Preterm birth is associated with proinflammatory conditions and alterations in adult cardiac shape and function. Neonatal exposure to high oxygen, a rat model of prematurity-related conditions, leads to cardiac remodeling, fibrosis, and dysfunction. TLR (Toll-like receptor) 4 signaling is a critical link between oxidative stress, inflammation, and the pathogenesis of cardiovascular diseases. The current study sought to investigate the role of TLR4 signaling in neonatal oxygen-induced cardiomyopathy. Male Sprague-Dawley pups were kept in 80% oxygen or room air from day 3 to 10 of life and treated with TLR4 antagonist lipopolysaccharide from the photosynthetic bacterium Rhodobacter sphaeroides (LPS-RS) or saline. Echocardiography was performed at 4, 7, and 12 weeks. At 12 weeks, intraarterial blood pressure was measured before euthanization for histological and biochemical analyses. At day 10, cardiac TLR4, Il (interleukin) 18, and Il1β expression were increased in oxygen-exposed compared with room air controls. At 4 weeks, compared with room air-saline, saline-, but not LPS-RS treated-, oxygen-exposed animals, exhibited increased left ventricle mass index, reduced ejection fraction, and cardiac output index. Findings were similar at 7 and 12 weeks. LPS-RS did not influence echocardiography in 12 weeks room air animals. Systolic blood pressure was higher in saline- but not LPS-RS treated-oxygen-exposed animals compared with room air-saline and -LPS-RS controls. LPS-RS prevented cardiac fibrosis and cardiomyocytes hypertrophy, the increased TLR4, Myd88, and Il18 gene expression, TRIF expression, and CD68+ macrophages infiltration associated with neonatal oxygen exposure, without impact in room air rats. This study indicates that neonatal exposure to high oxygen programs TLR4 activation, which contributes to cardiac remodeling and dysfunction.
Background and objectiveNeonatal outcome research and clinical follow-up principally focus on neurodevelopmental impairment (NDI) after extremely preterm birth, as defined by the scientific community, without parental input. This survey aimed to investigate parental perspectives about the health and development of their preterm children.MethodsParents of children aged 18 months to 7 years born <29 weeks’ gestational age presenting at a neonatal follow-up clinic over a 1-year period were asked to evaluate their children’s health and development. They were also asked the following question: ‘if you could improve two things about your child, what would they be?’ Responses were analysed using mixed methods. Logistic regressions were done to compare parental responses.Results248 parents of 213 children (mean gestational age 26.6±1.6 weeks, 20% with severe NDI) were recruited. Parents evaluated their children’s health at a median of 9/10. Parental priorities for health improvements were (1) development, mainly behaviour, emotional health and language/communication (55%); (2) respiratory heath and overall medical fragility (25%); and (3) feeding/growth issues (14%). Nineteen per cent explicitly mentioned ‘no improvements’. Parents were more likely to state ‘no improvements’ if child had no versus severe NDI OR 4.33 (95% CI 1.47 to 12.75)) or if parents had no versus at least a high school diploma (OR 4.01 (95% 1.99 to 8.10)).ConclusionsParents evaluate the health of their preterm children as being very good, with positive perspectives. Parental concerns outside the developmental sphere should also be addressed both in clinical follow-up and research.
Background Preterm birth is associated with higher risk of death and severe neurodevelopmental impairment. There is an increased risk in extremely preterm infants, raising questions among ethicists and clinicians as to whether providing active care to infants born at the lower extreme is worth the outcomes, and if these outcomes are a source of decisional regrets for parents. Objectives Explore decisional regrets in parents of extremely preterm children. Design/Methods We consecutively recruited all parents of infants born <29 weeks’ gestational age, aged between 18 months corrected age and 7 years, and seen for neonatal follow-up at a single tertiary center over a one-year period. We asked the following question: “Knowing what you know now, is there anything you would have done differently?” Answers were analyzed independently by two reviewers using qualitative methodology, and discrepancies were resolved by a third reviewer. Mixed methods were used to examine the frequency of each theme and associate parental answers to demographic and clinical factors. Results Responses were obtained from 249 parents (98% participation rate). The following main themes emerged: (1) Nothing – I did what I could or was told to do: 53%; (2) Regrets about self-care: 31%; “I would listen to the nurses’ advice to sleep more” (3) Guilt related to the impression preterm labor could have been prevented by them or the medical team: 19%; “I would have pushed for better care and monitoring during pregnancy. I felt as though I wasn’t listened to when I thought I was in labour when sure enough I was” (4) Regrets about parental role in decision-making: 15%; “I would speak up more at the beginning of the hospitalisation”. None of the parents reported on regretting any life-and-death decisions they made at birth and in the neonatal unit. Conclusion In our cohort, more than half of parents of surviving preterm infants did not have any regrets associated to their NICU experience. However, lessons can be learned to improve parental support, self-care and solutions to improve their role as parents. Unlike what can be stated using “opinion-based medicine”, limiting or forgoing intensive care is not a solution to eliminate decisional regrets in parents.
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