There is relatively little epidemiologic information about Ebstein anomaly (EA) ─ a rare congenital heart defect. Thus, we analyzed characteristics of EA in a geographically and ethnically diverse population. Data from the National Birth Defects Prevention Study were used to study infants born from 1997-2007 with EA. Birth prevalence and prevalence ratio (PR) estimates were derived from the number of affected infants per 10,000 live births in the catchment area. Case characteristics were examined, stratified by the presence of other cardiac and extracardiac defects. Predictive modeling using logistic regression was conducted to understand infant mortality risk factors. There were 249 cases with EA, for a birth prevalence of 0.55/10,000 live births. Other cardiac defects were present in 41.0% and extracardiac defects in 10% of cases. Prevalence was higher among multiple births compared to singletons (PR 2.41, 95% confidence interval (CI) 1.46-3.92) and preterm compared to term infants (PR 1.84, 95% CI 1.27-2.64). Compared to EA cases without other defects, those with additional defects were more likely to die (crude Odds Ratio (cOR) 4.07, 95% CI 1.71-9.93) or undergo cardiac surgery (cOR 6.06, 95% CI 2.78-13.49). Risk for death during infancy was increased by being small for gestational age (adjusted (a) OR 2.97, 95% CI 1.13-7.76) and having extracardiac defects (aOR 6.31, 95% CI 2.28-17.52). Some findings are consistent with previous work, but further studies of EA could clarify risk factors for occurrence and mortality. Knowing population characteristics could guide development of prevention strategies and may improve clinical care.

In the studies described in this dissertation, we investigated the roles of p53 in normal development, teratogen-induced apoptosis, and birth defects. In the first study, the activation of p53 and its target genes, p21, NOXA, and PUMA, were examined during neural tube closure in mouse embryos exposed to hyperthermia (HS) or 4- peroxycyclophosphamide (4CP), teratogens known to induce neural tube defects (NTDs). In the second study, using p53-deficient mice, we examined the expression of mRNAs and microRNAs (miRNAs) during neural tube closure. In the third study, the incidence of NTDs was investigated in p53- and p21-deficient mouse embryos exposed to HS. Finally, we examined the induction of apoptosis in p53-deficient mouse embryos exposed to HS. HS and 4CP induced the activation of p53 by phosphorylation and accumulation of the protein, leading to an increase in p21 proteins and mRNAs. Although HS and 4CP also induced the expression of Noxa and Puma mRNAs, no significant increases in NOXA and PUMA proteins were observed, suggesting a possible role of transcriptionindependent apoptosis. In the second study, we showed that the expression of 388 genes and 5 miRNAs were significantly altered in p53 -/- compared to p53 +/+ embryos. Finally, we showed that 10% of p53 -/- pups exhibit exencephaly, spina bifida, and/or preaxial polydactyly, whereas no malformations were observed among p21 -/- offspring in the absence of HS. HS resulted in an increased incidence of exencephaly in both p53 and p21 null mice indicating that these two proteins act as teratogen suppressors. Our preliminary data additionally showed that a decreased level of apoptosis was observed in HS-treated embryos lacking a p53 allele, suggesting that too little apoptosis may be causally linked to NTDs observed in embryos exposed to HS. Taken together, these studies suggest that precise control of apoptosis and cell cycle arrest pathways are critical for neural tube development and the prevention of teratogen-induced NTDs.

Demographic and sociological theories usually do not incorporate biological variable into their explanations. This dissertation addresses this void by examining the influence of age at menarche on age at first birth, the event of a first birth, and the number of children ever born (CEB). I expand on Demographic Transition theory by incorporating biology as one of the effects of modernization that has an effect on reducing fertility. Age at menarche decreases as a society modernizes. I use data from the 1995 Survey of Family Growth, Cycle V for the U.S., and the 1997 China Survey of Population and Reproductive Health. I further stratify the data into five race/ethnic groups: Chinese Han, Chinese minorities, U.S. Non-Hispanic Whites, U.S. Non-Hispanic Blacks, and U.S. Hispanics of Mexican origin. I use four different statistical methods to model my dependent variables: Ordinary Least Squares Regression, Cox Proportional Hazard Analysis, Poisson Regression, and Negative Binominal Regression. My first major finding is that the younger a woman is when reaching menarche, the younger she will be when giving birth to her first child. Second, the younger a woman is when reaching menarche, the longer the duration to a first birth and the less likely she is to experience a first birth. These two results are consistent in all the groups I analyze. Third, the younger a woman when reaching menarche, the fewer children she will produce. The U.S. Mexican-Origin women are an exception in this final outcome. It is well known that as a society modernizes, age at menarche decreases. Analyses in my dissertation indicate that as women’s ages at menarche decrease, their ages at giving birth to the first child also decrease, but their chances of having a first birth also decrease and their waiting time for having the first birth increases. Also, fertility will decline as age at menarche declines.

Thesis (M. Div.)--St. Vladimir's Orthodox Theological Seminary, Crestwood, N.Y., 2002. / Abstract. Includes bibliographical references (leaves 93-103) and index.

Thesis (M.A.)--York University, 2001. Graduate Programme in Interdisciplinary Studies. / Typescript. Includes bibliographical references (leaves 158-164). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pMQ71579.

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 69-103).

Thesis (M.A.)--West Virginia University, 2003. / Title from document title page. Document formatted into pages; contains iv, 46 p. Includes abstract. Includes bibliographical references (p. 35-44).

This thesis investigates Australian and Canadian legislation that regulated women's reproduction in the late nineteenth and early twentieth century and offers some explanation for their enactment. At the turn of the twentieth century, Australia and Canada enacted a series of laws that were aimed at limiting the control women could exercise over their reproductive functions. From the 1880s through to the first decade of the twentieth century, legislation that prohibited the advertisement of contraception, regulated maternity homes as well as criminal laws that proscribed abortion were promulgated by Australian and Canadian parliaments. This thesis investigates why such legislative activity occurred and proposes that the initiation of these measures targeting abortion, infanticide and birth control cannot be disassociated from the highly gendered and racialised rhetoric resonating throughout the British Empire. Concern about racial integrity, heightened by a fear generated by the declining birth rate, promoted a climate in which exercising control over women's fertility was seen as warranted. White women's reproductive capabilities were a vital ingredient in keeping the settler colonies of Australia and Canada white and British — white women were expected, quite literally, to give birth to the nation. As this thesis shows, when women did not adhere to these expectations of maternity, the law was used in an attempt to monitor and regulate their reproductive activities.

The fetal component of the human placenta is comprised of cells termed trophoblasts and the proper differentiation of these cells is pivotal for maintaining maternal and fetal health throughout pregnancy. The placental syncytiotrophoblast layer is a key secretory portion of the placenta and is produced through fusion of underlying progenitor cytotrophoblast cells with the multinucleated syncytiotrophoblast layer. The MacPhee laboratory has previously established that fusion or syncytialization of cytotrophoblasts is aided by expression of integrin-linked kinase (ILK), a cytoplasmic adapter protein. Nuclear enzyme Poly ADP-ribose Polymerase-1 (PARP-1) and the transcriptional repressor Snail-1 work with ILK to downregulate epithelial cell-cell adhesion. This process would also be necessary for proper trophoblast syncytialization. Thus, it was hypothesized that PARP-1 would be an important mediator of syncytiotrophoblast development. To test this hypothesis, immunofluorescence analysis of PARP-1 and Snail expression in human chorionic villi from first and second trimester as well as from term pregnancy was conducted. Furthermore, co-localization between PARP-1 and Snail-1 were evaluated. Lastly, human PARP-1 was overexpressed in the BeWo trophoblast derived cell line, under fusion promoting conditions, to directly test the ability of PARP-1 to regulate trophoblast fusion. Throughout the first and second trimester, PARP-1 and Snail were highly expressed and co-localized in villous cytotrophoblast nuclei. In contrast, PARP-1 was rarely detectable in syncytiotrophoblast nuclei, while Snail was highly expressed. Upon transient overexpression of PARP-1 in BeWo cells, fusion was robustly promoted. Furthermore, the mean number of nuclei per syncytium was markedly higher in PARP-overexpressing cells compared to control cells. However, PARP-1 overexpression did not regulate trophoblast hormonal differentiation. In conclusion, PARP-1 does appear to be a key enzyme in the process of trophoblast syncytialization. Lastly, a comparative analysis of PARP-1 was conducted in the mouse placenta. It was found that PARP-1 was highly detectable in nuclei of mononuclear trophoblast as well as the nuclei in the syncytiotrophoblast bilayer of the mouse labyrinth. Additionally, PARP-1 was localized to the nuclei of other trophoblast populations, including spongiotrophoblasts, trophoblast giant cell, and glycogen trophoblast giant cells, which are involved in the invasive pathway of trophoblast differentiation.

High birth weight (also known as macrosomia) is a problem that has as of yet received little attention by health researchers, in particular, health economists. High birth weight is a concern mostly due to the increased difficulties it presents during birth for both the mother and the baby but there is also concern that high birth weight may continue to present negative effects later in the baby’s life. Many factors have been attributed as risk factors for high birth weight including mother’s age, ethnicity, parity, obesity, weight gain during pregnancy, infant gender, and gestation length. However, there is a dearth of careful analysis dedicated to determining the extent of causality of these risk factors where endogeneity concerns are present. In this thesis, I examine various issues surrounding high birth weight. I describe the situation in New Zealand (Chapter 2) to see if our experience with high birth weight reflects that found in international research. I analyse the relationship between socio-economic status and high birth weight (Chapter 3) to explore whether high socio-economic status has a unique effect on high birth weight compared to other health disorders in which it generally helps alleviate the incidence. I further investigate the relationship between obesity and high birth weight (Chapter 4) in an attempt to disentangle the causal effect of obesity on high birth weight risk from the mere correlation that has been well documented. I explore the possibility of vitamin and mineral supplements taken during pregnancy being a risk factor for high birth weight (Chapter 5), then address the potential endogeneity issues to identify a causal impact. Finally, I return to the definition of high birth weight (Chapter 6) and consider the optimal way to define the “problematic” weight threshold and whether this threshold should depend on gestation length or the ethnicity of the mother. My findings suggest that in New Zealand, the incidence of macrosomia varies by the ethnicity and weight group of the mother and the gender of the infant. Socio-economic status does seem to affect high birth weight risk but the nature of the relationship is complex. Obesity only appears to have a significant causal effect on high birth weight risk for women who are morbidly obese, but even for these women conventional estimation that disregards the endogeneity of obesity greatly exaggerates the effect. There does appear to be a correlation between iron supplementation and high birth weight risk but the relationship does not withstand controlling for endogeneity. My findings indicate that the currently accepted threshold used to define macrosomia is justified as it does consistently predict adverse health outcomes. However, flexible definitions which consider different grades of macrosomia or different thresholds for different ethnicities could improve on the current definition.