Oxytocin stimulates glucagon and insulin secretion in fetal and neonatal sheep.

In adults of several species arginine vasopressin (AVP) and oxytocin (OT) stimulate pancreatic secretion of immunoreactive plasma glucagon (IRG). In fetal sheep AVP is an important stress hormone and may be simultaneously secreted with OT; however, their effects on IRG secretion are not known. We sought to determine if AVP and/or OT affected pancreatic IRG secretion in fetal and neonatal sheep. Either AVP or OT was infused for 30 min in chronically catheterized fetal and neonatal sheep, obtaining peripheral arterial and/or portal venous blood samples before; 10, 15, and 30 min during; and 15, 30, and 60 min after infusion for measurements of blood gases, hematocrit, IRG, immunoreactive plasma insulin (IRI) and plasma glucose. AVP did not affect IRG or IRI in fetal sheep (mean +/- SE, 133 +/- 1 days gestation), but small increases occurred in portal venous blood of lambs (2-49 days old). In contrast, OT (4.6 +/- 0.3 mU/min.kg; n = 12) increased fetal plasma IRG from 72 +/- 5 to 86 +/- 6 and 97 +/- 7 pg/ml (P less than 0.001) and IRI from 16 +/- 2 to 20 +/- 3 and 20 +/- 2 microU/ml (P less than 0.02) at 15 and 30 min, respectively; 157 +/- 11 microU OT/min.kg had no effect. In lambs (2-49 days old), 3.0 mU OT/min.kg increased arterial (n = 15) IRG from 139 +/- 19 to 367 +/- 43 and 483 +/- 76 pg/ml (P less than 0.01) and portal IRG (n = 8) from 167 +/- 39 to 341 +/- 72 and 502 +/- 148 pg/ml (P less than 0.01), respectively. Arterial and portal IRI also rose (P less than 0.01) from 36 +/- 4 to 82 +/- 12 and 105 +/- 32 microU/ml and from 29 +/- 5 to 65 +/- 13 and 51 +/- 7 microU/ml, respectively. Glucose was unchanged in all experiments. In fetal and neonatal sheep, AVP has minimal effects on IRG and IRI release. In contrast, OT increases both substantially; furthermore, there is a difference in fetal and neonatal responsiveness. OT may be important in modulating glucagon and insulin secretion during and after parturition.

Clinical diagnosis and management of respiratory distress in preterm neonates: effect of participation in a controlled trial.

The ability to generalize the results of a clinical trial depends on the ability to compare a population of patients with the population described in the trial, emphasizing the importance of objective diagnostic criteria in study design and clinical medicine. However, clinical decisions are often based on subjective interpretations of data. There is concern that bias that an experimental therapy is beneficial might lead to alterations in clinical diagnosis and management. To evaluate this concern, the authors reviewed a preexisting database comprising information obtained by trained personnel by chart review to investigate prospectively the frequency of the diagnosis of hyaline membrane disease and the use of mechanical ventilation before and during participation in a clinical trial of surfactant therapy during which such therapy was available exclusively through clinical trials. Major eligibility criteria for a randomized trial at the Medical University of South Carolina included mechanical ventilation and the diagnosis of hyaline membrane disease. Both the diagnosis of hyaline membrane disease and the use of mechanical ventilation increased between pre-surfactant and randomized trial periods (hyaline: 47.2% to 55.9%, P less than .05; ventilation: 55.6% to 66.3%, P less than .01). The possibility that enthusiasm for surfactant influenced clinical diagnosis and management of respiratory distress during this period cannot be dismissed.

Neonatal intracranial hemorrhage: I. Changing pattern in inborn low-birth-weight infants.

Many reports of the occurrence of periventricular-intraventricular hemorrhage (PVH-IVH) are biased by the inclusion of both inborn and outborn infants. To obviate this selection bias we examined a large inborn population of low-birth-weight infants to determine if the incidence of PVH-IVH changed over a 3-year interval from March, 1982 through February, 1985. Serial cranial ultrasonography was performed in 463 consecutive infants of birth weight less than or equal to 1500 g who survived for more than 8 h. The incidence of PVH-IVH decreased from 31.5% and 29.3% in years 1 and 2, respectively, to 23.7% in year 3 (P less than 0.05). The latter reflected a fall in the incidence of grades III and IV PVH-IVH, but no change in the incidence of grades I and II. This observation was not attributable to changes in mortality, the distribution of infants by birth weight and estimated gestational age in each year of the study, or infants excluded from the analysis. Contrary to most reports, 21.9% of all PVH-IVH during the 3 years were first diagnosed after 14 days postnatal age and were predominantly grade I. These results document not only a change in the epidemiology of PVH-IVH in an inborn population, but also the importance of serial cranial ultrasonography beyond the first week of life.

Neonatal intracranial hemorrhage: II. Risk factor analysis in an inborn population.

The ability to predict the occurrence of neonatal periventricular-intraventricular hemorrhage (PVH-IVH) would be useful in the design of clinical trials to prevent its occurrence. Therefore, data were collected from 463 consecutive infants less than or equal to 1500 g birth weight delivered between March 1, 1982 and February 28, 1985. This large population made it feasible to divide the infants into two groups, using one group to develop a model predictive of ICH and the second group to test the validity of the model. Infants were randomly grouped by sex, race, gestational age, birth weight, month of birth, mortality, and incidence and grade of worst PVH-IVH. In Group A (n = 232), respiratory distress syndrome, ventilator therapy, PaCO2 greater than or equal to 60 mmHg, PO2 less than or equal to 40 mmHg greater than or equal to 2 h, lower 1- and 5-min Apgar scores, lower pediatric estimation of gestational age, and pneumothorax were significantly associated with PVH-IVH by univariant analyses (chi 2, P less than 0.03). Multivariant discriminant analysis performed on Group A revealed that pneumothorax, cesarean section, PaCO2, and ventilator therapy were most predictive of PVH-IVH, but sensitivity was 55% and specificity 78%. Applying the model to Group B, sensitivity decreased to 21% while specificity rose to 93%. Logistic regression, which takes into account non-normally distributed variables, did not improve predictability.(ABSTRACT TRUNCATED AT 250 WORDS)

Randomized, controlled trial of nasopharyngeal continuous positive airway pressure in the extubation of very low birth weight infants.

We conducted a prospective, randomized controlled trial to determine whether extubation of very low birth weight infants was facilitated by the use of nasopharyngeal continuous positive airway pressure (CPAP). Eligible infants included patients weighing 600 to 1500 gm at birth who required tracheal intubation within 48 hours of birth and who met specific predetermined criteria for extubation by day 14 of life. We also sought to determine whether varying the duration of nasopharyngeal CPAP influenced the likelihood of successful extubation. Infants underwent random assignment to receive nasopharyngeal CPAP until resolution of lung disease (n = 40), 6 hours of nasopharyngeal CPAP (n = 42), or oxygen supplementation delivered by hood (n = 42). Extubation failure was predefined as a requirement for > or = 80% oxygen, pH < or = 7.20, severe apnea, or predefined clinical deterioration, and extubation success was predefined as the ability to remain free of a requirement for mechanical ventilation for 7 days and a 66% reduction in the need for supplemental oxygen. Each group was similar with regard to race, sex, and birth weight. Extubation was successful in 62%, 61%, and 60% of infants. After stratification by birth weight, there were no significant differences in the rates of successful extubation among the treatment groups. We conclude that nasopharyngeal CPAP does not improve the likelihood of successful extubation of very low birth weight infants who are ready for extubation within the first 2 weeks of life.