The study population consisted of over 1.1 million women with completed pregnancies, and was drawn from the Medicaid Analytical eXtract for 46 U.S. states and Washington, DC, for the period of 2000-2007. Montana and Connecticut were excluded because of difficulty in linking mothers and infants, Michigan was excluded because of incomplete data, and data from Arizona were not available. We identified all completed pregnancies in women aged 12-55 years linked to live-born infants. We estimated the date of last menstrual period (LMP) based on the delivery date combined with a validated algorithm based on diagnosis codes (6 (link)). The LMP was assigned to be 245 days before the delivery date for pregnancies that had maternal or infant ICD-9 codes indicative of preterm delivery (644.0, 644.2, and 765.x) and to be 270 days before the delivery date for all other pregnancies. Finally, we required all women to be Medicaid eligible throughout pregnancy. To ensure a complete, longitudinal stream of healthcare claims throughout pregnancy, we excluded women with supplementary private insurance, women with restricted benefits and women in selected capitated managed care plans. Derivation of this cohort has previously been described in detail elsewhere (7 (link)).
Filled prescriptions of opioid analgesics were identified using pharmacy-dispensing claims. We then defined three trimesters using the date of LMP; the first trimester extended from the LMP through day 90 of pregnancy, the second trimester was the following 90 days, and the third trimester began 181 days after estimated LMP and continued until delivery. Based on the dispensing date, each prescription was classified as dispensed in the respective trimester. We accumulated days supply for each filled opioid prescription to derive the cumulative days of opioid availability during pregnancy overall and during each trimester. We assumed that opioids were consumed regularly at the minimum specified interval even if prescribed on an as-needed basis. Cumulative days of opioid availability were reported as median (interquartile range (IQR)).In addition to prescriptions at the class level, we also explored prescriptions filled for individual opioid agents during each trimester. The opioids considered in our analysis included hydrocodone, codeine, oxycodone, propoxyphene, tramadol, meperidine, hydromorphone, morphine, fentanyl, buprenorphine, methadone, pentazocine, tapentadol, and oxymorphone.
Patient characteristics, including race, age, geographic region, most frequent pain diagnoses, and caesarean sections, were presented for women who did and did not fill an opioid prescription during pregnancy. Regional and time trends adjusting for demographic characteristics for prescription opioids fills were examined using mixed effects regression analyses. All analyses were conducted using SAS version 9.3 (SAS institute, Cary, NC). The use of this de-identified database for research was approved by the Institutional Review Board at the Brigham and Women’s Hospital.
Filled prescriptions of opioid analgesics were identified using pharmacy-dispensing claims. We then defined three trimesters using the date of LMP; the first trimester extended from the LMP through day 90 of pregnancy, the second trimester was the following 90 days, and the third trimester began 181 days after estimated LMP and continued until delivery. Based on the dispensing date, each prescription was classified as dispensed in the respective trimester. We accumulated days supply for each filled opioid prescription to derive the cumulative days of opioid availability during pregnancy overall and during each trimester. We assumed that opioids were consumed regularly at the minimum specified interval even if prescribed on an as-needed basis. Cumulative days of opioid availability were reported as median (interquartile range (IQR)).In addition to prescriptions at the class level, we also explored prescriptions filled for individual opioid agents during each trimester. The opioids considered in our analysis included hydrocodone, codeine, oxycodone, propoxyphene, tramadol, meperidine, hydromorphone, morphine, fentanyl, buprenorphine, methadone, pentazocine, tapentadol, and oxymorphone.
Patient characteristics, including race, age, geographic region, most frequent pain diagnoses, and caesarean sections, were presented for women who did and did not fill an opioid prescription during pregnancy. Regional and time trends adjusting for demographic characteristics for prescription opioids fills were examined using mixed effects regression analyses. All analyses were conducted using SAS version 9.3 (SAS institute, Cary, NC). The use of this de-identified database for research was approved by the Institutional Review Board at the Brigham and Women’s Hospital.
