<p> The National Database of Nurse Quality Indicators (NDNQI) contains many nurse sensitive indicators for benchmarking adult medical/surgical patient outcomes but no perinatal nurse sensitive indicators. Project objectives were to form a collaborative, identify a perinatal nurse sensitive indicator, metrics that would contribute to its success and methods to measure and report them. The researcher developed a theoretical framework and three phase process to support the formation of the collaborative based on empowerment theory, collective impact and the Plan, Do, Study, Act cycle. Seven Midwest magnet organizations participated and identified breastfeeding as the indicator, along with three metrics that promote it: baby to breast in the first 60 minutes, non-separation of mom and baby, and skin-to-skin contact during the recovery period. Methods to document, measure and report metrics were developed and a database was selected for data comparison. While all objectives were met, only three organizations remained at project completion.</p>

Squamous intraepithelial lesions (SIL) are believed to be precursors of in situ cervical neoplasia and of invasive cervical cancer. Though the burden of this disease has been greatly reduced thanks to the availability of an effective screening test, the worldwide morbidity and mortality remain high. / On the basis of a classic approach to analysis of data from a prospective cohort study, I correlated HPV status at enrollment with subsequent risk of incident SIL during up to three years of follow-up among women of Brazil enrolled to the Ludwig-McGill cohort. / The risk of occurrence of a first instance of SIL among women was strongly associated with HPV infection. After adjustment for a number of socio-demographic factors that have previously been established as risk factors for cervical cancer, the magnitude of association with high-risk HPVs remained unchanged while the association with low risk types was dampened, furthering the evidence for the role of oncogenic HPV types in the development of cervical cancer. / Parity was found to have an independent positive association with cervical precursor lesions, after adjustment for HPV status, age, previous history of Pap screening, number of sexual partners, age at first intercourse, and income. Income was also positively associated with the development of lesions.

Human papillomavirus (HPV) is the sexually-transmitted etiologic agent of cervical cancer. Despite screening programs, cervical cancer remains too common, particularly in developing countries. Various correlates of prevalent infections have been identified. However, the determinants of incident infections have never been studied. / Data were collected during a prospective cohort study conducted in Brazil. Incidence density rates of infection were calculated and determinants of incident infection were identified using Cox regression models. Analyses were done for HPV types classified into low-risk and high-risk depending on their association with cervical neoplasia. / The incidence density rates were 9.3 and 7.6 per 1000 women-months respectively for low-risk and high-risk HPV infection. Independent positive associations were found between the time of first occurrence of low-risk infection and age, number of sexual partners in the past 5 years, education level and use of non-commercial hygienic absorbents. The first occurrence of high-risk infection was independently predicted by age, age at first sexual intercourse, condom use (negative associations) and by the number of sexual partners in the past year (positive association). Elucidation of the dynamics of infection is a first step towards implementation of public health programs for reducing the risk of cervical cancer.

The purpose of this study was to assess the impact of a Maternity Cooperative Care Program (MCCP) on the prevalence of maternal and infant complications, maternal competence, social support, stress, and first-time-mothers' descriptions of their postpartum experience. Forty-one healthy, primiparous mothers who participated in a MCCP and forty-three healthy, primiparous mothers who received traditional maternity care were asked to complete the Perceived Competence Questionnaire, the Personal Resource Questionnaire, "The Help I Get" Questionnaire (spousal support), and three numerical rating scales relating to stress in general, as well as self- and infant-care stress 24-48 hours postpartum while in hospital and over the telephone at two weeks postpartum. Ten randomly selected mothers from each group also answered twelve open-ended questions during a home visit at 2-3 weeks postpartum. There were no statistically significant differences between the two groups for any of the outcome variables assessed. For both groups, competence with self- and infant-care increased over the two weeks postpartum, while support and stress remained stable. Interviews with the mothers revealed that the number of stressors increased once at home, while support continued to be of value in relieving stress and helping maternal adjustment and confidence. Results of a qualitative comparison between the groups suggests that the MCCP mothers felt more prepared to be discharged home, and identified their partner more often as an active participant during hospitalization.

A significant alteration in the pattern of secretion of gonadotropins is the hallmark of age-related loss of estrous cyclicity and reproductive capacity. Although various components of the reproductive axis contribute to altered gonadotropin secretion, neuroendocrine dysfunction is believed to play an important role in the age-related loss of estrous cyclicity in the rodent. Our studies examining the pituitary responsiveness to GnRH with age revealed that the pituitaries of C57BL/6J mice appear to be capable of sustaining normal endocrine function under appropriate stimulus even in old females. Thus we hypothesized that changes at the level of the hypothalamus may be responsible for the alteration in gonadotropin secretion. Our studies evaluating GnRH neuronal function demonstrated that there is no change in the capacity of GnRH neurons to release GnRH with age although the presence of the ovary appears to modulate the GnRH release. Neuroanatomical and pharmacological studies suggest that an age-related decline in the opiatergic influence is responsible, at least in part, for the altered GnRH release. Posttranslational processing of the opiate peptide, $ beta$-endorphin ($ beta$-endo) from its precursor proopiomelanocortin (POMC) and its further posttranslational modification determine the amount of opiate active and antagonist forms ultimately released at the synapse. We hypothesized that age-related alterations in the content of opiate active and antagonist forms of $ beta$-endo occur which contribute to the decline in opiatergic influences on reproductive function. Our data demonstrated that there is a significant increase in the opiate receptor inactive and antagonist forms of $ beta$-endo in middle aged but not in young or old mice. An important mechanism for the differential processing of $ beta$-endo in the anterior and intermediate lobes of pituitary in adult rodents and in the anterior lobe in neonates appears to lie in the relative levels of expression

It has previously been demonstrated that a large percentage of in vitro generated human embryos are chromosomally mosaic. The current thesis investigated this mosaicism in greater detail. It characterized the mosaicism present at each stage of preimplantation development in vitro. It examined the relevance of the different forms of the observed mosaicism to preimplantation embryo wastage, implantation failure, and fetal and placental mosaicism. Finally, it addressed the identification of the chromosomally mosaic embryos during preimplantation genetic diagnosis (PGD). For each of the studies presented within the thesis, blastomeres from "spare" in vitro generated embryos were assessed for chromosomal content using multi-color fluorescence in situ hybridization (FISH) DNA probes. Mosaicism was detected at all stages of preimplantation development, from the 2-cell stage to the blastocyst stage; it comprised of diploid, aneuploid, "chaotic", haploid, and polyploid chromosome patterns. Compared to blastocysts, arrested embryos or embryos at the earlier stages of development, showed a much higher incidence of mosaicism involving "chaotic" imbalances for multiple chromosomes and/or high percentages of abnormal cells. These results indicate that extensive post-zygotic abnormalities impair embryonic development to the blastocyst stage. The presence of mosaicism was not predicted by embryo morphology. Mosaicism may therefore contribute to the low rates of blastocyst formation in vitro and to the high rates of implantation failure following cleavage stage embryo transfer. Probe mixtures comprising of three autosomes, of one autosome and gonosomes, or of five autosomes could be applied for the identification of the mosaic embryos during cleavage stage PGD. Culture of isolated blastomeres from cleavage stage embryos for genetic diagnosis increases the number of cells available for analysis; however, the presence of nuclear defects and mosaicism among the cultured cells indica

Little is known about the factors stimulating placental progesterone (P4) production at the time of the luteo-placental shift (6-8 weeks post-conception). To explore the regulatory mechanism, the effects of various steroids and peptides on the production of P4 by placental explants were studied. / In early placental explant culture P4 production was stimulated by 19-nortestosterone (19-NT), androstenedione (A-dione), 5$ alpha$-androstane-3$ alpha,$17$ beta$ diol (3$ alpha$-diol) and 5$ alpha$-androstane-3$ beta,$17$ beta$ diol (3$ beta$-diol). Of all the compounds tested, 19-NT had maximal effect. At term, P4 production was stimulated only by 3$ beta$-diol. 19-NT and A-dione were poorly aromatized in early placental explants compared to another androgen (Androst-5-ene-3$ beta,$17$ beta$ diol). / In accord with the above observations, placental levels of 19-NT and A-dione were higher in early gestation while the diols were higher in late gestation. / 19-NT stimulated P4 production in early placenta by effects on the conversion of P4 both from 25-hydroxycholesterol and from pregnenolone. The stimulatory influences of A-dione and 3$ alpha$-diol were mediated by increasing the P450scc activity. The specific increase of the conversion of P4 from pregnenolone accounted for the P4 stimulation observed by 3$ beta$- diol treatment of culture. / Cyloheximide (CH) treatment abolished the stimulatory influences of the aforementioned steroids on P4 production except for the initial phase of P4 stimulation by 19-NT, suggesting that all but the latter are dependent on protein synthesis. / P4 production was also stimulated and prolonged to 30 days in the presence of human maternal serum (HMS); a good correlation (r = 0.74, P $<$ 0.05) was seen between the histological appearance of the explants and P4 production. The stimulatory activity of HMS was heat labile, non-dialyzable and non-extractable into an organic solvent, suggesting that it is protein in nature. / In conclusion, this study suggests that 19-NT and A-dione are important for placental P4 production at the time of the luteo-placental shift. For in vitro study of placental hormonal regulation, HMS is a better nutrient supplement than fetal bovine serum.

Using murine models of spontaneous and induced embryo resorption, we have investigated the role of macrophages in the mechanism of early embryo loss. The results showed that macrophage derived nitric oxide was associated with embryo resorption, and that decidual macrophages could be triggered by lipopolysaccharide (LPS) to produce nitric oxide, indicating that the decidual mononuclear cells were primed in situ. Using double immunostaining, we have shown that macrophages were the cellular source of the inducible nitric oxide production. We further showed that embryo abortion can be significantly decreased by inhibiting the production of nitric oxide in vivo. The results presented strongly suggested a role for nitric oxide as an effector molecule in mediating early embryo loss and showed that the in situ activation of decidual macrophages was an early event preceding spontaneous abortion. / It is known that interferon-$ gamma$ (IFN-$ gamma$) is the major cytokine responsible for the priming of macrophages and that LPS can trigger primed macrophages to produce nitric oxide. Therefore, the observation that exogenous LPS induced embryo abortion in most strains of pregnant mice suggested that the decidual macrophages have been previously primed in situ. To investigate the role of IFN-$ gamma$ as a potential priming signal for decidual macrophage activation, we studied the effect of the depletion of IFN-$ gamma$ on LPS induced pregnancy loss. The results showed that IFN-$ gamma$ deficient mice were more resistant to LPS induced abortion than control mice. This suggested that IFN-$ gamma$ was essential for the priming of decidual macrophages and that decidual macrophages from IFN-$ gamma$ deficient mice could not be activated when exposed to LPS both in vivo and in vitro. Our results also showed increased IFN-$ gamma$ mRNA expression simultaneously in the same embryos that also expressed elevated iNOS mRNA, a macrophage activation marker. This suggested that macrophage activation, subsequent nitric oxide production, and spontaneous embryo loss could be a consequence of local IFN-$ gamma$ over production. / While LPS serves as an exogenous triggering factor, endogenous TNF-$ alpha$ is known to trigger NO production by primed macrophages. Therefore, we investigated the role of TNF-$ alpha$, as a second signal, in mediating embryo loss. Our studies showed that the frequency of embryos with significantly increased TNF-$ alpha$ mRNA expression corresponded to the incidence of murine embryo abortion. In addition, the results showed that increased TNF-$ alpha$ mRNA was simultaneously expressed with iNOS mRNA suggesting a potential role for TNF-$ alpha$ in the triggering of decidual macrophages. / In summary, we demonstrated the presence of activated decidual macrophages in murine placentas, and that inducible nitric oxide produced by these macrophages was responsible for embryo death. We further showed that IFN-$ gamma$ was responsible for the priming of decidual macrophages, and that the expression of TNF-$ alpha$, a potential secondary signal was associated with decidual macrophage activation, NO production, and subsequent embryo loss.

Objectives. To determine the relationship between objective stress, subjective reaction, post-traumatic stress disorder (PTSD) symptoms and cortisol in pregnant women exposed to a natural disaster. / Methods. The Impact of Event Scale-Revised (IES-R) was used to measure PTSD symptoms in 193 subjects, and a Storm Questionnaire to assess objective and subjective stress. Seven salivary cortisol samples were collected from each subject; six were obtained between waking and bedtime on the first day, and then a seventh upon waking on the second day. / Results. Both objective stress and subjective reactions to the storm negatively predict cortisol, but size and significance of the effects vary according to trimesters of stress exposure. Across the four pregnancy groups, up to 42% of the variance in cortisol could be explained by objective stress and subjective reactions. / Conclusion. More severe PTSD symptoms are associated with lower cortisol levels, and pregnancy dampens a woman's physiological response to stress.

A prospective study of 116 pregnancies in epileptic women was carried out in order to assess the distribution of newborn growth parameters, and the risk of abnormal outcomes (spontaneous abortions, perinatal deaths, developmental anomalies, deformations or hernias). The putative risk factors associated with these outcomes were assessed by multivariable analyses. Major congenital anomalies were increased and head circumference was decreased relative to the general population. Maternal plasma phenytoin or phenobarbital levels were positively associated with developmental anomalies and total abnormal outcomes. An increase in maternal seizures and/or anticonvulsant drugs, as well as detoxification defects of phenytoin arene oxide metabolites were correlated with decreased head circumference, while family history of seizures was associated with reduced birth weight and/or length. Decreased blood folate levels were correlated with spontaneous abortion and developmental anomalies. The present study suggests that adverse pregnancy outcomes in epileptic women may have heterogeneous multifactorial etiologies and mechanisms.