Association of Growth During Infancy with Neurodevelopment and Obesity in Children Born Very Preterm: The Environmental Influences on Child Health Outcomes Cohort.

OBJECTIVE: To evaluate associations between change in weight z score after neonatal intensive care unit (NICU) discharge and neurodevelopmental outcomes and obesity at 12-48 months of age among individuals born very preterm. STUDY DESIGN: This secondary analysis used data from infants born very preterm participating in the Environmental influences on Child Health Outcomes cohort (n = 1400). Growth during infancy was calculated as change in weight z score between NICU discharge and follow-up at a mean of 27 months of age. Very low weight gain was defined as a change in weight z score <-1.67; very high weight gain was a change in weight z score >1.67. Neurodevelopmental outcomes included the Bayley Scales of Infant and Toddler Development, Child Behavior Checklist 1.5-5 years, and Modified Checklist for Autism in Toddlers. Multivariable linear regression was used to estimate associations between increase in weight z score and neurodevelopmental outcomes. RESULTS: Very low weight gain between NICU discharge and follow-up (experienced by 6.4% of participants) was associated with lower scores on cognitive (adjusted mean difference: -4.26; 95% CI: -8.55, -0.04) and language (adjusted mean difference: -4.80; 95% CI: -9.70, -0.11) assessments. Very high weight gain (experienced by 13.6% of participants) was associated with an increased obesity risk (adjusted relative risk: 6.20; 95% CI: 3.99, 9.66) but not with neurodevelopmental outcomes. CONCLUSIONS: Very high weight gain in the first 12-48 months after NICU discharge was associated with a higher risk of obesity at follow-up; very low weight gain was associated with lower scores on cognitive and language assessments.

Childhood Racism and Cardiometabolic Risk in Latina Mothers Across the First Postpartum Year.

OBJECTIVE: Immigrant Latinas, particularly of Mexican descent, initially achieve healthy perinatal outcomes. Although this advantage wears off across generations in the United States (US), the early life psychosocial mechanisms that may initiate a cascade of biological vulnerabilities remain elusive. The current investigation aimed to understand the extent to which childhood experiences of racism may contribute to elevated levels of C-reactive protein (CRP), an early indicator of cardiometabolic risk, during the first postpartum year. METHODS: Latinas from the Community and Child Health Network ( N = 457) retrospectively reported experiences of childhood racism and childhood country of residence via structured questionnaires. Interviewers collected CRP bloodspots and height and weight measurements for body mass index at 6 months and 1 year postpartum. RESULTS: Latinas who grew up in the US experienced a steeper increase of CRP levels across the first postpartum year ( ß = 0.131, p = .009) and had higher CRP levels 1 year postpartum than Latinas who grew up in Latin America. Based on Bayesian path analyses, Latinas who grew up in the US reported higher levels of childhood racism than Latinas who immigrated after childhood ( ß = 0.27; 95% credible interval = 0.16-0.37). In turn, childhood racism mediated the relationship between country of childhood residence and elevated CRP at 6 months and 1 year postpartum, even after adjusting for sociodemographic and behavioral covariates. After adjusting for body mass index, mediational relationships became nonsignificant. CONCLUSIONS: This study is an important first step toward understanding how childhood racism may contribute to postmigratory health patterns among Latinas, particularly cardiometabolic risk 1 year after childbirth.

GPAT1 Activity and Abundant Palmitic Acid Impair Insulin Suppression of Hepatic Glucose Production in Primary Mouse Hepatocytes.

BACKGROUND: Glycerol-3-phosphate acyltransferase (GPAT) activity is correlated with obesity and insulin resistance in mice and humans. However, insulin resistance exists in people with normal body weight, and individuals with obesity may be metabolically healthy, implying the presence of complex pathophysiologic mechanisms underpinning insulin resistance. OBJECTIVE: We asked what conditions related to GPAT1 must be met concurrently for hepatic insulin resistance to occur. METHODS: Mouse hepatocytes were overexpressed with GPATs via adenoviral infection or exposed to high or low concentrations of glucose. Glucose production by the cells and phosphatidic acid (PA) content in the cells were assayed, GPAT activity was measured, relative messenger RNA expressions of sterol-regulatory element-binding protein 1c (SREBP1c), carbohydrate response element-binding protein (ChREBP), and GPAT1 were analyzed, and insulin signaling transduction was examined. RESULTS: Overexpressing GPAT1 in mouse hepatocytes impaired insulin's suppression of glucose production, together with an increase in both N-ethylmaleimide-resistant GPAT activity and the content of di-16:0 PA. Akt-mediated insulin signaling was inhibited in hepatocytes that overexpressed GPAT1. When the cells were exposed to high-glucose concentrations, insulin suppression of glucose production was impaired, and adding palmitic acid exacerbated this impairment. High-glucose exposure increased the expression of SREBP1c, ChREBP, and GPAT1 by ∼2-, 5-, and 5.7-fold, respectively. The addition of 200 mM palmitic acid or linoleic acid to the culture media did not change the upregulation of expression of these genes by high glucose. High-glucose exposure increased di-16:0 PA content in the cells, and adding palmitic acid further increased di-16:0 PA content. The effect was specific to palmitic acid because linoleic acid did not show these effects. CONCLUSION: These data demonstrate that high-GPAT1 activity, whether induced by glucose exposure or acquired by transfection, and abundant palmitic acid can impair insulin's ability to suppress hepatic glucose production in primary mouse hepatocytes.

Neonatal inflammation and its association with asthma and obesity in late childhood among individuals born extremely preterm.

BACKGROUND: Asthma and obesity are frequent outcomes among individuals born extremely preterm and are associated with decreased lifespan. Neonatal inflammation is associated with chronic neurodevelopmental disorders; however, it is less studied in association with other later childhood chronic disorders in this population. METHODS: Fourteen hospitals in 5 U.S. states enrolled 1506 infants born before 28 weeks of gestation in the Extremely Low Gestational Age Newborn cohort in 2004-2014. Neonatal blood spots were collected on postnatal days 1, 7, 14, 21, and 28, and used to measure 14 inflammation-related proteins. Associations were evaluated between high (top quartile) levels of proteins and two chronic health disorders at ages 10 and 15 years: physician-diagnosed asthma and obesity (body mass index ≥95th percentile). RESULTS: Few associations were found between high levels of 14 inflammation-related proteins, either on a single day or on multiple days, and either asthma or obesity. Similarly, few associations were found in analyses stratified by sex or presence/absence of prenatal inflammation. CONCLUSIONS: In extremely preterm newborns, systemic elevations of inflammation-related proteins during the neonatal period were not associated with childhood asthma and obesity outcomes at 10 or 15 years of age. IMPACT: In the large multi-center Extremely Low Gestational Age Newborn (ELGAN) cohort, sustained elevation of neonatal levels of inflammation-related proteins was not consistently associated with asthma or obesity outcomes at 10 or 15 years of age. This finding contrasts with reported associations of perinatal inflammation with obesity at 2 years and neurodevelopmental disorders at 2-15 years in the ELGANs, suggesting that unlike neurodevelopment, peripubertal obesity and asthma may be driven by later childhood exposures. Future research on perinatal mechanisms of childhood asthma and obesity should account for both fetal and later exposures and pathways in addition to inflammation at birth.

Sexually dimorphic methylation patterns characterize the placenta and blood from extremely preterm newborns.

BACKGROUND: Health outcomes among children born prematurely are known to be sexually dimorphic, with male infants often more affected, yet the mechanism behind this observation is not clear. CpG methylation levels in the placenta and blood also differ by sex and are associated with adverse health outcomes. We contrasted CpG methylation levels in the placenta and neonatal blood (n = 358) from the Extremely Low Gestational Age Newborn (ELGAN) cohort based on the EPIC array, which assays over 850,000 CpG sites across the epigenome. Sex-specific epigenome-wide association analyses were conducted for the placenta and neonatal blood samples independently, and the results were compared to determine tissue-specific differences between the methylation patterns in males and females. All models were adjusted for cell type heterogeneity. Enrichment pathway analysis was performed to identify the biological functions of genes related to the sexually dimorphic CpG sites. RESULTS: Approximately 11,500 CpG sites were differentially methylated in relation to sex. Of these, 5949 were placenta-specific and 5361 were blood-specific, with only 233 CpG sites overlapping in both tissues. For placenta-specific CpG sites, 90% were hypermethylated in males. For blood-specific CpG sites, 95% were hypermethylated in females. In the placenta, keratinocyte differentiation biological pathways were enriched among the differentially methylated genes. No enrichment pathways were observed for blood. CONCLUSIONS: Distinct methylation patterns were observed between male and female children born extremely premature, and keratinocyte differentiation pathways were enriched in the placenta. These findings provide new insights into the epigenetic mechanisms underlying sexually dimorphic health outcomes among extremely premature infants.

Social Support Is Protective Against the Effects of Discrimination on Parental Mental Health Outcomes.

BACKGROUND: Discrimination, or unfair treatment based on individual characteristics such as gender, race, skin color, and or sexual orientation, is a pervasive social stressor that perpetuates health disparities by limiting social and economic opportunity and is associated with poor mental and physical health outcomes. AIMS: The purpose of the present study is to (1) examine the association between maternal experiences of discrimination and paternal experiences of discrimination; (2) explore how discrimination relates to parental (maternal and paternal) stress and depressive symptoms; and (3) examine whether social support exerts protective effects. METHODS: The sample was 2,510 mothers and 1,249 fathers from the Child Community Health Network study. Linear regression models were conducted to explore associations between maternal and paternal discrimination. In addition, mediation analyses were conducted to explore if social support functioned as a mediator between discrimination on parental stress and depressive symptoms. RESULTS: Most mothers (40.3%) and fathers (50.7%) identified race as the predominant reason for discrimination. Experiencing discrimination was significantly related to stress and depressive symptoms for both parents, and all forms of social support mediated these relationships. Our findings suggest that social support can act as a protective factor against the negative association between discrimination and both stress and depressive symptoms. CONCLUSIONS: These findings highlight the need to integrate social support into existing interventions and include fathers in mental health screenings in primary-care settings. Finally, we briefly describe the role of nurses and other allied health professionals in addressing discrimination in health care and health policy implications.

Growth During Infancy After Extremely Preterm Birth: Associations with Later Neurodevelopmental and Health Outcomes.

OBJECTIVE: To evaluate associations between changes in weight, length, and weight/length ratio during infancy and outcomes later in life among individuals born extremely preterm. STUDY DESIGN: Among participants in the Extremely Low Gestational Age Newborn (ELGAN) study, we measured weight and length at discharge from the neonatal intensive care unit (NICU) and at age 2 years and evaluated neurocognitive, psychiatric, and health outcomes at age 10 years and 15 years. Using multivariable logistic regression, we estimated associations between gains in weight, length, and weight/length ratio z-scores between discharge and 2 years and outcomes at 10 and 15 years. High gain was defined as the top quintile of change; low gain, as the bottom quintile of change. RESULTS: High gains in weight and weight/length were associated with greater odds of obesity at 10 years, but not at 15 years. These associations were found only for females. High gain in length z-score was associated with lower odds of obesity at 15 years. The only association found between high gains in growth measures and more favorable neurocognitive or psychiatric outcomes was between high gain in weight/length and lower odds of cognitive impairment at age 10 years. CONCLUSIONS: During the 2 years after NICU discharge, females born extremely preterm with high gains in weight/length or weight have greater odds of obesity at 10 years, but not at 15 years. Infants with high growth gains in the 2 years after NICU discharge have neurocognitive and psychiatric outcomes in middle childhood and adolescence similar to those of infants with lower gains in weight and weight/length.

Environmental influences on child health outcomes: cohorts of individuals born very preterm.

The National Institutes of Health's Environmental influences on Child Health Outcomes (ECHO) Program was designed to address solution-oriented research questions about the links between children's early life environment and their risks of pre-, peri-, and post-natal complications, asthma, obesity, neurodevelopmental disorders, and positive health. Children born very preterm are at increased risk for many of the outcomes on which ECHO focuses, but the contributions of environmental factors to this risk are not well characterized. Three ECHO cohorts consist almost exclusively of individuals born very preterm. Data provided to ECHO from cohorts can be used to address hypotheses about (1) differential risks of chronic health and developmental conditions between individuals born very preterm and those born at term; (2) health disparities across social determinants of health; and (3) mechanisms linking early-life exposures and later-life outcomes among individuals born very preterm. IMPACT: The National Institutes of Health's Environmental Influences on Child Health Outcomes Program is conducting solution-oriented research on the links between children's environment and health. Three ECHO cohorts comprise study participants born very preterm; these cohorts have enrolled, to date, 1751 individuals born in 14 states in the U.S. in between April 2002 and March 2020. Extensive data are available on early-life environmental exposures and child outcomes related to neurodevelopment, asthma, obesity, and positive health. Data from ECHO preterm cohorts can be used to address questions about the combined effects of preterm birth and environmental exposures on child health outcomes.

Child and family factors associated with positive outcomes among youth born extremely preterm.

BACKGROUND: To analyze the relationship of child behavioral and communication disorders, and adverse family events, to later-in-life child health and cognitive function among youth born extremely preterm. METHODS: The study participants were 694 children enrolled in the Extremely Low Gestational Age Newborn Study. At ages 2 and 10, we assessed internalizing and externalizing behaviors, and at age 10, we assessed adverse life events within the family. Associations were evaluated between these child and family factors and positive child health at age 10 years, and global health and cognitive function at age 15 years. RESULTS: Lower T-scores for internalizing or externalizing behaviors at age 2 were associated with more positive health at age 10. The absence of internalizing behaviors at age 10 was associated with better global child health and better cognitive function at age 15. The absence of communication deficits at age 10 was associated with better cognitive function at age 15. The absence of parent job loss was associated with better global child health at age 15. CONCLUSION: Among individuals born extremely preterm, child health and cognitive outcomes might be improved by timely interventions to address child behavioral symptoms and the impact of adverse life events in the family. IMPACT: The absence of child behavioral and communication disorders, and adverse family events, were associated with more positive health, higher global health, and better cognitive function among youth born extremely preterm. Interventions to address behavioral disorders in early childhood, and to reduce the impact of adverse life events on the family, might promote improved health and developmental outcomes for adolescents born extremely preterm.

CpG methylation patterns in placenta and neonatal blood are differentially associated with neonatal inflammation.

BACKGROUND: Infants born extremely premature are at increased risk for health complications later in life for which neonatal inflammation may be a contributing biological driver. Placental CpG methylation provides mechanistic information regarding the relationship between prenatal epigenetic programming, prematurity, neonatal inflammation, and later-in-life health. METHODS: We contrasted CpG methylation in the placenta and neonatal blood spots in relation to neonatal inflammation in the Extremely Low Gestational Age Newborn (ELGAN) cohort. Neonatal inflammation status was based on the expression of six inflammation-related proteins, assessed as (1) day-one inflammation (DOI) or (2) intermittent or sustained systemic inflammation (ISSI, inflammation on ≥2 days in the first 2 postnatal weeks). Epigenome-wide CpG methylation was assessed in 354 placental samples and 318 neonatal blood samples. RESULTS: Placental CpG methylation displayed the strongest association with ISSI (48 CpG sites) but was not associated with DOI. This was in contrast to CpG methylation in blood spots, which was associated with DOI (111 CpG sites) and not with ISSI (one CpG site). CONCLUSIONS: Placental CpG methylation was strongly associated with ISSI, a measure of inflammation previously linked to later-in-life cognitive impairment, while day-one neonatal blood methylation was associated with DOI. IMPACT: Neonatal inflammation increases the risk of adverse later-life outcomes, especially in infants born extremely preterm. CpG methylation in the placenta and neonatal blood spots were evaluated in relation to neonatal inflammation assessed via circulating proteins as either (i) day-one inflammation (DOI) or (ii) intermittent or sustained systemic inflammation (ISSI, inflammation on ≥2 days in the first 2 weeks). Tissue specificity was observed in epigenetic-inflammatory relationships: placental CpG methylation was associated with ISSI, neonatal blood CpG methylation was associated with DOI. Supporting the placental origins of disease framework, placental epigenetic patterns are associated with a propensity for ISSI in neonates.

The Effects of Maternal Perinatal Depression on Child IQ: A Systematic Review.

BACKGROUND: Maternal perinatal depression has been shown to have long lasting effects on children's development. Studies have described the relationship of perinatal depression on children's cognition, especially negative effects on intelligence quotient (IQ). However, a recent examination of the current studies to discern the patterns and strength of associations between perinatal depression and child IQ is not available. OBJECTIVE: The purpose of this systematic review is to discern the effects of perinatal depression, prenatally and within the first 12 months of the postpartum period, on the IQ of the child aged 0-18 years old. METHODS: We searched the electronic databases: PubMed and CINAHL. We identified 1633 studies, and included 17 studies in the final review based on pre-determined criteria. After the data was extracted, we assessed the strength of the study using the national heart, lung, and blood institute quality assessment tool for observational cohort and cross-sectional studies. This systematic review had a total sample of 10,757 participants. RESULTS: Across the studies, we identified a relationship between limited maternal responsiveness due to postpartum depression and a decrease in full IQ scores in younger children. Male children were found to be more sensitive to the postpartum depression, resulting in a decrease in IQs, in comparison to female children. CONCLUSIONS: Policies should be implemented to identify women suffering from perinatal depression to mitigate the effects of the disorder for both the mother and her child.

Maternal perinatal depression has been shown to have far-reaching effects on children's development. However, a recent examination of the current studies to discern the associations between perinatal depression and child IQ is not available. In this systematic review, we identified a relationship between limited maternal responsiveness due to postpartum depression and a decrease in full IQ scores in younger children. Male children were more sensitive to postpartum depression, resulting in a decrease in IQs, in comparison to female children..

Prevalence of sleep disorders in children with Congenital Zika Syndrome.

Studies have reported that children with Congenital Zika Syndrome (CZS) experience changes in their sleep patterns, which can result in mood disturbances, behavioral issues and delays in growth and development. This systematic review synthesized the available evidence on the prevalence of sleep disorders in children with CZS. Eligible studies were those with an observational design that reported sleep disorders in children with CZS using validated questionnaires, polysomnography/electroencephalographic recording or parent/caregiver reports. Searches were conducted in PubMed, Web of Science, SCOPUS and Embase, as well as a gray literature search using Google Scholar. The Freeman-Tukey double-arcsine transformation with a random-effects model was used to estimate the pooled prevalence of sleep disorders with a 95% confidence interval (CI). Five studies were included and data from 340 Brazilian children with CZS were analyzed. The overall prevalence of sleep disorders was 27.4% (95% CI 16.7-39.4), without differences among studies using validated questionnaires (29.4%, 95% CI 21.4-37.8) or report from parents and caregivers (27.4%, 95% CI 11.5-47.0). Sleep disorders are prevalent in children with CZS, impacting their development and quality of life. It is critical to examine the quality of sleep in these children to develop appropriate interventions that can mitigate these issues.

The article discusses a systematic review of studies that have explored the prevalence of sleep disorders in children with Congenital Zika Syndrome (CZS), a condition caused by the Zika virus. The study found that children with CZS often experience changes in their sleep patterns, which can lead to mood disturbances, behavioral issues and delays in growth and development. The review included five studies with a total of 340 Brazilian children with CZS, and the overall prevalence of sleep disorders was found to be 27.4%. This indicates that sleep disorders are prevalent in children with CZS and can significantly impact their development and quality of life. The authors suggest that further research is needed to develop appropriate interventions to mitigate these issues.

The role of social adversity on emotional dysregulation during infancy and early childhood.

PURPOSE: The purpose of this study was to investigate if social adversity is associated with mother reported emotional dysregulation behaviors and trajectories during infancy and early childhood. DESIGN & METHODS: A secondary data analysis from the Durham Child Health and Development study study included 206 child-mother dyads. Three models were used to explore the relationship between social adversity and mother reported emotional dysregulation during infancy (Infant Behavior Questionnaire-Revised) and early childhood (Child Behavior Checklist - Dysregulation Profile). Linear mixed effects models were adopted to investigate if social adversity was associated with mother reported emotional dysregulation longitudinally. Regression analysis was conducted to explore if social adversity was associated with maternal reported emotional dysregulation trajectory slope scores and maternal reported emotional dysregulation trajectory class. Maternal psychological distress and the child's sex assigned at birth were included as covariates in each analysis. RESULTS: Infants with greater social adversity scores had significantly higher maternal reported fear responses across the first year of life. Social adversity was associated with maternal reported distress to limitations trajectory, dysregulated recovery class, and dysregulated distress to limitations class. During early childhood social adversity was significantly associated with maternal reported emotional dysregulation but not trajectories which showed little variability. CONCLUSION & PRACTICAL IMPLICATIONS: Our results indicate that social adversity is associated with maternal reported emotional dysregulation during infancy and early childhood. Nursing and other professionals can participate in early screening to determine risk and provide intervention.

Psychological processing among caregivers of allogeneic bone marrow transplant recipients: Qualitative findings from a longitudinal study.

PURPOSE: To describe caregiver psychological processing during the 12 weeks after transplant and the potential role of positive emotions in caregiving experiences. METHODS: We conducted a longitudinal qualitative descriptive study and interviewed 11 BMT caregivers monthly for 12-weeks post-transplant about their experiences and psychological processing. We analyzed 38 interviews using directed content analysis based on guiding theories and inductive in vivo coding to develop themes. RESULTS: The majority of participants appraised caregiving as a challenge that needed to be met. Caregivers described feeling positive emotions throughout the time after transplant (gratitude, interest, and hope). We identified two new themes: mirroring (caregiver feelings reflecting patient status) and emotion regulation (hiding negative emotions and displaying positive emotions when with the patient). IMPLICATIONS: Findings provide further evidence that interventions focused on emotion regulation and positive emotion experiences during caregiving to reduce the negative effects of caregiving related stress may be promising.

Increasing the use of functional and multimodal genetic data in social science research.

Genetic studies in the social sciences could be augmented through the additional consideration of functional (transcriptome, methylome, metabolome) and/or multimodal genetic data when attempting to understand the genetics of social phenomena. Understanding the biological pathways linking genetics and the environment will allow scientists to better evaluate the functional importance of polygenic scores.

A roadmap for social determinants of health and biological nursing research in the National Institute of Nursing Research 2022-2026 Strategic Plan: Optimizing health and advancing health equity using antiracist framing.

BACKGROUND: Health equity is essential for improving the well-being of all individuals and groups, and research remains a critical element for understanding barriers to health equity. While considering how to best support research that acknowledges current health challenges, it is crucial to understand the role of social justice frameworks within health equity research and the contributions of minoritized researchers. Additionally, there should be an increased understanding of the influence of social determinants of health on biological mechanisms. PURPOSE: Biological health equity research seeks to understand and address health disparities among historically excluded populations. DISCUSSION: While there are examples of studies in this area led by minoritized researchers, some individuals and groups remain understudied due to underfunding. Research within minoritized populations must be prioritized to authentically achieve health equity. Furthermore, there should be increased funding from National Institutes of Health to support minoritized researchers working in this area.

Does Participation in Food Benefit Programs Reduce the Risk for Depressive Symptoms?

BACKGROUND: Food insecurity affects 15 million households in the United States and is associated with negative physical and mental health outcomes including Major Depressive Disorder. Governmental public assistance or food benefit programs including the Supplemental Nutrition Assistance Program (SNAP) and Women, Infants, and Children (WIC) are social intervention services that attempt to minimize food insecurity for low-income households. There is little consensus regarding the effects of food benefit participation on reducing risk of depressive symptoms. AIM: This study aims to explore the association between household food insecurity and food benefit participation (SNAP or WIC) on risk for depressive symptoms using nationally representative samples from the Center for Disease and Control and Prevention Nutritional Health and Nutrition Examination Survey 2013-2014 and 2015-2016 cohorts. We hypothesize that food insecurity is associated with increased risk of depressive symptoms and food benefit participation with reduced risk. METHOD: Cross-sectional analyses were conducted using survey-weighted logistic regression to explore the relationship between food insecurity, food benefit participation, and the risk of depressive symptoms controlling for relevant income and sociodemographic variables. RESULTS: When controlling for sociodemographic variables, food benefit participation did not reduce the risk of depressive symptoms, while high levels of food insecurity were associated with elevated risk. CONCLUSIONS: High levels of food insecurity are associated with elevated risk of depressive symptoms. Nurses and public health professionals can address food security needs through increased knowledge of referral and eligibility requirements. Implications on clinical practice, policy, and future directions for research are discussed.

Bioburden Method Suitability: A Practical Solution to Screening for Inhibition.

ANSI/AAMI/ISO 11737-1:2018 addresses validation of the method for determination of bioburden. Clause 7 states that validation shall consist of four items, one of which is "assessment of test method suitability to demonstrate lack of inhibition of growth." Information must be provided, either through a rationale or via testing, showing that no inhibitory properties from the product exist in the specified bioburden test. However, the standard has no guidance on specific test methods for this particular purpose. Therefore, a simple bioburden suitability screening presented here could be used to quickly assess whether a product that is tested for bioburden has inhibitory substances that would be manifested in the bioburden test. The screening procedure uses a vegetative microorganism, Staphylococcus aureus, inoculated onto the product or into the extract solution, followed by the bioburden test procedure. A recovery of 70% or greater is recommended as acceptable for confirming the bioburden test Suitability.

Differential placental CpG methylation is associated with chronic lung disease of prematurity.

BACKGROUND: Chronic lung disease (CLD) is the most common pulmonary morbidity in extremely preterm infants. It is unclear to what extent prenatal exposures influence the risk of CLD. Epigenetic variation in placenta DNA methylation may be associated with differential risk of CLD, and these associations may be dependent upon sex. METHODS: Data were obtained from a multi-center cohort of infants born extremely preterm (<28 weeks' gestation) and an epigenome-wide approach was used to identify associations between placental DNA methylation and CLD (n = 423). Associations were evaluated using robust linear regression adjusting for covariates, with a false discovery rate of 0.05. Analyses stratified by sex were used to assess differences in methylation-CLD associations. RESULTS: CLD was associated with differential methylation at 49 CpG sites representing 46 genes in the placenta. CLD was associated with differential methylation of probes within genes related to pathways involved in fetal lung development, such as p53 signaling and myo-inositol biosynthesis. Associations between CpG methylation and CLD differed by sex. CONCLUSIONS: Differential placental methylation within genes with key roles in fetal lung development may reflect complex cell signaling between the placenta and fetus which mediate CLD risk. These pathways appear to be distinct based on fetal sex. IMPACT: In extremely preterm infants, differential methylation of CpG sites within placental genes involved in pathways related to cell signaling, oxidative stress, and trophoblast invasion is associated with chronic lung disease of prematurity. DNA methylation patterns associated with chronic lung disease were distinctly based on fetal sex, suggesting a potential mechanism underlying dimorphic phenotypes. Mechanisms related to fetal hypoxia and placental myo-inositol signaling may play a role in fetal lung programming and the developmental origins of chronic lung disease. Continued research of the relationship between the placental epigenome and chronic lung disease could inform efforts to ameliorate or prevent this condition.

Maternal Social Risk, Gestational Age at Delivery, and Cognitive Outcomes among Adolescents Born Extremely Preterm.

Background: Children born extremely preterm (EP) are at increased risk of cognitive deficits that persist into adulthood. Few large cohort studies have examined differential impairment of cognitive function in EP-born adolescents in relation to early life risk factors, including maternal social disadvantage, gestational age at delivery, and neonatal morbidities prevalent among EP neonates. Objectives: To assess cognitive abilities in relation to early life risk factors in an EP-born cohort at 15 years of age. Methods: 681 of 1198 surviving participants (57%) enrolled from 2002 to 2004 in the Extremely Low Gestational Age Newborn Study returned at age 15 years for an assessment of cognitive abilities with the Wechsler Abbreviated Scale of Intelligence-II and the NIH Toolbox Cognition Battery (NTCB) verbal cognition and fluid processing composites, the latter of which measured executive functions and processing speed. Three cognitive outcomes, WASI-II IQ, NTCB verbal cognition, and NTCB fluid processing, were analyzed for associations with maternal social disadvantage and gestational age. Mediation of maternal social disadvantage by gestational age and mediation of gestational age by neonatal morbidities were also examined. Results: Test scores were lower for NTCB fluid processing relative to IQ and NTCB verbal abilities. Social disadvantage and gestational age were associated with all three cognitive outcomes. Mediation analyses indicated partial mediation of gestational age associations with all three outcomes by neonatal morbidities but did not support mediation by gestational age of social risk associations with cognitive outcomes. Conclusions: Greater maternal social disadvantage and lower gestational age are associated with less favorable cognitive outcomes among EP-born adolescents at 15 years of age. Neonatal morbidities partially mediate associations between lower gestational age and cognitive outcomes. These findings highlight the need for improved medical and remedial interventions to mitigate risk of poor cognitive outcomes among EP-born adolescents.