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Background. Amplitude-integrated electroencephalography is increasingly used for the neuromonitoring of premature infants. However, it is still not clear how bioelectrical activity changes in the smallest gestational age newborns. The aim of our study was to evaluate the bioelectrical activity of amplitude-integrated electroencephalograms in premature newborns of different gestational age to assess how gestational age and postnatal age influence patterns of amplitude-integrated electroencephalograms and to test the hypothesis of whether the bioelectrical activity of the brain matures faster after the birth of premature newborns than in utero. Methods. We prospectively included infants born before 32 weeks of gestational age between June 2020 and July 2022. Serial recordings of amplitude-integrated electroencephalograms were performed at three time points of age (days 1–3, 13–15, and 27–29). Recordings were analyzed for background patterns, the onset and appearance of cyclicity, and lower amplitude border and bandwidth, which were used to derive a composite Burdjalov score. Results. In total, 140 premature neonates were included in the study, and 112 of them completed the study. The median gestational age of the newborns enrolled in the study was 29 (27–30) weeks, and the mean weight was 1206 (350) g. Burdjalov scores increased with increasing gestational age. Higher scores were observed in every dimension of the amplitude-integrated electroencephalograms for newborns of lower gestational age when compared to newborns of higher gestational age of the same postmenstrual age. There was a significant correlation between gestational age and parameters of amplitude-integrated electroencephalograms at all time points. Conclusions. A higher gestational age has a positive effect on the bioelectrical activity of amplitude-integrated electroencephalograms. Increasing postnatal age affected amplitude-integrated electroencephalograms more than gestational age. Our hypothesis that the bioelectrical activity of the brain matures faster for premature newborns after birth than in the womb was confirmed. [ABSTRACT FROM AUTHOR]

This study was designed as a prospective, randomized controlled trial. A total of 90 preterm infants who underwent retinopathy of prematurity (ROP) examinations were categorized into three groups, a control group, a white noise group (WN), and a classical music group (CM), each comprising 30 preterm infants. The study data were obtained using an information form and the Premature Infant Pain Profile. During (WN: 9.70±3.02; CM: 11.2±2.28) and after the examination (WN: 3.60±2.11; CM: 3.77±1.83), the preterm infants in the WN and CM groups had lower mean pain scores and heart rates (181.17±15.76 and 3150.10±17.03 vs. 173.30±20.66 and 146.67±18.17, respectively; p<0.001) and higher mean oxygen saturation values (93.60±3.87 and 97.83±1.93 vs. 95.73±2.52 and 98.27±1.82, respectively; p<0.05) than those in the control group; the differences were statistically significant. The WN and CM listened to by the preterm infants during ROP examinations had positive effects on pain and heart rate and oxygen saturation values. [ABSTRACT FROM AUTHOR]

The newborn period poses the most vulnerable time in the development of epileptic seizures. The main predisposing factor is an increased neuronal excitability resulting from the incomplete maturation of a premature brain. From this point of view, premature newborns are at the highest risk of developing neonatal seizures. Early initiation of rational dia-gnostic and therapeutic intervention is often complicated by the vague or absent clinical manifestation of neonatal seizures. The variability of their clinical picture is reflected in the new draft of Neonatal Seizure Classification by International League Against Epilepsy (ILAE) from 2018. Timely dia-gnosis and initiation of adequate therapy with regard to etiology is, from the prognosis viewpoint, crucial. The strongest predictor of prognosis is etiology, as well as gestational age, initial findings during the neurological examination and ictal and interictal electroencephalographic features. [ABSTRACT FROM AUTHOR]

Background: The agreement between invasive and non-invasive blood pressure (BP) readings in the first days of life of preterm infants is contentiously debated. Objective: To compare mean, systolic and diastolic invasive (IBP) and non-invasive BP (NBP) readings obtained during routine care in the first four weeks of life of extremely preterm infants. Methods: We extracted pairs of IBP and NBP readings obtained from preterm infants born below 28 weeks of gestation from the local database. After exclusion of erroneous measurements, we investigated the repeated measures correlation and analyzed the agreement (bias) and precision adjusted for multiple measurements per individual. Results: Among 335 pairs of IBP and NBP readings obtained from 128 patients, we found correlation coefficients >0.65 for mean, systolic and diastolic BP values. The bias for mean BP readings was -0.4 mmHg (SD 6.1), for systolic BP readings 6.2 mmHg (SD 8.1), and for diastolic BP readings -4.3 mmHg (SD 6.5). Overestimation of systolic IBP and underestimation of diastolic IBP by the non-invasive measurement were found both in the group with gestational age from 23 to 25.9 weeks and in the group with gestational age from 26 to 27.9 weeks. Systolic NBP readings tended to exceed invasive readings in the range <50 mmHg (bias 9.9 mmHg) whereas diastolic NBP readings were lower than invasive values particularly in the range >30 mmHg (bias -5.5 mmHg). Conclusion: The disagreement between invasive and non-invasive BP readings in infants extends to the first four weeks of life. Biases differ for mean, systolic and diastolic BP values. Our observation implies that they may depend on the range of the blood pressure. Awareness of these biases and preemptive concomitant use of IBP and NPB readings may contribute to reducing over- or under-treatment. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study is to evaluate intestinal blood flow changes within the first 72 h in the late preterm infants in comparison with the healthy term neonates.Methods: In this prospective study, we analyzed Doppler flow velocity waveforms of superior mesenteric artery (SMA) and coeliac trunc (TC) in 20 late preterm and 20 term infants at the age of 2, 24, and 72 h.Results: Significant end-diastolic velocity (end-diastolic velocity (EDV)SMA) rise up to 24 h was documented in all patients (late preterm: -9.32 ± 9.48 to 17.01 ± 6.94; p < .05; term: -8 ± 5.74 to 12.39 ± 3.33; p < .001), associated with a conversion from negative values to positive ones. Reversed blood flow was documented in SMA at 2 h in 75% late preterm neonates. Preterm infants showed significantly higher mean peak systolic velocities (peak systolic velocity (PSV)SMA), end-diastolic velocities (EDVSMA) at 24 h and PSVTC at 72 h than term infants (p < .05). The resistance and pulsatility indices (PI) decreased within 24 h in both groups and inversely reflected the postnatal changes in EDVSMA. Mean PIAMS at 2 h was significantly higher in term neonates.Conclusion: Late preterm neonates show similar progressive postnatal increase in blood flow velocities accompanied with a decrease in vascular resistance in SMA and TC then term neonates. [ABSTRACT FROM AUTHOR]

A putative quantifier of consciousness, integrated information, was applied to preterm infant EEG data after novel pre-processing. Integrated information had a non-random structure as a function of the time lag over which it was computed. For most lags, it increased with age in early life, but even more so in infants exposed to Family Nurture Intervention (FNI), providing further evidence that FNI advances brain maturation in preterm infants. Also, it discriminated between conscious states (awake, REM sleep, NREM sleep), providing empirical support for the Integrated Information Theory of Consciousness in human infants. [ABSTRACT FROM AUTHOR]

Background: Optimum timing of umbilical cord clamping has not been established in preterm infants. Objectives: We compared the short- and long-term effects of umbilical cord milking (UCM) versus delayed cord clamping (DCC) on infants born at less than 37 weeks of gestation. Search methods: A systematic review and meta-analysis was conducted according to the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” statement. We searched CINAHL, CENTRAL, EMBASE, MEDLINE, PubMed and ClinicalTrials.gov for relevant randomized controlled trials (RCTs). Selection criteria: We included individual and clustered RCTs comparing UCM to DCC for infants born before 37 weeks of gestation. Data collection and analysis: Four reviewers independently assessed trial quality and eligibility for inclusion. Main results: Two trials (255 preterm infants, 23 0/7 to 32 6/7 weeks of gestation) were included in the analysis. UCM was associated with fewer intraventricular hemorrhages (IVHs) (two trials, 255 infants; relative risk [RR] 0.45, 95% confidence interval [CI] 0.20 to 0.98, low quality of evidence) and UCM was an increased proportion of infants with a Bayley score at 2 years of age (two trials, 174 infants; Cognitive: RR 1.14, 95% CI 1.03 to 1.26, Language: RR 1.24, 95% CI 1.03 to 1.49, low quality of evidence) compared to DCC. Conclusions: UCM wasn’t reduced in-hospital mortality and need for transfusion compared to DCC. But our study suggests that UCM may lower the risk of IVH and improve certain neurodevelopmental outcomes compared to DCC in preterm infants. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the direct effect of repetitive tactile stimulation on breathing effort of preterm infants at birth.Methods: This randomized controlled trial compared the effect of repetitive stimulation on respiratory effort during the first 4 min after birth with standard stimulation based on clinical indication in preterm infants with a gestational age of 27-32 weeks. All details of the stimulation performed were noted. The main study parameter measured was respiratory minute volume, other study parameters assessed measures of respiratory effort; tidal volumes, rate of rise to maximum tidal volumes, percentage of recruitment breaths, and oxygenation of the infant.Results: There was no significant difference in respiratory minute volume in the repetitive stimulation group when compared to the standard group. Oxygen saturation was significantly higher (87.6 ± 3.3% vs 81.7 ± 8.7%, p = .01) while the amount of FiO2 given during transport to the NICU was lower (28.2 (22.8-35.0)% vs 33.6 (29.4-44.1)%, p = .04). There was no significant difference in administration of positive pressure ventilation (52% vs 78%, p = .13), or the duration of ventilation (median (IQR) time 8 (0-118)s vs 35 (13-131)s, p = .23). Caregivers decided less often to administer caffeine in the delivery room to stimulate breathing in the repetitive stimulation group (10% vs 39%, p = .036).Conclusion: Although the increase in respiratory effort during repetitive stimulation did not reach significance, oxygenation significantly improved with a lower level of FiO2 at transport to the NICU. Repetitive tactile stimulation could be of added value to improve breathing effort at birth. [ABSTRACT FROM AUTHOR]

Phototherapy represents the most common therapeutic intervention at neonatology departments in the first days of life. The beneficial effects of light on the decrease of the serum bilirubin level were first described by Cremer et al. in 1950's (1). Since then phototherapy has been successfully used to treat severe hyperbilirubinaemia and has almost completely replaced exchange transfusion. Phototherapy is a relatively non-invasive method. However, along with decreasing bilirubin level, it can also influence some other functions: perfusion of organs, predominantly skin; periphe ral vascular resistance; distribution of blood flow; heart activity and, thus, also systemic blood pressure along with breathing. A side component of applied light is a certain amount of heat which warms the body surface up and, therefore, the risk of exogenous overheating and increased water loss through the skin arise. Maternal-infant separation, modification of calcium homeostasis, disturbed circadian rhythm, or changes of the hemodynamics of va rious organ systems are only a few of the undesired effects which prove phototherapy not to be a treatment without any side effects. Careful indication of phototherapy is essential, particularly in premature infants. [ABSTRACT FROM AUTHOR]

Aim: This Italian study evaluated whether painful procedures during the first four weeks of life were related to subsequent weight gain, head circumference (HC) and neurodevelopmental outcomes in preterm infants, METHODS: We evaluated the number of invasive procedures that infants born at less than 32 weeks of gestational age (GA) underwent in the Neonatal Intensive Care Unit of Careggi Hospital, Florence, from January to December 2015. Weight and HC were recorded at birth, 36 weeks of PMA and six and 12 months of CA. Neurological outcomes were assessed at six and 12 months of CA using the Bayley Scales of Infant and Toddler Development - Third Edition.Results: We studied 83 preterm infants with a GA of 28 ± 2 weeks and birth weight of 1098 ± 340 g. A higher number of invasive painful procedures were related to a lower HC standard deviation score at 36 weeks of PMA and six and 12 months of CA and with lower cognitive scores at six months. At 12 months, the relationship only remained significant for infants born at less than 28 weeks (p < 0.001).Conclusion: Invasive painful procedures affected regular HC growth and short-term cognitive scores in preterm infants in the first year of life. [ABSTRACT FROM AUTHOR]

Aim: This study evaluated poor weight gain as a risk factor for infants who required treatment for retinopathy of prematurity (ROP), by comparing those born before and after the implementation of higher oxygen saturation (SpO2 ) targets at the Queen Silvia Children's Hospital, Gothenburg, Sweden.Methods: We compared infants born at less than 31 weeks, who were screened and, or, treated for ROP: 127 in 2011-2012 when SpO2 targets were 88-92% and 142 in 2015-2016 when they were 91-95%. The subjects were reviewed for birth characteristics, weekly weight and ROP treatment. Data were analysed using the weight, insulin-like growth factor 1, neonatal, ROP (WINROP) prediction tool.Results: The 2011-2012 infants who needed ROP treatment (12.6%) had significantly poorer postnatal weight gain than those who did not, but this was not seen in the treated (17.6%) and nontreated ROP groups in 2015-2016. WINROP sensitivity decreased from 87.5% in 2011-12 to 48% in 2015-2016.Conclusion: After the SpO2 target range was increased from 88-92% to 91-95%, postnatal weight gain was no longer a significant risk factor and WINROP lost its ability to predict ROP requiring treatment. Risk factors clearly change as neonatal care develops. [ABSTRACT FROM AUTHOR]

Background: Betamethasone is widely used to enhance fetal lung maturation in case of threatened preterm labour. Fetal heart rate variability is one of the most important parameters to assess in fetal monitoring, since it is a reliable indicator for fetal distress.Aim: To describe the effect of betamethasone on fetal heart rate variability, by applying spectral analysis on non-invasive fetal electrocardiogram recordings.Study Design: Prospective cohort study.Subjects: Patients that require betamethasone, with a gestational age from 24 weeks onwards.Outcome Measures: Fetal heart rate variability parameters on day 1, 2, and 3 after betamethasone administration are compared to a reference measurement.Results: Following 68 inclusions, 12 patients remained with complete series of measurements and sufficient data quality. During day 1, an increase in absolute fetal heart rate variability values was seen. During day 2, a decrease in these values was seen. All trends indicate to return to pre-medication values on day 3. Normalised high- and low-frequency power show little changes during the study period.Conclusions: The changes in fetal heart rate variability following betamethasone administration show the same pattern when calculated by spectral analysis of the fetal electrocardiogram, as when calculated by cardiotocography. Since normalised spectral values show little changes, the influence of autonomic modulation seems minor. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) is a devastating condition that mainly affects premature infants. Advanced cases of NEC require surgical treatment, which in up to 70% of infants is associated with significant perioperative morbidity including anastomosis- or enterostomy-related complications, sepsis, peritonitis, and wound infections. Moreover, the perioperative complications may compromise the long-term gastrointestinal and neurodevelopmental outcome of patients requiring surgery for NEC. [ABSTRACT FROM AUTHOR]

Aim: The management of births at borderline viability continues to present dilemmas for health professionals and parents. The aim of the study was to review local outcomes of infants born between 22 and 24 weeks of gestation between 2004 and 2010 in Western Australia (WA) to aid perinatal counselling.Methods: Survival data for the study were sourced retrospectively from the Neonatal Clinical Care Unit and Department of Health records of births in WA. Neurodevelopmental follow-up outcomes were assessed using the most recent standardised assessment (Griffiths, Bayley-III and Wechsler Preschool and Primary Scale of Intelligence, 3rd Ed) and medical examination of infants/children 12 months to 8 years from follow-up clinic appointments.Results: At these gestations, 159 survivors represented 72% of neonatal intensive care unit admissions, 53% of WA live births and 26% of WA live and still births; 5% of live births survived at 22 weeks, 46% at 23 weeks and 77% at 24 weeks. Of the 14 outborn/retrieved infants, 4 survived (29%). At a median age of 59 months, disabilities were severe in 13% of children (22-23w = 19%; 24w = 11%). The median test quotient was 90. Moderate and severe cognitive disability was found in 16%, cerebral palsy was found in 7% (n = 11), and 55% of children were free from impairment as defined in this study.Conclusion: At these gestations, survival figures varied markedly with the chosen population denominator. Regional data are essential for valid population comparison. While many developmental difficulties occurred in these children, 78% were free from moderate or severe impairment at ages 3-5 years. [ABSTRACT FROM AUTHOR]

The autonomic nervous system (ANS) plays a major role in the human stress response and reflects physical and psychological adaptability to a changing environment. Long-term exposure to early life stressors may alter the function of the ANS. The present study examines differences in the ANS between children born very preterm and full-term as well as the association between the ANS and the hypothalamic-pituitary-adrenal (HPA) axis, the other main branch of the human stress system. Fifty-four healthy children born very preterm (<32nd gestational week) and 67 full-term children aged 7–12 years provided data for the present study. Polysomnography (PSG) assessments were obtained during a night at the children’s home in lying position at rest (wake) and during different sleep stages (stage 2 sleep, slow wave sleep, rapid-eye-movement sleep). Autonomic function was assessed by use of heart rate variability, specifically low frequency power (LF), high frequency power (HF), total spectral power (Tot Pow), and the LF/HF ratio. HPA axis activity was measured using salivary cortisol the next morning at awakening, 10, 20, and 30 min later. Children born very preterm had lower LF/HF ratio during wake and stage 2 sleep compared to full-term children. Moreover, higher LF, Tot Pow, and LF/HF ratio during wake, stage 2 sleep, and REM sleep were related to more post-awakening cortisol secretion. The present study provides evidence on long-term ANS alterations after very preterm birth. Moreover, findings suggest a relation between the ANS and the HPA axis and therefore support the notion of mutual feedback between the two human stress systems. [ABSTRACT FROM AUTHOR]

Preterm infants show abnormal structural and functional brain development, and have a high risk of long-term neurocognitive problems. The molecular and cellular mechanisms involved are poorly understood, but novelmethods now make it possible to address them by examining the relationship between common genetic variability and brain endophenotype. We addressed the hypothesis that variability in the Peroxisome Proliferator Activated Receptor (PPAR) pathway would be related to brain development. We employed machine learning in an unsupervised, unbiased, combined analysis of whole-brain diffusion tractography together with genomewide, single-nucleotide polymorphism (SNP)-based genotypes from a cohort of 272 preterm infants, using Sparse Reduced Rank Regression (sRRR) and correcting for ethnicity and age at birth and imaging. Empirical selection frequencies for SNPs associated with cerebral connectivity ranged from 0.663 to zero, with multiple highly selected SNPs mapping to genes for PPARG (six SNPs), ITGA6 (four SNPs), and FXR1 (two SNPs). SNPs in PPARG were significantly overrepresented (ranked 7-11 and 67 of 556,000 SNPs; P < 2.2 x 10-7), and were mostly in introns or regulatory regions with predicted effects including protein coding and nonsensemediated decay. Edge-centric graph-theoretic analysis showed that highly selected white-matter tracts were consistent across the group and important for information transfer (P < 2.2 x 10-17); they most often connected to the insula (P < 6 x 10-17). These results suggest that the inhibited brain development seen in humans exposed to the stress of a premature extrauterine environment is modulated by genetic factors, and that PPARG signaling has a previously unrecognized role in cerebral development. [ABSTRACT FROM AUTHOR]

Background: Despite advances in the health and long-term survival of infants born preterm, they continue to face developmental challenges including higher risk for autism spectrum disorder (ASD) and atypical sensory processing patterns.Aims: This secondary analysis aimed to describe sensory profiles and explore effects of combined dietary docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and gamma-linolenic acid (GLA) supplementation on parent-reported sensory processing in toddlers born preterm who were exhibiting ASD symptoms.Study Design: 90-day randomized, double blinded, placebo-controlled trial.Subjects: 31 children aged 18-38months who were born at ≤29weeks' gestation.Outcome Measure: Mixed effects regression analyses followed intent to treat and explored effects on parent-reported sensory processing measured by the Infant/Toddler Sensory Profile (ITSP).Results: Baseline ITSP scores reflected atypical sensory processing, with the majority of atypical scores falling below the mean. Sensory processing sections: auditory (above=0%, below=65%), vestibular (above=13%, below=48%), tactile (above=3%, below=35%), oral sensory (above=10%; below=26%), visual (above=10%, below=16%); sensory processing quadrants: low registration (above=3%; below=71%), sensation avoiding (above=3%; below=39%), sensory sensitivity (above=3%; below=35%), and sensation seeking (above=10%; below=19%). Twenty-eight of 31 children randomized had complete outcome data. Although not statistically significant (p=0.13), the magnitude of the effect for reduction in behaviors associated with sensory sensitivity was medium to large (effect size=0.57). No other scales reflected a similar magnitude of effect size (range: 0.10 to 0.32).Conclusions: The findings provide support for larger randomized trials of omega fatty acid supplementation for children at risk of sensory processing difficulties, especially those born preterm. [ABSTRACT FROM AUTHOR]

This narrative review is based on a literature search of PubMed and PsycINFO for research on preterm newborn pain published during the last ten years. The high prevalence of painful procedures being performed with preterm newborns without analgesia (79%), with a median of 75 painful procedures being received during hospitalization and as many as 51 painful procedures per day highlights the importance of this problem. This review covers the pain assessments that have been developed, the short-term effects of the painful procedures, the longer-term developmental outcomes and the pharmacological and alternative therapies that have been researched. The most immediate effects reported for repeated painful procedures include increased heart rate, oxidative stress and cortisol as well as decreased vagal activity. Lower body weight and head circumference have been noted at 32 weeks gestation. Blunted cortisol reactivity to stressors has been reported for three-month-olds and thinner gray matter in 21 of 66 cerebral regions and motor and cognitive developmental delays have been noted as early as eight months. Longer-term outcomes have been reported at school age including less cortical thickness, lower vagal activity, delayed visual- perceptual development, lower IQs and internalizing behavior. Pharmacological interventions and their side effects and non-pharmacological therapies are also reviewed including sucrose, milk and nonnutritive sucking which have been effective but thought to negatively affect breast-feeding. Full-body interventions have included tucking, swaddling, kangaroo care and massage therapy. Although these have been effective for alleviating immediate pain during invasive procedures, research is lacking on the routine use of these therapies for reducing long-term pain effects. Further, additional randomized controlled replication studies are needed. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate changes in leg joint coordination, intersegmental dynamics, and their relation in infants born preterm (PT) during the first months of life. Kicking actions were analyzed of 11 infants born PT at 6 and 15-weeks corrected age (CA) using three-dimensional kinematics and kinetics; results were compared to the kicking actions of 10 infants born full-term (FT). Both groups changed from a predominately in-phase coordination at 6-weeks CA to a less in-phase coordination at 15-weeks CA, however, at 6-weeks CA, infants born PT demonstrated less in-phase coordination of their ankle joints with their hip and knee joints. Between groups and across ages, both groups demonstrated consistent net and partitioned joint torque profiles, however, at 6-weeks CA infants born PT demonstrated more complex patterns of torque components. In both groups, less in-phase hip-knee coordination was associated with reduced active knee muscle torque and increased passive knee torques, however, passive knee torques had a greater influence on the kicks of infants born PT at 6-weeks CA. At 6-weeks CA, infants born PT, compared to FT, generated kicks with less in-phase hip-knee coordination, hip excursion, hip angular velocity, and hip muscle torque impulse. By 15-weeks CA, differences resolved in all variables except hip muscle torque impulse. These results highlight a different trajectory of leg joint coordination and torque production for infants born PT compared to FT. [ABSTRACT FROM AUTHOR]

Background The use of earmuffs can protect preterm infants against negative effects of high noise levels in the neonatal intensive care unit. This study was aimed at assessing the effectiveness of the earmuffs on the physiologic and behavioral responses in preterm infants. Methods A crossed over controlled trial was conducted at Aliasghar Hospital (Tehran, Iran) in 2014. Thirty-six preterm infants cared in closed incubators, 18 cases wore a pair of silicon earmuffs in the first day and the others were worn it at the second day. During 2 consecutive days, all subjects were observed as their own controls (without earmuffs). Physiologic (body temperature, heart rate, respiratory rate, systolic, diastolic pressures, arterial Oxygen Saturation) and behavioral responses (according to the Anderson behavioral state scoring system) were assessed every 2 h for 8 h long during daytime for two consecutive days. Results The application of earmuffs could decrease the rate of the heart and respiratory while could increase the amount of oxygen saturation ( p < 0.05). The results also showed that the preterm infants with earmuffs had lower ABSS score and a better light sleep compared to those without earmuffs (2.38 ± 0.47 versus 4.8 ± 0.97, p < 0.05). Conclusion The results indicated that using the earmuffs reduces the level of noise in NICUs following by improving the preterm neonates' physiological stability and behavioral states of ABSS. [ABSTRACT FROM AUTHOR]

Background: Many infants born prematurely experience growth failure following delivery, with subsequent catch-up growth. Traditionally catch-up was thought to be complete in the first few years of life. Most studies have focused on groups of infants defined by birth weight, for example <1500 g, resulting in disproportionate numbers of small for gestational age infants. This study aimed to determine whether appropriate weight for gestation (AGA) preterm born children reach their expected adult height when compared with term controls.Methodology: This UK based prospective longitudinal cohort study recruited 204 preterm children born at a tertiary neonatal unit during 1994 and 50 matched controls. Growth parameters have been assessed annually until the completion of growth.Results: There was no significant difference in the final height SD score (SDS) of children born at term (n=30) and those born prematurely and AGA (n=70) (0.45 term vs 0.22 preterm). Catch-up growth however, continued throughout the whole of childhood. When the difference between final height SDS and mid-parental height SDS were compared, there were again no significant differences (0.13 term vs 0.03 preterm).Conclusions: Those born prematurely with an AGA achieve a comparable adult height to children born at term, however, catch-up growth continues for much longer than traditionally thought. [ABSTRACT FROM AUTHOR]

Aim: Playing music during painful procedures has shown inconsistent benefits for preterm infants. This study observed preterm infants during a heel stick procedure to assess whether listening to the music their mothers listened to during pregnancy had any impact on their pain and physiological and behavioural parameters.Methods: We randomly exposed 42 preterm infants, with a mean gestational age of 31.8 ± 2.79 weeks, to the music their mothers listened to during pregnancy, recorded lullabies and no music, before, during and after a heel stick. Pain responses were measured using the Neonatal Pain, Agitation and Sedation Scale (N-PASS), and physiological and behavioural responses were recorded by a nurse blinded to the intervention.Results: N-PASS pain scores were lowest during mothers' music, with a mean of 1.40 (±1.28), compared to 2.33 (±1.64) for no music and 1.62 (±2.27) for the lullabies [F(3/121) = 4.86, p = 0.009]. Physiological parameters were not significantly different between the conditions. During the mothers' music, infants spent more time in a quiet alert state, with a significant decrease in their respiratory rates.Conclusion: The music mothers listened to during pregnancy was more beneficial for preterm infants, as it decreased pain and improved behavioural states during a heel stick. [ABSTRACT FROM AUTHOR]

Aim: Compared to infants born at term, children born very preterm are at increased risk of visual dysfunctions and neonatal systemic inflammation. Here, we explore whether these two propensities are related.Methods: As part of the ELGAN study, the concentrations of 16 mediators of inflammation were measured in blood obtained on postnatal days 1, 7, 14, 21 and 28 from 1062 children born before the 28th week of gestation. Presence of visual field deficit, strabismus and/or impaired visual fixation was recorded at age two. The concentrations of each protein were divided into quartiles within gestational week categories. We calculated odds ratios with 99% confidence intervals for having each disorder comparing children with concentration in the top quartile of each protein to children whose concentration was in the lower quartiles on the corresponding day. Analyses were adjusted for gestational age and birth weight Z-score.Results: Only one of 80 assessments (16 proteins on five different days) was significant for visual field deficit, and one for impaired fixation. No association was found between strabismus and any inflammatory mediator.Conclusion: None of the three neuro-ophthalmologic dysfunctions assessed at two years appears to be associated with systemic inflammation measured the first four postnatal weeks. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of low intensity recorded maternal voice on the physiologic reactions of healthy premature infants in the neonatal intensive care unit (NICU).Methods: Physiologic responses of 20 healthy preterm infants in the NICU of Shariati Hospital, Tehran, were obtained during a 15min intervention including three 5min periods (no-sound control, audio recorded playback of mother's voice, no-sound post-voice). The intervention was presented three times a day for three consecutive days. During each intervention, oxygen saturation (%, OSPR), heart rate (HR), and respiratory rate (RR) were recorded at 1min intervals over the 15min and then averaged over each 5min period, resulting in 3 averages for each variable for each intervention.Results: Repeated Measures Analysis of Variance were employed to examine each variable separately. Over the three days, comparison of oxygen saturation over each of the three periods (before, during voice, after) revealed an increase in oxygen saturation during the voice period, compared to the pre-voice period, which persisted over the post-voice period; there were no differences between the voice and post-voice periods. Analyses of the HR and RR data showed a decrease in both variables during the voice period compared to the pre-voice period which persisted over the post-voice period. Again, there were no differences between the voice and post-voice periods.Conclusion: Exposure to low intensity recorded maternal voice has positive effects on the preterm infants 'physiologic responses. [ABSTRACT FROM AUTHOR]

Background: In the UK, 1-2% of infants are born very preterm (<32 weeks of gestation) or have very low birth weight (<1500 g). Very preterm infants are initially unable to be fed nutritional volumes of milk and therefore require intravenous nutrition. Milk feeding strategies influence several long and short term health outcomes including growth, survival, infection (associated with intravenous nutrition) and necrotising enterocolitis (NEC); with both infection and NEC being key predictive factors of long term disability. Currently there is no consistent strategy for feeding preterm infants across the UK. The SIFT trial will test two speeds of increasing milk feeds with the primary aim of determining effects on survival without moderate or severe neurodevelopmental disability at 24 months of age, corrected for prematurity. The trial will also examine many secondary outcomes including infection, NEC, time taken to reach full feeds and growth.Methods/design: Two thousand eight hundred very preterm or very low birth weight infants will be recruited from approximately 30 hospitals across the UK to a randomised controlled trial. Infants with severe congenital anomaly or no realistic chance of survival will be excluded. Infants will be randomly allocated to either a faster (30 ml/kg/day) or slower (18 ml/kg/day) rate of increase in milk feeds. Data will be collected during the neonatal hospital stay on weight, infection rates, episodes of NEC, length of stay and time to reach full milk feeds. Long term health outcomes comprising vision, hearing, motor and cognitive impairment will be assessed at 24 months of age (corrected for prematurity) using a parent report questionnaire.Discussion: Extensive searches have found no active or proposed studies investigating the rate of increasing milk feeds. The results of this trial will have importance for optimising incremental milk feeding for very preterm and/or very low birth weight infants. No additional resources will be required to implement an optimal feeding strategy, and therefore if successful, the trial results could rapidly be adopted across the NHS at low cost.Trial Registration: ISRCTN Registry; ISRCTN76463425 on 5 March, 2013. [ABSTRACT FROM AUTHOR]

Objective: Despite decades of research on risk indicators of spontaneous preterm birth (PTB), reliable biomarkers are still not available to screen or diagnose high-risk pregnancies. Several biomarkers in maternal and fetal compartments have been mechanistically linked to PTB, but none of them are reliable predictors of pregnancy outcome. This systematic review was conducted to synthesize the knowledge on PTB biomarkers identified using multiplex analysis. Materials and methods: Three electronic databases (PubMed, EMBASE and Web of Science) were searched for studies in any language reporting the use of multiplex assays for maternal biomarkers associated with PTB published from January 2005 to March 2014. Results: Retrieved citations (3631) were screened, and relevant studies (33) were selected for full-text reading. Ten studies were included in the review. Forty-two PTB-related proteins were reported, and RANTES and IL-10 (three studies) followed by MIP-1β, GM-CSF, Eotaxin, and TNF-RI (two studies) were reported more than once in maternal serum. However, results could not be combined due to heterogeneity in type of sample, study population, assay, and analysis methods. Conclusion: By this systematic review, we conclude that multiplex assays are a potential technological advancement for identifying biomarkers of PTB, although no single or combination of biomarkers could be identified to predict PTB risk. [ABSTRACT FROM AUTHOR]

Bronchopulmonary dysplasia (BPD) is a chronic lung disease most commonly seen in premature infants who required mechanical ventilation and oxygen therapy for acute respiratory distress. While advances in neonatal care have resulted in improved survival rates of premature infants, limited progress has been made in reducing rates of BPD. Lack of progress may in part be attributed to the limited therapeutic options available for prevention and treatment of BPD. Several lung-protective strategies have been shown to reduce risks, including use of non-invasive support, as well as early extubation and volume ventilation when intubation is required. These approaches, along with optimal nutrition and medical therapy, decrease risk of BPD; however, impacts on long-term outcomes are poorly defined. Characterization of late outcomes remain a challenge as rapid advances in medical management result in current adult BPD survivors representing outdated neonatal care. While pulmonary disease improves with growth, long-term follow-up studies raise concerns for persistent pulmonary dysfunction; asthma-like symptoms and exercise intolerance in young adults after BPD. Abnormal ventilatory responses and pulmonary hypertension can further complicate disease. These pulmonary morbidities, combined with environmental and infectious exposures, may result in significant long-term pulmonary sequalae and represent a growing burden on health systems. Additional longitudinal studies are needed to determine outcomes beyond the second decade, and define risk factors and optimal treatment for late sequalae of disease. [ABSTRACT FROM AUTHOR]

Preterm children have an increased risk of neurodevelopmental impairments which include psychomotor and language retardation. The objectives of the present retrospective cohort study were to examine the effects of an individually adapted, home-based, and family-centred early developmental habilitation program on neurodevelopmental and behavioural outcomes of very preterm children compared with a standard follow-up at 2 years’ corrected age. Enrolled infants were retrospectively assigned to the intervention group (61 subjects) or to the control group (62 subjects) depending on whether they had or had not carried out a home-based family-centred early developmental habilitation program focused on environmental enrichment, parent-guided environmental interaction, and infant development. Developmental outcome was assessed for both groups at 24 months’ corrected age using the Bayley Scales of Infant Development 2nd Edition. Intervention significantly improved both cognitive and behavioural outcomes. In addition, males had significantly lower scores than females either before or after treatment. However, the treatment was effective in both genders to the same extent. In conclusion, a timely updated environment suitable to the infant’s developmental needs could provide the best substrate where the parent-infant relationship can be practised with the ultimate goal of achieving further developmental steps. [ABSTRACT FROM AUTHOR]

Purpose In 2010, approximately 14.9 million babies (11.1%) were born preterm. Because preterm infants suffer from an immature thermoregulatory system they have difficulty maintaining their core body temperature at a constant level. Therefore, it is essential to maintain their temperature at, ideally, around 37 °C. For this, mathematical models can provide detailed insight into heat transfer processes and body-environment interactions for clinical applications. Methods A new multi-node mathematical model of the thermoregulatory system of newborn infants is presented. It comprises seven compartments, one spherical and six cylindrical, which represent the head, thorax, abdomen, arms and legs, respectively. The model is customizable, i.e. it meets individual characteristics of the neonate (e.g. gestational age, postnatal age, weight and length) which play an important role in heat transfer mechanisms. The model was validated during thermal neutrality and in a transient thermal environment. Results During thermal neutrality the model accurately predicted skin and core temperatures. The difference in mean core temperature between measurements and simulations averaged 0.25±0.21 °C and that of skin temperature averaged 0.36±0.36 °C. During transient thermal conditions, our approach simulated the thermoregulatory dynamics/responses. Here, for all infants, the mean absolute error between core temperatures averaged 0.12±0.11 °C and that of skin temperatures hovered around 0.30 °C. Conclusions The mathematical model appears able to predict core and skin temperatures during thermal neutrality and in case of a transient thermal conditions. [ABSTRACT FROM AUTHOR]

Background: Extreme preterm birth confers risk of long-term impairments in lung function and exercise capacity. There are limited data on the factors contributing to exercise limitation following extreme preterm birth. This study examined respiratory mechanics and ventilatory response during exercise in a large cohort of children born extremely preterm (EP).Methods: This cohort study included children 8-12 years of age who were born EP (≤28 weeks gestation) between 1997 and 2004 and treated in a large regionalised neonatal intensive care unit in western Canada. EP children were divided into no/mild bronchopulmonary dysplasia (BPD) (ie, supplementary oxygen or ventilation ceased before 36 weeks gestational age; n=53) and moderate/severe BPD (ie, continued supplementary oxygen or ventilation at 36 weeks gestational age; n=50). Age-matched control children (n=65) were born at full term. All children attempted lung function and cardiopulmonary exercise testing measurements.Results: Compared with control children, EP children had lower airway flows and diffusion capacity but preserved total lung capacity. Children with moderate/severe BPD had evidence of gas trapping relative to other groups. The mean difference in exercise capacity (as measured by oxygen uptake (VO2)% predicted) in children with moderate/severe BPD was -18±5% and -14±5.0% below children with no/mild BPD and control children, respectively. Children with moderate/severe BPD demonstrated a potentiated ventilatory response and greater prevalence of expiratory flow limitation during exercise compared with other groups. Resting lung function did not correlate with exercise capacity.Conclusions: Expiratory flow limitation and an exaggerated ventilatory response contribute to respiratory limitation to exercise in children born EP with moderate/severe BPD. [ABSTRACT FROM AUTHOR]

Background and Objectives: Studies have shown that nutritional strategies instituted early in life will have a lifelong impact on mental and physical outcomes in neonates. The objective of the study is to compare two strategies for the advancement of enteral feeding in very low birth weight infants (VLBWIs). The primary outcome is the assessment of total days required to reach full enteral feeding without necrotizing enterocolitis (NEC). The weight gain at the end of the feeding protocol and the length of the hospital stay were recorded. Settings and Design: A prospective, randomized study of 101 VLBWI born or transferred to our institution for the period 2010–2014. Materials and Methods: One hundred and one infants enrolled, 85 infants (84.2%) completed the study and 16 infants (15.8%) either excluded or withdrawn from the study, 11 infants (10.9%) in frequency advancement (FA), and five infants (4.9%) in volume advancement (VA). FA, n = 38 infants (44.7%) started 8 hourly feeds and increased to every 3 h with increase in volume by only 10 ml/kg/day. Infants of VA n = 47 (55.3%) continued feeds at every 2 h interval; volume increased 20–25 ml/kg/day. Results: The two groups were comparable regarding gestational age, birth weight, and APGAR scores. It was observed that the infants in VA reached full enteral intake without NEC earlier than FA with a difference of 12 days (P < 0.001), and a significant difference at the end of the protocol weight gain between the two groups was (1496 g for FA vs. 1281 g for VA; P = 0.001). There were no statistically significant differences in the length of hospital stay between the two groups (P = 0.221). Conclusions: Among VLBWI, an increase in enteral feeds by 20–25 ml/kg/day as in VA compared to FA protocol is a safe practice. VA of enteral feeding resulted in faster attainment of full enteral feed. However, there was no significant difference in weight gain at the end of feeding protocol and the length of hospital stay. [ABSTRACT FROM AUTHOR]

Aim: Children born extremely preterm are at risk of visual processing problems related to brain damage. Damage in visual pathways can remain undetected by conventional magnetic resonance imaging (MRI) and functional consequences cannot always be predicted. The aim of this study was to assess the efficacy of processing visual information in infants born extremely preterm at a corrected age of 1 year using a communication-free visual function test based on eye tracking.Method: Infants born extremely preterm (<29wks' gestation) without apparent white and grey matter damage on conventional MRI at 30 weeks' postmenstrual age were included (19 males, 1.01y [0.96-1.24] (median [25th-75th centiles]); 11 females, 0.99y [0.98-1.01]). At the corrected age of 1 year, reaction times to fixation (RTF) of specific visual properties displayed on an eye-tracker monitor were quantified and compared with results from a comparison group (eight males, 1.28y [1.01-1.33]; nine females, 1.10y [0.90-1.20]).Results: The infants in the preterm group had longer response times in detecting colour patterns (red-green) and motion compared with infants in the comparison group. No impairments were detected in oculomotor functions (saccades, pursuit, and fixations).Interpretation: The data suggest that delays in processing visual information can be identified in children born extremely preterm. The delays might be ascribed to deficits in neuronal connectivity in visual pathways at a microstructural level. [ABSTRACT FROM AUTHOR]

Background Severe retinopathy of prematurity ( ROP) is associated with an increased risk for ophthalmologic morbidity, but the long-term impact in other domains is less clear. The aim of the current study was to determine whether severe ROP was related to poorer visual, cognitive, and educational outcomes in a representative sample of EP adolescents, and whether this persisted after adjusting for confounding neonatal risk factors. Method One hundred and eighty extremely preterm ( EP; <28 weeks) adolescents (17-18 years) were assessed on a range of neurodevelopmental measures, including visual processing, IQ, visual learning, visual-motor integration, and academic achievement. EP adolescents were grouped according to ROP status, (1) severe ROP (stage 3 or greater) in the worse eye; or (2) no or mild ROP and were compared on each outcome. Longitudinal data were compared at 2, 5, 8, and 17-18 years for general cognitive outcome. Results The severe ROP group performed more poorly and had more impairments than the non-severe ROP group on measures of visual processing, visual-motor integration, visual learning, IQ, and some academic achievement tests at 17-18 years of age. Group differences diminished after controlling for perinatal risk factors (severe white matter injury, post-natal corticosteroid, and surgery in the neonatal period), and only visual acuity scores remained significantly different between the groups. IQ scores remained consistently lower in the severe ROP group over time, but the magnitude reduced after adjusting for perinatal risk factors. Conclusions Extremely preterm children with severe ROP are at increased risk for ongoing visual processing difficulties and lower IQ compared with EP peers without severe ROP. While severe ROP is a predictor of long-term impairments, this association is largely mediated by other neonatal risk factors. [ABSTRACT FROM AUTHOR]

Background: Preterm infants follow an altered neurodevelopmental trajectory compared to their term born peers as a result of the influence of early birth, and the altered environment. Infant massage in the preterm infant has shown positive effects on weight gain and reduced length of hospital stay. There is however, limited current evidence of improved neurodevelopment or improved attachment, maternal mood or anxiety. The aim of this study is to investigate the effects of infant massage performed by the mother in very preterm (VPT) infants. Effects on the infant will be assessed at the electrophysiological, neuroradiological and clinical levels.  Effects on maternal mood, anxiety and mother-infant attachment will also be measured.Methods/design: A randomised controlled trial to investigate the effect of massage therapy in VPT infants. Sixty VPT infants, born at 28 to 32 weeks and 6 days gestational age, who are stable, off supplemental oxygen therapy and have normal cranial ultrasounds will be recruited and randomised to an intervention (infant massage) group or a control (standard care) group. Ten healthy term born infants will be recruited as a reference comparison group. The intervention group will receive standardised massage therapy administered by the mother from recruitment, until term equivalent age (TEA). The control group will receive care as usual (CAU). Infants and their mothers will be assessed at baseline, TEA, 12 months and 24 months corrected age (CA), with a battery of clinical, neuroimaging and electrophysiological measures, as well as structured questionnaires, psychoanalytic observations and neurodevelopmental assessments.Discussion: Optimising preterm infant neurodevelopment is a key aim of neonatal research, which could substantially improve long-term outcomes and reduce the socio-economic impact of VPT birth. This study has the potential to give insights into the mother-baby relationship and any positive effects of infant massage on neurodevelopment. An early intervention such as massage that is relatively easy to administer and could alter the trajectory of preterm infant brain development, holds potential to improve neurodevelopmental outcomes in this vulnerable population.Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12612000335897 . Date registered: 22/3/2012. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to retrospectively investigate the association between initial oxygen concentration in delivery room and short-term outcomes in preterm infants.Methods: Data from infants needing neonatal resuscitation, born at our department between January 2008 and December 2011, were analyzed. Patients were divided into three groups based on gestational age: between 32 and 36 weeks, between 31 and 28 weeks, and below 28 weeks.Results: The administration of each additional unit of oxygen up to 50% showed an association with a 5% increased need for mechanical ventilation (MV) in the neonatal intensive care unit in infants between 32 and 36 weeks [adjusted odds ratio 1.1, 95% confidence interval (CI) 1.04-1.1] and infants between 28 and 31 weeks (adjusted odds ratio 1.12, 95% CI 1.08-1.44). On the contrary, in infants below 28 weeks, increasing initial concentration of supplementary oxygen did not show any association with MV.Conclusions: Initial oxygen concentration seems to be associated with increased MV in the NICU. Our observations further stress the need for randomized controlled studies in order to obtain definitive recommendations for the optimal initial oxygen concentration during neonatal resuscitation of preterm infants. [ABSTRACT FROM AUTHOR]

Objective: Transition from fetal to neonatal circulation is characterized by multiple hemodynamic changes. The role of the microcirculation in this process is underexposed. Visualizing the cutaneous microcirculation can help us understand peripheral perfusion in a noninvasive manner. Methods: Cutaneous microcirculation of term and preterm infants born below 32 weeks of GA was measured in the first month of life using IDF imaging. Linear mixed modeling was used to identify clinical variables which influence the cutaneous microcirculation. Results: Sixty preterm and 33 term infants were included. TVD of preterm infants significantly decreased in the first month of life (31.7 mm/mm² day 1 vs 27.9 mm/mm² day 28), but remained significantly higher compared to TVD of term infants on day 1 (25.8 mm/mm²). Besides postnatal age, no clinical variables were associated with TVD. Infants born SGA had significantly higher TVD values directly after birth than those born appropriate for GA (35.4 mm/mm² vs 31.6 mm/mm²; p = 0.015). Conclusions: TVD decreases in the first month after birth and is higher in preterm infants compared to those born term. Differences in antenatal oxygen exposure might explain the adaptation of the microcirculation. [ABSTRACT FROM AUTHOR]

Aims: We investigated whether spontaneous antigravity limbs movements in very low birth weight preterm infants were insufficient compared to those in term infants. The relationship between the quality of general movements (GMs) and antigravity limbs movements was also examined.Methods: Preterm infants with very low birth weight without central nervous system disorders nor severe respiration disorders, and healthy term infants were recruited. The infants were set in a supine position. The distance between both hands and between both feet, and the height of both hands and feet from the floor were recorded at 1-3 corrected months for preterm infants, and at 1-3 months for term infants by a 3D motion capture system. The measurements were adjusted for body proportions. GMs in preterm and term infants were assessed similarly.Results: Thirteen preterm and 15 term infants completed the study. In preterm infants, the distance between both hands and between both feet were longer, and the height of both hands and feet were lower than those in term infants in all measurements. In term infants, the height of both hands and feet increased as they developed, but no change was observed in preterm infants. In preterm infants with abnormal GMs, the distance between both hands was longer, and the height of both hands and feet was lower than that in those with normal GMs. There were no such differences between preterm infants with normal GMs and term infants with normal GMs.Conclusion: Antigravity limbs movements in preterm infants within the first 3 month of corrected age were insufficient compared with those in term infants. Furthermore, no improvement with development was observed in preterm infants. In addition, preterm infants with abnormal GMs showed worse antigravity limbs movements than preterm and term infants with normal GMs. The preterm infants with normal GMs could behave similar to the full term infants. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to compare the effects of triggered pressure assist (TrPA) to nasal continuous positive airway pressure (nCPAP) on cerebral and splanchnic regional blood flow and tissue oxygenation. Methods: S table preterm neonates (<32 weeks gestation) receiving nCPAP had echocardiographic determination of hemodynamics and cerebral and splanchnic regional tissue oxygenation monitoring using near-infrared spectroscopy before and 3 h after switching to TrPA. Results: Ten neonates (birth weight; 1120 ± 450 g, gestation; 27.6 ± 1.5 weeks) were studied at 13.3 ± 12.4 days (mean ± standard deviation). The end-expiratory pressure was 5 ± 1 cm H2O in both modes. There were no significant differences in any of the hemodynamic measurements between nCPAP and TrPA. Cerebral regional tissue oxygen saturation (CrSO2; 74.5 ± 6.9 vs. 73.1 ± 5.8; P < 0.001) and splanchnic rSO2 (72.4 ± 10.4 vs. 68.0 ± 10.8; P < 0.001) were greater during TrPA compared to nCPAP. In addition, the splanchnic/CrSO2 ratio was higher on TrPA (0.97 ± 0.15 vs. 0.92 ± 0.15; P < 0.001). The measurements of splanchnic and CrSO2 were not affected by feedings. Conclusions: Switching from nCPAP to TrPA did not result in significant changes in cardiac output or hemodynamics when the end-expiratory pressure was held constant. TrPA was associated with a small increase in CrSO2 and a larger increase in splanchnic rSO2. These changes were independent of feeding. The clinical significance of these small magnitude changes is uncertain. [ABSTRACT FROM AUTHOR]

Background: This study sought to assess the pharmacokinetic and pharmacodynamic relationships of caffeine citrate therapy in preterm neonates who had therapeutic drug monitoring (TDM) in the post-extubation period. Methods: A retrospective observational study was conducted in preterm neonates who received caffeine citrate therapy for apnea of prematurity and had TDM done in the post-extubation period between January 2006 and October 2011. The relationships between pharmacodynamic effects (heart rate, respiratory rate, episodes of apnea, adverse events) and caffeine serum concentrations were explored. Results: A total of 177 blood samples were obtained from 115 preterm neonates with a median (range) gestational age of 29 (24 - 33) weeks and birth weight of 1230 (607 - 2304) kg. Caffeine citrate therapy was initiated at a median (interquartile range) postnatal age of 1 (1 - 3) day and TDM was performed at a postnatal age of 15 (10 - 24) days. No direct correlations were found between respiratory rate or apneic episodes and caffeine serum concentrations; however, heart rate and caffeine serum concentrations were significantly correlated (p < 0.05). Dosing regimen of 40/ 5 mg/kg q12h (loading dose/maintenance dose, time interval) led to similar endotracheal re-intubation rate but increased percentage of patients experiencing tachycardia compared to the standard regimen of 20/5 mg/kg q24h (44.7 % vs 10.2 %, p < 0.001). Conclusion: Based on this retrospective study, no correlation between episodes of apnea and caffeine serum concentrations was found in neonates who had TDM of caffeine citrate therapy in the post-extubation period, whereas a significant association between tachycardia and concentrations existed. Notwithstanding the absence of severe adverse reactions, TDM should be considered in critically ill neonates with unexplained adverse effects, such as tachycardia. [ABSTRACT FROM AUTHOR]

Objective: Preterm infants frequently receive blood transfusion (BT) and the aim of this study was to measure the effect of BT on cerebral blood flow and oxygenation in preterm infants in relation to chronological age.Patients: Preterm infants undergoing intensive care recruited to three chronological age groups: 1 to 7 (Group 1; n=20), 8 to 28 (Group 2; n=21) & ≥29days of life (Group 3; n=18).Methods: Pre and post-BT anterior cerebral artery (ACA) time averaged mean velocity (TAMV) and superior vena cava (SVC) flow were measured. Cerebral Tissue Haemoglobin Index (cTHI) and Oxygenation Index (cTOI) were measured from 15-20min before to 15-20min post-BT using NIRS. Vital parameters and blood pressure were measured continuously.Results: Mean BP increased significantly, and there was no significant change in vital parameters following BT. Pre-BT ACA TAMV was higher in Group 2 and 3 compared to Group 1 (p<0.001). Pre-BT ACA TAMV decreased significantly (p≤0.04) in all 3 groups; pre-BT SVC flow decreased significantly in Group 1 (p=0.03) and Group 3 (p<0.001) following BT. Pre-BT cTOI was significantly lower in Group 3 compared to Group 1 (p=0.02). cTHI (p<0.001) and cTOI (p<0.05) increased significantly post-BT in all three groups. PDA had no effect on these measurements.Conclusion: Baseline cTOI decreases and ACA TAMV increases with increasing chronological age. Blood transfusion increased cTOI and cTHI and decreased ACA TAMV in all groups. PDA had no impact on the baseline cerebral oximetry and blood flow as well as changes following blood transfusion. [ABSTRACT FROM AUTHOR]

Treg cells are crucial to prevent immune dysregulation, but little is known about the frequency of these cells in neonates, particularly in very/moderate and late preterm newborns studied as separate groups. The CD4+ CD25hi CD127lo FOXP3+Treg population was phenotypically characterized to assess maturation markers and gut-homing integrins by flow cytometry in the cord blood of healthy preterm newborns born at 30-336/7 gestation weeks (Group 1), at 34-366/7 gestation weeks (Group 2) and term newborns born at 37-41 gestation weeks (Group 3), compared to healthy adults. An inverse correlation of the Treg percentage and gestational age was found, with significantly higher frequencies in Group 1 compared to Groups 2 and 3 and in Group 2 compared to Group 3, and significantly higher Treg frequencies and numbers in the neonates compared to the adults. All of the newborns exhibited increased Treg frequencies with a naive phenotype compared to adults. Cytotoxic T-lymphocyte-associated protein 4 CTLA-4 expression in the naive Treg was decreased in both preterm groups compared with those from term newborns and adults, and in the memory Treg from Group 1 compared with the other groups. The frequencies of Treg expressing α4 β7 and α4 β1 integrins were higher in both preterm groups, but significantly different only in Group 1, when compared with those from the term newborns and the adults. In conclusion, although a high frequency of Treg is present in newborns, an immature phenotype with a higher expression of CD45 RA and α4 β7/ α4 β1 and a lower expression of CTLA-4 is found, particularly in the very preterm group. [ABSTRACT FROM AUTHOR]

Background: Few studies have differentiated risk factors for term-small for gestational age (SGA), preterm-appropriate for gestational age (AGA), and preterm-SGA, despite evidence of varying risk of child mortality and poor developmental outcomes.Methods: We analyzed birth outcome data from singleton infants, who were enrolled in a large randomized, double-blind, placebo-controlled trial of neonatal vitamin A supplementation conducted in Tanzania. SGA was defined as birth weight <10th percentile for gestation age and sex using INTERGROWTH standards and preterm birth as delivery at <37 complete weeks of gestation. Risk factors for term-SGA, preterm-AGA, and preterm-SGA were examined independently using log-binomial regression.Results: Among 19,269 singleton Tanzanian newborns included in this analysis, 68.3 % were term-AGA, 15.8 % term-SGA, 15.5 % preterm-AGA, and 0.3 % preterm-SGA. In multivariate analyses, significant risk factors for term-SGA included maternal age <20 years, starting antenatal care (ANC) in the 3(rd) trimester, short maternal stature, being firstborn, and male sex (all p < 0.05). Independent risk factors for preterm-AGA were maternal age <25 years, short maternal stature, firstborns, and decreased wealth (all p < 0.05). In addition, receiving ANC services in the 1(st) trimester significantly reduced the risk of preterm-AGA (p = 0.01). Significant risk factors for preterm-SGA included maternal age >30 years, being firstborn, and short maternal stature which appeared to carry a particularly strong risk (all p < 0.05).Conclusion: Over 30 % of newborns in this large urban and rural cohort of Tanzanian newborns were born preterm and/or SGA. Interventions to promote early attendance to ANC services, reduce unintended young pregnancies, increased maternal height, and reduce poverty may significantly decrease the burden of SGA and preterm birth in sub-Saharan Africa.Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12610000636055 , registered on 3(rd) August 2010. [ABSTRACT FROM AUTHOR]

Aim: Body mass index (BMI)-for-age curves have been developed in the USA, but not compared with other populations. This study created gender-specific intrauterine BMI-for-age curves for Italian preterm infants and compared them with the USA version.Methods: Data on 92 262 newborn infants, born at 26-42 weeks of gestational age in the north-eastern Italian region of Friuli Venezia Giulia between 2005 and 2013, were analysed to create gender-specific BMI-for-age curves. Gender-specific and age-specific BMI Z scores for Italian infants were calculated using the parameters of the USA growth curves and the World Health Organization charts.Results: Gender-specific BMI-for-age at birth curves were developed for premature Italian infants from 26 gestational weeks. The comparison with the USA charts showed no significant difference in BMI percentiles in Italian infants born at ≤33 gestational weeks, but infants born at ≥34 gestational weeks had a significantly higher BMI than the USA population, by 0.2 standard deviations.Conclusion: We developed the first European BMI-for-age at birth curves for premature infants. According to our findings, the Italian curves were comparable to the USA curves for the subgroup of infants born at ≤33 gestational weeks, but not ≥34 gestational weeks. [ABSTRACT FROM AUTHOR]

The aim of the study was to identify the impact of birth of a preterm baby on the emotional states of the parent. In addition to this, it also assessed the impact of preterm birth on various aspects of the family life. Keeping in mind, the assessment of the emotional quotient of parents of NICU admitted babies was carried out by using a prevalidated questionnaire by IBHQ. About 76 parents of NICU admitted babies from NKPSIMS &Lata Mangeshkar Hospital, Nagpur, India. The results show that, there is significant difference seen in the means of daily routine of parent, parental attitude and financial consequences of babies above and below 2 kg of body weight. There is a significant difference observed in the means of parental attitude of babies of primigravida and multipara women. The study also shows that parents' emotional state is positively correlated with their physical state, daily routine, & attitude as well as with financial state. Similarly, positive correlation is seen between their physical state with daily routine, attitude, and financial state. The daily routine of parents is positively correlated with their attitude. While there is a negative correlation observed between the financial state of parent with their daily routine and also with the parents' attitude. This study gives us a broad idea regarding the changes in the attitude of the parents due to the long stay in the NICU. This is also related to parents' counseling & communication skills by NICU staff &junior doctors. It also focuses on the need to improve the counselling abilities of junior doctors with a view to alleviate the anxiety of parents. [ABSTRACT FROM AUTHOR]

Background: Extremely preterm infants receive frequent blood transfusions in the first week of life. The aim of this study was to measure the effect of blood transfusion on intestinal blood flow and oxygenation during the first week of life in extremely preterm infants.Study Design and Methods: Superior mesenteric artery (SMA) peak systolic velocity (PSV) and diastolic velocities were measured 30 to 60 minutes before and after transfusion. Splanchnic tissue hemoglobin index (sTHI), splanchnic tissue oxygenation index (sTOI), and splanchnic fractional tissue oxygen extraction (sFTOE) were measured continuously from 15 to 20 minutes before to after transfusion along with vital variables.Results: Twenty infants were studied (median gestational age, 26 weeks). Ten infants were partially fed (15-68 mL/kg/day). Heart rate and SaO2 remained unaltered; blood pressure increased significantly (p < 0.01) after transfusion. Mean SMA PSV (p = 0.63) and diastolic velocity (p = 0.65) remained unaltered. Mean pretransfusion SMA PSV was similar in partially fed (0.78 m/sec) compared to unfed infants (0.52 m/sec; p = 0.06) and the response to transfusion was not dissimilar. There was a significant increase in sTHI (mean difference, 32.3%; p < 0.01) and sTOI (14.6%; p = 0.03) and decrease in sFTOE (22.1%; p < 0.01) after transfusion. There was no significant difference in sTHI or sTOI between fed and unfed infants and their response to transfusion.Conclusions: Blood transfusion increased blood pressure and intestinal tissue oxygenation but did not alter blood flow velocities. Partial feeding had no impact on intestinal blood flow and tissue oxygenation changes. [ABSTRACT FROM AUTHOR]

Background: Preterm infants suffering from intraventricular hemorrhage (IVH) are at increased risk for neurodevelopmental impairment. Observational data suggest that recombinant human erythropoietin (rEPO) improves long-term cognitive outcome in infants with IVH. Recent studies revealed a beneficial effect of early high-dose rEPO on white matter development in preterm infants determined by magnetic resonance imaging (MRI). Objectives: To summarize the current evidence and to delineate the study protocol of the EpoRepair trial (Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants). Methods: The study involves a review of the literature and the design of a double-blind, placebo-controlled, multicenter trial of repetitive high-dose rEPO administration, enrolling 120 very preterm infants with moderate-to-severe IVH diagnosed by cranial ultrasound in the first days of life, qualitative and quantitative MRI at term-equivalent age and long-term neurodevelopmental follow-up until 5 years of age. Results and Conclusions: The hypothesis generated by observational data that rEPO may improve long-term cognitive outcomes of preterm infants suffering from IVH are to be confirmed or refuted by the randomized controlled trial, EpoRepair. © 2015 The Author(s) Published by S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Hepcidin, a key regulatory peptide hormone in iron homeostasis, may in future serve as a non-invasive iron status parameter for monitoring iron supplementation in preterm infants. For this, coexisting influencing factors should be taken into account. Objectives: To evaluate the short-term effects of red blood cell (RBC) transfusions on hepcidin concentrations in serum (HepS) and urine (HepU) of preterm infants. Methods: This was a prospective, observational study conducted between May 2009 and September 2010 at a single neonatal unit (Tübingen University Hospital, Tübingen, Germany) in very preterm infants, i.e. with a gestational age (GA) of <32 weeks, who received clinically indicated RBC transfusions. The concentration of the mature, 25 amino-acid form of hepcidin was determined in serum und urine by competitive enzyme-linked immunosorbent assay together with cellular indices before and after transfusion. Results: Twenty preterm infants born at a median GA of 26 + 0/7 (interquartile range: 24 + 6/7 to 27 + 3/7) weeks received 27 RBC transfusions at a median corrected age of 31 + 3/7 (29 + 6/7 to 34 + 5/7) weeks. When measured shortly after transfusion (mean time: 10 h), haematocrit values increased from a mean of 26.6% (SD 2.8) to 40.9% (SD 3.2); p < 0.0001. HepS also increased [geometric mean: 44.3 (95% confidence interval 30.8-63.8) ng/ml vs. 58.0 (35.7-94.3) ng/ml; p < 0.05] but HepU remained unaffected. Conclusion: The data indicate that HepS concentrations increase shortly after RBC transfusion in preterm infants. Long-term observational studies are needed to understand the dynamics of hepcidin regulation in preterm infants. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: To evaluate the influence of body position on the displacement of nasal prongs in preterm infants. Methods: This prospective, randomized, crossover study enrolled infants born at a mean gestational age of 29.7±2 weeks, birth weight of 1353±280g and 2.9±2.2 days of life, submitted to continuous positive airway pressure by nasal prongs. The main outcome was the number of times that the nasal prongs were displaced following infant positioning in the following body positions: prone, right lateral, left lateral, and supine, according to a pre-established random order. Moreover, cardiorespiratory variables (respiratory rate, heart rate, and oxygen saturation) were evaluated for each body position. Data for each position were collected every 10 min, over a period of 60 min. An occurrence was defined when the nasal prongs were displaced from the nostrils after 3 min in the desired position, requiring intervention of the examiner. Results: Among the 16 studied infants, the occurrence of nasal prong displacement was only observed in the prone position (9 infants - 56.2%) and in the left lateral position (2 infants - 12.5%). The number of times that the prongs were displaced was 11 in the prone position (7 within the first 10min) and 2 in the left lateral position (1 within the first 10min). No clinically significant changes were observed in the cardiorespiratory variables. Conclusions: Maintenance of the nasal prongs to provide adequate noninvasive respiratory support was harder in the prone position. [ABSTRACT FROM AUTHOR]

Introduction: The cerebral cortex develops rapidly in the last trimester of pregnancy. In preterm infants, brain development is very vulnerable because of their often complicated extra-uterine conditions. The aim of this study was to quantitatively describe cortical development in a cohort of 85 preterm infants with and without brain injury imaged at 30 and 40 weeks postmenstrual age (PMA). Methods: In the acquired T2-weighted MR images, unmyelinated white matter (UWM), cortical grey matter (CoGM), and cerebrospinal fluid in the extracerebral space (CSF) were automatically segmented. Based on these segmentations, cortical descriptors evaluating volume, surface area, thickness, gyrification index, and global mean curvature were computed at both time points, for the whole brain, as well as for the frontal, temporal, parietal, and occipital lobes separately. Additionally, visual scoring of brain abnormality was performed using a conventional scoring system at 40 weeks PMA. Results: The evaluated descriptors showed larger change in the occipital lobes than in the other lobes. Moreover, the cortical descriptors showed an association with the abnormality scores: gyrification index and global mean curvature decreased, whereas, interestingly, median cortical thickness increased with increasing abnormality score. This was more pronounced at 40 weeks PMA than at 30 weeks PMA, suggesting that the period between 30 and 40 weeks PMA might provide a window of opportunity for intervention to prevent delay in cortical development. [ABSTRACT FROM AUTHOR]

Background: The perfusion index (PI) derived from pulse oximetry readings represents the ratio of pulsatile (arterial blood) and nonpulsatile contributors to infrared light absorption. PI has been shown to correlate with cardiac performance. In theory, PI is readily available on every pulse oximeter; therefore, no additional sensors or infant handling are required. Currently, reference values are lacking in (preterm) neonates and the association with common clinical conditions is unclear. Objectives: To establish reference values for the PI in premature infants and at the same time determine the influence of common clinical conditions. Methods: PI was prospectively monitored on the lower limb for 72 h in 311 neonates born with a gestational age <32 weeks between January 2011 and December 2013. Longitudinal mixed-effects modeling was used. Linear, quadratic, and cubic models were explored. Main effects and interactions were investigated. Results: A squared model (0-24 h) followed by a linear model (24-72 h) provided the best fit of the data. PI was lowest around 12-18 h after birth and showed a steady increase thereafter. PI was positively related with female gender, gestational age, and pulse pressure. Negative associations were found with SIMV/HFOV ventilation, dopamine administration, mean arterial blood pressure, and arterial oxygen saturation. Although more complex, the general association with a patent ductus arteriosus was positive. Conclusion: PI varied according to several clinical conditions. The association with common clinical factors suggests that PI might be used for monitoring neonatal hemodynamics and possibly as an additional guidance for interventions. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]