Tracheobronchomalacia in preterm infants with chronic lung disease

Tracheobronchomalacia is a treatable cause of persisting ventilatory requirements in the preterm neonate, and warrants a high index of suspicion. Five preterm infants with persisting ventilatory requirements with evidence of tracheobronchomalacia are reported. Four were diagnosed by tracheobronchogram and one by flexible endoscopy. All were successfully managed by continuous positive airway pressure (CPAP) via a tracheostomy. One infant died of unrelated causes. The oldest child in this series at the age of 2 years requires no further ventilatory support. Tracheobronchial anomalies should be considered in all preterm infants with persisting ventilatory requirements.     

Blood transfusion and chronic lung disease in preterm infants

Frequent blood transfusions may produce changes in iron status which can give rise to oxygen-derived free-radical (ODFR) generation and oxidative injury. Preterm infants developing chronic lung disease (CLD) receive significantly more transfusions. A total of 73 very preterm infants had weekly estimations of serum iron, transferrin, transferrin saturation, ferritin, caeruloplasmin, bleomycin detectable (‘free’) iron (BDI), and thiobarbituric acid reacting substances (TBARS) made over the first 28 days. Thirty infants remained oxygen dependent at 36 weeks postmenstrual age and were termed as having CLD. They were significantly lighter and less mature at birth and received more than twice as many transfusions during the 1st month. They had significantly lower transferrin levels initially but similar total iron and transferrin saturations as non-CLD infants. Ferritin and caeruloplasmin levels rose to significantly higher levels over the 1st month in CLD infants, and ferritin levels were significantly related to the number of transfusions given. Infants with higher ferritin levels were more likely to show BDI, although this was not associated with increased lipid peroxidation as evidenced by higher TBARS. Conclusion It is unlikely that oxidative injury from ODFRs induced by blood transfusion contributes to the risk of developing CLD in preterm infants.     

早产儿慢性肺疾病临床分析

随着机械通气和外源性肺泡表面活性物质的使用,早产儿、极低出生体重儿的存活率明显提高,早产儿慢性肺疾病(chronic lung d isease,CLD)的发生率有所上升,CLD已成为发达国家新生儿重症监护病房(NICU)最为棘手的问题之一。目前国内有关早产儿CLD的报道较少,对其各种临床表现形式     

Blood transfusion and chronic lung disease in preterm infants

Frequent blood transfusions may produce changes in iron status which can give rise to oxygen-derived free-radical (ODFR) generation and oxidative injury. Preterm infants developing chronic lung disease (CLD) receive significantly more transfusions. A total of 73 very preterm infants had weekly estimations of serum iron, transferrin, transferrin saturation, ferritin, caeruloplasmin, bleomycin detectable (‘free’) iron (BDI), and thiobarbituric acid reacting substances (TBARS) made over the first 28 days. Thirty infants remained oxygen dependent at 36 weeks postmenstrual age and were termed as having CLD. They were significantly lighter and less mature at birth and received more than twice as many transfusions during the 1st month. They had significantly lower transferrin levels initially but similar total iron and transferrin saturations as non-CLD infants. Ferritin and caeruloplasmin levels rose to significantly higher levels over the 1st month in CLD infants, and ferritin levels were significantly related to the number of transfusions given. Infants with higher ferritin levels were more likely to show BDI, although this was not associated with increased lipid peroxidation as evidenced by higher TBARS. Conclusion It is unlikely that oxidative injury from ODFRs induced by blood transfusion contributes to the risk of developing CLD in preterm infants. Received: 26 September 1995 / Accepted: 20 April 1996     

Antenatal endotoxin and glucocorticoid effects on lung morphometry in preterm lambs

In utero inflammation may accelerate fetal lung maturation but may also play a role in the pathogenesis of chronic lung disease. We examined the impact of endotoxin, a potent proinflammatory stimulus, on structural and functional maturation of preterm sheep lungs. Date bred ewes received 20 mg Escherichia coli endotoxin or saline by ultrasound guided intra-amniotic injection at 119 d gestation. A comparison group of animals received 0.5 mg/kg betamethasone, a known maturational agent, at 118 d gestation. Lambs were delivered by cesarean section at 125 d (term = 150 d) and ventilated for 40 min. Lung function data are reported elsewhere. Total and differential white cell counts were performed on amniotic fluid and fetal lung fluid samples. Morphometric analyses were performed on inflation fixed right upper lobes. Total cell count increased slightly but not significantly in both amniotic fluid and fetal lung fluid. Both endotoxin and betamethasone had similar effects on alveolarization: average alveolar volume increased by approximately 20% and total alveolar number decreased by almost 30%. Both treatments led to thinning of alveolar walls, although this was statistically significant in the betamethasone-treated group only. Although antenatal endotoxin leads to striking improvements in postnatal lung function, this may be at the expense of normal alveolar development.     

Impaired glucocorticoid synthesis in premature infants developing chronic lung disease

Premature infants have higher cortisol precursor concentrations than term infants; however, many sick preterm infants have surprisingly low cortisol concentrations. Those who develop chronic lung disease (CLD) have lower cortisol values than those who recover. We hypothesized that some infants have a decreased ability to synthesize cortisol, leading to physiologic disruptions including amplified inflammatory responses, thereby resulting in CLD. We measured cortisol, 11-deoxycortisol, 17-hydroxyprogesterone, 17-hydroxypregnenolone, dehydroepiandrosterone sulfate, and ACTH in 40 extremely low birth weight infants enrolled in a study of low-dose hydrocortisone therapy to prevent CLD. Thirty-four infants survived and 15 developed CLD. Hydrocortisone therapy did not suppress ACTH or any measured steroid value. Before study (<48 h of life), 17-OH progesterone was higher in CLD infants, as was the ratio of 17-OH progesterone to 11-deoxycortisol. On d 15-19 (> or =72 h after end of therapy), basal and stimulated cortisol concentrations were lower in CLD infants. In contrast, the basal ratio of 11-deoxycortisol to cortisol was higher in CLD infants, as were stimulated values of 17-OH progesterone and stimulated ratios of 17-OH progesterone to 11-deoxycortisol and 11-deoxycortisol to cortisol. Thus, infants who developed CLD had lower basal and stimulated cortisol values, but elevated cortisol precursors and precursor to product ratios, compared with infants who recovered. These data support the hypothesis that these immature infants have a decreased capacity to synthesize cortisol, which may lead to a relative adrenal insufficiency in the face of significant illness.     

Antenatal ambroxol treatment does not prevent the respiratory distress syndrome in premature infants

The effectiveness of ambroxol in the prevention of neonatal respiratory distress syndrome and in reducing the need for intermittent mandatory ventilation and oxygen therapy was studied in 88 mothers whose infants was born between 24 and 34 weeks of gestation and who were randomized either for treatment with ambroxol (group A = 42) or served as control (group B = 46). There were no significant differences in the mean gestational age, birth weight or Apgar score between the two groups. We found no significant differences in occurrence of respiratory distress syndrome (55% vs 45%), in support by intermittent mandatory ventilation (71% vs 72%) or oxygen therapy (74% vs 75%) at 12 h of age between groups A and B. Conclusion This study does not suggest the efficacy of antenatal ambroxol treatment both for the prevention of neonatal respiratory distress syndrome and for the reduction of its severity. Received: 12 October 1995 and in revised form: 30 August 1996 / Accepted: 10 September 1996     

Prenatal predictors of chronic lung disease in very preterm infants

OBJECTIVE: To identify prenatal risk factors for chronic lung disease (CLD) at 36 weeks postmenstrual age in very preterm infants. POPULATION: Data were collected prospectively as part of the ongoing audit of the Australian and New Zealand Neonatal Network (ANZNN) of all infants born at less than 32 weeks gestation admitted to all tertiary neonatal intensive care units in Australia and New Zealand. METHODS: Prenatal factors up to 1 minute of age were examined in the subset of infants born at gestational ages 22-31 weeks during 1998-2001, and who survived to 36 weeks postmenstrual age (n = 11 453). Factors that were significantly associated with CLD at 36 weeks were entered into a multivariate logistic regression model. RESULTS: After adjustment, low gestational age was the dominant risk factor, with an approximate doubling of the odds with each week of decreasing gestational age from 31 to less than 25 weeks (trend p<0.0001). Birth weight for gestational age also had a dose-response effect: the lower the birth weight for gestational age, the greater the risk, with infants below the third centile having 5.67 times greater odds of CLD than those between the 25th and 75th centile (trend p<0.0001). There was also a significantly increased risk for male infants (odds ratio 1.51 (95% confidence interval 1.36 to 1.68), p<0.0001). CONCLUSIONS: These population based data show that the prenatal factors low gestational age, low birth weight for gestational age, and male sex significantly predict the development of chronic respiratory insufficiency in very preterm infants and may assist clinical decision about delivery.     

Dexamethasone treatment and fluid balance in preterm infants at risk for chronic lung disease

The influence of dexamethasone on diuresis in preterm infants has not been well studied. We examined 15 preterm infants at risk for chronic lung disease with gestational ages ranging from 26 to 29 wk (median 27.6 wk) and birthweights ranging from 700 to 1485 g (median 965 g). Urine output, blood glucose, serum urea, serum creatinine, serum sodium and serum potassium, as well as systolic, diastolic and mean arterial pressure were measured on the day before, and on 4 consecutive days after starting treatment with dexamethasone (0.25 mg kg^-1 i.v., twice daily). We found an increase of diuresis of 30 ml kg^-1 d^-1, 48-96 h after starting dexamethasone treatment. This coincided with a gradual but significant increase of serum urea levels and arterial pressure. During the study period, fluid and protein intake remained constant. Blood glucose and serum creatinine levels did not change. Our findings suggest that the increased urine output following dexamethasone treatment might be caused by two factors: (1) pressure diuresis induced by the increase of arterial pressure and (2) an increase of the osmolar load to the kidney due to an increase of serum urea.­­Conclusions: This study demonstrates that a significant increase of diuresis occurs in preterm infants, 48-96 h after starting dexamethasone. A careful monitoring of fluid balance during the first days of dexamethasone treatment is recommended.     

丝裂原活化蛋白激酶与早产儿慢性肺疾病

早产儿慢性肺疾病是早产儿吸入高浓度氧、机械通气治疗和肺部感染后最常见的合并症.其详细的发病机制尚未完全明了,病理主要表现为早期的炎症反应,晚期的肺泡融合及间质成纤维细胞增生.丝裂原活化蛋白激酶(MAPK)是真核细胞内重要的信号传导通路,近来研究发现MAPK通过参与词节细胞炎症、增殖、分化、生存和凋亡等多种生物学行为,促进了早产儿慢性肺疾病的发生.     

丝裂原活化蛋白激酶与早产儿慢性肺疾病

早产儿慢性肺疾病是早产儿吸入高浓度氧、机械通气治疗和肺部感染后最常见的合并症.其详细的发病机制尚未完全明了,病理主要表现为早期的炎症反应,晚期的肺泡融合及间质成纤维细胞增生.丝裂原活化蛋白激酶(MAPK)是真核细胞内重要的信号传导通路,近来研究发现MAPK通过参与词节细胞炎症、增殖、分化、生存和凋亡等多种生物学行为,促进了早产儿慢性肺疾病的发生.     

Development of chronic lung disease in preterm infants treated with surfactant

BACKGROUND: Chronic lung disease (CLD) is generally known to develop among preterm infants who have severe respiratory distress syndrome (RDS) at birth. Many clinical trials have established the efficacy of surfactant replacement therapy to treat RDS at birth with differing doses. In this study, the preterm infants diagnosed to have RDS at birth and treated with one or two doses of surfactant, depending on the severity of the RDS, were studied to evaluate the effect of surfactant on the later development of CLD. METHODS: A retrospective examination of case records of preterm infants who were born at < or = 28 weeks gestation period were studied. The subjects received a natural surfactant product (survanta) between September 1994 and April 1996 at the Monash Medical Center, Australia. RESULTS: Despite less severe initial lung disease, the subsequent respiratory outcome of infants who received one dose of surfactant, showed a trend towards being poorer compared to those who were diagnosed as having severe RDS at birth and received two doses of surfactant. At the corrected gestational age of 36 weeks, 54% of those infants began with mild RDS required oxygen, while only 44% of those who started with a severe RDS required supplemental O2. CONCLUSION: This study reports the infants with severe RDS at birth had responded slightly better or equally, compared to those with mild RDS, in terms of later development of CLD under surfactant treatment proportional to the severity.