Unless otherwise noted, quotes are taken from the associated review article.
Does acetaminophen use during pregnancy lead to children developing autism?
NO.
[acetaminophen] is one of the most commonly used medications globally.
In the USA, [acetaminophen] is estimated to be used by up to 65% of
pregnant women. Worldwide, more than 50% of pregnant women are
estimated to use [acetaminophen]. [acetaminophen] has long been
considered an option by regulatory bodies such as the FDA and EMA for
use in pregnancy for pain and fever when used as directed, as NSAIDs
are contraindicated for use in pregnant women in later pregnancy.
Pharmacotherapy during pregnancy involves a benefit–risk assessment,
in which there is a trade‐off between the potential benefits to the
mother and fetus and possible risks to the fetus. The FDA has formerly
given [acetaminophen] a ‘B’ rating for use in pregnancy in all three
trimesters, meaning that animal studies have failed to demonstrate any
risks of congenital birth defects from fetal exposure and that no
adequate and well-controlled studies have been performed in pregnant
women. In addition, the EMA has found epidemiological data
inconclusive and that experimental data do not meet their standards.
Acetaminophen is a commonly used drug during pregnancy. There is no direct evidence that it is unsafe, and has been used for more than 150 years. The major professional body for obstetrics published the following statement in response to this review article:
A consensus statement that was recently published in the journal
Nature Reviews Endocrinology claims that a growing body of research
shows that prenatal exposure to paracetamol, or acetaminophen, may
alter fetal development and increase the risks of neurodevelopmental,
reproductive, and urogenital disorders.
ACOG and obstetrician-gynecologists across the country have always
identified acetaminophen as one of the only safe pain relievers for
pregnant individuals during pregnancy. This consensus statement, and
studies that have been conducted in the past, show no clear evidence
that proves a direct relationship between the prudent use of
acetaminophen during any trimester and fetal developmental issues.
Neurodevelopmental disorders, in particular, are multifactorial and
very difficult to associate with a singular cause. The brain does not
stop developing until at least 15 months of age, which leaves room for
children to be exposed to a number of factors that could potentially
lead to these issues.
The authors are not recommending anything counter to what is already
done by obstetrician-gynecologists when prescribing acetaminophen for
a given clinical condition. ACOG’s clinical guidance remains the same
and physicians should not change clinical practice until definitive
prospective research is done. Most importantly, patients should not be
frightened away from the many benefits of acetaminophen. However, as
always, any medication taken during pregnancy should be used only as
needed, in moderation, and after the pregnant patient has consulted
with their doctor.
Does the review article actually say anything inconsistent with this professional statement?
NO.
Acetaminophen is an interesting drug - it is very unlikely that it would, if discovered today, be an over-the-counter medication. The mechanism of action is broad and not well-understood, it has a number of fairly serious side effects, and the therapeutic range (the range between the dose that helps do what it's supposed to do and a toxic dose) is narrow, which is a particular risk for people who take it regularly. There are very real reasons to be concerned that it might be a risk.
The review article summarizes the summarizes studies about these risks:
Another study has demonstrated reduced AGD in boys exposed to the
combination of [acetaminophen] and NSAIDs during pregnancy, suggesting
a potential additive effect as exposure to [acetaminophen] alone did
not result in a significant difference in AGD. Similar additivity with
other analgesics has been seen for cryptorchidism, where the
association is strongest among mothers using more than one analgesic
during pregnancy. Moreover, exposure to [acetaminophen] for >2 weeks
increased the risk of cryptorchidism. Most associations for
cryptorchidism are seen following long-term [acetaminophen] exposure
(>2 weeks) during late first to early second trimester, which is
consistent with the critical time windows for development. Thus, these
data suggest that the timing and duration of maternal [acetaminophen]
use are critical factors and that short-term [acetaminophen] use might
be of limited risk.
There may be a correlation between taking acetaminophen and some physical developmental disorders, with long-term exposure during critical stages of fetal development.
The relationships between prenatal [acetaminophen] exposure and
adverse neurodevelopmental outcomes have been investigated in 29
observational studies in 14 cohorts including over 220,000
mother–child pairs from different parts of the world [...] Effect
sizes were generally modest but because exposure is widespread, even a
small effect size could translate into a large number of affected
children. [...] In many of these studies, associations were weak for
short-term exposure suggesting that short-term use might be of limited
risk. As with reproductive and urogenital outcomes, exposure timing is
important, as the highest risk seemed to occur from exposure during
the second and third trimesters of pregnancy (with some exceptions).
There may be a correlation between taking acetaminophen and some neurological developmental disorders, with long-term exposure during critical stages of fetal development.
The authors note the potential confounding effects that make these studies difficult, and which are very difficult to resolve when the treatment (acetaminophen) is so widespread. They also reference in passing some experimental results that are generally unconvincing, as if or how they'd translate to clinical practice is unknown, and I will omit for brevity. This review article does not reference any causal evidence for a link between acetaminophen and neurological disorders (which does not exist at this time), only correlative evidence and mechanistic speculation.
The specific guidence suggested by the authors of this review is as follows:
We recommend that women be counselled prior to or early in pregnancy
with the following guidance:
- Pregnant women should forego [acetaminophen] use unless medically
indicated.
- Pregnant women should consult with their physician or
pharmacist if they are uncertain whether use is indicated and before
using on a long-term basis.
- Pregnant women should minimize risk by
using the lowest effective [acetaminophen] dose for the shortest
possible time.
This is very similar to the guidance in place for obstetrics for the last 50 or so years. In short, there are potential risks with long-term acetaminophen treatment, and you should not take medications while pregnant without discussing it with your obstetrician.
Why are lawyers recruiting for class action lawsuits?
I have no idea.
I don't think this is by any means an easily winnable case, based on what we know right now medically. Perhaps we will learn more in the future and the link will be stronger. Perhaps the medical evidence doesn't matter and the expectation is that a jury will side with crying mothers. Tylenol is made by Johnson & Johnson, which is a massive deep-pocketed conglomerate, so there's money to be made if they can win (or settle). I can't predict the future of this case and won't try.
