Perinatal Screening for Congenital Malformations and Genetic Disorders: Current Status and Future Directions

Introduction Perinatal screening for congenital malformations and genetic disorders had its inception four decades ago, when testing of newborns for phenylketonuria began. Today, in part because of pilot studies conducted by the Southern California Permanente Medical Group (SCPMG) and The Permanente Medical Group (TPMG) (see next section), second-trimester prenatal screening for neural tube and abdominal wall defects, Down syndrome, and trisomy 18 is widely done by means of biochemical markers (alpha-fetoprotein, human chorionic gonadotropin, unconjugated estrogen, and inhibin A). Populationbased antenatal screening for additional disorders, such as cystic fibrosis, Tay-Sachs disease, and hemoglobinopathies, has also grown in popularity. Current research efforts are directed toward first-trimester screening for Down syndrome and identification of fetal cells within the maternal circulation. Newborn screening for phenylketonuria, galactosemia, and hypothyroidism is done in all 50 states. Selected states conduct additional screening for biotinidase deficiency, congenital adrenal hyperplasia, cystic fibrosis, hearing loss, homocystinuria, and maple-syrup urine disease, as well as for sickle cell disease and other disorders of hemoglobin production. Screening for amino acidemia, organic acidemia, and fatty acid oxidation disorders by tandem mass spectrometry is under active investigation in California and several other states and is already being utilized for suspected metabolic disorders by SCPMG’s Regional Genetic Testing Laboratory.