Long-term pulmonary sequelae of severe bronchopulmonary dysplasia.

OBJECTIVE: To evaluate the long-term pulmonary sequelae of survivors of bronchopulmonary dysplasia (BPD) of sufficient severity to have required supplemental oxygen for at least 1 month after term. STUDY DESIGN: Fifteen patients with a mean age of 1.1 years were matched to preterm infants of similar gestational age and age at time of study. Pulmonary function testing included spirometry, plethysmographic lung volumes, carbon monoxide diffusion capacity, and in 9 of 15 subjects with BPD, measurement of lung static elastic recoil pressures. RESULTS: The subjects with BPD had a mean expiratory volume in 1 second (FEV1) of 64% +/- 21% predicted (4 had an FEV1 < 50% predicted) compared with 85% +/- 11% (P < .01) for the preterm children in the control group. Subjects with BPD had a significant degree of gas trapping with a residual volume to total lung capacity ratio of 37% +/- 13% compared with 25% +/- 4% for the control group (P < .01). An inverse relationship was seen between the FEV1 and the time on supplemental oxygen (r = -0.84, P < .0001), with 3 of the 4 children whose FEV1 was < 50% requiring oxygen for more than 900 days. Those with the greatest degree of airflow limitation and gas trapping had the greatest abnormalities in both shape and position of the pressure volume curves of the lung. CONCLUSION: Severe BPD may result in moderate to severe long-term abnormalities in pulmonary function tests.

Exercise ability in survivors of severe bronchopulmonary dysplasia.

There is limited information concerning the exercise performance of long-term survivors of bronchopulmonary dysplasia (BPD), and much of what is available pertains to those with relatively mild disease. The present study was undertaken to describe exercise responses in patients with a history of severe BPD, defined as those patients with a clinical and radiographic diagnosis of BPD who required supplemental oxygen at least until they were 44 wk postconceptual age and who were discharged home on oxygen. Fifteen children with a history of severe BPD were matched for gestational age with 15 children who had previously had respiratory distress syndrome but who did not develop BPD (Prem). These Prem control children were subsequently compared with 13 healthy control children born at term (Control) who were of similar postnatal age. Participants underwent pulmonary function testing, progressive exercise testing on a cycle ergometer, and a steady-state exercise test with cardiac output determined by CO2-rebreathing. Despite the patients with BPD having a lower FEV1 than those in the Prem group, who had lower values than the Control group (BPD, 64 +/- 21%; Prem, 85 +/- 11%; Control, 95 +/- 8%), the exercise capacity did not differ between the BPD and the Prem and between the Prem and the Control groups (BPD, 84 +/- 15%; Prem, 81 +/- 17%; Control, 91 +/- 12%). However, the BPD patients used a greater percentage of their ventilatory reserve (VEmax/40 FEV1: BPD, 93 +/- 20%; Prem, 67 +/- 12%; Control, 59 +/- 13%). Of the four patients with BPD who had significant oxygen desaturation with exercise, three had the lowest values for FEV1. Cardiac output was appropriate for oxygen consumption in most patients.

Postnatal maturation of the blood-brain barrier for unbound bilirubin in newborn piglets.

The postnatal maturation of the blood-brain barrier (BBB) for unbound bilirubin was studied in 2-day- and 2-week-old piglets. Hyperbilirubinemia was induced by bolus infusion of bilirubin at 25 mg/kg followed by continuous infusion of 20 mg/kg/h for 3 h. During the study period, arterial blood pH and blood gas tensions, serum osmolarity, and mean arterial blood pressures were within the physiologic range. Brain bilirubin content and the brain/blood distribution ratio for bilirubin were higher in the 2-day-old than in the 2-week-old piglets. In both age groups, regional brain bilirubin concentration and brain/blood ratios were higher in subcortical regions (cerebellum and brainstem) than in the cerebral cortex. We conclude that in newborn piglets the blood-brain barrier for unbound bilirubin matures with increasing postnatal age and that irrespective of maturity the relative permeability of the BBB for bilirubin appears higher in subcortical than in cortical regions.

Portohepatic shunt in a Down syndrome patient with an interchange trisomy 47,XY,-2,+der(2),+der(21)t(2;21)(p13;q22.1)mat.

A rare vascular portohepatic anomaly was identified in a Down syndrome patient with a 47,XY,-2,+der(2),+der(21)t(2;21)(p13;q22.1) mat chromosomal complement. This vascular defect involves a direct communication between the right portal vein and the inferior vena cava (IVC). We discuss the possibility that this vascular defect is a rare manifestation in Down syndrome. Alternatively, the existence of these 2 rare events in the same patient raises the possibility that they are causally related.

Liquid-filled esophageal catheter for measuring pleural pressure in preterm neonates.

The precise measurement of esophageal pressure (Pes) as a reflection of pleural pressure (Ppl) is crucial to the measurement of lung mechanics in the newborn. The fidelity of Pes as a measurement of Ppl is determined by the occlusion test in which, during respiratory efforts against an occlusion at the airway opening, changes in pressure (delta Pao) (Pao is assumed to be equal to alveolar pressure) are shown to be equal to changes in Pes (delta Pes). Eight intubated premature infants (640-3,700 g) with chest wall distortion were studied using a water-filled catheter system to measure Pes. During the occlusion test, all patients had a finite region of the esophagus where delta Pes equaled delta Pao, which corresponded to points in the esophagus above the cardia but below the carina. In conclusion, even in the presence of chest wall distortion, a liquid-filled catheter with the tip between the cardia and carina can provide an accurate measurement of Ppl, even in the very small premature infant with chest wall distortion.

Family support system in newborn medicine: does it work? Follow-up study of infants at risk.

Acute illness in early childhood generates chronic anxiety in parents, which may manifest itself in part by inappropriate use of health care. To minimize this and the development of other psychosocial sequelae associated with neonatal illness, a family support system (FSS) was developed and implemented in a neonatal intensive care unit. The effectiveness of the FSS was assessed by the evaluation of emergency room and inpatient hospital service utilization in 80 patients born before, and 90 patients born after the institution of the program. At the outset, the groups had similar medical and social characteristics. There was no difference between the two groups in the utilization of emergency services in the first year after discharge. However, during the second year the control group used the emergency room twice as often as the study group did (P less than 0.025). During the first 2 years, half of the control group was readmitted, compared with less than a third of the study group (P less than 0.005). Overall, after discharge from the neonatal intensive care unit the control group spent an average of 9 days per patient in hospital, compared with a mean of 3 days per patient in the study group (P less than 0.025). It appears, therefore, that the FSS may be an effective way to reduce some of the psychosocial sequelae of illness in newborn infants requiring intensive care.

Interaction of caffeine and continuous distending airway pressure in neonatal apnea.

The interactive effect of caffeine and continuous distending airway pressure was evaluated in two premature neonates with apnea. The application of a continuous negative pressure around the chest wall decreased minute ventilation in both infants and blunted the stimulatory effect of caffeine. This potential interaction should be considered if the desired effects of caffeine or distending airway pressure on apnea control are not achieved when they are used concurrently.

Outcome at school-age after neonatal mechanical ventilation.

103 school-age children (5 to 12 years) who survived mechanical ventilation for neonatal respiratory failure were evaluated for growth, neurological, intellectual, psychological and school function in order to determine those children most at risk for handicap. A major handicap occurred in seven children, preventing attendance at normal school or normal classes. Neurological sequelae were significantly associated with perinatal asphyxia and with birthweights of 1500g or less, and neurological sequelae and socio-economic factors were the major determinants of ability. The effects of the Neonatal Intensive Care Unit (NICU) experience on parents and subsequent parent-child relationships were also investigated: 67 per cent of the mothers were very upset by the experience and many continue to worry excessively about the health of their child. Parents who visited their child in the NICU frequently were significantly more anxious and overprotective, restricting many activities even when the child was of school age.

Epidemiology of adverse drug reactions in the newborn.

A prospective study on the epidemiology of adverse drug reactions (ADR) in the 200 neonates consecutively admitted to a newborn intensive care unit had shown that 136 ADR occurred in 60 babies (incidence = 30%). 20 of these ADR (14.7%) were major (life-threatening), 34 (25%) were moderate (prolonged hospital stay) and 82 (60.3%) were minor (resolved spontaneously, no therapy required). Respiratory depression, cardiac arrhythmias, renal failure, metabolic abnormalities (hyperglycemia, electrolyte imbalance) and gastrointestinal bleeding were the most common major and moderate ADR. Hematologic (eosinophilia, thrombocytopenia) and metabolic (lipemia, hyperglycemia) were the most frequent minor ADR. The case fatality rate is 5%. Most commonly suspected drugs associated with the ADR were cardiovascular drugs (tolazoline, digoxin, methoxamine), antibiotics, diuretics and components of intravenous nutrition solutions.

Blood transfusion: a possible risk factor in retrolental fibroplasia.

The effect of blood transfusion on the occurrence of RLF was evaluated in 58 infants who weighed less than 1001 g at birth (Group I) and 70 oxygen treated infants of various birth weights (Group II). Although there was no significant difference between Group I infants with or without exchange transfusion as to birth weight, gestational age, duration of oxygen therapy, peak Pa02's, or multiple births, there was a significantly increased incidence of pre-retrolental fibroplasia in transfused over non-transfused Group II infants. When Group II infants were stratified for prematurity and oxygen duration, this difference persisted in those not already at risk for RLF. This increased incidence of retinopathy in transfused infants suggests that blood transfusion may be a risk factor in the pathogenesis of RLF.

Risk factors in retrolental fibroplasia.

Possible determinant factors that may increase the risk of the occurrence of retrolental fibroplasia (RLF) were analyzed in 80 infants born in 1975 and 1976 with birth weights between 501 and 1,500 gm and who survived. Active and/or cicatricial RLF occurred in 27 (33.8%) infants and the factors significantly associated with RLF were: gestational age (P less than .001); apnea requiring bag and mask resuscitation with oxygen (P less than .001); septicemia (P less than .005); degree of illness; blood transfusion; and mechanical ventilation. Severe cicatricial RLF developed in eight (10%) infants (grades 2 to 5). In the group of infants all of whom had apnea which required resuscitation, septicemia was also significantly associated with RLF (P less than .01). A highly significant association between RLF and severe myopia (P less than .001) was found in follow-up in all infants. Data show a resurgence and high incidence of RLF in low birth weight infants who survived. Infants with these factors should be considered to have greater risk for the occurrence of RLF and ophthalmologic examination prior to, and within three months following discharge is recommended.

Pharmacokinetic profile of caffeine in the premature newborn infant with apnea.

The pharmacokinetic profile of caffeine was studied in 32 premature newborn infants with apnea: 12 following a single intravenous dose; 3 after a single oral dose; 7 during treatment with an initial empirical (high) maintenance dose schedule; and 10 during treatment with a revised (lower) dose schedule. Mean (+/- SE) AV d, t 1/2, ke1, and clearance following a single intravenous dose were 0.916 +/- 0.070 1/kg, 102.9 +/- 17.9 hours, 0.009 +/- 0.001/hours and 8.9 +/- 1.5 ml/kg/hour, respectively. Rapid absorption was noted with plasma concentrations of 6 to 10 mg/l achieved within 30 minutes to two hours following an oral dose of 10 mg/kg. Cpss of caffeine in infants given a high empirical dose (11.2 +/- 1.5 mg/kg/day) ranged from 22.5 to 84.2 mg/l (mean = 45.3) whereas a dose schedule based on kinetic data (2.5 mg/kg/day) yielded plasma concentrations ranging from 7.4 to 19.4 mg/l (mean = 13.7). We suggest a loading dose of 10 mg/kg intravenously or orally followed by a daily maintenance dose of 2.5 mg/kg/day administered as a single dose for the treatment and prevention of neonatal apnea.

Peripheral total parenteral nutrition for premature infants with the respiratory distress syndrome: a controlled study.

In 40 premature infants, in whom severe respiratory distress precluded oral feeding, peripheral total parenteral nutrition consisting of casein hydrosylate, dextrose, and soybean emulsion was compared to nutrition with dextrose and electrolytes. The TPN group received more calories, and the total serum protein in them increased significantly. Metabolic complications did not occur. Transient thrombocytosis occurred in six infants who received TPN and eosinophilia occurred in nine. The case fatality rate in the TPN group (three of 20) was not significantly less than in the glucose group (six of 20). The differences suggested that infants who weigh less than 1,500 gm may receive the greater benefit from TPN.

Effectiveness of neonatal transport.

The condition of 259 infants transferred to the neonatal intensive care unit (NICU) of the Montreal Children's Hospital from Oct. 1, 1974 to Mar. 31, 1975 was evaluated. Their transport was provided by personnel and equipment from the Montreal Children's Hospital. When the transport team arrived at the referring hospital hypothermia (temperature of less than 36 degrees C) was present in 25.2% of the 163 infants for whom complete temperature measurements were available. Most (77.3%) of the infants were warmed during transport and only 3.1% arrived at the NICU with a temperature of less than 35 degrees C. The mortality was significantly higher in babies of all birth weight groups whose core temperature had been below the optimal temperature for survival (36 to 37 degrees C). It appears that the use of appropriate equipment and trained personnel can reduce the incidence of hypothermia and therefore the mortality in infants requiring transfer.

Long-term pulmonary sequelae of the Wilson-Mikity syndrome.

Five children born prematurely, eight to ten years ago, who survived the Wilson-Mikity syndrome were compared with six apparently normal prematurely born children and eight normal children born at term, by means of flow volume curves obtained while breathing air and while breathing a mixture of 80% helium and 20% oxygen. The flow rates in air of the group who survived the Wilson-Mikity syndrome were significantly lower than those of the prematurely born normal children (P less than 0.01), and than those of the eight normal children (P less than 0.001). The volume of isoflow while breathing air compared to that while breathing HeO2 was highly variable, but not significantly different in the three groups. Three of the five survivors of the Wilson-Mikity syndrome had a marked concavity in the shape of their flow volume curves. It is concluded that these abnormalities are due to focal increases of compliance or resistances or both of terminal lung units and result in adjacent areas of the lung emptying at different rates. The relationship between physiologic and anatomic abnormalities seen at autopsy in those who die to the disease suggests that they are due to the same pathologic process. Whether or not these abnormalities will disappear with future lung growth remains to be seen.

Long-term pulmonary sequelae of premature birth with and without idiopathic respiratory distress syndrome.

Seven children born prematurely who survived the respiratory distress syndrome, seven children born prematurely who had no neonatal lung disease, and seven normal children born at term were studied by comparison of flow volume curves obtained while breathing air to those obtained while breathing 80% helium and 20% oxygen. Expiratory flow rates in air both groups of prematurely born children were lower than flow rates of the children born at term, and the volumes of iso-flow were higher in the survivors of RDS than those of the children born at term. The differences in flow rates in air suggest an increase in large airway resistance in both groups of prematurely born children. It is speculated that this may be secondary to growth retardation related to prematurity. The elevated Viso V in the RDS group suggests an increase in small airway resistance secondary to the disease or to its therapy.