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
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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. Prenatal and postnatal (up to 18 months) acetaminophen exposure was assessed through maternal questionnaires or interviews. ASC and ADHD symptoms were assessed at 4–12 years of age using validated instruments. Children were classified as having borderline/clinical symptoms using recommended cutoffs for each instrument. Hospital diagnoses were also available in one cohort. Analyses were adjusted for child and maternal characteristics along with indications for acetaminophen use. Adjusted cohort-specific effect estimates were combined using random-effects meta-analysis. The proportion of children having borderline/clinical symptoms ranged between 0.9 and 12.9% for ASC and between 1.2 and 12.2% for ADHD. Results indicated that children prenatally exposed to acetaminophen were 19% and 21% more likely to subsequently have borderline or clinical ASC (OR = 1.19, 95% CI 1.07–1.33) and ADHD symptoms (OR = 1.21, 95% CI 1.07–1.36) compared to non-exposed children. 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.

From the Discussion section:

The results of our meta-analysis representing more than 70,000 children of six European population-based birth/child cohorts indicated that children prenatally exposed to acetaminophen were 19% and 21% more likely to subsequently have ASC and ADHD symptoms within the borderline/clinical range, respectively, compared with non-exposed children. The association with ASC was attenuated after omitting the largest cohort but remained positive. When stratifying by sex, these associations were slightly stronger among boys compared to girls but positive associations with effect sizes of similar magnitude were observed in both strata, especially in the case of ADHD. Postnatal exposure to acetaminophen was not associated with either of the outcome, thought there was evidence of between-study heterogeneity for the association with ASC symptoms.

From the Outcomes section:

ASC and ADHD symptoms were assessed using validated parent-reported questionnaires or linked hospital records. Autistic symptoms were assessed using the Development And Well-Being Assessment (DAWBA) [18] (ALSPAC), the Pervasive Developmental Problems (PDP) subscale of the Child Behaviour Checklist for Toddlers (CBCL1½–5) [19] (GASPII and The Generation R Study), the Childhood Autism Spectrum Test (CAST) [20] (INMA) and an ASC scale derived from the CBCL for 6–18 (CBCL6–18) [21] (RHEA). ADHD symptoms were assessed using the Development and Well-Being Assessment (DAWBA) [18] (ALSPAC); the Conner’s Parent Rating Scale Revised short form (CPRS-R:S) [22] (The Generation R Study), the Hyperactivity/Inattention subscale of the Strengths and Difficulties Questionnaire (SDQ) [23] (DNBC), the Attention Deficit and Hyperactivity problems subscale of the CBCL1½-5 and CBCL6/18 (GASPII and RHEA), and the ADHD Criteria of DSM-IV (DSM-ADHD Questionnaire) [24] (INMA). Higher scores indicate more symptoms.

    • sysgen [none/use name,they/them]
      ·
      4 years ago

      Sex, history of infection, parental age and education.

      These aren't very big risk factors for ADHD (though age is a big one for autism), mainly it's that we simply don't know of a lot of covariates for ASD and ADHD for now.

      • Chomsky [comrade/them]
        ·
        4 years ago

        Yeah, just saying that they try and do say that the controls were limited. I mean, we won't find the risk factors if we don't look.

        Like, if the study is funded by asparin manufacturers yeah it's problematic, but I don't see anything wrong at first glance.

        • sysgen [none/use name,they/them]
          ·
          4 years ago

          Sure, I'm just saying that OP's hypothesis that there is a third common factor is definitely possible, correlation isn't causation, etc...

          But yes, a solid mechanism and further studied are needed. Otherwise there isn't anything obviously wrong, but it's not sufficient for a causative link yet. There is probably something to it.

          For all we know they might have asked for thirty common medications and done p-hacking, or a dozen other things, which is why we can't jump to conclusions yet.

          Meanwhile you should take ibuprofen just in case lol

          • Chomsky [comrade/them]
            ·
            4 years ago

            Yeah. I have a friend that is a statistician and she does medical research. She does data mining, basically just throws numbers at the wall and sees what sticks and passes off correlations to other researchers for possible further study.

            Definitely a bit of a yikes for me because my son just finished teething and we use acetaminophen on days it was bad.

            • sputnik1 [comrade/them]
              ·
              3 years ago

              Postnatal exposure to acetaminophen was not associated with ASC or ADHD symptoms.