Development and Validation of a Model to Predict Neonatal Abstinence Syndrome.

OBJECTIVES: To develop and validate clinical risk prediction tools for neonatal abstinence syndrome (NAS). STUDY DESIGN: We developed prediction models for NAS based on a set of 30 demographic and antenatal exposure covariates collected during pregnancy. Data (outpatient prescription, vital, and administrative records), were obtained from enrollees in the Tennessee Medicaid Program from 2009 to 2014. Models were created using logistic regression and backward selection based on improvement in the Akaike information criterion, and internally validated using bootstrap cross-validation. RESULTS: A total of 218 020 maternal and infant dyads met inclusion criteria, of whom 3208 infants were diagnosed with NAS. The general population model included age, hepatitis C virus infection, days of opioid used by type, number of cigarettes used daily, and the following medications used in the last 30 day of pregnancy: bupropion, antinausea medicines, benzodiazepines, antipsychotics, and gabapentin. Infant characteristics included birthweight, small for gestational age, and infant sex. A high-risk model used a smaller number of predictive variables. Both models discriminated well with an area under the curve of 0.89 and were well-calibrated for low-risk infants. CONCLUSIONS: We developed 2 predictive models for NAS based on demographics and antenatal exposure during the last 30 days of pregnancy that were able to risk stratify infants at risk of developing the syndrome.

Individual short-acting opioids and the risk of opioid-related adverse events in adolescents.

PURPOSE: Hydrocodone, codeine, oxycodone, and tramadol are frequently prescribed to adolescents for moderate pain related to minor trauma or dental, surgical, or medical procedures. Pharmacokinetic and pharmacodynamic differences between these opioids could affect their relative safety. We aimed to compare occurrence of opioid-related adverse events in adolescents without cancer or other severe conditions taking hydrocodone, codeine, oxycodone, and tramadol. METHODS: Retrospective cohort study of 201 940 Tennessee Medicaid enrollees 12 to 17 years of age without cancer, other severe conditions, or evidence of substance abuse with 529 731 filled prescriptions for study opioids. Adverse events were defined as an emergency department visit, hospital admission, or death related to opioid use, confirmed by medical record review. Serious events had opioid-related escalation of care, hospitalization, or death. Propensity-score adjusted hazard ratios (HRs) were calculated with hydrocodone as the reference category. RESULTS: The incidence of opioid-related adverse events per 10 000 person-years of opioid exposure was 97.5 for hydrocodone (127 events/13 026 person-years), 91.2 for codeine (58/6,359), 229.7 for oxycodone (43/1,872), and 317.7 for tramadol (47/1479). The HRs for tramadol in comparison with hydrocodone for all and serious events were 2.98 (2.03-4.39) and 2.94 (1.81-4.75), respectively. Increased risk for tramadol was consistently present when the adverse events were restricted to those with neurologic-respiratory depression/other symptoms of possible overdose. CONCLUSION: In adolescents without cancer or other severe conditions prescribed short-acting opioids, the incidence of both all opioid-related adverse events and more serious events with opioid-related escalation of care, hospitalization, or death was consistently greater for tramadol than for hydrocodone.

Association Among County-Level Economic Factors, Clinician Supply, Metropolitan or Rural Location, and Neonatal Abstinence Syndrome.

Importance: Neonatal abstinence syndrome (NAS) has increased over the last 2 decades, but limited data exist on its association with economic conditions or clinician supply. Objective: To determine the association among long-term unemployment, clinician supply (as assessed by primary care and mental health clinician shortage areas), and rates of NAS and evaluate how associations differ based on rurality. Design, Setting, and Participants: Ecological time-series analysis of a retrospective, repeated cross-sectional study using outcome data from all 580 counties in Florida, Kentucky, Massachusetts, Michigan, New York, North Carolina, Tennessee, and Washington from 2009 to 2015 and economic data from 2000 to 2015. Negative binomial models were used with year and county-level fixed effects. Interactions were tested and stratified analyses were conducted by metropolitan counties, rural counties adjacent to metropolitan counties, and rural remote counties. Exposures: County-level 10-year unemployment rate and mental health and primary care clinician supply obtained from the Health Resources and Services Administration Area Health Resources Files. Main Outcomes and Measure: Rates of NAS, excluding iatrogenic withdrawal, obtained from state inpatient databases. Results: The sample included observations from 580 counties over 7 years (1803 county-years from metropolitan counties, 1268 county-years from rural counties adjacent to metropolitan counties, and 927 county-years from rural remote counties). During the study period, there were 6 302 497 births and 47 224 diagnoses of NAS. The median rate of NAS was 7.1 per 1000 hospital births (interquartile range [IQR], 2.2-15.8), the 10-year unemployment rate was 7.6% (IQR, 6.4%-9.0%), and 83.9% of county-years were partial or complete mental health shortage areas. In the adjusted analyses, mental health shortage areas had higher NAS rates (unadjusted rate in shortage areas of 14.0 per 1000 births vs unadjusted rate in nonshortage areas of 10.6 per 1000 births; adjusted incidence rate ratio [IRR], 1.17 [95% CI, 1.07-1.27]), occurring primarily in metropolitan counties (adjusted IRR, 1.28 [95% CI, 1.16-1.40]; P = .02 for test of equivalence between metropolitan counties and rural counties adjacent to metropolitan counties). There was no significant association between primary care shortage areas and rates of NAS. The 10-year unemployment rate was associated with higher rates of NAS (unadjusted rate in highest unemployment quartile of 20.1 per 1000 births vs 7.8 per 1000 births in lowest unemployment quartile; adjusted IRR, 1.11 [95% CI, 1.00-1.23]) occurring primarily in rural remote counties (adjusted IRR, 1.34 [95% CI, 1.05-1.70]; P = .04 for test of equivalence between metropolitan counties and rural remote counties). Conclusions and Relevance: In this ecological analysis of counties in 8 US states, there was a significant association among higher long-term unemployment, higher mental health clinician shortage areas, and higher county-level rates of neonatal abstinence syndrome.

Outpatient Pharmacotherapy for Neonatal Abstinence Syndrome.

OBJECTIVE: To determine differences in lengths of stay, length of therapy, emergency department (ED) utilization, and hospital readmissions between infants with neonatal abstinence syndrome (NAS) treated exclusively with inpatient pharmacotherapy compared with those discharged on outpatient pharmacotherapy. STUDY DESIGN: This retrospective cohort study of infants enrolled in the Tennessee Medicaid program used administrative and vital records data from 2009 to 2011. Medical record review was used to confirm cases of NAS and classify treatment type. Negative binomial regression was used to compare length of therapy and ordinal regression was used to determine frequency of ED visits and hospital readmissions. RESULTS: Among a cohort of 736 patients with confirmed NAS, 72.3% were treated with pharmacotherapy of which approximately one-half (45.5%) were discharged home on outpatient medications. For infants discharged on outpatient pharmacotherapy, initial hospital length of stay was shorter (11 vs 23 days; P < .001) and length of therapy was longer (60 vs 19 days; adjusted incidence rate ratio [aIRR] 2.84, 95%CI 2.31-3.52). After adjusting for potential confounders, infants discharged on outpatient pharmacotherapy had a greater number of ED visits within 6 months of discharge (adjusted odds ratio [aOR] 1.52, 95% CI 1.06-2.17) compared with those treated as inpatients alone. CONCLUSIONS: Outpatient pharmacotherapy for NAS was associated with higher length of therapy and higher rates of ED utilization when compared with infants treated exclusively as inpatients. Future research should focus on improving the efficiency of NAS management while minimizing postdischarge complications.

Adherence to transcranial Doppler screening guidelines among children with sickle cell disease.

BACKGROUND: Little is known about adherence to guidelines recommending yearly screening with transcranial Doppler (TCD) ultrasonography to detect stroke risk for children with severe sickle cell disease. The objective was to determine the proportion of children with hemoglobin SS (HbSS) or sickle-ß(0) -thalassemia (HbSß(0) ) aged 2-16 years who received recommended TCD screening from 1997 to 2008, and to identify factors associated with adherence. PROCEDURE: A retrospective cohort study included patients enrolled in Tennessee Medicaid with HbSS or HbSß(0) who received care at the two largest sickle cell centers in Tennessee. The outcome of interest was adherence with guidelines for annual screening TCD's, identified from computer claims and validated through medical record review. The cumulative rate of children who received a TCD per year was calculated using the Kaplan-Meier method. Cox proportional hazards regression was used to examine the association of child, family, and health care use characteristics with receiving a TCD. RESULTS: Among 338 TCD eligible at-risk children, 232 (68.6%) had at least one TCD during the study period. The yearly cumulative incidence of annual TCD's increased from 2.5% in 1997 to 68.3% in 2008. In multivariate models, calendar year, maternal education, and increased number of sickle cell related outpatient visits were associated with an increased rate of receiving a TCD. CONCLUSIONS: Publicly insured children with HbSS or HbSß(0) had increasing adherence with TCD screening guidelines between 1997 and 2008, though 31% had no TCD at all during follow-up. Increasing number of sickle cell related outpatient visits was associated with increasing adherence to screening guidelines.

Identifying suicidal behavior among adolescents using administrative claims data.

PURPOSE: To assess the safety of psychotropic medication use in children and adolescents, it is critical to be able to identify suicidal behaviors from medical claims data and distinguish them from other injuries. The purpose of this study was to develop an algorithm using administrative claims data to identify medically treated suicidal behavior in a cohort of children and adolescents. METHODS: The cohort included 80,183 youth (6-18 years) enrolled in Tennessee's Medicaid program from 1995-2006 who were prescribed antidepressants. Potential episodes of suicidal behavior were identified using external cause-of-injury codes (E-codes) and ICD-9-CM codes corresponding to the potential mechanisms of or injuries resulting from suicidal behavior. For each identified episode, medical records were reviewed to determine if the injury was self-inflicted and if intent to die was explicitly stated or could be inferred. RESULTS: Medical records were reviewed for 2676 episodes of potential self-harm identified through claims data. Among 1162 episodes that were classified as suicidal behavior, 1117 (96%) had a claim for suicide and self-inflicted injury, poisoning by drugs, or both. The positive predictive value of code groups to predict suicidal behavior ranged from 0-88% and improved when there was a concomitant hospitalization but with the limitation of excluding some episodes of confirmed suicidal behavior. CONCLUSIONS: Nearly all episodes of confirmed suicidal behavior in this cohort of youth included an ICD-9-CM code for suicide or poisoning by drugs. An algorithm combining these ICD-9-CM codes and hospital stay greatly improved the positive predictive value for identifying medically treated suicidal behavior.

Trends in the use of antiepileptic drugs among pregnant women in the US, 2001-2007: a medication exposure in pregnancy risk evaluation program study.

BACKGROUND: Little is known about the extent of antiepileptic drug (AED) use in pregnancy, particularly for newer agents. Our objective was to assess whether AED use has increased among pregnant women in the US, 2001-2007. METHODS: We analysed data from the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP) database, 1 January 2001 to 31 December 2007. We identified liveborn deliveries among women, aged 15-45 years on delivery date, who were members of MEPREP health plans (n=585615 deliveries). Pregnancy exposure to AEDs, determined through outpatient pharmacy dispensing files. Older AEDs were available for clinical use before 1993; other agents were considered newer AEDs. Information on sociodemographic and medical/reproductive factors was obtained from linked birth certificate files. Maternal diagnoses were identified based on ICD-9 codes. RESULTS: Prevalence of AED use during pregnancy increased between 2001 (15.7 per 1000 deliveries) and 2007 (21.9 per 1000 deliveries), driven primarily by a fivefold increase in the use of newer AEDs. Thirteen per cent of AED-exposed deliveries involved a combination of two or more AEDs. Psychiatric disorders were the most prevalent diagnoses, followed by epileptic and pain disorders, among AED users regardless of AED type, year of conception or gestational period. CONCLUSIONS: AED use during pregnancy increased between 2001 and 2007, driven by a fivefold increase in the use of newer AEDs. Nearly one in eight AED-exposed deliveries involved the concomitant use of more than one AED. Additional investigations of the reproductive safety of newer AEDs may be needed.

Hepatitis C Testing Among Perinatally Exposed Infants.

BACKGROUND: Hepatitis C virus (HCV) prevalence doubled among pregnant women from 2009 to 2014, reaching 3.4 per 1000 births nationwide. Infants exposed to HCV may acquire HCV by vertical transmission. National guidelines recommend that infants exposed to HCV be tested; however, it is unclear if these recommendations are being followed. Our objectives were to determine if infants exposed to HCV were tested and to determine hospital- and patient-level factors associated with differences in testing. METHODS: In this retrospective cohort study of infants exposed to HCV who were enrolled in the Tennessee Medicaid program, we used vital statistics-linked administrative data for infants born between January 1, 2005, and December 31, 2014. Infants were followed until 2 years old. Multilevel logistic regression was used to assess the association of HCV testing and hospital- and patient-level characteristics. RESULTS: Only 23% of 4072 infants exposed to HCV were tested. Infants whose mothers were white versus African American (96.6% vs 3.1%; P <.001), used tobacco (78% vs 70%; P <.001), and had HIV (1.3% vs 0.4%; P = .002) were more likely to be tested. Infants exposed to HCV who had a higher median of well-child visits (7 vs 6; P <.001) were more likely to be tested. After accounting for maternal and infant characteristics and health care use patterns, African American infants were less likely to undergo general testing (adjusted odds ratio 0.32; 95% confidence interval, 0.13-0.78). CONCLUSIONS: Testing occurred in <1 in 4 infants exposed to HCV and less frequently among African American infants. Public health systems need to be bolstered to ensure that infants exposed to HCV are tested for seroconversion.

Major congenital malformations after first-trimester exposure to ACE inhibitors.

BACKGROUND: Use of angiotensin-converting-enzyme (ACE) inhibitors during the second and third trimesters of pregnancy is contraindicated because of their association with an increased risk of fetopathy. In contrast, first-trimester use of ACE inhibitors has not been linked to adverse fetal outcomes. We conducted a study to assess the association between exposure to ACE inhibitors during the first trimester of pregnancy only and the risk of congenital malformations. METHODS: We studied a cohort of 29,507 infants enrolled in Tennessee Medicaid and born between 1985 and 2000 for whom there was no evidence of maternal diabetes. We identified 209 infants with exposure to ACE inhibitors in the first trimester alone, 202 infants with exposure to other antihypertensive medications in the first trimester alone, and 29,096 infants with no exposure to antihypertensive drugs at any time during gestation. Major congenital malformations were identified from linked vital records and hospitalization claims during the first year of life and confirmed by review of medical records. RESULTS: Infants with only first-trimester exposure to ACE inhibitors had an increased risk of major congenital malformations (risk ratio, 2.71; 95 percent confidence interval, 1.72 to 4.27) as compared with infants who had no exposure to antihypertensive medications. In contrast, fetal exposure to other antihypertensive medications during only the first trimester did not confer an increased risk (risk ratio, 0.66; 95 percent confidence interval, 0.25 to 1.75). Infants exposed to ACE inhibitors were at increased risk for malformations of the cardiovascular system (risk ratio, 3.72; 95 percent confidence interval, 1.89 to 7.30) and the central nervous system (risk ratio, 4.39; 95 percent confidence interval, 1.37 to 14.02). CONCLUSIONS: Exposure to ACE inhibitors during the first trimester cannot be considered safe and should be avoided.

Antibiotics potentially used in response to bioterrorism and the risk of major congenital malformations.

This study was designed to assess the association between pregnancy-related exposures to antibiotics recommended for use in the event of a bioterrorism attack and major congenital malformations. A retrospective cohort study included 30 049 infants from Tennessee Medicaid born between 1985 and 2000 identified from computerised state databases. Infants with fetal exposures to ciprofloxacin, azithromycin, doxycycline and amoxicillin (antibiotics recommended for potential bioterrorism attacks) (n = 24 521) and erythromycin (included as a positive control) (n = 2128) were compared with infants with no fetal exposure to any antibiotics (n = 3400). Major congenital malformations identified from computerised records were confirmed through medical record review. Overall, 869 (2.9%) of infants in the cohort had a confirmed major congenital malformation, with major malformations ranging from 2.5% to 3.0% among the antibiotic-specific exposure groups. No increased risk was present in multivariable analyses for any malformations and for malformations of specific organ systems. In conclusion, these data suggest that ciprofloxacin, azithromycin, doxycycline or amoxicillin use by pregnant women should not result in a greater incidence of overall major congenital malformations in infants whose mothers take these medications, though a large increase in risk cannot be ruled out.

Increased Severity of Neonatal Abstinence Syndrome Associated With Concomitant Antenatal Opioid and Benzodiazepine Exposure.

BACKGROUND: Polysubstance use is common among opioid-using women, yet its association with pharmacotherapy for neonatal abstinence syndrome (NAS) remains unclear. We hypothesized that benzodiazepine exposure would increase risk of an infant developing pharmacologically treated NAS. METHODS: We conducted a retrospective cohort study of maternal-infant dyads enrolled in Tennessee Medicaid, using individual-level data linkage of vital records and administrative (ie, outpatient, inpatient, and prescription) data from 2009 to 2011. These data underwent chart review from 2013 to 2016 to obtain clinically relevant exposure data (eg, toxicology testing). The association of antenatal exposures with pharmacologically treated NAS was evaluated by using multivariable logistic regression, controlling for maternal and infant factors and clustered by hospital. RESULTS: Among 112 029 maternal-infant dyads, we confirmed 822 cases of NAS, of which 598 (72.7%) were cases of pharmacologically treated NAS. Infants who developed pharmacologically treated NAS were more likely to have been exposed to antenatal benzodiazepines compared with infants with confirmed NAS not treated pharmacologically (40.9% vs 30.8%; P = .008). In adjusted analyses, benzodiazepine exposure was associated with greater risk of developing pharmacologically treated NAS (odds ratio: 1.51; 95% confidence interval: 1.04-2.21). Alternatively, exposure to tobacco, marijuana, cocaine, gabapentin, and selective serotonin reuptake inhibitors were not associated with increased risk of developing pharmacologically treated NAS. CONCLUSIONS: Among a population of infants with intrauterine polysubstance exposure, benzodiazepine exposure was an independent predictor of an infant developing pharmacologically treated NAS. Obtaining history of antenatal benzodiazepine exposure among opioid-exposed infants may allow for risk stratification and development of personalized care plans.

Positive Predictive Value of Administrative Data for Neonatal Abstinence Syndrome.

OBJECTIVES: Neonatal abstinence syndrome (NAS) is a postnatal withdrawal syndrome experienced by some infants with opioid exposure. Hospital administrative data are commonly used for research and surveillance but have not been validated for NAS. Our objectives for this study were to validate the diagnostic codes for NAS and to develop an algorithm to optimize identification. METHODS: Tennessee Medicaid claims from 2009 to 2011 (primary sample) and 2016 (secondary sample; post-International Classification of Diseases, 10th Revision, Clinical Modification [ICD-10-CM]) were obtained. Cases of NAS were identified by using International Classification of Diseases, Ninth Revision, Clinical Modification code (2009-2011) 779.5 and ICD-10-CM code (2016) P96.1. Medical record review cases were then conducted by 2 physicians using a standardized algorithm, and positive predictive value (PPV) was calculated. Algorithms were developed for optimizing the identification of NAS in administrative data. RESULTS: In our primary sample of 112 029 mother-infant dyads, 950 potential NAS cases were identified from Medicaid claims data and reviewed. Among reviewed records, 863 were confirmed as having NAS (including 628 [66.1%] cases identified as NAS requiring pharmacotherapy, 224 [23.5%] as NAS not requiring pharmacotherapy, and 11 [1.2%] as iatrogenic NAS), and 87 (9.2%) did not meet clinical criteria for NAS. The PPV of the International Classification of Diseases, Ninth Revision, Clinical Modification code for NAS in clinically confirmed NAS was 91% (95% confidence interval: 88.8%-92.5%). Similarly, the PPV for the ICD-10-CM code in the secondary sample was 98.2% (95% confidence interval: 95.4%-99.2%). Algorithms using elements from the Medicaid claims and from length of stay improved PPV. CONCLUSIONS: In a large population-based cohort of Medicaid participants, hospital administrative data had a high PPV in identifying cases of clinically diagnosed NAS.

Health plan notification and feedback to providers is associated with increased filling of preventer medications for children with asthma enrolled in Medicaid.

OBJECTIVE: To test the hypothesis that children enrolled in Medicaid managed care health plans that provide asthma-specific communication to providers would be more likely to have adequate asthma medication filling. STUDY DESIGN: We conducted a historical cohort study of 4498 children (2-17 years old) with moderate-severe asthma in Washington State and Tennessee Medicaid managed care programs from 2000 to 2002. Interviews with health plans were conducted to identify communication strategies health plans used to improve asthma care by providers in the plan. The main outcome measure was guideline-recommended filling of asthma preventer medications. RESULTS: Children in plans that provided specific feedback to providers about asthma quality and notified providers when children had an asthma-related event had the highest mean days plus or minus SE of filling in the 365-day follow-up period (164.6 +/- 13 days) compared with children in plans with neither (135.3 +/- 10.8 days; P < .05). In children with the greatest asthma severity, enrollment in a plan with both features was associated with 27.1 additional days of filling (95% CI, 0.7-53.4 days) during the follow-up period. CONCLUSION: Health plan communication to providers was associated with increased preventer filling in children with moderate-severe asthma in 2 state Medicaid programs.

Trends in healthcare usage attributable to diarrhea, 1995-2004.

OBJECTIVE: To determine current diarrhea-associated healthcare usage rates and associated sociodemographic factors. These data can be used to determine the impact of the rotavirus vaccine. STUDY DESIGN: Using discharge diagnosis codes, we determined diarrhea-associated visit rates for children aged 0 to 18 years enrolled in Tennessee Medicaid, 1995-2004. Poisson regression compared data across time and within strata. The winter residual excess method estimated the rotavirus burden. RESULTS: Analyzing approximately 500 000 person-years annually, outpatient and hospitalization rates remained stable from 1995 to 2004; emergency department (ED) rates approximately doubled, incidence rate ratio (IRR): 1.92 (1.81-2.04). White children used healthcare at greater rates than black children: outpatient IRR 1.90: (1.85-1.95), ED IRR: 1.69 (1.64-1.74), and inpatient IRR: 1.82 (1.73-1.92); and rural children greater than urban: outpatient IRR 1.66 (1.62-1.70), ED IRR 1.14 (1.11-1.17), inpatient IRR 1.88 (1.80-1.97). Children aged 0 to 35 months experienced 1627 outpatient and 792 ED visits, and 148 hospitalizations per 10 000 child-years; rotavirus may have affected up to 40% of these hospitalizations. CONCLUSIONS: Diarrhea-associated ED visit rates nearly doubled from 1995 to 2004. Future studies could explore factors resulting in increased healthcare usage by white children and those living in rural areas and document the rotavirus vaccine's impact after its release.

Positive predictive value of computerized records for major congenital malformations.

PURPOSE: To assess the positive predictive value of computerized records in a linked database of vital records and infant claims, with medical record confirmation to detect congenital malformations in a Medicaid population. METHODS: Study subjects were selected from cases identified for three studies of congenital malformations in the Tennessee Medicaid (TennCare) population including 173 827 (studies 1 and 2) and 519 465 (study 3) mother/infant pairs. Possible malformations were identified from computerized databases of birth certificates linked with maternal and infant claims. Medical records were reviewed for all possible congenital malformations and positive predictive values were calculated for each data source and for each malformation. RESULTS: Among 1430 potential congenital malformations identified from either birth certificates or inpatient claims, 67.7% were confirmed by medical record review. The positive predictive value varied considerably depending on the data source and the organ system. For example, cardiac defects had a very low positive predictive value when identified from birth certificates, and somewhat higher positive predictive value when identified from inpatient claims. Orofacial defects had 90.9% positive predictive value from birth certificates and inpatient claims. Requiring evidence of a diagnostic or therapeutic procedure increased the positive predictive value to >90% for specific defects, but substantially reduced the number of included cases. CONCLUSIONS: Depending on the defect, computerized claims data linked to vital records offer opportunities for identifying birth defects in populations of vulnerable persons. However, for many defects, medical record confirmation is likely to be required to provide valid identification of malformation occurrence.

Outpatient Opioid Prescriptions for Children and Opioid-Related Adverse Events.

BACKGROUND AND OBJECTIVES: Little is known about opioid prescribing for children without severe conditions. We studied the prevalence of and indications for outpatient opioid prescriptions and the incidence of opioid-related adverse events in this population. METHODS: This retrospective cohort study between 1999 and 2014 included Tennessee Medicaid children and adolescents aged 2 to 17 without major chronic diseases, prolonged hospitalization, institutional residence, or evidence of a substance use disorder. We estimated the annual prevalence of outpatient opioid prescriptions and incidence of opioid-related adverse events, defined as an emergency department visit, hospitalization, or death related to an opioid adverse effect. RESULTS: There were 1 362 503 outpatient opioid prescriptions; the annual mean prevalence of opioid prescriptions was 15.0%. The most common opioid indications were dental procedures (31.1% prescriptions), outpatient procedure and/or surgery (25.1%), trauma (18.1%), and infections (16.5%). There were 437 cases of opioid-related adverse events confirmed by medical record review; 88.6% were related to the child's prescription and 71.2% had no recorded evidence of deviation from the prescribed regimen. The cumulative incidence of opioid-related adverse events was 38.3 of 100 000 prescriptions. Adverse events increased with age (incidence rate ratio = 2.22; 95% confidence interval, 1.67-2.96; 12-17 vs 2-5 years of age) and higher opioid doses (incidence rate ratio = 1.86 [1.45-2.39]; upper versus lower dose tertiles). CONCLUSIONS: Children without severe conditions enrolled in Tennessee Medicaid frequently filled outpatient opioid prescriptions for acute, self-limited conditions. One of every 2611 study opioid prescriptions was followed by an opioid-related adverse event (71.2% of which were related to therapeutic use of the prescribed opioid).

Effect of regulatory warnings on antidepressant prescribing for children and adolescents.

OBJECTIVE: To evaluate the effect of UK and US warnings placed in response to reports of suicidal thinking in pediatric patients receiving selective serotonin reuptake inhibitor and selective norepinephrine reuptake inhibitor antidepressants on antidepressant prescribing for children and adolescents. DESIGN: Interrupted time-series analysis of antidepressant prescriptions. SETTING: Tennessee's Medicaid program, January 1, 2002, through September 30, 2005. PARTICIPANTS: A mean of 405,000 children and adolescents aged 2 to 17 years qualified each month. Main Exposure Piecewise linear regression models were used to estimate the cumulative effect of the warnings, which were considered the exposure of interest. MAIN OUTCOME MEASURES: Monthly proportions of study children and adolescents who were new users of antidepressants, had discontinuity in antidepressant use, or were users of other psychotropic drugs. RESULTS: During the 2 years preceding the UK warning, there was no trend in the monthly proportions of new antidepressant users, with 23 new users per 10 000 persons per month. This proportion subsequently decreased 33% (95% confidence interval, 23% to 41%; P < .001) by 21 months following the UK warning. The reduction was most pronounced for the nonfluoxetine selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors, where initiations decreased 54% (95% confidence interval, 46% to 62%; P < .001). In contrast, new users of fluoxetine increased 60% (95% confidence interval, 9% to 135%; P = .02). There was no increase in discontinuations of antidepressants, and there was no evidence of substitution of other psychotropic drugs. CONCLUSION: The regulatory warnings led to decreased use of antidepressants in children and adolescents, but the clinical and public health consequences of this change are unknown.

Male Sex Associated With Increased Risk of Neonatal Abstinence Syndrome.

BACKGROUND: Neonatal abstinence syndrome (NAS) is a postnatal opioid withdrawal syndrome. Factors associated with development of the syndrome are poorly understood; however, infant sex may influence the risk of NAS. Our objective was to determine if infant sex was associated with the development or severity of the syndrome in a large population-based cohort. METHODS: This retrospective cohort study used vital statistics and prescription, outpatient, and inpatient administrative data for mothers and infants enrolled in the Tennessee Medicaid program between 2009 and 2011. Multivariable logistic regression models were used to evaluate the association between male sex and diagnosis of NAS, accounting for potential demographic and clinical confounders. NAS severity, as evidenced by hospital length of stay, was modeled by using negative binomial regression. RESULTS: Of 102 695 infants, 927 infants were diagnosed with NAS (484 male subjects and 443 female subjects). Adjustments were made for the following: maternal age, race, and education; maternal hepatitis C infection, anxiety, or depression; in utero exposure to selective serotonin reuptake inhibitors and cigarettes; infant birth weight, small for gestational age, and year; and the interaction between opioid type and opioid amount. Male infants were more likely than female infants to be diagnosed with NAS (adjusted odds ratio, 1.18 [95% confidence interval, 1.05-1.33]) and NAS requiring treatment (adjusted odds ratio, 1.24 [95% confidence interval, 1.04-1.47]). However, there was no sex-based difference in severity for those diagnosed with NAS. CONCLUSIONS: Treatment of NAS should be tailored to an infant's individual risk for the syndrome. Clinicians should be mindful that male sex is an important risk factor in the diagnosis of NAS.

Prescription opioid epidemic and infant outcomes.

BACKGROUND AND OBJECTIVES: Although opioid pain relievers are commonly prescribed in pregnancy, their association with neonatal outcomes is poorly described. Our objectives were to identify neonatal complications associated with antenatal opioid pain reliever exposure and to establish predictors of neonatal abstinence syndrome (NAS). METHODS: We used prescription and administrative data linked to vital statistics for mothers and infants enrolled in the Tennessee Medicaid program between 2009 and 2011. A random sample of NAS cases was validated by medical record review. The association of antenatal exposures with NAS was evaluated by using multivariable logistic regression, controlling for maternal and infant characteristics. RESULTS: Of 112,029 pregnant women, 31,354 (28%) filled ≥ 1 opioid prescription. Women prescribed opioid pain relievers were more likely than those not prescribed opioids (P < .001) to have depression (5.3% vs 2.7%), anxiety disorder (4.3% vs 1.6%) and to smoke tobacco (41.8% vs 25.8%). Infants with NAS and opioid-exposed infants were more likely than unexposed infants to be born at a low birth weight (21.2% vs 11.8% vs 9.9%; P < .001). In a multivariable model, higher cumulative opioid exposure for short-acting preparations (P < .001), opioid type (P < .001), number of daily cigarettes smoked (P < .001), and selective serotonin reuptake inhibitor use (odds ratio: 2.08 [95% confidence interval: 1.67-2.60]) were associated with greater risk of developing NAS. CONCLUSIONS: Prescription opioid use in pregnancy is common and strongly associated with neonatal complications. Antenatal cumulative prescription opioid exposure, opioid type, tobacco use, and selective serotonin reuptake inhibitor use increase the risk of NAS.

Evaluation and disposition of Medicaid-insured children and adolescents with suicide attempts.

OBJECTIVE: Guidelines and quality of care measures for the evaluation of adolescent suicidal behavior recommend prompt mental health evaluation, hospitalization of high-risk youth, and specific follow-up plans-all of which may be influenced by sociodemographic factors. The aim of this study was to identify sociodemographic characteristics associated with variations in the evaluation of youth with suicidal behavior. METHODS: We conducted a large cohort study of youth, aged 7 to 18, enrolled in Tennessee Medicaid from 1995 to 2006, who filled prescriptions for antidepressants and who presented for evaluation of injuries that were determined to be suicidal on the basis of external cause-of-injury codes (E codes) and ICD-9-CM codes and review of individual medical records. Chi-square tests and logistic regression were performed to assess the relationship between sociodemographic characteristics and documentation of mental health evaluation, hospitalization, and discharge instructions. RESULTS: Of 929 episodes of suicidal behavior evaluated in an acute setting, rural-residing youth were less likely to be admitted to a psychiatric hospital (adjusted odds ratio [AOR] 0.72; 95% confidence interval [CI] 0.55-0.95) and more likely to be medically hospitalized only (AOR 1.92; 95% CI 1.39-2.65). Female subjects were less likely to be admitted to a psychiatric hospital (AOR 0.55; 95% CI 0.41-0.74) and more likely to be discharged home (AOR 1.44; 95% CI 1.01-2.04). Only 40% of those discharged to home had documentation of discharge instructions with both follow-up provider and date. CONCLUSIONS: In this statewide cohort of youth with suicidal behavior, there were significant differences in disposition associated with sociodemographic characteristics.