Pediatrics Xagena

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ADHD in children associated with Paracetamol during pregnancy

Paracetamol ( Acetaminophen ) when used appropriately, it is considered mostly harmless. Over recent decades, the drug, which has been marketed since the 1950s, has become the medication most commonly used by pregnant women for fevers and pain.

Now, a long-term study by UCLA, in collaboration with the University of Aarhus in Denmark, has raised concerns about the use of Paracetamol during pregnancy.

In a report in the JAMA Pediatrics, researchers from the UCLA Fielding School of Public Health have shown that taking Paracetamol during pregnancy is associated with a higher risk in children of attention-deficity/hyperactivity disorder and hyperkinetic disorder.
The data raises the question of whether the drug should be considered safe for use by pregnant women.

ADHD, one of the most common neurobehavioral disorders worldwide, is characterized by inattention, hyperactivity, increased impulsivity, and motivational and emotional dysregulation. Hyperkinetic disorder is a particularly severe form of ADHD.

The causes of ADHD and hyperkinetic disorder are not well understood, but both environmental and genetic factors clearly contribute. Researchers know there has been a rapid increase in childhood neurodevelopmental disorders, including ADHD, over the past decades, and it's likely that the rise is not solely attributable to better diagnoses or parental awareness. It's likely there are environmental components as well.

Part of the neuropathology may already be present at birth, making exposures during pregnancy and/or infancy of particular interest.
Paracetamol is the most commonly used medication for pain and fever during pregnancy.

The UCLA researchers used the Danish National Birth Cohort, a nationwide study of pregnancies and children, to examine pregnancy complications and diseases in offspring as a function of factors operating in early life. The cohort focuses especially on the side effects of medications and infections.

The researchers studied 64,322 children and mothers who were enrolled in the Danish cohort from 1996 to 2002.
Paracetamol use during pregnancy was determined using computer-assisted telephone interviews that were conducted up to three times during pregnancy and again six months after childbirth.

The researchers next followed up with parents when their children reached the age of 7. They first asked parents about any behavioral problems in their children using the Strength and Difficulties Questionnaire, a standard behavioral screening questionnaire used by scientists. It assesses five domains, including emotional symptoms, conduct problems, hyperactivity, peer relationship and social behavior in children and adolescents between the ages of 4 and 16.

In addition, they obtained diagnoses of hyperkinetic disorder among the cohort's children ( at an average age of 11 ) from the Danish National Hospital Registry or the Danish Psychiatric Central Registry. Last, they identified if ADHD medications, mainly Methylphenidate ( Ritalin ), were redeemed for the children using the Danish pharmaceutical prescription database.

More than half of all the mothers reported using Paracetamol while pregnant. The researchers found that children whose mothers used Paracetamol during pregnancy were at a 13 to 37% higher risk of later receiving a hospital diagnosis of hyperkinetic disorder, being treated with ADHD medications or having ADHD-like behaviors at age 7.
The longer Paracetamol was taken ( that is, into the second and third trimesters ) the stronger the associations. The risks for hyperkinetic disorder / ADHD in children were elevated 50% or more when the mothers had used the common painkiller for more than 20 weeks in pregnancy.

It's known from animal data that Paracetamol is a hormone disruptor, and abnormal hormonal exposures in pregnancy may influence fetal brain development.

Paracetamol can cross the placental barrier, and it is plausible that Paracetamol may interrupt fetal brain development by interfering with maternal hormones or through neurotoxicity, such as the induction of oxidative stress, which can cause the death of neurons.

Researchers need further research to verify these findings, but if these results reflect causal associations, then Paracetamol should no longer be considered a safe drug for use in pregnancy. ( Xagena )

Source: University of California - Los Angeles, 2014