Wisconsin’s newborn screening program implemented second-tier testing on specimens with elevated propionylcarnitine (C3) to aid in the identification of newborns with propionic and methylmalonic acidemias. The differential diagnosis for elevated C3 also includes acquired vitamin B12 deficiency, which is currently categorized as a false positive screen. The goal of this study was to summarize screening data and evaluate their effectiveness at establishing diagnoses and categorizing false positive cases. All Wisconsin newborns born between 2013 and 2019 with a positive first-tier screen for C3 were included in this study. For each case the first- and second-tier newborn screening data and confirmatory test results were compiled. The clinical determination for each case was reviewed and categorized into groups: inborn error of metabolism, maternal B12 deficiency, infant B12 deficiency, and false positive. A review of the screening data showed a significant overlap in the concentration of biomarkers for newborns with genetic versus acquired disease. Additionally, a review of confirmatory test results showed incomplete ascertainment of maternal vitamin B12 status. The Wisconsin newborn screening program recommended a confirmatory testing algorithm to aid in the diagnosis of inborn errors of metabolism and acquired vitamin B12 deficiency.

Propionic acidemia (PA) occurs at a higher incidence within the Amish; however, sensitivity of newborn screening and its impact on long-term clinical outcomes has not been reported in this population. This study reviewed screening data and health records of 20 Wisconsin Amish patients diagnosed with PA. Newborn screening did not identify all cases; however, early detection did offer appreciable long-term protection from neurological sequelae. This is the first report summarizing PA cases within the Amish.

Propionic acidemia (PA) is an inborn error of protein metabolism with a variable clinical presentation ranging from neonatal encephalopathy to seemingly asymptomatic individuals who present with cardiomyopathy or sudden death. PA is recognized in the Amish population, often with an early asymptomatic course and eventual cardiac complications. Thus, Amish women with PA may reach reproductive age without clinical sequelae, but are at increased risk for metabolic decompensation during pregnancy, delivery and postpartum period. We describe the care of an Amish woman with PA during her first pregnancy and delivery.

Study Design. A retrospective medical record review of cases with congenital vertebral malformations (CVMs) and controls with normal spine morphology. Objective. To determine the relative contribution of maternal environmental factors (MEFs) during pregnancy to CVM development. Summary of Background Data. CVMs represent defects in formation and segmentation of somites occurring with an estimated incidence of between 0.13 and 0.50 per 1000 live births. CVMs may be associated with various phenotypes and represent significant morbidity due to pain and cosmetic disfigurement. Methods. A multicenter retrospective medical record review of 229 cases with CVM and 267 controls with normal spine morphology between the ages of 1 and 50 years was performed to obtain the odds ratio (OR) of MEF related to CVM among cases versus controls. An imputation-based analysis was performed in which subjects with no documentation of MEF history were treated as “no maternal exposure.” Univariate and multivariate analyses were conducted to calculate the OR. Results. Of the 229 total cases, 104 cases had single or multiple CVMs without additional congenital malformations (group 1) and 125 cases had single or multiple CVMs and additional congenital malformations (group 2). Nineteen percent of total cases had an identified MEF. The OR for MEF history for group 1 was 6.0 (95% confidence interval, 2.4–15.1; P < 0.001) in the univariate analysis. The OR for MEF history in group 2 was 9.1 (95% confidence interval, 3.8–21.6, P < 0.001) in the univariate analysis. The results were confirmed in the multivariate analysis after adjusting for age, sex, and institution. Conclusions. These results support a hypothesis for an association between these MEFs during pregnancy and CVM and have implications for development of prevention strategies. Further prospective studies are needed to quantify association between CVMs and specific MEF. Level of Evidence: 4