Delineating morbidity patterns in preterm infants at near-term age using a data-driven approach.

BACKGROUND: Long-term survival after premature birth is significantly determined by development of morbidities, primarily affecting the cardio-respiratory or central nervous system. Existing studies are limited to pairwise morbidity associations, thereby lacking a holistic understanding of morbidity co-occurrence and respective risk profiles. METHODS: Our study, for the first time, aimed at delineating and characterizing morbidity profiles at near-term age and investigated the most prevalent morbidities in preterm infants: bronchopulmonary dysplasia (BPD), pulmonary hypertension (PH), mild cardiac defects, perinatal brain pathology and retinopathy of prematurity (ROP). For analysis, we employed two independent, prospective cohorts, comprising a total of 530 very preterm infants: AIRR ("Attention to Infants at Respiratory Risks") and NEuroSIS ("Neonatal European Study of Inhaled Steroids"). Using a data-driven strategy, we successfully characterized morbidity profiles of preterm infants in a stepwise approach and (1) quantified pairwise morbidity correlations, (2) assessed the discriminatory power of BPD (complemented by imaging-based structural and functional lung phenotyping) in relation to these morbidities, (3) investigated collective co-occurrence patterns, and (4) identified infant subgroups who share similar morbidity profiles using machine learning techniques. RESULTS: First, we showed that, in line with pathophysiologic understanding, BPD and ROP have the highest pairwise correlation, followed by BPD and PH as well as BPD and mild cardiac defects. Second, we revealed that BPD exhibits only limited capacity in discriminating morbidity occurrence, despite its prevalence and clinical indication as a driver of comorbidities. Further, we demonstrated that structural and functional lung phenotyping did not exhibit higher association with morbidity severity than BPD. Lastly, we identified patient clusters that share similar morbidity patterns using machine learning in AIRR (n=6 clusters) and NEuroSIS (n=8 clusters). CONCLUSIONS: By capturing correlations as well as more complex morbidity relations, we provided a comprehensive characterization of morbidity profiles at discharge, linked to shared disease pathophysiology. Future studies could benefit from identifying risk profiles to thereby develop personalized monitoring strategies. TRIAL REGISTRATION: AIRR: DRKS.de, DRKS00004600, 28/01/2013. NEuroSIS: ClinicalTrials.gov, NCT01035190, 18/12/2009.

A National Survey of Neonatologists' Perspectives on Probiotics Use in Neonatal Intensive Care Units in the U.S.A.

Introduction: Most recent clinical reports from the American Academy of Pediatrics (AAP) concluded current evidence does not support routine universal administration of probiotics to preterm infants, particularly those with birth weight <1000 grams. Despite this, the use of probiotics is increasing in US neonatal intensive care units (NICU).Objectives: Collaborating with the Perinatal Neonatal Medicine of AAP, we conducted a national survey to obtain neonatologist opinion on probiotics use.Methods: Survey questionnaires were sent to 3000 neonatologists via email.Results: Of 3000 potential respondents, 249 (8.3 %) completed the survey. Seventy-five (30%) neonatologists working in 23 different NICUs reported using probiotics in their practice, while 168 (70%) neonatologists working in 54 different NICUs reported not using probiotics. Of those not currently use probiotics, 49% indicated they would consider using probiotics in the future vs. 12% indicating they would not use probiotics. The most common indication for probiotics use was average gestational age < 32 weeks and mean birth weight < 1500 grams. Probiotics were discontinued at mean gestational age of 35 weeks. Respondents who prescribe probiotics were more likely to work in a setting without fellowship or residency training (48% vs 20%). Probiotics users were more often from the West (29 % vs 7%) and less often from Northeast (5% vs 34%) compared to non-users. The proportion of those using probiotics did not significantly differ by NICU size, NICU level, or years working in a NICU. Similac Tri-Blend, Evivo, and Culturelle were the top three probiotics used in the respondent's NICU.Conclusion: Though a majority of respondents are not currently using probiotics in their NICU, a large number of nonusers are interested in using probiotics in the future. Differences continue to exist in the brand of probiotics used in US NICUs.

Effects of oropharyngeal administration of own mother's milk on oral microbial colonization in very low birth weight infants fed by gastric tube: A randomized controlled trial.

AIMS: The aim of the present study was to explore the effect of oropharyngeal mother's milk administration on oral microbial colonization in infants fed by gastric tube at different time points. METHODS: Infants (n = 116) with birth weight <1500 g were randomly allocated into two groups which both received breast milk for enteral nutrition. The control group (n = 51) accepted oropharyngeal normal saline administration. The experimental group (n = 53) accepted oropharyngeal mother's milk administration before fed by gastric tube once every 3 h over 21 days after birth. We analyzed the oral microbiota at initiation and 7 and 14 and 21 days later using 16S DNA amplicon sequencing. RESULTS: There were no difference in oral microbial diversity between the two groups at any time point, but diversity decreased significantly over time in both groups. On the first day of life, the oral microbiota of the infant in the experimental and control groups consisted mainly of Firmicutes (7.75%, 6.18%) and Proteobacteria (68.65%, 68.69%), respectively. As time increases to 21 days after birth, Firmicutes (77.67%, 77.66%) had replaced Proteobacteria (68.65%, 68.69%) as the predominant phylum. DISCUSSION: From birth to 21 days after birth, oropharyngeal mother's milk administration did not change the diversity and structural composition of the oral microbiota. The oral microbial diversity of infants declined significantly over time. Firmicutes had replaced Proteobacteria as the predominant phylum.

Reduction in limb-movement complexity at term-equivalent age is associated with motor developmental delay in very-preterm or very-low-birth-weight infants.

Reduced complexity during the writhing period can be crucial in the spontaneous movements of high-risk infants for neurologic impairment. This study aimed to verify the association between quantified complexity of upper and lower-limb movements at term-equivalent age and motor development in very-preterm or very-low-birth-weight infants. Video images of spontaneous movements at term-equivalent age were collected from very-preterm or very-low-birth-weight infants. A pretrained pose-estimation model and sample entropy (SE) quantified the complexity of the upper- and lower-limb movements. Motor development was evaluated at 9 months of corrected age using Bayley Scales of Infant and Toddler Development, Third Edition. The SE measures were compared between infants with and without motor developmental delay (MDD). Among 90 infants, 11 exhibited MDD. SE measures at most of the upper and lower limbs were significantly reduced in infants with MDD compared to those without MDD (p < 0.05). Composite scores in the motor domain showed significant positive correlations with SE measures at most upper and lower limbs (p < 0.05). The results show that limb-movement complexity at term-equivalent age is reduced in infants with MDD at 9 months of corrected age. SE of limb movements can be a potentially useful kinematic parameter to detect high-risk infants for MDD.

Lactation support in neonatal intensive care units in Germany from the mothers' perspective - a mixed-method study of the current status and needs.

BACKGROUND: Establishing successful lactation in mothers of very low birth weight (VLBW, <1500g) infants requires structured lactation support. Little is known about mothers' perspectives on lactation support in German neonatal intensive care units (NICUs). METHODS: This paper features a convergent mixed-method approach that includes a retrospective, cross-sectional questionnaire and interview data to showcase mothers' perceptions of lactation support in NICUs. Content analysis of the interviews (n = 12) and a descriptive analysis of quantitative data (n = 533) were performed to illustrate the current status and need for lactation support in German NICUs. RESULTS: The results show that lactation support in German NICUs is often inadequate and does not comply with recommendations based on the existing literature to encourage pumping and breastfeeding in mothers. The data imply that even if lactation is successfully initiated in most cases, it is often not maintained over time, which may be due to a lack of personal support and consistent information. CONCLUSION: The overall structures and institutional guidelines for lactation support should be encouraged to promote nutrition with mother´s own milk in German NICUs.

Does the use of higher versus lower oxygen concentration improve neurodevelopmental outcomes at 18-24 months in very low birthweight infants?

BACKGROUND: Immediately after birth, the oxygen saturation is between 30 and 50%, which then increases to 85-95% within the first 10 min. Over the last 10 years, recommendations regarding the ideal level of the initial fraction of inspired oxygen (FiO2) for resuscitation in preterm infants have changed from 1.0, to room air to low levels of oxygen (< 0.3), up to moderate concentrations (0.3-0.65). This leaves clinicians in a challenging position, and a large multi-center international trial of sufficient sample size that is powered to look at safety outcomes such as mortality and adverse neurodevelopmental outcomes is required to provide the necessary evidence to guide clinical practice with confidence. METHODS: An international cluster, cross-over randomized trial of initial FiO2 of 0.3 or 0.6 during neonatal resuscitation in preterm infants at birth to increase survival free of major neurodevelopmental outcomes at 18 and 24 months corrected age will be conducted. Preterm infants born between 230/7 and 286/7 weeks' gestation will be eligible. Each participating hospital will be randomized to either an initial FiO2 concentration of either 0.3 or 0.6 to recruit for up to 12 months' and then crossed over to the other concentration for up to 12 months. The intervention will be initial FiO2 of 0.6, and the comparator will be initial FiO2 of 0.3 during respiratory support in the delivery room. The sample size will be 1200 preterm infants. This will yield 80% power, assuming a type 1 error of 5% to detect a 25% reduction in relative risk of the primary outcome from 35 to 26.5%. The primary outcome will be a composite of all-cause mortality or the presence of a major neurodevelopmental outcome between 18 and 24 months corrected age. Secondary outcomes will include the components of the primary outcome (death, cerebral palsy, major developmental delay involving cognition, speech, visual, or hearing impairment) in addition to neonatal morbidities (severe brain injury, bronchopulmonary dysplasia; and severe retinopathy of prematurity). DISCUSSION: The use of supplementary oxygen may be crucial but also potentially detrimental to preterm infants at birth. The HiLo trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants. Should 60% initial oxygen concertation increase survival free of major neurodevelopmental outcomes at 18-24 months corrected age, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice. TRIAL REGISTRATION: The trial was registered on January 31, 2019, at ClinicalTrials.gov with the Identifier: NCT03825835.

Time to full enteral feeds in hospitalised preterm and very low birth weight infants in Nigeria and Kenya.

BACKGROUND: Preterm (born < 37 weeks' gestation) and very low birthweight (VLBW; <1.5kg) infants are at the greatest risk of morbidity and mortality within the first 28 days of life. Establishing full enteral feeds is a vital aspect of their clinical care. Evidence predominantly from high income countries shows that early and rapid advancement of feeds is safe and reduces length of hospital stay and adverse health outcomes. However, there are limited data on feeding practices and factors that influence the attainment of full enteral feeds among these vulnerable infants in sub-Saharan Africa. AIM: To identify factors that influence the time to full enteral feeds, defined as tolerance of 120ml/kg/day, in hospitalised preterm and VLBW infants in neonatal units in two sub-Saharan African countries. METHODS: Demographic and clinical variables were collected for newborns admitted to 7 neonatal units in Nigeria and Kenya over 6-months. Multiple linear regression analysis was conducted to identify factors independently associated with time to full enteral feeds. RESULTS: Of the 2280 newborn infants admitted, 484 were preterm and VLBW. Overall, 222/484 (45.8%) infants died with over half of the deaths (136/222; 61.7%) occurring before the first feed. The median (inter-quartile range) time to first feed was 46 (27, 72) hours of life and time to full enteral feeds (tFEF) was 8 (4.5,12) days with marked variation between neonatal units. Independent predictors of tFEF were time to first feed (unstandardised coefficient B 1.69; 95% CI 1.11 to 2.26; p value <0.001), gestational age (1.77; 0.72 to 2.81; <0.001), the occurrence of respiratory distress (-1.89; -3.50 to -0.79; <0.002) and necrotising enterocolitis (4.31; 1.00 to 7.62; <0.011). CONCLUSION: The use of standardised feeding guidelines may decrease variations in clinical practice, shorten tFEF and thereby improve preterm and VLBW outcomes.

Effect of Donated Premature Milk in the Prevention of Bronchopulmonary Dysplasia.

INTRODUCTION: Breastfeeding is one of the strategies that has been shown to be effective in preventing severe forms of bronchopulmonary dysplasia (BPD). When mother's own milk (MOM) is not available, pasteurized donor milk (DM) is the best alternative. However, the evidence is inconclusive on the difference in the incidence of bronchopulmonary dysplasia (BPD) between patients fed MOM and those fed with DM. As standard DM is usually mature pooled milk donated by mothers who have delivered their babies at term, the potential benefits of preterm milk may be lost. MATERIALS AND METHODS: An observational, retrospective, single-center study was conducted in the neonatology department of a high-complexity hospital. The study included newborns <32 weeks of gestational age born between January 2020 and December 2022. When supplemental milk was needed, non-pooled preterm pasteurized donor milk (PDM) matched for gestational age and moment of lactation was used in this study, classifying preterm infants in two groups: mainly MOM (>50% of the milk) or mainly PDM (>50% of the milk). Two groups were established: those who received >50% MOM and those who received >50% PDM. They were also classified according to the diagnosis of DBP: one group included no BPD or grade 1 BPD (noBPD/1), while the other included grade 2 or 3 BPD (BPD 2-3). The objectives of this study were, firstly, to evaluate the incidence of BPD 2-3 among patients who predominantly received PDM versus MOM. Secondly, to analyze differences in the type of human milk received and its nutritional components, as well as to study the growth in patients with or without BPD. RESULTS: One hundred ninety-nine patients were included in the study. A comparison of noBPD/1 versus BPD 2-3 groups between those receiving mainly MOM versus PDM showed no significant differences (19% vs. 20%, p 0.95). PDM colostrum in BPD 2-3 compared to noBPD/1 was higher in protein content (2.24 g/100 mL (SD 0.37) vs. 2.02 g/100 mL (SD 0.29) p < 0.01), although the statistical significance decreased after adjustment for gestational age and birth weight z-score (OR 3.53 (0.86-14.51)). No differences were found in the macronutrients in the mature milk of patients feeding more than 50% PDM in both study groups. Growth of BPD 2-3 showed a greater decrease in the difference in z-scores for height at birth and at discharge compared to noBPD/1 (-1.64 vs. -0.43, p 0.03). CONCLUSIONS: The use of mainly MOM or PDM demonstrates a similar incidence of noBPD/1 or BPD 2-3. Non-pooled and matched by gestational age and time of lactation preterm donor milk can probably be an alternative when mother's own milk is not available, with a similar protective effect in the prevention of severe BPD.

Supervised contrastive learning enhances graph convolutional networks for predicting neurodevelopmental deficits in very preterm infants using brain structural connectome.

Very preterm (VPT) infants (born at less than 32 weeks gestational age) are at high risk for various adverse neurodevelopmental deficits. Unfortunately, most of these deficits cannot be accurately diagnosed until the age of 2-5 years old. Given the benefits of early interventions, accurate diagnosis and prediction soon after birth are urgently needed for VPT infants. Previous studies have applied deep learning models to learn the brain structural connectome (SC) to predict neurodevelopmental deficits in the preterm population. However, none of these models are specifically designed for graph-structured data, and thus may potentially miss certain topological information conveyed in the brain SC. In this study, we aim to develop deep learning models to learn the SC acquired at term-equivalent age for early prediction of neurodevelopmental deficits at 2 years corrected age in VPT infants. We directly treated the brain SC as a graph, and applied graph convolutional network (GCN) models to capture complex topological information of the SC. In addition, we applied the supervised contrastive learning (SCL) technique to mitigate the effects of the data scarcity problem, and enable robust training of GCN models. We hypothesize that SCL will enhance GCN models for early prediction of neurodevelopmental deficits in VPT infants using the SC. We used a regional prospective cohort of ∼280 VPT infants who underwent MRI examinations at term-equivalent age from the Cincinnati Infant Neurodevelopment Early Prediction Study (CINEPS). These VPT infants completed neurodevelopmental assessment at 2 years corrected age to evaluate cognition, language, and motor skills. Using the SCL technique, the GCN model achieved mean areas under the receiver operating characteristic curve (AUCs) in the range of 0.72∼0.75 for predicting three neurodevelopmental deficits, outperforming several competing models. Our results support our hypothesis that the SCL technique is able to enhance the GCN model in our prediction tasks.

Immediate postnatal prediction of death or bronchopulmonary dysplasia among very preterm and very low birth weight infants based on gradient boosting decision trees algorithm: A nationwide database study in Japan.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) poses a substantial global health burden. Individualized treatment strategies based on early prediction of the development of BPD can mitigate preterm birth complications; however, previously suggested predictive models lack early postnatal applicability. We aimed to develop predictive models for BPD and mortality based on immediate postnatal clinical data. METHODS: Clinical information on very preterm and very low birth weight infants born between 2008 and 2018 was extracted from a nationwide Japanese database. The gradient boosting decision trees (GBDT) algorithm was adopted to predict BPD and mortality, using predictors within the first 6 h postpartum. We assessed the temporal validity and evaluated model adequacy using Shapley additive explanations (SHAP) values. RESULTS: We developed three predictive models using data from 39,488, 39,096, and 40,291 infants to predict "death or BPD," "death or severe BPD," and "death before discharge," respectively. These well-calibrated models achieved areas under the receiver operating characteristic curve of 0.828 (95% CI: 0.828-0.828), 0.873 (0.873-0.873), and 0.887 (0.887-0.888), respectively, outperforming the multivariable logistic regression models. SHAP value analysis identified predictors of BPD, including gestational age, size at birth, male sex, and persistent pulmonary hypertension. In SHAP value-based case clustering, the "death or BPD" prediction model stratified infants by gestational age and persistent pulmonary hypertension, whereas the other models for "death or severe BPD" and "death before discharge" commonly formed clusters of low mortality, extreme prematurity, low Apgar scores, and persistent pulmonary hypertension of the newborn. CONCLUSIONS: GBDT models for predicting BPD and mortality, designed for use within 6 h postpartum, demonstrated superior prognostic performance. SHAP value-based clustering, a data-driven approach, formed clusters of clinical relevance. These findings suggest the efficacy of a GBDT algorithm for the early postnatal prediction of BPD.

Low and very low birthweight disadvantage in compulsory education achievement and the transition to upper secondary education in the Finnish birth cohorts of 1987 to 1997.

BACKGROUND: We compared the educational achievements of very low-birthweight (VLBW) and low-birthweight (LBW) adolescents (ages 16 to 19) to those of their normal-birthweight (NBW) peers in the complete Finnish birth cohorts of 1987 to 1997. We focused on three key phases of the education process: the end of compulsory education (9th-grade completion), and the transition to and the completion of upper secondary-level education. METHODS: We used register data on grades, educational transitions and completed education. We employed multiple indicators on the progression of the education process and estimated population-level and within-families linear probability (LPM) models with robustness checks at the population level using logistic regression. We tested whether parental education and the child's sex modify the association between (V)LBW and educational achievement. RESULTS: Results of both descriptive analysis and the population-level and within-family LPM models indicate that (V)LBW is associated with an increased risk of not being able to keep up with the normative education process and to compete for upper secondary education study places at the end of compulsory education. The modifying effect of parental education was robust, whereas that of the child's sex was not. Among (V)LBW students who were able to keep up with the normative education process, (V)LBW was not associated with a lower grade point average or with a meaningfully lower probability of completing upper secondary education by the normative age. CONCLUSIONS: The upper secondary-level educational choices and achievements of the children born with (V)LBW who managed to complete the standard compulsory education curriculum and complete the transition to upper secondary-level education within the expected time did not, in essence, differ from those of the NBW children. Some specific characteristics of the Finnish education system likely contributed to these results, such as the grading at compulsory education being only relatively loosely standardized.

Postnatal care and acceptability of emollient therapy in very low birthweight infants in Harare, Zimbabwe: a qualitative analysis.

BACKGROUND: Preterm birth (birth before 37 completed weeks of pregnancy) is the leading cause of neonatal and child under-five mortality globally, both of which are highest regionally in sub-Saharan Africa. The skin barrier plays a critical role in neonatal health and increasing evidence supports the use of topical emollient therapy to promote postnatal growth and reduce hospital-acquired infections in preterm infants. The World Health Organization (WHO) currently recommends emollient therapy in preterm or low birthweight infants globally but calls for further research on impacts of emollient use, especially in Africa. Little is known about postnatal skincare practices and the tradition of oil massage across sub-Saharan Africa. Further documentation is necessary to understand the context for future emollient intervention trials. METHODS: 61 semi-structured interviews with mothers who just delivered preterm or term infants and 4 focus group discussions (32 participants) with physician and nurse providers of newborn care were conducted at Sally Mugabe Central Hospital (SMCH), in Harare, Zimbabwe. SMCH is the principal public-sector tertiary care hospital for newborn infants in the northern part of the country. Mothers and healthcare professionals were questioned about newborn care at the hospital, current neonatal skincare and bathing practices, and the community's receptivity to a future emollient therapy clinical trial. RESULTS: Postnatal skincare is centrally important to Zimbabwean communities and petroleum jelly application is nearly universal. The use of cooking oil and other natural oils on infants is also part of traditional customs. The primary needs and desires of mothers who have just given birth to preterm infants are having greater agency in their children's care and financial support in purchasing prescribed medications while at the hospital. Community receptivity to emollient therapy as a cost-effective treatment is high, particularly if mothers are trained to assist with the intervention. CONCLUSION: Emollient therapy will likely be well-received by communities in and around Harare because of its accordance with current skincare practices and perceptions; however, cultural norms and the experiences of new mothers who have given birth at a facility highlight challenges and considerations for future clinical trial execution. TRIAL REGISTRATION: Clinicaltrials.gov NCT05461404.

Effect of early preventive supplementation with calcium and phosphorus on metabolic bone disease in premature infants.

OBJECTIVE: The objective was to study the effect of early preventive calcium and phosphorus supplementation on metabolic bone disease in preterm infants. METHODS: A retrospective analysis of 234 preterm infants with a gestational age < 32 weeks or birth weight < 1500 g who were hospitalized in the Neonatology Department of the Second Hospital of Shandong University from 01.2018 to 12.2020 was conducted. One hundred thirty-two premature infants hospitalized from 01.2018 to 06.2019 did not receive prophylactic calcium and phosphorus supplementation in the early postnatal period. These infants received calcium or phosphorus supplementation at the time of hypocalcaemia or hypophosphatemia diagnosis. One hundred two premature infants hospitalized from 07.2019 to 12.2020 received early preventive calcium and phosphorus supplementation after birth. The levels of serum calcium and phosphorus, alkaline phosphatase, 25-hydroxyvitamin D, calcitonin, and parathyroid hormone at different time points and growth indicators at six months of age were compared between the two groups of infants. The number of cases of metabolic bone disease and fracture between the two groups was compared. RESULTS: 1) A total of 12 infants (5.13%) among the 234 preterm infants were diagnosed with metabolic bone disease, including 2 (1.96%) in the prophylactic supplementation group and 10 (7.58%) in the nonprophylactic supplementation group. Fractures occurred in 3 premature infants (25.0%) with metabolic bone disease, all of whom were in the group that did not receive prophylactic supplementation. 2) There was no significant difference in serum calcium and calcitonin levels between the two groups. The levels of serum phosphorus and 25 hydroxyvitamin D in the prophylactic supplementation group were higher than those in the nonprophylactic supplementation group (P < 0.05). In comparison, alkaline phosphatase and parathyroid hormone levels were lower in the prophylactic supplementation group than in the nonprophylactic supplementation group (P < 0.05). Preterm infants in the prophylactic supplementation group had higher weight, length, head circumference, and bone density values than those in the nonprophylactic supplementation group (P < 0.05). CONCLUSION: Preventive supplementation with calcium and phosphorus after birth can effectively improve calcium and phosphorus metabolism, and reduce the incidence of metabolic bone disease and fractures in premature infants. This can be further publicized and used clinically.

Physiological-based cord clamping in very preterm infants: the Aeration, Breathing, Clamping 3 (ABC3) trial-statistical analysis plan for a multicenter randomized controlled trial.

BACKGROUND: Mortality, cerebral injury, and necrotizing enterocolitis (NEC) are common complications of very preterm birth. An important risk factor for these complications is hemodynamic instability. Pre-clinical studies suggest that the timing of umbilical cord clamping affects hemodynamic stability during transition. Standard care is time-based cord clamping (TBCC), with clamping irrespective of lung aeration. It is unknown whether delaying cord clamping until lung aeration and ventilation have been established (physiological-based cord clamping, PBCC) is more beneficial. This document describes the statistical analyses for the ABC3 trial, which aims to assess the efficacy and safety of PBCC, compared to TBCC. METHODS: The ABC3 trial is a multicenter, randomized trial investigating PBCC (intervention) versus TBCC (control) in very preterm infants. The trial is ethically approved. Preterm infants born before 30 weeks of gestation are randomized after parental informed consent. The primary outcome is intact survival, defined as the composite of survival without major cerebral injury and/or NEC. Secondary short-term outcomes are co-morbidities and adverse events assessed during NICU admission, parental reported outcomes, and long-term neurodevelopmental outcomes assessed at a corrected age of 2 years. To test the hypothesis that PBCC increases intact survival, a logistic regression model will be estimated using generalized estimating equations (accounting for correlation between siblings and observations in the same center) with treatment and gestational age as predictors. This plan is written and submitted without knowledge of the data. DISCUSSION: The findings of this trial will provide evidence for future clinical guidelines on optimal cord clamping management at birth. TRIAL REGISTRATION: ClinicalTrials.gov NCT03808051. Registered on 17 January 2019.

Comparison of prematurity-related outcomes and complications in very low birth weight (VLBW) neonates fed with mother`s own milk versus donor milk: a comparative study.

BACKGROUND: When mother`s own milk (MOM) is unavailable or insufficient, donor milk (DM) from a human milk bank serves as an alternative feeding option. Our study sought to investigate and compare the outcomes and complications of very low birth weight (VLBW) preterm infants who receive MOM versus DM. METHODS: In this retrospective cohort study conducted between 2018 and 2022, we compared 70 VLBW preterm infants exclusively fed with DM to 70 randomly selected counterparts fed with MOM. Both groups began enteral feeding within 72 hours of birth. Various clinical outcomes were investigated during a three-month follow-up. The clinical outcomes were compared via independent t-tests, Mann-Whitney U, and Fisher`s exact test. RESULTS: The mean gestational age of the infants who were included was 29.6 ± 1.6 weeks, 84 (60%) were males, and the average birth weight was 1217 ± 151 grams. Both groups had similar baseline characteristics. The results of the study demonstrated no statistically significant differences between the groups in terms of hospital length of stay (37±16.3 days in MOM vs 40.3±16.9 days in DM group, P= 0.17), growth rate (13±4 gram/day in MOM vs 13±4 gram/day in DM group, P=0.51), growth velocity (9.8±3.0g/kg/d in MOM vs 9.5±3.2 g/kg/d in DM group), infants with in-hospital vomiting (51 cases in MOM vs 59 cases in DM group, P=0.15),vomiting frequency (1.3±1.1 times in MOM vs 1.5±1.0 times in DM group), incidence of retinopathy of prematurity (ROP) (4 cases in MOM vs 5 cases in DM group, P > 0.999) and incidence of bronchopulmonary dysplasia (BPD) (7 cases in MOM vs 6 cases in DM group, P > 0.999). CONCLUSION: Our study findings indicate that the utilization of DM didn`t have a substantial negative impact on infants` outcomes nor any complications in comparison with MOM.

Analysis of perinatal risk factors for massive pulmonary hemorrhage in very low birth weight infant: A nationwide large cohort database.

OBJECTIVE: To determine perinatal risk factors for Massive pulmonary hemorrhage (MPH) and MPH-caused mortality to guide clinicians in implementing preventive measures at the beginning of life for improving the survival of very low birth weight infant (VLBWIs). STUDY DESIGN: A total of 13,826 VLBWIs born between 2013 and 2020 in the Korean Neonatal Network database were included. RESULTS: MPH occurred in 870 (6.3 %) VLBWIs. Among infants with MPH, 162 (18.6 %) VLBWIs died due to MPH. In the multivariate logistic regression analysis, independent risk factors for MPH were identified as small for gestational age, multiple gestation, high CRIB-II score, use of surfactant, and symptomatic patent ductus arteriosus (sPDA) in VLBIWs. Independent risk factors for MPH-caused mortality were identified as multiple gestation in VLBWIs. Receiving a complete course of antenatal corticosteroids (ACS) was found to be a significant independent protective factor for MPH-caused mortality in VLBWIs. CONCLUSION: Proactive managements for reducing unnecessary use of pulmonary surfactant and for decreasing the risk of sPDA at the beginning of life could be recommended as preventive strategies to reduce the risk of MPH in extremely preterm infants. ACS therapy is highly recommended for women with a high likelihood of giving birth preterm to reduce the risk of mortality caused by MPH.

Optimistic vs Pessimistic Message Framing in Communicating Prognosis to Parents of Very Preterm Infants: The COPE Randomized Clinical Trial.

Importance: In the neonatal intensive care unit, there is a lack of understanding about how best to communicate the prognosis of a serious complication to parents. Objective: To examine parental preferences and the effects of optimistic vs pessimistic message framing when providing prognostic information about a serious complication. Design, Setting, and Participants: This crossover randomized clinical trial was conducted at a single German university medical center between June and October 2021. Eligible participants were parents of surviving preterm infants with a birth weight under 1500 g. Data were analyzed between October 2021 and August 2022. Interventions: Alternating exposure to 2 scripted video vignettes showing a standardized conversation between a neonatologist and parents, portrayed by professional actors, about the prognosis of a hypothetical very preterm infant with severe intraventricular hemorrhage. The video vignettes differed in the framing of identical numerical outcome estimates as either probability of survival and probability of nonimpairment (optimistic framing) or a risk of death and impaired survival (pessimistic framing). Main Outcomes and Measures: The primary outcome was preference odds (ratio of preference for optimistic vs pessimistic framing). Secondary outcomes included state anxiety, perceptions of communication, and recall of numerical estimates. Results: Of 220 enrolled parents (142 [64.5%] mothers; mean [SD] age: mothers, 39.1 [5.6] years; fathers, 42.7 [6.9] years), 196 (89.1%) preferred optimistic and 24 (10.1%) preferred pessimistic framing (preference odds, 11.0; 95% CI, 6.28-19.10; P < .001). Preference for optimistic framing was more pronounced when presented second than when presented first (preference odds, 5.41; 95% CI, 1.77-16.48; P = .003). State anxiety scores were similar in both groups at baseline (mean difference, -0.34; -1.18 to 0.49; P = .42) and increased equally after the first video (mean difference, -0.55; 95% CI, -1.79 to 0.69; P = .39). After the second video, state anxiety scores decreased when optimistic framing followed pessimistic framing but remained unchanged when pessimistic framing followed optimistic framing (mean difference, 2.15; 95% CI, 0.91 to 3.39; P < .001). With optimistic framing, participants recalled numerical estimates more accurately for survival (odds ratio, 4.00; 95% CI, 1.64-9.79; P = .002) but not for impairment (odds ratio, 1.50; 95% CI, 0.85-2.63; P = .16). Conclusions and Relevance: When given prognostic information about a serious complication, parents of very preterm infants may prefer optimistic framing. Optimistic framing may lead to more realistic expectations for survival, but not for impairment. Trial Registration: German Clinical Trials Register (DRKS): DRKS00024466.

Physical activity and cognitive function in adults born very preterm or with very low birth weight-an individual participant data meta-analysis.

OBJECTIVE: Individuals born very preterm (<32 weeks of gestation) or with very low birthweight (<1500g) have lower cognitive function compared with term-born peers. Furthermore, some studies suggest that they are less physically active as young adults than controls, but the relationship between physical activity and cognitive function remains unclear. We performed an individual participant data meta-analysis to examine whether being born preterm/with very low birth weight is associated with physical activity in adulthood and examined if cognitive function mediates this association. STUDY DESIGN: Cohorts with data on physical activity and cognitive function in adults born very preterm/very low birth weight and term-born controls were recruited from the Research on European Children and Adults Born Preterm, and the Adults Born Preterm International Collaboration Consortia. A systematic literature search was performed in PubMed and Embase. RESULTS: Five cohorts with 1644 participants aged 22-28 years (595 very preterm/very low birth weight and 1049 controls) were included. Adults born very preterm/very low birth weight reported 1.11 (95% CI: 0.68 to 1.54) hours less moderate to vigorous physical activity per week than controls, adjusted for cohort, age and sex. The difference between individuals born very preterm/very low birth weight and controls was larger among women than among men. Neither intelligence quotient nor self-reported executive function mediated the association between very preterm/very low birth weight and moderate to vigorous physical activity. Results were essentially the same when we excluded individuals with neurosensory impairments. CONCLUSION: Adults born very preterm/very low birth weight, especially women, reported less moderate to vigorous physical activity than their term-born peers. Cognitive function did not mediate this association. Considering the risk of adverse health outcomes among individuals born preterm, physical activity could be a target for intervention.

A Systemic Review of the Difference Between Diets for Preterm Infants Containing Raw Mother's Own Milk and Frozen or Pasteurized Mother's Own Milk.

BACKGROUND: Raw, never stored or pasteurized mother's own milk (MOM) is not always available to feed preterm infants; however, storage and pasteurization of MOM diminishes some bioactive components. It can be difficult to feed raw MOM to preterm infants due to transportation and storage of small volumes that might be pumped away from the infant, and a concern that they might harbor bacteria. However, the higher availability of bioactive components in raw MOM may provide benefits to preterm infants compared to frozen or pasteurized MOM. RESEARCH AIM: To systematically review and summarize the results of studies on feeding raw MOM versus frozen or pasteurized MOM to preterm infants born at less than 37 weeks of gestation. METHODS: Four databases were searched (Cochrane, Embase, Ovid MEDLINE, and Web of Science) for this systematic review. Of 542 studies identified, nine met inclusion criteria and were critically evaluated using the quality assessment tool for quantitative studies by the Effective Public Health Practice Project. Studies were organized using the Breastfeeding Challenges Facing Preterm Mother-Infant Dyads theoretical framework. RESULTS: Included studies evaluated the outcomes of preterm infants fed raw versus pasteurized MOM (n = 7, 77.8%) or raw versus frozen MOM (n = 2, 22.2%). Researchers found that raw MOM did not increase infant infections and may have improved health and growth outcomes for study participants. CONCLUSION: There is laboratory evidence supporting the safety and efficacy of the use of raw MOM for preterm infants. A raw MOM diet is recommended for preterm infants by professional organizations. Despite this, it may not be universally prioritized and could require purposeful implementation by each institution. Further research is needed to pursue the potential benefits of a raw MOM diet for preterm infants.