2018 Study Highlights
- All nine studies suggest prenatal APAP is associated with adverse neurodevelopment.
- These neurodevelopmental endpoints include ADHD, ASD and lower IQ.
- Associations were strongest for hyperactivity and attention-related outcomes.
- Controlling for indication for use, when possible, did not explain associations.
- Given these findings, pregnant women should be cautioned against indiscriminate APAP use.
Abstract
Background
The non-prescription medication paracetamol (acetaminophen, APAP) is currently recommended as a safe pain and fever treatment during pregnancy. However, recent studies suggest a possible association between APAP use in pregnancy and offspring neurodevelopment.
Objectives
To conduct a review of publications reporting associations between prenatal APAP use and offspring neurodevelopmental outcomes.
Methods
Relevant sources were identified through a key word search of multiple databases (Medline, CINAHL, OVID and TOXNET) in September 2016. All English language observational studies of pregnancy APAP and three classes of neurodevelopmental outcomes (autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and intelligence quotient (IQ)) were included. One reviewer (AZB) independently screened all titles and abstracts, extracted and analyzed the data.
Results
64 studies were retrieved and 55 were ineligible. Nine prospective cohort studies fulfilled all inclusion criteria. Data pooling was not appropriate due to heterogeneity in outcomes. All included studies suggested an association between prenatal APAP exposure and the neurodevelopmental outcomes; ADHD, ASD, or lower IQ. Longer duration of APAP use was associated with increased risk. Associations were strongest for hyperactivity and attention-related outcomes. Little modification of associations by indication for use was reported.
Conclusions
Together, these nine studies suggest an increased risk of adverse neurodevelopmental outcomes following prenatal APAP exposure. Further studies are urgently needed with; precise indication of use and exposure assessment of use both in utero and in early life. Given the current findings, pregnant women should be cautioned against indiscriminate use of APAP. These results have substantial public health implications.