Table 6.
Association between study medication exposure during pregnancy and the risk of spontaneous abortion.
| Spontaneous abortion | ||||
|---|---|---|---|---|
| Characteristics | Cases n = 29,104 | Controls n = 287,607 | Crude OR (95% CI) | Adjusted OR (95% CI) |
| n (%) | ||||
| Study medication exposure during the pregnancy | ||||
| DHEa | 22 (0.08) | 64 (0.02) | 3.79 (1.27–11.34) | 2.59 (0.79–8.53) |
| Triptansb | 192 (0.66) | 713 (0.25) | 1.99 (1.67–2.38) | 1.63 (1.34–1.98) |
| Other medication exposure during pregnancy | ||||
| NSAIDsc | 2423 (8.33) | 8054 (2.80) | 2.70 (2.56–2.85) | 2.60 (2.46–2.76) |
| Opioidsd | 1529 (5.25) | 7433 (2.58) | 1.36 (1.27–1.45) | 1.53 (1.43–1.64) |
| Maternal age at the 1DGe—years | ||||
| Less than 35 | 22,253 (76.46) | 241,761 (83.96) | Ref | Ref |
| 35–39 | 4711 (16.19) | 37,291 (12.95) | 1.36 (1.32–1.41) | 1.69 (1.63–1.75) |
| 40 or more | 2140 (7.35) | 8,884 (3.09) | 2.60 (2.46–2.74) | 3.24 (3.06–3.43) |
| Adherent vs. welfare recipient | 20,730 (71.23) | 214,977 (74.66) | 0.85 (0.82–0.87) | 1.02 (0.99–1.06) |
| Urban dweller | 22,910 (78.72) | 231,234 (80.31) | 0.90 (0.87–0.93) | 0.97 (0.94–1.01) |
| Migraine diagnosis during pregnancy | 622 (2.14) | 5112 (1.78) | 1.20 (1.10–1.31) | 0.98 (0.89–1.08) |
| Maternal comorbidities in the year prior to 1DGf | ||||
| Hypertension | 929 (3.19) | 7820 (2.72) | 1.20 (1.11–1.29) | 1.06 (0.98–1.15) |
| Diabetes | 728 (2.50) | 8495 (2.95) | 0.75 (0.69–0.82) | 0.80 (0.74–0.88) |
| Asthma | 4375 (15.03) | 36,307 (12.61) | 1.19 (1.15–1.23) | 1.00 (0.96–1.04) |
| Thyroid disorders | 1322 (4.54) | 15,584 (5.41) | 0.78 (0.73–0.83) | 0.75 (0.71–0.80) |
| Diagnosis of dependence to | ||||
| Tobacco | 445 (1.53) | 2829 (0.98) | 1.56 (1.40–1.74) | 1.08 (0.96–1.22) |
| Alcohol | 228 (0.78) | 1035 (0.36) | 2.09 (1.79–2.44) | 1.31 (1.10–1.57) |
| Other drugs | 381 (1.31) | 2035 (0.71) | 1.83 (1.63–2.05) | 1.21 (1.06–1.38) |
| In the year prior to the 1DG | ||||
| Emergency visit or hospitalization | 12,059 (41.43) | 105,223 (36.54) | 1.21 (1.18–1.24) | 0.94 (0.91–0.97) |
| General practitioner visits | ||||
| 0 | 5217 (17.93) | 62,341 (21.65) | Ref | Ref |
| 1–3 | 9808 (33.70) | 108,303 (37.61) | 1.08 (1.04–1.12) | 1.04 (1.00–1.08) |
| 4 or more | 14,079 (48.37) | 117,292 (40.74) | 1.43 (1.38–1.48) | 1.12 (1.07–1.17) |
| Specialist visits | ||||
| 0 | 10,544 (36.23) | 112,271 (38.99) | Ref | Ref |
| 1–2 | 6828 (23.46) | 70,740 (24.57) | 1.03 (1.00–1.07) | 1.12 (1.08–1.17) |
| 3 or more | 11,732 (40.31) | 104,925 (36.44) | 1.18 (1.15–1.21) | 1.38 (1.33–1.43) |
| Other prescribed medicationsg | ||||
| 0 | 8144 (27.98) | 91,446 (31.76) | Ref | Ref |
| 1–2 | 9960 (34.22) | 105,108 (36.53) | 1.06 (1.03–1.09) | 1.02 (0.98–1.05) |
| 3 or more | 11,000 (37.80) | 91,310 (31.71) | 1.34 (1.30–1.39) | 1.19 (1.15–1.24) |
| Pregnancy follow–up by obstetrician | 3332 (11.45) | 121,836 (42.31) | 0.17 (0.16–0.18) | 0.15 (0.14–0.16) |
| Pregnancy in the year prior the 1DG | 5386 (18.51) | 42,971 (14.92) | 1.26 (1.22–1.31) | 1.10 (1.06–1.15) |
| High dose folic acid consumption before the end of the 1st trimester | 885 (3.04) | 12,691 (4.41) | 0.69 (0.64–0.74) | 0.69 (0.64–0.75) |
aDihydroergotamine; bIncluding almotriptan, eletriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan; cIncluding celecoxib, diclofenac, diflunisal, etodolac, fenoprophen, fentanyl, flurbiprofene, hydrocodone, hydromorphone, ibuprofen, indomethacin, ketoprofen, mefenamic acid, meloxicam, nabumetone, naproxen, piroxicam, rofecoxib, sulindac, tiaprofenic acid, tolmetin, and valdecoxib; dIncluding codeine, meperidine, morphine, oxaprozin, oxycodone, oxymorphone, pentazocine, tapentadol, propoxyphen, and tramadol.
Note: Pregnant women can use more than 1 study medication during pregnancy.
eFirst day of gestation defined as the first day of the last menstrual period; fComorbidities were assessed in the year prior to the 1DG using ICD-9 and ICD-10 diagnosis codes and prescribed medications; gOther prescribed medications than the study medications and the medications used for the identification of the comorbidities.