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In this open, randomized, multicenter trial involving extremely-low-birth-weight preterm infants, the use of a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity.

This report of the three BOOST II trials, undertaken to examine optimum oxygen saturation in extremely preterm infants, showed that targeting levels below 90% with the use of current oximeter calibrations was associated with increased mortality. The clinically appropriate range for oxygen saturation in preterm infants is unknown. Trials in the 1950s showed that unrestricted oxygen increased the rate of severe retinopathy of prematurity. However, when oxygen was subsequently restricted, increased mortality was observed. 1 The first Benefits of Oxygen Saturation Targeting (BOOST) trial showed that in preterm infants who were still receiving oxygen at 32 weeks' gestation, targeting a higher oxygen-saturation range prolonged oxygen dependence. 2 Observational studies suggested that higher oxygen-saturation levels may increase rates of retinopathy of prematurity. 3 – 5 In five randomized, masked trials with similar protocols conducted in the United States, 6 Australia, New Zealand, . . .

Background Bovine colostrum (BC) contains a range of milk bioactive components, and it is unknown how human milk fortification with BC affects glucose-regulatory hormones in very preterm infants (VPIs). This study aimed to investigate the associations between hormone concentrations and fortification type, birth weight (appropriate/small for gestational age, AGA/SGA), milk intake, postnatal age, and body growth. Methods 225 VPIs were randomized to fortification with BC or conventional fortifier (CF). Plasma hormones were measured before, one and two weeks after start of fortification. ΔZ-scores from birth to 35 weeks postmenstrual age were calculated. Results Compared with CF, infants fortified with BC had higher plasma GLP-1, GIP, glucagon, and leptin concentrations after start of fortification. Prior to fortification, leptin concentrations were negatively associated with growth, while IGF-1 concentrations associated positively with growth during fortification. In AGA infants, hormone concentrations generally increased after one week of fortification. Relative to AGA infants, SGA infants showed reduced IGF-1 and leptin concentrations. Conclusion Fortification with BC increased the plasma concentrations of several glucose-regulatory hormones. Concentrations of IGF-1 were positively, and leptin negatively, associated with growth. Glucose-regulatory hormone levels were affected by birth weight, milk intake and postnatal age, but not closely associated with growth in VPIs. Impact Little is known about the variation in glucose-regulatory hormones in the early life of very preterm infants (VPIs). This study shows that the levels of glucose-regulatory hormones in plasma of VPIs are highly variable and modified by birth weight (appropriate or small for gestational age, AGA or SGA), the type of fortifier, enteral nutritional intake, and advancing postnatal age. The results confirm that IGF-1 levels are positively associated with early postnatal growth in VPIs, yet the levels of both IGF-1 and other glucose-regulatory hormones appeared to explain only a small part of the overall variation in growth rates.

In two trials involving preterm infants, an oxygen-saturation target of 85 to 89% versus 91 to 95% resulted in nonsignificantly higher rates of death or disability at 2 years but in significantly increased risks of the combined outcome and of death alone in post hoc combined analyses. The determination of the range of oxygen saturation that minimizes the competing risks of death, retinopathy of prematurity, and later disability in preterm infants is important. 1 , 2 The U.K. and Australian Benefits of Oxygen Saturation Targeting (BOOST)–II trials are two of five comparative effectiveness trials of the targeting of oxygen saturation in infants born before 28 weeks’ gestation. 3 – 8 These trials, known collectively as the Neonatal Oxygen Prospective Meta-analysis (NeOProM) Collaboration, were designed to compare the effects of a lower oxygen-saturation target range (85 to 89%) versus a higher target range (91 to 95%) on a primary outcome of death . . .

Significance Newborns can hear their mother’s voice and heartbeat sounds before birth. However, it is unknown whether, how early, and to what extent the newborn's brain is shaped by exposure to such maternal sounds. This study provides evidence for experience-dependent plasticity in the auditory cortex in preterm newborns exposed to authentic recordings of maternal sounds before full-term brain maturation. We demonstrate that the auditory cortex is more adaptive to womb-like maternal sounds than to environmental noise. Results are supported by the biological fact that maternal sounds would otherwise be present in utero had the baby not been born prematurely. We theorize that exposure to maternal sounds may provide newborns with the auditory fitness necessary to shape the brain for hearing and language development. Brain development is largely shaped by early sensory experience. However, it is currently unknown whether, how early, and to what extent the newborn’s brain is shaped by exposure to maternal sounds when the brain is most sensitive to early life programming. The present study examined this question in 40 infants born extremely prematurely (between 25- and 32-wk gestation) in the first month of life. Newborns were randomized to receive auditory enrichment in the form of audio recordings of maternal sounds (including their mother’s voice and heartbeat) or routine exposure to hospital environmental noise. The groups were otherwise medically and demographically comparable. Cranial ultrasonography measurements were obtained at 30 ± 3 d of life. Results show that newborns exposed to maternal sounds had a significantly larger auditory cortex (AC) bilaterally compared with control newborns receiving standard care. The magnitude of the right and left AC thickness was significantly correlated with gestational age but not with the duration of sound exposure. Measurements of head circumference and the widths of the frontal horn (FH) and the corpus callosum (CC) were not significantly different between the two groups. This study provides evidence for experience-dependent plasticity in the primary AC before the brain has reached full-term maturation. Our results demonstrate that despite the immaturity of the auditory pathways, the AC is more adaptive to maternal sounds than environmental noise. Further studies are needed to better understand the neural processes underlying this early brain plasticity and its functional implications for future hearing and language development.

Background Preterm birth and its complications are the primary cause of death among children under the age of 5. Among the survivors, morbidity both perinatally and later in life is common. The dawn of novel technical platforms for comprehensive and sensitive analysis of protein profiles in blood has opened up new possibilities to study both health and disease with significant clinical accuracy, here used to study the preterm infant and the physiological changes of the transition from intrauterine to extrauterine life. Methods We have performed in-depth analysis of the protein profiles of 14 extremely preterm infants using longitudinal sampling. Medical variables were integrated with extensive profiling of 448 unique protein targets. Results The preterm infants have a distinct unified protein profile in blood directly at birth regardless of clinical background; however, the pattern changed profoundly postnatally, expressing more diverse profiles only 1 week later and further on up to term-equivalent age. Clusters of proteins depending on temporal trend were identified. Conclusion The protein profiles and the temporal trends here described will contribute to the understanding of the physiological changes in the intrauterine−extrauterine transition, which is essential to adjust early-in-life interventions to prone a normal development in the vulnerable preterm infants. Impact We have performed longitudinal and in-depth analysis of the protein profiles of 14 extremely preterm infants using a novel multiplex protein analysis platform. The preterm infants had a distinct unified protein profile in blood directly at birth regardless of clinical background. The pattern changed dramatically postnatally, expressing more diverse profiles only 1 week later and further on up to term-equivalent age. Certain clusters of proteins were identified depending on their temporal trend, including several liver and immune proteins. The study contributes to the understanding of the physiological changes in the intrauterine−extrauterine transition.

ObjectiveTo investigate the impact of breast milk (BM) intake on body composition at term in very preterm infants.DesignPreplanned secondary analysis of the Nutritional Evaluation and Optimisation in Neonates Study, a 2-by-2 factorial randomised controlled trial of preterm parenteral nutrition (PN).SettingFour National Health Service hospitals in London and South-East England.PatientsInfants born at <31 weeks of gestation; infants with life-threatening congenital abnormalities and those unable to receive trial PN within 24 hours of birth were ineligible. 133 infants survived and underwent whole-body MRI at term (37–44 weeks postmenstrual age).Main outcome measuresNon-adipose tissue mass (non-ATM), ATM and ATM as a percentage of body weight (% ATM) at term.ResultsCompared with the exclusively BM group (proportion of BM=100% milk, n=56), predominantly formula-fed infants (BM ≤50%, n=38) weighed 283.6 g (95% CI 121.6 to 445.6) more, had 257.4 g (139.1–375.7) more non-ATM and a greater positive weight Z-score change between birth and term. There were no significant differences in weight, non-ATM and weight Z-score change between the exclusively and predominantly BM (BM 51%–99%, n=39) groups. Compared with the exclusively BM group no significant differences were observed in ATM and %ATM in the predominantly BM and predominantly formula-fed groups.ConclusionsThe slower weight gain of preterm infants fed BM appears to be due to a deficit in non-ATM and may reflect lower protein intake. Whether this pattern persists into childhood, is altered by BM fortification or later diet, or relates to functional outcomes, are important research questions.Clinical trial registration ISRCTN29665319, post results.

Background The relationship between early antibiotic exposure, necrotizing enterocolitis (NEC), and growth faltering (GF) in extremely preterm infants is unknown. Methods We evaluated the association between peripartum and postnatal antibiotic exposure in the first week after birth with NEC and GF in this secondary analysis of Preterm Erythropoietin Neuroprotection Trial subjects. NEC was defined as Bell’s stage ≥ IIA; GF was defined as decreased weight, length, or head circumference (HC) z -score from birth to discharge of < −0.8. Multivariable analyses were adjusted with maternal and infant factors. Results A total of 891 infants survived the first week and were included in the NEC analyses, while 828 infants survived to discharge and were included in the growth analyses. For every 1-day increase in infant antibiotic exposure during the first week after birth, there was a significantly increased adjusted hazard of NEC (aHR/day 1.14 [1.01–1.28], p  = 0.034). Antibiotics for 3–4 days and 5–7 days total in the first week were associated with increased odds of weight GF (aOR 1.90 [1.21–2.99], aOR 2.32 [1.44–3.74]), length GF (aOR 1.76 [1.22–2.59], aOR 1.88 [1.26–2.80]), and HC GF (aOR 1.75 [1.08–2.84], aOR 1.87 [1.14–3.08]). Conclusion Increased antibiotic exposure in the first week after birth was associated with NEC and GF risk. Impact In this post-hoc analysis of a large multi-site trial, we found infant antibiotic exposure in the first week after birth was associated with an increased hazard of necrotizing enterocolitis in the extremely preterm infant after adjusting for maternal and infant factors. First week antibiotic exposure in the extremely preterm infant was associated with an increased odds of weight, linear, and head circumference growth faltering after adjusting for maternal and infant factors. These findings encourage the judicious use of early antibiotics in extremely preterm infants.

The SafeBoosC II, randomised clinical trial, showed that the burden of cerebral hypoxia was reduced with the combination of near infrared spectroscopy and a treatment guideline in extremely preterm infants during the first 72 hours after birth. We have previously reported that a high burden of cerebral hypoxia was associated with cerebral haemorrhage and EEG suppression towards the end of the 72-hour intervention period, regardless of allocation. In this study we describe the associations between the burden of cerebral hypoxia and the 2-year outcome. Cerebral oxygenation was continuously monitored from 3 to 72 hours after birth in 166 extremely preterm infants. At 2 years of age 114 of 133 surviving children participated in the follow-up program: medical examination, Bayley II or III test and the parental Ages and Stages Questionnaire. The infants were classified according to the burden of hypoxia: within the first three quartiles (n = 86, low burden) or within in the 4th quartile (n = 28, high burden). All analyses were conducted post hoc. There were no statistically significant differences between the quantitative assessments of neurodevelopment in the groups of infants with the low burden of cerebral hypoxia versus the group of infants with the high burden of cerebral hypoxia. The infants in the high hypoxia burden group had a higher-though again not statistically significant-rate of cerebral palsy (OR 2.14 (0.33-13.78)) and severe developmental impairment (OR 4.74 (0.74-30.49). The burden of cerebral hypoxia was not significantly associated with impaired 2-year neurodevelopmental outcome in this post-hoc analysis of a feasibility trial.

To evaluate the effect of patterned, frequency-modulated oro-somatosensory stimulation on time to full oral feeds in preterm infants born 26-30 weeks gestation. This is a multicenter randomized controlled trial. The experimental group (n = 109) received patterned, frequency-modulated oral stimulation via the NTrainer system through a pulsatile pacifier and the control group (n = 101) received a non-pulsatile pacifier. Intent-to-treat analysis (n = 210) was performed to compare the experimental and control groups and the outcomes were analyzed using generalized estimating equations. Time-to-event analyses for time to reach full oral feeds and length of hospital stay were conducted using Cox proportional hazards models. The experimental group had reduction in time to full oral feeds compared to the control group (-4.1 days, HR 1.37 (1.03, 1.82) p = 0.03). In the 29-30 weeks subgroup, infants in the experimental group had a significant reduction in time to discharge (-10 days, HR 1.87 (1.23, 2.84) p < 0.01). This difference was not observed in the 26-28 weeks subgroup. There was no difference in growth, mortality or morbidities between the two groups. Patterned, frequency-modulated oro-somatosensory stimulation improves feeding development in premature infants and reduces their length of hospitalization. ClinicalTrials.gov NCT01158391.