Adverse Birth Outcomes in U.S.- and Foreign-Born Black Women: A Conceptual and Empirical Analysis.

Background: This dissertation explored racism and birth outcomes in U.S.- and foreign-born Black women and examined the degree to which commonly-measured risk factors could explain why Black Caribbean immigrants have lower rates of preterm birth than African Americans. It included: a review of how race- and nativity-based disparities have been conceptualized in perinatal health research; an examination of preterm birth predictors among Caribbean- and U.S.-born Black women; and an assessment of preterm birth risk by maternal age and immigrants’ duration of U.S. residence. Methods: Systematic literature review coupled with logistic regression analyses utilizing birth records from New York City (2000-2010) and the U.S. Virgin Islands (2000-2004). Results: The review produced no generalizable evidence for suggested causes of racial or Black ethnic disparities in birth outcomes. However, there is modest support that racism is associated with adverse birth outcomes, and the perinatal health advantage for Black immigrants is ascribed to selective migration and culturally-linked factors, although the evidence is sparse. In this study, Caribbean-born immigrants in New York City sustained lower odds of preterm birth relative to U.S.-born Blacks (OR = 0.85, 95% CI: 0.76, 0.94) and Caribbean-born residents in the Virgin Islands (OR = 0.54, 95% CI: 0.34, 0.89) despite adjustment for demographic, behavioral, and medical risk factors. Age and education were most influential in explaining the preterm birth advantage for Black Caribbean immigrants, and there was modest support for selective migration. However, the risks of preterm birth with advancing maternal age were similar between Caribbean-born immigrants (OR = 1.13, 95% CI: 1.10, 1.15) and U.S.-born mothers (OR = 1.15, 95% CI: 1.13, 1.17) in New York City. Further, the odds of preterm birth among Caribbean immigrants increased 7% for every 5 years of U.S. residence (OR = 1.07, 95% CI: 1.04, 1.11). Conclusions: The “healthy migrant” effect for Black Caribbean immigrants is conditional on national origin and length of time in the U.S. The worsening of immigrant mothers’ preterm birth risks with increased duration of U.S. residence warrants additional research into contextual factors, including racism, to yield greater insight into perinatal health disparities among native and foreign-born Black women.PhDHealth Behavior and Health EducationUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111549/1/dccarty_1.pd

Neonatal mortality in NHS maternity units by timing and mode of birth: a retrospective linked cohort study

OBJECTIVES: To compare neonatal mortality in English hospitals by time of day and day of the week according to care pathway. DESIGN: Retrospective cohort linking birth registration, birth notification and hospital episode data. SETTING: National Health Service (NHS) hospitals in England. PARTICIPANTS: 6 054 536 liveborn singleton births from 2005 to 2014 in NHS maternity units in England. MAIN OUTCOME MEASURES: Neonatal mortality. RESULTS: After adjustment for confounders, there was no significant difference in the odds of neonatal mortality attributed to asphyxia, anoxia or trauma outside of working hours compared with working hours for spontaneous births or instrumental births. Stratification of emergency caesareans by onset of labour showed no difference in mortality by birth timing for emergency caesareans with spontaneous or induced onset of labour. Higher odds of neonatal mortality attributed to asphyxia, anoxia or trauma out of hours for emergency caesareans without labour translated to a small absolute difference in mortality risk. CONCLUSIONS: The apparent 'weekend effect' may result from deaths among the relatively small numbers of babies who were coded as born by emergency caesarean section without labour outside normal working hours. Further research should investigate the potential contribution of care-seeking and community-based factors as well as the adequacy of staffing for managing these relatively unusual emergencies

DNA methylation-based measures of biological age: meta-analysis predicting time to death.

Estimates of biological age based on DNA methylation patterns, often referred to as epigenetic age , DNAm age , have been shown to be robust biomarkers of age in humans. We previously demonstrated that independent of chronological age, epigenetic age assessed in blood predicted all-cause mortality in four human cohorts. Here, we expanded our original observation to 13 different cohorts for a total sample size of 13,089 individuals, including three racial/ethnic groups. In addition, we examined whether incorporating information on blood cell composition into the epigenetic age metrics improves their predictive power for mortality. All considered measures of epigenetic age acceleration were predictive of mortality (p≤8.2x10-9), independent of chronological age, even after adjusting for additional risk factors (p\u3c5.4x10-4), and within the racial/ethnic groups that we examined (non-Hispanic whites, Hispanics, African Americans). Epigenetic age estimates that incorporated information on blood cell composition led to the smallest p-values for time to death (p=7.5x10-43). Overall, this study a) strengthens the evidence that epigenetic age predicts all-cause mortality above and beyond chronological age and traditional risk factors, and b) demonstrates that epigenetic age estimates that incorporate information on blood cell counts lead to highly significant associations with all-cause mortality

Intracranial administration of deglycosylated C-terminal-specific anti-Aβ antibody efficiently clears amyloid plaques without activating microglia in amyloid-depositing transgenic mice

BACKGROUND: Antibodies against the Aß peptide clear Aß deposits when injected intracranially. Deglycosylated antibodies have reduced effector functions compared to their intact counterparts, potentially avoiding immune activation. METHODS: Deglycosylated or intact C-terminal specific high affinity anti-Aβ antibody (2H6) were intracranially injected into the right frontal cortex and hippocampus of amyloid precursor protein (APP) transgenic mice. The untreated left hemisphere was used to normalize for the extent of amyloid deposition present in each mouse. Control transgenic mice were injected with an antibody against a drosophila-specific protein (amnesiac). Tissues were examined for brain amyloid deposition and microglial responses 3 days after the injection. RESULTS: The deglycosylated 2H6 antibody had lower affinity for several murine Fcγ receptors and human complement than intact 2H6 without a change in affinity for Aß. Immunohistochemistry for Aβ and thioflavine-S staining revealed that both diffuse and compact deposits were reduced by both antibodies. In animals treated with the intact 2H6 antibody, a significant increase in Fcγ-receptor II/III immunostaining was observed compared to animals treated with the control IgG antibody. No increase in Fcγ-receptor II/III was found with the deglycosylated 2H6 antibody. Immunostaining for the microglial activation marker CD45 demonstrated a similar trend. CONCLUSION: These findings suggest that the deglycosylated 2H6 is capable of removing both compact and diffuse plaques without activating microglia. Thus, antibodies with reduced effector functions may clear amyloid without concomitant immune activation when tested as immunotherapy for Alzheimer's disease

Intracranial injection of AAV expressing NEP but not IDE reduces amyloid pathology in APP+PS1 transgenic mice

The accumulation of β-amyloid peptides in the brain has been recognized as an essential factor in Alzheimer\u27s disease pathology. Several proteases, including Neprilysin (NEP), endothelin converting enzyme (ECE), and insulin degrading enzyme (IDE), have been shown to cleave β-amyloid peptides (Aβ). We have previously reported reductions in amyloid in APP+PS1 mice with increased expression of ECE. In this study we compared the vector-induced increased expression of NEP and IDE. We used recombinant adeno-associated viral vectors expressing either native forms of NEP (NEP-n) or IDE (IDE-n), or engineered secreted forms of NEP (NEP-s) or IDE (IDE-s). In a six-week study, immunohistochemistry staining for total Aβ was significantly decreased in animals receiving the NEP-n and NEP-s but not for IDE-n or IDE-s in either the hippocampus or cortex. Congo red staining followed a similar trend revealing significant decreases in the hippocampus and the cortex for NEP-n and NEP-s treatment groups. Our results indicate that while rAAV-IDE does not have the same therapeutic potential as rAAV-NEP, rAAV-NEP-s and NEP-n are effective at reducing amyloid loads, and both of these vectors continue to have significant effects nine months post-injection. As such, they may be considered reasonable candidates for gene therapy trials in AD