Comparative proteomic analysis of donor human milk treated by high-pressure processing or Holder pasteurization on undigested proteins across dynamic simulated preterm infant digestion.

High-pressure processing (HPP) of donor human milk (DM) minimally impacts the concentration and bioactivity of some important bioactive proteins including lactoferrin, and bile salt-stimulated lipase (BSSL) compared to Holder pasteurization (HoP), yet the impact of HPP and subsequent digestion on the full array of proteins detectable by proteomics remains unclear. We investigated how HPP impacts undigested proteins in DM post-processing and across digestion by proteomic analysis. Each pool of milk (n = 3) remained raw, or was treated by HPP (500 MPa, 10 min) or HoP (62.5 °C, 30 min), and underwent dynamic in vitro digestion simulating the preterm infant. In the meal, major proteins were minimally changed post-processing. HPP-treated milk proteins better resisted proximal digestion (except for immunoglobulins, jejunum 180 min) and the extent of undigested proteins after gastric digestion of major proteins in HPP-treated milk was more similar to raw (e.g., BSSL, lactoferrin, macrophage-receptor-1, CD14, complement-c3/c4, xanthine dehydrogenase) than HoP.

The Cost of Opioid Use in High-Risk Hospitalized Infants.

INTRODUCTION: Hospitalizations of high-risk infants are among the most expensive in the United States, with many requiring surgery and months of intensive care. Healthcare costs and resource use associated with hospitalized infant opioid exposure are less well known. METHODS: A retrospective cohort of high-risk infants aged <1 y admitted from 47 children's hospitals from 2010 to 2020 was identified from Pediatric Healthcare Information System. High-risk infants were identified by International Classification of Diseases 9/10 codes for congenital heart disease procedures, medical and surgical necrotizing enterocolitis, extremely low birth weight, very low birth weight, hypoxemic ischemic encephalopathy, extracorporeal membrane oxygenation, and gastrointestinal tract malformations. Healthcare resource utilization was estimated using standardized unit costs (SUCs). The impact of opioid use on SUC was examined using general linear models and an instrumental variable. RESULTS: Overall, 126,897 high-risk infants were identified. The cohort was majority White (57.1%), non-Hispanic (72.0%), and male (55.4%). Prematurity occurred in 26.4% and a majority underwent surgery (77.9%). Median SUC was $120,585 (interquartile range: $57,602-$276,562) per infant. On instrumental variable analysis, each day of opioid use was associated with an increase of $4406 in SUC. When adjusting for biologic sex, race, ethnicity, insurance type, diagnosis category, number of comorbidities, mechanical ventilation, and total parental nutrition use, each day of opioid use was associated with an increase of $2177 per infant. CONCLUSIONS: Prolonged opioid use is significantly associated with healthcare utilization and costs for high-risk infants, even when accounting for comorbidities, intensive care, ventilation, and total parental nutrition use. Future studies are needed to estimate the long-term complications and additional costs resulting from prolonged opioid exposures in high-risk infants.

[Risk factors for initial non-invasive ventilation failure in very low birth weight infants with gestational age <32 weeks: a multicenter retrospective study]. / 胎龄<32å‘¨æžä½Žå‡ºç”Ÿä½“é‡å„¿åˆå§‹æ— åˆ›é€šæ°”å¤±è´¥çš„å½±å“å› ç´ åˆ†æžï¼šä¸€é¡¹å¤šä¸­å¿ƒå›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To investigate the risk factors and adverse prognosis associated with initial non-invasive ventilation (NIV) failure in very low birth weight infants (VLBWI) with gestational age <32 weeks. METHODS: A retrospective collection of clinical data from preterm infants admitted to the neonatal intensive care unit (NICU) in 28 tertiary hospitals in Jiangsu Province from January 2019 to December 2021 was conducted. Based on the outcomes of initial NIV, the infants were divided into a successful group and a failure group to analyze the risk factors for NIV failure and adverse prognosis. RESULTS: A total of 817 infants were included, with 453 males (55.4%) and 139 failures (17.0%). The failure group had lower gestational age, birth weight, and 1-minute and 5-minute Apgar scores compared to the successful group (P<0.05). The failure group also had a higher proportion of respiratory distress syndrome (RDS) diagnosed upon NICU admission, higher maximum positive end-expiratory pressure during NIV, and higher percentages of reaching the required maximum fraction of inspired oxygen (FiO2) ≥30%, ≥35%, and ≥40% throughout the initial NIV process compared to the successful group (P<0.05). Gestational age (OR=0.671, 95%CI: 0.581-0.772), RDS (OR=1.955, 95%CI: 1.181-3.366), and FiO2 ≥30% (OR=2.053, 95%CI: 1.106-4.044) were identified as risk factors for initial NIV failure in these infants with gestational age <32 weeks (P<0.05). The failure group had higher incidences of complications such as pulmonary infections, pneumothorax, retinopathy of prematurity, moderate to severe bronchopulmonary dysplasia, and severe intraventricular hemorrhage during hospitalization, as well as longer hospital stays and higher total costs compared to the successful group (P<0.05). CONCLUSIONS: Smaller gestational age, a diagnosis of RDS in the NICU, and achieving a maximum FiO2 ≥30% during the initial NIV process are risk factors for initial NIV failure in infants with gestational age <32 weeks. Initial NIV failure significantly increases the risk of adverse outcomes in this population.

Kidney Health Monitoring in Neonatal Intensive Care Unit Graduates: A Modified Delphi Consensus Statement.

Importance: Kidney disease is common in infants admitted to the neonatal intensive care unit (NICU). Despite the risk of chronic kidney disease (CKD) in infants discharged from the NICU, neither evidence- nor expert-based recommendations exist to guide clinical care after discharge. Objective: To develop recommendations for risk stratification and kidney health monitoring among infants after discharge from the NICU. Evidence Review: At the National Institute of Health-supported Consensus Workshop to Address Kidney Health in Neonatal Intensive Care Unit Graduates meeting conducted in February 2024, a panel of 51 neonatal nephrology experts focused on 3 at-risk groups: (1) preterm infants, (2) critically ill infants with acute kidney injury (AKI), and (3) infants with critical cardiac disease. Using established modified Delphi processes, workgroups derived consensus recommendations. Findings: In this modified Delphi consensus statement, the panel developed 10 consensus recommendations, identified gaps in knowledge, and prioritized areas of future research. Principal suggestions include risk stratification at time of hospital discharge, family and clinician education and counseling for subsequent kidney health follow-up, and blood pressure assessment as part of outpatient care. Conclusions and Relevance: Preterm infants, critically ill infants with AKI, and infants with critical cardiac disease are at increased risk of CKD. We recommend (1) risk assessment at the time of discharge, (2) clinician and family education, and (3) kidney health assessments based on the degree of risk. Future work should focus on improved risk stratification, identification of early kidney dysfunction, and development of interventions to improve long-term kidney health.

Efficacy of Lung Ultrasound vs Chest X-Ray in Detecting Lung Consolidation and Edema in Premature Infants in the NICU.

BACKGROUND The incidence of lung diseases in premature newborns is significantly higher than in full-term newborns due to their underdeveloped lungs. Ultrasound and X-ray are commonly-used bedside examinations in neonatology. This study primarily compares the efficacy of chest X-ray (CXR) and lung ultrasound (LUS) images in evaluating lung consolidation and edema in premature newborns at Neonatal Intensive Care Units (NICU). MATERIAL AND METHODS A retrospective analysis was conducted on LUS and CXR examination results, along with clinical records of premature newborns admitted to our hospital's NICU from November 1, 2019, to December 31, 2021. CXR and LUS scans were performed on the same newborn within a day. We evaluated the consolidations and edema by interpreting the CXR and LUS images, then compared the findings. RESULTS Out of 75 cases, 34 showed lung consolidations on LUS (45%), while only 14 exhibited consolidations on CXR (19%). The detection rate of consolidations by LUS was significantly higher compared to CXR (34/75 vs 14/75, P<0.001). Differences were observed between the 2 bedside examinations in identifying consolidations, with some cases seen only on LUS. CXR struggled to accurately assess the severity of lung edema visible on LUS, showing significant disparity in detecting interstitial edema (53/75 vs 21/75, P<0.001). CONCLUSIONS LUS outperforms chest CXR for bedside assessment of lung consolidation and edema in premature newborns.

[Introduction of complementary feeding and associated factors in preterm and low birthweight newborns: a prospective cohort study]. / Introdução da alimentação complementar e fatores associados em recém-nascidos pré-termo e com baixo peso: estudo de coorte prospectivo.

This study aimed to analyze the association between sociodemographic factors, maternal and neonatal characteristics and the time taken to introduce complementary feeding in low birthweight and preterm newborns. This is a prospective cohort study of 79 preterm newborns weighing less than or equal to 1,800g. Data were collected at the time of hospital discharge and at the 6th, 9th ,and 12th months of corrected gestational age (CGA), using a structured questionnaire to analyze the time taken to introduce complementary feeding and the texture of the foods introduced. Furthermore, the Survey of Well-being of Young Children (SWYC-BR) was used to assess the risk of developmental delay. Cox proportional hazards regression was used to analyze the variables. The introduction of complementary feeding was assessed in preterm newborns based on the median age of introduction of liquid foods (3.50; IQR: 2.50-5.00), followed by solid (4.70; IQR: 3.20-5.20) and soft foods (5.00; IQR: 4.50-5.50). There was also an association with gestational age (RR = 1.25; 95%CI: 1.02-1.52) throughout the process of food introduction. For solid and soft foods, those with the longest length of stay (RR = 1.03; 95%CI: 1.10-1.05) and on mixed breastfeeding (RR = 2.97; 95%CI: 1.24-7.09) delayed the introduction of complementary feeding the longest. For liquid foods, less severe preterm newborns (Score for Neonatal Acute Physiology and Perinatal Extension - SNAPPE II [RR = 0.96; 95%CI: 0.94-0.98]) and mothers who were breastfeeding at hospital discharge (RR = 11.49; 95%CI: 1.57-84.10) delayed the introduction of complementary feeding. Guidelines are needed to better advise professionals and parents and/or guardians on the ideal time to introduce feeding.

O objetivo deste artigo foi analisar a associação entre os fatores sociodemográficos, as características maternas e neonatais e o tempo de introdução da alimentação complementar em recém-nascidos pré-termo e com baixo peso. Trata-se de um estudo de coorte prospectivo feito com 79 recém-nascidos pré-termo com peso menor ou igual a 1.800g. Os dados foram coletados no momento da alta hospitalar e ao 6º, 9º e 12º mês de idade gestacional corrigida (IGC), com auxílio de um questionário estruturado para analisar o tempo de introdução da alimentação complementar e texturas dos alimentos introduzidos. Além disso, para avaliar o risco de atraso de desenvolvimento, utilizou-se o Survey of Well-being of Young Children (SWYC-BR). Para análise das variáveis, aplicou-se regressão de riscos proporcionais de Cox. A introdução da alimentação complementar foi observada nos recém-nascidos pré-termo, com a mediana de idade de introdução de alimentos líquidos (3,50; IQ: 2,50-5,00), seguido por sólidos (4,70; IQ: 3,20-5,20) e pastosos (5,00; IQ: 4,50-5.50). Ainda, verificou-se associação da idade gestacional (RR = 1.25; IC95%: 1,02-1,52) em todo o processo da introdução alimentar. Para os alimentos sólidos e pastosos, aqueles com o maior tempo de internação (RR = 1,03; IC95%: 1,10- 1,05) e em amamentação mista (RR = 2,97; IC95%: 1,24-7,09) adiaram mais o tempo para introduzir a alimentação complementar. Para alimentos líquidos, recém-nascidos pré-termo menos graves (Score for Neonatal Acute Physiology and Perinatal Extension - SNAPPE II [RR = 0,96; IC95%: 0,94-0,98]) e mães que estavam amamentando na alta hospitalar (RR = 11,49; IC95%: 1,57-84,10) postergaram a introdução alimentar. Diretrizes para melhor orientação de profissionais e pais e/ou responsáveis sobre o momento ideal de introdução alimentar se faz necessário.

El objetivo de este estudio fue analizar la asociación entre los factores sociodemográficos, características maternas y neonatales y el momento de introducción de la alimentación complementaria en recién nacidos pretérmino (recém-nascidos pré-termo) y de bajo peso. Se trata de un estudio de cohorte prospectivo realizado con 79 recém-nascidos pré-termo con un peso menor o igual a 1.800g. Los datos se recopilaron en el momento del alta hospitalaria y al 6º, 9º y 12º mes de edad gestacional corregida (EGC), con la ayuda de un cuestionario estructurado para analizar el momento de introducción de la alimentación complementaria y las texturas de los alimentos introducidos. Además, para evaluar el riesgo de retraso en el desarrollo, se utilizó la Survey of Well-being of Young Children (SWYC-BR). Para analizar las variables, se aplicó la regresión de riesgos proporcionales de Cox. La introducción de la alimentación complementaria se observó en los recém-nascidos pré-termo, con la mediana de edad de introducción de alimentos líquidos (3,50; IIC: 2,50-5,00), seguido de los sólidos (4,70; IIC: 3,20-5,20) y pastosos (5,00; IIC: 4,50-5,50). Además, se constató la asociación de la edad gestacional (RR = 1,25; IC95%: 1,02-1,52) durante todo el proceso de introducción alimentaria. En el caso de alimentos sólidos y pastosos, aquellos con mayor tiempo de hospitalización (RR = 1,03; IC95%: 1,10-1,05) y en lactancia mixta (RR = 2,97; IC95%: 1,24-7,09) retrasaron más la introducción de alimentación complementaria. En el caso de alimentos líquidos, los recém-nascidos pré-termo menos graves (Score for Neonatal Acute Physiology and Perinatal Extension - SNAPPE II [RR = 0,96; IC95%: 0,94-0,98]) y las madres que estaban amamantando al alta hospitalaria (RR = 11,49; IC95%: 1,57-84,10) pospusieron la introducción de alimentos. Se hacen necesarias pautas para una mejor orientación a profesionales y padres o tutores sobre el momento ideal para la introducción alimentaria.

Food-Protein-Induced Proctocolitis in Pre-Term Newborns with Bloody Stools in a Neonatal Intensive Care Unit.

The bloody stools of newborns may be a clue for several clinical entities of varying severity, ranging from idiopathic neonatal transient colitis to food-protein-induced allergic proctocolitis (FPIAP) or necrotizing enterocolitis (NEC). Distinguishing among them at an early stage is challenging but crucial, as the treatments and prognoses are different. We conducted a monocentric retrospective study including all pre-term infants with bloody stools admitted to the Neonatal Intensive Care Unit (NICU) of the Vittore Buzzi Children's Hospital (Milan) from December 2022 to May 2024. Patients diagnosed with NEC exhibited significantly lower eosinophil counts and higher procalcitonin levels than both patients with FPIAP and patients with idiopathic neonatal transient colitis, as well as a statistically significant increase in pathological features from abdomen ultrasounds and abdominal X-rays. In contrast, no lab markers or imaging techniques have been demonstrated to be useful in distinguishing between idiopathic neonatal transient colitis and FPIAP. Thus, after excluding a diagnosis of NEC, the only way to confirm FPIAP is through the oral food challenge, which can be performed in premature newborns presenting with bloody stools who are otherwise healthy and under medical supervision, in order to identify infants who may benefit from a cow's-milk-free diet.

Adults born preterm have lower peripheral skeletal muscle area and strength.

Prematurity is associated with lower exercise capacity, which relies on the integrity of the cardiovascular, pulmonary, and skeletal muscle systems. Our animal model mimicking prematurity-associated conditions showed altered muscle composition and atrophy in adulthood. This study aimed to compare muscle composition and strength in adults born preterm versus full-term controls. This observational cohort study recruited 55 adults born preterm, ≤ 29 weeks' of gestation and 53 full-term controls who underwent musculoskeletal ultrasound imaging to assess morphology of the rectus femoris at rest and during a maximal voluntary contraction. Maximal voluntary contraction of the hands and legs were measured by manual dynamometry. In adults born preterm, there was lower muscle strength (handgrip: - 4.8 kg, 95% CI - 9.1, - 0.6; knee extensor: - 44.6 N/m, 95% CI - 63.4, - 25.8) and smaller muscle area (- 130 mm2, 95% CI - 207, - 53), which was more pronounced with a history of bronchopulmonary dysplasia. Muscle stiffness was increased in the preterm versus term group (0.4 m/s, 95% CI 0.04, 0.7). Prematurity is associated with alterations in skeletal muscle composition, area, and function in adulthood. These findings highlight the necessity to implement preventive and/or curative approaches to improve muscle development and function following preterm birth to enhance overall health in this population.

Impact of implementation of 2019 European respiratory distress syndrome guidelines on bronchopulmonary dysplasia in very preterm infants.

BACKGROUND: To evaluate the impact of implementation of 2019 European respiratory distress syndrome (RDS) guidelines on the incidence of bronchopulmonary dysplasia (BPD). METHOD: We retrospectively collected the clinical data of very preterm infants (VPIs) born before 32 gestational weeks from January 1st 2018 to December 31st 2021. VPIs were divided into group A and group B according to their birth date which was before or at/after January 1st 2020, when the 2019 European RDS guidelines were introduced. BPD is considered as primary outcome. We statistically analyzed all the data, and we compared the general characteristics, ventilation support, medication, nutrition and the outcomes between the two groups. RESULTS: A total of 593 VPIs were enrolled, including 380 cases in group A and 213 cases in group B. There were no statistic differences regarding to gender ratio, gestational age, birth weight and delivery mode between the two groups. Compared with group A, group B showed higher rate of antenatal corticosteroid therapy (75.1% vs. 65.5%). The improvement of ventilation management in these latter patients included lower rate of invasive ventilation (40.4% vs. 50.0%), higher rate of volume guarantee (69.8% vs. 15.3%), higher positive end expiratory pressure (PEEP) [6 (5, 6) vs. 5 (5, 5) cmH2O] and higher rate of synchronized nasal intermittent positive pressure ventilation (sNIPPV) (36.2% vs. 5.6%). Compared with group A, group B received higher initial dose of pulmonary surfactant [200 (160, 200) vs. 170 (130, 200) mg/Kg], shorter antibiotic exposure time [13 (7, 23) vs. 17 (9, 33) days], more breast milk (86.4% vs. 70.3%) and earlier medication for hemodynamically significant patent ductus arteriosus (hsPDA) treatment [3 (3, 4) vs. 8 (4, 11) days] (p < 0.05). As the primary outcome, the incidence of BPD was significantly decreased (16.9% vs. 24.2%) (p < 0.05), along with lower extrauterine growth retardation (EUGR) rate (39.0% vs. 59.7%), while there were no statistic differences regarding to other secondary outcomes, including mortality, intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), retinopathy of preterm (ROP) and necrotizing enterocolitis (NEC). However, in the subgroups of infants less than 28 gestational weeks or infants less than 1,000 g, the incidence of BPD was not significantly decreased (p > 0.05). CONCLUSIONS: After implementation of 2019 European RDS guidelines, the overall incidence of BPD was significantly decreased in VPIs. Continuous quality improvement is still needed in order to decrease the incidence of BPD in smaller infants who are less than 28 gestational weeks or less than 1,000 g.

Prevalence and Risk Factors of Bronchopulmonary Dysplasia Among Very Premature Infants in a Tunisian Neonatal Intensive Care Unit.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) stands as the primary chronic respiratory complication in premature infants, posing a substantial public health concern due to its rising prevalence, potential mortality, and socioeconomic burden. AIM: The aim of this study was to determine the prevalence of BPD in very preterm infants and identify its associated risk factors. METHODS: We conducted a retrospective, descriptive, and analytical study including all premature infants born between 26 and 31 weeks of gestation age (GA) who survived beyond the 28th day of life, over a five-year period (2017-2021). Patients were divided into two groups based on the presence or absence of BPD, which was defined by the need for oxygen supplementation for at least 28 days. RESULTS: we included 231 newborns. The prevalence of BPD was 37.7% among survivors on the 28th day of life and 36.7% among those reaching 36 weeks postmenstrual age. BPD was mild, moderate and severe in 25.2%, 4.9% and 6.6% of cases, respectively. Multivariate analysis identified maternal hypertensive disorders (RR=6.15, 95%CI=[2.27-16.67], p<0.001), chorioamnionitis (RR=4.23, 95%CI=[1.25 -14.27], p=0.02), intrauterine growth restriction (IUGR) (RR =20.4, 95%CI=[3.39 -122.66], p=0.001), GA less than 30 weeks (RR=26.97, 95%CI=[10.23 -71.14], p<0.001), and mechanical ventilation (MV) (RR=5.33, 95%CI=[1.95-14.54], p=0.001) as independent factors associated with BPD occurrence. The mortality rate was 10.3% among patients with BPD versus 0.7% in patients without BPD (p = 0.001). CONCLUSION: Our study revealed a high prevalence of BPD in very preterm infants and identified several independent risk factors such as maternal hypertensive disorders, IUGR, chorioamnionitis, MV, and GA less than 30 weeks.

Synbiotics in patients at risk for spontaneous preterm birth: protocol for a multi-centre, double-blind, randomised placebo-controlled trial (PRIORI).

BACKGROUND: Prematurity remains one of the main causes of neonatal morbidity and mortality. Approximately two thirds of preterm births are spontaneous, i.e. secondary to preterm labour, preterm prelabour rupture of membranes (PPROM) or cervical insufficiency. Etiologically, the vaginal microbiome plays an important role in spontaneous preterm birth (sPTB). Vaginal dysbiosis and bacterial vaginosis are well-known risk factors for ascending lower genital tract infections and sPTB, while a Lactobacillus crispatus-dominated vaginal microbiome is associated with term deliveries. Synbiotics may help to achieve and/or maintain a normal, Lactobacillus-dominated vaginal microbiome. METHODS: We will perform a multi-centre, double-blind, randomised, placebo-controlled trial. Women aged 18 years or older with a singleton pregnancy are eligible for inclusion at 80/7-106/7 weeks gestational age if they have one or more of the following risk factors for sPTB: previous sPTB at 240/7-356/7 weeks, prior PPROM before 360/7 weeks, or spontaneous pregnancy loss at 140/7-236/7 weeks of gestation. Exclusion criteria are multiple gestation, cervix conisation, inflammatory bowel disease, uterine anomaly, and the use of pro-/pre-/synbiotics. Patients will be randomised to oral synbiotics or placebo, starting before 11 weeks of gestation until delivery. The oral synbiotic consists of eight Lactobacillus species (including L. crispatus) and prebiotics. The primary outcome is the gestational age at delivery. Vaginal microbiome analysis once per trimester (at approximately 9, 20, and 30 weeks) and delivery will be performed using metataxonomic sequencing (16S rRNA gene) and microbial culture. Secondary outcomes include PPROM, the use of antibiotics, antenatal admission information, and neonatal outcomes. DISCUSSION: This study will evaluate the effect of oral synbiotics on the vaginal microbiome during pregnancy in a high-risk population and correlate the microbial changes with the gestational age at delivery and relevant pregnancy outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05966649. Registered on April 5, 2024.

Smaller Left Ventricular Size But Preserved Function in Adolescents and Adults Born Preterm.

BACKGROUND: Prematurely born adults have increased risk for cardiovascular disease. There are limited cardiac data on US-born preterm individuals. We aimed to determine whether adolescents and adults born prematurely have altered left ventricular (LV) structure and function, and to interrogate diastolic function using isometric handgrip exercise. METHODS AND RESULTS: Adolescents and adults born moderately to extremely preterm (≤32 weeks gestation or <1500 g birth weight) were recruited from the Parkland Health Neonatal Intensive Care Unit Registry. Full-term participants were recruited from the local area. Study procedures included anthropometrics and vitals, handgrip testing, and echocardiography performed at rest and during isometric handgrip exercise. Data were reported as mean±SD. The study enrolled 107 preterm and 48 term participants. Preterm participants (gestational age: 29.5±2.5 weeks) were shorter with higher body mass index (P<0.001) compared with term participants. Preterm participants exhibited smaller LV end-diastolic volume index (50.8±10.1 versus 56.9±10.0 mL/m2, P<0.001), LV stroke volume index (29.6±6.0 versus 34.1±6.5 mL/m2, P<0.001), and LV mass index (67.2±13.1 versus 73.3±14.2 g/m2, P=0.002) compared with term individuals. Preterm participants also had subclinical reductions in LV peak systolic tissue velocity and peak early diastolic tissue velocity lateral at rest. Isometric handgrip exercise promoted a reduction in diastolic function and an increase in hemodynamic measures, but changes during isometric handgrip exercise were similar between groups. CONCLUSIONS: Adolescents and adults born preterm exhibit overall normal cardiac function despite smaller cardiac volumes and mass compared with individuals born full term. Effects are most pronounced at the lowest gestational ages.

Urinary cystatin-C and urinary NGAL associated with sepsis predicts longer hospital stay in premature newborns.

Aim: To evaluate the urinary biomarkers related to sepsis in preterm newborns (NBs) and to investigate the predictive capacity of these biomarkers for a longer hospital stay.Methods: Serum and urine were collected from 27 healthy NBs, 24 NBs with neonatal infection without sepsis and 11 NBs with sepsis for the measurement of sindecan-1, lipocalin associated with urinary neutrophil gelatinase (uNGAL), urinary cystatin-C (uCysC) and urinary kidney injury molecule-1.Results: Levels of uNGAL and urinary cystatin-C were elevated in NBs with sepsis and neonatal infection, and uNGAL was significant predictor of hospital stay longer than 30 days (odds ratio: 1.052; 95% CI: 1.012-1.093; p = 0.01).Conclusion: uNGAL was associated with sepsis in preterm NBs and was useful to predict extended hospital stay.

[Box: see text].

Adjusted versus Targeted Fortification in Extremely Low Birth Weight Preterm Infants: Fortin Study-A Randomized Clinical Trial.

Fortified human milk is the first choice for preterm infants. Although individualized fortification is recommended, the optimal method for this population remains uncertain. We conducted a comparative study assessing the growth effects of adjusted (AF) and targeted fortification (TF) in extremely low birth weight (ELBW) infants. This single-center, randomized, controlled clinical trial was conducted at a tertiary neonatal unit in Spain. Eligible participants were premature infants with a birthweight of <1000 g exclusively fed with human milk. A total of 38 patients were enrolled, 15 of them randomized to AF group and 23 to TF group. AF was based on blood urea nitrogen (BUN) concentration and TF on human milk analysis. The primary outcome was weight gain velocity (g/kg/day). No significant differences were found in weight gain velocity at 28 days, at 36 weeks of postmenstrual age, at discharge, nor during the intervention. Protein intake was significantly higher in the AF group (5.02 g/kg/day vs. 4.48 g/kg/day, p = 0.001). No differences were found in the lipid, carbohydrate, and energy intake; in the weight z score change between the different time points; nor in the length and head circumference growth. Both AF and TF are comparable methods of fortification and provide the appropriate growth rate in ELBW infants.

Impact of Clinical Use of Probiotics on Preterm-Related Outcomes in Infants with Extremely Low Birth Weight.

Background: Preterm birth significantly contributes to mortality and morbidities, with recent studies linking these issues to gut microbiota imbalances. Probiotic supplementation shows promise in mitigating adverse outcomes in preterm infants, but optimal timing and guidelines remain unclear. This study assesses the benefits of probiotic supplementation for preterm infants without consistent guidelines. Methods: This retrospective study examined extremely low-birth-weight (ELBW) infants in neonatal intensive care units from 2017 to 2021. Mortality and preterm-related outcomes were compared between infants receiving probiotics and those not. Subgroup analyses based on probiotic initiation timing were conducted: early (≤14 days), late (>14 days), and non-probiotic groups. Results: The study included 330 ELBW infants: 206 received probiotics (60 early, 146 late), while 124 did not. Probiotic supplementation was associated with lower overall mortality (adjusted OR 0.22, 95% CI 0.09-0.48) and decreased mortality from necrotizing enterocolitis (NEC) or late-onset sepsis (LOS) (adjusted OR 0.12, 95% CI 0.03-0.45). Early probiotics reduced overall mortality, NEC/LOS-related mortality, and NEC/LOS-unrelated mortality. Late probiotics decreased overall mortality and NEC/LOS-related mortality. Early probiotic use also expedited full enteral feeding achievement. Conclusions: Probiotic supplementation reduces mortality and improves feeding tolerance in preterm infants. Establishing guidelines for probiotic use in this population is crucial.

Supplemental Iron and Recombinant Erythropoietin for Anemia in Infants Born Very Preterm: A Survey of Clinical Practice in Europe.

OBJECTIVES: To survey practices of iron and recombinant human erythropoietin (rhEpo) administration to infants born preterm across Europe. STUDY DESIGN: Over a three-month period, we conducted an online survey in 597 neonatal intensive care units (NICUs) of 18 European countries treating infants born with a gestational age (GA) <32 weeks. RESULTS: 343 NICUs (response rate 56·3%) completed the survey. Almost all (97·7%) NICUs routinely supplement enteral iron, and 74·3% of respondents to all infants born <32 weeks' GA. 65·3% of NICUs routinely evaluate erythropoiesis and iron parameters beyond day 28 after birth. Most NICUs initiate iron supplementation at postnatal age of two weeks and stop after 6 (34·3%) or 12 months (34·3%). Routine use of rhEpo was reported in 22·2% of NICUs, and in individual cases in 6·9%. RhEpo was mostly administered subcutaneously (70·1%) and most frequently at a dose of 250 U/kg 3 times a week (44·3%), but the dose varied greatly between centers. CONCLUSION: This survey highlights wide heterogeneity in evaluating erythropoietic activity and iron deficiency in infants born preterm. Variation in iron supplementation during infancy likely reflects an inadequate evidence base. Current evidence on the efficacy and safety profile of rhEpo is only poorly translated into clinical practice. This survey demonstrates a need for standards to optimize patient blood management in anemia of prematurity.

Necrotising enterocolitis suspicion in newborns with duct-dependent congenital heart disease: prognosis and risk factor.

INTRODUCTION: The main risk factors of necrotising enterocolitis (NEC) are prematurity and low birth weight. The aim of our study was to identify risk factors for NEC in patients with duct-dependent congenital heart disease (CHD). STUDY DESIGN: Newborns with duct-dependent CHD and NEC were matched 1:1 to those without NEC. Matched criteria were gestational age, birth weight, antenatal versus postnatal diagnosis and type of CHD. RESULTS: Twenty-three infants were included in each group. In the NEC group, mortality, length of intensive care unit stay and length of hospital stay were significantly higher (p=0.035; p<0.0001; p<0.0001). Lower diastolic blood pressure (DBP), negative flow balance, peritoneal dialysis and epinephrine-infusion were significantly associated with NEC (respectively, p=0.008, p=0.002, p=0.007, p=0.017). In multivariate analysis, DBP≤30 mm Hg remained the only independent risk factor of NEC (OR=8.70; 95% CI (1.46 to 53.50), p=0.019). CONCLUSION: A DBP lower than 30 mm Hg was in our matched population of newborns with duct-dependent CHD, independently associated with NEC.

Preterm birth as a determinant of neurodevelopment and cognition in children (PRENCOG): protocol for an exposure-based cohort study in the UK.

INTRODUCTION: Preterm birth (PTB) is strongly associated with encephalopathy of prematurity (EoP) and neurocognitive impairment. The biological axes linking PTB with atypical brain development are uncertain. We aim to elucidate the roles of neuroendocrine stress activation and immune dysregulation in linking PTB with EoP. METHODS AND ANALYSIS: PRENCOG (PREterm birth as a determinant of Neurodevelopment and COGnition in children: mechanisms and causal evidence) is an exposure-based cohort study at the University of Edinburgh. Three hundred mother-infant dyads comprising 200 preterm births (gestational age, GA <32 weeks, exposed) and 100 term births (GA >37 weeks, non-exposed), will be recruited between January 2023 and December 2027. We will collect parental and infant medical, demographic, socioeconomic characteristics and biological data which include placental tissue, umbilical cord blood, maternal and infant hair, infant saliva, infant dried blood spots, faecal material, and structural and diffusion MRI. Infant biosamples will be collected between birth and 44 weeks GA.EoP will be characterised by MRI using morphometric similarity networks (MSNs), hierarchical complexity (HC) and magnetisation transfer saturation imaging (MTsat). We will conduct: first, multivariable regressions and statistical association assessments to test how PTB-associated risk factors (PTB-RFs) relate to MSNs, HC and or MTsat; second, structural equation modelling to investigate neuroendocrine stress activation and immune dysregulation as mediators of PTB-RFs on features of EoP. PTB-RF selection will be informed by the variables that predict real-world educational outcomes, ascertained by linking the UK National Neonatal Research Database with the National Pupil Database. ETHICS AND DISSEMINATION: A favourable ethical opinion has been given by the South East Scotland Research Ethics Committee 02 (23/SS/0067) and NHS Lothian Research and Development (2023/0150). Results will be reported to the Medical Research Council, in scientific media, via stakeholder partners and on a website in accessible language (https://www.ed.ac.uk/centre-reproductive-health/prencog).

Caregivers' experiences on preterm infants' management in a tertiary care facility in Ghana: a qualitative exploratory study.

BACKGROUND: Preterm birth is a process that fundamentally alters parental or caregiver roles, particularly in the early weeks of childbirth. Caregiver experiences can be distressing due to struggles with an unfamiliar and potentially threatening environment of the Neonatal Intensive Care Unit (NICU). These experiences can affect the development of parenting or caregiving roles to a greater extent. Supporting caregivers of preterm infants through education and information sharing can significantly improve neonatal outcomes. This study sought to explore the experiences of caregivers with hospitalized preterm infants regarding the education and information they received from healthcare workers on the care of preterm infants. METHOD: An exploratory descriptive qualitative study that explored caregivers' experiences with the management of preterm infants hospitalized at the Level III Neonatal Intensive Care Unit (NICU) of a tertiary level facility with an annual delivery of almost 7500 and a bed capacity of 26. The study utilized a deductive approach and a purposive sampling technique to recruit 16 caregivers who participated in an in-depth interview using a piloted semi-structured interview guide. The interviews were audio-recorded, transcribed, and analyzed using thematic analysis. FINDINGS: The study identified three major themes, which were (1) preterm infant feeding and keeping infants warm, (2) routine procedures and activities at the NICU, and (3) preparation towards homecare after discharge. Seven (7) sub-themes were generated. Caregivers were satisfied with the education and information they received on infant feeding and keeping the infant ward. They also had adequate education that prepared them for home care of the preterm infant. Caregivers did not receive timely information and education on the health status of their infants and the care processes of the NICU. They felt they were left out as they were not involved in decision-making. Regarding the care of the preterm infant. The inadequate flow of information and use of medical terminologies were a great source of worry and frustration for participants. The study showed that although the NICU staff were willing to offer health education to caregivers, information giving and education were not structured and hence did not address all the needs of the caregivers. CONCLUSION: Healthcare providers caring for preterm infants include caregiver education in their routine NICU activities and procedures. These processes start from the period of admission till discharge. Their education sessions primarily focus on breastfeeding, keeping the infant warm and adequate preparation of caregivers for preterm infant home care. This notwithstanding there are gaps in caregiver education and information on routine procedures in the NICU as well as information on the health needs of the infant. Participants are not fully involved in the decision-making processes and the use of medical terminologies compound caregivers' frustrations and anxieties. It is important to develop structured educational programs tailored to address the information needs faced by caregivers to ensure optimal health outcomes for their preterm infants.

Vitamin D and gut microbiome in preterm infants.

BACKGROUND: The incidence of vitamin D deficiency among pregnant women remains high and is associated with vitamin D deficiency in infants. In normally breastfed infants, Bifidobacteriaceae and Lactobacillaceae are known to help in maintaining immunotolerance and prevent infection. Vitamin D in the gastrointestinal tract plays a role in determining the composition and function of intestinal bacteria. Preterm infants are vulnerable to intestinal dysbiosis and sepsis due to bacterial translocation. This study aimed to determine the association between vitamin D levels and intestinal dysbiosis. METHODS: It was a cohort study conducted in the Neonatal Unit, Cipto Mangunkusumo Hospital, Tertiary hospital in Indonesia, from November 2019 to January 2021. The inclusion criteria in this study were preterm infants with a gestational age of less than 32 weeks or a birth weight of less than 1500 g. Total 25-hydroxyvitamin D (25(OH)D) levels were collected from the umbilical cords of very preterm or very low birth weight infants. A fecal examination was performed on the seventh day of life to assess intestinal bacteria using real-time PCR for four bacterial genera: Bifidobacteriaceae, Lactobacillaceae, Enterobacteriaceae, and Clostridiaceae. RESULTS: A total of 43 infants were included in this study. Among the subjects, 53.4% had vitamin D deficiency. There was no association identified between vitamin D deficiency and intestinal dysbiosis (RR 0.67; 95% CI (0.15-2.82), p-value = 0.531). However, the ratio of Lactobacillacecae to Enterobacteriaceae was lower in those with vitamin D deficiency. CONCLUSION: Vitamin D deficiency was not associated with dysbiosis in preterm infants. However, this study found that the ratio of Lactobacillaceae to Enterobacteriaceae in those with vitamin D deficiency was lower than in those without vitamin D deficiency. Further research is warranted to confirm this finding.