The tandem mass spectrometry newborn screening experience in North Carolina: 1997-2005.

North Carolina (NC) was the first US state to initiate universal tandem mass spectrometry (MS/MS) newborn screening. This began as a statewide pilot project in 1997 to determine the incidence and feasibility of screening for fatty acid oxidation, organic acid and selected amino acid disorders. The MS/MS analyses were done by a commercial laboratory and all follow-up and confirmatory testing was performed through the NC Newborn Screening (NBS) Program. In April 1999, the NC NBS Laboratory began the MS/MS analyses in-house. Between 28 July 1997 and 28 July 2005, 944,078 infants were screened and 219 diagnoses were confirmed on newborns with elevated screening results, for an overall incidence of 1:4,300. Ninety-nine infants were identified with fatty acid oxidation disorders, 58 with organic acidaemias and 62 with aminoacidopathies. Medium-chain acyl-CoA dehydrogenase deficiency, 3-methylcrotonyl-CoA carboxylase deficiency and disorders of phenylalanine metabolism were the most common disorders detected. Identification of affected infants has allowed retrospective testing of other family members, resulting in an additional 16 diagnoses. Seven neonates died from complications of their metabolic disorders/prematurity despite timely MS/MS screening. In addition, there were six infants who were not identified by elevated NBS results but who presented with symptoms later in infancy. The NC MS/MS NBS Program uses a two-tier system, categorizing results as either 'borderline' or 'diagnostic' elevated, for both the cutoffs and follow-up protocol. Infants with an initial borderline result had only a repeat screen. Infants with a diagnostic or two borderline results were referred for confirmatory testing. The positive predictive value of the NC MS/MS NBS for those infants requiring confirmatory testing was 53% for 2003 and 2004. The success of the NC MS/MS NBS Program in identifying infants with metabolic disorders was dependent on a comprehensive follow-up protocol integrating the public health laboratory and the academic metabolic centres.

Analytical and clinical evaluation of refractive index-matched anomalous diffraction (RIMAD) for assessment of fetal lung maturation.

We have evaluated refractive index-matched anomalous defraction (RIMAD) (Dubin SB, Clin Chem 1988;34:938-43) as a potential method for assessment of fetal lung maturity (FLM). This method determines the total light scattered by the surfactant-containing lamellar bodies by subtraction of the A650 from amniotic fluid diluted in glycerol from that of amniotic fluid diluted in distilled water. It is not significantly affected by such contaminating chromogens as hemoglobin and bilirubin up to 2.0 g/L and 11.0 mg/L, respectively. However, the addition of as little as 2.5 microL of erythrocytes as whole blood resulted in significant interference. RIMADs for normal respiratory outcomes (n = 78) ranged from 0.018 to 0.471. RIMADs for respiratory distress syndrome (RDS) outcomes (n = 8) ranged from 0.004 to 0.036. Use of a RIMAD referent value of > 0.040 to indicate maturity yielded sensitivity, specificity, predictive value (PV)RDS, and PVmaturity of 100%, 96.2%, 72.2%, and 100%, respectively. The areas under the receiver-operating characteristic curves were 0.997 for the RIMAD assay, 0.993 (P = 0.3) for the TDx-FLM assay, 0.89 (P = 0.017) for the lecithin/sphingomyelin ratio, and 0.87 (P = 0.023) for the foam stability index.

A NlaIII polymorphism within the human factor VII gene.

The polymorphism is located within exon 5 of the human coagulation factor VII gene and is silent at the amino acid level. The distribution pattern is similar in Caucasians and African Americans. This polymorphism may be useful for restriction fragment length polymorphism (RFLP) diagnosis of factor X deficiency as well as factor VII deficiency, since the factor X gene is closely linked to the factor VII locus.