Screening for fetal alcohol syndrome in primary schools: a feasibility study.

BACKGROUND: This project was undertaken as a feasibility study to determine the possibility of screening for fetal alcohol syndrome (FAS) in early school-age children for epidemiological and interventional purposes. METHODS: All elementary schools in two counties in Washington State were asked to screen first graders for possible FAS. A child was screen positive if found to be growth deficient, to have certain specific facial abnormalities, or have a known history of substantial alcohol exposure in gestation. All screen-positive children were invited to "special diagnostic clinics" for final diagnosis and treatment planning. RESULTS: In County A, virtually all students were screened. In County B only about 25% of children were screened. This difference was related to the number of schools that agreed to participate in the project and the methods employed by each county to obtain parental permission. In each county, only about one-half of the screen-positive children were seen in the special clinics for diagnostic considerations. Only one of the seven children found to have FAS had been diagnosed previously. The minimal prevalence of FAS in County A was 3.1 in 1,000 students. The minimal prevalence of FAS in County B could not be calculated. The most efficient component in the screening process leading to a diagnosis of FAS was finding the specific facial features of the disorder. The diagnosis of FAS was generally helpful in improving educational planning. CONCLUSIONS: This study demonstrated that population-based FAS screening within a school system may be possible, but participation is dependent on local trust and understanding of the project before its inception within the schools and the community at large.

Should genetic health care providers attempt to influence reproductive outcome using directive counseling techniques? A public health prospective.

Many areas of agreement exist among genetic health care (GHC) professionals (i.e., MD and PhD clinical geneticists, master's level genetic counselors, and others) and public health (PH) professionals. However, there are in our opinion at least two areas or tenets where a distinct difference of opinion exists. Two tenets widely expressed by prenatal GHC professionals are: (1) they should never attempt to influence the outcome of a pregnancy, and (2) they should only use non-directive genetic counseling techniques. From a PH perspective, these tenets could be viewed in some instances as counterproductive and contrary to a major goal of PH (i.e., to improve the health and well-being of all residents, including newborns). For example, PH's message regarding fetal alcohol syndrome (FAS) prevention is clear: If you are pregnant, don't drink; and if you drink, don't get pregnant. PH's message regarding neural tube defect (NTD) prevention is equally clear: all women of childbearing age who are capable of becoming pregnant should consume 0.4 mg of folic acid daily to reduce the risk of NTDs. In the past, issues such as eugenics, abortion of affected fetuses, and a lack of methods for the primary prevention of birth defects and genetic disorders have caused GHC providers to perform genetic counseling according to the two tenets mentioned above. Clearly, there are no moral or ethical reasons why children who are at risk for FAS, NTDs, fetal rubella syndrome, or many other conditions should not have the opportunity to be born healthy. Also, we know of no laws that prohibit providers from telling a woman to do something to improve her baby's chance of being born healthy. In our opinion, it is time for prenatal GHC professionals to re-examine the two tenets noted above on a case-by-case basis to determine when it is appropriate to use directive counseling techniques to improve reproductive outcomes in accordance with the goals of PH. A framework is provided here that could serve as: (1) a guide for future discussions dealing with these issues, and (2) a method to ensure that prenatal GHC policy and practice regarding these issues conform with one another.

Assessment of two 'low-tech' genetic health care procedures performed by prenatal care providers in Washington state: implications for future policy development activities.

Equity in health care demands that patients be treated fairly, impartially and with justice. Health care professionals and others have long been aware of the concept of equity, and the many inequities that exist in our health care system. As part of our analysis of postpartum data collected between 1993 and 1996 by the Washington Pregnancy Risk Assessment Monitoring System (PRAMS) from self-administered patient surveys, we explored equity as it pertains to two 'low-tech' prenatal genetic health care procedures: (1) whether or not prenatal care providers asked their patients about a family history of birth defects/genetic disorders, and (2) whether or not prenatal care providers talked to their patients about prenatal testing for birth defects/genetic disorders. Overall, about 80% of pregnant women reported that they had been asked about their family history of birth defects/genetic disorders, and about 85% said that their prenatal care provider(s) had talked to them about prenatal testing. Maternal characteristics associated with a lower likelihood of receiving these two low-tech genetic health care procedures appeared to be young maternal age, and low education and income levels, regardless of where women with these attributes received their prenatal care (e.g. community, migrant, health department or military health care clinics, private physicians, or health maintenance organizations).

Qualifications of public health geneticists?

Public health genetics is a rapidly emerging field that is not well defined. One way of helping to define the field is to describe the competences of the professionals who participate in it. The information presented here attempts to define the knowledge base, skills, and attitudes needed to be a public health geneticist. It is hoped that this information will be used to create a uniform definition of public health genetics, and also help education programs train individuals who want to participate in the field.

Why can't a woman be more like a man? A renaissance perspective on the biological basis for female inferiority.

Western biomedical theory supported the idea of human female inferiority. The Aristotelian formulation was: Nature intends to produce the perfect male form with external genitalia; the female with internal genitalia is less than perfect and thus a defect of nature. In the Renaissance, peripubertal virilization in females was interpreted as further evidence that females were "defective" males capable of developing into the more perfect male form.

Factors which influence the rate of receiving a routine second newborn screening test in Washington State.

This study was conducted to determine whether newborns from different ethnic and socioeconomic groups in Washington State are equally likely to have a routine second newborn screening (NBS) test and if there are identifiable factors associated with not having a second test. For many years, the standard of care for NBS in Washington has been that newborns should receive a routine second screening test at age 7-10 days. However, data collected by State Department of Health (DOH) staff for the past several years indicated that only about 80% of newborns receive a routine second NBS test. The data presented here suggest that identifiable factors (i.e., barriers) exist in accessing a routine second NBS test in Washington. Increased educational efforts targeting certain high-risk infants, their parent/caretakers, and primary care providers are apparently needed to ensure equal access to a routine second test.

Epidemiology of congenital hydrocephalus in Utah, 1940-1979: report of an iatrogenically related "epidemic".

As part of an epidemiological study of congenital hydrocephalus in Utah, we focused on the effect of ascertainment sources and temporal variability to further delineate the causes of this relatively common, handicapping birth defect. The incidence and distribution of 934 reported cases diagnosed prior to age 6 months, and born to Utah residents from 1940 to 1979, were analyzed. Data were ascertained by examination of multiple sources, e.g., 982,066 birth, 11,161 fetal death, and 248,208 death certificates, and selected hospital and clinic records. Of the 934 reported cases, 700 met our selection criteria for congenital hydrocephalus, which results in a crude incidence of 0.70 per 1,000 live and stillbirths. Seventy-one cases (10.1%) had additional, multiple congenital anomalies. The male/female sex ratios of the 619 cases of isolated congenital hydrocephalus (occurring as a single entity or in the absence of other reported or known birth defects) and those with multiple congenital anomalies (71 cases) were virtually identical, being 1.45 and 1.48, respectively. A significant 85% increase in the rate of reported cases was observed for the period 1966 to 1970. However, examination of patients' records from 1966 to 1975 in the hospital responsible for almost all of this increase suggests that this was an iatrogenically related "epidemic" caused by several factors: the introduction and possible misinterpretation of pneumoencephalograms (PEG) in the diagnosis of hydrocephalus (PEG was replaced by CAT scanning in the early 1970s), inappropriate diagnosis, and incorrect recording of age at time of diagnosis.

Of monsters and prodigies: the interpretation of birth defects in the sixteenth century.

In the sixteenth century, a time of religious and social upheaval, naturalistic theories of generation were joined to ideas that monstrous births were divine signs. In this paper, we explore how medicine and theology were combined to explain the almost cataclysmic religious, social, and political events of the century.

Prenatal diagnosis of a large heteromorphic region in a chromosome 5: implications for genetic counseling.

We performed an amniotic fluid chromosome study at 16 weeks of gestation because of advanced maternal age. G-band chromosome analysis demonstrated that one 5q was significantly longer than its homologue. The region subjacent to the centromere appeared similar to a 9qh region. Subsequent Giemsa-11 and C-band staining results of this area were positive. Cytogenetic studies in this family demonstrated several other individuals who have the same chromosome 5qh+ as the proposita. All are asymptomatic. The clinical insignificance of the chromosome heteromorphism in this family readily demonstrates the need for special cytogenetic and family chromosome studies before performing genetic counseling.

Report of two cases of distal deletion of the long arm of chromosome 6.

We report on two patients with distal deletions of 6q. In one case a de novo translocation between chromosomes 6 and 7 resulted in del(6q25----6qter). The other case had a de novo deletion, also from 6q25 to 6qter. There have been eight previous reports of distal deletions of 6q. These patients have developmental retardation, microcephaly, craniofacial anomalies, various types of congenital heart defects, and anomalies of hands and feet. The facial similarities of our two patients and those in six published photographs are subtle and may represent an emerging phenotype.

Animal model: dysmorphogenesis and death in a chicken embryo model.

The chicken embryo is a useful animal model for investigating problems in developmental biology and teratology. Here we report data that further define the causes of 2 different patterns of malformation (one associated with amnion abnormalities, the other with isolated neural tube defects) and death induced by making a window in the shell and subshell membranes during the first day of incubation. The interpretation of these data suggests to us the following hypotheses. An early amnion deficit spectrum or syndrome (EADS) in chicken embryos is caused by a brief (less than 10 sec) perturbation that occurs during the windowing procedure. This perturbation results in an acute increase in mechanical tension to the developing embryo and support structures, dehydration localized to the area of the blastoderm, and/or increased friction between the blastoderm and overlying vitelline and shell membranes. Isolated neural tube defects (NTDs) are caused by a longer perturbation (greater than 3 hr) consisting of increased mechanical stress across the blastoderm. The mechanical stress is associated with the introduction of a new air space over the animal pole of the yolk during windowing. The new air space causes the shape of the yolk to change (ie, to be deformed), resulting in an increase in mechanical tension across the vitelline membrane and blastoderm. NTDs involving the head are associated with significant early embryonic mortality, whereas those involving the trunk are not. Death may also be caused by cardiovascular anomalies observed in EADS. It is concluded that disturbances in morphogenesis and death in this model are, therefore, the result of extrinsic forces (eg, mechanical stress, localized dehydration, or friction) acting on different tissue types at various critical times in development. Intensity and duration of these forces on the developing blastoderm are important variables.

Causes of windowing-induced dysmorphogenesis (neural tube defects and early amnion deficit spectrum) in chicken embryos.

Previous reports suggest that windowing the shells of chicken eggs during the first day of incubation frequently results in dysmorphogenesis of the central nervous system. We report here data that further delineate the neural tube defects associated with this animal model. In addition, we describe another birth defect syndrome associated with windowing: the early amnion deficit spectrum (EADS). Several components of the egg are altered structurally by windowing: the shell, outer and inner shell membranes, yolk, and air space at the blunt end of the egg. A new air space is formed over the embryo as the original one at the blunt end is obliterated. A series of studies (pH, oxygen and carbon dioxide tensions, relative humidity, temperature, and deformation of the yolk documented with magnetic resonance imaging) examining individual steps of the windowing procedure and additional techniques that stimulate windowing suggest that mechanical stress causes isolated neural tube defects and dehydration causes amnion defects. These amnion defects are associated with other embryonic abnormalities suggestive of deformations consistent with EADS.

Stable gene amplification and overexpression of sodium- and potassium-activated ATPase in HeLa cells.

Cell lines stably resistant to ouabain were isolated from an unstably resistant HeLa line after growth in nonselective medium. Stable resistant lines bound ouabain at levels 10-fold higher than did HeLa cells and at similar levels to those bound by the unstable C+ line previously described (J. F. Ash, R. M. Fineman, T. Kalka, M. Morgan, and B. Wire, J. Cell Biol. 99: 971-983). Expression and synthesis of the Na+, K+ -ATPase alpha chain showed a similar amplification over that for HeLa cells by Western blots and [35S]methionine pulse-labeling. In addition, a glycoprotein labeled with [3H]fucose and comigrating with the Na+, K+ -ATPase beta chain was eight- to ninefold amplified in stably resistant lines. Dot blots with a cDNA clone specific for Na+, K+ -ATPase alpha chain gene sequences confirmed the amplification of this gene. Karyotyping suggested that the amplification is associated with an expanded, abnormal banded region on the long (q) arm of one chromosome 17.

Peters' anomaly as a consequence of genetic and nongenetic syndromes.

A new syndrome includes Peters' anomaly and short-limbed dwarfism. A balanced chromosomal translocation in the brother (patient 1) appears to be coincidental to the physical abnormalities, because his sister (patient 2) has identical findings but normal fibroblast and lymphocyte karyotypes. Peters' anomaly, which includes corneal clouding, iris and/or lens adhesions to the cornea, and the absence of endothelium and Descemet's membrane, is often associated with systemic abnormalities. Since there are different genetic and nongenetic systemic conditions that include Peters' anomaly, and there are several ocular syndromes with features overlapping this disorder, we believe that Peters' anomaly is a morphologic finding rather than a distinct entity.

Phenotypic variation in the del(12p) syndrome.

Previous reports suggested the existence of a del(12p) syndrome. Phenotypic abnormalities associated with del(12p) appear to be mental retardation, microcephaly, and micrognathia. The patient with del(12p) reported here was normocephalic and large for gestational age. She probably had sclerocornea, a finding not previously associated with del(12p). Phenotypic variation in del(12p) syndrome is probably caused by differences in the size of the deleted segment and/or the presence or absence of mutant genes on the homologous 12p segment.

Amplification of sodium- and potassium-activated adenosinetriphosphatase in HeLa cells by ouabain step selection.

A multistep selection for ouabain resistance was used to isolate a clone of HeLa S3 cells that overproduces the plasma membrane sodium, potassium activated adenosinetriphosphatase (Na+,K+-ATPase). Measurements of specific [3H]ouabain-binding to the resistant clone, C+, and parental HeLa cells indicated that C+ cells contain 8-10 X 10(6) ouabain binding sites per cell compared with 8 X 10(5) per HeLa cell. Plasma membranes isolated from C+ cells by a vesiculation procedure and analyzed for ouabain-dependent incorporation of [32P]phosphate into a 100,000-mol-wt peptide demonstrated a ten- to twelvefold increase in Na+,K+-ATPase catalytic subunit. The affinity of the enzyme for ouabain on the C+ cells was reduced and the time for half maximal ouabain binding was increased compared with the values for the parental cells. The population doubling time for cultures of C+ cells grown in dishes was increased and C+ cells were unable to grow in suspension. Growth of C+ cells in ouabain-free medium resulted in revertant cells, C-, with biochemical and growth properties identical with HeLa. Karyotype analysis revealed that the ouabain-resistant phenotype of the C+ cells was associated with the presence of minute chromosomes which are absent in HeLa and C- cells. This suggests that a gene amplification event is responsible for the Na+,K+-ATPase increase in C+ cells.