Outcomes at 7 Years of Age of Former Very Preterm Neonates with Repeated Surfactant Treatment for Prolonged Respiratory Distress in the Neonatal Period.

This study aimed at evaluating the 7-year outcomes of 118 very preterm newborns (VPNs, gestational age = 26 ± 1.4 w) involved in a randomized controlled trial. They presented neonatal respiratory distress (RDS), requiring ventilation for 14 ± 2 days post-natal age (PNA). A repeated instillation of 200 mg/kg poractant alfa (SURF) did not improve early bronchopulmonary dysplasia, but the SURF infants needed less re-hospitalization than the controls for respiratory problems at 1- and 2-year PNA. There was no growth difference at 7.1 ± 0.3 years between 41 SURF infants and 36 controls (80% of the eligible children), and 7.9% SURF infants vs. 28.6% controls presented asthma (p = 0.021). The children underwent cognitive assessment (WISC IV) and pulmonary function testing (PFT), measuring their spirometry, lung volume, and airway resistance. The spirometry measures showed differences (p < 0.05) between the SURF infants and the controls (mean ± standard deviation (median z-score)) for FEV1 (L/s) (1.188 ± 0.690(-0.803) vs. 1.080 ± 0.243 (-1.446)); FEV1 after betamimetics (1.244 ± 0.183(-0.525) vs. 1.091 ± 0.20(-1.342)); FVC (L) (1.402 ± 0.217 (-0.406) vs. 1.265 ± 0.267 (-1.141)), and FVC after betamimetics (1.452 ± 0.237 (-0.241) vs. 1.279 ± 0.264 (-1.020)). PFT showed no differences in the volumes or airway resistance. The global IQ median (interquartile range) was 89 (82:99) vs. 89 (76:98), with 61% of the children >85 in both groups. Repeated surfactant treatment in VPNs presenting severe RDS led to the attenuation of early lung injuries, with an impact on long-term pulmonary sequelae, without differences in neurodevelopmental outcomes.

Influence of body mobility on attention networks in school-aged prematurely born children: A controlled trial.

School-aged prematurely born children (PC) have a higher risk of academic difficulties, which may be partly explained by attention difficulties. It has been suggested that children's attentional performance might be influenced by their body posture and spontaneous body motion. The aim of this study (ClinicalTrials.gov - NCT03125447) was to test the influence of three body mobility conditions on the three functions of attention (alertness, orienting, and executive control) among school-aged PC vs. term-born children (TC). Notably, 21 PC and 21 TC performed the Attention Network Test for Children in three body mobility conditions, namely, sitting and standing imposed fixed postures and a free-to-move condition. The children's median reaction times were compared between trials (1) with and without alerting cues, (2) with valid and invalid orienting cues, and (3) with and without distracting information, to calculate the performance of alertness, orienting, and executive control, respectively. Results showed that with distracting information, PC exhibited significantly slower responses in the standing-still posture than in the sitting-still posture (1,077 ± 240 vs. 1,175 ± 273 ms, p < 0.05), but not TC. No difference was observed with the free-to-move condition. PC and TC did not significantly differ in alertness or orienting, regardless of body mobility condition. These data suggest that PC must use executive resources to stand still and maintain position, which impairs their performance during executive tasks. We speculate that these results may be related to less developed postural control and motor inhibition in PC.

[Supporting the suffering of caregivers in neonatal palliative care]. / Accompagner la souffrance des soignants exerçant en soins palliatifs néonataux.

Accompanying newborns in palliative care remains difficult for professionals. Representations, fears and real difficulties are all factors that put them to the test. Supervision in conjunction with a pediatric palliative care resource team could be an effective way to prevent burnout and improve the quality of care.

Body Mobility and Attention Networks in 6- to 7-Year-Old Children.

Learning in 6- to 7-year-old children is strongly influenced by three functions of attention: alertness, orienting, and executive control. These functions share a close relationship with body mobility, such as the posture adopted or a request to stay still during tasks. The aim of this study (ClinicalTrials.gov) was to analyze the influence of body posture (standing versus sitting) and the influence of these imposed postures compared to a free body mobility on attention functions in 6- to 7-year-old children. Twenty-one children (11 girls) with a mean age of 6.7±0.6years performed the Attention Network Test for Children in three-body mobility conditions: sitting still, standing still, and free to move. Three attentional scores were calculated which would separately reflect performance of alertness, orienting, and executive control. Overall, no difference in alertness performance was found between the three bodily mobility conditions. In addition, our results suggest a general poor orienting performance in children, whatever the body mobility condition, which might be related to their young age. Finally, children improved their executive control performance when they stood still, probably due to an improvement in arousal and mental state.

Mobility may impact attention abilities in healthy term or prematurely born children at 7-years of age: protocol for an intervention controlled trial.

BACKGROUND: Seven years of age is a milestone for learning basic knowledge that is strongly related to attention abilities such as Alerting, Orienting, and Inhibition function, allowing for appropriate adaptation to primary school. These attention abilities are also influenced by gestational age at birth in a complex manner, indicating an area of weakness in prematurely born children. Furthermore, recent studies suggest that allowing children to have freedom of movement during learning may improve their attention level and school performance. The purpose of the present study is to determine the influence of mobility on the attentional components that may impact learning abilities in children aged 7-years who were born at term and prematurely. METHODS: This prospective, randomized, controlled trial will focus on psychometric testing of attentional abilities assessed with the Attention Network Test for Child (Child ANT) and involves a mixed measurement design. Forty-eight children aged 7-years, half of whom were premature at birth and in their expected grade without learning difficulties will be included after parental consent. They will be equipped with a head-mounted display in which the Child ANT will be presented. The association of different flankers and pre-cues will allow the measurement of the development level of Alerting, Orienting, and Inhibition function. The task will be composed of one experimental block of trials randomly performed per posture: seated, standing, or free. DISCUSSION: This study will assess the contribution of mobility in specific attentional contexts that are usually present during fundamental learning in children. New pedagogical formats of teaching could consider these findings, and new pedagogical tools enabling free spontaneous child mobility might be designed. Moreover, a small percentage of children integrating into the educational system are born prematurely. These children, often considered immature and hyperactive, could benefit from educational innovations that enhance their attention abilities, thereby improving their adaptation to primary school. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov ( NCT03125447 ).

Expiratory Flow - Vital Capacity: Airway - Lung Dysanapsis in 7 Year Olds Born Very Preterm?

An index normalizing airway dimension for lung size derived from spirometry was found inversely correlated to lung size in school children born very preterm, indicating larger alveolar volumes draining into comparatively smaller airways. In contrast in children born full term the index was independent of lung size.

Late Surfactant Administration in Very Preterm Neonates With Prolonged Respiratory Distress and Pulmonary Outcome at 1 Year of Age: A Randomized Clinical Trial.

IMPORTANCE: Although immature neonate survival has improved, there is an increased risk of developing bronchopulmonary dysplasia, leading to significant respiratory morbidity. Measures to reduce bronchopulmonary dysplasia are not always effective or have important adverse effects. OBJECTIVE: To evaluate the effect of late surfactant administration in infants with prolonged respiratory distress on ventilation duration, respiratory outcome at 36 weeks' postmenstrual age, and at 1 year postnatal age. DESIGN, SETTING, AND PARTICIPANTS: Double-blind randomized clinical trial at 13 level III French perinatal centers. Participants included 118 neonates at less than 33 weeks' gestation who still required mechanical ventilation on day 14 (SD, 2) with fraction of inspired oxygen of more than 0.30. All survivors were eligible for follow-up. We performed an intent-to-treat analysis. INTERVENTIONS: Infants received 200 mg/kg of poractant alfa (surfactant) or air after randomization. At 1 year, after parents' interview, infants underwent physical examination by pediatricians not aware of the randomization. MAIN OUTCOMES AND MEASURES: The duration of ventilation was the primary outcome. The combined outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age and respiratory morbidity at 1 year of age were the main secondary outcome measures. RESULTS: Of the 118 infants who participated in the study, 65 (55%) were male. Fraction of inspired oxygen requirements dropped after surfactant, but not air, for up to 24 hours after instillation (0.36 [0.11] vs 0.43 [0.18]; P < .005). Severe bronchopulmonary dysplasia/death rates at 36 weeks' postmenstrual age were similar (27.1% vs 35.6%; P = .32). Less surfactant-treated infants needed rehospitalization for respiratory problems after discharge (28.3% vs 51.1%; P = .03); 39.5% vs 50% needed respiratory physical therapy (P = .35). No difference was observed for weight (7.8 [1.2] kg vs 7.6 [1.1] kg), height (69 [5] cm vs 69 [3] cm), and head circumference (44.4 [1.7] cm vs 44.2 [1.7] cm) measured at follow-up, nor for neurodevelopment outcome. CONCLUSIONS AND RELEVANCE: Late surfactant administration did not alter the early course of bronchopulmonary dysplasia. However, surfactant-treated infants had reduced respiratory morbidity prior to 1 year of age. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01039285.

Exercise-induced bronchoconstriction in school-age children born extremely preterm.

BACKGROUND: School children born preterm often show airway hyperresponsiveness to methacholine or histamine. Less attention has been paid to their airway response to exercise, an important point because of the role of exercise in the child's daily life. The aim of this study was to describe the characteristics of, and potential determinants to, the airway response to exercise in children born extremely preterm. METHODS: Forty-two nonasthmatic nonatopic children born before 32 wk gestation were compared with 27 healthy nonasthmatic nonatopic term children at age 7. Spirometry and respiratory impedance were measured at baseline and repeated after a single-step 6-min treadmill exercise in a climate-controlled room. RESULTS: The preterm group showed significant broncho-constriction induced by exercise. Prematurity, but not low baseline lung function, neonatal oxygen supplementation, mechanical ventilation, chronic lung disease, or maternal smoking, was a determinant of exercise-induced bronchoconstriction. CONCLUSION: Children born extremely preterm present significant exercise-induced airway obstruction at age 7. The response has different characteristics from that occurring in asthmatics and is likely to express airway noneosinophilic inflammation.

CPAP and the preterm infant: lessons from the COIN trial and other studies.

Bronchopulmonary dysplasia is associated with ventilation. Nasal continuous positive airway pressure (nCPAP) allows earlier weaning in ventilated infants. Starting nCPAP from shortly after birth to prevent ventilation has been questioned because it prevents an early use of surfactant. The efficacy of early surfactant was assessed in infants electively intubated, few having received antenatal steroids. Recent trials using nCPAP from birth in 25 to 28 week infants describe more customised strategies: in the COIN trial, 27-28 week infants breathing at birth benefit the most from nCPAP. Fewer infants received oxygen on day 28; they had fewer days of ventilation and no increase in morbidities despite having more pneumothoraces. The REVE trial suggests that intubation with early surfactant administration followed by nCPAP mostly benefits to 25-26 week infants. Thus, nCPAP is feasible from birth. The overall strategy should take into account infants' gestational age, maturation and behaviour in the delivery room.

[Infants of drug-addicted mothers: pitfalls of replacement therapy]. / Enfants de mères toxicomanes: les aléas de la substitution.

Maternal drug addiction can cause problems for the fetus and the newborn, and hamper long-term development. The prevalence of drug addiction during pregnancy varies from 1 % to more than 10 % depending on the country and the maternity unit. Management of these mothers can be further complicated by medical, social and psychological problems. Compared to methadone, heroin replacement therapy with buprenorphine provides better stabilization of the mother and causes fewer withdrawal symptoms in the newborn. Despite numerous publications on the effects of this partly preventive medication, data on buprenorphine pharmacology at birth are scarce. In this study, 20 newborns of mothers using oral buprenorphine were observed until the end of the withdrawal syndrome, when present. Buprenorphine plasma levels were determined with HPLC and mass spectrometry in the mother at delivery and in the newborn at birth (cord blood), 24 and 48 hours. Fifteen newborns were born at term (mean +/- SD birth weight 3029 +/- 273 g), and the other five between 32 and 36 weeks. All Apgar scores were > or =7. Withdrawal symptoms were observed in 8 of the 15 infants born to mothers taking buprenorphine alone, and lasted between 5 and 35 days. The newborns were classified in three groups. Groups I (N8) and II (N7) comprised newborns with and without withdrawal symptoms, respectively. In group III (N5), the mothers were polyintoxicated (as shown by urinary drug or neurotropic substance screening) and the newborns were symptomatic for 1 to 69 days. Buprenorphine plasma levels in the mothers ranged from 0 to 2.9 microg/L, suggesting large differences in adherence. At birth there was no significant difference in the mean plasma buprenorphine level between newborns with and without withdrawal symptoms; the respective values were 0.7 (0.4-1.3) and 0.5 (0-0.6) microg/L. In asymptomatic newborns (group II), buprenorphine was no longer detectable at 48 h, whereas in symptomatic newborns (group I), the mean level rose from 0.7 microg/l at birth to 1.5 microg/L at 48 h (+114 %). In the absence of breastfeeding, this increase appears to be related to tissue release of this strongly lipophilic compound. The difference in plasma buprenorphine kinetics between groups I and II might be explained by genetic polymorphism of drug-metabolizing enzymes. The paradoxically high plasma buprenorphine levels at 48 hours in infants with withdrawal symptoms are intriguing. One possibility is that the mothers missed one or several doses of buprenorphine around the time of delivery, in the same way that smoking mothers tend to cut down during the last days of their pregnancy. If buprenorphine plasma levels at birth appear to reflect maternal adherence, cord blood levels do not predict the risk of a withdrawal syndrome. In contrast, the level at 48 h might help to discriminate between high- and low-risk newborns. Pregnant women on opiate replacement therapy must be delivered in maternity units with adequate neonatal facilities.

Early inhaled nitric oxide improves oxidative balance in very preterm infants.

Inhaled nitric oxide (iNO) improves oxygenation in premature infants, but concern has been raised about its potential oxidative toxicity. We designed this study to assess the oxidative balance in premature infants who were exposed to low dose iNO and the relationship with their clinical outcome on day 28 of life. A total of 274 infants who were <32 wk gestation were randomized at birth to receive 5 ppm of iNO if they presented with hypoxemic respiratory failure. Nonhypoxemic infants were studied as the reference group. Blood samples were withdrawn 24 h apart, within the first 4 d of life, to assess malondialdehyde (MDA) concentration as oxidative stress marker and total plasmatic glutathione (GSH), intraerythrocyte GSH peroxidase, and GSH reductase activities as antioxidant defenses. After 24 h, the rise in MDA was blunted in the iNO group compared with controls and was close to the reference infants. Conversely, GSH was more stable in the iNO group, when there was no difference for the GSH peroxidase and GSH reductase activities. On day 28, Oxygen dependence was linked with a higher increase in MDA as was the risk for death, whereas intraventricular hemorrhage was associated with a higher initial drop in GSH. Early low-dose iNO in hypoxemic preterm infants improves oxidative balance and seems to be clinically beneficial up to day 28 of life.