Sitting Postural Management to Prevent Migration Percentage Progression in Non-Ambulatory Children with Cerebral Palsy: Randomized Controlled Trial Preliminary Data.

Background/Objectives: To determine whether a sitting position with the femoral heads centered into the acetabulum is more effective than the usual sitting position in preventing migration percentage progression in non-ambulatory children with bilateral cerebral palsy. Methods: This was a multicenter, randomized controlled trial. INCLUSION CRITERIA: spastic or dyskinetic cerebral palsy, Gross Motor Function Classification System level IV-V, age 1-6 years, migration percentage <41%, and informed consent. EXCLUSION CRITERIA: contractures affecting the hip, anterior luxation, previous hip surgery, and lumbar scoliosis. The treatment group sat with their hips significantly abducted to reduce the head into the acetabulum in a customized system for at least five hours/day for two years. Controls sat with the pelvis and lower limbs aligned but the hips less abducted in an adaptive seating system. The primary outcome was migration percentage (MP) progression. Health-related quality of life and family satisfaction were among the secondary outcomes. The study was approved by the local ethics board and conducted in accordance with CONSORT reporting guidelines. CLINICALTRIALS: gov ID: NCT04603625. RESULTS: Overall median MP progression was 1.6 after the first year and 2.5 after the second year. No significant differences were observed between the groups. MP exceeded 40% and 50% in 1.8% and 0% of the experimental group and 5.4% and 3.6% of controls in years 1 and 2, respectively. Both groups expressed satisfaction with the postural system and stable health-related quality of life. Conclusions: MP remained stable over the two-year period in both groups. Considering outliers which progressed over 50%, a more protective trend of the hip-centering sitting approach emerged, but this needs to be confirmed in a final, larger dataset.

Maternal singing sustains preterm hospitalized newborns' autonomic nervous system maturation: an RCT.

BACKGROUND: Premature birth is known to affect the newborn's autonomic nervous system (ANS) maturation, with potential short and long-term impact on their neurobehavioral development. The purpose of the study was to investigate the effects of maternal directed singing and speaking on the preterm infants' autonomic nervous system (ANS) maturation as measured by the heart rate variability (HRV) parameters. METHODS: In this multi-center randomized clinical trial, 30 stable preterm infants (m = 29,6 weeks of gestational age), without any abnormalities were randomized into an intervention (16) or a control group (14). HRV was measured weekly, for a total of 80 recordings during hospitalization, as well as before and after each session of singing or speaking. RESULTS: The intervention group showed a significant increase of the percentage value of HRV power in the high frequency range when compared to the control group (p = 0.044). More specifically, the maternal singing significantly increased the high frequency power and decreased the low/high frequency power ratio (p = 0.037). CONCLUSIONS: The preterm infant's vagal activity significantly increased in the intervention group, potentially enhancing their ANS maturation. The effect is specifically evidenced in the singing condition. IMPACT: Maternal singing affects the autonomic nervous system maturation of preterm hospitalized newborns in the NICU. No previous studies investigated how early vocal parental intervention can affect preterm infants developement, throught their autonomic nervous system maturation. Early Vocal Contact as an early intervention involving parents has a positive impact on preterm infant's development and it can be easily implemented in the care of preterm infants. TRIAL REGISTRATION: NCT04759573, retrospectively registered, 17 February 2021.

In-hospital growth and long-term neurodevelopmental outcomes of very low birth weight infants.

Background and Objectives: Very low birth weight infants (VLBW) are at risk for adverse growth and neurodevelopmental outcomes. We aimed to evaluate the association between growth during Neonatal Intensive Care Unit (NICU) stay and long-term neurodevelopmental outcomes in a cohort of preterm VLBW newborns. Methods: We conducted a longitudinal observational study in the Follow-up Service of our Clinic from January 2014 to April 2017. All preterm VLBW infants born at our hospital and enrolled in our follow-up program were considered eligible for the study. The neurodevelopmental assessment was performed using the Griffiths Mental Development Scales at 12 and 24 months corrected age. Results: Study population included 172 subjects (47.1% males) with a mean gestational age of 29 weeks and a mean birth weight of 1,117 g. A unitarian Δz-score increase in head circumference from birth to discharge was associated with a 1.6-point increase in General Quotient at 24 months corrected age. An association with subscales C and D was also found. Likewise, an increase in length Δz-score was associated with better 24-month subscale C scores although not reaching statistical significance. No relationship with the outcome at 24 months was found for weight gain. Conclusions: Growth during NICU stay appears to be related to a more favorable neurodevelopmental outcome at 24 months corrected age, especially in the hearing and language domain (subscale C). The longitudinal evaluation of auxological parameters during hospitalization can contribute to the identification of subjects at risk for adverse neurodevelopmental outcomes in the first years of life.

Development of a new scoring method in the neurofunctional assessment of preterm infants.

Infants born preterm are at high risk of presenting neurodevelopmental delay. The Neurofunctional Assessment (NFA) describes infants' neurodevelopment through the evaluation of six different domains. This study aimed to evaluate how, in a cohort of preterm infants, each NFA domain assessed at 3 months of corrected age (CA) was associated with neurodevelopment at 2 years of CA using the Griffiths Mental Developmental Scales Extended Revised (GMDS-ER). In addition, by introducing the NFA complexity score (CS), the study aimed to define a threshold that can help clinicians discriminate infants at higher risk of later neurodevelopmental delay. We conducted an observational, longitudinal study including 211 preterm infants. At 3 months of CA, infants who had normal scores in each domain showed a significantly higher GMDS-ER global quotient (GQ) at 2 years of CA. In addition, linear model results showed a significant negative relationship between the NFA CS and 2-year GMDS-ER GQ (estimate: - 0.27; 95% CI - 0.35, - 0.20; p value < 0.001). Each 10-point increase in the NFA CS was associated with an average 2.7-point decrease in the GMDS GQ. These results highlight how the NFA domains and NFA CS are compelling instruments for the early identification of children at risk for long-term adverse outcomes.

Maternal Singing but Not Speech Enhances Vagal Activity in Preterm Infants during Hospitalization: Preliminary Results.

BACKGROUND: Early parental interventions in the Neonatal Intensive Care Units (NICUs) have beneficial effects on preterm infants' short and long-term outcomes. The aim of this study was to investigate the effects of Early Vocal Contact (EVC)-singing and speaking-on preterm infants' vagal activity and autonomic nervous system (ANS) maturation. METHODS: In this multi-center randomized clinical trial, twenty-four stable preterm infants, born at 25-32 weeks gestational age, were randomized to either the EVC group or control group, where mothers did not interact with the babies but observed their behavior. Heart Rate Variability (HRV) was acquired before intervention (pre-condition), during vocal contact, and after it (post condition). RESULTS: No significant effect of the vocal contact, singing and speaking, was found in HRV when the intervention group was compared to the control group. However, a significant difference between the singing and the pre and post conditions, respectively, preceding and following the singing intervention, was found in the Low and High Frequency power nu, and in the low/high frequency features (p = 0.037). By contrast, no significant effect of the speaking was found. CONCLUSIONS: Maternal singing, but not speaking, enhances preterm infants' vagal activity in the short-term, thus improving the ANS stability. Future analyses will investigate the effect of enhanced vagal activity on short and long-term developmental outcomes of preterm infants in the NICU.

Red blood cell transfusions in preterm newborns and neurodevelopmental outcomes at 2 and 5 years of age.

BACKGROUND: Red blood cell (RBC) transfusion is often considered a life-saving measure in preterm neonates. However, it has been associated with detrimental effects on short-term morbidities and, recently, on brain development. The aim of the present study was to evaluate the association between RBC and long-term neurodevelopmental outcome in a cohort of preterm infants. MATERIALS AND METHODS: This retrospective cohort study was carried out in the period 2007-2013. Preterm infants with a gestational age (GA) ≤ 32 weeks and birthweight (BW) <1,500 g were included. Infants underwent Griffiths assessment at 24±6 months corrected age (CA) and at 5±1 years of age. We used a multivariate regression model to assess the association of RBC transfusions and long-term neurodevelopment after controlling for GA, being small for GA, major neonatal morbidities, and socio-economic status. We also evaluated the impact of early RBC administration (within the first 28 days of life) compared to those performed after the first month of life. RESULTS: We enrolled 644 preterm infants, among whom 54.3% were transfused during their stay in the neonatal intensive care unit (NICU). In infants with a longitudinal follow-up evaluation (n=360), each RBC transfusion was independently associated with a reduction in the Griffiths General Quotient (GQ) by -0.96 (p=0.002) at 24 months CA. Early RBC administration had the biggest impact, especially in children without brain lesions, where the reduction in Griffiths GQ for each additional transfusion was -2.12 (p=0.001) at 24 months CA and -1.31 (p=0.006) at 5 years of age, respectively. DISCUSSION: In preterm infants, RBC transfusions are associated with long-term neurodevelopmental outcome, with a cumulative effect. Early RBC administration is associated with a greater reduction in Griffiths scores. The impact of RBC transfusion on neurodevelopment is greater at 24 months CA, but persists, although to a lesser degree, at 5 years of age.

Newborns' early attuning to hand-to-mouth coordinated actions.

Already inside the womb, fetuses frequently bring their hands to the mouth, anticipating hand-to-mouth contact by opening the mouth. Here, we explored whether 2-day-old newborns discriminate between hand actions directed towards different targets of the face-that is, a thumb that reaches the mouth and a thumb that reaches the chin. Newborns looked longer towards the thumb-to-mouth compared to the thumb-to-chin action only in the presence, and not absence, of anticipatory mouth opening movements, preceding the thumb arrival. Overall, our results show that newborns are sensitive to hand-to-face coordinated actions, being capable to discriminate between body-related actions directed towards different targets of the face, but only when a salient visual cue that anticipates the target of the action is present. The role of newborns' sensorimotor experience with hand-to-mouth gestures in driving this capacity is discussed.

Neuroprem 2: An Italian Study of Neurodevelopmental Outcomes of Very Low Birth Weight Infants.

Background: Despite the increased survival of preterm newborns worldwide, the risk of neurodevelopmental disabilities remains high. Analyzing the outcomes of the preterm population can identify risk factors and enable specific early interventions. Aims: Neuroprem is a prospective cohort study of very low birth weight (VLBW) infants that aims to evaluate the neurodevelopmental outcomes and risk factors for severe functional disability at 2 years of corrected age. Methods: Nine Italian neonatal intensive care units participated in the network. The Griffiths Mental Developmental Scales (GMDS-R) or the Bayley Scales of Infant and Toddler Development (BSDI III) and a neuro-functional evaluation (according to the International Classification of Disability and Health and Neuro-Functional Assessment, or NFA ICF-CY) were administered to VLBW infants at 24 months of corrected age. The primary outcome measure was severe functional disability, defined as cerebral palsy, bilateral blindness, deafness, an NFA ICF-CY of >2, a BSDI III cognitive composite score of <2 SD, or a GMDS-R global quotient score of <2 SD. Perinatal risk factors for severe functional disability were assessed through multivariate logistic regression analysis. Results: Among 502 VLBW survivors who completed the 24-month follow-up, 48 (9.6%) presented severe functional disability, of whom 27 had cerebral palsy (5.4%). Rates of severe functional disability and cerebral palsy were higher in neonates with a lower gestational age (p < 0.001). Overall, 147 infants (29.3%) were referred to neuromotor intervention. In the multivariate regression model, gestational age at birth OR 0.79; 95% CI 0.67-0.90; p = 0.001) and periventricular-intraventricular hemorrhage (OR 2.51; 95% CI 1.19-5.26; p = 0.015) were significantly associated with severe functional disability. Conclusion: Neuroprem 2 provides updated information on the neurodevelopmental outcomes of VLBW infants in a large Italian cohort. The overall rate of neurodevelopmental disabilities was quite lower than reported in the previous literature. These data indicate the need for structured follow-up programs from a national neonatal network perspective.

An Automated Approach for General Movement Assessment: A Pilot Study.

Objective: The objective of the study was to develop an automatic quantitative approach to identify infants with abnormal movements of the limbs at term equivalent age (TEA) compared with general movement assessment (GMA). Methods: GMA was performed at TEA by a trained operator in neonates with neurological risk. GMs were classified as normal (N) or abnormal (Ab), which included poor repertoire and cramped synchronized movements. The signals from four micro-accelerometers placed on all limbs were recorded for 10 min simultaneously. A global index (KC_index), quantifying the characteristics of individual limb movements and the coordination among the limbs, was obtained by adding normalized kurtosis of the distribution of the first principal component of the acceleration signals to the cross-correlation of the jerk for the upper and lower limbs. Results: Sixty-eight infants were studied. A KC_index cut-off of 201.5 (95% CI: 199.9-205.0) provided specificity = 0.86 and sensitivity = 0.88 in identifying infants with Ab movements. Conclusions: KC_index provides an automatic and quantitative measure that may allow the identification of infants who require further neurological evaluation.

Effects of Early Vocal Contact in the Neonatal Intensive Care Unit: Study Protocol for a Multi-Centre, Randomised Clinical Trial.

Preterm infants are at risk for developing altered trajectories of cognitive, social, and linguistic competences compared to a term population. This is mainly due to medical and environmental factors, as they are exposed to an atypical auditory environment and simultaneously, long periods of early separation from their parents. The short-term effects of early vocal contact (EVC) on an infant's early stability have been investigated. However, there is limited evidence of its impact on the infant's autonomic nervous system maturation, as indexed by heart rate variability, and its long-term impact on infant neurodevelopment. Our multi-centric study aims to investigate the effects of EVC on a preterm infant's physiology, neurobehaviour, and development. Eighty stable preterm infants, born at 25-32 weeks and 6 days gestational age, without specific abnormalities, will be enrolled and randomised to either an intervention or control group. The intervention group will receive EVC, where mothers will talk and sing to their infants for 10 min three times per week for 2 weeks. Mothers in the control group will be encouraged to spend the same amount of time next to the incubator and observe the infant's behaviour through a standard cluster of indicators. Infants will be assessed at baseline; the end of the intervention; term equivalent age; and 3, 6, 12, and 24 months corrected age, with a battery of physiological, neurobehavioral, and developmental measures. Early interventions in the neonatal intensive care unit have demonstrated effects on the neurodevelopment of preterm infants, thereby lowering the negative long-term effects of an atypical auditory and interactional environment. Our proposed study will provide new insight into mother-infant early contact as a protective intervention against the sequelae of prematurity during this sensitive period of development. Early intervention, such as EVC, is intuitive and easy to implement in the daily care of preterm infants. However, its long-term effects on infant neurodevelopment and maternal sensitivity and stress are still unclear. Trial Registration: NCT04759573, retrospectively registered, 17 February 2021.

Being adults with cerebral palsy: results of a multicenter Italian study on quality of life and participation.

Cerebral palsy (CP) is still the most common cause of disability developing in infancy. How such a complex disorder affects adult life raises important questions on the critical issues to consider and the most appropriate care pathway right from early childhood. We conducted a multicenter study on a sample of 109 individuals with CP followed up from infancy and recalled for an assessment at ages ranging between 18 and 50 years (mean age 26 years). Semi-structured interviews and specific questionnaires (SF36, LIFE-H and Hollingshead Index) were conducted to assess general psychological state, quality of life, and socio-economic conditions. Our findings showed a globally positive perception of quality of life, albeit with lower scores for physical than for mental health. Our cases generally showed good scores on participation scales, though those with more severe forms scored lower on parameters such as mobility, autonomy, and self-care. These findings were investigated in more depth in interviews, in which our participants painted a picture showing that gradual improvements have been made in several aspects over the years, in the academic attainment and employment, for instance. On the downside, our sample reported persistent limitations on autonomy in daily life. As for the more profound psychological domain, there was evidence of suffering due to isolation and relational difficulties in most cases that had not emerged from the questionnaires. Our data have possible implications for the management of CP during childhood, suggesting the need to avoid an exclusive focus on motor function goals, and to promote strategies to facilitate communication, participation, autonomy, and social relations.

Mind-mindedness and parenting stress in mothers of preterm and full-term infants: The moderating role of perceived social support.

The goal of this study was to examine the effects of preterm birth and maternal childbirth-related posttraumatic stress and parenting stress on maternal mind-mindedness (MM). The study also investigated the effects of perceived social support on parenting stress and MM. Sixty-five preterm (N = 32) and full-term (N = 33) mother-infant dyads were observed at 6 months. Measures of maternal MM were obtained from observations of mother-infant interaction. Mothers also provided ratings of their posttraumatic stress disorder (PTSD) symptoms, parenting stress, and perceived social support via an online survey. Experiencing a preterm birth did not affect mothers' use of mental state descriptors during mother-infant interaction. Neither childbirth-related posttraumatic stress nor parenting stress directly affected maternal ability to comment on the child's mental states appropriately. However, at medium and high levels of perceived social support, a negative association between parenting stress and MM was observed. Maternal perception of being emotionally supported by significant others promoted MM in mothers showing low or mild levels of parenting stress, but not in mothers experiencing high stress in parenting their infants. Results suggest that a proclivity to MM might be affected by the interaction between parenting stress and social support, rather than by childbirth-related variables, such as prematurity.

El propósito de este estudio fue examinar los efectos del nacimiento prematuro y el estrés materno postraumático relacionado con dar a luz, y el estrés de la crianza sobre la disposición de la mente (MM). El estudio también investigó los efectos que la percepción del apoyo social tiene en el estrés de la crianza y la disposición de la mente. Se observaron 65 díadas de madre-infantes prematuros (N = 32) y de gestación completa (N = 33) a los 6 meses. Las medidas de la disposición mental materna se obtuvieron de observaciones de la interacción madre-infante. Las madres también suministraron los puntajes de sus síntomas de PTSD, el estrés de la crianza y la percepción del apoyo social por medio de una encuesta electrónica. El experimentar un nacimiento prematuro no afectó el uso por parte de las madres de los factores de descripción del estado mental durante la interacción madre-infante. Ni el estrés postraumático relacionado con el dar a luz ni el estrés de la crianza directamente afectaron la habilidad materna para comentar de manera apropiada sobre los estados mentales del niño. Sin embargo, al nivel medio y alto de la percepción de apoyo social, se observó una asociación negativa entre el estrés de crianza y la disposición de la mente. La percepción materna de contar con el apoyo emocional de su pareja promovió la disposición mental de las madres que mostraban bajos o leves niveles de estrés de crianza, aunque no así en aquellas madres que experimentaban un nivel alto de estrés en la crianza de sus infantes. Los resultados sugieren que una propensión a la disposición mental pudiera ser afectada por la interacción entre el estrés de crianza y el apoyo social, en vez de las variables relacionadas con el dar a luz, tal como el nacimiento prematuro.

Le but de cette étude était d'examiner les effets du stress posttraumatique lié à la naissance avant terme et à l'accouchement maternel et le stress de parentage sur l'Etat d'esprit/Orientation mentale (abrégé ici EE/OM). L'étude s'est aussi penchée sur les effets du soutien social perçu du stress de parentage et de l'EE/OM maternel. Soixante-cinq dyades mères-bébés nés avant terme (N = 32) et à plein terme (N = 33) ont été observées à 6 mois. Les mesures d'EE/FM maternel ont été obtenues d'observations de l'interaction mère-bébé. Les mères ont aussi offert des évaluations de leurs propres symptômes ESPT, du stress de parentage, et du soutien social perçu au travers d'un questionnaire en ligne. Le fait d'avoir fait l'expérience d'une naissance avant terme n'a pas affecté l'utilisation de descripteurs de santé mentale des mères durant l'interaction mère-bébé. Ni le stress posttraumatique lié à l'accouchement ni le stress de parentage n'ont affecté directement la capacité maternelle à commenter les états mentaux de l'enfant de manière appropriée. Cependant, à des niveaux moyens et élevés de soutien social perçu, une association négative entre le stress de parentage et l'EE/OM a été observée. La perception maternelle d'être soutenue émotionnellement par leurs partenaires a promu l'EE/FM chez les mères faisant preuve de niveaux bas ou peu élevés de stress de parentage, mais pas chez les mères faisant preuve de stress élevé dans le parentage de leurs bébés. Les résultats suggèrent qu'une tendance à l'EE/OM peut être affectée par l'interaction entre le stress de parentage et le soutien social, plutôt que par des variables liées à l'accouchement, comme la prématurité.

Mind-Mindedness and Parenting Stress: A Cross-Sectional Study in a Cohort of Mothers of 3-Month-Old Full-Term and Preterm Infants.

The preterm birth of a child is a sudden event that can disturb the overall family system and its functioning. Many studies have been conducted with the aim of exploring how and the degree to which this event affects the early mother-infant dyadic relationship and maternal well-being, with often mixed findings. The present study investigates the combined effect of preterm birth and parenting stress on mind-mindedness, a parenting dimension that captures how parents represent and treat their children as separate individuals with their own mental states and activities. A hundred and ten mothers and their three-month-old infants (preterm = 54; full-term = 56) participated in the study. Mind-mindedness was assessed by coding mothers' comments about infant's mental states during dyadic face-to-face interaction. Parenting stress was evaluated with the Parenting Stress Index Short Form questionnaire. Mothers of preterm infants reported similar levels of appropriate and non-attuned mind-related comments to mothers of full-term infants. The reported parenting stress levels were also comparable. Interestingly, only mothers of preterm infants who reported higher stress in parenting showed more non-attuned comments during the interaction. The results underline the need to address preterm birth as a complex event, going beyond group differences and considering its interplay with other risk or protective factors in shaping children's and parents' adjustments and well-being.

Early detection of general movements trajectories in very low birth weight infants.

The aim of the study was to investigate General Movements'(GMs) neonatal trajectories and their association with neurodevelopment at three months corrected age (CA) in preterm infants. We conducted an observational, longitudinal study in 216 very low birth weight infants. GMs were recorded at 31 ± 1, 35 ± 1, 40 ± 1 weeks of postmenstrual age and at three months of corrected age (CA). More than 90% of infants showing neonatal trajectories with persistent Normal (N-N) or initial Poor Repertoire to Normal (PR-N) movements presented fidgety pattern at three months CA. On the contrary, fidgety movements were not detected in any infant with a trajectory of persistent Cramped-Synchronized (CS-CS) or an initial Poor-Repertoire to Cramped-Synchronized (PR-CS) movements. Trajectories with initial Normal to Poor-Repertoire (N-PR) or persistent Poor-Repertoire (PR-PR) movements showed an increased risk of having a non-normal Fidgety pattern compared with the N-N group (OR = 8.43, 95% CI: 2.26-31.45 and OR = 15.02, 95% CI: 6.40-35.26, respectively). These results highlight the importance to evaluate neonatal GMs' trajectory to predict infants' neurodevelopment. N-N or PR-N trajectories suggest normal short-term neurodevelopment, especially a lower risk of Cerebral Palsy; whereas findings of N-PR and PR-PR trajectories indicate the need for closer follow up to avoid delay in programming intervention strategies.

Neurodevelopmental Outcome and Adaptive Behavior in Preterm Multiples and Singletons at 1 and 2 Years of Corrected Age.

BACKGROUND: Recent literature has investigated the role of multiple birth on neurodevelopmental outcomes of premature infants, especially extremely preterm ones. Multiple gestations are often associated to increased neurodevelopmental disability. Actually, research findings are controversial. OBJECTIVE: To compare the neurodevelopmental and behavioral outcomes of multiples and singletons in a cohort of preterm infants ≤28 weeks gestational age at 1 and 2 years of corrected age. METHODS: The study included 86 infants, born from January 2014 to September 2017 and enrolled in the follow-up program provided at authors' Institution. Exclusion criteria included: major brain lesions and malformations, severe neuro-sensorial deficits, genetic syndromes, single-twin survivors. Thirty four multiples were compared to 52 singletons, using the Griffiths Mental Development Scales and the Child Behavior Checklist 1½-5. Statistical analysis was based on ANOVA techniques to test group differences. A p < 0.05 was considered statistically significant. RESULTS: The neurodevelopmental outcomes of multiples and singletons at 1 and 2 years of corrected age did not significantly differ at a general level (p > 0.05). Multiples showed significantly lower mean scores than singletons at 1 year in Locomotor (87.15 ± 11.94 vs. 92.48 ± 11.59) and Personal-Social (84.88 ± 10.25 vs. 89.63 ± 8.19) subscales. Considering the behavioral outcomes, higher rates of externalizing problems were observed in multiples at 2 years (54.27 ± 9.64 vs. 49.31 ± 10.39). CONCLUSION: The slightly lower neurodevelopmental outcome showed by multiples, especially in the gross-motor and personal-social domains at 1 year, might be related to the specific environmental condition they experience. Multiple birth may affect mother's sensitivity to infant's needs and infant's acquisition of emotional and behavioral regulation. This affects the separation process and the acquisition of the independent walking and other gross-motor skills. Being multiples might also induce an hyperstimulation and this could explain their higher vulnerability to externalizing problems (impulsiveness, hyperactivity, attention deficits). Additionally, males are more affected by the multiple condition than females.

A case series of CHARGE syndrome: identification of key features for a neonatal diagnosis.

BACKGROUND: An early diagnosis of CHARGE syndrome is challenging, especially for the primary care physicians who often take care of neonates with multiple congenital anomalies. Here we report eight cases of CHARGE syndrome whose diagnosis was made early in life with the intent to identify the most helpful features allowing a prompt clinical diagnosis. METHODS: Medical records of patients with CHARGE syndrome whose diagnosis was made at the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan, Italy were retrospectively reviewed. RESULTS: Taken together, these patients reflect the considerable phenotypic variability of the syndrome; in one patient, the diagnosis was made immediately after birth because all the major criteria were met. In six patients, presenting with relatively nonspecific defects, a temporal bone computerized tomography scan was essential to achieve the correct diagnosis. In one patient, the diagnosis was made later than the others were. A careful examination revealed the presence of outer, middle, and inner ear anomalies: these elements, in the absence of any additional major criteria, represented for us an important diagnostic clue. CONCLUSIONS: This article suggests that an accurate evaluation of the ear should be made every time CHARGE syndrome is considered as a likely diagnosis even when the standard criteria are not fulfilled.

Neuroprem: the Neuro-developmental outcome of very low birth weight infants in an Italian region.

INTRODUCTION: The survival of preterm babies has increased worldwide, but the risk of neuro-developmental disabilities remains high, which is of concern to both the public and professionals. The early identification of children at risk of neuro-developmental disabilities may increase access to intervention, potentially influencing the outcome. AIMS: Neuroprem is an area-based prospective cohort study on the neuro-developmental outcome of very low birth weight (VLBW) infants that aims to define severe functional disability at 2 years of age. METHODS: Surviving VLBW infants from an Italian network of 7 neonatal intensive care units (NICUs) were assessed for 24 months through the Griffiths Mental Developmental Scales (GMDS-R) or the Bayley Scales of Infant and Toddler Development (BSDI III) and neuro-functional evaluation according to the International Classification of Disability and Health (ICF-CY). The primary outcome measure was severe functional disability at 2 years of age, defined as cerebral palsy, a BSDI III cognitive composite score < 2 standard deviation (SD) or a GMDS-R global quotients score < 2 SD, bilateral blindness or deafness. RESULTS: Among 211 surviving VLBW infants, 153 completed follow-up at 24 months (72.5%). Thirteen patients (8.5%) developed a severe functional disability, of whom 7 presented with cerebral palsy (overall rate of 4.5%). Patients with cerebral palsy were all classified with ICF-CY scores of 3 or 4. BSDI III composite scores and GMDS-R subscales were significantly correlated with ICF-CY scores (p < 0.01). CONCLUSION: Neuroprem represents an Italian network of NICUs aiming to work together to ensure preterm neuro-developmental assessment. This study updates information on VLBW outcomes in an Italian region, showing a rate of cerebral palsy and major developmental disabilities in line with or even lower than those of similar international studies. Therefore, Neuroprem provides encouraging data on VLBW neurological outcomes and supports the implementation of a preterm follow-up programme from a national network perspective.

Minimally invasive fetal surgery for myelomeningocele: preliminary report from a single center.

OBJECTIVE: Recent trials have shown the safety and benefits of fetoscopic treatment of myelomeningocele (MMC). The authors' aim was to report their preliminary results of prenatal fetoscopic treatment of MMC using a biocellulose patch, focusing on neurological outcomes, fetal and maternal complications, neonatal CSF leakage, postnatal hydrocephalus, and radiological outcomes. METHODS: Preoperative assessment included clinical examination, ultrasound imaging, and MRI of the fetus. Patients underwent purely fetoscopic in utero MMC repair, followed by postoperative in utero and postnatal MRI. All participants received multidisciplinary follow-up. RESULTS: Five pregnant women carrying fetuses affected by MMC signed informed consent for the fetoscopic treatment of the defect. The mean MMC size was 30.4 mm (range 19-49 mm). Defect locations were L1 (2 cases), L5 (2 cases), and L4 (1 case). Hindbrain herniation and ventriculomegaly were documented in all cases. The mean gestational age at surgery was 28.2 weeks (range 27.8-28.8 weeks). Fetoscopic repair was performed in all cases. The mean gestational age at delivery was 33.9 weeks (range 29.3-37.4 weeks). After surgery, reversal of hindbrain herniation was documented in all cases. Three newborns developed signs of hydrocephalus requiring CSF diversion. Neurological outcomes in terms of motor level were favorable in all cases, but a premature newborn died due to CSF infection and sepsis. CONCLUSIONS: The authors' preliminary results suggest that fetoscopic treatment of MMC is feasible, reproducible, and safe for mothers and their babies. Neurological outcomes were favorable and similar to those in the available literature. As known, prematurity was the greatest complication.

Seven Years Cognitive Functioning and Early Assessment in Extremely Low Birth Weight Children.

Infants born preterm are at high risk for the onset of cognitive dysfunctions at school age. The aim of this study was to investigate the association between early neurodevelopmental assessment and the risk of adverse cognitive outcome in extremely low birth weight children. We enrolled all newborns (January 2002 - April 2007) consecutively admitted to our Institution, with a birthweight < 1000 g. Exclusion criteria were genetic abnormalities, severe neurofunctional impairment, and/or neurosensory disabilities. Ninety-nine children were assessed at 1 year of corrected age using the Griffiths Mental Development Scales Revised. The same children were re-assessed at school age through the Wechsler Intelligence Scale for Children. Children with impaired Griffiths General Quotient (i.e., <1 SD) at 1 year of corrected age showed a significantly lower Full Scale Intelligence Quotient at 7 years of chronological age when compared to children who scored in the normal range at 1 year (p < 0.01). Considering the Griffiths Sub-quotients separately, a poor score in the Performance or in the Personal-Social Sub-quotients at 1 year was associated with significantly worse cognitive outcomes both in the Verbal and in the Performance Intelligence Quotients at 7 years (p < 0.01 and p < 0.05, respectively). A score <1 SD in the Locomotor or in the Eye and Hand Coordination Sub-quotients were specifically associated with poorer Performance or Verbal Intelligence Quotients, respectively (p < 0.05). Our findings suggest that a poor score on the Griffiths Scales at 1 year is associated with a higher risk of cognitive impairment at school age. Larger confirmation studies are needed.