Background Chromosome 17q23.1-q23.2 deletion syndrome is a rare genetic disorder characterized by various congenital defects, including microcephaly, heart and lung defects, limb abnormalities, and mild-to-severe developmental delay. Respiratory distress and severe pulmonary hypertension (PH) are possible initial symptoms. Case presentation We report two cases of full-term neonates with respiratory distress presenting shortly after birth. They both presented with severe PH in the early postnatal period, with oxygenation indices exceeding 70. Their symptoms were temporarily relieved with comprehensive treatment but PH either persisted into, or reappeared in infancy. Case 1 had an anomalous origin of the right upper lobe bronchus on chest computed tomography (CT) imaging, while Case 2 had an atrial septal defect and cor triatriatum sinister on echocardiography. Case 2 also exhibited bilateral inner ear malformations and bilateral irregularities in the morphology of the auditory ossicles on temporal bone CT imaging. Whole-exome sequencing revealed a 2.0-2.3 Mb de novo heterozygous deletion at 17q23.1-q23.2 encompassing T-box transcription factor 2 and 4 genes in both infants, which were confirmed by quantitative real-time PCR. Despite receiving intensive care, they succumbed to irreversible PH and respiratory and heart failure, with one passing away at 3 months and the other at 20 months of age. Conclusions This is the first report of two cases of chromosome 17q23.1-q23.2 deletion syndrome diagnosed after birth in China, both associated with intractable PH, expanding the current clinical phenotype spectrum of this disorder.

Background Intracranial hemorrhage (IVH) and periventricular leukomalacia (PVL) are common complications in preterm infants with a gestational age (GA) < 32 weeks. Severe IVH (Grades 3–4) and PVL can lead to long-term neurological sequelae, including cerebral palsy, epilepsy, and intellectual disabilities. The safety and efficacy of inhaled nitric oxide (iNO) in infants with GA < 32 weeks remains controversial. Some studies suggest that iNO can improve oxygenation but may affect coagulation and increase the risk of IVH. Objective This study aimed to identify the factors influencing the occurrence of severe brain injury (sBI) in preterm infants with GA < 32 weeks receiving iNO treatment, using propensity score matching (PSM) analysis. Methods A multicenter retrospective cohort study was conducted, including preterm infants born at GA < 32 weeks who received iNO treatment for more than 3 hours across eight hospitals in China between 2013 and 2022. Infants were divided into two groups based on the occurrence of sBI. PSM was used to match the infants in a 1:1 ratio based on covariates such as GA, birth weight, and gender. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for sBI. Repeated-measures ANOVA and mediation analysis were used to assess the significance of risk factors and their potential mediating effects on the occurrence of sBI. Results After matching, baseline characteristics between the sBI and non-sBI groups were balanced. Univariate and multivariate analyses showed that reduced platelet count was an independent risk factor for sBI. The total invasive high-frequency mechanical ventilation time, P/F ratio at 3 hours and 6 hours post-iNO treatment were statistically significant in univariate analysis but not in multivariate analysis. Mediation analysis revealed no mediating effect of mechanical ventilation time or P/F ratio on the relationship between platelet count and sBI. Repeated-measures ANOVA showed that iNO treatment significantly affected the P/F ratio, which improved over time. However, no significant difference in P/F ratio changes was observed between the sBI and non-sBI groups. Conclusion This study suggests that reduced platelet count is an independent risk factor for the occurrence of sBI in preterm infants with GA < 32 weeks receiving iNO treatment. Although total invasive high-frequency mechanical ventilation time and P/F ratio changes may also affect sBI occurrence, they do not mediate the relationship between platelet count and sBI.

BACKGROUND:Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth and may lead to difficulties with oxygen control even at home. How oxygenation is managed outside the hospital and in high and low resourced settings is unclear. AIMS:To determine clinician perspectives for managing oxygenation after hospital discharge in infants with BPD. METHODS:An opportunistic, anonymous, online survey was developed in English and translated into Mandarin, Vietnamese and Korean. The survey was disseminated three times to neonatal clinicians between December 2022 and August 2023. Responses were classified using the World Bank Income Classification. RESULTS:Overall, 610 clinicians from 44 countries responded, with 453 (74%, 453/610) from high- and upper-middle-income countries (HMIC) and 153 (25%, 153/610) from low- and lower-middle-income countries (LMIC). Most clinicians (84%, 510/610) would advocate discharge on home oxygen therapy (HOT), but this was less possible in LMIC (65% vs. 91%, p < 0.001). Most clinicians perceived HOT to improve growth (73%, 370/510) and neurodevelopment (72%, 366/510). HMIC respondents were more likely to use home oximetry (78% vs. LMIC 67%, p = 0.012). There were wide variations in oxygen saturation targets, pre-discharge oximetry use, and parameters for weaning. Most clinicians perceived novel technologies such as wearable oximetry with parent-led oxygen control as important (77%, 460/596) and useful (84%, 499/595) for improving oxygen management at home. CONCLUSION:Most neonatal clinicians would prescribe HOT for infants with BPD but are limited by barriers to sufficient resourcing, especially in LMIC. Evaluation of cost-effective novel monitoring techniques may improve accessibility and control of HOT.

Background:Neonatal Listeria monocytogenes (L. monocytogenes) sepsis is rare but clinically severe. Existing research primarily focused on epidemiology, clinical characteristics, and prognosis, whereas WGS-based descriptions of virulence gene repertoires in neonatal isolates remain limited. Methods:This multicenter retrospective case series analyzed 11 neonates diagnosed with culture-confirmed L. monocytogenes sepsis. Perinatal data, clinical presentations, interventions, complications, and outcomes were recorded. Whole-genome sequencing (WGS) was performed on four available L. monocytogenes isolates, with virulence gene profiles annotated against public databases. We summarized the carriage of selected virulence genes, including inlP, actA, auto, vip, and bsh, and interpreted these profiles together with case-level clinical severity and phylogenetic background. Results:All cases were early onset, predominantly affecting preterm infants, requiring respiratory support, and with a high incidence of severe complications. All four sequenced isolates harbored core virulence genes associated with adhesion, invasion, motility, and stress survival. The nSOFA scores for Cases 1-4 were 4, 7, 2, and 2, respectively. Case-level differences were observed in the carriage of virulence genes, including actA, auto, vip, etc. Core-genome SNP phylogenetic analysis revealed that the four isolates belonged to different clonal complexes, with Cases 1 and 2 belonging to the CC1/lineage I, and Cases 3 and 4 belonging to the lineage II-related clonal complex, including CC155 and CC121. Expanded analysis incorporating 39 public reference genomes suggested that the selected accessory virulence genes, particularly actA and bsh carriage, should be interpreted within the MLST lineage background rather than as direct indicators of clinical severity. Conclusion:This multicenter study provides preliminary clinical and genomic data on neonatal L. monocytogenes sepsis. The observed heterogeneity in virulence gene profiles indicates genomic diversity among isolates and should be interpreted within a phylogenetic context. Larger-scale, lineage-matched cohort studies and functional investigations are needed before any genotype-phenotype relationships can be inferred.

To analyse early risk factors for mortality in preterm infants treated with inhaled nitric oxide (iNO) in China. A retrospective observational case-control study. 8 tertiary hospitals in 5 regions of China. 726 preterm infants treated with iNO for hypoxic respiratory failure or persistent pulmonary hypertension of newborns. None. The primary outcome was survival status at discharge. (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. 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. The study was registered in the Chinese Clinical Trials Registry (http://www.chictr.org.cn; registration number: ChiCTR2200066935).

Despite the lack of consensus, the use of inhaled nitric oxide (iNO) in preterm infants with a gestational age (GA) of less than 34 weeks has been increasing in recent years. At present, there are no multi-center studies in China on the use of iNO in this population. This study aims to investigate the use of iNO in preterm infants under 34 weeks of gestation over the past 10 years in China, and provides evidence-based medical proof for the use of iNO in these neonates. Using a retrospective study method, clinical data were collected from infants with a GA of less than 34 weeks who received iNO therapy in the neonatal units of five tertiary hospitals in China from January 2013 to December 2022. The infants were divided into two groups: Group A (2013–2017) and Group B (2018–2022). The differences in clinical characteristics, iNO use, and short-term outcomes between the two groups were analyzed. Over the past decade, the use of iNO in preterm infants with a GA of less than 34 weeks has increased gradually, with a more pronounced rise in its use among preterm infants born at 24–27 weeks. The proportion of infants receiving iNO therapy has increased from 1.23

This study aimed to investigate clinical features of inhaled nitric oxide (iNO) in preterm infants with a gestational age (GA) < 34 weeks in China.The clinical data of 434 preterm infants with GA < 34 weeks, treated with iNO in the neonatology departments of eight Class A tertiary hospitals in China over a 10-year period from January 2013 to December 2022, were included in this retrospective multicenter investigation. The infants were divided into three groups based on GA: 24 to 27 weeks (extremely preterm infants), 28 to 31 weeks (very preterm infants), and 32 to 33 weeks (moderate preterm infants). The use of iNO, perinatal data, incidence and mortality of indication for iNO treatment, therapeutic effects of iNO, incidence of short-term complications for iNO treatment, and mortality were compared among these three groups.Over the past 10 years, the proportion of iNO use was highest in extremely preterm infants each year. The lower the GA, the higher the iNO use rate: 4.20% for GA 24 to 27 weeks, 1.54% for GA 28 to 31 weeks, and 0.85% for GA 32 to 33 weeks. There was no significant difference in the therapeutic effect of iNO among the three groups. The incidence of neonatal pulmonary hemorrhage, neonatal shock, late-onset diseases, retinopathy of prematurity requiring intervention, intracranial hemorrhage (grade 3 or 4), periventricular leukomalacia, neonatal necrotizing enterocolitis (≥stage II), and moderate to severe bronchopulmonary dysplasia was highest in extremely preterm infants and increased with decreasing GA. Mortality was negatively correlated with GA and birth weight. The highest rate of iNO treatment in 24 to 27 weeks' preterm infants was due to hypoxic respiratory failure (HRF), whereas the highest rate of iNO treatment in 32 to 33 weeks' preterm infants was due to documented persistent pulmonary hypertension of the newborn (PPHN). The rates of iNO treatment due to HRF and documented PPHN were 54.3 and 60.6%, respectively, in extremely preterm infants, significantly higher than in very preterm and moderate preterm infants (all p < 0.05). Within the same GA group, the proportion of preterm infants treated with iNO for HRF was lower than that for documented PPHN (all p < 0.05), but there was no statistically significant difference in mortality between HRF and documented PPHN treated with iNO (all p > 0.05).Among preterm infants with GA < 34 weeks, the rate of iNO usage was highest in extremely preterm infants. However, iNO failed to improve the clinical outcome of extremely preterm infants with refractory hypoxemia, and there was no significant difference in the therapeutic effect of iNO among preterm infants with different GAs.

BackgroundBronchopulmonary 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.ObjectiveTo 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).MethodsWe 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).ResultsA 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 < 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.ConclusionA 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.

BackgroundHyperglycemia in pregnancy (HGP) has generally been considered a risk factor associated with adverse outcomes in offspring, but its impact on the short-term outcomes of very preterm infants remains unclear.MethodsA secondary analysis was performed based on clinical data collected prospectively from 28 hospitals in seven regions of China from September 2019 to December 2020. According to maternal HGP, all infants were divided into the HGP group or the non-HGP group. A propensity score matching analysis was used to adjust for confounding factors, including gestational age, twin or multiple births, sex, antenatal steroid administration, delivery mode and hypertensive disorders of pregnancy. The main complications and the short-term growth status during hospitalization were evaluated in the HGP and non-HGP groups.ResultsA total of 2,514 infants were eligible for analysis. After matching, there were 437 infants in the HGP group and 874 infants in the non-HGP group. There was no significant difference between the two groups in main complications including respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity, patent ductus arteriosus, culture positive sepsis, intraventricular hemorrhage, periventricular leukomalacia, anemia, feeding intolerance, metabolic bone disease of prematurity, or parenteral nutrition-associated cholestasis. The incidences of extrauterine growth retardation and increased growth retardation for weight and head circumference in the non-HGP group were all higher than those in the HGP group after matching (P < 0.05).ConclusionsHGP did not worsen the short-term outcomes of the surviving very preterm infants, as it did not lead to a higher risk of the main neonatal complications, and the infants’ growth improved during hospitalization.

Objective: To investigate the use of inhaled nitric oxide (iNO) in hospitalized preterm infants in China over 10 years and its clinical outcomes. Methods: A total of 616 premature infants who were administered iNO in the Neonatology Departments of 5 Class A tertiary hospitals in China for ten years from January 2013 to December 2022 were included retrospectively. Based on their enrollment periods, the patients were divided into two groups: Group 1 from January 2013 to December 2017 and Group 2 from January 2018 to December 2022, respectively. The perinatal characteristics, short-term clinical outcomes, and mortality rates were compared between these two groups. Results: The utilization of iNO in preterm infants grew annually over the past10 years; the utilization of iNO in Group 2 infants increased approximately one-fold when compared with Group 1 (1.52% vs. 0.80%, p < .001), and the increase was greater in gestational age (GA) < 34 weeks compared with 34-36 weeks preterm infants. Moreover, the iNO usage in Group 1 infants with GA < 34 weeks increased from 1.14% to 2.46% and 0.60% to 0.99% in 34-36 weeks preterm infants (p < .001) in Group 2, respectively. Apart from a smaller GA (32.9 w vs. 33.5 w, p < .001) and birth weight (BW, 1900 g vs. 2141 g, p < .001), the initial [14 parts per million (ppm) versus 10 ppm, p < .001] and maximum (15 ppm vs. 10 ppm, p < .001) doses of Group 2 were larger; however, their recent clinical outcomes did not improve with increasing iNO utilization (p > .05)as compared to Group 1, respectively. Although the overall iNO preterm mortality rates over the past 10 years were 25.8%, the mortality rates for preterm infants at 34-36 weeks were significantly lower than for preterm infants at GA < 34 weeks (15.4% vs. 33.8%, p < .001). Nonetheless, no improvement in mortality was observed in Group 2 preterm infants with GA < 34 weeks for the past 5 years when compared with Group 1 (32.9% vs. 35.8%, p > .05) infants, and significantly lower mortality rates were noticed in preterm infants with 34-36 weeks (11.2% vs. 22.7%, p < .001). Patients with hypoxic respiratory failure (HRF) or persistent pulmonary hypertension of the newborn (PPHN) iNO preterm infants did not show lower mortality rates with the increase of iNO use rate (p > .05). The overall mortality rates of preterm PPHN infants with iNO were lower than that of HRF (20.2% vs. 36.5%, p < .001), while the mortality rates of Group 2 preterm PPHN infants with iNO significantly lower than that of HRF (17.7% vs 36.0%, p < .001). Conclusion: The iNO has been extensively used in Chinese preterm infants over the past 10 years, this increase was more significant in preterm infants with GA < 34 weeks. Moreover, preterm infants using iNO have lower GA and BW, larger initial and maximum doses, and more aggressive strategies in the last past 5 years. Although iNO use in preterm infants with GA of 34-36 weeks has significantly reduced mortality, mortality rates and short-term clinical outcomes of iNO in preterm infants <34 weeks of GA has no obvious improvement. Further studies are required to investigate the efficacy and safety of iNO in preterm infants <34 weeks of GA.

Objectives: To examine the risk factors for severe bronchopulmonary dysplasia (BPD) in a cohort of very preterm infants (VPIs) in China, as BPD is common among VPIs and associated with a high mortality rate. Methods: In this multicenter retrospective study, medical records from infants with BPD born at gestation age (GA) of <32 weeks with birth weight (BW) of <1,500 grams (g) in 7 regions of China were included. The cohort was stratified into different BPD severity groups based on their fraction of inspired oxygen requirement at a modified GA of 36 weeks or post discharge. Risk factors were identified using logistic regression analysis. Results: A significant inverse correlation was revealed between BPD severity and both GA and BW ( p <0.001). Independent risk factors for severe BPD (sBPD) were identified as invasive mechanical ventilation (>= 7d), multiple blood transfusion (>= 3), nosocomial infection (NI), hemodynamically significant patent ductus arteriosus (hsPDA), delayed initiation of enteral nutrition, and longer time to achieve total caloric intake of 110 kcal/kg. Conversely, administration of antenatal steroids was associated with reduced risk of sBPD. Conclusion: Our study not only reaffirmed the established risk factors of low GA and BW for sBPD in VPIs, but also identified additional, potentially modifiable risk factors. Further research is warranted to explore whether intervention in these modifiable factors might reduce the risk of sBPD.

Background Necrotizing enterocolitis (NEC) is a serious gastrointestinal disease, primarily affects preterm newborns and occurs after 7 days of life (late-onset NEC, LO-NEC). Unfortunately, over the past several decades, not much progress has been made in its treatment or prevention. This study aimed to analyze the risk factors for LO-NEC, and the impact of LO-NEC on short-term outcomes in very preterm infants (VPIs) with a focus on nutrition and different onset times. Method Clinical data of VPIs were retrospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. A total of 2509 enrolled VPIs were divided into 2 groups: the LO-NEC group and non-LO-NEC group. The LO-NEC group was divided into 2 subgroups based on the onset time: LO-NEC occurring between 8 ~ 14d group and LO-NEC occurring after 14d group. Clinical characteristics, nutritional status, and the short-term clinical outcomes were analyzed and compared among these groups. Results Compared with the non-LO-NEC group, the LO-NEC group had a higher proportion of anemia, blood transfusion, and invasive mechanical ventilation (IMV) treatments before NEC; the LO-NEC group infants had a longer fasting time, required longer duration to achieve the target total caloric intake (110 kcal/kg) and regain birthweight, and showed slower weight growth velocity; the cumulative dose of the medium-chain and long-chain triglyceride (MCT/LCT) emulsion intake in the first week after birth was higher and breastfeeding rate was lower. Additionally, similar results including a higher proportion of IMV, lower breastfeeding rate, more MCT/LCT emulsion intake, slower growth velocity were also found in the LO-NEC group occurring between 8 ~ 14d when compared to the LO-NEC group occurring after 14 d (all ( P < 0.05). After adjustment for the confounding factors, high proportion of breastfeeding were identified as protective factors and long fasting time before NEC were identified as risk factors for LO-NEC; early feeding were identified as protective factors and low gestational age, grade III ~ IV neonatal respiratory distress syndrome (NRDS), high accumulation of the MCT/LCT emulsion in the first week were identified as risk factors for LO-NEC occurring between 8 ~ 14d. Logistic regression analysis showed that LO-NEC was a risk factor for late-onset sepsis, parenteral nutrition-associated cholestasis, metabolic bone disease of prematurity, and extrauterine growth retardation. Conclusion Actively preventing premature birth, standardizing the treatment of grade III ~ IV NRDS, and optimizing enteral and parenteral nutrition strategies may help reduce the risk of LO-NEC, especially those occurring between 8 ~ 14d, which may further ameliorate the short-term clinical outcome of VPIs. Trial registration ChiCTR1900023418 (26/05/2019).

Abstract The aim of this study was to develop a real-time risk prediction model for extrauterine growth retardation (EUGR). A total of 2514 very preterm infants were allocated into a training set and an external validation set. The most appropriate independent variables were screened using univariate analysis and Lasso regression with tenfold cross-validation, while the prediction model was designed using binary multivariate logistic regression. A visualization of the risk variables was created using a nomogram, while the calibration plot and receiver operating characteristic (ROC) curves were used to calibrate the prediction model. Clinical efficacy was assessed using the decision curve analysis (DCA) curves. Eight optimal predictors that namely birth weight, small for gestation age (SGA), hypertensive disease complicating pregnancy (HDCP), gestational diabetes mellitus (GDM), multiple births, cumulative duration of fasting, growth velocity and postnatal corticosteroids were introduced into the logistic regression equation to construct the EUGR prediction model. The area under the ROC curve of the training set and the external verification set was 83.1% and 84.6%, respectively. The calibration curve indicate that the model fits well. The DCA curve shows that the risk threshold for clinical application is 0–95% in both set. Introducing Birth weight, SGA, HDCP, GDM, Multiple births, Cumulative duration of fasting, Growth velocity and Postnatal corticosteroids into the nomogram increased its usefulness for predicting EUGR risk in very preterm infants.

IntroductionAntenatal corticosteroids (ACS) administration is a standardized prenatal care for accelerating fetal maturation before anticipated preterm delivery, however, its effect on nutrition and growth is yet uncertain. This study aimed to examine if ACS application is associated with improvement in postnatal growth and nutrition in very preterm infants (VPIs).MethodsThis was a secondary analysis of a multicenter prospective survey included infants born before 32 weeks gestation and admitted to 28 tertiary neonatal intensive care units throughout China from September 2019 to December 2020. Infants were divided into no ACS, partial ACS and complete ACS groups according to the steroids exposure. For infants exposed to antenatal corticosteroids, complete ACS was defined as receiving all doses of steroids 24 h-7 days before delivery, otherwise it was referred to partial ACS. The primary outcomes of postnatal growth were compared among the 3 groups. The multivariable regression analyses were applied to evaluate the association of different steroids coverage with postnatal growth and nutritional outcomes while adjusting for potential confounders. For each outcome, no ACS coverage was defined as the reference group. Data were presented as unstandardized coefficients or adjusted odds ratios with 95% confidence intervals, P < 0.05 (2-sided) indicated statistical significance.ResultsAmong 2,514 infants included, complete ACS, partial ACS and no ACS group accounted for 48.7% (1,224/2,514), 29.2% (735/2,514) and 22.1% (555/2,514), respectively. The median weight growth velocity was 14.6 g/kg/d, 14.1 g/kg/d and 13.5 g/kg/d in complete, partial and no ACS group respectively with significant difference (P < 0.001). In multivariable analyses, both complete and partial ACS coverage were associated with shorter cumulative fasting time, faster weight growth velocity, less dramatic decline in Z-score of weight, and lower incidence of extrauterine growth restriction [aOR (95%CI): 0.603 (0.460, 0.789) and 0.636 (0.476,0.851), respectively] when compared with no ACS. Moreover, the faster length growth velocity and earlier enteral feeding start time were observed only in infants with complete ACS coverage.ConclusionsBoth complete and partial ACS are associated with better postnatal growth outcomes in very preterm infants. This efficacy appeared to be more obvious in infants exposed to complete ACS.

Abstract Objective: To analyze the real-world growth pattern of very premature infants (VPI) with small for gestational age (SGA) after birth by using the ΔZ value of weight at discharge and evaluate the occurrence and risk factors of extrauterine growth retardation (EUGR). Methods: The clinical data of VPI with SGA were prospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. They were divided into the EUGR group and the non-EUGR group according to the criterion of ΔZ value of weight at discharge < –1.28. Results: This study included 133 eligible VPI with SGA. Following the criterion for the weight at discharge as the 10th percentile of the Fenton curve, the incidence of EUGR was found to be 98.50% (131/133), and following the criterion of ΔZ value of weight at discharge < –1.28, the incidence of EUGR was 36.84% (49/133). The birth weight, the 5-minute Apgar score, and the proportion of male infants in the EUGR group were lower than those in the non-EUGR group (P < 0.05). The average invasive ventilation time, cumulative duration of the administration of antibiotics, blood transfusion time, blood transfusion ratio, and total days of hospitalization were significantly higher in the EUGR group than those in the non-EUGR group (P < 0.05). The time to start enteral feeding, the quantity of milk added with human milk fortifier (HMF), the time to reach full fortification, the cumulative fasting time, the time to reach full enteral feeding, the duration of parenteral nutrition (PN), days to reach the target total calorie intake and oral calorie intake (both 110 kcal/kg/d), and the age of recovering birth weight in the EUGR group were significantly higher than that in the non-EUGR group (P < 0.05). The average weight gain velocity (GV) was significantly lower in the EUGR group than that in the non-EUGR group (P < 0.001). The incidences of patent ductus arteriosus with hemodynamic changes (hsPDA), neonatal necrotizing enterocolitis (NEC) ³ stage 2, late-onset sepsis (LOS), and feeding intolerance (FI) in the EUGR group were significantly higher than that in the non-EUGR group (P < 0.05). Multivariate logistic regression analysis showed that birth weight, sex (male), and GV were the protective factors for EUGR, while a long time to achieve full-dose fortification, slow recovery of birth weight, and NEC ³ stage 2 were the independent risk factors. Conclusion: SGA in VPI can reflect the occurrence of EUGR more accurately by using the ΔZ value of weight at discharge than using the p-value of weight. Strengthening enteral nutrition support, achieving full breast milk fortification more earlier increasing GV, shortening the recovery time of birth weight, and avoiding NEC can effectively reduce the incidence of EUGR.

Background:In China, the number of preterm infants is the second largest globally. Compared with those in developed countries, the mortality rate and proportion of treatment abandonment for extremely preterm infants (EPIs) are higher in China. It would be valuable to conduct a multicenter study and develop predictive models for the mortality risk. This study aimed to identify a predictive model among EPIs who received complete care in northern China in recent years.Methods:This study included EPIs admitted to eighteen neonatal intensive care units (NICUs) within 72 hours of birth for receiving complete care in northern China between January 1, 2015, and December 31, 2018. Infants were randomly assigned into a training dataset and validation dataset with a ratio of 7:3. Univariate Cox regression analysis and multiple regression analysis were used to select the predictive factors and to construct the best-fitting model for predicting in-hospital mortality. A nomogram was plotted and the discrimination ability was tested by an area under the receiver operating characteristic curve (AUROC). The calibration ability was tested by a calibration curve along with the Hosmer-Lemeshow (HL) test. In addition, the clinical effectiveness was examined by decision curve analysis (DCA).Results:A total of 568 EPIs were included and divided into the training dataset and validation dataset. Seven variables [birth weight (BW), being inborn, chest compression in the delivery room (DR), severe respiratory distress syndrome, pulmonary hemorrhage, invasive mechanical ventilation, and shock] were selected to establish a predictive nomogram. The AUROC values for the training and validation datasets were 0.863 [95% confidence interval (CI): 0.813-0.914] and 0.886 (95% CI: 0.827-0.945), respectively. The calibration plots and HL test indicated satisfactory accuracy. The DCA demonstrated that positive net benefits were shown when the threshold was >0.6.Conclusions:A nomogram based on seven risk factors is developed in this study and might help clinicians identify EPIs with risk of poor prognoses early.

Abstract Introduction The potential adverse effects of prolonged exposure to anesthetics in pediatric patients with severe‐to‐profound sensorineural hearing loss remain unclear. This study aimed to examine whether early bilateral cochlear implantation involving long‐duration anesthetic exposure caused greater developmental impairment than that with unilateral cochlear implantation. Methods This prospective observational study included normally developing infants with bilateral severe‐to‐profound sensorineural hearing loss aged 6 months to 2 years who were candidates for unilateral/bilateral cochlear implantation surgery. Baseline (T0), 6‐month (T1), and 1‐year (T2) Gesell Scale scores were measured. The outcomes included fine motor, adaptability, gross motor, language, and social skills scale 6 and 12 months postoperatively. Result The 90 enrolled children with bilateral severe‐to‐profound sensorineural hearing loss (unilateral n = 43; bilateral n = 47) had a younger bilateral group (11.00 ± 3.66 vs. 15.63 ± 6.99 months, p < .001). Anesthesia duration was longer in the bilateral group (271.57 ± 36.09 vs. 148.81 ± 25.60 min, p < .001). Gross motor, fine motor, adaptability, and language scores improved in both groups, and no significant between‐group differences occurred in the fine motor scale at T1 and T2. Language developmental quotients improved significantly in the bilateral group compared with the unilateral group at T1 (mean differences: 25.07 ± 4.37 vs. 10.88 ± 4.61, p < .001) and T2 (mean differences: 34.98 ± 5.94 vs. 15.28 ± 6.55, p < .001). Stepwise regression revealed that gross motor, adaptability, language, and social skill developmental quotients at T1 were positively correlated with those at T0. Gross motor, fine motor, and social skill developmental quotients at T2 were negatively correlated with age at operation. Language developmental quotients were positively correlated with T0 values (p < .001) and in the bilateral group (p < .001) at T1 and T2. Conclusions When evaluating young children with bilateral severe‐to‐profound sensorineural hearing loss, despite longer exposures to general anesthesia, bilateral cochlear implantations were associated with more improvement in language scores and no differences in other skills compared with those with only unilateral implantation.

Abstract Background Infants with rule-out infections are responsible for the majority of empirical antibiotics treatment (EAT) in neonatal intensive care units (NICUs), particularly very preterm infants (VPIs). Antibiotic overuse has been linked to adverse outcomes. There is a paucity of data on the association between EAT and clinical outcomes (containing the nutritional outcomes) of VPIs without infection-related morbidities. Methods Clinical data of VPIs admitted in 28 hospitals in 20 provinces of China from September 2019 to December 2020 were collected. EAT of VPIs was calculated as the number of days with initial usage in the first week after birth, and then categorized into 3 groups (antibiotic exposure: none, 1-4 days, and > 4 days). Clinical characteristics, nutritional status , and the short-term clinical outcomes among 3 groups were compared and analyzed. Results In total, 1834 VPIs without infection-related morbidities in the first postnatal week were enrolled, including 152 cases (8.3%) without antibiotics, 374 cases (20.4%) with EAT ≤4 days and 1308 cases (71.3%) with EAT > 4 days. After adjusting for the confounding variables, longer duration of EAT was associated with decreased weight growth velocity and increased duration of reach of full enteral feeding in EAT > 4 days group (aβ: -4.83, 95% CI: − 6.12 ~ − 3.53; aβ: 2.77, 95% CI: 0.25 ~ 5.87, respectively) than those receiving no antibiotics. In addition, the risk of feeding intolerance (FI) in EAT > 4 days group was 4 times higher than that in non-antibiotic group (aOR: 4.14, 95%CI: 1.49 ~ 13.56) and 1.8 times higher than that in EAT ≤4 days group (aOR: 1.82, 95%CI: 1.08 ~ 3.17). EAT > 4 days was also a risk factor for greater than or equal to stage 2 necrotizing enterocolitis (NEC) than those who did not receive antibiotics (aOR: 7.68, 95%CI: 1.14 ~ 54.75) and those who received EAT ≤4 days antibiotics (aOR: 5.42, 95%CI: 1.94 ~ 14.80). Conclusions The EAT rate among uninfected VPIs was high in Chinese NICUs. Prolonged antibiotic exposure was associated with decreased weight growth velocity, longer duration of reach of full enteral feeding, increased risk of feeding intolerance and NEC ≥ stage 2. Future stewardship interventions to reduce EAT use should be designed and implemented.

Objectives: The management of enteral nutrition in very preterm infants (VPIs) is still controversial, and there is no consensus on the optimal time point after birth at which enteral nutrition can be started. The aim of this study was to investigate the effect of early initiation of enteral nutrition on the short-term clinical outcomes of VPIs.Methods: Data of infants (n = 2514) born before 32 wk of gestation were collected from 28 hospitals located in seven different regions of China. Based on whether enteral feeding was initiated within or after 24 h since birth, the infants were divided into an early initiation of enteral feeding (EIEF) group and a delayed initiation of enteral feeding (DIEF) group.Results: Compared with the DIEF group, the EIEF group was more likely to tolerate enteral nutrition and had less need for parenteral nutrition (all P < 0.05). The EIEF group was associated with lower incidence rates of feeding intolerance, extrauterine growth restriction (EUGR), and late-onset sepsis (LOS) (all P < 0.05). There was no significant difference in the incidence of necrotizing enterocolitis (NEC) (Bell stage >2) between the two groups (P = 0.118). The multivariate logistic regression analysis revealed that EIEF was a protective factor against EUGR (odds ratio [OR], 0.621; 95% confidence interval [CI], 0.544-0.735; P < 0.001), feeding intoler-ance (OR, 0.658; 95% CI, 0.554-0.782; P < 0.001), and LOS (OR, 0.706; 95% CI, 0.550-0.906; P = 0.006).Conclusions: Early initiation of enteral feeding was associated with less frequency of feeding intolerance, EUGR, and LOS, and it may shorten the time to reach total enteral feeding without increasing the risk of NEC.(c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Background: The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a major threat to global public health. CRKP infections are challenging to treat owing to the limited number of antibiotic species, especially in preterm infants. Ceftazidime-avibactam (CAZ-AVI) is a novel antibiotic with activity against CRKP. At present, there have been no reports of using CAZ-AVI to treat osteoarthritis in premature infants.Methods: We describe 2 preterm infants with CRKP osteoarthritis treated with CAZ-AVI in a tertiary children's hospital in China. Clinical characteristics, laboratory and microbiologic data, treatment and follow-up information were retrospectively collected and analyzed.Results: The 2 cases were both premature infants who contracted sepsis and CRKP osteoarthritis. Meropenem and polymyxin B were initially chosen for the first infant. CAZ-AVI was then used due to persistent infection. The second infant was commenced immediately on CAZ-AVI after receipt of antimicrobial susceptibility on the 4th day after admission. Both recovered with CAZ-AVI (50 mg/kg q8h) and surgical incision and drainage. Neither had a joint deformity or limb length discrepancy at 36 and 34 months, respectively.Conclusions: This is the first report on the use of CAZ-AVI to treat CRKP osteoarthritis in premature infants. Successful treatment depends on prompt recognition of the pathogen and treatment with a combination of antibiotics with or without surgery. Further study is needed to determine the pharmacokinetics and pharmacodynamics of CAZ-AVI for treating preterm infants with serious CRKP osteoarthritis.