David K. Edwards

Bronchopulmonary dysplasia: The pulmonary pathologic sequel of necrotizing bronchiolitis and pulmonary fibrosis

A light and electron microscopic study was carried out in 21 infants in whom the pathologic diagnosis of bronchopulmonary dysplasia had been made. All the infants except two had the respiratory distress syndrome at birth, and all 21 had been treated with respirator and oxygen therapy for various periods of time. The pathologic alterations observed in all the infants studied were primarily damage of the bronchial and bronchiolar ciliary apparatus and mucous membranes, severe necrotizing bronchiolitis, and marked bronchiolar and alveolar fibrosis. These changes were more pronounced in infants who survived the longest period of time. Such inflammatory and fibrotic changes are known to predispose to destruction of lung tissue, emphysema, and pulmonary hypertension. Six of these 21 infants developed symptoms and signs of cardiac atrial or ventricular stress, including cor pulmonale, prior to their demise. These infants were among those that survived the longest periods of time, had the longest exposure to supplemental oxygen, and showed histopathologically severe pulmonary fibrosis and emphysema.

Newborn tracheal aspirate cytology: Classification during respiratory distress syndrome and bronchopulmonary dysplasia†

Cytopathologic examinations of tracheobronchial aspirates from 108 infants sampled during mechanical ventilation demonstrated a well-defined progression of cytologic changes in bronchial cells that could be divided into three classes. Seventy percent of infants with respiratory distress syndrome who developed bronchopulmonary dysplasia had pulmonary effluent cytology designated Class III; no infants with RDS but without BPD had these cytologic findings. Additionally, a temporal progression of events involving polymorphonuclear leukocyte and macrophage populations occurred in the absence of infection; these events were associated with duration of assisted ventilation and oxygen exposure. The technique described provides a useful way to monitor the progression of lung injury and repair and offers a cytologic method to predict and diagnose the development of bronchopulmonary dysplasia.

Randomized, placebo-controlled trial of human surfactant given at birth versus rescue administration in very low birth weight infants with lung immaturity

A randomized, placebo-controlled trial of human surfactant given intratracheally at birth (prophylactic) versus rescue administration after the onset of severe respiratory distress syndrome (RDS) was conducted among preterm infants born at 24 to 29 weeks of gestation. Singleton fetuses were randomly assigned to receive (1) placebo (air), (2) prophylactic surfactant treatment, or (3) rescue surfactant treatment; infants of multiple births received either (1) prophylactic or (2) rescue treatment. Of 282 potentially eligible fetuses, 246 infants received treatments at birth and 200 infants had RDS. Outcomes are presented both as an intention-to-treat analysis (including infants who met exclusion criteria at or after birth) and as a full treatment protocol analysis for those infants with RDS and likely to benefit from surfactant. Preterm infants (mean 1.0 kg birth weight, 27 to 28 weeks of gestational age) randomly assigned to receive prophylactic treatment received surfactant soon after birth; those assigned to receive rescue surfactant had instillation at a mean age of 220 minutes if the lecithin-sphingomyelin ratio was less than or equal to 2.0 and no phosphatidylglycerol was detected in either amniotic fluid or initial airway aspirate, oxygen requirements were a fraction of inspired oxygen of greater than 0.5, and mean airway pressure was greater than or equal to 7 cm H2O from 2 to 12 hours after birth. Up to four treatment doses (or air) were permitted within 48 hours; approximately 60% of surfactant-treated infants required two or more doses. Surfactant-treated infants had significantly less pulmonary interstitial emphysema than placebo-treated infants (p = 0.02), but there were no other significant differences in mortality rates or morbidity. Indexes of oxygenation and ventilation were improved in surfactant recipients during the first 24 hours. An intention-to-treat analysis found no significant differences between infants given placebo and surfactant-treated infants or between prophylactic- and rescue-treated infants; an improved total mortality rate (p = 0.002) was found among surfactant-treated infants in Helsinki but not in San Diego. Among infants with RDS, the total mortality rate was significantly improved (p = 0.004) with surfactant treatment but not the proportion alive and without bronchopulmonary dysplasia at 28 days (p = 0.052), or the proportion alive and without bronchopulmonary dysplasia at 38 weeks of postconceptional age (p = 0.18) to adjust for differences in prematurity. Deaths caused by RDS or bronchopulmonary dysplasia were significantly reduced among surfactant recipients (p = 0.0001). Neither among singletons nor among multiple-birth infants was there a selective advantage to prophylactic versus rescue treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Cytomegalovirus Infection and Bronchopulmonary Dysplasia in Premature Infants

During a five-year period, 32 preterm infants weighing less than 2000 g were diagnosed as having postnatally acquired cytomegalovirus (CMV) infection in a neonatal intensive care unit. These CMV-infected infants were matched with 32 uninfected controls for gestational age, birth weight, and birth date; the two groups did not differ in Apgar scores or the incidence of respiratory distress syndrome and patent ductus arteriosus. Roentgenographic evidence of bronchopulmonary dysplasia (BPD) developed in 24 (75%) of 32 CMV-infected infants, an incidence significantly greater than that observed in control infants (12/32; 38%). Infants with acquired CMV infection required more respiratory support and longer hospitalization than uninfected controls. This association between acquired CMV infection in premature infants and the development of chronic lung disease provides further evidence that vigorous efforts to prevent CMV infection in hospitalized neonates is warranted.

Radiographic-pathologic correlation in bronchopulmonary dysplasia

THE CHEST RADIOGRAPH is an essential modality in the diagnosis and monitoring of patients with bronchopulmonary dysplasia. 1 Some authors have questioned the degree of correlation of the radiographic staging of BPD with the pathologic staging of the diseaseY 3 Determining this correlation could facilitate attempts to establish prognosis, using changes in the chest radiograph as one of the clinical markers. The purpose of this study was to compare retrospectively the radiographic staging of BPD with the histopathologic staging of changes in the lungs of a series of patients with respiratory distress syndrome who died after receiving mechanically assisted ventilation and supplemental oxygen therapy.

Vascular pathogenesis of unilateral craniofacial defects

The term hemifacial microsomia refers to unilateral defects in development of structures derived from the first and second branchial arches. Recently we evaluated three unrelated children who had a similar pattern of unilateral craniofacial defects that was associated with other structural abnormalities having a disruptive vascular pathogenesis. The clinical findings in these patients suggest that one cause of hemifacial microsomia is in utero interruption of blood flow.

Patent ductus arteriosus treated with ligation orindomethacin: A follow-up study

The course and complications of fifty-two infants with patent ductus arteriosus requiring closure were assessed prospectively. Twenty-six infants with a PDA received indomethacin for pharmacologic closure of the PDA, and 26 underwent ligation. The current study analyzes and compares the longitudinal follow-up with respect to somatic growth, neurologic function, psychomotor and mental development, and renal, ophthalmologic, and audiologic function in 21 infants in each group who entered the follow-up. No selective morbidity was attributable to PDA closure with indomethacin when compared to surgically treated infants.

1243 ASSOCIATION OF EARLY AORTOGRAMS & PDA LIGATION WITH INTRAVENTRICULAR HEMORRHAGE (IVH)

Thirty-three sick infants (<34 wk gest.) with RDS, PDA & subependymal hemorrhage (SEH) &/or minor IVH (without ventricular enlargement) were followed with frequent ultrasound brain studies to detect changes in IVH/SEH. Twenty-six had PDA ligation before 96 hours of life (“early”) & 7 after 96 hrs (“late”). Sixteen of 23 infants increased their IVH/SEH after early ligation. No changes occurred in those ligated late.Ligated infants who increased tneir IVH/SEH had aortograms more frequently than infants without IVH/SEH change. Both procedures might result in an acute increase in arterial blood pressure in infants lacking cerebral blood flow autoregulation. Early PDA ligation preceded by aortogram may be a risk factor for major IVH/SEH.

Bronchopulmonary Dysplasia Today

In 1967, Northway, Rosan, and Porter1 described a form of chronic lung disease that developed in certain infants who had received supplemental oxygenation and assisted ventilation for respiratory distress syndrome; they named this disease bronchopulmonary dysplasia to emphasize the pathological involvement of all lung tissues in the disease process. Subsequently, this disease was observed by numerous investigators and described under a variety of names, including bronchopulmonary dysplasia,2–10 pulmonary fibroplasia,11–13 respirator lung disease,14 chronic pulmonary disease,15 and other descriptive terms.16–22 This plethora of names is confusing and adds little to understanding of the disease. Further, despite minor theoretical objections,23 as Lynne Reid has remarked, the term bronchopulmonary dysplasia has much to commend it: it does not stipulate an etiology, and it presents the idea of a disturbance of growth.24

107 MOTOR TESTS OF INTERHEMISPHERIC CONTROL AND COGNITIVE FUNCTION IN VERY PRETERM INFANTS AT EIGHT YEARS

We have previously reported that damage to the posterior corpus callosum might explain some of the subtle cognitive processing deficits found later in many preterm infants. To test this hypothesis we carried out motor tests of interhemispheric control in 197 consecutively examined very preterm infants(<33 weeks gestation) at eight years. In addition to the Kaufman Assessment Battery for Children (K-ABC) and other studies, two tests of mirrorwise(Tm) and alternate(Ta) forearm diadochokinetic (pronation-supination) movements were performed. The alternate movement represents the most complicated form of interhemispheric control and reciprocal inhibition. The time difference between the two movements (Ta-Tm) is considered to give an indication of the efficiency of transfer of motor information between the hemispheres (particularly the posterior corpus callosum). There was a significant and linear relation between this time difference and the Kaufman Mental Processing Composite (K-MPC) score (p<0.002, DF 2). We conclude that the corpus callosum has an important role in cognitive development and posterior corpus callosum efficiency is related to cognitive outcome.