{\it In vivo\/} induction of DNA changes in cervicovaginal epithelium by perinatal estrogen exposure

Epidemiological studies have associated estrogens with human neoplasm such as the endometrium, cervix, vagina, breast, and liver. Perinatal exposure to natural (17$\beta$-estradiol (17$\beta$-E$\sb2)\rbrack$ and synthetic (diethylstilbestrol (DES)) estrogens induces neoplastic changes in humans and rodents. Previous studies demonstrated that neonatal 17$\beta$-E$\sb2$ treatment increased the nuclear DNA content of mouse cervicovaginal epithelium that preceded histologically evident neoplasia. In order to determine whether this effect was specific to 17$\beta$-E$\sb2,$ associated with chromosomal changes, and relevant to the human, female BALB/c mice were treated neonatally with either 17$\alpha$-estradiol (17$\alpha$-E$\sb2)$ and 5$\beta$-dihydrotestosterone ($5\beta$-DHT), both inactive steroids in adult reproductive tissue, or 17$\beta$-E$\sb2.$ Ten-day-old mice received pellet implants of 17$\beta$-E$\sb2,$ 17$\alpha$-E$\sb2,$ $5\beta$-DHT, or cholesterol. Seventy-day-old cervicovaginal tracts were examined histologically and flow cytometrically. 17$\beta$-E$\sb2$-treated animals were evaluated by fluorescent in situ hybridization (FISH) using a probe specific for chromosome 1. Trisomy of chromosomes 1, 7, 11, and 17 was evaluated by FISH in cervicovaginal material from 19 DES-exposed and 19 control patients.^ $17\beta$-E$\sb2, 17\alpha$-E$\sb2$, and $5\beta$-DHT-induced dramatic developmental and histological changes in the cervicovaginal tract, including hypospadia, hyperplasia, and persistent cornification. The changes induced by 17$\alpha$-E$\sb2$ were equivalent to 17$\beta$-E$\sb2.$ Neonatal 17$\alpha$-E$\sb2$-induced adenosquamous cervicovaginal tumors at 24 months. 17$\alpha$-E$\sb2$ and $5\beta$-DHT significantly increased the nuclear DNA content over control animals, but at significantly lower levels than 17$\beta$-E$\sb2.$ DNA ploidy changes were highest (80%) in animals treated neonatally and secondarily with 17$\beta$-E$\sb2.$ Secondary 17$\alpha$-E$\sb2$ and $5\beta$-DHT administration, unlike 17$\beta$-E$\sb2,$ didn't significantly increase DNA content. Chromosome 1 trisomy incidence was 66% in neonatal 17$\beta$-E$\sb2$-treated animals. Trisomy was evident in 4 DES-exposed patients: one patient with trisomy of chromosomes 1, 7, and 11; one patient with chromosome 7 trisomy; and two patients with chromosome 1 trisomy. These data demonstrated the biological effects of 17$\alpha$-E$\sb2$ and $5\beta$-DHT were age-dependent, 17$\alpha$-E$\sb2$ was equivalent to 17$\beta$-E$\sb2$ and tumorigenic when administered neonatally, and histological changes were not steroid specific. Chromosomal changes were associated with increased nuclear DNA content and chromosomal changes may be an early event in the development of tumors in human DES-exposed tissues. ^

A comparative analysis of CHIP Perinatal policy in twelve states

The purpose of this comparative analysis of CHIP Perinatal policy (42 CFR § 457) was to provide a basis for understanding the variation in policy outputs across the twelve states that, as of June 2007, implemented the Unborn Child rule. This Department of Health and Human Services regulation expanded in 2002 the definition of “child” to include the period from conception to birth, allowing states to consider an unborn child a “targeted low-income child” and therefore eligible for SCHIP coverage. ^ Specific study aims were to (1) describe typologically the structural and contextual features of the twelve states that adopted a CHIP Perinatal policy; (2) describe and differentiate among the various designs of CHIP Perinatal policy implemented in the states; and (3) develop a conceptual model that links the structural and contextual features of the adopting states to differences in the forms the policy assumed, once it was implemented. ^ Secondary data were collected from publicly available information sources to describe characteristics of states’ political system, health system, economic system, sociodemographic context and implemented policy attributes. I posited that socio-demographic differences, political system differences and health system differences would directly account for the observed differences in policy output among the states. ^ Exploratory data analysis techniques, which included median polishing and multidimensional scaling, were employed to identify compelling patterns in the data. Scaled results across model components showed that economic system was most closely related to policy output, followed by health system. Political system and socio-demographic characteristics were shown to be weakly associated with policy output. Goodness-of-fit measures for MDS solutions implemented across states and model components, in one- and two-dimensions, were very good. ^ This comparative policy analysis of twelve states that adopted and implemented HHS Regulation 42 C.F.R. § 457 contributes to existing knowledge in three areas: CHIP Perinatal policy, public health policy and policy sciences. First, the framework allows for the identification of CHIP Perinatal program design possibilities and provides a basis for future studies that evaluate policy impact or performance. Second, studies of policy determinants are not well represented in the health policy literature. Thus, this study contributes to the development of the literature in public health policy. Finally, the conceptual framework for policy determinants developed in this study suggests new ways for policy makers and practitioners to frame policy arguments, encouraging policy change or reform. ^

Obesity during pregnancy on vagal tone, hemoglobin A1c, oxygenation, and perinatal outcomes

Purpose: To examine the effect of obesity and gestational weight gain on heart rate variability (HRV), oxygenation (HbO 2 and SpO2), hemoglobin A1c (HbA1c) and the frequency of pregnancy complications in obese (O) and non-obese (NO) women.^ Design: The study was an observational comparison study with a repeated measures design. ^ Setting: The setting was a low risk prenatal, university clinic located in a large southeastern metropolitan city. ^ Sample: The sample consisted of a volunteer group of 41 pregnant women who were observed at the three time points of 20, 28, and 36 weeks gestation. ^ Analysis: Analysis included general linear modeling with repeated measures to test for group differences with changes over time on vagal response, HbA1c, and oxygenation. Odds ratios were computed to compare the frequency of birth outcomes. ^ Findings: The interaction effect of time between O and NO women on HbO2 was significant. The mean HP, RSA, and HbO2 changed significantly over time within the NO women. The mean HbA 1c increased significantly over time within the O women. Women with excess gestational weight gain had significantly lower heart period than women with weight gain within the IOM recommendations. Obese women were more likely to have Group B streptococcal infections, gestational hypertension, give birth by cesarean or instrument assistance, and have at least one postnatal event. ^ Conclusions: Monitoring HRV, oxygenation, and HbA1c using minimally invasive measures may permit early identification of alterations in autonomic response. Implementation of interventions to promote vagal tone may help to reduce risks for adverse perinatal outcomes related to obesity. Future studies should examine the effect of obesity on the vagal response and perinatal outcomes. ^

Missed opportunities in the prevention of perinatal human immunodeficiency syndrome virus transmission

Mother to child transmission of human immunodeficiency virus (HIV) has decreased dramatically in the United States since the mid-1990s. Without antiretroviral therapy the risk of perinatal infection is as high as 25%; with treatment the risk drops to <1-2%. However, state surveillance data show a recent rise in the percentage of babies being born with HIV in Texas. No studies of perinatal HIV transmission in Texas have focused on the individual cases and identified what social/institutional barriers stood in the way of the index woman, her support system and her health providers in negotiating access to prenatal care and HIV treatment.^ The Texas Department of State Health Services identifies the babies born in Texas with HIV infection. This two year study will use mixed methods to identify barriers to the diagnosis and treatment of maternal HIV. In-depth interviews and chart reviews will be used to conduct the study. The abstracted medical record will give us demographic data and details of the timing of testing and treatment; interviews will provide information as to the individual and environmental factors that may have delayed testing and treatment. Little research has been done to assess the factors contributing to late prenatal HIV diagnosis and care in Texas and the interventions identified by mothers of affected babies that might overcome these obstacles.^ Conclusions from this study will guide the development of interventions to better educate the public, reduce structural barriers common to the underserved, and/or educate health care professionals. The study will also serve as a model for other states to undertake evaluation of their cases of perinatal infection. ^

Confidential inquiry into perinatal mortality in the Lower Rio Grande Valley, 1988

A review of 1985 neonatal death statistics in the Lower Rio Grande Valley of Texas revealed an excessive perinatal death rate among Hispanics compared to Anglos. In order to identify factors contributing to perinatal mortality in the region and to determine if existing perinatal services were adequate, a confidential inquiry into each 1988 perinatal death was performed.^ Medical risk factors in the mothers were infrequent. The most commonly noted pregnancy complication was polyhydramnios. This complication is often associated with anencephalus which was the most frequent birth anomaly detected in the region.^ The study results did not reveal an association between lay midwife deliveries in the region and excessive perinatal mortality nor did perinatal mortality appear to be associated with a lack of neonatal intensive care facilities. Lack of prenatal care was the most commonly encountered preventable factor associated with perinatal death. It was not possible to determine if the level of care for Anglos and Hispanics differed because of the low number of Anglo deaths although the socioeconomic level of deaths in each of the ethnic groups was the same. ^

Perinatal mortality and quality of care at the National Institute of Perinatology: A 3-year analysis

Quality of medical care has been indirectly assessed through the collection of negative outcomes. A preventable death is one that could have been avoided if optimum care had been offered. The general objective of the present project was to analyze the perinatal mortality at the National Institute of Perinatology (located in Mexico City) by social, biological and some available components of quality of care such as avoidability, provider responsibility, and structure and process deficiencies in the delivery of medical care. A Perinatal Mortality Committee data base was utilized. The study population consisted of all singleton perinatal deaths occurring between January 1, 1988 and June 30, 1991 (n = 522). A proportionate study was designed.^ The population studied mostly corresponded to married young adult mothers, who were residents of urban areas, with an educational level of junior high school or more, two to three pregnancies, and intermediate prenatal care. The mean gestational age at birth was 33.4 $\pm$ 3.9 completed weeks and the mean birthweight at birth was 1,791.9 $\pm$ 853.1 grams.^ Thirty-five percent of perinatal deaths were categorized as avoidable. Postnatal infection and premature rupture of membranes were the most frequent primary causes of avoidable perinatal death. The avoidable perinatal mortality rate was 8.7 per 1000 and significantly declined during the study period (p $<$.05). Preventable perinatal mortality aggregated data suggested that at least part of the mortality decline for amenable conditions was due to better medical care.^ Structure deficiencies were present in 35% of avoidable deaths and process deficiencies were present in 79%. Structure deficiencies remained constant over time. Process deficiencies consisted of diagnosis failures (45.8%) and treatment failures (87.3%), they also remained constant through the years. Party responsibility was as follows: Obstetric (35.4%), pediatric (41.4%), institutional (26.5%), and patient (6.6%). Obstetric responsibility significantly increased during the study period (p $<$.05). Pediatric responsibility declined only for newborns less than 1500 g (p $<$.05). Institutional responsibility remained constant.^ Process deficiencies increased the risk for an avoidable death eightfold (confidence interval 1.7-41.4, p $<$.01) and provider responsibility ninety-fivefold (confidence interval 14.8-612.1, p $<$.001), after adjustment for several confounding variables. Perinatal mortality due to prematurity, barotrauma and nosocomial infection, was highly preventable, but not that due to transpartum asphyxia. Once specific deficiencies in the quality of care have been identified, quality assurance actions should begin. ^

Process and outcome evaluation of the hepatitis B perinatal vaccination program in Houston, Texas, 1991--1993

A retrospective cohort study was designed to evaluate the compliance of vaccination dose schedules and vaccination effectiveness at 12 months of age among a total of 226 high-risk infants born to HBsAg-positive pregnant women who participated in the HBV Perinatal Vaccination Program in Houston, Texas, 1991-1993.^ The seroprevalence of HBsAg-positivity was 0.5% among pregnant women who attended prenatal clinics in Houston, Texas, 1991-1993. The Asian women had the highest seroprevalence rate (5.9%), followed by black (1.9%), white (0.7%), and Hispanic women (0.3%). The seroprevalence of HBsAg increased with age (p =.02); the highest seroprevalence rate found among the $>$40 group (5.4%), followed by the 20-40 age group, and the $<$20 age. A steady increase was observed in the number of infants, from 45 in 1991, to 103 in 1993. The majority of these infants were black (58.0%), followed by Hispanic (28.8%), Asian (8.4%), and white infants (4.0%). Significant increases were observed from 1991 to 1993 in the number of infants who initiated vaccination (86.7% to 98.1%, p =.02) and in those infants who were post-tested at 12 months of age (24.4% to 44.7%, p =.04). During the same period an increase was also observed in the number of infants who completed the vaccination dose schedules (62.2% to 72.8%, p =.37). The compliance rates were not statistically significant regarding gender, race or ethnicity, health service area, medical referral source, and residential geographic areas. About 56.0% of the reasons cited for non-compliance among the 144 infants who neither completed the vaccination dose schedules nor received the 12-month post-test were "moved," and "no response/not at home." A total of 82 infants completed the vaccination dose schedules and were post-tested at 12 months of age for anti-HBs-positivity, and 96.3% of these infants seroconverted. A race-specific statistically significant seroconversion difference was found among infants who received all vaccination doses and were post-tested at 12 months of age (100% for the black and the white, 96.3% for the Hispanic, and 80.0% for the Asians infants, p =.05).^ From a public health perspective, the HBV Perinatal Vaccination Program improved during its first three years (1991-1993). It was effective in preventing perinatal HBV infection in almost 97.0% of infants who were vaccinated and post-tested. To increase the efficiency and efficacy of the program, the following recommendations are proposed: (1) Increase the vaccination compliance rate by educating and improving the tracking, communication and coordination channels with those individuals involved in the process and by increasing staff resources. (2) Reduce the post-test vaccination non-compliance by post-testing infants simultaneously with third vaccination dose at 6 months of age, and only post-test those infants who are anti-HBs-negative at 9-12 months of age. (Abstract shortened by UMI.) ^

Evaluation of CHIP perinatal program outcomes in Harris County, Texas

This study compared initial year trends in prenatal care and birth outcomes of women enrolled in the Texas Children's Health Insurance Program (CHIP) Perinatal program to trends in Medicaid program women. The study utilized claims data from Community Health Choice (CHC), a health plan in Harris County, Texas that provides coverage to both populations. Quarterly data was analyzed and compared for the first two years of the CHIP Perinatal program (2007-2008) to determine if outcome trends for the CHIP program improved over the outcome trends seen with those enrolled in Medicaid. Study findings indicate an increase in the quarterly prenatal care utilization for the CHIP Perinatal population from 2007 to 2008 and the associated birth weights of babies delivered also had marginal improvements during the same timeframe. Enrollees in Medicaid continued to have overall better outcomes than those enrolled within the CHIP Perinatal program. However, the study showed that the rate of improvement in both prenatal care utilization and birth outcomes were greater for the CHIP Perinatal enrollees than those enrolled in Medicaid. ^ The majority of these improvements were significant when comparing each coverage program and from year to year. Lastly, the study showed that there was a correlation between prenatal care utilization and birth outcomes. However, further analysis of the data could not conclusively indicate that access to prenatal care services provided by the CHIP Perinatal program contributed to the increases observed in utilization and birth outcomes for the study's sample population.^

Epidemiology of perinatal mortality: Birthweight, crown -heel length, gestational age, and weight -for -height

Studies suggest that slim infants (low weight-for-height) experienced higher mortality rates than average or high weight-for-height infants (Miller and Hassanein, 1973; Hoffman, Meirik, and Bakketeig, 1984). In this study, the 1980 National Natality Survey and the National Fetal Mortality Survey were used to examine the association of weight, height and perinatal mortality. All singleton births to white married mothers, between 18 and 34 years of age and of parity less than 4, for whom both mother's and hospital questionnaires were completed in those two surveys (3796 live births and 2043 fetal deaths) were selected for analysis. Overall, low weight and height infants had excess mortality rates. However, after adjustment for low birthweight and preterm birth status, low weight and height infants had only slightly higher mortality rates than their medium or high weight and height counterparts. The current study consists of relatively well-educated white married mothers of optimal reproductive age and low parity. Therefore, lower than expected mortality rates for slim infants may be attributed to these favorable demographic factors in this sample as compared with previous studies, or because of advances in perinatal medicine, slim infants may be prevented from achieving the high mortality seen in earlier studies. ^