Executive Functions Rehabilitation in Premature Children Using an Adaptive Motion-Interaction Videogame Platform: A Randomized Controlled Trial.

Background: Premature children are at increased risk of executive functions (EF) deficits and these difficulties persist into adolescence and adulthood, potentially undermining their development and academic achievements. The aim of the present randomized controlled trial (RCT) is to evaluate the efficacy of the Intendu trainer, an adaptive virtual reality platform, at ameliorating EF in preterm children. Methods: A single-center, RCT was conducted. The intervention group was exposed to game session with the Intendu software in addition to the standard of care in use in our center. The main outcome was the proportion of children with a 10-point increase in the processing speed quotient as measured by WPPSI-III after 4 weeks from the baseline assessment. Results: Forty-seven children born before 36 + 5 weeks were randomized to the experimental (n = 24) or control arm (n = 23). Five children were lost to follow-up. Thirteen of 23 children (56%) reached the main outcome in the experimental group and 5 of 19 (26%) in the control group (P = 0.049, per-protocol analysis) with an absolute benefit increase (ABI) of 30% reconfirmed by the intention-to-treat analysis (P = 0.022, ABI of 32%). Conclusion: Intendu brain-trainer showed promising short-term results on EF in pre-term children, however, larger studies with longer periods of follow-up are warranted to better investigate the role of this or similar technology in promoting better EF in preterm children.

Early-Life Nutrition in Preterm Infants and Risk of Respiratory Infections and Wheezing: A Scoping Review.

INTRODUCTION: Preterm birth is a common early-life event that can lead to long-term consequences. The incidence of wheezing, asthma, and respiratory tract infections is higher in children born prematurely than in the general population. The purpose of this review was to synthesize the existing literature on the role of early-life nutrition in the later risk of respiratory morbidities. METHODS: A scoping review of the literature was performed by searching three online databases. Inclusion criteria were: infants born <37 GWk, comparing human milk versus any other type of milk feeding formulation. Our primary outcomes were wheezing or asthma or respiratory tract infections after discharge. Two authors independently screened the results and extracted study characteristics using a predefined charting form. RESULTS: Nine articles were included (eight cohort studies and one randomized trial). Four studies supported the protective effect of breastfeeding on wheezing or respiratory infections or both. Four studies did not confirm this association. One study confirmed the protective role of breastfeeding only on the subgroup of girls. There was a high heterogeneity among the included studies, in the type of milk feeding, outcomes, and age at follow-up. CONCLUSIONS: The current evidence is conflicting. The high heterogeneity and methodological flaws could have influenced the results of the studies. Carefully designed studies are required to define the role of early-life nutrition among preterm infants on their long-term respiratory outcomes.

Neonatal Early Onset Sepsis (EOS) Calculator plus Universal Serial Physical Examination (SPE): A Prospective Two-Step Implementation of a Neonatal EOS Prevention Protocol for Reduction of Sepsis Workup and Antibiotic Treatment.

Current neonatal early-onset sepsis (EOS) guidelines lack consensus. Recent studies suggest three different options for EOS risk assessment among infants born ≥35 wks gestational age (GA), leading to different behaviors in the sepsis workup and antibiotic administration. A broad disparity in clinical practice is found in Neonatal Units, with a large number of non-infected newborns evaluated and treated for EOS. Broad spectrum antibiotics in early life may induce different short- and long-term adverse effects, longer hospitalization, and early mother-child separation. In this single-center prospective study, a total of 3002 neonates born in three periods between 2016 and 2020 were studied, and three different workup algorithms were compared: the first one was based on the categorical risk assessment; the second one was based on a Serial Physical Examination (SPE) strategy for infants with EOS risk factors; the third one associated an informatic tool (Neonatal EOS calculator) with a universal extension of the SPE strategy. The main objective of this study was to reduce the number of neonatal sepsis workups and the rate of antibiotic administration and favor rooming-in and mother−infant bonding without increasing the risk of sepsis and mortality. The combined strategy of universal SPE with the EOS Calculator showed a significant reduction of laboratory tests (from 33% to 6.6%; p < 0.01) and antibiotic treatments (from 8.5% to 1.4%; p < 0.01) in term and near-term newborns. EOS and mortality did not change significantly during the study period.

Cognitive, Behavioral and Socioemotional Development in a Cohort of Preterm Infants at School Age: A Cross-Sectional Study.

More than 50% of children who survive prematurity have an atypical course of development at school age, as environmental demands become more demanding. This study examines the effects of preterm birth on the cognitive, behavioral and socioemotional development of 185 children at ages five and seven years. Weaknesses were found in attention, working memory, processing speed and the ability to correctly interpret emotions at both ages five and seven. Significant correlations were found in regression and moderation models. These findings suggest that school-age children who were preterm infants are at increased risk of exhibiting impairments in several developmental domains that may affect their overall quality of life.

Monochorionic Twins and the Early Mother-Infant Relationship: An Exploratory Observational Study of Mother-Infant Interaction in the Post-Partum Period.

The extraordinary increase in twin rates and specifically monochorionic twin pregnancies represents a major public health issue due to the associated increased risks for the mother, the child and their relationship. The aim of the present study was to examine the quality of mothers' behaviour during mother-infant interaction in the early postpartum period by comparing mothers of twins and mothers of singletons during face-to-face interaction with their infants. Demographic and clinical information was collected by trained research psychologists from the mothers' and the childrens' clinical records and from interviews with the mothers. At three months (corrected for prematurity), the interactions of the dyads (11 mother-twin infant dyads and 11 mother-singleton dyads) were filmed at participants' homes in accordance with the procedure of the Global Rating Scales. Maternal behaviour during interactions was assessed and rated by two trained research psychologists. With regard to the mothers' interaction with each twin, no differences were found between mothers' scores in every GRS subscale, indicating that mothers did not interact differently with their twins. Comparisons between mothers of MC twins and mothers of singletons showed that the quality of maternal sensitive behaviour during the interactions were lower in mothers of twins (0.35) Mothers of twins were also more distant during interactions with their babies and more likely to experience depression symptoms than mothers of singletons (0.05). Future research should examine mother-infant relationships following twin birth with larger samples. Such research will be especially useful in evaluating the potential benefits of interventions to promote positive mother-infant interactions.

Management of asymptomatic hypoglycemia with 40% oral dextrose gel in near term at-risk infants to reduce intensive care need and promote breastfeeding.

BACKGROUND: Neonatal hypoglycemia is a common disorder especially in at-risk infants and it can be associated with poor long-term neurological outcomes. Several therapeutic interventions are suggested, from the implementation of breastfeeding to the glucose intravenous administration. Oral dextrose gel massaged into the infant's inner cheek is a recent treatment option of asymptomatic hypoglycemia, after which oral feeding is encouraged. This approach seems to reduce the admission of infants to neonatal intensive care unit (NICU) so favouring maternal bonding and breastfeeding success at discharge. METHODS: In our ward, we prospectively compared a group of near-term neonates, (Gr2, n = 308) at risk for hypoglycemia, treated with an innovative protocol based on the addition of 40% oral dextrose gel (Destrogel, Orsana®,Italy) administered by massaging gums and cheek with historical matching newborns (Gr1, n = 389) treated with a formerly used protocol, as control group. The primary outcome was occurrence of NICU admission and the requirement of intravenous glucose administration; while discharge with full breastfeeding was the secondary outcome. RESULTS: In Gr1, 39/389 (10%) infants presented with asymptomatic hypoglycemia, 19/39 were transferred to the NICU, and 14/39 required intravenous glucose treatment. In Gr2, among the 30/308 infants with asymptomatic hypoglycemia managed according to the new protocol, 3/30 were transferred to the NICU and received intravenous glucose infusion. The mean duration of hospitalization respectively was 6.43 (± 6.36) and 3.73 ± 1.53 days (p <  0.001). At discharge, 7.7% of the infants in Gr1 and 30% of the infants in Gr2 were exclusively breastfed (p = 0.02). Considering Gr1 vs Gr2, the number of patients that were transferred to NICU was 19 (48.7%) vs 3 (10%) (p = 0.001) and the number of infants that needed intravenous glucose infusion was 14 (35.9%) vs 3 (10%) (p = 0.01), respectively. CONCLUSIONS: In our population of near term infants, the introduction of 40% oral dextrose gel to the protocol, helped in the safe management of asymptomatic hypoglycemia and, at the same time, implemented breastfeeding.

Efficacy of Everolimus Low-Dose Treatment for Cardiac Rhabdomyomas in Neonatal Tuberous Sclerosis: Case Report and Literature Review.

Background: Cardiac rhabdomyomas (CRs) are the most common cardiac tumors in newborns. Approximately 80-90% of cases are associated with tuberous sclerosis complex (TSC). In selective cases, Everolimus has resulted in a remarkable tumoral regression effect in children with TS. The optimal dosage for neonates is still unknown. Case presentation: We describe the use of Everolimus in a neonate with multiple biventricular CRs, causing subaortic obstruction, in which a low-dose treatment (0.1 mg/die), in an effort to maintain serum trough levels of 3-7 ng/mL, was successfully used off-label, without adverse effects. Conclusions: We showed that a low-dose Everolimus regimen may be an effective and safe treatment for CR regression in TS neonates, when the minimum therapeutic range was maintained.

Lung recruitment maneuver during volume guarantee ventilation of preterm infants with acute respiratory distress syndrome.

Preterm infants need the achievement of adequate lung volume. Lung recruitment maneuver (LRM) is applied during high-frequency oscillatory ventilation. We investigated the effect of an LRM with positive end-expiratory pressure (PEEP) on oxygenation and outcomes in infants conventionally ventilated for respiratory distress syndrome (RDS). Preterm infants in assisted controlled ventilation+volume guarantee for RDS after surfactant randomly received an LRM (group A) or did not (group B). LRM entailed increments of 0.2 cm H (2)O PEEP every 5 minutes, until fraction of inspired oxygen (Fi O(2))=0.25. Then PEEP was reduced and the lung volume was set on the deflation limb of the pressure/volume curve. When saturation of peripheral oxygen fell and Fi O(2) rose, we reincremented PEEP until Sp O(2) became stable. Group A ( N=10) and group B ( N=10) infants were similar: gestational age 25 ± 2 versus 25 ± 2 weeks; body weight 747 ± 233 versus 737 ± 219 g; clinical risk index for babies 9.8 versus 8.1; initial Fi O(2) 56 ± 24 versus 52 ± 21, respectively. LRM began at 86 ± 69 minutes of age and lasted for 61 ± 18 minutes. Groups A and B showed different max PEEP during the first 12 hours of life (6.1 ± 0.3 versus 5.3 ± 0.3 cm H (2)O, P=0.00), time to lowest Fi O(2) (94 ± 24 versus 435 ± 221 minutes; P=0.000) and O(2) dependency (29 ± 12 versus 45 ± 17 days; P=0.04). No adverse events and no differences in the outcomes were observed. LRM led to the earlier lowest Fi O(2) of the first 12 hours of life and a shorter O (2) dependency.

Nasal continuous positive airway pressure (CPAP) versus bi-level nasal CPAP in preterm babies with respiratory distress syndrome: a randomised control trial.

OBJECTIVE: To evaluate the clinical course, respiratory outcomes and markers of inflammation in preterm infants with moderate respiratory distress syndrome (RDS) assigned from birth to nasal continuous positive airway pressure (NCPAP) or bi-level NCPAP. METHODS: A total of 40 infants with a gestational age (GA) of 28-34 weeks (<35 weeks' GA), affected by moderate RDS, were considered eligible and were randomised to NCPAP (group A; n=20, CPAP level=6 cm H(2)O) or to bi-level NCPAP (group B; n=20, lower CPAP level=4.5 cm H(2)O, higher CPAP level=8 cm H(2)O), provided with variable flow devices. Inflammatory response was the primary outcome; serum cytokines were measured on days 1 and 7 of life. Length of ventilation, oxygen dependency, need for intubation and occurrence of air leaks were considered as secondary outcomes. RESULTS: Infants showed similar characteristics at birth (group A vs group B: GA 30.3+/-2 vs 30.2+/-2 weeks, birth weight 1429+/-545 vs 1411+/-560 g) and showed similar serum cytokine levels at all times. Group A underwent longer respiratory support (6.2+/-2 days vs 3.8+/-1 days, p=0.025), longer O(2) dependency (13.8+/-8 days vs 6.5+/-4 days, p=0.027) and was discharged later (GA at discharge 36.7+/-2.5 weeks vs 35.6+/-1.2 weeks, p=0.02). All infants survived. No bronchopulmonary dysplasia (BPD) or neurological disorders occurred. CONCLUSIONS: Bi-level NCPAP was associated with better respiratory outcomes versus NCPAP, and allowed earlier discharge, inducing the same changes in the cytokine levels. It was found to be well tolerated and safe in the study population.

Early myoclonic encephalopathy and nonketotic hyperglycinemia.

Early myoclonic encephalopathy is an epileptic syndrome with different etiologies. Nonketotic hyperglycinemia is one cause. We describe two cases of early myoclonic encephalopathy, secondary to nonketotic hyperglycinemia, with fatal evolution in the neonatal period. These two cases may better clarify clinical findings that can be associated with impairment of glycine metabolism. Distinguishing features include agenesis of the corpus callosum in patient 1, and weight loss exceeding 10%, associated with metabolic acidosis, in patient 2. The burst-suppression electroencephalography pattern is relatively common in neonatal encephalopathies, and is frequently associated with seizures. Nonketotic hyperglycinemia is an inborn error of metabolism caused by mutations in genes encoding protein in the mitochondrial glycine cleavage system. The neonatal form is a severe, frequently lethal neurologic disease. When associated with electro-clinical features, progressive lethargy and hypotonia occur in the first days of life, progressing to apnea and often death. Prospective treatment with oral sodium benzoate, the N-methyl-d-aspartate receptor antagonist ketamine, and dextromethorphan can favorably modify the early neonatal course of severe nonketotic hyperglycinemia, but does not prevent poor long-term outcomes.