Biomedical subjects
Publications and source records attributed to M Miodovnik.
Two pregnant women were treated for both insulin-dependent diabetes and sickle cell disease. Careful application of treatments developed for each of these conditions allowed both pregnancies to be successfully carried to term.
Insulin-dependent diabetic pregnant women are at risk for magnesium deficiency, predominantly because of increased urinary magnesium losses. They also have a high incidence of spontaneous abortion, possibly related to major lethal malformations. We tested the hypothesis that adverse fetal outcome (fetal loss before 20 weeks' gestation and/or congenital major malformations) is related to magnesium status (as assessed by determining serum magnesium levels) in insulin-dependent diabetic pregnant women, even after sonographic documentation of fetal viability. Eighty-four insulin-dependent diabetic women (class B to RT) with 96 pregnancies were recruited prospectively in a program project. Serum magnesium and blood glycohemoglobin were measured at about nine weeks' gestation. Blood glycohemoglobin was higher (P = .039) and serum magnesium concentration lower (P = .05) in the 21 pregnancies that ended in adverse fetal outcome, compared with the other (75) successful pregnancies. When compared with the "successful pregnancy" group, blood glycohemoglobin was higher (P = .012) and serum magnesium lower (P = .037) in the subgroup of nine pregnancies with fetal cardiac activity present by ten weeks and ending in adverse fetal outcome, compared with the 64 equivalent pregnancies in the "successful" group. We speculate that decreased magnesium status may contribute to the high spontaneous abortion and malformation rate in insulin-dependent diabetic pregnant women.
We have recently shown that, with the current management of insulin-dependent diabetes during pregnancy, infants of diabetic mothers are at no greater risk of respiratory distress syndrome (RDS) than an appropriately matched control population. A previous study suggested a selective inhibition of surfactant associated protein of 35,000 daltons (SAP-35) in the amniotic fluid of diabetic pregnancies. In order to determine whether a selective inhibition of SAP-35 occurs in well controlled, insulin-dependent diabetic pregnancies, we compared SAP-35 concentration and lecithin/sphingomyelin (L/S) ratios in amniotic fluid from 30 well controlled, insulin-dependent women with 30 nondiabetic pregnant women pair-matched for gestational age, race, and indication for amniocentesis. Gestational ages ranged from 30-43 weeks, with a mean of 36.5 +/- 2.5 weeks, in both groups. Surfactant associated protein-35 was measured by an enzyme-linked capture immunoassay specific for SAP-35 and its oligomers. Mean +/- SEM SAP-35 was 3.7 +/- 0.4 micrograms/mL (N = 30) in the diabetic group, not significantly different from 5.0 +/- 1.1 micrograms/mL (N = 30) in the control group (P greater than .05). Mean L/S ratios were also not different: 2.4 +/- 0.1 (diabetic) compared with 2.3 +/- 0.1 (control); P greater than .05. The rate of RDS was similar in both groups. We conclude that in well controlled diabetic pregnancies, fetal lung maturation, as assessed by the L/S ratio, SAP-35 concentration, and outcome, is not adversely affected.
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Amniotic fluid samples from 21 diabetic pregnant women were pair-matched for gestational age with 21 samples obtained from nondiabetic women, and analyzed for magnesium concentration. Mean +/- standard deviation amniotic fluid magnesium concentration (mg/dL) was 0.86 +/- 0.21 in the diabetic group and 1.06 +/- 0.22 in the control group (P less than .001). It is concluded that in the diabetic pregnancy, a state of fetal magnesium deficiency exists. This deficient state may contribute to neonatal hypocalcemia in infants of diabetic mothers.
The purpose of this study was to test the hypothesis that diabetes in pregnancy in the 1980s no longer represents a direct risk factor for the development of respiratory distress syndrome (RDS) independent of gestational age, race, sex, mode of delivery, and neonatal asphyxia. We pair-matched 127 infants of diabetic mothers (diabetic group) with 127 infants of nondiabetic mothers (controls) for the above factors. Diabetic mothers enrolled before nine weeks' gestation were randomly assigned to one of two groups: I. "strict management," to achieve euglycemic (fasting blood glucose less than 80 mg/dL, 1.5-hour-postprandial blood glucose less than 120 mg/dL); II. "customary management," to provide care "as practiced in the community" (fasting blood glucose 100 mg/dL or less, postprandial blood glucose less than 140 mg/dL). A group enrolled after the first trimester (III) was managed identically to group II. Infants of diabetic mothers had a rate of RDS of 13.4%, not significantly different from the rate of 15% in controls (P greater than .05). When analyzed by gestational age groups of less than 36, or 36 or more weeks' gestation, there was also no difference in frequency of RDS between the diabetic group and controls. By logistic regression analysis, the presence of RDS in infants of diabetic mothers significantly correlated with lower gestational age (P less than .0001), and delivery by cesarean section not preceded by labor (P less than .01)(ABSTRACT TRUNCATED AT 250 WORDS)
Nine cases of pregnancy complicated by diabetes and prior renal transplantation are reviewed. Maternal and fetal death occurred in a patient with foot and leg ulcers associated with preexisting peripheral vascular disease. Pregnancy-induced hypertension occurred in six cases. Spontaneous weight-bearing fractures occurred in two patients. No episodes of renal allograft rejection occurred. Evidence of fetal compromise was present in six cases. All fetuses were delivered by cesarean section prior to term, with live births occurring from 31 1/2 to 36 weeks' gestation. A single case of hypospadias was the only congenital defect. Prepregnancy screening for complications of diabetes and renal transplantation is advised and euglycemia should be achieved before and during pregnancy. Advanced diabetic vascular disease puts these gestations at significant risk.
Hypomagnesemia (serum magnesium concentration, less than 1.5 mg/dL [0.62 mmol/L]) and hypocalcemia (serum calcium concentration, less than 8 mg/dL [2.00 mmol/L]) have been reported in polycythemic infants, as well as in infants of diabetic mothers (IDMs). These latter infants are at risk for neonatal polycythemia (venous hematocrit, greater than or equal to 65% [0.65]). We tested the hypothesis that neonatal polycythemia in IDMs is associated with increased serum calcitonin concentration, hypomagnesemia, and hypocalcemia. Serum magnesium and calcium concentrations were measured at 24 and 72 hours of age in 76 IDMs; serum calcitonin concentration was measured at 24 hours of age. Peripheral venous spun hematocrit was measured between 2 and 4 hours of age. The rates of hypomagnesemia and hypocalcemia were similar in polycythemic and nonpolycythemic IDMs (0% vs 9% and 56% vs 49%, respectively). The serum calcitonin concentration was similar in both groups. There was no correlation between hematocrit and the serum magnesium or calcium concentration; a significant association existed between hypocalcemia and hypomagnesemia.
The fetus of the pregnant diabetic woman is exposed to hyperglycemia frequently accompanied by ketoacidosis. Previous studies have demonstrated that beta-hydroxybutyrate, a major ketone body, crosses the ovine placenta in significant amounts, leading to significant reductions in fetal PaO2 and increased fetal heart rate. In the present study the pregnant ewe was used to evaluate the maternal and fetal cardiovascular and metabolic responses to hyperketonemia in the presence of hyperglycemia and to determine if the combined diabetic insults were more detrimental to the fetus than hyperketonemia alone. A glucose priming dose of 25 gm was administered in the maternal femoral vein followed by a continuous glucose infusion of 200 mg/min to achieve steady maternal plasma glucose levels of 180 mg/dl. Once glucose levels were stable, beta-hydroxybutyrate was infused for 2 hours at a rate of 0.39 mmol/100 ml of uterine blood flow into both left and right uterine arteries. Infusion of glucose alone did not significantly alter fetal cardiovascular and blood gas parameters but did increase the fetal glucose level from 17 +/- 4 to 58 +/- 8 mg/dl. The simultaneous infusion of beta-hydroxybutyrate and glucose produced significant decreases in fetal PaO2 and oxygen content as were reported for hyperketonemia alone and significant time-related increases in fetal lactate levels and fetal heart rate. These data suggest that hyperketonemia in the pregnant ewe leads to quantitatively similar changes in oxygenation in both normoglycemic and hyperglycemic fetuses. These observations may in part help explain the increased perinatal mortality in the pregnant woman with uncontrolled diabetes.
Insulin-dependent diabetic women without adequate glucose control have a higher spontaneous abortion rate when compared with the general population. The present study examined whether the increased rate of spontaneous abortions in insulin-dependent diabetic women was associated with poor glycemic control in the early postconceptional period or close to the abortive event itself. Measurements of glycohemoglobin A1 at eight to nine weeks' gestation provide retrospective indexes of glucose control during the early postconceptional period, whereas measurement of glycosylated serum albumin and serum protein at the same time reflects short-term glycemic control before the abortive event. This study evaluated 84 consecutive pregnancies occurring in 68 insulin-dependent diabetic women; 66 pregnancies progressed beyond 20 weeks with no malformation or death, and 18 pregnancies terminated in spontaneous abortions before 20 weeks' gestation. The mean glycohemoglobin A1 concentrations of women experiencing spontaneous abortions were significantly greater than that of women who did not abort (P less than .05). In contrast, maternal glycosylated proteins and glycosylated albumin concentrations did not differ between groups. The authors suggest that poor control of diabetes in the early conceptional period, rather than that just before abortion, increases the risk of spontaneous abortion.
The rate of neonatal polycythemia was determined prospectively in 34 infants of diabetic mothers pair-matched to 34 infants of nondiabetic mothers (control group) for site of sampling, time of sampling, time of cord clamping, gestational age, mode of delivery, and one- and five-minute Apgar scores. Polycythemia (venous hematocrit greater than or equal to 65%) was present in 29.4% of infants of diabetic mothers and 5.9% of control subjects (P less than .03). Mean nucleated red blood cell counts were significantly higher in infants of diabetic mothers than in controls. Polycythemia did not correlate with higher maternal hemoglobin A1 concentration or with increased infant weight percentile, but did correlate with neonatal hypoglycemia. The authors speculate that increased erythropoiesis exists in infants of diabetic mothers and might be subsequent to fetal hypoxemia due to fetal hyperglycemia, hyperinsulinism, and hyperketonemia.
Insulin-dependent diabetic women without adequate glucose control have a higher rate of spontaneous abortions than does the general population of pregnant women. The present study examined whether insulin-dependent diabetic women who experienced spontaneous abortions had higher levels of glycohemoglobin in the first trimester than did insulin-dependent diabetic women who had normal pregnancy outcomes. Measurement of glycohemoglobin during the first trimester provides an integrated, retrospective index of glucose control during the phase of organogenesis. This study evaluated 116 pregnancies in 75 insulin-dependent diabetic women. Ninety pregnancies progressed beyond 20 weeks, with normal outcome. Twenty-six pregnancies terminated in spontaneous abortions before 20 weeks. The mean gestational ages for sampling of glycohemoglobin for the women who experienced spontaneous abortion and those for the women with pregnancies of more than 20 weeks were not significantly different. The mean level of glycohemoglobin for the women who experienced spontaneous abortions was significantly greater than that for the women with pregnancies of more than 20 weeks (p less than 0.05). Individual levels of glycohemoglobin of less than 12% at 8 to 9 weeks' gestation were associated with favorable outcomes, whereas levels of glycohemoglobin of more than 12% were predictive of a greater incidence of spontaneous abortions (p less than 0.05). These data suggest that the poorly controlled pregnant diabetic patient, as reflected by high levels of glycohemoglobin early in pregnancy, has an increased risk of spontaneous abortion.
Serum unconjugated estriol and estetrol were assayed daily in seven nondiabetic, uncomplicated third-trimester pregnancies to define the daily variation of these compounds. When compared to the mean of the three preceding days' values, or to the highest mean of three consecutive daily values previously obtained in a pregnancy, daily estriol and estetrol values fell greater than or equal to 40% on 1.2 and 0% of occasions, respectively. Isolated estriol values represented falls of greater than or equal to 40% from previously obtained single estriol values on 2% of occasions, and no isolated estetrol values fell greater than or equal to 40% from any other isolated values obtained in a given pregnancy. These results define the stability of daily serum estriol and estetrol in late-gestation normal pregnancy, although they emphasize the large variability encountered when comparing isolated estriol values.
This retrospective study was designed to analyze the safety and efficacy of beta-sympathomimetic agents used to treat premature labor in insulin-dependent diabetic women. The study evaluated 12 insulin-dependent diabetic women who experienced 15 pregnancies complicated by premature labor. A group of 30 insulin-dependent diabetic women who delivered at term served as matched controls. Treatment consisted of parenteral and oral administration of beta-sympathomimetic drugs (ritodrine and isoxsuprine). Premature labor was diagnosed, and tocolytic treatment was initiated at a mean gestational age of 31.5 +/- 0.9 weeks. The mean gestational age at the time of delivery was 35.8 +/- 0.5 weeks. Delivery was delayed in the study group by a mean of 30.5 +/- 6.6 days. No fetal or infant deaths occurred in the study group, and there was no difference between the two groups in the incidence of neonatal morbidity. No maternal complications occurred. There were no significant differences in hemoglobin A1 levels between the two groups at any period of gestation. Thus, beta-sympathomimetic drugs may be used safely to treat premature labor in patients with insulin-dependent diabetes, provided they are administered under strictly controlled clinical settings.
A prospective study was undertaken to evaluate the frequency of spontaneous abortion in clinically apparent pregnancies among insulin-dependent diabetic women evaluated prior to pregnancy. The study was done in 132 pregnancies occurring in 91 diabetic women. The spontaneous abortion rate was 30%; 70% of the pregnancies progressed beyond 20 weeks. The abortion rates for Classes B, C, D, and F through RT were 0%, 25%, 44%, and 22%, respectively. Initial serum levels of the beta-subunit of human chorionic gonadotropin above 6000 mIU were usually associated with favorable outcome while levels below 6000 mIU were not predictive of outcome. Data from this study suggest that the risk of spontaneous abortion among insulin-dependent diabetic women may be substantially higher than for the general population. Higher abortion rates were generally associated with more advanced White classification of diabetes. Age at diagnosis was the only factor which showed a significant contribution to the risk of abortion.
Estetrol is produced by the fetal liver and has been suggested to be a sensitive indicator of fetal well-being. Although the uterine vascular effects of estrogens (17 beta-estradiol, estriol, and estrone) have been extensively investigated in our laboratory and those of others, the ability of estetrol to dilate the ovine uterine vasculature is not presently known. The present experiment was designed to compare the vasoactivity of estetrol to that of a second pregnancy-associated estrogen, estriol. Five nonpregnant oophorectomized ewes were chronically instrumented with catheters in the femoral artery, femoral vein, uterine arteries, and electromagnetic flow probes on both uterine arteries. Upon recovering from operation, animals received unilateral intra-arterial (uterine) injections of either estriol (0.1, 0.3, 1, and 3 micrograms) or estetrol (1, 3, 10, and 30 micrograms). Ewes received only one dose of either estetrol or estriol daily and all doses were given in a randomized order. Uterine blood flow responses were continuously monitored and the time of onset, peak, and duration were recorded. The time of onset (38 +/- 2 minutes), time of peak response (75 +/- 1 minute), and duration (189 +/- 7 minutes) were approximately equal to those observed for estriol. On the basis of the data obtained in the present study we have determined that estetrol is 15 to 30 times less potent than estriol as a uterine vasodilator.
The relationship between gestational age and reactivity during the nonstress test was evaluated in 297 high-risk patients. When the incidence of nonreactive tests at gestational ages of 28 to 44 weeks was evaluated week-by-week, either on the basis of tests performed or patients tested, there was no statistically significant relationship between reactivity and gestational age (P = .184 tests; P = .222 patients). Four grouped gestational-age intervals were evaluated. Interval A consisted of the period from 28 to 32 weeks' gestation, interval B consisted of the period from 33 to 36 weeks' gestation, interval C consisted of the period from 37 to 41 weeks' gestation, and interval D consisted of the period from 42 to 44 weeks' gestation. The incidences of nonreactive tests were 15.3, 3.9, 2.5, and 5.9% in intervals A, B, C, and D, respectively. The differences in the incidences of nonreactive tests between those performed in intervals A and B and intervals A and C were highly statistically significant (P less than .001). Differences in the incidences between other intervals did not reach statistical significance. The incidences of patients who experienced a nonreactive test were 10.2, 2.4, 2.8, and 4.7% in intervals A, B, C, and D, respectively. The differences in the incidences of patients who experienced a nonreactive test in intervals A and B and intervals A and C were highly statistically significant (P less than .001). Differences in the incidences between other intervals did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
A clinical investigation was undertaken to challenge the commonly accepted view that the interval between the birth of the first and second twins should be preferably within 15 minutes and certainly no more than 30 minutes. During 1981 and 1982, 115 patients with live-born twins at 34 or more weeks' gestation underwent an attempted vaginal delivery at four regional perinatal centers. The interval between vaginal delivery of the first and second twins (mean, 21 minutes, range, one to 134 minutes) was 15 minutes or less in 70 (61%) cases and more than 15 minutes in 45 (39%) cases. Excluding conditions associated primarily with prematurity, all second twins delivered beyond 15 minutes did well despite the delay and had no signs of excess trauma or low five-minute Apgar scores. Maternal complications were also uncommon, although combined vaginal-abdominal delivery was more frequent if there was a delay of more than 15 minutes (eight of 45 versus two of 70, P less than .02). The authors conclude that if there is continuous fetal and uterine monitoring, a time restriction for the delivery interval between the first and second infants is not necessary.