Table 1.
Association between study medication exposure during pregnancy and the risk of prematurity.
| Characteristics | Prematurity < 37 completed weeks of gestation | |||
|---|---|---|---|---|
| Yes n = 15,688 | No n = 218,212 | Crude RR (95% CI) | Adjusted RR (95% CI) | |
| n (%) | ||||
| Study medication exposure during the pregnancy | ||||
| DHEa | 19 (0.12) | 59 (0.03) | 3.97 (1.09–14.43) | 4.12 (1.21–13.99) |
| Triptansb | 61 (0.39) | 465 (0.21) | 1.61 (1.22–2.12) | 1.31 (0.99–1.74) |
| Other medication use during pregnancy | ||||
| NSAIDs | 551 (3.51) | 5992 (2.75) | 1.18 (1.08–1.30) | 1.05 (0.95–13.14) |
| Opioidsd | 1070 (6.82) | 11,390 (5.22) | 1.23 (1.15–1.32) | 1.08 (1.01–1.16) |
| Maternal age at the 1DGe—mean (SD) (years) | 28.12 ± 5.99 | 28.29 ± 5.43 | 1.00 (1.00–1.00) | 1.00 (1.00–1.00) |
| Adherent vs. welfare recipient | 10,922 69.62) | 169,503 (77.68) | 0.68 (0.65–0.70) | 0.73 (0.70–0.76) |
| Urban dweller | 12,935 (82.45) | 179,671 (82.34) | 1.01 (0.97–1.05) | 0.97 (0.92–1.01) |
| Migraine diagnosis during pregnancy | 446 (2.84) | 4,966 (2.28) | 1.22 (1.10–1.35) | 1.08 (0.97–1.19) |
| Maternal comorbidities in the year prior to 1DGf | ||||
| Hypertension | 667 (4.25) | 5328 (2.44) | 1.66 (1.53–1.81) | 1.42 (1.31–1.55) |
| Diabetes | 620 (3.95) | 4688 (2.15) | 1.80 (1.64–1.97) | 1.52 (1.39–1.67) |
| Asthma | 2275 (14.50) | 26,046 (11.94) | 1.21 (1.16–1.27) | 1.04 (0.99–1.09) |
| Thyroid disorders | 744 (4.74) | 9640 (4.42) | 1.07 (0.99–1.16) | 0.97 (0.90–1.05) |
| Diagnosis of dependence to | ||||
| Tobacco | 852 (5.43) | 6531 (2.99) | 1.77 (1.64–1.91) | 1.52 (1.41–1.65) |
| Alcohol | 124 (0.79) | 805 (0.37) | 2.04 (1.67–2.48) | 1.11 (0.90–1.37) |
| Other drugs | 372 (2.37) | 2022 (0.93) | 2.44 (2.17–2.74) | 1.82 (1.60–2.05) |
| In the year prior to the 1DG | ||||
| Emergency visit or hospitalization | 6147 (39.18) | 73,409 (33.64) | 1.24 (1.20–1.28) | 1.07 (1.03–1.11) |
| General practitioner visits | ||||
| 0 | 2980 (19.00) | 46,466 (21.29) | Ref | Ref |
| 1–3 | 5523 (35.21) | 82,992 (38.03) | 1.03 (0.99–1.08) | 0.99 (0.95–1.04) |
| 4 or more | 7185 (45.80) | 88,754 (40.67) | 1.22 (1.17–1.28) | 1.05 (1.00–1.10) |
| Specialist visits | ||||
| 0 | 5,543 (35.33) | 86,234 (39.52) | Ref | Ref |
| 1–2 | 3,654 (23.29) | 54,578 (25.01) | 1.04 (0.99–1.08) | 0.98 (0.93–1.02) |
| 3 or more | 6,491 (41.38) | 77,400 (35.47) | 1.27 (1.23–1.32) | 1.08 (1.03–1.13) |
| Other prescribed medicationsg | ||||
| 0 | 4257 (27.14) | 69,390 (31.80) | Ref | Ref |
| 1–2 | 5618 (35.81) | 81,480 (37.34) | 1.12 (1.08–1.17) | 1.08 (1.03–1.12) |
| 3 or more | 5813 (37.05) | 67,342 (30.86) | 1.36 (1.31–1.42) | 1.14 (1.08–1.19) |
| Pregnancy follow–up by obstetrician | 959 (61.13 | 124,180 (56.91) | 1.19 (1.15–1.24) | 1.19 (1.15–1.23) |
| Pregnancy in the year prior the 1DG | 1497 (9.54) | 18,613 (8.53) | 1.12 (1.06–1.18) | 0.99 (0.93–1.05) |
| High dose folic acid consumption before the end of the 1st trimester | 773 (4.93) | 8005 (3.67) | 1.33 (1.23–1.44) | 1.16 (1.07–1.26) |
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.