Pregnant Women Should Avoid Paracetamol Which Is Linked to ADHD And Autism.
A recent study conducted by John Hopkins University that involved an international collaboration, shows that Acetaminophen
l) use during pregnancy
may be linked to an increased risk of childhood attention-deficit hyperactivity disorder
) and autism
spectrum disorder (ASD
is the most commonly used drug to prevent or reduce fever and to relieve pain amongst mothers during pregnancy
and infants in early life. Despite its use in this context, previous studies in both animal models and humans suggest a link between prenatal paracetamol
exposure and increased risk of conditions such as; asthma, cryptorchidism, ADHD
. Human studies have shown that paracetamol
can cross the placental barrier and can remain in an infant’s circulation for a long duration.
Typically in adults (with normal liver function) approximately 5–10% of paracetamol
is processed into a highly toxic metabolite called N-acetyl-p-benzoquinoneimine which is responsible for the hepatotoxicity (chemical-driven liver damage) of paracetamol
and is detoxified as 3-(N-acetyl-L-cystein-S-yl)-acetaminophen
. Due to a neonate’s limited capacity to metabolize the toxic metabolites, they can remain for a longer duration, resulting in increased in utero exposure.
Dr Jeffrey Keelan, Deputy Director of the Women and Infants Research Foundation, University of Western Australia commented on the available evidence linking paracetamol
exposure in pregnancy and neurodevelopmental conditions: in an interview with Thailand Medical
News “There is considerable evidence from a variety of studies that suggests there is a link between paracetamol (Acetaminophen) exposure in pregnancy and an increased risk of neurodevelopmental/behavioral problems, such as attention deficit/hyperactivity disorder (A
) and autism
spectrum disorders (ASD
He further added, “However, due to the nature of the evidence and potential uncertainties in its interpretation, there is still considerable debate as to whether or not there is sufficient evidence to formally advise women against taking this medication during pregnancy
The study, published in JAMA Psychiatry, aimed to examine the prospective link between cord plasma paracetamol
metabolites and the following physician-diagnosed conditions; ADHD
, and developmental disabilities in childhood. Nine hundred and ninety-six mother-infant dyads were analyzed; they were enrolled at birth and followed up prospectively from 1998 to 2018.
There were 996 participants studied (55% male) with a mean age of 9.8 years. The 996 participants had the following diagnoses: 25.8% with ADHD
only, 6.6% with ASD
only, 4.2% with ADHD
30.5% with other developmental disabilities, 32.8% with Neurotypical (individuals of typical developmental, intellectual, and cognitive abilities)
Blood samples from the umbilical cord from were examined for traces of paracetamol
metabolites were measured using umbilical cord plasma samples that had been collected at birth, maternal plasma paracetamol metabolites were also collected within three days of delivery. Levels of metabolite in both samples were measured using liquid chromatography–tandem mass spectrometry.
The medical study concluded that “cord biomarkers of fetal exposure to paracetamol
were linked to a significantly increased risk of childhood ADHD
in a dose-response fashion.”
Dr Anthony J. Hannan, NHMRC Principal Research Fellow from The Florey Institute of Neuroscience and Mental Health, University of Melbourne and Melbourne Brain Centre, provided expert comment on the study findings: "This new research article provides additional evidence that a woman’s use of the common drug paracetamol
could increase the risk of two major disorders of brain development, autism
spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD
). Both disorders result from complex combinations of genetic and environmental factors which remain poorly understood. This new evidence raises important public health issues. Can pregnant women avoid taking this drug without compromising their own health? Much more research into the causes of ASD
is required. Furthermore, if women are advised to not take paracetamol during pregnancy, then alternative treatments to this drug need to be explored, which will also require more research."
The researchers explain that whilst their findings support previous findings that show there is indeed a link between perinatal paracetamol
exposure and childhood neurodevelopmental risk, additional investigation is warranted.
The strengths of the study are that, for the first time, researchers have actual blood paracetamol
measurements to link exposure and dose with outcome, rather than indirect evidence of exposure at some point in pregnancy
. The study also is quite large, adding to its credibility.
Reference Ji, et al. (2019) Association of Cord Plasma Biomarkers of In Utero Acetaminophen Exposure With Risk of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in Childhood. JAMA Psychiatry. DOI: 10.1001/jamapsychiatry.2019.3259