Identifying newborn discharge to child protective services: Comparing discharge codes from birth hospitalization records and child protection case files.

PURPOSE: Newborn removal by North America's child protective services (CPS) disproportionately impacts Indigenous and Black families, yet its implications for population health inequities are not well understood. To guide this as a domain for future research, we measured validity of birth hospitalization discharge codes categorizing newborns discharged to CPS. METHODS: Using data from 309,260 births in Manitoba, Canada, we compared data on newborns discharged to CPS from hospital discharge codes with the presumed gold standard of custody status from CPS case reports in overall population and separately by First Nations status (categorization used in Canada for Indigenous peoples who are members of a First Nation). RESULTS: Of 309,260 newborns, 4562 (1.48%) were in CPS custody at hospital discharge according to CPS case reports and 2678 (0.87%) were coded by hospitals as discharged to CPS. Sensitivity of discharge codes was low (47.8%), however codes were highly specific (99.8%) with a positive predictive value (PPV) of 81.4%, and a negative predictive value (NPV) of 99.2%. Sensitivity, PPV and specificity were equal for all newborns but NPV was lower for First Nations newborns. CONCLUSIONS: Canadian hospital discharge records underestimate newborn discharge to CPS, with no difference in misclassication based on First Nations status.

Infant rates of child protective services contact and termination of parental rights by first nations status from 1998 to 2019: An example of intergenerational transmission of colonial harm.

BACKGROUND: Rates of child removal by child protective services (CPS) in Manitoba are the highest in Canada with a profoundly disproportionate impact on First Nations families. Despite infants constituting the highest proportion of children affected, no research has examined population-level rates of infant contact with CPS. OBJECTIVE: We examined the incidence of infant contact with different levels of CPS, including termination of parental rights (TPR), according to First Nations status. PARTICIPANTS: We identified 217,261 infants (47,416 First Nations; 169,845 non-First Nations) born between 1998 and 2014 in Manitoba, Canada and residing in the province until at least age 5. METHODS: We used linked administrative data to calculate population-level rates of contact with different levels of CPS by First Nations status, including an open file before age 1, out-of-home placement before age 1, and TPR before age 5. RESULTS: Overall 35.8 % of First Nations infants had an open file, 8.5 % experienced out-of-home placement, and 5.4 % experienced TPR. Among other infants, 8.5 % had an open file, 1.3 % experienced out-of-home placement and 0.7 % experienced TPR. The rate of early-stage contact increased the fastest among First Nations infants, with a rise of 22.4 % in our study period, compared to a rise of 1.7 % among all other infants. CONCLUSIONS: CPS contact was exceptionally high among First Nations infants compared to other infants, with early-stage contact accelerating most dramatically over time. Findings support calls to greatly reduce the disruption of system contact in the lives of First Nations families.

Human Hematopoietic Stem Cell Engrafted IL-15 Transgenic NSG Mice Support Robust NK Cell Responses and Sustained HIV-1 Infection.

Mice reconstituted with human immune systems are instrumental in the investigation of HIV-1 pathogenesis and therapeutics. Natural killer (NK) cells have long been recognized as a key mediator of innate anti-HIV responses. However, established humanized mouse models do not support robust human NK cell development from engrafted human hematopoietic stem cells (HSCs). A major obstacle to human NK cell reconstitution is the lack of human interleukin-15 (IL-15) signaling, as murine IL-15 is a poor stimulator of the human IL-15 receptor. Here, we demonstrate that immunodeficient NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice expressing a transgene encoding human IL-15 (NSG-Tg(IL-15)) have physiological levels of human IL-15 and support long-term engraftment of human NK cells when transplanted with human umbilical-cord-blood-derived HSCs. These Hu-NSG-Tg(IL-15) mice demonstrate robust and long-term reconstitution with human immune cells, but do not develop graft-versus-host disease (GVHD), allowing for long-term studies of human NK cells. Finally, we show that these HSC engrafted mice can sustain HIV-1 infection, resulting in human NK cell responses in HIV-infected mice. We conclude that Hu-NSG-Tg(IL-15) mice are a robust novel model to study NK cell responses to HIV-1.

Dynamic Natural Killer Cell and T Cell Responses to Influenza Infection.

Influenza viruses have perplexed scientists for over a hundred years. Yearly vaccines limit their spread, but they do not prevent all infections. Therapeutic treatments for those experiencing severe infection are limited; further advances are held back by insufficient understanding of the fundamental immune mechanisms responsible for immunopathology. NK cells and T cells are essential in host responses to influenza infection. They produce immunomodulatory cytokines and mediate the cytotoxic response to infection. An imbalance in NK and T cell responses can lead to two outcomes: excessive inflammation and tissue damage or insufficient anti-viral functions and uncontrolled infection. The main cause of death in influenza patients is the former, mediated by hyperinflammatory responses termed "cytokine storm." NK cells and T cells contribute to cytokine storm, but they are also required for viral clearance. Many studies have attempted to distinguish protective and pathogenic components of the NK cell and T cell influenza response, but it has become clear that they are dynamic and integrated processes. This review will analyze how NK cell and T cell effector functions during influenza infection affect the host response and correlate with morbidity and mortality outcomes.

Alcohol dependence promotes systemic IFN-γ and IL-17 responses in mice.

Alcohol use disorder (AUD) is a chronic relapsing disorder characterized by an impaired ability to stop or control alcohol use despite adverse social, occupational, or health consequences. AUD is associated with a variety of physiological changes and is a substantial risk factor for numerous diseases. We aimed to characterize systemic alterations in immune responses using a well-established mouse model of chronic intermittent alcohol exposure to induce alcohol dependence. We exposed mice to chronic intermittent ethanol vapor for 4 weeks and analyzed the expression of cytokines IFN-γ, IL-4, IL-10, IL-12 and IL-17 by different immune cells in the blood, spleen and liver of alcohol dependent and non-dependent control mice through multiparametric flow cytometry. We found increases in IFN-γ and IL-17 expression in a cell type- and organ-specific manner. Often, B cells and neutrophils were primary contributors to increased IFN-γ and IL-17 levels while other cell types played a secondary role. We conclude that chronic alcohol exposure promotes systemic pro-inflammatory IFN-γ and IL-17 responses in mice. These responses are likely important in the development of alcohol-related diseases, but further characterization is necessary to understand the initiation and effects of systemic inflammatory responses to chronic alcohol exposure.