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A new study backs up the link between paracetamol use during pregnancy and autism and ADHD symptoms.

Researchers from the Barcelona Institute for Global Health (ISGlobal) conducted an epidemiological study that they claim addresses some of the flaws in previous, similar studies and supports a link between maternal paracetamol (acetaminophen) use during pregnancy and symptoms of attention deficit hyperactivity disorder (ADHD) and autism spectrum conditions (ASC) in their children. Children exposed to paracetamol before birth were 19% more likely to have ASC symptoms and 21% more likely to acquire ADHD symptoms than those who were not exposed, according to a recent study including over 70,000 children from six European cohorts.

Jordi Sunyer, PhD, researcher at ISGlobal and co-author of the team's work published in the European Journal of Epidemiology, said, "Our results address some of the limitations of prior meta-analyses." “After reviewing all of the information on paracetamol usage and neurological development, we agree with prior recommendations that, while paracetamol should not be avoided in pregnant women or children, it should only be taken when absolutely necessary.”

The paper was publish under title, “Prenatal and postnatal exposure to acetaminophen in relation to autism spectrum and attention‑deficit and hyperactivity symptoms in childhood: Meta‑analysis in six European population‑based cohorts.”

Paracetamol, the safest analgesic/antipyretic for pregnant women and children, is used by an estimated 46-56 percent of pregnant women in developed countries at some point during their pregnancy. Prenatal paracetamol exposure, on the other hand, has been related to lower cognitive function, greater behavioral issues, and ASC and ADHD symptoms, according to the authors.

Previous meta-analyses of the association between prenatal paracetamol usage and ASC and ADHD symptoms have been criticized for their heterogeneity in terms of outcome assessment techniques and instruments, statistical methodologies, and confounders. Furthermore, the team concluded, “These investigations did not address significant unanswered problems regarding the connection between early acetaminophen exposure and ASC and ADHD symptoms.”

The purpose of the recently published study was to rectify flaws in past research. Slvia Alemany, PhD, ISGlobal researcher and lead study author, noted, “An effort was made to reconcile the assessment of ADHD and ASC symptoms, as well as the characterization of paracetamol exposure.” The Avon Longitudinal Study of Parents and Children (ALSPAC), DNBC, Gene and Environment: Prospective Study on Infancy in Italy (GASPII), the Generation R Study, INMA (including four subcohorts), and the Mother–Child Cohort in Crete were all used in the study (RHEA). From 1991 through 2008, mother–child couples were sought.

“The sample is vast, with cohorts from several European nations, including the United Kingdom, Denmark, the Netherlands, Italy, Greece, and Spain,” Alemany added. “We also employed the same criterion across all cohorts, eliminating the variety of criteria that has plagued past research.”

The researchers looked at 73,881 children who had data on prenatal or postnatal paracetamol exposure, at least one symptom of ASC or ADHD, and key variables. 14 percent to 56 percent of moms reported taking paracetamol while pregnant, depending on the cohort. When compared to non-exposed children, children who were prenatally exposed to acetaminophen were 19% and 21% more likely to develop ASC and ADHD symptoms in the borderline/clinical range, respectively.

For males, the relationship was just marginally stronger. “When stratified by sex, these relationships were marginally stronger among boys compared to girls, but positive relationships with effect sizes of equal magnitude were detected in both strata, especially in the case of ADHD,” the researchers explained. “Our data imply that if there are any differential sex effects of acetaminophen on ASC and ADHD symptoms, they are minor and may be contingent on the number of patients, outcome definition, and assessment,” the researchers write. “We also discovered that prenatal exposure to paracetamol affects males and girls in the same way, as we detected practically no differences,” Alemany noted.

According to the researchers, the relationship between prenatal acetaminophen exposure and ADHD symptoms had the most consistent pattern of results. “Regardless of the cohort removed in the leave-one-out analysis, positive correlations were identified in all cohorts and were of similar magnitude. This finding is consistent with a prior meta-analysis, which found that prenatal acetaminophen exposure increased the chance of ADHD by 25% to 34%. Even after excluding the largest cohort, the link between prenatal acetaminophen use and ASC symptoms remained remained positive.

The study also looked at postnatal paracetamol exposure and found no link between childhood paracetamol use and ASC symptoms. Nonetheless, considering the heterogeneity of postnatal paracetamol exposure among the three cohorts, which ranged from 6–92.8 percent, the research team concluded that more research is needed.

Despite acknowledging the study's limitations, the researchers concluded that "...the homogeneity of the findings among the different cohorts, the novel assessment of postnatal acetaminophen exposure, and the use of a harmonized definition of exposure and outcome as well as common statistical approaches overcomes the criticisms of previous meta-analysis."

“These findings suggest providing explicit information to pregnant women and their partners about potential long-term consequences of acetaminophen use,” the researchers stated. When all research on paracetamol and neurodevelopment is considered, they concur with earlier recommendations that “...paracetamol should not be repressed in pregnant women or children, but it should be taken sparingly when necessary.”

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