Search

We measured hematocrit and serum albumin concentration at birth and red blood cell and plasma volume soon after birth in prematurely born infants with erythroblastosis fetalis of varying severity and examined the realtionships between these variables and the presence and severity of hydrops fetalis. Blood volumes in most of these infants were similar to the established normals for newborn infants without erythroblastosis. There was no simple association between blood volume and the presence of hydrops. Nonhydropic and severely hydropic infants had, on the average, similar and normal blood volumes, while mildly hydropic infants had low blood volumes. Anemia correlated fairly well with severity of hydrops but almost a quarter of the infants with severe hydrops were only mildly anemic. Red blood cell volume decreased and plasma volume increased proportionally with the degree of anemia at birth. Thus, hydropic infants with severe anemia had large plasma volumes while those with milder anemia did not. On the other hand, hypoalbuminemia was common and correlated closely with severity of hydrops. We suggest that hydrops results at least in part from low plasma colloid osmotic pressure due to hypoalbuminemia.

There was meconium staining of the amniotic fluid in 8.8% of 1,000 consecutive newly born infants. At birthmeconium was present in the tracheas of 56% of those with meconium staining. From all infants who became "sick", meconium was aspirated from their airways; eight had meconium below the vocal cords, but none in the mouth or larynx. Twenty percent of those who were meconium stained had pulmonary disease which required increased ambient oxygen to maintain the Pa O 2 above 50 mm Hg andlor had a pneumothorax or pneumomediastinum during the first three days of life. All infants survived, including two who required mechanical ventilation for respiratory failure.

Sixty-six nonhydropic fetuses received intra-uterine transfusions for severe erythroblastosis fetalis; 24 survived the neonatal period–the youngest is now more than 1 year and the oldest 5 years of age. Serial evaluations of growth and development of the survivors were compared with their course in the perinatal period. Twenty-one were normal; one suffered severe central nervous system damage associated with severe cardiorespiratory failure, prolonged acidosis, and hypoxia during the neonatal period; one has a handicap due to hearing loss and one has a speech handicap. The results support the use of intra-uterine transfusion in appropriately selected fetuses when combined with aggressive treatment of cardiorespiratory distress and hyperbilirubinemia during the neonatal period.

We applied a continuous positive airway pressure to 20 infants (birth weight 930 to 3800 g) severely ill with the idiopathic respiratory-distress syndrome. They breathed spontaneously. Pressure, up to 12 mm of mercury, was delivered through an endotracheal tube to 18 infants and via a pressure chamber around the infant's head to two. Arterial oxygen tension rose in all, permitting us to lower the inspired oxygen an average of 37.5 per cent within 12 hours. Minute ventilation decreased with increased continuous positive airway pressure, but this had little effect on arterial carbon dioxide tension, pH, arterial blood pressure and lung compliance. Sixteen infants survived, including seven of 10 weighing less than 1500 g at birth.

Indwelling umbilical arterial catheters were used without difficulty to measure direct arterial blood pressure in newborn infants. Normal values were determined for mean aortic blood pressure during the first 12 hours of life in 45 infants who were expected, from history, to be subject to cardiopulmonary insufficiency at birth but who, after birth, were judged to be clinically well. Birth weights of these infants ranged from 1,050 to 4,220 gm, and gestational age ranged from 26 to 41 weeks. All infants were of appropriate weight for gestational age. Mean blood pressure correlated closely with birth weight and the relationship was best described by a parabolic regression [y = 35.53 + 0.36 (x) + 1.01 (x2)], where y = mean aortic blood pressure in millimeters mercury and x = birth weight in kilograms. The lower limit of normal mean aortic blood pressure was 30 mm Hg at 1,001 to 2,000 gm, 35 mm Hg at 3,000 gm, and 43 mm Hg at 4,000 gm. It is recommended that aortic blood pressure be measured routinely in all infants who are apt to develop cardiopulmonary insufficiency and have indwelling umbilical arterial catheters.

Suspensions of rigid microspheres, varying from 7.5 to 80 μ diameter, were injected into the left ventricle or ascending aorta of five anesthetized rabbits. After injection, an exposed branch of the femoral artery was frozen ultrarapidly, then removed; after histologic preparation, serial cross sections were studied microscopically. The radial distribution of the spheres within the vessel lumen was uneven, with a progressively decreasing concentration peripherally. This appeared to be proportional to sphere diameter and extended too far in from the periphery to be explained by entrance effect only. Microspheres of 7.5 to 10 μ diameter had the radial distribution which most closely approached that of erythrocytes in these same arteries.

We wish to call attention to an apparently common misconception about the efficiency of exchange transfusions. The mechanics of the procedure are: a substance (bilirubin and/or antibody-coated red cells) is washed out of a compartment (the baby's blood volume) by the removal of a fraction of that compartment and its replacement by an equal volume of diluent (donor blood). This flushing process is repeated many times, usually until the total volume replaced is 2 to 3 times the volume of the compartment itself.

Renal tissue was obtained by percutaneous biopsy in 11 patients with hemolytic uremic syndrome from 9 to 365 days after onset of disease; by autopsy in 5 after 6 to 58 days of illness. By light microscopy, the early histologic lesion (up to 30 days) was characterized by glomerular capillary ectasia and intracapillary eosinophilic depositions (fibrin-like material). Regardless of duration or severity, electron microscopy revealed irregular swelling and fragmentation of basement membrane, swelling of endothelial cytoplasm and deposition of granular and fibrillar electron-dense material with periodicity of fibrin between the basement membrane and endothelium and in the mesangium, most pronounced during the early course of disease. Tissue from 8 patients was studied by immunofluorescent technics after 6 to 42 days of illness. Fluorescein-conjugated rabbit anti-human IgG, IgM, IgA and B1A–1C sera produced no staining; antifibrinogen serum produced intense smooth staining along capillary walls and diffuse staining in cytoplasm of endothelial and mesangial cells. The thrombocytopenia responded to heparinization in 6 patients; in 3, heparinization was discontinued prematurely—in each, platelet counts fell and rose again coincident with cessation and reinstitution of heparin therapy.

Seven infants 50 mm Hg in 100% O2, were candidates for mechanical ventilation and had probabilities of survival from 0–0.3 [STAHLMAN et al., New Engl. J. Med. 276: 303, 1967]. After application of CPAP up to 12 mm Hg, PaO2 rose at once in all. In 6/7 adequate oxygenation was maintained by CPAP until recovery; 1 died of IRDS despite use of CPAP and subsequent mechanical ventilation. The effect of CPAP on PaO2 was measured in the 7 infants and on 30/31 occasions PaO2 rose 10–300 mm Hg within 5 min. There were no consistent changes in arterial CO2 tension or pH. Aortic blood pressure was measured in all infants. Application of CPAP never caused narrowing of pulse pressure or fall in mean aortic pressure (Pao) but resulted in a rise in Pao in 8/20 occasions. In 3 infants serial measurements of the effects of CPAP on heart and respiratory rates, tidal volume, esophageal pressure and dynamic compliance, made on 9 occasions, showed no consistent changes. Less than 20% of the CPAP was transmitted to the intrathoracic space (by esophageal pressure). CPAP results in improved oxygenation in severe IRDS without mechanical ventilation, and without adverse effects on arterial CO2 tension, acid base or cardiovascular status or survival. (Supported in part by HEO 6285.)

Dr. Anderson has questioned our study on two counts. He asked whether the infants in our study could be considered normal when normality was based oniy on physical examination, hematocrit, and arterial blood gases and pH. This is an important point, but we think it is adequately covered in the Discussion section of our report. He also questioned whether the indications for umbilical arterial catheterization in some infants were valid in view of the potential hazards associated with the procedure.

We performed spectrophotometric analyses (technique of Liley) on 595 amniotic fluid specimens from 310 Rh-sensitized women; 1 or more specimens from 84 women had concentrations of pigment above levels which are generally considered to predict, with 95 % confidence, intrauterine death before 34 weeks gestation; 30 of these 84 fetuses were not transfused and 18 were liveborn (gest. age 34 weeks, SD 1.9,) of whom 9 (30 %) survived. We transfused 54 infants in utero (IUT) on 96 occasions. Of these, 25 had marked ascites at the time of transfusion: 13 died in utero, within 48 h of the procedure; 11 were born alive (gest. age 32.2 weeks, SD 2.1), were hydropic and died of the respiratory distress syndrome (RDS) in the neonatal period; 1 (4 %) was not hydropic at birth and survived. 29 did not have ascites at the time of transfusion: 13 died in utero, 12 within 48 h of the procedure; 6 were borne alive (gest. age 33 weeks; SD 1.3) and were hydropic, of whom 4 survived and 2 died with RDS; 10 were born alive (gest. age 34.6 weeks, SD 1.6) without hydrops, 1 died with RDS and 9 survived (45 %). We conclude that serial spectrophotometric analysis of amniotic fluid is required to adequately establish the need for IUT since single or paired analyses may be misleading, and that an intrauterine transfusion, particularly in an infant with ascites or performed earlier than 26 weeks gestation carriers a high mortality. (Supported by USPHS Grant HE-06285) (APS)

To determine if hypoxia has a direct effect on pulmonary microvascular fluid and protein transfer, we measured steady-state lung lymph flow (Qlym) and protein transport (Qprot) in 7 unanesthetized sheep breathing 10% O2 in N2 for 4 hr and in 2 sheep breathing the same gas for 48 hr. We surgically prepared the animals to isolate and collect lung lymph and to measure mean pulmonary artery (Ppa) and left atrial (Pla) pressures. After recovery, the sheep breathed air through a tracheostomy for 2-4 hr, followed by 4 or 48 hr of hypoxia. In 12 4-hr studies, mean PaO2 fell from 97 to 38 torr; Ppa rose from 20 to 33 cmH2O; Qlym and Qprot were unchanged. During 48 hr hypoxia, with a sustained elevation in Ppa and a decline in Pla, Qlym and Qprot diminished progressively, with a decrease in the lymph-plasma protein ratio (L/P) from 0.70 to 0.60. We conclude that 4 hr of severe hypoxia did not increase lung fluid filtration or protein permeability, a finding supported by normal post-mortem histology and a mean extravascular lung water content of 4.27 ml/g dry bloodless lung. The decreased Qlym, Qprot and L/P during prolonged hypoxia are unexplained, but indicate that no increase in vascular permeability to plasma proteins occurred. [Supported in part by HL14201 (SCOR).]

This scientific history of Rh-isoimmune hemolytic disease deals with a clinical disease that is packed with emotion and a series of discoveries that progress from initial delineation of the disease through development of a successful treatment to a simple method of prevention, all within a period of just two generations. Mr. Zimmerman tells the story nicely by orienting all the earlier history around the final series of investigations in the 1960s that produced effective prophylaxis. At that time, a group in Liverpool, England, led by Drs. Finn and Clarke, and a group in New York City, Drs. Freda, Gorman, and Pollack, independently developed the concept of using anti-Rh antibody injections to prevent sensitization of Rh-negative mothers. The English workers arrived at the idea from the "basic science" approach, when the studies they were doing to answer purely genetic questions produced the clue that led them to this idea. The American

We studied effects of intra-uterine asphyxia on neonatal blood volume in 11 fetal lambs (gestational age 130-147 days, birth weight 2.65-4.71 kg) with the ewes under spinal anesthesia. Fetal and maternal blood gases, pH and blood pressures were measured. We determined feto-placental red blood cell volumes (RBCV) with Cr51 tagged red cells and plasma volumes (PV) with I125 albumin. In 6 animals varying degrees of asphyxia were produced by maternal hypotension caused by hemorrhage; in 5 no attempt was made to cause fetal asphyxia. The lambs were delivered; umbilical cords were clamped before the first breath. Ranges of fetal hind limb arterial blood gases and pH at birth were oxygen tension (Po2) 9-24 mmHg, pH 6.98-7.41, carbon dioxide tension (Pco2 34-70mmHg. After resuscitation, neonatal RBCV and PV were measured with a second injection of the same labels. We expressed neonatal blood volumes both as ml/kg and % of feto-placental volumes (%FP). Neonatal RBCV and PV (ml/kg) correlated closely with birth weight (p