Systemic and local immune responses to enhanced-potency inactivated poliovirus vaccine in premature and term infants.

Serum neutralizing, nasopharyngeal neutralizing, and IgA antibodies to polioviruses 1, 2, and 3 were detected in preterm and term infants who had received three doses of an enhanced-potency inactivated poliovirus vaccine at 2, 4, and 12 months of age. After the third dose of this vaccine, 95% or more of the infants tested had detectable serum neutralizing antibodies to polioviruses types 1, 2, and 3. Nasopharyngeal neutralizing and IgA antibodies were detected in 43% to 91% of the infants. The peak geometric mean titers of serum and nasopharyngeal antibodies against polioviruses types 1, 2, and 3 were similar for both groups. These preliminary data indicate that preterm infants are capable of mounting systemic and local immune responses to enhanced-potency inactivated poliovirus vaccine that are comparable to those made by term infants.

Use of surfactant in the delivery room.

Surfactant supplementation in prevention and treatment of surfactant deficient hyaline membrane disease has been widely studied. This article focuses on the prevention of HMD by preventilatory, tracheal instillation of surfactant in the delivery room.

Reduced incidence of hyaline membrane disease in extremely premature infants following delay of delivery in mother with preterm labor: use of ritodrine and betamethasone.

Data from two groups of infants (24 to 28 weeks' gestational age) excluded from a controlled trial of the use of calf lung surfactant extract for the prevention of hyaline membrane disease are reported. The two groups were excluded from the trial because the mothers had received betamethasone for greater than 24 hours prior to delivery or because, on admission to the hospital, labor was too far advanced for proper informed consent to enter the trial. Attempts were made to delay delivery of threatened premature labor by the use of ritodrine in all mothers without evidence of infection, heavy vaginal bleeding, or severe preeclampsia and to induce surfactant production by maternal injection of betamethasone. A prospective scoring system and respiratory support variables were used to compare the groups. Infants born to mothers who successfully completed this regimen had a 28% incidence of hyaline membrane disease v a 68% incidence in infants in whose mothers it was unsuccessful due to inability to stop advanced labor (P = .001). Inspired oxygen, mean airway pressure, and ventilator rate were lower and the ventilator efficiency index was higher in the treated group during the first 48 hours of life. An aggressive approach to postpone premature delivery and to induce surfactant production by using tocolysis and a regimen of glucocorticoids reduces the incidence of hyaline membrane disease in very premature infants, 24 to 28 weeks' gestation.

Rabbit tissue composition: developmental aspects of tissue fluid and fractional exclusion of albumin.

The maturational changes in tissue water spaces and in the fractional exclusion of albumin from the interstitial gel were studied in the developing rabbit using multiple radioactive tracers. Total tissue water and extracellular water decrease with age in all organs studied. Intracellular water decreases in the heart and brain, transiently increases in the muscle, and is unchanged in the ileum and lung. However, the percentage of extravascular water located in the cell increases with age in all organs. Fractional exclusion of albumin is unchanged in the muscle and brain, fluctuates in the lung, increases in the ileum, and decreases in the heart. Possible mechanisms for regional differences in fluid and albumin changes with maturation are discussed. Until the role of the fractional exclusion of albumin in the interstitial matrix in the maintenance of tissue fluid balance is elucidated, the physiological impact of these developmental changes will not be evident.

Double-blind clinical trial of calf lung surfactant extract for the prevention of hyaline membrane disease in extremely premature infants.

A prospective, double-blind, controlled trial was conducted to determine whether instillation of an exogenous surfactant into the lungs before the first breath could prevent hyaline membrane disease. The surfactant is calf lung lipid extracted from saline lung lavage. Entry was limited to infants who were 24 to 28 weeks' gestation, who were born at Children's Hospital of Buffalo, and whose mothers had not received betamethasone for more than 24 hours before birth. Treated infants received 3 mL (90 mg) of calf lung surfactant extract instilled into their trachea before the first breath; control infants received 3 mL of normal saline. A prospective scoring system and respiratory support variables were used to compare the groups. At 48 hours of age, only two of 14 calf lung surfactant extract-treated infants (14%) had hyaline membrane disease compared with seven of 13 control infants (54%) (P = .033). Inspired oxygen, mean airway pressure, ventilator rate and ventilator efficiency index were also lower in the treated group during the first 48 hours of life (P less than .01 to P less than .001). Calf lung surfactant extract instillation at birth appears to be an effective material and method of preventing hyaline membrane disease in extremely premature infants.

Lung surfactant replacement in premature lambs with extracted lipids from bovine lung lavage: effects of dose, dispersion technique, and gestational age.

Extracted bovine calf lung lipids (CLL) with minimal protein (approximately 1%) were instilled prior to ventilation in groups of premature lambs of average gestational ages of 127 and 133 days. Aqueous dispersions of CLL were prepared by two techniques prior to instillation: sonication in an ice bath (S) and mechanical vortexing at room temperature (V). A low surfactant dose (15 mg CLL/kg animal weight) and a high dose (100 mg/kg) were investigated for each dispersion technique. Following tracheal instillation of surfactant, lambs were ventilated with 100% oxygen for 2 h with umbilical circulation intact, and for up to an additional 10 h after separation. A clear improvement in blood oxygenation and lung compliance was found over controls for lambs given 15 mg/kg and 100 mg/kg CLL(V), and 100 mg/kg CLL(S). Lambs treated with 15 mg/kg CLL(S) failed to improve over controls. Experimental groups treated with equal doses of CLL(V) and CLL(S) had similar amounts of lung lavage phospholipid, with values progressively declining during ventilation. Analyses of in vitro surface properties showed that both vortexed and sonicated CLL dispersions adsorbed to equilibrium surface pressures of 45-47 dynes/cm in seconds at concentrations greater than or equal to 0.25 mg CLL/ml. Both dispersions also lowered surface tension to less than 1 dyne/cm under dynamic compression at 37 degrees C in 100% humidity, although CLL(V) showed some enhancement over CLL(S) in dynamic surface activity at low subphase concentration (0.5 mg/ml). Moreover, CLL(V) and CLL(S) differed markedly in their effects on pressure-volume mechanics in a surfactant-deficient excised rat lung model. Instilled CLL(V) dispersions improved excised lung pressure-volume mechanics at significantly lower concentrations than CLL(S) dispersions.

Validation of [57Co]cyanocobalamin as an extracellular fluid marker and measurement of albumin exclusion from the interstitium in the rabbit.

The use of [57Co]cyanocobalamin as an extracellular marker has been validated. Its simultaneous use with 51Cr-labeled erythrocytes and 125I-human serum albumin allows quantitative measurement of tissue water and the fractional exclusion of albumin from the interstitial compartment. The extravascular extracellular spaces of rabbit tissue are lung, 32 +/- 4%; heart, 25 +/- 2%; gut, 24 +/- 4%; and muscle, 13 +/- 1%. The fractional excluded albumin spaces are lung, 0.78 +/- 0.05; heart, 0.37 +/- 0.03; gut, 0.69 +/- 0.05; and muscle 0.58 +/- 0.03. The oversimplification that the extravascular extracellular space is a homogeneous region defined by a small tracer molecule and has the composition of lymph must be reconsidered. Albumin has a vastly different distribution in the interstitial spaces of different organs. Use of the three tracers reported here allows efficient measurement of blood volume, interstitial space, and interstitial albumin exclusion in whole tissues and organs, and thus can lead to further understanding of the in vivo changes occurring in various physiologic and disease states.

Avoiding prematurity in elective repeat cesarean section. A role for amniotic fluid phosphatidylglycerol.

A prospective study was undertaken in 107 elective repeat cesarean deliveries in which the lecithin/sphingomyelin (L/S) ratio was positive. The frequency of neonatal complications in 87 of these women having positive amniotic fluid (AF) phosphatidylglycerol (PG) was compared with the frequency in the remaining 20 patients exhibiting a negative PG. Hyaline membrane disease (HMD) did not occur in either group. However, neonatal complications and related clinical procedures were significantly increased in the PG-negative patients. These neonatal complications included increased frequency of admissions to the neonatal intensive care unit, physiologic jaundice, poor feeding, transient tachypnea, prolonged oxygen therapy, arterial blood gas determinations, chest X-ray and placement of a peripheral intravenous line. The cause of this increased frequency in neonatal complications appears to be mild prematurity in patients exhibiting a positive AF L/S with a negative PG. This study suggests that, in hospitals where PG determinations are available, neonatal complications could be reduced further by awaiting the AF PG result before electively performing a repeat cesarean section.

Natural and artificial lung surfactant replacement therapy in premature lambs.

The effect of tracheal instillation of surface-active mixtures in premature lambs was studied as an animal model of exogenous surfactant replacement therapy for the respiratory distress syndrome (RDS). Specific mixtures studied were 7:3 (molar ratio) dipalmitoyl phosphatidylcholine (DPPC):egg phosphatidylglycerol (PG) and extracted mixed lipids (with 1% protein) from cow lung lavage (CLL). Preventilatory tracheal instillation of greater than 15 mg/kg of CLL in 10 ml 0.15 M NaCl to premature lambs gave improved alveolar-arterial O2 gradient and blood gases and increased lung compliance, compared with control lambs over a 15-h period. Lambs receiving 7:3 DPPC:PG dispersions were not improved over controls with regard to pressure-volume characteristics and were worse than controls in arterial oxygenation. In terms of in vitro surface properties, both extracted natural CLL and 7:3 DPPC:egg PG were able to lower aqueous surface tension to 1 dyn/cm under dynamic compression. However, the dynamic respreading of CLL films on successive surface cycles was superior to that of 7:3 DPPC:PG. Moreover, after dispersal in 0.15 M NaCl by vortexing (5 mg/80 ml), CLL adsorbed to surface pressure (tau values of 45 dyn/cm within 10 min. 7:3 DPPC:PG adsorbed to significantly lower tau values after subphase dispersal by a variety of methods.

Transient tachypnea of the newborn: the relationship to preterm delivery and significant neonatal morbidity.

Early studies suggest that transient tachypnea of the newborn is a benign disease of uncertain etiology. Consequently, prevention of this complication has not been a primary concern of obstetricians. In this study of amniotic fluid phospholipids, 55 pregnancies in which the neonate developed transient tachypnea were compared to 355 pregnancies after which respiratory distress did not occur. Thirteen neonatal complications and procedures, often associated with prematurity, were significantly increased in the infants who developed transient tachypnea. Potential risk factors for transient tachypnea were examined by stepwise discriminant analysis. Negative amniotic fluid phosphatidylglycerol, prematurity (less than 38 weeks), and 1-minute Apgar score less than 7 all made an independent contribution to the overall characterization of infants at increased risk for transient tachypnea. These findings suggest that mild fetal lung immaturity may be a factor in the pathophysiology of this syndrome, and that the relationship of perinatal factors associated with transient tachypnea of the newborn in previous studies, including maternal diabetes mellitus and cesarean birth, may be partially mediated through a neonatal surfactant deficiency.

Histidine decarboxylase activity in fetal intrauterine growth-retarded rats.

Fetal intrauterine growth retardation was induced in nine rats at 17 days' gestation by ligating the blood supply to one of the uterine horn. The 27 festuses from the uterine vessel ligated side were the intrauterine growth retarded fetuses (IUGR) and the 37 fetuses from the nonligated side were controls. The mean weight of the IUGR fetuses was 3.4 +/- 0.3 g which was significantly smaller (P less than 0.005) than the mean weight of the control fetuses, 4.0 +/- 0.3 g. Whole body histidine decarboxylase (HDC) activity was assayed by a radioisotope method. The HDC activity per g tissue was not correlated to body weight in the control fetuses. This is in contrast to the IUGR festuses in which the HDC per g tissue was significantly and inversely related to body weight (r - 0.48, P less than 0.001).