Does using nonsteroidal anti-inflammatory drugs during pregnancy increase the risk of adverse events? - NSAIDs

Journal of Family Practice, May, 2001 by Sukanya Srinivasan, Goutham Rao

Nielsen GL, Sorensen HT, Larsen H, Pedersen L. Risk of adverse birth outcome and miscarriage in pregnant users of non-steroidal anti-inflammatory drugs: population based observational study and case-control study. BMJ 2001; 322:266-70.

* BACKGROUND The safety of NSAIDs is not well documented, even through they are often used during pregnancy. The authors of this study estimated the risk of adverse pregnancy outcomes by examining NSAID prescription use in a large population of Danish women.

* POPULATION STUDIED The researchers assembled 2 separate study groups drawn from one county in Denmark. In one group 1462 pregnant women who had filled prescriptions for NSAIDs were compared with 17,259 controls to assess unfavorable birth outcomes. Those who had filled NSAID prescriptions anywhere from 30 days before conception up to the date of delivery were included. In the other group 4268 women who had first miscarriages were compared with 29,750 primiparous women with live births as controls. Patient information for both study groups was identified using a prescription registry, the Danish birth registry, and the county's hospital discharge registry.

* STUDY DESIGN AND VALIDITY The incidence of adverse birth outcomes was assessed through a retrospective cohort design. The risk of miscarriage was determined by a case-control study. Information was collected for each subject on the number of NSAID prescriptions filled (specifically ibuprofen 400 or 600 mg), maternal age, smoking status, gravity, parity, gestational age at delivery, and size of the neonate. A subset of prescription data was verified by examining physician and hospital records.

Studies of this type can show association but not necessarily causation. For example, the apparent increased rate of miscarriage in this study was associated with NSAID use. This increased rate might be due to the NSAID or conversely the NSAID use might be because of the pain of the impending miscarriage

The authors adjusted for several potential confounders in the cohort portion of the study but less completely in the case-control portion where smoking status was unavailable. However, one major concern of this study is that the number of prescriptions filled may not be related to the pattern of NSAID use, since compliance varies and many women may use nonprescription NSAIDs. Additionally, this study only examined risks related to ibuprofen. Different medications in this class may be associated with differing risks of adverse events.

* OUTCOMES MEASURED Primary outcomes included congenital abnormality (type not specified), low birth weight (less than 2500 g), preterm birth ([is less than] 37 weeks' gestation), and miscarriage.

* RESULTS Congenital abnormality, low birth weight, and preterm birth incidence were not higher in offspring of women who had taken a NSAID during pregnancy. Miscarriages were significantly higher in women who had filled a prescription for an NSAID the week before miscarriage (odds ratio=6.99; 95% confidence interval, 2.75-17.74). Miscarriage was not associated with prescriptions filled 10 to 12 weeks before the date of miscarriage.

RECOMMENDATIONS FOR CLINICAL PRACTICE

This study contributes valuable information for physicians and their pregnant patients contemplating use of NSAIDs. Women who have used NSAIDs before or during pregnancy may be reassured that there is no evidence of increased risk of congenital abnormality, low birth weight, or preterm birth. Also, women contemplating pregnancy should be warned about the association of miscarriage with NSAIDs. It seems prudent for women with a history of recurrent miscarriage to avoid NSAIDs.

Sukanya Srinivasan, MD Goutham Rao, MD UPMC St. Margaret Family Practice Residency Pittsburgh, Pennsylvania E-mail: srinivasans@msx.upmc.edu