Bronchopulmonary dysplasia: an enduring challenge.

Abstract

After completing this article, readers should be able to: Despite clinical advances in antepartum, intrapartum, and neonatal care, bronchopulmonary dysplasia (BPD) continues to challenge infants who have been in neonatal intensive care units and their caretakers. BPD is the most common cause of chronic respiratory disease during infancy and remains a major cause of long-term medical, pulmonary, and neurodevelopmental morbidity, increasing the cost of health care and the utilization of medical and educational resources throughout childhood.BPD is a clinical diagnosis, defined by oxygen dependence for a specific period of time after birth and accompanied by characteristic radiographic findings that correspond to anatomic abnormalities. Thus far, a precise physiologic definition of BPD is lacking. As the clinical presentation has evolved over the past 30 years, so has the definition. As originally described by Northway in the 1960s, the diagnosis of classic BPD was based on progressive radiographic changes in preterm infants who were treated for severe respiratory distress syndrome (RDS) immediately after birth and had prolonged ventilator and oxygen dependence. This form of BPD occurred in larger, relatively mature preterm infants, who required treatment with high-pressure mechanical ventilation and high concentrations of oxygen. Although the acute respiratory disease initially improved in these infants, oxygen requirements increased 7 to 10 days after birth and persisted for at least 28 days. The definition of BPD subsequently was modified by Bancalari to include preterm infants who had less severe RDS that initially required short-term mechanical ventilation, but who also developed persistent respiratory symptoms and an oxygen requirement for at least 28 days after birth accompanied by radiographic abnormalities. The presentation of BPD continued to evolve with the advent of antenatal steroids and postnatal surfactant administration, which reduced the incidence and severity of RDS and increased the survival of extremely small, very immature infants (<30 weeks’ gestation or <1,250 g birthweight). These infants had milder chronic pulmonary problems that often resolved by discharge. Shennan noted that the need for supplemental oxygen until at least 36 weeks postconceptual age (PCA) in these infants was much more predictive of later pulmonary morbidity. He, therefore, recommended that oxygen dependence at 36 weeks PCA, instead of 28 days after birth, be used as a more clinically relevant definition of BPD.Some very low-birthweight (VLBW), extremely preterm infants born between 23 and 28 weeks’ gestation and weighing less than 1,250 g develop increasing oxygen requirements 1 to 2 weeks after birth, even without preceding lung disease, mechanical ventilation, or oxygen therapy. This form of atypical BPD is reminiscent of Wilson-Mikity disease that was described contemporaneously with classic BPD. The clinical onset of atypical BPD is characterized by a delayed, gradual increase in oxygen dependence, milder symptoms overall, and more rapid resolution of symptoms and weaning to room air. The term chronic lung disease (CLD) often is used instead of BPD to denote persistent pulmonary insufficiency and oxygen requirement beyond 36 weeks PCA regardless of the cause or need for mechanical ventilation. Defining BPD by the need for supplemental oxygen alone at a specific point in time does not take into account different parameters for oxygen use or adjunctive therapies, such as diuretics, fluid restriction, bronchodilators, or steroids, that affect the need for supplemental oxygen. Consequently, it is difficult to determine accurately the incidence and prevalence of BPD or to compare treatments or outcomes among different neonatal centers.The risk of BPD is multifactorial. It is related directly to the severity of the initial lung disease (most often RDS) and the duration of mechanical ventilation and oxygen administration. BPD is related inversely to birthweight and gestational age, with the smallest, sickest, most immature infants being at highest risk. The increased susceptibility of the very preterm infant may reflect the anatomic, developmental, and reparative immaturity of the neonatal lung at the time of lung injury. The risk of BPD is also increased by a hemodynamically significant patent ductus arteriosus, postnatal sepsis, antenatal maternal infection (eg, chorioamnionitis), and maternal or neonatal colonization with Ureaplasma histolyticum. In the case of maternal infection, it is postulated that circulating maternal cytokines gain access to the fetal circulation and injure fetal tissues, including lung and brain, thereby increasing the risk of BPD as well as brain injury. Although some studies report an association between a family history of atopy or asthma and BPD, others have failed to confirm this relationship.Term and near-term infants also are at risk for BPD following severe respiratory failure treated with very high oxygen concentrations, mechanical ventilation, and extracorporeal membrane oxygenation (ECMO). BPD occurs in up to 27% of term or near-term infants who have very severe primary respiratory disease (ie, RDS, meconium aspiration, pneumonia, sepsis) and in up to 50% of those who have underlying pulmonary hypoplasia (eg, congenital diaphragmatic hernia) and are treated with or are eligible for ECMO.Advances in neonatal care have decreased the incidence of BPD only in larger, more mature preterm infants. The risk of BPD in VLBW infants is not reduced by antenatal steroids, surfactant administration, or any specific type of respiratory support (eg, conventional ventilation or high-frequency ventilation), although the disease is less severe than in the past. However, there are substantial differences in the incidence of BPD between individual neonatal units, suggesting that the overall approach to respiratory support is important. Centers that emphasize “gentle” ventilation that minimizes lung injury (eg, permissive hypercapnea, lower airway pressures, avoidance of intubation or early extubation) have substantially lower rates of BPD. Vitamin A, known to protect epithelial integrity and promote normal cell differentiation and growth, is associated with a small, but significant decrease in the risk of BPD when administered parenterally immediately after birth. Postnatal dexamethasone has been reported by some to decrease oxygen dependence at 36 weeks after birth, but serious short- and long-term complications preclude routine use. Prevention of BPD remains elusive, ultimately depending on avoiding or delaying premature delivery whenever possible, reducing antenatal and postnatal infections, and minimizing postnatal exposure to noxious agents, such as intubation, oxygen, and ventilation. It is possible that for the most immature infants, even exposure to room air is injurious.As noted previously, the incidence of BPD depends on the definition used. Fewer than 50% of extremely preterm infants who require supplemental oxygen at 28 days after birth remain oxygen-dependent at 36 weeks PCA, and fewer still remain oxygen-dependent at 42 weeks PCA. For all VLBW neonates (<1,500 g at birth), the incidence of oxygen dependence at 28 days is about 30% to 50%; at 36 weeks PCA, the incidence of oxygen dependence in these same infants falls to 4% to 30%. For VLBW infants who require mechanical ventilation and surfactant, approximately 60% are oxygen-dependent at 28 days, and 30% remain oxygen-dependent at 36 weeks PCA. In some series, up to one third of VLBW infants have the milder form of atypical BPD. Because the incidence of BPD is highest in the most premature and lowest birthweight infants and because more of these very immature neonates now survive, the total number of children living with BPD is increasing, albeit in a clinically less severe form than seen previously.BPD appears to be the final common path of lung injury. Initially it was believed to be the consequence of direct trauma from mechanical ventilation and oxygen toxicity. As the clinical presentation of BPD has changed and oxygen dependence has developed in the absence of RDS or initial oxygen exposure, inflammation has emerged as the central disease process. Anatomic and developmental immaturity modify the lung’s response to trauma and inflammation. Evidence of an inflammatory response that accompanies RDS, including activated inflammatory cells, inflammatory mediators, and cytokines, persists in infants who develop BPD.Barotrauma and volutrauma from mechanical ventilation may injury airways and lung parenchyma directly and indirectly. Intubation traumatizes local tissue surfaces, destroys normal ciliary action, and introduces pathogens and exogenous gases directly into the airway. Air leaks (eg, pulmonary interstitial emphysema) further disrupt lung tissue. Oxygen exposure generates toxic free radicals that cause acute tissue injury, incite inflammation, and inhibit normal repair and development.Developmentally immature lung tissue may be both more susceptible to injury and less effective at tissue repair. At autopsy, infants dying of BPD have evidence of abnormal lung morphology and development, with decreased alveolarization and septation. Ultimately, BPD must be “outgrown.” As airways become larger, alveolarization proceeds, and the previously injured lung represents a smaller proportion of total lung volume. Fortunately, alveolar growth continues up to 5 years of age, allowing most infants who have BPD to recover clinically even though pathologic and radiologic abnormalities often persist into adulthood.BPD results in chronic respiratory insufficiency and prolonged oxygen dependence for many weeks or months. Clinical manifestations include tachypnea, retractions, wheezing, and rales. Ventilation/perfusion mismatch and increased physiologic dead space result in hypercapnia and hypoxemia. The risk of superimposed infection is increased. For all forms of BPD and CLD, oxygen requirements begin to increase at the end of the first week after birth, reaching a stable plateau by the beginning of the third week. Clinical exacerbations occur in association with pulmonary edema, superimposed infection, or right heart failure.Northway described four distinct radiographic stages of BPD: I-RDS, II-diffusely hazy, III-diffusely bubbly, interstitial pattern, and IV-hyperaeration, focal hyperlucency, alternating strands of opacification. These stages correspond to a pathologic progression from acute RDS to interstitial and airway edema, inflammation, and squamous metaplasia and finally to areas of emphysema, fibrosis, and atelectasis and increased peribronchiolar and perivascular smooth muscle. Milder or atypical BPD is radiographically less severe, with diffuse haziness or interstitial prominence, often with normal inflation, and less severe anatomic abnormalities.Bronchospasm, episodes of cyanosis, and chronic hypoxemia often accompany BPD. Early pulmonary function abnormalities in infants who have BPD include decreased lung compliance, ventilation perfusion mismatch, and increased lung volume, airway resistance, and air trapping.Clinical improvement in BPD usually is heralded by improvement in somatic growth. Infants who develop BPD are at increased risk of patent ductus arteriosus, sepsis, intraventricular hemorrhage (IVH), retinopathy of prematurity, and death.The treatment goals of BPD focus on relieving respiratory symptoms, improving lung function, minimizing ongoing lung injury, reducing inflammation, maintaining adequate oxygenation, and facilitating lung growth. BPD itself, as well as the treatment regimens used to improve respiratory function, results in an assortment of associated problems (Table 1). Although diuretics can reduce pulmonary edema and oxygen requirements, they also cause electrolyte depletion, bone loss, and nephrocalcinosis. High-dose systemic corticosteroids facilitate extubation and decrease neonatal respiratory support and oxygen exposure. However, these short-term benefits are achieved at the expense of serious neonatal complications (eg, hyperglycemia, hypertension, intestinal perforation, infection), poor brain and somatic growth, and substantially worse neuromotor and developmental outcomes, including cerebral palsy (CP), in early childhood. Postnatal corticosteroids have not been shown to convey any long-term respiratory benefit. It is not known whether the deleterious effects of systemic steroids are related to the specific type of steroid administered, the pharmacologic doses used, or the duration of treatment. Although aerosolized steroids are associated with fewer complications, they are also less effective therapeutically. Randomized, controlled trials are needed to define the role, if any, of postnatal steroids or other anti-inflammatory agents. Because of concerns about short- and long-term adverse effects, it is recommended that postnatal steroids be used only in exceptional clinical circumstances (eg, severe respiratory failure with maximal ventilatory and oxygen support). It is possible that the treatments used to reduce oxygen dependence may be more detrimental to the infant than oxygen itself and that the efforts to reduce oxygen dependence are misguided.A nurturing home environment improves physical growth and psychosocial development. Infants who have BPD should be discharged from the hospital to consistent caretakers as soon as feasible. This often necessitates continuing complex treatments at home, including oxygen, hypercaloric feedings, fluid restriction, diuretics, bronchodilators, and cardiorespiratory monitors. Medical treatment and home oxygen therapy may be needed for many months or even years. The abrupt transition from intensive care to the home is difficult for families and requires comprehensive parent education before discharge and ongoing psychosocial and medical support. A specific plan must be in place at discharge, including how the parent will monitor the infant’s respiratory status, when to provide extra oxygen, which physician to call when respiratory problems arise, and when to call for emergency transport. Acute respiratory exacerbations are likely and can be life-threatening. Valuable time will be lost unless the parent knows when and who to call for help.Parents need to be aware of the high risk of superimposed respiratory infection and rehospitalization despite optimal care and appropriate precautions. Understanding the rationale for their infant’s treatment regimen (eg, hypercaloric feedings, fluid restriction, medications, oxygen, monitors, immunization, respiratory syncytial virus [RSV] prophylaxis), the anticipated time course of treatment, and the need for close medical follow-up encourages compliance and helps the parents cope with the inevitable ups and downs that accompany slowly improving BPD.Home cardiorespiratory monitors are recommended for children receiving oxygen at home. Oxygen saturation should be monitored intermittently to detect unsuspected periods of hypoxemia, especially during both activity and sleep, until supplemental oxygen, fluid restriction, or medications no longer are needed to maintain adequate oxygenation. Continuous oximetry rarely is needed, except for children who have severe disease and require frequent changes in oxygen delivery throughout the day to maintain adequate oxygen saturation. Oxygen, medications, and fluid restriction each should be weaned slowly, one at time, to be sure that changes in treatment are well tolerated. Children who have BPD and are discharged from the hospital on oxygen or medications should be followed closely by pediatric pulmonary specialists in addition to their primary pediatrician until the disease has resolved clinically.Optimal nutrition, including sufficient energy, substrate, and vitamins, is essential for lung growth and repair. Malnutrition has deleterious effects on both lung function and size. Children who have BPD often grow poorly due to increased rates of energy expenditure, increased nutrient and caloric requirements, and suboptimal nutrition. Feeding intolerance, gastroesophageal reflux (GER), oral aversion, fluid and caloric restriction, hypoxemia, recurrent infection, and rehospitalization all make feeding difficult and contribute to growth failure. Poor weight gain may be a sign of unsuspected hypoxemia, especially at night when oxygen saturation falls during sleep. Therapeutic strategies must focus on limiting catabolism, promoting an anabolic state, and providing extra calories and nutrients necessary for tissue repair and growth. After discharge, children who have BPD continue to need extra calories and nutrients to “catch up” and to sustain normal growth. Extra nutrition support may be required for at least 1 year PCA.Individual nutrients hypothesized to be important in the prevention or treatment of BPD include inositol; fatty acids; carnitine; cysteine; and vitamins A, C, and E. Thus far, only parenteral vitamin A, administered shortly after birth, has been shown to have a small, specific benefit in reducing the risk of BPD. Providing sufficient energy and nutrients as soon as possible is essential. Beginning parenteral nutrition with protein, fat, carbohydrate, vitamins, and minerals within 24 to 48 hours after birth limits protein loss, minimizes catabolism, prevents essential fatty acid deficiency, and provides vitamins and trace elements. Early initiation and establishment of enteric feeding allows higher caloric intake with less fluid intake.Use of human milk improves utilization of nutrients and confers specific immunologic advantages to the infant who has BPD. However, fortification of human milk is required to provide adequate protein, calories, and minerals to all infants whose birthweights are less than 1,500 g. Preterm adapted formula is an alternative if human milk is unavailable for VLBW infants. Both fortified human milk and preterm adapted formula provide nutritionally balanced, calorically dense feedings that can be increased up to 30 kcal/oz when fluids are restricted to reduce lung water and pulmonary edema. Enriched feedings may be needed for many months. Even in healthy VLBW infants who do not have chronic disease, the use of preterm adapted formulas until 9 to 12 months PCA appears to improve long-term growth. Frequent assessment of growth parameters, including length and head circumference, as well as weight is necessary to assure that nutrition requirements for growth are being met adequately.Postdischarge complications related to BPD are shown in Table 2. When pulmonary outcome initially was described for infants who had classic BPD, 24% continued to have respiratory symptoms as adolescents and young adults. Although less severe BPD is associated with a better long-term outcome, children who have BPD still have twice the risk of developing wheezing or asthma or lower respiratory tract infections, and of being rehospitalized due to respiratory illness during infancy and early childhood compared with gestational age-matched preterm infants who do not have BPD. In several reports, 50% of all VLBW children who had a history of BPD had been rehospitalized in the first 12 to 24 months after birth, and 50% had a history of wheezing or asthma at mid-childhood. RSV prophylaxis during infancy has been shown to halve the risk of hospitalization for RSV and to reduce both the length of stay and the duration of oxygen therapy if the infant is hospitalized. GER, which is common in preterm infants, contributes to acute and chronic airway inflammation, edema, aspiration pneumonia, and feeding difficulties.Approximately 25% of infants who have BPD have a transient recurrence or worsening of apnea following initial immunization. This risk appears to decrease with subsequent immunizations. The risk of an acute life-threatening event (20%) or of sudden infant death (3%) is higher in VLBW infants who have BPD. Fortunately, the small number of affected children who require tracheostomy due to airway obstruction or the need for prolonged ventilation is decreasing steadily. However, moderate-to-severe airway compromise by tracheomalacia and subglottic stenosis has been found by bronchoscopy in 27% of infants who have BPD and is associated with a longer duration of intubation, larger endotracheal tubes, increased numbers of intubations, higher initial mean airway pressure, clinically severe BPD, and lower gestational age. Two thirds of these infants had respiratory symptoms during infancy, abnormal vocalization (eg, stridor, aphonia, or hoarseness), and apnea. Death after discharge home is less common than previously, but it occurs in up to 6% of infants who have BPD, usually due to cardiopulmonary complications.Pulmonary function test (PFT) abnormalities are found consistently in school-age children who have a history of BPD. These abnormalities include decreased forced vital capacity, forced expiratory volume, and forced expiratory flow and increased residual volume. Laboratory evidence of expiratory airflow obstruction and gas trapping persist throughout childhood, even among clinically asymptomatic children. The severity and persistence of the PFT abnormalities and exercise intolerance correlate with the duration of mechanical ventilation, oxygen therapy, and treatment. Except for increased airway resistance, PFT abnormalities usually improve by 7 to 11 years of age and resolve by early adulthood. At least 50% of children who have a history of BPD have laboratory evidence of bronchial hyperreactivity, even without a clinical history of wheezing or reactive airway disease. Radiographic abnormalities (eg, hyperlucency, bullae, multiple fibrotic strands, and atelectasis) also persist throughout childhood. Despite the abnormal results of PFTs and chest radiographs, most children have normal exercise tolerance by late childhood. The long-term effect of BPD on pulmonary response to respiratory irritants, pulmonary function, and respiratory disease in later life is unknown, especially with respect to the risk of chronic obstructive pulmonary disease. Families and children should be counseled to avoid tobacco use, second-hand smoke, and other respiratory irritants.Catch-up growth is delayed in infants who have BPD. Poor somatic growth may reflect insufficient food intake to meet metabolic or energy needs or chronic oxygen desaturation, especially during sleep. Although adolescents and young adults who have a history of classic BPD were smaller than controls in one study, their growth still was within the normal range. More recent studies of children who have milder BPD do not demonstrate significant differences in height and weight at school age compared with preterm controls who did not have BPD, although children who had BPD do tend to have lower lean body mass and lower bone mineral content.Recurrent episodes of hypoxemia and cyanosis may lead to pulmonary hypertension, cor pulmonale, and heart failure. Systemic hypertension occurs in 6% to 11% of infants, often is not evident until after discharge, and may progress to left heart failure if unrecognized and untreated. Although nephrocalcinosis usually disappears after diuretics are discontinued, it may persist and can be associated with abnormalities of renal function. Renal calcifications should be followed by renal ultrasonography until resolution. Children who have BPD also are at increased risk for otitis media, bronchitis, hearing loss, and visual impairment. Inguinal hernias are twice as common among VLBW preterm infants who have BPD (23% versus 12%), and the hernias often enlarge progressively, sometimes to dramatic proportions. Inguinal hernias may be associated with discomfort and irritability and should be repaired as soon as feasible before discharge to home.<!- -->Neurodevelopmental outcome is multifactorial, being most strongly influenced by neonatal brain injury (eg, IVH, periventricular leukomalacia [PVL]), gestational age or birthweight, race, socioeconomic status, and parental education. In general, neonatal issues (eg, severity of neonatal disease, birthweight, or gestational age) are better predictors of short-term outcome at fewer than 24 months PCA, and long-term outcome is determined by external influences, such as socioeconomic status and parental education. The ability to assess neurodevelopmental outcome accurately changes over time as diagnostic capabilities improve and the child’s own developmental repertoire expands. The evaluation of outcome in children who have BPD is confounded by the varying definitions of BPD, the changing clinical presentation of BPD and neonatal care over time, small sample size, and selection bias. Many studies, especially at school age, exclude children who have severe disabilities.At any postnatal age examined thus far, neurodevelopmental outcome is affected adversely by BPD. When outcome is controlled for other important predictors, such as gestational age, birthweight, brain injury (IVH and PVL), race, gender, socioeconomic status, and parental education, BPD independently accounts for adverse outcome, primarily in areas of motor function. Neurodevelopmental outcome, as with medical and pulmonary outcome, is predicted better by the need for supplemental oxygen at 36 weeks PCA rather than at 28 days after birth. Long-term outcome studies of more immature, less severely ill preterm infants born in the 1990s, after the routine use of antenatal steroids and surfactant, are just beginning to appear. Although antenatal steroids have been associated with a decreased risk of severe IVH and CP during this decade, postnatal steroids, widely used simultaneously, have been associated with an increased risk of neuromotor problems, including CP. It is, therefore, possible that neurodevelopmental outcome for these children actually may be worse than previously described.BPD is specifically associated with an increased risk of neuromotor abnormalities. Studies of children born in the 1980s reported that those who had BPD had a similar incidence of CP (6% to 13%) and a higher risk of overall disability (40% versus 23%) compared with preterm controls. Progressive brainstem deterioration and cerebral encephalopathy as well as an extrapyramidal movement disorder associated with restless, chorealike limb movements and oral-buccal-lingual dyskinesia have been described during infancy in children who had very severe BPD. These infants had prolonged hospitalization, frequent and persistent episodes of hypoxemia, recurrent respiratory decompensation, or heart failure. In infants who have less severe BPD, gross motor delay frequently is observed during infancy. The motor delay resolves concomitantly with improvement in respiratory symptoms, exercise tolerance, and somatic growth. In these children, developmental progress usually is preserved better in those areas of development less dependent on large muscle strength, such as adaptive, language, fine motor, and personal/social domains.Follow-up studies of school and academic performance in middle childhood have compared children who have a history of milder BPD born in the 1980s with preterm controls. Those who had a history of BPD were more likely to require special school resources or classes (48% versus 38%), to have academic delay (51% versus 47%), and to have poorer math, reading, and spelling skills. They also had more adverse neuropsychological and educational outcomes, including lower verbal and performance IQs, increased hyperactivity, and worse fine motor function, receptive vocabulary, visual-perceptual integration, and memory. At 9 to 10 years of age, 71% of the children who required oxygen at home for more than 1 month after discharge from the neonatal intensive care unit have been reported to have suspect or abnormal findings on neuromotor examinations, including sensorimotor difficulties, eye-hand incoordination, poor postural stability, poor motor coordination (“clumsiness”), or motor difficulties. The severity of BPD (ie, duration of hospitalization and oxygen therapy, severity of PFT abnormalities) and lower socioeconomic status were the only independent predictors of these neurologic abnormalities. Such neuromotor and neurobehavioral abnormalities would be expected to have adverse effects on school performance.The outcomes of children who have had the more recent, less severe forms of BPD are similarly concerning. A well-controlled study in VLBW children who received antenatal steroids and surfactant noted that those who had a history of BPD were more likely than preterm controls to have mental (21% versus 11%) or motor (20% versus 9%) retardation at 3 years corrected age. Of the multiple risk factors examined, only BPD and the neurologic risk score, reflecting the severity of neonatal brain injury, independently decreased standardized motor scores on the Bayley Scales of Infant Development (BPD: −12 points, neurologic risk: −14 points). In contrast, cognitive function was predicted independently by neurologic risk, minority race, and social class, but not by BPD. In this same group, after controlling for IQ, BPD adversely affected preschool language outcome and was associated with both receptive language impairment and poorer expressive language skills. The physiologic basis for the adverse effect of BPD on neurodevelopmental outcome is unknown, but prolonged and recurrent hypoxemia, malnutrition, lack of specific nutrients, toxic effect of drug therapies, and lack of appropriate environmental stimulation all may play a part in altering brain growth, development, and function.BPD is an excellent marker for high neurologic, developmental, and academic risk throughout childhood that identifies children who require longitudinal neurodevelopmental evaluation. Although most neurodevelopmental follow-up programs, government funding, and intervention services are focused primarily on infants and young children, the most profound developmental effects of BPD or prematurity in general appear during the school years. Because many of the neurodevelopmental abnormalities associated with BPD are subtle and not readily evident, high-risk children who have a history of BPD are served best by standardized, comprehensive preschool and school-age assessments performed by experienced personnel.Children who have BPD need a readily available, consistent primary pediatric care clinician to coordinate medical and developmental care from neonatal intensive care unit discharge to adulthood (Table 3). Initial goals include promoting optimal growth, ensuring adequate oxygenation, preventing infection by RSV immunoprophylaxis and immunization, assuring appropriate developmental evaluation and support, and helping the family cope with the physical and psychological difficulties of caring for a medically fragile child. The primary care practitioner who is cognizant of potential neurodevelopmental, behavioral, and educational risks will be a valuable advocate, helping assure that appropriate psychosocial and educational assessments are performed and that appropriate school and interventional resources are made available throughout childhood. Despite their early physical difficulties and increased neurodevelopmental risks, most children who have BPD have an excellent prospect of becoming well-functioning, healthy adults who are satisfied with their quality of life and are able to contribute positively to their families and society.