Physiology and Predictors of Impaired Gas Exchange in Infants with Bronchopulmonary Dysplasia

Svedenkrans, Jenny; Stoecklin, Benjamin; Jones, J.G.; Doherty, Dorota A.; Pillow, J. Jane

doi:10.1164/rccm.201810-2037oc

Cited by 46 publications

(43 citation statements)

References 19 publications

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“…Accordingly, we believe this important clinical variable must be defined and quantified objectively in each premature infant through a physiological challenge. More sophisticated algorithms for SpO2 analysis 33 , and the addition of other physiological parameters to understand ventilatory instability and cardio-respiratory coupling 30,31 , may further refine BPD severity assessment. Our studies provide compelling new evidence that these physiological tests to determine O2 requirements should be conducted at 36 weeks PMA and at later points (e.g.…”

Section: Discussionmentioning

confidence: 99%

Validation of a new predictive model to improve risk stratification in bronchopulmonary dysplasia

Niño

Mansoor

Pérez

et al. 2020

Sci Rep

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We need a better risk stratification system for the increasing number of survivors of extreme prematurity suffering the most severe forms of bronchopulmonary dysplasia (BPD). However, there is still a paucity of studies providing scientific evidence to guide future updates of BPD severity definitions. Our goal was to validate a new predictive model for BPD severity that incorporates respiratory assessments beyond 36 weeks postmenstrual age (PMA). We hypothesized that this approach improves BPD risk assessment, particularly in extremely premature infants. This is a longitudinal cohort of premature infants (≤32 weeks PMA, n = 188; Washington D.C). We performed receiver operating characteristic analysis to define optimal BPD severity levels using the duration of supplementary O2 as predictor and respiratory hospitalization after discharge as outcome. Internal validation included lung X-ray imaging and phenotypical characterization of BPD severity levels. External validation was conducted in an independent longitudinal cohort of premature infants (≤36 weeks PMA, n = 130; Bogota). We found that incorporating the total number of days requiring O2 (without restricting at 36 weeks PMA) improved the prediction of respiratory outcomes according to BPD severity. In addition, we defined a new severity category (level IV) with prolonged exposure to supplemental O2 (≥120 days) that has the highest risk of respiratory hospitalizations after discharge. We confirmed these findings in our validation cohort using ambulatory determination of O2 requirements. In conclusion, a new predictive model for BPD severity that incorporates respiratory assessments beyond 36 weeks improves risk stratification and should be considered when updating current BPD severity definitions.

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Section: Discussionmentioning

confidence: 99%

Validation of a new predictive model to improve risk stratification in bronchopulmonary dysplasia

Niño

Mansoor

Pérez

et al. 2020

Sci Rep

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“…In the database maintained by the National Perinatal Registry of the Netherlands, only 67% of preterm infants were correctly categorized according to the NHLBI workshop definition 110 , owing predominantly to a false-negative diagnosis rate of 31%, including 9% with severe BPD. A bedside analysis of the 'shift' of the oxyhaemoglobin dissociation curve (accomplished through simultaneous measurement of FiO 2 and peripheral saturation at a single time point) was proposed as an objective test for the presence and severity of BPD 111,112 . This measurement would provide more accurate assessment of oxygen need than the Walsh 'physiological test', but would be difficult to accomplish in most infants outside a research protocol.…”

Section: Current Challenges In Defining Bpd-for Most Diseases Diagnmentioning

confidence: 99%

Bronchopulmonary dysplasia

Thébaud

Goss

Laughon

et al. 2019

Nat Rev Dis Primers

588

545

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The strongest risk factors for BPD are prematurity and low birth weight 19-25. Almost 80% of infants who are born at 22-24 weeks of gestation are diagnosed with BPD 26 , whereas only 20% of infants born at 28 weeks of gestation develop BPD. Among infants with BPD, 95% are VLBW 27. Other perinatal risk factors include intrauterine growth restriction (IUGR) 13 , male sex 13,20,23 and, inconsistently, chorioamnionitis 28 , race or ethnicity 13,20,23 , and smoking 29,30. Genetic risk factors may also contribute to the development of BPD, as indicated by twin studies 31,32 , and there is an ongoing search for genetic markers for BPD 33-37. Early respiratory patterns of premature infants provide insight into risk factors for BPD. An early study suggested that peak inspiratory ventilator pressure and requirement for assisted ventilation on day 4 of life are early predictors of BPD 38. Subsequent studies found that three patterns of lung disease generally emerge in the first 2 weeks of life 39-45 (FIG. 2). In the first pattern, infants have fairly minimal lung disease and progressively recover. In the second pattern, early persistent pulmonary deterioration (EPPD), substantial and prolonged respiratory support is required from birth. In the third pattern, an initial improvement in lung disease in the first week of life is followed by a respiratory decompensation termed pulmonary deterioration, which often requires mechanical ventilation and an increase in supplemental oxygen. Risk factors that may be associated with pulmonary deterioration include late surfactant deficiency 46 , sepsis, increased levels of inflammatory proteins (such as RANTES) 47 and patent ductus arteriosus 40,43. Almost 50% of infants with pulmonary deterioration and almost 70% of infants with EPPD develop BPD 48. The National Institute of Child Health and Human Development (NICHD) Neonatal Research Network developed an online, publicly available risk estimator (https:// neonatal.rti.org/index.cfm) that accurately estimates the risk of developing BPD by postnatal day 49. Investigators identified risk factors for BPD, and the competing outcome of death, among gestational age, birth weight, ethnicity and sex, ventilatory support (ranging from no support (breathing room air without positive airway pressure) to high frequency ventilation) and fraction of inspired oxygen (FiO 2), on postnatal days 1, 3, 7, 14, 21 and 28 in 3,636 infants born at 23-30 weeks of gestation. The BPD prediction tool is internally and externally validated. The models predict the correct level of BPD or the occurrence of death in >80% of cases and have the highest area under the curve (AUC) among current BPD risk predictors 50. This tool is used to provide counselling to families and to quantify risk for determining patient inclusion in early phase therapeutic trials. Interestingly, systemic inflammation occurs early in the neonatal period and precedes clinical symptoms in infants with BPD 51. This finding suggests that a therapeutic window of opportunity exists during the early p...

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“…Although eight of the studied index children lacked information about oxygen supplementation at 36 weeks, a power calculation shows that the sample size should have been enough to show a difference of 15 min in MVPA. However, BPD diagnosis does not always predict pulmonary outcome, which decreases the likelihood to show a correlation to PA [ 32 , 48 , 49 ]. Consequently, a correlation between lung function and PA cannot be excluded and would require measures of lung function at the time of accelerometry, which is not included in our present data.…”

Section: Discussionmentioning

confidence: 99%

Physical Activity in 6.5-Year-Old Children Born Extremely Preterm

Svedenkrans

Ekblom

Domellöf

et al. 2020

JCM

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Physical activity (PA) can prevent cardiovascular diseases. Because of increased risks of impairments affecting motor activity, PA in children born preterm may differ from that in children born at term. In this prospective cohort study, we compared objectively measured PA in 71 children born extremely preterm (<27 weeks gestational age), to their 87 peers born at term, at 6.5 years of age. PA measured with accelerometer on the non-dominant wrist for 7 consecutive days was compared between index and control children and analyzed for associations to prenatal growth, major neonatal brain injury, bronchopulmonary dysplasia and neonatal septicemia, using ANOVA. Boys born extremely preterm spent on average 22 min less time per day in moderate to vigorous physical activity (MVPA) than control boys (95% CI: −8, −37). There was no difference in girls. Amongst children born extremely preterm, major neonatal brain injury was associated with 56 min less time in MVPA per day (95%CI: −88, −26). Subgroups of children born extremely preterm exhibit lower levels of physical activity which may be a contributory factor in the development of cardiovascular diseases as adults.

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Physiology and Predictors of Impaired Gas Exchange in Infants with Bronchopulmonary Dysplasia

Cited by 46 publications

References 19 publications

Validation of a new predictive model to improve risk stratification in bronchopulmonary dysplasia

Validation of a new predictive model to improve risk stratification in bronchopulmonary dysplasia

Bronchopulmonary dysplasia

Physical Activity in 6.5-Year-Old Children Born Extremely Preterm

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