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Our aim was to examine changes from normal in the composition of amniotic fluid in fetal lambs with mild and severe hypoxemia and intrauterine growth restriction.Pregnant sheep underwent maternal catheterization at 88 to 93 days' gestation and fetal catheterization at 105-112 days' gestation. Twelve pregnancies (group 1) provided control data (fetal PaO 2 18-22 mm Hg), in 12 fetuses (group 2) mild hypoxemia (PaO 2 16-19 mm Hg) was induced by prevention of the normal expansion of maternal blood volume, and in 7 fetuses (group 3) chronic hypoxemia (PaO 2 12-18 mm Hg) developed spontaneously.In group 2 amniotic fluid osmolality and sodium concentrations were lower (approximately 30 mOsm/kg and 10 mEq/L, P.05) and urea nitrogen level was higher (10 mg/dL, P.05) than in group 1. In group 3 osmolality and sodium concentrations at approximately 120 days' gestation were similar to those in group 1. Whereas these values decreased with gestation in groups 1 and 2 (P.05), they remained unchanged or increased in all fetuses in group 3. Mortality rates in groups 1, 2, and 3 were 1 of 12, 4 of 12 (difference not significant), and 5 of 7 (P.05), respectively.Absence of normal decrease in amniotic fluid osmolality with gestation, in association with a high perinatal mortality rate, was found in severely but not in mildly hypoxemic fetuses with intrauterine growth restriction.

Thirty-four infants who had a diagnosis of severe persistent pulmonary hypertension of the newborn at birth (alveolar-arterial oxygen difference greater than 600) were treated without paralysis or hyperventilation to induce alkalosis. All survived. Twenty-seven of these 34 eligible infants (79%) underwent neurologic, intelligence, and audiologic testing between 10 months and 6 years of age. Children who were younger than 1 year of age at the initial hearing test were retested after they reached 2 years of age. The average IQ was within the normal range (mean = 96.23). None had sensorineural hearing loss. Severe neurologic abnormalities were seen in 4 children, 3 of whom had been severely asphyxiated at birth (determined by biochemical criteria). Mild neurologic abnormalities were observed in 5 children. Two infants had bronchopulmonary dysplasia because they required supplemental oxygen for 29 and 66 days, respectively, and had abnormal chest roentgenograms; 1 patient takes intermittent doses of albuterol (Ventolin) and neither currently requires supplemental oxygen. This study of 27 infants with severe persistent pulmonary hypertension of the newborn suggests that conservative management without induced alkalosis or respiratory paralysis is accompanied by no sensorineural hearing loss and a good neurologic outcome.

(1991). Defining the Sudden Infant Death Syndrome (Sids): Deliberations of an Expert Panel Convened by the National Institute of Child Health and Human Development. Pediatric Pathology: Vol. 11, No. 5, pp. 677-684.

A multicenter, prospective randomized controlled trial was performed comparing the efficacy of a single intratracheal dose of modified bovine surfactant extract (Survanta, 100 mg/kg, Abbott Laboratory, North Chicago, IL) with air placebo in preventing respiratory distress syndrome. Infants were enrolled if they were estimated to be between 24 and 30 weeks' gestation, weighed between 750 and 1250 g, and were intubated and stabilized within 15 minutes after birth. A total of 160 infants were treated (79 with surfactant, 81 with air placebo) between 4 and 37 minutes after birth (median time 12 minutes). Of these, 5 infants were excluded from the final analysis. The 72-hour average values for the arterial-alveolar oxygen ratio, fraction of inspired oxygen, and mean airway pressure were calculated from the area under the curve of scheduled values measured throughout 72 hours. Clinical status was classified using five ordered categories (no supplemental oxygen or assisted ventilation, supplemental oxygen only, continuous positive airway pressure or assisted ventilation with intermittent mandatory ventilation less than or equal to 6 breaths/min, assisted ventilation with intermittent mandatory ventilation greater than 6 breaths/min, death). Chest radiographs at 24 hours were graded for severity of respiratory distress syndrome. Infants receiving Survanta had less severe radiographic changes at 24 hours of age and decreased average fraction of inspired oxygen (31% vs 42%, P = .002) compared with control infants. No differences were noted in the average arterial-alveolar oxygen ratio, mean airway pressure, or clinical status on days 7 and 28. A beneficial effect was noted in the incidence of pneumothorax (P = .057) and an increase was noted in the incidence of necrotizing enterocolitis (P = .052). No differences in incidence of patent ductus arteriosus, intraventricular hemorrhage, sepsis, or bronchopulmonary dysplasia were seen. According to results of a secondary analysis, there was improvement in the fraction of inspired oxygen and a greater number of survivors without bronchopulmonary dysplasia in the subgroup of infants weighing less than 1000 g who were treated with surfactant. It was concluded that a single dose of Survanta given shortly after birth resulted in decreased severity of chest radiographic findings 24 hours after treatment and improved oxygenation during 72 hours after treatment, but did not improve other acute measures of disease severity or clinical status later in the neonatal period. The group at highest risk for respiratory distress syndrome (infants with birth weights between 750 and 999 g) may benefit the most from preventive therapy.

The fluorescence polarization of 116 amniotic fluid specimens obtained from 22 isoimmunized pregnant women was determined. The degree of fluorescence polarization of amniotic fluid provides an index of microvisocity in lipid aggregates that is dependent on the lecithin-to-sphingomyelin ratio and the degree of saturation of fatty acid side chains. We confirmed the reproducibility of the measurement of amniotic fluid microviscosity (coefficient of variation, 2.0%). The measurements are not effected by bilirubin concentration or amniotic fluid dilution. The pattern of change of amniotic fluid microviscosity during gestation parallels the expected development of the surfactant system. Amniotic fluid microviscosity is high during early gestation and abruptly and sequentially decreases between the 28th and 36th week of gestation. Since the measurements are an accurate reflection of the biochemical properties of amniotic fluid lipids and parallel the development of the surfactant system, we conclude that amniotic fluid microviscosity may well serve as an indicator of the process of fetal lung maturation.

A system of instrumentation for continuous measurement of oxygen consumption (VO2), carbon dioxide production (VCO2) and minute ventilation (V1) in human newborns on assisted ventilation is described. VO2 and VCO2 are measured by open-circuit indirect calorimetry utilizing a Servomex OA 184 differential paramagnetic oxygen analyzer and a Beckman LB 2 infrared CO2 analyzer. Minute volume is measured with a body plethysmograph. Bench performance is described, limitations of the system are defined, and sample clinical data are presented. The instrumentation can measure safely, accurately, and continuously physiologic variables in sick infants on assisted ventilation.

Summary: Smoking during pregnancy results in offspring with an average birth weight 200 g less than those of non-smoking mothers. The pathogenesis of this effect is still unknown and there is no general agreement about the causal relationship between maternal smoking and subsequent fetal growth retardation. In the present study, a model of maternal smoking during pregnancy in the rat was established using the P & I Walton Exposure Machine. The study consisted of three groups: control, pair-fed, and smokeexposed. Smoke-exposed animals were exposed continuously to tobacco smoke for cycles of 7 min, 16 times a day from d 5 to d 20 of gestation. On d 21 of gestation, fetuses from all groups were removed by cesarean section, weighed, and dissected. The fetal brain, liver, and lungs as well as the placentas were weighed and analyzed for nucleic acid content. Fetal weight was found to be significantly reduced in both pair-fed and smoke-exposed groups compared with the control group. There was also a significant reduction in fetal body weight of the animals in the smoke-exposed group in comparison to those in the pair-fed group. Exposing the mother to smoke affected neither fetal brain weight nor nucleic acid content whereas fetal liver and lungs showed a significant decrease in both weight and nucleic acid content. These results indicate that the fetal growth retardation associated with maternal exposure to tobacco smoke in the rat corresponds to a disproportionate type. In addition, the present results indicate that the maternal tobacco smoke exposure induced fetal growth retardation without placental growth retardation.

This paper presents an innovative integration of library services and continuing education (CE). While print material is an important continuing education information source for physicians, its volume is overwhelming. Librarians have developed the use of a variety of methods, including online data bases such as MEDLINE, to simplify and expedite access to printed information. Combining a library information delivery system with formal continuing education course activities can enhance the educational potential of two popular learning methods.

We drained amniotic fluid for periods of 5 and 10 days at various times in gestation between days 40 and 55 in the guinea pig (term is 67 days). We analyzed the impact of this procedure on fetal lung growth and used untouched littermate fetuses as controls. During the canalicular stage of lung development, total lung DNA per gram of fetal weight was significantly reduced after only 5 days of oligohydramnios and the percent change did not vary between the two consecutive 5-day periods studied (period A, days 40 to 45, delta of -0.047 mg, p = 0.004; period B, days 45 to 50, delta of -0.042 mg, p = 0.002). The impact of the same duration of oligohydramnios on lung growth later in gestation, during the terminal sac stage of lung development, was less (period C, days 50 to 55, delta of -0.027 mg, p = 0.097). This reduction in effect between period A or B and C was significant at the 0.05 level using a one-way analysis of variance. Two overlapping 10-day periods were also studied. In both experiments, the percent changes in lung DNA per gram of fetal weight between experimental and littermate controls were significant (period D, days 40 to 50, delta of -0.072 mg, p = 0.001; period E, days 45 to 55, delta of -0.047 mg, p = 0.001). The inhibitory effect of oligohydramnios on lung growth was more marked in period D than E (significant at the 0.05 level).(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship between concentrations of vasopressin in plasma and cerebrospinal fluid (CSF) was examined under basal and hypoxic conditions in unanesthetized and unrestrained adult female sheep. Under basal conditions mean (+/- SE) concentration of vasopressin (4.1 +/- 0.3 pg/ml) in CSF was significantly (p less than 0.001) higher than the concentration in arterial plasma (2.4 +/- 0.2 pg/ml). There was a significant positive correlation between CSF and plasma vasopressin concentrations (r = 0.66, p less than 0.01). The introduction of severe hypoxia by exposure of the sheep to an inspired gas mixture of 5% O2 in N2, a known stimulus to systemic release of vasopressin, was associated with an increase in the concentration of vasopressin in plasma to 339 +/- 65 pg/ml and CSF to 19 +/- 3.9 pg/ml. This increase of vasopressin in CSF was delayed in time with respect to the increases in the plasma and of a lesser magnitude. With moderate hypoxia (10% O2 in N2 exposure) no increase in CSF or plasma vasopressin concentration was observed, suggesting a threshold response. Intravenous infusion of vasopressin to achieve plasma values comparable to those seen with hypoxia was not accompanied by a significant increase in CSF vasopressin concentration. Thus, severe hypoxia is a potent stimulus for release of vasopressin into both CSF and plasma. Furthermore, data suggest that vasopressin may be released into CSF via a separate route from that released into plasma.

Gentamicin absorption was measured after oral administration in 18 neonates treated prophylactically in an attempt to decrease the incidence of necrotizing enterocolitis. Patients were given 10 mg/kg/day in four divided doses via nasogastric tube for a total of 10 days. Levels were assayed using the Emit system. Serum levels ranged between 0 and 2.2 micrograms/ml. Mean levels over 10 days were 0.42 +/- (SD) 0.47 micrograms/ml and did not vary significantly from day to day. From these data we conclude that enterally administered gentamicin is not absorbed to a degree that would result in toxic or even therapeutic serum concentrations.

Hypoxia is a potent stimulus to the release of vasopressin in fetal sheep, and plasma concentrations of the hormone correlate inversely with fetal oxygenation. Since the fetal kidney contributes to vasopressin clearance, we propose that measurement of increased amounts of vasopressin in amniotic fluid would be indicative of fetal hypoxia. Therefore, we measured concentrations of vasopressin in amniotic fluid under resting conditions, during and after fetal hypoxia, and with intravenous and intra-amniotic administration of vasopressin in 15 chronically instrumented fetal lambs between 111 and 141 days gestation. In the resting state, mean (+/- SE) vasopressin concentrations in amniotic fluid (1.6 +/- 0.3 pg ml-1) did not differ from those in maternal (1.4 +/- 0.4 pg ml-1) or fetal (1.8 +/- 0.2 pg ml-1) plasma. Following exposure of the ewe to 10% O2 or partial occlusion of the umbilical cord, vasopressin concentrations in fetal plasma increased significantly (P less than 0.001) to 200 +/- 59 pg ml-1 with a delayed increase in amniotic fluid concentrations (P less than 0.03) to 15.8 +/- 4.5 pg ml-1. This rise in concentration of vasopressin in amniotic fluid was sustained for at least 24 h and levels at that time were highly correlated with peak plasma concentrations (r = 0.83; P less than 0.001). Intravenous infusion of vasopressin into the fetus was accompanied by an equally significant (P less than 0.02) and sustained increase of vasopressin in amniotic fluid. Following intra-amniotic injection of vasopressin, levels remained increased for at least 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

In a prospective study of maternal genital colonization with group B streptococci (GBS) at the time of delivery, epidemiological data, including blood type (ABO group), were recorded for the 1,062 patients studied. Blood type B was found in a statistically significant higher proportion of patients colonized with CBS (28%) compared with the total population (16.4%) (P < .005, x2 = 8.43). Women with blood type B were twice as likely to be colonized as those with types 0 or A. Hypotheses to explain this observation include the possibilities that GBS possess a B-like antigen, rendering parturients who lack anti-B antibody at increased risk for GBS colonization, or that GBS possess a receptor site for B surface antigens. One may speculate that a mutation toward an affinity for the human ABO blood group type B accounts for the advent of the group B Streptococcus as a significant perinatal pathogen.

The structural development of the fetal guinea pig lung is described and quantified morphometrically in this report. At 35 days gestation the lung is in the pseudoglandular phase of growth, by 40 days it is in the canalicular phase, and at 50 days the saccular growth phase has begun. At term (67 days), the fetal guinea pig lung appears mature. From the beginning of the canalicular to the end of the saccular phases, the correlation coefficient between lung volume and gestational age is +.98, between internal surface area and gestational age is +.94 and between total number of saccules and gestational age is +.97. Internal surface area (ISA) correlates closely with lung volume (r = +.99) and the correlation coefficient between total number of saccules and lung volume is +.98. At term, lung volume is 4.22 ml. ISA is 0.5 M2, and total number of saccules is 253 million. Parenchymal growth is achieved by increases in both number and size of airspaces in the canalicular phase, primarily by increases in number during the early saccular phase and largely by increases in airspace size near term. The total length of parenchymal elastic tissue increases from 223 M at 45 days gestation to 5,253 M at term. Elastic tissue fibers first appear in the parenchyma of the fetal guinea pig lung during the canalicular phase, when the rate of saccule formation is high. The quantitative increase in elastic tissue correlates closely with the increase in the total number of saccules from day 45 to day 60 of gestation (r = +.99). The rate of elastic tissue growth increases sharply in the late saccular phase, coinciding with the period of greatest saccular expansion. These data suggest an interdependent relationship between saccular growth, i.e., proliferation and expansion, and the development of lung parenchymal elastic tissue.

The successful management of 15 infants suffering from persistence of fetal pulmonary circulation and in severe respiratory failure is presented. The treatment regimen focused on minimizing barotrauma. Infants were intubated nasotracheally and ventilated with intermittent mandatory ventilation. Peak inspiratory pressures were determined by the clinical assessment of chest excursion. Ventilator settings and fractional inspiratory oxygen (FiO2) were selected to maintain a PaO2 between 50 and 70 mm Hg; PaCO2 was not a controlling parameter and was allowed to increase as high as 60 mm Hg. Hyperventilation and muscle relaxants were not used. High ventilator rate was used in ten infants who required high inspiratory pressure to maintain chest excursion, with a favorable response in five. Tolazoline was given to 14 infants of whom ten showed an improvement in oxygenation; dopamine was given to three infants who were oliguric. All infants survived, and only one infant developed chronic lung disease which was defined by the infant's need for supplemental oxygen beyond 30 days of life.

Marked elevations in the vasopressin concentrations in human umbilical cord blood have been reported previously (4, 8). This could either be a part of generalized increase in the activity of fetal endocrine system at the time of birth, a phenomenon that has led to the concept of fetal participation in the onset of labor, or simply due to the stress of delivery. The present study is an attempt to examine the later possibility. Plasma vasopressin was determined by radioimmunoassay [9] in separately collected arterial and venous blood from the umbilical cords of 24 babies spontaneously delivered and 14 babies born after Caesarian Section in the absence of labor. Arterial acid-base determinations were done in each case. The Apgar Score was evaluated by one individual. In order to obtain a general idea of circulating concentration of this hormone in the neonatal period, vasopressin concentrations were determined in the systemic venous blood of 12 normal and 10 stressed babies. Vasopressin concentrations in the umbilical arterial blood of babies born after spontaneous delivery were remarkably high, as compared to all the other groups. Despite a wide range, between 5-2200 pg/ml, there was no correlation between the magnitude of vasopressin elevation and the severity of fetal asphyxia (Fig. 1). The present finding in part, confirms and expands previously observed increased vasopressin levels in the cord blood after spontaneous vaginal delivery. In addition, a lack of correlation between fetal asphyxia and the vasopressin levels suggests that these high levels may not be related to this form of stress.

Response of the fetal kidney to metabolic acidosis was studied in five fetal lambs, 115-125 days gestation, in order to evaluate the renal contribution to elimination of hydrogen ion during intra-uterine development. Experiments were conducted on healthy unanesthetized fetuses, intact in utero, with catheters implanted at hysterotomy into a fetal femoral artery and vein and into the bladder via the urachus, four or more days prior to the study. A metabolic acidosis was induced by infusion of isotonic lactic acid, 15 m mole/kg, intravenously over a period of 90 minutes. Serial arterial samples were taken and urine collected in fractions before, during and for three hours following the infusion, for measurements of pH, bicarbonate, lactate and electrolytes as well as urine output. During the infusion, urine pH fell from 6.65 to 6.25 and was 6.34 three hours later (Figs. 1 to 4, Tabs. III to IV). Lactic acid infusion caused a prompt increase in urine output from a mean rate of 0.12 to a maximum of 0.28 ml/kg/min at the end of the infusion, returning to control rates three hours later. Lactate excretion increased from 0.05 to a maximum of 4.6 mumole/kg/min at the end of infusion; titratable acid increased from 0.22 to a maximum of 4 muEq/kg/min; the rates of excretion of lactate and titratable acid were still higher than control at the end of three hours. Ammonia excretion increased from 0.21 to a maximum of 0.56 muEq/kg/min three hours after the end of infusion. The acid infusion caused a small but significant fall in excretion of bicarbonate. During the 90 minutes of infusion and over the following three hours, about 800 mumole lactate was excreted while net acid excretion over the same period was no more than half that amount. The diuresis was also accompanied by a net loss of sodium and chloride, the excretion of these ions increasing more than threefold following acid infusion; excretion of potassium decreased to one-third its rate prior to the infusion. During the 90 minutes of infusion, blood pH fell from 7.36 to 7.13, base deficit rose from 3.8 to 16.4 mEq/L and lactate rose from 2.2 to 14.8 mM/L; there was also a small but significant rise in both blood PCO2 and PO2 (Figs. 1 to 2, Tabs. I to II). During the following three hours of recovery, pH rose gradually to 7.29, base deficit and lactate fell to 7.4 mEq/L and 8.7 mM/L respectively. Since renal excretion of net acid and lactate was small, the decrease in blood base deficit and lactate levels during the recovery must therefore be mainly due to equilibration in various fetal compartments as well as placental transfer. These experiments indicate that, in the lamb fetus, intact in utero, the kidney although limited by immaturity of several mechanisms, is capable of responding to an acid load and thus can make a small contribution to fetal homeostasis. The increase in excretion of net acid is accompanied by loss of sodium and chloride in the urine.

The role of vasopressin (VP) and the kidney in the maintenance of solute and volume homeostasis was studied in chronically instrumented fetal lambs during the third trimester. Plasma VP, urine and plasma osmolality, and urine output were measured in 74 simultaneous samples. The results show a strong positive nonlinear correlation between plasma VP and osmolality when a latter is higher than 290 mosmol/kg (r = 0.803, P = 0.03) and between plasma VP and urine osmolality (r = 0.806, P = 0.05). No correlation was found between fetal and maternal plasma VP. However, linear correlations were found in plasma osmolality and sodium concentrations between mother and fetus; mean maternal-fetal gradients were 4 mosmol/kg and 3.1 meq/liter, respectively. The highest values for plasma VP and osmolality found in our study were 7.0 pg/ml and 317 mosmol/kg, respectively. There values corresponded to urine output of 0.02 ml.kg-1.min-1 and osmolality of 517 mosmol/kg. In conclusion, there studies demonstrate that the relationship among plasma osmolality, plasma vasopressin concentration, and urine osmolality in the lamb fetus are qualitatively similar to those of the adult. The results suggest that the fetal neurohypophysis and kidney may participate in the maintenance of fetal osmolar and volume homeostasis.

Summary: Continuous measurements of minute ventilation (vI), oxygen consumption (vO2), heart rate (HR), activity, and temperature were made in eleven low birth weight infants during the interval between feedings. Significant increases in vI, vO2, and HR were noted between quiet and active sleep. (vI Active − vI Quiet/vI Quiet) × 100 = 18.4% vO2 Active − vO2 Quiet/vO2 Quiet) × 100 = 10.1% and HRActive − HRQuiet/HRQuiet) × 100 = 6.4%. Significant differences were also noted within epochs of the same state of sleep: mean slope vI versus time in epoch (t) = −156 ml/kg·min/hr, vO2 versus t. = 1.49 ml/kg·min/hr and HR versus t = −15.0 beats/min/hr. Differences between successive epochs of the same state of sleep were also observed: vI, +5.9 to 46.6%; vO2, 4.7 to 24.6%; HR, 1.0 to 9.7%. These differences were related to the length of time after feeding. These data indicate that steady state conditions do not occur in growing low birth weight infants and that the design of studies of respiration and metabolism in these infants should include continuous assessment of the state of sleep or activity and time after feeding to ensure that experimental and control periods are truly comparable. Speculation: The significant variability in minute ventilation, oxygen consumption, and heart rate which occurs spontaneously in low birth weight infants secondary to changes in activity and postprandial interval must be acknowledged in the design of clinical research. It is probable that these factors influence not only mean levels of metabolic and respiratory activity but also the sensitivity to experimental stimuli such as hypoxia, hypercarbia, and drugs.

An automated method for detecting fetal breathing and an analytic technique for providing significant data reduction that take the episodic nature of fetal breathing activity into account are described. The aim of the new technique, called epoch analysis, is to derive parameters of breathing and apnea that both summarize the activity and permit examination of its relationship to changes that occur naturally during day and night and with fetal maturation. The discussion covers: the acquisition of data from pregnant baboons; the breath detection process, for which a program was written; the recognition of breathing; computer recognition of artifacts; epoch characterization; validation of the methods of breath detection and epoch characterization; and application of the method. It is found that the technique has a broad capacity for data reduction and provides summaries of the activity that are amenable to analysis with standard statistical techniques. >

The ductus arteriosus may appear as a left mediastinal mass, the "ductus bump," on chest roentgenograms of the newborn infant. "Airblock" (pneumomediastinum) accentuates the findings. The current knowledge of the first day of life hemodynamic adjustments is reviewed, including catheterization and cine-angiographic studies. These lead to the conclusion that the ductus bump is a "normal" mass, transient and physiologic, presenting on chest roentgenogram of infants in the first day of life.

SUMMARY The absorption of oxygen from the gastro-intestinal tract was studied in nine asphyxiated and 20 normal infants. There was no evidence of transfer of detectable amounts of oxygen from the gastrointestinal tract to the systemic blood in the asphyxiated group when absorption from the lungs was pathologically impaired or prevented by occlusion of an endotracheal tube. High oxygen levels were promptly achieved when pulmonary ventilation was instituted. Relatively high levels of oxygen in the portal venous blood of normal infants breathing room air could not be attributed to added absorption from the gut since similar values were seen when intragastric nitrous oxide was given. The technique of administering gas into the stomach is not a benign procedure and carries definite dangers. It cannot be considered of any value for resuscitation, nor as an additional source of oxygen for the sick infant.

The effect of pentobarbital, given to the mother, on maternal and fetal blood gas tensions was examined. Pentobarbital anesthesia reduced the rate of acid accumulation during asphyxia in fetal monkeys, increased the duration of primary apnea and of gasping, accelerated the establishment of rhythmic breathing on resuscitation, and reduced the incidence and severity of permanent brain damage assessed by histologic examination.

1. 1. The method of closed chest cardiac resuscitation was used in 5 full-term newborn infants for periods ranging from 6 minutes to 2½ hours. In the case in which direct measurements were made, it was found to be effective in producing adequate blood pressures and improvement of the electrocardiographic patterns without inadvertent trauma to the bony structures or viscera. 2. 2. The one permanent survivor, at 16 months of age, is healthy, developing normally, and has no demonstrable neurological sequelae. The other infants had been exposed to either severe asphyxia in utero or prolonged delays in instituting the cardiac massage. 3. 3. The prime advantages of this technique to the newborn infant are the ease with which it can be instituted and the avoidance of a thoracotomy. 4. 4. The initial results with this method of cardiac resuscitation are encouraging and warrant further serious consideration and investigation.

Newborn infants lose heat rapidly at birth and during the first half hour of life. This investigation was undertaken to determine whether the initial heat loss was due principally to evaporation, and whether or not establishment of breathing would be irregular or delayed if the initial cold stress was reduced. Five groups, each of 10 infants, were studied during the first half hour of life. Infants in Groups I and IV remained wet and were exposed to either room air or placed under a radiant heater. Those in Groups II, III, and V were dried promptly and exposed to room air, wrapped in a blanket or warmed by means of a radiant heater. Heat loss due to radiation and convection together was twice that from evaporation. Reduction of cold stress by placing the infant under a radiant heater as soon as he is born does not impede or delay the onset of breathing. Wet infants exposed to room air lost nearly five times more heat than those who were dried and warmed. In vigorous infants, the simple maneuver of drying and wrapping in a warm blanket is almost as effective in diminishing heat loss as placing them under a radiant heater. However, in depressed or immature infants who may be more asphyxiated or have reduced energy stores, radiant heat maintains body temperature while allowing access to the patient.

Thirty-three mature infants became ill in the neonatal period after suffering undue asphyxiation at birth. Dyspnea was a prominent symptom. Nineteen died and 14 recovered. The transverse diameter of the cardiac silhouette in most cases was greater than the average in healthy infants. The progressively increasing size of the heart between 1) healthy infants, 2) those who appeared healthy, but had suffered undue asphyxiation at birth, and 3) those in whom signs of illness developed after asphyxia, indicated that the illness and cardiac enlargement were related. Dilatation rather than hypertrophy was the likely cause of the greater roentgenographic size. This was most obvious on the right. There was also evidence suggestive of left ventricular dilatation. The size of the heart diminished as the infants recovered. In three infants who died serial films showed that enlargement remained or increased, and hypertrophy of both ventricles was present at necropsy in the one who survived the longest time. Roentgenographic changes in the lungs did not correlate well with either the signs of illness or with the presence of cardiac enlargement. The possibility existed that vascular congestion and transudation could be responsible for abnormal appearances in the lungs, when these were present. Biochemical changes resulting from severe asphyxia were observed soon after birth in four cases, and their presence in the others at this time was inferred from the depressed state of the infant as judged by the Apgar score. The quick recovery of the deranged acid base status which occurs after normal birth was not seen in most of the patients. Exceptions were those in whom the illness was brief. The abnormal biochemical status was characterized by arterial hypoxia and metabolic acidosis. The partial pressure of arterial carbon dioxide was distributed over a wide range. These findings are compatible with the presence of left ventricular failure. The left atrial pressure was high in comparison with that of healthy newborn infants. Venous pressure was also increased on the right. Consideration of the results of the three different kinds of investigation led to the suggestion that left ventricular failure occurred early in the illness. Disproportion between different signs in individual cases might have been related to attempted compensation by the heart and to the rate at which failure of the right heart might follow, as well as to the severity of the illness and the rate of recovery. While atelectasis and infection may have been present, there was evidence that heart failure could be the explanation of dyspnea in life and pulmonary vascular congestion at necropsy. The cause of failure is not known. It is related to the metabolic disorder from undue birth asphyxia. A disturbance in hemodynamics that requires more investigation is present.

In a prospective study of colonization with group B streptococci (GBS) among 6,706 parturients, we found statistically increased incidences of premature rupture of membranes (PROM) and preterm delivery at less than 32 weeks' gestation among women colonized with GBS. PROM occurred in 8.1% of the total population but in 15.3% of the colonized population (p less than 0.005). Preterm delivery at less than 32 weeks' gestation occurred in 1.8% of the total population but among 5.4% of women colonized with GBS (p less than 0.005). The data suggest a causal relationship between GBS colonization and events leading to preterm birth. The possible impact of eradication of colonization with GBS on prematurity is considered.

The fluorescence polarization of 116 amniotic fluid specimens obtained from 22 isoimmunized pregnant women was determined. The degree of fluorescence polarization of amniotic fluid provides an index of microvisocity in lipid aggregates that is dependent on the lecithin-to-sphingomyelin ratio and the degree of saturation of fatty acid side chains. We confirmed the reproducibility of the measurement of amniotic fluid microviscosity (coefficient of variation, 2.0%). The measurements are not effected by bilirubin concentration of amniotic fluid dilution. The pattern of change of amniotic fluid microviscosity during gestation parallels the expected development of the surfactant system. Amniotic fluid microviscosity is high during early gestation and abruptly and sequentially decreases between the 28th and 36th week of gestation. Since the measurements are an accurate reflection of the biochemical properties of amniotic fluid lipids and parallel the development of the surfactant system, we conclude that amniotic fluid microviscosity may well serve as an indicator of the process of fetal lung maturation.

We designed and validated a system for determining the state of sleep or wakefulness in both term and preterm infants. The system is based on independent assessments of behavioral and electroencephalographic (EEG) patterns. Overall agreement between observers in coding individual behavioral patterns was 77.6%. Agreement between observers in coding EEG patterns was 87.4%. Designation of an infant's state is made by combining concurrent behavioral and EEG scores into a single two-number code. The distribution of sleep state for eight infants greater than 36 wk postconceptional age (PCA) was the following: quiet sleep (QS), 30.4%; active sleep (AS), 50.0%; indeterminate sleep (IS), 11.4%, and wakefulness (W), 7.5%. The distribution of sleep state for 15 infants less than 36 wk PCA was as follows: QS, 18.9%; AS, 52.9%; IS, 16.4%; and W, 10.5%. Our experience with the system suggests that it is useful for relating sleep state to physiologic variables during neonatal experimental studies.

Renal function was studied serially in 17 healthy term infants during the hours immediately following birth. Of 14 infants delivered vaginally eight received placental blood transfusion and six did not. The remaining three infants were delivered by cesarean section and received placental blood transfusion. Results indicate that the general pattern of change in urine output (V), clearance of inulin (CIN), and p-aminohippuric acid (CPAH), was similar in all infants despite a wide range in each of the functions measured. The pattern showed an initial increase in V, CIN, and CPAH followed by a decline to low values in all infants by 3 hours of age. Urine osmolality and output generally changed in opposite directions. During the first hour the values for V ranged from 0.02 to 0.47 ml/min; for CIN, from 0.5 to 9.1 ml/min; for CPAH, from 1.4 to 21.8 ml/min; and for osmolality, from 98 to 457 mOsm/kg. By 4 hours of age the values for V ranged from 0.01 to 0.15 ml/min; for CIN, from 0.8 to 3.7 ml/min; for CPAH, from 0.8 to 7.5 ml/min; and for osmolality, from 240 to 520 mOsm/kg. The initial values of V, CIN, and CPAH, as well as the changes, were greatest in those infants who received a placental transfusion; however, there were no statistical differences among the means of the various groups. By 4 hours of age, the range of values observed in the initial measurement was much less pronounced. This probably reflects the achievement of stability of renal circulation following adaptation to a variety of stresses during the intrapartum period.

The effects of terbutaline on the mother and fetus were evaluated in 8 near-term pregnant baboons. Significant suppression of postoperative spontaneous and oxytocin-augmented uterine activity was achieved with infusion rates of 0.36 and 0.56 microgram/kg/min, respectively. Maternal and fetal blood pressure and acid-base states as well as fetal heart rate were unaffected by the administration of terbutaline to the mother, but a mild maternal tachycardia was observed. Both maternal and fetal blood glucose increased during terbutaline infusion. Direct administration of terbutaline to the fetus did not alter the fetal cardiovascular or acid-base state. It is concluded that in the baboon, terbutaline is an effective tocolytic agent with minimal untoward effects on either mother or fetus.

Diazoxide, a labor inhibiting agent, was administered intravenously at various rates to seven pregnant, near-term sheep to evaluate its effect on cardiovascular and uterine hemodynamics. Uterine blood flow was measured with electromagnetic flow transducers. Rapid administration of diazoxide resulted in a profound maternal tachycardia with hypotension, an increase in uterine vascular resistance, and a significant decrease in uterine blood flow. With slow infusion of the drug, the changes in heart rate and blood pressure were minimized, uterine vascular resistance was decreased, and uterine blood flow was maintained. Therefore, slow infusion appears to be the preferred method for inhibiting labor with diazoxide.

A system of instrumentation for continuous measurement of gaseous metabolism and minute volume (VI) in the human newborn is described. O2 uptake and CO2 production are measured by open-circuit techniques utilizing a Servomex OA184 differential paramagnetic O2 analyzer and a BEckman LB-2 infrared CO2 analyzer. VI is measured with bias-flow pneumotachometry. Bench performance is described, methodological errors are defined, and clinical data are presented. The instrumentation is capable of safe, accurate, and continuous measurement of respiratory and metabolic variables in low-birth-weight infants.

These studies were implemented to assess the relationship between fetal vasopressin secretion and the progression of parturition as well as the contribution of specific stimuli to vasopressin release during labor. In chronically catheterized fetal lamb preparations, labor was induced by infusion of adrenocorticotropin (12.5 mg/kg/hr) to seven fetuses at 130 +/- 1 day of gestation. Before labor, fetal plasma vasopressin concentrations were 2.1 +/- 1.4 pg/ml and remained low (5.3 +/- 3.4 pg/ml) during prodromal and early phases of labor, but rose significantly in the active and expulsive phases (39.6 +/- 27.5 and 173.3 +/- 152.9 pg/ml) to reach peak values at delivery (584.2 +/- 433 pg/ml) and decrease by 30 min after birth (359.8 +/- 90.0 pg/ml). At delivery, fetal plasma vasopressin concentrations were strongly correlated (P less than 0.001) with hormone values obtained during the latter phases of labor. Fetal arterial pH and oxygen tension was inversely correlated with plasma vasopressin (P less than 0.01). No similar correlations were found with arterial PCO2, K, Na, Cl, osmolality, or packed cell volume. Unexpectedly, we observed a significant (P less than 0.001) and progressive decrease in fetal oxygen tension during the induction process. Other characteristics of adrenocorticotropin-induced parturition seemed to mimic those of spontaneous labor.

A tether system, conditioning procedures and surgical techniques were designed to maintain chronic catheters and electrodes in the pregnant baboon and her fetus. The tether system was comprised of a lightweight metal backpack containing catheters and electrodes, couplers, pressure transducers and electrical cabling. The backpack was held snugly in place by shoulder and body straps. A flexible metal tether connected the pack to a ball bearing assembly mounted on the top of the animal's home cage. Attached to the assembly were two infusion pumps, fluid reservoir and slip ring electrical connector. The entire system rotated freely with the movements of the animal; thus, the instrumentation and connectors were secure while access was maintained for continuous physiologic recording and intravascular infusion or intermittent blood sampling with minimal physical restraint. Animals were conditioned to accept the system prior to pregnancy and animals who demonstrated tolerance were bred. An initial group of 10 pregnant animals were sham tethered during pregnancy at 102 +/- 7 days with term gestation estimated at 180 days. Surgical procedures were done at 136 +/- 4 days with placement of catheters in the maternal femoral artery and vein, fetal carotid artery jugular vein and trachea, amniotic fluid cavity, and electrodes for fetal electrocardiogram and electroencephalogram. The mean fetal survival time was 9.3 (range 0 to 29) days. The major complications which led to early delivery were placental abruption and rupture of amniotic membranes. With ultrasonic localization of the placenta and determination of fetal position before surgery, these complications may be avoided.(ABSTRACT TRUNCATED AT 250 WORDS)

A comprehensive computerized perinatal data management system was used to acquire and process FHR data and to link this information to a set of control and outcome variable for 1000 deliveries. Multivariate correlation analyses and stepwise linear regression techniques were used to study the interrelationships between risk factors of pregnancy and labor, monitored data, obstetric interventions, and outcome. It was found that while some FHR characteristics, such as moderate-to-severe bradycardia, lack of beat-to-beat variability, and severe variable decelerations were significantly associated with poor outcome, others, such as accelerations, early decelerations, mild bradycardia, and mild-to-moderate tachycardia, were positively correlated with good outcome. Several statistical models for outcome prediction were developed using FHR data alone and also in conjunction with small subsets of control variables.

The successful management of 15 infants suffering from persistence of fetal pulmonary circulation and in severe respiratory failure is presented. The treatment regimen focused on minimizing barotrauma. Infants were intubated nasotracheally and ventilated with intermittent mandatory ventilation. Peak inspiratory pressures were determined by the clinical assessment of chest excursion. Ventilator settings and fractional inspiratory oxygen (FiO2) were selected to maintain a PaO2 between 50 and 70 mm Hg; PaCO2 was not a controlling parameter and was allowed to increase as high as 60 mm Hg. Hyperventilation and muscle relaxants were not used. High ventilator rate was used in ten infants who required high inspiratory pressure to maintain chest excursion, with a favorable response in five. Tolazoline was given to 14 infants of whom ten showed an improvement in oxygenation; dopamine was given to three infants who were oliguric. All infants survived, and only one infant developed chronic lung disease which was defined by the infant's need for supplemental oxygen beyond 30 days of life.