Table 4.
Association between study medication exposure during the 1st trimester and the risk of major congenital malformations.
| Characteristics | Major congenital malformation | |||
|---|---|---|---|---|
| Yes n = 24,539 | No n = 209,361 | Crude RR (95% CI) | Adjusted RR (95% CI) | |
| n (%) | ||||
| Study medication exposure during the 1st trimester of pregnancy | ||||
| DHEa | 7 (0.03) | 71 (0.03) | 0.99 (0.33–2.97) | 1.01 (0.32–3.19) |
| Triptansb | 61 (0.25) | 406 (0.19) | 1.21 (0.92–1.58) | 1.04 (0.79–1.37) |
| Other medication use during the 1st trimester of pregnancy | ||||
| NSAIDs | 673 (2.74) | 4624 (2.21) | 1.20 (1.10–1.30) | 1.13 (1.04–1.23) |
| Opioidsd | 581 (2.37) | 3,904 (1.86) | 1.23 (1.12–1.34) | 1.14 (1.04–1.24) |
| Maternal age at the 1DGe-mean (SD) (years) | 28.27 ± 5.62 | 28.22 ± 5.59 | 1.00 (1.00–1.00) | 1.00 (1.00–1.00) |
| Adherent vs. welfare recipient | 18,695 (76.18) | 161,730 (77.25) | 0.95 (0.92–0.98) | 1.00 (0.97–1.03) |
| Urban dweller | 20,511 (83.59) | 172,095 (82.20) | 1.10 (1.06–1.14) | 1.08 (1.04–1.12) |
| Migraine diagnosis during pregnancy | 674 (2.75) | 4738 (2.26) | 1.21 (1.12–1.32) | 1.14 (1.05–1.24) |
| Maternal comorbidities in the year prior to 1DGf | ||||
| Hypertension | 781 (3.18) | 5214 (2.49) | 1.27 (1.18–1.38) | 1.14 (1.05–1.23) |
| Diabetes | 794 (3.24) | 4514 (2.16) | 1.51 (1.40–1.63) | 1.32 (1.22–1.43) |
| Asthma | 3327 (13.56) | 24,994 (11.94) | 1.15 (1.11–1.20) | 1.09 (1.04–1.13) |
| Thyroid disorders | 1279 (5.21) | 9105 (4.35) | 1.21 (1.14–1.29) | 1.14 (1.08–1.22) |
| Diagnosis of dependence to | ||||
| Tobacco | 944 (3.85) | 1.25 (1.17–1.35) | 1.21 (1.12–1.30) | |
| Alcohol | 122 (0.50) | 1.29 (1.06–1.56) | 1.01 (0.83–1.23) | |
| Other drugs | 354 (1.44) | 2040 (0.97) | 1.48 (1.32–1.66) | 1.35 (1.20–1.52) |
| In the year prior to the 1DG | ||||
| Emergency visit or hospitalization | 9201 (37.50) | 70,355 (33.60) | 1.18 (1.15–1.22) | 1.15 (1.12–1.19) |
| General practitioner visits | ||||
| 0 | 4909 (20.00) | 44,537 (21.27) | Ref | Ref |
| 1–3 | 9184 (37.43) | 79,331 (37.89) | 1.05 (1.01–1.09) | 1.02 (0.98–1.06) |
| 4 or more | 10,446 (42.57) | 85,493 (40.84) | 1.10 (1.07–1.14) | 1.01 (0.96–1.15) |
| Specialist visits | ||||
| 0 | 9229 (36.40) | 82,504 (39.59) | Ref | Ref |
| 1–2 | 6419 (25.32) | 51,780 (24.85) | 1.11 (1.07–1.15) | 0.98 (0.95–1.02) |
| 3 or more | 9703 (38.27) | 74,113 (35.56) | 1.17 (1.13–1.20) | 0.95 (0.92–0.99) |
| Other prescribed medicationsg | ||||
| 0 | 7337 (29.90) | 66,310 (31.67) | Ref | Ref |
| 1–2 | 8842 (36.03) | 78,256 (37.38) | 1.02 (0.99–1.06) | 1.00 (0.97–1.03) |
| 3 or more | 8360 (34.07) | 64,795 (30.95) | 1.16 (1.12–1.20) | 1.05 (1.01–1.09) |
| Pregnancy follow–up by obstetrician | 15,316 (62.41) | 118,454 (56.58) | 1.27 (1.24–1.31) | 1.27 (1.23–1.31) |
| Pregnancy in the year prior the 1DG | 2269 (9.25) | 17,841 (8.52) | 1.09 (1.04–1.14) | 1.02 (0.97–1.07) |
| High dose folic acid consumption before the end of the 1st trimester | 1185 (4.83) | 7593 (3.63) | 1.34 (1.26–1.43) | 1.23 (1.15–1.31) |
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.