2026-08-14 | Association of caffeine citrate administration with necrotising enterocolitis in infants < 32 weeks' gestation: a retrospective cohort study.
To examine the association between caffeine citrate administration and necrotising enterocolitis (NEC) in very preterm infants (VPIs). A multicentre retrospective cohort study. Level III neonatal intensive care units participating in the Chinese Neonatal Network. The participants comprised neonates with a gestational age of under 32 weeks. Exposure to caffeine citrate administration after birth. Primary outcome measures were the incidence of NEC (≥stage IIA) and surgical NEC. Secondary outcome measures included severe neonatal morbidities, including severe intraventricular haemorrhages, severe retinopathy of prematurity, late-onset sepsis, bronchopulmonary dysplasia, death, duration of parenteral nutrition and length of neonatal intensive care unit stay. A total of 45 624 VPIs were included. Among 36 514 who received at least one dose of caffeine citrate, 2315 (6.3%) developed NEC (≥stage IIA) and 849 (2.3%) experienced surgical NEC. Among 9110 VPIs without caffeine exposure, 544 (6.0%) developed NEC (≥stage IIA) and 263 (2.9%) experienced surgical NEC. Caffeine citrate exposure did not affect the incidence of NEC (≥stage IIA) between groups (adjusted OR (aOR), 1.01; 95% CI 0.83 to 1.24; adjusted absolute risk (aAR), -0.15; 95% CI -1.21 to 0.92); however, its early administration (within 72 hours after birth) was associated with a lower incidence of surgical NEC (aOR, 0.76; 95% CI 0.64 to 0.89; aAR, -0.92; 95% CI -1.55 to -0.29). In subgroup analysis, caffeine citrate administration was associated with a reduction in the incidence of NEC (≥stage IIA) among VPIs receiving invasive ventilation at admission (aOR, 0.8; 95% CI 0.67 to 0.94; aAR, -2.04; 95% CI -3.82 to -0.25) and vasopressors before NEC occurred (aOR, 0.64; 95% CI 0.52 to 0.78; aAR, -5.17; 95% CI -7.94 to -2.39). While the incidence of NEC (≥stage IIA) in VPIs has not been affected by caffeine citrate, early administration (within 72 hours after birth) was associated with a reduced incidence of surgical NEC. Furthermore, among VPIs who received invasive ventilation at admission and vasopressors, the administration of caffeine citrate was potentially correlated with a decreased occurrence of NEC (≥stage IIA).
Open article ↗
2026-08-12 | Neonatal refeeding syndrome and postnatal growth in extremely low birth weight infants.
We aimed to compare the first-week trajectories of phosphorus, potassium, magnesium, calcium, and glucose between small for gestational age (SGA) and non-SGA infants, and to evaluate the association between neonatal refeeding syndrome (RS) and postnatal growth and clinical outcomes. A retrospective cohort study of 122 ELBW infants. The overall incidences of hypophosphatemia, hypokalemia, hypomagnesemia, hypercalcemia, and hyperglycemia in the total population were 38.5%, 19.7%, 4.1%, 18.0%, and 49.2%, respectively. Phosphorus, potassium, and magnesium levels were significantly lower in SGA infants than in non-SGA infants during the first week. The severity of RS was associated with growth failure (weight <10th percentile at NICU discharge, p = 0.0004) and bronchopulmonary dysplasia (BPD, p = 0.005) despite less early weight loss and more rapid recovery to birth weight. Neonatal RS was associated with postnatal growth failure at discharge and BPD. Long-term follow up is warranted in infants with RS.
Open article ↗
2026-08-08 | Brain-derived neurotrophic factor (BDNF) in neonatal blood: associations with respiratory disease in extremely preterm infants.
Neurotrophins, including brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4), have been associated with the development of bronchopulmonary dysplasia (BPD) in preterm infants. To evaluate relationships between early postnatal BDNF and NT-4 levels and adverse pulmonary outcomes among preterm infants. We analyzed data from the Extremely Low Gestational Age Newborn (ELGAN) cohort. Serum BDNF and NT-4 were measured at birth and postnatal days 7, 14, 21, and 28. Pulmonary outcomes included BPD and early respiratory patterns predictive of BPD, specifically, pulmonary deterioration (PD) and early and persistent pulmonary dysfunction (EPPD). Associations were evaluated using regression models adjusted for perinatal confounders. NT-4 levels were not associated with BPD risk. Persistently high BDNF trajectories were associated with reduced risk, while persistently low BDNF was associated with increased risk of BPD, PD, and EPPD (BPD: OR 2.75; 95% CI 1.83-4.15; PD: OR 3.13; 95% CI 1.60-6.14; and EPPD: OR 7.94; 95% CI 3.70-17.04). Infants with persistently low and intermediate BDNF trajectories had higher risk of adverse pulmonary outcomes compared with those with persistently high BDNF levels. Longitudinal BDNF trajectories identify subgroups of preterm infants at differential risk for adverse respiratory outcomes. Persistently high BDNF during the first month of life may be protective and a potential target for preventive strategies. Persistently low brain-derived neurotrophic factor (BDNF) levels during the first postnatal month are associated with increased risk and severity of bronchopulmonary dysplasia (BPD) and early adverse respiratory phenotypes in extremely preterm infants. Longitudinal BDNF trajectories provide greater discrimination of respiratory risk than single time-point measurements. Infants with persistently high BDNF have the lowest risk of pulmonary deterioration, early persistent pulmonary dysfunction, and severe BPD. These findings support BDNF as a potential early biomarker of lung disease progression in preterm infants.
Open article ↗
2026-08-07 | Human Umbilical Cord Mesenchymal Stem Cell-Derived Microvesicles Alleviate Bronchopulmonary Dysplasia in Preterm Rats by Inhibiting Neutrophil Extracellular Trap Formation.
Among preterm infants, bronchopulmonary dysplasia (BPD) is the most prevalent chronic pulmonary disorder. Its pathogenesis involves a complex interplay between prenatal inflammatory exposure and abnormal immune activation. Neutrophil extracellular traps (NETs) are mediators of tissue damage, but whether they bridge intrauterine inflammation and the subsequent development of BPD is not yet clear. We used a prenatal lipopolysaccharide (LPS)-exposed rat model to ask two questions: first, whether excessive NETs drive BPD pathogenesis, and second, whether human umbilical cord mesenchymal stem cell-derived microvesicles (hUCMSC-MVs) can alleviate lung injury by inhibiting this process. We established a BPD model in preterm rats via prenatal LPS exposure and assessed lung morphometry, neutrophil infiltration, and NETs markers. We then compared the therapeutic effects of hUCMSC-MVs with NET extrusion (NETosis) inhibitors in vivo and also examined direct neutrophil effects in vitro. Prenatal LPS exposure led to significantly elevated NET markers in both lung tissue and circulation, which correlated with severe alveolar simplification. Neutrophils in this model exhibited a "primed" phenotype with enhanced potential for NETs release. In vivo, hUCMSC-MVs suppressed NET formation, attenuated neutrophilic inflammation, and restored alveolar structure, matching the efficacy of conventional NETosis inhibitors. In vitro, they were internalized by neutrophils and abrogated LPS-induced NETosis. These findings point to excessive NETosis as a key mechanistic link between prenatal inflammation and postnatal lung impairment. hUCMSC-MVs directly inhibit this pathological process and alleviate BPD-like lung injury. This work advances the mechanistic understanding of BPD and supports hUCMSC-MVs as a promising cell-free therapeutic candidate.
Open article ↗
2026-08-06 | Characteristics and outcomes of infants with bronchopulmonary dysplasia discharged on home oxygen at Charlotte Maxeke Johannesburg Academic Hospital, South Africa.
Bronchopulmonary dysplasia (BPD) poses a considerable burden of disease in preterm infants, with incidence rising as survival of preterm infants improves. Home oxygen plays a role in the management of infants with BPD, allowing for earlier hospital discharge while requiring supplemental oxygen. To describe the incidence, clinical characteristics and outcomes of infants with BPD at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), South Africa, focusing on those discharged on home oxygen. A secondary objective was to compare characteristics of infants discharged on home oxygen with those discharged on room air. A retrospective descriptive study of infants diagnosed with BPD was conducted at CMJAH between 1 January 2015 and 31 December 2021. Clinical features, respiratory support and outcomes were described and compared between infants discharged on home oxygen and those discharged on room air. Among 866 infants, the incidence of BPD was 9.8% overall and 28.1% in very low-birthweight infants. Most cases (93.5%) were mild to moderate. Home oxygen use was low (2.1%), and systemic steroid use was high at 59.4%. Infants discharged on home oxygen had a longer hospital stay (85.1 days v. 58.3 days, p<0.001) and higher discharge weight (2 528 g v. 1 834 g, p<0.001). No significant differences in perinatal factors and comorbidities were found. By 1 year corrected age, 54.5% of those on home oxygen had been weaned off it, and 33.3% had had readmissions, mainly for respiratory tract infections. The incidence of BPD is increasing locally, but home oxygen use remains low compared with high-income countries. Limited uptake may contribute to prolonged hospitalisation. Development of local guidelines and prospective evaluation of home oxygen use are needed to optimise outcomes and reduce the healthcare burden in resource-limited settings. What the study adds. Our study showed a high incidence of bronchopulmonary dysplasia (BPD), exceeding earlier local rates but remaining below those of high-income countries. Notably, home oxygen use was low. Infants discharged on home oxygen had longer hospital stays than those discharged on room air, and no clear predictors for home oxygen use were identified.Implications of the findings. Development of standardised local protocols for home oxygen use in infants with BPD is essential. Earlier integration of home oxygen into management plans should be considered, as timely initiation may facilitate shorter hospital stay.
Open article ↗
