BACKGROUND AND OBJECTIVES: Stabilization of preterm infants after birth frequently requires oxygen supplementation. At present the optimal initial oxygen inspiratory fraction (Fio2) for preterm stabilization after birth is still under debate. We aimed to compare neurodevelopmental outcomes of extremely preterm infants at 24 months corrected age randomly assigned to be stabilized after birth with an initial Fio2 of 0.3 versus 0.6 to 0.65 in 3 academic centers from Spain and the Netherlands.METHODS: Randomized, controlled, double-blinded, multicenter, international clinical trial enrolling preterm infants <32 weeks’ gestation assigned to an initial Fio2 of 0.3 (Lowox group) or 0.6 to 0.65 (Hiox group). During stabilization, arterial pulse oxygen saturation and heart rate were continuously monitored and Fio2 was individually titrated to keep infants within recommended ranges. At 24 months, blinded researchers used the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) to assess visual acuity, neurosensory deafness, and language skills.RESULTS: A total of 253 infants were recruited and 206 (81.4%) completed follow-up. No differences in perinatal characteristics, oxidative stress, or morbidities during the neonatal period were assessed. Mortality at hospital discharge or when follow-up was completed didn’t show differences between the groups. No differences regarding Bayley-III scale scores (motor, cognitive, and language composites), neurosensorial handicaps, cerebral palsy, or language skills between groups were found.CONCLUSIONS: The use of an initial lower (0.3) or higher (0.6–0.65) Fio2 during stabilization of extremely preterm infants in the delivery room does not influence survival or neurodevelopmental outcomes at 24 months.

Human milk contains non-nutritional factors that promote intestinal maturation and protect against infectious and inflammatory conditions. In the Neonatal Intensive Care Unit (NICU) setting, donor milk (DM) is recommended when availability of own mother’s milk (OMM) is not enough. Our aim was to compare the incidence of necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in very preterm infants (VPI) after the introduction of DM. Growth and breastfeeding rates were examined as secondary outcomes. Single center, observational and retrospective cohort study comparing 227 VPI admitted to our neonatal unit before (Group 1, n = 99) and after (Group 2, n = 128) DM introduction. Enteral nutrition was started earlier after DM availability (2.6 ± 1.1 vs. 2.1 ± 1 days, p = 0.001). Incidence of NEC decreased in group 2 (9.1% vs. 3.4%, p = 0.055), especially in those born between 28 and 32 weeks (5.4 vs. 0.0%, p = 0.044). Surgical NEC was also less frequent. Suffering NEC was 4 times more likely in group 1 (multivariate analysis). Availability of DM did not impact breastfeeding rates or preterm growth. Our findings support the protective role of DM against NEC, particularly in non-extreme VPI, a group less frequently included in clinical guidelines and research studies on the use of DM.

Aim: To analyze different methods to assess postnatal growth in a cohort of very premature infants (VPI) in a clinical setting and identify potential early markers of growth failure. Methods: Study of growth determinants in VPI (≤32 weeks) during hospital stay. Nutritional intakes and clinical evolution were recorded. Growth velocity (GV: g/kg/day), extrauterine growth restriction (%) (EUGR: weight < 10th centile, z-score < −1.28) and postnatal growth failure (PGF: fall in z-score > 1.34) at 36 weeks postmenstrual age (PMA) were calculated. Associations between growth and clinical or nutritional variables were explored (linear and logistic regression). Results: Sample: 197 VPI. GV in IUGR patients was higher than in non-IUGRs (28 days of life and discharge). At 36 weeks PMA 66.0% of VPIs, including all but one of the IUGR patients, were EUGR. Prevalence of PGF at the same time was 67.4% (IUGR patients: 48.1%; non-IUGRs: 70.5% (p = 0.022)). Variables related to PGF at 36 weeks PMA were initial weight loss (%), need for oxygen and lower parenteral lipids in the first week. Conclusions: The analysis of z-scores was better suited to identify postnatal growth faltering. PGF could be reduced by minimising initial weight loss and assuring adequate nutrition in patients at risk.

There is evidence that delivery room resuscitation of very preterm infants often deviates from internationally recommended guidelines. There were no published data in Spain regarding the quality of neonatal resuscitation. Therefore, we decided to evaluate resuscitation team adherence to neonatal resuscitation guidelines after birth in very preterm infants. We conducted an observational study. We video recorded resuscitations of preterm infants < 32 weeks’ gestational age and evaluated every step during resuscitation according to a score-sheet specifically designed for this purpose, following Carbine’s method, where higher scores indicated that more intense resuscitation maneuvers were required. We divided the score achieved by the total possible points per patient to obtain the percentage of adherence to the algorithm. We also compared resuscitations performed by staff neonatologists to those performed by pediatricians on-call. We compared percentages of adherence to the algorithm with the Chi-square test for large groups and Fisher’s exact test for smaller groups. We compared assigned Apgar scores with those given after analyzing the recordings and described them by their median and interquartile range. We measured the interrater agreement between Apgar scores with Cohen’s kappa coefficient. Linear and logarithmic regressions were drawn to characterize the pattern of algorithm adherence. Statistical analysis was performed using SPSS V.20. A p-value < 0.05 was considered significant. Our Hospital Ethics Committee approved this project, and we obtained parental written consent beforehand. Sixteen percent of our resuscitations followed the algorithm. The number of mistakes per resuscitation was low. Global adherence to the algorithm was 80.9%. Ventilation and surfactant administration were performed best, whereas preparation and initial steps were done with worse adherence to the algorithm. Intubation required, on average, 2.2 attempts; success on the first attempt happened in 33.3% of cases. Only 12.5% of intubations were achieved within the allotted 30 s. Many errors were attributable to timing. Resuscitations led by pediatricians on-call were performed as correctly as those by staff neonatologists. Resuscitation often deviates from the internationally recognized algorithm. Perfectly performed resuscitations are infrequent, although global adherence to the algorithm is high. Neonatologists and pediatricians need intubation training.

Very preterm infants (VPI, born at or before 32 weeks of gestation) are at risk of adverse health outcomes, from which they might be partially protected with appropriate postnatal nutrition and growth. Metabolic processes or biochemical markers associated to extrauterine growth restriction (EUGR) have not been identified. We applied untargeted metabolomics to plasma samples of VPI with adequate weight for gestational age at birth and with different growth trajectories (29 well-grown, 22 EUGR) at the time of hospital discharge. A multivariate analysis showed significantly higher levels of amino-acids in well-grown patients. Other metabolites were also identified as statistically significant in the comparison between groups. Relevant differences (with corrections for multiple comparison) were found in levels of glycerophospholipids, sphingolipids and other lipids. Levels of many of the biochemical species decreased progressively as the level of growth restriction increased in severity. In conclusion, an untargeted metabolomic approach uncovered previously unknown differences in the levels of a range of plasma metabolites between well grown and EUGR infants at the time of discharge. Our findings open speculation about pathways involved in growth failure in preterm infants and the long-term relevance of this metabolic differences, as well as helping in the definition of potential biomarkers.