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Artificial placentas (APs) are technologies that mimic the human placenta to treat extremely preterm infants. Being an invasive and risky technology, it will raise important ethical questions for human trials. Hence, in this Topic Piece we provide a blueprint of further issues to investigate. First, counselling will have the double role of providing trial information as well as (non) treatment counselling. This requires extra training and the development of ad hoc decision aids to support counselling and parents' decision-making. Second, more stakeholder involvement is needed. Direct stakeholders, such as parents, clinicians, and researchers, can help develop the decision aids and provide insight on potentially overlooked issues. Society should also be involved to determine whether AP trials and implementation should be subsidized, and the ethical implications of not subsidizing. Third, a proper cost-benefit analysis should be conducted to determine the exact cost of the technology. [ABSTRACT FROM AUTHOR]

Aim: We investigated the associations between motor performance and IQ at 5 years of age and school difficulties and grade point averages (GPAs) at 18 years of age. Additionally, the accuracy of preschool IQ in predicting school difficulties was examined. Methods: A nationwide follow‐up study of children born in 1994–1995 who were <28 weeks of gestation or had a birthweight <1000 g. The Danish personal identification number was used to merge data from a national cohort study with population‐based registries. Logistic regression analyses examined the associations between motor performance/IQ and school difficulties. Linear regression analyses and the area under the receiver operator curve (AUC) were used to examine the relationship between IQ and GPAs. Results: The study population comprised 248 children, 37% were classified with school difficulties. Motor performance and IQ were associated with school difficulties. The odds of having school difficulties increased as IQ decreased, and the same pattern was observed for GPAs. IQ predicted school difficulties, with an AUC of 0.80 (confidence interval: 0.74–0.86). Conclusion: Preschool motor performance and IQ were associated with school difficulties. Additionally, IQ was linked to GPAs. As a screening tool, the predictive ability of preschool IQ for academic difficulties was moderate/high in this cohort. [ABSTRACT FROM AUTHOR]

Objective: Hyperglycemia in preterm infants is usually treated with adjustment of glucose intake and, if persistent, with continuous insulin infusion. However, hypoglycemia is a well-known complication of intravenous (iv) insulin treatment. The aim of this study was to evaluate the feasibility of continuous subcutaneous insulin infusion (CSII) in extremely preterm infants. Methods: Clinical data from extremely premature infants (<28 weeks of gestation) undergoing CSII treatment for severe hyperglycemia in the neonatal intensive care unit were included. Blood glucose levels during CSII, as well as the nutritional intake and insulin intake were recorded. Data were analyzed and compared to a control group of very preterm infants receiving iv insulin therapy. Results: Normoglycemia rates were best in the iv insulin-cohort (n=22, 50.3%) compared to the CSII group (n=15, 15.6%). Hypoglycemia was very rare in both groups (0.4% vs. 0.0%). CSII therapy appears to require higher insulin doses compared to continuous iv therapy to achieve a similar effect. Subcutaneous Insulin therapy in extremely preterm infants is feasible, at least for prevention of hypoglycemia. However, dose control needs to be improved. Conclusion: The results justify further model validation and clinical trial research to explore a model-based protocol and the use of CSII in this population. [ABSTRACT FROM AUTHOR]

Objective To identify risk factors for moderate to severe bronchopulmonary dysplasia (BPD) in extremely preterm infants born at less than 32 weeks' gestational age and to develop an early predictive nomogram model. Methods A retrospective analysis was conducted on extremely preterm infants born between January 2019 and December 2020 at the Third Affiliated Hospital of Guangzhou Medical University who developed BPD. Perinatal data and clinical information during hospitalization were collected, and risk factors for moderate to severe BPD were identified using logistic regression analysis. Based on these findings, a nomogram prediction model was constructed and internally validated using the Bootstrap method. An external validation cohort was selected from infants born between January 2021 and June 2021 meeting the same inclusion and exclusion criteria. Both the training and validation groups were used to assess the model's discrimination and accuracy. Results A total of 266 extremely preterm infants with BPD were included in the model development cohort, comprising 189 cases of mild BPD (71.1%) and 77 cases of moderate to severe BPD (28.9%). Multivariate logistic regression analysis indicated that preeclampsia, pneumonia, duration of invasive ventilation, and hemodynamically significant patent ductus arteriosus (hsPDA) were significant risk factors for moderate to severe BPD (P<0.05). The nomogram model constructed using these four factors demonstrated an area under the curve (AUC) of 0.810 (95% CI: 0.750-0.870) in the model development cohort and 0. 900 (95% CI: 0.826-0.975) in the validation cohort, with calibration curves close to the ideal diagonal line, indicating good calibration. Conclusion Preeclampsia, pneumonia, duration of invasive ventilation, and hsPDA are independent risk factors for moderate to severe BPD in extremely preterm infants. The nomogram model combining these four indicators demonstrates good predictive value, aiding in early identification of infants at risk of moderate to severe BPD to improve prevention and management outcomes. [ABSTRACT FROM AUTHOR]

Background: Skin-to-skin care (SSC) is an evidence-based care method for preterm-born infants. Staff may hesitate to initiate early SSC, the first or second week of life, for the most extremely preterm infants; 1 reason could be nurses' attitudes. Purpose: The aim was to investigate the attitudes and experiences of neonatal nurses regarding early SSC for the most extremely preterm infants, born at gestational week (GW) 22-23, using an exploratory and descriptive approach. Methods: A web-based survey was sent to all nurses across the 6 Swedish units routinely caring for the most extremely preterm infants. Descriptive statistics and qualitative content analysis were used to analyze the data. Results: The response rate was 258 out of 547 (47%). This study reveals a spectrum of attitudes and experiences among nurses, ranging from viewing early SSC as an integral aspect of infant care to deeming it very challenging or simply not feasible. The outcomes are presented in 2 categories, describing both facilitators and challenges associated with early SSC. Noteworthy, facilitators include well-implemented guidelines that support early SSC. Conversely, challenges encompass knowledge gaps and the scarcity of scientific evidence demonstrating the safety of all SSC, including early, for the most extremely preterm infants. Implications for practice and research: This study underscores the importance of spreading knowledge, and has clinical adapted guidelines about the practical aspects of SSC for infants born at 22-23 GW. Future research is required to clarify safety aspects pertaining to SSC for the most extremely preterm infants. [ABSTRACT FROM AUTHOR]

Importance: Objective measures of lung function are critical for assessing respiratory outcomes of prematurity. Among extremely low gestational age neonates (ELGANs) (< 29 weeks gestational age), high rates of neurodevelopmental impairment may interfere with lung function testing. Impulse oscillometry (IOS) is a noninvasive test of respiratory system mechanics not requiring forced expiration. Objective: To describe a multicenter study design for respiratory follow‐up testing in a cohort with a high rate of extreme prematurity. Methods: School‐age children enrolled in two prior trials of ELGANs and term controls were assessed by IOS at five centers. Groups consisted of children with prematurity with a high incidence of bronchopulmonary dysplasia, children with prematurity with no or minimal lung disease, and healthy term children. A rigorous centralized review process reviewed IOS studies for technical acceptability. Approach to design and implementation, rates of feasibility and success, and characteristics of participants are described. Results: A total of 243 children were recruited, of whom 239 (98%) attempted oscillometry. There were high rates of technical acceptability across all three cohorts (85%–90% of attempted tests), and across all five centers (80%–94% of attempted tests). Respiratory and neuromotor clinical factors associated with testing failure included a higher number of days on ventilation during neonatal intensive care, a history of intraventricular hemorrhage grade 3 or 4, and gross motor functional impairment. Interpretation: We report high rates of feasibility and success of oscillometry in a large multicenter ELGAN population, in whom neurological and developmental comorbidities likely play a confounding role. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study identified early neonatal factors predicting pre-discharge mortality among extremely preterm infants (EPIs) or extremely low birth weight infants (ELBWIs) in China, where data are scarce. Methods: We conducted a retrospective analysis of 211 (92 deaths) neonates born <28 weeks of gestation or with a birth weight <1000 g, admitted to University Affiliated Hospitals from 2013 to 2024 in Guangzhou, China. Data on 26 neonatal factors before the first 24 h of life and pre-discharge mortality were collected. LASSO–Cox regression was employed to screen predictive factors, followed by stepwise Cox regression to develop the final mortality prediction model. The model's performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic, calibration curves, and decision curve analysis. Results: The LASSO–Cox model identified 13 predictors that showed strong predictive accuracy (AUC: 0.806/0.864 in the training/validation sets), with sensitivity and specificity rates above 70%. Among them, six predictors remained significant in the final stepwise Cox model and generated similar predictive accuracy (AUC: 0.830; 95% CI: 0.775–0.885). Besides the well-established predictors (e.g., gestational age, 5 min Apgar scores, and multiplicity), this study highlights the predictive value of the maximum FiO2. It emphasizes the significance of the early use of additional doses of surfactant and umbilical vein catheterization (UVC) in reducing mortality. Conclusions: We identified six significant predictors for pre-discharge mortality. The findings highlighted the modifiable factors (FiO2, surfactant, and UVC) as crucial neonatal factors for predicting mortality risk in EPIs or ELBWIs, and offer valuable guidance for early clinical management. [ABSTRACT FROM AUTHOR]

ABSTRACT Importance Objective measures of lung function are critical for assessing respiratory outcomes of prematurity. Among extremely low gestational age neonates (ELGANs) (< 29 weeks gestational age), high rates of neurodevelopmental impairment may interfere with lung function testing. Impulse oscillometry (IOS) is a noninvasive test of respiratory system mechanics not requiring forced expiration. Objective To describe a multicenter study design for respiratory follow‐up testing in a cohort with a high rate of extreme prematurity. Methods School‐age children enrolled in two prior trials of ELGANs and term controls were assessed by IOS at five centers. Groups consisted of children with prematurity with a high incidence of bronchopulmonary dysplasia, children with prematurity with no or minimal lung disease, and healthy term children. A rigorous centralized review process reviewed IOS studies for technical acceptability. Approach to design and implementation, rates of feasibility and success, and characteristics of participants are described. Results A total of 243 children were recruited, of whom 239 (98%) attempted oscillometry. There were high rates of technical acceptability across all three cohorts (85%–90% of attempted tests), and across all five centers (80%–94% of attempted tests). Respiratory and neuromotor clinical factors associated with testing failure included a higher number of days on ventilation during neonatal intensive care, a history of intraventricular hemorrhage grade 3 or 4, and gross motor functional impairment. Interpretation We report high rates of feasibility and success of oscillometry in a large multicenter ELGAN population, in whom neurological and developmental comorbidities likely play a confounding role.

Abstract Background Cytokines and growth factors (GF) have been implicated in the development of retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD). We hypothesize that even small coordinated changes in inflammatory proteins or GFs may reveal changes in underlying regulating mechanisms that do not induce obvious changes in concentration of individual proteins. We therefore applied correlation network analysis of serum factors to determine early characteristics of these conditions. Methods Concentrations of 17 cytokines and five GFs were measured and analysed in blood samples from cord blood, on day one and during the following month in 72 extremely preterm infants. Spearman’s correlation networks distinguishing BPD and severe ROP patients from non-affected were created. Results Most cytokine concentrations correlated positively with each other and negatively with GFs. Very few individual cytokines differed between patients with and without ROP or BPD. However, networks of differently correlated serum factors were characteristic of the diseases and changed with time. In ROP networks, EPO, G-CSF and IL-8 (cord blood), BDNF and VEGF-A (first month) were prominent. In BPD networks, IL-1β, IGF-1 and IL-17 (day one) were noted. Conclusions Network analysis identifies protein signatures related to ROP or BPD in extremely preterm infants. The identified interactions between serum factors are not evident from the analysis of their individual levels, but may reveal underlying pathophysiological mechanisms in the development of these diseases.

Background: Cytokines and growth factors (GF) have been implicated in the development of retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD). We hypothesize that even small coordinated changes in inflammatory proteins or GFs may reveal changes in underlying regulating mechanisms that do not induce obvious changes in concentration of individual proteins. We therefore applied correlation network analysis of serum factors to determine early characteristics of these conditions. Methods: Concentrations of 17 cytokines and five GFs were measured and analysed in blood samples from cord blood, on day one and during the following month in 72 extremely preterm infants. Spearman's correlation networks distinguishing BPD and severe ROP patients from non-affected were created. Results: Most cytokine concentrations correlated positively with each other and negatively with GFs. Very few individual cytokines differed between patients with and without ROP or BPD. However, networks of differently correlated serum factors were characteristic of the diseases and changed with time. In ROP networks, EPO, G-CSF and IL-8 (cord blood), BDNF and VEGF-A (first month) were prominent. In BPD networks, IL-1β, IGF-1 and IL-17 (day one) were noted. Conclusions: Network analysis identifies protein signatures related to ROP or BPD in extremely preterm infants. The identified interactions between serum factors are not evident from the analysis of their individual levels, but may reveal underlying pathophysiological mechanisms in the development of these diseases. [ABSTRACT FROM AUTHOR]

Introduction: Despite advances in neonatal care, late-onset sepsis remains an important cause of preventable morbidity and mortality. Neonatal late-onset sepsis rates have decreased in some countries, while in others they have not. Our objective was to compare trends in late-onset sepsis rates in 9 population-based networks from 10 countries and to assess the associated mortality within 7 days of late-onset sepsis. Methods: We performed a retrospective population-based cohort study. Infants born at 24–28 weeks' gestation between 2007 and 2019 were eligible for inclusion. Late-onset sepsis was defined as a positive blood or cerebrospinal fluid culture. Late-onset sepsis rates were calculated for 3 epochs (2007–11, 2012–15, and 2016–19). Adjusted risk ratios (aRRs) for late-onset sepsis were calculated for each network. Results: Of a total of 82,850 infants, 16,914 (20.4%) had late-onset sepsis, with Japan having the lowest rate (7.1%) and Spain the highest (44.6%). Late-onset sepsis rates decreased in most networks and remained unchanged in a few. Israel, Sweden, and Finland showed the largest decrease in late-onset sepsis rates. The aRRs for late-onset sepsis showed wide variations between networks. The rate of mortality temporally related to late-onset sepsis was 10.9%. The adjusted mean length of stay for infants with late-onset sepsis was increased by 5–18 days compared to infants with no late-onset sepsis. Conclusions: One in 5 neonates of 24–28 weeks' gestation develops late-onset sepsis. Wide variability in late-onset sepsis rates exists between networks with most networks exhibiting improvement. Late-onset sepsis was associated with increased mortality and length of stay. [ABSTRACT FROM AUTHOR]

Introduction: Infants born extremely preterm are at high risk for neurodevelopmental problems. However, their neurodevelopment exhibits a variety of trajectories. This study aimed to investigate the association between changes in neurodevelopmental outcomes and clinical characteristics among extremely preterm infants. Methods: This is a retrospective study of surviving children born at gestational age 22–28 weeks in Kyushu University Hospital between 2010 and 2020. We collected perinatal and post-discharge data and investigated the association between clinical characteristics and changes in developmental quotient (DQ) scores between 1.5 and 3 years of corrected age. Results: Out of the 179 eligible extremely preterm infants, 115 (64%) underwent neurological evaluations at 1.5 and 3 years of corrected age. Among them, 33 (29%) showed improvement in their DQ scores (+10 or more), 62 (54%) showed no change (−9 to +9), and 20 (17%) showed a decline (−10 or less). Gestational age, birth weight, and perinatal complications during the NICU stay did not affect individual changes in DQ scores. Multivariable analysis revealed that greater growth in height until age 3 years was a significant predictor of increasing DQ scores, while male sex and having siblings had a negative effect on changes in the DQ scores. Conclusion: We first demonstrate clinical data conceptualizing that growth in height, sex, and sibling status, rather than perinatal complications, are biologically linked with favorable or unfavorable neurodevelopmental changes of extremely preterm infants during the first 3 years of life. [ABSTRACT FROM AUTHOR]

Abstract Background Due to regional and cultural differences, the current status of extremely preterm infants(EPIs) treatment across different areas of mainland China remains unclear. This study investigated the survival rate and incidence of major diseases among EPIs in the southwest area of Fujian province. Method This retrospective and multicenter study collected perinatal data from EPIs with gestational ages between 22–27+ 6w and born in the southwest area of Fujian province. The study population was divided into 6 groups based on gestational age at delivery. The primary outcome was the survival status at ordered hospital discharge or correct gestational age of 40 weeks, and the secondary outcome was the incidence of major diseases. The study analyzed the actual survival status of EPIs in the area. Result A total of 2004 preterm infants with gestational ages of 22–27+ 6 weeks were enrolled in this study. Among them, 1535 cases (76.6%) were born in the delivery room but did not survive, 469 cases (23.4%) were transferred to the neonatal department for treatment, 101 cases (5.0%) received partial treatment, and 368 cases (18.4%) received complete treatment. The overall all-cause mortality rate was 84.4% (1691/2004). The survival rate and survival rate without major serious disease for EPIs who received complete treatment were 85.1% (313/368) and 31.5% (116/318), respectively. The survival rates for gestational ages 22–22+ 6w, 23–23+ 6w, 24–24+ 6w, 25–25+ 6w, 26–26+ 6w, and 27–27+ 6w were 0%, 0%, 59.1% (13/22), 83% (39/47), 88.8% (87/98), and 89.7% (174/198), respectively. The survival rates without major serious disease were 0%, 0%, 9.1% (2/22), 19.1% (9/47), 27.6% (27/98), and 40.2% (78/194), respectively. Conclusion The all-cause mortality of EPIs in the southwest area of Fujian Province remains high, with a significant number of infants were given up after birth in the delivery room being the main influencing factor. The survival rate of EPIs who received complete treatment at 25–27 weeks in the NICU was similar to that in developed countries. However, the survival rate without major serious disease was significantly lower compared to high-income countries.

Abstract Background Extremely preterm infants (EPIs) frequently encounter challenges in feeding due to their underdeveloped digestive systems. Attaining full enteral feeding at the earliest possible stage can facilitate the removal of vascular catheters and decrease catheter-related complications. Methods We performed a retrospective cohort study comprising 145 extremely preterm infants with a gestational age

Background: Due to regional and cultural differences, the current status of extremely preterm infants(EPIs) treatment across different areas of mainland China remains unclear. This study investigated the survival rate and incidence of major diseases among EPIs in the southwest area of Fujian province. Method: This retrospective and multicenter study collected perinatal data from EPIs with gestational ages between 22–27+ 6w and born in the southwest area of Fujian province. The study population was divided into 6 groups based on gestational age at delivery. The primary outcome was the survival status at ordered hospital discharge or correct gestational age of 40 weeks, and the secondary outcome was the incidence of major diseases. The study analyzed the actual survival status of EPIs in the area. Result: A total of 2004 preterm infants with gestational ages of 22–27+ 6 weeks were enrolled in this study. Among them, 1535 cases (76.6%) were born in the delivery room but did not survive, 469 cases (23.4%) were transferred to the neonatal department for treatment, 101 cases (5.0%) received partial treatment, and 368 cases (18.4%) received complete treatment. The overall all-cause mortality rate was 84.4% (1691/2004). The survival rate and survival rate without major serious disease for EPIs who received complete treatment were 85.1% (313/368) and 31.5% (116/318), respectively. The survival rates for gestational ages 22–22+ 6w, 23–23+ 6w, 24–24+ 6w, 25–25+ 6w, 26–26+ 6w, and 27–27+ 6w were 0%, 0%, 59.1% (13/22), 83% (39/47), 88.8% (87/98), and 89.7% (174/198), respectively. The survival rates without major serious disease were 0%, 0%, 9.1% (2/22), 19.1% (9/47), 27.6% (27/98), and 40.2% (78/194), respectively. Conclusion: The all-cause mortality of EPIs in the southwest area of Fujian Province remains high, with a significant number of infants were given up after birth in the delivery room being the main influencing factor. The survival rate of EPIs who received complete treatment at 25–27 weeks in the NICU was similar to that in developed countries. However, the survival rate without major serious disease was significantly lower compared to high-income countries. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to assess the predictive capability of synthetic MRI in assessing neurodevelopmental outcomes for extremely preterm neonates with low-grade Germinal Matrix-Intraventricular Hemorrhage (GMH-IVH). The study also investigates the potential enhancement of predictive performance by combining relaxation times from different brain regions. Materials and methods: In this prospective study, 80 extremely preterm neonates with GMH-IVH underwent synthetic MRI around 38 weeks, between January 2020 and June 2022. Neurodevelopmental assessments at 18 months of corrected age categorized the infants into two groups: those without disability (n = 40) and those with disability (n = 40), with cognitive and motor outcome scores recorded. T1, T2 relaxation times, and Proton Density (PD) values were measured in different brain regions. Logistic regression analysis was utilized to correlate MRI values with neurodevelopmental outcome scores. Synthetic MRI metrics linked to disability were identified, and combined models with independent predictors were established. The predictability of synthetic MRI metrics in different brain regions and their combinations were evaluated and compared with internal validation using bootstrap resampling. Results: Elevated T1 and T2 relaxation times in the frontal white matter (FWM) and caudate were significantly associated with disability (p < 0.05). The T1- FWM, T1-Caudate, T2-FWM, and T2-Caudate models exhibited overall predictive performance with AUC values of 0.751, 0.695, 0.856, and 0.872, respectively. Combining these models into T1-FWM + T1-Caudate + T2-FWM + T2-Caudate resulted in an improved AUC of 0.955, surpassing individual models (p < 0.05). Bootstrap resampling confirmed the validity of the models. Conclusion: Synthetic MRI proves effective in early predicting adverse outcomes in extremely preterm infants with GMH-IVH. The combination of T1-FWM + T1- Caudate + T2-FWM + T2-Caudate further enhances predictive accuracy, offering valuable insights for early intervention strategies. [ABSTRACT FROM AUTHOR]

Background: Extremely preterm infants (EPIs) frequently encounter challenges in feeding due to their underdeveloped digestive systems. Attaining full enteral feeding at the earliest possible stage can facilitate the removal of vascular catheters and decrease catheter-related complications. Methods: We performed a retrospective cohort study comprising 145 extremely preterm infants with a gestational age < 28 weeks who underwent non-invasive mechanical ventilation at Shenzhen Maternity & Child Healthcare Hospital between January 2019 and June 2020. The KMC group received standard nursing care along with KMC, while the control group received standard nursing care without KMC. KMC initiation took place three weeks after admission and continued for a period of two weeks or more while maintaining stable vital signs. We evaluated the rate of exclusive breastmilk feeding within 24 h prior to discharge and the time to full enteral feeding throughout hospitalization. Additionally, we conducted a multiple linear regression analysis to identify the independent factors associated with exclusive breastmilk feeding rates and the time to full enteral feeding. Results: The KMC group exhibited a significantly higher rate of exclusive breastmilk feeding in the 24 h before discharge in comparison to the Non-KMC group (52.8% vs. 31.5%, OR 2.43; 95% CI 1.24, 4.78). Moreover, the KMC group achieved full enteral feeding in a shorter duration than the Non-KMC group (43.1 ± 9.6 days vs. 48.7 ± 6.9 days, p < 0.001). Multiple linear regression analysis revealed that KMC was an independent protective factor associated with improved exclusive breastmilk feeding rates (OR 2.43; 95% CI 1.24, 4.78) and a reduction in the time to full enteral feeding (β -5.35, p < 0.001) in extremely preterm infants. Conclusion: Kangaroo Mother Care (KMC) can expedite the achievement of full enteral feeding and enhance exclusive breastmilk feeding rates in extremely preterm infants receiving non-invasive assisted ventilation. These findings highlight the beneficial effects of KMC on the feeding outcomes of this vulnerable population, underscoring the importance of implementing KMC as a part of comprehensive care for extremely preterm infants. [ABSTRACT FROM AUTHOR]

Background Aim Study Design Results Conclusions Relevance to Clinical Practice Kangaroo care (KC) is an evidence‐based best practice that can prevent major health complications in preterm infants. However, there is a lack of evidence on the feasibility and safety of placing extremely preterm infants under 28 weeks gestational age in KC position.To compare thermal stability 60 min after the first KC session in the lateral versus prone position in extremely preterm infants under 28 weeks gestational age.This is a single‐centre, randomized, non‐inferiority, parallel clinical trial. The patients were extremely preterm infants during their first 5 days of life. Infants in the intervention group received KC in the lateral position while those in the control group received KC in the prone position. All infants receiving KC were inside their polyethylene bags but maintained skin‐to‐skin contact. The primary outcome was the axillary temperature of the infants, and the secondary outcome was the development of intraventricular haemorrhage.Seventy infants were randomized (35 per group). The mean gestational age was 26 +1(1+1) in both groups. In the first KC session, the infant temperature at 60 minutes was 36.79°C (0.43) in lateral KC position, and 36.78°C (0.38) in prone KC position (p = .022). In lateral KC position, 7.69% (2) of the children who, according to the cranial ultrasound performed before the first session, had no haemorrhage presented with intraventricular haemorrhage after the first session. In prone KC position, new haemorrhages appeared after the first session in 29.17% (7) (p = .08).The lateral KC position is an alternative to the conventional prone KC position and maintains normothermia in infants under 28 weeks gestational age.Extremely preterm infants are candidates for KC. Lateral KC position is an evidence‐based best practice that can be applied to preterm infants under 28 weeks GA. This evidence is particularly useful in performing umbilical catheterization on these patients. [ABSTRACT FROM AUTHOR]

This study aims to evaluate in extremely premature infants the severity of brain structural injury causing total absence or near-total absence of cerebellar hemispheres by using MRI visual and volumetric scoring systems. It also aims to assess the role of the score systems in predicting motor outcome. We developed qualitative and quantitative MRI scoring systems to grade the overall brain damage severity in 16 infants with total absence or near-total absence of cerebellar hemispheres. The qualitative scoring system assessed the severity of macrostructural abnormalities of cerebellum, brainstem, supratentorial gray and white matters, ventricles while the quantitative scoring system weighted the loss of brain tissue volumes, and gross motor function classification system (GMFCS) was used to assess motor function at 1- and 5-year follow-ups. Positive correlations between both MRI scores and GMFCS scales were detected at follow-ups (p > 0.05), but only the volumetric score could identify those infants developing higher levels of motor impairment. Brain volumetric MRI offers an unbiassed assessment of prenatal brain damage. The quantitative scoring system, performed at term equivalent age, can be a helpful tool for predicting the long-term motor outcome in extremely preterm infants with a near-total absence of cerebellum. [ABSTRACT FROM AUTHOR]

Aim: The current study determined the neurodevelopmental outcome of extremely preterm infants at 2 years of age. Methods: All live-born infants 23-27 weeks of gestation born between 2011 and 2020 in Austria were included in a prospective registry. Neurodevelopmental outcome at 2 years of corrected age was assessed using Bayley Scales of Infant Development for both motor and cognitive scores, along with a neurological examination and an assessment of neurosensory function. Results: 2378 out of 2905 (81.9%) live-born infants survived to 2 years of corrected age. Follow-up data were available for 1488 children (62.6%). Overall, 43.0% had no, 35.0% mild and 22.0% moderate-to-severe impairment. The percentage of children with moderate-to-severe neurodevelopmental impairment decreased with increasing gestational age and was 31.4%, 30.5%, 23.3%, 19.0% and 16.5% at 23, 24, 25, 26 and 27 weeks gestational age (p < 0.001). Results did not change over the 10-year period. In multivariate analysis, neonatal complications as well as male sex were significantly associated with an increased risk of neurodevelopmental impairment. Conclusion: In this cohort study, a 22.0% rate of moderate-to-severe neurodevelopmental impairment was observed among children born extremely preterm. This national data is important for both counselling parents and guiding the allocation of health resources. [ABSTRACT FROM AUTHOR]

BackgroundSerum lactate levels are used as biomarkers for perinatal asphyxia, while their value for outcome prediction in preterm infants is uncertain. It was the aim of this observational study to determine the association of the first postnatal serum-lactate levels on day 1 of life and short-term outcome in preterm infants less than 29 gestational weeks.MethodsWe analysed data in a population-based cohort of German Neonatal Network (GNN) preterm infants with available first postnatal lactate levels enrolled at 22–28 weeks of gestational age (GA) between 1st of April 2009 and 31st December 2020. We hypothesized that high lactate levels as measured in mmol/L increase the risk of intraventricular haemorrhage (IVH) and bronchopulmonary dysplasia (BPD) in infants with VLBW regardless of small-for-gestational-age (SGA) status. Hypotheses were evaluated in univariate analyses and multiple logistic regression models.ResultsFirst postnatal lactate levels were available in 2499 infants. The study population had a median GA of 26.7 [IQR 25.2–27.9] weeks and birth weight of 840 g [IQR 665–995]. Infants with short-term complications such as IVH and BPD had higher initial lactate levels than non-affected infants. The positive predictive value of a lactate cut-off of 4 mmol/L was 0.28 for IVH and 0.30 for BPD. After adjustment for known confounding variables, each 1 mmol/L increase of day 1 lactate levels was associated with a modestly increased risk of IVH (OR 1.18; 95% CI 1.03–1.37; p = 0.002) and BPD (OR 1.23; 95% CI 1.06–1.43; p = 0.005) but not with sepsis or mortality. Notably, SGA was associated with lower risk of any grade and severe IVH (OR 0.70; 95% CI 0.54–0.85; p = 0.001).ConclusionsIn our observational cohort study higher initial lactate levels were associated with adverse outcome regardless of SGA status. However, the predictive value of lactate cut-off levels such as 4 mmol/L is low.

Background Early hypocapnia in extremely preterm infants is associated with intraventricular hemorrhage (IVH) and bronchopulmonary dysplasia (BPD). The results of foreign studies show that high frequency oscillatory ventilation combined with volume guarantee ventilation (HFOV+VG) has been confirmed to reduce hypocapnia in preterm infants, but less is known of using HFOV+VG in extremely preterm infants born at 0.05) . Conclusion Compared with SIMV ventilation, HFOV+VG ventilation in extremely preterm infants born at

Data from the Neonatal Oxygenation Prospective Meta-analysis (NeOProM) indicate that targeting a higher (91–95%) versus lower (85–89%) pulse oximeter saturation (SpO2) range may reduce mortality and necrotizing enterocolitis (NEC) and increase retinopathy of prematurity (ROP). Aiming to re-evaluate the strength of this evidence, we conducted a Bayesian reanalysis of the NeOProM data. We used Bayes factors (BFs) to evaluate the likelihood of the data under the combination of models assuming the presence vs. absence of effect, heterogeneity, and moderation by sex. The Bayesian reanalysis showed moderate evidence in favor of no differences between SpO2 targets (BF10 = 0.30) in death or major disability, but moderate evidence (BF10 = 3.60) in favor of a lower mortality in the higher SpO2 group. Evidence in favor of differences was observed for bronchopulmonary dysplasia (BPD) (BF10 = 14.44, lower rate with lower SpO2), severe NEC (BF10 = 9.94), and treated ROP (BF10 = 3.36). The only outcome with moderate evidence in favor of sex differences was BPD. This reanalysis of the NeOProM trials confirmed that exposure to a lower versus higher SpO2 range is associated with a higher mortality and risk of NEC, but a lower risk of ROP and BPD. The Bayesian approach can help in assessing the strength of evidence supporting clinical decisions. [ABSTRACT FROM AUTHOR]

To investigate the effect of perinatal interventions on the risk of severe BPD (sBPD) and death in extremely preterm infants (EPIs) and their synergistic effects. This was a secondary analysis of the prospective cohort Chinese Neonatal Network (CHNN). Infants with a birth weight of 500 to 1250 g or 24–28 weeks completed gestational age were recruited. The impacts and the synergistic effects of six evidence-based perinatal interventions on the primary outcomes of sBPD and death were assessed by univariate and multivariable logistic regression modeling. Totally, 6568 EPIs were finally enrolled. Antenatal corticosteroid (adjusted OR, aOR, 0.74; 95%CI, 0.65–083), birth in centers with tertiary NICU (aOR, 0.64; 95%CI, 0.57–0.72), preventing intubation in the delivery room (aOR, 0.65; 95%CI, 0.58–0.73), early caffeine therapy (aOR, 0.59; 95%CI, 0.52–0.66), and early extubating (aOR, 0.42; 95%CI 0.37–0.47), were strongly associated with a lower risk of sBPD and death while early surfactant administration was associated with a lower risk of death (aOR, 0.84; 95%CI, 0.72, 0.98). Compared with achieving 0/1 perinatal interventions, achieving more than one intervention was associated with decreased rates (46.6% in 0/1 groups while 38.5%, 29.6%, 22.2%, 16.2%, and 11.7% in 2/3/4/5/6-intervention groups respectively) and reduced risks of sBPD/death with aORs of 0.76(0.60, 0.96), 0.55(0.43, 0.69), 0.38(0.30, 0.48), 0.28(0.22, 0.36), and 0.20(0.15, 0.27) in 2, 3, 4, 5, and 6 intervention groups respectively. Subgroup analyses showed consistent results. Conclusion: Six perinatal interventions can effectively reduce the risk of sBPD and death in a synergistic form. What is Known: • Bronchopulmonary dysplasia (BPD) is a multifactorial chronic lung disease associated with prematurity. The effective management of BPD requires a comprehensive set of interventions. However, the extent to which these interventions can mitigate the risk of severe outcomes, such as severe BPD or mortality, or if they possess synergistic effects remains unknown. What is New: • The implementation of various perinatal interventions, such as prenatal steroids, birth in centers with tertiary NICU, early non-Invasive respiratory support, surfactant administration within 2 hours after birth, early caffeine initiation within 3 days, and early extubation within 7 days after birth has shown promising results in the prevention of severe bronchopulmonary dysplasia (BPD) or mortality in extremely preterm infants. Moreover, these interventions have demonstrated synergistic effects when implemented in combination. [ABSTRACT FROM AUTHOR]

This meta-analysis assessed short-term outcomes after using human milk-derived fortifiers (HMFs) compared with bovine milk fortifiers (BMFs) in preterm infants fed an exclusive human milk (HM) diet, either mother's own milk (MOM) or donor human milk (DHM). We searched PubMed, Embase, Google Scholar, CENTRAL and CINHAL between January 2015 and August 2023 for studies reporting outcomes in infants with ≤28 weeks gestation and/or birthweight ≤ 1500 g on an exclusive human milk diet fortified with HMF versus BMF. The primary outcomes were death and NEC (stage ≥ 2). Four studies with a total of 681 infants were included. Mortality was significantly lower in infants fed with an HM-HMFs diet (four studies, 681 infants; RR = 0.50, 95% CI = 0.26–0.94; p = 0.03; I2 = 0%), NEC was similar between the two groups (four studies, 681 infants; RR = 0.48, 95% CI = 0.20–1.17; p = 0.11; I2= 39%). BPD was higher in the HM-BMFs group (four studies, 663 infants; RR = 0.83, 95% CI = 0.69–1.000; p = 0.05, I2 = 0%), although not statistically significant. No differences were found for sepsis (RR = 0.97, 95% CI = 0.66–1.42; p = 0.96; I2 = 26%) or combined ROP (four studies, 671 infants; RR = 0.64, 95% CI = 0.53–1.07; p = 0.28; I2 = 69%). An HM-HMFs diet could possibly be associated with decreased mortality with no association with NEC, BPD, sepsis, or ROP. This meta-analysis was limited by the small number of studies included. However, the results should not be refuted for this reason as they provide an impetus for subsequent clinical trials to assess the observed associations. [ABSTRACT FROM AUTHOR]

Background and Objectives: The purpose of this study to investigate if the early variations in the hematological profile could be a useful tool in the prediction and evaluation of intraventricular hemorrhage. Materials and Methods: It is a retrospective study conducted between 1 January 2017 and 31 December 2022, in a tertiary academic center. In-born infants ≤ 28 weeks of gestation (n = 134) were enrolled. The study group of infants with all grades of IVH was further divided into mild IVH subgroups (grades 1 and 2) and severe IVH subgroups (grades 3 and 4); the control group included infants without IVH. Results: The prevalence of IVH was 35.8% (n = 48 of 134 infants—study group). We identified significantly lower median values of HGB (p = 0.0312) and HCT (p = 0.0172) in all grades of the IVH group at birth as compared with control, followed by a significantly higher drop in MCV (p = 0.0146) and MCH (p = 0.0002) in the fourth day of life. Conclusions: Extremely preterm infants with IVH may have lower HTC and HGB values at birth, together with a decrease in MCH and MCHC and increase in MPV. The predictive model based on logistic regression analysis could predict the probability of the occurrence of IVH according to their values. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study identified early neonatal factors predicting pre-discharge mortality among extremely preterm infants (EPIs) or extremely low birth weight infants (ELBWIs) in China, where data are scarce. Methods: We conducted a retrospective analysis of 211 (92 deaths) neonates born 2. It emphasizes the significance of the early use of additional doses of surfactant and umbilical vein catheterization (UVC) in reducing mortality. Conclusions: We identified six significant predictors for pre-discharge mortality. The findings highlighted the modifiable factors (FiO2, surfactant, and UVC) as crucial neonatal factors for predicting mortality risk in EPIs or ELBWIs, and offer valuable guidance for early clinical management.

IntroductionThe association between neonatal intensive care unit (NICU) related stress in preterm infants and their health-related quality of life (HRQoL) in the first year following preterm birth remains unexplored. Understanding this association is crucial for enhancing preventive and supportive measures for infants and parents within and beyond the NICU.MethodsFrom a single center observational cohort study, we included infants with gestational ages below 30 weeks and/or birth weights under 1,000 grams. HRQoL was quantified using the Infant Quality of Life Instrument (IQI) at 3-, 6-, 9- and 12-months corrected age, covering seven domains. NICU stress was quantified using the Neonatal Infant Stressor Scale (NISS) for the first week of life. We performed Spearman's correlation analyses to test this association.ResultsOf the 45 included infants, the IQI was completed for 27 (60%) at 3, 15 (33%) at 6, 14 (31%) at 9 and 15 (33%) at 12 months. The HRQoL sum scores were related to neonatal stress at 9 and 12 months (ρ = 0.643 and 0.591, p = 0.013 and p = 0.019, respectively) but not at 3 and 6 months (ρ = −0.001 and −0.077 respectively, p > 0.05). Higher NICU stress tended to be associated with more respiratory and mood problems throughout the first year.DiscussionFrom a parental perspective on infant HRQoL, extremely preterm infants with higher stress exposure show more problems in the second half-year of life, mainly breathing and possibly mood-related problems. This knowledge may help improve our neonatal care, both during NICU stay and in follow-up clinics, by implementing targeted interventions.

Background: Adequate perinatal management is essential in caring for extremely preterm (EP) infants. We aimed to evaluate and compare the impact of different protocols on short-term outcomes. Methods: A retrospective study was conducted on EP infants in a Romanian perinatal tertiary center during 2008–2012 and 2018–2022. Results: Data on 270 EP infants (121 in period I, 149 in period II) were analyzed collectively and stratified into two subgroups by gestational age. Initial FiO2 administration (100% vs. 40%% p < 0.001), lung recruitment at birth (19.0% vs. 55.7% p < 0.001), early rescue surfactant administration (34.7% vs. 65.8%; p < 0.001), and the mechanical ventilation rate (98.3% vs. 58.4%; p < 0.001) were significantly improved during period II. Survival rates of EP infants significantly improved from 41.3% to 72.5%, particularly in the 26–28 weeks subgroup (63.8% to 83%). Compared to period I, the overall frequency of severe IVH decreased in period II from 30.6% to 14.1%; also, BPD rates were lower (36.6% vs. 23.4%; p = 0.045) in the 26–28 weeks subgroup. Despite improvements, there were no significant differences in the frequencies of NEC, sepsis, PVL, ROP, or PDA. Conclusions: Implementing evidence-based clinical guidelines can improve short-term outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background Bilirubin neurotoxicity (BN) occurs in premature infants at lower total serum bilirubin levels than term infants and causes neurodevelopmental impairment. Usual dose lipid infusions in preterm infants may increase free fatty acids sufficiently to cause bilirubin displacement from albumin, increasing passage of unbound bilirubin (UB) into the brain leading to BN and neurodevelopmental impairment not reliably identifiable in infancy. These risks may be influenced by whether cycled or continuous phototherapy is used to control bilirubin levels. Objective To assess differences in wave V latency measured by brainstem auditory evoked responses (BAER) at 34–36 weeks gestational age in infants born ≤ 750 g or

IntroductionExtremely preterm infants (EPIs) have high morbidity and mortality, and are recommended to be born in a tertiary perinatal center (inborn). However, many EPIs in central China are born in lower-level hospitals and transferred postnatally, the outcomes of which remain to be investigated.MethodsEPIs admitted to the Department of Neonatology, Maternal and Child Health Hospital of Hubei Province from January 2013 to December 2022 were retrospectively recruited and divided into the control (inborn) and transfer groups (born in other hospitals). The neonatal and maternal characteristics, neonatal outcomes, and the treatment of survival EPIs were analyzed.ResultsA total of 174 and 109 EPIs were recruited in the control and transfer groups, respectively. EPIs in the transfer group have a higher birth weight and a lower proportion of multiple pregnancies than the control group (all P 0.05). However, the transfer group had higher proportions of severe birth asphyxia (34.86% vs. 13.22%, P

Summary: Background: The optimal treatment strategy for patent ductus arteriosus (PDA) in extremely preterm infants is currently highly controversial. This study aimed to evaluate the association between PDA treatment and short-term outcomes among extremely preterm infants. Methods: This cohort study included all extremely preterm infants (≤27 and 6/7 weeks) who were admitted to hospitals participating in the Chinese Neonatal Network from January 2019 to December 2021, and were diagnosed to have PDA by echocardiogram. PDA treatment was defined as medical treatment and/or surgical ligation of PDA during hospitalization. Short-term outcomes included death, bronchopulmonary dysplasia (BPD), death/BPD, retinopathy of prematurity, necrotizing enterocolitis, and severe brain injury. Multivariate logistic regression was used to evaluate the association between PDA treatment and outcomes. Subgroup analysis were performed among infants with different respiratory support on 3 and 7 days of life. Findings: A total of 2494 extremely preterm infants with the diagnosis of PDA were enrolled, of which 1299 (52.1%) received PDA treatment. PDA treatment was significantly associated with lower risk of death (adjusted odds ratio, 0.48; 95% confidence interval, 0.38–0.60). The decreased risk of death was accompanied by increased risk of BPD and death/BPD. In subgroup analysis according to respiratory support, PDA treatment was associated with lower risk of death among infants who required invasive ventilation. However, the beneficial effect on death was not significant among infants who did not require invasive ventilation. Interpretation: PDA treatment was associated with reduced mortality in extremely preterm infants, but this beneficial effect was mainly present among infants who required invasive ventilation. Funding: This study was funded by the Shanghai Science and Technology Commission's Scientific and Technological Innovation Action Plan (21Y21900800) and the Canadian Institutes of Health Research (CTP87518).

ObjectivesNeonatologists and obstetricians are crucial decision-makers regarding the resuscitation of extremely preterm infants (EPIs). However, there is a scarcity of research regarding the differing perspectives on EPI resuscitation between these medical professionals. We aim to determine the differences and influential factors of their attitudes towards EPIs resuscitation in China.MethodsThis cross-sectional study was conducted in public hospitals of 31 provinces in Chinese mainland from June to July 2021. Influential factors of binary variables and those of ordinal variables were analyzed by modified Poisson regression models and multinomial logistic regression models due to the invalid parallel line assumption of ordinal logistic regression models.ResultsA total of 832 neonatologists and 1,478 obstetricians who were deputy chief physicians or chief physicians participated. Compared with obstetricians, neonatologists delivered a larger proportion of infants of

Objective This study aimed to identify extremely premature infants (< 31 weeks of gestation and/or <1,500 g) affected by congenital hypothyroidism (CH) with delayed elevation of thyrotropin (TSH) and to evaluate the detection strategy for this pathology in our reference screening population. Study Design A descriptive and retrospective study was carried out with samples collected from western Andalusia and the autonomous city of Ceuta. Results This protocol allowed us to detect six neonates with delayed TSH elevation. One of them, due to serious heart problems, died without being able to confirm CH. In two neonates, however, it was possible to detect CH, another two presented a persistent TSH elevation but normal free T4, and another one presented a temporary TSH elevation. Conclusion It is essential to repeat the CH screening in extremely premature infants, not only at the age of 15 days but also with a third sample at the moment of hospital discharge to detect cases with delayed TSH elevation. Key Points The Newborn Screening Programs are an essential activity of preventive medicine. Extremely preterm infants have a very high risk of CH. Optimal management of thyroid dysfunction in this population remains to be established. [ABSTRACT FROM AUTHOR]

Objectives: Corticosteroids are used to prevent or treat lung disease of prematurity. While neurological side effects have been reported, detailed effects on cerebellar growth are unknown. This study aimed to compare cerebellar growth in premature infants who received dexamethasone or hydrocortisone to premature infants who did not receive postnatal corticosteroids. Study Design: Retrospective case-control study in infants born at a gestational age of <29 weeks and admitted to two level 3 neonatal intensive care units. Exclusion criteria were severe congenital anomalies and cerebellar or severe supratentorial lesions. Infants were treated with dexamethasone (unit 1) or hydrocortisone (unit 2) for chronic lung disease. Controls (unit 1) did not receive postnatal corticosteroids. Sequential head circumference (HC) and ultrasound measurements of transcerebellar diameter (TCD), biparietal diameter (BPD), and corpus callosum-fastigium length (CCFL) were performed until 40 weeks' postmenstrual age (PMA). Growth was assessed using linear mixed models correcting for PMA at measurement, sex, HC z-score at birth, and a propensity score indicating illness severity. Group differences before treatment were assessed using linear regression. Results: 346 infants were included (68 dexamethasone, 37 hydrocortisone, 241 controls). Before starting corticosteroids, TCD, BPD, and HC measurements did not differ between patients and controls at a comparable PMA. After starting treatment, both types of corticosteroid had a negative association with TCD growth. BPD, CCFL, and HC growth were not negatively affected. Conclusion: Administration of dexamethasone and hydrocortisone are both associated with impaired cerebellar growth in premature infants without evident negative associations with cerebral growth. [ABSTRACT FROM AUTHOR]

Aim: To describe the circumstances, causes and timing of death in extremely preterm infants. Methods: We included from the EPIPAGE‐2 study infants born at 24–26 weeks in 2011 admitted to neonatal intensive care units (NICU). Vital status and circumstances of death were used to define three groups of infants: alive at discharge, death with or without withholding or withdrawing life‐sustaining treatment (WWLST). The main cause of death was classified as respiratory disease, necrotizing enterocolitis, infection, central nervous system (CNS) injury, other or unknown. Results: Among 768 infants admitted to NICU, 224 died among which 89 died without WWLST and 135 with WWLST. The main causes of death were respiratory disease (38%), CNS injury (30%) and infection (12%). Among the infants who died with WWLST, CNS injury was the main cause of death (47%), whereas respiratory disease (56%) and infection (20%) were the main causes in case of death without WWLST. Half (51%) of all deaths occurred within the first 7 days of life, and 35% occurred within 8 and 28 days. Conclusion: The death of extremely preterm infants in NICU is a complex phenomenon in which the circumstances and causes of death are intertwined. [ABSTRACT FROM AUTHOR]

Objective This study aimed to determine the association between daily fluid intake and the duration of hemodynamically significant patent ductus arteriosus (hsPDA). Study Design This is a retrospective cohort study of extremely preterm infants (<29 weeks) admitted in the Neonatal Intensive Care Unit of the Advent Health for Children from January 2013 to March 2016, if hsPDA was diagnosed in first week of life and serial echocardiograms were available. Diagnosis of hsPDA was based on a scoring system and its duration was estimated from serial echocardiograms. Cohort was divided into two groups based on duration of hsPDA (<1week, group A and ≥1 week, group B). Daily fluid intake was categorized as prescribed and actual. Prescribed volume was ordered by clinicians based on birth weight, not including trophic feeds, intravenous (IV) boluses or transfusions, etc. Actual intake was calculated by the electronic medical records based on daily weights and included all enteral or parenteral fluids. Multivariate analysis was performed to determine an association between total daily fluid intake over the first week of life and the duration of hsPDA. Two groups were compared to observe the difference between prescribed and actual daily fluid intakes. Results We enrolled 50 infants in group A and 76 in group B. Infants in group B were of significantly lower gestation and required prolonged ventilation and hospitalization. An association between higher fluid intake in the first 2 days of life and prolonged duration of hsPDA was confirmed by multivariate analysis. Actual fluid intake was significantly higher than prescribed total fluid intake in first 4 days of life for infants in both groups. Conclusion In extremely preterm infants, higher fluid intake in first 2 days of life is associated with prolonged duration of hsPDA. Actual daily fluid intake can be significantly higher than prescribed daily fluids due to daily weight changes and additional fluid administration. Key Points In preterm infants, actual daily fluid intake may be higher than prescribed volume. Higher daily fluid intake in first week of life is associated with prolonged duration of PDA. PDA scoring system can be helpful for objective assessment of PDA in preterm infants. [ABSTRACT FROM AUTHOR]

Objective The study aimed to evaluate the association between bronchopulmonary dysplasia (BPD) development at 36 weeks' postmenstrual age (PMA) and Gram-negative bacteria in tracheal aspirate cultures among extremely preterm infants. Study Design This study has a retrospective cohort. Patients were 155 infants aged less than or equal to 26 gestational weeks who were admitted to the neonatal intensive care unit of Osaka Women's and Children's Hospital from 2009 to 2018. Primary outcome was respiratory outcomes expressed as BPD development. Multivariable logistic regression analysis was used to identify neonatal and bacterial factors associated with BPD. Results After adjusting for gestational age, birth weight, sex, chorioamnionitis, Gram-positive cocci (GPC) and Gram-negative rods (GNRs) in tracheal aspirate cultures within 28 days after birth, GNRs were significantly associated with BPD development (odds ratio [OR]: 3.88, 95% confidence interval [CI]: 1.68–8.94). In contrast, GPCs were not associated with BPD development (OR: 0.47, 95% CI: 0.05–1.61). Conclusion Gram-negative bacteria in tracheal cultures within 28 days of birth are associated with BPD development in infants aged less than or equal to 26 gestational weeks. Key Points BPD is a factor for morbidity in extremely preterm infants. Respiratory infection is an adverse outcome of BPD. GNRs in tracheal cultures soon after birth disturb BPD development. GPC was not associated with BPD development. [ABSTRACT FROM AUTHOR]

Mothers of extremely preterm infants experience high rates of mental health disorders that impair maternal–infant interaction and lead to worse infant developmental outcomes. Therapist Education and Massage for Parent–Infant Outcomes (TEMPO) is a therapist-led program that standardizes the nature and frequency of parent education through weekly scheduled therapy sessions. Using a family-centered approach, the therapist facilitates positive maternal–infant interactions and massage interventions from birth throughout hospitalization with the goal of improving maternal mental health. This qualitative study presents the results of 19 parent interviews and of a focus group of four TEMPO interventionists to elicit feedback about the program. Overall, parents and therapists viewed the program positively. Parents and therapists valued the focus on parent education and engagement to increase parent competence and bonding opportunities. Both groups acknowledged that infant massage had both infant-centered and parent-centered benefits. One area where parent and therapist views did not align was regarding feasibility of TEMPO. Parents noted multiple logistical challenges to regular NICU visitation, but ultimately agreed that attending weekly therapy sessions was feasible. Therapists noted increased time and effort required of TEMPO and felt that institutional and system-level changes would be necessary to implement weekly parent education as standard of care. [ABSTRACT FROM AUTHOR]

Social determinants of health (SDoH) are defined as the conditions in which people are born, grow, live, work, and age. The distribution of these conditions is influenced by underlying structural factors and may be linked to adverse pregnancy outcomes through epigenetic modifications of gestational tissues. A promising modification is epigenetic gestational age (eGA), which captures ‘biological’ age at birth. Measuring eGA in placenta, an organ critical for foetal development, may provide information about how SDoH ‘get under the skin’ during pregnancy to influence birth outcomes and ethnic/racial disparities. We examined relationships of placental eGA with sociodemographic factors, smoking, and two key clinical outcomes: Apgar scores and NICU length of stay. Using the Robust Placental Clock, we estimated eGA for placental samples from the Extremely Low Gestational Age Newborns cohort (N = 408). Regression modelling revealed smoking during pregnancy was associated with placental eGA acceleration (i.e., eGA higher than chronologic gestational age). This association differed by maternal race: among infants born to mothers racialized as Black, we observed greater eGA acceleration (+0.89 week, 95% CI: 0.38, 1.40) as compared to those racialized as white (+0.27 week, 95% CI: −0.06, 0.59). Placental eGA acceleration was also correlated with shorter NICU lengths of stay, but only among infants born to mothers racialized as Black (−0.08 d/week-eGA, 95% CI: −0.12, −0.05). Together, these observed associations suggest that interpretations of epigenetic gestational aging may be tissue-specific.

Background: Bilirubin neurotoxicity (BN) occurs in premature infants at lower total serum bilirubin levels than term infants and causes neurodevelopmental impairment. Usual dose lipid infusions in preterm infants may increase free fatty acids sufficiently to cause bilirubin displacement from albumin, increasing passage of unbound bilirubin (UB) into the brain leading to BN and neurodevelopmental impairment not reliably identifiable in infancy. These risks may be influenced by whether cycled or continuous phototherapy is used to control bilirubin levels. Objective: To assess differences in wave V latency measured by brainstem auditory evoked responses (BAER) at 34–36 weeks gestational age in infants born ≤ 750 g or < 27 weeks' gestational age randomized to receive usual or reduced dose lipid emulsion (half of the usual dose) irrespective of whether cycled or continuous phototherapy is administered. Methods: Pilot factorial randomized controlled trial (RCT) of lipid dosing (usual and reduced) with treatment groups balanced between cycled or continuous phototherapy assignment. Eligible infants are born at ≤ 750 g or < 27 weeks' gestational age enrolled in the NICHD Neonatal Research Network RCT of cycled or continuous phototherapy. Infants will randomize 1:1 to reduced or usual dose lipid assignment during the first 2 weeks after birth and stratified by phototherapy assignment. Free fatty acids and UB will be measured daily using a novel probe. BAER testing will be performed at 34–36 weeks postmenstrual age or prior to discharge. Blinded neurodevelopmental assessments will be performed at 22–26 months. Intention-to-treat analyses will be performed with generalized linear mixed models with lipid dose and phototherapy assignments as random effects covariates, and assessment for interactions. Bayesian analyses will be performed as a secondary analysis. Discussion: Pragmatic trials are needed to evaluate whether lipid emulsion dosing modifies the effect of phototherapy on BN. This factorial design presents a unique opportunity to evaluate both therapies and their interaction. This study aims to address basic controversial questions about the relationships between lipid administration, free fatty acids, UB, and BN. Findings suggesting a reduced lipid dose can diminish the risk of BN would support the need for a large multicenter RCT of reduced versus usual lipid dosing. Trial registration: Clinical Trials.gov, NCT04584983, Registered 14 October 2020, https://clinicaltrials.gov/ct2/show/NCT04584983 Protocol version: Version 3.2 (10/5/2022). [ABSTRACT FROM AUTHOR]

Preterm infants risk deficits of long-chain polyunsaturated fatty acids (LCPUFAs) that may contribute to morbidities and hamper neurodevelopment. We aimed to determine longitudinal serum fatty acid profiles in preterm infants and how the profiles are affected by enteral and parenteral lipid sources. Cohort study analyzing fatty acid data from the Mega Donna Mega study, a randomized control trial with infants born <28 weeks of gestation (n = 204) receiving standard nutrition or daily enteral lipid supplementation with arachidonic acid (AA):docosahexaenoic acid (DHA) (100:50 mg/kg/day). Infants received an intravenous lipid emulsion containing olive oil:soybean oil (4:1). Infants were followed from birth to postmenstrual age 40 weeks. Levels of 31 different fatty acids from serum phospholipids were determined by GC–MS and reported in relative (mol%) and absolute concentration (μmol l−1) units. Higher parenteral lipid administration resulted in lower serum proportion of AA and DHA relative to other fatty acids during the first 13 weeks of life (p < 0.001 for the 25th vs the 75th percentile). The enteral AA:DHA supplement increased the target fatty acids with little impact on other fatty acids. The absolute concentration of total phospholipid fatty acids changed rapidly in the first weeks of life, peaking at day 3, median (Q1-Q3) 4452 (3645–5466) μmol l−1, and was positively correlated to the intake of parenteral lipids. Overall, infants displayed common fatty acid trajectories over the study period. However, remarkable differences in fatty acid patterns were observed depending on whether levels were expressed in relative or absolute units. For example, the relative levels of many LCPUFAs, including DHA and AA, declined rapidly after birth while their absolute concentrations increased in the first week of life. For DHA, absolute levels were significantly higher compared to cord blood from day 1 until postnatal week 16 (p < 0.001). For AA, absolute postnatal levels were lower compared to cord blood from week 4 throughout the study period (p < 0.05). Our data show that parenteral lipids aggravate the postnatal loss of LCPUFAs seen in preterm infants and that serum AA available for accretion is below that in utero. Further research is needed to establish optimal postnatal fatty acid supplementation and profiles in extremely preterm infants to promote development and long-term health. ClinicalTrials.gov, identifier: NCT03201588. [ABSTRACT FROM AUTHOR]

Data from the Neonatal Oxygenation Prospective Meta-analysis (NeOProM) indicate that targeting a higher (91–95%) versus lower (85–89%) pulse oximeter saturation (SpO2) range may reduce mortality and necrotizing enterocolitis (NEC) and increase retinopathy of prematurity (ROP). Aiming to re-evaluate the strength of this evidence, we conducted a Bayesian reanalysis of the NeOProM data. We used Bayes factors (BFs) to evaluate the likelihood of the data under the combination of models assuming the presence vs. absence of effect, heterogeneity, and moderation by sex. The Bayesian reanalysis showed moderate evidence in favor of no differences between SpO2 targets (BF10 = 0.30) in death or major disability, but moderate evidence (BF10 = 3.60) in favor of a lower mortality in the higher SpO2 group. Evidence in favor of differences was observed for bronchopulmonary dysplasia (BPD) (BF10 = 14.44, lower rate with lower SpO2), severe NEC (BF10 = 9.94), and treated ROP (BF10 = 3.36). The only outcome with moderate evidence in favor of sex differences was BPD. This reanalysis of the NeOProM trials confirmed that exposure to a lower versus higher SpO2 range is associated with a higher mortality and risk of NEC, but a lower risk of ROP and BPD. The Bayesian approach can help in assessing the strength of evidence supporting clinical decisions.

Summary: Background: Gestational age (GA) and associated level of gastrointestinal tract maturation are major factors driving the initial gut microbiota composition in preterm infants. Besides, compared to term infants, premature infants often receive antibiotics to treat infections and probiotics to restore optimal gut microbiota. How GA, antibiotics, and probiotics modulate the microbiota’s core characteristics, gut resistome and mobilome, remains nascent. Methods: We analysed metagenomic data from a longitudinal observational study in six Norwegian neonatal intensive care units to describe the bacterial microbiota of infants of varying GA and receiving different treatments. The cohort consisted of probiotic-supplemented and antibiotic-exposed extremely preterm infants (n = 29), antibiotic-exposed very preterm (n = 25), antibiotic-unexposed very preterm (n = 8), and antibiotic-unexposed full-term (n = 10) infants. The stool samples were collected on days of life 7, 28, 120, and 365, and DNA extraction was followed by shotgun metagenome sequencing and bioinformatical analysis. Findings: The top predictors of microbiota maturation were hospitalisation length and GA. Probiotic administration rendered the gut microbiota and resistome of extremely preterm infants more alike to term infants on day 7 and ameliorated GA-driven loss of microbiota interconnectivity and stability. GA, hospitalisation, and both microbiota-modifying treatments (antibiotics and probiotics) contributed to an elevated carriage of mobile genetic elements in preterm infants compared to term controls. Finally, Escherichia coli was associated with the highest number of antibiotic-resistance genes, followed by Klebsiella pneumoniae and Klebsiella aerogenes. Interpretation: Prolonged hospitalisation, antibiotics, and probiotic intervention contribute to dynamic alterations in resistome and mobilome, gut microbiota characteristics relevant to infection risk. Funding: Odd-Berg Group, Northern Norway Regional Health Authority.

Objective: Exploratory secondary analysis of the CORSAD trial compared a new resuscitation system (rPAP) to the standard T-piece system. This analysis focused on the subgroup of infants who were not intubated in the delivery room. The aim was to compare the use of noninvasive positive pressure ventilation (PPV), oxygen saturation, and Apgar scores for the two resuscitation systems during the 30-min intervention period. Methods: This is secondary analysis of CORSAD trial using data from the intervention period in the delivery room. Infants in the original randomized system groups were divided into intubated and nonintubated groups. For nonintubated breathing infants, we compared demographics, the use of PPV, Apgar scores, and oxygen saturation at 5 and 10 min after birth. Generalized linear models were applied to calculate the risk difference and odds ratio with 95% CI between the two groups. Results: Among nonintubated infants, the use of PPV repeatedly (defined as PPV with at least 1 min of spontaneous breathing between PPV cycles) was less frequent in the rPAP group (26.8% vs. 43.3%, %RD −16.5, 95% CI [−31.7 to −1.1], p 0.04). The use of PPV after 5 min of age was also less common in the rPAP group (23.2% vs. 38.8%, %RD −15.6, 95% CI [−30.7 to −0.8], p 0.04). There were no statistically significant differences in Apgar scores or oxygen saturation levels between the groups. Conclusion: In the CORSAD trial, less PPV was needed to establish stable breathing in extremely preterm infants using the rPAP compared to using the standard T-piece without significant difference in Apgar scores or oxygenation. [ABSTRACT FROM AUTHOR]

Advances in neonatal care have pushed the limit of viability to incrementally lower gestations over the last decades. However, surviving extremely premature neonates are prone to long-term neurodevelopmental handicaps. This makes ethics a crucial dimension of periviable birth management. At 22 weeks, survival ranges from 1 to 15%, and profound disabilities in survivors are common. Consequently, there is no beneficence-based obligation to offer any aggressive perinatal management. At 23 weeks, survival ranges from 8 to 54%, and survival without severe handicap ranges from 7 to 23%. If fetal indication for cesarean delivery appears, the procedure may be offered when neonatal resuscitation is planned. At a gestational age ≥24 weeks, up to 51% neonates are expected to survive the neonatal period. Survival without profound neurologic disability ranges from 12 to 38%. Beneficence-based obligation to intervene is reasonable at these gestations. Nevertheless, autonomy of parents should also be respected, and parental consent should be sought prior to any intervention. Optimal counselling of parents involves harmonized cooperation of obstetric and neonatal care providers. Every fetus/neonate and every pregnant woman are different and have the right to be considered individually when treatment decisions are being made. [ABSTRACT FROM AUTHOR]

Infections remain a leading cause of neonatal death, especially among the extremely preterm infants. To evaluate the incidence, pathogenesis, and in-hospital outcomes associated with sepsis among hospitalized extremely preterm infants born at 24–0/7 to 27–6/7 weeks of gestation, we designed a post hoc analysis of data collected prospectively during the Preterm Epo Neuroprotection (PENUT) Trial, NCT #01378273. We analyzed culture positive infection data, as well as type and duration of antibiotic course and described their association with in-hospital morbidities and mortality. Of 936 included infants, 229 (24%) had at least one positive blood culture during their hospitalization. Early onset sepsis (EOS, ≤3 days after birth) occurred in 6% of the infants, with Coagulase negative Staphylococci (CoNS) and Escherichia Coli the most frequent pathogens. Late onset sepsis (LOS, >day 3) occurred in 20% of the infants. Nearly all infants were treated with antibiotics for presumed sepsis at least once during their hospitalization. The risk of confirmed or presumed EOS was lower with increasing birthweight. Confirmed EOS had no significant association with in-hospital outcomes or death while LOS was associated with increased risk of necrotizing enterocolitis and death. Extremely premature infants with presumed sepsis as compared to culture positive sepsis had lower rates of morbidities. In conclusion, the use of antibiotics for presumed sepsis remains much higher than confirmed infection rates. Ongoing work exploring antibiotic stewardship and presumed, culture-negative sepsis in extremely preterm infants is needed. [ABSTRACT FROM AUTHOR]