Search Results (93)

Background: Extremely premature neonates are at increased risk for respiratory complications, often resulting in recurrent hospitalizations during early childhood. Early identification of preterm infants at highest risk of respiratory hospitalizations could enable targeted preventive interventions. While clinical and demographic factors offer some prognostic value, integrating transcriptomic data may improve predictive accuracy. Objective: To determine whether early-life gene expression profiles can predict respiratory-related hospitalizations within the first four years of life in extremely preterm neonates. Methods: We conducted a retrospective cohort study of 58 neonates born at <32 weeks’ gestational age, using publicly available transcriptomic data from peripheral blood samples collected on days 5, 14, and 28 of life. Random forest models were trained to predict unplanned respiratory readmissions. Model performance was evaluated using sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC). Results: All three models, built using transcriptomic data from days 5, 14, and 28, demonstrated strong predictive performance (AUC = 0.90), though confidence intervals were wide due to small sample size. We identified 31 genes and eight biological pathways that were differentially expressed between preterm neonates with and without subsequent respiratory readmissions. Conclusions: Transcriptomic data from the neonatal period, combined with machine learning, accurately predicted respiratory-related rehospitalizations in extremely preterm neonates. The identified gene signatures offer insight into early biological disruptions that may predispose preterm neonates to chronic respiratory morbidity. Validation in larger, diverse cohorts is needed to support clinical translation. Full article

Objectives: Kangaroo care is vital for the development of premature and low-birthweight infants. However, detailed data on skin-to-skin times, especially for extremely preterm infants in NICUs, is lacking. This study quantifies skin-to-skin times for these infants at the neonatology department in Salzburg, considering factors like the COVID-19 pandemic, the opening of Ronald McDonald House, and sibling presence. Methods: We retrospectively analyzed data from the first eight weeks of life of 93 extremely preterm infants (<28 gestational weeks, <1500 g birth weight) treated at the Salzburg NICU from 2019 to 2023. Skin-to-skin times were recorded to the minute. Results: The mean value skin-to-skin time per visiting day was 241 min (±83), skin-to-skin was performed on 79.0% (±16.8) of the days of stay examined. During the pandemic, skin-to-skin care was performed on 64% of visit days, after the pandemic on 91% (p < 0.001). Before the Ronald McDonald House opened, the skin-to-skin time per visiting day was 215 min (±57.9), afterwards it was 273 min (±97) (p = 0.001). For Primipara the Kangaroo-Care time per day of visit was 257 min (±93), for Multipara 217 min (±52) (p = 0.043). Conclusions: Skin-to-skin is crucial for extremely premature infants and can be implemented for many hours a day. It is an integral part of parent-child interaction in a neonatal intensive care unit. External factors such as infrastructure, pandemic restrictions or siblings have a significant impact on skin-to-skin. Full article

Background: Metabolic Bone Disease of Prematurity (MBDP) is common in extremely preterm infants (≤28 weeks gestation). Parenteral nutrition (PN) with higher calcium (Ca) and phosphorus (P) concentration started soon after birth may improve bone health in preterm infants. We compared the effect of two standard PN formulations on the incidence of MBDP and explored the predictive ability of biochemical markers for diagnosing MBDP. Methods: This retrospective study included eligible preterm infants ≤ 28 weeks gestation. Infants in group 1 (January 2016–December 2017) received PN 1 formulation with lower Ca (1.6 mmol/kg/day) and P concentration (1.4 mmol/kg/day). Infants in group 2 (June 2018–May 2020) received PN 2 formulation with higher Ca (2.3 mmol/kg/day) and P concentration (1.8 mmol/kg/day). We reviewed the biochemical and radiological investigations performed for diagnosing MBDP. Results: The incidence of MBDP reduced from 82.8% (77/93) in group 1 to 47.3% (27/57) in group 2. Grade 2–3 MBDP reduced significantly from 14% in group 1 to none in group 2 (p < 0.01). Serum phosphate < 1.5 mmol/L had a sensitivity of 79% and specificity of 77%, and alkaline phosphatase > 500 U/L showed a sensitivity of 72% and specificity of 71% for diagnosing radiological MBDP. There was no increase in hypercalcemia, hypophosphatemia or nephrocalcinosis from PN 2 formulation. Conclusions: A higher Ca and P concentration in PN reduced MBDP and eliminated grade 2–3 MBDP in our cohort without an increase in adverse events. Low serum phosphate and high serum alkaline phosphatase were the best predictors for diagnosing MBDP. Full article

Extremely premature infants are at significant risk for developing bronchopulmonary dysplasia (BPD) and neurodevelopmental impairment (NDI). Although BPD is a predictor of poor neurodevelopmental outcomes, it is currently unknown how BPD contributes to brain injury and long-term NDI in pre-term infants. Extracellular vesicles (EVs) are small, membrane-bound structures released from cells into the surrounding environment. EVs are involved in inter-organ communication in diverse pathological processes. Inflammasomes are large, multiprotein complexes that are part of the innate immune system and are responsible for triggering inflammatory responses and cell death. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is pivotal in inflammasome assembly and activating inflammatory caspase-1. Activated caspase-1 cleaves gasdermin D (GSDMD) to release a 30 kD N-terminal domain that can form membrane pores, leading to lytic cell death, also known as pyroptosis. Activated caspase-1 can also cleave pro-IL-1β and pro-IL-18 to their active forms, which can be rapidly released through the GSDMD pores to induce inflammation. Recent evidence has emerged that activation of inflammasomes is associated with neonatal lung and brain injury, and inhibition of inflammasomes reduces hyperoxia-induced neonatal lung and brain injury. Additionally, multiple studies have demonstrated that hyperoxia stimulates the release of lung-derived EVs that contain inflammasome cargos. Adoptive transfer of these EVs into the circulation of normal neonatal mice and rats induces brain inflammatory injury. This review focuses on EV–inflammasomes’ roles in mediating lung-to-brain crosstalk via EV-dependent and EV-independent mechanisms critical in BPD, brain injury, and NDI pathogenesis. EV–inflammasomes will be discussed as potential therapeutic targets for neonatal lung and brain injury. Full article

Background/Objectives: Identifying nutritional interventions in extremely low-birth-weight (ELBW) infants (<1000 g) that are associated with favorable clinical outcomes is important. Delayed enteral feeding initiation (>3 days) has been associated with increased odds of developing morbidity. Therefore, the aim of this study is to evaluate the relationship between hour of life at enteral feeding initiation and associated clinical outcomes. Methods: An IRB-approved retrospective chart review evaluated ELBW infants. Birth acuity was evaluated using CRIB II scoring and incidence of various morbidities (bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and spontaneous intestinal perforation (SIP)) and mortality was assessed after adjustment. p < 0.05 was statistically significant. Results: A total of 27/61 (44.3%) initiated enteral feeding <12 h of life. CRIB II scores were lower in infants with earlier enteral feeding initiation. There were no statistical differences in NEC, SIP, or death between categories of hour of life at enteral feeding initiation. After adjusting for CRIB II scores, enteral feeding initiation ≥12 h of life was associated with more days receiving oxygen >21% inspired air (β = 32.7; p = 0.040), approximately 7-fold higher odds of developing moderate/severe BPD (95% CI 1.2.8–38.28; p = 0.025), and 9-fold higher odds of being discharged home while receiving oxygen therapy (95% CI 1.03–79.81; p = 0.047). Conclusions: Timing of enteral feeding initiation may be delayed in ELBW infants with higher clinical acuity, yet later initiation by hour of life is associated with worsened clinical respiratory outcomes. Early initiation within the first 12 h of life is feasible and was not associated with gastrointestinal morbidity in this single-center cohort of ELBW infants. Full article

Recent research highlights a growing interest in early interactions between fathers and their infants, acknowledging the significant influence these interactions have on developmental outcomes. However, there is a limited understanding of the specific characteristics of paternal infant-directed speech (IDS), especially in the context of premature birth. This study aimed to analyze the functional and morpho-syntactic features of paternal IDS to full-term (FT) and preterm (PT) infants at 3 months, comparing it with maternal communicative style. Additionally, the study explored the influence of the severity of preterm birth according to birth weight, further distinguishing between extremely low-birth-weight (ELBW) and very low-birth-weight (VLBW) infants. Seventy-one father–infant and mother–infant dyads (24 FT, 22 ELBW, 25 VLBW) were recruited at 3 months (corrected age for PTs). Parent–infant interactions were video recorded to assess lexical, syntactic, and functional aspects of paternal and maternal speech. Results revealed lower verbosity and lexical variability in paternal IDS compared to the maternal one. No differences were found between parents of the PT and FT groups. Overall, these findings could contribute to better understanding the patterns of parent–infant communications in both FT and PT dyads, confirming the importance of involving both mothers and fathers from the early stages of development. Full article

Objectives: To assess whether continuous non-invasive pCO₂ monitoring by transcutaneous pCO₂ monitor (TCpCO₂) among extremely low birth weight (ELBW) premature infants, during the first week of life, will decrease the rate of high-grade intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL) or the combined outcome of IVH/PVL and death. Methods: This was a prospective, observational, multicenter study. Due to ethical constraints, allocation was based on TCpCO₂ monitor availability. ELBW infants were either monitored by TCpCO₂ monitor (Sentec, Therwil, Switzerland) (study group), or recruited to the control group if a TCpCO₂ monitor was not available. Results: A total of 132 ELBW infants participated in the study. The size of the study group (106 infants) and the control group (26 infants) differed because monitor availability increased during the study period reflecting change in standard of care. The groups had comparable gestational age and baseline characteristics. No difference was found in the rate of IVH/PVL in the study vs. control groups (10% vs. 4%; p = 0.7, respectively), or in the combined outcome of PVL/IVH and death (16% vs. 15%; p = 1.0, respectively). Conclusions: This study demonstrates the challenges in conducting a prospective controlled trial in a rapidly evolving medical field. While the study began with a clear equipoise, this balance shifted as the care team gained more experience with TCpCO₂ monitoring among the study population, despite the absence of new clinical evidence to justify such a shift. Consequently, the small control group limited our ability to draw definitive conclusions regarding the study’s objective. However, our findings may increase awareness of continuous non-invasive pCO₂ monitoring in extremely premature infants. Full article

Polyunsaturated fatty acids (PUFAs), especially arachidonic acid (ARA) and docosahexaenoic acid (DHA), are extremely important fatty acids for brain development in the fetus and early childhood. Premature infants face challenges obtaining these two fatty acids from their mothers. It has been reported that supplementation with triacylglycerols (TAGs) with an ARA:DHA (w/w) ratio of 2:1 may be optimal for preterm infants, as presented in commercial formulas such as Formulaid™. This study explored methods to produce TAGs with a 2:1 ratio (ARA:DHA), particularly at the more bioavailable sn-2 position of the glycerol backbone. Blending and enzymatic acidolysis of microalgae oil (rich in DHA) and ARA-rich oil yielded products with the desired ARA:DHA ratio, enhancing sn-2 composition compared to Formulaid™ (1.6 for blending and 2.3 for acidolysis versus 0.9 in Formulaid™). Optimal acidolysis conditions were 45 °C, a 1:3 substrate molar ratio, 10% Candida antarctica lipase, and 4 h. The process was reproducible, and scalable, and the lipase could be reused. In vitro digestion showed that 75.5% of the final product mixture was bio-accessible, comprising 19.1% monoacylglycerols, ~50% free fatty acids, 14.6% TAGs, and 10.1% diacylglycerols, indicating better bio-accessibility than precursor oils. Full article

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

Background: Significant improvement in neonatal care has enabled increasing survival of preterm infants. Metabolic bone disease of prematurity is often overlooked due to other comorbidities of preterm birth. The best approach is screening and prevention of the disease in high-risk infants such as preterm infants. Aim: We followed up the clinical, radiological, and serum biochemical markers of metabolic bone disease in extremely preterm infants (<28 weeks of gestation). The clinical applicability and validation of C-terminal telopeptide of type I collagen (CTX-I) as a novel bone turnover marker were assessed. Standard and novel biochemical bone turnover markers and quantitative ultrasound were compared. Method: Patients’ data were collected from medical records. Assessments of calcium, phosphate, alkaline phosphatase, bone-alkaline phosphatase, CTX-I, and quantitative ultrasound were prospectively performed twice in 42 extremely preterm infants at postmenstrual ages of 30–32 weeks and 36–40 weeks. Bone mineral density was measured by quantitative ultrasound. Conclusion: Phosphate, alkaline phosphatase, bone alkaline phosphatase, calcium, or ionized calcium are not related to gestational age, but bone mineral density, measured by quantitative ultrasound, is related. There is no correlation between standard and novel biochemical markers and quantitative ultrasound for the identification of metabolic bone disease. Full article

Background: while most gut microbiota research has focused on term infants, the health outcomes of preterm infants are equally important. Very-low-birth-weight (VLBW) or extremely-low-birth-weight (ELBW) preterm infants have a unique gut microbiota structure, and probiotics have been reported to somewhat accelerate the maturation of the gut microbiota and reduce intestinal inflammation in very-low preterm infants, thereby improving their long-term outcomes. The aim of this study was to investigate the structure of gut microbiota in ELBW neonates to facilitate the early identification of different types of low-birth-weight (LBW) preterm infants. Methods: a total of 98 fecal samples from 39 low-birth-weight preterm infants were included in this study. Three groups were categorized according to different birth weights: ELBW (n = 39), VLBW (n = 39), and LBW (n = 20). The gut microbiota structure of neonates was obtained by 16S rRNA gene sequencing, and microbiome analysis was conducted. The community state type (CST) of the microbiota was predicted, and correlation analysis was conducted with clinical indicators. Differences in the gut microbiota composition among ELBW, VLBW, and LBW were compared. The value of gut microbiota composition in the diagnosis of extremely low birth weight was assessed via a random forest-machine learning approach. Results: we briefly analyzed the structure of the gut microbiota of preterm infants with low birth weight and found that the ELBW, VLBW, and LBW groups exhibited gut microbiota with heterogeneous compositions. Low-birth-weight preterm infants showed five CSTs dominated by Enterococcus, Staphylococcus, Klebsiella, Streptococcus, Pseudescherichia, and Acinetobacter. The birth weight and clinical indicators related to prematurity were associated with the CST. We found the composition of the gut microbiota was specific to the different types of low-birth-weight premature infants, namely, ELBW, VLBW, and LBW. The ELBW group exhibited significantly more of the potentially harmful intestinal bacteria Acinetobacter relative to the VLBW and LBW groups, as well as a significantly lower abundance of the intestinal probiotic Bifidobacterium. Based on the gut microbiota’s composition and its correlation with low weight, we constructed random forest model classifiers to distinguish ELBW and VLBW/LBW infants. The area under the curve of the classifiers constructed with Enterococcus, Klebsiella, and Acinetobacter was found to reach 0.836 by machine learning evaluation, suggesting that gut microbiota composition may be a potential biomarker for ELBW preterm infants. Conclusions: the gut bacteria of preterm infants showed a CST with Enterococcus, Klebsiella, and Acinetobacter as the dominant genera. ELBW preterm infants exhibit an increase in the abundance of potentially harmful bacteria in the gut and a decrease in beneficial bacteria. These potentially harmful bacteria may be potential biomarkers for ELBW preterm infants. Full article

Background: This study evaluated early childhood comorbidities of cerebral palsy (CP) in low birth weight (LBW) children and assessed the impact of maternal bio-psychosocial factors on CP risk in preterm infants of varying birth weights (BWs). Methods: Data from 15,181 preterm infants (2009–2013) and 151,810 controls were analyzed using Taiwan’s National Health Insurance Research Database. CP prevalence and LBW-associated comorbidities were examined, and odds ratios (ORs) were calculated. Results: This study confirmed increasing prematurity and LBW rates in Taiwan, with LBW infants showing higher CP prevalence. Significant maternal risk factors included age extremes (<20 and >40 years). LBW infants exhibited higher risks for respiratory, circulatory, nervous system, and psycho-developmental comorbidities compared with controls, with the lowest BW having even higher ORs. Maternal factors such as family income, the number of hospital admissions, and length of hospital stay were remarkably correlated with BW and subsequent complications. Each additional gestational week crucially reduced the risk of complications in premature infants. Conclusions: LBW infants are at a higher risk for CP and various comorbidities, with maternal bio-psychosocial factors playing a critical role. Addressing these factors in prenatal care and interventions is essential to improve outcomes for premature infants. Full article

Advances in perinatal intensive care have significantly enhanced the survival rates of extremely low gestation-al-age neonates but with continued high rates of bronchopulmonary dysplasia (BPD). Nevertheless, as the survival of these infants improves, there is a growing awareness of associated abnormalities in pulmonary vascular development and hemodynamics within the pulmonary circulation. Premature infants, now born as early as 22 weeks, face heightened risks of adverse development in both pulmonary arterial and venous systems. This risk is compounded by parenchymal and airway abnormalities, as well as factors such as inflammation, fibrosis, and adverse growth trajectory. The presence of pulmonary hypertension in bronchopulmonary dysplasia (BPD-PH) has been linked to an increased mortality and substantial morbidities, including a greater susceptibility to later neurodevelopmental challenges. BPD-PH is now recognized to be a spectrum of disease, with a multifactorial pathophysiology. This review discusses the challenges associated with the identification and management of BPD-PH, both of which are important in minimizing further disease progression and improving cardiopulmonary morbidity in the BPD infant. Full article

Familial hypercholesterolemia, a genetic disorder marked by elevated low-density lipoprotein cholesterol (LDL-C), poses significant risks for premature atherosclerosis and cardiovascular diseases, particularly during pregnancy. One of the safe methods of treating this condition in pregnancy is with the use of LDL apheresis. We present a 38-year-old primigravida with homozygous Familial Hypercholesterolemia (HoFH), ischemic cardiomyopathy, and angina pectoris. Two years before conception, extremely elevated lipid levels prompted statin therapy and lifestyle changes. Stent placements followed acute myocardial infarction. When planning pregnancy, statins were discontinued, but lipid levels elevated. LDL apheresis was initiated, achieving a 60% reduction. Throughout pregnancy, 16 LDL apheresis sessions were performed every 14 days, maintaining optimal lipid profiles. A cesarean section was performed in the 38th week of gestation, delivering a healthy infant. The patient resumed statin therapy after 8 months of breastfeeding. The patient maintained cardiovascular health, demonstrating the feasibility of controlled HoFH pregnancies. This case highlights the successful management of HoFH during pregnancy using LDL apheresis, ensuring maternal and fetal well-being. Future research on novel treatments and their safety during pregnancy is essential for refining therapeutic approaches in similar cases. Full article