Table 2.
Definition of exposure and reference groups for contrasts of interest
| Cohort and outcome | Exposure group | Reference group | Definition |
|---|---|---|---|
| Cohort 1: | |||
| Congenital malformations | ≥1 duloxetine dispensing LMP to LMP+90 | Unexposed | No duloxetine dispensing between LMP–90 and LMP+90 |
| SSRI* | ≥1 SSRI dispensing LMP to LMP+90 | ||
| Venlafaxine† | ≥1 venlafaxine dispensing LMP to LMP+90 | ||
| Duloxetine discontinuers‡ | ≥1 duloxetine dispensing between 6 months and 60 days before LMP but not during first trimester | ||
| Early exposure | |||
| Cohorts 2 and 3: | |||
| Preterm birth, small for gestational age infant, pre-eclampsia | ≥1 duloxetine dispensing LMP to LMP+140 | Unexposed | No duloxetine dispensing between LMP–90 and LMP+140 |
| SSRI* | ≥1 SSRI dispensing LMP to LMP+140 | ||
| Venlafaxine† | ≥1 venlafaxine dispensing LMP to LMP+140 | ||
| Late exposure | |||
| Cohorts 2 and 3: | |||
| Preterm birth, small for gestational age infant, pre-eclampsia | ≥1 duloxetine dispensing LMP+141 to LMP+245 | Unexposed | No duloxetine dispensing between LMP–90 and LMP+245 |
| SSRI* | ≥1 SSRI dispensing LMP+141 to LMP+245 | ||
| Venlafaxine† | ≥1 venlafaxine dispensing LMP+141 to LMP+245 | ||
| Cohort 4: | |||
| Postpartum hemorrhage | ≥1 duloxetine dispensing delivery–30 to delivery | Unexposed | No duloxetine dispensing between LMP–90 and delivery |
| SSRI* | ≥1 SSRI dispensing delivery–30 to delivery | ||
| Venlafaxine† | ≥1 venlafaxine dispensing delivery–30 to delivery | ||
LMP=last menstrual period; SSRI-selective serotonin reuptake inhibitor.
Excludes women with dispensing for both duloxetine and SSRI during exposure window or baseline period from cohort. No exclusions based on use of antidepressants other than duloxetine and SSRIs.
Excludes women with dispensing for both duloxetine and venlafaxine during exposure window or baseline period from cohort. No exclusions based on use of antidepressants other than duloxetine and venlafaxine.
To reduce likelihood of misclassification as unexposed women who still had medication from last fill available to consume early in pregnancy, gap between last prescription fill and start of pregnancy for discontinuers was set at 8 weeks.