A new April 2024 study in JAMA finds that prenatal exposure to acetaminophen during pregnancy does not reveal an increased risk of autism, ADHD or intellectual disability in children. The article documents extensive international concern that prenatal use of paracetamol can be dangerous. The concern is based on a number of extensive studies in recent years. These have led to a recommendation in the journal Nature and a public call from renowned doctors and scientists from all over the world to use paracetamol with extreme caution during pregnancy.

Please read: https://www.nature.com/articles/s41574-021-00553-7

Here is the translation of the summary: “Paracetamol (N-acetyl-p-aminophenol (APAP), also known as acetaminophen) is the active ingredient in more than 600 medications used to relieve mild to moderate pain and reduce fever. APAP is often taken by pregnant women because authorities, including the FDA and EMA, have long considered APAP to be appropriate for use during pregnancy when used as prescribed. However, increasing experimental and epidemiological research suggests that prenatal exposure to APAP may alter fetal development, which could increase the risk of some neurological, reproductive, and urogenital disorders. We summarize these findings and call for precautionary measures to be taken through targeted research efforts and awareness raising among healthcare professionals and pregnant women. APAP is an important medication, and alternatives to treat high fever and severe pain are limited. We recommend warning pregnant women early in pregnancy to: avoid APAP unless its use is medically indicated; to consult a doctor or pharmacist if unsure whether use is indicated and before long-term use; and minimize exposure by using the lowest effective dose for the shortest possible time. We propose specific measures to implement these recommendations. This consensus statement reflects our concerns and is currently supported by 91 scientists, clinicians and health experts from around the world.”

The main results are summarized in the following figures:

Fig. 1: In vivo, in vitro and ex vivo studies have shown that N-acetyl-p-aminophenol (APAP) directly disrupts hormone-dependent processes, leading to impaired reproductive and neurodevelopment in both sexes . In rodents, fetal exposure has been experimentally demonstrated to cause reproductive abnormalities in the male urogenital tract, including abnormalities in testicular function, abnormalities in sperm, and sexual behavior. Experiments have shown that the development of female ovaries is disrupted, leading to a reduced number of eggs and subsequent early ovarian failure and therefore reduced fertility. Fetal exposure to APAP has been shown to cause changes in neurotransmission in the brain, resulting in altered cognitive function, behavior and movement patterns. The studies have shown that the effect of APAP depends on the timing of exposure in relation to certain developmental processes and the duration and dose. AGD, anogenital distance. Source: Bauer, AZ, Swan, SH, Kriebel, D. et al. Paracetamol use during pregnancy — a call for precautionary action. Nat Rev Endocrinol 17, 757–766 (2021). https://doi.org/10.1038/s41574-021-00553-7


Figure 2. Human observational studies suggest that prenatal N-acetyl-p-aminophenol (APAP) exposure may be associated with both reproductive and neurobehavioral abnormalities in both sexes. APAP exposure during pregnancy could increase the risk of abnormalities of the male genitourinary and reproductive tract, as studies have shown an increased risk of undescended testicles (cryptorchidism) and a reduced distance between the anus and the base of the penis, called the anogenital distance (AGD). will have determined. Both reduced AGD and cryptorchidism are indicators of impaired masculinization and risk factors for reproductive disorders later in life. Prenatal APAP exposure has also been associated with earlier female pubertal development. In addition, epidemiological studies consistently suggest that prenatal APAP exposure may increase the risk of adverse neurodevelopmental and behavioral effects, such as: E.g. Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder, Speech Delay (in Girls) and Reduced Intelligence Quotient. Overall, the studies suggest that the timing and duration of maternal APAP use are critical factors. Source: Bauer, AZ, Swan, SH, Kriebel, D. et al. Paracetamol use during pregnancy — a call for precautionary action. Nat Rev Endocrinol 17, 757–766 (2021). https://doi.org/10.1038/s41574-021-00553-7

The new study from April 2024 in JAMA comes to the conclusion that taking paracetamol during pregnancy does not reveal any increased risk in children of autism, ADHD or mental retardation. The study does not represent an all-clear in several respects. It was retrospectively examined among women who were prescribed paracetamol during pregnancy and this was documented by a doctor. The data from women who took paracetamol through self-medication are unknown. Studies estimate that up to 60% of women do this independently during pregnancy. In addition, only effects on autism, ADHD and intellectual disability were examined. Here it was found that no effects could be uncovered. However, not finding something does not mean that you can rule out what has been found in numerous other studies. The authors therefore say even for paracetamol: “ The results should not be interpreted as a measure of safety. The dose in this study only reflected the prescribed medications, but not the actual intake of these medications or the use of over-the-counter medications.” The study data does not address information about prenatal exposure to paracetamol on later fertility, genital deformities, allergies, asthma, etc. It is precisely these risks that are warned about, among other things, prenatal exposure to paracetamol.

The now extensively proven risks of paracetamol in pain therapy and its largely ineffectiveness, especially for everyday causes of pain, must not be trivialized and pregnant women should not be denied the information they need to make informed, free decisions. Paracetamol is recommended without approval off-label for pregnant women to treat severe migraine attacks, a measure that would hardly be taken outside of pregnancy. It is depressing enough that previously pregnant women were not aware of these facts. It is all the more important that they become public and included in care. The concern that taking paracetamol during pregnancy poses lifelong risks for children is well founded based on current data. Even if the consequences for the unborn life have not yet been clarified in all possible details, when it comes to a drug that is largely ineffective for the most common everyday pains and has possible life-long consequences for the child, it is important to consider: it is better not to take it! There are alternatives in pain therapy. It's time to rethink.

Bauer AZ, Swan SH, Kriebel D, et al. Paracetamol use during pregnancy — a call for precautionary action. Nat Rev Endocrinol 17 , 757–766 (2021). https://doi.org/10.1038/s41574-021-00553-7

Ahlqvist VH , Sjöqvist H , Dalman C, et al. Acetaminophen Use During Pregnancy and Children's Risk of Autism, ADHD, and Intellectual Disability. JAMA. 2024;331(14):1205–1214. doi:10.1001/jama.2024.3172

https:// painklinik.de/paracetamol-in-der-schwangerschaft-zeit-umzudenken/