Impact of COVID-19 pandemic on neurodevelopmental outcomes of premature infants: a retrospective national cohort study.

OBJECTIVE: To compare the neurodevelopmental outcomes of preterm infants before and during the COVID-19 pandemic. DESIGN: Premature infants born in 2018 were assigned to the pre-pandemic group, while those born in 2019 were assigned to the during-pandemic group. SETTING: Nationwide cohort study. PATIENTS: Very low birthweight premature infants registered in the Taiwan Premature Infant Follow-up Network database. INTERVENTIONS: Anti-epidemic measures, including quarantine and isolation protocols, social distancing, the closure of public spaces and restrictions on travel and gatherings during COVID-19 pandemic. MAIN OUTCOME MEASURES: Outcomes were measured by Bayley Scales of Infant and Toddler Development Third Edition at corrected ages of 6, 12 and 24 months old. Generalised estimating equation (GEE) was applied to incorporate all measurements into a single model. RESULTS: Among the 1939 premature infants who were enrolled, 985 developed before the pandemic, while 954 developed during the pandemic. Premature infants whose development occurred during the pandemic exhibited better cognitive composite at the corrected age of 6 months (beta=2.358; 95% CI, 1.07 to 3.65; p<0.001), and motor composite at corrected ages of 12 months (beta=1.680; 95% CI, 0.34 to 3.02; p=0.014). GEE analysis showed that infants who had grown during the pandemic achieved higher scores in cognitive composite (beta=1.416; 95% CI, 0.36 to 2.48; p=0.009). CONCLUSION: Premature infants in Taiwan who developed during the pandemic showed better neurodevelopment compared with those born before the pandemic.

Safe and efficient practice of parenteral nutrition in neonates and children aged 0-18 years - The role of licensed multi-chamber bags.

Parenteral nutrition (PN) is recognized as a complex high-risk therapy. Its practice is highly variable and frequently suboptimal in pediatric patients. Optimizing care requires evidence, consensus-based guidelines, audits of practice, and standardized strategies. Several pediatric scientific organizations, expert panels, and authorities have recently recommended that standardized PN should generally be used over individualized PN in the majority of pediatric patients including very low birth weight premature infants. In addition, PN admixtures produced and validated by a suitably qualified institution are recommended over locally produced PN. Licensed multi chamber bags are standardized PN bags that comply with Good Manufacturing Practice and high-quality standards for the finished product in the frame of their full manufacturing license. The purpose of this article is to review the practical aspects of PN and the evidence for using such multi-chamber bags in pediatric patients. It highlights the safety characteristics and the limitations of the different PN practices and provides some guidance for ensuring safe and efficient therapy in pediatric patients.

Risk factors for mortality in culture-negative neonatal sepsis in Malawi: a propensity score-matched analysis.

We conducted a propensity score-matched multivariable regression analysis of 1050 culture-negative neonatal sepsis cases in Malawi, where 160 (15.2%) died. Mortality among neonates with culture-negative sepsis was associated with very low birth weight (adjusted OR (AOR) 12.82, 95% CI 1.23 to 137.49), respiratory distress syndrome (AOR 13.20, 95% CI 2.58 to 83.66), a low Apgar score at 1 min (AOR 3.50, 95% CI 1.21 to 10.72) and at 5 min (AOR 4.77, 95% CI 1.94 to 12.50). Addressing maternal and perinatal factors around health and delivery of care is key to improving outcomes in the context of culture-negative sepsis in neonates from low-income country settings like Malawi.

RBC transfusion and necrotizing enterocolitis in very preterm infants: a multicenter observational study.

The causal relationship between Packed red blood cell (RBC) transfusion and necrotizing enterocolitis (NEC) remains uncertain. This study aims to provide an exploration of transfusion and NEC in very preterm infants. Using data from the Chinese Neonatal Network cohort study between 2019 and 2021, the analysis focused on very preterm infants (with a birth weight of < 1500 g or a gestational age of < 32 weeks) who developed NEC after receiving transfusions. The time interval between the prior transfusion and NEC was analyzed. An uneven distribution of the time interval implies an association of transfusion and NEC. Additionally, multivariable logistic analysis was conducted to detect the prognosis of defined transfusion-associated NEC(TANEC). Of the 16,494 infants received RBC transfusions, NEC was noted in 1281 (7.7%) cases, including 409 occurred after transfusion. Notably, 36.4% (149/409) of post-transfusion NEC occurred within 2 days after transfusion. The time interval distribution showed a non-normal pattern (Shapiro-Wilk test, W = 0.513, P < 0.001), indicating a possible link between transfusion and NEC. TANEC was defined as NEC occurred within 2 days after transfusion. Infants with TANEC had a higher incidence of death (adjusted OR 1.69; 95% CI 1.08 to 2.64), severe bronchopulmonary dysplasia (adjusted OR 2.03; 95% CI 1.41 to 2.91) and late-onset sepsis (adjusted OR 2.06; 95% CI 1.37 to 3.09) compared with infants without NEC after transfusion. Unevenly high number of NEC cases after RBC transfusions implies transfusion is associated with NEC. TANEC is associated with a poor prognosis. Further research is warranted to enhance our understanding of TANEC.

Early Antibiotic Exposure and Bronchopulmonary Dysplasia in Very Preterm Infants at Low Risk of Early-Onset Sepsis.

Importance: The overutilization of antibiotics in very preterm infants (VPIs) at low risk of early-onset sepsis (EOS) is associated with increased mortality and morbidities. Nevertheless, the association of early antibiotic exposure with bronchopulmonary dysplasia (BPD) remains equivocal. Objective: To evaluate the association of varying durations and types of early antibiotic exposure with the incidence of BPD in VPIs at low risk of EOS. Design, Setting, and Participants: This national multicenter cohort study utilized data from the Chinese Neonatal Network (CHNN) which prospectively collected data from January 1, 2019, to December 31, 2021. VPIs less than 32 weeks' gestational age or with birth weight less than 1500 g at low risk of EOS, defined as those born via cesarean delivery, without labor or rupture of membranes, and no clinical evidence of chorioamnionitis, were included. Data analysis was conducted from October 2022 to December 2023. Exposure: Early antibiotic exposure was defined as the total number of calendar days antibiotics were administered within the first week of life, which were further categorized as no exposure, 1 to 4 days of exposure, and 5 to 7 days of exposure. Main Outcomes and Measures: The primary outcome was the composite of moderate to severe BPD or mortality at 36 weeks' post menstrual age (PMA). Logistic regression was employed to assess factors associated with BPD or mortality using 2 different models. Results: Of the 27 176 VPIs included in the CHNN during the study period (14 874 male [54.7%] and 12 302 female [45.3%]), 6510 (23.9%; 3373 male [51.8%] and 3137 female [48.2.%]) were categorized as low risk for EOS. Among them, 1324 (20.3%) had no antibiotic exposure, 1134 (17.4%) received 1 to 4 days of antibiotics treatment, and 4052 (62.2%) received 5 to 7 days of antibiotics treatment. Of the 5186 VPIs who received antibiotics, 4098 (79.0%) received broad-spectrum antibiotics, 888 (17.1%) received narrow-spectrum antibiotics, and 200 (3.9%) received antifungals or other antibiotics. Prolonged exposure (5-7 days) was associated with increased likelihood of moderate to severe BPD or death (adjusted odds ratio [aOR], 1.23; 95% CI, 1.01-1.50). The use of broad-spectrum antibiotics (1-7 days) was also associated with a higher risk of moderate to severe BPD or death (aOR, 1.27; 95% CI, 1.04-1.55). Conclusions and Relevance: In this cohort study of VPIs at low risk for EOS, exposure to prolonged or broad-spectrum antibiotics was associated with increased risk of developing moderate to severe BPD or mortality. These findings suggest that VPIs exposed to prolonged or broad-spectrum antibiotics early in life should be monitored for adverse outcomes.

Association of oropharyngeal colostrum administration with decreased inflammatory indices in premature newborns weighing less than 1500 g.

BACKGROUND: The administration of colostrum through its absorption at the oropharyngeal level stimulates the mucosa-associated lymphoid tissue, providing a local immunological protection barrier. The study aimed to investigate the association of oropharyngeal colostrum administration with the reduction of inflammatory indices. MATERIALS AND METHODS: This was an observational, ambispective, analytical study of newborns < 32 weeks of gestation at risk of sepsis. Oropharyngeal colostrum was administered at 0.2 mL every 4 h for 5 days. Inflammatory indices were analyzed. Statistical analysis included frequencies, percentages, mean and Standard deviation, contingency coefficient, and Kolmogorov-Smirnov test for the distribution curve of the numerical data. RESULTS: There were 50 patients, 33 (66%) female and 17 (34%) male, with a median gestational age of 30-31 weeks (95% confidence interval [CI]). Nineteen patients had sepsis. A lower positivity rate in C-reactive protein was found, with a median of 0.5-0.6 (95% CI) at 5 days of colostrum administration versus 0.5-1.1 (95% CI) as the initial C-reactive protein. Analysis with χ2 yielded a p = 0.13, and the contingency coefficient showed a p = 0.196, indicating an association. CONCLUSION: Oropharyngeal colostrum administration was associated with a lower C-reactive protein positivity rate and clinical improvement in premature newborns at risk of sepsis.

INTRODUCCIÓN: La administración del calostro a través de su absorción a nivel orofaríngeo estimula el tejido linfoide asociado a mucosas, proporcionando una barrera de protección local e inmunológica. Conocer la asociación de la administración de calostro orofaríngeo con la disminución de los índices inflamatorios. MATERIAL Y MÉTODOS: Observacional, ambispectivo, analítico, recién nacidos < 32 semanas de gestación con riesgo de sepsis, se administró calostro orofaríngeo 0.2 ml cada 4 horas durante 5 días. se analizó índices inflamatorios, evolución clínica. Análisis estadístico: frecuencias, porcentajes, media y DS, coeficiente de contingencia y prueba de Kolmogorov Smirnov para la curva de distribución de los datos numéricos. RESULTADOS: Fueron 50 pacientes, 33 (66%) femenino, 17 (34%) masculino, edad gestacional mediana 30-31 semanas (IC 95%), 19 pacientes cursaron con sepsis encontrando menor índice de positividad en la PCR, mediana de 0.5-0.6 (IC 95%) a los 5 días de administración de calostro vs 0.5-1.1 (IC 95%) como PCR inicial, analizando con Chi cuadrada con valor p = 0.13, mediante coeficiente de contingencia con p = 0.196, traduciendo asociación. CONCLUSIÓN: La calostroterapia se asoció con menor índice de positividad en la PCR; clínicamente hacia la mejoría, en recién nacidos prematuros con riesgo de sepsis.

Patent ductus arteriosus management in very-low-birth-weight prematurity: a place for an early operation?

OBJECTIVES: The goal was to evaluate neonatal outcomes based on treatment strategies and time points for haemodynamically significant patent ductus arteriosus (hsPDA) in very-low-birth-weight preterm infants, with a particular focus on surgical closure. METHODS: This retrospective study included very-low-birth-weight infants born between 2014 and 2021 who received active treatment for hsPDA. Neonatal outcomes were compared between (i) primary surgical closure versus primary ibuprofen; (ii) early (<14th post-natal day) versus late primary surgical closure (≥14th post-natal day); and (iii) primary versus secondary surgical closure after ibuprofen failure. Further analysis using 1:1 propensity score matching was performed. Logistic regression was conducted to analyse the risk factors for post-ligation cardiac syndrome (PLCS) and/or acute kidney injury (AKI). RESULTS: A total of 145 infants with hsPDA underwent active treatment for closure. The in-hospital death rate and the incidence of severe bronchopulmonary dysplasia (BPD) were similar between the primary surgical closure group and the primary ibuprofen group in a 1:1 matched analysis. Severe BPD was significantly higher in the late surgical closure group than in the early primary surgical closure group with 1:1 propensity score matching (72.7% vs 40.9%, P=0.033). The secondary surgical closure group showed the mildest clinical condition; however, the probability of PLCS/AKI was highest (38.6%) compared to the early (15.2%) or the late primary surgical group (28.1%, P<0.001), especially in extremely premature infants (gestational age < 28 weeks). CONCLUSIONS: Surgical patent ductus arteriosus closure is not inferior to pharmacologic treatment. Considering the harmful effect of a prolonged patent ductus arteriosus shunt exposure, a timely decision and timely efforts should be made to minimize the risk of severe BPD and PLCS/AKI after surgical closure.

Effects of an early transfer from incubator to a warming crib in very low birthweight preterm infants.

PURPOSE: Very low birth weight infants are cared for postnatally in the incubator because of adverse consequences of hypothermia. Data on the optimal weight of transfer to a warming crib are rare. The aim of this study was to determine the course of temperature and body weight during a standardized transfer to a warming crib at a set weight. METHODS: Prospective intervention study in very low birthweight infants who were transferred from the incubator to a warming crib at a current weight between 1500 g and 1650 g. RESULTS: No infant had to be transferred back to an incubator. Length of hospital stay was equal compared to a historical cohort from the two years directly before the intervention. The intervention group showed an increase in the volume fed orally on the day after transfer to the warming crib, although this did not translate into an earlier discontinuation of gavage feedings. Compared to the historical group, infants in the intervention group could be transferred to an unheated crib at an earlier postmenstrual age and weight. CONCLUSIONS: Early transfer from the incubator to a warming crib between 1500 g and 1650 g is feasible and not associated with adverse short-term events or outcomes. TRIAL REGISTRATION: DRKS-IDDRKS00031832.

Predicting early mortality and severe intraventricular hemorrhage in very-low birth weight preterm infants: a nationwide, multicenter study using machine learning.

Our aim was to develop a machine learning-based predictor for early mortality and severe intraventricular hemorrhage (IVH) in very-low birth weight (VLBW) preterm infants in Taiwan. We collected retrospective data from VLBW infants, dividing them into two cohorts: one for model development and internal validation (Cohort 1, 2016-2021), and another for external validation (Cohort 2, 2022). Primary outcomes included early mortality, severe IVH, and early poor outcomes (a combination of both). Data preprocessing involved 23 variables, with the top four predictors identified as gestational age, birth body weight, 5-min Apgar score, and endotracheal tube ventilation. Six machine learning algorithms were employed. Among 7471 infants analyzed, the selected predictors consistently performed well across all outcomes. Logistic regression and neural network models showed the highest predictive performance (AUC 0.81-0.90 in both internal and external validation) and were well-calibrated, confirmed by calibration plots and the lowest two mean Brier scores (0.0685 and 0.0691). We developed a robust machine learning-based outcome predictor using only four accessible variables, offering valuable prognostic information for parents and aiding healthcare providers in decision-making.

The effect of developmental care on the length of hospital stay and family centered care practice for very low birth weight infants in neonatal intensive care units: A cluster randomized controlled trial.

BACKGROUND: Despite previous studies suggesting that developmental care can provide benign stimulation to promote neural development of newborns, more evidence is needed regarding the other clinical benefits of developmental care. OBJECTIVE: To evaluate the effect of implementing developmental care on the length of hospital stay, the improvement of care practice in neonatal intensive care units, as well as the short-term outcome of very low birth weight infants. DESIGN: Cluster-randomized controlled trial. SETTING(S) AND PARTICIPANTS: From March 1, 2021 to March 1, 2022, 1400 very low birth weight infants were recruited from 14 tertiary neonatal intensive care units in China. METHODS: We assigned 14 neonatal intensive care units to either developmental care or standard care. The length of hospital stay of the infants was the primary outcome analyzed at the individual level. Secondary outcomes were family centered care practice including parental involvement, the skin to skin care, exclusive breast milk, oral immune therapy and breastfeeding. The environmental management (noise and light) and the short-term outcomes were also evaluated. RESULTS: The length of hospital stay for the developmental care group was 65 % as long as that for the control group (HR: 0.65, 95 % CI, 0.451-0936, p = 0.021). After controlling the covariables, the adjusted HR = 0.755 (95 % CI, 0.515 to 1.107, p = 0.150). When compared to the control group, the developmental care group had greater access to SSC, with 22 infants (3.8 %) in the developmental care group compared to 13 infants (1.7 %) in the standard care group (p = 0.013). A greater proportion of infants in the developmental care group were fed at the breast, than those in the standard care group (136 [23.6 %] vs 9 [1.1 %]; p = 0.029). Compared to the control group, exclusively breast milk was significantly more favorable in the developmental care group (435 [75.6 %] vs 114 [15.0 %]; p = 0.001). The difference remained significant even after adjusting for covariates. However, the rate of oral immune therapy and parental involvement was similar in the two groups. The average noise and light levels in the developmental care group were significantly lower than those in the standard care group. After adjusting for confounders, the difference remained significant. There were no significant differences among groups in the mortality and major morbidity. CONCLUSIONS: Developmental care might have developed an accumulated effect over time on the length of hospital stay among very low birth weight infants. The implementation of developmental care can greatly improve family centered care practices and the neonatal intensive care unit environment. REGISTRATION: ClinicalTrials.govNCT05166720. Registration date: 1 March, 2021.

Estimation of the causal effect of sex on neonatal intensive care unit outcomes among very low birth weight infants.

OBJECTIVE: Estimate the causal effect of sex on outcomes in the neonatal intensive care unit (NICU) among very low birth weight (VLBW) infants. STUDY DESIGN: Retrospective cohort study using Vermont Oxford Network data to compare NICU outcomes for VLBW males versus females. Odds ratios (OR) for outcomes that differed significantly by sex were computed using standard unweighted analysis and inverse probability weighted (IPW) analysis to correct for selection bias. RESULTS: Using standard analysis, males were significantly more likely to die before discharge and experience six other adverse outcomes. From IPW analysis, male sex caused a 56% increase in the odds of death before discharge (OR = 1.56, 95% confidence interval: 1.18-1.94). Standard unweighted results were significantly biased towards increased risk of adverse outcomes for males (p = 0.005) compared to IPW results for which three outcomes were no longer significantly associated with male sex. CONCLUSION: Standard statistical methods generally overestimate the casual effect of sex among VLBW infants.

Predicting severe intraventricular hemorrhage or early death using machine learning algorithms in VLBWI of the Korean Neonatal Network Database.

Severe intraventricular hemorrhage (IVH) in premature infants can lead to serious neurological complications. This retrospective cohort study used the Korean Neonatal Network (KNN) dataset to develop prediction models for severe IVH or early death in very-low-birth-weight infants (VLBWIs) using machine-learning algorithms. The study included VLBWIs registered in the KNN database. The outcome was the diagnosis of IVH Grades 3-4 or death within one week of birth. Predictors were categorized into three groups based on their observed stage during the perinatal period. The dataset was divided into derivation and validation sets at an 8:2 ratio. Models were built using Logistic Regression with Ridge Regulation (LR), Random Forest, and eXtreme Gradient Boosting (XGB). Stage 1 models, based on predictors observed before birth, exhibited similar performance. Stage 2 models, based on predictors observed up to one hour after birth, showed improved performance in all models compared to Stage 1 models. Stage 3 models, based on predictors observed up to one week after birth, showed the best performance, particularly in the XGB model. Its integration into treatment and management protocols can potentially reduce the incidence of permanent brain injury caused by IVH during the early stages of birth.

Time to full enteral feeding and its predictors among very low birth weight (VLBW) neonates admitted to the neonatal intensive care units (NICU) in comprehensive specialized hospitals in Northwest Ethiopia.

BACKGROUND: Time to full enteral feeding is the time when neonates start to receive all of their prescribed nutrition as milk feeds. Delayed to achieve full enteral feeding had resulted in short- and long-term physical and neurological sequelae. However, there are limited studies to assess the time to full enteral feeding and its predictors among very low birth-weight neonates in Ethiopia. Therefore, this study aimed to assess the time to full enteral feeding and its predictors among very low birth-weight neonates admitted to comprehensive specialized hospitals in Northwest Ethiopia. METHODS: A multi-center institutional-based retrospective follow-up study was conducted among 409 VLBW neonates from March 1, 2019 to February 30, 2023. A simple random sampling method was used to select study participants. Data were entered into EpiData version 4.2 and then exported into STATA version 16 for analysis. The Kaplan-Meier survival curve together with the log-rank test was fitted to test for the presence of differences among groups. Proportional hazard assumptions were checked using a global test. Variables having a p- value < 0.25 in the bivariable Cox-proportional hazard model were candidates for multivariable analysis. An adjusted Hazard Ratio (AHR) with 95% Confidence Intervals (CI) was computed to report the strength of association, and variables having a P-value < 0.05 at the 95% confidence interval were considered statistically significant predictor variables. RESULT: The median time to full enteral feeding was 10 (CI: 10-11) days. Very Low Birth-Weight (VLBW) neonates who received a formula feeding (AHR: 0.71, 95% CI: 0.53, 0.96), gestational age of 32-37 weeks (AHR: 1.66, 95% CI: 1.23, 2.23), without Necrotizing Enterocolitis (NEC) (AHR: 2.16, 95% CI: 1.65, 2.84), and single birth outcome (AHR: 1.42, 95% CI: 1.07, 1.88) were statistically significant variables with time to full enteral feeding. CONCLUSION AND RECOMMENDATIONS: This study found that the median time to full enteral feeding was high. Type of feeding, Necrotizing Enterocolitis (NEC), Gestational Age (GA) at birth, and birth outcome were predictor variables. Special attention and follow-up are needed for those VLBW neonates with NEC, had a GA of less than 32 weeks, and had multiple birth outcomes.

First-year outcomes of very low birth weight preterm singleton infants with hypoxemic respiratory failure treated with milrinone and inhaled nitric oxide (iNO) compared to iNO alone: A nationwide retrospective study.

BACKGROUND: Inhaled nitric oxide (iNO) has a beneficial effect on hypoxemic respiratory failure. The increased use of concurrent iNO and milrinone was observed. We aimed to report the trends of iNO use in the past 15 years in Taiwan and compare the first-year outcomes of combining iNO and milrinone to the iNO alone in very low birth weight preterm (VLBWP) infants under mechanical ventilation. METHODS: This nationwide cohort study enrolled preterm singleton infants with birth weight <1500g treated with iNO from 2004 to 2019. Infants were divided into two groups, with a combination of intravenous milrinone (Group 2, n = 166) and without milrinone (Group 1, n = 591). After propensity score matching (PSM), each group's sample size is 124. The primary outcomes were all-cause mortality and the respiratory condition, including ventilator use and duration. The secondary outcomes were preterm morbidities within one year after birth. RESULTS: After PSM, more infants in Group 2 needed inotropes. The mortality rate was significantly higher in Group 2 than in Group 1 from one month after birth till 1 year of age (55.1% vs. 13.5%) with the adjusted hazard ratio of 4.25 (95%CI = 2.42-7.47, p <0.001). For infants who died before 36 weeks of postmenstrual age (PMA), Group 2 had longer hospital stays compared to Group 1. For infants who survived after 36 weeks PMA, the incidence of moderate and severe bronchopulmonary dysplasia (BPD) was significantly higher in Group 2 than in Group 1. For infants who survived until one year of age, the incidence of pneumonia was significantly higher in Group 2 (28.30%) compared to Group 1 (12.62%) (p = 0.0153). CONCLUSION: Combined treatment of iNO and milrinone is increasingly applied in VLBWP infants in Taiwan. This retrospective study did not support the benefits of combining iNO and milrinone on one-year survival and BPD prevention. A future prospective study is warranted.

Rates of bronchopulmonary dysplasia in very low birth weight neonates: a systematic review and meta-analysis.

IMPORTANCE: Large-scale estimates of bronchopulmonary dysplasia (BPD) are warranted for adequate prevention and treatment. However, systematic approaches to ascertain rates of BPD are lacking. OBJECTIVE: To conduct a systematic review and meta-analysis to assess the prevalence of BPD in very low birth weight (≤ 1,500 g) or very low gestational age (< 32 weeks) neonates. DATA SOURCES: A search of MEDLINE from January 1990 until September 2019 using search terms related to BPD and prevalence was performed. STUDY SELECTION: Randomized controlled trials and observational studies evaluating rates of BPD in very low birth weight or very low gestational age infants were eligible. Included studies defined BPD as positive pressure ventilation or oxygen requirement at 28 days (BPD28) or at 36 weeks postmenstrual age (BPD36). DATA EXTRACTION AND SYNTHESIS: Two reviewers independently conducted all stages of the review. Random-effects meta-analysis was used to calculate the pooled prevalence. Subgroup analyses included gestational age group, birth weight group, setting, study period, continent, and gross domestic product. Sensitivity analyses were performed to reduce study heterogeneity. MAIN OUTCOMES AND MEASURES: Prevalence of BPD defined as BPD28, BPD36, and by subgroups. RESULTS: A total of 105 articles or databases and 780,936 patients were included in this review. The pooled prevalence was 35% (95% CI, 28-42%) for BPD28 (n = 26 datasets, 132,247 neonates), and 21% (95% CI, 19-24%) for BPD36 (n = 70 studies, 672,769 neonates). In subgroup meta-analyses, birth weight category, gestational age category, and continent were strong drivers of the pooled prevalence of BPD. CONCLUSIONS AND RELEVANCE: This study provides a global estimation of BPD prevalence in very low birth weight/low gestation neonates.

Risk factors for PDA ligation and neurodevelopmental outcomes at corrected 18-24 months in very low birth weight infants.

BACKGROUND: Patent ductus arteriosus (PDA) is commonly encountered morbidity which often occurs as up to 60% of extremely preterm infants born at < 29 weeks gestational age (GA). PURPOSE: This study aims to assess the clinical risk factors associated with PDA ligation among very low birth weight infants (VLBWI) and evaluate the neurodevelopmental outcomes of those who underwent PDA ligation. METHODS: A total of 540 VLBWI were initially diagnosed with PDA in our 50-bed level IV NICU at Seoul St. Mary's Hospital, The Catholic University of Korea, between January 2015 and June 2023. Among these 540 VLBWI with PDA, only 221 had consistent hemodynamically significant (hs) PDA which required intervention including fluid restriction, medical treatment, or surgical ligation. In this study, only those 221 VLBWI with hsPDA who underwent neurodevelopmental assessment at corrected 18-24 months of age were included in this study analysis. RESULTS: Out of 221 VLBWI diagnosed with hemodynamically significant (hs) PDA, 133 (60.2%) underwent PDA ligation, while the remaining 88 (39.8%) had their hs PDAs closed either medically or with fluid restriction. The mean gestational age and birth weight were significantly lower in PDA ligation group compared to no PDA ligation group (27.02 ± 2.17 vs. 27.98 ± 2.36, 907.31 ± 258.36 vs. 1006.07 ± 283.65, p = 0.001, 0.008). Resuscitation including intubation at delivery and intraventricular hemorrhage (IVH) (grade ≥ 3) were significantly higher in PDA ligation group. The clinical outcomes in the PDA ligation group revealed significantly worse oucomes compared to the no PDA ligation group. Both resuscitation, including intubation at delivery, and IVH (grade ≥ 3), consistently exhibited an increased risk for PDA ligation in a multivariable logistic regression analysis. Concerning neurodevelopmental outcomes, infants who underwent PDA ligation demonstrated significantly lower cognitive scores. However, only IVH (grade ≥ 3) and PVL were consistently associated with an increased risk of abnormal neurodevelopment at the corrected age of 18-24 months. CONCLUSION: In our study, despite the consistent association between cognitive developmental delays in VLBWI who underwent PDA ligation, we observed that sicker and more vulnerable VLBWIs, specifically those experincing severe IVH, consistently exhibited an increased risk for both PDA ligation and abnormal neurodevelopment at the corrected age of 18-24 months.

Early-life nutrition is associated with processing speed at age 5 in children born preterm with very low birth weight.

OBJECTIVE: Processing speed is suboptimal among preterm-born children which is of concern as it is a foundational skill supporting higher-level cognitive functions. The study objective was to evaluate associations between early-life nutrition and processing speed in childhood. METHODS: Macronutrient and human milk (mother's own, donor) intakes from 137 children born preterm with very low birth weight enrolled in a nutrition feeding trial were included. Processing speed was evaluated at age 5 using the Wechsler Preschool and Primary Scale of Intelligence-fourth edition Processing Speed Index. Associations between early-life nutrition and processing speed were explored through linear regression. RESULTS: Children had a mean (standard deviation [SD]) birth gestational age of 28.1 (2.5) weeks, weight of 1036 (260) g and 52% were male. The mean (SD) assessment age was 5.7 (0.2) years. Sex-dependent relationships were identified between first postnatal month protein, lipid and energy intakes and processing speed at 5 years. For females, lower protein (per 0.1 g/kg/d: -0.88, 95% confidence interval [CI]: -1.53, -0.23; p = 0.01) and energy (per 10 kcal/kg/d: -2.38, 95% CI: -4.70, -0.05; p = 0.03) intakes were related to higher processing speed scores. Mother's milk provision was positively associated (per 10% increase: 0.80, 95% CI: 0.22, 1.37; p = 0.01) and donor milk was negatively associated (per 10% increase: -1.15, 95% CI: -2.22, -0.08; p = 0.04) with processing speed scores; no sex differences were observed. CONCLUSIONS: First postnatal month nutrition was related to processing speed at age 5 in children born preterm with very low birth weight. Early-life nutrition that supports processing speed may be leveraged to improve later cognitive outcomes for this vulnerable population.

Noise or sound management in the neonatal intensive care unit for preterm or very low birth weight infants.

BACKGROUND: Infants in the neonatal intensive care unit (NICU) are subjected to different types of stress, including sounds of high intensity. The sound levels in NICUs often exceed the maximum acceptable level recommended by the American Academy of Pediatrics, which is 45 decibels (dB). Hearing impairment is diagnosed in 2% to 10% of preterm infants compared to only 0.1% of the general paediatric population. Bringing sound levels under 45 dB can be achieved by lowering the sound levels in an entire unit; by treating the infant in a section of a NICU, in a 'private' room, or in incubators in which the sound levels are controlled; or by reducing sound levels at the individual level using earmuffs or earplugs. By lowering sound levels, the resulting stress can be diminished, thereby promoting growth and reducing adverse neonatal outcomes. This review is an update of one originally published in 2015 and first updated in 2020. OBJECTIVES: To determine the benefits and harms of sound reduction on the growth and long-term neurodevelopmental outcomes of neonates. SEARCH METHODS: We used standard, extensive Cochrane search methods. On 21 and 22 August 2023, a Cochrane Information Specialist searched CENTRAL, PubMed, Embase, two other databases, two trials registers, and grey literature via Google Scholar and conference abstracts from Pediatric Academic Societies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs in preterm infants (less than 32 weeks' postmenstrual age (PMA) or less than 1500 g birth weight) cared for in the resuscitation area, during transport, or once admitted to a NICU or stepdown unit. We specified three types of intervention: 1) intervention at the unit level (i.e. the entire neonatal department), 2) at the section or room level, or 3) at the individual level (e.g. hearing protection). DATA COLLECTION AND ANALYSIS: We used the standardised review methods of Cochrane Neonatal to assess the risk of bias in the studies. We used the risk ratio (RR) and risk difference (RD), with their 95% confidence intervals (CIs), for dichotomous data. We used the mean difference (MD) for continuous data. Our primary outcome was major neurodevelopmental disability. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included one RCT, which enroled 34 newborn infants randomised to the use of silicone earplugs versus no earplugs for hearing protection. It was a single-centre study conducted at the University of Texas Medical School in Houston, Texas, USA. Earplugs were positioned at the time of randomisation and worn continuously until the infants were 35 weeks' postmenstrual age (PMA) or discharged (whichever came first). Newborns in the control group received standard care. The evidence is very uncertain about the effects of silicone earplugs on the following outcomes. • Cerebral palsy (RR 3.00, 95% CI 0.15 to 61.74)and Mental Developmental Index (MDI) (Bayley II) at 18 to 22 months' corrected age (MD 14.00, 95% CI 3.13 to 24.87); no other indicators of major neurodevelopmental disability were reported. • Normal auditory functioning at discharge (RR 1.65, 95% CI 0.93 to 2.94) • All-cause mortality during hospital stay (RR 2.07, 95% CI 0.64 to 6.70; RD 0.20, 95% CI -0.09 to 0.50) • Weight (kg) at 18 to 22 months' corrected age (MD 0.31, 95% CI -1.53 to 2.16) • Height (cm) at 18 to 22 months' corrected age (MD 2.70, 95% CI -3.13 to 8.53) • Days of assisted ventilation (MD -1.44, 95% CI -23.29 to 20.41) • Days of initial hospitalisation (MD 1.36, 95% CI -31.03 to 33.75) For all outcomes, we judged the certainty of evidence as very low. We identified one ongoing RCT that will compare the effects of reduced noise levels and cycled light on visual and neural development in preterm infants. AUTHORS' CONCLUSIONS: No studies evaluated interventions to reduce sound levels below 45 dB across the whole neonatal unit or in a room within it. We found only one study that evaluated the benefits of sound reduction in the neonatal intensive care unit for hearing protection in preterm infants. The study compared the use of silicone earplugs versus no earplugs in newborns of very low birth weight (less than 1500 g). Considering the very small sample size, imprecise results, and high risk of attrition bias, the evidence based on this research is very uncertain and no conclusions can be drawn. As there is a lack of evidence to inform healthcare or policy decisions, large, well designed, well conducted, and fully reported RCTs that analyse different aspects of noise reduction in NICUs are needed. They should report both short- and long-term outcomes.

Impact of Nutrient Intake on Body Composition in Very Low-Birth Weight Infants Following Early Progressive Enteral Feeding.

Preterm infants have increased body adiposity at term-equivalent age and risk of adverse metabolic outcomes. The aim of the study was to define how nutrient intake may impact body composition (BC) of very low-birth weight infants fed with early progressive enteral feeding and standard fortification. Eighty-six infants with <1500 g birth weight were included in the BC study and stratified into extremely preterm (EP) and very preterm (VP) groups. Nutrient intake was calculated during the first 28 days and BC assessed by dual X-ray absorptiometry at discharge and by skinfold thickness at 12 months of corrected age (CA). Total nutrient intake did not differ between the groups. EP infants had a higher fat mass percentage at discharge than VP infants (24.8% vs. 19.4%, p < 0.001); lean mass did not differ. None of the nutrients had any impact on BC of EP infants. Protein intake did not result in a higher lean mass in either group; fat intake was a significant predictor of increased fat mass percentage in VP infants at discharge (p = 0.007) and body adiposity at 12 months of CA (p = 0.021). Nutritional needs may depend on gestational age and routine fortification should be used with caution in more mature infants.