Antibiotics and beyond: Unraveling the dynamics of bronchopulmonary dysplasia in very preterm infants.

BACKGROUND: Bronchopulmonary dysplasia (BPD) remains a significant challenge in neonatal care. Prenatal inflammation and neonatal sepsis contribute to the multifactorial nature of BPD. A potential association between empirical antibiotic therapy and BPD risk has been proposed due to microbiota dysbiosis in very low birth weight premature infants. METHODS: A single centered retrospective cohort study of preterm infants (24-32 weeks gestation) from 2014 to 2021. The study compared groups that received empirical antibiotics in the first days of life and those that did not receive any antibiotic in the first days of life. The primary outcomes studied were BPD, death, and the combined outcome of BPD/death. Statistical analysis employed t-tests, Mann-Whitney U, Chi-square, and logistic regression. RESULTS: Of 454 preterm infants, 61.5% received antibiotics. This group had lower gestational age, birth weight, and Apgar scores. Antibiotic use was associated with higher incidence of BPD (35.5% vs. 10.3%), death (21.5% vs. 8.6%), and combined outcomes (54.5% vs. 18.3%). In multivariate analysis, antibiotic use independently associated with BPD (OR 2.58, p < 0.001) and combined outcome BPD/death (OR 2.06, p < 0.02). Antenatal corticosteroids provided protection against BPD, but not mortality. CONCLUSION: This study suggests an association between early empirical antibiotic use and BPD in preterm infants, emphasizing the need for judicious antibiotic practices in neonatal care.

Recovery from parenteral nutrition-associated cholestasis takes approximately two months in very low birth weight infants.

AIM: To investigate the clinical characteristics and course of parenteral nutrition-associated cholestasis (PNAC) in very low birth weight (VLBW) infants. METHODS: The charts of VLBW infants were retrospectively reviewed. The clinical characteristics of infants with and without PNAC were compared, trends in liver enzymes were investigated, and the characteristics of infants with PNAC were analysed based on age of onset. RESULTS: PNAC was observed in 53 (13.2%) of 403 infants who survived and completed follow-up and was associated with significantly lower gestational age, birth weight, and adverse neonatal outcomes. PNAC started at a median 32 (interquartile range 23-47) days, PN was applied for 53 (34.5-64.5) days, the maximum direct bilirubin (DB) was observed at 63 (50-76) postnatal days, and PNAC resolved at 94 (79-122) postnatal days postnatal age. PNAC lasted 61 (38-89.5) days. AST and ALT normalised at 111 (100.3-142.0) and 109.5 (97-161.3) postnatal days. Infants with early-onset PNAC had significantly longer PN duration, higher maximum DB, and higher maximum AST than those with late-onset PNAC. CONCLUSION: Elevated DB, AST, and ALT persist for a long period after discontinuing PN. We suggest a cautious approach that involves waiting and reducing the frequency of additional repetitive examinations.

Gut microbiota in preterm infants receiving breast milk or mixed feeding.

BACKGROUND: Preterm birth is the leading cause of mortality in newborns, with very-low-birth-weight infants usually experiencing several complications. Breast milk is considered the gold standard of nutrition, especially for preterm infants with delayed gut colonization, because it contains beneficial microorganisms, such as Lactobacilli and Bifidobacteria. AIM: To analyze the gut microbiota of breastfed preterm infants with a birth weight of 1500 g or less. METHODS: An observational study was performed on preterm infants with up to 36.6 wk of gestation and a birth weight of 1500 g or less, born at the University Hospital Dr. José Eleuterio González at Monterrey, Mexico. A total of 40 preterm neonates were classified into breast milk feeding (BM) and mixed feeding (MF) groups (21 in the BM group and 19 in the MF group), from October 2017 to June 2019. Fecal samples were collected before they were introduced to any feeding type. After full enteral feeding was achieved, the composition of the gut microbiota was analyzed using 16S rRNA gene sequencing. Numerical variables were compared using Student's t-test or using the Mann-Whitney U test for nonparametric variables. Dominance, evenness, equitability, Margalef's index, Fisher's alpha, Chao-1 index, and Shannon's diversity index were also calculated. RESULTS: No significant differences were observed at the genus level between the groups. Class comparison indicated higher counts of Alphaproteobacteria and Betaproteobacteria in the initial compared to the final sample of the BM group (P < 0.011). In addition, higher counts of Gammaproteobacteria were detected in the final than in the initial sample (P = 0.040). According to the Margalef index, Fisher's alpha, and Chao-1 index, a decrease in species richness from the initial to the final sample, regardless of the feeding type, was observed (P < 0.050). The four predominant phyla were Bacteroidetes, Actinobacteria, Firmicutes, and Proteobacteria, with Proteobacteria being the most abundant. However, no significant differences were observed between the initial and final samples at the phylum level. CONCLUSION: Breastfeeding is associated with a decrease in Alphaproteobacteria and Betaproteobacteria and an increase of Gammaproteobacteria, contributing to the literature of the gut microbiota structure of very low-birth-weight, preterm.

Early nutritional influences on brain regions related to processing speed in children born preterm: A secondary analysis of a randomized trial.

BACKGROUND: Processing speed is a foundational skill supporting intelligence and executive function, areas often delayed in preterm-born children. The impact of early-life nutrition on gray matter facilitating processing speed for this vulnerable population is unknown. METHODS: Magnetic resonance imaging and the Wechsler Preschool and Primary Scale of Intelligence-IV Processing Speed Index were acquired in forty 5-year-old children born preterm with very low birth weight. Macronutrient (grams per kilogram per day) and mother's milk (percentage of feeds) intakes were prospectively collected in the first postnatal month and associations between early-life nutrition and the primary outcome of brain regions supporting processing speed were investigated. RESULTS: Children had a mean (SD) gestational age of 27.8 (1.8) weeks and 45% were male. Macronutrient intakes were unrelated, but mother's milk was positively related, to greater volumes in brain regions, including total cortical gray matter, cingulate gyri, and occipital gyri. CONCLUSION: First postnatal month macronutrient intakes showed no association, but mother's milk was positively associated, with volumetric measures of total and regional cortical gray matter related to processing speed in preterm-born children. This exploratory analysis suggests early-life mother's milk supports processing speed by impacting structural underpinnings. Further research is needed on this potential strategy to improve preterm outcomes.

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OBJECTIVES: To develop effective measures to reduce antibiotic use duration in very low birth weight (VLBW) preterm infants in the neonatal intensive care unit through quality improvement methods. METHODS: The study population consisted of hospitalized VLBW preterm infants, with the percentage of hospitalization time during which antibiotics were used from November 2020 to June 2021 serving as the baseline. The specific quality improvement goal was to reduce the duration of antibiotic use. Factors affecting antibiotic use duration in preterm infants were analyzed using Pareto charts. Key drivers were identified, and specific interventions were formulated based on the stages of antibiotic use. Changes in the percentage of antibiotic use duration were monitored with run charts until the quality improvement target was achieved. RESULTS: From November 2020 to June 2021, the baseline antibiotic use duration percentage was 49%, with a quality improvement target to reduce this by 10% within 12 months. The Pareto analysis indicated that major factors influencing antibiotic duration included non-standard antibiotic use; delayed cessation of antibiotics when no infection evidence was present; prolonged central venous catheter placement; insufficient application of kangaroo care; and delayed progress in enteral nutrition. The interventions implemented included: (1) establishing sepsis evaluation and management standards; (2) educating medical staff on the rational use of antibiotics for preterm infants; (3) supervising the enforcement of antibiotic use standards during ward rounds; (4) for those without clear signs of infection and with negative blood cultures, discontinued the use of antibiotics 36 hours after initiation; (5) reducing the duration of central venous catheterization and parenteral nutrition to lower the risk of infection in preterm infants. The control chart showed that with continuous implementation of interventions, the percentage of antibiotic use duration was reduced from 49% to 32%, a statistically significant decrease. CONCLUSIONS: The application of quality improvement tools based on statistical principles and process control may significantly reduce the antibiotic use duration in VLBW preterm infants. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 736-742.

The impact of impaired intrauterine growth on male fertility: A systematic review and meta-analysis.

BACKGROUND: Adverse intrauterine environment was believed to have deleterious effects on the gonadal function. However, the association between impaired intrauterine growth and fertility in adult males has not been established. OBJECTIVES: To compare the reproductive rates of males born small for gestational age (SGA), with low birth weight (LBW) or very low birth weight (VLBW) with control groups. METHODS: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was followed to search PubMed, Web of Science, Cochrane Library, and Embase databases from inception to June 16, 2023. Cohort studies investigating the reproductive rates of males born SGA, with LBW or VLBW were included. A random or fixed effects model was used for different exposures. RESULTS: A total of 10 studies out of 3,801 records were included. Males born SGA showed a higher risk of infertility than the control group (odds ratio, OR = 0.91, 95% confidence interval, 95% CI 0.89-0.93, p = 0.000). The reproductive rates of individuals born with LBW or VLBW were lower than the control group (OR = 0.86, 95% CI 0.78-0.94, p = 0.001; OR = 0.57, 95% CI 0.40-0.81, p = 0.002, respectively). Participants were further divided into two age groups of 18-35 and 35-45 years. In both subgroups, the reproductive rates were lower in males born SGA, with LBW or VLBW compared with controls. Sensitivity analysis showed the robustness of the pooled estimates among LBW and VLBW. CONCLUSION: In summary, SGA, LBW, and VLBW were associated with a higher risk of male infertility in both early and middle adulthood. Achieving optimal intrauterine growth would be helpful to prevent male infertility.

Association between type of feeding at hospital discharge and nutritional status of Brazilian very preterm infants: a multicenter study.

OBJECTIVES: To examine trends over time in diet and size of very preterm infants, and associations of diet with size at hospital discharge/transfer. METHODS: The authors studied 4062 surviving very preterm infants born < 32 weeks' gestational age and < 1500 g between January 2012 and December 2020 from 12 Brazilian Neonatal Intensive Care Units. Diet type at discharge/transfer was classified as exclusive human milk, exclusive formula, or mixed. Outcomes were weight and head circumference at hospital discharge and the change in each from birth to discharge. The authors used linear regression to estimate adjusted associations of diet type with infant size, overall, and stratified by fetal growth category (small vs. appropriate for gestational age). The authors also examined trends in diet and infant size at discharge over the years. RESULTS: Infants' mean gestational age at birth was 29.3 weeks, and the mean birth weight was 1136 g. Diet at discharge/transfer was exclusive human milk for 22 %, mixed for 62 %, and exclusive formula for 16 %. Infant size in weight and head circumference were substantially below the growth chart reference for all diets. Infants fed human milk and mixed diets were lighter and had smaller heads at discharge/transfer than infants fed formula only (weight z: -2.0, -1.8, and -1.5; head z: -1.3, -1.2 and -1.1 for exclusive human milk, mixed and exclusive formula respectively). CONCLUSION: Results suggest high human milk use but gaps in nutrient delivery among hospitalized Brazilian very preterm infants, with little evidence of improvement over time.

Gestational age at birth, birth weight, and gestational age when intrauterine brain sparing occurs determines the neonatal outcome in growth-restricted infants born before 32 weeks of gestation: a retrospective cohort analysis.

Background: Preterm birth and fetal growth restriction are the main determinants of perinatal mortality. In the absence of therapeutic interventions, management is restricted to the observation of fetal growth and fetoplacental perfusion to determine the timing of delivery. Fetal circulatory redistribution, known as "brain sparing," represents a sign of fetal hypoxia and has been implemented in algorithms for when to deliver. In the absence of any other option, the nitric oxide donor pentaerythrityl tetranitrate (PETN), which has been shown to improve fetoplacental flow and reduce preterm birth in high-risk patients, is offered to patients as a personal therapy attempt. The aim of this study was to evaluate determinants related to pregnancy, including PETN intake during pregnancy, on immediate neonatal outcomes in a cohort of growth-restricted infants born before 32 completed weeks of gestation. Methods: We performed a retrospective cohort study of 98 infants born with a birth weight below the 10th percentile before 32 completed weeks of gestation at our tertiary care center between 2010 and 2019. PETN was offered to all mothers with a history of severe adverse pregnancy outcomes who were at high risk of developing fetal growth restriction as an individual therapy attempt. Results: The mean gestational age at birth was 188.5 days, and the mean birth weight was 549 g, corresponding to a median percentile of three. In 73 (79.3%) cases, brain sparing occurred during pregnancy. A total of 22 (22.4%) neonates were stillborn, 20 died postnatally, and 37.3% developed a severe complication. Multivariable analysis revealed birth weight percentile, gestational age at birth, and gestational age when brain sparing first occurred to be robust predictors of mortality or severe neonatal morbidity. In 39 neonates of mothers taking PETN, this impact of brain sparing was not observed. Conclusion: Our study is the first to demonstrate a significant association between the early occurrence of brain-sparing and severe neonatal outcomes in a cohort of very early preterm, growth-restricted newborns. The data suggest that PETN intake may ameliorate the effect of brain sparing in the affected neonates.

Testing the reported long-term advantages of protein-fortified human milk in very low birth weight neonates.

Preterm infants are at-risk for extrauterine growth restriction and downward percentile-crossing between birth and discharge. Increased energy and protein intake through fortification of human milk during the first weeks of life has been associated with improved short-term growth and better developmental outcomes. The aim of this study was to evaluate whether these benefits persist up to children school age. The study was designed as an observational study. During hospitalization, 22 very low birth weight preterm infants were fed with increasing protein fortification of human milk (protein supplemented group, PSG). As a control group (CG), 11 preterm infants were fed with standard nutrition regimen. At children school age (9-11 years), we assessed anthropometric data (weight, height, BMI), global health (renal function), and specific psychological outcomes (Child Behavior Checklist 6-18). A global homogeneity between CG and PSG groups emerged: we found no significant differences in weight, height, and BMI, nor in internalizing symptom outcomes (all ps > 0.05). However, mothers reported significantly higher externalizing symptoms for the PSG infants compared to CG infants. Therefore, neonatal enteral protein supplementation in very low birth weight preterm infants leads to no positive nor adverse consequences in long-term assessment, suggesting that benefits are restricted to the neonatal term and first years of age.

Early- and late-onset candidemia in very low birth weight infants in the Korean neonatal network, 2013-2017.

BACKGROUND: Candidiasis is a critical infection that is associated with very low birth weight (VLBW; <1500 g). This study investigated the characteristics and clinical presentation of candidiasis in Korean VLBW infants according to the onset of candidemia. METHODS: All VLBW infants with candidemia, defined as blood culture-positive candidiasis and registered in a multicenter database with data from 70 neonatal units of the Korean Neonatal Network between 2013 and 2017, were included in this study. Early-onset candidemia (EOC; ≤10 days) and late-onset candidemia (LOC; >10 days) were analyzed. The demographic characteristics, clinical presentations, and outcomes of candidemia were also determined. RESULTS: The overall incidence of candidemia was 2% (209/10,397) and 4% (173/3934) in VLBW and extremely very low birth weight (ELBW; <1000 g) infants, respectively. In ELBW infants, gestational age was significantly younger at EOC than at LOC (P = 0.015). Cesarean section, respiratory distress syndrome, severe bronchopulmonary disease, pulmonary hemorrhage, prior-bacteremia, neonatal seizures, and periventricular leukomalacia were significantly more common in the LOC group than in the EOC group (P < 0.05). The duration of invasive ventilation, total parenteral nutrition, and hospital stay were significantly longer in the LOC group than in the EOC group (P < 0.05). Most infections were caused by Candida spp. (91.8%). The mortality rate of ELBW infants with candidemia was 41%, which was higher than that of those without candidemia (29%) (P < 0.001). Mortality due to infection was also higher in infants with candidemia (55%) than in those without candidemia (15%) (P < 0.001); however, there were no significant differences between the EOC and LOC groups. CONCLUSIONS: LOC was more common than EOC in VLBW infants. Considering the risk factors of LOC, active weaning from invasive ventilators and aggressive enteral feeding are required to decrease LOC. Furthermore, preventing candidemia is necessary to reduce mortality in VLBW infants.

Gender and sex hormone effects on neonatal innate immune function.

OBJECTIVES: Scientific evidence provides a widened view of differences in immune response between male and female neonates. The X-chromosome codes for several genes important in the innate immune response and neonatal innate immune cells express receptors for, and are inhibited by, maternal sex hormones. We hypothesized that sex differences in innate immune responses may be present in the neonatal population which may contribute to the increased susceptibility of premature males to sepsis. We aimed to examine the in vitro effect of pro-inflammatory stimuli and hormones in neutrophils and monocytes of male and female neonates, to examine the expression of X-linked genes involved in innate immunity and the miRNA profiles in these populations. METHODS: Preterm infants (n = 21) and term control (n = 19) infants were recruited from the Coombe Women and Infants University Hospital Dublin with ethical approval and explicit consent. The preterm neonates (eight female, 13 male) were recruited with a mean gestation at birth (mean ± SD) of 28 ± 2 weeks and corrected gestation at the time of sampling was 30 + 2.6 weeks. The mean birth weight of preterm neonates was 1084 ± 246 g. Peripheral blood samples were used to analyze immune cell phenotypes, miRNA human panel, and RNA profiles for inflammasome and inflammatory genes. RESULTS: Dividing neutrophil results by sex showed no differences in baseline CD11b between sexes among either term or preterm neonates. Examining monocyte CD11b by sex shows, that at baseline, total and classical monocytes have higher CD11b in preterm females than preterm males. Neutrophil TLR2 did not differ between sexes at baseline or following lipopolysaccharide (LPS) exposure. CD11b expression was higher in preterm male non-classical monocytes following Pam3CSK treatment when compared to females, a finding which is unique to our study. Preterm neonates had higher TLR2 expression at baseline in total monocytes, classical monocytes and non-classical monocytes than term. A sex difference was evident between preterm females and term females in TLR2 expression only. Hormone treatment showed no sex differences and there was no detectable difference between males and females in X-linked gene expression. Two miRNAs, miR-212-3p and miR-218-2-3p had significantly higher expression in preterm female than preterm male neonates. CONCLUSIONS: This study examined immune cell phenotypes and x-linked gene expression in preterm neonates and stratified according to gender. Our findings suggest that the responses of females mature with advancing gestation, whereas male term and preterm neonates have very similar responses. Female preterm neonates have improved monocyte activation than males, which likely reflects improved innate immune function as reflected clinically by their lower risk of sepsis. Dividing results by sex showed changes in preterm and term infants at baseline and following LPS stimulation, a difference which is reflected clinically by infection susceptibility. The sex difference noted is novel and may be limited to the preterm or early neonatal population as TLR2 expression on monocytes of older children does not differ between males and females. The differences shown in female and male innate immune cells likely reflect a superior innate immune defense system in females with sex differences in immune cell maturation. Existing human studies on sex differences in miRNA expression do not include preterm patients, and most frequently use either adult blood or cord blood. Our findings suggest that miRNA profiles are similar in neonates of opposite sexes at term but require further investigation in the preterm population. Our findings, while novel, provide only very limited insights into sex differences in infection susceptibility in the preterm population leaving many areas that require further study. These represent important areas for ongoing clinical and laboratory study and our findings represent an important contribution to exiting literature.

Association between Ureaplasma colonization and bronchopulmonary dysplasia defined by different criteria in very low birth weight infants: A retrospective cohort study.

OBJECTIVE: To study the association between Ureaplasma colonization and bronchopulmonary dysplasia (BPD) with different definitions in very low birth weight (VLBW) infants. METHODS: A retrospective cohort study was performed with VLBW infants admitted from January 2019 to October 2021. Neonates with a positive respiratory tract Ureaplasma culture were included in the study group. Control group infants, matched for gestational age (±1 week), birth weight (±100 g), and birth year, had a negative respiratory tract Ureaplasma culture during the same period. The primary outcomes included the incidence and severity of BPD, defined by various criteria. RESULTS: The study included 302 neonates (151 in the study group and 151 in the control group). After adjusting for confounders, Ureaplasma colonization was not associated with BPD as defined by the National Institutes of Health (NIH) in 2001 (adjusted odds ratio [aOR]: 0.820, 95% confidence interval [CI]: 0.362-1.860, p = .635). However, it was associated with BPD as defined by the NIH in 2018 (aOR: 2.490, 95% CI: 1.128-5.497, p = .024) and the Neonatal Research Network (NRN) in 2019 (aOR: 2.352, 95% CI: 1.077-5.134, p = .032). Additionally, VLBW infants with Ureaplasma colonization had a higher risk of moderate-severe BPD according to the NIH 2001 (aOR: 2.352, 95% CI: 1.077-5.134, p = .032), NIH 2018 (aOR: 6.339, 95% CI: 1.686-23.836, p = .006), and NRN 2019 definitions (aOR: 3.542, 95% CI: 1.267-9.904, p = .016). CONCLUSIONS: Ureaplasma colonization is not associated with BPD by the NIH 2001 definition, but is associated with an increased incidence by the NIH 2018 or NRN 2019 definitions.

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.

Clinical Features of iatrogenic Pharyngo-esophageal perforation in very low birth weight infants.

BACKGROUND: Iatrogenic pharyngoesophageal perforation (IPEP) is one of the complications of gastric tube insertion and it tends to occur more frequently in premature infants. Although the frequency is significantly low, attention should be paid as it can lead to serious outcomes with high mortality. This study will help raise awareness with respect to early diagnosis, management, and prevention. METHODS: We performed a retrospective cohort study of all very low birth weight infants diagnosed with IPEP between 1993 and 2022. RESULTS: A total of 6 patients (0.27% of very low birth weight infants) with the diagnosis of IPEP were included. The median gestational age was 27 + 1 weeks (range 23+5-28 + 6 weeks), and the median birth weight was 823 g (range 630-1232 g). Symptoms included difficulty with gastric tube insertion, bloody secretions in the oral cavity, and increased oral secretions. X-rays revealed aberrant running of the gastric tube in all patients. In three cases, contrast studies demonstrated contrasted mediastinum tapering like a bead. Laryngoscope was used to view the perforation sites but this was not useful in the smallest patient. All patients were treated conservatively with antibiotics and survived. CONCLUSIONS: When inserting a gastric tube for premature infants, it is critical to remember that these infants are at risk of IPEP. In addition to a frontal X-ray, a lateral X-ray and contrast study may be useful for early diagnosis.

Cerebral tissue oxygen desaturations and increased fractional oxygen extraction events vary by gestational age in preterm infants.

BACKGROUND AND OBJECTIVES: Cerebral tissue oxygen saturation (SctO2) and cerebral fractional tissue oxygen extraction (cFTOE) changes with GA in preterm infants. This study examines changes in frequency, duration, and severity of SctO2 desaturation and increased cFTOE with GA. STUDY DESIGN: The lower limit of normal SctO2, the event threshold, was calculated using a tolerance interval method with 95% confidence interval (CI) and 90% probability. Cerebral desaturation events were defined as: 1) a drop below event threshold for at least 30 s (s), 2) preceded by a period above the event threshold for at least 30s, and 3) followed by a period above the threshold for at least 60s. RESULTS: 86% of infants <28 wk experienced one or more SctO2 desaturation event compared to 57% in >28 wk, odds ratios (OR) 4.5 (CI:1.3-15.3, p = 0.016). The severity of SctO2 desaturation events decreases at a rate of 77.9 units per wk increase in GA (p < 0.001). 39.3% of infants <28 wk experienced one or more increased cFTOE events compared to 28.6% in >28 wk, OR 1.6 (CI:0.6-4.4, p = 0.35). The severity of increasing cFTOE events decreased by 69.7 units per wk increase in GA (p < 0.001). CONCLUSION: Cerebral tissue oxygen desaturation events decrease in frequency and severity with increasing GA. The severity of increased cFTOE episodes decrease with GA.

Postnatal Growth Assessment and Prediction of Neurodevelopment and Long-Term Growth in Very Low Birth Weight Infants: A Nationwide Cohort Study in Korea.

Background/Objectives: Extrauterine growth restriction (EUGR) is associated with high mortality and an increased incidence of poor neurodevelopmental outcomes in preterm infants. In this study, we aimed to compare the Intergrowth-21ST (IG-21ST) and Fenton charts in predicting long-term neurodevelopmental and anthropometric outcomes of very low birth weight (VLBW) infants. Methods: Data were collected from 2649 VLBW infants registered in the Korean Neonatal Network born between 240/7 and 316/7 weeks of gestational age from January 2013 to December 2017. Follow-up assessments were conducted at 18-24 months of age, corrected for prematurity. Multiple logistic regression analysis was performed to evaluate the association between EUGR and long-term outcomes. Results: Among the 2649 VLBW infants, 60.0% (1606/2649) and 36.9% (977/2649) were diagnosed as having EUGR defined by the Fenton chart (EUGRF) and by the IG-21ST chart (EUGRIG), respectively. The EUGRIG group exhibited a higher proportion of infants with cerebral palsy, neurodevelopmental impairment (NDI), and growth failure. In multiple logistic regression analysis, adjusted for risk factors for long-term outcome, the EUGRIG group showed higher risk of cerebral palsy (adjusted odds ratio [aOR], 1.66; 95% confidence interval [CI], 1.04-2.65), NDI (aOR, 2.09; 95% CI, 1.71-2.55), and growth failure (aOR, 1.57; 95% CI, 1.16-2.13). Infants with EUGRF tended to develop NDI (aOR, 1.29; 95%CI, 1.03-1.63) and experience growth failure (aOR, 2.44; 95% CI, 1.77-3.40). Conclusions: The IG-21ST chart demonstrated a more effective prediction of long-term neurodevelopmental outcomes, whereas the Fenton chart may be more suitable for predicting growth failure at 18-24 months.

Foveal thickness and its association with visual acuity in adults born preterm with very low birth weight: A two-country birth cohort study.

PURPOSE: To explore foveal and parafoveal thickness in adults born preterm with very low birth weight (VLBW) and its association with best-corrected visual acuity (BCVA) and gestational age (GA) compared to adults born at term. METHODS: In a joint study of the Helsinki Study of Very Low Birth Weight Adults (Finland) and the NTNU Low Birth Weight Life study (Norway), 106 VLBW and 143 term-born controls were examined with spectral-domain optical coherence tomography and BCVA at age 31-43 years. Thickness of retinal layers was segmented in the foveal and parafoveal areas of the macula. RESULTS: The total retinal thickness in the foveal area was thicker in VLBW adults compared with controls; mean (SD): 292.5 µm (28.2) and 272.4 µm (20.2); p < 0.001, and thinner in the parafoveal areas of the macula. These findings could be explained by a thicker inner retinal layer in the foveal area found in VLBW adults compared with controls (mean difference 20.4 µm; CI: 15.0 to 25.9), where a thicker fovea was associated with lower GA, but not BCVA. CONCLUSION: Adults born preterm with VLBW had a thicker retina in the foveal area than controls and this was associated with GA, but not with BCVA. These changes seem to be related to a thicker inner retinal layer in VLBW adults. The findings imply that signs of macular underdevelopment are still present in adulthood, but not necessarily related to reduced visual function.

Furosemide and Ductus Arteriosus Closure in Very-Low-Birth-Weight Preterm Infants: A Comprehensive Retrospective Study.

Ductus arteriosus closure may be delayed in preterm infants, and prostaglandin, a vasodilator, can affect ductal patency. Furosemide can increase renal prostaglandin synthesis, so its net effect on patent ductus arteriosus (PDA) is uncertain. Our goal is to explore the relationship between furosemide and spontaneous ductal closure in very-low-birth-weight preterm infants. Our treatment for PDA involves fluid restriction initially and furosemide administration for hemodynamically significant PDA until closure is confirmed by the echocardiogram. We enrolled 105 infants from 1 January 2019 to 30 June 2022 and evaluated the impact of furosemide on ductal closure, including exposure duration and cumulative dose. There is no correlation between furosemide exposure and spontaneous ductal closure (p = 0.384). Furosemide exposure does not delay the postmenstrual age at which spontaneous ductal closure occurs (p = 0.558). The time for spontaneous ductal closure is positively associated with furosemide prescription days (coefficient value = 0.547, p = 0.026) and negatively with gestational age (coefficient value = -0.384, p = 0.062). The prescription of furosemide does not impact the probability or time duration of ductus arteriosus spontaneous closure. The cumulative dose of furosemide has minimal impact on ductal closure. The correlation between furosemide exposure duration and ductal patency duration is likely due to our treatment protocol, with gestational age being a significant factor.

Risk factors for acute kidney injury in very-low birth weight newborns: a systematic review with meta-analysis.

This study aims to analyze the main risk factors for acute kidney injury in the subgroup of very-low birth weight newborns, using the diagnosing criteria of the Kidney Disease Improving Global Outcomes (KDIGO) or the Acute Kidney Injury Network (AKIN). A systematic review of the literature was performed on the EMBASE® and PubMed® platforms. Studies that evaluated the risk factors for developing AKI in VLBW newborns were included. For the meta-analysis, we only included the risk factors that were associated with AKI in the univariate analysis of at least two studies. After an initial screening, abstract readings, and full-text readings, 10 articles were included in the systematic review and 9 in the meta-analysis. The incidence of AKI varied from 11.6 to 55.8%. All the studies have performed multivariate analysis, and the risk factors that appeared most were PDA and hemodynamic instability (use of inotropes or hypotension), sepsis, and invasive mechanical ventilation. After the meta-analysis, only cesarian delivery did not show an increased risk of AKI, all the other variables remained as important risk factors. Moreover, in our meta-analysis, we found a pooled increased risk of death in newborns with AKI almost 7 times.  Conclusion: AKI in VLBW has several risk factors and must be seen as a multifactorial disease. The most common risk factors were PDA, hemodynamic instability, sepsis, and invasive mechanical ventilation. What is known: • Acute kidney injury is associated with worst outcomes in all ages. It´s prevention can help diminish mortality. What is new: • A synthesis of the main risk factors associated with AKI in very low birth weight newborns.

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.