2017 - March - BPD Complication of Prematurity.pdf

2017 - March - BPD Complication of Prematurity.pdf - lNl Al...

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Unformatted text preview: lNl Al Bronchopulmonary Dysplasza BPD: Complication of prematurity llr Bass is chief medical information officer and associate professor of medicine and of pediatrics, Louisiana State University Health Sciences Center— Shreveport. The author has nothing to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in any part of this article. Despite advances in perinatal care and a decline in mortality, preventing bronchopulmonary dysplasia is still a challenge to care for children born prematurely. PAT F BASS III, MD, MS, MPH Bronchopulmonary dysplasia (BPD) is a chronic lung disease usually following me- chanical ventilation and oxygen therapy in premature infants requiring treatment for acute respiratory distress. Despite im- provements in obstetric and neonatal care leading to increased survival of premature infants, little progress has been made in the prevention of BPD. Pediatricians need to be aware of changing definitions, risk fac- tors, prevention, and long-term health out— comes of BPD in their premature patients. Definition of BPD The definition of BPD has undergone mul~ tiple changes since N orthway’s1 original description in 1967. A 2001 workshop spon- sored by the National Institute of Child Health and Human Development (NICHD) proposed to define BPD based on severity?5 [See "What is bronchopulmonary dyspla- sia," page 17.) Although not part of the official defini— tion, confirmation of physiologic oxygen 16 CONTEMPORARYPEDiATHrcs.COM | MARCH 2017 requirement with an oxygen reduction tes1 was also recommended. The NICHD definition was shown to better predict pulmonary outcomes (cg, requirement for pulmonary medication, rehospitalization) and neurodevelopment outcomes at age 18 to 22 months (eg, lower development index scores, cerebral palsy hearing loss, blindness) compared with pre- vious definitions.‘s The definition is still un- der significant debate and research. More recent investigations found that significant respiratory morbidity is best predictec' by oxygen use and respiratory support a‘ 40 weeks postmenstrual age (PMA). Also more recent studies find the prediction 0‘ neurosensory impairment to be less strong" In terms of pathology of the lung disease airway injury, inflammation, and fibro- sis were seen prior to development of sur- factant as a treatment in the 19805. In thf “new” postsurfactant BPD, the more prom inent pathology is reduced surface are: availability for gas exchange from alveola: hypoplasia and fewer and larger alveoli Dysregulation of the pulmonary vascula ture also contributes?9 SHUTTEHSTDCK.COM!MINDFULNESS Risk factors Bronchopulmonary dysplasia is a multifactorial disease, including both antenatal and postnatal fac- tors, leading to a disruption in pul- monary development, inflamma- tion, and damage to the lungs.10 [See "Risk factors,” page 18.231949) Higher levels of inflammatory markers are noted in infants that develop BPD. However, whether this inflammation is attributed to anoth- er disease process such as chorioam- nionitis, the exact role of inflamma- tion in the pathogenesis remains a significant area of study. 2" Likewise, whether there is a genetic predispo- sition to BPD remains controversial as recent research has demonstrated mixed results.“"-"’ Prevention Current strategies for prevention of and treatment for BPD include: ANTENATAL STEROIDS Decreasing the number of prema- ture infants by advancing obstetric care will decrease the number of in- fants at risk for BPD. Antenatal ste- roids given to pregnant women from 23 to 34 weeks gestational age (GA) who are at risk for preterm deliv- ery decreases the risk of respiratory distress syndrome, intraventricular hemorrhage, and overall mortality related to preterm delivery.“ How- ever, this has not resulted in a de- creased incidence of BPD. Although multifactorial, the reason is possibly that more infants are surviving and thus are at increased risk for BPD.“-26 POSTNATAL STEROIDS Postnatal steroids for the prevention of BPD is an area of great debate in neonatology. Although there is evi- WHAT IS clinical feature BHUNCHUPULMUNAHY DYSPLASIA? A 2001 workshop sponsored by the National institute of Child Health and Human Development (NICHD) proposed to define bronchopulmonary dysplasia (BPD) in the following manner based on severity: 0 Oxygen use iorzs Ii. 0 Assessment based on gestational age (GA): 0 If <32 wk GA, infants are assessed at 36 wk postmenstrual age iPMA] or at discharge. 05h"- 32 wk GA, assessment occurs at age 29 to 55 d or when discharged home; a and/or respiratory support atthe GA assessment: . 'in‘fants breathing room air at 36 wk. BPD: infants requiring 30% fraction ofinspired oxygen dence that administration of steroids decreases the incidence of BPD, ad- verse effects appear to diminish any benefit. In addition to short-term ad- verse events such as hyperglycemia, hypertension, and increased infec- tion risk, long-term follow-up has demonstrated poor neurodevelop- ment outcomes including cerebral palsy.2 There are some instances in which steroids may be beneficial, but the type of steroid and which patients to consider need to be in- dividualizedfii‘” Similarly, inhaled steroids are not routinely recom- mended and have not been found to prevent BPD, but may be useful in certain limited scenarios.”33 MARCH 2017 I CONTEMPOHARYPEDIATRICS.COM 17 - clinical feature RISK FACTORS Bronchopulmonary dysplasia (BPD) is a multifactorial disease with both antenatal and postnatal factors, leading to a disruption in pulmonary development, inflammation, and damage to the lungs.10 PREMATURI'I’Y The period between 23 wk and 32 wk gestational age (GA) is the highest riskfor lung damage because of decreased levels of surfactant, decreased compliance of lung tissue, poor clearance offluid, and immature antioxidant mechanisms.“"‘-‘2 FETAL GROWTH RESTRICTION lndependentpredictor of BPD.13 SMALL FOR GESTATIONALAGE Independent predictor of BPD.13 EBHANICAL PATENT DUCTUS AHTEBIOSUS IPDAl This risk is primarily seen in ventilated patients. As a result, treatment of BPD increasingly includes noninvasive ventilation modalities and avoids high tidal volumes when mechanical ventilation is needed." DXYG EN TOXICITY Although exact levels are not known, high oxygen concentrations damage the lungs through the development of cytotoxic reactive oxygen metabolitesthat overwhelm the infant's immature antioxidant system.2 18 CONTEMPORARYPEDIATRICS.COM l ANTENATAL AND POSTNATAI. INFECTIONS Chorioamnionitis, particularly with exposure to Ureaplasma urealyticum, seems to increase risk of BPD. One possible mechanism is through an impaired response to surfactantfi‘fi PREECLAMPSIA Mothers with preeclampsia are more likelyto have infants that develop BPD. Impaired angiogenesis that triggers preeclampsia in the mother is thought to be. transfe " MARCH 2017 SURFACTANT Surfactant, as mentioned previous— ly, has changed the pathophysiol- ogy of BPD. However, it has not de- creased the incidence of BPD for reasons similar to those for ante— natal steroids. A strategy called the INSURE [INtubation-SURfactant- Extubation) approach combining brief intubation after birth for ad— ministration of surfactant and fol- lowed by extubation/use of nasal continuous positive airway pres sure (CPAP) has demonstrated a de- creased risk of BPDPI34 MECHANICAL VENTILATION A number of different ventilation strategies haye been employed to attempt to decrease rates of BPD. In addition to the INSURE approach, volume targeted strategies have decreased BPD compared with pressure-limited strategies of ven- tilation.35 Other ventilatory modes that demonstrate possible decreas- es in BPD include nasal intermittent mandatory ventilation, while per- missive hypercapnia and jet venti- lation have not decreased rates oi BPD-3569 VITAMIN A Low vitamin A levels are associatec with development of BPD, and vita min A is part of the internal process- es for lung development and repair Whereas administration of vitamir A decreases risk of BPD, there ha: not been a decrease in neurodevel opment complications associatet with BPD.2 AZITHROMYCIN Although this antibiotic has not de creased BPD rates overall, its admin istration decreases BPD in the previ - clinical feature ously mentioned group at higher risk because of Ureaplasma ureatyticum infection.2 NUTRITION AND FLUID RESTRICTION Preterm infants at risk of BPD are of- ten fluid restricted as volume over- load in the first 10 days of life is hypothesized (and supported by ret- rospective research) as a risk factor 'for the development of BPD.“ How- ever, trials of fluid restriction have been small and produced mixed re— sults.‘“"2 Given the outcomes associ— ated with BPD, modest fluid restric- tion may be warranted, especially in the setting of patients with patent ductus arteriosus (PDA). CAFFEINE Administration of caffeine for the treatment of apnea of prematurity demonstrated a decrease in BPD?"44 NITRIC OXIDE Nitric oxide has not demonstrated a benefit in the prevention of BPD, unlike its use for treating persistent pulmonary hypertension. Although some studies have demonstrated a benefit, no systematic review shows advantages related to pulmonary outcomes, survival, or neurodevel- opment outcomes. Neither the Na- tional Institute of Health consen- sus conference“ or a 2014 American Academy of Pediatrics clinical re— port“; recommend routine adminis- tration of nitric oxide for the preven- tion of BPD. Long-term health consequences Bronchopulmonary dysplasia also can lead to health problems for these infants later in life, such as: 2|]. CONTEMPORARYPEDIATRICS.COM i MORE READING ON BPD infants with bronchopulmonary dyspiasia (BPD) are at high risk for rehospitalization. In this article, Boston Children’s Hospitai's Center for Healthy Infant Lung Development shares best practices for keeping these kids out of acute care and safe at home. Go to BontemporaryPediatries.comlhuspital-zone-0115 A One of Boston Children's BPD patients. Top left/right: Brady is born on July 8, 2001. In the NICU with BPD, October 19. 2007. Bottom left] right: Brady at home with his tracheotomy, December 23, 2007. Brady as a big boy. May 28, 2009. ASTHMA-LIKE SYMPTOMS Asthma-like symptoms and recur- rent wheezing are extremely com- mon in children with BPD. However, the pathophysiology is different in that airway hyperresponsiveness is less common and symptoms are less responsive to bronchodilators and inhaled corticosteroids.‘7'“ PULMONARY ARTERIAL HYPERTENSION {PAH} Whereas PAH generally resolves as the infant gets older, it is a signifi- cant cause of mortality in patients MARCH 2017 with BPD.“‘*“’ Optimal timing for screening has not yet been estab- lished, however, guidelines from the American Heart Association and the American Thoracic Society recom- mend screening all infants with BPD for PAH and continue serial echocar— diograms until the clinical picture is stabilized if PAH is present.51 CENTRAL AIR WAY DISEASE A number of problems with the cen- tral airways can complicate BPD and can persist as an infant ages. Acquired tracheobronchomalacie is more common in the presurfac— tant treatment period of BPD and is associated with both barotrauma and infection. Because the airway is more compliant and collaps- ible, the infant is at risk for "BPD spells" or abrupt sleep apnea is associated with de- creased intelligence quotient (IQ) and executive function, as well as possible neuronal injury.56 Hypoventilation and hypox- emic episodes during sleep are more likely to occur episodes of apnea that The American in infants with a his- may lead to a cyanot- Heart ASSUCIEUO“ tory of BPD and may ic episode that can recomnrpends" persist as children get , _ scree mg a 57:53 , _ be life threatening infants with BPD older. Thls can re or chronic wheezing for PAH. suit in further narrow- that does not respond to treatment.52 Subglottic stenosis and laryngeal injury manifested as postextubation stridor may be seen in infants requiring prolonged or fre- quent intubations. Infants may ex- perience chronic symptoms or only experience symptoms with upper respiratory tract infections.53 Tra- cheal and bronchial stenosis also are reported but are more likely a result of intubation and sectioning rather than from lung disease. Neverthe- less, lobar emphysema, atelectasis, and overdistension can result. UPPER AIRWA Y PROBLEMS Chronic snoring and sleep apnea are more common among premature in- fants as they get older.“55 Untreated ing of airways as well as problems with pacemaker activities ofthe heart,55 growth (:ielay,60 and cognitive development?3 RESPIRATORY INFECTIONS Hospitalization during the first 2 years of life is common among pa- tients with BPD.51 Mostly attributed to viral infections that can further impair respiratory function, respira- tory syncytial virus (RSV) infections can be particularly severe, especial- ly for infants still with an oxygen re- quirements“? An RSV infection in a BPD patient during the first 2 years of life is associated with worse long- term health outcomes (cg, increased costs and decreased lung function) compared with a BPD patient not having an RSV infection.62 clinical feature NEURODEVELOPMENT OUTCOMES Infants with BPD are at risk for long term neurodevelopment impair ment as evidenced by decreaset scores on the mental and meta scales of the Bayley Scales of Infan Development.” These low scores have been fount to persist at 3 years of age in additior to lower expressive and receptive language sltills.‘54"55 Other report: have demonstrated that these 1300] neurodevelopment outcomes persisr through age 10 years.‘*"-"7 In general, the severity of the BPD is associated with the severity of the neurodevel- opment disability. Summary Bronchopulmonary dysplasia is a chronic disease that can impact the pediatric patient well beyond ear- ly life. The pediatrician needs to be aware of both strategies for preven- tion as well as the long-term conse- quences that need to be managed to improve the health and outcomes of these patients. I 0 For references. go to J ContemporaryPediatricsmmi BPD-and—prematurity CONTEMPORARY PEDIATRICS CLINICAL VIDEO EXCLUSIVE Dr. Bobby Lazza ra discusses a recent study 9 ATSJmmII: _w 1- hm...) _ a...’ :4 mimmmnwtwm m ' - pubiished in the Journal of Respiratory and Critical Care Medicine that iooked at whether asthma in childhod contributes to the development of childhood obesity. BontemporaryPediatrics.comlasthma-ohesity MARCH 2017 | CONTEMPORARYPEDJATRICS.COM 21 ...
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