Three-Year Outcomes for Low Birth Weight Infants: Differential Effects of Early Medical Complications

This study evaluated the effects of several specific medicalcomplications associated with prematurity on the intellectual,communication, and motoric development of low birth weight (LBW)infants. This study extends the findings of a previous reportto the 36-month time point and includes a full-term comparisongroup of comparable socioeconomic status. LBW infants (n = 99)were grouped according to the following complications at birth:(a) in-traventricular hemorrhage (Grades I and II) (IVH group);(b) respiratory distress syndrome (RDS group); (c) bronchopulmonarydysplasia with and without IVH (BPD group); (d) IVH (GradesIII and IV) with associated hydrocephalus (IVH-HYD group). TheLBW infants and a group of full-term controls (n = 26) weregiven standardized tests of cognitive and motoric developmentat 36 months. Results show that by 36 months, BPD and IVH-HYDgroups scored significantly below full-term and RDS groups onmental and motor measures. All LBW groups scored significantlybelow full-terms on perceptual performance and expressive languagemeasures. Additional analysis showed that length of hospitalizationenhanced predictions of outcome within the BPD group. This studydemonstrates the importance of separately considering IVH-HYDand BPD infants when reporting outcomes and developing interventions.     

外周血内皮祖细胞与极低出生体重早产儿并发症发生相关性

目的分析内皮祖细胞（EPCs）与极低出生体重早产儿发生支气管肺发育不良（BPD）、早产儿视网膜病（ROP）和脑室内出血（IVH）并发症的相关性。方法选取于复旦大学附属儿科医院NICU住院的胎龄〈32周、出生体重〈1500g的早产儿,分别于出生时、生后7、14、21和28d及纠正胎龄36周时收集外周血,流式细胞仪检测EPCs水平,酶联免疫法检测血管内皮生长因子（VEGF）、基质细胞衍生因子等水平。结果68例极低出生体重早产儿纳入分析,其中对照组30例,BPD组20例,ROP组10例,IVH组8例。BPD组与对照组出生时EPCs水平差异无统计学意义,生后7d时点EPCs水平较对照组明显降低,CD34＋KDR＋：（0．019±0．009）％伽（0．026±0．012）％,P〈0．05;KDR＋CDl33＋：（0．004±D．002）％傩（0．008±0．004）％,P〈0．01;CD34＋KDR＋CDl33＋：（0．005±0．002）％船（0．008±0．004）％,P〈0．05。从出生时至生后21d,BPD组血浆VEGF水平均明显低于对照组。ROP组出生时至生后28d的EPCs水平与对照组差异无统计学意义,纠正胎龄36周时KDR＋CDl33＋和CD34＋KDR＋CDl33＋EPCs与对照组相比略有升高趋势。与对照组相比,IVH组生后不同时点的EPCs水平差异均无统计学意义。结论生后早期的EPCs和VEGF水平降低可能参与了早产儿BPD的发生,但其具体机制仍需进一步研究。     

The pathogenesis of neonatal post-hemorrhagic hydrocephalus

Hydrocephalus after intraventricular hemorrhage (IVH) has emerged as a major complication of preterm birth and is especially problematic to treat. The hydrocephalus is usually ascribed to fibrosing arachnoiditis, meningeal fibrosis and subependymal gliosis, which impair flow and resorption of cerebrospinal fluid (CSF). Recent experimental studies have suggested that acute parenchymal compression and ischemic damage, and increased parenchymal and perivascular deposition of extracellular matrix proteins--probably due at least partly to upregulation of transforming growth factor-beta (TGF-beta)--are further important contributors to the development of the hydrocephalus. IVH is associated with damage to periventricular white matter and the damage is exacerbated by the development of hydrocephalus; combinations of pressure, distortion, ischaemia, inflammation, and free radical-mediated injury are probably responsible. The damage to white matter accounts for the high frequency of cerebral palsy in this group of infants. The identification of mechanisms and mediators of hydrocephalus and white matter damage is leading to the development of new treatments to prevent permanent hydrocephalus and its neurological complications, and to avoid shunt dependence.     

Early Sodium and Fluid Intake and Severe Intraventricular Hemorrhage in Extremely Low Birth Weight Infants

Hypernatremic dehydration is an important cause of intracranial hemorrhage. A possible association of intraventricular hemorrhage (IVH) with hypernatremia and/or high sodium intake has been suggested in preterm infants. To investigate the associations of early fluid and sodium intake or serum sodium concentrations with severe intraventricular hemorrhage (IVH) in extremely low birth weight (ELBW) infants, we reviewed the medical records of 169 inborn ELBW infants. Daily fluid and sodium intake, urine output, weight loss and serum sodium concentration during the first 4 days of life were obtained. Patients were divided into the severe IVH (grade 3/4) and the control (no or grade 1/2 IVH) group. The maximum serum sodium concentration and the incidence of hypernatremia did not differ between the two groups. Related to the fluid balance and sodium intake, the risk for severe IVH was strongly associated with total fluid and sodium intake during the initial four days of life. With respect to the fluids other than transfusion, severe IVH can be discriminated only by sodium intake but not by fluid intake. Large randomized controlled trials are required to clarify the causal relationship between the early sodium intake and severe IVH in ELBW infants.

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Is Severity of Respiratory Disease Associated With Differences in Neurodevelopmental Patterns in Preterm Infants?

Neurodevelopmental outcomes were assessed at 6, 12, and 24 months of age for preterm infants (PT; n = 169) and full-term infants (FT; n = 120) to determine if neurodevelopmental patterns were related to severity of respiratory diagnosis, especially for infants with chronic lung disease. PT infants' respiratory diagnoses were either acute (transient respiratory distress: n = 55; respiratory distress syndrome: n = 48) or chronic (chronic pulmonary insufficiency of the preterm [CPIP]: n = 30; bronchopulmonary dysplasia [BPD]: n = 36). BPD and CPIP infant groups showed no differences in neurodevelopmental patterns, and both groups displayed poorer development in cognitive, language, daily living, and motor skills and more persistent neurological abnormalities across 24 months than infants with less severe respiratory diagnoses and FT infants.     

Prospective evaluation of perinatal risk factors for cerebral palsy and delayed development in high risk infants.

Prematurity, intrauterine infection and perinatal brain injury have been reported to be significant risk factors of cerebral palsy (CP). We examined the perinatal predictors of cerebral palsy and delayed development (DD) in 184 high risk infants. Thirty-five infants were diagnosed as cerebral palsy and delayed development at 12 months corrected age. Antenatal, intrapartum, and neonatal factors were prospectively evaluated in 2 groups of high risk infants compared with controls; Group A (n = 79), infants weighing less than 2,000 g; Group B (n = 43), infants weighing 2,000 g or more. In univariate analysis, there were no significant antenatal and intrapartum factors associated with cerebral palsy and delayed development in either group. We found that significant postnatal risk factors of CP in group A included sepsis (p = 0.008), BPD (bronchopulmonary dysplasia) (p = 0.028), IVH (intraventricular hemorrhage) (p = 0.042), ventriculomegaly (VM) (p = 0.001) and a longer duration of mechanical ventilation (p = 0.001); while in group B, sepsis (p = 0.047) and neonatal seizure (p = 0.027) were significant risk factors. In multivariate analysis, sepsis in group B was a moderate risk factor of CP (OR (odds ratio) 1.47; 95% CI (confidence interval) 1.02-2.13). In conclusion, neonatal sepsis may contribute to the development of cerebral palsy and delayed development. We suggest that high risk infants who have sepsis should be carefully followed for cerebral palsy and delayed development. The prevention of cerebral palsy may be feasible by decreasing neonatal risk factors such as sepsis during the neonatal period.     

Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants.

BACKGROUND: The prophylactic administration of indomethacin reduces the frequency of patent ductus arteriosus and severe intraventricular hemorrhage in very-low-birth-weight infants (those with birth weights below 1500 g). Whether prophylaxis with indomethacin confers any long-term benefits that outweigh the risks of drug-induced reductions in renal, intestinal, and cerebral blood flow is not known. METHODS: Soon after they were born, we randomly assigned 1202 infants with birth weights of 500 to 999 g (extremely low birth weight) to receive either indomethacin (0.1 mg per kilogram of body weight) or placebo intravenously once daily for three days. The primary outcome was a composite of death, cerebral palsy, cognitive delay, deafness, and blindness at a corrected age of 18 months. Secondary long-term outcomes were hydrocephalus necessitating the placement of a shunt, seizure disorder, and microcephaly within the same time frame. Secondary short-term outcomes were patent ductus arteriosus, pulmonary hemorrhage, chronic lung disease, ultrasonographic evidence of intracranial abnormalities, necrotizing enterocolitis, and retinopathy. RESULTS: Of the 574 infants with data on the primary outcome who were assigned to prophylaxis with indomethacin, 271 (47 percent) died or survived with impairments, as compared with 261 of the 569 infants (46 percent) assigned to placebo (odds ratio, 1.1; 95 percent confidence interval, 0.8 to 1.4; P=0.61). Indomethacin reduced the incidence of patent ductus arteriosus (24 percent vs. 50 percent in the placebo group; odds ratio, 0.3; P<0.001) and of severe periventricular and intraventricular hemorrhage (9 percent vs. 13 percent in the placebo group; odds ratio, 0.6; P=0.02). No other outcomes were altered by the prophylactic administration of indomethacin. CONCLUSIONS: In extremely-low-birth-weight infants, prophylaxis with indomethacin does not improve the rate of survival without neurosensory impairment at 18 months, despite the fact that it reduces the frequency of patent ductus arteriosus and severe periventricular and intraventricular hemorrhage.     

Neurodevelopmental Outcomes at 18–24 Months of Corrected Age in Very Low Birth Weight Infants with Late-onset Sepsis

BackgroundPreterm infants are prone to sepsis owing to their immature innate immunity and prolonged hospitalization. We aimed to evaluate the association between late-onset sepsis (LOS) during hospitalization and neurodevelopmental delay at 18–24 months of corrected age in very low birth weight infants (VLBWIs), and to ascertain this association when adjusted for perinatal risk factors.MethodsThis is a population-based study of VLBWIs born at 23–32 weeks of gestation between January 2014 and December 2017 who were enrolled in the Korean Neonatal Network. Bayley scales of infant development were evaluated at 18–24 months of corrected age in 2,098 infants. To test for LOS as a risk factor for neurodevelopmental delay, multiple logistic regression was used and adjusted for parental education status and clinical variables.ResultsBlood culture positive LOS was identified in 419 (20.0%) infants. Cognitive and motor delays were found in 392 (18.7%) and 347 (16.5%) infants, respectively. When multivariate analysis was performed, LOS had a significant association with cognitive delay (odds ratio, 1.48; 95% confidence interval, 1.02–2.16), but no association with motor delay in VLBWIs. Both delays were significantly more frequent in cases of intraventricular hemorrhage (IVH) ≥ grade 3, periventricular leukomalacia (PVL), and intrauterine growth restriction (IUGR) and duration of mechanical ventilation. Male sex and necrotizing enterocolitis ≥ grade 2 had an effect on motor delay, whereas paternal college graduation affected cognitive delay.ConclusionIn VLBWIs with LOS, there is a heightened risk of cognitive delays at 18–24 months of corrected age. Brain injury, such as severe IVH and PVL, duration of mechanical ventilation, and IUGR, were also associated with cognitive and motor delays.     

Tracheal aspirate cytology and bronchopulmonary dysplasia

Sequential tracheal aspirates from 39 neonates with hyaline membrane disease were examined to correlate cytological findings with the development of bronchopulmonary dysplasia (BPD). A total of 224 tracheal aspirates were examined from these infants, 15 of whom developed BPD as diagnosed by conventional clinical and radiological criteria. Hyperplastic and metaplastic epithelial changes were observed in all infants studied. Dysplastic changes occurred in 14 of 15 who developed BPD, and 14 of 24 who had a normal outcome (P less than 0.02). The exfoliation of dysplastic metaplastic bronchial cells was thus 95% specific and 71% sensitive for the subsequent development of BPD. Factors associated with the development of BPD were very low birth weight and gestational age, persistence of a patent ductus arteriosus, high peak inspiratory pressure (cm of H2O/kg), prolonged assisted ventilation, and rapidity of development of class III (dysplastic) changes in tracheal aspirates.     

Blast-like cells in cerebrospinal fluid of neonates. Possible germinal matrix origin

Primitive cell clusters (PCCs) composed of immature blast-like cells were observed in Wright's-stained cerebrospinal fluid (CSF) cytocentrifuge specimens from four infants over an 18-month period. All of these patients had hydrocephalus; in three this was secondary to subependymal germinal matrix intraventricular hemorrhage (IVH) associated with prematurity. The fourth was associated with Arnold-Chiari malformation, Chiari type II. In the CSF samples from the patients with IVH, hemosiderin-laden macrophages were also prominent and, in some cases, were intimately admixed with the PCCs. Immunoperoxidase staining of cytocentrifuge preparations from one of the patients revealed that the PCCs stained with neuron-specific enolase (NSE) but not with pan-leukocyte antibodies. Cells with similar morphologic characteristics to PCCs in the CSF of infants have been infrequently illustrated in the literature and thought to be of hematopoietic origin. However, the immunohistochemical findings and the clinical presentation suggest that PCCs are most likely germinal matrix cells.     

The association of γδ-T cells with bronchopulmonary dysplasia in premature infants

BackgroundAs the survival rate of premature infants increases, the incidence of bronchopulmonary dysplasia (BPD), a chronic complication of premature infants, is also higher than before. The pathogenesis of BPD is complicated, and immune imbalance and inflammatory response may play important roles in it.ObjectiveTo investigate the correlation between lymphocyte subsets in peripheral blood, especially γδ-T cells, and BPD of preterm infants.Materials and methodThe study was carried out with the peripheral blood of premature infants (GA < 32 weeks, BW < 1500 g), which were collected at 24 h or 3–4 weeks after birth. The infants were divided into non-BPD groups and BPD groups that were classified as mild or moderate and severe in preterm infants based on the magnitude of respiratory support at 28 days age and 36 weeks postmenstrual age. The γδ-T, CD3+, CD4+, CD8+ and total lymphocyte subsets in peripheral blood were detected by flow cytometry.ResultsThe percentages of T lymphocyte subsets in peripheral blood were not different between BPD and non-BPD within 24 h after birth. And no significant difference was found in T lymphocyte subsets among neonates with BPD of different severities. However, the infants who developed BPD had a significant increase in γδ-T cells compared to non-BPD ones within 3–4 weeks after birth.ConclusionsIt seems that γδ-T cells in peripheral blood are correlated with BPD. However, the causality of BPD and various lymphocytes remains unclear, which need to be further studied.     

A statistical study of autopsied cases of neonatal intraventricular hemorrhage

We have performed a statistical study of 1218 autopsies of neonates to extract the factors related to fatal neonatal intraventricular hemorrhage (IVH). Prematurity indicated by a short gestational period or a low birth weight was the most significant factor for IVH. Many other factors considered to be related to IVH were also related closely to prematurity. Therefore, we pose the following question throughout the study: Did the factors independently relate to IVH without any confounding effects of prematurity? To obtain the answer, we tried a statistical adjustment for gestational age to eliminate the confounding effects of prematurity. After the adjustment was made, we concluded that the following 10 items, in order, were the actual factors related to fatal IVH: prematurity, subependymal hemorrhage, subarachnoidal hemorrhage, respiratory distress syndrome, hyaline membrane disease, respiratory acidosis, intracerebral hemorrhage, cyanosis, respirator care, and low Apgar score. There were two distinctive categories in the factors that were eliminated by the adjustment. One was a group that has no significance whatsoever in any subdivided gestational groups, such as meconium aspiration syndrome, due to purely the result of the confounding effect. The other was a group that showed its statistical significance only in a certain period of gestation, such as breech presentation.     

Predictors of Developmental Outcomes for Medically Fragile Early Intervention Participants

Little is documented about the determinants of developmentaloutcomes for medically fragile infants who receive early intervention.In this controlled longitudinal study 65 premature infants withintraventricular hemorrhage (IVH) were randomly assigned tointervention groups beginning at 3 months adjusted age (Early)or 12 months adjusted age (Delayed). The sample was 65% AfricanAmerican and 35% Caucasian, and over half the youngsters werebeing raised by single mothers. Although cost analyses revealedthat it was almost twice as expensive to begin sensorimotorintervention at the earlier age, annual comprehensive assessmentsrevealed no significant differences in developmental outcomesbased on age at start. Stepwise multiple regression analysesrevealed that Maternal Education and Neonatal Medical Problemswere significant predictors of outcomes at years 1, 3, 5, and7 regardless of age at start. Related findings from other studiesare discussed along with implications for policy and futureresearch.     

High Incidence of Rickets in Extremely Low Birth Weight Infants with Severe Parenteral Nutrition-Associated Cholestasis and Bronchopulmonary Dysplasia

Risk factors for rickets of prematurity have not been re-examined since introduction of high mineral formula, particularly in ELBW infants. We analyzed the incidence and the risk factors of rickets in extremely low birth weight (ELBW) infants. As a retrospective case-control study from 2004 to 2008, risk factors were analyzed in 24 patients with rickets versus 31 patients without. The frequency of rickets in ELBW infants was 24/55 (44%). Infants with rickets were diagnosed at 48.2 ± 16.1 days of age, and improved by 85.3 ± 25.3 days. By radiologic evaluation, 29% were grade 1 rickets, 58% grade 2 and 13% grade 3. In univariate analysis, infants with rickets had significantly higher incidence of patent ductus arteriosus, parenteral nutrition associated cholestasis (PNAC), severe PNAC and moderate/severe bronchopulmonary dysplasia (BPD). In multiple regression analysis, after adjustment for gestation and birth weight, rickets significantly correlated with severe PNAC and with moderate/severe BPD. Serum peak alkaline phosphatase levels were significantly elevated in rickets (P < 0.001). In ELBW infants, the incidence of rickets of prematurity remains high and the incidence of severe PNAC and moderate/severe BPD was significantly increased 18 and 3 times, respectively.     

Incidence of bronchopulmonary dysplasia in Korea

A nationwide survey was conducted to determine the incidence of bronchopulmonary dysplasia (BPD) in Korea and the intercenter differences in survival and BPD rates among preterm infants. Questionnaires were sent to all registered neonatal intensive care units (NICUs). The questionnaires inquired about the survival and BPD rates of very low birth weight (VLBW, < 1,500 g) infants who had been admitted to each NICU from 2007 to 2008. BPD was defined as requiring oxygen at 36 weeks' postmenstrual age. Almost all level III NICUs replied. During the study period, 3,841 VLBW infants were born in the NICUs that responded to the survey. The survival rate was 81% and the BPD rate was 18%. Combined outcome of BPD or death rate was 37%. The BPD rate and combined outcome of BPD or death rate varied considerably from 5% to 50% and 11% to 73%, respectively across the centers. There was no significant correlation between the survival rate and the BPD rate across the centers. In conclusion, the incidence of BPD among VLBW infants in Korea during the study period was 18%, and a considerable intercenter difference in BPD rates was noted.     

Comparative Analysis of the Patients with Spontaneous Thalamic Hemorrhage with Concurrent Intraventricular Hemorrhage and Those without Intraventricular Hemorrhage

BackgroundThis study aimed to compare the characteristics of patients with spontaneous thalamic hemorrhage (STH) accompanied by intraventricular hemorrhage (IVH) with those of patients without IVH.MethodsThe medical records of consecutive patients with STH admitted to our institute between January 2000 and December 2018 were reviewed retrospectively. The laboratory and radiological results, mortality, and functional recovery were compared between the STH patients with IVH and those without IVH.ResultsAmong 2,389 patients with spontaneous intracerebral hemorrhage, 233 (9.8%) patients were included in this study. Concurrent IVH was detected in 159 (68.2%) patients with STH, and more frequently in those with body mass index ≥ 25, Glasgow Coma Scale score of 3–8, underlying disease, family history of stoke, posterior/medial/global location of hematoma, ventriculomegaly, large volume of hemorrhage, and midline shift ≥ 5 mm. The 3-month mortality was 25.8% and 8.1% (P = 0.039), the rate of good functional recovery at 6 months was 52.2% and 31.0% (P = 0.040), and incidence of delayed normal pressure hydrocephalus (NPH) at 12 months was 10.8% and 24.5% (P = 0.062) in the STH patients with IVH and those without IVH, respectively. At 12 months, delayed NPH developed in 28 of 47 (59.6%) patients who received external ventricular drainage (EVD)-based treatment, 5 of 45 (11.1%) patients who underwent endoscopic evacuation-based treatment, and 8 of 45 (17.8%) patients who underwent other surgeries.ConclusionConcurrent IVH is strongly associated with mortality in patients with STH. Delayed NPH may develop more frequently in STH patients with IVH who were treated with EVD.     

系统评价早产对儿童智力发育的影响及早期干预作用

目的评价早产对儿童智力发育的影响及早期干预的作用。方法检索Cochrane图书馆、PubMed、EMBASE、万方数据库、中国期刊全文数据库和中国维普数据库,检索起止时间均为1980年1月至2011年11月。由2名系统评价员进行资料提取和质量评价,数据分析采用RevMan5.0.13软件,检验异质性,并根据异质性结果选择相应的效应模型。结果共纳入18项研究评价早产对儿童智力发育的影响,15项研究（16篇文献）评价早期干预对早产儿智力心理发育的作用。9篇文献提及随机分配方法,9篇文献提及分配方案隐藏,9篇文献提及对研究对象、治疗方案实施者、研究结果测量者采用盲法,12篇文献提及结果数据的完整性,10篇文献提及选择性报告研究结果,没有文献提及其他偏倚来源。早产儿智商（IQ）明显低于足月儿（SMD=-11.62,95%CI：-13.21--10.03）,差异有统计学意义（Z=14.37,P〈0.001）。对胎龄与IQ的关系进行分层分析,发现胎龄越低,IQ越低,儿童期随访,IQ从胎龄34-36周的112.7逐渐降至胎龄25周的82.1。对早期干预的作用进行了评价,各组婴儿（早产儿纠正年龄）于生后6、12、18、24、36个月采用贝利婴儿发育量表（BSID）测定智力发育指数（MDI）和运动发育指数（PDI）,结果表明早期干预组MDI与PDI均较对照组显著提高,P均〈0.01。早期干预可显著降低早产儿智力异常的发生率（OR=0.25,95%CI：0.15-0.41）。结论本Meta分析表明早产儿IQ明显低于足月儿,并随着胎龄的降低而逐渐减低,对早产儿早期干预可明显改善早产儿智力水平,降低智力异常的发生率。但早产儿干预仍缺少长期的随访研究,需要进一步的评价。     

系统评价胎龄小于32周早产儿预防性经鼻持续气道正压通气的作用

目的评价早产儿早期应用经鼻持续气道正压通气（NCPAP）预防呼吸窘迫综合征（RDS）,减少呼吸机应用、病死率和并发症的发生。方法以（prophylactic nasal CPAP OR early nasal CPAP）AND （preterm infants OR low birth weightinfants） ,经鼻持续气道正压通气AND（早产儿OR低出生体重儿）为英中文关键词,检索PubMed、EMBASE、Cochrane临床对照试验库、维普中文科技期刊数据库、中国知网和万方数据库,检索时间均从建库至2011年12月,并辅以手工检索。应用RevMan5．0软件进行Meta分析,根据异质性结果选择相应的效应模型分析;无法进行Meta分析时采用描述性分析。结果8篇RCT文献进入分析。Meta分析结果显示：NCPAP组未能显著降低早产儿气管插管呼吸机应用率（RR=-0．09,95％CI：-0．19～0．02,P=0．09）、RDS发生率（RR=0．81,95％CI：0．59—1．1,P=0．18）和病死率（RR=0．88,95％CI：0．72～1．09,P=0．25）;NCPAP组能显著减少早产儿肺表面活性物质应用率（RR=0．72,95％CI：0．64—0．80,P〈0．00001）。NCPAP组未能显著减少气管插管呼吸机通气时间（MD=-1．91d,95％CI：-6．47～4．45d,P=0．72）及氧气应用时间（MD=-0．46d,95％CI：-6．55—5．63d,P=0．88）。NCPAP组除增加气胸的发生率外,并未明显增加支气管肺发育不良、颅内出血、早产儿视网膜病、败血症、新生儿坏死性小肠结肠炎和动脉导管未闭等并发症的发生率。结论目前的证据表明早期应用NCPAP可减少肺表面活性物质应用,但增加了气胸的发生率;未能减少早产儿呼吸机应用、RDS发生率和病死率,未增加除气胸外的其他并发症发生率。     

Neonatal Morbidities Associated with Histologic Chorioamnionitis Defined Based on the Site and Extent of Inflammation in Very Low Birth Weight Infants

Conflicting results on the influences of histologic chorioamnionitis (HC) on neonatal morbidities might be partly originated from using different definition of HC. The aim of this study was to determine the relationship between HC and neonatal morbidities using definition of HC that reflects the site and extent of inflammation. This was a retrospective cohort study of 261 very low birth weight (VLBW) infants admitted at a tertiary academic center. Based on the site of inflammation, HC was categorized: any HC; amnionitis; funisitis; amnionitis+funisitis. The extent of inflammation in each site was reflected by sub-defining high grade (HG). The incidences of morbidities in infants with and without HC were compared. The bronchopulmonary dysplasia (BPD) rate was significantly higher in infants with amnionitis and the severe retinopathy of prematurity (ROP) rate was significantly higher in infants with any HC and funisitis. After adjustment for both gestational age and birth weight, the respiratory distress syndrome (RDS) rate was significantly lower in infants with all categories of HC except for HG amnionitis and HG funisitis, which are not associated with lower RDS rate. HG amnionitis was significantly associated with increased BPD rate but the association of HC with severe ROP disappeared. In conclusion, HC is significantly associated with decreased RDS and HG amnionitis with increased BPD while lacking association with other neonatal morbidities in VLBW infants. The association with HC and neonatal morbidities differs by the site and extent of chorioamnionitis.

Graphical Abstract

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The Prediction of Bronchopulmonary Dysplasia in Very Low Birth Weight Infants through Clinical Indicators within 1 Hour of Delivery

BackgroundDespite the advances in neonatology, the incidence of bronchopulmonary dysplasia (BPD) is increasing. It is important to prevent the development of BPD in the first place. The online BPD outcome estimator from National Institute of Children Health and Human Development and Neonatal Research Network is available. However, it is not applicable for Asians. Moreover, limits are set for birth weight and gestational weeks excluding those who may still have BPD. The aim of this study was to develop a prediction model for BPD using first hour perinatal and neonatal factors in Korean very low birth weight infants (VLBWIs).MethodsData were collected for 8,022 VLBWIs with gestational age (GA) ≥ 22 weeks who were born between January 1, 2013 and December 31, 2016, and admitted to the neonatal intensive care units of the KNN. Multiple logistic regression models reanalyzed by stepwise selection with significant clinical indicators for BPD. PROC package was used to calculate the area under curve (AUC) and corresponding 95% confidence intervals. Moreover, it was used to search the best cut-off value. External validation was performed with the 2017 Korean neonatal network (KNN) data.ResultsAfter all missing data were excluded, 4,600 VLBWIs were included in the training dataset of the prediction model. Predictability of presence of BPD was 90.8% and prediction P value cut off was 0.550. Five-minute Apgar score, birth weight, GA, sex, surfactant use were significant indicators. Predictability of severe BPD was 81.5% and prediction P value cut off was 0.160. Five-minute Apgar score, birth weight, maternal PIH, chronic maternal hypertension, GA, sex, respiratory distress syndrome, need of resuscitation at birth were significant indicators. After external validation, sensitivity and specificity did not change significantly.ConclusionFrom this study, high predictability was obtained using clinical parameters obtained within one hour of life. P value for prediction of each grade of BPD and equation for calculation was presented. It can be helpful for the early prediction of BPD in Korean VLBWI. This study will contribute to the prediction of BPD in Asians especially Korean VLBWIs, not currently included in the NICHD BPD online BPD predictor. In addition, the predictive power may be continuously increased with the cumulative data of KNN.