Is Tylenol safe during pregnancy? Trick question.

Medicine Drug Pills on Plate

There aren’t many choices for safe drugs in pregnancy. Photo by, CC-BY

Tylenol use in pregnancy is now linked to ADHD. Tylenol was considered the safest analgesic (pain relief) for pregnant women, but in truth there is only one way for pregnant women to avoid potentially dangerous medication:

Don’t get sick.

There are vanishingly few drugs that are officially considered safe in pregnancy. The system we use in the US is a letter-graded pregnancy category. The top ranking, category A, is awarded to drugs where “adequate and well-controlled studies” have looked for risks in the first trimester, and failed to find any. Those studies don’t have to examine the second and third trimesters, but if a study does turn up a risk in later pregnancy, the drug is disqualified from Category A.

Which means that this, the safest category, has a lot of blind spots. But I’ll bite. Which drugs fall into Category A? Is it a big list?

Not exactly: according to the SafeFetus lookup, it comprises thyroid medications, a few vitamins, and a salt solution used to stave off preterm labor. That’s it.

What we should be asking instead

“Is this safe?” is a trick question. Drugs mess with the biochemistry of your body in myriad ways, and many drugs aren’t tested on pregnant women at all. (In fact, until 1993 drugs could not be tested on “women of childbearing potential” in the US.) We have a serious lack of evidence of risks, which is not the same as knowing something is safe.

The question that’s most important to answer is, instead, this: If I’m pregnant and in pain, what can I do? (Or, from the doctor’s perspective: My patient is pregnant and in pain, should I prescribe something and, if so, what?)

Here’s a table of over-the-counter pain medications from American Family Physician that shows what our hypothetical pregnant lady is up against:


Drug name FDA pregnancy risk classification by trimester (1st/2nd/3rd) Drug class Crosses placenta? Use in pregnancy
Acetaminophen (Tylenol) B/B/B Non-narcotic analgesic/antipyretic Yes Pain reliever of choice
Aspirin D/D/D Salicylate analgesic/antipyretic Yes Not recommended except for specific indications*
Ibuprofen (Advil, Motrin) B/B/D NSAID analgesic Yes Use with caution; avoid in third trimester†
Ketoprofen (Orudis) B/B/D NSAID analgesic Yes Use with caution; avoid in third trimester†
Naproxen (Aleve) B/B/D NSAID analgesic Yes Use with caution; avoid in third trimester†

OTC = over-the-counter; FDA = U.S. Food and Drug Administration; NSAID = nonsteroidal anti-inflammatory drug.

*—Associated with increased perinatal mortality, neonatal hemorrhage, decreased birth weight, prolonged gestation and labor, and possible teratogenicity.5

†—Associated with oligohydramnios, premature closure of the fetal ductus arteriosus with subsequent persistent pulmonary hypertension of the newborn, fetal nephrotoxicity, and periventricular hemorrhage.6

Information from Collins E. Maternal and fetal effects of acetaminophen and salicylates in pregnancy. Obstet Gynecol 1981;58(5 Suppl):57S–62S, and Macones GA, Marder SJ, Clothier B, Stamilio DM. The controversy surrounding indomethacin for tocolysis. Am J Obstet Gynecol 2001;184:264–72.


Even if acetaminophen (Tylenol) is a factor in developing ADHD, does it change the answer to the real question?

Tara Haelle breaks down the study and its caveats here: the risk is very small (most women in the study did not have children with ADHD), and there are plenty of confounding factors that can’t be ruled out. The most affected kids came from mothers who took acetaminophen for over 20 weeks of their pregnancy; if someone is popping Tylenol for five months straight, they may have an underlying condition that separates them from people who aren’t. And it might not be fair to compare them with somebody who takes Tylenol just occasionally.

That’s not to say the study is wrong; the link may be real. But consider this: given that information, as well as what we know about the risks of ibuprofen and other alternatives (see table), what should you take if you’re pregnant and in pain?

Maybe, given these results, you might try to tough it out a little longer without drugs. That may be an option for some women, depending on what the source of their pain is, and whether it responds to non-medical treatments like rest, massage, hydration, or the simple “Doctor, it hurts when I do this.” / “So don’t do that.”

But if you need some kind of medication? We’re comparing Tylenol, which is Category B all through pregnancy with meds that have Category D rankings in the third trimester or more. Take a look at the risks there: ibuprofen (Advil) and naproxen (Aleve) are associated with “oligohydramnios, premature closure of the fetal ductus arteriosus with subsequent persistent pulmonary hypertension of the newborn, fetal nephrotoxicity, and periventricular hemorrhage.” It’s your call, but in those cases–at least in the third trimester–I’d stick with Tylenol.

Why this is so hard

Risk assessment is tricky when complicated and incomplete information has to funnel into a yes-or-no decision. In fact, the FDA’s letter grade system is on its way out, for many reasons. Among them: a lack of data can earn a drug a high grade–after all, we don’t know of any risks. The grades also gloss over differences in safety or dosage that may occur during pregnancy. Drugs may be perceived as safer than they are, or vice-versa. Instead, the grades will be replaced with summaries describing what risks are known, and what evidence they’re based on.

The Society for Maternal-Fetal Medicine issued a statement today on the Tylenol case that included this sage piece of advice from president Vincenzo Berghella: “We need prospective studies of all drugs used in pregnancy and lactation*, not just acetaminophen, so that pregnant women or women considering pregnancy can make informed decisions about treatment.” The absence of pregnant women in drug trials is a serious problem that medicine has been dancing around for years: nobody wants to give untested drugs to pregnant women, which results in pregnant women taking drugs that are untested. Ruth Macklin pointed out in a Lancet editorial that the thalidomide tragedy can be pinned on a lack of testing in pregnant women: when it appeared in pharmacies, nobody had any idea it would be dangerous.

Pregnant women deserve drug trials, Melinda Wenner-Moyer wrote a few years ago. It’s still true. In the meantime, we need to drop the safe/unsafe dichotomy and take a smart look at what little data we have on risks.

* Don’t get me started on lactation. Many health care professionals don’t realize that for most medications, the risk from medication is outweighed by the benefit of continuing breastfeeding. Check LactMed for information on your favorite drugs.

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