Importance:The Apgar score, the first clinical assessment to direct measures to stabilize newborn infants, is also used for risk assessment. Its accuracy in estimating outcomes remains poor among very preterm (VPT) infants. Objective:To assess the utility of the combined 5-minute Apgar score and umbilical artery pH (UA-pH) for estimating risks of mortality and severe neonatal morbidity among VPT infants. Design, Setting, and Participants:This cohort study (Effective Perinatal Intensive Care in Europe [EPICE]) analyzed infants born at less than 32 weeks' gestation between April 2011 and September 2012 across 11 European countries. All liveborn VPT infants with Apgar scores and UA-pH data were included. Data were analyzed between February and December 2025. Exposures:Apgar score at 5 minutes and UA-pH. The Apgar score was classified as lower than 7 and 7 or higher, and the UA-pH values were categorized as low (<7.20) and normal (≥7.20). Four groups that combined these 2 measures were defined: Apgar score lower than 7 and low UA-pH; Apgar score lower than 7 and normal UA-pH; Apgar score 7 or higher and low UA-pH; and Apgar score 7 or higher and normal UA-pH. Main Outcomes and Measures:Combined outcome of mortality and/or any adverse morbidity (intraventricular hemorrhage [IVH] >grade 2, cystic periventricular leukomalacia, moderate or severe bronchopulmonary dysplasia [BPD], retinopathy of prematurity ≥stage 2, and necrotizing enterocolitis). Modified Poisson regression was used to estimate relative risks (RRs) between the exposure and the combined mortality and morbidity outcome and 3 individual components: mortality, IVH, and BPD. Models were adjusted for perinatal variables associated with Apgar score and UA-pH and adverse neonatal outcomes. Results:Of 7900 liveborn infants in the EPICE cohort, 4174 (52.8%) had information on Apgar score and UA-pH. These infants included 2249 males (53.9%) and had a median [IQR] gestational age of 29.9 [27.9-31.0] weeks and median [IQR] birth weight of 1240 [960-1520] g. A total of 367 infants (8.8%) had an Apgar score 7 or higher but a low UA-pH, 558 (13.4%) had an Apgar score lower than 7 but a normal UA-pH, and 196 (4.7%) had an Apgar score lower than 7 and a low UA-pH. Infants with an Apgar score lower than 7 had a higher frequency of the combined outcome among those with a normal UA-pH (270 [48.4%] vs 596 [19.5%]) and a low UA-pH (108 [55.1%] vs 596 [19.5%]), with similar adjusted RRs (ARRs; low: 1.4 [95% CI, 1.2-1.7]; normal: 1.4 [95% CI, 1.3-1.6]). For mortality risk, associations were robust for an Apgar score lower than 7 and a low UA-pH (ARR, 2.4; 95% CI, 1.7-3.3) and absent with an Apgar score of 7 or higher and a low UA-pH (ARR, 1.2; 95% CI, 0.8-1.8). IVH risk was increased in all 3 subcategories, including an Apgar score of 7 or higher with a low UA-pH (ARR, 2.0; 95% CI, 1.3-3.0). BPD risk was associated only with an Apgar score lower than 7 and a normal UA-pH (ARR, 1.4; 95% CI, 1.2-1.7). Conclusions and Relevance:In this cohort study of VPT infants, combining information on UA-pH with the 5-minute Apgar score was associated with improved accuracy in estimating the risk of some adverse outcomes-notably mortality and IVH, which occurred soon after birth. These results highlight the importance of exploring the associations of early markers of risk with neonatal mortality and key neonatal morbidities separately.

BACKGROUND:Extremely preterm infants require respiratory support with supplemental oxygen and have frequent hypoxaemic episodes. These episodes, and exposure to inadequately high concentrations of oxygen, are associated with major complications and death. Closed-loop automated control of the fractional concentration of oxygen in inspired air (FiO2-C) reduces the time below and above the target range for the pulse oximeter oxygen saturation (SpO2) and caregivers' workload. We aimed to study whether FiO2-C during respiratory support versus routine manual control might also improve clinical outcomes. METHODS:This multicentre, parallel-group, randomised, controlled, superiority trial was done in 32 neonatal intensive care units in China, Germany, the Netherlands, and the UK. Infants born at 23+0 weeks to 27+6 weeks postmenstrual age were included and randomly assigned to FiO2-C or routine manual care stratified within centres by postmenstrual age at birth and sex. FiO2-C was provided in addition to routine manual control of FiO2 using infant ventilators. The composite primary endpoint was death, necrotising enterocolitis, or bronchopulmonary dysplasia up to 36 weeks postmenstrual age, or severe retinopathy of prematurity by 44 weeks postmenstrual age. Secondary endpoints were the components of the primary endpoint and the maximum retinopathy of prematurity severity score in either eye on the International Neonatal Consortium Retinopathy of Prematurity Activity Scale. The trial was stopped early because of poor recruitment. The primary analysis included the intention-to-treat population with non-missing primary outcome data. This trial was registered with ClinicalTrials.gov (NCT03168516) and is closed. FINDINGS:Between July 1, 2018, and Oct 31, 2023, 1082 infants were enrolled and randomly assigned to the FiO2-C group (n=539) or routine manual control group (n=543). Median postmenstrual age was 26+1 weeks (IQR 24+6-27+1). 557 (51%) of 1082 infants were male and 525 (49%) were female. The primary endpoint occurred in 206 (39%) of 534 infants in the FiO2-C group versus 222 (41%) of 538 infants in the routine manual control group (adjusted odds ratio 0·90, 97·5% CI 0·65-1·24; p=0·47). Rates of death (48 [9%] of 536 infants vs 50 [9%] of 541 infants), necrotising enterocolitis (27 [5%] of 538 vs 36 [7%] of 542), bronchopulmonary dysplasia (104 [21%] of 486 vs 110 [23%] of 485), and severe retinopathy of prematurity (86 [18%] of 491 vs 95 [19%] of 496) were also similar between groups. The maximum retinopathy of prematurity severity score was similar between groups (median 7 [IQR 0-9]; p=0·24). Overall, 197 serious adverse events were reported in the FiO2-C group and 192 in the routine manual control group, with no evidence of harm related to the intervention. Postnatal age at death and primary causes of death were similar in both groups. Four serious incidents related to software function without apparent harm to affected infants were reported. INTERPRETATION:FiO2-C did not improve neonatal clinical outcomes. The long-term application of FiO2-C to reduce caregivers' workload might be considered safe. FiO2-C algorithms should be tested before routine application. FUNDING:German Federal Ministry of Education and Research.

Animal models of bronchopulmonary dysplasia (BPD) have allowed the discovery of pathological and disease-management pathways. The laboratory mouse is the go-to model for first-step experimental in vivo studies. BPD encompasses disturbances to lung structure and function, including breathing patterns and gas exchange. Despite advances in quantitative assessment of lung structure in mice, most mouse modeling studies continue to use disordered lung structure as the primary experimental endpoint. Technical challenges associated with lung function studies in neonatal mice have limited enthusiasm for drawing correlations between lung structure and lung function. As this represents a key limitation of mouse BPD models, methodologies were developed here to adapt two established techniques: unrestrained whole body plethysmography (WBP) and the forced oscillation technique (FOT), enabling reliable conscious and anesthetized assessments of lung function in mouse pups. Diseased mice presented with alveolar simplification as well as a reduced tidal volume and breathing frequency, as assessed by WBP. Changes in respiratory mechanics, namely reduced tissue damping and tissue elastance, were revealed by FOT. Alterations to pressure/volume loops suggested an obstructive pattern of disease. In a clinical cohort of 65 patients with BPD, decreased tidal volume but unchanged breathing frequency was noted. Thus, with some exceptions, disturbances to lung function in experimentally modeled elements of BPD in mice paralleled those of infants with BPD. This report serves the dual function of reporting an innovative methodology, describing protocols for using WBP and FOT in neonatal mice, while reporting functional respiratory mechanics outcomes in mice in which BPD was experimentally modeled.NEW & NOTEWORTHY Clinically, respiratory disease in newborns is diagnosed and managed using lung function tests; while in animal models of newborn lung disease, lung structure is the primary experimental endpoint. Here, a comprehensive experimental protocol for assessing lung function in newborn mice is provided. Observed disturbances in lung function were discussed in the context of parallel structural changes to the lung architecture, and comparisons were drawn with clinical lung function studies in infants with BPD.

Preterm birth continues to affect 5 to 12% of all live births in Europe and remains a leading cause of neonatal mortality and short- and long-term morbidity. Despite decades of research and clinical innovation, the overall burden has not substantially declined, and in several European settings rates are rising. This paper is a European Association of Perinatal Medicine (EAPM) Good Practice Recommendation which synthesises current evidence on spontaneous PTB (sPTB) risk and management, and examines why preterm birth persists as a clinical and public health challenge. We review the epidemiology, classification, and aetiology of sPTB; the role of the maternal microbiome; evidence-based preventive strategies; perinatal management; and neonatal care. We highlight the importance of a multicomponent and evidence-based approach, focusing on primary, secondary and tertiary prevention, to reduce the human and societal cost of preterm birth across Europe.

Background: Early discharge with home nasogastric (NGT) feeding has been associated with favorable infant outcomes and high parental satisfaction. However, its impact on parental mental health has been insufficiently studied. We aimed to evaluate symptoms of anxiety and depression in mothers and fathers of very preterm infants discharged with or without NGT feeding. Methods: This prospective cohort study was conducted at a German tertiary perinatal center between October 2020 and May 2024. A total of 238 preterm infants with a birth weight ≤ 1500 g and/or a postmenstrual age (PMA) ≤ 32 weeks were included; 131 were discharged with full oral feeding and 107 with NGT feeding. Symptoms of anxiety and depression were assessed in mothers and fathers using the Hospital Anxiety and Depression Scale (HADS-D) at discharge and at three months corrected age (CA). A total of 201 parent-infant dyads were included. HADS-D assessments were completed by 155 mothers and 135 fathers at discharge and by 121 mothers and 119 fathers at three months CA. Results: At discharge, depression and anxiety scores did not differ between parents of infants discharged with and without NGT feeding. At three months CA, mothers of infants discharged on full oral feeding had higher depression and anxiety scores than mothers of infants discharged with NGT feeding (4.95 ± 3.62 vs. 3.18 ± 2.89; p ≤ 0.01 and 6.42 ± 3.85 vs. 4.79 ± 3.72; p = 0.04), and clinically significant depression scores (≥8) were more frequent (23.53% vs. 10.45%; p = 0.04). Similarly, fathers in the non-tube-feeding group had higher depression scores at 3 months CA (4.78 ± 3.74 vs. 3.48 ± 2.72; p = 0.04), with a trend towards a greater proportion showing clinically significant depression scores (24.14% vs. 13.11%; p = 0.12. Conclusions: Early discharge of very preterm infants with home NGT feeding was not associated with increased parental psychological distress at discharge and at 3 months CA. Across the outcomes, parental distress tended to be lower at 3 months CA with NGT feeding at discharge. However, as no NGT × time interaction was statistically significant after correction for multiple testing, these group differences should be interpreted as exploratory in nature.

Abstract Background Phenotype disruption of lung resident mesenchymal stem cells (MSC) is a key event in the pathogenesis of bronchopulmonary dysplasia (BPD). Hyperoxia (HOX) constitutes one major harmful factor resulting in growth arrest and changes of functional properties including downregulation of PDGFRα. FGF-10, HGF, IGF-1 and PDGF-AA constitute promising cytokines to preserve lung growth. We studied their preventive application before HOX exposure of MSC cultures. Results As described before, HOX inhibited spontaneous proliferation of MSC and induced cell death. Growth inhibition was larger at HOX80% than at HOX40%. The one-time preventive application of FGF-10, HGF, IGF-1 or PDGF-AA in therapeutic dosage or the repetitive application during HOX (40% or 80%) did not attenuate the growth inhibition and cell death induction by HOX even during the milder HOX40% exposure. Furthermore, the phenotype disruption with downregulation of PDGFRα as critical hallmark event remained unchanged. Conclusion Our data indicate that the deleterious effects of HOX to lung resident MSC are that pronounced that single lung growth promoting cytokines cannot attenuate their phenotype disruption, growth inhibition and cell death by HOX. The results demand focus on MSC functionality when the therapeutic potential of lung growth promoting factors and other therapeutics intended to prevent BPD is studied.

Maternal exposure to various insults during pregnancy can influence early-life organ development. Whether this applies to seemingly mild stressors remains unclearly defined. Better understanding of the nature and strength of prenatal exposure factor to trigger fetal programming effect in the lung may help to optimize perinatal-neonatal health care. Pregnant wild type C57BL/6J mice were randomized at 15.5 day post coitum (dpc) or 18.5 dpc to intraperitoneal (i.p.) injection of sterile physiological saline. Mice undergoing a natural process of pregnancy without any intervention served as blank controls. Newborn mice were euthanized at postnatal day 1 for lung harvests. Lung tissues were subjected to Weigert staining to visualize elastic fiber distribution and quantify total parenchymal cells. Additionally, qPCR, immunofluorescence staining and western blot were performed to assess the expression of signature markers of the lung epithelium and other compartments. No adverse perinatal outcomes occurred except a non-significant reduction in maternal weight gain after i.p. injection of sterile physiological saline. Pups demonstrated similar birth weights across groups. The total number of lung parenchymal cells increased in exposed pups compared with blank controls, with no significant difference in elastin fiber distribution. Enhanced macrophage infiltration with predominant type 2 cytokine responses was observed in newborn mice lungs following maternal i.p. injection of saline. There was an elevated surfactant protein C (Sftpc) expression in alveolar type 2 (AT2) cells in the 15.5 dpc exposure group compared to blank controls. No sex-dependent difference was demonstrated in Sftpc expression. Correlational analysis of signature gene expression indicated crosstalk between AT2 cells and other lung cellular compartments. The expression of stem cell antigen (Sca1) in lung mesenchymal progenitor cells demonstrated a time-related response without sex differentiation upon prenatal exposure to maternal i.p. injection of sterile physiological saline. Results of this preclinical study in newborn mice contribute to current understanding of fetal programming by showing that maternal exposure to even non-infectious mild stressors before birth is able to modulate early-life lung development. This underscores an intensified sensibility of unborn fetus to seemingly harmless low-magnitude maternal stressors.

Objectives To study the efficacy of different modes of backup nasal intermittent positive pressure ventilation (NIPPV) during nasal continuous positive airway pressure (nCPAP) therapy to keep extremely preterm (EPT) infants within the oxygen saturation (SpO2) target range.Design Single-centre randomised cross-over trial.Setting Level 3 neonatal intensive care unit.Participants 24 EPT infants (median gestational age of 24+1 and median postnatal age of 43 days).Interventions EPT infants on nCPAP therapy with backup NIPPV during apnoea >4 s were assigned in random sequence to immediate cessation of backup NIPPV or to stepwise reduction of backup NIPPV support on restart of spontaneous respiration.Main outcome measures Primary outcome was time spent within the SpO2 target range (88%–95%). Secondary outcomes included frequency and duration of hypoxaemic and hyperoxaemic episodes, impact on cerebral tissue oxygenation, parameters of gas exchange and vital signs.Results The mean percentage of time spent within the SpO2 target range did not differ between immediate cessation of backup NIPPV on restart of spontaneous respiration compared with the stepwise reduction of backup NIPPV (61.1% vs 64.7%, p=0.15). There were no differences in the time spent below or above the SpO2 target range, the number of prolonged (>30 s) and severe (<80% and <70%) desaturations and in the parameters of cerebral tissue oxygenation. The stepwise reduction of backup NIPPV resulted in a significant increase in mean airway pressure (7.2 cm H20 vs 5.6 cm H20, p<0.01) and reduction in respiratory frequency (60.1 vs 63.8, p=0.02) compared with the immediate cessation of backup NIPPV on restart of spontaneous respiration, while mean fraction of inspired oxygen, transcutaneous carbon dioxide pressure and heart rate did not vary between the two interventions.Conclusion Our findings underpin that new sophisticated ventilation modes like stepwise reduction of backup NIPPV do not necessarily provide a clinical benefit compared with the standard mode. For this, technological advances require robust evaluation within well-designed clinical trials demonstrating the safety and efficacy before being used in everyday clinical practice.Trial registration German Clinical Trials Register; registration number: DRKS00031956 (https://drks.de/search/en/trial/DRKS00031956), date of registration: 26 May 2023.

OBJECTIVE:Central apnoea due to immaturity of the respiratory drive constitutes the main cause of frequent and prolonged desaturations in extremely preterm (EPT) infants <28 weeks. We investigated the impact of varying the duration of apnoea before backup ventilation (BUV) on the measures of oxygenation in EPT infants during nasal continuous positive airway pressure (nCPAP) therapy. DESIGN:Single-centre randomised cross-over trial. SETTING:Level 3 neonatal intensive care unit. PATIENTS:24 EPT infants on nCPAP with BUV. MAIN OUTCOME MEASURES:The primary outcome was the time spent within a predefined oxygen saturation (SpO2) target (88%-95% or ≥88% with fraction of inspired oxygen (FiO2) =0.21) during start of BUV after 4 s of apnoea duration (AD 4) or 16 s of apnoea duration (AD 16) RESULTS: The study was successfully completed in 22 children (median gestational age 24+5 weeks, birth weight 628 g, postnatal age 48 days). Mean time spent within the SpO2 target didn't differ between AD 4 and AD 16 (66.9% vs 67.2%, p=0.88). There were no differences in the time below or above the SpO2 target, prolonged (>30 s, >60 s, >120 s) and severe (<80%, <70%) episodes of hypoxaemias and cerebral tissue oxygenation. Mean FiO2, mean airway pressure, transcutaneous carbon dioxide pressure, heart rate and respiratory frequency did not differ while the rate of BUV was significantly higher during AD 4. CONCLUSION:Reducing the time of apnoea until start of BUV didn't improve the time spent within the SpO2 target in respiratory unstable EPT infants. Our data demand intensified efforts to specify these settings of non-invasive respiratory support that better achieve this important clinical goal. TRIAL REGISTRATION NUMBER:DRKS00031911.

OBJECTIVE:To investigate respiratory practices to prevent or treat evolving bronchopulmonary dysplasia in neonatal intensive care units (NICUs) across Europe. STUDY DESIGN:Between March and July 2024, a web-based survey was sent to European NICUs caring for infants born preterm with gestational age <28 weeks. RESULTS:We received replies from 447 of 721 (62%) NICUs across 24 European countries. Almost 16% of NICUs routinely intubate at birth, especially if the gestational age is <24 weeks. During transition most NICUs use continuous positive airway pressure ≥5 cmH2O and start with an FiO2 0.3. Volume-targeted ventilation is the primary ventilation mode in 60% of the NICUs. Permissive hypercapnia is a common practice. Higher SpO2 target limits have been adopted, although alarm settings vary across NICUs. Caffeine is routinely started (96%). Surfactant is used in all NICUs, mostly rescue (74%) via less invasive administration (81%). Prophylactic inhaled nitric oxide is not used. Treatment of patent ductus arteriosus varies; half of NICUs pharmacologically treat patent ductus arteriosus early, based on echocardiographic findings. Ureaplasma screening is done in 22% of NICUs. Most (97%) NICUs use postnatal corticosteroids, with dexamethasone being the preferred drug (65%) and starting 2-3 weeks after birth. Only 5% use corticosteroids prophylactically. After 2-3 weeks, diuretics are used frequently, inhaled corticosteroids/bronchodilators to a much lesser extent. CONCLUSIONS:This large survey shows considerable practice variation in preventing and treating evolving bronchopulmonary dysplasia across Europe, especially for interventions with limited evidence.

Aberrant microbial colonization of premature infants is increasingly recognized as a risk factor for severe acute morbidities. The aim of this study was to evaluate the correlation of bacterial upper airway colonization within the first 6 weeks of life in preterm infants <1000g and risk of moderate/severe bronchopulmonary dysplasia (BPD). In this retrospective two-center cohort study postnatal upper airway bacterial colonization of premature infants with a birth weight <1000g was analyzed. Bacteria were categorized into facultative- and highly pathogenic. Within 242 infants, a birth weight cutoff of 800g prevailed as the most relevant discriminator for risk of BPD. Furthermore, center, male sex, duration of antibiotic therapy, and delayed detection of facultative pathogenic bacteria after week 4 was associated with the development of BPD. Using classification tree analyses for the binary outcome, antibiotic therapy was more importance in infants <800g, whereas in those with a birth weight ≥800g, delayed colonization with facultative pathogenic bacteria was more relevant than antibiotic exposure. We add delayed colonization of the upper airway with facultative pathogenic bacteria to the risks for BPD. The variations of microbial colonization should be considered in future studies on the pathogenesis of BPD and new treatment modalities.

Bronchopulmonary dysplasia (BPD) is one common and severe complication of preterm births. Prenatal infection/inflammation is the major cause driving preterm deliveries, but its contribution to the early-life lung development remains unclear. Pregnant C57BL/6J mice were randomized at 15.5 or 18.5 days post coitum (dpc) to receive intraperitoneal injection of sterile saline, lipopolysaccharide (LPS) 50 μg/kg, or LPS 100 μg/kg. Animal experiments were performed compliantly to the ARRIVE guidelines. Lungs of newborn pups of mixed genders were harvested at the first postnatal day (P1) for histopathology to investigate prenatal LPS-induced structural changes. Expression of key pro- and anti-inflammatory mediators was assessed at both transcriptional and translational levels. Based on bulk RNA sequencing and exploratory transcriptomic analysis, signature gene and phenotypical expression of two major mesenchymal fibroblasts subsets, myofibroblasts (MYFs) and lipofibroblasts (LIFs), were analyzed with qPCR, immunofluorescence, and western blot. Human embryo-derived WI-38 fibroblast cell line was used as an in vitro model to investigate LPS-induced fibroblast inflammatory responses and MYFs-LIFs differentiation. Newborn mice exposed to prenatal LPS exhibited enlarged air spaces and thinner septal walls, with an enhanced interleukin 6 (IL6) response in lung tissues. The degree of lung structural changes is LPS dose- and timing-dependent. Exploratory transcriptomic analysis revealed the enrichment in myofibrogenic pathways in LPS-exposed lungs. Platelet-derived growth factor receptor alpha (PDGFRA)-expressing progenitor lung fibroblasts were generally suppressed by prenatal LPS exposure. The expression of MYFs signature markers (ELN and ACTA2) in relation to LIFs (PLIN2 and FGF10) demonstrated a highly heterogeneous and dynamic pattern, depending on LPS doses and timing. Upon LPS exposure, human WI-38 fibroblasts upregulated a panel of pro-inflammatory mediators via nuclear factor kappa B signaling and displayed diverse MYFs and LIFs differentiation depending on the dose and duration of LPS stimulation. Prenatal LPS exposure induces heterogeneous structural and molecular changes in the newborn mice lung, showing LPS dose- and time-dependent modulation of mesenchymal fibroblast differentiation. These findings may contribute to refine the risk stratification of preterm infants exposed to prenatal infection/inflammation. Mesenchymal fibroblast plasticity and MYFs-LIFs phenotypic shifts may inspire preventive and therapeutic strategies for BPD.

ZusammenfassungDie fetale und neonatale Alloimmunthrombozytopenie (FNAIT) wird durch mütterliche Antikörper hervorgerufen, die gegen ein vom Vater ererbtes Blutgruppenmerkmal an fetalen Thrombozyten gerichtet sind. Während Teil 1 des Beitrags Ausgabe die Ätiologie, die Pathogenese und die Diagnostik der FNAIT thematisiert hatte, widmet sich dieser 2. Teil der Risikostratifizierung und Behandlung 1.

AIM:To compare discrimination and calibration of prognostic models for pulmonary outcomes in very preterm (VPT) infants born < 32 weeks' gestation when including the mean airway pressure (MAP), the fraction of supplemental oxygen (FiO2) and the respiratory severity score (RSS) reflecting parameters of ventilation and oxygenation during the first 24 and 72 h of life. METHODS:In this retrospective single center study of 168 VPT infants, the mean airway pressure (MAP), the fraction of supplemental oxygen (FiO2) or RSS (considering MAP and FiO2) were added to a baseline model of clinical risk factors to assess the improvements for prediction of bronchopulmonary dysplasia (BPD). RESULTS:The baseline model demonstrated good calibration (slope 1.02) and discrimination (AUC 0.85) for overall BPD (BPD28), and adding any of the parameters of ventilation resulted only in slight improvement in discrimination (AUC 0.86). For moderate/severe BPD (BPD36), overprediction in the lower extremes and underprediction in the upper extremes became evident for the baseline model. While adding MAP rendered optimal specificity (81%), sensitivity (91%) was highest for FiO2. MAP was substantially better at improving calibration for BPD36 (slope 0.98) than FiO2 (slope 0.87). Using RSS and expanding the models to the first 72 h of life did not result in any improvements. CONCLUSION:Adding parameters of ventilation and oxygenation improves baseline models to predict the risk of BPD28 and BPD36 early after birth. Particularly, our data encourage considering MAP as potential predictor in the development of future risk models to improve the prediction accuracy and to solidify early treatment decisions intended to prevent BPD.

Background:The longer-term effects of early high-dose vitamin A to support lung development in preterm infants remain to be clarified. The aim of the NeoVitaA follow-up study was to assess the effects of early postnatal additional high-dose fat-soluble enteral vitamin A supplementation (HD-VitA) vs. placebo (control) for 28 days on respiratory complications and neurodevelopmental outcome in ELBW infants receiving recommended basic vitamin A supplementation, specified as secondary outcome parameters in the NeoVitaA trial. Methods:The trial was approved by the ethics committee of Saarland, Saarbruecken, Germany (file number: 70/2011) as well as by all local ethics committees and the Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM, Bonn, Germany). The NeoVitaA trial was registered with EudraCT (2013-001998-24) and DRKS (DRKS00006541). This follow-up covers secondary endpoints at 12 and 24 months as mentioned in the registration. Follow-up took place between September 2019 and June 2024. Follow-up assessment at 12 and 24 months' corrected age (CA) of infants enrolled in the NeoVitaA-trial included anthropometric data, number of antibiotic treatments, antibiotic treatments for pulmonary infections, hospital admissions, and hospital admissions for pulmonary infections, composite scores of the Bayley Scale of Infant and Toddler Development, second (Bayley-II) or third edition (Baley-III), other medical diagnoses and medical treatments. Findings:Follow-up examinations were available for 759 infants (83.0%). HD-VitA had no effect on number of antibiotics needed for pulmonary infections or number of hospital admissions for pulmonary infections at 12 or 24 months' CA. At 24 months' CA, the median number of antibiotic courses for pulmonary infections was one for both the HD-VitA and control group; the median number of hospital admissions for pulmonary infections per patient was 0 (HD-VitA) and 1 (control).Successful Bayley assessment was completed in 618/759 infants (92 Bayley-II, 526 Bayley-III). The median Mental Development Index score for Bayley-II was 95 vs. 97 (median difference -5.0, 95%-CI [-12.0, 2.0]) and Psychomotor Development Index 96 vs. 92 (median difference 3.0, 95%-CI [-4.0, 8.0]), with intervention and placebo, respectively. The median cognitive composite score for Bayley-III was 95 vs. 95 (median difference 0.0, 95%-CI [-5.0, 0.0]) and motor score was 92 vs. 92 (median difference 0.0, 95%-CI [-4.0, 3.0]), respectively. Interpretation:Early postnatal high-dose enteral fat-soluble vitamin A supplementation in ELBW infants did not affect pulmonary or developmental outcomes at 24 months' CA. Funding:The NeoVitaA trial was funded by the Deutsche Forschungsgemeinschaft ME 3827/1-1/2 and European Clinical Research Infrastructures Network.

Background: Antibodies of the mother, which are directed against paternal antigens on platelets of the child, can lead to the destruction of the fetal blood cells in the circulation after diaplacental passage. The clinical picture of fetal-neonatal alloimmune thrombocytopenia (FNAIT) is characterized by bleeding, of which intracranial bleeding is particularly feared. Our understanding of the pathophysiology of FNAIT and its targeted prophylaxis and therapy has improved significantly in recent years. Summary: FNAIT by anti-HPA-1a is the best studied. How exactly the mother is immunized is not known for certain, but, in clinically apparent cases, immunization usually occurs in the first pregnancy of an HLA-DRB3*01:01-positive, HPA-1a-negative woman. There is no convincing basis for assigning immunization against HPA-5b and against HLA class I any significance in the development of fetal thrombocytopenia. Newborns of mothers with anti-HPA-1a present a broad clinical picture ranging from isolated, clinically unremarkable thrombocytopenia to intracranial hemorrhage (ICH; in approx. 1–10% of cases). ICH usually occurs intrauterine (before week 28). There are indications that, in addition to the fetal platelets, the placenta can also be affected by anti-HPA-1a. As there are no screening programmes, the index diagnosis of FNAIT is random. It is made by serological and genetic laboratory tests. Predicting outcome in a subsequent pregnancy is problematic if the child is antigen-positive. Key Messages: With a first-born child with severe thrombocytopenia, the probability of a recurrence of severe thrombocytopenia is around 70%. Without ICH, the probability of ICH in the subsequent pregnancy is low but not zero, and with ICH the recurrence rate is high. There is no established laboratory diagnostic method to predict the severity of thrombocytopenia or the occurrence of ICH. Prophylaxis with immunoglobulins (IVIgs) is considered effective. Pharmaceutics that block placental transport are currently undergoing clinical trials and may replace IVIgs in the future. Intrauterine platelet transfusions should no longer be performed. For the mature, thrombocytopenic newborn without internal hemorrhage, a platelet transfusion is advisable for platelet counts <25 g/L.