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Background: Availability of the galactose-1-phosphate uridyltransferase (GALT) assay for newborn (NB) screening has improved identification of classic galactosemia. Previously defined critical cutoffs for total galactose (Gal), typically 1.110 mmol/L (20 mg/dL), are still in use in laboratories measuring total Gal for the diagnosis of nonclassic galactosemias. Urgent notification/referral to a treatment center follows, although few of the NBs will need treatment. Methods: We reviewed all NB galactosemia-screening results and their corresponding clinical outcomes over a 5-year period (first phase, 1.32 × 106 NBs) and then over a 2-year period (second phase, 274 960 NBs). Each NB was screened for Gal and GALT. When Gal was increased and/or GALT was deficient, testing for percentage galactose-1-phosphate and/or DNA testing for common GALT mutations were performed. Results: Of 209 reported positive results, 89% did not indicate GALT deficiency. These non–GALT-deficient results represented mostly clinically benign cases with a Gal threshold of ≥1.110 mmol/L (≥20 mg/dL). The positive predictive value of a GALT cutoff of ≤40 μmol/L was 83%. After a protocol change that redefined a critical result as a GALT value ≤40 μmol/L and/or a Gal value ≥1.665 mmol/L (≥30 mg/dL), results were monitored for an additional 2 years. The new protocol dramatically reduced the number of urgent calls/referrals and reduced the total number of referrals by nearly half. Conclusions: Use of a GALT cutoff of ≤40 μmol/L/L and a Gal cutoff of ≥1.665 mmol/L (≥30 mg/dL) for urgent notification/referral dramatically reduces false positives and unnecessary follow-up, thereby reducing the stress on healthcare resources.

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Measurement of the production of surfactant is the most direct means of prenatally assessing fetal pulmonary maturity. We review assays which have evolved for measuring surfactant, classifying them into two general categories: biochemical quantitation and biophysical measurements. Biochemical quantitation assays include the amniotic fluid lecithin/sphingomyelin ratio and quantitation of lecithin and other surfactant phospholipids. Biophysical measurements include measurement of surface-tension-lowering ability of extracts of amniotic fluid lipid and evaluation of surface-tension-related properties such as foam stability and microviscosity. Assays of surfactant are subject to certain pre-analysis sources of variation over which the analyst has no control, such as variability in total in vivo amniotic fluid volume, incomplete in vivo mixing of surfactant with amniotic fluid, and presence of contaminating blood or meconium. We also examine other factors such as centrifugation speed and time, and storage of the amniotic specimen before analysis. These factors can dramatically affect analyses, and must be carefully controlled by the analyst. In general, both biochemical and biophysical approaches to surfactant analysis are useful diagnostically. When properly performed, both approaches give results that correlate well, both with each other and with clinical outcome. Because "mature" and "immature" values overlap, none of the assays can completely eliminate false predictions, whether of fetal maturity or fetal immaturity.

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