Initial respiratory management in preterm infants and bronchopulmonary dysplasia

BACKGROUND:

Ventilator injury has been implicated in the pathogenesis of bronchopulmonary dysplasia. Avoiding invasive ventilation could reduce lung injury, and early respiratory management may affect pulmonary outcomes.

OBJECTIVE:

To analyze the effect of initial respiratory support on survival without bronchopulmonary dysplasia at a gestational age of 36 weeks.

DESIGN/METHODS:

A prospective 3-year observational study. Preterm infants of <32 weeks gestational age were classified into 4 groups according to the support needed during the first 2 hours of life: room air, nasal continuous positive airway pressure, intubation/surfactant/extubation and prolonged mechanical ventilation (defined as needing mechanical ventilation for more than 2 hours).

RESULTS:

Of the 329 eligible patients, a total of 49% did not need intubation, and 68.4% did not require prolonged mechanical ventilation. At a gestational age of 26 weeks, there was a significant correlation between survival without bronchopulmonary dysplasia and initial respiratory support. Preterm infants requiring mechanical ventilation showed a higher risk of death and bronchopulmonary dysplasia. After controlling for gestational age, antenatal corticosteroid use, maternal preeclampsia and chorioamnionitis, the survival rate without bronchopulmonary dysplasia remained significantly lower in the mechanically ventilated group.

CONCLUSIONS:

In our population, the need for more than 2 hours of mechanical ventilation predicted the development of bronchopulmonary dysplasia in preterm infants with a gestational age >26 weeks (sensitivity = 89.5% and specificity = 67%). The need for prolonged mechanical ventilation could be an early marker for the development of bronchopulmonary dysplasia. This finding could help identify a target population with a high risk of chronic lung disease. Future research is needed to determine other strategies to prevent bronchopulmonary dysplasia in this high-risk group of patients.     

Characterization of ureaplasmas isolated from preterm infants with and without bronchopulmonary dysplasia

A PCR assay was used to analyze endotracheal aspirates from preterm infants for Ureaplasma parvum versus U. urealyticum. U. parvum was detected more often than U. urealyticum. There was no significant difference or trend in the prevalence of either species between infants with or without bronchopulmonary dysplasia when isolated alone.     

早产儿支气管肺发育不良症临床分析

目的了解早产儿支气管肺发育不良（BPD）的临床特点。方法 2007年1月至2009年12月本院新生儿重症监护病房收住920例早产儿,对其胎龄、出生体重、原发疾病、肺部X线表现、治疗经过等临床资料进行分析。结果 920例早产儿中24例发生BPD,胎龄〈28周6例,28～30周13例,～32周3例,～35周2例;出生体重〈1000g 6例,1000～1500g 13例,～2500g 5例;轻度BPD 13例,中度BPD 6例,重度BPD 5例;需要机械通气时间为（1.04±26.35）d,需吸氧时间为（47.22±22.49）d,住院时间为（65.29±23.46）d。BPD患儿中合并肺部感染37.5%,脑积水16.7%,早产儿视网膜病16.7%,动脉导管未闭20.8%。所有病例经综合治疗治愈14例,放弃治疗后死亡5例,好转5例,其中3例出院后6个月内均因肺部感染再次住院。结论早产儿肺发育不成熟、长时间吸氧及机械通气、肺部感染是BPD发生的主要因素,故积极预防早产,尽量避免机械通气以及减少机械通气、吸氧时间,积极预防和治疗肺部感染及关闭动脉导管可能会减少BPD的发生。     

A quantitative analysis of Ureaplasma urealyticum and Ureaplasma parvum compared with host immune response in preterm neonates at risk of developing bronchopulmonary dysplasia

Multiplex, real-time PCR for the identification of Ureaplasma urealyticum and Ureaplasma parvum was performed on nucleic acids extracted from sequential endotracheal aspirates obtained from preterm neonates born at <29 weeks of gestation and ventilated for more than 48 h admitted to two level 3 neonatal intensive care units. Specimens were obtained shortly after birth and sequentially up until extubation. One hundred fifty-two specimens (93.8%) contained material suitable for analysis. Ureaplasma spp. were identified in 5 of 13 neonates studied. In most cases, the DNA load of the detected Ureaplasma species was low and decreased over time. In addition, changes in detectable Ureaplasma species DNA did not relate to changes in the inflammatory marker C-reactive protein (CRP) or respiratory status. All but two blood samples obtained at times of suspected sepsis were culture positive for other microorganisms; the species cultured were typically coagulase-negative staphylococci and were associated with increased levels of CRP (>10 mg/liter). This study was limited by the small number of patients examined and does not have the power to support or contradict the hypothesis that postnatal lung infection with Ureaplasma parvum is causally related to bronchopulmonary dysplasia (BPD) or adverse respiratory outcomes after preterm birth. However, in this study, increases in CRP levels were not associated with patients in whom Ureaplasma parvum was detected, in contrast to the detection of other bacterial species.     

Ophthalmological morbidity in very-low-birthweight infants with bronchopulmonary dysplasia.

This study was undertaken to determine the relationship between retinopathy of prematurity, ocular sequelae of retinopathy, and bronchopulmonary dysplasia in infants weighing < 1250 g at birth prior to the introduction of steroid therapy for chronic lung disease. Ophthalmological data from 67 infants (22 with severe bronchopulmonary dysplasia and 45 controls) who were enrolled prospectively in an early intervention program were analyzed. The infants had two or more eye examinations prior to discharge and a follow-up examination at 12 to 18 months postconceptual age. The incidence of any retinopathy of prematurity was 33%, and severe retinopathy was 25%. Infants with severe bronchopulmonary dysplasia were 1.7 times more likely to develop any retinopathy and 1.8 times more likely to develop severe retinopathy than controls. The incidence of ocular sequelae, was 45%. Infants with any retinopathy had a 2.3 odds of developing sequelae, and infants with severe retinopathy had a 2.64 odds ratio. When adjusted for bronchopulmonary dysplasia, the odds ratio for developing sequelae was 1.36 in infants with any retinopathy and 1.27 in those with severe retinopathy. The predictors of retinopathy were lower birthweight and gestational age, acidosis, and hypoxemia. Bronchopulmonary dysplasia per se has an adverse effect on ophthalmologic morbidity. Evaluation of the adverse effect of any therapy for chronic lung disease on retinopathy of prematurity should make adjustments for the underlying lung disease.     

Respiratory outcomes and atopy in school-age children who were preterm at birth, with and without bronchopulmonary dysplasia

OBJECTIVE:

To assess pulmonary function and the prevalence of atopy in school-age children who were very low birth weight as infants and to compare those who had bronchopulmonary dysplasia to those who did not.

METHOD:

We studied 85 (39 male and 46 female) at a mean age of 84 (range, 62 to 107) months who were very low birth weight infants. Bronchopulmonary dysplasia was defined as oxygen dependency at 36 weeks gestational age. We excluded 8 patients (4 for cerebral palsy and 4 for no collaboration). Detailed perinatal and clinical data were collected. Lung function was evaluated using conventional spirometry. Atopy (assessed by the allergy skin-prick test) was considered when at least one positive skin test occurred in a panel of the most common environmental allergens in the local region. Comparisons between the bronchopulmonary dysplasia and no bronchopulmonary dysplasia groups were performed using the Mann-Whitney, χ2 and Fisher''s exact tests.

RESULTS:

We compared the bronchopulmonary dysplasia (n = 13) and no bronchopulmonary dysplasia (n = 64) groups. Atopy was observed in 4 (30.8%) of the bronchopulmonary dysplasia patients and in 17 (26.6%) of the no bronchopulmonary dysplasia patients (p = 0.742). Two (15.4%) patients with bronchopulmonary dysplasia had a family history of atopy vs. 17 (26.6%) in the no bronchopulmonary dysplasia group (p = 0.5). Lung function tests showed airway obstruction in 2 (15.4%) of the bronchopulmonary dysplasia patients and in 10 (15.6%) of the no bronchopulmonary dysplasia patients (p = 1.0). Four (33.3%) of the bronchopulmonary dysplasia patients had small airway obstruction vs. 14 (22.2%) of the no bronchopulmonary dysplasia patients (p = 0.466).

CONCLUSION:

Our data showed no significant differences in lung function between bronchopulmonary dysplasia and no bronchopulmonary dysplasia patients at school age and no evidence of an association between atopy and bronchopulmonary dysplasia.     

An open-loop controlled active lung simulator for preterm infants

We describe the underlying theory, design and experimental evaluation of an electromechanical analogue infant lung to simulate spontaneous breathing patterns of preterm infants. The aim of this work is to test the possibility to obtain breathing patterns of preterm infants by taking into consideration the air compressibility. Respiratory volume function represents the actuation pattern, and pulmonary pressure and flow-rate waveforms are mathematically obtained through the application of the perfect gas and adiabatic laws. The mathematical model reduces the simulation interval into a step shorter than 1 ms, allowing to consider an entire respiratory act as composed of a large number of almost instantaneous adiabatic transformations. The device consists of a spherical chamber where the air is compressed by four cylinder-pistons, moved by stepper motors, and flows through a fluid-dynamic resistance, which also works as flow-rate sensor. Specifically designed software generates the actuators motion, based on the desired ventilation parameters, without controlling the gas pneumatic parameters with a closed-loop. The system is able to simulate tidal volumes from 3 to 8 ml, breathing frequencies from 60 to 120 bpm and functional residual capacities from 25 to 80 ml. The simulated waveforms appear very close to the measured ones. Percentage differences on the tidal volume waveform vary from 7% for the tidal volume of 3 ml, down to 2.2-3.5% for tidal volumes in the range of 4-7 ml, and 1.3% for the tidal volume equal to 8 ml in the whole breathing frequency and functional residual capacity ranges. The open-loop electromechanical simulator shows that gas compressibility can be theoretically assessed in the typical pneumatic variable range of preterm infant respiratory mechanics.     

A sleep disturbance in high risk for SIDS infants

A developmentally immature sleep pattern has been identified in infants with a recent history of an unexplained life-threatening episode of sleep apnoea who are considered at risk for SIDS. In these infants there is a persistence of Sleep Onset REM Periods (SOREMPS) after prolonged wakefulness when compared to controls matched for age, sex, birthweight and race. This sleep characteristic has not been previously reported.     

早产儿视网膜病发病情况及高危因素的探讨

目的 探讨早产儿视网病（retinopathy of prematurity，ROP）的发病率、高危因素及防治措施。方法对194例早产儿生后72h内及生后4w开始定期检查眼底，发现ROP者密切随访至生后1年。结果72h内早期眼底检查眼底异常包括视乳头水肿、视网膜水肿、视网膜血管改变及出血等。生4w后检出ROP患儿12例（6．2％），高危因素分别为低出生体重，小孕周、长期或高浓度吸氧。结论建议出生体重小于2000g和／或孕周小于35w的早产儿，在生后第3w或胎龄达34w时常规行首次眼底检查，以早期发现ROP并给予及时治疗。     

Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: a randomized, controlled trial

BACKGROUND: There is growing interest in the potential role of anti-inflammatory n-3 polyunsaturated fatty acids (n-3 PUFAs) in the prevention of allergic disease. OBJECTIVE: We sought to determine whether maternal dietary supplementation with n-3 PUFAs during pregnancy could modify immune responses in infants. METHODS: In a randomized, controlled trial 98 atopic, pregnant women received fish oil (3.7 g n-3 PUFAs per day) or placebo from 20 weeks' gestation until delivery. Neonatal PUFA levels and immunologic response to allergens were measured at birth. RESULTS: Eighty-three women completed the study. Fish oil supplementation (n = 40) achieved significantly higher proportions of n-3 PUFAs in neonatal erythrocyte membranes (mean +/- SD, 17.75% +/- 1.85% as a percentage of total fatty acids) compared with the control group (n = 43, 13.69% +/- 1.22%, P <.001). All neonatal cytokine (IL-5, IL-13, IL-10, and IFN-gamma) responses (to all allergens) tended to be lower in the fish oil group (statistically significant only for IL-10 in response to cat). Although this study was not designed to examine clinical effects, we noted that infants in the fish oil group were 3 times less likely to have a positive skin prick test to egg at 1 year of age (odds ratio, 0.34; 95% confidence interval, 0.11 to 1.02; P =.055). Although there was no difference in the frequency of atopic dermatitis at 1 year of age, infants in the fish oil group also had significantly less severe disease (odds ratio, 0.09; 95% confidence interval, 0.01 to 0.94; P =.045). CONCLUSIONS: These data suggest a potential reduction in subsequent infant allergy after maternal PUFA supplementation. More detailed follow-up studies are required in larger cohorts to establish the robustness of these findings and to ascertain their significance in relation to longer-term modification of allergic disease in children.     

A clinical study on plasma biomarkers for deciding the use of adjuvant corticosteroid therapy in bronchopulmonary dysplasia of premature infants

Objective: The study was designed to investigate some plasma markers which help us to decide the use of adjuvant corticosteroid therapy in bronchopulmonary dysplasia (BPD) of premature infants.Methods: Thirty BPD infants were treated by dexamethasone. Among these cases, dexamethasone was significant effective in 10 cases, and no significant effective in 20 cases. These patients were divided into two groups as the significant effect (SE) group (n=10) and the non-significant effect (NE) group (n=20) according to the curative effect of dexamethasone. Fifteen non-BPD infants with gestational age and gender matching were selected as the control group. Plasma samples before and after dexamethasone treatment were collected from three infants chosen randomly from SEG for the data-independent acquisition (DIA) analysis. ELISA was further used to detect the levels of differential proteins LRP1 and S100A8 in all individuals, including SE, NE and control groups.Results: DIA analysis results showed that after dexamethasone treatment, there were a total of 52 plasma proteins that showed significant differences, of which 43 proteins were down-regulated and 9 proteins were up-regulated. LRP1 and S100A8 were two plasma proteins that were significantly changed after dexamethasone treatment. Compared with the control group, plasma LRP1 was significantly increased in BPD. Interestingly, the plasma concentration of LRP1 in the NE group was significantly higher than that in the SE group. S100A8, as an indicator of plasma inflammation, was significantly higher in BPD than the control group. Unlike LRP1, there was no significantly difference between the SE and NE group (P=0.279) before dexamethasone treatment.Conclusion: Elevated plasma LRP1 and S100A8 in BPD infants are two indicators that correlated with the efficacy of dexamethasone, and might be used as biomarkers for deciding the use of adjuvant corticosteroids therapy in the BPD.     

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.     

The contribution of postnatal steroid administration to early brain damage in preterm babies with bronchopulmonary dysplasia

Background/aimPostnatal corticosteroids are commonly used to treat bronchopulmonary dysplasia (BPD). We aimed to show whether S100 calcium-binding B (S100B), neuron-specific enolase (NSE), Tau protein or microtubule-associated protein tau (MAPT), and glial fibrillary acid protein (GFAP) levels would provide any evidence of early neurological damage in premature infants receiving postnatal low dose dexamethasone therapy for BPD treatment.Materials and methods In this cohort study, 136 preterm infants diagnosed with BPD at ≤32 weeks of gestation formed the study group, and 64 preterm infants formed the control group. NSE, S100B, GFAP, and MAPT levels were first measured before the postnatal corticosteroid treatment in both the patient and the control group on the 28th day and, for a second time, after treatment termination in the patient group.Results There were significant differences between the measured GFAP, MAPT, and NSE values of the BPD and control groups on the 28th day, whereas there was no significant difference between the measured S100B values of the two groups. There were a statistically significant difference between the NSE values measured on the 28th day and after the treatment within the BPD group, whereas no significant difference existed between the GFAP, MAPT, and S100B values.Conclusion NSE levels, which indicate brain damage in the early period, increased in preterm babies with BPD who had been administered postnatal dexamethasone.     

Problem-solving education to prevent depression among low-income mothers of preterm infants: a randomized controlled pilot trial

We sought to assess the feasibility and document key study processes of a problem-solving intervention to prevent depression among low-income mothers of preterm infants. A randomized controlled pilot trial (n = 50) of problem-solving education (PSE) was conducted. We assessed intervention provider training and fidelity; recruitment and retention of subjects; intervention acceptability; and investigators' ability to conduct monthly outcome assessments, from which we could obtain empirical estimates of depression symptoms, stress, and functioning over 6 months. Four of four bachelor-level providers were able to deliver PSE appropriately with standardized subjects within 4 weeks of training. Of 12 randomly audited PSE sessions with actual subjects, all met treatment fidelity criteria. Nineteen of 25 PSE subjects (76%) received full four-session courses; no subjects reported negative experiences with PSE. Eighty-eight percent of scheduled follow-up assessments were completed. Forty-four percent of control group mothers experienced an episode of moderately severe depression symptoms over the follow-up period, compared to 24% of PSE mothers. Control mothers experienced an average 1.19 symptomatic episodes over the 6 months of follow-up, compared to 0.52 among PSE mothers. PSE appears feasible and may be a promising strategy to prevent depression among mothers of preterm infants.     

Pulmonary antioxidant defenses in the preterm newborn with respiratory distress and bronchopulmonary dysplasia in evolution: implications for antioxidant therapy

Preterm neonates with respiratory distress are exposed not only to the relative hyperoxia ex utero, but also to life-saving mechanical ventilation with high inspired oxygen (O2) concentrations, which is considered a major risk factor for the development of bronchopulmonary dysplasia, also referred to as chronic lung disease of infancy. O2 toxicity is mediated through reactive oxygen species (ROS). ROS are constantly generated as byproducts of normal cellular metabolism, but their production is increased in various pathological states, and also upon exposure to exogenous oxidants, such as hyperoxia. Antioxidants, either enzymatic or nonenzymatic, protect the lung against the deleterious effects of ROS. Expression of various pulmonary antioxidants is developmentally regulated in many species so that the expression is increased toward term gestation, as if in anticipation of birth into an O2-rich extrauterine environment. Therefore, the lungs of prematurely born infants may be ill-adapted for protection against ROS. While premature birth interrupts normal lung development, the clinical condition necessitating the administration of high inhaled O2 concentrations may lead to permanent impairment of alveolar development. An understanding of the processes involved in lung growth, especially in alveolarization and vascularization, as well as in repair of injured lung tissue, may facilitate development of strategies to enhance these processes.