Grosse, Scott D.

Abstract Context Single-tier newborn screening (NBS) for congenital adrenal hyperplasia (CAH) using 17-hydroxyprogesterone (17OHP) measured by fluoroimmunoassay (FIA) in samples collected at 24 to 48 hours produces a high false-positive rate (FPR). Second-tier steroid testing can reduce the FPR and has been widely implemented. Objective We investigated the accuracy of an alternative multitier CAH NBS protocol that incorporates molecular testing of the CYP21A2 gene and reduces the first-tier 17OHP cutoff to minimize missed cases. Methods We create a Minnesota-specific CYP21A2 pathogenic variants panel; developed a rapid, high-throughput multiplex, allele-specific-primer-extension assay; and performed a 1-year retrospective analysis of Minnesota NBS results comparing metrics between a conventional steroid-based 2-tier protocol and a molecular-based multitier NBS protocol, applied post hoc. Results CYP21A2 gene sequencing of 103 Minnesota families resulted in a Minnesota-specific panel of 21 pathogenic variants. The Centers for Disease Control and Prevention created a molecular assay with 100% accuracy and reproducibility. Two-tier steroid-based screening of 68 659 live births during 2015 resulted in 2 false negatives (FNs), 91 FPs, and 1 true positive (TP). A 3-tier protocol with a lower first-tier steroid cutoff, second-tier 21-variant CYP21A2 panel, and third-tier CYP21A2 sequencing would have resulted in 0 FNs, 52 FPs, and 3 TPs. Conclusion Incorporation of molecular testing could improve the accuracy of CAH NBS, although some distinct challenges of molecular testing may need to be considered before implementation by NBS programs.

AbstractBackgroundDue to invasive treatments and stressors related to heart health, adults with congenital heart defects (CHDs) may have an increased risk of post‐traumatic stress disorder (PTSD), anxiety, and/or depressive disorders. Our objectives were to estimate the prevalence of these disorders among individuals with CHDs.MethodsUsing IBM® MarketScan® Databases, we identified adults age 18–49 years with ≥2 outpatient anxiety/depressive disorder claims on separate dates or ≥1 inpatient anxiety/depressive disorder claim in 2017. CHDs were defined as ≥2 outpatient CHD claims ≥30 days apart or ≥1 inpatient CHD claim documented in 2007–2017. We used log‐binomial regression to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for associations between CHDs and anxiety/depressive disorders.ResultsOf 13,807 adults with CHDs, 12.4% were diagnosed with an anxiety or depressive disorder. Adults with CHDs, compared to the 5,408,094 without CHDs, had higher prevalence of PTSD (0.8% vs. 0.5%; aPR: 1.5 [CI: 1.2–1.8]), anxiety disorders (9.9% vs. 7.5%; aPR: 1.3 [CI: 1.3–1.4]), and depressive disorders (6.3% vs. 4.9%; aPR: 1.3 [CI: 1.2–1.4]). Among individuals with CHDs, female sex (aPR range: 1.6–3.3) and inpatient admission (aPR range 1.1–1.9) were associated with anxiety/depressive disorders.ConclusionOver 1 in 8 adults with CHDs had diagnosed PTSD and/or other anxiety/depressive disorders, 30–50% higher than adults without CHDs. PTSD was rare, but three times more common in women with CHDs than men. Screening and referral for services for these conditions in people with CHDs may be beneficial.

AbstractBackgroundSome studies have reported associations between prenatal use of venlafaxine, a serotonin‐norepinephrine reuptake inhibitor used for depressive and anxiety disorders, and some birth defects. We described the prevalence of venlafaxine prescription claims among privately insured women of reproductive age and pregnant women.MethodsVenlafaxine prescription claims were examined using the IBM MarketScan Commercial Databases. We included women of reproductive age (15–44 years) who had ≤45 days of lapsed enrollment during the calendar year of interest (2011–2016) in a non‐capitated healthcare plan sponsored by a large, self‐insured employer with prescription drug coverage and no mental health service carve‐out. Annual cohorts of pregnant women were identified among eligible women of reproductive age via pregnancy diagnosis and procedure codes. Venlafaxine prescriptions were identified via National Drug Codes in outpatient pharmacy claims and we estimated the annual proportion of women with venlafaxine claims by pregnancy trimester (pregnant women only), age, and Census division.ResultsEach year during 2011–2016, approximately 1.2% of eligible reproductive‐aged and 0.3% of eligible pregnant women filled a venlafaxine prescription. Among pregnant women, the proportion with venlafaxine claims was highest during the first trimester and decreased during the second and third trimesters. Small temporal increases in venlafaxine claims were observed for reproductive‐aged and pregnant women, with the largest among women aged 15–19 years.ConclusionsVenlafaxine prescription claims were low among women of reproductive age and pregnant women during 2011–2016, with some increasing use over time among women aged 15–19 years.