That's What She NSAID - The Original Kings of County

With anywhere from 15-25% of pregnancies naturally terminating prior to the end of the first trimester, spontaneous abortions are common¹. We frequently see UCG+ patients with vaginal bleeding and pain present to our ER. During my Gyn Sono rotation, I noticed that both the attending and I would reflexively want to give these patients acetaminophen instead of an NSAID for pain control, presumably because we both felt that Tylenol was safer in pregnancy. I know I saw that they were category D for pregnancy somewhere, but what is the evidence for this? Was there some evidence-based reason we learned back in medical school behind this predilection? NSAIDS seem like a reasonable choice for female GU complaints; after all, NSAIDs are a medicine cabinet staple of women everywhere for painful menstrual cramps because of their anti-inflammatory (inhibition of prostaglandins) and analgesic effects (raise the threshold of polymodal nociceptors)².

Questions:

Are NSAIDs really bad in pregnancy? Does their effect by trimester vary? What FDA pregnancy category are NSAIDS?

Answers:

The safety of NSAIDS depends on the trimester.

In the first trimester, NSAIDS are Class B. A few years ago, a much-publicized case-control study from Canada suggested that NSAIDS might be associated with an increased risk of SAB (odds ratio 2.4, 95% CI 2.1-2.8)³. This study’s conclusion coupled with the well-known side effects of NSAIDS in the third trimester may very well have been what prompted many in the medical community to hedge away from NSAIDS use in ALL pregnant women. Unfortunately, this study had multiple confounding factors that were not controlled for in addition to recall bias. Furthermore, more recent well-designed studies, including a large cohort study that looked at obstetric outcomes for nearly 70,000 pregnancies found that there was no significant effect of NSAIDS on SAB⁴⁵⁶⁷.

In the second trimester, NSAIDS are also Class B⁵.

In the third trimester, NSAIDS are Class D because human trials have shown that it can cause oligohydramnios, premature closure of the ductus arteriosus (Remember, this is why we give Indomethacin in PDA), intestinal perforation, hydrops fetalis, and renal failure. NSAIDS should therefore be avoided. Even as a tocolytic, it is not recommended after 32 weeks because of the side effect profile⁸.

In conclusion, there are no good data demonstrating teratogenicity when NSAIDS are taken from the time a women becomes UCG + up to the third trimester. This is great news for the 1 in 5 US women who have taken NSAIDS at least once during their pregnancy. In my opinion, while there is no harm to providing our 1^st and 2^nd trimester patients with NSAIDS while in the ER, it may be prudent to avoid prescribing it as a home medication to our < 20 weeks pregnant patients because the patient may inadvertently continue to take the medication into their third trimester where known hazards do exist.

By Dr. Wendy Chan

References

1. Regan, Lesley, and Raj Rai. “Epidemiology and the medical causes of miscarriage.” Best practice & research Clinical obstetrics & gynaecology 14.5 (2000): 839-854.

2. Dugowson, C. E., MD, MPH, and P. Gnanashanmugam, MD. “Nonsteroidal Anti-Inﬂammatory Drugs.” Phys Med Rehabil Clin N Am 17 (2006): 347-54.

3. Nakhai-Pour, H. R., P. Broy, O. Sheehy, and A. Berard. “Use of Nonaspirin Nonsteroidal Anti-inflammatory Drugs during Pregnancy and the Risk of Spontaneous Abortion.” Canadian Medical Association Journal 183.15 (2011): 1713-720.

4. Edwards, Digna, Tiara Aldridge, Donna Baird, Michele Funk, David Savitz, and Katherine Hartmann. “Periconceptional Over-the-Counter Nonsteroidal Anti-Inflammatory Drug Exposure and Risk for Spontaneous Abortion.” Obstetrical & Gynecological Survey 67.11 (2012).

5. Solomon, Daniel. “Use of Antiinflammatory and Immunosuppressive Drugs in Rheumatic Diseases during Pregnancy and Lactation.” UptoDate. N.p., 28 Jan. 2013. Web. 3 Nov. 2013.

6. Werler, M., A. Mitchell, S. Hernandezdiaz, and M. Honein. “Use of Over-the-counter Medications during Pregnancy.” American Journal of Obstetrics and Gynecology 193.3 (2005): 771-77.

7. Daniel, S., G. Koren, E. Lunenfeld, and A. Levy. “OC004—Fetal Exposure To Nonsteroidal Antiinflammatory Drugs (Nsaid) And Spontaneous Abortions.” Clinical Therapeutics 35.8 (2013): E2.

8. Koren, G. “Nonsteroidal Antiinflammatory Drugs During Third Trimester and the Risk of Premature Closure of the Ductus Arteriosus: A Meta-Analysis.” Annals of Pharmacotherapy 40.5 (2006): 824-29.

The views expressed on this blog are the author's own and do not reflect the views of their employer. Please read our full disclaimer here. Any references to clinical cases refer to patients treated at a virtual hospital, Janus General Hospital.