Alveolar macrophages (AMs) are sentinels in the airways, where they sense and respond to invading microbes and other stimuli. Unlike macrophages in other locations, AMs can remain responsive to Gram-negative lipopolysaccharides (LPS) after they have responded to LPS in vivo (they do not develop “endotoxin tolerance”), suggesting that the alveolar microenvironment may influence their responses. Although alveolar epithelial cells (AECs) normally limit AMs’ innate responses, preventing inflammation induced by harmless antigens in the lung, how AECs influence the innate responses of AMs to infectious agents has been uncertain. Here we report that (1) after exposure to aspirated (intranasal instillation) LPS, AMs increase their responses to TLR agonists and elevate their phagocytic and bactericidal activities in mice; (2) Aspirated LPS pre-exposure increases host resistance to pulmonary infection caused by Gram-negative bacteria and the protection effect lasts for at least 35 days; (3) LPS stimulation of AECs both increases AMs’ innate immune responses and prevents AMs from developing tolerance in vitro; (4) Upon LPS stimulation, AMs secreted TNF-α induces AECs to release GM-CSF, which potentiates AMs’ response. These experiments have revealed a previously unappreciated role that AECs may play in boosting the innate responses of AMs and promoting resistance to pulmonary infections.

Background:Spontaneous intestinal perforation (SIP) is one of the most serious surgical bowel conditions affecting preterm infants. There are limited data on the mortality and morbidities of very preterm infants [VPIs, <32 weeks' gestational age (GA)] with SIP in China. The study aimed to describe the prevalence, treatment, and outcomes of SIP among VPIs in China.Methods:This retrospective cohort study included all infants born at 24+0-31+6 weeks GA from January 1, 2019, to December 31, 2020, and admitted within seven days after birth to the neonatal intensive care units in the Chinese Neonatal Network. The primary outcome was survival without major morbidities. The association between SIP and neonatal outcomes was evaluated using multivariate logistic regression controlling for possible confounders.Results:Out of the 15,814 enrolled infants, 150 (1.0%) developed SIP with a median onset age of four (IQR 2-6) days. Infants with GA 24+0-25+6 weeks had the highest incidence of SIP (13/532, 2.4%), followed by those with GA 26+0-27+6 weeks (22/2,005, 1.1%), 28+0-29+6 weeks (44/5,269, 0.8%) and 30+0-31+6 weeks (71/8,008, 0.9%). Ten SIP cases were lost to follow-up with unknown survival status and 41 (29.3%) of the remaining 140 infants with SIP died during hospitalization. Only 29.3% of infants with SIP survived without major morbidities, significantly lower than those without SIP (59.2%; P<0.01). Multivariate analysis revealed SIP was associated with a higher risk of overall death (adjusted OR 3.36; 95% CI: 1.85 to 6.08), late-onset sepsis (adjusted OR 2.10; 95% CI: 1.02 to 4.31), and bronchopulmonary dysplasia (adjusted OR 2.49; 95% CI: 1.44 to 4.30). Among all infants with SIP, 28 (18.7%) did not receive any surgical intervention. Laparotomy was provided to 113 (92.6%) of the remaining 122 infants, solely (84/122, 68.9%) or following peritoneal drainage (29/122, 23.8%), while nine (7.4%) infants underwent peritoneal drainage only.Conclusions:Around 1% of VPIs in China developed SIP, associated with increased risk of mortality and morbidities. Over 90% of VPIs with SIP underwent laparotomy as initial or subsequent surgical treatment. Effective and evidence-based strategies are needed for the prevention and management of SIP.

Background With the increasing survival rate of smaller newborns and twins, previous growth curves may not accurately assess the growth of extremely preterm infants (EPIs). Our study aimed to establish birth weight percentile curves for singletons and twins in EPIs from China and the USA and compare the differences between them.Methods In China, EPIs were from 31 provinces, from 2010 to 2021. The collected information was sex, gestational age, birth weight, singletons and twins. We used the generalised additive models for location scale and shape method to construct the birth weight percentile curves by gestational age and sex for EPIs. The National Vital Statistics System database from 2016 to 2021 was also analysed. We compared the differences between the 50th birth weight percentile curves of the two databases.Results We identified 8768 neonates in China (5536 singletons and 3232 twins) and 121 933 neonates in the USA (97 329 singletons and 24 604 twins). We established the 3rd, 10th, 25th, 50th, 75th, 90th and 97th birth weight reference curves for China and the USA. The results showed that males had higher birth weights than females. In China, for the same gestational age and sex, birth weights in singletons and twins were found to be similar, though singleton males born in China had slightly higher birth weights than male twins. In the USA, birth weights were also similar for females and males, with the same gestational age in singletons and twins.Conclusion We established birth weight reference percentile curves by gestational age and sex for singletons and twins among EPIs in China and the USA.

The patient, a male newborn, was admitted to the hospital 2 hours after birth due to prematurity (gestational age 27+5 weeks) and respiratory distress occurring 2 hours postnatally. After admission, the infant developed fever and elevated C-reactive protein levels. On the fourth day after birth, metagenomic next-generation sequencing of cerebrospinal fluid indicated a positive result for Mycoplasma hominis (9 898 reads). On the eighth day, a retest of cerebrospinal fluid metagenomics confirmed Mycoplasma hominis (56 806 reads). The diagnosis of purulent meningitis caused by Mycoplasma hominis was established, and the antibiotic treatment was switched to moxifloxacin [5 mg/(kg·day)] administered intravenously for a total of 4 weeks. After treatment, the patient's cerebrospinal fluid tests returned to normal, and he was discharged as cured on the 76th day after birth. This article focuses on the diagnosis and treatment of neonatal Mycoplasma hominis purulent meningitis, introducing the multidisciplinary diagnosis and treatment of the condition in extremely preterm infants.

A boy, aged 3 hours, was admitted due to a prenatal diagnosis of fetal hydrops at 3 hours after resuscitation for birth asphyxia. Prenatal examination at 5 months of gestation showed massive ascites in the fetus, and after birth, the boy had the manifestations of systemic hydroderma, massive ascites, coarse face, and hepatomegaly. Genetic testing revealed heterozygous mutations in the SLC17A5 gene, and there was a significant increase in urinary free sialic acid. Placental pathology showed extensive vacuolization in villous stromal cells, Hofbauer cells, cytotrophoblast cells, and syncytiotrophoblast cells in human placental chorionic villi. The boy was finally diagnosed with free sialic acid storage disorders (FSASDs). This is the first case of FSASDs with the initial symptom of fetal hydrops reported in China. The possibility of FSASDs should be considered for cases with non-immune hydrops fetalis, and examinations such as placental pathology and urinary free sialic acid may help with early diagnosis and clinical decision making.

Background Echocardiography has poor accuracy in grading the severity of pulmonary hypertension (PH) compared to cardiac catheterization. However, the relationship between degree of PH and prognostic outcomes remains uncertain. Our primary objective was to determine whether echocardiogram-assessed PH severity is associated with mortality and hospital readmission in the first year of life. Methods A retrospective cohort study of infants born less than 32 weeks of gestational age with bronchopulmonary dysplasia (BPD) underwent echocardiography was performed. Echocardiograms were performed at 36–38 weeks postmenstrual age. Data during hospitalization and post-discharge collected at 1-year age were analyzed with cox regression models and logistic regression models to identify the association of PH severity with mortality and readmission. Area under curve (AUC) was calculated to examine the accuracy of these models to reflect the likelihood of outcomes. Results Fifty-six of 237 (23.6%) infants were diagnosed as PH. Moderate and severe PH was significantly associated with mortality during the first one year of life (moderate PH vs. none HR =26.58, 95% CI: 4.40–160.78, P<0.001; severe PH vs. none HR =36.49, 95% CI: 5.65–235.84, P<0.001). Male, preeclampsia and inhaled nitric oxide were also associated with mortality. Mild PH was significantly associated with readmission (OR =2.42, 95% CI: 1.12–5.26, P=0.025), but not associated with mortality (HR =2.09, 95% CI: 0.43–10.18, P=0.36). The PH severity model based on echocardiography accurately informed mortality (AUC 0.79). Conclusions Echocardiogram-assessed PH severity is associated with prognostic outcomes, including mortality and readmission in very preterm infants with BPD. The severity of PH based on echocardiography is a potential predictor of mortality in the first year of life.

Metabolic bone disease (MBD) is one of the major complications of prematurity. Ultrasonic backscatter technique has the potential to be a portable and noninvasive method for early diagnosis of MBD. This study firstly applied CAS to neonates, which was defined as a linear combination of the apparent integrated backscatter coefficient (AIB) and spectral centroid shift (SCS). The objective was to evaluate the feasibility of ultrasonic backscatter technique for assessing neonatal bone health using AIB, SCS, and CAS. Ultrasonic backscatter measurements at 3.5 MHz, 5.0 MHz, and 7.5 MHz were performed on a total of 505 newborns within 48 hours after birth. The values of backscatter parameters were calculated and compared among gestational age groups. Correlations between backscatter parameters, gestational age, anthropometric indices, and biochemical markers were analyzed. The optimal predicting models for CAS were determined. The results showed term infants had lower SCS and higher AIB and CAS than preterm infants. Gestational age and anthropometric indices were negatively correlated with SCS (|r| = 0.45 – 0.57, P < 0.001), and positively correlated with AIB (|r| = 0.36 – 0.60, P < 0.001) and CAS (|r| = 0.56 – 0.69, P < 0.001). Biochemical markers yielded weak or nonsignificant correlations with backscatter parameters. CAS had relatively stronger correlations with the neonatal variables than AIB and SCS. At 3.5 MHz and 5.0 MHz, only gestational age (P < 0.001) independently contributed to the measurements of CAS, and could explain up to 40.5% – 44.3% of CAS variation. At 7.5 MHz, the combination of gestational age (P < 0.001), head circumference (P = 0.002), and serum calcium (P = 0.037) explained up to 40.3% of CAS variation. This study suggested ultrasonic backscatter technique was feasible to evaluate neonatal bone status. CAS was a promising parameter to provide more information about bone health than AIB or SCS alone.

Metabolic bone disease (MBD) impacts the prognosis of premature infants. There is an urgent need for a portable, noninvasive, and radiation-free method for assessing neonatal bone status. The objective of this study is to evaluate the feasibility of the ultrasonic backscatter technique for assessing and monitoring cancellous bone status in neonates. Ultrasonic backscatter measurements were performed on 766 infants at birth and followed up weekly during hospitalization, utilizing transducers with central frequencies of 3.5 MHz and 5.0 MHz. Backscatter parameters, including apparent integrated backscatter (AIB), frequency intercept of apparent backscatter (FIAB), and frequency slope of apparent backscatter (FSAB) were calculated. Correlations were analyzed with both anthropometric and biochemical indices. We found that AIB (|r| = 0.40-0.47, p <; 0.001), FIAB (|r| = 0.36-0.45, p <; 0.001), and FSAB (|r| = 0.10-0.25, p <; 0.01) were significantly correlated with gestational age, weight, length, and head circumference at birth at both the 3.5 MHz and 5.0 MHz frequencies. Backscatter parameters showed regular changes at different postnatal age and correlations with anthropometric indices persisted during the first month of life. Significant differences were also found in subgroup analyses based on gestational age, birth weight, gender, multiple births, and intrauterine growth. AIB and FIAB were shown to be more effective than FSAB. This study suggests the ultrasonic backscatter technique is feasible for neonatal cancellous bone status evaluation at birth and for dynamic monitoring.

支气管肺发育不良(bronchopulmonary dysplasia, BPD)是早产儿常见的并发症,是多种因素共同作用的结果.除高氧血症、长时间机械通气造成的容量伤和气压伤、感染等因素外,生后营养不良也是重要致病因素之一 [1].合理的营养策略可能具有预防高危早产儿BPD的潜力.母乳喂养是早产儿营养支持的首选方式,与婴儿配方粉相比,具有经济、便利的优点,也可改善早产儿的短期预后,增强免疫功能、提高喂养耐受性,促进神经系统发育,降低新生儿坏死性小肠结肠炎(necrotizing enterocolitis,NEC)和早产儿视网膜病变发生率 [ 2 - 6 ].有关母乳喂养是否能降低早产儿BPD 发生率方面,近年国内外开始进行有关的研究.本文对母乳喂养在预防 BPD 发生发展中的作用阐述如下.

支气管肺发育不良(bronchopulmonary dysplasia,BPD)是导致早产儿不良预后的重要原因,具有很高的发病率[1].目前BPD防治手段十分有限,由于炎症在BPD发病机制中起非常重要的作用[2],激素具有良好的抗炎作用,在20世纪90年代曾被广泛应用于BPD的防治[3].大量临床研究表明地塞米松能够降低BPD的发生率、加快撤机等,具有较好的近期疗效[4],但伴随而来的是严重的不良反应,如高血压、高血糖、坏死性小肠结肠炎、感染、肾上腺功能抑制等[4].许多多中心随机对照研究远期随访结果显示应用地塞米松的早产儿较对照组表现出更明显的神经系统功能障碍,因此目前不再推荐高剂量地塞米松作为防治BPD的常规药物[5],推荐使用低剂量地塞米松,并限于生后2周仍依赖有创呼吸支持者[6].然而,随着激素应用减少,早产儿BPD发病率有所上升[7].因此,寻求疗效相近而不良反应更小的替代药物成为研究热点[8],如氢化可的松.本文将对氢化可的松防治BPD的研究进展进行综述.

Metabolic bone disease of prematurity remains a significant problem for preterm infants. Quantitative ultrasound (QUS) has potential as a non-invasive tool for assessing bone health of newborns. The aim of this study was to assess bone health in preterm and term newborns using ultrasonic backscatter difference measurement. This study analyzed a total of 493 neonates, including 239 full-term infants (gestational age [GA] >37 wk), 201 preterm I infants (GA: 32-37 wk) and 53 extreme preterm II infants (GA <32 wk). Ultrasonic backscatter measurements were performed on the calcaneus of infants at birth, and the normalized mean of the backscatter difference spectrum (nMBD) was calculated as an ultrasonic index of neonatal bone status. Simple and multiple linear regressions were performed to determine the association of ultrasonic nMBD with GA, anthropometric characteristics and biochemical markers. Statistically significant differences in GA, anthropometric characteristics (birth weight, birth length [BL], birth head circumference and body mass index IBMII) and biochemical markers (alkaline phosphatase, serum calcium and serum phosphate) were observed among preterm and term infants. The nMBD for term infants (median = 3.72 dB/mu s, interquartile range [IR] = 1.95 dB/mu s) was significantly higher than that for preterm I infants (median = 1.95 dB/mu s, IR = 3.12 dB/mu s), which was, in turn, significantly higher than that for preterm II infants (median = 0.19 dB/mu s, IR = 3.50 dB/mu s). The nMBD yielded moderate correlations (rho = 0.57-0.62, p < 0.001) with GA and anthropometric characteristics and weak correlations (vertical bar rho vertical bar = 0.08-0.21, p < 0.001 or not significant) with biochemical markers. Multivariate regressions revealed that only BL (p = 0.002) and BMI (p = 0.032) yielded significantly independent contributions to the nMBD measurement, and combinations of BL and BMI could explain up to 42% of the variation of nMBD in newborn infants. This study found that ultrasonic backscatter difference measurement might be helpful in bone health evaluation in preterm and term newborns. The utility of ultrasonic backscatter measurement in diagnosis of metabolic bone disease in infants should be investigated further. (C) 2019 World Federation for Ultrasound in Medicine & Biology. All rights reserved.

Pulmonary infection is the most common risk factor for acute lung injury (ALI). Innate immune responses induced by Microbe-Associated Molecular Pattern (MAMP) molecules are essential for lung defense but can lead to tissue injury. Little is known about how MAMP molecules are degraded in the lung or how MAMP degradation/inactivation helps prevent or ameliorate the harmful inflammation that produces ALI. Acyloxyacyl hydrolase (AOAH) is a host lipase that inactivates Gram-negative bacterial endotoxin (lipopolysaccharide, or LPS). We report here that alveolar macrophages increase AOAH expression upon exposure to LPS and that Aoah+/+ mice recover more rapidly than do Aoah-/- mice from ALI induced by nasally instilled LPS or Klebsiella pneumoniae. Aoah-/- mouse lungs had more prolonged leukocyte infiltration, greater pro- and anti-inflammatory cytokine expression, and longer-lasting alveolar barrier damage. We also describe evidence that the persistently bioactive LPS in Aoah-/- alveoli can stimulate alveolar macrophages directly and epithelial cells indirectly to produce chemoattractants that recruit neutrophils to the lung and may prevent their clearance. Distinct from the prolonged tolerance observed in LPS-exposed Aoah-/- peritoneal macrophages, alveolar macrophages that lacked AOAH maintained or increased their responses to bioactive LPS and sustained inflammation. Inactivation of LPS by AOAH is a previously unappreciated mechanism for promoting resolution of pulmonary inflammation/injury induced by Gram-negative bacterial infection.