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Objective: To determine the normative values of cerebral blood flow (CBF) velocities in very low birth weight (VLBW) neonates during the first 28 days of life., Method: In this prospective observational study, doppler assessment of CBF velocities was performed from the anterior cerebral artery (ACA), middle cerebral artery (MCA) and basilar artery (BA) at 2-8 hours, 24 hours, day 3, 7, 14 and 28 of life. Neonates with gross congenital malformations, those requiring extensive resuscitation at birth, mechanical ventilation with mean airway pressure >12 mbar, requiring inotropes, or those who developed intraventricular hemorrhage (grade II or more) were excluded., Results: A total of 103 VLBW neonates were enrolled, in whom 1178 doppler measurements were recorded. The mean (SD) peak systolic velocity, end diastolic velocity and mean velocity (cm/s) in ACA increased from 26.53 (8.56) to 51.35 (9.36), 9.22 (2.91) to 13.9 (3.24) and 17.75 (3.97) to 25.84 (3.27) respectively from 2 to 8 hours to day 28 of life. In MCA and BA also, CBF velocities increased with post-natal age., Conclusion: We report normative data of CBF velocities in VLBW neonates in first 28 days of life.

Introduction: Maternal speech has been shown to benefit premature infants by improving feeding outcomes and potentiating the development of the auditory cortex. To our knowledge, limited studies have addressed the benefits of exposure to maternal speech on neural development in premature infants. The objective of this study was to investigate the effect of early controlled exposure to maternal recording a passage of speech on heart rate variability (obtained before, during, and after playback of a test stimulus of a female stranger speaking the same passage) in very low-birth-weight premature infants tracked weekly from 28 to 34 weeks., Methods: Prospective, randomized controlled trial, longitudinal, and repeated-measures design were conducted on 49 subjects. Infants heard a recording of their mother's speech twice a day from either 28 to 34 weeks (group 1) or from 32 to 34 weeks (group 2). Spectral analysis was measured weekly for 45 seconds before, during, and after playback of maternal speech. A generalized linear mixed model was conducted to examine the 2-way interaction in the log high-frequency power between groups, genders, sessions, and conditions., Results: It was found that there were no significant differences between groups before, during, and after playback of the stimulus. A significant difference, however, was noted between conditions (before vs during period)., Conclusion: It can be concluded cautiously that playing back of maternal speech recordings to the premature infant has a beneficial impact on neural development after 32 weeks gestational age., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Individuals born very preterm (<32 weeks of gestation) or with very low birthweight (<1500g) have lower cognitive function compared with term-born peers. Furthermore, some studies suggest that they are less physically active as young adults than controls, but the relationship between physical activity and cognitive function remains unclear. We performed an individual participant data meta-analysis to examine whether being born preterm/with very low birth weight is associated with physical activity in adulthood and examined if cognitive function mediates this association., Study Design: Cohorts with data on physical activity and cognitive function in adults born very preterm/very low birth weight and term-born controls were recruited from the Research on European Children and Adults Born Preterm, and the Adults Born Preterm International Collaboration Consortia. A systematic literature search was performed in PubMed and Embase., Results: Five cohorts with 1644 participants aged 22-28 years (595 very preterm/very low birth weight and 1049 controls) were included. Adults born very preterm/very low birth weight reported 1.11 (95% CI: 0.68 to 1.54) hours less moderate to vigorous physical activity per week than controls, adjusted for cohort, age and sex. The difference between individuals born very preterm/very low birth weight and controls was larger among women than among men. Neither intelligence quotient nor self-reported executive function mediated the association between very preterm/very low birth weight and moderate to vigorous physical activity. Results were essentially the same when we excluded individuals with neurosensory impairments., Conclusion: Adults born very preterm/very low birth weight, especially women, reported less moderate to vigorous physical activity than their term-born peers. Cognitive function did not mediate this association. Considering the risk of adverse health outcomes among individuals born preterm, physical activity could be a target for intervention., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Aakvik et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Individuals born with very low birth weight (VLBW; < 1500 g) have a higher risk of reduced visual function and brain alterations. In a longitudinal cohort study, we assessed differences in visual outcomes and diffusion metrics from diffusion tensor imaging (DTI) at 3 tesla in the visual white matter pathway and primary visual cortex at age 26 in VLBW adults versus controls and explored whether DTI metrics at 26 years was associated with visual outcomes at 32 years. Thirty-three VLBW adults and 50 term-born controls was included in the study. Visual outcomes included best corrected visual acuity, contrast sensitivity, P100 latency, and retinal nerve fibre layer thickness. Mean diffusivity, axial diffusivity, radial diffusivity, and fractional anisotropy was extracted from seven regions of interest in the visual pathway: splenium, genu, and body of corpus callosum, optic radiations, lateral geniculate nucleus, inferior-fronto occipital fasciculus, and primary visual cortex. On average the VLBW group had lower contrast sensitivity, a thicker retinal nerve fibre layer and higher axial diffusivity and radial diffusivity in genu of corpus callosum and higher radial diffusivity in optic radiations than the control group. Higher fractional anisotropy in corpus callosum areas were associated with better visual function in the VLBW group but not the control group., (© 2024. The Author(s).)

Background: Preterm survivors have increased risk for impaired cardiometabolic health. We assessed glucose regulation and cardiometabolic biomarkers in adult very low birth weight (VLBW, <1500 g) survivors, using siblings as controls., Methods: VLBW-participants were matched with term-born, same-sex siblings. At mean age 29.2 years (SD 3.9), 74 VLBW-adults and 70 siblings underwent a 2-h 75 g oral glucose tolerance test and blood tests for assessment of cardiometabolic biomarkers., Results: Of participants, 23 (31%) VLBW and 11 (16%) sibling-controls met World Health Organization criteria for impaired glucose regulation (OR adjusted for age and sex 2.5, 95% CI: 1.1 to 5.8). Adjusting for age and sex, VLBW-participants showed 9.2% higher 2-h glucose (95% CI: 0.4% to 18.8%) than their siblings. Also, fasting (13.4%, -0.3% to 29.0%) and 2-h free fatty acids (15.6%, -2.4% to 36.9%) were higher in VLBW-participants. These differences were statistically significant only after further adjusting for confounders. No statistically significant differences were found regarding other measured biomarkers, including insulin resistance, atherogenic lipid profiles or liver tests., Conclusions: VLBW-adults showed more impaired fatty acid metabolism and glucose regulation. Differences in cardiometabolic biomarkers were smaller than in previous non-sibling studies. This may partly be explained by shared familial, genetic, or environmental factors., Impact: At young adult age, odds for impaired glucose regulation were 3.4-fold in those born at very low birth weight, compared to same-sex term-born siblings. Taking into consideration possible unmeasured, shared familial confounders, we compared cardiometabolic markers in adults born preterm at very low birth weight with term-born siblings. Prematurity increased risk for impaired glucose regulation, unrelated to current participant characteristics, including body mass index. In contrast to previous studies, differences in insulin resistance were not apparent, suggesting that insulin resistance may partially be explained by factors shared between siblings. Also, common cardiometabolic biomarkers were similar within sibling pairs., (© 2023. The Author(s).)

Background: Executive function difficulties are common among children born very preterm and/or very low birthweight (<1500 g; VLBW), but little is known about whether they persist into adulthood., Objectives: Examine the nature and pattern of self-reported executive functioning at 23 and 28 years of age using data from a national cohort study of adults born VLBW and a comparison group of same-age full-term (FT) born adults. Also examined were associations between executive function difficulties and socio-economic outcomes., Methods: All infants born VLBW in New Zealand during 1986 were prospectively included in an audit of retinopathy of prematurity (n = 413), with 250 (77% of survivors) followed to median age 28 years. A comparison group of FT adults was also recruited at age 23 and followed to 28 years (n = 100). Across both adult assessments, executive functioning was assessed using the Behaviour Rating Inventory of Executive Function-Adult Version (BRIEF-A) and analysed with semi-parametric models to examine the effects of age and group on executive function., Results: At 23 and 28 years, VLBW adults had increased risk of executive function impairment compared with FT adults in behaviour regulation (relative risk [CI] 2.37, 95% confidence interval (CI)1.27, 4.45), meta-cognition (RR 6.03, 95% CI 2.18, 16.78) and global functioning (RR 3.20, 95% CI 1.40, 7.28). Impaired global executive functioning was associated with lower socio-economic status (regression estimate [b] = -0.43, 95% CI -0.59, -0.27) and a reduced likelihood of home ownership by age 28 years (RR 0.98, 95% CI 0.96, 1.00), even after controlling for sex, ethnicity and parental socio-economic backgrounds for both groups., Conclusion(s): VLBW-born adults continue to experience more executive function difficulties in their everyday life relative to term controls at age 28 years. These difficulties were negatively associated with their socio-economic opportunities as young adults., (© 2022 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

The measurement of blood pressure in the very low birth weight newborn infant is not simple and may be erroneous because of numerous factors. Assessment of cardiovascular insufficiency in this population should be based on multiple parameters and not only on numeric blood pressure readings. The decision to treat cardiovascular insufficiency should be made after considering the potential complications of such treatment. There are numerous potential strategies to avoid or mitigate hypoperfusion states in the very low birth weight infant., (Copyright © 2022 by the American Academy of Pediatrics.)

Background: Delayed onset of minimal enteral nutrition compromises the immune response of preterm infants, increasing the risk of colonization and clinical complications (e.g., late-onset sepsis). This study aimed to analyze associations between late-onset sepsis in very low birth weight infants (<1500 g) and days of parenteral nutrition, days to reach full enteral nutrition, and maternal and nutritional factors., Methods: A cross-sectional study was carried out with very low birth weight infants admitted to a neonatal intensive care unit (NICU) of a reference maternity hospital of high-risk deliveries. Data regarding days of parenteral nutrition, days to reach full enteral nutrition, fasting days, extrauterine growth restriction, and NICU length of stay were extracted from online medical records. Late-onset sepsis was diagnosed (clinical or laboratory) after 48 h of life. Chi-squared, Mann-Whitney tests, and binary logistic regression were applied., Results: A total of 97 preterm infants were included. Of those, 75 presented late-onset sepsis with clinical ( n = 40) or laboratory ( n = 35) diagnosis. Maternal urinary tract infection, prolonged parenteral nutrition (>14 days), and extrauterine growth restriction presented 4.24-fold, 4.86-fold, and 4.90-fold higher chance of late-onset sepsis, respectively., Conclusion: Very low birth weight infants with late-onset sepsis had prolonged parenteral nutrition and took longer to reach full enteral nutrition. They also presented a higher prevalence of extrauterine growth restriction than infants without late-onset sepsis.

Background: The thermal servo-controlled systems are routinely used in neonatal intensive care units (NICUs) to accurately manage patient temperature, but their role during the immediate postnatal phase has not been previously assessed., Objective: To compare two modalities of thermal management (with and without the use of a servo-controlled system) immediately after birth., Study Design and Setting: Multicentre, unblinded, randomised trial conducted 15 Italian tertiary hospitals., Participants: Infants with estimated birth weight <1500 g and/or gestational age <30 +6 weeks., Intervention: Thermal management with or without a thermal servo-controlled system during stabilisation in the delivery room., Primary Outcome: Proportion of normothermia at NICU admission (axillary temperature 36.5°C-37.5°C)., Results: At NICU admission, normothermia was achieved in 89/225 neonates (39.6%) with the thermal servo-controlled system and 95/225 neonates (42.2%) without the thermal servo-controlled system (risk ratio 0.94, 95% CI 0.75 to 1.17). Thermal servo-controlled system was associated with increased mild hypothermia (36°C-36.4°C) (risk ratio 1.48, 95% CI 1.09 to 2.01)., Conclusions: In very low birthweight infants, thermal management with the servo-controlled system conferred no advantage in maintaining normothermia at NICU admission, while it was associated with increased mild hypothermia. Thermal management of preterm infants immediately after birth remains a challenge., Trial Registration Number: NCT03844204., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Several observations suggest an impact of prematurity on the claustrum. First, the claustrum's development appears to depend on transient subplate neurons of intra-uterine brain development, which are affected by prematurity. Second, the claustrum is the most densely connected region of the mammalian forebrain relative to its volume; due to its effect on pre-oligodendrocytes, prematurity impacts white matter connections and thereby the development of sources and targets of such connections, potentially including the claustrum. Third, due to its high connection degree, the claustrum contributes to general cognitive functioning (e.g., selective attention and task switching/maintaining); general cognitive functioning, however, is at risk in prematurity. Thus, we hypothesized altered claustrum structure after premature birth, with these alterations being associated with impaired general cognitive performance in premature born persons. Using T1-weighted and diffusion-weighted magnetic resonance imaging in 70 very preterm/very low-birth-weight (VP/VLBW) born adults and 87 term-born adults, we found specifically increased mean diffusivity in the claustrum of VP/VLBW adults, associated both with low birth weight and at-trend with reduced IQ. This result demonstrates altered claustrum microstructure after premature birth. Data suggest aberrant claustrum development, which is potentially related with aberrant subplate neuron and forebrain connection development of prematurity., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Hypotension in the early stages of life appears in 20% of very low birth weight (VLBW) infants. The gestational age and birth weight are the risk factors highly related to the postnatal hypotension. Other risk factors slightly differ between different studies. So, we evaluated the risk factors and prognosis that are associated with infants treated with hypotension in the early stages of life, after excluding the influences of gestational age and small for gestational age (SGA). VLBW infants registered in the Korean Neonatal Network between 2013 and 2015 treated for hypotension within a week after their birth were selected as study subjects. The rest were used as a control group. Risk factors and the prevalence of severe complications, including mortality, were investigated and compared after matching for gestational age and SGA. The treatment rate for hypotension within the first postnatal week was inversely related to decreasing gestational ages and birth weights. In particular, 63.4% of preterm infants born at ≤ 24 weeks' gestation and 66.9% of those with a birth weight < 500 g were treated for hypotension within a week of birth. Regression analysis after matching showed that 1-minute Apgar score, neonatal cardiac massage or epinephrine administration, symptomatic patent ductus arteriosus, early onset sepsis, and chorioamnionitis were significantly associated with hypotension. In the hypotension group, mortality, grade 3 or higher intraventricular hemorrhage, periventricular leukomalacia, and moderate to severe bronchopulmonary dysplasia rates were significantly higher after the matching for gestational age and SGA. Hypotension during the first postnatal week is very closely related to the prematurity and the condition of the infant shortly after birth. Regular prenatal care including careful monitoring and appropriate neonatal resuscitation are very crucial to decrease the risk of hypotension in the early stages of life., Competing Interests: The authors have declared that no competing interests exist.

Assessment of the characteristics of spontaneous movements and behaviour in early infancy helps in estimating developmental outcomes. We introduced the Infant Behaviour Checklist (IBC) and examined the relationship between the behavioural characteristics of low-birth-weight infants and neurodevelopmental outcomes at 6 years of age. The behavioural characteristics during the neonatal (36-43 weeks, adjusted) and early infancy periods (49-60 weeks, adjusted) were assessed in very-low-birth-weight infants. The IBC includes 44 common behaviours. We assessed the appearance of individual behavioural characteristics at each period according to the neurodevelopmental outcome. Of the 143 infants assessed during the neonatal period, 89 had typical development (TD), 30 had intellectual disability (ID), and 24 had autism spectrum disorder (ASD). In 78 infants assessed during early infancy, 40, 21, and 17 had TD, ID, and ASD, respectively. The frequency of appearance of three behaviour-related items was significantly lower in the ID group than in the TD group. The frequency of appearance of three posture- and behaviour-related items was significantly lower, while that of two posture-related items was significantly higher, in the ASD group than in the TD group. Behavioural assessment using the IBC may provide promising clues when considering early intervention for low-birth-weight infants., (© 2021. The Author(s).)

Objective: The present study seeks to assess the impact of gestational hypertensive disorders on premature newborns below 34 weeks and to establish the main morbidities and mortality in the neonatal period and at 18 months., Materials and Methods: A retrospective observational study was carried out with 695 premature newborns of gestational age (GA) between 24 and 33 weeks and 6 days, born alive in the Neonatal ICU of Brasília's Mother and Child Hospital (HMIB), in the period from January 1, 2014, to July 31, 2019. In total, 308 infants were born to hypertensive mothers (G1) and 387 to normotensive mothers (G2). Twin pregnancies and diabetic patients with severe malformations were excluded. Outcomes during hospitalization and outcomes of interest were evaluated: respiratory distress syndrome (RDS), brain ultrasonography, diagnosis of bronchopulmonary dysplasia (BPD), diagnosis of necrotizing enterocolitis, retinopathy of prematurity, breastfeeding rate at discharge, survival at discharge and at 18 months of chronological age and relationship between weight and gestational age., Results: Newborns with hypertensive mothers had significantly lower measurements of birth weight and head circumference. The G1 group had a higher risk small for gestational age (OR 2.4; CI 95% 1.6-3.6; p <0.00), as well as a greater risk of being born with a weight less than 850 g (OR 2.4; 95% CI 1.2-3.5; p <0.00). Newborns of mothers with hypertension presented more necrotizing enterocolitis (OR 2.0; CI 95% 1.1-3.7); however, resuscitation in the delivery room and the need to use surfactant did not differ between groups, nor did the length of stay on mechanical ventilation, or dependence on oxygen at 36 weeks of gestational age. Survival was better in newborns of normotensive mothers, and this was a protective factor against death (OR 0.7; 95% CI 0.5-0.9; p <0.01). In the follow-up clinic, survival at 18 months of chronological age was similar between groups, with rates of 95.3% and 92.1% among hypertensive and normotensive mothers, respectively. Exclusive breastfeeding at discharge was 73.4% in the group of hypertensive women and 77.3% in the group of normotensive mothers. There were no significant differences between groups., Conclusion: Among the analyzed outcomes, arterial hypertension during pregnancy can increase the risk of low weight, small babies for gestational age (SGA), deaths in the neonatal period and enterocolitis, with no differences in weight and survival at 18 months of chronological age. Arterial hypertension presents a high risk of prematurity in the neonatal period, with no difference at 18 months of age., Competing Interests: The authors have declared that no competing interests exist.

Preterm very low birth weight infants (VLBWi) are known to be at greater risk of adverse neurodevelopmental outcome. Identifying early factors associated with outcome is essential in order to refer patients for early intervention. Few studies have investigated neurodevelopmental outcome in Italian VLBWi. The aim of our longitudinal study is to describe neurodevelopmental outcome at 24 months of corrected age in an eleven-year cohort of 502 Italian preterm VLBWi and to identify associations with outcome. At 24 months, Griffiths' Mental Developmental Scales were administered. Neurodevelopmental outcome was classified as: normal, minor sequelae (minor neurological signs, General Quotient between 76 and 87), major sequelae (cerebral palsy; General Quotient ≤ 75; severe sensory impairment). 75.3% showed a normal outcome, 13.9% minor sequelae and 10.8% major sequelae (3.8% cerebral palsy). Male gender, bronchopulmonary dysplasia, abnormal neonatal neurological assessment and severe brain ultrasound abnormalities were independently associated with poor outcome on multivariate ordered logistic regression. Rates of major sequelae are in line with international studies, as is the prevalence of developmental delay over cerebral palsy. Analysis of perinatal complications and the combination of close cUS monitoring and neurological assessment are still essential for early identification of infants with adverse outcome., (© 2021. The Author(s).)

Background: The relationship between severe anemia, red blood cell transfusion and Neonatal necrotizing enterocolitis (NEC) remains controversial. The purpose of this study was to determine the association of severe anemia and RBC transfusion with NEC in neonates., Methods: The clinical characteristics of NEC were observed in 467 infants with different birth weights from January 2012 to July 2020. A 1:1 ratio case-control study was performed in very low birth weight (VLBW) infants. Severe anemia, RBC transfusion, and confounding factors, including maternal and perinatal complications, feeding, and antibiotics administration were collected in both groups. Univariate and multivariate analyses were used to investigate effects on the risk of NEC., Results: The day of NEC onset and mortality were inversely associated with birth weight. In VLBW infants, adjusting for other factors, severe anemia within 72 h [OR = 2.404, P = 0.016], RBC transfusion within 24 h [OR = 4.905, P = 0.016], within 48 h [OR = 5.587, P = 0.008], and within 72 h [OR = 2.858, P = 0.011] increased the risk of NEC., Conclusion: Both severe anemia and RBC transfusion appears to increase the risk of NEC in VLBW infants. The early prevention and treatment of anemia, strict evaluation of the indications for transfusion and enhanced monitoring after transfusion is encouraged in the NICU., Competing Interests: The authors have declared that no competing interests exist.

Background: We evaluated the rates of placental pathologic lesions and their relationship with two-year neurodevelopmental outcomes in very-low-birth-weight (VLBW) infants., Methods: This is a cohort observational study comprising 595 VLBW infants during 2007 to 2015. Neurodevelopmental assessment was carried out at 24 months corrected age., Results: In univariate analysis the rates of survival with normal neurodevelopmental outcomes were lower in pregnancies with severe histologic chorioamnionitis (38 of 43, 88.4% when compared with 305 of 450, 67.8%), severe maternal vascular malperfusion (MVM) (17 of 37, 45.9% when compared with 326/492, 66.3%), and intravillous hemorrhage (37 of 82, 45.1% when compared with 306 of 449, 68.1%). In logistic models, severe MVM (adjusted odds ratio [adj. OR] = 0.45, 95% confidence interval [CI] = 0.22 to 0.92), severe fetal vascular malperfusion (FVM) (adj. OR = 0.46, 95% CI = 0.22 to 0.45), and intravillous hemorrhage (adj. OR = 0.38, 95% CI = 0.22 to 0.62) were associated with lower rates of infant survival with normal neurodevelopmental outcome. FVM (adj. OR = 0.46, 95% CI = 0.21 to 0.97) and intravillous hemorrhage (adj. OR = 0.37, 95% CI = 0.22 to 0.62) were also the only placental lesions that were independent predictors of a lower rate of intact survival in stepwise analysis for prognostic factors of the entire cohort., Conclusions: Placental pathologic findings such as severe MVM, FVM, and intravillous hemorrhage are significant predictors of neonatal survival and subsequent adverse neurodevelopmental outcomes. Data on the placental pathology could be useful in the neurodevelopmental follow-up of VLBW infants., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To report the current incidence of bronchopulmonary dysplasia (BPD) and to compare changes in weight and head circumference between infants who developed BPD and infants who did not., Design: Retrospective, whole-population study., Setting: All neonatal units in England between 2014 and 2018., Patients: All liveborn infants born <28 completed weeks of gestation., Interventions: The change in weight z-score (ΔWz) was calculated by subtracting the birthweight z-score from the weight z-score at 36 weeks postmenstrual age (PMA) and at discharge. The change in head circumference z-score (ΔHz) was calculated by subtracting the birth head circumference z-score from the head circumference z-score at discharge., Main Outcome Measure: BPD was defined as the need for any respiratory support at 36 weeks PMA., Results: 11 806 infants were included in the analysis. The incidence of BPD was 57.5%, and 18.9% of the infants died before 36 weeks PMA. The median (IQR) ΔWz from birth to 36 weeks PMA was significantly smaller in infants who developed BPD (-0.69 (-1.28 to -0.14), n=6105) than in those who did not develop BPD (-0.89 (-1.40 to -0.33), n=2390; adjusted p<0.001). The median (IQR) ΔHz from birth to discharge was significantly smaller in infants who developed BPD (-0.33 (-1.69 to 0.71)) than in those who did not develop BPD (-0.61 (-1.85 to 0.35); adjusted p<0.001)., Conclusions: Postnatal growth was better in infants diagnosed with BPD compared with infants without BPD possibly due to more aggressive nutrition strategies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To obtain reference data on the early motor repertoire of very preterm infants compared with healthy term infants at three months' post-term age., Study Design: In this observational study, using Prechtl's method on the assessment of the early motor repertoire, we compared the quality of fidgety movements and the concurrent motor optimality score - revised of infants with a gestational age <30 weeks and/or a birth weight <1000 g with healthy infants with a gestational age of 37-42 weeks., Results: One hundred eighty very preterm and 180 healthy term infants participated. The median motor optimality scores - revised of very preterm infants were significantly lower in comparison to those of term infants, with scores of 24 (25th-75th percentiles: 23-26) and 26 (25th-75th percentiles: 26-28), respectively. Fidgety movements were aberrant (abnormal or absent) more often in very preterm infants than in term infants. The odds ratio was 4.59 (95% CI, 1.51-13.92). Compared with term infants, very preterm infants had poorer scores on the subscales age-adequate movement repertoire, observed postural patterns, and movement character with odds ratios ≥2.97. We found no differences regarding observed movement patterns., Conclusion: This study provides reference data on the early motor repertoire of very preterm and healthy term infants. It demonstrates that the early motor repertoire of very preterm infants is poorer than that of term infants, a finding consistent with existing knowledge that prematurity increases the risk of poor neurodevelopment., Competing Interests: Declaration of competing interest Prof. Dr. A.F. Bos is a certified tutor of the GM Trust. No other disclosures were reported., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Perinatal events may alter psychosexual development. We aimed to assess whether a preterm birth at very low birth weight (VLBW; <1500 g) or antenatal synthetic glucocorticoids (sGC) given to the mother are associated with altered sex-typical behavior in childhood., Methods: Sex-typical behavior was assessed using the Pre-school Activities Inventory (PSAI) at the mean age of 4.9 years (SD 1.6) in 879 children, of whom 143 were preterm with VLBW (PT <1500 g, all exposed to sGC), 282 were preterm with birth weight ≥1500 g (PT ≥1500 g, 171 exposed to sGC), and 454 were full term (FT, 166 exposed to sGC)., Results: Antenatal sGC was not associated with PSAI scores in either sex. PT <1500 g boys had less male-typical PSAI scores than other boys, even in multivariate model adjusting for age, maternal age, antenatal sGC, number of brothers and sisters, and motor or cognitive impairment. PT <1500 g girls had less female-typical PSAI scores than other girls in the multivariate model. The effect size was small (d = 0.03) for both sexes., Conclusions: Preterm birth with VLBW is associated with reduced sex-typical behavior in childhood, which is in line with the previous data indicating altered psychosexual development in adults born preterm. Mechanisms underlying these observations are not fully understood., Impact: Preterm birth is associated with reduced rates of marriage and reproduction in adulthood, but sex-typical behavior in children born preterm has not been studied before. The results of this study indicate that preterm birth with very low birth weight <1500 g is associated with reduced sex-typical behavior in childhood in both sexes. These observations are in line with the previous data indicating altered psychosexual development in adults born preterm. Mechanisms underlying these observations are not fully understood and require further studies.

Purpose: Preterm birth is associated with adverse pulmonary outcomes. We aimed to evaluate respiratory morbidities and lung function of very low birth weight (VLBW) Polish children followed up at the age of 7 years old, and to compare with electrical impedance segmentography (EIS) results recorded at 4 years of age., Materials and Methods: VLBW children were compared with term controls using impulse oscillometry and spirometry. Perinatal data and current respiratory morbidities were analyzed and pulmonary function test results were compared with previous EIS results., Results: We included 40 VLBW children and 30 controls in the analysis. Elevated total airway resistance and forced expiratory volume in the first second below the lower limit of normal were more prevalent in VLBW children compared with term controls (15 vs 0%; 18 vs 0%). A positive bronchodilator response was more common in VLBW children (R 5 Hz : 46 vs 13.3%; R 5-20 ​Hz : 65 vs 36.7%). Children with bronchopulmonary dysplasia (BPD) had higher total airway resistance (R 5 Hz /R 5 Hz pred : 1.35 vs 0.95; p ​< ​0.001), large airway resistance (R 20 Hz /R 20 Hz pred : 0.89 vs 0.66; p ​= ​0.001), small airway resistance (R 5-20 ​Hz : 0.57 vs 0.34 ​kPa ​L -1  ​s -1 ; p ​= ​0.009), than controls. Strong correlation between BDR in EIS and R 5 Hz /R 5 Hz pred was observed in children with BPD (r ​= ​0.7)., Conclusion: VLBW school-aged children with BPD presented with substantial respiratory morbidity and persistent reduction of lung function, affecting small and large airways and lung parenchyma. EIS may be an alternative tool for lung function assessment in children with BPD., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2020 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Background: Nasal continuous positive airway pressure (NCPAP) can be applied via binasal prongs or nasal masks; both may be associated with air leak and intermittent hypoxia. We investigated whether the latter is more frequent with nasal masks or prongs., Methods: Continuous 24 hours recordings of inspired oxygen fraction (FiO 2 ), pulse rate, respiratory rate, pulse oximeter saturation (SpO 2 ) and CPAP level were made in preterm infants with respiratory insufficiency (n=20) managed on CPAP in the NICU at the Royal Hobart Hospital. As part of routine care, nasal interfaces were alternated 4-hourly between mask and prongs. In each recording, the first two segments containing at least 3 hours of artefact-free signal for each interface were selected. Recordings were analysed for episodes with hypoxaemia (SpO 2 <80% for ≥10 s) and bradycardia (pulse rate <80/min for ≥4 s) and for episodes of pressure loss at the nasal interface. Data were compared using Wilcoxon-matched pairs test and are reported as median (IQR)., Results: Infants had a gestational age at birth of 26 (25-27) weeks and postnatal age of 17 (14-24) days. There was no difference in %time with interface leak between prong and mask (0.9 (0-8)% vs 1.1 (0-18)%, p=0.82), %time with SpO 2 <80% (0.15 (0-1.2)% vs 0.06 (0-0.8)%, p=0.74) or heart rate <80/min (0.03 (0-0.2)% vs 0 (0-0.2)%, p=0.64). Three infants had interface leak for >10% of the time with prongs and 5 with the mask., Conclusion: Both interfaces resulted in a similarly stable provision of positive airway pressure, and there was also no difference in the occurrence of intermittent hypoxia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To determine IQ at 26 to 30 years in very-low-birthweight (VLBW) adults compared with term-born controls; and to examine the stability of IQ in VLBW individuals between 7 to 8 years and 26 to 30 years, identify perinatal and social predictors of IQ, and assess the contribution of brain volume to IQ., Method: At 26 to 30 years, 229 VLBW adults (71% survivors of prospectively enrolled national cohort) and 100 term-born controls were tested on the Wechsler Abbreviated Scale of Intelligence. For VLBW, IQ at 7 to 8 years, perinatal and social data were extracted from the data set, and 150 adults underwent volumetric cranial magnetic resonance imaging (MRI)., Results: At 26 to 30 years, the mean adjusted difference between VLBW and controls for total IQ was 9.4 (95% CI 6.5-12.4) points. In VLBW individuals the correlation between IQ scores at 7 to 8 years and 26 to 30 years was 0.78. On multiple regression analysis, parental education was the strongest predictor of verbal and total IQ at both ages. Birthweight was a strong predictor of perceptual and total IQ. In VLBW individuals with MRI scans, the addition of brain volume as a variable increased the variance explained for perceptual and total IQ., Interpretation: VLBW adults have mean IQ scores 9 to 11 points below controls. Parental education and birthweight are the strongest predictors of IQ., (© 2020 Mac Keith Press.)

Introduction: The characteristics of catch-up growth in very low birth weight infants (VLBW) have not been clearly established. The aim of this study was to analyse the height catch-up and some associated factors in a cohort of VLBW (birth weight<1,500g) from birth to age 14 years., Methods: We obtained retrospective data on weight and height at birth and ages one, 2, 3, 4, 6, 8, 10, 12 and 14 years in a cohort of 170 VLBW. We compared these anthropometric values with those documented in a control group., Results: Thirty-seven children (21.8%) were born with an extremely low birth weight and 32 (18.8%) extremely preterm. At 10 years of age, 7% of VLBW (1,000-1,500g) and 35% of extremely low birth weight (<1,500g) children had short stature (P=.001). Almost all VLBW children who had a normal height at ages 2, 4 and 10 years had exhibited adequate weight catch-up in previous evaluations. We found that extremely low birth weight and extremely preterm were independent predictors for inadequate height catch-up., Conclusion: The growth pattern of VLBW children has specific characteristics. The catch-up in weight seems to be an important factor for catch-up in height, and therefore a thorough nutritional follow-up is recommended in these children., (Copyright © 2019 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Rationale: Congenital syphilis (CS) can manifest as a variety of clinical presentations according to the severity in symptomatic infants during neonatal period. Preterm neonates with CS may have more clinical evidences of infection and be more severely affected by CS compared with term ones. With increasing survival of markedly premature infants for recent decades, CS may be a challenging problem in those with severe manifestations associated with combined pathophysiologies of CS and prematurity., Patient Concerns: A very low birth weight infant at 32 weeks gestation presented with an unusual CS presentation consisting of prematurity-associated severe neonatal morbidities including meconium obstruction, prolonged cholestatic jaundice with elevated liver enzymes, and disseminated intravascular coagulation with a bleeding diathesis, in addition to common or typical manifestations of CS., Diagnoses: Congenital syphilis., Interventions: Therapy consisting of a complete course of parenteral penicillin, blood component therapy, proximal ileotomy with inspissated meconium evacuation and distal loop ileostomy, and other conservative treatments., Outcomes: Resolution with normal gastrointestinal function and improved liver function was observed., Lessons: This case suggests that in premature infants CS may manifest as unusual severe neonatal morbidities that may result from combination of syphilitic pathologies and contributors or conditions associated with prematurity including multisystem immaturity.

Background: Preterm infants, especially those with very low birth weight, are more susceptible to nutritional deficiencies and growth restriction after hospital discharge than term infants., Aims: To investigate the association between energy and protein intake and nutritional evolution of preterm infants during the first year of life of corrected age after hospital discharge., Study Design: This is a retrospective longitudinal study with 131 preterm infants born at a high-risk neonatal clinic., Subjects: Neonates born at <32 weeks of gestational age and with birth weight < 1500 g were included in the study., Outcomes Measures: Growth was assessed by z-scores for weight- and length-to age. Energy and protein intake were assessed by caloric and protein intake rate per kilogram of body weight. Changes in growth were evaluated according to caloric rate and energy intake using linear mixed-effect models., Results: We found that most of the followed-up children (62.3%) had an average daily energy intake <120 kcal/kg of body weight. At the end of the first year of life based on corrected age, the variation in weight gain was greater among those with more severe nutritional deficit at born and who had daily intakes over 130 kcal/kg of body weight (p=0.02) or over 3.5 g of protein/kg of body weight (p=0.03)., Conclusion: Individualized dietary plans for preterm infants should be based on the continuous assessment of growth and weight gain., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: High mortality among premature and very low birth weight (VLBW) babies necessitates the need to formulate and use scoring systems like CRIB score to predict the mortality in this vulnerable group. Objective of the study was to determine the strength of Clinical Risk Index For Babies (CRIB) score in detecting neonatal mortality in babies presenting with very low birth weight so that timely intervention can be done. It was a cross-sectional study, conducted at NICU, Children Hospital, Pakistan Institute of Medical Sciences Islamabad (PIMS) in nine months starting from First July 2017., Methods: A total of two hundred and fifty-four (n=254) new-borns with birth weight of between 500-1500 grams and gestational age lesser than 35 weeks were included in the study. CRIB score was calculated in all neonates and its association was assessed with mortality during NICU stay. Recorded data was analysed for demographic variables. Means and standard deviation was calculated for numeric variables. Chi-square test was applied to find p-value for the correlation between the main variables., Results: 54.3% (n=138) patients were males and 45.7% (n=116) were females. Mean gestational age was 33.3 weeks±1.04 SD and mean birth weight of study population was 1129.9 grams±210.6 SD. Mean CRIB score among the study population was 6.3±3.1SD and overall mortality was found to be 54.7% (n=139). Mean CRIB score was found to be 8.27±2.1 SD among mortality group and it was 3.87±3.4 SD among newborns who were discharged (p<0.05). Mortality was present in 4.3% (n=4) of neonates with CRIB score between 1 to 5, 87.1% (n=121) who had CRIB score between 6 to 10 and 100% (n=14) of neonates who had CRIB score level 11-15 (p<0.05), so a significantly higher percentage mortality was noted among neonates with higher CRIB scores., Conclusions: According to our study mean CRIB score is a significant predictor of neonatal mortality.

Background: Recently a new continuous non-invasive cardiac output measurement, bioreactance, has become available. Bioreactance measurement of cardiac output has been shown to correlate with left ventricular output detected by echocardiography in healthy term and preterm neonates., Aims: Our aim was to correlate cardiac output measurements by bioreactance in the first 48 h of life with adverse outcomes attributable to hypoperfusion (peri/intraventricular haemorrhage (PIVH) and/or necrotising enterocolitis (NEC)) in the cohort of extremely preterm infants., Study Design: A prospective observational cohort study., Subjects: Preterm infants with birth weight less than 1250 g., Outcome Measures: Cardiac output was measured between six and 48 h of age by bioreactance. Our primary outcome was a difference in cardiac output between infants with an adverse outcome attributable to hypoperfusion (Group 1), and infants without the predefined adverse outcome (Group 2)., Results: There were 39 infants enrolled in the study. There were six infants in Group 1. These infants had a significantly lower minimal cardiac output measurement compared to Group 2 (mean 36.7 ml/kg/min vs 64.5 ml/kg/min, p = .0006). The mean cardiac output in Group 1 was significantly lower on day one of life, followed by a significant increase in cardiac output on day two of life compared to Group 2., Conclusions: Infants with birth weight less than 1250 g and PIVH and/or NEC had significantly lower cardiac output compared to infants without these complications on day one of life. This low cardiac output was then followed by a significant increase on day two of life., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Deficits in executive functioning, especially in inhibitory control, are present in children born very premature and/or with very low birth weight (VP/VLBW) and in children with attention-deficit/hyperactivity disorder (ADHD)., Objective: To evaluate whether ADHD imposes additional inhibitory control (IC) deficits in preschoolers born VP/VLBW., Methods: 79 VP/VLBW (4 to 7 years) children were assessed for ADHD using the Schedule for Affective Disorders and Schizophrenia for School Aged Children - Present and Lifetime Version (K-SADS-PL). IC was measured with Conners' Kiddie Continuous Performance Test (K-CPT 2) and the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P).Results: No significant differences were found between ADHD (n = 24) and non-ADHD children (n = 55) for any of the measures (p = 0.062 to p = 0.903). Both groups had deficits in most K-CPT 2 scores compared to normative samples, indicating poor IC and inconsistent reaction times., Conclusions: ADHD does not aggravate IC deficits in VP/VLBW children. Either neuropsychological tasks and parent reports of executive functions (EFs) may not be sensitive enough to differentiate VP/VLBW preschoolers with and without ADHD, or these children's EFs are already so impaired that there is not much room for additional impairments imposed by ADHD.

The goal of this study is to investigate the effectiveness of the neonatal diagnosis-related group scheme in patients affected by respiratory distress syndrome. The variable costs of individual patients in the same group are examined. This study uses the data of infants (N = 243) hospitalized in the Neonatal Intensive Care Unit of the Gaslini Children's Hospital in Italy in 2016. The care unit's operating and management costs are employed to estimate the average cost per patient. Operating costs include those related to personnel, drugs, medical supplies, treatment tools, examinations, radiology, and laboratory services. Management costs relate to administration, maintenance, and depreciation cost of medical equipment. Cluster analysis and Tobit regression are employed, allowing for the assessment of the total cost per patient per day taking into account the main cost determinants: birth weight, gestational age, and discharge status. The findings highlight great variability in the costs for patients in the same diagnosis-related group, ranging from a minimum of €267 to a maximum of €265,669. This suggests the inefficiency of the diagnosis-related group system. Patients with very low birth weight incurred costs approximately twice the reimbursement set by the policy; a loss of €36,420 is estimated for every surviving baby with a birth weight lower than 1,170 grams. On the contrary, at term, newborns cost about €20,000 less than the diagnosis-related group reimbursement. The actual system benefits hospitals that mainly treat term infants with respiratory distress syndrome and penalizes hospitals taking care of very low birth weight patients. As a result, strategic behavior and "up-coding" might occur. We conduct a cluster analysis that suggests a birth weight adjustment to determine new fees that would be fairer than the current costs., Competing Interests: The authors have declared that no competing interests exist.

The aim of the study was to investigate General Movements'(GMs) neonatal trajectories and their association with neurodevelopment at three months corrected age (CA) in preterm infants. We conducted an observational, longitudinal study in 216 very low birth weight infants. GMs were recorded at 31 ± 1, 35 ± 1, 40 ± 1 weeks of postmenstrual age and at three months of corrected age (CA). More than 90% of infants showing neonatal trajectories with persistent Normal (N-N) or initial Poor Repertoire to Normal (PR-N) movements presented fidgety pattern at three months CA. On the contrary, fidgety movements were not detected in any infant with a trajectory of persistent Cramped-Synchronized (CS-CS) or an initial Poor-Repertoire to Cramped-Synchronized (PR-CS) movements. Trajectories with initial Normal to Poor-Repertoire (N-PR) or persistent Poor-Repertoire (PR-PR) movements showed an increased risk of having a non-normal Fidgety pattern compared with the N-N group (OR = 8.43, 95% CI: 2.26-31.45 and OR = 15.02, 95% CI: 6.40-35.26, respectively). These results highlight the importance to evaluate neonatal GMs' trajectory to predict infants' neurodevelopment. N-N or PR-N trajectories suggest normal short-term neurodevelopment, especially a lower risk of Cerebral Palsy; whereas findings of N-PR and PR-PR trajectories indicate the need for closer follow up to avoid delay in programming intervention strategies.

Objective: Predictive models for preterm infant mortality have been developed internationally, albeit not valid for all populations. This study aimed to develop and validate different mortality predictive models, using Spanish data, to be applicable to centers with similar morbidity and mortality., Methods: Infants born alive, admitted to NICU (BW<1500 g or GA<30 w), and registered in the SEN1500 database, were included. There were two time periods; development of the predictive models (2009-2012) and validation (2013-2015). Three models were produced; prenatal (1), first 24 hours of life (2), and whilst admitted (3). For the statistical analysis, hospital mortality was the dependent variable. Significant variables were used in multivariable regression models. Specificity, sensitivity, accuracy, and area under the curve (AUC), for all models, were calculated., Results: Out of 14953 included newborns, 2015 died; 373 (18.5%) in their first 24 hours, 1315 (65.3%) during the first month, and 327 (16.2%) thereafter, before discharge. In the development stage, mortality prediction AUC was 0.834 (95% CI: 0.822-0.846) (p<0.001) in model 1 and 0.872 (95% CI: 0.860-0.884) (p<0.001) in model 2. Model 3's AUC was 0.989 (95% CI: 0.983-0.996) (p<0.001) and 0.942 (95% CI: 0.929-0.956) (p<0.001) during the 0-30 and >30 days of life, respectively. During validation, models 1 and 2 showed moderate concordance, whilst that of model 3 was good., Conclusion: Using dynamic models to predict individual mortality can improve outcome estimations. Development of models in the prenatal period, first 24 hours, and during hospital admission, cover key stages of mortality prediction in preterm infants., Competing Interests: The authors have declared that no competing interests exist.

Objective: We determined thromboelastographic (TEG) profiles of healthy very low birthweight infants (VLBWIs) of the day of birth and at set intervals during their first month., Design: Prospective observational study with blinded clinical and laboratory follow-up., Setting: Level III neonatal intensive care unit (June 2015 to June 2018)., Patients: Consecutive qualifying VLBWIs were enrolled at birth and followed up for 30 days., Interventions and Main Outcomes Measures: Laboratory (citrated-native TEG, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, blood count) and clinical variables were retrieved at birth, 3rd-5th, 10th and 30th day of life. Blood samples temporally related to events with a potential hemostatic impact (sepsis, bleeding, platelets/plasma transfusions, ibuprofen/indomethacin administration) were excluded from analysis., Results: We enrolled 201 VLBWIs and 72 full-term neonates. Sixty-seven of the healthy VLBWIs completed the 30-day follow-up. 541 TEG traces were analysed.On day 1, the median (minimum-maximum) TEG values were as follows: reaction time (R), 8.2 min (1-21.8); kinetics (K), 2.8 min (0.8-16); α angle, 51° (14.2-80.6); maximum amplitude (MA), 54.9 mm (23.9-76.8). PT and APTT were 15.9 s (11.7-51.2) and 59 s (37.8-97.5), respectively. The above parameters suggest minor hypocoagulability compared with term infants. On day 30, the median (minimum-maximum) R was 5 (1-16.9), K 1 (0.8-4.1), α 74.7 (41.1-86.7) and MA 70.2 (35.8-79.7). PT and APTT were 12.1 (10.4-16.6) and 38.8 (29.6-51.4), respectively. Those parameters are consistent with a relatively hypercoagulable phenotype, compared with term infants., Conclusions: Healthy VLBWIs have a prolonged PT and APTT, but their TEG profiles suggest a relatively balanced hemostatic system, with slight hypocoagulability initially (compared with term neonates), gradually evolving to a somewhat more procoagulant phenotype over the first month., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: In the neonatal intensive care unit, preterm infants are exposed to several stressful stimuli. Inappropriate stimulation led to high risk for short- and long-term neurocognitive disabilities. This study aimed to evaluate whether the sequence of execution of weighing/bathing nursing procedures and postmenstrual age (PMA) have any effect on preterm infants' stress responses., Design and Methods: Prospective cross-sectional study on a sample of 21 preterm infants. Responses to the procedures were assessed using an observational sheet based on Als's Synactive Theory of Development. Autonomic and motor responses were scored according to five-point Likert scales. The order of execution of weighing/bathing nursing procedures and PMA were documented. Effects of weighing/bathing execution sequence and PMA on autonomic and motor response scores were analyzed by linear multiple regression analysis., Results: The sequence of execution had a significant effect on the autonomic score during weighing (p = .035), evidencing more stress when weighing was executed first. A higher level of stress response on the autonomic score during both weighing (p = .015) and bathing (p = .018) procedure was independently associated with a lower infant PMA., Conclusions and Practice Implications: The real-time recognition of adaptive/maladaptive responses allows nurses to personalize their approach to preterm infants, taking into account PMA and adjusting the appropriate sequence of execution of weighing/bathing nursing procedures., (© 2020 Wiley Periodicals, Inc.)

Objectives: Unplanned extubations (UEs) in adult and pediatric populations are associated with poor clinical outcomes and increased costs. In-hospital outcomes and costs of UE in the NICU are not reported. Our objective was to determine the association of UE with clinical outcomes and costs in very-low-birth-weight infants., Methods: We performed a retrospective matched cohort study in our level 4 NICU from 2014 to 2016. Very-low-birth-weight infants without congenital anomalies admitted by 72 hours of age, who received mechanical ventilation (MV), were included. Cases (+UE) were matched 1:1 with controls (-UE) on the basis of having an equivalent MV duration at the time of UE in the case, gestational age, and Clinical Risk Index for Babies score. We compared MV days after UE in cases or the equivalent date in controls (postmatching MV), in-hospital morbidities, and hospital costs between the matched pairs using raw and adjusted analyses., Results: Of 345 infants who met inclusion criteria, 58 had ≥1 UE, and 56 out of 58 (97%) were matched with appropriate controls. Postmatching MV was longer in cases than controls (median: 12.5 days; interquartile range [IQR]: 7 to 25.8 vs median 6 days; IQR: 2 to 12.3; adjusted odds ratio: 4.3; 95% confidence interval: 1.9-9.5). Inflation-adjusted total hospital costs were higher in cases (median difference: $49 587; IQR: -15 063 to 119 826; adjusted odds ratio: 3.8; 95% confidence interval: 1.6-8.9)., Conclusions: UEs in preterm infants are associated with worse outcomes and increased hospital costs. Improvements in UE rates in NICUs may improve clinical outcomes and lower hospital costs., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Background: Cardiovascular and renal disease are nowadays among the leading cause of morbidity and mortality in Western Countries. Low birth weight has been recently considered a key factor in determining cardiovascular disease and long-term renal disease in adulthood., Methods: In our study we analyzed, through echocardiography, eco color Doppler of carotid arteries, ultrasound of abdominal aorta and kidneys, morphological characteristics of cardiovascular and renal system, in a group of children born preterm with very low birth weight, (birth weight<1500 grams) and in a group of children, age and sex matched, born at term with weight appropriate for gestational age. Fifteen children born very low birth weight preterm (cases), aged from 3 to 5 years, and 15, age and sex matched children, born appropriate for gestational age at term (controls) were enrolled in the study., Results: The two groups were homogeneous for interventricular septum diameter, left ventricular end-systolic diameter, left atrial diameter, and ejection fraction. Left ventricular end diastolic diameter was higher in case compared to controls (P=0.04), while aortic diameter root smaller (P=0.005). E and A waves peak velocities and E/A ratio resulted lower in cases compared to controls (P=0.02, P<0.001and P<0.001, respectively). Tei index, S, e' and a' waves velocities were similar in the two groups, while E/e' ratio was higher in cases (P=0.046). Intima-media thickness and antero-posterior diameter of abdominal aorta values did not differ in cases versus controls. Longitudinal diameters of both kidneys were reduced in cases compared to controls (P<0.05)., Conclusions: Although limited by the small sample size, our study highlighted an increased size of the left ventricle and altered left ventricular diastolic function in children born very low birth weight preterm, but no long-term consequences on systolic performance and vascular structure have been found. The finding of smaller kidneys in ex-preterm very low birth weight children could explain their higher susceptibility to develop renal disease in adulthood.

The objective of this commentary was to analyze the causes and outcomes of gut microbiome dysbiosis in preterm infants who are born at very low birth weight (VLBW). The intrauterine development of VLBW infants is interrupted abruptly with preterm birth and followed by extrauterine, health-threatening conditions and sequelae. These infants develop intestinal microbial dysbiosis characterized by low diversity, an overall reduction in beneficial and/or commensal bacteria, and enrichment of opportunistic pathogens of the Gammaproteobacteria class. The origin of VLBW infant dysbiosis is not well understood and is likely the result of a combination of immaturity and medical care. We propose that these factors interact to produce inflammation in the gut, which further perpetuates dysbiosis. Understanding the sources of dysbiosis could result in interventions to reduce gut inflammation, decrease enteric pathology, and improve health outcomes for these vulnerable infants., (Copyright © 2020. Published by Elsevier Inc.)

Sepsis is commonly known to affect neonatal outcomes. We assessed how much center-to-center variability of the sepsis rate affects the outcomes of very-low-birth-weight infants (VLBWIs). 7,493 VLBWIs registered in the Korean Neonatal Network from 2013 to 2016 were classified into three groups according to the sepsis rate: low sepsis group (LS) < 25 th percentile versus intermediate sepsis group (IS) 25 th -75 th versus high sepsis group (HS) ≥ 75 th . The incidence density of sepsis for the LS, IS, and HS groups were 1.17, 3.17, and 8.88 cases/1,000 person-days. After propensity score matching was done for multiple antenatal and perinatal factors, the odds ratio of death, moderate to severe bronchopulmonary dysplasia and/or death, periventricular leukomalacia, and survival without major morbidities for the HS group were 2.0 (95% confidence interval 1.4-2.8), 1.9 (1.5-2.4), 1.5 (1.1-2.3) and 0.7 (0.5-0.8) when compared with the IS group, and 2.2 (1.6-3.2), 2.3 (1.8-2.9), 2.0 (1.3-2.9), and 0.7 (0.6-0.9) when compared with the LS group. There were no significant differences in those outcomes between the LS and IS groups. Hence, nationwide quality improvements to control the sepsis rate especially in units with a high sepsis rate will be helpful to improve the outcomes of VLBWIs.

Purpose: The purpose of this review was to ascertain the impact of thermoregulation quality improvement initiatives (QIs) on the admission temperatures of premature/very-low-birth-weight infants in neonatal intensive care units (NICUs)., Methods: A systematic search of databases Cumulative Index to Nursing and Allied Health Literature, Medline, Embase, and the Cochrane library was carried out. Specific inclusion and exclusion criteria were adhered to, with no publication date limitations added. The chosen studies were examined for quality, data were extracted and analysed, before a narrative synthesis was performed. The last search occurred on January 7, 2019, with PRISMA flow diagrams completed for identified studies., Results: Ten studies of varying methodology design were included in this review. Variations of thermoregulation interventions were included in the 10 studies. Nevertheless, all of them demonstrated that admission temperature rates can be significantly improved by implementing a thermoregulation QI. The multidisciplinary team and ongoing education were seen as much needed components to the overall sustainability, and continuing success of the QI's., Practical Implications: This systematic review determines that thermoregulation QIs can positively impact the admission temperatures of premature/very-low-birth-weight infants in the NICU. Prevention of hypothermia is aimed at reducing the risks of developing major neonatal morbidities. The pooling of the results from the 10 studies helps in the sharing of outcome measures and thus, improving quantitative synthesis. More frequent monitoring of the axillary temperature would help in preventing hypothermia and hyperthermia occurring. Ongoing education and staff training are essential for managing thermoregulation successfully. Examining the compliance rates to such quality initiatives, and the variations in interventions would benefit from further research to ensure better standardisation of clinical practice., (© 2020 Wiley Periodicals, Inc.)

Background: Preterm childbirth increases the risk of developmental problems. The aim of the present study was to examine the effects of temperament and attention on the cognition of school-age children who were born preterm, controlling for socioeconomic variables., Material and Methods: The sample was composed of 50 six-year-old children who were born preterm with very low birth weight. The children were evaluated using the Wechsler Intelligence Scale for Children (WISC-III) and the Cancellation Attention Test. The mothers were interviewed using the Children's Behavior Questionnaire (CBQ). Statistical multiple linear regression analyses were performed., Results: 70% of the children presented average or above-average full intellectual quotient (IQ). In the attention total score, 74% of the children were also within the average range or above. High verbal IQ associated with high maternal schooling explained 73% variability of the full IQ. High attention and maternal schooling, associated with children's temperament with more effortful control, explained 35% variability of the verbal IQ. High attention, associated with high maternal schooling and socioeconomic level, explained 37% variability of the performance IQ. The neonatal clinical variables (gestational age, birth weight, 5th-minute Apgar, and length of stay in neonatal intensive care unit (NICU) and hospital) were not predictors of cognitive outcomes., Conclusion: The majority of the children who were born preterm presented average or above-average cognitive and attentional performances at school age, demonstrating potential resources for learning. Taken together, attention and temperament, associated with maternal schooling and socioeconomic status, were predictors of cognitive outcomes of children born preterm at school age.

Background: Postnatal growth failure (PGF) in very low birthweight (VLBW) infants is a result of factors such as prematurity, acute illness and suboptimal nutritional support. Before this project began, 84% of appropriately grown VLBW infants in our neonatal intensive care unit experienced PGF. The aims of this quality improvement project were to reduce the percentage of infants discharged with PGF to less than 50% within 2 years and to maintain a rate of PGF under 50%., Methods: All inborn VLBW infants were eligible for this study. Infants with congenital anomalies were excluded. We determined key drivers for optimal nutrition and identified potentially better practices (process measures) based on a review of the literature, which included more rapid initiation of starter total parenteral nutrition (TPN), aggressive use and advancement of regular TPN, and fortification of human milk when the volume of intake reached 80 mL/kg/day. Three Plan-Do-Study-Act (PDSA) cycles were tested., Results: Time to initiation of starter TPN was significantly reduced from 5.5 hours to under 3 hours. Regular TPN provided the goals for amino acids and lipids at increased frequency after the first two PDSA cycles. The proportion of infants whose milk was fortified at 80 mL/kg/day increased after the third PDSA cycle., Conclusions: We found a sustained decrease in the percentage of infants discharged with PGF from 84% at baseline to fewer than 50% beginning in 2010-2011 through 2016, with 23.1% of infants experiencing PGF in 2016. We have achieved improved nutritional support for VLBW infants using the model for improvement., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the effect of range-of-motion exercise program on bone mineralization and somatic growth of very low birth weight (VLBW) infants., Study Design: A total of 36 VLBW infants were randomized into 18 VLBW infants receiving range-of-motion exercise and 18 VLBW control infants receiving tactile stimulation for 4 weeks. Laboratory investigations were performed at baseline and postexercise and included serum calcium, serum phosphorus (s.PO 4 ), magnesium, alkaline phosphatase (ALP), urinary calcium/phosphate ratio, and serum carboxy-terminal cross-linked telopeptide of type 1 collagen (CTX). Dual-energy X-ray absorptiometry was performed at the end of the exercise protocol to measure bone mineral content, bone mineral density (BMD), bone area, lean mass, and fat mass., Results: The weight and the rate of weight gain were significantly higher ( p  < 0.001) in the exercise group compared with controls postexercise. Also, higher s.PO 4 , lower ALP, and lower urinary calcium/phosphate ratio were observed postexercise in the exercise group ( p  = 0.001, p  = 0.005, and p  = 0.04, respectively), whereas serum CTX showed no difference between the two groups ( p  = 0.254). Postexercise BMD significantly improved in the exercise group ( p  < 0.001) compared with controls., Conclusion: Although the sample size was small, we may be able to suggest favorable effects of range-of-motion exercise versus tactile stimulation on bone metabolism, BMD, and short-term growth in VLBW infants., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Much remains unknown about the consequences of very low birth weight (VLBW) and bronchopulmonary dysplasia (BPD) on adult lungs. We hypothesized that VLBW adults would have impaired lung function compared with controls, and those with a history of BPD would have worse lung function than those without., Methods: At age 26 to 30 years, 226 VLBW survivors of the New Zealand VLBW cohort and 100 term controls born in 1986 underwent lung function tests including spirometry, plethysmographic lung volumes, diffusing capacity of the lung for carbon monoxide, and single-breath nitrogen washout (SBN 2 )., Results: An obstructive spirometry pattern was identified in 35% VLBW subjects versus 14% controls, with the majority showing mild obstruction. Compared with controls, VLBW survivors demonstrated significantly lower forced expiratory volume in 1 second (FEV 1 ), FEV 1 /forced vital capacity (FVC) ratio (FEV 1 /FVC), forced expiratory flow at 25% to 75% of FVC and higher residual volume (RV), RV/total lung capacity (TLC) ratio (RV/TLC), decreased diffusing capacity of the lung for carbon monoxide, and increased phase III slope for SBN 2 . The differences persisted after adjustment for sex and smoking status. Within the VLBW group, subjects with BPD showed significant reduction in FEV 1 , FEV 1 /FVC, and forced expiratory flow at 25% to 75% of FVC, and increase in RV, RV/TLC, and phase III slope for SBN 2 , versus subjects without. The differences remained after adjustment for confounders., Conclusions: Adult VLBW survivors showed a higher incidence of airflow obstruction, gas trapping, reduced gas exchange, and increased ventilatory inhomogeneity versus controls. The findings suggest pulmonary effects due to VLBW persist into adulthood, and BPD is a further insult on small airway function., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Objective: To assess site variability and concomitant respiratory support related to the timing of caffeine discontinuation, and compare clinical characteristics of infants who discontinued caffeine before vs. within the last week of hospitalization., Study Design: Cohort study of 81,110 infants <35 weeks gestational age and <1500 g birth weight discharged from 304 neonatal intensive care units from 2001-2016., Results: The mean postmenstrual age at caffeine discontinuation ranged from 32 to 37 weeks among sites. Respiratory support at the time of discontinuation was common, but variable, with 0-57% of infants receiving positive airway pressure at caffeine discontinuation by site. Infants who discontinued caffeine within the last week of hospitalization had longer total duration of caffeine, but were discharged from the hospital at an earlier postmenstrual age., Conclusion: There was substantial variability among sites in the timing of caffeine discontinuation before discharge and respiratory support at the time of caffeine discontinuation.

Objective: To assess the impact of in vitro fertilization (IVF) on school performance and long-term outcomes in very preterm children aged 8-16 years., Methods: Seventy-nine children born after IVF were compared with 79 randomly selected matched controls born after spontaneous conception (SC). Information was obtained from parents via a questionnaire administered through telephone interviews looking into school performance, including preschool education, repeated grades, extra lessons, special education needs, and learning difficulties; long-term status, including incidence of attention deficit hyperactivity disorder and autism; and family profile. Gross motor function was assessed against the gross motor function classification system based on information given by the subjects' families., Results: Mothers of IVF children were more likely to have a high educational level than mothers of SC children. Moreover, a greater proportion of IVF children had received preschool education than SC children. After adjusting for potential confounders, there was no difference in the school performance or long-term outcomes between IVF and SC children., Conclusion: In our study, the school performance and long-term outcomes of very preterm children born after IVF and of their spontaneously conceived peers were comparable. This information can help provide guidance to families and educators.

Background: Neonatal infections are a leading cause of morbi-mortality despite advances in antimicrobials and neonatal care. Preterm infants have greater susceptibility to sepsis due to an immature immune system and lower immunoglobulin levels. Intravenous immunoglobulins (IVIG) have been used in several studies as an adjuvant treatment to improve this physiological immune deficiency, with different outcomes., Methods: Very low birth weight (VLBW) infants who developed sepsis in the neonatal ICU were studied. They were randomly divided in 2 groups: one group was treated with antibiotics (Group I), and the other received antibiotics plus a 500 mg/kg/day of IVIG during 7 days (Group II). Serum IgG concentration was determined at initiation, during and after treatment Group I, and daily during the 7 days of therapy in Group II., Results: The baseline IgG concentration in group II was 486 g/dL, and increased to 852 mg/dL after the first dose of IVIG (p < 0.01). After the seventh day of infusion a mean IgG level of 1898 mg/dL was achieved. A direct correlation (r = 0.94) between IgG concentration and days of treatment was observed. Blood cultures were positive in 70% of the infants in group I and 75.5% in group II. Staphylococcus epidermidis was the most frequent isolated bacteria in blood cultures. The lethality rate was 25.0% in group I and 5.0% in Group II (p < 0.03). We did not observe collateral effects with the administration of IVIG., Conclusions: Prolonged therapy with IVIG seems to be safe and effective as an adjuvant treatment in VLBW infants with sepsis.

Background: Family-centered intervention for preterm infants has shown short- to medium-term developmental benefits; however, the neurological effects of intervention have rarely been explored., Objective: The objectives of this study were to examine the effect of a family-centered intervention program (FCIP) on neurophysiological functions in preterm infants with very low birth weight (VLBW; birth weight of < 1500 g) in Taiwan, to compare the effect of the FCIP with that of a usual-care program (UCP), and to explore the FCIP-induced changes in neurobehavioral and neurophysiological functions., Design: This was a multicenter, single-blind randomized controlled trial., Setting: The study took place in 3 medical centers in northern and southern Taiwan., Participants: Two hundred fifty-one preterm infants with VLBW were included., Intervention: The FCIP group received a family-centered intervention and the UCP group received standard care during hospitalization., Measurements: Infants were assessed in terms of neurobehavioral performance using the Neonatal Neurobehavioral Examination-Chinese version, and their neurophysiological function was assessed using electroencephalography/event-related potentials during sleep and during an auditory oddball task during the neonatal period., Results: The FCIP promoted more mature neurophysiological function than the UCP, including greater negative mean amplitudes of mismatch negativities in the left frontal region in the oddball task in all infants, lower intrahemispheric prefrontal-central coherence during sleep in infants who were small for gestational age, and higher interhemispheric frontal coherence during sleep in those who were appropriate for gestational age. Furthermore, interhemispheric coherence was positively associated with the total neurobehavioral score in preterm infants who were appropriate for gestational age (r = 0.20)., Limitations: The fact that more parental adherence strategies were used in the FCIP group than in the UCP group might have favored the intervention effect in this study., Conclusions: Family-centered intervention facilitates short-term neurophysiological maturation in preterm infants with VLBW in Taiwan., (©2019 American Physical Therapy Association.)

Objective: To determine the prevalence and risk factors for poor neurodevelopmental outcome in a cohort of very low birth weight (VLBW) infants., Subjects and Methods: Four hundred and twenty-two infants of a total of 643 VLBW survivors from a teaching hospital in South India were followed up to assess their neurodevelopmental outcomes., Results: Among the 422 children who completed the assessment, results of 359 children whose assessments were done between 18 and 24 months were analysed. Thirty-seven children (10.31%) had poor neurodevelopmental outcome, six children [1.67%] had cerebral palsy, one child had visual impairment and another had hearing impairment. Poor post-natal growth was independently associated with poor neurodevelopmental outcomes in the multivariate analysis (p = 0.045). Neonatal complications were not associated with the developmental outcome., Conclusion: Despite lower rates of neonatal complications compared with Western cohorts, significant proportion of VLBW infants had poor neurodevelopmental outcomes. Poor post-natal growth was an important determinant of the developmental outcome., (© The Author(s) [2019]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The role of donated breast milk and formula feeding in very low birth weight infants (VLBWIs) remains unclear., Objective: The objective for this study was to evaluate the efficacy and safety of breast milk and formula for feeding VLBWIs., Methods: A comprehensive search of PubMed databases was conducted on November 30, 2018, to identify related randomized controlled trials (RCTs). Pooled odds ratio (OR) and mean differences (MD) with 95% confidence intervals (CI) were calculated using either a fixed or random-effects model., Results: Seven RCTs with a total of 876 infants were included. The formula showed more advantages in increasing infant weight (MD = -6.58, 95% CI: -11.19 to -1.98) and length (MD = -0.30, 95% CI: -0.41 to -0.20) than donated breast milk, but formula could also significantly increase the risks of necrotizing enterocolitis (OR = 0.33, 95% CI: 0.18 to 0.59) and length of hospital stay (MD = -3.78, 95% CI: -6.84 to -0.72) when compared with donated breast milk. No significant differences on the head circumference gain (MD = -0.16, 95% CI: -0.33 to 0.01), sepsis (OR = 1.21, 95% CI: 0.84 to 1.75), retinopathy of prematurity (OR = 1.22, 95% CI: 0.73 to 2.05) and mortality (OR = 0.84, 95% CI: 0.47 to 1.52) were found., Linking Evidence to Action: The donated breast milk shows more advantages in reducing the incidence of NEC and length of hospital stay, but also more disadvantages in increasing the weight and length of VLBWIs and ELBWIs when compared with preterm formula feeding. Currently, there is no solid evidence demonstrating a significant advantage of donated breast milk over formula in the feeding of VLBWIs. Larger-scale RCTs with rigorous designs are needed to elucidate the feeding plans of VLBWIs., (© 2019 The Authors. Worldviews on Evidence-based Nursing published by Wiley Periodicals, Inc. on behalf of Sigma Theta Tau International.)