Bronchopulmonary dysplasia (BPD) is a major complication of prematurity frequently accompanied by life-threatening pulmonary hypertension (PH). Pirfenidone (PFD), an antifibrotic drug approved for adults, exhibits multimodal properties, but its therapeutic efficacy and underlying mechanisms in neonatal BPD-associated PH (BPD-PH) remain to be elucidated. This study aimed to evaluate the therapeutic potential of PFD and its underlying mechanisms in a hyperoxia-induced mouse model of BPD. We found that PFD treatment enhanced alveolarization, reduced pulmonary fibrosis, attenuated pulmonary vascular remodeling, and right ventricular hypertrophy. These protective effects were accompanied by decreased expression of inflammatory cytokines, improved oxidative stress profiles, and concomitant suppression of Wnt5A signaling and transforming growth factor-β1/Smad pathway activation. Collectively, these findings identify PFD as a potential modulator of lung injury and vascular remodeling in experimental BPD. However, as these observations are derived from a preclinical model, further studies are required to define safety, dosing, and efficacy before clinical translation.NEW & NOTEWORTHY This study demonstrates that PFD, an antifibrotic drug, alleviates alveolar simplification, pulmonary vascular remodeling, and right ventricular hypertrophy in a hyperoxia-induced neonatal mouse model of BPD. These protective effects were associated with suppression of Wnt5A-mediated noncanonical signaling and TGF-β/Smad activation, together with reduced inflammation and oxidative stress. These findings reveal a previously unrecognized mechanism underlying the protective effects of PFD and support its potential repurposing as a therapeutic strategy for BPD-PH.

Objective To assess the healthcare burden of bronchopulmonary dysplasia (BPD) among very preterm infants in China.Design A prospective cohort study between 2022 and 2023.Setting Chinese Neonatal Network (CHNN) participating centres.Patients Infants with gestational age <32 weeks admitted to CHNN neonatal intensive care units.Main outcome measures A composite rate of BPD or mortality at 36 weeks’ postmenstrual age (PMA), major comorbidities, clinical resources utilisation and outcome at discharge. BPD severity was classified by Jensen et al’s criteria.Results Among 17 793 eligible infants, 568 (3.2%) infants died before 36 weeks’ PMA, 1729 (9.7%) were discharged against medical advice before 36 weeks’ PMA, 9895 (55.6%) were classified as no BPD, 2751 (15.5%) developed Grade 1 BPD, 2634 (14.8%) developed Grade 2 BPD and 216 (1.2%) developed Grade 3 BPD. Infants with BPD had significantly longer hospital stays than those without BPD (median (IQR), 67 (52–84) vs 44 (34–56) days) and incurred higher total hospitalisation charges (median (IQR), 127 (91–177) vs 73 (52–103) thousand CNY) and charge per day (median (IQR), 1975 (1638–2361) vs 1714 (1409–2048) CNY). Mortality at discharge increased with BPD severity, with rates of 0.2% (18/9895) for infants without BPD, 0.5% (15/2751) for Grade 1 BPD, 2.1% (56/2634) for Grade 2 and 26.9% (58/216) for Grade 3. Similarly, the rates of major comorbidities and the need for home oxygen therapy increased with BPD severity.Conclusions Greater BPD severity was associated with increased comorbidities, higher in-hospital mortality and greater utilisation of healthcare resources. These findings emphasised the ongoing need to develop cost-saving strategies to reduce the risk and severity of BPD in this vulnerable population and improve overall care.

Background and Aims:To analyze the distribution pattern of maternal age and the impact of different maternal age subgroups on pregnancy adverse outcomes in China. Methods:This is a multicenter retrospective cohort study from 2010 to 2017. Live-born singletons were included. The pregnancy and perinatal adverse outcomes were collected. The χ2 test was used to compare the frequencies among categorical data, Student's t-test, or Kruskal-Wallis H-test for continuous variables. Each adverse outcome (p-value < 0.2 in univariate analysis) was entered into a multinomial multivariate logistic regression to compare maternal age subgroups (< 20 years, 21-24 years, 30-34 years, and ≥ 35 years) with the 25-29 years group, adjusting for parity. Results:There were 216,404 mothers with a mean age of 27.4 ± 4.9 years. The proportion of mothers of < 20 years, 21-24 years, 25-29 years, 30-34 years, and ≥ 35 years was 2.5%, 26.0%, 42.5%, 20.1%, and 9.0%, respectively. Mean gestational age at delivery and birthweight were inverted U-shaped associated with the maternal age. The incidence of preterm delivery was high in the maternal age < 20 years (11.4%) and ≥ 35 years (10.7%) categories. Compared with maternal age 25-29 years, age < 20 years and age 20-24 years were associated with preterm delivery, low birthweight infants, very low birthweight infants, Apgar score ≤ 5 at 5 min, and eclampsia. Maternal age ≥ 35 years and age 30-34 years were associated with the elevated risk of preterm delivery, macrosomia, low birthweight infants, very-low-birthweight infant delivery, gestational diabetes mellitus, gestational hypertension, pre-eclampsia, eclampsia, placenta previa, elective and emergency cesarean delivery. Maternal age ≥ 35 years was associated with a high risk of Apgar score ≤ 5 at 5 min. The overall incidence of cesarean delivery was 41.7% (56.7% in age ≥ 35 years). Conclusion:This large cohort study demonstrated a significant impact of maternal age on pregnancy adverse outcomes in China, with the < 20 years, 20-24 years, 30-34 years, and ≥ 35 years age groups being associated with an enhanced risk compared with the 25-29 years age group. The high cesarean delivery rate was alarming.

BACKGROUND:Birth weight (BW) Z-score is associated with outcomes in very preterm infants (VPIs). This study aimed to investigate the association between BW Z-score and the adverse outcomes in VPIs. METHODS:This retrospective cohort study included VPIs admitted to a tertiary neonatal intensive care unit between 1 January 2014 and 31 December 2023. Restricted cubic splines and multivariable logistic regression models were employed to assess associations between BW Z-score and primary outcomes. Infants were categorised based on the identified turning point of Z=-0.35 in the Z-score distribution, where the risk gradient changed most sharply. The primary outcome was bronchopulmonary dysplasia (BPD) or mortality at 36 weeks postmenstrual age or discharge. RESULTS:Among 4632 included VPIs, a turning point at Z=-0.35 was identified. Compared with those with Z≥-0.35, VPIs with Z<-1 exhibited higher risks of primary outcomes (OR 3.10, 95% CI 2.53 to 3.79), while those with BW Z-score between -1 and -0.35 also showed increased risks (OR 1.81, 95% CI 1.52 to 2.15). Subgroup and sensitivity analyses further supported the robustness of these findings. CONCLUSION:Compared with BW Z-score above -0.35, both substantially negative BW Z-score<-1 and moderate lower BW Z-score between -1 and -0.35 are associated with increased risk of BPD and mortality in VPIs. The findings underscore the importance of considering BW Z-score as a continuous variable in risk stratification and management of VPIs.

Background:Bronchopulmonary dysplasia (BPD) is a common complication in preterm infants, with dysmorphic microvascular development being a key factor in the pathogenesis of BPD. WNT5A plays a role in angiogenesis and vascular development and is closely associated with lung disease. This study aimed to investigate the role and underlying mechanism of WNT5A in hyperoxia-induced pulmonary microvascular impairment in BPD. Methods:A hyperoxia exposure mouse model (85% oxygen for 14 days) simulating preterm BPD was used, and was sampled on postnatal day (P) 3, 7, and 14. Western blot (WB) was used to detect the expression of endothelial cell markers von Willebrand factor (vWF) and WNT5A. Mouse pulmonary microvascular endothelial cells (PMVECs) and human umbilical vein endothelial cells (HUVECs) were cultured in 85% oxygen for 48 hours. WNT5A expression and secretion were measured through WB and enzyme-linked immunosorbent assay (ELISA). WNT5A inhibitors or recombinant WNT5A (rWNT5A) were co-cultured with cells, and the cell function was assessed. Total RNA was extracted from PMVECs, followed by RNA sequencing. Results:WNT5A expression was decreased in the lungs of hyperoxia-exposed mice at P7. Consistently, in vitro hyperoxia exposure reduced WNT5A expression and its downstream effector CaMKIIγ in endothelial cells compared with normoxia-exposed controls. Both WNT5A inhibition and rWNT5A changed the migration and tube formation functions of HUVECs in normoxic and hyperoxic conditions. RNA sequencing revealed differentially expressed genes (DEGs), and suggested enrichment in the ErbB, MAPK, and Hippo pathways in the hyperoxia group. Conclusions:Hyperoxia decreased the WNT5A expression and impaired endothelial cell function, potentially through WNT5A-CaMKIIγ.

Background The association between hypertensive disorders of pregnancy (HDP) and bronchopulmonary dysplasia (BPD) in preterm infants remains controversial due to inconsistent findings in previous studies. However, systematic studies and meta-analyses evaluating the association remain limited.Methods The study followed the Meta-analysis of Observational Studies in Epidemiology (PRISMA) reporting guideline. The PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and the Chinese Science and Technology Periodical Database (VPCS) databases were searched from January 1997 to October 2024. Search terms included gestational hypertension, preeclampsia, eclampsia, or superimposed preeclampsia on chronic hypertension; bronchopulmonary dysplasia; Premature Birth; and Stillbirth, Fetal Death or Perinatal Mortality. A random-effects meta-analysis model was used to clarify the relationships between HDP and 1) survival without BPD, 2) BPD, and 3) perinatal mortality.Results A total of 29538 publications were found, of which 21 were included in the meta-analysis. HDP was associated with reduced survival without BPD (RR 0.875, 95% CI 0.818, 0.935) and increased BPD risk (RR 1.211, 95% CI 1.101, 1.332), while no significant link with perinatal mortality (RR 1.005, 95% CI 0.781, 1.291). Stratified analyses suggested that gestational age, publication year, and geographic region may partly explain the heterogeneity among previous findings.Conclusions HDP negatively correlates with survival without BPD and positively correlates with BPD in preterm infants, underscoring the need for targeted postnatal pulmonary monitoring.

INTRODUCTION:Severe intraventricular hemorrhage (sIVH) remains a significant complication for very preterm infants (VPIs). This study aimed to assess heritable and environmental contributions to sIVH. METHODS:A total of 2,074 twin pairs born at gestational age <32 weeks with known sIVH status were identified. Three statistical methods were applied, including the Pearson χ2 test, intra-class correlation (ICC), and ACE modeling. RESULTS:Both Pearson's χ2 test (p = 0.224) and ICC analysis (p = 0.534) revealed no significant difference after comparing neither, one, or both of the monochorionic and dichorionic twin pairs who developed sIVH. ACE modeling revealed no contribution of heritability to sIVH risk, while the common environmental impacts on sIVH development were 27.9% (95% CI [23.9%, 31.9%]) and 72.1% (95% CI [68.1%, 76.1%]), respectively. Assisted conception (aOR 1.45, 95% CI [1.06, 1.97]), inotropes (<3 days) (aOR 1.71, 95% CI [1.22, 2.39]), invasive mechanical ventilation (<3 days) (aOR 2.38, 95% CI [1.56, 3.64]), and sedations (<7 days) (aOR 2.25, 95% CI [1.55, 2.06]) had contribution to sIVH, while larger gestational age (aOR 0.77 [0.71, 0.85]) and early surfactant administration (≤2 h) (aOR 0.58, 95% CI [0.42, 0.79]) prevented VPIs from sIVH. CONCLUSIONS:We recognized that environmental factors instead of heritability may play major contribution to the development of sIVH. Quality improvement studies focusing on the potential environmental factors to decrease the incidence of sIVH are warranted.

OBJECTIVE:To investigate whether gestational diabetes mellitus (GDM) was associated with survival without bronchopulmonary dysplasia (BPD) in very preterm infants (VPIs). DESIGN:Retrospective multicentre cohort study. SETTING:A total of 79 neonatal intensive care units across China, January 2019 to December 2021. PARTICIPANTS:A total of 23 752 VPIs (<32 weeks' gestation) or very low birth weight infants (<1500 g), comprising 4452 GDM-exposed and 19 300 unexposed infants. MAIN OUTCOME MEASURES:The primary outcomes are survival without BPD at 36 weeks' postmenstrual age (PMA) and its components. RESULTS:Infants exposed to GDM were associated with a higher rate of survival without BPD (aOR 1.12, 95% CI 1.04 to 1.21) at 36 weeks PMA and lower mortality (aOR 0.75, 95% CI 0.64 to 0.84) before 36 weeks PMA than unexposed infants. However, no significant association was observed between GDM and BPD at 36 weeks PMA (aOR 0.94, 95% CI 0.87 to 1.02), respiratory distress syndrome, need for advanced resuscitation or mechanical ventilation. After propensity score matching, GDM-exposed VPIs maintained higher survival without BPD (aOR 1.13, 95% CI 1.02 to 1.26) and lower mortality (aOR 0.81, 95% CI 0.68 to 0.97). These associations were strongest in infants born before 28 weeks (aOR 1.32, 95% CI 1.11 to 1.57) and those small for gestational age (aOR 1.41, 95% CI 1.11 to 1.80). CONCLUSIONS:GDM was not associated with worsened BPD in VPIs. The positive association with survival and survival without BPD warrants could reflect a selection bias.

Background Preterm birth is a leading cause of neonatal morbidity and mortality worldwide. Maternal infections, including Chlamydia trachomatis, have been linked to adverse pregnancy outcomes, yet their influence on the timing of delivery remains unclear. Most studies have examined preterm birth as a binary outcome, overlooking the variations in gestational age. This study evaluates the association between maternal Chlamydia trachomatis infection and gestational age at delivery using time-to-event analysis in a large, population-based cohort. Methods This retrospective cohort study utilized data from the National Vital Statistics System (NVSS) in the United States, comprising singleton live births from January 1, 2021, to December 31, 2023. Maternal Chlamydia infection during pregnancy was identified from standardized electronic birth records. Following 1:4 propensity score matching on key maternal and neonatal covariates, 171,695 Chlamydia-exposed pregnancies were compared with 686,780 unexposed controls. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for preterm birth (< 37 weeks), early preterm birth (< 34 weeks), very preterm birth (< 32 weeks), and extremely preterm birth (< 28 weeks). Logistic regression models evaluated secondary outcomes including low birthweight and neonatal intensive care unit admission. Results Prenatal Chlamydia exposure was associated with a modest but statistically significant increased risk of preterm birth before 37 weeks (HR 1.07, 95% CI 1.06–1.09). Elevated risks were also observed for early preterm birth before 34 weeks (HR 1.10, 95% CI 1.07–1.13) and very preterm birth before 32 weeks (HR 1.07, 95% CI 1.03–1.12). No significant association was identified for extremely preterm birth before 28 weeks (HR 1.04, 95% CI 0.97–1.11). Secondary outcomes demonstrated higher odds of NICU admission and assisted ventilation in Chlamydia-exposed infants. Subgroup analyses showed generally consistent associations across maternal and neonatal characteristics. Conclusion Maternal Chlamydia trachomatis infection is associated with an increased hazard of early delivery, particularly at earlier gestational ages. These findings emphasize the need for targeted prenatal screening and timely treatment to reduce infection related risks for preterm birth and improve perinatal outcomes.

BACKGROUND:Despite the established correlation between small for gestational age (SGA) and heightened necrotizing enterocolitis (NEC) risk, the relationship between intrauterine growth, including SGA, and the occurrence of NEC remains ambiguous. METHODS:This study utilized data of very preterm infants (VPIs) with a gestational age <32 weeks from the Chinese Neonatal Network cohort study. Intrauterine growth status was categorized through birthweight (BW) percentile delineated by the Fenton growth chart. RESULTS:The cohort comprised 23,702 VPIs containing 1186 cases of NEC. A non-linear relationship between BW percentiles and death or NEC was identified. Infants with a BW percentile ≤23rd showed an increased risk of death or NEC. The multivariate analysis indicated a significantly higher risk of death or NEC in infants categorized between the 10th and 23rd percentiles (adjusted odds ratio [aOR] = 1.41; 95% confidence interval [CI], 1.22-1.63) and those below 10th percentile (aOR = 2.09; 95% CI, 1.74-2.52), comparing with infants in the above 23rd percentile group. Subgroup analyses yielded analogous results. CONCLUSIONS:Intrauterine growth restriction significantly increases the risk of mortality or NEC among VPIs. The increased risk also extends to infants, particularly those within the 10th to 23rd percentile range, emphasizing the need for heightened surveillance and care. IMPACT:This study explores the relationship between intrauterine growth and the occurrence of necrotizing enterocolitis (NEC). In this multicenter cohort study that included 23,702 very preterm infants (VPIs), a non-linear relationship between birth weight percentiles and death or NEC was identified. Infants with a birth weight percentile at or below 23rd showed an increased risk of death or NEC. Intrauterine growth restriction significantly increases mortality or NEC risk among VPIs with birth weight at or below the 23rd percentile. This risk extends to infants, particularly within the 10th to 23rd percentile range, highlighting the need for heightened surveillance and care.

BACKGROUND:Mutations in the MECOM gene have been recognized as a causative factor in MECOM-associated syndrome, which encompasses a spectrum of hematologic and extra-hematologic manifestations. Hematologic features range from isolated thrombocytopenia to severe bone marrow failure, while extra-hematologic manifestations may include skeletal, cardiac, renal, and other abnormalities. Here, we present a case of a Han Chinese newborn with a previously unreported variant in the MECOM gene. CASE PRESENTATION:We report a 0-day-old female Han Chinese neonate who presented with severe thrombocytopenia and intracranial hemorrhage, ultimately succumbing to multiple organ failure and intracranial hemorrhage on the third day after birth. Genetic sequencing identified a heterozygous frameshift variant, c.157_158del, within the MECOM gene. This variant led to a substitution of the 53rd amino acid from methionine to glycine, terminating at the 54th amino acid. A comprehensive review of literature indicated that MECOM gene mutations included missense (68.3%), deletion (8.5%), splice site (8.5%), frameshift (7.3%), and nonsense (7.3%) mutations. Patients with missense mutations frequently exhibited radioulnar synostosis, while bone marrow failure was more commonly associated with the other four types of mutations. CONCLUSION:This study adds a novel variant of the MECOM gene to the current body of knowledge. In addition, we provide a comprehensive summary of previously reported cases. This case expands the phenotypic spectrum of MECOM variants and underscores the potential for rapid progression to a life-threatening condition.

INTRODUCTION:The impact of intrauterine growth status as measured by BW percentiles on retinopathy of prematurity (ROP) pathogenesis remains inadequately characterized. The objectives of the study were to establish BW percentile-specific risk gradients for ROP development. METHODS:A multicenter cohort study was conducted with data were collected from Chinese Neonatal Network between January, 2019 and December, 2021. The exposure was GA- and sex-specific BW percentile. The primary outcome was incidence of ROP. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated, adjusted for potential confounders, and stratified by GA, infant sex, maternal hypertension, singleton/multiple birth. RESULTS:Totally 17,882 preterm infants were enrolled, BW was 1,300.0 (1,100.0-1,500.0) g and GA was 29.9 (28.6-31.0) weeks. The incidence was 27% for any stage ROP and 3.7% for severe ROP (stage 3 or above). Each decrease of BW percentile by 10% was associated with 15% increase of odds for either any stage ROP (aOR 0.85 [95% CI: 0.83-0.86]) or severe ROP (aOR 0.85 [95% CI: 0.82-0.89]). The optimal discriminative BW percentile on receiver operating characteristic curve was 26% for predicting any stage ROP and 19% for predicting severe ROP. Lower BW percentile under these cut-offs were associated with elevated odds of any stage ROP (aOR 2.20 [95% CI: 1.97-2.47] and severe ROP (aOR 2.91 [95% CI: 2.22-3.80]). CONCLUSIONS:ROP incidence was negatively associated with BW percentile. Each 10% decreased BW percentile was associated with 15% increased odds of any stage ROP and severe ROP.

Antenatal corticosteroids (ACS) can improve the outcomes of preterm infants and have been widely adopted as the standard practice in managing pregnancies at high risk of preterm delivery between 22+0 and 33+6 weeks. Due to their significant benefit for the majority of pregnant women, several guidelines also state that maternal diabetes is not a contraindication for the use of ACS. However, no such evidence has been obtained from diabetic pregnancies. The Chinese Neonatal Network (CHNN), a national multicenter cohort study, recruited 31,915 very preterm infants (VPIs) from 79 NICUs. The outcomes were mortality and morbidity in hospital. Logistic regression models were employed to calculate the odds ratios (ORs) and its 95

Background:Delayed cord clamping (DCC) has the potential to alleviate respiratory distress by augmenting blood volume and oxygenation, although there is currently a lack of direct evidence to support this. Late preterm and early term infants born via elective cesarean section (CS) are known to be more vulnerable to the neonatal respiratory distress (NRD). This study was designed to examine the effect of DCC on NRD of these infants. Methods:Conducted from January 1, 2019 to January 31, 2024 at Shanghai First Maternity and Infant Hospital, this single-centre, phase Ⅲ, open-label randomised controlled trial included newborns delivered via elective CS between 34+0 and 38+6 weeks of gestation. Participants were excluded if fetus had suspected or confirmed congenital malformations, metabolic diseases, intrauterine growth restriction, late fetal heart rate deceleration or fetal distress. Pregnant women and their infants were randomised into immediate cord clamping (ICC) within 10 s of birth or DCC for 60 s and stratified by late preterm or early term. The primary outcome was the incidence of NRD which was defined as requiring oxygen or airway pressure support within the first 24 h of life. This study was approved from the Ethics Committee of Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University (KS 18126, KS1947). Chinese Clinical Trial Registry (ChiCTR1800017865), registered on August 18th, 2018. Findings:Of 2610 randomised women, 1418 neonates were included in the DCC group and 1419 in the ICC group. The mean maternal age for both groups was 33 (4) years, and all mothers were of Han ethnicity. The mean gestational age of the neonates was 37.9 (0.9) weeks in both groups. NRD occurred in 119 (8.4%) in DCC versus 135 (9.5%) in ICC (Adjusted Relative Risk [aRR] 0.93, 95% CI 0.75-1.14). There were no significant differences in infant and maternal adverse events such as low Apgar score (aRR 0.74, 95% CI 0.25-2.19), hypothermia (aRR 1.00, 95% CI 0.89-1.12), hypoglycemia (aRR 1.04, 95% CI 0.77-1.38), maternal intrapartum massive bleeding (aRR 0.96, 95% CI 0.76-1.19), or the requirement for transfusion (aRR 0.34, 95% CI 0.10-1.15). Interpretation:Delayed cord clamping was safe for both mothers and infants in late preterm and early term delivered by elective cesarean section, while it did not reduce the risk of early respiratory diseases. Funding:This trial was funded by Shanghai Municipal Health Commission, China in 2019 (201940140) and National Natural Science Foundation of China in 2022 (82204047).

The relationship between gestational age throughout the entire term period (37-41 weeks) and the occurrence of respiratory illness remains not fully understood. This population-based cohort study used birth data submitted by 50 states and the District of Columbia to the National Vital Statistics System database in USA to assess the association between gestational age and the incidence of neonatal respiratory failure (NRF) in term infants. Term singleton infants born from January 2021 to December 2022 were included in the analyses. The exposure variable of interest was the gestational age at birth. Primary outcome was NRF, defined by the need for assisted ventilation for over 6 h within the first days of life. Adjusted Odds ratios (aORs) compared NRF risk across gestational ages, with 39 weeks as the reference, adjusted for maternal and perinatal factors. In 4,978,703 term infants, NRF incidence at 37, 38, 39, 40, and 41 weeks was 1.7%, 0.9%, 0.6%, 0.7%, 0.8%, respectively. Compared to 39 weeks, the risk of NRF was higher at 37 weeks (aOR 2.08; 95% CI, 2.02-2.14), 38 weeks (aOR 1.27; 95% CI, 1.23-1.30), 40 weeks (aOR 1.18; 95% CI, 1.15-1.22), and 41 weeks (aOR 1.30; 95% CI, 1.25-1.35). Subgroup analyses confirmed similar trends across sex (male: aOR 2.07 at 37 weeks, 1.37 at 38 weeks, 1.12 at 40 weeks, 1.39 at 41 weeks; female: aOR 2.00 at 37 weeks, 1.34 at 38 weeks, 1.12 at 40 weeks, 1.40 at 41 weeks), delivery mode (vaginal delivery: aOR 1.96 at 37 weeks, 1.33 at 38 weeks, 1.10 at 40 weeks, 1.34 at 41 weeks; cesarean section: aOR 2.10 at 37 weeks, 1.37 at 38 weeks, 1.15 at 40 weeks, 1.48 at 41 weeks), and in infants born via elective cesarean section (aOR 2.51 at 37 weeks, 1.37 at 38 weeks, 1.09 at 40 weeks, 1.35 at 41 weeks). These findings highlight associations between gestational age within the term range and NRF risk, suggesting that careful consideration of delivery timing may be important for reducing respiratory complications in term infants.

OBJECTIVES:To investigate the associations between maternal fine particulate matter (PM2.5) and PM<10 µm in aerodynamic diameter (PM10) exposure during pregnancy and bronchopulmonary dysplasia (BPD) incidence in very preterm infants (VPIs, gestational age (GA)<32 weeks), with emphasis on trimester-specific susceptibility and effect modification by clinical and environmental factors. DESIGN:Retrospective observational cohort study. SETTING:A tertiary neonatal intensive care unit in China, 2016-2022. PARTICIPANTS:2223 VPIs hospitalised during the study were enrolled after excluding infants with severe congenital malformations, those who abandoned treatment and those who died before discharge. Of these, 59.8% were male. PRIMARY AND SECONDARY OUTCOME MEASURES:We evaluated the effect of maternal PM2.5 and PM10 exposure on BPD, adjusted for additional ambient air pollutants (ozone and nitrogen dioxide) as well as demographic and clinical characteristics. We also calculated trimester-specific PM exposure effects and conducted stratified analyses by sex, GA, birth weight (BW) and conception season, with formal interaction testing. RESULTS:Among 2223 VPIs included in this study, 684 (30.8%) were diagnosed with BPD. Strong correlations were observed between PM exposure and BPD, with each IQR increase during the entire gestational period associated with ORs of 1.254 (95% CI 1.062 to 1.484) for PM2.5 and 1.350 (95% CI 1.142 to 1.596) for PM10 in the single-pollutant model. The strongest associations were observed during the second trimester, and the same association was also identified in the two-pollutant model. Stratified analysis revealed a larger OR estimate in subgroups with lower BW (<1500 g) and smaller GA (<28 weeks). CONCLUSIONS:Maternal PM exposure, particularly during the second trimester, is significantly associated with BPD in VPIs, with heightened vulnerability in males and infants with lower GA and BW. These findings underscore the need for prenatal air quality interventions and targeted monitoring of high-risk subgroups. Future research should explore PM-induced mechanisms of fetal lung injury and validate these associations in multicentre cohorts.

This study aimed to investigate the association between prenatal Chlamydia exposure and early neonatal respiratory failure (NRF) in very preterm infants (VPIs).This population-based cohort study utilized birth data submitted by 50 states and the District of Columbia to the National Vital Statistics System database in the United States. The study included all VPIs with a gestational age of 24 to 31 weeks from January 1, 2021, to December 31, 2022. Infants exposed to Chlamydia were compared with unexposed infants (no Chlamydia exposure) selected through propensity score matching at a 1:2 ratio, adjusting for confounding factors. The primary outcome was NRF, defined as the requirement for assisted ventilation for more than 6 hours, as recorded in the database.After propensity score matching, 2,757 Chlamydia-exposed infants and 5,507 no Chlamydia-exposure infants were compared. Infants with Chlamydia exposure had a significantly higher relative risk of NRF compared to no Chlamydia-exposure infants (30.5%, 840/2,757 vs. 25.4%, 1,401/5,507; risk ratio [RR] = 1.20 [95% CI, 1.13-1.29]). Additionally, the risk of assisted ventilation required immediately following delivery was higher in the Chlamydia-exposed group (47.2%, 1,300/2,757 vs. 41.5%, 2,283/5,507; RR = 1.15 [95% CI, 1.10-1.20]). Subgroup analyses by gestational age, sex, and other factors demonstrated consistent results for the primary outcome. Sensitivity analyses, including total infants, 1:1 propensity score matching, and 1:3 propensity score matching, yielded similar findings.Prenatal Chlamydia exposure is significantly associated with an increased risk of NRF in VPIs. Further investigation is warranted to develop intervention strategies aimed at preventing NRF in high-risk infants with prenatal Chlamydia exposure. · NRF remains the leading cause of early neonatal death in VPIs.. · There is limited and inconclusive evidence regarding prenatal Chlamydia and NRF.. · VPIs with Chlamydia exposure had a significantly higher risk of NRF..

BACKGROUND AND OBJECTIVES:Antenatal corticosteroids (ACS) exposure in term infants potentially cause short and long-term negative consequence. This study aims to estimate the prevalence of ACS exposure among term infants, identify associated risk factors, and assess the impact on neonatal respiratory failure (NRF). METHODS:A population-based, retrospective cohort analysis was conducted using the 2022 National Vital Statistics System data from USA, focusing on term infants (37-41 weeks' gestation). We defined ACS exposure based on any record of corticosteroid administration to the mother before delivery. Logistic regression models analyzed the risk factors of ACS exposure while propensity score matching(PSM) were used to evaluate the association between ACS exposure and NRF. RESULTS:Of the 2,883,280 term infants studied, 34,986 (1.2 %) were exposed to ACS. Logistic regression model demonstrated that factors significantly linked to ACS exposure (adjusted Odds Ratios, aORs > 2) included multiple gestation (aOR 2.36, 95 % CI 2.26-2.46), lower gestational age (37 weeks vs. 39 weeks, aOR 3.92, 95 % CI 3.81-4.04), and SGA status (aOR 3.72, 95 % CI 3.63-3.81). After PSM, ACS-exposed infants exhibited a higher risk of NRF compared to non-exposed infants (3.9 % vs. 1.6 %; OR 2.58, 95 % CI 2.34-2.85; p < 0.001). Subgroup analyses demonstrated a consistent elevation of NRF risk associated with ACS exposure across various gestational ages, delivery methods, and maternal health conditions. CONCLUSION:ACS exposure occurs in a notable percentage of term births and is associated with increased risks of NRF, challenging the primary objective of ACS use in term infants. The findings underline the need for more cautious and targeted administration of ACS to avoid unnecessary exposure and mitigate adverse outcomes in term infants.

Hypertensive disorders of pregnancy (HDP) may affect fetal development and result in preterm delivery. Necrotizing enterocolitis (NEC) is a severe gastrointestinal emergency in very preterm infants (VPIs, gestational age less than 32 weeks). The relationship between maternal HDP and NEC is controversial. Objective To investigate the association between maternal HDP and NEC in VPIs.This was a multicenter retrospective cohort study based on the data from the Chinese Neonatal Network (CHNN) which were collected between January 1, 2019 and December 31, 2021. Preterm infants born between 24+0 and 31+6 weeks of gestation were divided into HDP and no-HDP groups according to the 2015 Chinese guidelines for HDP. The primary outcome was the incidence of Bell’s stage II or higher NEC. Secondary outcomes included mortality and spontaneous intestinal perforation (SIP). Of 27,660 women were included in the study analysis, 5405 (19.5%) were HDP and 22256 (80.5%) were no-HDP. NEC occurred in 5.2% (283/5,404) among HDP mothers and 5.3% (1,191/22,256) among no-HDP mothers. No significant association was observed between HDP and Bell’s stage II or higher NEC (aOR 0.87, 95% CI [0.72, 1.05]). However, even after adjustment, maternal HDP appeared to be protective for NEC requiring surgical intervention (aOR 0.60, 95% CI [0.43, 0.83]). There was no significant correlation between maternal HDP and neonatal mortality and SIP. Maternal HDP was not significantly associated with the incidence of Bell’s stage II or higher NEC. However, it was associated with the lower rate of NEC requiring surgical intervention.