Background: Early life stress exposure in preterm infants may alter DNA methylation of NR3C1 and HSD11B2, disrupting neurobehaviors needed for oral feeding (PO) skill development. Purpose: To (1) examine the feasibility of the study protocol; (2) describe early life stress, DNA methylation of NR3C1 and HSD11B2, and PO skill development; and (3) explore the association between DNA methylation of NR3C1 and HSD11B2 and infant characteristics, early life stress, and PO skill development. Method: We employed a longitudinal descriptive pilot study (N = 10). Infant characteristics were collected from the infant’s electronic medical record. Early life stress was assessed via the modified Neonatal Infant Stressor Scale. DNA methylation of NR3C1 exon 1F and HSD11B2 promoter regions was analyzed from the infant’s buccal samples. PO skill development was evaluated using the Early Feeding Skills Assessment. Results: Infants who experienced more acute and chronic stress during their neonatal intensive care unit hospitalization demonstrated higher DNA methylation at CpG 17 and 31 of the NR3C1 exon 1F and at CpG 4 and 28 of the HSD11B2 promoter regions. Infants with higher DNA methylation at these CpG sites also exhibited less optimal PO skill development and experienced longer transition from first to full PO. Implications for Practice and Research: Our findings revealed relationships among early life stress, DNA methylation of NR3C1 and HSD11B2, and PO skill development in preterm infants. Future research is warranted to examine the multiomics pathways whereby early life stress influences the phenotypes of infant outcomes.

Background Stress exposure, operationalized as a count of painful or skin-breaking breaking procedures, is an important concept for inclusion in studies of preterm infants. The Neonatal Infant Stressor Scale (NISS) was developed to also account for nonpainful and environmental stressors; however, validity of this measure is unknown. Aims The purpose of this review was to define the breadth of use of the NISS in neonatal research studies and determine its predictive and concurrent validity. Methods Using the methods for integrative review, a systematic search of the literature was conducted using PubMed, CINAHL, PsycINFO, and Embase with keywords “NISS” OR “Neonatal Infant Stressor Scale”. Study findings were narratively synthesized. Results Twenty-nine articles were retained for the review and included two cross-sectional studies describing development or adaptation of the measure, two protocols for empirical studies, and 25 empirical studies of preterm infants. Modifications to the original NISS were common and included addition or exclusion of specific stressors and use of unweighted scores. Although findings were inconsistent across studies, limited data support the predictive validity of the NISS, as higher NISS scores have been associated with abnormal brain development and cognitive, motor, and behavioral deficits. Two studies found concurrent associations between NISS scores and cortisol. Conclusion The NISS may be a useful tool to quantify stressors experienced by preterm infants; however, there are only limited data to support its predictive or concurrent validity. The NISS may be particularly useful as a method to bring awareness to the infant's stress burden in clinical practice. Additional research is needed to validate inclusion of specific stressors in the NISS.

Background: Preterm infants face challenges to feed orally, which may lead to failure to thrive. Oral feeding skill development requires intact neurobehaviors. Early life stress results in DNA methylation of NR3C1 and HSD11B2, which may disrupt neurobehaviors. Yet, the extent to which early life stress impairs oral feeding skill development and the biomechanism whereby this occurs remains unknown. Our team is conducting an NIH funded study (K23NR019847, 2022-2024) to address this knowledge gap. Purpose: To describe an ongoing study protocol to determine the extent to which early life stress, reflected by DNA methylation of NR3C1 and HSD11B2 promoter regions, compromises oral feeding skill development. Methods: This protocol employs a longitudinal prospective cohort study. Preterm infants born between 26 and 34 weeks gestational age have been enrolled. We evaluate early life stress, DNA methylation, cortisol reactivity, neurobehaviors, and oral feeding skill development during neonatal intensive care unit hospitalization and at 2-week post-discharge. Results: To date, we have enrolled 70 infants. We have completed the data collection. Currently, we are in the data analysis phase of the study, and expect to disseminate the findings in 2025. Implications for Practice and Research: The findings from this study will serve as a foundation for future clinical and scientific inquiries that support oral feeding and nutrition, reduce post-discharge feeding difficulties and lifelong risk of maladaptive feeding behaviors and poor health outcomes. Findings from this study will also provide further support for the implementation of interventions to minimize stress in the vulnerable preterm infant population.

Public health challenges rapidly escalated during the COVID-19 pandemic. In response to a severe lack of resources and support in the near western suburbs of Chicago, the COVID Equity Response Collaborative: Loyola (CERCL) was established by an interprofessional team of Loyola University Chicago students, staff, and faculty. CERCL sought to minimize the negative impact of COVID-19 on vulnerable communities, those that are largely Black, Hispanic, or low-income. From April 2020 to the present, the collaborative utilized community-academic partnerships and interdisciplinary collaborations to conduct programming. CERCL's programming included free community-based testing, screening for and assistance with social determinants of health, dissemination of relevant and reliable COVID-related information, provision of personal protective equipment, and facilitation of access to vaccines. With partners, the collaborative conducted 1,500 COVID-19 tests, trained 80 individuals in contact tracing, provided over 100 individuals with specifically tailored resources to address social and legal needs, distributed 5,000 resource bags, held 20 community conversations, canvassed 3,735 homes, and hosted 19 vaccine clinics. Community-academic partnerships with the health system, community and governmental agencies, and the local public health department have been critical to CERCL efforts. The interdisciplinary and interprofessional successes demonstrated in this case study lends the example of a relevant, sustainable, and practical intervention to address nuanced public health issues.

BACKGROUND:Preterm infants are uniquely vulnerable to early toxic stress exposure while in the neonatal intensive care unit (NICU) and also being at risk for suboptimal neurodevelopmental outcomes. However, the complex biological mechanisms responsible for variations in preterm infants' neurodevelopmental outcomes because of early toxic stress exposure in the NICU remain unknown. Innovative preterm behavioral epigenetics research offers a possible mechanism and describes how early toxic stress exposure may lead to epigenetic alterations, potentially affecting short- and long-term outcomes. OBJECTIVE:The aim of this study was to review the relationships between early toxic stress exposures in the NICU and epigenetic alterations in preterm infants. The measurement of early toxic stress exposure in the NICU and effect of epigenetic alterations on neurodevelopmental outcomes in preterm infants were also examined. METHODS:We conducted a scoping review of the literature published between January 2011 and December 2021 using databases PubMed, CINAHL, Cochrance Library, PsycINFO, and Web of Science. Primary data-based research that examined epigenetics, stress, and preterm infants or NICU were included. RESULTS:A total of 13 articles from nine studies were included. DNA methylations of six specific genes were studied in relation to early toxic stress exposure in the NICU: SLC6A4, SLC6A3, OPRMI, NR3C1, HSD11B2, and PLAGL1. These genes are responsible for regulating serotonin, dopamine, and cortisol. Poorer neurodevelopmental outcomes were associated with alterations in DNA methylation of SLC6A4, NR3C1, and HSD11B2. Measurements of early toxic stress exposure in the NICU were inconsistent among the studies. DISCUSSION:Epigenetic alterations secondary to early toxic stress exposures in the NICU may be associated with future neurodevelopmental outcomes in preterm infants. Common data elements of toxic stress exposure in preterm infants are needed. Identification of the epigenome and mechanisms by which early toxic stress exposure leads to epigenetic alterations in this vulnerable population will provide evidence to design and test individualized intervention.

Purpose:Seventy percent of preterm infants experience challenges with oral feeding and commonly require tube feedings. Yet it is not well understood how these behaviors change over time while infants are receiving tube feedings only and through the transition to oral feedings. The purpose of this pilot study was to describe the change in behaviors surrounding feeding and with respect to advancing Post Menstrual Age (PMA) for preterm infants who received extended tube feedings during hospitalization in the Neonatal Intensive Care Unit (NICU).Methods and measures:A prospective pilot study was conducted in a NICU. We recruited thirty-five infants who were born between 28 to 32 weeks gestational age and expected to have at least two weeks of tube feedings. Infant health status and feeding progression were obtained from the medical record. Behaviors surrounding feeding included infant state, social interactive behaviors, orally directed behaviors, and hunger/satiation cues were evaluated via weekly recorded videos.Results:During the pre-feeding segment, we noted an increase over time for awake, facial gaze, gaze aversion, tongue protrusion, fussing, mouthing, vocalization, and interest in the pacifier. During the intra-feeding segment, we found an increase over time for fussing, and a decrease for eye widening, eye searching, and vocalization.Conclusion:To our knowledge, this was the first pilot study to comprehensively describe the changes in behaviors surrounding feeding over time and with respect to advancing PMA for preterm infants who received extended tube feedings during the NICU hospitalization. Infants demonstrated distinct behaviors surrounding feeding as young as 28 weeks post menstrual age. These behaviors may vary among infants and change significantly with advancing post-menstrual age. Assessment of subtle behaviors surrounding feeding is important to ensure oral feeding readiness.

Background: A successful transition from the NICU to home is fundamental for the long-term health and wellbeing of preterm infants. Post-NICU discharge, parents may experience a lack of support and resources during the transition to home. The purpose of this scoping review was to identify post-NICU discharge interventions that may reduce parental stress and provide support to families with preterm infants. Method: Systematic searches of databases, i.e., PubMed, Web of Science, and CINAHL. Inclusion criteria were databased articles: 1) published in English between 2011 and 2021, 2) published in peer-reviewed journals, (3) focused on families with preterm infants, and (4) focused on interventions to reduce parental stress and provide support to families with preterm infants post-NICU discharge. Results: 26 articles were included and synthesized. We identified the following face-to-face and remote communication interventions: in-person home visits, phone/video calls, text messages, periodic email questionnaires, mobile/website apps, and online social networking sites. Discussion: Families may highly benefit from a comprehensive family-focused post-NICU discharge follow-up intervention that includes face-to-face and remote communication and support. Post-NICU discharge interventions are imperative to provide education related to infant care and health, increase parental confidence and competency, increase parent-infant relationship, promote emotional and social support, reduce unplanned hospital visits, parental stress, and maternal post-partum depression. (c) 2022 Elsevier Inc. All rights reserved.

Background The aim of this study was to investigate the influence of early-life pain/stress and medical characteristics on neurobehavioral outcomes in preterm infants. Methods A prospective cohort study was conducted with 92 preterm infants (28–32 weeks gestational age [GA]). Early-life pain/stress was measured via the Neonatal Infant Stressor Scale (NISS) during the first 28 days of NICU hospitalization. Neurobehavioral outcomes were evaluated using the NICU Network Neurobehavioral Scale at 36–38 weeks post-menstrual age. Functional regression and machine learning models were performed to investigate the predictors of neurobehavioral outcomes. Results Infants experienced daily acute pain/stress (24.99 ± 7.13 frequencies) and chronic events (41.13 ± 17.81 h). Up to 12 days after birth, both higher acute and chronic NISS scores were associated with higher stress scores; and higher chronic NISS scores were also related to lower self-regulation and quality of movement. Younger GA predicted worse neurobehavioral outcomes; GA < 31.57 weeks predicted worse stress/abstinence, self-regulation, and excitability; GA < 30.57 weeks predicted poor quality of movement. A higher proportion of maternal breastmilk intake predicted better self-regulation, excitability, and quality of movement in older GA infants. Conclusions Preterm infants are vulnerable to the impact of early-life pain/stress. Neurobehavioral outcomes are positively associated with increased GA and higher maternal breastmilk intake. Impact During the first 12 days of life, preterm infant neurobehavioral outcomes were vulnerable to the negative impact of acute and chronic pain/stress. Future research is warranted to investigate the long-term effects of early-life pain/stress on neurobehavioral outcomes. Gestational age remains one of the critical factors to predict neurobehavioral outcomes in preterm infants; older gestational age significantly predicted better neurobehavioral outcomes. Feeding with a higher proportion of maternal breastmilk predicted better neurobehavioral outcomes. Future research is warranted to investigate how maternal breastmilk may buffer the negative effects of early-life pain/stress on neurobehavioral outcomes.

BACKGROUND Preterm infants experience a multitude of prenatal and postnatal stressors, resulting in cumulative stress exposure, which may jeopardize the timely attainment of developmental milestones, such as achieving oral feeding. Up to 70% of preterm infants admitted to the neonatal intensive care unit experience challenges while initiating oral feeding. Oral feeding skills require intact neurobehavioral development. Evolving evidence demonstrates that cumulative stress exposure results in epigenetic modification of glucocorticoid-related genes. Epigenetics is a field of study that focuses on phenotypic changes that do not involve alterations in the DNA sequence. Epigenetic modification of glucocorticoid-related genes alters cortisol reactivity to environmental stimuli, which may influence neurobehavioral development, and is the essence of the evolving field of Preterm Behavioral Epigenetics. It is plausible that early-life cumulative stress exposure and the ensuing epigenetic modification of glucocorticoid-related genes impair neurobehavioral development required for achievement of oral feeding skills in preterm infants. PURPOSE The purpose of this article is to build upon the evolving science of Preterm Behavioral Epigenetics and present a conceptual model that explicates how cumulative stress exposure affects neurobehavioral development and achievement of oral feeding skills through epigenetic modification of glucocorticoid-related genes. METHODS/RESULTS Using the Preterm Behavioral Epigenetics framework and supporting literature, we present a conceptual model in which early-life cumulative stress exposure, reflected by DNA methylation of glucocorticoid-related genes and altered cortisol reactivity, disrupts neurobehavioral development critical for achievement of oral feeding skills. IMPLICATIONS FOR PRACTICE AND RESEARCH Future investigations guided by the proposed conceptual model will benefit preterm infant outcomes by introducing epigenetic-based approaches to assess and monitor preterm infant oral feeding skills. Furthermore, the proposed model can guide future investigations that develop and test epigenetic protective interventions to improve clinical outcomes, representing an innovation in neonatal care.

BACKGROUND:The term "oral feeding success" (OFS) is frequently used in clinical practice and research. However, OFS is inconsistently defined, which impacts the ability to adequately evaluate OFS, identify risk factors, and implement interventions in clinical practice and research.PURPOSE:To develop the defining attributes, antecedents, and consequences for the concept of OFS in preterm infants during their initial hospitalization.METHODS:PubMed, CINAHL, and PsycINFO databases were searched for English articles containing the key words "oral feeding success" and "preterm infants." The Walker and Avant method for concept analysis was employed.RESULTS:Sixteen articles revealed the defining attributes, antecedents, and consequences. Defining attributes included (1) physiologic stability; (2) full oral feeding; and (3) combined criteria of feeding proficiency (≥30% of the prescribed volume during the first 5 minutes), feeding efficiency (≥1.5 mL/min over the entire feeding), and intake quantity (≥80% of the prescribed volume).IMPLICATIONS FOR PRACTICE:The 3 defining attributes may be used in clinical practice to consistently evaluate OFS. The antecedents of OFS provide clinicians with a frame of reference to assess oral feeding readiness, identify risk factors, and implement effective interventions. The consequences of OFS allow clinicians to anticipate challenges when OFS is not achieved and create a care plan to support the infants.IMPLICATIONS FOR RESEARCH:The empirical referents of OFS provide consistent and clear operational definitions of OFS for use in research. The antecedents and consequences may guide researchers to select specific measures or covariates to evaluate valid measures of OFS.

Background: The term “oral feeding success” (OFS) is frequently used in clinical practice and research. However, OFS is inconsistently defined, which impacts the ability to adequately evaluate OFS, identify risk factors, and implement interventions in clinical practice and research. Purpose: To develop the defining attributes, antecedents, and consequences for the concept of OFS in preterm infants during their initial hospitalization. Methods: PubMed, CINAHL, and PsycINFO databases were searched for English articles containing the key words “oral feeding success” and “preterm infants.” The Walker and Avant method for concept analysis was employed. Results: Sixteen articles revealed the defining attributes, antecedents, and consequences. Defining attributes included (1) physiologic stability; (2) full oral feeding; and (3) combined criteria of feeding proficiency (≥30% of the prescribed volume during the first 5 minutes), feeding efficiency (≥1.5 mL/min over the entire feeding), and intake quantity (≥80% of the prescribed volume). Implications for Practice: The 3 defining attributes may be used in clinical practice to consistently evaluate OFS. The antecedents of OFS provide clinicians with a frame of reference to assess oral feeding readiness, identify risk factors, and implement effective interventions. The consequences of OFS allow clinicians to anticipate challenges when OFS is not achieved and create a care plan to support the infants. Implications for Research: The empirical referents of OFS provide consistent and clear operational definitions of OFS for use in research. The antecedents and consequences may guide researchers to select specific measures or covariates to evaluate valid measures of OFS.

Objective: Primary: to identify the potential relationship between duration of tube feeding and success of oral feeding in preterm infants; secondary: to identify the potential relationships among duration of tube feeding and alert behavioral states, orally directed behaviors, and nutritive sucking. Design: A descriptive correlational study. Setting: A Level III NICU at an inner-city hospital. Participants: Twenty-eight preterm infants who were born between 28 and 32 weeks gestational age, were clinically stable, and were expected to have at least 1 week of tube feeding during their initial hospitalizations. Methods: Data were collected daily from participants' electronic medical records and at one-time oral feeding evaluations within 48 hours after the removal of the feeding tube. Results: We found a significant negative correlation between duration of tube feeding and oral feeding success (p = .000). We found no correlations between duration of tube feeding and alert behavioral states, orally directed behaviors, or nutritive sucking. Conclusion: Although the duration of tube feeding is a nonmodifiable factor, preterm infants who are anticipated to have extended durations of tube feeding may be at risk for delayed oral feeding success.

Studies show that 40% to 70% of premature infants exhibit both immature and atypical feeding ability. To establish thresholds of performance and develop efficacious treatments for initiating and advancing oral feedings, we must first identify the nutritive sucking performance measures impacted by preterm birth.To compare objective measures of neonatal nutritive sucking between full term and preterm infants at hospital discharge.This was a prospective observational study including full term (FT; N = 32) and preterm (PT; N = 44) infants. Nutritive sucking performance at discharge was assessed. The outcome measures of interest were means and coefficients of variability of nutritive sucking peak amplitude, frequency, duration, and smoothness, and feeding-related length of stay.There was a significant difference in sucking performance between groups; FT infants demonstrated significantly lower mean suck frequency, with longer suck duration and greater suck smoothness as compared to PT. PT infants had significantly less variability in suck amplitude and frequency as compared to FT, while FT infants had significantly less variability in suck smoothness as compared to PT. Post hoc regression analyses found suck frequency alone accounted for 28% of the variance in feeding length of stay for PT; suck smoothness alone accounted for 34% of the variance in feeding length of stay for FT.Suck frequency may be an important intervention target for PT infants having difficulty transitioning to oral feeding. Suck smoothness may be a sensitive marker for identifying infants at high risk for feeding challenges.

Background: The relationship between behavioral states (alert, sleep, drowsy, and crying) and oral feeding efficiency in preterm infants is not well understood. Purpose: To determine the relationship between behavioral states and feeding efficiency in preterm infants. Methods: This correlational study was conducted as a secondary analysis from a randomized controlled trial. Medically stable preterm infants born between 29 and 34 weeks' gestational age participated. Baseline data from the randomized controlled trial (week 0), 1 minute prior to feeding, were used. Behavioral states were coded by 2 blinded coders. Oral feeding efficiency (mL/min) was calculated as the amount of intake over the first 10 minutes of feeding. Results: Data from 147 infants were included. The proportion of time spent in alert states (β = .76, F = 11.29, P ≤ .05), sleep states (β = −1.08, F = 25.26, P ≤ .05), and crying (β = 1.50, F = 12.51, P ≤ .05) uniquely predicted oral feeding efficiency. Implications for Practice: Comprehensive assessment of behavioral states and infant characteristics for oral feeding readiness is crucial. Alert states are optimal for oral feeding. Forced oral feeding when infants are sleeping should be avoided. Infants in crying or drowsy states prior to feeding should be closely evaluated. Sleeping or drowsy infants may benefit from interventions (eg, oral sensory stimulation, nonnutritive sucking, or multisensory intervention) to support transition to alert states prior to feeding. Implications for Research: Future research should evaluate behavioral states prior to and during feeding and their relationship to oral feeding efficiency.