Comparison of "IN-REC-SUR-E" and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN-REC-LISA trial).

BACKGROUND: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. METHODS: In this study, 382 infants born at 24+0-27+6 weeks' gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks' postmenstrual age. The secondary outcomes are BPD at 36 weeks' postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). DISCUSSION: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0-27+6 weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Breastfeeding premature infants affects the microbiota composition of breast milk.

AIM: To determine whether and how breast feeding of premature infants influences the human milk (HM) bacterial communities. METHODS: HM samples before and after breastfeeding were collected from 40 preterm infant mothers at 24-366/7 weeks of gestational age in the neonatal intensive care unit of our hospital. Of these 40 babies, 11 at 24-276/7 weeks of gestational age and 12 at 28-316/7 weeks were grouped into an extremely premature (EPM) group and a very premature (VPM) group, respectively. In addition, 11 with a birth weight (BWT) of 1000 g ≤ BWT < 1500 g were classified as a very low birth weight (VLBW) group and 12 with BWT < 1000 g an extremely low birth weight (ELBW) group. Breast feeding and kangaroo mother care were given once a day for 7 days, from 14 to 21 days of age. The bacterial composition of HM was analyzed using high-throughput sequencing before and after feeding. RESULTS: Linear discriminant analysis effect size of HM samples before and after feeding showed that Bacillus, Prevotella and Fusobacterium were significantly enriched in HM before breastfeeding (P < 0.05). Post-feeding HM for the EPM group showed significant enrichment in Lactobacillales, Streptococcus, Desulfuromonadales, Ruminococcus, Geobacteraceae, Geobacter and Elizabethkingia_meningoseptica (P < 0.05). Bacillus was significantly enriched in the HM for EPM group before feeding (P < 0.05). For mothers with VLBW infants, Bacillus was enriched before feeding, while Lactobacillales was predominant after feeding (P < 0.05). There was a moderate correlation between the diversity of HM bacteria and infant development and immune outcomes. CONCLUSION: Breastfeeding of preterm infants can significantly affect the bacterial diversity in HM.

Assessment of inflammatory biomarkers to identify surgical/death necrotizing enterocolitis in preterm infants without pneumoperitoneum.

BACKGROUND: Necrotizing enterocolitis (NEC) is a life-threatening disease that affects premature infants. However, the role of inflammatory biomarkers in identifying surgical/death NEC without pneumoperitoneum remains elusive. PURPOSE: We aimed to verify the value of platelet-to-lymphocyte ratio (PLR) and the combination of white blood cell (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), neutrophil lymphocyte ratio (NLR), PLR, C reactive protein (CRP) and procalcitonin (PCT) in predicting the severity of NEC, and to construct a model to differ surgically NEC from non-surgically NEC. METHODS: A retrospective analysis was performed on 191 premature infants with NEC. Based on the inclusion and exclusion criteria, 90 infants with Stage II and IIIA NEC were enrolled in this study, including surgical/death NEC (n = 38) and medical NEC (n = 52). The values of inflammatory biomarkers were collected within 24 h of onset. RESULTS: The univariate analysis revealed that the values of WBC (p = 0.040), ANC (p = 0.048), PLR (p = 0.009), CRP (p = 0.016) and PCT (p < 0.01) in surgical/death NEC cohort were significantly higher than medical NEC cohort. Binary multivariate logistic regression analysis indicates that ANC, PLR, CRP, and PCT are capable of distinguishing infants with surgical/death NEC, and the AUC of the regression equation was 0.79 (95% CI 0.64-0.89; sensitivity 0.63; specificity 0.88), suggesting the equation has a good discrimination. IMPLICATIONS FOR PRACTICE AND RESEARCH: Elevated PLR is associated with severe inflammation in surgical/death NEC patients. The prediction modelling of combination of ANC, PLR, CRP and PCT can differentiate surgical/death NEC from infants with medical NEC, which may improve risk awareness and facilitate effective communication between nurses and clinicians. However, multicentre research is needed to verify these findings for better clinical management of NEC.

Introduction of Solid Foods in Preterm Infants and Its Impact on Growth in the First Year of Life-A Prospective Observational Study.

The aim of this study was to investigate whether age at introduction of solid foods in preterm infants influences growth in the first year of life. This was a prospective observational study in very low birth weight infants stratified to an early (<17 weeks corrected age) or a late (≥17 weeks corrected age) feeding group according to the individual timing of weaning. In total, 115 infants were assigned to the early group, and 82 were assigned to the late group. Mean birth weight and gestational age were comparable between groups (early: 926 g, 26 + 6 weeks; late: 881 g, 26 + 5 weeks). Mean age at weaning was 13.2 weeks corrected age in the early group and 20.4 weeks corrected age in the late group. At 12 months corrected age, anthropometric parameters showed no significant differences between groups (early vs. late, mean length 75.0 vs. 74.1 cm, weight 9.2 vs. 8.9 kg, head circumference 45.5 vs. 45.0 cm). A machine learning model showed no effect of age at weaning on length and length z-scores at 12 months corrected age. Infants with comorbidities had significantly lower anthropometric z-scores compared to infants without comorbidities. Therefore, regardless of growth considerations, we recommend weaning preterm infants according to their neurological abilities.

Association of cord blood Ang-1 and sCD105 levels with bronchopulmonary dysplasia in preterm infants.

BACKGROUND: To investigate the relationship between cord blood levels of Angiopoietin-1 (Ang-1) and S-endoglin (sCD105) and bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: Sixty-one preterm infants admitted to the neonatal intensive care unit of the study hospital between July 2021 and September 2022 were included. Cord blood was collected after the birth of premature infants. Ang-1 and sCD105 levels were quantified using the vascular endothelial growth factor enzyme-linked immunosorbent assay. Preterm infants were divided into BPD and non-BPD groups, and differences in Ang-1 and sCD105 levels between the two groups were compared. A binary logistic model was used to assess the association between low and high levels Ang-1 and BPD in preterm infants. RESULTS: In the study, there were 20 preterm infants with BPD (32.8%) and 41 preterm infants with non-BPD (67.2%). Ang-1 concentration levels were lower in the BPD group than in the non-BPD group (7105.43 (5617.01-8523.00) pg/ml vs. 10488.03 (7946.19-15962.77) pg/ml, P = 0.027). However, the sCD105 concentration levels were not significantly different between the BPD and non-BPD groups (P = 0.246). A median Ang-1 concentration of 8800.40 pg/ml was calculated. Logistic regression analysis showed that after adjusting for gestational age, birth weight, and maternal prenatal steroid hormone application, the odds ratio (OR) was 8.577 for the risk of BPD in preterm infants with Ang-1 concentrations of ≤ 8800.40 pg/ml compared to those with Ang-1 concentrations of > 8800.40 pg/ml (OR: 8.577, 95% confidence interval: 1.265-58.155, P = 0.028). CONCLUSION: Our study indicated that Ang-1 levels in the cord blood of preterm infants may be associated the risk of BPD. In the future, we will continue to conduct study with large samples.

Retrospective analysis of reference intervals for dried blood spot based ms/ms newborn screening programs in Chinese preterm neonates: a nationwide study.

OBJECTIVES: Although recent discoveries regarding the biomarkers of newborn screening (NBS) programs by tandem mass spectrometry (MS/MS) highlight the critical need to establish reference intervals (RIs) specifically for preterm infants, no such RIs has been formally published yet. This study addressed the gap by offering a comprehensive set of reference intervals (RIs) for preterm neonates, and illustrating the dynamic changes of each biomarker with age. DESIGN AND METHODS: The NBS data of 199,693 preterm newborns (< 37 weeks of gestation) who met the inclusion and exclusion criteria from the NNSCP database were included in study analysis. The birth weight stratified dynamic trend of each biomarker were captured by their concentrations over age. Reference partitions were determined by the method of Harris and Boyd. RIs, corresponding to the 2.5th and 97.5th percentiles, as well as the 0.5th, 25th, 50th, 75th and 99.5th percentiles were calculated using a non-parametric rank approach. RESULTS: Increasing birth weight is associated with an elevation in the levels of arginine, citrulline, glycine, leucine and isobarics, methionine, ornithine, phenylalanine, and valine, whereas the levels of alanine, proline and tyrosine decrease. Additionally, two short-chain acylcarnitines (butyrylcarnitine + isobutyrylcarnitine and isovalerylcarnitine + methylbutyrylcarnitine) and a median-chain acylcarnitine (octenoylcarnitine) decrease, while four long-chain acylcarnitines (tetradecanoylcarnitine, palmitoylcarnitine, palmitoleylcarnitine and oleoylcarnitine) increase with increasing birth weight. Age impacts the levels of all MS/MS NBS biomarkers, while sex only affects the level of malonylcarnitine + 3-hydroxybutyrylcarnitine (C3-DC + C4-OH) in very low birth weight preterm neonates. CONCLUSION: The current study developed reference intervals (RIs) specific to birth weight, age, and/or sex for 35 MS/MS biomarkers, which can help in the timely evaluation of the health and disease of preterm neonates.

Doctor-Parent Disagreement for Preterm Infants Born in the Grey Zone: Do Ethical Frameworks Help?

OBJECTIVE: To examine i) how ethical frameworks can be used in concrete cases of parent-doctors' disagreements for extremely preterm infants born in the grey zone to guide such difficult decision-making; and ii) what challenges stakeholders may encounter in using these frameworks. DESIGN: We did a case analysis of a concrete case of parent-doctor disagreement in the grey zone using two ethical frameworks: the best interest standard and the zone of parental discretion. RESULTS: Both ethical frameworks entailed similar advantages and challenges. They have the potential 1) to facilitate decision-making because they follow a structured method; 2) to clarify the situation because all relevant ethical issues are explored; and 3) to facilitate reaching an agreement because all parties can explain their views. We identified three main challenges. First, how to objectively evaluate the risk of severe disability. Second, parents' interests should be considered but it is not clear to what extent. Third, this is a value-laden situation and different people have different values, meaning that the frameworks are at least partially subjective. CONCLUSIONS: These challenges do not mean that the ethical frameworks are faulty; rather, they reflect the complexity and the sensitivity of cases in the grey zone.

Instructional guidelines and group discussion effects on new nurses' competency regarding nursing care of preterm infants.

Background: Premature birth was once one of the leading causes of infant mortality. Premature infants require improved medical and nursing skills from a highly competent nursing team. Purpose: This investigation aimed to assess the effects of instructional guidelines and group discussion on new nurses' competency in preterm infants caring at the Neonatal Intensive Care Unit (NICU). Methods: A single-anonymized, two-group pre-test and post-test study design was accompanied in 2022. The study was accompanied for 50 newly graduated nurses concerned with competence in nursing management of preterm infants at the Neonatal Intensive Care Unit (NICU) in two hospitals: Al-Namas General Hospital, KSA, and the Pediatric Hospital of Assiut University, Egypt. Two groups were randomly selected from among the nurses to be trained on preterm infant nursing care competence either through an instructional guideline or group discussion. Nursing attitudes and practices were measured before and after training using questionnaires and checklists. Results: There was no significant difference between the instructional guideline group and the group discussion in the mean total score of attitudes (11.72 and 14.65, P = 0.455) and practices (14.36 and 14.80, P = 0.494) towards caring for preterm infants before intervention. While mean nurses' attitude and practice scores increased significantly in both groups after the intervention, in the discussion group, nurses' practice scores increased significantly (p = 0.001). Still, there were no significant changes in the instructional guideline group (P = 0.202). Conclusion: Both methods were effective on the newly graduated nurses' attitude; however, the instructional guidelines did not affect their practice regard nursing care of preterm infants. However, group discussion training techniques can effectively improve the nurses' attitude and practice toward nursing care of preterm infants. Relevance to clinical practice: The group discussion training method should be the approved and proven method for hospitals to train new nurses to increase clinical practices, especially during nursing care for premature infants, because this method has proven its worth in increasing the skill of nurses. It enables a group to talk about a specific subject and exchange personal stories. This approach involves a group leader facilitating communication and interaction between participants.

Establishment and Validation of a Risk Prediction Model for Non-Invasive Ventilation Failure After Birth in Premature Infants with Gestational Age < 32 Weeks.

OBJECTIVES: This study was performed to construct and validate a risk prediction model for non-invasive ventilation (NIV) failure after birth in premature infants with gestational age < 32 weeks. METHODS: The data were derived from the multicenter retrospective study program - Jiangsu Provincial Neonatal Respiratory Failure Collaboration Network from Jan 2019 to Dec 2021. The subjects finally included were preterm infants using NIV after birth with gestational age less than 32 weeks and admission age within 72 h. After screening by inclusion and exclusion criteria, 1436 babies were subsequently recruited in the study, including 1235 infants in the successful NIV group and 201 infants in the failed NIV group. RESULTS: (1) Gestational age, 5 min Apgar, Max FiO2 during NIV, and FiO2 fluctuation value during NIV were selected by univariate and multivariate analysis. (2) The area under the curve of the prediction model was 0.807 (95% CI: 0.767-0.847) in the training set and 0.825 (95% CI: 0.766-0.883) in the test set. The calibration curve showed good agreement between the predicted probability and the actual observed probability (Mean absolute error = 0.008 for the training set; Mean absolute error = 0.012 for the test set). Decision curve analysis showed good clinical validity of the risk model in the training and test cohorts. CONCLUSION: This model performed well on dimensions of discrimination, calibration, and clinical validity. This model can serve as a useful tool for neonatologists to predict whether premature infants will experience NIV failure after birth.

Effectiveness of Oral-Motor Stimulation on Oral Feeding in Premature Infants: A Protocol for Systematic Review and Meta-Analysis of Controlled Randomized Trials.

Objectives: Premature infants (born before 37 weeks of gestational age) frequently experience feeding difficulties due to underdeveloped oral motor skills and poor chewing, swallowing, and breathing coordination. In order to improve oral feeding efficiency in these infants, Oral-Motor Stimulation (OMS) has been used in various studies. This systematic review study will aim to assess the effectiveness of OMS for oral feeding in preterm infants. Materials & Methods: The authors will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. They will conduct a search in electronic databases, including PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials in The Cochrane Library (CENTRAL), Medline via PubMed, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) for nursing and related healthcare texts without language restrictions from the first month of 1991 to the fifth month of 2024 to achieve the study objectives. All Randomized Controlled Clinical Trials (RCT) examining the effect of OMS on oral feeding in preterm infants will be included in this study. Results: The primary outcome of this systematic review will be oral feeding, and the secondary outcomes will include duration of hospitalization, weight gain, and feeding efficiency. Two independent reviewers will select and extract data for the study. The Cochrane Risk of Bias Tool (RoB2) will be used to evaluate potential biases in the study. Publication bias will be evaluated using funnel plots, Begg's, and Egger's tests. The degree of heterogeneity among the studies will be assessed using the I2 statistic and the χ2 test. Analyses of subgroups will also be carried out. All meta-analyses will be conducted using Stata V.14. Conclusion: This systematic review protocol for preterm infants will aim to promote evidence-based decision-making and support the development of clinical practice guidelines in preterm feeding.

Linking preterm infant gut microbiota to nasograstric enteral feeding tubes: exploring potential interactions and microbial strain transmission.

Introduction: Preterm birth is a growing problem worldwide. Staying at a neonatal intensive care unit (NICU) after birth is critical for the survival of preterm infants whose feeding often requires the use of nasogastric enteral feeding tubes (NEFT). These can be colonized by hospital-associated pathobionts that can access the gut of the preterm infants through this route. Since the gut microbiota is the most impactful factor on maturation of the immune system, any disturbance in this may condition their health. Therefore, the aim of this study is to assess the impact of NEFT-associated microbial communities on the establishment of the gut microbiota in preterm infants. Material and methods: A metataxonomic analysis of fecal and NEFT-related samples obtained during the first 2 weeks of life of preterm infants was performed. The potential sharing of strains isolated from the same set of samples of bacterial species involved in NICU's outbreaks, was assessed by Random Amplification of Polymorphic DNA (RAPD) genotyping. Results: In the samples taken 48 h after birth (NEFT-1 and Me/F1), Staphylococcus spp. was the most abundant genera (62% and 14%, respectively) and it was latter displaced to 5.5% and 0.45%, respectively by Enterobacteriaceae. Significant differences in beta diversity were detected in NEFT and fecal samples taken at day 17 after birth (NEFT-3 and F3) (p = 0.003 and p = 0.024, respectively). Significant positive correlations were found between the most relevant genera detected in NEFT-3 and F3. 28% of the patients shared at least one RAPD-PCR profile in fecal and NEFT samples and 11% of the total profiles were found at least once simultaneously in NEFT and fecal samples from the same patient. Conclusion: The results indicate a parallel bacterial colonization of the gut of preterm neonates and the NEFTs used for feeding, potentially involving strain sharing between these niches. Moreover, the same bacterial RAPD profiles were found in neonates hospitalized in different boxes, suggesting a microbial transference within the NICU environment. This study may assist clinical staff in implementing best practices to mitigate the spread of pathogens that could threaten the health of preterm infants.

Hypertensive Disorders of Pregnancy and Risk of Early Brain Abnormalities on Magnetic Resonance Imaging at Term among Infants Born at ≤32 Weeks' Gestational Age.

OBJECTIVE: To evaluate the proximal effects of hypertensive disorders of pregnancy (HDP) on a validated measure of brain abnormalities in infants born at ≤32 weeks' gestational age (GA) using magnetic resonance imaging at term-equivalent age. STUDY DESIGN: In a multisite prospective cohort study, 395 infants born at ≤32 weeks' GA, underwent 3T magnetic resonance imaging scan between 39 and 44 weeks' postmenstrual age. A single neuroradiologist, blinded to clinical history, evaluated the standardized Kidokoro global brain abnormality score as the primary outcome. We classified infants as HDP-exposed by maternal diagnosis of chronic hypertension, gestational hypertension, pre-eclampsia, or eclampsia. Linear regression analysis identified the independent effects of HDP on infant brain abnormalities, adjusting for histologic chorioamnionitis, maternal smoking, antenatal steroids, magnesium sulfate, and infant sex. Mediation analyses quantified the indirect effect of HDP mediated via impaired intrauterine growth and prematurity and remaining direct effects on brain abnormalities. RESULTS: A total of 170/395 infants (43%) were HDP-exposed. Adjusted multivariable analyses revealed HDP-exposed infants had 27% (95% CI 5%-53%) higher brain abnormality scores than those without HDP exposure (P = .02), primarily driven by increased white matter injury/abnormality scores (P = .01). Mediation analyses showed HDP-induced impaired intrauterine growth significantly (P = .02) contributed to brain abnormality scores (22% of the total effect). CONCLUSIONS: Maternal hypertension independently increased the risk for early brain injury and/or maturational delays in infants born at ≤32 weeks' GA with an indirect effect of 22% resulting from impaired intrauterine growth. Enhanced prevention/treatment of maternal hypertension may mitigate the risk of infant brain abnormalities and potential neurodevelopmental impairments.

Family-Centered Care for LGBTQ+ Parents of Infants in the Neonatal Intensive Care Unit: An Integrative Review.

BACKGROUND: Having an infant in the Neonatal Intensive Care Unit (NICU) can disrupt parent well-being, the transition to parenthood, and the typical trajectories of infant and child health. For lesbian, gay, bisexual, transgender, queer, or other sexual and gender minority identity (LGBTQ+) parents, this stress may be compounded by health disparities and fear of stigma and discrimination; however, research is lacking about LGBTQ+ parents of infants in the NICU. OBJECTIVES: The purpose of this integrative review was to better understand the experiences of LGBTQ+ parents of NICU infants, with a focus on experiences of stigma and discrimination, sources of strength and resilience, and provision of family-centered care. METHOD: We searched EBSCOHost, ProQuest, Web of Science, and Google Scholar between 30 May 2023 and 18 September 2023 for empirical studies published in English in peer-reviewed scholarly journals in which LGBTQ+ parents shared their experiences with having infants admitted to the NICU. RESULTS: We identified six articles that met inclusion criteria, all of which were qualitative studies that included 12-14 LGBTQ+ parents of NICU infants. CONCLUSIONS: LGBTQ+ parents in all studies reported instances of perceived stigma and discrimination while their infants were in the NICU, whereas parents in two studies mentioned strength and resilience, and parents in three studies described elements of family-centered care. There is a need for rigorous research on family-centered NICU care that includes questions about sources of strength and resilience in addition to challenges. We propose that future researchers use community engaged methods to center perspectives of LGBTQ+ parents.

Intubation at Birth Is Associated with Death after Pulmonary Hemorrhage in Very Low Birth Weight Infants.

OBJECTIVE: This retrospective cohort study was performed to clarify the association between intubation in the delivery room and the mortality after pulmonary hemorrhage in very low birth weight infants (VLBWIs) during hospitalization. METHODS: The study participants were screened from the VLBWIs admitted to the neonatal intensive care unit (NICU) of the Children's Hospital Affiliated to Nanjing Medical University from 31 July 2019 to 31 July 2022. The newborns who ultimately were included were those infants who survived until pulmonary hemorrhage was diagnosed. These subjects were divided into the intubation-at-birth group (n = 29) and the non-intubation-at-birth group (n = 35), retrospectively. RESULTS: Univariate analysis found that the intubation group had a higher mortality and shorter hospital stay than the non-intubation group (p < 0.05) (for mortality: 25/29 (86.21%) in intubation group versus 14/35 (40.00%) in non-intubation group). By multivariate analysis, the result further showed that intubation in the delivery room was related to shorter survival time and higher risk of death (adjusted hazard ratio: 2.341, 95% confidence interval: 1.094-5.009). CONCLUSIONS: Intubation at birth suggested a higher mortality in the VLBWIs when pulmonary hemorrhage occurred in the NICU.

Evaluation of the Relationship between Pain Exposure and Somatosensory Evoked Potentials in Preterm Infants: A Prospective Cohort Study.

BACKGROUND AND AIM: First, to compare somatosensory evoked potentials (SEPs) in preterm newborns without major brain injury studied at term equivalent age (TEA) with a term historical control group. Second, to investigate the impact of pain exposure during the first 28 days after birth on SEPs. Third, to evaluate the association between SEPs and Bayley-III at 2 years corrected age (CA). METHODS: Infants born at <32 weeks' gestational age (GA) were studied with continuous-SEPs. First, SEP differences between preterm and term infants were analyzed. Second, regression analyses were conducted to explore the association between SEPs and painful procedures, and then between SEPs and neurodevelopment. RESULTS: 86 preterm infants were prospectively enrolled. Preterm infants exhibited prolonged N1 latencies, central conduction times (CCTs), lower N1-P1 amplitudes, and more recurrently abnormal SEPs compared to term infants. Higher pain exposure predicted longer N1 latency and slower CCT (all p < 0.005), adjusting for clinical risk factors. Younger GA and postmenstrual age (PMA) at SEP recording were associated with longer N1 latency and lower N1-P1 amplitude (all p < 0.005). A normal SEP at TEA positively predicted cognitive outcome at 2 years CA (p < 0.005). CONCLUSION: Pain exposure and prematurity were risk factors for altered SEP parameters at TEA. SEPs predicted cognitive outcome.

Evidence and Perspectives for Choline Supplementation during Parenteral Nutrition-A Narrative Review.

Choline is an essential nutrient, with high requirements during fetal and postnatal growth. Tissue concentrations of total choline are tightly regulated, requiring an increase in its pool size proportional to growth. Phosphatidylcholine and sphingomyelin, containing a choline headgroup, are constitutive membrane phospholipids, accounting for >85% of total choline, indicating that choline requirements are particularly high during growth. Daily phosphatidylcholine secretion via bile for lipid digestion and very low-density lipoproteins for plasma transport of arachidonic and docosahexaenoic acid to other organs exceed 50% of its hepatic pool. Moreover, phosphatidylcholine is required for converting pro-apoptotic ceramides to sphingomyelin, while choline is the source of betaine as a methyl donor for creatine synthesis, DNA methylation/repair and kidney function. Interrupted choline supply, as during current total parenteral nutrition (TPN), causes a rapid drop in plasma choline concentration and accumulating deficit. The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) defined choline as critical to all infants requiring TPN, claiming its inclusion in parenteral feeding regimes. We performed a systematic literature search in Pubmed with the terms "choline" and "parenteral nutrition", resulting in 47 relevant publications. Their results, together with cross-references, are discussed. While studies on parenteral choline administration in neonates and older children are lacking, preclinical and observational studies, as well as small randomized controlled trials in adults, suggest choline deficiency as a major contributor to acute and chronic TPN-associated liver disease, and the safety and efficacy of parenteral choline administration for its prevention. Hence, we call for choline formulations suitable to be added to TPN solutions and clinical trials to study their efficacy, particularly in growing children including preterm infants.

A preliminary study of the effectiveness of video visitation on depression and stress in mothers with preterm infants during the pandemic.

BACKGROUND AND PURPOSE: Parents of preterm infants experience anxiety and stress in the neonatal intensive care unit (NICU). Visitation restrictions due to COVID-19 have increased maternal pressure and limited bonding opportunities. Little research exists in Taiwan on using video conferencing as a solution. This study investigates depression and stress levels in mothers of preterm infants and evaluates the effectiveness of video visitation during NICU restrictions. METHODS: This study adopts a cross-sectional design and a qualitative survey. Mothers of premature infants were recruited and they participated in the study. Interventions for video visits were scheduled on the third day of admission to the NICU (T1) and during the second week of the study (T2). After each video visit, participants completed an online survey. The study's online survey used structured questionnaires including demographics, the Edinburgh Postnatal Depression Scale (EPDS) and the Parental Stress Scale (PSS): Infant Hospitalization (IH). RESULTS: A total of 51 mothers of preterm infants participated in the study. During the T1 and T2 periods, single mothers with lower educational levels and those aged below 30 experienced depression and high levels of stress. Lower birth weight and gestational age were associated with maternal depression. Video visitation intervention led to a significant decrease in depression scores (EPDS, T1: 11.3 ± 5.5 vs. T2: 10.1 ± 5.2, p = 0.039). Positive correlations were observed between EPDS and PSS: IH scores (p < 0 .005). CONCLUSION: Video visitation intervention can reduce maternal depression in mothers with preterm infants. Since it is practical, video visitation may be applied even after the pandemic.

Optimal Strategies of Mechanical Ventilation: Can We Avoid or Reduce Lung Injury?

BACKGROUND: Despite the increasing use of non-invasive support modalities, many preterm infants still need invasive mechanical ventilation. Mechanical ventilation can lead to so-called ventilator-induced lung injury, which is considered an important risk factor in the development of bronchopulmonary dysplasia. Understanding the concepts of lung protective ventilation strategies is imperative to reduce the risk of BPD. SUMMARY: Overdistension, atelectasis, and oxygen toxicity are the most important risk factors for VILI. A lung protective ventilation strategy should therefore optimize lung volume (resolve atelectasis), limit tidal volumes, and reduce oxygen exposure. Executing such a lung protective ventilation strategy requires basic knowledge on neonatal lung physiology. Studies have shown that volume-targeted ventilation (VTV) stabilizes tidal volume delivery, reduces VILI, and reduces BPD in preterm infants with respiratory distress syndrome. High-frequency ventilation (HFV) also reduces BPD although the effect is modest and inconsistent. It is unclear if these benefits also apply to infants with more heterogeneous lung disease. KEY MESSAGES: Understanding basic physiology and the concept of ventilator-induced lung injury is essential in neonatal mechanical ventilation. Current evidence suggests that the principles of lung protective ventilation are best captured by VTV and HFV.

The relationship between neonatal stress in preterm infants and developmental outcomes at the corrected age of 24-30 months.

Aim: The aim of research was to study the relationship between the stress experienced by preterm infants in the neonatal intensive care unit (NICU) and developmental status in the follow up, and to establish factors, associated with their neurodevelopment. Methods: The first stage of research involved measuring stress markers (cortisol, melatonin) in infants (n = 56) during their NICU stay; the second phase assessed the developmental status at the corrected age of 24-30 months. Results: The total ASQ-3 score, communication, problem solving, and personal-social skills scores at the corrected age of 24-30 months were positively correlated with melatonin level determined in the neonatal period (r = 0.31, p = 0.026; r = 0.36, p = 0.009; r = 0.30, p = 0.033, and r = 0.32; p = 0.022 respectively). In the same time, ASQ-3 communication and personal-social scores were negatively correlated with cortisol level (r = -0.31, p = 0.043; r = -0.35, p = 0.022). The ROC-curve analysis revealed that a decrease of melatonin below 3.44 ng/mL and 3.71 ng/mL during the neonatal period could predict communication and problem-solving delay, respectively. An increase in cortisol above 0.64 mcg/dl is predictive in personal-social delay. Negative correlation was identified between the NICU and total hospital stay duration and ASQ-3 communication scores in the follow-up (r = -0.27; p = 0.049 and r = -0.41; p = 0.002, respectively). The duration of mechanical ventilation was negatively correlated with gross motor scores (r = -0.46; p = 0.043). Apgar score was positively correlated with ASQ-3 communication (r = 0.29; p = 0.032) and personal-social scores (r = 0.28; p = 0.034); maternal age-with ASQ-3 total (r = 0.29; p = 0.034), communication (r = 0.37; p = 0.006), and personal-social scores (r = 0.29; p = 0.041). Positive correlations were observed between gestational age and communication scores (r = 0.28; p = 0.033). Infants who suffered neonatal sepsis had significantly often delay of communication (p = 0.014) and gross motor skills (p = 0.016). Children who required mechanical ventilation were more likely to have communication delay (p = 0.034). Conclusion: Developmental outcomes in preterm infants at the corrected age of 24-30 months were associated with neonatal stress. Correlations between the communication, problem-solving and personal-social development in the follow up and cortisol and melatonin levels determined in the neonatal period supported this evidence. Factors as low gestational age, duration of hospital and NICU stay, mechanical ventilation, and sepsis were associated with more frequent delays in communication, gross motor and problems-solving skills.

Single-cell transcriptomic analysis reveals heterogeneous features of myeloid-derived suppressor cells in newborns.

The transitory emergence of myeloid-derived suppressor cells (MDSCs) in infants is important for the homeostasis of the immune system in early life. The composition and functional heterogeneity of MDSCs in newborns remain elusive, hampering the understanding of the importance of MDSCs in neonates. In this study, we unraveled the maturation trajectory of polymorphonuclear (PMN)-MDSCs from the peripheral blood of human newborns by performing single-cell RNA sequencing. Results indicated that neonatal PMN-MDSCs differentiated from self-renewal progenitors, antimicrobial PMN-MDSCs, and immunosuppressive PMN-MDSCs to late PMN-MDSCs with reduced antimicrobial capacity. We also established a simple framework to distinguish these distinct stages by CD177 and CXCR2. Importantly, preterm newborns displayed a reduced abundance of classical PMN-MDSCs but increased late PMN-MDSCs, consistent with their higher susceptibility to infections and inflammation. Furthermore, newborn PMN-MDSCs were distinct from those from cancer patients, which displayed minimum expression of genes about antimicrobial capacity. This study indicates that the heterogeneity of PMN-MDSCs is associated with the maturity of human newborns.