Risk factors for the development of bronchopulmonary dysplasia: a case-control study

doi:10.1016/j.arcmed.2004.07.001

Archives of Medical Research

Volume 35, Issue 6, November–December 2004, Pages 549-553

https://doi.org/10.1016/j.arcmed.2004.07.001 Get rights and content

Background

Advances in neonatal care over the past decades have meant that an increasing number of very premature infants survive today than in years past. One of the main factors contributing to the survival of these infants is development in ventilatory support. However, this has lead to lung injury and an increase in the incidence of bronchopulmonary dysplasia (BDP).

Methods

A case-control study was conducted at the National Institute of Perinatology Neonatal Intensive Care Unit in Mexico City, Mexico to evaluate the risk factors associated with the development of BPD in premature infants requiring ventilatory support within the first days of life for respiratory failure. Twenty two cases and 22 control premature infants admitted to the Neonatal Unit requiring assisted ventilation and that survived for more than 28 days were included. The neonatal and maternal risk factors that were considered for analysis were the following; mode of delivery, antenatal steroids, gestational age, birth weight, Apgar scores, sepsis, patent ductus arteriosus, and ventilation parameters.

Results

Factors associated with the development of BPD were late sepsis (OR 7.29, 95% CI 1.61–35.8, p = 0.002), and two or more episodes of sepsis (OR 7.60, 95% CI 1.46–44.6, p = 0.004). Other risk factors were low birth weight and younger gestational age at birth.

Conclusions

Similar to what has been reported by other investigators in developed countries, our study showed that neonatal sepsis, low birth weight, and gestational age were associated with BPD in our patients.

Introduction

Bronchopulmonary dysplasia (BPD) was first described by Northway and colleagues in 1967 as a lung injury in preterm infants resulting from oxygen and mechanical ventilation (1). With advances in neonatal care over the past decades, BPD is now frequently seen in infants with very low birth weight who initially had minimal or no lung disease and who develop increasing oxygen and ventilatory requirements over the first several weeks of life. Many of these patients require supplementary oxygen upon discharge 4 home (2).

The overall incidence of BPD in preterm newborns who require mechanical ventilation at birth has been reported to be approximately 20%, and 15–47% in those infants weighting <1,500 g at birth 3, 4, 5. In our institution a 43% incidence of BPD in infants with birth weight <1,500 g has been reported by Cardona et al. (6), with an increase in incidence to 52% in those infants weighing <1,000 g at birth (6).

The mortality of patients with BPD has been reported to be between 30 and 40% (7). The main causes of death in this group of patients are respiratory failure, systemic infections and cor pulmonale (7). Those patients who survive the first month of life have a 30% increased risk of dying in the first year of life (7).

Patients with BPD have more frequent respiratory infections during the first 2 years of life and an increased frequency of bronchial hyperactivity has been found in severe cases of BPD, with reports in patients of remission at approximately 8 years of age (7). Neurological development is affected in approximately 40% of patients with BPD 8, 9, 10. Motor, auditory abnormalities and long term disability have been reported in up to 16% of patients 8, 9, 10.

The exact mechanism responsible for the severe alterations in the pulmonary structure and function of the neonate with BPD is still unknown. There are many factors, alone or in combination, that have been implicated in the pathogenesis of BPD. Some of them are mechanical trauma and oxygen toxicity; these are crucial factors in the pathogenesis of BPD (11). Another factor that appears to play an important role in the pathogenesis of BPD is inflammation (alone or in association with infection, and pulmonary edema resulting from PDA or excess fluid administration). The presence of maternal chorioamnionitis has also been associated with an increased risk of BPD (11).

The epidemiology of BPD has been well studied in industrialized nations; however, studies to identify risk factors associated with BPD in premature neonates in developing countries is lacking. The objective of our study was to identify the main risk factors associated with BPD in a neonatal setting in a tertiary referral center in Mexico City, Mexico.

Section snippets

Subjects and methods

This study was performed at the National Institute of Perinatology, Mexico City, Mexico, from 1996 to 1999. Premature newborns admitted to the neonatal unit and requiring mechanical ventilation for respiratory failure during the study period were included in this case-control study. The cases consisted of infants needing ventilatory assistance during the first days of life who developed BPD defined as oxygen supplementation and an abnormal chest x-ray finding at 28 days of life (12). Control

Results

Between January 1, 1996 and December 31, 1999 44 premature infants with respiratory failure admitted to the neonatal intensive care unit at the National Institute of Perinatology were the subjects of the study. All patients required mechanical ventilation during the first days of life and survived for more than 28 days. Twenty two infants developed BPD and were compared with 22 infants without BPD.

Discussion

Immaturity, barotrauma and oxygen toxicity have been considered the main risk factors for the development of BPD. Nevertheless, these factors do not explain the development of BPD in newborns who only show mild RDS and who do not require mechanical ventilation. As mentioned previously, inflammation, as well as sepsis, pneumonia and PDA, seem to play an important role in the physiopathology of BPD (11).

To our knowledge no previous studies have been published in our patient population to identify

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Phenotypes of Bronchopulmonary Dysplasia in Adults
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Citation Excerpt :
With the introduction of commercially available exogenous surfactant in the 1980s and the resultant increase in the viability of extremely preterm infants, the form of BPD now termed the “old” form began to be supplanted by a “new” form reflecting the results of a variety of insults to the lung at an earlier stage of lung development.9 Injurious factors believed to be associated with the development of BPD include surgical closure of a patent ductus arteriosus, neonatal sepsis, fluid overload resulting in pulmonary congestion, and barotrauma secondary to mechanical ventilation.10,11 Recently, maternal preeclampsia also has been found to be associated with a higher incidence of BPD, defined as oxygen dependency at 36 weeks’ gestation.12
Bronchopulmonary dysplasia (BPD), first described by Northway in 1967, is a process of neonatal lung injury that is most strongly associated with prematurity. The “old” form of the disease associated with the oxidative damage and volutrauma from perinatal mechanical ventilation has been increasingly supplanted by a “new” form resulting from interrupted growth of the lung at earlier stages of fetal development. Given the significant improvement in the survival of children with BPD since the 1980s, many more of these patients are living into adulthood and are being seen in adult pulmonary practices. In this review, we present three brief vignettes of patients from our practice to introduce three of the major patterns of disease seen in adult survivors of BPD, namely, asthma-like disease, obstructive lung disease, and pulmonary hypertension. Additional factors shown to affect the lives of adult BPD survivors are also discussed. Finally, we discuss insights into the process of transitioning these complex patients from pediatric to adult pulmonary practices. As survivors of BPD enter adulthood and continue to require specialty pulmonary care, awareness of the disease’s varied manifestations and responses to treatment will become increasingly important.
Persistent ductus arteriosus and development of bronchopulmonary dysplasia in infants with very low birth weight
2012, Pediatria
La displasia broncopulmonar se ha relacionado con múltiples factores de riesgo: bajo peso al nacer, corta edad de gestación, síndrome de dificultad respiratoria, toxicidad del oxígeno, infección, exceso de líquidos (especialmente, durante la primera semana de vida) y conducto arterial persistente.
Determinar la incidencia de displasia broncopulmonar y evaluar la presencia de conducto arterial persistente como factor de riesgo en un centro de referencia de cuarto nivel en Medellín, Colombia.
Se llevó a cabo un estudio observacional de cohorte en recién nacidos prematuros con peso de 1.500 g o menos al nacer. La exposición fue el diagnóstico de conducto arterial persistente y, el desenlace, la presencia de displasia broncopulmonar moderada o grave. Se compararon las características perinatales del recién nacido y su tratamiento, en los pacientes con y sin displasia broncopulmonar y con conducto arterial persistente y sin él con las pruebas t de Student, U de Mann–Whitney o de χ²-Las variables de confusión se ajustaron empleando regresión logística múltiple.
La incidencia general de displasia broncopulmonar fue de 3 7%, la cual fue mayor en los pacientes con conducto arterial persistente (57,9%) que en los no expuestos (28,2%) (OR = 3,5; IC₉₅% 2,0-6,12; p < 0,001). Esta asociación se mantuvo después del análisis multivariado (OR = 2,57; IC₉₅% 1,36-4,83; p < 0,001). La corioamnionitis, el síndrome de dificultad respiratoria y el peso menor de 1.000 g también se asociaron con un mayor riesgo de displasia broncopulmonar, mientras que el trastorno hipertensivo asociado al embarazo fue un factor protector. Los pacientes con conducto arterial persistente requirieron más asistencia respiratoria mecánica con FIO₂ mayor de 40% (46,5% Vs. 53,5%; p < 0,001), presión inspiratoria pico más elevadas (59,6% Vs. 40,4%; p < 0,001) y una mayor duración de la asistencia respiratoria mecánica (4 Vs. 0 p < 0,001).
La persistencia del conducto arterial persistente en neonatos prematuros menores de 1500 g se asocia con un mayor riesgo de displasia broncopulmonar. Se requieren más estudios para evaluar la asociación entre sepsis, conducto arterial persistente y displasia broncopulmonar.
Bronchopulmonary dysplasia has been associated with multiple risk factors: low birth weight, low gestational age, respiratory distress syndrome, oxygen toxicity, infection, excessive fluids (especially during the first week of life) and persistent ductus arteriosus.
To determine the incidence of bronchopulmonary dysplasia and to assess the role of persistent ductus arteriosus as a risk factor for Bronchopulmonary dysplasia in a fourth-level institution in Medellm, Colombia.
An observational cohort study in preterm infants weighing < 1500 g at birth was conducted. Ductus arteriosus was the exposure; while the presence of moderate or severe bronchopulmonary dysplasia was the outcome. The characteristics (perinatal, neonatal and therapeutic) of patients with and without persistent ductus arteriosus and with and without bronchopulmonary dysplasia were analyzed using the Student t, the Mann Whitney U or chi² tests. Confounding variables were adjusted for using multiple logistic regresion.
The overall incidence of bronchopulmonary dysplasia was 37%, and it was higher in patients with persistent ductus arteriosus (57.9 per cent) than in those without it (28.2%) (OR = 3.5; 95% CI 2.0-6.12; p < 0.001). This association remained after multivariate analysis (OR = 2.57; 95% CI 1.36-4,83; p < 0.001). Chorioamnionitis, RDS and weight < 1000 g were also associated with an increased risk of bronchopulmonary dysplasia, while hypertensive disorders during pregnancy was a protective factor. Persistent ductus arteriosus patients required more mechanical ventilation with FI0₂ > 40% (46.5% vs. 53.5%; p < 0.001), higher PIP (59.6% vs. 40.4%; p < 0.001) and a longer duration of mechanical ventilation (4 vs. 0 days; p < 0.001).
Persistent ductus arteriosus in preterm infants less than 1500 g is associated with an increased risk of bronchopulmonary dysplasia. More studies are required to assess the association between sepsis, persistent ductus arteriosus and bronchopulmonary dysplasia.
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Original articleRisk factors for the development of bronchopulmonary dysplasia: a case-control study

Background

Methods

Results

Conclusions

Introduction

Section snippets

Subjects and methods

Results

Discussion

J Pediatr

Eur J Obstet Gynecol Reprod B

Am J Obstet Gynecol

Am J Obstet Gynecol

J Pediatr

J Pediatr

J Pediatr

Early Human Dev

Semin Neonatol

Pulmonary disease following respiratory therapy or hyaline-membrane disease: bronchopulmonary dysplasia

New Engl J Med

Epidemiology and risk factor for the “new” bronchopulmonary dysplasia

Pediatr Neorev

Is chronic lung disease in low birth weight infants preventable? A survey of eight centers

Pediatrics

Original article
Risk factors for the development of bronchopulmonary dysplasia: a case-control study