Search Results (832)

Background/Objectives: Lactating mothers have increased nutritional requirements, but nutritional adequacy is difficult to achieve. Additionally, human milk (HM) composition depends on maternal diet. However, the nutritional intake and status of mothers with hospitalized very preterm infants (MHVPIs) (<32 weeks of gestational age) have rarely been assessed. Hence, the aim of the present study was to determine the intake of macronutrients, micronutrients, and lipids, as well as the nutritional status of MHVPIs. The results were compared with a group of HM donors (HMDs), and associations with HM composition were evaluated using multiple linear regression. Methods: For dietary assessment, a 5-day dietary record including supplement intake was completed by 15 MHVPIs and 110 HMDs. Vitamins and fatty acids (FA) were determined in plasma and erythrocytes; minerals and methylmalonic acid were determined in urine; and macronutrients, vitamins, minerals, and the lipid profile were determined in HM. Results: Considering dietary reference intakes, the dietary evaluation of MHVPIs revealed a high percentage of inadequate nutrient intake in relation to total energy, as well as for iodine and vitamins B8, B9, C, D, and E. A high protein intake was observed. The percentage of energy from carbohydrates was low, whereas the percentage of energy from fat was high. However, the diet of MHVPIs did not differ substantially from the diet of HMDs. Associations were observed between the study groups (MHVPI vs. HMD) and the HM concentration of protein, several micronutrients, and fatty acids independent from intake and status. Conclusions: Deficient nutrient intakes did not appear to be exclusively related to MHVPI but rather seemed to be widespread in both study groups. However, for preterm infants, an insufficient supply of nutrients is critical and should be addressed in order to improve preterm infant’s outcomes. Furthermore, we provided additional insights into the exploration of HM by relating its composition to prematurity. Full article

Background/Objectives: Intraventricular hemorrhage (IVH) frequently occurs in premature infants and adults with intracerebral or subarachnoid hemorrhage. It is a major cause of cerebral palsy in premature infants and a risk factor for poor outcome in adult cerebral hemorrhage. Posthemorrhagic hydrocephalus is a common complication of IVH and aggravates brain damage. Hemoglobin (Hb), released from the hemorrhage after IVH, has been implicated in IVH-induced hydrocephalus. The aim of the current study was to examine the impact of Hb on the choroid plexuses (CPs) that reside in the ventricular system. Methods: Experiments were performed in freshly isolated CPs, in primary cultures of CP epithelial cells (CPECs), and in the Z310 cell line exposed to Hb with MTT assay, scratch wound healing assay, cell counting/total cell protein measurement and RT-qPCR. Results: We found that Hb significantly induced CPEC proliferation (e.g., 37–65% higher than control by MTT assay and 56% higher than control by cell counting), and upregulated mRNA expression of growth factors in isolated CP tissue (e.g., IGF-2 and NGF were 39% and 79% higher than control by RT-PCR). Hb also remarkably induced mRNA expression of NKCC1 (50%) and claudin-2 (154%), two proteins involved in CSF secretion, in isolated CP tissue. Conclusions: These results indicate that Hb-induced growth factor-mediated CP proliferation and upregulation of CSF secretion-related proteins might contribute to PHH and suggest there may be alternate therapeutic targets for PHH. Full article

Background/Objectives: Preterm neonates with a birth weight (BW) of 500–1250 g who receive prophylactic methylxanthine have a lower rate of bronchopulmonary dysplasia and neurodevelopmental disability than their counterparts. In a meta-analysis of previous studies (published during 1985–1993, with no routine continuous positive airway pressure), extubation failure rates in preterm neonates with BW < 2500 g who received and did not receive methylxanthine were 25.0% and 50.6%, respectively (risk difference, −0.27; 95% confidence interval [CI], −0.39 to −0.15). However, no study to date has assessed the effects of prophylactic methylxanthine use on endotracheal extubation in infants weighing 1250–2499 g until now. Methods: First-time extubation was compared between 1:1 propensity score-matched methylxanthine and non-methylxanthine groups from a retrospective cohort of 541 neonates (born during 2014–2024). Results: The domains from the overall cohort and propensity-matched data included 541 and 192 neonates, respectively. In the propensity score-matched sample, the mean gestational age and BW were 30.9 ± 1.9 weeks and 1584 ± 273 g, respectively. The median 5-min Apgar score was 9 (range of 7–9). Extubation failure within 7 days occurred in 10 (10.4%) and 13 (13.5%) neonates in the methylxanthine (n = 96) and non-methylxanthine (n = 96) groups, respectively, with a risk difference (95% CI) of −0.03 (−0.12 to 0.06), p = 0.50, and hazard ratio (95% CI) of 0.76 (0.33 to 1.72), p = 0.51. Conclusions: In the current era with new non-invasive ventilation approaches, extubation failure in preterm neonates with a BW of 1250–2499 g is not significantly affected by the use of methylxanthine. Full article

Background: Docosahexaenoic acid (DHA) is the most important fatty acid (FA) for the development and function of brain and retina. Mother’s milk is the predominant source of DHA for the baby’s postnatal life, and the omega 3 FA content of a mother’s diet is highly correlated with the cognitive and visual functions of the infant. However, clinical trials aimed at increasing the DHA content of mother’s milk and thereby improving infant cognitive function have been inconclusive. Methods: In this study, we tested the hypothesis that the molecular form of dietary DHA is important in enriching DHA in mother’s milk as well as in pup tissues. Lactating dams were fed defined diets containing DHA either in the form of triacylglycerol (TAG) or lysophosphatidylcholine (LPC), and the FA composition of mother’s milk and pup tissues was determined on postnatal day 16. Results: The results showed that LPC-DHA was 5-fold more efficient than TAG-DHA in enriching milk DHA. Moreover, DHA content was increased by 31% in the brain, 56% in the retina, and 14% in the liver of the pups by LPC-DHA in the maternal diet, whereas no increases were observed with TAG-DHA. The DHA content of the pup adipose tissue, however, was increased equally by the DHA supplements. Conclusions: These results show that dietary LPC-DHA is a promising new strategy to increase milk DHA content and to potentially improve brain and retinal health in infants. This strategy may be more important in the care of premature infants who miss the critical prenatal period of DHA accretion in the last trimester of pregnancy. Full article

Background: Recently, vitamin D deficiency (VDD) has been described as a pandemic, affecting all groups of the population. Pregnant women and preterm infants are particularly vulnerable to vitamin D deficiency. Objectives: We aimed to evaluate the maternal and neonatal vitamin D status in relation with maternal vitamin D supplementations during pregnancy and to identify demographic, social, and healthcare risk factors for maternal VDD and vitamin D insufficiency in women delivering at ≤32 weeks of gestation. Methods: This prospective observational study was developed in the regional level III maternity unit of the Clinical County Emergency Hospital Sibiu. It included all admitted mothers who delivered at ≤32 weeks of gestation and their infants between 1 March 2022 and 28 February 2025. Infant deaths in the first 24 h of life, major congenital defects, chromosomal abnormalities, the admission of outborn infants without their mothers, or the transfer of the mother more than 48 h after birth were used as exclusion criteria. Maternal and neonatal data were collected from medical records. Data on maternal vitamin D supplementation were collected through interviews. Univariate and multivariate logistic regressions, linear regression, and predictive models were performed for data analysis. Results: A total of 146 mothers (median (IQR) age 30 (24–35) years) and their 164 preterm infants born at ≤32 weeks of gestation (median gestational age of 30 (27–31) weeks and birth weight of 1200 (900–1527) g) were included in this study. Only 43.15% of the mothers used multivitamins containing vitamin D during pregnancy, and 10.96% used specific vitamin D supplements. Vitamin D supplementation was used for a median of 4 (3–5) months at a median dose of 800 (250–1500) IU/day. Severe VDD (25(OH)D < 10 ng/mL), VDD (25(OH)D < 20 ng/mL), VDI (25(OH)D 20–29 ng/mL) were found in 19.86%, 55.48%, and 23.97% of the mothers and 16.46%, 58.53%, and 25.61% of their infants, respectively. A significant correlation was found between the maternal and neonatal status (r = 0.684, r² = 0.468, p < 0.001, B = 0.62). Both the maternal and neonatal vitamin D status were correlated with the vitamin D duration and dose used for supplementation during pregnancy. The logistic regression analysis showed that birth during a cold season and increased parity are independently associated with severe maternal VDD, while birth during the cold season and a lower educational status were independently associated with maternal VDD. Only an absent vitamin D supplementation (in the form of a multivitamin or specific vitamin D supplements) has been proven as an independent risk factor for VDI. Conclusions: Our findings revealed a worrisome prevalence of severe VDD, VDD, and VDI in mothers delivering very prematurely and in their infants. Additionally, less than half of the mothers in this study used vitamin D supplements during pregnancy despite the national recommendations. The professionals involved in advising pregnant women and policymakers should find solutions to improve the vitamin D status in these vulnerable groups of the population. Full article

This research aimed to assess the influence of prenatal and postnatal factors on the remodeling of the pulmonary microvasculature. Methods: The investigation analyzed 67 cases of preterm infants, whose lifespans ranged from 1 day to 149 days. After selecting the cases from the autopsy database, two lung tissue microarrays were created. Histological slides were stained using the hematoxylin and eosin technique to precisely capture the microscopic details. For the assessment of pulmonary microvascularization and the media layer of the vascular walls, an immunohistochemical analysis was performed utilizing CD34 and SMA markers. Results: Following the assessment of the quantity of capillaries positive for CD34, a negative correlation was identified between the average capillary count per alveolus and the duration of oxygen therapy. Preterm infants who developed pulmonary fibrosis exhibited an average reduction of 5.43 capillaries in comparison to other newborns. Preterm neonates born to mothers with preeclampsia exhibited an average reduction of 2.82 capillaries compared to those born to mothers unaffected by this pregnancy complication. A positive correlation was evident between increased thickness of the arteriolar media, lifespan, and the duration of oxygen therapy, as well as in those preterm infants who developed pulmonary fibrosis. Conclusions: Antenatal risk factors did not exert a significant impact on pulmonary vascular remodeling, whereas postnatal influences, particularly oxygen therapy, demonstrated a detrimental effect on the density of capillary structures within the alveolocapillary membrane. Premature neonates with increased thickness of the arteriolar media had a greater susceptibility to pulmonary hypertension. Full article

Background/Objectives: Optimal feeding regimens for preterm neonates, including the role of multi-nutrient fortification, are unknown, leading to large practice variation in comparing different feeding regimens that include fortification and their impact on outcomes for preterm infants. Methods: Using a network meta-analyses design, two reviewers independently extracted data. A Cochrane CENTRAL, Medline, Embase, and CINAHL search was conducted for all studies published up to 27 June 2023. Randomized clinical trials of feeding regimens for preterm infants that included multi-nutrient fortification were included. Outcomes were mortality, necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), sepsis, periventricular leukomalacia (PVL), bronchopulmonary dysplasia (BPD), time to full enteral feeds, and the Bayley II MDI developmental score. Results: Fifty-nine studies were included. For mortality, NEC, and time to reach full enteral feeds, the top-ranked treatment class was the mother’s own milk with donor milk and a human-milk-based fortifier. For ROP and BPD, the top-ranked treatment class was mother’s own milk with a phosphorus fortifier. For sepsis, the top-ranked treatment class was mother’s own milk with formula. For PVL, the top-ranked treatment classes were mother’s own milk and mother’s own milk with donor milk and a bovine fortifier in the two disconnected networks. For the Bayley II MDI score, the top-ranked treatment class was mother’s own milk with formula and bovine fortification. Conclusions: Treatment rankings are consistent with the underlying hypothesis that increased mother’s own milk intake appears to be associated with better clinical outcomes. This review provides the first global view of interventions and highlights insufficient high-quality evidence to support or refute one fortification feeding regimen over another. Full article

Background/Objectives: Extrauterine growth restriction (EUGR) and exclusive breastfeeding (EBF) are critical factors influencing early post-discharge growth in preterm infants. Although EBF is recommended in Kangaroo Mother Care (KMC) programs, its association with early anthropometric recovery remains unclear. This study evaluated the association between EUGR at 40 weeks of corrected age and EBF at 40 weeks, 3 months, and 6 months with anthropometric growth and acute malnutrition in preterm infants during the first six months of corrected age. Methods: A retrospective longitudinal cohort study was conducted, including 117 preterm infants (≤34 weeks of gestation) enrolled in the KMC program. Changes in weight, length, and head circumference z-scores and the incidence of acute malnutrition were analyzed using generalized estimating equations (GEEs). EUGR was defined as weight <10th percentile at 40 weeks. Acute malnutrition was defined as a weight-for-length z-score ≤−2. Results: EUGR was observed in 23.9% of the infants. EBF prevalence was 53% at 40 weeks and 40% at three and six months, respectively. EBF at 40 weeks was associated with a reduced weight z-score (coefficient: −0.29; p = 0.030), EBF at 3 months increased the weight z-score (coefficient: 0.34; p = 0.014), and EBF at 6 months reduced the risk of acute malnutrition (coefficient: −1.02; p = 0.036). Infants with EUGR showed greater weight gain over time (coefficient: 0.37; p = 0.020) yet remained below their non-EUGR peers. Conclusions: EBF during the first six months post-discharge supports weight gain and reduces the risk of malnutrition. However, EBF at 40 weeks may not ensure the immediate recovery of weight. EUGR is a key determinant of early growth. Full article

Background/Objectives: Even with improvements in perinatal care, bronchopulmonary dysplasia (BPD) continues to be a major challenge, especially in smaller and more premature infants. Early detection of severe BPD can improve treatment outcomes. This study aims to evaluate the correlation between the oxygen saturation index (OSI) and severe BPD/death in preterm infants, with a focus on the OSI’s predictive value. Methods: In this retrospective observational study, infants with a gestational age of less than 32 weeks who required either invasive or non-invasive mechanical ventilation were included. Ventilator settings and OSI values were collected on days 3, 7, 14, 21, and 28 of life. The correlations between postnatal OSIs and outcomes such as death or severe BPD were analyzed using logistic regression. Results: Out of the 210 eligible infants, 54 (25.7%) either died or were diagnosed with severe BPD. In our study, OSI values on postnatal days 14, 21, and 28 were significantly higher in preterm infants who developed severe BPD or died, with mean OSI-14, OSI-21, and OSI-28 values of 4.9, 3.5, and 2.8, respectively. The OSI showed the highest sensitivity and specificity on postnatal days 14 and 21, with cut-off points of 3.6 and 3.1, respectively. We built a basic chart to predict severe BPD/death with OSI-14 and OSI-21 and delivery room intubation with 86% sensitivity and 84.5% specificity (increasing up to 98.8% specificity). Conclusions: This study showed that the diagnostic power of the OSI in predicting severe BPD or death was highest for OSI-14 and OSI-21. We demonstrated that calculating the OSI, a non-invasive clinical tool, can predict severe BPD/death in infants born before 32 weeks as early as the 14th day of life. Full article

Background/Objectives: Premature infants frequently experience feeding difficulties due to the disrupted coordination of sucking, swallowing, and breathing, increasing the risk of airway compromise. In adults with dysphagia, cold liquids can enhance swallowing by stimulating sensory receptors in the pharyngeal mucosa. We previously demonstrated that short-duration feeding with cold liquid significantly reduces dysphagia in preterm infants; however, the impact of an entire feeding with cold milk remains unexplored. This study aimed to evaluate the safety of cold milk feedings in preterm infants with uncoordinated feeding patterns and their impact on their feeding performance. Methods: Preterm infants with uncoordinated feeding patterns (n = 26) were randomized to be fed milk at either room temperature (RT) or cold temperature (CT) using an experimental, randomized crossover design. We monitored axillary and gastric content temperatures, mesenteric blood flow, and feeding performance. Results: There were no significant differences in mesenteric blood flow Doppler measurements or axillary body temperatures between the CT and RT feeding conditions. However, a reduction in gastric content temperatures of 3.6 °F and 2.7 °F was observed at one and thirty minutes following CT feeding, respectively. No evidence of cold stress, increased episodes of apnea or bradycardia, gastric residuals, or emesis was noted in infants during or after the CT feeding condition. Feeding performance outcomes did not differ significantly regarding milk transfer rate (p = 0.781) or proficiency (p = 0.425). However, the quality score on the Infant-Driven Feeding Scale (IDFS) showed a significant improvement following CT feeding (p = 0.001). Conclusions: Cold milk feeding can be a safe therapeutic option for preterm infants. This underscores the potential for further comprehensive investigations to evaluate cold milk feeding as an effective therapeutic strategy for managing feeding and swallowing difficulties in preterm infants. The study was registered at clinicaltrials.org under #NCT04421482. Full article

Background/Objectives: Multi-lumen devices that limit physicochemical incompatibilities (PCIs) are frequently used in neonatal intensive care units where premature infants receive numerous infusions. The aim of the study was to investigate a PCI that occurred despite the use of a device of this type (EDELVAISS^® Multiline NEO, Doran International, Toussieu, France). Case Summary: A 7-week-old preterm infant received ganciclovir at therapeutic dosage for cytomegalovirus (CMV) infection. After the fifth administration of ganciclovir, a PCI occurred, leading to a white precipitate. The peripheral inserted central catheter (PICC) (PREMICATH^®2Fr, Vygon, Ecouen, France) had to be replaced. Laboratory reproduction of the administrations during 72 h, nuclear magnetic resonance (NMR) analysis and particle counting were carried out to analyse the occurrence of events leading to PCIs. The precipitate was linked to a PCI of parenteral nutrition associated with a dilution error of ganciclovir (omission of a 10-fold dilution step, resulting in ganciclovir being administered at 30 mg/L instead of 3 mg/L). Due to the presence of lipids in the parenteral nutrition, visual detection of the white precipitate was difficult. Conclusions: Multi-lumen infusion devices limit but do not prevent the occurrence of PCIs, particularly in the event of a preparation error. Despite the use of this type of device, great vigilance is still required, particularly with regard to prescription analysis and reconstitution procedures. Full article

Premature white matter injury (PWMI) represents the principal form of brain injury in preterm infants, and effective therapies remain elusive. Transplantation of oligodendrocyte precursor cells (OPCs) emerges as a potential treatment for PWMI, yet the injury-induced inflammatory response may impact these cells’ functionality. To date, no studies have explored the influence of inflammatory factors on the functionality of human (h) OPCs. The predominant inflammatory cytokines identified in PWMI lesions are tumor necrosis factor (TNF)-α and interleukin (IL)-1β. This study investigates the impact of these cytokines on hOPC migration, proliferation, and differentiation using the human adult neural stem cell amplification and differentiation system in vitro. Results indicate that IL-1β significantly impedes hOPC migration, while both TNF-α and IL-1β hinder proliferation and differentiation. In summary, inflammatory factors overexpressed following PWMI impede OPCs from realizing their regenerative potential. These findings underscore the necessity of modulating the post-PWMI inflammatory milieu to enhance the efficacy of transplanted cells concerning migration, proliferation, and differentiation. Full article

Background/Objectives: Preterm neonates receiving parenteral nutrition (PN) are at risk of developing refeeding syndrome (RS). Risk factors and the related consequences remain largely undefined. In particular, the reason why only some preterm neonates out of a group receiving the same nutritional protocol will develop RS is yet to be fully understood. The aims of this study were to explore the clinical and nutritional factors contributing to RS and to assess the clinical consequences of this condition. Methods: A retrospective study was conducted, including all newborns with gestational age ≤ 34 weeks and/or body birth weight ≤ 1500 g who were consecutively admitted to the neonatal intensive care unit (NICU) of “Umberto I” Hospital, Sapienza University of Rome, from 2015 to 2022. The population was divided into two groups comprising newborns who developed RS (cases) and infants who did not develop the condition (controls) up to the first 2 weeks of life. The enrolled newborns were compared for clinical and nutritional factors and main morbidities. Results: A total of 412 neonates were enrolled, consisting of 53 cases and 359 controls. The main prenatal risk factor for RS was found to be fetal distress (p = 0.028). The occurrence of RS was identified as statistically significantly associated (p = 0.010; p = 0.007) with the development of extrauterine growth restriction (EUGR) and retinopathy of prematurity (ROP). Conclusions: Fetal distress is the predominant perinatal risk factor associated with the development of RS in preterm neonates managed with early currently recommended PN. These findings suggest an increased risk of ROP and EUGR in preterm neonates with RS. Full article

Background/Objectives: Metabolic bone disease of prematurity (MBDP) is a multifactorial disorder resulting from disrupted transplacental mineral transfer and postnatal nutritional deficits, particularly affecting preterm neonates born before 32 weeks of gestation or weighing under 1500 g. Although substantial research has focused on skeletal outcomes, few studies have explored the association between MBDP and neonatal neurological impairment. This narrative review is the first to integrate the pathophysiological mechanisms, diagnostic methods, and preventive strategies for MBDP, while simultaneously investigating its potential impact on neurodevelopment. Methods: A narrative review of recent peer-reviewed studies, systematic reviews, and clinical trials was performed focusing on biochemical markers (alkaline phosphatase, FGF23, calcium, and phosphorus), emerging tools such as bioelectrical impedance analysis (BIA), and the effects of early nutritional interventions on both skeletal and neurodevelopmental outcomes in preterm infants (n = seven included articles). Results: Early elevations in ALP, particularly when combined with low serum phosphorus and FGF23 levels, provide sensitive markers for identifying MBDP. Furthermore, insufficient vitamin D levels during gestation and in the neonatal period have been associated with increased risks of seizures, hypotonia, and developmental delays. Studies suggest that enhanced vitamin D supplementation in preterm infants (up to 800 IU/day) may improve mineral absorption and bone formation and confer neuroprotective benefits through anti-inflammatory and antioxidant mechanisms. Conclusions: This is the first review on the neurological implications of biochemical actors of MBDP. As a result, diagnostic and therapeutic strategies, including vitamin D supplementation, can improve bone and neurodevelopmental outcomes. Future prospective studies are required to standardize diagnostic criteria and optimize therapeutic regimens for enhanced long-term benefits. Full article