Background: Necrotizing enterocolitis (NEC) is the leading cause of death among preterm infants born at < 30 weeks’ gestation. The incidence of NEC is reduced when infants are fed human milk. However, in many neonatal intensive care units (NICUs), it is standard practice to freeze and/or pasteurize human milk, which deactivates bioactive components that may offer additional protective benefits. Indeed, our pilot study showed that one feed of fresh mother’s own milk per day was safe, feasible, and can reduce morbidity in preterm infants. To further evaluate the benefits of fresh human milk in the NICU, a randomized controlled trial is needed.Methods: Our prospective multicenter, double-blinded, randomized, controlled trial will include infants born at < 30 weeks’ gestation and admitted to one of 29 tertiary NICUs in China. Infants in the intervention (fresh human milk) group (n = 1549) will receive at least two feeds of fresh human milk (i.e., within 4 h of expression) per day from the time of enrollment until 32 weeks’ corrected age or discharge to home. Infants in the control group (n = 1549) will receive previously frozen human milk following the current standard protocols. Following informed consent, enrolled infants will be randomly allocated to the control or fresh human milk groups. The primary outcome is the composite outcome mortality or NEC ≥ stage 2 at 32 weeks’ corrected age, and the secondary outcomes are mortality, NEC ≥ stage 2, NEC needing surgery, late-onset sepsis, retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), weight gain, change in weight, increase in length, increase in head circumference, time to full enteral feeds, and finally, the number and type of critical incident reports, including feeding errors.Discussion: Our double-blinded, randomized, controlled trial aims to examine whether fresh human milk can improve infant outcomes. The results of this study will impact both Chinese and international medical practice and feeding policy for preterm infants. In addition, data from our study will inform changes in health policy in NICUs across China, such that mothers are encouraged to enter the NICU and express fresh milk for their infants.Trial registration: Chinese Clinical Trial Registry; #ChiCTR1900020577; registered January 1, 2019;http://www.chictr.org.cn/showprojen.aspx?proj=34276

Aim: This study aims to construct a prediction model for histological chorioamnionitis (HCA) and analyze the associations between the predicted risk of HCA and adverse outcomes in preterm infants.Methods: In total, 673 subjects were included in this cohort study and divided into HCA group (n = 195) and non-HCA group (n = 478). A stepwise method was used to screen the predictors for HCA, binary logistic regression was used to construct the prediction model, and the associations between the predicted risk of HCA and adverse outcomes were analyzed.Results: HCA occurred in 195 patients, accounting for 29.0%. The sensitivity of the prediction model was 0.821 [95% confidence interval (CI): 0.767–0.874)], the specificity was 0.684 (95% CI: 0.642–0.726), the positive predictive value was 0.514 (0.459–0.570), the negative predictive value was 0.903 (95% CI: 0.873–0.934), the area under the curve was 0.821 (95% CI: 0.786–0.855), and the accuracy was 0.724 (95% CI: 0.690–0.757). The predicted risk of HCA was associated with a higher risk of bronchopulmonary dysplasia (BPD) [odds ratio (OR) = 3.48, 95% CI: 1.10–10.95)], sepsis (OR = 6.66, 95% CI: 2.17–20.43), and neonatal infections (OR = 9.85, 95% CI: 3.59–26.98), but not necrotizing enterocolitis (OR = 0.67, 95% CI: 0.24–1.88), retinopathy of prematurity (OR = 1.59, 95% CI: 0.37–6.85), and brain damage (OR = 1.77, 95% CI: 0.82–3.83). After adjusting for confounders including gestational week at birth and birth weight, the risk of neonatal infections (OR = 5.03, 95% CI: 2.69–9.41) was increased in preterm infants’ exposure to HCA.Conclusion: The model showed good predictive performance for identifying pregnant women with a higher risk of HCA. In addition, HCA was associated with the risk of BPD, sepsis, and infections in neonates.

Objective: To analyse early risk factors for mortality in preterm infants treated with inhaled nitric oxide (iNO) in China. Design: A retrospective observational case-control study. Setting: 8 tertiary hospitals in 5 regions of China. Patients: 726 preterm infants treated with iNO for hypoxic respiratory failure or persistent pulmonary hypertension of newborns. Interventions: None. Measurements: The primary outcome was survival status at discharge. Main results: (1) The mortality rate was 27.1% (197/726), and which significantly reduced with increasing gestational age (GA) and birth weight. (2) Compared with the survival group, the death group had significantly greater use of assisted reproductive technology, higher multiple pregnancy rates and lower caesarean section rates. Infants in the death group had a significantly higher incidence of small for GA (SGA), Apgar score ≤3 at 1 min after birth, pneumorrhagia, sepsis and shock. In the death group, the utilisation rate of a pulmonary surfactant (PS) was significantly lower, whereas the oxygenation index (OI) before iNO treatment was significantly higher. The maximum dose of iNO in the death group was significantly higher than that in the survival group. (3) The Cox proportional hazard model showed that SGA (HR 1.800, 95% CI (1.113 to 2.911)), sepsis (HR 1.488, 95% CI (1.093 to 2.027)), shock (HR 1.473, 95% CI (1.033 to 2.100)), OI before iNO treatment (HR 1.016, 95% CI (1.006 to 1.026)) and the maximum dose of iNO treatment (HR 1.070, 95% CI (1.035 to 1.105)) were risk factors for death in preterm infants treated with iNO. Furthermore, GA (HR 0.876, 95% CI (0.831 to 0.924)), PS (HR 0.433, 95% CI (0.296 to 0.633)) and a higher initial dose of iNO (HR 0.926, 95% CI (0.891 to 0.962)) were identified as protective factors. (4) Stratified analysis and sensitivity analysis determined the stability of the core results in preterm infants with GA between 28 and 36 ⁺⁶ weeks. Conclusion: Premature infants treated with iNO had a high mortality rate. SGA, sepsis, shock and higher OI before iNO treatment increased the mortality risk in infants with GA between 28 and 36 ⁺⁶ weeks. A higher GA the use of PS, and a higher initial iNO dose could improve the survival outcome of these babies. Trial registration number: The study was registered in the Chinese Clinical Trials Registry ( http://www.chictr.org.cn ; registration number: ChiCTR2200066935).

Background: Brain injury (BI) is prevalent in premature infants with twin-to-twin transfusion syndrome (TTTS), while risk factors of BI in these patients remains unknown. Our study aims to discern potential risk factors that contribute to BI in premature infants with TTTS. Methods: We conducted a retrospective cohort and analyzed clinical data of premature infants diagnosed with TTTS at the Northwest Women’s and Children’s Hospital between January 1, 2015 and January 1, 2020. Data included the infants’ perinatal information, key postnatal examinations, laboratory tests, and treatments. Results: Of the 84 patients enrolled in the study, 22 (26.2%) were categorized in the BI group and 62 (73.8%) in the non-BI group, based on cranial imaging. No significant differences were found at baseline between the groups in relation to the proportion of males (40.9% vs. 35.5%, P=0.845), median gestational age (weeks) [31.9 (31.5, 33.4) vs. 34.2 (31.6, 35.4), P=0.061], average weight (g) (1,676.4±567.5 vs. 1,845.2±511.7, P=0.200), maternal age (years) [29.5 (26.0, 31.0) vs. 28.5 (27.8, 31.0), P=0.656], the proportion of in-vitro fertilization (9.1% vs. 16.1%, P=0.648), cesarean sections (86.4% vs. 93.5%, P=0.549) or TTTS donor infants (50.0% vs. 51.6%, P=0.897). Multivariate logistic regression analysis indicated that invasive mechanical ventilation [invasive mechanical ventilation (IMV); odds ratio (OR) =4.365; 95% confidence interval (CI): 1.066–17.870; P=0.040], [necrotizing enterocolitis (NEC); OR =8.632; 95% CI: 1.542–48.318; P=0.014], [single intrauterine fetal demise (sIUFD); OR =14.067; 95% CI: 1.298–224.421; P=0.031], and a 5-minute Apgar score <9 (OR =4.663; 95% CI: 1.015–21.419; P=0.048) were strongly associated with BI in TTTS premature infants. Conclusions: Our study identifies IMV, NEC, sIUFD, and a 5-minute Apgar score <9 as independent risk factors for BI in premature infants with TTTS.

Background: Bronchopulmonary Dysplasia (BPD) is a chronic lung disease affecting preterm infants, with limited prevention and treatment options. Inhaled Nitric Oxide (iNO) is sometimes used to treat Persistent Pulmonary Hypertension of the Newborn (PPHN) and Hypoxemic Respiratory Failure (HRF), and its impact on BPD development remains debated.Objective: To assess whether iNO-related factors are potential contributors to the development of BPD Grade Ⅱ-Ⅲ in very premature infants (VPI) diagnosed with PPHN or HRF at birth using Propensity Score Matching (PSM).Methods: We conducted a retrospective cohort study of infants born at 22–32 weeks gestation with PPHN or HRF, treated with iNO for over 3 h. PSM matched groups by gestational age, birth weight, and gender, etc. Multivariate logistic regression evaluated the association between iNO treatment and BPD outcomes to identify influencing factors, while Restricted Cubic Spline (RCS) and mediation analysis examined iNO dose effects and potential mediators like mechanical ventilation time and oxygenation index (OI).Results: A higher initial iNO dose was significantly associated with a reduced risk of BPD Grade Ⅱ-Ⅲ (adjusted OR = 0.68, 95% CI: 0.52–0.89, p &lt; 0.01). Additionally, administration of iNO within the first 7 days of life was identified as an important influencing factor No significant mediation effects were observed for factors such as mechanical ventilation time and OI.Conclusion: A higher initial iNO dose within the first 7 days was associated with a reduced risk of BPD Grade Ⅱ-Ⅲ in VPI with PPHN or HRF.