��������Ƥ�ʼ���Ԥ�������������֧���ܷη�������������

??Postnatal glucocorticoid is an effective therapy for preventing or treating bronchopulmonary dysplasia??BPD?? among extremely preterm infants??but the side-effect profile limits its use and makes it an unacceptable option for many patients. Early low-dose hydrocortisone therapy may be beneficial to premature infants with intrauterine chorioamnionitis??but concerns remain about possible adverse effects such as gastrointestinal perforation. Late??after the first week of life?? postnatal steroids may have a better benefit-to-harm ratio than early steroids. Postnatal dexamethasone??DEX?? in 2-3 weeks after birth should mainly be reserved for infants who cannot be weaned from mechanical ventilation and the dose and duration should be kept to a minimum. However??early inhalation of budesonide or intratracheal instillation of budesonide using surfactant as a vehicle can reduce the incidence of BPD??but its safety needs further evaluation. Future studies are required to identify the preferred type??dose and timing of therapy that will provide maximal benefit with minimal side effects.     

The association between the microbes in the tracheobronchial aspirate fluid and bronchopulmonary dysplasia in preterm infants

ObjectiveThe study aimed to evaluate the association between microbes in the lower respiratory tract (LRT) and the srisk for severe bronchopulmonary dysplasia (sBPD) in premature infants.MethodsWe conducted a retrospective, single-center study of preterm infants who were admitted to the neonatal intensive care unit (NICU) of Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan, China, between January 2015 and December 2017. The microbes in the LRT were screened by using tracheobronchial aspirate fluid (TAF) culture.ResultsOne hundred and fifty-five infants were included in the analysis. Among 155 infants, 41 were diagnosed with sBPD, and 114 were diagnosed without sBPD. There were significant differences between infants with and without sBPD in regard to birth weight (BW), gestational age (GA), the duration of endotracheal ventilation and supplemental oxygen. The incidence of retinopathy (ROP) and sepsis was higher in the sBPD infants than in the infants without sBPD. There was a difference in the detection rate of Gram-negative bacteria (GNB) between the two groups. Stenotrophomonas maltophilia and Klebsiella pneumoniae were mainly detected in TAF.ConclusionsThe LRT microbes were different between infants with and without sBPD, and GNB is more frequently detected in sBPD infants.     

Different degrees of maternal Ureaplasma colonization and its correlation with bronchopulmonary dysplasia in <32 weeks' preterm infants

BackgroundUreaplasma spp. is a known risk factor for bronchopulmonary dysplasia (BPD). However, little is known about the effect of different degrees of maternal Ureaplasma colonization and their adverse outcomes. Hence, the aim of this study was to determine the effects of different degrees of maternal Ureaplasma colonization on BPD.MethodsA retrospective cohort study of preterm infants delivered at <32 weeks' gestational age (GA) was performed. The infants were divided according to maternal Ureaplasma status as follows: high-colonization (≥10⁴ CCU/ml, UUH), low-colonization (<10⁴ CCU/ml, UUL), and noncolonization (controls). Subgroup analysis according to neonatal respiratory Ureaplasma (n-UU) was also performed to evaluate vertical transmission.ResultsIn total, 245 infants were included in this study (UUH = 105, UUL = 47, controls = 93). The rates of preterm labor and histological chorioamnionitis were significantly different. The rate of BPD was significantly high in UUH (P = 0.044). The transmission rate of n-UU colonization was 36% in UUH and 32% in UUL (P = 0.609). The rate of BPD was 78% in n-UU (+) of UUH but 43% in n-UU (−) of UUL (P = 0.027).ConclusionsHigh-degree colonization of maternal Ureaplasma was associated with preterm labor, histological chorioamnionitis, and neonatal BPD. The incidence of BPD was significantly higher in Ureaplasma-colonized infants born to women with high-degree colonization.     

Conductive hearing loss in preterm infants with bronchopulmonary dysplasia

OBJECTIVE: To determine the risk of conductive hearing loss in preterm infants with bronchopulmonary dysplasia (BPD) and preterm controls. METHODOLOGY: The study population consisted of 78 infants with BPD of 26-33 weeks gestation and 78 controls of similar gestational age matched for broad-based birthweight categories. An auditory brainstem response (ABR) audiology was performed shortly before hospital discharge. Visual reinforcement orientation audiometry (VROA) and impedance audiometry were performed at 8-12 months corrected for prematurity. Infants with persistent audiological abnormalities were referred for evaluation to paediatric ENT surgeons. RESULTS: Infants with BPD had a significantly higher rate of ABR abnormalities (BPD: 22%, controls: 9%; P = 0.028). On VROA and impedance audiometry, the infants with BPD also had a higher rate of persistent abnormalities. Following ENT assessment, 22.1% of infants with BPD and 7.7% of controls had persistent conductive dysfunction requiring myringotomy and grommet tube insertion (P = 0.03). Most of these infants had normal ABR audiometry at hospital discharge. CONCLUSIONS: Preterm infants with BPD are at high risk of persistent conductive hearing loss late in the first year of life compared to controls. An ABR audiology conducted at the time of hospital discharge does not predict accurately later conductive hearing problems. Infants with BPD should have routine audiological evaluation toward the end of the first year of life.     

Psychoeducational outcome at school age of preterm infants with bronchopulmonary dysplasia

OBJECTIVE: To investigate the cognitive performance and educational attainment at school-age of children with bronchopulmonary dysplasia (BPD), compared with a preterm control group of children. METHODS: Seventy preterm infants with BPD and 61 birth weight matched controls were prospectively followed-up to school-age. The Weschler Intelligence Scale for Children - III (WISC), the Wide Range Achievement Test (WRAT) and the Developmental Test of Visual Motor Integration (VMI) were administered. The results were compared between the two groups and multiple regression analyses were performed to determine the effect of confounding variables. RESULTS: The children in the BPD group performed less well on the Full Scale IQ (mean 86.7 vs 93.5; 95% CI, 1.9-11.7), Verbal IQ (mean 87.1 vs 94.1; 95% CI, 2.0-12.0) and the Performance IQ (mean 88.6 vs 95.2; 95% CI, 2.0-11.2) of the WISC, the reading component of the WRAT (mean 93.8 vs 98.9; 95% CI, 0.3-9.8) and the VMI (mean 88.9 vs 93.3; 95%, CI 1.1-7.8). Despite controlling for social and biological variables, statistical differences persisted for Full Scale and Verbal IQ and reading. A Verbal IQ >1 SD below the mean was found in 41% of BPD children compared to 21% of controls, while on the reading component of the WRAT a greater proportion of BPD children also had scores>1 SD below the mean. CONCLUSION: Impaired psychoeducational performance was found in preterm children with BPD compared to controls, especially in the areas of language abilities and reading skills. This supports a greater need for special educational services and counseling for parents for these children.     

Increased volume of tracheal aspirate fluid predicts the development of bronchopulmonary dysplasia

Background

Elevated cytokine concentrations were observed in tracheal aspirate fluid (TAF) of infants on mechanical ventilation who subsequently developed bronchopulmonary dysplasia (BPD). However, there are few reports that systematically evaluate the amount of TAF as an indicator of BPD development.

Aim

To clarify whether TAF volume during the first week of life predicts BPD development in extremely low gestational age newborns (ELGANs).

Study design

We analyzed 51 infants, born at gestational age of < 28 weeks and ventilated for more than 7 days after birth, among whom, 26 were diagnosed with BPD based on the clinical definition of oxygen dependence at 36 weeks postmenstrual age (BPD group) and 25 were included in the non-BPD group. Sum of TAF scores (STS) was calculated by semi-quantification of TAF volume at each suctioning and the suctioning frequency during the first week of life.

Results

STS was significantly higher in the BPD group than in the non-BPD group (median (interquartile range): 77 (29–126) vs. 28 (22–59), p < 0.001). STS (cut-off, 60) with area under the curve in receiver operating analysis of 0.75 was significantly predictive of BPD development. Multivariate logistic regression analysis adjusted for perinatal characteristics showed that STS ≥ 60 was a significant risk factor for BPD development (odds ratio, 7.50; confidence interval, 1.16–48.40, p = 0.034).

Conclusion

Increased TAF volume during the first week of life was an independent predictor for BPD development in ventilated ELGANs, indicating that increased pulmonary capillary permeability may influence the pathogenesis of BPD.     

氢化可的松防治早产儿支气管肺发育不良的研究进展

正支气管肺发育不良(bronchopulmonary dyspla-sia,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     

Mesenchymal stem cells for the prevention of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is a chronic lung disease in preterm infants who have been treated with supplemental oxygen and mechanical ventilation. Despite major advances in perinatal and neonatal medicine, limited progress has been made in reducing BPD rates. The use of mesenchymal stem cells (MSC) is a promising and innovative therapy for several diseases because they are easy to extract and they have low immunogenicity, anti‐inflammatory properties, and regenerative ability. According to several pre‐clinical studies that have used BPD animal models, one mechanism of action for MSC in BPD is mainly due to the paracrine effects of MSC‐derived humoral factors, such as interleukin (IL)‐6, IL‐8, vascular endothelial growth factor, collagen, and elastin, rather than the multilineage and regenerative capacities of MSC. Cell‐free preparations derived from MSC, including conditioned media and exosomes, remain a pre‐clinical technology despite their great clinical potential. A first‐in‐human clinical trial of MSC treatment for BPD was performed as a phase I dose‐escalation trial using umbilical cord blood‐derived MSC. That trial demonstrated the short‐ and long‐term safety and feasibility of MSC, given that significantly reduced inflammatory marker expression was observed in tracheal aspirates. As of recently, several clinical trials of MSC use for BPD are ongoing or are planned in some countries to investigate the efficacy of MSC in the prevention or treatment of BPD in premature infants. Many clinicians are currently awaiting the results from these trials so that MSC can be used clinically for human BPD.     

早产儿支气管肺发育不良的表型演变

支气管肺发育不良(bronchopulmonary dysplasia,BPD)是早产儿最常见的慢性肺部疾病,与婴儿死亡率、呼吸系统发病率增加有关。随着新生儿重症医学取得进展的同时,BPD的表型已从主要影响晚期早产儿、肺纤维囊性变演变为主要影响胎龄小于28周的超早产儿、肺实质受损和血管生长失调。文章评估了BPD定义演变、病理生理演变、影像演变及临床表型的演变特点,以期寻找新的循证预防和管理策略,改善疾病表型分类,早期识别高危早产儿的临床特点,以改善其预后。     

Chorioamnionitis/funisitis and the development of bronchopulmonary dysplasia

OBJECTIVE: To examine the association between chorioamnionitis with or without funisitis and bronchopulmonary dysplasia in infants less than 30 completed weeks gestation given the current standards of antenatal steroid and surfactant use. METHODS: Infants included in the study were those delivered at less than 30 completed weeks gestation from January 1996 to July 2001, identified from a prospectively managed database. Placental pathology was reviewed for the presence or absence of chorioamnionitis and funisitis. Infants were divided into three groups depending on degree of exposure to fetal inflammation (no inflammation, chorioamnionitis only and chorioamnionitis and funisitis). Data relating to gestational age, sex, antenatal steroid exposure, surfactant treatment, days of positive pressure ventilation and days of oxygen required were collected. Bronchopulmonary dysplasia was defined as death due to respiratory failure or any oxygen requirement at 36 weeks postmenstrual age. RESULTS: Two hundred and forty-one infants were included in the study. The mean gestational age was 27.7 weeks and mean birthweight 1089 g. One hundred and sixty-one infants were not exposed to any in utero inflammation, 40 showed chorioamnionitis and 40 showed chorioamnionitis and funisitis. There was no significant difference between antenatal steroid and surfactant treatment between the three groups. There was no significant difference between the three groups in the development of bronchopulmonary dysplasia. Low gestational age was the most significant predictor of developing bronchopulmonary dysplasia. CONCLUSION: The risk of developing bronchopulmonary dysplasia is not increased following exposure to chorioamnionitis or funisitis in the context of current antenatal steroid and surfactant use. The most significant predictor for developing bronchopulmonary dysplasia is gestational age at the time of delivery.     

Hypocarbia in the ventilated preterm infant and its effect on intraventricular haemorrhage and bronchopulmonary dysplasia

OBJECTIVE: To examine the relationship between PaCO2 levels in ventilated very preterm infants and (i) the incidence of severe intraventricular haemorrhage (IVH) and periventricular leukomalacia (PVL); and (ii) bronchopulmonary dysplasia (BPD). METHODS: A retrospective cohort analysis of preterm infants comparing PaCO2 levels with the incidence of severe IVH/PVL and BPD was carried out on patients born at less than 29 weeks gestation from 1992 to 1994 and admitted to the tertiary neonatal intensive care unit at the King Edward Memorial Hospital (314 infants). During the first 96 h, PaCO2 levels were examined including lowest and highest PaCO2 levels, mean PaCO2 levels and duration of hypocarbia both pre- and post-surfactant administration. RESULTS: Of the 314 infants, there were 40 early neonatal deaths (less than 48 h) who were not included in the analysis. Of the 274 surviving infants, 72 (26%) infants had severe IVH. Infants whose PaCO2 fell below 30 mmHg at any stage in the first 48 h of life had an increased risk of severe IVH or PVL (odds ratio 2.38; 95% CI 1.27-4.49; P = 0.007). Of the 265 survivors to 36 weeks corrected gestational age, 134 (51%) had BPD. Infants with at least three PaCO2 values less than 30 mmHg in the first 24 h of life had an increased risk of BPD (odds ratio 2.21; 95% CI 1.05-4.57; P = 0.036). CONCLUSIONS: The risk of severe IVH/PVL was significantly increased by hypocarbia. There was also an association between hypocarbia and BPD, particularly when hypocarbia was prolonged. These findings suggest that avoidance of hypocarbia may reduce the incidence of severe IVH/PVL and BPD in preterm infants.     

血管内皮生长因子在支气管肺发育不良方面的研究进展

支气管肺发育不良(BPD)是早产儿中常见的慢性呼吸系统疾病,以肺泡发育受损和血管生长异常为特征的"新型BPD"的发生率呈逐年增高趋势。肺血管生长是影响肺发育的关键,血管内皮生长因子(VEGF),作为血管发生的核心因子,与BPD发生存在一定的相关性。研究表明,BPD的早产儿及高氧BPD模型动物,体内血管内皮生长因子表达水平在不同时间点可有不同程度的下降;抑制动物血管发育,可导致肺血管数目减少,辐射状肺泡计数下降,出现BPD样结构改变。通过病毒介导基因干预或肌肉注射等方式,将适量外源性VEGF带入BPD模型动物体内,则可改善肺血管发育,增加辐射状肺泡计数;但VEGF过表达也可导致肺水肿、肺出血等不良反应。文章综述了临床BPD及BPD模型动物VEGF蛋白表达,及VEDF在BPD动物模型治疗方面的研究进展。     

Interleukin‐6 polymorphism and bronchopulmonary dysplasia risk in very low‐birthweight infants

Background: The aim of the present study was to evaluate the role of interleukin (IL)‐6‐634 polymorphism in neonatal disorders such as bronchopulmonary dysplasia (BPD) and periventricular leukomalacia (PVL) in very low‐birthweight (VLBW) infants. Methods: This prospective cohort study included 202 infants (gestational age at birth, 23–34 weeks; birthweight, 500–1499 g). Genotypic analysis (polymerase chain reaction–restriction fragment length polymorphism) was performed with DNA extracted from whole‐blood samples. Results: Genotype distribution (66.8% CC, 28.2% CG, 5.0% GG) was similar to that in the adult Japanese population. BPD occurred in 85 infants (42.1%) among 202 VLBW infants. The duration of O₂ therapy in infants with CG/GG genotypes was significantly longer than that in infants with the CC genotype (CG/GG vs CC: 40.3 ± 52.2 days vs 28.4 ± 32.6 days, P < 0.05), but the prevalence of BPD was not associated with the CG/GG genotype (CG/GG, 40.0%; CC, 46.3%, P= 0.24). Infants with CG/GG genotypes were more likely to have received postnatal corticosteroid therapy for BPD than those with the CC genotype (CG/GG vs CC: 20.9% vs 11.1%, P= 0.05). PVL occurred in six infants (3.0%). There was no significant difference in the prevalence of PVL among IL‐6‐634 polymorphisms (CG/GG, 3.0%; CC, 3.0%, P= 0.65). Conclusions: IL‐6‐634 polymorphism is associated with duration of oxygen therapy in VLBW infants. This suggests that the IL‐6‐634 polymorphism G allele is an aggravating factor of BPD. IL‐6‐634 polymorphism is not associated with PVL.     

肺表面活性物质蛋白B基因多态性与早产儿支气管肺发育不良的相关性

目的 研究肺表面活性物质蛋白B(Sp-B)基因单核苷酸多态性的分布及其与早产儿支气管肺发育不良(BPD)的关系.方法 采用前瞻性研究方法,选择42例BPD早产儿(BPD组)和65例非BPD早产儿(对照组)作为研究对象,应用PCR-限制性片段长度多态性技术检测SP-B-18A/C、SP-B 1580C/T、SP-B8714G/C位点的单核甘酸多态性,分析3个位点多态性与BPD的关系.结果 BPD组和对照组SP-B-18A/C基因型频率CC、AC、AA分别为35.7％、52.4％、11.9％和32.3％、47.7％、20.0％;SP-B 8714G/C:CC、GC、GG分别为26.2％、54.8％、19.0％和27.7％、58.5％、13.8％;1580C/T基因型CC、CT、TT分别为66.7％、26.2％、7.1％和40.0％、47.7％、12.3％.BPD组和对照组SP-B-18A/C等位基因:C位基因、A等位基因分别为61.9％、38.1％和56.2％、43.8％;SP-B 8714G/C:G等位基因、C等位基因分别为53.6％、46.8％和56.9％、43.1％;SP-B 1580C/T:C等位基因、T等位基因分别为79.8％、20.2％和63.8％、36.2％.SP-B-18A/C、SP-B1580C/T、SP-B 8714G/C 3个位点均存在多态性,与对照组比较,BPD患儿SP-B 1580C/T位点基因型以CC明显增多(x2=7.26,P＜0.05),C等位基因分布频率显著增高(x2=6.17,P＜0.05),携带C等位基因的个体患BPD的风险是非携带者的2.23倍(OR=2.23,95％CI:1.18～4.24).SP-B-18A/C、SP-B 8714G/C位点的基因型和等位基因分布频率均无明显变化,差异均无统计学意义(P均＞0.05).结论 SP-B 1580C/T多态性与BPD有关,SP-B 1580C/T可能是BPD的易感基因,携带SP-B 1580C等位基因的个体患BPD的风险增加.SP-B-18A/C、SP-B 8714G/C与BPD无关.     

Infection and preterm birth: evidence of a common causal relationship with bronchopulmonary dysplasia and cerebral palsy

Subclinical genital tract infection has been clearly established as a significant cause of spontaneous preterm birth, particularly in early gestations. Bacterial vaginosis organisms rank highly among the pathogens involved in preterm labour and there is considerable beneficial evidence from the use of prophylactic antibiotics for women at high risk of preterm birth. The pathogenesis involves activation of macrophages and the generation of pro-inflammatory cytokines. Bronchopulmonary dysplasia is seen in the most immature of survivors and appears to be secondary to interruption of normal development and maturation of the lungs. The link between chorioamnionitis and lung injury in utero and subsequent development of bronchopulmonary dysplasia has now been substantiated. Exposure to pro-inflammatory cytokines is implicated in the impairment of the fetal lung. A significant body of evidence supports the association between chorioamnionitis, periventricular leukomalacia and cerebral palsy. Biological mechanisms that explain the association between chorioamnionitis and fetal brain injury involve pro-inflammatory cytokines. Similarity in the pattern of expression of cytokines suggests a common pathway for the initiation of preterm labour and also injury to the lung and the central nervous system of the fetus.     

Rehospitalization and growth of infants with bronchopulmonary dysplasia: A matched control study

Objectives: To determine the risk of hospitalization and the growth during the first year of life in infants with bronchopulmonary dysplasia (BPD) and birthweight matched controls.
Methodology: The study population consists of 78 infants of 26 to 33 weeks gestation with BPD of whom 20 were discharged on home oxygen therapy. The 78 control infants were matched with the study infants for broad based birthweight categories. Infants were reviewed at 4,8 and 12 months corrected for prematurity at which time the history of rehospitalization was recorded and growth parameters were measured.
Results: Infants with BPD were found to have a higher overall rate of rehospitalization (58 vs 35%, relative risk (RR) 1.7,95% confidence interval (Cl) 1.2-2.4) and were more likely to be readmitted for respiratory illnesses (39 vs 20%, RR 1.9, 95% Cl 1.1-3.2) and for poor growth (14 vs 1%, RR 14, 95% Cl 1.7-82) than the control group. Many infants, both study and control, remained below the 10th percentile at 1 year of age. More BPD infants were below the 10th percentile in weight at the 4 month visit than the control infants (30 vs 15%, P = 0.034). This difference was neither present at subsequent visits nor in the other major growth parameters. The 20 BPD infants who were on home oxygen therapy were more frequently hospitalized for concerns with failure to thrive (30 vs 9%, RR 3.3,95% Cl 1.2-8.9) than the remaining 58 BPD infants. No significant differences were detected in the overall rate of rehospitalization. Poor growth at the corrected age of 1 year was similar in the two subgroups of infants.
Conclusions: BPD infants are at increased for risk rehospitalization during the first year of life. While many infants with BPD have growth failure, it is suggested that the provision of appropriate supplemental oxygen at home may result in those infants having similar growth patterns when compared to birthweight matched preterm infants without BPD.