Table 5.
Estimates for the risk of neonatal abstinence syndrome (NAS) based on the timing of prescription opioid use during pregnancy, Medicaid data 2000-07
| Population | Total NAS cases/sample size | Absolute NAS risks per 1000 deliveries (95% CI) based on timing of prescription opioid use | Relative risks (95% CI) for late v early prescription opioid use | |||||
|---|---|---|---|---|---|---|---|---|
| Late use* | Early use* | Late use | Early use | Unadjusted | Adjusted† | |||
| Whole cohort | 1042/134 361 | 663/156 244 | 7.8 (7.3 to 8.2) | 4.2 (3.9 to 4.6) | 1.83 (1.66 to 2.01) | 1.24 (1.12 to 1.38) | ||
| Study groups based on hierarchical NAS risk factors‡ | ||||||||
| Group 1: Documented history of opioid drug abuse/dependence | 571/2836 | 414/1980 | 201.3 (185.2 to 218.6) | 209.1 (189.4 to 230.2) | 0.96 (0.86 to 1.08) | 1.01 (0.89 to 1.15) | ||
| Group 2: Documented history of alcohol/non-opioid drug abuse | 211/14 144 | 108/14 409 | 14.9 (13 to 17.1) | 7.5 (6.1 to 9.0) | 1.99 (1.58 to 2.51) | 1.74 (1.35 to 2.25) | ||
| Group 3: Exposure to other psychotropic medications§ in the third trimester | 120/20 775 | 28/13 948 | 5.8 (4.8 to 6.9) | 2.0 (1.3 to 2.9) | 2.88 (1.91 to 4.34) | 2.50 (1.61 to 3.87) | ||
| Group 4: Documented smoking history | 38/13 366 | 24/15 146 | 2.8 (2 to 3.9) | 1.6 (1.0 to 2.4) | 1.79 (1.08 to 2.99) | 1.85 (1.07 to 3.19) | ||
| Group 5: No history of above listed four risk factors | 102/83 240 | 89/110 761 | 1.2 (1 to 1.5) | 0.8 (0.6 to 1.0) | 1.53 (1.15 to 2.03) | 1.48 (1.09 to 2.01) | ||
NAS=neonatal abstinence syndrome, CI=confidence interval.
*Early use included filled prescriptions only in the first two trimesters but no newly dispensed opioid prescription in the last 90 days before delivery; late use included at least one filled prescription in the last 90 days before delivery, irrespective of earlier use.
†Propensity score (PS) matching of late users with early users was used to adjust for confounding factors including age, geographic region, race, pain condition diagnoses, calendar year of delivery, and other NAS risk factors. Risk ratios derived using generalized estimating equations with log link and exchangeable working correlation matrix to account for clustering due to inclusion of mothers with multiple deliveries in the cohort.
‡Five mutually exclusive groups were created hierarchically based on the presence of four risk factors. Everyone in group 1 had a history of opioid abuse/dependence; everyone in group 2 had a history of alcohol/non-opioid drug abuse but no opioid abuse or dependence history; everyone in group 3 had exposure to other psychotropic medications in the third trimester but no history of opioid abuse/dependence or alcohol/non-opioid drug abuse; everyone in group 4 had history of smoking but no history of opioid abuse/dependence or alcohol/non-opioid drug abuse or exposure to other psychotropic medications in the third trimester; and everyone in group 5 had none of the four identified risk factors.
§Other psychotropic medication included were tricyclic antidepressants, selective serotonin re-uptake inhibitors, selective nor epinephrine re-uptake inhibitor, benzodiazepines, antipsychotics, antiepileptics, and non-benzodiazepine sedative hypnotic.