus. For example, high maternal fever has been associated with an increased risk of miscarriage and certain congenital abnormalities, including neural tube and heart defects (Zvanca et al., 2018). Similarly, unmanaged pain may contribute to depression, anxiety, and hypertension in the mother, which can indirectly affect foetal development. As a result, effective pain and fever management during pregnancy is essential. 

Paracetamol is frequently chosen over alternative analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, as well as opioids such as codeine or morphine, and high doses of aspirin (Zvanca et al., 2018). These alternatives are associated with increased risks during pregnancy, including miscarriage, congenital abnormalities, and complications later in gestation. This further explains why paracetamol remains the preferred option when medication is required. 

When a pregnant woman takes paracetamol, it crosses the placenta and can pass the foetal blood-brain barrier (Andrade, 2016). This transfer is described as flow-limited, meaning that the amount crossing the placenta depends on placental blood flow. Paracetamol primarily crosses via passive diffusion, moving from areas of higher concentration in maternal blood to lower concentrations in foetal tissues. During pregnancy, paracetamol clearance increases, meaning the drug is removed from the mother’s bloodstream more rapidly (Zvanca et al., 2018). This may reduce pain relief for the mother and raise the possibility of higher dosing, which could increase the formation of oxidative toxic metabolites produced during drug metabolism (pr & pr, 2020).

Animal studies have suggested that a higher proportion of paracetamol may reach the foetal brain compared to the maternal brain (Andrade, 2016). Research in pregnant rats has shown that approximately 21% of paracetamol reaches the maternal brain, compared to 45% reaching the foetal brain. This suggests that the developing foetal brain may be exposed to relatively higher concentrations of paracetamol during critical stages of neurodevelopment, even when maternal pain relief is limited. 

Over the past decade, numerous studies have examined potential associations between prenatal paracetamol exposure and autism development (Afadassa et al., 2016). However, findings remain inconsistent due to methodological variation, including differences in dosage measurement, exposure timing, and confounding variables (Sheikh et al., 2025). Some research suggests that paracetamol may influence neurodevelopmental pathways linked to ASD, potentially through increased oxidative stress or inflammation, both of which can disrupt normal brain development (pr & pr, 2020). Paracetamol has also been described as having endocrine-disrupting properties, which may interfere with hormones such as oestrogen and progesterone that are essential for maintaining pregnancy and supporting foetal growth through placental function (pr & pr, 2020). 

Despite these findings, many organisations highlight the limitations of studies suggesting a causal relationship. A major issue is reliance on retrospective self-reporting, where mothers recall paracetamol use years after pregnancy, increasing the risk of recall bias (Sheikh et al., 2025). Additionally, confounding factors such as genetics, underlying illness, and environmental influences are difficult to fully control. 

A large Swedish cohort study published in JAMA in 2024 analysed data from 2.48 million children and found no evidence that prenatal paracetamol exposure increases the risk of autism, ADHD, or intellectual disability (Ahlqvist et al., 2024). While initial analyses suggested a possible association, sibling comparison analyses-where one sibling was exposed and the other was not-showed no difference in neurodevelopmental outcomes. This indicates that earlier associations may reflect shared genetic or environmental factors rather than a direct effect of paracetamol (Ahlqvist et al., 2024). Due to its scale and rigorous methodology, this study is widely regarded as a gold standard in this field. 

Health authorities worldwide currently recommend a precautionary approach. Organisations including the European Medicines Agency (EMA), the American College of Obstetricians and Gynecologists (ACOG), the Royal College of Obstetricians and Gynaecologists (RCOG), and the NHS advise that paracetamol should be used during pregnancy only when necessary, at the lowest effective dose and for the shortest possible duration (ENTIS, 2025). This guidance aims to balance effective symptom management with minimising unnecessary medication exposure. 

Pregnant women are also encouraged to consult healthcare professionals before taking any medication. This ensures decisions are tailored to individual medical history, symptoms, and stage of pregnancy. In many cases, a short course of paracetamol remains the safest and most effective option for managing pain or fever, both of which can pose risks if left untreated (University of Oxford, 2025).

Experts also advise against switching to alternatives such as ibuprofen or other NSAIDs, which are generally not recommended during pregnancy (Zvanca et al., 2018). These drugs can affect foetal heart development, kidney function, and circulation, particularly in later stages of pregnancy. Consequently, paracetamol remains the preferred choice when analgesia is required. 

Overall, the current global consensus is that paracetamol is safe and effective for use during pregnancy when taken responsibly (ENTIS, 2025). Ongoing research continues to refine understanding of potential risks, but experts agree that the dangers associated with untreated pain or fever outweigh the theoretical risks of paracetamol when used appropriately (Ahlqvist et al., 2024). Pregnant women are therefore advised to use paracetamol cautiously, only when necessary, and under medical guidance. 

Sources 

Ahlqvist, V.H., Sjöqvist, H., Dalman, C., Karlsson, H., Stephansson, O., Johansson, S., Magnusson, C., Gardner, R.M. and Lee, B.K. (2024). Acetaminophen use during pregnancy and children’s risk of autism, ADHD, and intellectual disability. JAMA. Available at: https://www.semanticscholar.org/paper/bb1de5a4fb93329d862a224add98ad0ca425c794 (Accessed: 10/11/24). 

Afadassa, S., Soares, D. and Marroun, H.E. (2016). The association of prenatal exposure to paracetamol and neurodevelopmental disorders in childhood: A systematic review. Available at: 

https://www.semanticscholar.org/paper/450083515528f7b97c22cf74c645cbd0d808a852 (Accessed: 10/11/24). 

Andrade, C. (2016). Use of acetaminophen (paracetamol) during pregnancy and the risk of autism spectrum disorder in the offspring. The Journal of Clinical Psychiatry. Available at: https://www.semanticscholar.org/paper/51524be99c85e0fa8fdf93fd17f94ff11a402b6d (Accessed: 10/11/24). 

ENTIS (2025). Paracetamol in pregnancy and autism spectrum disorder – ENTIS position statement. Available at: 

https://www.entis-org.eu/entis-news/entis-position-statement-paracetamol-in-pregnancy-and autism-spectrum-disorder (Accessed: 10/11/24). 

Nariai, H., Okubo, Y., Hayakawa, I. and Sugitate, R. (2025). Maternal acetaminophen use and offspring’s neurodevelopmental outcome: A nationwide birth cohort study. Paediatric and Perinatal Epidemiology. doi: https://doi.org/10.1111/ppe.70071. 

pr, M. and pr, S. (2020). Role of paracetamol in the pathogenesis of autism spectrum disorder: A growing perspective. Available at: 

https://www.ejmanager.com/fulltextpdf.php?mno=93113 (Accessed: 10/11/24).

Sheikh, J., Allotey, J., Sobhy, S. and Plana, M. (2025). Maternal paracetamol (acetaminophen) use during pregnancy and risk of autism spectrum disorder and attention deficit/hyperactivity disorder in offspring: Umbrella review. BMJ. Available at: https://www.bmj.com/content/391/bmj-2025-088141.short (Accessed: 10/11/24). 

University of Oxford (2025). No evidence that paracetamol use in pregnancy causes autism spectrum disorder. Available at:  https://www.wrh.ox.ac.uk/news/no-evidence-that-paracetamol-use-in-pregnancy-causes-auti sm-spectrum-disorder (Accessed: 10/11/24). 

Zvanca, M.E., Petca, A., Vladareanu, S., Tecuci, A. and Boț, M. (2018). Paracetamol during pregnancy: How safe is it? Ginecologia Ro. doi: 

https://doi.org/10.26416/gine.20.2.2018.1711.