Functional studies of homeobox gene {\it Cart1\/} during mouse development

Cart1 is a paired-class homeobox-containing gene that is expressed in head mesenchyme, branchial arches, limb buds, and various cartilages during embryogenesis. To understand the role of Cart1 during mammalian development, I generated Cart1-mutant mice by gene targeting in mouse embryonic stem cells. Cart1-homozygous mutants were born alive but all died soon after birth. Most had acrania (absence of the cranial vault) and meroanencephaly (absence of part of the brain). In situ hybridization studies showed that Cart1 is expressed specifically in forebrain mesenchyme but not in midbrain or hindbrain mesenchyme nor in the neural tube. Developmental studies revealed a transient deficiency of forebrain mesenchyme cells due to apoptosis associated with a delay in neural tube closure in that region. Subsequently, the forebrain region became filled with mesenchyme and closed, however, the midbrain neural tube region never initiated closure and remained open. These results suggest that Cart1 is required for the survival of forebrain mesenchyme and that its absence disrupts cranial neural tube morphogenesis by blocking the initiation of closure in the midbrain region, and this ultimately leads to the generation of lethal craniofacial defects. Prenatal treatment of Cart1 homozygous mutants with folic acid suppressed the development of the acrania/meroanencephaly phenotype. Thus, Cart1 mutant mice provide a novel animal model for understanding the cellular, molecular, and genetic etiology of neural tube defects and for the development of prenatal therapeutic protocols using folic acid. ^

Development and testing of a procedure for systematically assigning gestational age for clinical and research use

A graphing method was developed and tested to estimate gestational ages pre-and postnatally in a consistent manner for epidemiological research and clinical purposes on feti/infants of women with few consistent prenatal estimators of gestational age. Each patient's available data was plotted on a single page graph to give a comprehensive overview of that patient. A hierarchical classification of gestational age determination was then applied in a systematic manner, and reasonable gestational age estimates were produced. The method was tested for validity and reliability on 50 women who had known dates for their last menstrual period or dates of conception, and multiple ultrasound examinations and other gestational age estimating measures. The feasibility of the procedure was then tested on 1223 low income women with few gestational age estimators. The graphing method proved to have high inter- and intrarater reliability. It was quick, easy to use, inexpensive, and did not require special equipment. The graphing method estimate of gestational age for each infant was tested against the last menstrual period gestational age estimate using paired t-Tests, F tests and the Kolmogorov-Smirnov test of similar populations, producing a 98 percent probability or better that the means and data populations were the same. Less than 5 percent of the infants' gestational ages were misclassified using the graphing method, much lower than the amount of misclassification produced by ultrasound or neonatal examination estimates. ^

Factors affecting prenatal care use and pregnancy outcome in Texas: A comparative study among and within Black, Anglo, and Hispanic populations

This research project is a study in the field of public health to test the relationships of demographic, socioeconomic, behavioral, and biological factors with (1) prenatal care use and (2) pregnancy outcome, measured by birth weight. It has been postulated that demographic, socioeconomic, and behavioral factors are associated with differences in the use of prenatal care services. It has also been postulated that differences in demographic, socioeconomic, behavioral, and biological factors result in differences in birth weight. This research attempts to test these two basic conceptual frameworks. At the same time, an attempt is made to determine the population groups and subgroups that are at increased risk (1) of using fewer prenatal care visits, and (2) of displaying a higher incidence of low birth weight babies. An understanding of these relationships of the demographic, socioeconomic, behavioral, and biological factors in the use of prenatal care visits and pregnancy outcome, measured by birth weight, will potentially offer guidance in the planning and policy development of maternal and child health services. The research considers four major components of maternal characteristics: (1) Demographic factors. Ethnicity, household size, maternal parity, and maternal age; (2) Socioeconomic factors. Maternal education, family income, maternal employment, health insurance coverage, and household dwelling; (3) Behavioral factors. Maternal smoking, attendance at child development classes, mother's first prenatal care visit, total number of prenatal care visits, and adequacy of care; and, (4) Biological factors. Maternal weight gain during pregnancy.^ The research considers 16 independent variables and two dependent variables.^ It was concluded that: (1) Generally, differences in demographic, socioeconomic, and behavioral factors were associated with differences in the average number of prenatal care visits between and within population groups and subgroups. The Hispanic mothers were the lowest users of prenatal care services. (2) In some cases, differences in demographic, socioeconomic, behavioral, and biological factors demonstrated differences in the average birth weight of infants between and within population groups and subgroups. (3) Differences in demographic, socioeconomic, behavioral, and biological factors resulted in differences in the rates of low birth weight babies between and within population groups and subgroups. The Black mothers delivered the highest incidence of low birth weight infants.^ These findings could provide guidance in the formulation of public health policies such as MCH services, an increase in the use of prenatal care services by prospective mothers, resulting in reduction of the incidence of low birth weight babies, and consequently aid in reducing the rates of infant mortality. ^

Ethnographic and epidemiologic approaches for the programming of prenatal and birth services in Mesa los Hornos, Mexico

The investigator conducted an action-oriented investigation of pregnancy and birth among the women of Mesa los Hornos, an urban squatter slum in Mexico City. Three aims guided the project: (1) To obtain information for improving prenatal and maternity service utilization; (2) To examine the utility of rapid ethnographic and epidemiologic assessment methodologies; (3) To cultivate community involvement in health development.^ Viewing service utilization as a culturally-bound decision, the study included a qualitative phase to explore women's cognition of pregnancy and birth, their perceived needs during pregnancy, and their criteria of service acceptability. A probability-based community survey delineated parameters of service utilization and pregnancy health events, and probed reasons for decisions to use medical services, lay midwives, or other sources of prenatal and labor and delivery assistance. Qualitative survey of service providers at relevant clinics, hospitals, and practices contributed information on service availability and access, and on coordination among private, social security, and public assistance health service sectors. The ethnographic approach to exploring the rationale for use or non-use of services provided a necessary complement to conventional barrier-based assessment, to inform planning of culturally appropriate interventions.^ Information collection and interpretation was conducted under the aegis of an advisory committee of community residents and service agency representatives; the residents' committee formulated recommendations for action based on findings, and forwarded the mandate to governmental social and urban development offices. Recommendations were designed to inform and develop community participation in health care decision-making.^ Rapid research methods are powerful tools for achieving community-based empowerment toward investigation and resolution of local health problems. But while ethnography works well in synergy with quantitative assessment approaches to strengthen the validity and richness of short-term field work, the author strongly urges caution in application of Rapid Ethnographic Assessments. An ethnographic sensibility is essential to the research enterprise for the development of an active and cooperative community base, the design and use of quantitative instruments, the appropriate use of qualitative techniques, and the interpretation of culturally-oriented information. However, prescribed and standardized Rapid Ethnographic Assessment techniques are counter-productive if used as research short-cuts before locale- and subject-specific cultural understanding is achieved. ^