Acetaminophen is an essential guideline and evidence-based medication that resides in my personal and clinical toolbox for pain relief. Acetaminophen is often combined with opioids to reduce the side effects of the opioids and provide multimodal (multiple agents) pain control. Acetaminophen is the evidence-based medication for treating pain in pregnancy.
I have four years of experience working with OB physicians in a high-risk pregnancy clinic. I was constantly asked what the risk of teratogenicity (the ability of a substance or agent to cause structural or functional defects in a developing fetus or embryo) is when taking prescribed or over-the-counter medications during pregnancy. The categories were A, B, C, D, and X. Category A is no risk demonstrated in human studies. Category B is no risk demonstrated in animal studies, and no controlled human studies are available, or the risk seen in animals wasn’t confirmed in humans. Acetaminophen is in category B. Category C is adverse effects shown in animal studies, but no adequate human studies exist. The potential benefits may justify use despite risks. Category D is evidence that human fetal risk exists, but benefits may be acceptable in serious situations, such as life-threatening illness where safer drugs are not effective. Category X includes studies in humans or animals that show fetal abnormalities, and the risks clearly outweigh any potential benefits. This category comprises medications that are contraindicated for prescribe in pregnancy.
The American College of Obstetrics and Gynecology (September 25, 2025) reaffirms that acetaminophen remains the analgesic and antipyretic of choice during pregnancy. Judicious use at the lowest effective dose for the shortest necessary duration, in consultation with an obstetrician–gynecologist or other obstetric care professional, remains consistent with best practice.
The current weight of evidence does not support a causal link between prenatal acetaminophen use and neurodevelopmental disorders. At this time, no change in clinical practice is warranted based on new publications, and ACOG’s recommendations for the use of acetaminophen for specific indications remain current (Obstet Gynecol 2022;139:944–72).
I have spent many decades learning how to evaluate medication studies. Every healthcare professional must critically analyze each trial and decide if the study is relevant and valid. Questions applied to each research trial include the methodology, potential biases, statistical analysis, power (ensuring enough patients were studied to show that the outcome is not due to random chance), and whether the conclusions correlate with the study’s findings.
On September 22, 2025, the U.S. Food and Drug Administration (FDA) initiated a label change to suggest that acetaminophen use by pregnant women may be associated with an increased risk of neurological conditions such as autism and attention-deficit/hyperactivity disorder (ADHD) in children (https://www.fda.gov/news-events/press-announcements/fda-responds-evidence-possible-association-between-autism-and-acetaminophen-use-during-pregnancy).
An expert healthcare professional review identified recurring methodological limitations in the studies linking acetaminophen use in pregnancy to neurodevelopmental outcomes. The flaws in the studies used included reliance on maternal self-report with its potential for recall bias, lack of detailed data on dosage, duration, and timing of exposure heterogeneous outcome assessments (time when an exposure or treatment is initiated or changes of child neurodevelopment), often relying on parental or teacher surveys (non-healthcare-trained observations), failure to control for genetic and familial confounders, and neglect of postnatal acetaminophen exposure, which is common and biologically relevant.
I will play devil’s advocate. If the data were strong, with well-designed, unbiased, and highly powered studies showing a causal relationship of acetaminophen to autism, OB physicians would need to drastically change how they treat pain and fever during pregnancy. Opioids are not the answer due to the side effect of respiratory depression. Using NSAIDs like ibuprofen (Motrin) and naproxen (Aleve) in pregnancy, especially after 20 weeks, can cause serious problems for the baby, including kidney issues, low levels of amniotic fluid, and premature closure of a key fetal blood vessel (ductus arteriosus). The FDA recommends avoiding these drugs after 20 weeks of pregnancy, and using them only under a doctor’s supervision if necessary. After 30 weeks, NSAID use is not recommended due to the increased risk of the ductus arteriosus closing too early. Ductus arteriosus is a blood vessel in a fetus that carries blood from the placenta and bypasses the lungs. Acetaminophen is the safest and best option for pain during pregnancy; however, doses of acetaminophen are not to exceed 4 grams per day. Doses over 4 grams of acetaminophen may lead to liver toxicity.
Two studies, previous to this declaration by the FDA on September 22, 2025, found no correlation between acetaminophen use and autism or ADHD in children. In 2015, the FDA reviewed the available literature and determined that the evidence was inconclusive regarding a causal relationship between prenatal acetaminophen and ADHD. In 2017, the Society for Maternal-Fetal Medicine (SMFM) conducted an independent review of extensive cohort studies and reached the same conclusion: No clear causal relationship had been established (Autism Res 2016;9:951–8 and Am J Obstet Gynecol 2017;216:B14–5).
A trial titled Acetaminophen Use During Pregnancy and Children’s Risk of Autism, ADHD, and Intellectual Disability was published on April 9, 2024. It was a highly powered study that utilized an interesting methodology studying sibling groups in the same family (JAMA 2024;331(14):1205-1214). This trial was a nationwide cohort study with sibling control analysis, which included a population-based sample of 2,480,797 children born in 1995–2019 in Sweden, with follow-up through December 31, 2021. Sweden keeps track of the health records of entire families with similar genetic characteristics. Previous studies found a small association between acetaminophen and autism when they compared people in general populations. Per Brian K. Lee, PhD, who was one of the primary investigators in this study, “when looking at siblings, within the same family where the mom took acetaminophen for one pregnancy and not another, the increased risk of acetaminophen causing autism completely disappeared. There was no evidence to say that there was any effect whatsoever.” One of the limitations of this study is that the mothers may not have accurately reported how much acetaminophen they took and how often. A Japanese study of 200,000 pregnancies showed the same results as the Swedish study. There was a slightly increased risk of autism from acetaminophen, but when siblings were only analyzed with similar genetic makeup, there was no link (Paediatr Perinat Epidemio. 2025 September 2).
Not all studies are created equal. Brian Lee, PhD, reminded me that cause-and-effect studies can lead to false assumptions due to confounding factors. Dr. Lee related the association between eating ice cream and drowning. Hot weather increases a person’s ice cream consumption and their propensity to go swimming, leading to an increased risk of drowning. Of course, this is not true. The best solution is ensuring you are listening to the healthcare providers who are using ACOG guidelines for pain relief. Be well and fly safe.
