Ji and co-authors conducted a cohort study in 2020 on 996 mother-infant pairs enrolled in the Boston Birth Cohort [17]. We found recent and better evidence because this study did not rely on interviews and questionnaires, only decreasing the recall bias. Instead, it included cord blood samples collected at birth and measured three acetaminophen metabolites in the plasma. Unchanged acetaminophen was present in all samples. Maternal plasma acetaminophen metabolites collected three days after the delivery was also measured. The children were followed up prospectively from 1998 to 2018. Another aspect of the study providing better evidence is that physician-based diagnoses were used to collect children's medical records. Cord acetaminophen burden was calculated for each outcome. We found that acetaminophen use during pregnancy was more strongly associated with an increased risk of ADHD and ASD than other neurodevelopmental outcomes in a dose-response fashion. After adjusting the confounders, the results were consistent. The interactions were performed between each covariate and cord acetaminophen burden, but these were not significant.
Tovo-Rodrigues and co-authors studied this association to investigate emotional and hyperactivity/inattention symptoms in 4231 children in 2018 in the Brazilian population using data from the 2004 Pelotas Birth Cohort [18]. This study showed that boys exposed to acetaminophen during pregnancy were more likely to have emotional and hyperactivity symptoms at six years of age than at 11 years. The study didn't show this association in girls.
Bornehag and co-authors also studied this association in 2018 using data from the Swedish Environmental, Longitudinal, Mother and child, Asthma and allergy (SELMA), with a sample of 754 mother-child pairs [19]. This study used adjusted urinary acetaminophen concentration in addition to maternal interviews. In addition, it provided stronger evidence by using trained practitioners for language assessment in the offspring at 30 months of age. Acetaminophen was measurable in all urinary samples, and the concentration was compatible with the amount of acetaminophen taken prenatally. Boys had more language delays than girls. But both the number of acetaminophen tablets taken and the urinary acetaminophen concentration were associated with greater language delay in girls but not in boys.
Vlenterie and co-authors conducted a study in 2016 on 51,200 mother-child pairs extracting data from the Norwegian Mother and Child Cohort Study (MoBa) and observed the psychomotor development in children at 18 months [20]. It showed similar results of delayed motor milestones, especially walking, with long-term use of acetaminophen. We also observed a weak association of communication deficits, gross motor impairment, sociability, and shyness with long-term use but not with short-term. This study also estimated the Numbers Needed to Harm (NNH) for motor and communication milestones as 48 and 67, respectively.
Avella-Garcia and co-authors conducted a study in 2016, a subset of the Spanish Birth Cohort Study, on 2644 mothers and children who were evaluated at one and five years [21]. The results were consistent with an increased risk of developing Autism related symptoms in boys with prenatal use of acetaminophen. But the effects on hyperactivity/inattention-related symptoms were the same in all children (boys and girls), and these effects were more strongly associated with increased frequency of use.
A Danish cohort study in 2016 by Liew and co-authors using data from Danish National Birth Cohort (1996-2002) conducted on 1491 mother-child pairs reported acetaminophen adverse effects on child IQ, attention, and executive function, at five years of age [26,22].
We concluded that using acetaminophen during pregnancy was associated with attention problems and poorer executive development in children, especially with a longer duration of acetaminophen use [22]. Only attention deficits were related to first-trimester acetaminophen use, and the effects were not sex-dependent, but parent-related executive deficits were more prevalent in boys. The results were consistent even after adjusting the common confounders of maternal fever, infection, inflammation, pain, or other diseases during the pregnancy [22].
For IQ development, children whose mothers used acetaminophen but didn't have the fever had lower performance IQ, and normal verbal IQ scores compared to kids whose mothers did not have a fever and used acetaminophen [26]. The children whose mothers had a fever and did not use acetaminophen had lower performance and verbal IQ scores at five years. This effect was stronger for first and second-trimester use, and no cumulative effect was seen. Effect modification by child's sex was not seen.
Recently in 2020, Parker and co-authors conducted a study on 560 mother-child pairs using data from the Ontario Birth Study (OBS) to evaluate this association but found a contrast between mother and teacher-reported behavioral problems in children [23]. We found from this data source that scores for behavioral problems in children were higher from maternal data than from the teacher's report giving us an insight to urgently develop more precise and reliable methods or investigations to estimate the role of acetaminophen in developmental disorders.
In addition, Arneja and co-authors studied the effects of acetaminophen on preterm birth, small for gestation age, and low birth weight among children, which are being studied as precursors of neurodevelopmental disorders [24]. Children of mothers who used acetaminophen pre-pregnancy were at higher risk of being small for gestation age and having low birth weight. Increased frequency of acetaminophen use was associated with higher risks of these outcomes. But acetaminophen use during pregnancy did not show any association with these outcomes....
Ovo je samo dio istraživanja, bez da sam citirao ona povezana sa ADHD-om te ostalim neurodegenerativnim poremećajima...