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Biomedical subjects

M Miodovnik

Publications and source records attributed to M Miodovnik.

At least 109 records · Page 6Linked to original sources

Minor congenital malformations in infants of insulin-dependent diabetic women: association with poor glycemic control.

A prospective study of 171 insulin-dependent diabetic pregnant women was undertaken to establish the relationship of glycemic control with minor congenital malformations. Each live-born infant was assessed systematically by two independent examiners using a standardized checklist. There were 32 infants with minor congenital malformations (18.7%). There were significant differences in mean glycohemoglobin A1 between the group with minor congenital malformations and the group without congenital malformations at 12, 16, and 20 weeks, but not at 8 or 24 weeks. Logistic regression analysis showed that maternal age, race, gravidity, White class, duration of diabetes, maternal vasculopathy, and cigarette smoking were not significant variables correlated with minor congenital malformations. Because glycohemoglobin levels from 12-20 weeks are believed to reflect glycemic control from approximately 6-20 weeks, we conclude that poor glycemic control during late embryogenesis and early fetal development is associated with an increased risk of minor congenital malformations. We speculate that improvement of glycemic control during this period should decrease the risk of minor congenital malformations.

Blood Glucose↗

Spontaneous abortions in repeat diabetic pregnancies: a relationship with glycemic control.

In previous studies, we reported a high rate of spontaneous abortions in insulin-dependent diabetic pregnancies. Abortions were associated with poor first-trimester glycemic control. We hypothesized that improvement of glycemic control from one pregnancy to the other would improve fetal outcome and that deterioration of glycemic control would increase the likelihood of abortion. We studied prospectively 43 insulin-dependent diabetic women (White class B-RF) with two consecutive pregnancies, recruited before 9 weeks' gestation. Preprandial and 90-minute postprandial blood glucose concentrations were measured at each weekly visit. Glycohemoglobin A1 was measured at 9 weeks' gestation. Twenty women had two successful pregnancies and 15 had an abortion followed by a successful pregnancy (abortion-no abortion); the sample sizes for other sequences (no abortion-abortion, N = 5; and abortion-abortion, N = 3) were too small to allow for analysis. Glycohemoglobin A1 concentrations were stable in the sequence no abortion-no abortion (9.7 +/- 0.5 versus 9.8 +/- 0.4%, mean +/- SEM; not significant), whereas in the sequence abortion-no abortion, there was a significant decrease in glycohemoglobin A1 values from the nonsuccessful to the successful pregnancy (10.7 +/- 0.6 versus 9.3 +/- 0.4%; P = .01). Similarly, in the sequence abortion-no abortion, there was a significant decrease in mean postprandial blood glucose from first to second pregnancy (166 +/- 13 versus 135 +/- 11 mg/dL; P = .04), whereas in the sequence no abortion-no abortion, mean postprandial blood glucose did not change significantly (160 +/- 14 versus 144 +/- 11 mg/dL; not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Spontaneous↗

Alloxan-induced diabetes mellitus in the pregnant ewe: metabolic and cardiovascular effects on the mother and her fetus.

Diabetes mellitus was acutely produced in nine pregnant sheep by the intravenous administration of alloxan 40 mg/kg in the maternal inferior vena cava. Maternal and fetal plasma concentrations of glucose, lactate, beta-hydroxybutyrate, insulin, glucagon, and PaO2, oxygen content, and pH were determined before and at days 1, 3, and 5 after the injection of alloxan. Two animals aborted between days 1 and 3 after alloxan administration. In the other animals, significant changes occurred from baseline to day 5: maternal hyperglycemia (56.8 +/- 5.2 vs. 227.3 +/- 54.6 mg/dl; p less than 0.01), maternal hypoinsulinemia (6.2 +/- 3.5 vs. 1.0 +/- 0.4 microU/ml, p = 0.016); maternal hyperketonemia (beta-hydroxybutyrate: 0.79 +/- 0.27 vs. 4.69 +/- 2.64 mmol/L, p less than 0.01); fetal hyperglycemia (17.0 +/- 2.6 vs. 86.0 +/- 16.2 mg/dl, p less than 0.001); fetal hyperinsulinemia (8.4 +/- 4.5 vs. 19.2 +/- 6.4 microU/ml, p less than 0.001); fetal hyperketonemia (beta-hydroxybutyrate: 0.03 +/- 0.03 vs. 0.06 +/- 0.02 mmol/L, p less than 0.05); fetal hypoxemia (arterial PO2: 21.6 +/- 1.8 vs. 18.0 +/- 2.8 mm Hg, p less than 0.05, and oxygen content: 7.1 +/- 0.5 vs. 4.5 +/- 1.9 vol/dl, p less than 0.02). Thus alloxan administered in the pregnant ewe can produce major metabolic and endocrine derangements acutely simulating those occurring in human insulin-dependent diabetic pregnancy.

Animals↗

Biphasic intrauterine growth in insulin-dependent diabetic pregnancies.

Early fetal growth delay (7-14 weeks of gestation) has been reported in insulin-dependent diabetic (IDD) pregnancies and in several animal models. Macrosomia is a classic feature of the infant of the IDD mother. We hypothesized therefore that a biphasic pattern of fetal growth exists in IDD pregnancies. We compared fetal growth measurements [biparietal diameter (BPD) and abdominal circumference (AC)] obtained sonographically from 106 IDD pregnancies (Class B-RT) to similar data obtained from 117 normal, nondiabetic patients. The goals for diabetic glycemic control were: fasting blood sugar less than or equal to 100 mg/dl and postprandial blood sugar less than 140 mg/dl. From one to five ultrasonographic measurements were performed at varying gestational ages in all study patients. For data analysis, one examination from each pregnancy was randomly selected by computer. Gestational age (GA) was calculated from last menstrual period and corroborated by infant physical examination (Ballard score) at birth. BPD growth pattern was biphasic in the diabetic group, described by a cubic equation: BPD = 4.99 - 0.567GA + 0.037(GA)2 - 0.0005(GA)3, R2 = 0.935. Such a biphasic pattern did not exist in the control population [BPD = -3.0323 + 0.473(gestation) - (-0.0040)(gestation)2, R2 = 0.9173]. Early growth delay was greater in fetuses that subsequently developed macrosomia (p less than 0.01). Similar results were found for AC measurements. We conclude that fetal growth delay occurs in the first half of the IDD pregnancy, followed by a phase of increased growth. The mechanism of the early growth delay is unclear. We speculate that early growth delay may be due to a "toxic" effect of glucose or other metabolite; and subsequent increased growth relates to fetal hyperinsulinism which develops from weeks 15 to 20 of gestation.

Diabetes Mellitus, Type 1↗

Macrosomia in infants of insulin-dependent diabetic mothers.

The purpose of the present study was to evaluate factors affecting the rate of macrosomia and related complications in a population of infants of insulin-dependent diabetic mothers. The following factors were hypothesized to be predisposing to macrosomia: increased maternal weight gain during gestation, increased number of births until infant No. 3, white race, increased maternal age, poor glycemic control from the 20th week of gestation, and increased insulin dose. Advance White classification and increased duration of diabetes were predicted to be inversely related. In addition, macrosomia was hypothesized to predispose to selected adverse perinatal outcomes including premature labor, birth asphyxia, birth injury, hypoglycemia, polycythemia, and respiratory distress syndrome. From 1978 to 1986, 127 pregnancies were prospectively studied, 86 of the total number of women were entered prior to 10 weeks' gestation, and 41 were entered after 10 weeks' gestation. Patients monitored blood glucose at least twice daily with glycemic control achieved by "split-dosage" regimens of insulin. Glycohemoglobin was measured monthly. Pregnancy dating was based on the date of the last menstrual period and the Ballard score of the infant at birth. Macrosomia was defined as a birth weight greater than the 90th percentile of the intrauterine growth curves of Lubchenco. Of the babies born to mothers with insulin-dependent diabetes, 43% were large for gestational age and 57% were appropriate for gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗

Perinatal asphyxia in infants of insulin-dependent diabetic mothers.

Infants of diabetic mothers are thought to be at risk for perinatal asphyxia. We hypothesized that the following are significant risk factors for perinatal asphyxia: poor third-trimester glycemic control, diabetic vascular disease (nephropathy, retinopathy) appearing in pregnancy, pregnancy-associated hypertension, smoking, prematurity, fetal macrosomia, and maternal hyperglycemia and hypoglycemia within 6 hours preceding delivery. We prospectively studied 162 infants born to 149 diabetic mothers (White classes B through R-T). Perinatal asphyxia was defined clinically as fetal distress during labor (late decelerations, persistent fetal bradycardia, or both), 1-minute Apgar score less than or equal to 6, or intrauterine fetal death. Forty-four infants (26.7%) had perinatal asphyxia. The presence of perinatal asphyxia did not correlate with third-trimester glycemic control, pregnancy-associated hypertension, smoking, fetal macrosomia, or maternal hypoglycemia before delivery, but it did correlate significantly with nephropathy appearing in pregnancy, maternal hyperglycemia before delivery, and prematurity. We speculate that (1) the appearance of diabetic vasculopathy (nephropathy) during pregnancy is accompanied by placental vascular disease and subsequently by fetal compromise and (2) in pregnancy complicated by diabetes, maternal and subsequently fetal hyperglycemia before delivery leads to fetal hypoxemia.

Adult↗

Rate of spontaneous abortion after first trimester sonographic demonstration of fetal cardiac activity.

The incidence of spontaneous abortion once embryonic development has reached the stage of sonographically demonstrable cardiac activity has not been precisely determined in a large population. This retrospective study was designed to determine the risk of pregnancy loss after first trimester sonographic confirmation of fetal cardiac activity. A total of 840 patients were referred for ultrasound examination to the Perinatal Center, University of Cincinnati, between January 1, 1979 and December 31, 1985 who fulfilled the criteria of singleton pregnancy with sonographically visible fetal cardiac activity and crown-rump length consistent with gestational age less than or equal to 12 weeks. Patients were grouped into two categories based on the absence (control) or presence of vaginal bleeding (bleeding) prior to or at the time of the ultrasound examination. The abortion rates for the two groups were 5.2 and 16.4%, respectively (P less than 0.001). The relative risk of abortion in patients with vaginal bleeding was nearly four-fold greater than the control population. In the control group there was a significantly greater incidence of pregnancy loss in the greater than or equal to 34 years age group compared to less than 34 years age patients (4.4 versus 11.1%, P less than 0.05). Although there was no significant effect of race on abortion rates, low socioeconomic status almost doubled the relative risk of miscarriage. We conclude that the presence of visible fetal cardiac activity in the first trimester predicts a decreased risk for spontaneous abortion compared to generally reported rates. The significant risk factors for increased chance of abortion are vaginal bleeding, advanced maternal age, and low socioeconomic status.

Abortion, Spontaneous↗

Review of fetal cardiovascular and metabolic responses to diabetic insults in the pregnant ewe.

Studies with pregnant sheep are reviewed, which were designed to investigate whether short-term episodes of maternal hyperglycemia or hyperketonemia were detrimental to the fetus, whether ketones can cross the ovine placenta, and whether the combination of maternal hyperglycemia and hyperketonemia would contribute to an increased risk of fetal morbidity. It is concluded that acute increases in maternal ketones appear to be more detrimental to the fetus than acute increases in maternal glucose, as assessed by fetal cardiovascular, metabolic, and blood gas changes.

Animals↗

Serum unconjugated estriols in insulin-dependent diabetic pregnancies: normative data and clinical relevance.

The purpose of this study was to establish normative reference values for serum unconjugated estriol (E3) concentrations in insulin-dependent diabetic pregnancy. There were 1973 samples analyzed in 63 diabetic pregnancies not complicated by fetal distress and/or neonatal asphyxia. These samples were compared with 867 samples collected in 25 pregnancies complicated by fetal distress and/or neonatal asphyxia and 103 samples collected in seven nondiabetic, uncomplicated pregnancies. E3 values were found to be significantly higher in diabetic compared with nondiabetic healthy gravid women, correlating with infant birthweight. The percent change of daily E3 values from the highest previous 3 days mean (maximum mean) was 1 +/- 27% (mean +/- SD). The 95% confidence limit for this percent change indicates that a decrease of 52% or more is theoretically seen in 2.5% of the observations. Using the traditional decrease of 40% currently used in the literature, there were false-negative and false-positive predictions of fetal distress and/or neonatal asphyxia at rates unacceptable for patient management. The use of E3 determinations in combination with nonstress test-contraction stress test did not improve the predictability of this latter test. Serum E3 determinations are of little clinical value in the management of insulin-dependent diabetic pregnant women.

Asphyxia Neonatorum↗

Decreased bone mineral content in infants of diabetic mothers.

The present study was conducted to test the hypothesis that infants of diabetic mothers (IDMs) have decreased bone mineral content at birth, and whether or not decreased infant bone mineral content in IDMs correlates with poor control of diabetes during pregnancy, maternal bone mineral content, and the development of neonatal hypocalcemia. Forty-five pregnant diabetic women and their infants were enrolled in a prospective trial. In addition, 55 normal newborn infants of nondiabetic mothers were used as controls. Bone mineral content was measured before delivery in all diabetic pregnant patients and at birth in all infants by photon absorptiometry. Bone mineral content was significantly decreased in infants of diabetic mothers compared with control infants and correlated inversely with mean first trimester maternal capillary blood glucose; it did not correlate with cord serum 1,25-dihydroxyvitamin D concentrations. By stepwise multiple regression analysis, in infants of diabetic mothers, bone mineral content correlated inversely with mean first trimester capillary blood glucose and maternal bone mineral content, but did not correlate with maternal blood glycosylated hemoglobin, infant gestational age, infant birthweight or weight percentile, or development of neonatal hypocalcemia.

Blood Glucose↗

Impact of pregnancy on complications of insulin-dependent diabetes mellitus.

The effects of pregnancy on acute metabolic complications of diabetes may have important consequences for both mother and fetus. The consequences of pregnancy for chronic complications of diabetes, including retinopathy, nephropathy, neuropathy, and hypertension, are not clear. Recent data are reviewed so that health care providers will be able to provide reasonable advice to insulin-dependent diabetic women contemplating pregnancy both for problems that may potentially arise during gestation and those that may affect long-term health and survival. Diabetic ketoacidosis is an uncommon problem that arises during gestation. Acute alterations in pH and electrolyte concentrations as well as hyperglycemia, however, may have important consequences for mother and fetus, including perinatal asphyxia and reduced fetal oxygen delivery. Hypoglycemia, on the other hand, may result in maternal coma or seizures and, when frequent, has been associated with infant respiratory distress syndrome. Background retinopathy often worsens during gestation, with regression common postpartum. Data suggest that progression of background disease is related to both glycemic control and the acute institution of intensive insulin therapy with those patients with poor control requiring more aggressive therapeutic intervention most adversely affected. The course of proliferative retinopathy is more variable, with both progression and regression reported. Preconception photocoagulation may prevent progression. Preconceptional ophthalmologic evaluation with frequent assessments during pregnancy is advised. Increases in 24-hour protein excretion are common during gestation in patients with preexisting renal disease and resolve in many patients postpartum. Serum creatinine and creatinine clearance increase during the first trimester and generally do not change during the remainder of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 1↗

Periconceptional metabolic status and risk for spontaneous abortion in insulin-dependent diabetic pregnancies.

The rate of clinically apparent spontaneous abortions in insulin-dependent diabetic pregnancies has been prospectively determined to be twice as frequent as for the general population (29.5% versus 10 to 15%). In a series of several successive studies, we have shown that spontaneous abortions are associated with poor metabolic control around conception and/or in the early weeks of pregnancy, but not in the 1 to 2 weeks preceding the abortive event itself. There is also a significant relationship between decreased maternal magnesium status (as assessed by maternal serum magnesium concentration) and adverse fetal outcome (spontaneous abortion and/or major congenital malformations) in insulin-dependent diabetic women. We speculate that improvement of glycemic control and of magnesium status before conception and in the very early phases of organogenesis might improve embryonic and fetal survival.

Abortion, Spontaneous↗

Major malformations in infants of IDDM women. Vasculopathy and early first-trimester poor glycemic control.

From animal and in vitro studies, it has been suggested that high environmental glucose, ketone, or insulin concentrations and low glucose or insulin concentrations may be etiologic factors for congenital malformations (CMs) in infants of diabetic mothers (IDMs). Transplacental passage of antibody-bound insulin has been demonstrated in humans. Controversy exists regarding the pathophysiology of CMs in human insulin-dependent diabetes mellitus (IDDM) pregnancies. We hypothesized that CMs in IDMs are associated with maternal vasculopathy, poor first-trimester glycemic control (i.e., hyper- and/or hypoglycemia), advanced White class, and high insulin requirements. We studied 165 first pregnancies of women with IDDM from 1978 to 1986. The goals of glucose control were a fasting blood glucose of less than 100 mg/dl and a 90-min postprandial blood glucose of less than 140 mg/dl. Insulin requirements, body weight, and pre- and postprandial blood glucose were recorded at weekly clinic visits. Maternal blood HbA1 was measured on entry and every 4 wk to confirm that adequate glycemic control was achieved. Women who enrolled in the project were interviewed during gestation by a geneticist/dysmorphologist who obtained genetic and environmental histories using a standard questionnaire. All live-born infants and stillbirths were examined. Each live-born infant was assessed systematically by two independent examiners, a neonatologist and a geneticist/dysmorphologist; examination with standardized checklists was performed in the newborn nursery as soon after birth as was practical. In first pregnancies in the study, there were 13 IDMs with major CMs (7.9%).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

High spontaneous premature labor rate in insulin-dependent diabetic pregnant women: an association with poor glycemic control and urogenital infection.

The incidence of spontaneously occurring premature labor in insulin-dependent diabetic pregnancies is unclear, because previous studies have been confounded by a high rate of iatrogenic prematurity. The purpose of this study was to determine, in a large population of insulin-dependent diabetic pregnant women, the rate of spontaneous occurrence of premature labor and the various factors that may affect it. We hypothesized a priori that spontaneously occurring premature labor occurs at a high rate in insulin-dependent diabetic pregnant women, mainly because of poor control of diabetes during pregnancy, and is related to the presence of polyhydramnios and hypomagnesemia. One hundred forty-five insulin-dependent diabetic women undergoing 181 pregnancies were recruited since 1978 in an interdisciplinary prospective study. The goals of glucose control were a fasting blood glucose less than 100 mg/dL and a 90-minute postprandial glucose less than 140 mg/dL. The rate of spontaneous premature labor, 31.1%, was significantly higher (P less than .01) than that in a control population managed by the same obstetricians in similar clinical settings (20.2%). The following variables were not significantly associated with the onset of premature labor: maternal age, parity, gravidity, diabetic class according to White, presence of renal disease or retinopathy, previous elective abortion, chronic hypertension or pregnancy-induced hypertension, cigarette smoking, first-trimester or post-20 weeks' gestation vaginal bleeding, maternal serum magnesium concentration, or polyhydramnios.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Management of the insulin-dependent diabetic during labor and delivery. Influences on neonatal outcome.

Infants of insulin-dependent diabetic mothers are at risk for neonatal polycythemia, hyperbilirubinemia, respiratory distress syndrome (RDS), and hypoglycemia. The purpose of this study was to determine whether labor and delivery management of diabetes may influence the rate of these complications. We hypothesized a priori that: infants of diabetic mothers delivered by cesarean section have a lower rate of neonatal polycythemia and hyperbilirubinemia, but a higher rate of RDS, than infants of diabetic mothers delivered by vaginal route, and poor glycemic control during labor increases the rate of neonatal hypoglycemia. We therefore prospectively studied 122 pregnancies in 100 well-controlled insulin-dependent diabetic mothers. Intravenous glucose and/or insulin was infused during labor to maintain capillary glucose concentration between 70 and 100 mg/dl. Fifty-six pregnancies were concluded by primary or elective cesarean section (group 1), 36 by cesarean section following spontaneous or induced labor (group 2), and 30 by spontaneous or induced vaginal delivery (group 3). Hemoglobin A1, birthweight, and gestational age were similar in all three groups. The rate of neonatal polycythemia was significantly lower in the cesarean section subjects, groups 1 and 2, as compared to group 3 (P less than 0.04). The rate of neonatal hyperbilirubinemia was significantly lower in group 1 (P less than 0.05) as compared to groups 2 and 3. The rate of RDS was higher in group 1 (versus groups 2 or 3), but did not reach significance on initial analysis (P = 0.06); however, group 1 was associated with a significant risk for RDS when corrected for the confounding variables of gestational age and neonatal asphyxia as defined by Apgar scores.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Amniotic fluid osteocalcin concentrations in pregnancies uncomplicated by fetal bone disease.

Osteocalcin is the major noncollagenous bone protein. Serum osteocalcin concentrations increase in conditions when bone turnover is increased, reflecting enhanced osteoblastic activity. The presence of osteocalcin in amniotic fluid (AF) has not been reported. We undertook this study to determine if osteocalcin is present in AF and to establish standards for AF osteocalcin concentrations, to be used in pregnancies at risk for diseases with increased fetal bone turnover. One hundred and thirty-one samples of AF from 15 to 43 weeks gestation were analyzed for osteocalcin by a radioimmunoassay detecting greater than or equal to 0.1 ng/ml, with a coefficient of variation of 6%. Osteocalcin measured in AF had the same gel-filtration characteristics as serum osteocalcin and the standard curves for serum and AF osteocalcin were parallel. Indications for amniocentesis were genetic study (n = 15) and fetal lung maturation (n = 116). None of the pregnancies studied produced an infant with bone mineral disorder. In 67% of the AF samples, osteocalcin was undetected; in 95% of the samples the concentration was less than 2.4 ng/ml. Concentrations of AF osteocalcin did not correlate with gestational age or birthweight, and were lower than the reported concentrations in cord serum or maternal serum. Thus normal amniotic fluid osteocalcin concentrations are less than 2.4 ng/ml; we speculate that its elevation in fetal bone disorders may provide a genetic counselling tool.

Amniotic Fluid↗