Francesco Morandi

Serotonin Transporter Gene (SLC6A4) Methylation Associates With Neonatal Intensive Care Unit Stay and 3-Month-Old Temperament in Preterm Infants

Preterm birth and Neonatal Intensive Care Unit (NICU) stay are early adverse stressful experiences, which may result in an altered temperamental profile. The serotonin transporter gene (SLC6A4), which has been linked to infant temperament, is susceptible to epigenetic regulation associated with early stressful experience. This study examined a moderation model in which the exposure to NICU-related stress and SLC6A4 methylation moderated infant temperament at 3 months of age. SLC6A4 methylation at 20 CpG sites was quantified in preterm infants (N = 48) and full-term infants (N = 30) from Italian middle-class families. Results suggested that in preterm infants NICU-related stress might be associated with alterations of serotonergic tone as a consequence of SLC6A4 methylation, which in turn, might associate with temperamental difficulties assessed at 3 months of age.

Pain-related stress in the Neonatal Intensive Care Unit and salivary cortisol reactivity to socio-emotional stress in 3-month-old very preterm infants

Very preterm (VPT) infants are hospitalized in the Neonatal Intensive Care Unit (NICU) and exposed to varying levels of skin-breaking procedures (pain-related stress), even in absence of severe clinical conditions. Repeated and prolonged pain exposure may alter hypothalamic-pituitary-adrenal (HPA) axis reactivity in VPT infants. During the post-discharge period, altered HPA axis reactivity has been documented in response to non-social stressors, using salivary cortisol as a biomarker. However, little is known about the effects of NICU pain-related stress on subsequent HPA axis reactivity to socio-emotional stress in infants. We examined the relationship between pain-related stress in NICU and HPA axis reactivity (i.e., salivary cortisol reactivity) to an age-appropriate socio-emotional condition in 37 healthy VPT infants compared to 53 full-term (FT) controls. The number of skin-breaking procedures was obtained across NICU stay for VPT infants. At 3 months (corrected age for prematurity), all infants participated in the maternal Face-to-Face Still-Face (FFSF) procedure, in order to assess HPA axis reactivity to socio-emotional stress (i.e., maternal unresponsiveness). VPT infants exhibited a blunted salivary cortisol reactivity, which was associated with the amount of skin-breaking procedures during NICU: greater pain-related stress predicted lower salivary cortisol reactivity, adjusting for neonatal confounders. These findings further advance our knowledge of how early exposure to pain-related stress in NICU contributes to the programming of an altered HPA axis reactivity to socio-emotional stress in 3-month-old VPT infants, even in the absence of major perinatal complications.

SLC6A4 promoter region methylation and socio-emotional stress response in very preterm and full-term infants

AIM The present study is part of a prospective micro-longitudinal research project and reports on the association between SLC6A4 methylation and socio-emotional stress response in very preterm (VPT) and full-term (FT) infants. MATERIALS & METHODS SLC6A4 methylation was assessed at birth and discharge in 32 VPT infants, and at birth in 27 FT infants. Socio-emotional stress response (i.e., negative emotionality) was assessed at 3 months (corrected age). RESULTS Negative emotionality was higher in VPTs compared with FT counterpart. In VPT infants only, stress response was associated with SLC6A4 methylation status at discharge, which was predictive of greater negative emotionality. CONCLUSION The present study extends previous reports, suggesting that altered SLC6A4 methylation associates with greater socio-emotional stress sensitivity in 3-month-old VPT infants.

The Role of Negative Maternal Affective States and Infant Temperament in Early Interactions Between Infants With Cleft Lip and Their Mothers

OBJECTIVES The study examined the early interaction between mothers and their infants with cleft lip, assessing the role of maternal affective state and expressiveness and differences in infant temperament. METHODS Mother-infant interactions were assessed in 25 2-month-old infants with cleft lip and 25 age-matched healthy infants. Self-report and behavioral observations were used to assess maternal depressive symptoms and expressions. Mothers rated infant temperament. RESULTS Infants with cleft lip were less engaged and their mothers showed more difficulty in interaction than control group dyads. Mothers of infants with cleft lip displayed more negative affectivity, but did not report more self-rated depressive symptoms than control group mothers. No group differences were found in infant temperament. CONCLUSIONS In order to support the mothers experience and facilitate her ongoing parental role, findings highlight the importance of identifying maternal negative affectivity during early interactions, even when they seem have little awareness of their depressive symptoms.

Four-month-old infants' long-term memory for a stressful social event.

Infants clearly show an early capacity for memory for inanimate emotionally neutral events. However, their memory for social stress events has received far less attention. The aim of the study was to investigate infants’ memory for a stressful social event (i.e., maternal unresponsiveness during the Still-Face paradigm) after a 15-day recall interval using changes in behavioral responses and salivary post-stress cortisol reactivity as measures of memory. Thirty-seven infants were exposed to social stress two times (experimental condition); the first time when they were 4 months of age and second exposure after a 2 week interval. Infants in the control condition (N = 37) were exposed to social stress just one time, at the age corresponding to the second exposure for infants in the experimental condition (4 months plus 2 weeks). Given individual differences in infants’ reactivity to social stress events, we categorized infants as increasers or decreasers based on their cortisol reactivity after their initial exposure to the stress of the maternal still-face. Infants in the experimental condition, both increasers and decreasers, showed a significant change in cortisol response after the second exposure to the maternal still-face, though change was different for each reactivity group. In contrast, age-matched infants with no prior exposure to the maternal still-face showed similar post-stress cortisol reactivity to the reactivity of the experimental infants at their first exposure. There were no behavioral differences between increasers and decreasers during the Still-Face paradigm and exposures to the social stress. Thus differences between the experimental and control groups’ post-stress cortisol reactivity was associated with the experimental group having previous experience with the social stress. These findings indicate long-term memory for social stress in infants as young as 4 months of age.

A new device for the care of Congenital Central Hypoventilation Syndrome patients during sleep

Congenital Central Hypoventilation Syndrome (CCHS) is a genetic disease that causes an autonomous nervous system dysregulation. Patients are unable to have a correct ventilation, especially during sleep, facing risk of death. Therefore, most of them are mechanically ventilated during night and their blood oxygenation is monitored, while a supervisor keeps watch over them. If low oxygen levels are detected by the pulse-oximeter, an alarm fires; the supervisor deals with the situation and, if there is neither a technical problem nor a false alarm, wakes the subject, as CCHS patients usually recover from hypoxia when roused from sleep. During a single night multiple alarms may occur, causing fractioned sleep for the subject and a lasting state of anxiety for supervisors. In this work we introduce a novel device that can: acquire realtime data from a pulse-oximeter; provide a multisensory stimulation (e.g. by means of an air fan, a vibrating pillow, and a buzzer), if saturation falls under a threshold; stop the stimulation if oxygenation recovers; wake up the patient or the supervisor if the suffering state lasts beyond a safe interval. The main aim of this work is to lessen the number of awakenings, improving the quality of sleep and life for patients and their supervisors, and to increase young and adult CCHS patients autonomy. Initial testing of the device on a CCHS patient and his supervisor has provided encouraging preliminary results.

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.

Maternal Sensitivity Buffers the Association between SLC6A4 Methylation and Socio-Emotional Stress Response in 3-Month-Old Full Term, but not very Preterm Infants

Background Very preterm (VPT) infants are hospitalized in Neonatal Intensive Care Units (NICUs) and are exposed to life-saving procedures eliciting pain-related stress. Recent research documented that pain-related stress might result in birth-to-discharge increased methylation of serotonin transporter gene (SLC6A4) in VPT infants, leading to poorer stress regulation at 3 months of age in VPT infants compared to their full-term (FT) counterparts. Maternal sensitivity is thought to support infants’ stress response, but its role in moderating the effects of altered SLC6A4 methylation is unknown. Main aim To assess the role of maternal sensitivity in moderating the association between altered SLC6A4 methylation and stress response in 3-month-old VPT and FT infants. Methods 53 infants (27 VPTs, 26 FTs) and their mothers were enrolled. SLC6A4 methylation was obtained from peripheral blood samples at NICU discharge for VPT infants and from cord blood at birth for FT infants. At 3 months (age corrected for prematurity), both groups participated to the face-to-face still-face (FFSF) paradigm to measure both infants’ stress response (i.e., negative emotionality) and maternal sensitivity. Results Maternal sensitivity did not significantly differ between VPT and FT infants’ mothers. In VPT infants, higher SLC6A4 methylation at hospital discharge associates with higher negative emotionality during the FFSF. In FT infants, SLC6A4 methylation and maternal sensitivity significantly interacted to predict stress response: a positive significant association between SLC6A4 methylation and negative emotionality emerged only in FT infants of less-sensitive mothers. Discussion Although no differences emerged in caregiving behavior in the two groups of mothers, maternal sensitivity was effective in moderating the effects of SLC6A4 methylation in FT infants, but not in VPT infants at 3 months. Speculatively, the buffering effect of maternal sensitivity observed in FT infants was disrupted by the altered early mother–infant contact due to NICU stay of the VPT group. These findings indirectly support that the effects of maternal sensitivity on infants’ socio-emotional development might be time dependent, and that mother–infant interventions in the NICU need to be provided precociously within a narrow sensitive period after VPT birth.

Modalità interattive nella relazione precoce tra madre e bambino affetto da labio-palato-schisi. Studio osservativo su un campione italiano

I bambini affetti da labio-palato-schisi (LPS) possono presentare difficolta nell’interazione socio-emozionale con la madre. L’obiettivo dello studio e analizzare la qualita degli scambi affettivi in una fase precoce dello sviluppo. Hanno preso parte alla ricerca due gruppi (clinico e di controllo) composti entrambi da 16 diadi madre-bambino. Un’interazione di cinque minuti viso-a-viso e stata vi- deo-registrata quando il bambino aveva 2 mesi di vita. I comportamenti e lo stile interattivo della madre e del bambino sono stati codificati mediante il sistema GRS - Global Rating Scales [29]. E stato inoltre somministrato il questionario BDI - Beck Depression Inventory - compilato dalle madri per valutare la sintomatologia depressiva. I risultati evidenziano che rispetto ai bambini del gruppo di controllo i bambini con LPS manifestano una ridotta partecipazione allo scambio relazionale con la madre. Le madri del gruppo clinico appaiono meno sensibili rispetto alle madri del gruppo di controllo. Tra i due gruppi di madri non emergono differenze ai punteggi ottenuti al questionario sulla sintomatologia depressiva. Tuttavia, nel corso dell’interazione con il loro bambino le madri del gruppo clinico manifestavano segni di natura depressiva. Globalmente le interazioni madrebambino affetto da LPS risultano meno fluide e con un minor numero di scambi comunicativi positivi. In conclusione, la presenza di LPS nel bambino interferisce in modo rilevante sulla qualita dell’interazione precoce madre-bambino. Questi risultati suggeriscono l’importanza di pianificare interventi precoci indirizzati a facilitare la relazione tra la madre e il bambino affetto da LPS.