A Customizable Digital Cognitive Aid for Neonatal Resuscitation: A Simulation-Based Randomized Controlled Trial.

OBJECTIVE: Adherence to the International Liaison Committee on Resuscitation (ILCOR) algorithm optimizes the initial management of critically ill neonates. In this randomized controlled trial, we assessed the impact of a customizable sequential digital cognitive aid (DCA), adapted from the 2020 ILCOR recommendations, compared with a poster cognitive aid (standard of care [SOC]), on technical and nontechnical performance of junior trainees during a simulated critical neonatal event at birth. METHODS: For this prospective, bicentric video-recorded study, students were recruited on a voluntary basis, and randomized into groups of 3 composed of a pediatric resident and two midwife students. They encountered a simulated cardiac arrest at birth either (1) with DCA use and ILCOR algorithm poster displayed on the wall (intervention group) or (2) with sole ILCOR algorithm poster (poster cognitive aid [SOC]). Technical and nontechnical skills (NTS) between the two groups were assessed using a standardized scoring of videotaped performances. A neonate specific NTS score was created from the adult Team score. RESULTS: 108 students (36 groups of three) attended the study, 20 groups of 3 in the intervention group and 16 groups of 3 in the poster cognitive aid (SOC) group. The intervention group showed a significant improvement in the technical score (P < 0.001) with an average of 24/27 points (24.0 [23.5-25.0]) versus 20.8/27 (20.8 [19.9-22.5]) in poster cognitive aid (SOC) group. No nontechnical score difference was observed. Feedback on the application was positive. CONCLUSIONS: During a simulated critical neonatal event, use of a DCA was associated with higher technical scores in junior trainees, compared with the sole use of ILCOR poster algorithm.

Predictors of the Outcome at 2 Years in Neonates With Congenital Cytomegalovirus Infection.

BACKGROUND: Approximately 20% of neonates with congenital cytomegalovirus (cCMV) develop long-term sequelae. The ability to accurately predict long-term outcomes as early as the neonatal period would help to provide for appropriate parental counseling and treatment indications. With this study, we aimed to identify neonatal predictive markers of cCMV long-term outcomes. METHODS: As this study's subjects, we chose neonates diagnosed with cCMV in 13 hospitals throughout France recruited from 2013 to 2017 and evaluated for at least 2 years with thorough clinical, audiology, and imaging evaluations and psychomotor development tests. RESULTS: A total of 253 neonates were included, and 3 were later excluded because of the identification of a genetic disorder. A total of 227 were followed up for 2 years: 187/227 (82%) and 34/227 (15%) were infected after a maternal primary or nonprimary infection, respectively, 91/227 (40%) were symptomatic at birth, and 44/227 (19%) had cCMV sequelae. Maternal primary infection in the first trimester was the strongest prognosis factor (odds ratio = 38.34 [95% confidence interval, 5.02-293], P < .001). A predictive model of no risk of sequelae at 2 years of age according to normal hearing loss at birth, normal cerebral ultrasound, and normal platelet count had 98% specificity, 69% sensitivity, and 0.89 area under the curve (95% confidence interval, 0.83-0.96). CONCLUSIONS: In the studied population, children with normal hearing at birth, normal platelet count at birth, and a normal cranial ultrasound had no risk of neurologic sequelae and a low risk of delayed unilateral sensorineural hearing loss. The use of this model based on readily available neonatal markers should help clinicians establish a personalized care pathway for each cCMV neonate.

Creation of a rating scale to teach Less Invasive Surfactant Administration (LISA) in simulation.

BACKGROUND: Simulation-based training is gaining increasing prominence in neonatology training. The Less Invasive Surfactant Administration (LISA) method is starting to be taught in simulation. The aim of this educational study was to develop and validate a rating scale for teaching the LISA method in simulation. METHODS: The Downing framework was used to create this performance-rating scale. A first version of the scale was submitted to 12 French and Belgian experts to obtain their opinions. Consensus was reached using a modified Delphi method. The performance of 40 pediatricians was then evaluated with this scale on a preterm neonate manikin simulating a neonatal respiratory distress syndrome. Each run was evaluated using the scale by two independent observers based on video recordings. RESULTS: The Cronbach alpha score of the rating scale was 0.72. The intraclass correlation coefficient (ICC) was 0.91 and the scores between raters were not significantly different. Finally, this rating scale correctly distinguished the experienced from the inexperienced learners (p < 0.01). CONCLUSIONS: This rating scale is one of the first rating scales for the evaluation and teaching of the LISA method in simulation. This tool has ample potential for use in clinical practice to evaluate the performance of surfactant administration in preterm neonates.

Cognitive Training for Visuospatial Processing in Children Aged 5½ to 6 Years Born Very Preterm With Working Memory Dysfunction: A Randomized Clinical Trial.

Importance: Compared with term-born peers, children born very preterm generally perform poorly in executive functions, particularly in working memory and inhibition. By taking advantage of neuroplasticity, computerized cognitive training of working memory in those children could improve visuospatial processing by boosting visual inhibition via working memory. Objective: To evaluate the long-term effect of cognitive working memory training on visuospatial processing in children aged 5½ to 6 years born very preterm who have working memory impairment. Design, Setting, and Participants: This multicenter (18 French university hospitals), open-label randomized clinical trial with 2 parallel groups (EPIREMED) was conducted from November 2016 to April 2018, with the last follow-up during August 2019. Eligible children from the EPIPAGE 2 cohort were aged 5½ to 6 years, were born between 24 and 34 weeks' gestation, and had a global intelligence quotient greater than 70 and a working memory index less than 85. Data were analyzed from February to December 2020. Intervention: Children were randomized 1:1 to standard care management and a working memory cognitive training program (Cogmed software) for 8 weeks (25 sessions) (intervention) or to standard management (control). Main Outcomes and Measures: The primary outcome was the visuospatial index score from the Wechsler Preschool and Primary Scale of Intelligence, 4th Edition. Secondary outcomes were working memory, intellectual functioning, executive and attention processes, language skills, behavior, quality of life, and schooling. Neurobehavioral assessments were performed at inclusion and after finishing training at 6 months (intermeditate assessment; secondary outcomes) and at 16 months (final assessment; primary outcome). Results: There were 169 children randomized, with a mean (SD) age of 5 years 11 months (2 months); 91 (54%) were female. Of the participants, 84 were in the intervention group (57 of whom [68%] completed at least 15 cognitive training sessions) and 85 were in the control group. The posttraining visuospatial index score was not different between groups at a mean (SD) of 3.0 (1.8) months (difference, -0.6 points; 95% CI, -4.7 to 3.5 points) or 12.9 (2.6) months (difference, 0.1 points; 95% CI, -5.4 to 5.1 points). The working memory index score in the intervention group significantly improved from baseline at the intermediate time point (difference, 4.7 points; 95% CI, 1.2-8.1 points), but this improvement was not maintained at the final assessment. Conclusions and Relevance: This randomized clinical trial found no lasting effect of a cognitive training program on visuospatial processing in children aged 5½ to 6 years with working memory disorders who were born very preterm. The findings suggest that this training has limited long-term benefits for improving executive function. Transient benefits seemed to be associated with the developmental state of executive functions. Trial Registration: ClinicalTrials.gov Identifier: NCT02757794.

Consequences of General Anesthesia in Infancy on Behavior and Brain Structure.

BACKGROUND: One in 7 children will need general anesthesia (GA) before the age of 3. Brain toxicity of anesthetics is controversial. Our objective was to clarify whether exposure of GA to the developing brain could lead to lasting behavioral and structural brain changes. METHODS: A first study was performed in mice. The behaviors (fear conditioning, Y-maze, and actimetry) and brain anatomy (high-resolution magnetic resonance imaging) of 6- to 8-week-old Swiss mice exposed or not exposed to GA from 4 to 10 days old were evaluated. A second study was a complementary analysis from the preexisting APprentissages EXécutifs et cerveau chez les enfants d'âge scolaire (APEX) cohort to assess the replicability of our data in humans. The behaviors (behavior rating inventory of executive function, emotional control, and working memory score, Backward Digit Span, and Raven 36) and brain anatomy (high-resolution magnetic resonance imaging) were compared in 102 children 9 to 10 years of age exposed or not exposed to a single GA (surgery) during infancy. RESULTS: The animal study revealed chronic exacerbated fear behavior in the adult mice (95% confidence interval [CI], 4-80; P = .03) exposed to postnatal GA; this was associated with an 11% (95% CI, 7.5-14.5) reduction of the periaqueductal gray matter (P = .046). The study in humans suggested lower emotional control (95% CI, 0.33-9.10; P = .06) and a 6.1% (95% CI, 4.3-7.8) reduction in the posterior part of the right inferior frontal gyrus (P = .019) in the children who had been exposed to a single GA procedure. CONCLUSIONS: The preclinical and clinical findings of these independent studies suggest lasting effects of early life exposure to anesthetics on later emotional control behaviors and brain structures.

Clinical Value of Serial Quantitative Analysis of Cytomegalovirus DNA in Blood and Saliva Over the First 24 Months of Life in Congenital Infection: The French Cymepedia Cohort.

OBJECTIVE: To evaluate cytomegalovirus (CMV) viral load dynamics in blood and saliva during the first 2 years of life in symptomatic and asymptomatic infected infants and to identify whether these kinetics could have practical clinical implications. STUDY DESIGN: The Cymepedia cohort prospectively included 256 congenitally infected neonates followed for 2 years. Whole blood and saliva were collected at inclusion and months 4 and 12, and saliva at months 18 and 24. Real-time CMV polymerase chain reaction (PCR) was performed, results expressed as log10 IU/mL in blood and in copies per milliliter in saliva. RESULTS: Viral load in saliva progressively decreased from 7.5 log10 at birth to 3.3 log10 at month 24. CMV PCR in saliva was positive in 100% and 96% of infants at 6 and 12 months, respectively. In the first month of life, neonatal saliva viral load of less than 5 log10 was related to a late CMV transplacental passage. Detection in blood was positive in 92% of neonates (147/159) in the first month of life. No viral load threshold values in blood or saliva could be associated with a high risk of sequelae. Neonatal blood viral load of less than 3 log10 IU/mL had a 100% negative predictive value for long-term sequelae. CONCLUSIONS: Viral loads in blood and saliva by CMV PCR testing in congenital infection fall over the first 24 months. In this study of infants affected mainly after primary maternal infection during pregnancy, all salivary samples were positive in the first 6 months of life and sequelae were not seen in infants with neonatal blood viral load of less than 3 log10 IU/mL.

Somatosensory prediction in the premature neonate brain.

Sensory prediction (SP) is at the core of early cognitive development. Impaired SP may be a key to understanding the emergence of neurodevelopmental disorders, however there is little data on how and when this skill emerges. We set out to provide evidence of SP in the brain of premature neonates in the fundamental sensory modality: touch. Using Diffuse Correlation Spectroscopy, we measured blood flow changes in the somatosensory cortex of premature neonates presented with a vibrotactile stimulation-omission sequence. When ISI was fixed, participants presented a decrease in blood flow during stimulus omissions, starting when a stimulus should begin: the expectation of a certain stimulus onset induced deactivation of the somatosensory cortex. When ISI was jittered, we observed an increase in blood flow during omissions: the expectation of a likely but not certain stimulus onset induced activation of the somatosensory cortex. Our results reveal SP in the brain as early as four weeks before term, based on the temporal structure of a unimodal somatosensory stimulation, and show that SP produces opposite regulation of activity in the somatosensory cortex depending on how liable is stimulus onset. Future studies will investigate the predictive value of somatosensory prediction on neurodevelopment in this vulnerable population.

Randomized Controlled Study of a Training Program for Knee and Shoulder Arthrocentesis on Procedural Simulators with Assessment on Cadavers.

OBJECTIVE: The study objective was to assess the efficacy of simulators in improving the competence of students in performing a knee and shoulder arthrocentesis on cadavers and to determine the minimum number of simulator training procedures needed to achieve competence in arthrocentesis. METHODS: Two groups of 15 medical students were each trained to perform a single joint arthrocentesis ("knee group" and "shoulder group") on a simulator to serve as a control for the other. The two groups received the same theoretical training (anatomy, arthrocentesis techniques, ultrasound, and hybrid simulation). Each student punctured the two joints on a cadaver. A student was considered "competent on the cadaver" if they succeeded at two or more arthrocentesis procedures out of the three tests on the joint on which they were trained. The minimum threshold value to be competent was calculated by a receiver operating characteristic curve and the Youden index. An assessment of theoretical knowledge and confidence level in joint arthrocentesis was carried out at the start and end of the study. RESULTS: Twenty-two out of 29 students (75.8%) achieved competence in arthrocentesis at the joint for which they were trained. Of the students in the knee group, 79% were competent on the cadaver's knee versus 60% of the students in the shoulder group (P = 0.43). Of students in the shoulder group, 74% were competent on the cadaver's shoulder versus 57% of students in the knee group (P = 0.45). Four training punctures on a simulator are necessary to achieve competence on a cadaver. The students' confidence level in arthrocentesis increased significantly during the study, as did the students' theoretical knowledge. CONCLUSION: Knee and shoulder arthrocentesis success rates were not statistically different between the two training groups. A minimum number of 4.0 training arthrocentesis on a simulator is needed to achieve competency on a cadaver.

An educational programme in neonatal intensive care units (SEPREVEN): a stepped-wedge, cluster-randomised controlled trial.

BACKGROUND: Patients in neonatal intensive care units (NICUs) are at high risk of adverse events. The effects of medical and paramedical education programmes to reduce these have not yet been assessed. METHODS: In this multicentre, stepped-wedge, cluster-randomised controlled trial done in France, we randomly assigned 12 NICUs to three clusters of four units. Eligible neonates were inpatients in a participating unit for at least 2 days, with a postmenstrual age of 42 weeks or less on admission. Each cluster followed a 4-month multifaceted programme including education about root-cause analysis and care bundles. The primary outcome was the rate of adverse events per 1000 patient-days, measured with a retrospective trigger-tool based chart review masked to allocation of randomly selected files. Analyses used mixed-effects Poisson modelling that adjusted for time. This trial is registered with ClinicalTrials.gov, NCT02598609. FINDINGS: Between Nov 23, 2015, and Nov 2, 2017, event rates were analysed for 3454 patients of these 12 NICUs for 65 830 patient-days. The event rate per 1000 patient-days reduced significantly from the control to the intervention period (33·9 vs 22·6; incidence rate ratio 0·67; 95% CI 0·50-0·88; p=0·0048). INTERPRETATION: A multiprofessional safety-promoting programme in NICUs reduced the rate of adverse events and severe and preventable adverse events in highly vulnerable patients. This programme could significantly improve care offered to critically ill neonates. FUNDING: Solidarity and Health Ministry, France.

The forest, the trees, and the leaves in preterm children: the impact of prematurity on a visual search task containing three-level hierarchical stimuli.

Very preterm (VPT; < 33 gestational weeks) children are at risk of developing visuospatial deficits, including local/global attention deficits. They are also more likely to develop poorer inhibitory control. Here, we investigated, using the same stimuli, the potential local/global attention and inhibitory control deficits of VPT children using three levels compound stimuli (global, intermediate, and local levels), more ecological than the ones used in a classic global/local task (Navon task). We compared the results from 22 VPT children to those of a control group of 21 children to investigate (1) how VPT children processed compound stimuli with three-level information and (2) how inhibitory control in a visual task differs between VPT and control children. The results revealed that VPT children had no difficulty processing information presented at the local level. By contrast, VPT children were impaired when considering the intermediate and global levels of processing in comparison to control children. Finally, a reduced efficiency in VPT children in inhibiting visual distractors was evidenced for the conditions with a larger number of distractors. These results are discussed in terms of neurodevelopmental disorders of both dorsal stream (global visual processing) and prefrontal regions (inhibitory control) in VPT children. Given the central role of visuospatial and inhibitory control in day-to-day situations, the present results provide important clues for pedagogical implications regarding the organization of visual information presented to VPT children.

Variations in patterns of care across neonatal units and their associations with outcomes in very preterm infants: the French EPIPAGE-2 cohort study.

OBJECTIVES: To describe patterns of care for very preterm (VP) babies across neonatal intensive care units (NICUs) and associations with outcomes. DESIGN: Prospective cohort study, EPIPAGE-2. SETTING: France, 2011. PARTICIPANTS: 53 (NICUs); 2135 VP neonates born at 27 to 31 weeks. OUTCOME MEASURES: Clusters of units, defined by the association of practices in five neonatal care domains - respiratory, cardiovascular, nutrition, pain management and neurodevelopmental care. Mortality at 2 years corrected age (CA) or severe/moderate neuro-motor or sensory disabilities and proportion of children with scores below threshold on the neurodevelopmental Ages and Stages Questionnaire (ASQ). METHODS: Hierarchical cluster analysis to identify clusters of units. Comparison of outcomes between clusters, after adjustment for potential cofounders. RESULTS: Three clusters were identified: Cluster 1 with higher proportions of neonates free of mechanical ventilation at 24 hours of life, receiving early enteral feeding, and neurodevelopmental care practices (26 units; n=1118 babies); Cluster 2 with higher levels of patent ductus arteriosus and pain screening (11 units; n=398 babies); Cluster 3 with higher use of respiratory, cardiovascular and pain treatments (16 units; n=619 babies). No difference was observed between clusters for the baseline maternal and babies' characteristics. No differences in outcomes were observed between Clusters 1 and 3. Compared with Cluster 1, mortality at 2 years CA or severe/moderate neuro-motor or sensory disabilities was lower in Cluster 2 (adjusted OR 0.46, 95% CI 0.25 to 0.84) but with higher proportion of children with an ASQ below threshold (adjusted OR 1.49, 95% CI 1.07 to 2.08). CONCLUSION: In French NICUs, care practices for VP babies were non-randomly associated. Differences between clusters were poorly explained by unit or population differences, but were associated with mortality and development at 2 years. Better understanding these variations may help to improve outcomes for VPT babies, as it is likely that some of these discrepancies are unwarranted.

Complex and subtle structural changes in prefrontal cortex induced by inhibitory control training from childhood to adolescence.

A number of training interventions have been designed to improve executive functions and inhibitory control (IC) across the lifespan. Surprisingly, no study has investigated the structural neuroplasticity induced by IC training from childhood to late adolescence, a developmental period characterized by IC efficiency improvement and protracted maturation of prefrontal cortex (PFC) subregions involved in IC. The aim of the present study was to investigate the behavioral and structural changes induced by a 5-week computerized and adaptive IC training in school-aged children (10-year-olds) and in adolescents (16-year-olds). Sixty-four children and 59 adolescents were randomly assigned to an IC (i.e. Color-Word Stroop and Stop-Signal tasks) or an active control (AC) (knowledge- and vocabulary-based tasks) training group. In the pre- and posttraining sessions, participants performed the Color-Word Stroop and Stop-signal tasks, and an anatomical resonance imaging (MRI) was acquired for each of them. Children's IC efficiency improved from the pre- to the posttraining session in boys but not in girls. In adolescents, IC efficiency did not improve after IC training. Similar to the neuroplastic mechanisms observed during brain maturation, we observed IC training-related changes in cortical thickness and cortical surface area in several PFC subregions (e.g. the pars opercularis, triangularis, and orbitalis of the inferior frontal gyri) that were age- and gender-specific. Because no correction for multiple comparisons was applied, the results of our study provide only preliminary evidence of the complex structural neuroplastic mechanisms at the root of behavioral changes in IC efficiency from pre- to posttraining in school-aged children and adolescents.

Comparative study of preterm infants fed new and existing human milk fortifiers showed favourable markers of gastrointestinal status.

AIM: This study examined the influence of different human milk fortifiers on biomarkers of gastrointestinal immaturity and inflammation in preterm infants. METHODS: We report secondary outcomes from a controlled, double-blind, randomised, parallel group study conducted from 2011 to 2014 in neonatal intensive care units at 11 metropolitan hospitals in France, Belgium, Germany, Switzerland and Italy. Preterm infants born at up to 32 weeks or weighing up to 1500 g were randomised to a new powdered human milk fortifier (n = 77) or a control fortifier (n = 76) for a minimum of 21 days. We analysed faecal markers of gut inflammation, namely alpha-1 antitrypsin and calprotectin, and maturity, namely elastase-1. RESULTS: Faecal alpha-1 antitrypsin was slightly lower in the new than control fortifier group after 21 days of full enteral feeding, with a geometric mean and standard deviation of 1.52 ± 1.32 vs 1.82 ± 1.44 mg/g stools (P = .01). There was no significant difference in faecal calprotectin (median [Q1-Q3] of 296 [136-565] µg/g stools in both groups combined at study day 21). Faecal elastase-1 was lower in the new fortifier than control fortifier group (202.5 ± 1.6 vs 257.7 ± 1.5 µg/g stools, P = .016). CONCLUSION: Mean values for each parameter were within the ranges in healthy term infants, indicating favourable markers of gastrointestinal status in both groups. In addition, for faecal calprotectin, the relatively high concentration observed in preterm infants fed fortified human milk suggests that the threshold level for detecting necrotising enterocolitis should be revised.

[Evolution of practices in neonatology]. / Évolution des pratiques en néonatalogie.

The care of newborns has benefited from significant progress over the last twenty years. The discovery of new treatments and technologies, the development of care centred on the infants and their family, ethical reflection, the organisation of support and training for professionals are just some examples. The place of the parents in decision-making processes however needs to be reinforced.

Effect of multi-lumen perfusion line on catheter-related bacteremia in premature infants: study protocol for a cluster-randomized crossover trial.

BACKGROUND: Catheter-related bacteremia (CRB) is the most frequent nosocomial infection in neonatal intensive care unit (NICU) patients, especially in very low-birth-weight infants. Administration of injectable drugs in premature newborn infants has many particularities and several types of infusion incidents have been reported. The Edelvaiss® Multiline NEO device is a novel multi-lumen access infusion device adapted to the specificities of infusion in neonatology. This multicenter, randomized, controlled study was therefore designed to determine whether or not Edelvaiss® Multiline NEO reduces the risk of CRB in preterm newborn infants in an NICU. METHODS/DESIGN: This is a multicenter, randomized, controlled trial, using a cluster-randomized crossover design. Four investigator centers (four clusters) will participate in the study and will be randomized into two groups, corresponding to two different sequences (either the Edelvaiss® Multiline NEO or standard infusion system sequence, then vice versa). A total of 280 patients will be recruited. Infants will be enrolled in the study at the time of placing a single-lumen central venous catheter. Three visits recording specific data are planned in the study protocol. The primary outcome measure is the incidence density (ID) of CRB. For each patient, the total number of catheters and CRB incidents as well as the duration of stay in the NICU will be computed and considered for analysis. DISCUSSION: The study will provide high-quality evidence to determine whether the Multiline NEO device reduces the risk of CRB in preterm newborns in NICUs or not. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02633124 . Registered on 7 December 2015.

Sequelae of Congenital Cytomegalovirus Following Maternal Primary Infections Are Limited to Those Acquired in the First Trimester of Pregnancy.

BACKGROUND: The known relationship between the gestational age at maternal primary infection an the outcome of congenital CMV is based on small, retrospective studies conducted between 1980 and 2011. They reported that 32% and 15% of cases had sequelae following a maternal primary infection in the first and second or the third trimester, respectively. We aimed to revisit this relationship prospectively between 2011 and 2017, using accurate virological tools. METHODS: We collected data on women with a primary infection and an infected child aged at least 1 year at the time of analysis. An accurate determination of the timing of the primary infection was based upon serial measurements of immunoglobulin (Ig) M and IgG and on IgG avidity in sera collected at each trimester. The case outcome was assessed according to a structured follow-up between birth and 48 months. RESULTS: We included 255 women and their 260 fetuses/neonates. The dating of the maternal infection was prospective in 86% of cases and retrospective in 14%. At a median follow-up of 24 months, the proportion of sensorineural hearing loss and/or neurologic sequelae were 32.4% (95% confidence interval [CI] 23.72-42.09) after a maternal primary infection in the first trimester, 0 (95% CI 0-6.49) after an infection in the second trimester, and 0 (95% CI 0-11.95) after an infection in the third trimester (P < .0001). CONCLUSIONS: These results suggest that a cytomegalovirus infection can be severe only when the virus hits the fetus in the embryonic or early fetal period. Recent guidelines recommend auditory follow-ups for at least 5 years for all infected children. This raises parental anxiety and generates significant costs. We suggest that auditory and specialized neurologic follow-ups may be recommended only in cases of a maternal infection in the first trimester.

Growth and Nutritional Biomarkers of Preterm Infants Fed a New Powdered Human Milk Fortifier: A Randomized Trial.

OBJECTIVES: The aim of this study was to assess growth and nutritional biomarkers of preterm infants fed human milk (HM) supplemented with a new powdered HM fortifier (nHMF) or a control HM fortifier (cHMF). The nHMF provides similar energy content, 16% more protein (partially hydrolyzed whey), and higher micronutrient levels than the cHMF, along with medium-chain triglycerides and docosahexaenoic acid. METHODS: In this controlled, multicenter, double-blind study, a sample of preterm infants ≤32 weeks or ≤1500 g were randomized to receive nHMF (n = 77) or cHMF (n = 76) for a minimum of 21 days. Weight gain was evaluated for noninferiority (margin = -1 g/day) and superiority (margin = 0 g/day). Nutritional status and gut inflammation were assessed by blood, urine, and fecal biochemistries. Adverse events were monitored. RESULTS: Adjusted mean weight gain (analysis of covariance) was 2.3 g/day greater in nHMF versus cHMF; the lower limit of the 95% CI (0.4 g/day) exceeded both noninferiority (P < 0.001) and superiority margins (P = 0.01). Weight gain rate (unadjusted) was 18.3 (nHMF) and 16.8 g ·â€Škg ·â€Šday (cHMF) between study days 1 and 21 (D1-D21). Length and head circumference (HC) gains between D1 and D21 were not different. Adjusted weight-for-age z score at D21 and HC-for-age z score at week 40 corrected age were greater in nHMF versus cHMF (P = 0.013, P = 0.003 respectively). nHMF had higher serum blood urea nitrogen, pre-albumin, alkaline phosphatase, and calcium (all within normal ranges; all P ≤ 0.019) at D21 versus cHMF. Both HMFs were well tolerated with similar incidence of gastrointestinal adverse events. CONCLUSIONS: nHMF providing more protein and fat compared to a control fortifier is safe, well-tolerated, and improves the weight gain of preterm infants.

The manual orienting response habituation to repeated tactile stimuli in preterm neonates: Discrimination of stimulus locations and interstimulus intervals.

Preterm infants frequently develop atypical sensory profiles, the tactile modality being particularly affected. However, there is a lack of recent investigation of neonatal tactile perception in a passive context, especially in preterms who are particularly exposed to this tactile stimuli. Our aims were to provide evidence of orienting responses (behavioral modifications directing subject's attention towards stimuli) and habituation to passive tactile stimuli in preterm neonates, to explore their ability to perceive spatial and temporal aspects of the stimulus, and to evaluate the effect of clinical factors on these abilities. We included 61 preterm neonates, born between 32 and 34 weeks of gestational age. At 35 weeks of corrected gestational age, we measured orienting responses (forearm, hand, and fingers movements) during vibrotactile stimulation of their hand and forearm; during a habituation and dishabituation paradigm, the dishabituation being either a location change or a pause in the stimulation sequence. Preterm newborns displayed a manual orienting response to vibrotactile stimuli which significantly decreased when the stimulus was repeated, regardless of the stimulated location on the limb. Habituation was delayed in subjects born at a younger gestational age, smaller birth weight, and having experienced more painful care procedures. Preterm neonates perceived changes in stimulus location and interstimulus time interval. Our findings provide insights on several aspects of the perception of repeated tactile stimuli by preterm neonates, and the first evidence of the early development of temporal processing abilities in the tactile modality. Future work will investigate the links between this ability and neurodevelopmental disorders.

Effects of an intervention program on maternal and paternal parenting stress after preterm birth: A randomized trial.

BACKGROUND: Preterm birth causes parenting stress and increases the risk of developmental disorders in children. Our objective was to assess the impact of an early psychological intervention, Triadic parent-infant Relationship Therapy (TRT), on parenting stress, parental mental health and preterm infant development in the motor, language, social, behavioral and emotional domains at a corrected age of 18months. METHODS: Sixty-five families of preterm infants were randomly assigned to the intervention group (n=33) or the control group (n=32). Families of full-term children (n=24) were also recruited. Intervention focused on the triadic relationship and aimed to improve parenting stress by supporting parental mental health to promote infant development. The main outcome was assessed with the Parenting Stress Index Short Form (PSI-SF). RESULTS: Highly significant differences at 18months were observed for the mother and father in overall PSI-SF scores, with 16.6, and 11.7 points, respectively, in favor of the intervention group. Children in the intervention group demonstrated higher full-scale developmental quotients than the preterm controls (an 8.7-point difference) along with lower scores on behavioral tests (a 5.8-point difference at 18months). At 18months, results for children in the intervention group showed no significant differences compared to the full-term group or were even better. CONCLUSIONS: Our study provides sound evidence for the efficiency of the TRT program to reduce parenting stress and improve parental mental health for both parents, thus fostering the infant's overall development.