Adverse Maternal Environment and Postweaning Western Diet Alter Hepatic CD36 Expression and Methylation Concurrently with Nonalcoholic Fatty Liver Disease in Mouse Offspring.

BACKGROUND: The role of an adverse maternal environment (AME) in conjunction with a postweaning Western diet (WD) in the development of nonalcoholic fatty liver disease (NAFLD) in adult offspring has not been explored. Likewise, the molecular mechanisms associated with AME-induced NAFLD have not been studied. The fatty acid translocase or cluster of differentiation 36 (CD36) has been implicated to play a causal role in the pathogenesis of WD-induced steatosis. However, it is unknown if CD36 plays a role in AME-induced NAFLD. OBJECTIVE: This study was designed to evaluate the isolated and additive impact of AME and postweaning WD on the expression and DNA methylation of hepatic Cd36 in association with the development of NAFLD in a novel mouse model. METHODS: AME constituted maternal WD and maternal stress, whereas the control (Con) group had neither. Female C57BL/6J mice were fed a WD [40% fat energy, 29.1% sucrose energy, and 0.15% cholesterol (wt/wt)] 5 wk prior to pregnancy and throughout lactation. Non invasive variable stressors (random frequent cage changing, limited bedding, novel object, etc.) were applied to WD dams during the last third of pregnancy to produce an AME. Con dams consumed the control diet (CD) (10% fat energy, no sucrose or cholesterol) and were not exposed to stress. Male offspring were weaned onto either CD or WD, creating 4 experimental groups: Con-CD, Con-WD, AME-CD, and AME-WD, and evaluated for metabolic and molecular parameters at 120 d of age. RESULTS: AME and postweaning WD independently and additively increased the development of hepatic steatosis in adult male offspring. AME and WD independently and additively upregulated hepatic CD36 protein and mRNA expression and hypomethylated promoters 2 and 3 of the Cd36 gene. CONCLUSIONS: Using a mouse AME model together with postweaning WD, this study demonstrates a role for CD36 in AME-induced NAFLD in offspring and reveals 2 regions of environmentally induced epigenetic heterogeneity within Cd36.

Ethical Cultures in Perinatal Care: Do They Exist? Correlation of Provider Attitudes with Periviability Practices at Six Centers.

OBJECTIVE: This study aimed to compare attitudes of providers regarding perinatal management and outcomes for periviable newborns of caregivers at centers with higher resuscitation (HR) and lower resuscitation (LR) rates in the delivery room. STUDY DESIGN: All obstetric and neonatal clinical providers at six U.S. sites were invited to complete an anonymous online survey. Survey responses were compared with clinical data collected from a previous retrospective study comparing centers' rates of planned resuscitation. Responses were analyzed by multivariable logistic and linear regression to assess how HR versus LR center respondents differed in management preferences and outcome predictions. RESULTS: Paradoxically, HR versus LR respondents, when adjusting for other variables, were less likely to respond that interventions such as antenatal steroids (odds ratio: 0.61, 95% confidence interval [CI]: 0.42-0.88, p < 0.009) and resuscitation (OR: 0.59, 95% CI: 0.44-0.78, p < 0.001) should be given at 22 weeks. HR versus LR respondents also reported lower likelihood of survival and acceptable quality of life (OR: 0.7, 95% CI: 0.53-0.93, p = 0.012) at 23 weeks. CONCLUSION: Despite higher rates of planned resuscitation at 22 and 23 weeks, steroid usage and survival rates did not differ between HR and LR sites. In this subsequent survey, respondents from HR centers had a less favorable outlook on interventions for these newborns than those at LR centers, suggesting that instead of driving practices, attitudes may be more closely associated with experiences of clinical outcomes.

Antenatal Periviability Counseling and Decision Making: A Retrospective Examination by the Investigating Neonatal Decisions for Extremely Early Deliveries Study Group.

OBJECTIVE: To describe periviability counseling practices and decision making. STUDY DESIGN: This is a retrospective review of mothers and newborns delivering between 22 and 24 completed weeks from 2011 to 2015 at six U.S. centers. Maternal and fetal/neonatal clinical and maternal sociodemographic data from medical records and geocoded sociodemographic information were collected. Separate analyses examined characteristics surrounding receiving neonatology consultation; planning neonatal resuscitation; and centers' planned resuscitation rates. RESULTS: Neonatology consultations were documented for 40, 63, and 72% of 498 mothers delivering at 22, 23, and 24 weeks, respectively. Consult versus no-consult mothers had longer median admission-to-delivery intervals (58.7 vs. 8.7 h, p < 0.001). Consultations were seen more frequently when parental decision making was evident. In total, 76% of mothers had neonatal resuscitation planned. Resuscitation versus no-resuscitation newborns had higher mean gestational ages (24.0 vs. 22.9 weeks, p < 0.001) and birthweights (618 vs. 469 g, p < 0.001). Planned resuscitation rates differed at higher (HR) versus lower (LR) rate centers at 22 (43 vs. 7%, p < 0.001) and 23 (85 vs. 58%, p < 0.001) weeks. HR versus LR centers' populations had more socioeconomic hardship markers but fewer social work consultations (odds ratio: 0.31; confidence interval: 0.15-0.59, p < 0.001). CONCLUSION: Areas requiring improvement included delivery/content of neonatology consultations, social work support, consideration of centers' patient populations, and opportunities for shared decisions.

Health-related quality of life, educational and family outcomes in survivors of congenital diaphragmatic hernia.

PURPOSE: Congenital diaphragmatic hernia (CDH) survivors experience increased risk of medical and neurodevelopmental challenges. This study describes the health-related quality of life (HRQOL), special education utilization and the family impact among neonatal CDH survivors. METHODS: A single-center prospective cohort of CDH survivors born between 1995 and 2006 was followed. Parents completed the PedsQL HRQOL index and a Family Impact survey to assess the need for medical equipment, home health services, and special education and quantify the burden placed on the family by their child's medical needs. RESULTS: Parents of 32 survivors participated at a mean survivor age of 8 ± 4 years. Many survivors utilized medical equipment (62%), home health services (18%) and special education (28%). CDH survivor HRQOL (79 ± 17) did not differ significantly from that of healthy children (83 ± 15, p = 0.12). HRQOL was diminished among survivors who required special education (67 ± 8 vs 82 ± 3; p = 0.04) and those reporting increased Family Impact score (p = 0.001). CONCLUSION: Many CDH survivors continue to require home medical equipment and home health services at school age. Most survivors have normal parent-reported HRQOL; however, the need for special education and higher family impact of neonatal CDH correlates with decreased HRQOL.

Intention to treat: obstetrical management at the threshold of viability.

BACKGROUND: Despite medical advances in the care of extremely preterm neonates and growing acceptance of resuscitation at 23 and even 22 weeks gestation, controversy remains concerning the use of antepartum obstetric intervention s that are intended to improve outcomes in the setting of anticipated extremely preterm birth. In the absence of demonstrated benefit at <23 weeks gestation and with uncertain benefit at 23 weeks gestation, previous obstetric committee opinions have advised against their use at these gestational ages. OBJECTIVE: The purpose of this study was to review the use of obstetric intervention s at the threshold of viability based on neonatal resuscitation plan and to review the odds of survival to neonatal intensive care unit discharge based on use of obstetric intervention s with adjustment for neonatal factors. STUDY DESIGN: This retrospective study of 6 study centers reviewed pregnant patients who were admitted between 22+0/7 and 24+6/7 weeks gestation facing delivery from 2011-2015. Patients with known anomalies or missing data were excluded. Records were reviewed for demographics, resuscitation plan, and obstetric intervention s. Mode of delivery, delivery room care, and final infant dispositions were recorded. Multiple gestations were included as 1 pregnancy in regard to the use of obstetric intervention s and were excluded from survival analysis. RESULTS: Four hundred seventy-eight mothers met the inclusion criteria. When resuscitation was planned, mothers were more likely to receive all conventional obstetric intervention s (antenatal steroids, magnesium sulfate for neuroprotection, tocolytics, and Group Beta Streptococcus prophylaxis), regardless of gestational age at admission, and were more likely to be delivered by cesarean section (P<.05). Analyzed as a group, when antenatal steroids, magnesium sulfate, tocolytics and Group Beta Streptococcus prophylaxis were administered, the odds of survival to neonatal intensive care unit discharge increased for newborn infants who were born at 22 (odds ratio, 11.33; 95% confidence interval, 1.405-91.4) and 23 weeks gestation (odds ratio, 15.5; 95% confidence interval, 3.747-64.11; P<.05). In singletons, the odds of survival to neonatal intensive care unit discharge was not improved by cesarean delivery vs vaginal delivery, even after adjustment for the use of additional interventions, weight, gender, and gestational age (odds ratio, 1.0; 95% confidence interval, 0.59-1.8; P=.912). CONCLUSION: In this study, when postnatal resuscitation was planned at 22 and 23 weeks gestation, women were more likely to receive antenatal steroids, magnesium sulfate, and antibiotics; provision of this bundle imparted survival benefit at 23 weeks gestation but could not be demonstrated at 22 weeks gestation because of the small sample size. These findings support of neonate-oriented obstetric interventions in the setting of delivery at 23 weeks gestation when resuscitation is planned and further exploration of optimal obstetric care when resuscitation of infants who were born at 22 weeks gestation is anticipated.

Development and validation of PRISM: a survey tool to identify diabetes self-management barriers.

AIMS: Although most children with type 1 diabetes do not achieve optimal glycemic control, no systematic method exists to identify and address self-management barriers. This study develops and validates PRISM (Problem Recognition in Illness Self-Management), a survey-based tool for efficiently identifying self-management barriers experienced by children/adolescents with diabetes and their parents. METHODS: Adolescents 13 years and older and parents of children 8 years and older visiting for routine diabetes management (n=425) were surveyed about self-management barriers. HbA1c was abstracted from the electronic health record. To develop PRISM, exploratory and confirmatory factor analyses were used. To assess validity, the association of PRISM scores with HbA1c was examined using linear regression. RESULTS: Factor analyses of adolescent and parent data yielded well-fitting models of self-management barriers, reflecting the following domains: (1) Understanding and Organizing Care, (2) Regimen Pain and Bother, (3) Denial of Disease and Consequences, and (4) Healthcare Team, (5) Family, or (6) Peer Interactions. All models exhibited good fit, with χ(2) ratios<2.21, root mean square errors of approximation<0.09, Confirmatory Fit Indices and Tucker-Lewis Indices both >0.92, and weighted root mean square residuals<1.71. Greater PRISM barrier scores were significantly associated with higher HbA1cs. CONCLUSIONS: Our findings suggest at least six different domains exist within self-management barriers, nearly all of which are significantly related to HbA1c. PRISM could be used in clinical practice to identify each child and family's unique self-management barriers, allowing existing self-management resources to be tailored to the family's barriers, ultimately improving effectiveness of such services.