Daniel P. Lindstrom

Evidence from twin study implies possible genetic susceptibility to bronchopulmonary dysplasia

To investigate the possibility that susceptibility to bronchopulmonary dysplasia (BPD) is affected by genetic factors, we analyzed risk factors for BPD in 108 twin pairs of infants having birth weight < or = 1,500 g. When BPD occurred in a first born twin (n = 23), it also occurred in 65% (n = 15) of the second born twins, and when BPD did not occur in the first twin (n = 85), it only occurred in 8% (n = 7) of the second twins (crude odds ratio = 20.9). After adjusting for potentially significant risk factors including birth weight, gestational age, gender, diagnosis of hyaline membrane disease, pneumothorax, symptomatic patent ductus arteriosus, and year of admission, using multiple logistic regression on the entire database (1,872 admissions < or = 1,500 g), BPD status of a first twin remained a highly significant predictor of BPD in the second twin (adjusted odds ratio = 12.3, P < .001). Other factors including birth order of twins, twin gestation, inborn/outborn status, cesarean section delivery, 1- and 5-minute Apgar scores, maternal race, maternal diabetes, and antepartum corticosteroid treatment were not significant predictors of BPD. These results are consistent with genetic factors affecting the susceptibility of very low birth weight premature infants to BPD, but we cannot exclude the possibility that factors not included in our analysis are also involved.

The Physiologic Effects of Surfactant Treatment on Gas Exchange in Newborn Premature Infants with Hyaline Membrane Disease

ABSTRACT: To describe the physiologic effects of surfactant treatment on gas exchange in human premature infants with hyaline membrane disease, functional residual capacity (FRC), tidal volume (VT), the alveolar portion of tidal volume (VA), alveolar ventilation (VA), nitrogen clearance index, effective breath fraction calculated as VA/VT, compliance of the respiratory system, and arterial oxygen and carbon dioxide tensions were measured in 17 patients before and 0.5, 2, and 6 h after the administration of a single dose of either a synthetic surfactant (SS), Exosurf (n = 10), or a bovine surfactant (BS), Survanta (n = 7). By 2 h, treatment with either BS or SS was followed by an increase in the arterial/alveolar ratio of Po2 (a/A) and in FRC (p < 0.01 for both a/A and FRC). The a/A and FRC improved sooner (p < 0.001) and to a greater extent (p < 0.01) after BS than after SS. Compliance of the respiratory system and VT were decreased after either BS or SS at 0.5 h (p < 0.01) and remained decreased after SS at 2 h (p < 0.01). There was no significant change in VA or VA after either BS or SS. Because FRC and a/A increased without an accompanying increase in VA, VA, or compliance of the respiratory system, we believe that the immediate increase in FRC in this study was caused by stabilization of gas exchange units already being ventilated in addition to recruitment of new units. Nitrogen clearance index decreased and effective breath fraction increased after treatment, indicating an improved efficiency in gas mixing also thought to result from stabilization and maintenance of patency of distal airways by surfactant.

Increased survival rate in very low birth weight infants (1500 grams or less): No association with increased incidence of handicaps

The incidence of major handicaps was studied in a selected high-risk population of 1919 very low birth weight (less than or equal to 1500 gm) infants born between 1976 and 1985. Seventy-four percent of these infants were discharged alive. We have handicap information on 632 infants who have been followed for up to 7 years of age; 462 were evaluated at 18 months or later. Patients lost to follow-up represent 55% of the eligible population, but inpatient morbidity factors were available for the entire population and were used to calculate synthetic estimates of handicap rates. The overall incidence of severe major handicaps at 18 months was 18.0% (83/462). Cerebral palsy was found in 7.6%, and 6.5% were mentally retarded (IQ less than or equal to 70). Severe retinopathy of prematurity was present in 5.5%, and 5.4% of the infants had neurosensory hearing loss. Thirty-one infants (6.7%) had more than one handicap, the most common combination being cerebral palsy and mental retardation. Outcome of infants grouped by 250 gm birth weight intervals was compared for two periods (1976 to 1980, and 1981 to 1985); the numbers of survivors in each birth weight group increased during the second period, especially in the 500 to 750 gm and the 751 to 1000 gm groups. The observed incidence of major handicaps decreased from the first 5-year period to the second 5-year period (p less than 0.001). The largest decreases in the observed proportion handicapped occurred in the two lowest birth weight groups. The incidence of multiple handicaps also dropped; again, the two lowest birth weight groups showed the largest decrease. We conclude that an increased survival rate of very low birth weight infants need not be associated with an increased incidence of major handicaps.

Recurrence of symptomatic patent ductus arteriosus in extremely premature infants, treated with indomethacin

The administration of a single intravenous injection of indomethacin was followed by a major constrictive effect on the ductus in 36 of 42 very-low-birth-weight (less than or equal to 1000 gm) infants with symptomatic patent ductus arteriosus (PDA). In 26 of the 36 responders, the effect was sustained; symptomatic PDA recurred in the remaining 10. Infants who experienced a recurrence of symptomatic PDA had lower birth weights and had received indomethacin at an earlier postnatal age than did infants with a sustained effect. These results may be explained by differences in the production and clearance of prostaglandins or in the sensitivity of the ductus to prostaglandin effects between infants with a recurrence and infants with sustained constriction of PDA.

Model-based diagnosis in intensive care monitoring: The YAQ approach

YAQ is an ontology for model-based reasoning in physiologic domains. YAQ is based on a hybrid algebra of qualitative and numerical values, and is designed to benefit from the rich and ever-changing nature of information available in a critical care monitoring environment. The focus of the project is on diagnosis of clinical conditions, prediction of the effects of therapy, and therapy management assistance. Two models of diagnosis are implemented in YAQ: diagnosis based on associations, and model-based diagnosis. The ontology is applied to the domain of ventilator management in infants with respiratory distress syndrome (RDS). The article describes the diagnostic capabilities of YAQ, illustrates these concepts on examples taken from actual patient records, and reports the results of an evaluation of the diagnostic performance on the RDS/assisted ventilation domain model.

The SIMON project: model-based signal acquisition, analysis, and interpretation in intelligent patient monitoring

The authors describe SIMON (signal interpretation and monitoring), an approach which combines static domain-specific information, which relates variables and alarm events, with dynamic information provided by a model. It is currently being tested for the monitoring of neonates in the intensive care unit. The model component is responsible for estimating the state of the monitored system, predicting the evolution of the systems variables and parameters, and establishing a monitoring contest. This information is then used by the DA (data abstraction) and the data acquisition modules to plan a monitoring strategy to filter, rank, and abstract incoming data. Faults and artifact models included in the DA permit the low-level detection of noise-contaminated episodes. The adaptation of the monitoring strategy to these changes in the environment effectively shields the model from untrustworthy information and thus increases the reliability and robustness of the system. The scheduling mechanism included in the DA permits a continuous evaluation of the system load as well as an ability to process all its tasks.<<ETX>>

Early prediction of symptomatic patent ductus arteriosus from perinatal risk factors. A discriminant analysis model

ABSTRACT. Cotton, R. B., Lindstrom, D. P. and Stahlman, M. T. (Depaitment of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA). Early prediction of symptomatic patent ductus arteriosus from perinatal risk factors: a discriminant analysis model. Acta Paediatr Scand, 70:723,.–A scoring system based on discriminant analysis was devised to predict, within 24 hours after birth, whether or not a premature infant will subsequently develop a symptomatic PDA. Five risk factors including birth weight, the diagnosis of hyaline membrane disease, intrauterine growth retardation, acute perinatal stress, and treatment with distending airway pressure were reduced to a discriminant score which separated infants with symptomatic PDA from infants without sympomatic PDA. Based on this score, the likelihood that an individual infant would later develop symptomatic PDA could be expressed as a probability function. When applied prospectively, this score predicted the correct outcome of 80 % of infants in a test population. This predictive model should be useful in clinical trials and other applications requiring a quantitative expression of risk for developing symptomatic ductus shunting.

Cimetidine Does Not Prevent Lung Injury in Newborn Premature Infants

Animal studies have shown that induction of cytochrome P450 (CYP) in the lung by oxygen exposure may result in the release of free radical oxidants and arachidonic acid metabolites, which can cause lung injury that is reduced by treatment with cimetidine, a CYP inhibitor. To determine whether cimetidine would reduce lung injury in human infants at risk for chronic lung disease, we conducted a randomized clinical trial in which we administered either cimetidine or a placebo for 10 d beginning <24 h after birth to 84 newborn infants weighing ≤1250 g who were receiving O2 and mechanical ventilation. Cimetidine had no significant effect on severity of respiratory insufficiency assessed at 10 d postnatal age. F2-isoprostane levels (a marker of oxidant injury) in tracheal aspirates were significantly higher in the cimetidine group at 4 d and at 10 d. There were no significant differences between the groups in tracheal aspirate levels of inflammatory markers (leukotriene B4, IL-8, and nucleated cell count) or arachidonic acid metabolites. We conclude that cimetidine does not reduce lung injury in newborn premature infants receiving O2 and mechanical ventilation. It is possible that cimetidine was not an adequate CYP inhibitor in this context.

Surfactant replacement therapy improves ventilation inhomogeneity in infants with respiratory distress syndrome

Surfactant deficiency in newborn infants with hyaline membrane disease (HMD) reduces peripheral airway stability, leading to lung atelectasis, inhomogeneity of distribution of ventilation, ventilation/perfusion mismatch, and hypoxemia. The aim of this study was to evaluate the immediate effect of exogenous surfactant treatment on ventilation inhomogeneity (VIH) in infants with HMD. Homogeneity of ventilation was measured repeatedly in ten infants (median gestational age 30 weeks and birthweight 1.50 kg) after Exosurf®, and in six infants (median gestational age 30 weeks and birthweight 1.42 kg) after Survanta® treatment. Lung function was measured before and 0.5, 2, and 6 hours after administration of a single dose of surfactant. The multiple breath nitrogen washout method was used to measure the time pattern of nitrogen elimination from the lungs. VIH was evaluated by using both a compartmental lung model and a model‐independent moment analysis.

Neonatal Cerebral Blood Flow Velocity I.: An In Vitro Validation of the Pulsed Doppler Technique

ABSTRACT. A combined pulsed and continuous Doppler instrument was used to assess flow velocities in an in vitro model designed to simulate small deeply lying arterial vessels. Diameters of the model vessels, depth under the transducers and the pulsatile flow patterns were chosen to simulate the corresponding conditions that can be expected when cerebral blood flow velocities are measured with this technique through the anterior fontanel in newborn infants. Computer analysis of the space average velocity signal from the pulsed Doppler mode, showed that the area under this curve, which corresponds to distance, was closely correlated to true flow over a wide range of flows in vessels of different diameters. This variable is suggested to be the closest estimate of true flow, when the diameter of the vessel under study cannot be accurately measured.