Judith A. Dudley

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.

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.

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.

Increase in Incidence of Medically Treated Thyroid Disease in Children With Down Syndrome After Rerelease of American Academy of Pediatrics Health Supervision Guidelines

OBJECTIVE. The purpose of this work was to estimate the incidence of medically treated thyroid disease in children with Down syndrome enrolled in Tennessee Medicaid (TennCare) during 1995–2005 and to determine whether rates increased after rerelease of American Academy of Pediatrics guidelines in 2001. PATIENTS AND METHODS. We conducted a population-based retrospective cohort study in which we identified children with Down syndrome by using TennCare files and birth certificates. We included 1- to 18-year-olds who were continuously enrolled in TennCare and did not fill a prescription for thyroid medication during a 90-day prestudy period. The rate of medically treated thyroid disease (prescription filled for thyroid medication) was the main outcome. We used Poisson regression to estimate rates of medically treated thyroid disease according to study year, age, gender, race, region of residence, and payer type. RESULTS. During the 11-year study period, 1257 children with Down syndrome (28% black, 72% white) met inclusion criteria. Overall, 10.8% filled a new prescription for thyroid medication. Rates of medically treated thyroid disease per 1000 child-years were 13.25 (1995–1997), 13.34 (1998–1999), 13.62 (2000–2001), 22.37 (2002–2003), and 22.51 (2004–2005). After adjusting for child age and race, there was an increased rate of medically treated thyroid disease in 2002–2003 and 2004–2005 compared with 1995–1997. In a comparison cohort of children without Down syndrome, there was a smaller increase in the rate of medically treated thyroid disease when comparing 2002–2003 and 2004–2005 with 1995–1997. CONCLUSIONS. Over the 11-year period, 10.8% of children with Down syndrome filled a new prescription for a thyroid medication. A 73% increase in the incidence of medically treated thyroid disease occurred after rerelease of American Academy of Pediatrics guidelines, which may have influenced screening.

Comparative effectiveness of antibiotic treatment strategies for pediatric skin and soft-tissue infections.

OBJECTIVE: To compare the effectiveness of clindamycin, trimethoprim-sulfamethoxazole, and β-lactams for the treatment of pediatric skin and soft-tissue infections (SSTIs). METHODS: A retrospective cohort of children 0 to 17 years of age who were enrolled in Tennessee Medicaid, experienced an incident SSTI between 2004 and 2007, and received treatment with clindamycin (reference), trimethoprim-sulfamethoxazole, or a β-lactam was created. Outcomes included treatment failure and recurrence, defined as an SSTI within 14 days and between 15 and 365 days after the incident SSTI, respectively. Adjusted models stratified according to drainage status were used to estimate the risk of treatment failure and time to recurrence. RESULTS: Among the 6407 children who underwent drainage, there were 568 treatment failures (8.9%) and 994 recurrences (22.8%). The adjusted odds ratios for treatment failure were 1.92 (95% confidence interval [CI]: 1.49–2.47) for trimethoprim-sulfamethoxazole and 2.23 (95% CI: 1.71–2.90) for β-lactams. The adjusted hazard ratios for recurrence were 1.26 (95% CI: 1.06–1.49) for trimethoprim-sulfamethoxazole and 1.42 (95% CI: 1.19–1.69) for β-lactams. Among the 41 094 children without a drainage procedure, there were 2435 treatment failures (5.9%) and 5436 recurrences (18.2%). The adjusted odds ratios for treatment failure were 1.67 (95% CI: 1.44–1.95) for trimethoprim-sulfamethoxazole and 1.22 (95% CI: 1.06–1.41) for β-lactams; the adjusted hazard ratios for recurrence were 1.30 (95% CI: 1.18–1.44) for trimethoprim-sulfamethoxazole and 1.08 (95% CI: 0.99–1.18) for β-lactams. CONCLUSIONS: Compared with clindamycin, use of trimethoprim-sulfamethoxazole or β-lactams was associated with increased risks of treatment failure and recurrence. Associations were stronger for those with a drainage procedure.

Antidepressants and Suicide Attempts in Children

OBJECTIVES: Recent data showing possible increased risk for suicidal behavior among children and adolescents treated with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) antidepressants have created significant concern among patients, families, and providers, including concerns about the risk of individual antidepressants. This study was designed to compare the risk for medically treated suicide attempts among new users of sertraline, paroxetine, citalopram, escitalopram, and venlafaxine to risk for new users of fluoxetine. METHODS: A retrospective cohort study included 36 842 children aged 6 to 18 years enrolled in Tennessee Medicaid between 1995 and 2006 who were new users of 1 of the antidepressant medications of interest (defined as filling no prescriptions for antidepressants in the preceding 365 days). Medically treated suicide attempts were identified from Medicaid files and vital records and confirmed with medical record review. RESULTS: Four hundred nineteen cohort members had a medically treated suicide attempt with explicit or inferred attempt to die confirmed through medical record review, including 4 who completed suicide. The rate of confirmed suicide attempts for the study drugs ranged from 24.0 per 1000 person-years to 29.1 per 1000 person-years. The adjusted rate of suicide attempts did not differ significantly among current users of SSRI and SNRI antidepressants compared with current users of fluoxetine. Users of multiple antidepressants concomitantly had increased risk for suicide attempt. CONCLUSIONS: In this population-based study of children recently initiating an antidepressant, there was no evidence that risk of suicide attempts differed for commonly prescribed SSRI and SNRI antidepressants.

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

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‐β0‐thalassemia (HbSβ0) aged 2–16 years who received recommended TCD screening from 1997 to 2008, and to identify factors associated with adherence.

Identifying suicidal behavior among adolescents using administrative claims data

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.

Stool Cultures and Antimicrobial Prescriptions Related to Infectious Diarrhea

Stool cultures can be important in guiding antimicrobial therapy for diarrhea. From among 11.64 million person-years of Tennessee Medicaid enrollment data collected from 1995 through 2004, 315,828 diarrheal episodes were identified. Stool cultures were performed for only 15,820 episodes (5.0%). Antimicrobials were prescribed for 32,949 episodes (10.4%), 89.4% of which were not accompanied by a stool culture. White race and urban residence were associated with higher rates of stool culture. Frequent use of antimicrobials for diarrhea without stool culture may indicate inappropriate antimicrobial use and has critical implications for public health.

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 vaccines impact after its release.