Table 3.
Adverse fetal outcomes according to exposure to immunosuppressive medications during the first trimester of pregnancy.
| First Trimester Exposures to Immunosuppressive Medicationsa
|
No use of immunosuppressive medications (n=171) (Reference) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Methotrexateb (n=23) | TNF-Ic (n=56) | Hydroxychloroquined (n=194) | Other immunosuppressivee (n=129) | |||||||||||
|
| ||||||||||||||
| N | % | Risk Ratiof (95% CI) | N | % | Risk Ratio (95% CI) | N | % | Risk Ratio (95% CI) | N | % | Risk Ratio (95% CI) | N | % | |
|
|
||||||||||||||
| Congenital malformations | 1 | 4.3 | 1.96 | 2 | 3.6 | 1.59 | 13 | 6.7 | 3.11 | 4 | 3.1 | 1.42 | 4 | 2.3 |
| (0.23,17.00) | (0.30,8.47) | (0.99,9.77) | (0.38,5.40) | |||||||||||
| Fetal death | 2 | 8.7 | 3.18 | 0 | 0 | - | 2 | 1.0 | 0.35 | 2 | 1.6 | 0.55 | 4 | 2.3 |
| (0.54,18.62) | - | (0.05,2.44) | (0.11,2.68) | |||||||||||
| Neonatal complicationsg | ||||||||||||||
| Preterm (n=108)h | 0 | 0 | - | 3 | 33.3 | 1.74 | 10 | 22.2 | 1.09 | 4 | 21.1 | 1.05 | 6 | 18.8 |
| - | (0.54,5.61) | (0.41,2.91) | (0.34,3.24) | |||||||||||
| Term (n=455)i | 1 | 5.6 | 5.90 | 1 | 2.1 | 2.60 | 4 | 2.7 | 2.77 | 2 | 1.9 | 2.01 | 1 | 0.7 |
| (0.34,103.86) | (0.19,36.27) | (0.26,29.06) | (0.19,21.28) | |||||||||||
| Any adverse fetal outcomej | 3 | 13.0 | 1.39 | 5 | 8.9 | 0.98 | 25 | 12.9 | 1.33 | 12 | 9.3 | 0.98 | 15 | 8.8 |
| (0.43,4.53) | (0.38,2.55) | (0.69,2.55) | (0.48,1.98) | |||||||||||
Outcomes for 35 pregnancies with exposure to study medications in the 2nd or 3rd trimesters only are included in the text.
Methotrexate users may have filled prescriptions for other immunosuppressive medications.
TNF-I=tumor necrosis factor inhibitors included etanercept, infliximab, adalimumab, in the absence of methotrexate. One infant had two defects (diaphragmatic hernia and aortic insufficiency).
In the absence of methotrexate or TNF-I.
Other immunosuppressive medications included gold, sulfasalazine, leflunomide, azathioprine, and minocycline in the absence of methotrexate, TNF-I, or hydroxychloroquine.
Risk ratios estimated with Poisson regression adjusting for the propensity score. Reference group for all analyses is women who filled immunosuppressive medications before pregnancy but not during. Generalized estimating equations with Huber-White sandwich estimators were used to account for multiple pregnancies for a woman and for multiple gestations.
Adverse neonatal complications included respiratory failure, seizures, jaundice, or sepsis.
Included 3 preterm infants with methotrexate exposure, 9 with TNF-I exposures, 45 with hydroxychloroquine exposures, 19 with other immunosuppressive exposures, and 32 infants with no exposure to the medications of interest during pregnancy. Results for exposures during the 2nd or 3rd trimester are shown in the text.
Included 18 term infants with methotrexate exposures, 47 with TNF-I exposures, 147 with hydroxychloroquine exposures, 108 with other immunosuppressive exposures, and 135 infants with no exposure to the medications of interest during pregnancy. Results for exposures during the 2nd or 3rd trimester are shown in the text.
Infants may have experienced more than one outcome; thus, numbers of outcomes in the columns may not sum to the total of any adverse fetal outcome.