Safety of Mecobalamin (Vitamin B12) and Etoricoxib in First Trimester
Mecobalamin (Vitamin B12) is safe during the first trimester and should be continued, while etoricoxib should be avoided due to lack of safety data and potential risks associated with COX-2 inhibitors.
Mecobalamin (Vitamin B12) Safety
Vitamin B12 supplementation is safe and beneficial throughout pregnancy, including the first trimester. 1
- Vitamin B12 deficiency during pregnancy may increase the risk of neural tube defects, preterm delivery, and inadequate fetal stores that can lead to infant deficiency 2
- Low maternal vitamin B12 status may be associated with fetal growth retardation, fetal insulin resistance, and excess adiposity 1
- Clinical vitamin B12 deficiency may contribute to infertility or recurrent spontaneous abortion if present before pregnancy 2
- Women planning pregnancy should have vitamin B12 deficiency checked before starting high-dose folic acid supplementation (5 mg), particularly those with BMI >30 kg/m² or type 2 diabetes 3
The evidence strongly supports continuing or initiating vitamin B12 supplementation during the first trimester without safety concerns. 1, 2
Etoricoxib (COX-2 Inhibitor) Safety
Etoricoxib should be avoided during the first trimester due to insufficient safety data and the general recommendation against COX-2 inhibitors in pregnancy. 3
Guideline Recommendations
- The 2020 American College of Rheumatology conditionally recommends nonselective NSAIDs over COX-2-specific inhibitors in the first two trimesters due to lack of data on COX-2-specific inhibitors 3
- The 2025 EULAR recommendations state that data for COX-2 inhibitors are limited, with most reassuring evidence available for ibuprofen and diclofenac rather than selective COX-2 inhibitors 3
- All NSAIDs, including COX-2 inhibitors, must be discontinued after gestational week 28 (end of second trimester) due to risks of oligohydramnios and premature ductus arteriosus closure 3
Available Safety Data
- A 2018 prospective cohort study of 174 first-trimester coxib exposures found no significant increase in major birth defects (2.9% vs 2.7% in controls), though the evidence basis remains limited 4
- The study showed no increased risk of spontaneous abortion with coxib exposure, but the authors emphasized that well-established alternatives should be preferred given limited evidence 4
Safer Alternatives
If anti-inflammatory medication is needed during the first trimester, nonselective NSAIDs with short half-lives are preferred. 3
- Ibuprofen has the most reassuring safety data for early pregnancy exposure, showing no evidence of increased miscarriage or teratogenicity 3
- Diclofenac is the second-best option with adequate safety data 3
- If NSAIDs are used, limit to short-term use (7-10 days) at the lowest effective dose 3
- NSAIDs can interfere with ovulation when used continuously during the periovulatory period 3
Clinical Approach
Continue mecobalamin throughout pregnancy without dose adjustment concerns, as it addresses potential deficiency that could harm fetal development 1, 2
Discontinue etoricoxib immediately upon pregnancy recognition or when planning conception 3
If pain/inflammation control is needed, substitute with ibuprofen at the lowest effective dose for the shortest duration (maximum 7-10 days) 3
Ensure all NSAIDs are stopped by gestational week 28 to prevent third-trimester complications 3
Important Caveats
- The first trimester represents the period of highest teratogenic risk for medications, making avoidance of poorly studied drugs particularly important 5
- While one observational study suggests coxibs may not be major teratogens, the limited evidence base and availability of better-studied alternatives make etoricoxib inappropriate for first-trimester use 4
- Vitamin B12 supplementation is particularly important for women with previous bariatric surgery, as prevalence of cobalamin deficiency in pregnancy is rising with increased obesity surgery rates 1