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Created September 24, 2025, last updated 2 months ago.
Collection: 172, Score: 403, Trend score: 0, Read count: 403, Articles count: 13, Created: 2025-09-24 04:54:43 UTC. Updated: 2025-09-24 23:05:32 UTC.Notes
From the best-available current evidence (Ahlqvist 2024): NO
The American Academy of Obstetrics and Gynecology's journal ACOG, summarises it best in Damkier et al.'s 2025 review article:
"According to the current scientific evidence, in utero exposure to acetaminophen is unlikely to confer a clinically important increased risk of childhood ADHD or ASD." - Damkier (2025)
Ahlqvist et al's 2024 Swedish cohort study of 2.48 million children showed that when controlling for family confounders by using sibiling controls, there was no association between paracetamol/acetaminophen use and various neurodevelopmental problems:
"Acetaminophen use during pregnancy was not associated with children's risk of autism, ADHD, or intellectual disability in sibling control analysis." - Ahlqvist (2024)
The problem with many of the earlier (and often contradictory) studies that showed a possible association, was that by necessity these were observational studies that struggled to control for confounders. The classic "association is not causation" trap. Ahlqvist et al's very large study, while still observational, uses matched sibling controls to neutralise "unobserved confounding" – and reassuringly, the association dissapears.
Nonetheless, it’s worthwhile being aware of the body of evidence and how it has evolved over the last decade. Professional obstetric organisation advice remains unchanged: paracetamol is appropriate to use in pregnancy when managing fever and pain, which untreated have their own detrimental fetal effects.
Daniel Jolley
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Collected Articles
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Obstetrics and gynecology · Feb 2025
ReviewAcetaminophen in Pregnancy and Attention-Deficit and Hyperactivity Disorder and Autism Spectrum Disorder.
"According to the current scientific evidence, in utero exposure to acetaminophen is unlikely to confer a clinically important increased risk of childhood ADHD or ASD."
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Acetaminophen Use During Pregnancy and Children's Risk of Autism, ADHD, and Intellectual Disability.
Acetaminophen use during pregnancy was not associated with children's risk of autism, ADHD, or intellectual disability in sibling control analysis.
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Paracetamol is widely used to manage fever and pain during pregnancy worldwide. However, paracetamol may affect the pregnant woman and fetus, once this drug crosses the placental barrier after therapeutic doses and may impair fetal liver function, affecting fetus growth and development. Thus, this study aimed to investigate the association between paracetamol use during pregnancy and perinatal outcomes as preterm birth, low birth weight, and small for gestational age. ⋯ The findings of this study do not suggest an increased risk of perinatal outcomes. However, it should not be assumed that paracetamol is a risk-free medication and its use must be rational.
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Review
[Pain management during pregnancy : An expert-based interdisciplinary consensus recommendation].
Pregnancy and pain of different origins is an unfavorable combination that presents all practitioners with special challenges. Pain negatively affects the homeostasis of humans. Patient compliance and in-depth knowledge of the fetotoxicity and teratogenicity of the substances are necessary to maintain a balance between therapy for the mother and safety of the unborn child. ⋯ A deliberated concept for pain therapy during pregnancy should be initiated with a non-pharmacological intervention and, if necessary, supplemented with pharmacological agents.
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Paracetamol (acetaminophen) is the most commonly used drug in the world, with a long record of use in acute and chronic pain. In recent years, the benefits of paracetamol use in chronic conditions has been questioned, notably in the areas of osteoarthritis and lower back pain. Over the same period, concerns over the long-term adverse effects of paracetamol use have increased, initially in the field of hypertension, but more recently in other areas as well. ⋯ In particular, an increased risk of gastrointestinal bleeding and a small (~4 mmHg) increase in systolic blood pressure are adverse effects for which the evidence is particularly strong, and which show a degree of dose dependence. As our estimation of the benefits decreases, an accurate assessment of the harms is ever more important. The present review summarizes the current evidence on the harms associated with chronic paracetamol use, focusing on cardiovascular disease, asthma and renal injury, and the effects of in utero exposure.
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Paracetamol is commonly used to treat fever and pain in pregnant women, but there are growing concerns that this may cause attention deficit hyperactivity disorder and autism spectrum disorder in the offspring. A growing number of epidemiological studies suggests that relative risks for these disorders increase by an average of about 25% following intrauterine paracetamol exposure. The data analyzed point to a dose-effect relationship but cannot fully account for unmeasured confounders, notably indication and genetic transmission. ⋯ It reduces prostaglandin formation via competitive inhibition of the peroxidase moiety of prostaglandin H2 synthase, while its metabolite N-arachidonoyl-phenolamine activates transient vanilloid-subtype 1 receptors and interferes with cannabinoid receptor signaling. The metabolite N-acetyl-p-benzo-quinone-imine, which is pivotal for liver damage after overdosing, exerts oxidative stress and depletes glutathione in the brain already at dosages below the hepatic toxicity threshold. Given the widespread use of paracetamol during pregnancy and the lack of safe alternatives, its impact on the developing brain deserves further investigation.
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Acetaminophen (paracetamol) is available over the counter in most countries and is widely considered to be safe for use during pregnancy; studies report gestational exposures to acetaminophen that lie in the 46%-65% range. Acetaminophen influences inflammatory and immunologic mechanisms and may predispose to oxidative stress; these and other effects are hypothesized to have the potential to compromise neurodevelopment in the fetal and infant brain. Two ecological studies suggested that population-level trends in the use of acetaminophen were associated with trends in the incidence/prevalence of autism; one of these studies specifically examined acetaminophen use during pregnancy. ⋯ A very recent large cohort study with a 12.7-year follow-up found that gestational exposure to acetaminophen was associated with an increased risk of autism spectrum disorder, but only when a hyperkinetic disorder was also present. In the light of existing data associating acetaminophen use during pregnancy and subsequent risk of attention-deficit/hyperactivity disorder, this new finding suggests that the predisposition, if any, is toward the hyperkinetic syndrome rather than to autism. In summary, the empirical data are very limited, but whatever empirical data exist do not support the suggestion that the use of acetaminophen during pregnancy increases the risk of autism in the offspring.
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Acetaminophen is extensively used during pregnancy. But there is a lack of population-representative cohort studies evaluating its effects on a range of neuropsychological and behavioural endpoints. We aimed to assess whether prenatal exposure to acetaminophen is adversely associated with neurodevelopmental outcomes at 1 and 5 years of age. ⋯ Prenatal acetaminophen exposure was associated with a greater number of autism spectrum symptoms in males and showed adverse effects on attention-related outcomes for both genders. These associations seem to be dependent on the frequency of exposure.
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The potential etiological role of early acetaminophen exposure on Autism Spectrum Conditions (ASC) and Attention-Deficit/Hyperactivity Disorder (ADHD) is inconclusive. We aimed to study this association in a collaborative study of six European population-based birth/child cohorts. A total of 73,881 mother-child pairs were included in the study. ⋯ Boys and girls showed higher odds for ASC and ADHD symptoms after prenatal exposure, though these associations were slightly stronger among boys. Postnatal exposure to acetaminophen was not associated with ASC or ADHD symptoms. These results replicate previous work and support providing clear information to pregnant women and their partners about potential long-term risks of acetaminophen use.
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Hormones and behavior · May 2018
ReviewPrenatal paracetamol exposure and child neurodevelopment: A review.
The non-prescription medication paracetamol (acetaminophen, APAP) is currently recommended as a safe pain and fever treatment during pregnancy. However, recent studies suggest a possible association between APAP use in pregnancy and offspring neurodevelopment. ⋯ Together, these nine studies suggest an increased risk of adverse neurodevelopmental outcomes following prenatal APAP exposure. Further studies are urgently needed with; precise indication of use and exposure assessment of use both in utero and in early life. Given the current findings, pregnant women should be cautioned against indiscriminate use of APAP. These results have substantial public health implications.
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Prior studies have raised concern about maternal acetaminophen use during pregnancy and increased risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in their children; however, most studies have relied on maternal self-report. ⋯ Cord biomarkers of fetal exposure to acetaminophen were associated with significantly increased risk of childhood ADHD and ASD in a dose-response fashion. Our findings support previous studies regarding the association between prenatal and perinatal acetaminophen exposure and childhood neurodevelopmental risk and warrant additional investigations.
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Dev Med Child Neurol · Aug 2015
ReviewUse of paracetamol during pregnancy and child neurological development.
Paracetamol (acetaminophen) remains the first line for the treatment of pain and fever in pregnancy. Recently published epidemiological studies suggested a possible association between paracetamol exposure in utero and attention-deficit-hyperactivity disorder/hyperkinetic disorder (ADHD/HKD) or adverse development issues in children. However, the effects observed are in the weak to moderate range, and limitations in the studies' design prevent inference on a causal association with ADHD/HKD or child neurological development. ⋯ However, no firm conclusion can be made on the relevance of these observations to humans. We conclude that additional well-designed cohort studies are necessary to confirm or disprove the association. In the context of current knowledge, paracetamol is still to be considered safe in pregnancy and should remain the first-line treatment for pain and fever.
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Acetaminophen (paracetamol) is the most commonly used pain and fever medication during pregnancy. Previously, a positive ecological correlation between acetaminophen use and autism spectrum disorders (ASD) has been reported but evidence from larger studies based on prospective data is lacking. We followed 64,322 children and mothers enrolled in the Danish National Birth Cohort (DNBC; 1996-2002) for average 12.7 years to investigate whether acetaminophen use in pregnancy is associated with increased risk of ASD in the offspring. ⋯ Longer duration of use (i.e., use for >20 weeks in gestation) increased the risk of ASD or infantile autism with hyperkinetic symptoms almost twofold. Maternal use of acetaminophen in pregnancy was associated with ASD with hyperkinetic symptoms only, suggesting acetaminophen exposure early in fetal life may specifically impact this hyperactive behavioral phenotype. Autism Res 2016, 9: 951-958. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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