LI DK, et al. - The impact of non-steroidal anti-inflammatory drugs (NSAIDs) use in early pregnancy on the risk of miscarriage, especially regarding the timing and duration of use, was examined. Increased risk of miscarriage was noted in association with NSAID use around conception with a dose-response relationship, after controlling for confounding by indication. Furthermore, women with lower BMI seemed particularly vulnerable to the effects of NSAID use around the time of embryonic implantation. However, confirmation of this new observation is required in future studies.

Methods

• Among pregnant members of Kaiser Permanente Northern California (KPNC), an integrated health care delivery system, a cohort study was conducted.
• To achieve optimal ascertainment of miscarriage, including early miscarriages, which are often missed in studies of miscarriages, researchers recruited pregnant KPNC members (N=1,097) very early in pregnancy (median gestational age at enrollment was 39 days).
• They formed 3 cohorts based on use of NSAIDs and acetaminophen, which has similar indication as NSAIDs: women who used NSAIDs only, women who used acetaminophen only (to control for indication) and women who used neither NSAIDs nor acetaminophen (unexposed controls).
• In this study, 63% of all eligible women participated.
• From both electronic medical record data and directly from interviews with participants, they ascertained miscarriages.
• They examined the risk of miscarriage associated with use of NSAIDs and acetaminophen during pregnancy, using the Cox proportional hazards model with accommodation for left truncation, while controlling for potential confounders.

Results

• Researchers noted an association of NSAID use during pregnancy with a statistically significant increased risk of miscarriage compared to both unexposed controls (adjusted hazard ratio (aHR)=1.59, 95% confidence interval (CI): 1.13 to 2.24) and acetaminophen users (indication controls) (aHR=1.45, 95% CI: 1.01 to 2.08) after adjusting for multiple confounders including maternal age, previous miscarriage, multivitamin use, caffeine drinking and smoking during pregnancy.
• As per findings, the risk was largely due to NSAID use around conception (aHR=1.89, 95% CI: 1.31 to 2.71) with a statistically significant dose-response relationship: aHR=1.37 (95% CI: 0.70 to 2.71) for NSAID use of 14 days or less, and aHR=1.85 (95% CI: 1.24 to 2.78) for NSAID use of 15 days or more.
• For early miscarriage (<8 weeks gestational age), the association was stronger: aHR=4.08 (95% CI: 2.25 to 7.41).
• Women with lower BMI (<25) seemed to have higher susceptibility to the effect of NSAID use around conception (aHR=3.78, 95% CI: 2.04 to 6.99) than women with high BMI (≥25) (aHR=1.03, 95% CI: 0.61 to 1.72).