Methyldopa hepatotoxicity in pregnancy: a case report.

A case of hepatotoxicity in a multiparous Native woman, who was begun on a regimen of methyldopa for control of chronic hypertension, is described. The patient was first seen for clinical evidence of hepatotoxicity approximately 3 weeks after initiation of treatment. At presentation the aspartate aminotransferase level was 1800 IU/L and alanine amniotransferase was 2415 IU/L. There was also a significant prolongation of clotting time, which required therapy. Resolution of symptoms occurred after cessation of the medication. Although methyldopa is considered to have a wide margin of safety in the treatment of chronic hypertension in pregnancy, potentially serious adverse effects can occur. It is important to monitor serum aminotransferase levels after initiation of methyldopa therapy.

The probability of fetal metabolic acidosis during labor in a population at risk as determined by clinical factors.

The clinical data derived from 2,772 pregnancies managed in an intrapartum intensive care unit have been analyzed to establish which criteria will indicate in a more definite manner the probability that fetal metabolic acidosis will occur during labor and delivery. All antepartum and intrapartum clinical factors indicate a pregnancy and fetus with an increased probability of fetal metabolic acidosis. However, there is a remarkably consistent relationship between decreasing fetal weight in each week of gestational age and in increasing probability of fetal metabolic acidosis that will permit the magnitude of the risk to be determined with greater precision. The following clinical guidelines are proposed: (1) Current antepartum and intrapartum risk factors are appropriate for the selection of patients for intrapartum intensive care. (2) An accurate gestational age and an estimate of fetal weight within 200 gm will provide an indication of the probability of fetal metabolic acidosis in the individual fetus ranging from 15% to 50%. (3) The presence of meconium in the amniotic fluid increases the probability of metabolic acidosis as defined by fetal weight in relation to gestational age.

Effects of reduction of placental size in sheep.

The number of uterine caruncles was reduced by electrocautery in nonpregnancy sheep. Subsequent pregnancies were studied as chronic fetal sheep preparations between 110 days' gestation and term; findings were compared with those for control chronic fetal sheep preparations at a similar gestational age. As a result of decreased weight and reduced number of cotyledons, the placenta in experimental animals was significantly smaller compared with that in controls. The weights of the fetal liver and heart were decreased, fetal PO2 was decreased, and fetal PCO2 and hematocrit levels were increased in the experimental group. Fetal plasma fructose levels were decreased in experimental animals, but fetal blood lactate, pyruvate, and plasma glucose levels were similar in both groups. No differences were demonstrated in fetal plasma or amniotic fluid cortisol levels and amniotic fluid lecithin : sphingomyelin ratios. Fetal respiratory-like activity was significantly depressed in the experimental group.

The prediction of intrapartum fetal metabolic acidosis by fetal heart rate monitoring.

Fetal heart rate characteristics during the 8 hours prior to delivery have been studied in 200 patients in whom the fetus had evidence of a metabolic acidosis at delivery, and compared to those in 200 patients in whom the fetus had a normal acid-base at delivery. Baseline fetal heart rate moderate bradycardia and tachycardia, decreased baseline variability, and decreased fetal heart rate accelerations are predictors of intrapartum fetal hypoxia with metabolic acidosis. Marked patterns of total decelerations and late decelerations are predictive of intrapartum fetal hypoxia with metabolic acidosis. The probability of fetal metabolic acidosis in the presence of a marked pattern of total decelerations is 25%, and with late decelerations it is 48%, in a population of high-risk pregnancies.

The effect of maternal, labor, and fetal factors upon fetal heart rate during the intrapartum period.

The effect of maternal labor, and fetal characteristics upon fetal heart rate behavior during the intrapartum period has been studied in 400 patients. Abnormal labor in comparison to normal labor has a higher baseline fetal heart rate with an increased incidence of baseline tachycardia and an increased incidence of absent or decreased baseline variability. A decreasing fetal weight gestational age percentile is associated with an increased incidence of variable decelerations. Segmental epidural and Demerol analgesia carefully administered has little effect upon fetal heart rate behavior.

The clinical prediction of intrauterine growth retardation.

From a total study group of 8,030 deliveries, 2,788 patients with risk factors and 292 representative patients from the 5,242 patients without risk factors were selected for detailed analysis of predictors of intrauterine growth retardation (IUGR). Two thirds of the IUGR infants came from the population with risk factors and a weighting was assigned to individual risk factors. One third of the IUGR infants came from the population without risk factors, and their mothers demonstrated significantly differing maternal characteristics from those with a normally grown infant. The perinatal mortality rate was higher in the IUGR group and particularly in the population with risk factors.

Modification of ovine fetal respiratory-like activity by chronic diazepam administration.

Chronic maternal administration of diazepam resulted in a modification of fetal respiratory-like activity (FRLA) in the sheep. An over-all increase in this activity occurred. This increase was probably due to a rebound effect following periods of acute suppression with each administration of diazepam. Loss of central control in the regulation of FRLA was implied. A complete reversal of a circadian rhythm of FRLA was observed in animals receiving diazepam. These changes have implications with respect to the antenatal monitoring of the fetus and sequelae in the newborn infant.

Intrapartum fetal asphyxia: clinical characteristics, diagnosis, and significance in relation to pattern of development.

The clinical and fetal heart rates and acid-base characteristics and their sequelae have been reviewed in 587 patients. The relevant clinical factors in the asphyxia group were the preterm fetus, the intrauterine growth retarded fetus, maternal toxemia, and midforceps delivery. The duration of the developing metabolic acidosis in the asphyxia group ranged from terminal to the last two hours of labor. Marked patterns of total decelerations and moderate and marked patterns of late decelerations are of predictive value in the diagnosis of intrapartum fetal asphyxia with a trend to an increased incidence in the longer duration categories, between four and two hours prior to delivery, and a significant increase in all categories during the last two hours of labor. The significance of intrapartum fetal asphyxia to the newborn infant is evident from the low Apgar scores, increased incidence of moderate and severe respiratory distress syndrome, and central nervous system complications in the asphixia group in relation to the normal group.

The relationship of cortisol and cortisone to saturated lecithin concentration in ovine amniotic fluid and fetal lung liquid.

Cortisol and cortisone concentrations in ovine amniotic fluid and fetal lung liquid were analyzed with respect to gestational age and fetal lung maturation as reflected by saturated lecithin concentration. In amniotic fluid, the cortisol concentration rises as a function of gestational age while that of cortisone falls (P less than 0.001). The ratio of cortisol/cortisone is significantly related to gestational age (r=0.693, P less than 0.001), and shows an even stronger correlation with saturated lecithin concentration (r=0.832, P less than 0.001). When examined independently of gestational age, the correlation of the cortisol/cortisone ratio to saturated lecithin concentration remains highly significant (r=0.641, P less than 0.001). Similar findings were observed in fetal lung liquid, except that in this fluid both the saturated lecithin concentration and the ratio of cortisol/cortisone are significantly higher than simultaneously determined values in amniotic fluid. These observations provide further evidence that the process of fetal lung maturation is closely linked to the fetal hormonal milieu.

Alteration of ovine fetal respiratory-like activity by diazepam, caffeine, and doxapram.

The effects of diazepam, caffeine citrate, and doxapram on fetal respiratory-like activity (RLA) were studied in 10 chronic sheep preparations (90 to 130 days' gestation). We define fetal RLA as regular changes in fetal tracheal pressure occurring with a frequency of at least 1 Hz and an amplitude greater than -5 mm. Hg in the absence of fluctuations in amniotic cavity pressure. In all maternal (8) and fetal (7) intravenous infusions of diazepam (5 to 10 mg.), RLA ceased almost instantaneously. The duration of fetal apnea varied from 29 to 70 minutes with a mean of 57 minutes, and on occasion, a gasping pattern preceded recovery of RLA. Maternal and fetal plasma concentrations of diazepam indicated rapid bidirectional placental transfer. Intravenous infusion of doxapram (3 mg.) to the fetus immediately initiated a transient episode of RLA in 19 of 20 trials. Fetal infusion of caffeine citrate (10 to 20 mg.), especially via the carotid artery, was also associated with the rapid onset of a transient episode of fetal breathing. Saline control infusions were without effect. Fetal blood gases and pH were not altered by the administration of diazepam, caffeine citrate, or doxapram. It is suggested that each drug owes its action on RLA to an effect on fetal central nervous system. The influence of pharmacologic agents on the process and interpretation of fetal monitoring requires continued attention.