Long-term impact of late pulmonary hypertension requiring medication in extremely preterm infants with severe bronchopulmonary dysplasia.

This study investigated whether late pulmonary hypertension (LPH) independently increases the risk of long-term mortality or neurodevelopmental delay (NDD) in extremely preterm infants (EPIs) with severe bronchopulmonary dysplasia (BPD). Using prospectively collected data from the Korean Neonatal Network, we included EPIs with severe BPD born at 22-27 weeks' gestation between 2013 and 2021. EPIs having severe BPD with LPH (LPH, n = 124) were matched 1:3 with those without pulmonary hypertension (PH) as controls (CON, n = 372), via propensity score matching. LPH was defined as PH with the initiation of medication after 36 weeks' corrected age (CA). Long-term mortality after 36 weeks' CA or NDD at 18-24 months' CA was analyzed. NDD was assessed using composite scores based on various neurodevelopmental assessment modalities. LPH had significantly higher long-term mortality or NDD (45.2% vs. 23.1%, P < 0.001), mortality (24.2% vs. 4.84%, P < 0.001), and NDD (68.4% vs. 37.8%, P = 0.001), respectively than CON, even after adjusting for different demographic factors. Multivariable regression demonstrated that LPH independently increased the risk of mortality or NDD (adjusted odds ratio, 1.95; 95% confidence intervals, 1.17-3.25). When LPH occurs in EPIs with severe BPD, special monitoring and meticulous care for long-term survival and neurodevelopment are continuously needed.

Probiotic supplementation and risk of necrotizing enterocolitis and mortality among extremely preterm infants-the Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial: study protocol for a multicenter, double-blinded, placebo-controlled, and registry-based randomized controlled trial.

BACKGROUND: Extremely preterm infants, defined as those born before 28 weeks' gestational age, are a very vulnerable patient group at high risk for adverse outcomes, such as necrotizing enterocolitis and death. Necrotizing enterocolitis is an inflammatory gastrointestinal disease with high incidence in this cohort and has severe implications on morbidity and mortality. Previous randomized controlled trials have shown reduced incidence of necrotizing enterocolitis among older preterm infants following probiotic supplementation. However, these trials were underpowered for extremely preterm infants, rendering evidence for probiotic supplementation in this population insufficient to date. METHODS: The Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial is a multicenter, double-blinded, placebo-controlled and registry-based randomized controlled trial conducted among extremely preterm infants (n = 1620) born at six tertiary neonatal units in Sweden and four units in Denmark. Enrolled infants will be allocated to receive either probiotic supplementation with ProPrems® (Bifidobacterium infantis, Bifidobacterium lactis, and Streptococcus thermophilus) diluted in 3 mL breastmilk or placebo (0.5 g maltodextrin powder) diluted in 3 mL breastmilk per day until gestational week 34. The primary composite outcome is incidence of necrotizing enterocolitis and/or mortality. Secondary outcomes include incidence of late-onset sepsis, length of hospitalization, use of antibiotics, feeding tolerance, growth, and body composition at age of full-term and 3 months corrected age after hospital discharge. DISCUSSION: Current recommendations for probiotic supplementation in Sweden and Denmark do not include extremely preterm infants due to lack of evidence in this population. However, this young subgroup is notably the most at risk for experiencing adverse outcomes. This trial aims to investigate the effects of probiotic supplementation on necrotizing enterocolitis, death, and other relevant outcomes to provide sufficiently powered, high-quality evidence to inform probiotic supplementation guidelines in this population. The results could have implications for clinical practice both in Sweden and Denmark and worldwide. TRIAL REGISTRATION: ( Clinicaltrials.gov ): NCT05604846.

Alternative consent methods used in the multinational, pragmatic, randomised clinical trial SafeBoosC-III.

BACKGROUND: The process of obtaining prior informed consent for experimental treatment does not fit well into the clinical reality of acute and intensive care. The therapeutic window of interventions is often short, which may reduce the validity of the consent and the rate of enrolled participants, to delay trial completion and reduce the external validity of the results. Deferred consent and 'opt-out' are alternative consent methods. The SafeBoosC-III trial was a randomised clinical trial investigating the benefits and harms of cerebral oximetry monitoring in extremely preterm infants during the first 3 days after birth, starting within the first 6 h after birth. Prior, deferred and opt-out consent were all allowed by protocol. This study aimed to evaluate the use of different consent methods in the SafeBoosC-III trial, Furthermore, we aimed to describe and analyse concerns or complaints that arose during the first 6 months of trial conduct. METHODS: All 70 principal investigators were invited to join this descriptive ancillary study. Each principal investigator received a questionnaire on the use of consent methods in their centre during the SafeBoosC-III trial, including the possibility to describe any concerns related to the consent methods used during the first 6 months of the trial, as raised by the parents or the clinical staff. RESULTS: Data from 61 centres were available. In 43 centres, only prior informed consent was used: in seven, only deferred consent. No centres used the opt-out method only, but five centres used prior and deferred, five used prior, deferred and opt-out (all possibilities) and one used both deferred and opt-out. Six centres applied to use the opt-out method by their local research ethics committee but were denied using it. One centre applied to use deferred consent but was denied. There were only 23 registered concerns during the execution of the trial. CONCLUSIONS: Consent by opt-out was allowed by the protocol in this multinational trial but only a few investigators opted for it and some research ethics boards did not accept its use. It is likely to need promotion by the clinical research community to unfold its potential.

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.

[A cross-sectional survey of delivery room transitional care management for very/extremely preterm infants in 24 hospitals in Shenzhen City]. / 深圳市24家医院极/è¶ æ—©äº§å„¿äº§æˆ¿è¿‡æ¸¡æœŸç®¡ç†çš„æ¨ªæ–­é¢è°ƒæŸ¥.

OBJECTIVES: To investigate the current status of delivery room transitional care management for very/extremely preterm infants in Shenzhen City. METHODS: A cross-sectional survey was conducted in November 2022, involving 24 tertiary hospitals participating in the Shenzhen Neonatal Data Network. The survey assessed the implementation of transitional care management in the delivery room, including prenatal preparation, delivery room resuscitation, and post-resuscitation management in the neonatal intensive care unit. Very/extremely preterm infants were divided into four groups based on gestational age: <26 weeks, 26-28+6 weeks, 29-30+6 weeks, and 31-31+6 weeks. Descriptive analysis was performed on the results. RESULTS: A total of 140 very/extremely preterm infants were included, with 10 cases in the <26 weeks group, 45 cases in the 26-28+6 weeks group, 49 cases in the 29-30+6 weeks group, and 36 cases in the 31-31+6 weeks group. Among these infants, 99 (70.7%) received prenatal counseling, predominantly provided by obstetricians (79.8%). The main personnel involved in resuscitation during delivery were midwives (96.4%) and neonatal resident physicians (62.1%). Delayed cord clamping was performed in 52 cases (37.1%), with an average delay time of (45±17) seconds. Postnatal radiant warmer was used in 137 cases (97.9%) for thermoregulation. Positive pressure ventilation was required in 110 cases (78.6%), with 67 cases (60.9%) using T-piece resuscitators and 42 cases (38.2%) using a blended oxygen device. Blood oxygen saturation was monitored during resuscitation in 119 cases (85.0%). The median time from initiating transitional care measures to closing the incubator door was 87 minutes. CONCLUSIONS: The implementation of delivery room transitional care management for very/extremely preterm infants in the hospitals participating in the Shenzhen Neonatal Data Network shows varying degrees of deviation from the corresponding expert consensus in China. It is necessary to bridge the gap through continuous quality improvement and multicenter collaboration to improve the quality of the transitional care management and outcomes in very/extremely preterm infants.

Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula: A Randomized Clinical Trial.

Importance: Maternal milk feeding of extremely preterm infants during the birth hospitalization has been associated with better neurodevelopmental outcomes compared with preterm formula. For infants receiving no or minimal maternal milk, it is unknown whether donor human milk conveys similar neurodevelopmental advantages vs preterm formula. Objective: To determine if nutrient-fortified, pasteurized donor human milk improves neurodevelopmental outcomes at 22 to 26 months' corrected age compared with preterm infant formula among extremely preterm infants who received minimal maternal milk. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 15 US academic medical centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants younger than 29 weeks 0 days' gestation or with a birth weight of less than 1000 g were enrolled between September 2012 and March 2019. Intervention: Preterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge. Main Outcomes and Measures: The primary outcome was the Bayley Scales of Infant and Toddler Development (BSID) cognitive score measured at 22 to 26 months' corrected age; a score of 54 (score range, 54-155; a score of ≥85 indicates no neurodevelopmental delay) was assigned to infants who died between randomization and 22 to 26 months' corrected age. The 24 secondary outcomes included BSID language and motor scores, in-hospital growth, necrotizing enterocolitis, and death. Results: Of 1965 eligible infants, 483 were randomized (239 in the donor milk group and 244 in the preterm formula group); the median gestational age was 26 weeks (IQR, 25-27 weeks), the median birth weight was 840 g (IQR, 676-986 g), and 52% were female. The birthing parent's race was self-reported as Black for 52% (247/478), White for 43% (206/478), and other for 5% (25/478). There were 54 infants who died prior to follow-up; 88% (376/429) of survivors were assessed at 22 to 26 months' corrected age. The adjusted mean BSID cognitive score was 80.7 (SD, 17.4) for the donor milk group vs 81.1 (SD, 16.7) for the preterm formula group (adjusted mean difference, -0.77 [95% CI, -3.93 to 2.39], which was not significant); the adjusted mean BSID language and motor scores also did not differ. Mortality (death prior to follow-up) was 13% (29/231) in the donor milk group vs 11% (25/233) in the preterm formula group (adjusted risk difference, -1% [95% CI, -4% to 2%]). Necrotizing enterocolitis occurred in 4.2% of infants (10/239) in the donor milk group vs 9.0% of infants (22/244) in the preterm formula group (adjusted risk difference, -5% [95% CI, -9% to -2%]). Weight gain was slower in the donor milk group (22.3 g/kg/d [95% CI, 21.3 to 23.3 g/kg/d]) compared with the preterm formula group (24.6 g/kg/d [95% CI, 23.6 to 25.6 g/kg/d]). Conclusions and Relevance: Among extremely preterm neonates fed minimal maternal milk, neurodevelopmental outcomes at 22 to 26 months' corrected age did not differ between infants fed donor milk or preterm formula. Trial Registration: ClinicalTrials.gov Identifier: NCT01534481.

Weaning from mechanical ventilation and assessment of extubation readiness.

Tremendous advancements in neonatal respiratory care have contributed to the improved survival of extremely preterm infants (gestational age ≤ 28 weeks). While mechanical ventilation is often considered one of the most important breakthroughs in neonatology, it is also associated with numerous short and long-term complications. For those reasons, clinical research has focused on strategies to avoid or reduce exposure to mechanical ventilation. Nonetheless, in the extreme preterm population, 70-100% of infants born 22-28 weeks of gestation are exposed to mechanical ventilation, with nearly 50% being ventilated for ≥ 3 weeks. As contemporary practices have shifted towards selectively reserving mechanical ventilation for those patients, mechanical ventilation weaning and extubation remain a priority yet offer a heightened challenge for clinicians. In this review, we will summarize the evidence for different strategies to expedite weaning and assess extubation readiness in preterm infants, with a particular focus on extremely preterm infants.

Volume-targeted ventilation.

Despite strong evidence of important benefits of volume-targeted ventilation, many high-risk extremely preterm infants continue to receive traditional pressure-controlled ventilation in the United States and elesewhere. Reluctance to abandon one's comfort zone, lack of suitable equipment and a lack of understanding of the subtleties of volume-targeted ventilation appear to contribute to the relatively slow uptake of volume-targeted ventilation. This review will underscore the benefits of using tidal volume as the primary control variable, to improve clinicians' understanding of the way volume-targeted ventilation interacts with the awake, breathing infant and to provide information about evidence-based tidal volume targets in various circmstances. Focus on underlying lung pathophysiology, individualized ventilator settings and tidal volume targets are essential to successful use of this approach thereby improving important clinical outcomes.

Mitochondrial DNA mutations in extremely preterm infants with bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a serious chronic lung disease affecting extremely preterm infants. While mitochondrial dysfunction has been investigated in various medical conditions, limited research has explored mitochondrial DNA (mtDNA) gene mutations, specifically in BPD. This study aimed to evaluate mitochondrial mtDNA gene mutations in extremely preterm infants with BPD. In this prospective observational study, we enrolled a cohort of extremely preterm infants diagnosed with BPD. Clinical data were collected to provide comprehensive patient profiles. Peripheral blood mononuclear cells were isolated from whole-blood samples obtained within a defined timeframe. Subsequently, mtDNA extraction and sequencing using next-generation sequencing technology were performed to identify mtDNA gene mutations. Among the cohort of ten extremely preterm infants with BPD, mtDNA sequencing revealed the presence of mutations in seven patients, resulting in a total of twenty-one point mutations. Notably, many of these mutations were identified in loci associated with critical components of the respiratory chain complexes, vital for proper mitochondrial function and cellular energy production. This pilot study provides evidence of mtDNA point mutations in a subset of extremely preterm infants with BPD. These findings suggest a potential association between mitochondrial dysfunction and the pathogenesis of BPD. Further extensive investigations are warranted to unravel the mechanisms underlying mtDNA mutations in BPD.

The Diaphragmatic Initiated Ventilatory Assist (DIVA) trial: study protocol for a randomized controlled trial comparing rates of extubation failure in extremely premature infants undergoing extubation to non-invasive neurally adjusted ventilatory assist versus non-synchronized nasal intermittent positive pressure ventilation.

BACKGROUND: Invasive mechanical ventilation contributes to bronchopulmonary dysplasia (BPD), the most common complication of prematurity and the leading respiratory cause of childhood morbidity. Non-invasive ventilation (NIV) may limit invasive ventilation exposure and can be either synchronized or non-synchronized (NS). Pooled data suggest synchronized forms may be superior. Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) delivers NIV synchronized to the neural signal for breathing, which is detected with a specialized catheter. The DIVA (Diaphragmatic Initiated Ventilatory Assist) trial aims to determine in infants born 240/7-276/7 weeks' gestation undergoing extubation whether NIV-NAVA compared to non-synchronized nasal intermittent positive pressure ventilation (NS-NIPPV) reduces the incidence of extubation failure within 5 days of extubation. METHODS: This is a prospective, unblinded, pragmatic, multicenter phase III randomized clinical trial. Inclusion criteria are preterm infants 24-276/7 weeks gestational age who were intubated within the first 7 days of life for at least 12 h and are undergoing extubation in the first 28 postnatal days. All sites will enter an initial run-in phase, where all infants are allocated to NIV-NAVA, and an independent technical committee assesses site performance. Subsequently, all enrolled infants are randomized to NIV-NAVA or NS-NIPPV at extubation. The primary outcome is extubation failure within 5 days of extubation, defined as any of the following: (1) rise in FiO2 at least 20% from pre-extubation for > 2 h, (2) pH ≤ 7.20 or pCO2 ≥ 70 mmHg; (3) > 1 apnea requiring positive pressure ventilation (PPV) or ≥ 6 apneas requiring stimulation within 6 h; (4) emergent intubation for cardiovascular instability or surgery. Our sample size of 478 provides 90% power to detect a 15% absolute reduction in the primary outcome. Enrolled infants will be followed for safety and secondary outcomes through 36 weeks' postmenstrual age, discharge, death, or transfer. DISCUSSION: The DIVA trial is the first large multicenter trial designed to assess the impact of NIV-NAVA on relevant clinical outcomes for preterm infants. The DIVA trial design incorporates input from clinical NAVA experts and includes innovative features, such as a run-in phase, to ensure consistent technical performance across sites. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , trial identifier NCT05446272 , registered July 6, 2022.

Umbilical cord blood cell characteristics in very preterm neonates for autologous cell therapy of preterm-associated complications.

BACKGROUND: There are emerging clinical evidence for umbilical cord blood mononuclear cells (UCBMNCs) intervention to improve preterm complications. The first critical step in cell therapy is to obtain high-quality cells. This retrospective study aimed to investigate the quantity and quality of UCBMNCs from very preterm infants (VPIs) for the purpose of autologous cell therapy in prevention and treatment of preterm complications. METHODS: Very preterm infants (VPIs) born in Guangdong Women and Children Hospital from January 1, 2017, to December 8, 2022, from whom cord blood was successfully collected and separated for public or private banking, were enrolled. The UCBMNCs characters from route cord blood tests performed in cord blood bank, impact of perinatal factors on UCBMNCs, the relationship between UCBMNCs characteristics and preterm outcomes, and the correlation of UCBMNCs characteristics and peripheral blood cells in VPIs were analyzed. RESULTS: Totally, 89 VPIs underwent UCB collection and processing successfully. The median cell number post processing was 2.6 × 108. To infuse a dose of 5 × 107 cells/kg, only 3.4% of infants required a volume of more than 20 mL/kg, which exceeded the maximum safe volume limit for VPIs. However, when infusing 10 × 107 cells/kg, 25.8% of infants required a volume of more than 20 ml/kg volume. Antenatal glucocorticoids use and preeclampsia was associated with lower original UCBMNCs concentration. Both CD34+ hematopoietic stem cells (HSC) frequency and colony forming unit - granulocyte and macrophage (CFU-GM) number correlated negatively with gestational age (GA). UCBMNCs characters had no significant effect on preterm outcomes, whereas a significant positive correlation was observed between UCBMNCs concentration and total white blood cell, neutrophil, lymphocyte and PLT counts in peripheral blood. CONCLUSION: UCBMNCs collected from VPIs was feasible for autologous cell therapy in improving preterm complications. Setting the infusion dose of 5 × 107 cells/kg guaranteed a safe infusion volume in more than 95% of the targeted infants. UCBMNCs characters did not affect preterm complications; however, the effect of UCBMNCs concentration on peripheral blood classification count should be considered when evaluating the immunomodulation of UCBMNCs transfusion.

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.

The Early Hematological Profile and Its Variations: A Useful Tool in the Prediction of Intraventricular Hemorrhage in Extremely Preterm Infants.

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.

Size and Location of Preterm Brain Injury and Associations With Neurodevelopmental Outcomes.

BACKGROUND AND OBJECTIVES: We examined associations of white matter injury (WMI) and periventricular hemorrhagic infarction (PVHI) volume and location with 18-month neurodevelopment in very preterm infants. METHODS: A total of 254 infants born <32 weeks' gestational age were prospectively recruited across 3 tertiary neonatal intensive care units (NICUs). Infants underwent early-life (median 33.1 weeks) and/or term-equivalent-age (median 41.9 weeks) MRI. WMI and PVHI were manually segmented for quantification in 92 infants. Highest maternal education level was included as a marker of socioeconomic status and was defined as group 1 = primary/secondary school; group 2 = undergraduate degree; and group 3 = postgraduate degree. Eighteen-month neurodevelopmental assessments were completed with Bayley Scales of Infant and Toddler Development, Third Edition. Adverse outcomes were defined as a score of less than 85 points. Multivariable linear regression models were used to examine associations of brain injury (WMI and PVHI) volume with neurodevelopmental outcomes. Voxel-wise lesion symptom maps were developed to assess relationships between brain injury location and neurodevelopmental outcomes. RESULTS: Greater brain injury volume was associated with lower 18-month Motor scores (ß = -5.7, 95% CI -9.2 to -2.2, p = 0.002) while higher maternal education level was significantly associated with higher Cognitive scores (group 3 compared 1: ß = 14.5, 95% CI -2.1 to 26.9, p = 0.03). In voxel-wise lesion symptom maps, brain injury involving the central and parietal white matter was associated with an increased risk of poorer motor outcomes. DISCUSSION: We found that brain injury volume and location were significant predictors of motor, but not cognitive outcomes, suggesting that different pathways may mediate outcomes across domains of neurodevelopment in preterm infants. Specifically, assessing lesion size and location may allow for more accurate identification of infants with brain injury at highest risk of poorer motor outcomes. These data also highlight the importance of socioeconomic status in cognitive outcomes, even in preterm infants with brain injury.

Active versus restrictive ligation strategy for patent ductus arteriosus - A retrospective two-center study of extremely preterm infants born between 22 + 0 and 25 + 6 weeks of gestational age.

BACKGROUND: Patent ductus arteriosus (PDA) in premature infants is associated with adverse clinical outcomes. Mode and timing of treatment are still controversial. Data are limited in the most extremely premature infants <26 weeks of gestational age (GA), where clinical problems are most significant and patients are most vulnerable. AIMS: To investigate whether different approaches to surgical closure of PDA in two large Swedish centers has an impact on clinical outcomes including mortality in extremely preterm infants born <26 weeks GA. STUDY DESIGN: Retrospective, two-center, cohort study. SUBJECTS: Infants born at 22+0-25+6 weeks GA between 2010 and 2016 at Uppsala University Children's Hospital (UUCH; n = 228) and Queen Silvia Children's Hospital Gothenburg (QSCHG; n = 220). MAIN OUTCOME MEASURES: Survival, bronchopulmonary dysplasia (BPD), and retinopathy of prematurity (ROP). RESULTS: Surgical closure of PDA was more common and performed earlier at QSCHG (50 % vs 16 %; median age 11 vs 44 days; p < 0.01). Survival was similar in both centres. There was a higher incidence of severe BPD and longer duration of mechanical ventilation at UUCH (p < 0.01). There was a higher incidence of ROP, IVH and sepsis at QSCH (p < 0.05, p < 0.01 and p < 0.01). A sub-group analysis matching all surgically treated infants at QSCHG with infants at UUCH with the same GA showed similar results as the total cohort. CONCLUSION: Earlier and higher rate of surgical PDA closure in this cohort of extremely preterms born <26 weeks GA did not impact mortality but was associated with lower rates of severe BPD and higher rates of severe ROP.

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.

Neonatal Intensive Care Unit Resource Use for Infants at 22 Weeks' Gestation in the US, 2008-2021.

Importance: During the past decade, clinical guidance about the provision of intensive care for infants born at 22 weeks' gestation has changed. The impact of these changes on neonatal intensive care unit (NICU) resource utilization is unknown. Objective: To characterize recent trends in NICU resource utilization for infants born at 22 weeks' gestation compared with other extremely preterm infants (≤28 weeks' gestation) and other NICU-admitted infants. Design, Setting, and Participants: This is a serial cross-sectional study of 137 continuously participating NICUs in 29 US states from January 1, 2008, through December 31, 2021. Participants included infants admitted to the NICU. Data analysis was performed from October 2022 to August 2023. Exposures: Year and gestational age at birth. Main Outcomes and Measures: Measures of resource utilization included NICU admissions, NICU bed-days, and ventilator-days. Results: Of 825 112 infants admitted from 2008 to 2021, 60 944 were extremely preterm and 872 (466 [53.4%] male; 18 [2.1%] Asian; 318 [36.5%] Black non-Hispanic; 218 [25.0%] Hispanic; 232 [26.6%] White non-Hispanic; 86 [9.8%] other or unknown) were born at 22 weeks' gestation. NICU admissions at 22 weeks' gestation increased by 388%, from 5.7 per 1000 extremely preterm admissions in 2008 to 2009 to 27.8 per 1000 extremely preterm admissions in 2020 to 2021. The number of NICU admissions remained stable before the publication of updated clinical guidance in 2014 to 2016 and substantially increased thereafter. During the study period, bed-days for infants born at 22 weeks increased by 732%, from 2.5 per 1000 to 20.8 per 1000 extremely preterm NICU bed-days; ventilator-days increased by 946%, from 5.0 per 1000 to 52.3 per 1000 extremely preterm ventilator-days. The proportion of NICUs admitting infants born at 22 weeks increased from 22.6% to 45.3%. Increases in NICU resource utilization during the period were also observed for infants born at less than 22 and at 23 weeks but not for other gestational ages. In 2020 to 2021, infants born at less than or equal to 23 weeks' gestation comprised 1 in 117 NICU admissions, 1 in 34 of all NICU bed-days, and 1 in 6 of all ventilator-days. Conclusions and Relevance: In this serial cross-sectional study of 137 US NICUs from 2008 to 2021, an increasing share of resources in US NICUs was allocated to infants born at 22 weeks' gestation, corresponding with changes in national clinical guidance.

Quality improvement in the golden hour for premature infants: a scoping review.

BACKGROUND AND OBJECTIVE: Evidence-based research has shown that golden hour quality improvement (QI) measures can improve the quality of care and reduce serious complications of premature infants. Herein, we sought to review golden hour QI studies to evaluate the impact on the outcome of preterm infants. METHODS: A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, and SinoMed databases from inception to April 03, 2023. Only studies describing QI interventions in the golden hour of preterm infants were included. Outcomes were summarized and qualitative synthesis was performed. RESULTS: Ten studies were eligible for inclusion. All studies were from single centers, of which nine were conducted in the USA and one in Israel. Seven were pre-post comparative studies and three were observational studies. Most included studies were of medium quality (80%). The most common primary outcome was admission temperatures and glucose. Five studies (n = 2308) reported improvements in the admission temperature and three studies (n = 2052) reported improvements in hypoglycemia after QI. Four studies (n = 907) showed that the incidence of bronchopulmonary dysplasia (BPD) was lower in preterm infants after QI: 106/408 (26.0%) vs. 122/424(29.5%) [OR = 0.68, 95% CI 0.48-0.97, p = 0.04]. CONCLUSIONS: Our study showed that the golden hour QI bundle can improve the short-term and long-term outcomes for extremely preterm infants. There was considerable heterogeneity and deficiencies in the included studies, and the variation in impact on outcomes suggests the need to use standardized and validated measures. Future studies are needed to develop locally appropriate, high-quality, and replicable QI projects.

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.