John W.C. Johnson

Long-term effects of betamethasone on fetal development

In previous studies, we noted that treatment of pregnant rhesus monkeys with betamethasone resulted in a marked increase in fetal lung distensibility. The purpose of the present study was to determine whether these changes persisted during subsequent in utero development. Pregnant rhesus monkeys were treated with 2 mg of betamethasone intramuscularly from day 120 to day 133 and underwent delivery by cesarean section one month later. The treated fetuses were found to have smaller lungs (-31%; p less than 0.005), and lower alveolar stability (-14%; p less than 0.025) than the control fetuses. Additional findings included smaller weights for the brain (p less than 0.01), liver, pancreas, and heart (p less than 0.05). Smaller adrenal (p less than 0.025) and larger pituitary weights (p less than 0.05) and lower plasma corticoid concentrations (p less than 0.001) indicated long-standing adrenal insufficiency in the treated fetuses. These persistent sequelae caution the indiscriminate and prolonged use of these potent glucocorticoids during pregnancy.

The glucose tolerance test as a means of identifying intrauterine growth retardation

The purpose of this prospective, nonconcurrent study was to determine whether maternal hypoglycemia, as measured by a 3-hour glucose tolerance test, is associated with pregnancies resulting in growth-retarded infants. Our results demonstrate that maternal hypoglycemia is significantly associated with intrauterine growth retardation other than the low birth weight type and that the 3-hour glucose tolerance test is an effective early screening test in detecting pregnancies at risk of fetal growth retardation.

Hazards of using hypertonic saline for therapeutic abortion.

Abstract Some of the complications associated with the intrauterine instillation of hypertonic saline, as reported in the literature, are discussed. Two case reports from the experience at The Johns Hopkins Hospital are presented illustrating the possibility of hypotensive and apneic episodes with this procedure. Possible etiologic mechanisms are reviewed based upon published reports as well as recent animal experimentation carried out by 2 of the authors (J. W. C. J. and N. L. S.). The currently employed technique is described, with emphasis on those precautions which would seemingly prevent these complications.

Amniotic fluid oxygen tensions in severe maternal anemia

Abstract In an attempt to determine the role of intrauterine hypoxia in the high incidence of fetal death observed in severe maternal anemia, amniotic fluid oxygen tensions were studied in a group of anemic and nonanemic patients that were 20 to 32 weeks pregnant. A highly significant positive correlation was found between maternal hematocrit values and the oxygen tensions of amniotic fluid. In addition, a high fetal mortality rate was observed in the markedly anemic patients. These results support the theory that in this patient group severe maternal anemia results in intrauterine hypoxia and thus predisposes to fetal death in utero. Theoretical consideration is given to some of the variables affecting amniotic fluid oxygen tension, in addition to the apparent value of 100 per cent oxygen in the emergency treatment of severe anemia.

The relative significance of human placental lactogen in the diagnosis of retarded fetal growth

The purpose of this prospective study was to determine whether serial maternal venous hPL determinations could identify pregnancies resulting in growth-retarded infants from a selected population at presumed high risk for IUGR. Our results demonstrated that mean hPL levels in IUGR outcome pregnancies were significantly lower than normal after 33 weeks gestation. Mean hPL was also lower in some pregnancies resulting in normal-weight neonates with abnormally low PI or short CHL, suggesting that these neonates, despite normal birth weight achievement, may represent previously unsuspected.

Urinary estrogens in postterm pregnancy

A 40-month retrospective review of 677 postterm pregnancies was undertaken to determine the usefulness of 24-hour urinary estrogen per gram of creatinine (E/Cr) in monitoring such pregnancies. The cutoff value between normal and low E/Cr values was chosen at the tenth percentile (18 mg/gm). The corrected perinatal mortality rate (PMR) in post-term pregnancies with normal E/Cr was 0.23% (1/426) and was not different from that at term (0.23%; 4/1,775). However, in post-term pregnancies with low E/Cr, the corrected PMR was 9.2% (4/43), representing a 40-fold increase (P less than 0.001). The incidence of fetal distress was also significantly higher in patients with low E/Cr (57%) than in those with normal E/Cr (5.5%; P less than 0.001). It was worrisome to note that three of four stillborn infants had antepartum fetal heart testing within 4 days, which indicated fetal well-being. The E/Cr appears to be a reliable test for identifying those postterm pregnancies at risk that might benefit from obstetric intervention.

Amniotic fluid absorbance at 650 nm: Its relationship to the lecithin/sphingomyelin ratio and neonatal pulmonary sufficiency☆

In the present study, we sought to assess the clinical efficacy of the optical density of amniotic fluid at 650 nm (A650) to predict lung maturity in the human fetus. The A650 of 113 samples of amniotic fluid obtained from 16 to 45 weeks gestation was determined. Mature values (A650 greater than or equal to 0.11) were not observed until 35 weeks gestation but were always present after 39 weeks gestation. In those infants delivered within 48 hours of amniocentesis, the absence rates of respiratory distress syndrome were the same with a mature lecithin/sphingomyelin (L/S) ratio (97.9%) and a mature A650 (97.3%). However, immature values in both tests were poor prognosticators of respiratory distress syndrome, with a rate of 37.5% with the immature L/S ratio and 15.8% with the immature A650. A mature A650 may be substituted for the L/S ratio, but an immature A650 is less reliable. In addition, we found that differences in centrifugation altered the A650 value, whereas exposure to light and cold storage did not.

Glucocorticoids, hyperinsulinemia, and fetal lung maturation

Glucocorticoids are reported to accelerate fetal lung development, whereas insulin is alleged to interfere with this effect of glucocorticoids. A paradox exists, however, in that glucocorticoids also induce hyperinsulinemia. The purpose of this study was to explore the interrelationships of betamethasone, hyperinsulinemia, and hyperglycemia to fetal lung maturation. In this rhesus preparation, maternal betamethasone administration produced an alarming increase in maternal and fetal plasma insulin values. A significant increase in total lung volumes also occurred, but lung surfactant properties (as measured by amniotic fluid lecithin/sphingomyelin concentrations, lung alveolar deflation stability, and lung phosphatidylcholine concentrations) remained unchanged. These findings are consistent with the following hypotheses: (1) Betamethasone-induced hyperinsulinemia impairs acceleration of surfactant production but does not negate increases in maximum lung volume; (2) betamethasone-induced increases in maximum lung volume occur through mechanisms other than alveolar surfactant alterations.

Respiratory distress in the newborn

Summary Further studies in newborn lambs have demonstrated that the pulmonary instillation of amniotic fluid produces a respiratory disturbance very similar to that previously observed after the instillation of allantoic fluid. These lambs exhibited labored respirations with a high incidence of spontaneous death, and their lungs were found to have elevated surface tensions and microscopic atelectasis. In addition, the fluid-instilled lambs were found to have lungs with increased retractive forces that appeared to be related to elevations in lung extract surface tensions. The possible mechanisms by which excess intraalveolar fluid might produce these changes and their relevance to the respiratory distress syndrome of the human newborn have been discussed.