Long Term Neurodevelopmental Outcomes after Sevoflurane Neonatal Exposure of Extremely Preterm Children: A Cross-Sectional Observationnal Study.

Sevoflurane, a volatile anesthetic, is used when extremely preterm neonates (EPT) undergo painful procedures. Currently, no existing studies analyze sevoflurane's long-term effects during the EPT's immediate neonatal period. Our primary objective was to compare the EPT's neurocognitive development regardless of any sevoflurane exposure prior to 45 weeks corrected gestational age (GA). We analyzed those live discharges, less than 28 weeks GA, who were either exposed, unexposed, and/or multiply exposed to sevoflurane before 45 weeks GA. All data were obtained from a cross-sectional multicenter study (GPQoL study, NCT01675726). Children, both exposed and non-exposed to sevoflurane, were sampled using a propensity-guided approach. Neurological examinations (Touwen), cognitive and executive functions (WISC IV, NEPSY, Rey figure), and assessments when the children were between 7 and 10 years old, were correlated to their neonatal sevoflurane exposure. There were 139 children in the study. The mean gestational age was 26.2 weeks (±0.8) GA and the mean birth weight was 898 g (±173). The mean age of their evaluation was 8.47 years old (±0.70). Exposure to sevoflurane to the mean corrected age 27.10 (3.37) weeks GA had a significant correlation with cerebral palsy (adjusted odds ratio (aOR): 6.70 (CI 95%: 1.84-32.11)) and other major disorders (cerebral palsy and/or severe cognitive retardation) (aOR: 2.81 [95% CI: 1.13-7.35]). Our results demonstrate the possibility of long-term effects on EPT infants who had a sevoflurane exposure before 45 weeks corrected GA. However, these results will require further confirmation by randomized controlled trials.

Neurobehavioral Phenotype and Dysexecutive Syndrome of Preterm Children: Comorbidity or Trigger? An Update.

Premature birth is a worldwide public health priority. One in ten children is born before 37 weeks of gestational age and, in developed countries, survival rates without major neonatal morbidity are increasing. Although severe sequelae associated with these births have decreased, their neurobehavioral difficulties, often associated in multiple fields, remain stable but still widespread. These neurobehavioral difficulties hamper the normal development of academic achievements and societal integration and intensify the children's needs for rehabilitation during their preschool and academic years. Severe sequelae increase when gestational age decreases. This is even truer if the socio-cultural background is impeded by low income, education and language skills as compared with defined averages. However, moderate and/or minor neurocognitive and/or behavioral difficulties are almost identical for a moderate or a late preterm birth. Obtaining a better clinical description of neurobehavioral characteristics of those pretermly born, once they reach preschool age, is essential to detect behavioral issues as well as early specific cognitive difficulties (working memory, planning, inhibition, language expression and reception, attention and fine motor skills, etc.). Such information would provide a better understanding of the executive functions' role in brain connectivity, neurodevelopment and neuroanatomical correlation with premature encephalopathy.

Effect of Massage with Oil Balanced in Essential Fatty Acids on Development and Lipid Parameters in Very Premature Neonates: A Randomized, Controlled Study.

Background: Oil massage versus only massage can increase preterm newborn development, especially weight gain, via a supposed percutaneous absorption of oil lipids, but data are contradictory. Aims: Investigating whether massage with a vegetable oil balanced in essential fatty acids improves neonatal weight gain, and digestive autonomy as proxy for neuro-development outcomes. Methods: A prospective monocentric randomized study was conducted in very premature newborns who received massage with oil (isio4 10 mL/kg/day, n = 18) versus with no oil (n = 18) for five consecutive days (10-min session twice daily) at a corrected gestational age of 34−35 weeks. Anthropometrics and clinical characteristics were recorded. Plasma triglyceride and total cholesterol concentrations were analyzed with an enzymatic kit. The fatty acid composition (weight%, mg/mL) of total plasma lipids and of red blood cell (RBC) membrane was analyzed by gas chromatography. Results: Weight gain velocity at the end of massage period was 12.3 ± 1.4 g/kg/day with oil vs. 9.8 ± 1.4 g/kg/day with no oil (p = 0.1). Digestive autonomy, plasma lipid parameters, polyunsaturated fatty acids in plasma total lipids or in RBC were comparable. The no oil group displayed a higher RBC level in nervonic acid at discharge (4.3 ± 0.2 vs. 3.4 ± 0.2%; p = 0.025) and in C18:1n-9 plasmalogen species at the end of the massage period and at discharge (0.73 ± 0.06 vs. 0.48 ± 0.06; 0.92 ± 0.06 vs. 0.69 ± 0.06%; p < 0.01), two molecules that are involved in neurodevelopment. Conclusions: The use of isio4 oil did not provide additional benefits for the development of very premature newborns, neither changed lipid metabolism nor polyunsaturated fatty acid biological status, which did not corroborate the existence of a percutaneous route for oil lipid absorption. The reason for different levels of nervonic acid and plasmalogen in RBC remains to be explored.

Predictive value of brain MRI at term-equivalent age in extremely preterm children on neurodevelopmental outcome at school-age.

This study's objective was to correlate the abnormalities in brain MRIs performed at corrected-term age for minor or moderate neurocognitive disorders in children school-age born extremely premature (EPT) and without serious sequelae such as autism, cerebral palsy, mental impairment. Data were issued from a cross-sectional multicenter study (GP-Qol study, number NCT01675726). Clinical examination and psychometric assessments were performed when the children were between 7 and 10 years old during a day-long evaluation. Term-equivalent age brain MRIs on EPT were analyzed with a standardized scoring system. There were 114 children included in the study. The mean age at the time of evaluation, was 8.47 years old (± 0.70). 59% of children with at least one cognitive impairment and 53% who had a dysexecutive disorder. Only ten EPT (8.7%) presented moderate to severe white and grey matter abnormalities. These moderate to severe grey matter abnormalities were associated with at least two abnormal executive functions [OR 3.08 (95% CI 1.04-8.79), p = 0.04] and language delay [OR 3.25 (95% CI 1.03-9.80), p = 0.04]. These results remained significant in the multivariate analysis. Moderate to severe ventricular dilatation abnormalities (15%, n = 17) were associated with ideomotor dyspraxia [OR 7.49 (95% CI 1.48-35.95), p = 0.02] and remained significant in multivariate analysis [OR 11.2 (95% CI 1.45-131.4), p = 0.02]. Biparietal corrected diameters were moderate abnormal in 20% of cases (n = 23) and were associated to visuo spatial integration delay [OR 4.13 (95% CI 1.23-13.63), p = 0.02]. Cerebral MRI at term-equivalent age with scoring system analysis can provide information on long-term neuropsychological outcomes at school-age in EPTs children having no severe disability.

Cardio-Respiratory Events and Food Autonomy Responses to Early Uni-Modal Orofacial Stimulation in Very Premature Babies: A Randomized, Controlled Study.

Uni-modal orofacial stimulation (OFS) for preventing very preterm infants' oral disorders is highly controversial. Our study sought to demonstrate that OFS reduced cardio-respiratory events and improved food autonomy in a population of very preterm infants. Our study was randomized, controlled, prospective, and unicentric. The preterm included were born between 26-29 weeks gestational age (GA) with a corrected postnatal age <33 weeks GA. They were randomized into two groups: the experimental group underwent OFS, according to a protocol established, over 10 consecutive days, and the control group underwent no OFS. The primary outcome was the number of cardiorespiratory events: apnea-bradycardia (with or without desaturations) or number of isolated desaturations, which were evaluated at four separate times. Measurements occurred during the first, fourth and eighth independent feedings. Seventeen patients were included in the experimental group and 18 in the control group. The number of cardiorespiratory events for all independent feeding times was significantly reduced in the OFS group (p = 0.003) with univariate analysis, but not with multivariable analysis. The quantity of milk ingested during the first autonomous feeding was higher in the experimental group. The acquisition of food autonomy and the duration of hospitalization were similar in the two groups. While our study does not affirm that an early unimodal OFS improves premature infants' cardiorespiratory evolution and/or the acquisition of food autonomy, it does indicate an improved food efficiency during their first autonomous feedings.

Sevoflurane for central catheter placement in neonatal intensive care: a randomized trial.

OBJECTIVE: To compare the efficacy and safety of sevoflurane deep sedation with glucose and nonnutritive sucking (GNNS) in reducing the duration of the procedure and in preventing pain-related effects during peripherally inserted central catheter (PICC) placement. BACKGROUND: PICC placement in neonatal intensive care is a delicate and stressful procedure that requires pain prevention. GNNS has been recommended in this situation but remain often inefficient. METHODS: We designed a randomized controlled study in a sixteen-bed pediatric and neonatal unit in a tertiary hospital. Fifty-nine neonates at >28 weeks of gestation with continuous positive airway pressure or invasive mechanical ventilation and requiring PICC placement were included. Patients were randomized to receive inhaled sevoflurane (IS) or glucose and non-nutritive sucking (GNNS). Procedural duration and conditions, hemodynamic and respiratory parameters, occurrence of movements and complications were compared (http://clinicaltrials.gov trial register no. NCT00420693). RESULTS: The two groups had similar demographics. There were no between-group differences in procedural duration (P = 0.84) despite greater immobility in IS group (P = 0.017). IS was also associated with fewer episodes of hypertension (P = 0.003), tachycardia (P < 0.001), and bradycardia (P = 0.02). Occurrences of hypotension were not different between the groups (P = 0.06). The GNNS group showed more desaturation during the 4 h after the procedure (P = 0.03). Complications during intensive care stay did not differ between groups. CONCLUSION: Inhaled sevoflurane does not make easier catheters placement but prevent pain-related symptoms. Because sevoflurane is responsible for hypotension, it requires careful monitoring and treatment adaptation.

Analgesic Effect of Maternal Human Milk Odor on Premature Neonates: A Randomized Controlled Trial.

BACKGROUND: Two studies have demonstrated an analgesic effect of maternal milk odor in preterm neonates, without specifying the method of olfactory stimulation. Research aim: This study aimed to assess the analgesic effect of maternal milk odor in preterm neonates by using a standardized method of olfactory stimulation. METHODS: This trial was prospective, randomized, controlled, double blinded, and centrally administered. The inclusion criteria for breastfed infants included being born between 30 and 36 weeks + 6 days gestational age and being less than 10 days postnatal age. There were two groups: (a) A maternal milk odor group underwent a venipuncture with a diffuser emitting their own mother's milk odor and (2) a control group underwent a venipuncture with an odorless diffuser. The primary outcome was the Premature Infant Pain Profile (PIPP) score, with secondary outcomes being the French scale of neonatal pain-Douleur Aiguë du Nouveau-né (DAN) scale-and crying duration. All neonates were given a dummy. RESULTS: Our study included 16 neonates in the maternal milk odor group and 17 in the control group. Neonates exposed to their own mother's milk odor had a significantly lower median PIPP score during venipuncture compared with the control group (6.3 [interquartile range (IQR) = 5-10] versus 12.0 [IQR = 7-13], p = .03). There was no significant difference between the DAN scores in the two groups ( p = .06). Maternal milk odor significantly reduced crying duration after venipuncture (0 [IQR = 0-0] versus 0 [IQR = 0-18], p = .04). CONCLUSION: Maternal milk odor has an analgesic effect on preterm neonates.