Objective: Nutritional deficiency soon after birth is a risk factor of chronic lung disease (bronchopulmonary dysplasia, BPD). Afflicted infants are further prone to inadequate growth during hospitalization (extrauterine growth restriction, EUGR). This multi-center retrospective study investigated risk factors of EUGR, specifically in very preterm infants with BPD. Method: Data of infants with BPD who were born less than 32 weeks gestation (n = 1010) were collected from 7 regions of China. All infants were non-small for gestational age at birth. Infants were characterized as EUGR or non-EUGR at 36 weeks gestation or discharge, or stratified by gestational age or birthweight. Logistic regression analysis was applied. Results: In 65.5% of the population, the BPD was mild. Infants with severe BPD (8.3%) had the highest rate of EUGR (72.6%, P < 0.001). Groups stratified by gestational age did not differ in rates of EUGR, but the birthweight of the EUGR group was significantly lower than that of the non-EUGR (P < 0.001). Birthweights of < 1000, 1000–1499, and ≥ 1500 g showed EUGR rates of 65.9%, 43.4%, and 23.8%, respectively (P < 0.001). Overall, the independent risk factors of EUGR were: moderate-to-severe BPD, gestational hypertension, cesarean section, cumulative fasting time, time required to achieve 110 kcal/kg/d, and hemodynamically significant patent ductus arteriosus (hsPDA). Conclusion: In very preterm infants with BPD, the lower the birthweight or the more severe the BPD, the greater the risk of EUGR. In those with hsPDA, or moderate-to-severe BPD, it is especially important to prevent EUGR through perinatal management, enteral nutrition, and nutritional strategies.

To evaluate the association of NOS1 and NOS3 gene polymorphisms with the risk/severity of neonatal respiratory distress syndrome (RDS) among preterm infants. The patient group was 189 preterm infants diagnosed with RDS. The control group was 227 preterm neonates who did not develop RDS. NOS genotyping was performed using an improved multiplex ligation detection reaction (iMLDR) technique based on LDR. It was found that genotype and allele frequencies of rs2682826 of the NOS1 gene and rs1799983 of the NOS3 gene were not significantly different between the RDS group and the control group. However, when the preterm infants were divided into two and three groups based on gestational age and birth weight, a study of the SNP rs1799983 of the NOS3 gene showed that the GG genotype and G allele frequencies were significantly increased in the RDS groups, the GT genotype and A allele were less frequent among the RDS groups in 26–32.9 weeks of gestational age and in a birth weight subgroup of <1.5 Kg. Our study raises the possibility that a genetic variation of NOS3 could be implicated in the pathophysiology of RDS in the Chinese Han population, especially in very preterm and very low birth weight infants.

Importance: The impact of antenatal corticosteroids (ACS) on bronchopulmonary dysplasia (BPD) in very preterm infants remains controversial, with limited evidence on causal mediation pathways. Objective: To evaluate the association between ACS and BPD in very preterm infants and assess whether respiratory distress syndrome (RDS) and invasive mechanical ventilation (IMV) have mediating roles. Design, Setting, and Participants: This prospective multicenter cohort study included preterm infants from 28 tertiary centers in China between September 1, 2019, and December 31, 2020. Inclusion criteria were gestational age (GA) less than 30 weeks, admission to the neonatal intensive care unit with 24 hours of birth, and neonatal hospitalization for more than 2 weeks. Analysis was done from April 1 to May 1, 2025. Exposure: Complete or incomplete ACS courses (vs no ACS). Main Outcomes and Measures: The primary outcome was moderate-to-severe BPD (using National Institute of Child Health and Human Development 2001 criteria) assessed at corrected GA of 36 weeks. Secondary outcomes were severe RDS (grade 3-4) and IMV duration. Regression models adjusted for demographic, pregnancy, and birth characteristics. Results: A total of 1097 preterm infants were enrolled, with median gestational age of 28.71 weeks (IQR, 27.71-29.29 weeks), median birth weight of 1150 g (IQR, 1000-1310 g), and median IMV duration of 2.0 days (IQR, 0.0-7.0 days). Of 1075 infants with available sex data, 599 (56%) were males. A total of 1069 infants had known ACS data; ACS were given in 832 cases (78%), with 518 (48%) receiving complete courses. Moderate-to-severe BPD occurred in 309 of 1097 infants (28%) and severe RDS in 237 of 1085 (22%). Complete ACS courses showed negative associations with risk of moderate-to-severe BPD (adjusted risk ratio [ARR], 0.68; 95% CI, 0.55-0.84), severe RDS (ARR, 0.67; 95% CI, 0.51-0.88), and IMV duration (β, −2.003; 95% CI, −3.391 to −0.614). Significant associations with lower BPD risk were observed in infants with GA of 28 weeks to 28 weeks 6 days (ARR, 0.47; 95% CI, 0.29-0.74), singletons (ARR, 0.67; 95% CI, 0.50-0.88), and vaginal deliveries (ARR, 0.62; 95% CI, 0.46-0.83). Mediation analysis suggested that ACS was associated with reduced risk of BPD (β, −0.050; 95% CI, −0.081 to −0.017) through direct (β, −0.031; 95% CI, −0.061 to −0.001) and indirect (β, −0.019; 95% CI, −0.032 to −0.007) effects, with the latter comprising both single and serial mediation pathways. Conclusions and Relevance: In this cohort study of preterm infants, complete ACS courses in high-risk pregnancies were associated with a reduction in neonatal BPD, potentially mediated through multifactorial pathways. Emphasizing the importance of timely ACS completion and postnatal airway management may help optimize neonatal pulmonary outcomes.

To evaluate the association between respiratory tract microorganisms at birth and the subsequent development and severity of bronchopulmonary dysplasia (BPD) in preterm infants. This prospective cohort study enrolled 98 preterm infants (gestational age < 32 weeks, birth weight < 2,000 g). Tracheal aspirate samples were collected through endotracheal intubation within 2 h after birth. Using 16S rRNA sequencing, we characterized the airway microbiome and performed co-occurrence network analysis with compositionally robust methods. Among 98 preterm infants analyzed, the incidence of BPD was 68.4%, comprising 31 grade I, 20 grade II, and 16 grade III cases. Airway microbiota in infants with BPD exhibited distinct severity-stage patterns: Escherichia-Shigella and Streptococcus were significantly enriched in grade I, while Chryseobacterium increased markedly in grade III, accompanied by a significant reduction in Streptococcus . Microbial co-occurrence network analysis yielded three key insights. (i) Network complexity declined sharply with BPD severity, being sparsest in grade III. (ii) Distinct keystone taxa were identified across different groups: Acinetobacter and Fusobacterium in the non-BPD group; Brevundimonas and Fusobacterium in grade I; Fusobacterium and Acinetobacter at grade II and grade III. (iii) In a multivariable model adjusted for key clinical confounders, a higher microbial network density at birth was independently associated with a substantially reduced risk (OR = 0.12, P < 0.05). The ecological architecture of the neonatal airway microbiome at birth, defined by network complexity and keystone taxa, is associated with BPD severity. This highlights microbial network stability as a novel factor and ecological interactions as a target for future research. IMPORTANCE: Bronchopulmonary dysplasia (BPD) remains the most common chronic lung disease in preterm infants. While its pathogenesis is incompletely understood, the role of the early respiratory microbe is increasingly recognized. Previous studies have largely focused on individual pathogenic taxa, overlooking the complex ecological interactions within microbial communities. Our analysis reveals that the architecture of microbial co-occurrence networks in the neonatal airway varies significantly with BPD severity. Notably, network complexity decreased markedly as BPD severity increased. We identified specific keystone taxa uniquely associated with disease outcomes, suggesting that microbial ecosystem stability rather than individual species may be a critical factor in BPD pathogenesis. These findings shift the focus from single microbes to the stability of the microbial ecosystem as a novel risk factor for severe BPD, offering new avenues for risk stratification and early intervention.