In this New Zealand birth cohort study with prospective follow up we found that the children of mothers who used acetamino- phen during pregnancy were at increased risk of having symptoms of ADHD as defined by screening questionnaires (the SDQ and Connors Rating System) at 7 and 11 years of age. These findings strengthen the contention that acetaminophen exposure in pregnancy increases the risk of ADHD-like behaviours, as published by Liew et al [1]. Our study also supports the earlier report that the findings are specific to acetaminophen, as there were no associations found with other commonly used drugs in pregnancy (aspirin, antacids and antibiotics).
More specifically, there was a significant effect of acetamino- phen use on parent scored SDQ total difficulties at age 7 after controlling for potential confounders. Particularly problematic at age 7 were emotional and conduct problems. Child- but not parent-reported total difficulties at age 11 remained significant in multivariable analyses. Child-reported problems with conduct and hyperactivity/inattention were particularly salient. The hyperac- tivity-inattention subscale consists of the following items: ‘restless,
overactive, cannot stay still for long’, ‘constantly fidgeting or squirming’, ‘easily distracted, concentration wanders’, ‘can stop and think things out before acting’ and ‘sees tasks through to the end, good attention span’.
There was also a significant effect of acetaminophen use on parent scored CRS:R-L ADHD symptoms at age 7 after controlling for the potential confounders. These were specific to subscales relating to the DSM-IV diagnostic criteria for ADHD Hyperactive-Impulsive type. Other subscales showing a significant multivariable effect included the CGI Restless-Impulsive subscale (indicates symptoms of restlessness, impulsivity and inattentiveness) and the CGI Emotional Liability subscale (identifies individuals who are prone to emotional responses and behaviours than would be expected to be typical, such as outbursts of crying or anger). Interestingly, for the CRS:R-L the association between acetamin- ophen use during pregnancy and parent-reported ADHD symptoms was not consistent at 11 years. It is not clear why the finding did not remain significant.
It is also not clear why the SDQ child reported ADHD symptoms remained significant at age 11 but not parent-reported problems. Self-reported problem behaviour has been shown to be a more valid indicator of mental and physical health than parent- reported problems [15–17]. It is also well known that ADHD has a complex etiology. It could be that other, more positive and enriching, environmental exposures begin to dilute the neurolog- ical outcome of acetaminophen over time. Acetaminophen was hypothesized to act as a hormone disrupter and thus alter fetal brain development [1]. Unfortunately we do not yet have data relating to ADHD symptoms measured after puberty. We also did not have information on dosage of acetaminophen use or trimester of use. Early life acetaminophen exposure may be significant determinants ADHD only at higher doses of the pain killer. In addition, other environmental factors not measured may also act through epigenetics to modify disease risk and neurological outcomes. More research is needed to provide a more precise assessment of risk and consequences of acetaminophen use during pregnancy.
Other limitations should be considered while interpreting our results. Firstly, the follow-up rate of 59 to 70% of the original population is clearly a potential source of bias. Nonetheless, this is unlikely to cause any systematic bias because the percentage of