How has research changed our clinical practice in the last years?

Research plays an important role in influencing clinical decisions and building up a safe clinical practice although it must be taken into consideration that the practice of the evidence based medicine derives from the integration of the best available external clinical evidence from systematic research with own individual clinical expertise. The practice of neonatology aims to provide the optimal individualized care for the mother and her baby. In this paper we will address some of the main research findings that have brought recent changes in neonatal clinical practice although frequently raising new questions and therefore making research pathways still incomplete. © 2013 Elsevier Ireland Ltd

Mutational analysis in a group of patients with Noonan syndrome, new mutations identified in SOS1

Introduction: Noonan Syndrome (NS) is an autosomal dominant congenital syndrome characterized by typical facial dysmorphology, heart defects and short stature. NS is genetically heterogeneous, germline mutations in four genes (PTPN11 , KRAS, SOS1 and RAF1) have been found, accounting for approximately 65% of cases. Methods and Results: We investigated 32 patients with NS diagnosed on the basis on Van der Burgt criteria, and we identified PTPN11 mutations in 50% of cases. The 16 patients negative for PTPN11 and KRAS mutations, underwent sequencing of the nine exons of SOS1, where mutations had been previously identified. In 4 cases (25%) one novel mutation (R497Q) and 3 previously described heterozygous mutations (M269T, Q477R and Y207H) were found. The M269T, Q477R mutations were found to be de novo, while the R497Q and Y207H mutations were found to be familial. The novel R497Q mutation was shown in the proband’s father and grandfather and it was not found in 300 control chromosomes from normal individuals. This proband’s showed the NS typical face and cardiac defects while the father and the grandfather showed only some abnormal ectodermal manifestations. The Y207H mutation was present in the proband’s mother, brother and grandfather, all of them carrying NS features. Clinically, all 4 patients with SOS1 mutations exhibited a clear NS phenotype, but, interestingly, these patients had normal stature with values ranging from the 9th to 49th centile, while short stature with or without GH deficiency was present in 70% of cases carrying the PTPN11 mutations. Conclusions: Four heterozygous SOS1 mutations have been found in 25% of NS patients negative for PTPN11 mutations. One SOS1 mutation (R497Q) has not yet been described. In contrast to the high frequency of short stature in patients carrying PTPN11 mutations, the SOS1 mutations do not seem to be associated with short stature

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

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

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

SLC6A4 methylation is associated with social stress response in 3-month-old preterm infants

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A Comparison of Maternal and Paternal Experiences of Becoming Parents of a Very Preterm Infant

OBJECTIVE: To compare maternal and paternal experiences of very preterm (VPT) birth (gestational age< 32weeks) and the NICU stay. DESIGN: Qualitative study. SETTING: Data collection took place at parents' homes 3 to 6months after NICU discharge. PARTICIPANTS: Ten parental couples participated in the study (20 parents). All VPT infants were healthy, without any neonatal or postnatal complications or injuries. METHODS: Computer-assisted content analysis was used to highlight thematic clusters from parents' narratives, which were labeled through qualitative interpretation. RESULTS: Two main dimensions (Adjustment Process to Preterm Birth and Parental Role Assumption) and three main thematic clusters (Facing the Unexpected, Learning to Parent, and Finally Back Home) described the parental experience. Mothers focused mostly on the Finally Back Home cluster, which was characterized by moderate levels of adjustment to preterm birth and by awareness of their own maternal roles. Fathers focused mostly on the Learning to Parent cluster, which was characterized by low to moderate levels of adjustment to preterm birth and by a limited assumption of paternal role. CONCLUSION: To our knowledge, this study is unique in that we compared mothers and fathers who experienced the VPT births of their infants and described their experiences of the NICU stay. We found that the VPT birth experience for parents involves a dynamic adjustment. Differences in maternal and paternal experiences may indicate the need for tailored supportive interventions in the NICU

From early stress to 12-month development in very preterm infants: Preliminary findings on epigenetic mechanisms and brain growth

<div><p>Very preterm (VPT) infants admitted to Neonatal Intensive Care Unit (NICU) are at risk for altered brain growth and less-than-optimal socio-emotional development. Recent research suggests that early NICU-related stress contributes to socio-emotional impairments in VPT infants at 3 months through epigenetic regulation (i.e., DNA methylation) of the serotonin transporter gene (<i>SLC6A4</i>). In the present longitudinal study we assessed: (a) the effects of NICU-related stress and <i>SLC6A4</i> methylation variations from birth to discharge on brain development at term equivalent age (TEA); (b) the association between brain volume at TEA and socio-emotional development (i.e., Personal-Social scale of Griffith Mental Development Scales, GMDS) at 12 months corrected age (CA). Twenty-four infants had complete data at 12-month-age. <i>SLC6A4</i> methylation was measured at a specific CpG previously associated with NICU-related stress and socio-emotional stress. Findings confirmed that higher NICU-related stress associated with greater increase of <i>SLC6A4</i> methylation at NICU discharge. Moreover, higher <i>SLC6A4</i> discharge methylation was associated with reduced anterior temporal lobe (ATL) volume at TEA, which in turn was significantly associated with less-than-optimal GMDS Personal-Social scale score at 12 months CA. The reduced ATL volume at TEA mediated the pathway linking stress-related increase in <i>SLC6A4</i> methylation at NICU discharge and socio-emotional development at 12 months CA. These findings suggest that early adversity-related epigenetic changes might contribute to the long-lasting programming of socio-emotional development in VPT infants through epigenetic regulation and structural modifications of the developing brain.</p></div