Mary Ellen Avery

Association between maternal diabetes and the respiratory-distress syndrome in the newborn.

Abstract Perinatal data on 805 infants of diabetic mothers and 10,152 infants of nondiabetic mothers were examined for a relation between maternal diabetes and respiratory-distress syndrome of the newborn. The syndrome occurred in 23.4 per cent of the diabetic vs. 1.3 per cent of the nondiabetic group. The risk of the syndrome in an infant of a diabetic mother was 23.7 times greater than that for an infant of a non diabetic mother (P < 0.00001). Further analysis to control for features associated with diabetes but also in themselves risk factors, such as gestational age and route of delivery, showed that respiratory-distress syndrome in infants of diabetic mothers was 5.6 times as likely to develop as in infants of nondiabetic mothers (P < 0.00001). Thus, maternal diabetes mellitus per se predisposes to newborn respiratory-distress syndrome. (N Engl J Med 294:357–360, 1976)

Bronchopulmonary dysplasia: Possible relationship to pulmonary edema

The pathogenesis of bronchopulmonary dysplasia is controversial. Oxygen toxicity, mechanical trauma to the lung secondary to respirator therapy, and congestive heart failure with a left to right shunt through a patent ductus arteriosus have all been implicated. Our data suggest that in addition to these three conditions, all of which are edemagenic, infants with bronchopulmonary dysplasia have a significantly greater mean fluid intake in the first five days of life when compared with infants with respiratory distress syndrome or patent ductus arteriosus alone. We suggest that the addition of a fluid load may potentiate the effects of other factors and increase the risk of bronchopulmonary dysplasia in infants with respiratory distress syndrome who require respiratory support.

Correlations of Mechanical Stability, Morphology, Pulmonary Surfactant, and Phospholipid Content in the Developing Lamb Lung*

Pressure-volume characteristics and surface tension measurements of the lamb of 120 to 130 days gestational age were typical of the mature lung in the upper lobes and the immature lung in the lower lobes. By term both upper and lower lobes had findings characteristic of the mature animal. Phospholipid concentration per milligram DNA and per cent saturated fatty acids on pulmonary phosphatidyl choline were relatively constant from 60 to 120 days gestational age; thereafter there was a significant increase in both measurements. These changes usually coincided with an increase in osmiophilic inclusion bodies in the large alveolar cell.A concentration of disaturated phosphatidyl choline per milligram DNA in excess of 0.170 mg per mg was associated with a minimal surface tension below 13 dynes per cm (p < 0.001). Newborn animal lungs contained over 3 times this critical concentration, whereas adult lungs contained 1.5 times this value. The excess disaturated phosphatidyl choline per milligram DNA may represent a reservoir of pulmonary surfactant.

Insulin antagonism of cortisol action on lecithin synthesis by cultured fetal lung cells

In monolayer cel cultures from late gestation (28-day) rabbit fetal lungs, cortisol (5.5 X 10(-6)M) enhances lecithin synthesis and reduced cellular growth. The addition of insulin (25-100 muU/ml) abolishes the stimulatory effect of cortisol on lecithin synthesis but does not affect its growth-inhibiting activity.

Lung Injury from Oxygen in Lambs: The Role of Artificial Ventilation

Eighty to 100 per cent oxygen, breathed by lambs one or two weeks of age, is lethal after two to four days. Artificial ventilation did not aggravate or significantly ameliorate the pulmonary response. Lambs ventilated with air on respirators for comparable periods had no significant pulmonary damage. The cause of death of the oxygen-treated lambs was the pulmonary injury, characterized by edema. Studies of the excised lungs showed that the lesion was spotty, that the normal-appearing portions of the lung were normally distensible, and no significant alterations in pulmonary surfactant occurred. Several methods of assessment of the mechanical derangements are presented.

Early high dose antioxidant vitamins do not prevent bronchopulmonary dysplasia in premature baboons exposed to prolonged hyperoxia: A pilot study

The antioxidant vitamins ascorbic acid (AA) and α-tocopherol(α-TP) effectively inhibit oxygen free radical-induced lipid peroxidation. Using a premature baboon model of hyperoxiainduced bronchopulmonary dysplasia (BPD), we measured concentrations of AA,α-TP, and conjugated dienes (CD, marker of lipid peroxidation) in four animals (hyperoxic antioxidant group) receiving high dose antioxidant vitamin supplementation (AA, 100 mg·kg·-1·d-1;α-TP; 20 mg·kg·-1·d-1) and one animal receiving standard dose antioxidant vitamin supplementation (AA, 10 mg·kg·-1·d-1; α-TP, 1 mg·kg·-1·d-1). Respiratory and histopathologic data were compared with data from 10 historical animals exposed to hyperoxia (hyperoxic control group) and 11 historical animals treated as required with oxygen (normoxic control group) who had received standard dose antioxidant vitamin supplementation. Compared with standard dose antioxidant vitamin supplementation, high dose antioxidant vitamin supplementation, effectively raised AA concentrations in plasma (37 ± 22 μmol/L and 395 ± 216 μmol/L, respectively) and tracheal aspirates (62 ± 35 μmol/L and 286 ± 205 μmol/L, respectively), and α-TP concentrations in plasma (10.1 ± 2.5μmol/L and 24.6 ± 17.5 μmol/L, respectively). However, there was no apparent effect on tracheal aspirate CD concentrations (482 ± 333μmol/L and 1050 ± 1111 μmol/L, respectively), and respiratory parameters in the hyperoxic antioxidant group were comparable to those of the hyperoxic control group but significantly worse than in the normoxic control group. Finally, no protective effect of high dose antioxidant vitamin supplementation was noted at the histopathologic level.

A 50-year overview of perinatal medicine

Infant mortality in 1990 was approximately one-tenth that of 1950 in most of the industrialized countries of the world. The forces of change included the social-political climate, advent of neonatal intensive care, better insight into nutritional requirements of preterm infants and application of basic science to the study of events around the time of birth, and illnesses of the neonate. Attention has been paid to the advantages of human milk for the newborn infant, the importance of maternal bonding and involvement of both parents in care of the infant. Prenatal diagnosis, with option of abortion, has reduced the prevalence of some serious disorders of the fetus.

Paradoxical Reduction in Tissue Hydration with Weight Gain in Neonatal Rabbit Pups

Summary: We measured body hydration of healthy, term rabbit pups at birth and 72 hr of age. In addition, we measured hydration of individual tissues: skin, skeletal muscle, liver, and brain. At birth, the hydration of lean body mass, skin, and skeletal muscle, expressed as cc water per g fat-free dry weight (FFDW) was inversely proportional to birth weight. Low birth weight animals were significantly better hydrated than their larger littermates.During the first 72 hr of life, the nursing pups gained an average 31.39% of birth weight. Simultaneously, lean body hydration decreased by 23% (5.48 to 4.86 cc/g FFDW). The hydration change varied substantially among organs. The greatest loss occurred in skin (24%). Skeletal muscle lost 5.8%, and the brain lost 3.1%.When hydration at 72 hr was compared to weight gain and by inference fluid intake, a paradoxical result was obtained. Lean body, skin, and skeletal muscle hydration was inversely related to weight gain. The animals that gained the most weight retained the least water. In contrast, the hydration of brain and liver was significantly higher in animals that gained the most weight.We conclude that the newborn rabbit is endowed with a reservoir of fluid at birth, predominantly stored in skin and skeletal muscle. The rate of release of this store depends on fluid intake. It is rapidly lost if ample fluid intake is provided. In conditions of restricted fluid intake, the release is substantially slower.Speculation: At least two processes regulate tissue hydration in the newborn rabbit. The first, a function of growth, is responsible for the progressive accretion of intracellular water during gestation and postnatal development. It is illustrated by the increase in tissue hydration of brain and liver in well-nourished pups during the first 72 hr of life.The second process may be under hormonal regulation on a time scale of hr to days. It accounts for the relatively high level of tissue hydration at birth, and provides a supply of water and sodium to maintain plasma volume during the first days of life, thereby preventing dehydration during this period of variable fluid intake.

The Effects of Airway Occlusion After Oxygen Breathing on the lungs of Newborn Infants Radiologic Demonstration in the Experimental Animal

Abnormal ventilatory patterns and mechanical obstruction of airways are common problems in infants with respiratory failure. Chest radiographs are often requested after ventilation with 80 to 100% oxygen. Previous experiments have shown that bronchial occlusion after breathing pure oxygen results in gas-freeing of an obstructed lobe. Rapid complete pulmonary opacification on radiographs has been observed in some infants and it is suspected that this is due to rapid oxygen resorption during respiratory arrest. This was demonstrated in a puppy following oxygen breathing for 25 to 50 minutes through an endotracheal tube. Occlusion of the tube resulted in complete gas-freeing of the lungs in 3 to 5 minutes.

RESPIRATORY CENTER OUTPUT IN INFANTS AS INDICATED BY INSPIRATORY PRESSURE DURING AIRWAY OCCLUSION

The pressure generated by inspiratory muscles against an obstructed airway at functional residual capacity is an index of respiratory center output that is relatively independent of body size and lung mechanics. We have utilized this approach, that also assesses effects of afferent vagal activity, to measure output of the respiratory center in 6 full term infants on 15 occasions during the first week of life. While an infant was breathing room air or rebreathing carbon dioxide in oxygen, the face mask was occluded for 1 to 5 inspiratory efforts. Flow, tidal volume, inspiratory pressure, and carbon dioxide were measured continuously.Tidal volume, peak inspiratory pressure, inspiratory pressure at 0.1 sec after occlusion, and minute ventilation all increased with increasing carbon dioxide. The sequential increase in pressure during 5 occluded inspiratory efforts serves as an index of respiratory sensitivity to increasing chemical drive. Application of these techniques to infants with respiratory control problems can simultaneously differentiate nervous (vagal) and chemical influences on respiratory center output.