Newborn screening for cystic fibrosis in Wisconsin: first application of population-based molecular genetics testing.

Infants born in Wisconsin are being screened for cystic fibrosis (CF) associated with the F508 mutation. This screening program has been developed during 9 years of research supported by the National Institutes of Health and involves a unique, two-tier system employing measurement of immunoreactive trypsinogen (IRT) initially. When the IRT level is high, DNA is extracted from the neonatal dried blood specimen and analyzed for the F508 mutant allele, following polymerase chain reaction (PCR) amplification; the F508 mutation is present in more than 90% of CF patients and accounts for the common, severe form of the disease. Infants with a positive DNA test are either CF heterozygote carriers or CF patients, depending on the results of a sweat test, which should be performed at 4 weeks of age. Screening the newborn population for CF provides the opportunity for early nutritional and respiratory interventions, as well as genetic counseling. This represents the first population-based application of molecular genetics for detection of a major congenital disorder causing serious public health problems. The process by which the recommendation was reached to screen for CF is described in this article, along with new information on the pathogenesis of CF, its clinical presentation, the rationale for newborn screening, and the method developed for the screening program.

The effect of maternal cigarette smoking on low birth weight and preterm birth in Wisconsin, 1991.

Cigarette smoking is one of the most preventable causes of low birth weight in the United States. This paper presents new data on the relationship between low birth weight and maternal cigarette smoking in Wisconsin based on an analysis of 1991 birth certificates. In Wisconsin in 1991, 22.5% of mothers reported smoking cigarettes during pregnancy. Mothers who smoked cigarettes were twice as likely to bear low birth weight infants as were non-smokers. Low birth weight accounted for 49% of newborn hospital charges totaling $60.7 million. A 50% reduction in maternal smoking could potentially save $5 million in newborn hospital costs. A women is more likely to quit smoking during pregnancy. Physicians are in a unique position to encourage positive behavior change that will reduce the risk for low birth weight and have long term benefits for her and her family.

Alcohol use during pregnancy: implications for physicians.

There has been concern since antiquity that the ingestion of alcohol by the pregnant woman could damage the fetus, but it was not until 1973 that the fetal alcohol syndrome was first described. The broad effect of alcohol-related birth defects, including fetal alcohol effects (FAE), has become apparent even more recently. Physicians can play a central role in the prevention of alcohol-related birth defects through early detection, education of the mother, and appropriate referrals. This paper reviews the effects of maternal alcohol use on the fetus, discusses the importance of assessing alcohol use among all women of child bearing age, and examines intervention strategies that physicians can use to help pregnant women stop or reduce alcohol use. Funding for this paper was provided by the Maternal and Child Health Block Grant.

Cocaine use during pregnancy: implications for physicians.

The growing use of cocaine among pregnant women and its effect on the fetus have become issues of great concern to physicians and society in general. In this paper, we review the available data about the incidence of cocaine use during pregnancy in the United States and in Wisconsin. The pharmacology of the drug is examined as well as its effect on pregnancy outcomes. Medical, neurobehavioral, and developmental effects on the fetus, newborn, and infant are discussed, as well as the relationship to the timing of drug use during pregnancy. Suggestions relevant to physicians for prevention and treatment are given.

Sensitization to epithelial antigens in chronic mucosal inflammatory disease. I. Purification, characterization, and immune reactivity of murine epithelial cell-associated components (ECAC).

To explore the autoantigenic potential of mucosal epithelium that is the site of several chronic, progressive, inflammatory and yet idiopathic diseases, epithelial cell-associated components (designated ECAC) have been isolated in aqueous-soluble form from everted, inflated loops of murine small intestine, initially characterized biochemically and immunologically, and then purified to homogeneity and studied for a disease association through quantitating, by microcytotoxicity assay, their reactivity with patient mononuclear cells and sera. Hydroxyapatite chromatography successfully separated ECAC into several series of major and minor components, with each series (designated 1, 2A, 2B, and 2C) having a unique chemical profile in terms of total carbohydrate, protein, and specific sugars (sialic acid, fucose, galactose). Furthermore, components within each series were shown not to behave as simple blood group substances antigenically, to be free of contaminating intestinal proteases (less than 0.25 micrograms chymotrypsin or equivalent per milliliter) and to possess shared as well as unique antigenic determinants (1 through 4), all of which appeared to be organ-specific for intestine. Gel filtration on Sephacryl S-200 gave a four-peak elution profile for ECAC consistent with a m.w. for components of 3000 to 232,000. Preparative polyacrylamide gel electrophoresis did isolate individual constituents of ECAC, four of which (P1, P2, P4, and P5) were homogeneous and that could, by a hemagglutination inhibition technique, be shown to possess unique organ-specific antigenic determinants. ECAC-specific reactivity of peripheral blood mononuclear cells and sera from patients in the active phase of a chronic inflammatory disorder involving mucosal epithelium indicated autosensitization had occurred, with involvement of several purified epithelium-derived macromolecules. This reactivity appeared to be antibody dependent, occurred at relatively low effector to target ratios, and was not simultaneously directed to control antigens, isolated from kidney in a manner analogous to that used for ECAC. ECAC, isolated by these techniques, may be sufficiently purified to allow an evaluation of their role in the initiation and/or progression of chronic autoaggressive processes occurring in mucosa.