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Abstract Aims This study aims to identify important risk factors for intracranial hemorrhage (ICH) in very preterm infants at our institution and develop a predictive nomogram for early detection of ICH. Methods We retrospectively analyzed neonates with a gestational age (GA) under 32 weeks, admitted to the neonatal intensive care unit from March 2022 to July 2023. Infants were categorized into two groups based on ultrasound findings and assessed for thirteen variables including gender, GA, birth weight (BW), acidosis, among others. We used multivariate logistic regression analysis to build a prediction model and identify independent risk factors for ICH. We build a prediction model by assigning 241 cases to the training set and 103 to the validation set (ratio 7:3). Results Among 344 very preterm infants, the incidence of ICH was 36.9% (89 cases) in training set. Significant differences were observed in gestational age, birth weight, antenatal corticosteroids, mechanical ventilation days, and acidosis between cases and controls. Logistic regression analysis identified gestational age (OR = 0.674), antenatal corticosteroids (OR = 0.257), acidosis (OR = 2.556), and mechanical ventilation mechanical ventilation days(OR = 0.257) as independent risk factors for ICH. The C-index of the training and validation sets was 0.814 (95% CI: 0.762–0.869) and 0.784 (95% CI: 0.693–0.875), respectively. According to decision curve analysis, our model outperformed the “None” and “All” baseline lines over a wide range of risk thresholds (0.12–0.92). Conclusion Acidosis and mechanical ventilation are independent risk factors for ICH in very preterm neonates, while higher gestational age and antenatal corticosteroid use are protective. The nomogram developed from these four factors demonstrates strong predictive accuracy and calibration, which can aid clinicians in identifying preterm infants at high risk for ICH and facilitate early diagnosis and management.

Aims: This study aims to identify important risk factors for intracranial hemorrhage (ICH) in very preterm infants at our institution and develop a predictive nomogram for early detection of ICH. Methods: We retrospectively analyzed neonates with a gestational age (GA) under 32 weeks, admitted to the neonatal intensive care unit from March 2022 to July 2023. Infants were categorized into two groups based on ultrasound findings and assessed for thirteen variables including gender, GA, birth weight (BW), acidosis, among others. We used multivariate logistic regression analysis to build a prediction model and identify independent risk factors for ICH. We build a prediction model by assigning 241 cases to the training set and 103 to the validation set (ratio 7:3). Results: Among 344 very preterm infants, the incidence of ICH was 36.9% (89 cases) in training set. Significant differences were observed in gestational age, birth weight, antenatal corticosteroids, mechanical ventilation days, and acidosis between cases and controls. Logistic regression analysis identified gestational age (OR = 0.674), antenatal corticosteroids (OR = 0.257), acidosis (OR = 2.556), and mechanical ventilation mechanical ventilation days(OR = 0.257) as independent risk factors for ICH. The C-index of the training and validation sets was 0.814 (95% CI: 0.762–0.869) and 0.784 (95% CI: 0.693–0.875), respectively. According to decision curve analysis, our model outperformed the "None" and "All" baseline lines over a wide range of risk thresholds (0.12–0.92). Conclusion: Acidosis and mechanical ventilation are independent risk factors for ICH in very preterm neonates, while higher gestational age and antenatal corticosteroid use are protective. The nomogram developed from these four factors demonstrates strong predictive accuracy and calibration, which can aid clinicians in identifying preterm infants at high risk for ICH and facilitate early diagnosis and management. [ABSTRACT FROM AUTHOR]

Summary: Background: Data on preschool neurodevelopment of preterm infants according to the duration of their neonatal exposure to opioids with/without midazolam is limited. We aimed to assess neurodevelopment outcome in children aged five years, born very preterm (24–31 weeks), according to exposure to these drugs. Methods: Secondary analysis from the French prospective cohort study EPIPAGE-2 (Etude Epidémiologique sur les Petits Ages Gestationnels, 2011). Exposure to opioids with/without midazolam was classified as none, ≤7 or >7 days. Percentages were weighted to account for the study design. The primary outcome was moderate/severe neurodevelopmental disabilities (NDD). Analyses were conducted using logistic regression and adjusted for perinatal confounders. Findings: Among 3117 survivors, 1165 (35.9%) were exposed (762/1165 (68.0%) ≤7 days, 403/1165 (32.0%) >7 days). Of these 49.5% received opioids only, 41.4% opioids and midazolam, and 9.1% midazolam only. Moderate/severe NDD occurred in 17.8%, 18.9%, and 31.7% in the unexposed, exposed ≤7 days, and exposed >7 days groups, respectively. After adjustment for baseline confounders, only exposure >7 days was associated with increased rates of moderate/severe NDD (adjusted odds ratio 2.07; 95% CI 1.32–3.26). After additional adjustment for severe neonatal morbidities no significant association was found between any duration of exposure and NDD. Interpretation: Exposure to opioids with/without midazolam >7 days might be associated with a higher prevalence of moderate/severe NDD at five years in very preterm born children but severe neonatal morbidities are a major modulator of this association. Funding: French Institute of Public Health Research, National Institute of Health and Medical Research, National Institute of Cancer, National Solidarity Fund for Autonomy, PremUp, APICIL Foundations.

Introduction: Preterm neonates often receive a variety of duration of antibiotic exposure during admission. The aim of the study was to evaluate whether neonatal antibiotic exposure is relevant with longitudinal growth problems in preterm-birth children. Methods: This prospective study enrolled 481 infants who were born <32 weeks of gestation, discharged, and longitudinally followed from corrected age (CA) 6–60 months. After excluding 153 infants with blood culture-confirmed bacteremia, necrotizing enterocolitis, severe cerebral palsy, intestinal ostomy, and congenital anomaly, 328 infants were included for analysis. Covariates included perinatal demographics, neonatal morbidities, extrauterine growth restriction, and antibiotic exposure accumulated by term equivalent age. The primary outcome was the anthropometric trajectories in z-score of bodyweight (zBW), body height (zBH), and body mass index (zBMI) from CA 6–60 months. Results: Antibiotic exposure duration was significantly negatively associated with zBW and zBH at CA 6, 12, and 60 months, and zBMI at CA 60 months. Multivariate generalized estimating equation analyses showed antibiotic exposure duration had significantly faltering z-score increment from CA 6 to 60 months in zBW and zBH (adjusted mean [95% CI]; ΔzBW: −0.021 [−0.041 to −0.001], p = 0.042; ΔzBH: −0.019 [−0.035 to −0.002], p = 0.027) after adjustment. Children with neonatal antibiotic exposure duration >15 days were significantly lower in the mean anthropometric zBW, zBH, and zBMI at CA 6, 12, 24, and 60 months compared with children with neonatal antibiotic exposure ≤15 days (all p < 0.01). Conclusions: Growth increments were negatively associated with antibiotic exposure duration in preterm neonates implicating that antibiotic stewardship and growth follow-up for preterm neonates are thus warranted. Plain Language Summary: Preterm infants often receive a variety of antibiotic exposure duration during admission. This study was to evaluate whether neonatal antibiotic exposure is associated with longitudinal growth problems in preterm-birth children. This study followed a cohort of 328 very preterm infants born <32 weeks of gestation, who were discharged from a tertiary hospital without documented neonatal bacterial infection from 2004 to 2016 and received longitudinal follow-up for growth outcomes at their corrected age (CA) 6, 12, 24, and 60 months. We collected perinatal demographics, neonatal morbidities, extrauterine growth restriction, and antibiotic exposure duration by term equivalent age, to associate with trajectories in z-scores of bodyweight (zBW), body height (zBH), and body mass index (zBMI) from CA 6–60 months. We found antibiotic exposure duration was negatively associated with zBW and zBH at CA 6, 12, and 60 months, and zBMI at CA 60 months. After adjustments, antibiotic exposure duration was associated with decreased growth velocity in zBW and zBH from CA 6–60 months. Children with longer antibiotic exposure >15 days had significantly lower zBW, zBH, and zBMI at CA 6, 12, 24, and 60 months compared with children with antibiotic exposure ≤15 days (all p < 0.01), suggesting that longer antibiotic exposure duration was associated with inferior weight and height gains. This study concludes that long-term growth increments may negatively associate with neonatal antibiotic exposure duration in children born very premature, implicating that antibiotic stewardship and growth follow-up for preterm neonates are thus warranted. [ABSTRACT FROM AUTHOR]

Background High protein intake in very preterm neonates (VPN) is important for growth. However, preterm kidneys have fewer functional nephrons and many of the ones present may be immature. Studies have shown that high protein intake induces nephron hypertrophy, proteinuria, and glomerular sclerosis, which lead to tubular injury. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a biomarker that is released during proximal tubular cell injury. The uNGAL to creatinine (uNGAL/Cr) ratio is commonly performed for normalization. Objective To assess for a possible association between protein intake and uNGAL/Cr ratio in VPN. Methods A prospective cohort study was conducted in two NICUs in Jakarta. Subjects’ urine specimens were collected at 0-48 hours, 72 hours, and 21 days after birth to determine uNGAL/Cr ratio as a biomarker of tubular injury. Protein was administered according to study sites NICU guidelines. Protein intake was recorded daily from 14-21 days of age for formula and measured twice with a human milk analyzer for breast milk. ELISA was used to measure uNGAL concentration. Low protein intake was defined as

Background High protein intake in very preterm neonates (VPN) is important for growth. However, preterm kidneys have fewer functional nephrons and many of the ones present may be immature. Studies have shown that high protein intake induces nephron hypertrophy, proteinuria, and glomerular sclerosis, which lead to tubular injury. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a biomarker that is released during proximal tubular cell injury. The uNGAL to creatinine (uNGAL/Cr) ratio is commonly performed for normalization. Objective To assess for a possible association between protein intake and uNGAL/Cr ratio in VPN. Methods A prospective cohort study was conducted in two NICUs in Jakarta. Subjects' urine specimens were collected at 0-48 hours, 72 hours, and 21 days after birth to determine uNGAL/Cr ratio as a biomarker of tubular injury. Protein was administered according to study sites NICU guidelines. Protein intake was recorded daily from 14-21 days of age for formula and measured twice with a human milk analyzer for breast milk. ELISA was used to measure uNGAL concentration. Low protein intake was defined as <3g/kg/day and high protein intake was defined as ≥3g/kg/day. Maternal and perinatal variables were recorded from medical records. Results Fifty-nine VPN were recruited, of whom 39 completed the study. Median uNGAL/Cr ratio ranged from 0.32-104.11 ng/mg. The uNGAL/Cr ratio was not correlated with protein intake but was inversely correlated with gestational age and birth weight [r=-0.320, P=0.019 for the 72-hr (T2) urinary collection]. Higher uNGAL/Cr levels were associated with maternal infection [14.4 (range 4.4-104.1) vs. 7.2 (range 0.5-32.4) ng/mg, P=0.004 at the 0-48-hr (T1)], maternal anemia [6.9 (range 1.2-66.6) vs. 1.7 (range 0.3-89.2) ng/mg, P=0.001 at the 21-day (T3)] and nephrotoxic medication [15.9 (range 1.3-63.8) vs. 1.0 (range 0.4-8.6) ng/mg, P=0.026 at the 72-hr]. Conclusion Protein intake according to current nutritional guidelines does not correlate with tubular injury in VPN, as measured by uNGAL/Cr ratio. Maternal infection, maternal anemia, lower birth weight, and nephrotoxic medication, are associated with higher uNGAL/Cr levels in VPN. [ABSTRACT FROM AUTHOR]

Choosing the appropriate management approach for the preterm infant with low blood pressure during the transition period generally involved intervening when the blood pressure drifted below a certain threshold. It is now clear that this approach is too simplistic and does not address the underlying physiology. In this chapter, we explore the many monitoring tools available for evaluation of the hypotensive preterm and assess the evidence base supporting or refuting their use. The key challenge relates to incorporating these outputs with the clinical status of the patient and choosing the appropriate management strategy. [ABSTRACT FROM AUTHOR]

This study analyzed the longitudinal evolution of intestinal microbiota in very preterm neonates (PN) during and after their hospitalization. The bacterial 16S rRNA gene sequencing approach was applied for the analysis of fecal samples ( n = 1,307) from 596 PN. Samples were collected at one week after birth, at one month, at the neonatal intensive care unit discharge, and at 3.5 years of age. Over time, the intestinal microbiota of the infants matured progressively, with increasing alpha diversity and decreasing beta diversity. Based on a Dirichlet multinomial mixture clustering approach (DMM), during hospitalization, infants progressed among ten different clusters. At 3.5 years of age, only three clusters were identified. The influence of the gestational age, the neonatal antibiotic administration, and the maternal antibiotic therapy during delivery on the gut microbiota varied over time and depended on the sampling period. Preconceptional maternal body mass index (BMI) was associated with the gut microbiota of infants during the hospitalization period and at 3.5 years of age. Infants with a lower gestational age or those born by Cesarean section shifted between clusters more frequently. Using PICRUSt2, the inferred metabolic pathways revealed a change in the functional capacities of the intestinal microbiota over time. We found that preconceptional maternal BMI was the only consistent perinatal factor influencing the development of the gut microbiota over time. After hospital discharge, infants exhibited a transition toward a microbiota community similar to that of adults by 3.5 years of age, in accordance with the functional metabolic pathways of the gut microbiota.IMPORTANCEThis study is among the very few reports analyzing the gut microbiota development in very preterm infants over time in a large, multicenter population of 596 children from a well-described nationwide birth cohort, with a follow-up until the age of 3.5 years. The maturation of the intestinal microbiota was confirmed to occur over time, with increased alpha diversity and decreased beta diversity. Specifically, 13 microbiota clusters were identified during the hospitalization period, while and only three clusters were observed at 3.5 years. Infants born prematurely or via Cesarean section exhibited a less stable microbiota, frequently shifting clusters. A number of perinatal factors were identified as influencing the development of the microbiota. Among these, the preconceptional maternal BMI emerged as the only consistent factor up to 3.5 years. The metabolic pathways of the microbiota evolved over time, in accordance with the maturation of the gut microbiota.

Summary: Background: Bronchopulmonary dysplasia (BPD) is the primary severe complication of preterm birth. Severe BPD was associated with higher risks of mortality, more postnatal growth failure, long term respiratory and neurological developmental retardation. Inflammation plays a central role in alveolar simplification and dysregulated vascularization of BPD. There is no effective treatment to improve BPD severity in clinical practice. Our previous clinical study showed autologous cord blood mononuclear cells (ACBMNCs) infusion could reduce the respiratory support duration safely and potential improved BPD severity. Abundant preclinical studies have reported the immunomodulation effect as an important mechanism underlying the beneficial results of stem cell therapies in preventing and treating BPD. However, clinical studies assessing the immunomodulatory effect after stem cells therapy were rare. This study was to investigate the effect of ACBMNCs infusion soon after birth on prevention for severe BPD and long term outcomes in very preterm neonates. The immune cells and inflammatory biomarkers were detected to investigate the underlying immunomodulatory mechanisms. Methods: This single-center, prospective, investigator-initiated, non-randomized trial with blinded outcome assessment aimed to assess the effect of a single intravenous infusion of ACBMNCs in preventing severe BPD (moderate or severe BPD at 36 weeks of gestational age or discharge home) in surviving very preterm neonates less than 32 gestational weeks. Patients admitted to the Neonatal Intensive Care Unit (NICU) of Guangdong Women and Children Hospital from July 01, 2018 to January 1, 2020 were assigned to receiving a targeted dosage of 5 × 107 cells/kg ACBMNC or normal saline intravenously within 24 h after enrollment. Incidence of moderate or severe BPD in survivors were investigated as the primary short term outcome. Growth, respiratory and neurological development were assessed as long term outcomes at corrected age of 18–24 month-old. Immune cells and inflammatory biomarkers were detected for potential mechanism investigation. The trial was registered at ClinicalTrials.gov (NCT02999373). Findings: Six-two infants were enrolled, of which 29 were enrolled to intervention group, 33 to control group. Moderate or severe BPD in survivors significantly decreased in intervention group (adjusted p = 0.021). The number of patients needed to treat to gain one moderate or severe BPD-free survival was 5 (95% confidence interval: 3–20). Survivors in the intervention group had a significantly higher chance to be extubated than infants in the control group (adjusted p = 0.018). There was no statistical significant difference in total BPD incidence (adjusted p = 0.106) or mortality (p = 1.000). Incidence of developmental delay reduced in intervention group in long term follow-up (adjusted p = 0.047). Specific immune cells including proportion of T cells (p = 0.04) and CD4+ T cells in lymphocytes (p = 0.03), and CD4+ CD25+ forkhead box protein 3 (FoxP3)+ regulatory T cells in CD4+ T cells increased significantly after ACBMNCs intervention (p ＜ 0.001). Anti-inflammatory factor IL-10 was higher (p = 0.03), while pro-inflammatory factor such as TNF-a (p = 0.03) and C reactive protein (p ＜ 0.001) level was lower in intervention group than in control group after intervention. Interpretation: ACBMNCs could prevent moderate or severe BPD in surviving very premature neonates and might improve neurodevelopmental outcomes in long term. An immunomodulatory effect of MNCs contributed to the improvement of BPD severity. Funding: This work was supported by National Key R&D Program of China (2021YFC2701700), National Natural Science Foundation of China (82101817, 82171714, 8187060625), Guangzhou science and technology program (202102080104).

Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, its optimal dose remains unknown. A 50% dose reduction was proposed to decrease the potential dose-related long-term neurodevelopmental side effects, including psychological development, sleep, and emotional disorders. Because noninferiority of the half dose in terms of the need for exogenous surfactant was not shown in the primary analysis, its impact on survival without major neonatal morbidity needs to be investigated. This study aimed to investigate the impact of antenatal betamethasone dose reduction on survival of very preterm infants without severe neonatal morbidity, a factor known to have a strong correlation with long-term outcomes. We performed a post hoc secondary analysis of a randomized, multicenter, double-blind, placebo-controlled, noninferiority trial, testing half (11.4 mg once; n=1620) vs full (11.4 mg twice, 24 hours apart; n=1624) antenatal betamethasone doses in women at risk of preterm delivery. To measure survival without severe neonatal morbidity at hospital discharge among neonates born before 32 weeks of gestation, we used the definition of the French national prospective study on preterm children, EPIPAGE 2, comprising 1 of the following morbidities: grade 3 to 4 intraventricular hemorrhage, cystic periventricular leukomalacia, necrotizing enterocolitis stage ≥2, retinopathy of prematurity requiring anti-vascular endothelial growth factor therapy or laser, and moderate-to-severe bronchopulmonary dysplasia. After exclusion of women who withdrew consent or had pregnancy termination and of participants lost to follow-up (8 in the half-dose and 10 in the full-dose group), the rate of survival without severe neonatal morbidity among neonates born before 32 weeks of gestation was 300 of 451 (66.5%) and 304 of 462 (65.8%) in the half-dose and full-dose group, respectively (risk difference, +0.7%; 95% confidence interval, −5.6 to +7.1). There were no significant between-group differences in the cumulative number of neonatal morbidities. Results were similar when using 2 other internationally recognized definitions of severe neonatal morbidity and when considering the overall population recruited in the trial. In the BETADOSE trial, severe morbidity at discharge of newborns delivered before 32 weeks of gestation was found to be similar among those exposed to 11.4-mg and 22.8-mg antenatal betamethasone. Additional studies are needed to confirm these findings. [Display omitted] [ABSTRACT FROM AUTHOR]

This study aims to identify clinical variables that could affect successful weaning from nasal continuous positive airway pressure (NCPAP) in very preterm infants. Infants born at a gestational age (GA) of <32 weeks were retrospectively enrolled. Weaning from NCPAP was initiated when the infants were clinically stable. In the univariate analysis, GA, birth weight, body weight (BW) z-score at the time of successful NCPAP weaning, intubation, total duration of intubation, respiratory distress syndrome grade, APGAR score at the 1 and 5 min, initial shock, anemia, bronchopulmonary dysplasia, number of blood transfusions, total duration of dopamine use, administration of more than two doses of surfactant, use of aminophylline, use of a diuretic, and total duration of total parenteral nutrition were significantly associated with postmenstrual age (PMA) at the time of successful NCPAP weaning. Multivariate analysis showed that the total duration of intubation, bronchopulmonary dysplasia, and administration of more than two doses of surfactant were positively associated with PMA at the time of successful NCPAP weaning. A reverse association was noted between BW z-score and PMA at the time of successful NCPAP weaning. Sufficient nutrition and avoidance of further ventilator-induced lung injury could decrease NCPAP duration in very preterm infants. [ABSTRACT FROM AUTHOR]

Choosing the appropriate management approach for the preterm infant with low blood pressure during the transition period generally involved intervening when the blood pressure drifted below a certain threshold. It is now clear that this approach is too simplistic and does not address the underlying physiology. In this chapter, we explore the many monitoring tools available for evaluation of the hypotensive preterm and assess the evidence base supporting or refuting their use. The key challenge relates to incorporating these outputs with the clinical status of the patient and choosing the appropriate management strategy.

This study aims to identify clinical variables that could affect successful weaning from nasal continuous positive airway pressure (NCPAP) in very preterm infants. Infants born at a gestational age (GA) of

Context Very preterm neonates (VPNs) are unable to digest breast milk and therefore rely on parenteral nutrition (PN) formulations. This systematic review was prepared following PRISMA-P 2015 guidelines. For the purpose of this review, desirable mean plasma arginine concentration is defined as ≥80 micromoles/L. Objective The review was performed to answer the following research question: "In VPNs, are high amounts of arginine in PN, compared with low amounts of arginine, associated with appropriate circulating concentrations of arginine?" Therefore, the aims were to 1) quantify the relationship between parenteral arginine intakes and plasma arginine concentrations in PN-dependent VPNs; 2) identify any features of study design that affect this relationship; and 3) estimate the target parenteral arginine dose to achieve desirable preterm plasma arginine concentrations. Data Sources The PubMed, Scopus, Web of Science, and Cochrane databases were searched regardless of study design; review articles were not included. Data Extraction Only articles that discussed amino acid (AA) intake and measured plasma AA profile post PN in VPNs were included. Data were obtained using a data extraction checklist that was devised for the purpose of this review. Data Analysis Twelve articles met the inclusion criteria. The dose–concentration relationship of arginine content (%) and absolute arginine intake (mg/(kg × d)) with plasma arginine concentrations showed a significant positive correlation (P < 0.001). Conclusion Future studies using AA solutions with arginine content of 17%–20% and protein intakes of 3.5–4.0 g/kg per day may be needed to achieve higher plasma arginine concentrations. [ABSTRACT FROM AUTHOR]

Perinatal exposure of the neonatal lung to inflammation leads to decreased lung angiogenesis and the development of bronchopulmonary dysplasia (BPD). Notably, autologous cord blood mononuclear cells (ACBMNCs) can substantially prevent severe BPD and decrease the inflammatory response in surviving very preterm neonates. Angiopoietin-like protein 7 (Angptl7) is one of the main paracrine cytokines in cord blood stem cells, and is capable of stimulating human hematopoietic stem and progenitor cell expansion. The present study compared Angptl7 levels between the ACBMNCs infusion and control groups (cohort 1). Subsequently, the association between cord blood Angptl7 levels and BPD incidence in a cohort of very preterm neonates was assessed (cohort 2). The hypothesis was further verified in a lipopolysaccharide (LPS)-induced lung injury mouse model. The mRNA expression levels and protein concentrations of inflammatory cytokines in the lung tissue and mouse serum were measured using reverse transcription-quantitative PCR and ELISA, respectively. The number and diameter of lung vessels and macrophage infiltration were assessed using immunofluorescence staining. Compared with in the control group, Angptl7 levels were significantly higher in the ACBMNCs infusion group in cohort 1. In cohort 2, the cord blood Angptl7 levels were significantly lower in infants who later developed BPD. Multiple linear regression analysis showed that higher Angptl7 level was an independent protective factor for BPD. The concentrations of interleukin-6 and monocyte chemoattractant protein-1 were negatively correlated with cord blood Angptl7 level; whereas, vascular endothelial growth factor-A levels were positively correlated with Angptl7 levels. In the LPS-induced lung injury mouse model, the LPS group presented with a significant loss of pulmonary vessels and smaller vessel diameters, which were ameliorated in the Angptl7 treatment group. Furthermore, LPS-induced lung inflammation and macrophage infiltration were alleviated by Angptl7 treatment (P<0.05). In conclusion, the anti-inflammatory and proangiogenic effects of Angptl7 derived from cord blood stem cells may ameliorate BPD severity. The trial for cohort 1 was registered at ClinicalTrials.gov (trial registration no. NCT02999373; date registered, December 21, 2016). [ABSTRACT FROM AUTHOR]

Background: We intend to investigate the association of bolus orogastric tube (BOG) and nipple bottle (N) feedings with postnatal growth in very premature neonates (VPN: gestational age between 28 and 33 weeks)., Material and Methods: The days of life (DOL) to achieve full combined oral and gastric enteral nutrition (FEN) and attain body weight (BW) of 2200 g (Wt22) and the length of hospitalization (LOH) were retrospectively associated with clinical and BOG and N feeding-related variables via multivariate regression analyses. Correlations were performed to ascertain the strength of associations., Results: In a cohort of 127 VPN, FEN demonstrated negative associations with gestational age (GA) and LOH and Wt22 with birth weight (BW). FEN showed positive associations with nil by mouth and intravenous fluid-nutrition days and with DOL to start and achieve full nipple feeding. LOH was associated with days on antibiotics and DOL to start and achieve full nipple feeding. Wt22 was associated with DOL to achieve full nipple feeding. The start day of BOG feeding had no independent associations and weak, highly significant positive correlations with Wt22, LOH, and FEN., Conclusion: Bolus orogastric tube feeding has no independent implications for postnatal growth, duration of hospitalization, or chronological age to attain full enteral nutrition in VPN unless combined with nipple feeding to provide enteral nutrition. Oral bottle feeding accelerates postnatal catch-up growth and full enteral nutrition acquisition while reducing hospitalization duration. Initiating nipple feeding at 32 weeks of postmenstrual age may be safe in stable VPN. Antibiotic therapy increases hospitalization duration., (© 2024 Rita P. Verma et al., published by Sciendo.)

Background: A patent ductus arteriosus (PDA) is frequently found in very preterm neonates and is associated with increased risk of morbidity and mortality. A shunt across a PDA can result in an unfavorable distribution of the cardiac output and may in turn result in poor renal perfusion. Urinary Neutrophil Gelatinase-associated Lipocalin (U-NGAL) is a marker of renal ischemia and may add to the evaluation of PDA. Our primary aim was to investigate if U-NGAL is associated with PDA in very preterm neonates. Secondary, to investigate whether U-NGAL and PDA are associated with AKI and renal dysfunction evaluated by fractional excretion of sodium (FENa) and urine albumin in a cohort of very preterm neonates.Methods: A cohort of 146 neonates born at a gestational age less than 32 weeks were consecutively examined with echocardiography for PDA and serum sodium, and urine albumin and sodium were measured on postnatal day 3 and U-NGAL and serum creatinine day 3 and 6. AKI was defined according to modified neonatal Acute Kidney Injury Network (AKIN) criteria. The association between U-NGAL and PDA was investigated. And secondly we investigated if PDA and U-NGAL was associated with AKI and renal dysfunction.Results: U-NGAL was not associated with a PDA day 3 when adjusted for gestational age and gender. A PDA day 3 was not associated with AKI when adjusted for gestational age and gender; however, it was associated with urine albumin. U-NGAL was not associated with AKI, but was found to be associated with urine albumin and FENa.Conclusions: Based on our study U-NGAL is not considered useful as a diagnostic marker to identify very preterm neonates with a PDA causing hemodynamic changes resulting in early renal morbidity. The interpretation of NGAL in preterm neonates remains to be fully elucidated. [ABSTRACT FROM AUTHOR]

Background Size at birth is an important predictor of neonatal outcomes, but there are inconsistencies on the definitions and optimal cut-offs. Aims The aim of this study is to compute birth size percentiles for Italian very preterm singleton infants and assess relationship with hospital mortality. Study design Prospective area-based cohort study. Subjects All singleton Italian infants with gestational age 22–31 weeks admitted to neonatal care in 6 Italian regions (Friuli Venezia-Giulia, Lombardia, Marche, Tuscany, Lazio and Calabria) (n. 1605). Outcome measure Hospital mortality. Methods Anthropometric reference charts were derived, separately for males and females, using the lambda (λ) mu (μ) and sigma (σ) method (LMS). Logistic regression analysis was used to estimate mortality rates by gestational age and birth weight centile class, adjusting for sex, congenital anomalies and region. Results At any gestational age, mortality decreased as birth weight centile increased, with lowest values observed between the 50th and the 89th centiles interval. Using the 75th–89th centile class as reference, adjusted mortality odds ratios were 7.94 (95% CI 4.18–15.08) below 10th centile; 3.04 (95% CI 1.63–5.65) between the 10th and 24th; 1.96 (95% CI 1.07–3.62) between the 25th and the 49th; 1.25 (95% CI 0.68–2.30) between the 50 h and the 74th; and 2.07 (95% CI 1.01–4.25) at the 90th and above. Conclusions Compared to the reference, we found significantly increasing adjusted risk of death up to the 49th centile, challenging the usual 10th centile criterion as risk indicator. Continuous measures such as the birthweight z-score may be more appropriate to explore the relationship between growth retardation and adverse perinatal outcomes. [ABSTRACT FROM AUTHOR]

Introduction: The effects of "aggressive" neonatal feeding policies of very preterm neonates (VPN) and the risk of metabolic syndrome later in life remain questionable. We aimed to evaluate the effect of our "aggressive" nutrition policies of VPN during hospitalisation on body mass index (BMI) at ages 2 and 8 years. Materials and Methods: Eighty four VPN, who received "aggressive" nutrition during hospitalisation in an effort to minimise postnatal growth restriction (PGR) (group A), and 62 term neonates, as controls (group B), were enrolled in the study. Group A was further divided in four subgroups depending on the type (A1: fortified expressed breast milk and preterm formula; A2: exclusively preterm formula) and quantity of milk received (A3: maximum feeds 180–210 mL/kg/day; A4: maximum feeds 210 and up to 260 mL/kg/day). BMI was calculated at ages 2 and 8 years and plotted on the centile charts. Results: There was no significant difference in BMI between groups A and B at 2 and 8 years, respectively, in both absolute BMI values and their centile chart distribution. There was no significant difference in BMI at 2 and 8 years either between subgroups A1 and A2 or between subgroups A3 and A4. Conclusions: "Aggressive" and individualised feeding policy for VPN did not affect the BMI and obesity rates at ages of 2 and 8 years in our study population. The type and quantity of milk feeds had no impact on their BMI at school age. Further larger studies are needed to confirm our results. [ABSTRACT FROM AUTHOR]

The FEEDMI Study (NCT03663556) evaluated the influence of infant feeding (mother's own milk (MOM), donor human milk (DHM) and formula) on the fecal microbiota composition and alkaline phosphatase (ALP) activity in extremely and very preterm infants (≤32 gestational weeks). In this observational study, preterm infants were recruited within the first 24 h after birth. Meconium and fecal samples were collected at four time points (between the 2nd and the 26th postnatal days. Fecal microbiota was analyzed by RT-PCR and by 16S rRNA sequencing. Fecal ALP activity, a proposed specific biomarker of necrotizing enterocolitis (NEC), was evaluated by spectrophotometry at the 26th postnatal day. A total of 389 fecal samples were analyzed from 117 very preterm neonates. Human milk was positively associated with beneficial bacteria, such as Bifidobacterium, Bacteroides ovatus, and Akkermancia muciniphila, as well as bacterial richness. Neonates fed with human milk during the first week of life had increased Bifidobacterium content and fecal ALP activity on the 26th postnatal day. These findings point out the importance of MOM and DHM in the establishment of fecal microbiota on neonates prematurely delivered. Moreover, these results suggest an ALP pathway by which human milk may protect against NEC. [ABSTRACT FROM AUTHOR]

Background: Caffeine has been commonly used for prevention and treatment of apnea-related symptoms in premature infants. However, its side effects have not been thoroughly studied. We investigated whether caffeine affects gastric motility in very-preterm (VP) neonates. Methods: The study is a randomized crossover clinical trial. Twenty-two neonates with mean birth weight (BW) (standard deviation—SD) 1077 (229) g and mean gestational age (GA) (SD) 28.6 (2.1) weeks were recruited. Each neonate had its gastric emptying time checked twice with ultrasound assessment of changes in antral cross sectional area (ACSA). All neonates were sequentially allocated to the caffeine group (A) and the control group (B). Complications from the gastrointestinal tract were documented throughout the study. Results: Statistically significant difference was found with regards to the gastric emptying time [median, (range)] between caffeine and control group (p = 0.040). Additionally, in the neonates with BW 1000–1500 g and GA ≥ 28 weeks, the gastric emptying time (minutes) was significantly longer during caffeine treatment [44.5 (36–68.2)] and [40 (34.5–66.5)] respectively, as compared to the gastric emptying time during no caffeine treatment [27 (24.2–30)] (p = 0.002) and [27 (24.5–30)] (p = 0.001). The incidence of gastrointestinal (GI) complications was significantly greater in neonates receiving caffeine [6 (27.%)] as compared with those without caffeine treatment [1 (4.6%)] (p = 0.039). Conclusions: During caffeine treatment, a significantly delayed gastric emptying time was noted in all study neonates, especially in these with BW 1000–1500 g and those with GA ≥ 28 weeks. Further larger studies are necessary in order to confirm this interesting finding. [ABSTRACT FROM AUTHOR]