To improve quality of newborn screening by tandem mass spectrometry with a novel approach made possible by the collaboration of 154 laboratories in 49 countries. A database of 767,464 results from 12,721 cases affected with 60 conditions was used to build multivariate pattern recognition software that generates tools integrating multiple clinically significant results into a single score. This score is determined by the overlap between normal and disease ranges, penetration within the disease range, differences between conditions, and weighted correction factors. Ninety tools target either a single condition or the differential diagnosis between multiple conditions. Scores are expressed as the percentile rank among all cases with the same condition and are compared to interpretation guidelines. Retrospective evaluation of past cases suggests that these tools could have avoided at least half of 279 false-positive outcomes caused by carrier status for fatty-acid oxidation disorders and could have prevented 88% of known false-negative events. Application of this computational approach to raw data is independent from single analyte cutoff values. In Minnesota, the tools have been a major contributing factor to the sustained achievement of a false-positive rate below 0.1% and a positive predictive value above 60%. Genet Med advance online publication 16 February 2012

Background: Pregnancy is characterized by a complexity of metabolic processes that may impact fetal development and infant health outcome. Normal fetal growth and development depend on a continuous supply of nutrients via the placenta. The placenta transports, utilizes, produces, and interconverts amino acids (AAs). Findings: Concentrations of both nonessential and essential AAs in maternal plasma decrease in early pregnancy and persist at low concentrations throughout. The decline is greatest for the glucogenic AAs and AAs of the urea cycle. Additionally, there is a large placental utilization of the branched-chain AAs, some of which are transaminated to alpha ketoacids and contribute to placental ammonia production. Both nonessential and essential AAs regulate key metabolic pathways to improve health, survival, growth, development, lactation, and reproduction of organisms. Some of the nonessential AAs (e.g. glutamine, glutamate, and arginine) play also important roles in regulating gene expression, cell signaling, antioxidant responses, immunity, and neurological function. Conclusions: Nutritional support during pregnancy is of great interest focusing not only to common pregnancies but also to those with low socioeconomic status, vegan–vegetarian groups, and pregnant women with metabolic disorders, the most known maternal phenylketonuria. The latter is of great interest because phenylalanine must be within the recommended range throughout pregnancy in addition to other nutrients such as vitamin B12, folate, etc. Loss of the adherence to this specific diet results in congenital malformations of the fetus. In addition to the routine laboratory test, quantitation of plasma AAs may be necessary throughout pregnancy.