Pain-related increase in serotonin transporter gene methylation associates with emotional regulation in 4.5-year-old preterm-born children.

AIM: The main goal of this study was to assess the association between pain-related increase in serotonin transporter gene (SLC6A4) methylation and emotional dysregulation in 4.5-year-old preterm children compared with full-term matched counterparts. METHODS: Preterm (n = 29) and full-term (n = 26) children recruited from two Italian hospitals were followed-up from October 2011 to December 2017. SLC6A4 methylation was assessed from cord blood at birth from both groups and peripheral blood at discharge for preterm ones. At 4.5 years, emotional regulation (ie, anger, fear and sadness) was assessed through an observational standardised procedure. RESULTS: Preterm children (18 females; mean age = 4.5, range = 4.3-4.8) showed greater anger display compared with full-term controls (14 females; mean age = 4.5, range = 4.4-4.9) in response to emotional stress. Controlling for adverse life events occurrence from discharge to 4.5 years and SLC6A4 methylation at birth, CpG-specific SLC6A4 methylation in the neonatal period was predictive of greater anger display in preterm children but not in full-term ones. CONCLUSION: These findings contribute to highlight how epigenetic regulation of serotonin transporter gene in response to NICU pain exposure contributes to long-lasting programming of anger regulation in preterm children.

Functional Evaluation of Eating Difficulties Scale to predict oral motor skills in infants with neurodevelopmental disorders: a longitudinal study.

AIM: To assess the predictive validity of the Functional Evaluation of Eating Difficulties Scale (FEEDS) on long-term eating developmental outcomes in infants with neurodevelopmental disorders. METHOD: In total, 144 infants (69 females, 75 males) aged 0 to 12 months (mean [SD] 5.34mo [3.42]) with neurodevelopmental disorders and requiring enteral nutrition support, hospitalized between January 2004 and December 2017, were included. The FEEDS was administered at the onset of hospitalization. Follow-up evaluations of feeding modalities occurred at discharge and at 6 months, 12 months, and 24 months after discharge. FEEDS score was tested as a predictor of infants' feeding modality (percutaneous endoscopic gastrostomy, nasogastric tube, mixed, oral feeding) and time to autonomous oral feeding. Percentages of false-positive and negative cases were checked. RESULTS: Lower FEEDS scores significantly predicted infants' feeding modality (0.40≤R2 ≤0.61). A 1-point increase in FEEDS score was associated with increased risk (6%-14%; p<0.05) of being non-autonomous feeders at the different follow-up points in infants who had a FEEDS score above the clinical cut-off. INTERPRETATION: The FEEDS appears to be a clinically valid assessment to predict the presence of eating difficulties in infants with neurodevelopmental disabilities. WHAT THIS PAPER ADDS: Functional Evaluation of Eating Difficulties Scale (FEEDS) significantly predicted eating difficulties in infants with neurodevelopmental disabilities. Lower FEEDS score is significantly associated with autonomous feeding at the 24-month follow-up. FEEDS cut-off identified infants at low-risk and high-risk for eating disorder.

EVALUACIÓN FUNCIONAL DE LA ESCALA DE DIFICULTADES EN LA ALIMENTACIÓN (FEEDS) PARA PREDECIR LAS HABILIDADES MOTORAS ORALES EN BEBÉS CON TRASTORNOS DEL DESARROLLO NEUROLÓGICO: UN ESTUDIO LONGITUDINAL: OBJETIVO: Evaluar la validez predictiva de la Escala de Evaluación Funcional de Dificultades de la Alimentación (FEEDS) en los resultados del desarrollo alimentario a largo plazo en lactantes con trastornos del desarrollo neurológico. MÉTODO: En total, se incluyeron 144 bebés (69 femeninos y 75 masculinos) de 0 a 12 meses (media [DE] 5.34 meses [3.42]) con trastornos del desarrollo neurológico y que requieren apoyo nutricional enteral, hospitalizados entre enero del 2.004 y diciembre de 2.017. El FEEDS se administró al inicio de la hospitalización. Las evaluaciones de seguimiento de las modalidades de alimentación ocurrieron al alta y a los 6 meses, 12 meses y 24 meses después del alta. La puntuación FEEDS se probó como un factor predictivo de la modalidad de alimentación de los bebés (gastrostomía endoscópica percutánea, sonda nasogástrica, alimentación mixta, oral) y el tiempo hasta la alimentación oral autónoma. Se verificaron los porcentajes de falsos positivos y negativos. RESULTADOS: Las puntuaciones FEEDS más bajas predijeron significativamente la modalidad de alimentación de los bebés (0.40 ≤R2 ≤0.61). Un aumento de 1 punto en la puntuación FEEDS se asoció con un mayor riesgo (6% -14%; p <0,05) de tener un patrón de alimentación no autónomos en los diferentes puntos de seguimiento en los lactantes que tuvieron una puntuación FEEDS por encima del límite clínico. INTERPRETACIÓN: Las FEEDS parecen ser una evaluación clínicamente válida para predecir la presencia de dificultades para comer en bebés con alteraciones del desarrollo neurológico.

ESCALA DE AVALIAÇÃO FUNCIONAL DE DIFICULDADES DE ALIMENTAÇÃO ( FEEDS) PARA PREDIZER HABILIDADES MOTORAS ORAIS EM LACTENTES COM TRANSTORNOS DO DESENVOLVIMENTO: UM ESTUDO LONGITUDINAL: OBJETIVO: Avaliar o valor preditivo da Escala de Avaliação Funcional de Dificuldades de Alimentacão (FEEDS) nos resultados desenvolvimentais de alimentação de longo prazo em lactentes com transtornos do desenvolvimento. MÉTODO: No total, 144 lactentes (69 do sexo feminino, 75 do sexo masculino) com idades de 0 a 12 meses (média [DP] 5,34m [3,42]) com transtornos neurodesenvolvimentais e que requeriam suporte nutricional enteral, hospitalizados entre Janeiro de 2004 e Dezembro de 2017, foram incluídos. A FEEDS foi administrada no início da hospitalização. Avaliações de acompanhamento das modalidades de alimentação ocorreram no momento da alta e com 6, 12 e 24 meses após a alta. Os escores da FEEDS foram testados como preditores da modalidade de alimentação da criança (gastrostomia percutânea endoscópica, tubo nasogástrico, mista, alimentação oral) e o tempo para a alimentação oral autônoma. Porcentagens de casos falsos positivos e falsos negativos foram checadas. RESULTADOS: Menores escores na FEEDS predizeram significativamente a modalidade de alimentação dos lacentes (0,40≤R2 ≤0,61). Um aumento de 1 ponto no escore da FEEDS foi associado com risco aumentado (6%-14%; p<0,05) de não ter alimentacão autônoma em diferentes pontos do acompanhamento em lactentes que tiveram escore FEEDS acima do ponto de corte clínico. INTERPRETAÇÃO: A FEEDS parece ser uma avaliação clinicamente válida para predizer a presença de dificuldades de alimentação em crianças com deficiências neurodesenvolvimentais.

Predictors and outcomes of the Neonatal Oral Motor Assessment Scale (NOMAS) performance: a systematic review.

The NOMAS is by far the most used tool to screen early oral-motor skills in newborns. Here we provide an updated review of scientific literature on the use of the Neonatal Oral Motor Assessment Scale (NOMAS) to screen early oral-motor skills in newborns. An integrative review has been carried out consistent with PRISMA guidelines and standardized qualitative appraisal. Data abstracting and synthesis were executed by two independent co-authors who solved disagreement in conference. Twenty records have been included and reviewed. The efficacy of the NOMAS in screening and identifying precocious oral-motor skills received inconsistent support. Moderate validity and low reliability emerged. Moreover, despite the NOMAS' adequately screen efficient and inefficient feeders, limited evidence emerged for predictive value of NOMAS score on feeding and psychomotor developmental trajectories during the first 2 years of age. CONCLUSION: The present review highlights benefits and limitations of the NOMAS. Future research is needed to develop observational and clinically-relevant tools to better identify newborns which are at lower- and higher-risk of developing less-than-optimal feeding behaviors and to guide with greater precision the diagnostic and therapeutic journey of these newborns. What is Known: • The assessment of oral-motor skills in newborns and infants is critical for early intervention • The NOMAS is the most adopted tool to assess oral-motor skills in newborns and infants What is New: • The ability of the NOMAS to target newborn at risk for feeding disorders is confirmed • Nonetheless, the capacity to predict long-term developmental outcomes is limited.

More than words: methodological potentials of graphical elicitation with parents of preterm infants.

BACKGROUND: Word-based tools, such as interviews, can only partially provide access to the lived experience of parents of preterm infants. This study explores the lived experience of parents of preterm infants between 3 and 6 months after discharge by means of visual method (i.e., graphical elicitation). METHODS: A qualitative study with graphic elicitation analysis was used to assess the lived experience of four parental couples of very preterm infants in a home-based session occurred between 3 and 6 months after Neonatal Intensive Care Unit (NICU) discharge. RESULTS: The use of graphical elicitation revealed three dimensions of the experience of being parents of preterm infants: 1) different use of time-lining elements suggested a different involvement of cognitive and/or emotional coping mechanisms in facing the unexpected birth and NICU stay; 2) the explicit or implicit use of emotional graphical elements and words was suggestive of different degrees of openness to disclose their experience; 3) the role of textual elements in support or substitution of graphical elements indicated different levels of integration of cognitive and emotional representations. CONCLUSIONS: The use of visual methods holds the potentials for revealing specific aspects of the parental experience of preterm birth and NICU stay. The clinical implications of this approach are further discussed with reference to its potential implementation within parental support intervention.

Maternal caregiving and DNA methylation in human infants and children: Systematic review.

The integration of behavioral epigenetics' principles (eg, DNA methylation) into the study of human infants' development has mainly focused on the effects of early adverse exposures, paying less attention to protective caregiving experiences. The present review focused on DNA methylation linked to variations in maternal behavior in human infants and children. Literature search occurred on three databases (PubMed, Scopus and Web of Science) and 11 records were selected. Key variables were abstracted from each article including: sample size and characteristics, time and type of maternal caregiving behavior exposure, time and locus of methylation biomarker, presence/absence, time and type of adverse exposure. Six out of eleven records documented the predictive effect of maternal caregiving on DNA methylation, whereas the remaining five reported on the role of maternal behavior as an influencing factor of the adversity-to-methylation link. Consistent with evidence from the animal model, the quality of maternal caregiving in humans (a) might be associated with variations in DNA methylation status of specific genes involved in socio-emotional development and (b) might partially buffer the association between early adversities and epigenetic variations in infants and children. Current evidence suggests that the quality of maternal caregiving can contribute to behavioral development trajectories of human infants and children at least partially through epigenetic regulation. Open questions and methodological aspects are discussed to guide future human developmental research in behavioral epigenetics.

Disentangling the Dyadic Dance: Theoretical, Methodological and Outcomes Systematic Review of Mother-Infant Dyadic Processes.

Background: During the last decades, the research on mother-infant dyad has produced a great amount of data, methods and theories, which largely contributed to set a revolution in the way we look at developmental changes during infancy and childhood. Very different constructs depict the different aspects of the "dyadic dance" occurring between a mother and her infant; nonetheless, a comprehensive and consistent systematization of these concepts in a coherent theoretical landscape is still lacking. Aim: In the present work, we aim at disentangling the different theoretical and methodological definitions of 9 dyadic constructs and we highlight their effects on infants' and children developmental outcomes. Methods: A literature search has been conducted on three databases-PubMed, Scopus, Web of Science. Three different reviews are reported here: (1) a review on the theoretical definitions of dyadic constructs; (2) a review of operational definitions, settings and methods of dyadic processes; (3) a systematic review of dyadic processes' outcomes for infants' and children developmental trajectories. Results: Two constructs emerged as wide meta-theoretical concepts (reciprocity and mutuality) and seven described specific processes (attunement, contingency, coordination, matching, mirroring, reparation, synchrony). A global model resuming the relationships among different processes is reported, which highlights the emergence of two specific cycles of dyadic functioning (i.e., matching-mismatching-reparation-synchrony; contingency, coordination, attunement, mirroring). A comprehensive review of the adopted measures is also provided. Finally, all the processes provided significant contributions to infants' behavioral, cognitive, and socio-emotional development during the first 3 years of age, but limited research has been conducted on specific processes (e.g. reparation and mirroring). Conclusion: The present study provides an original research-grounded framework to consider the different nature of mother-infant dyadic processes within a unified dyadic eco-system. Different levels of evidence emerged for the role of diverse mother-infant dyadic processes on infants' and children development. Open questions and future research directions are highlighted.

Pain exposure associates with telomere length erosion in very preterm infants.

Very preterm (VPT) infants (gestational age < 32 weeks) require long-lasting hospitalization in the Neonatal Intensive Care Unit (NICU), even in absence of severe morbidities. During NICU stay, life-saving interventions occur and include invasive and painful skin-breaking procedures (NICU-related stress), which constitute a major early adverse experience for VPT infants. Telomeres are repeat-sequence at the end of chromosomes, which shorten with age and are highly susceptible to life adversities: the exposure to early adverse experiences is associated with shorter telomere length (TL). Nonetheless, previous research did not assess longitudinally the association between NICU-related stress and TL in VPT infants. In the present study, leukocyte TL was assessed from cord blood at birth in 46 VPT infants and in a group of 31 full-term (FT) infants, as well as at NICU discharge in VPTs only. NICU-related stress was measured as the number of skin-breaking procedures occurring throughout the NICU stay. A significant difference emerged for TL between VPT infants and FT counterparts at birth. TL decreased from birth to discharge in VPT infants, although the change was not significant in the group as a whole. The amount of NICU-related stress emerged as the primary predictor of TL erosion in VPT infants, even controlling for neonatal and clinical confounders. Furthermore, VPT infants exposed to high NICU-related stress exhibited a marked and significant decrease in TL, whereas VPT exposed to low NICU-related stress exhibited a non-significant increase. The present study confirms previous evidence of longer telomeres in VPT infants at birth compared to FT controls. Moreover, NICU-related stress emerged as a key regulator of TL erosion from birth to discharge in VPT infants. Future research is warranted to further explore TL erosion in VPT infants and the factors associated with individual differences in NICU-related stress susceptibility at the epigenetic level.

Telomere Length in Preterm Infants: A Promising Biomarker of Early Adversity and Care in the Neonatal Intensive Care Unit?

Preterm infants present an immature neurobehavioral profile at birth, even in absence of severe brain injuries and perinatal complications. As such, they require a long-lasting hospitalization in the Neonatal Intensive Care Unit (NICU), which is thought to grant at-risk newborns' survival, but still entails a number of physical, painful, and socio-emotional stressors. Hence, preterm birth and NICU stay represent an early adverse experience, which has been linked to detrimental consequences for neurological, neuro-endocrinal, behavioral, and socio-emotional development, as well as to disease later in life. Recent advances in the behavioral epigenetic field are helping us to unveil the potential mechanisms through which early NICU-related stress may lead to negative developmental outcomes. From this perspective, telomere regulation might be a key programming mechanism. Telomeres are the terminal portion of chromosomes and are known to get shorter with age. Moreover, telomere length (TL) is affected by the exposure to stress during early development. As such, TL might be an innovative biomarker of early adverse exposures in young infants and children. Unfortunately, there is paucity of studies investigating TL in populations of preterm infants and its association with known NICU-related stressors remains unexplored. In the present paper, the potential relevance of TL for research and clinical work with preterm infants will be underlined in the light of recent contributions linking progressive telomere shortening and early exposure to adverse experiences and stressful environments in humans. Finally, insights will be provided to guide clinically relevant translational research on TL in the field of VPT birth and NICU stay.

Study Protocol for the Preschooler Regulation of Emotional Stress (PRES) Procedure.

Background: Emotional stress regulation (ESR) rapidly develops during the first months of age and includes different behavioral strategies which largely contribute to children's behavioral and emotional adjustment later in life. The assessment of ESR during the first years of life is critical to identify preschool children who are at developmental risk. Although ESR is generally included in larger temperament batteries [e.g., the Laboratory Temperament Assessment Battery (Lab-TAB)], there is no standardized observational procedure to specifically assess and measure ESR in preschool aged children. Aim: Here, we describe the development of an observational procedure to assess ESR in preschool aged children [i.e., the Preschooler Regulation of Emotional Stress (PRES) Procedure] and the related coding system. Methods: Four Lab-TAB emotional stress episodes (i.e., the Stranger, the Perfect Circle, the Missing Sticker, and the Transparent Box) have been selected. Independent coders developed a list of ESR codes resulting in two general indexes (i.e., active engagement and stress level) and five specific indexes (i.e., anger, control, fear, inhibition, sadness). Finally, specific actions have been planned to assess the validity and the coding system reliability of PRES procedure. Ethics and Dissemination: The study has been approved by the Ethical Committee of the Scientific Institute IRCCS Eugenio Medea, Bosisio Parini (Italy). The PRES validation and reliability assessment as well as its use with healthy and at-risk populations of preschool children will be object of future scientific publications and international conference presentations.