Hyderabad: For decades, paracetamol has been the go-to painkiller for pregnant women worldwide – the only over-the-counter option considered safe when fever or pain strikes. Then came September 2025, and suddenly that reassurance evaporated.

With studies suggesting links to autism and ADHD, FDA label updates, and warnings from US President Donald Trump, expectant mothers were left bewildered: had they been taking a dangerous drug all along?

The discussion on paracetamol use took a 180-degree turn

However, the answer, according to the most comprehensive research published in The Lancet Obstetrics, Gynaecology & Women’s Health, is no.

Maternal paracetamol use during pregnancy does not increase the risk of autism, ADHD or intellectual disability. But this raises an uncomfortable question: if the drug is safe, why did earlier studies suggest otherwise?

The difference comes down to something most people never consider when reading health headlines: research methodology. Not all scientific studies are created equal and the quality of a study’s design can mean the difference between finding a genuine health risk and creating unnecessary panic.

When associations aren’t what they seem

The FDA’s September 2025 label update reflected studies suggesting a possible association between prenatal paracetamol use and neurodevelopmental conditions. Research over the past decade had indeed suggested a potential link, particularly when paracetamol was used repeatedly or in later stages of pregnancy.

However, the FDA itself acknowledged a crucial limitation: “Whilst an association between acetaminophen and neurological conditions has been described in many studies, a causal relationship has not been established.”

Some studies showed no link, and scientific debate continued over how to interpret the data.

Commissioner Marty Makary framed the label update as making ‘parents and doctors aware of a considerable body of evidence about potential risks,’ whilst emphasising that ‘the ultimate choice remains with parents.’

The Lancet research team, led by Professor Asma Khalil from City St George’s, University of London, set out to determine whether this ‘considerable body of evidence’ truly supported the concerns being raised.

The gold standard: Sibling comparison studies

Researchers conducted a systematic review and meta-analysis of 43 existing studies, but with a critical difference from earlier analyses. They focused on the highest quality research methods, particularly sibling comparison studies.

These studies compare pregnancies from the same mother where one pregnancy involved paracetamol exposure and another did not. This design helps control for shared genetics, family environment and long-term parental characteristics that traditional studies cannot fully account for.

The distinction is crucial.

Earlier studies were ‘prone to biases, including being limited by the type of data collected and not exploring comparisons between siblings to account for family history,’ the research team noted.

Many earlier analyses relied on maternal self-report of paracetamol use, which is susceptible to recall bias. Mothers of children later identified with a neurodevelopmental condition might be more likely to recall or over-report medication use, creating a false association.

The numbers: A compelling case

The scale of the sibling-comparison analysis is significant.

Data included 262,852 children assessed for autism, 335,255 for ADHD, and 406,681 for intellectual disability.

The results were consistent across all three conditions. When compared to pregnancies with no exposure to paracetamol, maternal use showed no association with increased risk:

Autism spectrum disorder: odds ratio 0.98

ADHD: odds ratio 0.95

Intellectual disability: odds ratio 0.93

To understand what these numbers mean: an odds ratio of 1.0 indicates no difference in risk between groups. Values close to 1.0 – like 0.98, 0.95, or 0.93 – show virtually no effect. For context, a meaningful increased risk typically begins around 1.2 or higher (representing a 20% increase), whilst a substantial risk would be 2.0 or above (double the risk).

These odds ratios are so close to 1.0 that they confirm no meaningful association exists.

The lack of association remained even when researchers restricted their analysis to studies deemed at low risk of bias (the highest quality studies) and those with longer follow-up periods of over five years.

Why earlier studies showed different results

Earlier meta-analyses had suggested increased likelihood of autism spectrum disorder (pooled risk ratio approximately 1.19, representing a 19% increase) and ADHD (pooled risk ratio approximately 1.34, representing a 34% increase). These values seemed concerning at the time.

So, what changed?

The Lancet researchers found these earlier analyses 'were characterised by high heterogeneity and by reliance on conventional observational designs susceptible to residual confounding.’

Professor Khalil explained: “Our findings suggest that previously reported links are likely to be explained by genetic predisposition or other maternal factors such as fever or underlying pain, rather than a direct effect of the paracetamol itself.”

This phenomenon is known as ‘confounding by indication.’ The underlying condition that prompted paracetamol use – fever, pain or the maternal health issue causing these symptoms – might be more important in shaping neurodevelopmental outcomes than the drug itself.

The study noted that ‘prolonged analgesic use might coincide with underlying maternal health conditions,’ but the null findings in sibling designs indicate that ‘familial and genetic factors, including the well-established tendency for autistic traits to run in families, are more plausible explanations for previously observed associations than any direct effect of paracetamol.’

When studies fail to account for these shared family factors, they can mistake correlation for causation.

Several biological mechanisms had been proposed to explain how paracetamol might affect foetal neurodevelopment, including endocrine disruption, oxidative stress, altered prostaglandin signalling and epigenetic modifications. The immature foetal liver has limited detoxification capacity, potentially increasing susceptibility to these pathways.

However, the Lancet study noted that ‘most supporting evidence has been obtained from animal or in-vitro studies, and no human data have established causality.’

A pattern of flawed research

The paracetamol controversy reflects a broader issue in medical research. The World Health Organisation has dealt with similar patterns regarding vaccines and autism.

WHO emphasised that there is robust, high-quality evidence showing no link between childhood vaccines and autism. “A robust, extensive evidence base exists showing childhood vaccines do not cause autism,” WHO stated, stressing that original studies suggesting otherwise were flawed and have been discredited.

Since 1999, independent experts advising WHO have consistently confirmed that vaccines, including those containing thiomersal or aluminium, are not associated with autism or other developmental disorders.

WHO noted that global immunisation schedules have been adopted by all countries and are credited with saving at least 154 million lives over the past five decades. The agency warned that disruptions or delays in vaccination schedules increase risks not only for children but also for vulnerable populations.

In both cases – vaccines and paracetamol – methodologically rigorous research has contradicted initial alarm based on weaker studies.

The real risks of avoidance

Paracetamol remains one of the most widely used medicines in pregnancy, commonly taken for pain or fever. It is the only over-the-counter drug approved for use to treat fevers during pregnancy, with alternatives such as aspirin or ibuprofen carrying well-documented foetal risks.

The Lancet study emphasised that ‘avoidance of paracetamol based on inconclusive evidence could expose pregnant women and their babies to known risks associated with untreated fever or severe pain.’

Untreated maternal fever has been linked to miscarriage, congenital anomalies, preterm birth and differences in neurodevelopment. “For this reason, discouraging the appropriate use of paracetamol has the potential to cause greater harm than the drug itself,” the researchers noted.

The FDA itself acknowledged that most low-grade fevers do not require medication, but when treatment is necessary, paracetamol can be used under medical supervision. The agency advised clinicians to ‘consider minimising the use of acetaminophen during pregnancy for routine low-grade fevers,’ whilst balancing benefits for medically necessary cases.

The overuse problem: When safe becomes harmful

Whilst the Lancet research confirms paracetamol’s safety profile during pregnancy, concerns about overuse represent a separate and significant issue, particularly in countries like India.

Dr Raj noted that in India, paracetamol is extremely common in households, often used even for mild fever. “Anybody with any pain, slight headache, or small fever uses paracetamol just like chocolate,” he observed. Its easy availability and perceived safety contribute to widespread self-medication.

The concern isn’t about the medication’s inherent safety, but about when and how it’s being used. International guidelines recommend treating fevers only when necessary, typically above 102°F (38.8°C), but in India, paracetamol is often given at 99-100°F.

“Fever is not just a symptom; it is your immune system reacting to incoming pathogens,” Dr Raj explained. Suppressing fever too early can impair the function of T and B cells, reducing the child's ability to fight infections and develop acquired immunity.

Early intervention can compromise immune development, potentially weakening children’s immunity over time. Dr Raj advised that parents should use non-medication approaches first, including adequate hydration, rest, lukewarm sponge baths and light clothing.

“Taking paracetamol in the right dose and under medical supervision is helpful, but misuse can harm both mother and child,” Dr Raj emphasised. He supported the FDA’s label update, describing it as ‘a risk-management strategy to make parents and doctors aware of potential risks. Given that 1 in 31 children in the USA is autistic, timely awareness and careful use are crucial.’

Practical guidance for parents

The Lancet researchers and medical experts converge on clear guidance for appropriate paracetamol use:

Dr Raj advised physicians to guide parents carefully: “Paracetamol should not be used casually for mild discomfort; it should be reserved for medically indicated situations.”

His recommendations include using the minimum effective dose for the shortest duration, avoiding self-medication, checking combination drug labels to prevent double-dosing, and considering non-drug therapies where possible.

The FDA similarly advised that clinicians should counsel patients on proper dosing, limit the duration of use, and monitor for combination medications to avoid accidental double-dosing.

Parents are encouraged to avoid casual or prolonged use of paracetamol and consult healthcare professionals to ensure it is administered only when medically necessary. Dr Raj also stressed monitoring underlying conditions, particularly for mothers with liver or kidney issues or those consuming alcohol.

The current scientific consensus about paracetamol’s use

Professor Khalil’s message was unequivocal: “The message is clear - paracetamol remains a safe option during pregnancy when taken as guided. This is important as paracetamol is the first-line medication we recommend for pregnant women in pain or with a fever, and so they should feel reassured that they still have a safe option to relieve them of their symptoms.”

The Lancet findings align with guidance from leading professional organisations worldwide, including the American College of Obstetricians and Gynaecologists, the Royal College of Obstetricians and Gynaecologists, the International Federation of Gynaecology and Obstetrics, and the Society for Maternal-Fetal Medicine.

These organisations continue to recommend paracetamol as the first-line analgesic and antipyretic in pregnancy when used as directed.

Regulatory agencies such as the European Medicines Agency, the UK Medicines and Healthcare products Regulatory Agency and Health Canada hold similar positions.

The researchers hope that this gold-standard review will put an end to scepticism about using paracetamol during pregnancy.

As they concluded: “Maternal use of paracetamol during pregnancy does not seem to increase the likelihood of autism spectrum disorder, ADHD, or intellectual disability. This finding supports the recommendations made by major medical organisations regarding its use.”

Understanding the bigger picture

The paracetamol controversy illustrates why understanding research methodology matters. Not all studies are created equal, and associations observed in poorly controlled studies can disappear entirely when proper scientific methods are applied.

The key lesson for parents and healthcare providers is distinguishing between appropriate use and overuse. Paracetamol is safe for pregnant women who genuinely need it for medically indicated purposes. The risks lie not in the medication itself when properly used, but in two extremes: avoiding it when it’s truly needed (exposing mother and baby to the dangers of untreated fever or severe pain) or using it casually for minor discomfort that doesn't warrant medication.

With informed guidance and responsible use, paracetamol remains a safe and essential option for managing pain and fever during pregnancy, protecting both maternal and child health.