Recurrence of gestational diabetes mellitus: identification of risk factors.

The objective of this paper is to evaluate the influence of maternal and neonatal factors on the recurrence of gestational diabetes mellitus (GDM). A study was conducted on 164 predominantly Hispanic patients whose index pregnancy was complicated by GDM and whose subsequent consecutive pregnancy was managed at our institution between January 1988 and December 1992. The diagnosis of GDM was based on the criteria recommended by the National Diabetes Data Group using a 100-g oral glucose tolerance test. One-hundred and eleven (68%) of the 164 women had recurrence of GDM. Fifty-three (32%) did not demonstrate recurrence in their subsequent pregnancy. Patients with recurrence had GDM diagnosed earlier (30.3 vs 32.5 weeks, p = 0.03), frequently required insulin (25 vs. 8%, p <0.05) and had more hospital admissions (32 vs. 10% p <0.05) in their index pregnancy compared to women who did not have recurrence of GDM. Women who had recurrence had elevated mean third-trimester plasma glucose values: fasting 87.6 vs. 83 mg/dL, (p = 0.009) and 2-hr postprandial 109.7 vs. 102.2 mg/dL, (p = 0.008). Neonates of patients with recurrence were heavier (3656 vs. 3373 g, p = 0.004) and had an increased incidence of macrosomia (26 vs. 10%, p <0.05). No significant differences were observed in maternal age, prepregnancy body mass index, HbgA1C values, second-trimester blood glucose levels, method of delivery, incidence of shoulder dystocia and Apgar scores between the two groups of women. Hispanic patients with history of GDM have significant risk of recurrence in their subsequent pregnancy. The risk for recurrence in women is increased if GDM is diagnosed earlier, they require insulin, have elevated third-trimester plasma glucose level, and deliver macrosomic infants in their index pregnancy. It appears that obesity does not increase the risk of recurrence of gestational diabetes in Hispanics.

Pulsatile oxytocin administered to ewes at 120 to 140 days gestational age increases the rate of maturation of the fetal electrocorticogram and nuchal activity.

Spontaneous, long lasting epochs of myometrial contractility, contractures, occur throughout the majority of pregnancy in sheep. Contractures are temporally related to a switch in fetal electroencephalogram (ECoG) patterns from low to high voltage. In late gestation, fetal ECoG increases in voltage. We have previously suggested that contractures may influence fetal ECoG maturation. In the present study, we hypothesized that a sustained increase in the frequency of myometrial contractures in pregnant sheep at 120-140 days gestation would accelerate maturation of the fetal ECoG. Five pregnant ewes were pulsed with oxytocin 600 microU.kg-1.min-1 intravenously for five minutes in every 30 minutes from 127.8 +/- 1.5 days gestational age for a minimum of six days. Six control ewes received pulses of saline. Fetuses of all eleven ewes were instrumented with bilateral electrodes to record fetal ECoG and nuchal muscle activity. Fetal high voltage (HV) ECoG increased in amplitude in both groups but the rate of increase was faster in the fetuses of ewes receiving oxytocin. There were no differences between the two groups in the duration of HV ECoG. The percentage increase in the amount of time the fetal nuchal muscles were active compared with the baseline day before infusion was only significant in the oxytocin infused group on the first day of oxytocin infusion. These findings support the hypothesis that myometrial activity during pregnancy has the capacity to influence fetal neural development.

Oxytocin given in a pulsatile manner to the ewe at 120 to 140 days' gestational age increases fetal sheep plasma cortisol.

A single intravenous injection of oxytocin into pregnant sheep (123 to 144 days' gestational age) causes a bout of myometrial activity and an increase in fetal plasma corticotropin levels. We hypothesized that a sustained increased frequency of myometrial contractures accelerates the normal increase in fetal adrenal secretion in sheep in the last 3 weeks of gestation. To test this hypothesis, pulses of saline solution (group 1, 9 ewes and 10 fetuses) or oxytocin (group 2, 11 ewes and 12 fetuses) 600 or 960 microU/kg/min for 5 of every 30 minutes were infused into the maternal jugular vein for 6 days beginning at day 128 +/- 2 (mean +/- SD) days' gestational age. Total myometrial activity increased to 160% of baseline in group 2 by day 6. Myometrial activity did not change throughout the study in group 1. Maternal plasma cortisol concentrations did not rise during oxytocin infusion when compared with their own baselines (group 2) and were not different from concentrations in saline-infused ewes (group 1). By day 4 of oxytocin administration fetal plasma cortisol concentrations had risen significantly above baseline in group 2 (p less than 0.05). Fetal plasma cortisol concentrations did not rise in group 1. Corticotropin levels were not elevated in the fetal carotid arterial plasma of either group. A small but significant decrease occurred in fetal carotid arterial PO2 in group 2 by day 6 but not in group 1. In conclusion, increased myometrial activity produced by pulsed oxytocin is accompanied by increased fetal plasma cortisol concentrations, demonstrating that long-term alteration of myometrial activity affects fetal adrenal function over several days at this critical period of gestation.

Zinc supplementation during pregnancy: effects on selected blood constituents and on progress and outcome of pregnancy in low-income women of Mexican descent.

The effects of zinc supplementation on levels of various blood constituents and the outcome of pregnancy in 213 Hispanic women attending a prenatal clinic in Los Angeles was assessed in this double-blind study. The women were randomized into either a control (C) or a zinc-supplemented (Z) group and received similar vitamin and mineral supplements except that 20 mg zinc was added to the Z group's capsules. At the final interview, women (C + Z) with low serum Zn levels (less than or equal to 53 micrograms/dl) had higher (p less than 0.01) mean ribonuclease activity and lower (p less than 0.01) mean delta-aminolevulinic acid dehydratase activity than women with acceptable serum zinc levels. The incidence of pregnancy-induced hypertension was higher (p less than 0.003) in the C than in the Z group, but pregnancy-induced hypertension was not associated with low serum zinc levels at either the initial or final interview. The expected increase in serum copper levels was greater (less than 0.001) in women with pregnancy-induced hypertension (C + Z) than in normotensives. Except for pregnancy-induced hypertension, there was a higher incidence of abnormal outcomes of pregnancy in the noncompliers than in the compliers (C + Z).

Androstenedione, testosterone, and estradiol concentrations in fetal and maternal plasma in late pregnancy in the sheep.

Fetal and maternal plasma concentrations of androstenedione, testosterone, and estradiol were measured in chronically catheterized pregnant sheep during late gestation, spontaneous term delivery, and premature delivery induced by the infusion of low doses of synthetic ACTH-(1-24) (ACTH) to the fetus at 120-130 days gestation. RIAs employing two different antisera directed at different sites of each molecule were used in combination with Celite column chromatography to ensure the specificity of the hormone measurements. Fetal plasma concentrations of all three hormones were greater than the respective maternal concentration at all periods investigated, except immediately before ACTH-induced delivery when fetal testosterone and estradiol concentrations were lower. These observations further support the hypothesis that delivery in the sheep is associated with the induction of placental 17 alpha-hydroxylase and 17,20-lyase by the increased conversion of progesterone to estrogens. The higher values of androstenedione than of testosterone also support the view that estrone is produced in larger quantities than estradiol and that estrone and estrone sulfate are good endocrine markers of the progress of the endocrine changes occurring immediately before parturition in the sheep.

Effect of abolition of fetal movement on fetal intravascular PO2 and incidence of tonic myometrial contractures in the pregnant ewe at 114 to 134 days' gestation.

The possibility that fetal movements play a role in the initiation of the bursts of tonic myometrial activity (contractures) that occur throughout the second half of pregnancy in the sheep has been examined by the administration of the curare derivative pancuronium to abolish fetal movement. The duration and frequency of the electromyographic bursts associated with contractures, as well as the increase in intrauterine pressure generated by the contractures, were unchanged. However, within 1 hour of the abolition of fetal movement, fetal jugular venous PO2 was significantly elevated and remained elevated for at least 6 hours. This observation is in keeping with the view that fetal skeletal muscle movement consumes significant amounts of oxygen.

Erythrocyte enzymes in sheep: comparison of activity in fetal, newborn, maternal and nonpregnant ewe erythrocytes.

Hematological data and the activities of 21 red cell enzymes were measured in 8 nonpregnant ewes, 13 chronically catheterized fetuses at 125-135 days of gestation, and 8 of their mothers. In addition, 7 lambs were followed from birth to 17 days of age. Fetal sheep red cells have dramatically increased activities for 17 of 21 enzymes measured compared with adult nonpregnant ewes. The pattern of decline of enzyme activities with development varies considerably among enzymes. The activity of seven enzymes showed an orderly decline from fetal to adult life. For seven enzymes very little or no decline in activity was observed between 125 and 135 days of gestation and birth. Pyruvate kinase activity declined to adult levels by birth. Phosphoglucose isomerase and nucleoside phosphorylase activity increased, and glutathione peroxidase activity decreased in newborn lamb red cells compared to fetal cells. Differences in blood cell variables were also found among these groups.

Midazolam and diazepam: maternal and fetal effects in the pregnant ewe.

Maternal and fetal hemodynamic effects and placental transfer of midazolam (RO 21-3981, Hoffman-LaRoche) and diazepam were studied in chronically instrumented pregnant ewes. Diazepam administration resulted in greater increases of maternal and fetal heart rates and maternal blood pressure, and greater alteration of total uterine blood flow than did administration of comparable doses of midazolam. Neither drug altered fetal mean arterial pressure or maternal and fetal respiratory gases. Although the absolute blood concentrations were higher, the fetal:maternal drug concentration ratios were consistently less for midazolam than for diazepam, suggesting less placental permeability of midazolam.

Vascular reactivity to angiotensin II in the normotensive and hypertensive pregnant ewe.

The circulatory responses to progressively increasing doses of angiotensin II were studied in the same group of chronically instrumented unanesthetized pregnant sheep during three consecutive periods: a) normotensive with intact kidneys; b) normotensive with unilateral nephrectomy; and c) one-kidney hypertension. The results show that 1) the pressor response to a given dose of angiotensin was significantly greater in the normotensive than in the hypertensive condition; 2) uterine blood flow decreased markedly with the development of hypertension; 3) uterine circulatory response to angiotensin depended on the dosage; the response was less the the hypertensive than in the normotensive condition; 4) renal blood flow decreased and renal vascular resistance increased during angiotensin infusion, but the response was less in the hypertensive than in the normotensive condition; the response of the renal circulation decreased with increasing doses of angiotensin. These observations suggest a generalized vascular refractoriness to exogenous angiotensin II in the pregnant ewe with experimental renal hypertension.

Effect of dopamine on hypotension induced by spinal anesthesia.

Chronically instrumented, near-term pregnant sheep were subjected to autonomic blockade with spinal anesthesia. Systemic arterial pressure, heart rate, and uterine blood flow decreased and uterine vascular resistance increased during the spinal blockade. Infusion of dopamine during the spinal hypotension corrected the disturbed circulatory parameters. These data provide evidence that: (1) the peripheral circulation of the near-term pregnant sheep is as sensitive as that of pregnant women to autonomic blockade, (2) the sensitivity is probably related to factors other than the changes in venous pressure in areas below the pelvis, and (3) dopamine represents a useful agent in the management of spinal hypotension.