Postnatal Cytokine Trajectories in Very Preterm Infants.

Inflammation often accompanies preterm birth and contributes to poor neurodevelopment in preterm infants. The purpose of this study was to describe postnatal cytokine trajectories among non-infected very preterm infants during the first weeks of life. Blood samples for cytokine analysis were collected weekly from infants born between 28 and 31 weeks post-menstrual age. We used linear mixed models to calculate slopes for each cytokine and allowed the slopes to differ by infant biological sex and post-menstrual age at birth. Levels of interleukin-6, interleukin-8, and interleukin-1 receptor antagonist decreased, on average, during the neonatal period. Monocyte chemoattractant protein-1 levels increased over time, and tumor necrosis factor-alpha levels were stable. Interleukin-6 and interleukin-8 slopes differed by post-menstrual age at birth but were unaffected by infant sex. Knowledge of average cytokine trajectories may be useful in identifying infants with unresolving inflammation that increases their risk for poor neurodevelopment.

Patterns of Growth and Nutrition From Birth to 6 Months in Infants With Complex Congenital Cardiac Defects.

BACKGROUND: Infants with complex congenital heart defects (CCHDs) experience alterations in growth that develop following surgical intervention and persist throughout early infancy, but the roles of nutritional intake and method of feeding require further exploration as their roles are not fully explained. OBJECTIVES: The purpose of this study was to characterize trends in growth and nutritional intake during the first 6 months of life in infants with CCHD. METHODS: We conducted a secondary analysis of growth and nutritional data from a pilot study designed to test the feasibility of nurse-guided participatory intervention with parents of infants with CCHD. Measures included demographic data, anthropometric data at birth, hospital discharge, and 6 months of age, nutritional intake at 2 and 6 months of age from parent-completed 24-hour nutrition diaries, and assessment of oral-motor skills between 1 and 2 months of age. Descriptive statistics and correlation and group differences were examined. RESULTS: Data for 28 infants were analyzed. Infants demonstrated a decrease in weight-for-age z score (WAZ) and length-for-age z score (LAZ) from birth to hospital discharge and an increase in WAZ and LAZ by 6 months of age. Many of the infants developed failure to thrive. Across the study period, one third of the infants were receiving enteral nutrition. Infants who were orally fed had better growth WAZ and LAZ at 6 months of age when compared to infants who were enterally fed. DISCUSSION: Infants with CCHD exhibit growth faltering throughout early infancy. Reliance on enteral nutrition did not improve growth outcomes in these infants. Findings suggest nutritional intake may not be enough to meet the nutrient requirements to stimulate catch-up growth.

Inflammatory predictors of neurobehavior in very preterm infants.

BACKGROUND: Preterm infants are at risk for impaired neurodevelopment. Inflammation may be an important modifiable mediator of preterm birth and neurodevelopmental impairment, but few studies have examined longitudinal measures of inflammation. OBJECTIVE: To determine the relationship between longitudinal measures of inflammation and neurobehavior in very preterm infants. STUDY DESIGN: Non-experimental, repeated measures cohort study. METHODS: Very preterm infants were enrolled between October 2017 and December 2018. Blood was collected weekly until 35 weeks post-menstrual age for the quantification of plasma cytokines. Neurobehavior was assessed at 35 weeks post-menstrual age using the cluster scores for motor development and vigor and alertness/orientation from the Neurobehavioral Assessment of the Preterm Infant. Multiple linear regression models with robust standard errors were used to analyze the data. Average levels of individual cytokines, cytokine trends, and composite scores were used as measures of inflammation. RESULTS: Seventy-three infants were enrolled in the study. Interleukin-1 receptor antagonist was associated with motor development and vigor scores. Interleukin-6 was associated with alertness/orientation scores. Tumor necrosis factor-alpha and composite scores of inflammation were associated with motor development and vigor and alertness/orientation scores. There were interactions with post-menstrual age at birth and infant sex. CONCLUSION: Inflammation may be an important predictor of short-term neurobehavior in preterm infants. Interleukin-1 receptor antagonist, interleukin-6, and tumor necrosis factor-alpha are key cytokines for studies of preterm infants, but composite scores may be a better measure of inflammation than individual cytokines. Inflammation can be damaging to the immature brain and may be a specific target for future interventions to improve outcomes.

Inflammatory mediators of stress exposure and neurodevelopment in very preterm infants: Protocol for the stress neuro-immune study.

AIMS: (a) Determine relationships among stress exposure, inflammation, and neurodevelopment in very preterm infants and determine the mediated effect of inflammation on the relationship between stress exposure and neurodevelopment; (b) describe cytokine trajectories following birth and determine the effect of stress exposure on these trajectories; and (c) examine relationships between stress exposure and chronic stress responses in very preterm infants. DESIGN: Non-experimental, repeated measures. METHODS: Very preterm infants born 28-31 weeks post menstrual age will be enrolled. Cumulative stress exposure over the first 14 days of life will be measured using the Neonatal Infant Stressor Scale. Blood will be collected weekly for the quantification of cytokines. Neurodevelopment will be assessed using the Neurobehavioral Assessment of the Preterm Infant and hair for quantification of hair cortisol will be collected at 35 weeks post menstrual age. Multiple linear regression and conditional process analysis will be used to analyse the relationships among stress exposure, inflammation and neurodevelopment. Linear mixed models will be used to determine inflammatory trajectories over time. IRB approval for the study was received May 2017, and funding from the National Institute of Nursing Research was awarded July 2017. DISCUSSION: This study will determine the extent to which inflammation mediates the relationship between stress exposure and neurodevelopment. Interventions to attenuate inflammation in preterm infants may improve outcomes. IMPACT: Determining the potentially modifiable mediators of stress exposure and neurodevelopment in preterm infants is critical to improving long-term outcomes.

The biological embedding of neonatal stress exposure: A conceptual model describing the mechanisms of stress-induced neurodevelopmental impairment in preterm infants.

The biological embedding of early life stress exposure may result in life-long neurodevelopmental impairment in preterm infants. Infants hospitalized in the neonatal intensive care unit are exposed to significant experiential, environmental, and physiologic stressors over the course of their extended hospitalization. Stress exposure during the sensitive period of brain development may alter biological processes, including functioning of the immune system, the autonomic nervous system, and the hypothalamic-pituitary-adrenal axis as well as gene expression. These alterations may subsequently affect brain structure and function. Changes to these processes may mediate the relationship between neonatal stress exposure and neurodevelopment in preterm infants and represent potential therapeutic targets to improve long-term outcomes. The purpose of this paper is to introduce a conceptual model, based on published research, that describes the mechanisms mediating stress exposure and neurodevelopment impairment in preterm infants and to provide the theoretical foundation on which to base future descriptive research, intervention studies, and clinical care.

Expanding Regulation Theory With Oxytocin: A Psychoneurobiological Model for Infant Development.

BACKGROUND: Oxytocin (OT), an affiliation hormone released during supportive social interactions, provides an exemplar of how social environments are reflected in our neurobiology from the beginning of life. A growing body of OT research has uncovered previously unknown functions of OT, including modulation of parenting behaviors, neuroprotection, affiliation, and bonding. Regulation theory provides a strong framework for describing how the maternal care environment affects infant neurodevelopment through a symphony of molecules that form the neurobiological milieu of the developing infant brain. OBJECTIVES: The purpose of this article was to expand on regulation theory by discussing how OT-based processes contribute to infant neurobiology and by proposing a new model for maternal-infant nursing practice and research. APPROACH: We structure our discussion of the socially based, neurobiological processes of OT through its effects in the nested hierarchies of genetic, epigenetic, molecular, cellular, neural circuit, multiorgan, and behavioral levels. Our discussion is also presented chronologically, as OT works through a positive feedback loop during infant neurodevelopment, beginning prenatally and continuing after birth. IMPLICATIONS: Nurses are in a unique position to use innovative discoveries made by the biologic sciences to generate new nursing theories that inform clinical practice and inspire the development of innovative interventions that maximize the infant's exposure to supportive maternal care.

A qualitative study of nurse observations of symptoms in infants at end-of-life in the neonatal intensive care unit.

OBJECTIVES: Assessment and management of symptoms exhibited by infants can be challenging, especially at the end-of-life, because of immature physiology, non-verbal status, and limited symptoms assessment tools for staff nurses to utilize. This study explored how nurses observed and managed infant symptoms at the end-of-life in a neonatal intensive care unit. METHODOLOGY/DESIGNMETHODS: This was a qualitative, exploratory study utilizing semi-structured face-to-face interviews, which were tape-recorded, transcribed verbatim, and then analyzed using the Framework Approach. SETTING: The sample included 14 staff nurses who cared for 20 infants who died at a large children's hospital in the Midwestern United States. MAIN OUTCOME MEASURES: Nurses had difficulty recalling and identifying infant symptoms. Barriers to symptom identification were discovered based on the nursing tasks associated with the level of care provided. RESULTS: Three core concepts emerged from analyses of the transcripts: Uncertainty, Discomfort, and Chaos. Nurses struggled with difficulties related to infant prognosis, time of transition to end-of-life care, symptom recognition and treatment, lack of knowledge related to various cultural and religious customs, and limited formal end-of-life education. CONCLUSION: Continued research is needed to improve symptom assessment of infants and increase nurse comfort with the provision of end-of-life care in the neonatal intensive care unit.

Medical record documentation and symptom management at the end of life in the NICU.

PURPOSE: In neonates, the course of illness is often unpredictable and symptom assessment is difficult. This is even truer at the end of life (EOL). Time to death can take minutes to days, and ongoing management of the infant is needed during the time between discontinuation of life-sustaining treatment and death to ensure that the infant remains free of pain and suffering. The symptoms experienced by neonates as they die, as well as best ways to treat those symptoms, are understudied. The purpose of this study was to examine symptoms exhibited by neonates at the EOL and the treatments used to manage those symptoms as documented in the medical record during the last 24 hours of life. SUBJECTS: The sample included 20 neonates who died at a large children's hospital. DESIGN: This was an exploratory, descriptive study. METHODS: Descriptive data, such as diagnosis, ongoing therapy at time of treatment withdrawal or withholding, pharmacologic and nonpharmacologic interventions associated with treatment withdrawal, time of treatment withdrawal and death, age at time of death, signs and symptoms exhibited during EOL care, and pain scores, were abstracted from the infant's medical record. MAIN OUTCOME MEASURES: Inadequate documentation in the medical record resulted in missing data that made it not possible to fully explore aspects of symptom management during the last 24 hours of life; however, some important results were found. RESULTS: This study showed a difference in the way neonates approach the EOL period. Other findings were that most infants in the study received pain medication, even though pain scores were infrequently documented and drug dosages varied across infants. Finally, documentation of nonpharmacologic interventions utilized at the EOL was also lacking.

A new framework to evaluate the quality of a neonatal death.

Management of the infant in the neonatal intensive care unit (NICU) focuses on stabilization and survival but sometimes death is an inevitable outcome. Dying neonates deserve a good death. It is unknown whether we are providing neonates with a good death. This article introduces a framework describing components needed for a good death in the NICU. Initially based on an adult model, this new framework incorporates appropriate components of Emanuel and Emanuel's framework ( 1998 ) and puts them into a context applicable to neonates. The proposed concepts and relationships will require future testing and revision as indicated by the evidence.

Schore's regulation theory: maternal-infant interaction in the NICU as a mechanism for reducing the effects of allostatic load on neurodevelopment in premature infants.

Premature infants confront numerous physiologic and environmental stressors in the neonatal intensive care unit (NICU) that have the potential to permanently alter their neurodevelopment. Schore's regulation theory postulates that positive maternal-infant interactions can shape the infant's developmental outcomes through inducing mechanistic changes in brain structure and function. The purposes of this article are to explain the regulation of infant neurobiological processes during interactions between mothers and healthy infants in the context of Schore's theory, to identify threats to these processes for premature infants, and to propose principles of clinical practice and areas of research necessary to establish a supportive environment and prevent or reduce maladaptive consequences for these vulnerable infants. A premature birth results in the disruption of neurodevelopment at a critical time. Chronic exposure to stressors related to the NICU environment overwhelms immature physiologic and stress systems, resulting in significant allostatic load, as measured by long-term neurodevelopmental impairments in the premature infant. Positive maternal-infant interactions during NICU hospitalization and beyond have the potential to reduce neurologic deficits and maximize positive neurodevelopmental outcomes in premature infants. The quality of the maternal-infant interaction is affected not only by the infant's developing neurobiology but also by the mother's responses to the stressors surrounding a premature birth and mothering an infant in the NICU environment. Nurses can empower mothers to overcome these stressors, promote sensitive interactions with their infants, and facilitate neurodevelopment. Research is critically needed to develop and test nursing interventions directed at assisting mothers in supporting optimal neurodevelopment for their infants.

Extremely low birthweight infants: issues related to growth.

While survival rates are increasing in the extremely low birthweight (ELBW) group of preterm infants, the most common morbidity among these infants is inadequate growth. By the time of discharge from the neonatal intensive care unit, many ELBW infants develop extrauterine growth restriction. Several issues related to improving the growth of ELBW infants, including defining adequate growth and developing evidence-based nutritional strategies, are discussed in this article. Suggestions for future research are also presented.

Intrauterine growth retardation in full-term newborn infants with birth weights greater than 2,500 g.

Intrauterine growth retardation (IUGR) is an overlooked problem in full-term infants with birth weights greater than 2,500 g. Birth weight less than the 10th percentile underestimates the presence of IUGR. The purpose of this study was to determine the prevalence of IUGR in full-term infants and to identify sociodemographic and maternal characteristics associated with IUGR. The Ohio Department of Health Vital Statistics database was used to obtain data related to sociodemographic and maternal characteristics. The fetal growth ratio (FGR) was used to determine the presence of IUGR. The sample consisted of 1,569 infants with normal ratios and 1,364 infants classified as IUGR. Infants with IUGR were more often male and African American or Asian American. Maternal characteristics associated with IUGR included history of smoking during pregnancy, lower pre-pregnancy weight, lower weight gain during pregnancy, and inadequate prenatal care. IUGR is present in a significant number of full-term infants with birth weights greater than 2,500 g. The long-term effects of IUGR in these infants remain to be determined.

Selection of growth parameters to define failure to thrive.

Failure to thrive (FTT) is a syndrome of growth failure due to undernutrition. Determining whether an infant has FTT is based on the use of an anthropometric indicator and a selected cutoff value for that indicator. These anthropometric indicators include weight for age, weight for length, and length for age, and the cutoff values include the 10th, 5th, and 3rd percentiles. Each indicator and selected cutoff value provide unique information about an infant's growth. However, these parameters are often used interchangeably to explain the same growth phenomenon. The sensitivity and specificity of each anthropometric indicator are a function of the cutoff value selected and dictate which infants will be classified as having FTT and which infants will be classified as healthy. Depending on the sensitivity and specificity of the indicator, some infants with FTT will be classified as healthy, and some healthy infants will be classified as having FTT. A clear rationale for the selection of an anthropometric indicator and a cutoff value for defining FTT are important for increasing the generalizability of research findings and thereby expanding the current knowledge base related to FTT.

Caring for medically fragile children in the home: an alternative theoretical approach.

Medically fragile children require extensive, ongoing care that is typically provided in the home environment. The phenomenon of "caregiver burden" has been the topic of many studies in which the hardships and everyday life stressors of families with medically fragile children are examined. These studies are limited in that they focus merely on the difficulties of care, which represent only one dimension of the larger phenomenon of caregiving. It is the purpose of this article to review the literature from an alternative perspective in an attempt to provide a more thorough understanding of the dynamic of caregiving for a medically fragile child.

Infant feeding responsiveness: a conceptual analysis.

BACKGROUND: The phenomenon of infant responsiveness to the caregiver during feeding interactions has been of interest to researchers for many years, because of its associated implications for child growth and development. Although many studies have examined feeding responsiveness in caregiver-infant dyads, it is infrequently and inconsistently defined in the literature. SPECIFIC AIMS: The purpose of this paper is to clarify the concept of infant feeding responsiveness through the provision of a working definition of the concept for further study and usage. METHODS: Medline, CINAHL, and PschInfo databases from the year 1970 to the present were searched for English articles containing the keywords 'infant', 'feeding', 'responsiveness', 'synchrony', and/or 'interaction'. Articles were selected for inclusion according to whether or not the phenomenon of infant feeding responsiveness was defined or assessed. Walker and Avant's (1995) method for concept analysis was employed for the development of defining attributes, case examples, antecedents, and consequences for further clarification of the concept of infant feeding responsiveness. FINDINGS: Infant feeding responsiveness was defined as the manifestation of physiologically influenced visual, expressive, vocal and motor reactive behaviours expressed by an infant in reaction to a caregiver's feeding attempts, indicating a readiness to feed. CONCLUSIONS: Implications for nursing are explored as well as the need for refinement of measures of this concept.

Growth patterns of extremely low-birth-weight hospitalized preterm infants.

OBJECTIVE: To characterize the growth of extremely low-birth-weight (ELBW) infants during hospitalization in terms of weight gain, growth velocity, and relative change in weight. DESIGN: Retrospective, descriptive design. SETTING: Two neonatal intensive-care units located in the midwestern United States. PATIENTS: Thirty-five ELBW infants with a birth weight less than 1,000 g and appropriate for gestational age. MAIN OUTCOME MEASURES: Clinical data related to the infant's growth and nutrition were obtained from a chart review. Birth weight and discharge weight were compared following conversion of the weights to z scores. The discharge weight was compared to the median weight of a fetus of comparable gestational age based on an intrauterine growth reference. Growth velocity was determined (grams/day). RESULTS: Weight-for-age z scores decreased significantly between birth and discharge. By discharge, 89% of the infants had discharge weights less than the 10th percentile. The mean discharge weight was significantly less than the median weight of a fetus of comparable gestational age. Days to regain birth weight significantly affected growth outcomes. CONCLUSION: ELBW infants develop a growth deficit during the first few weeks of life that not only persists but also worsens during hospitalization. Potential causes of this growth deficit include the medical and nutritional management that are part of the usual care of ELBW infants. Because these infants are discharged with this growth deficit, catch-up growth will have to occur at home.