Antepartum fetal monitoring in insulin-dependent diabetic pregnancies

In order to minimize unexplained stillbirths in insulin-dependent diabetic pregnancies, fetal well-being was assessed by antepartum monitoring while development of pulmonary maturity was awaited. Antepartum monitoring consisted of outpatient nonstress tests beginning at 32 weeks' gestation. Fetuses with nonreactive nonstress tests were further evaluated by contraction stress tests and were delivered if tests were positive. With use of this system there were no unexplained stillbirths during management of 119 insulin-dependent diabetic pregnancies. Of 14 infants delivered because of positive contraction stress tests, six were found to have major disorders; the other eight had no major residual neonatal morbidity. Thus this system of antepartum fetal surveillance: eliminated unexplained stillbirths, identified a subgroup of insulin-dependent diabetic pregnancies with a high rate of major fetal abnormalities, and allowed for identification and subsequent timely delivery of the other distressed fetuses that were at a high risk of neonatal morbidity and/or mortality, such that potential long-term adverse outcomes were avoided.     

The lecithin/sphingomyelin ratio in 132 insulin-dependent diabetic pregnancies.

A total of 228 determinations of L/S ratios were performed in 132 insulin-dependent diabetic pregnancies. A declining L/S ratio was observed in 6 per cent of the cases without adverse effects on the fetus. No significant difference in the percentage of mature L/S ratios by weeks of pregnancy was found in the different classes of diabetes. An immature L/S ratio was associated with a significant increase of low Apgar scores. At each stage of pregnancy, there was no significant difference in the percentage of mature L/S ratios according to the sex of the baby nor according to the presence or absence of polyhydramnios. Among the five infants with HMD two had a mature L/S ratio within 2 days of birth. This represents 3 per cent incidence of false-positive results. Despite this finding, we feel that the determination of L/S ratio is a useful advance in the management of diabetic pregnancies.     

Reassessment of White's classification and Pedersen's prognostically bad signs of diabetic pregnancies in insulin-dependent diabetic pregnancies

The classification systems developed over 20 years ago by White and Pedersen identified diabetic pregnancies at increased risk for perinatal mortality. To assess whether these same criteria would currently be valid, 199 diabetic pregnancies with deliveries from 1977 to 1983 were reviewed. Perinatal mortality rates for White's Classes B gestational (n = 72), B (n = 27), C (n = 67), and D + F + R (n = 33) were 2.9%, 11.1%, 14.9%, and 21.1%, respectively (p less than 0.05). White's classes were also predictive of pulmonary morbidity (12.5%, 18.5%, 22.4%, and 42.4%, respectively). The presence of one or more of the prognostically bad signs of pregnancy (n = 76) increased the perinatal mortality rate to 17.1% versus 7.3% among insulin-dependent diabetic pregnancies without prognostically bad signs (p less than 0.05). The presence of any prognostically bad signs of pregnancy was also predictive of pulmonary morbidity in general (31.6% versus 16.3%, respectively) and hyaline membrane disease in particular (13.2% versus 4.1%, respectively). Thus with use of modern obstetric management and medical care of the pregnant diabetic patient, both White's classification and Pedersen's prognostically bad signs of pregnancy continue to be predictive of perinatal mortality.     

Parathyroid hormone and calcitriol changes in normal and insulin-dependent diabetic pregnancies

In pregnancy, an increase in serum calcitriol and parathyroid hormone concentrations has been reported in several studies, though the increase in parathyroid hormone remains controversial. In magnesium deficiency states, parathyroid hormone and calcitriol secretion may be decreased. Because magnesium deficiency may occur in insulin-dependent diabetic patients, mainly because of urinary magnesium losses, we hypothesized that serum parathyroid hormone and calcitriol do not increase in the diabetic pregnancy. We studied, in a prospective longitudinal manner, 35 nondiabetic and 199 insulin-dependent diabetic pregnancies. In diabetic women, the goals of glycemic control were fasting blood glucose below 100 mg/dL and postprandial blood glucose less than 140 mg/dL. Serum magnesium, calcium, parathyroid hormone (whole molecule; ie, 1-84 fragment), and calcitriol were measured three times: 1) 8-12 weeks, 2) 22-28 weeks, and 3) 32-38 weeks' gestation. In normal women, serum parathyroid hormone did not change significantly over pregnancy, and a wide scatter of values was observed. Serum calcitriol increased significantly with advancing gestation. In diabetic women, serum parathyroid hormone had a narrow scatter, but values were within the low-normal range. During the third trimester there was no increase, and even a decrease, in serum calcitriol concentrations. Diabetics had, throughout pregnancy, significantly reduced serum magnesium concentrations when compared with controls. Their serum calcium and ionized calcium concentrations were similar to those of controls, except in the third trimester, when diabetic women had significantly lower serum calcium and ionized calcium concentrations than controls. We speculate that mineral metabolism abnormalities in diabetic pregnancies might be due to relative magnesium and/or insulin deficiency.     

Birth outcomes in teenage pregnancies.

OBJECTIVE: To evaluate and characterize the racial/ethnic differences in obstetric outcomes of early and late teenagers in California. METHODS: A data-set linking birth and death certificates with maternal and neonatal hospital discharge records in California was utilized to identify nulliparous women (11 to 29 years of age) who delivered between January 1,1992 and December 31,1997. Pregnancy outcomes of early (11-15 year) and late (16-19 year) teenagers were compared to those of a control group of women aged 20-29. RESULTS: Early (n = 31 232) and late teens (n = 271 470) demonstrated greater neonatal and infant mortality and major neonatal morbidities (delivery < 37 weeks of gestation and birthweight < 2500 g) when compared to pregnancies in the older control women (n = 662 752). Ethnicity adversely affected outcome with African-Americans of all ages having worse outcomes than whites. The higher rate of adverse obstetric outcomes among the teenage pregnancies occurred despite a lower cesarean section rate and was consistent across all ethnic groups. CONCLUSIONS: When compared to women aged 20-29, all teen pregnancies were associated with higher rates of poor obstetric outcomes. Other factors besides teen pregnancy appear to be responsible for poor outcomes in certain ethnic groups.     

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.     

Short term variability of fetal heart rate during insulin-dependent diabetic pregnancies

The clinical significance of quantified short term variability of antepartal fetal heart rate (FHR) in prediction of fetal distress in labor was assessed in 120 insulin-dependent diabetic pregnancies. FHR was recorded by abdominal fetal electrocardiography (aFECG), from which the differential indices (DI) describing the short term variability of FHR were analyzed by a microprocessor-based on-line method. The analysis was successful in 308 of 350 trials (87%). In ten pregnancies, no acceptable a FECG was obtained. Fetal distress developed in 28 of the 110 pregnancies with successful FHR analysis. There were no intrauterine deaths in this series, but two newborn infants died (perinatal mortality 1.7%). Ninety-three pregnancies with FHR analyses within one week of delivery were included in the assessment of the test. DI predicted 2 of the 17 cases of fetal distress (sensitivity 67%). Twelve of the 18 cases with a pathological DI developed fetal distress (predictive value 71%). DIs were normal in 67 of the 73 pregnancies without fetal distress (specificity 92%). Risk of fetal distress after a pathological DI was 8.5 times that after normal DIs (relative risk), which is highly significant.     

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.     

Fetal surveillance in pregnancies complicated by insulin-dependent diabetes mellitus.

OBJECTIVE: Our objective was to determine whether maternal vascular disease and/or glycemic control can be related to tests of fetal condition in diabetic pregnancies. STUDY DESIGN: A total of 114 women with insulin-dependent diabetes who used a memory-based glucose reflectance meter were prospectively evaluated. Nonstress testing was begun weekly at 28 to 30 weeks and twice weekly at 32 weeks. A nonreactive nonstress test was followed by a biophysical profile in all cases. RESULTS: A total of 1676 nonstress tests was performed (14.7 +/- 3.2 tests per patient). Eight percent (n = 134) were nonreactive, necessitating a biophysical profile. A comparison of ambulatory glucose profile data, including mean blood glucose level, variation, and excursions from the median, revealed no significant differences in patients with reactive versus nonreactive nonstress tests. Ten patients, including eight with vascular disease, were delivered because of abnormal test results of fetal condition. Nephropathy or hypertension was associated with intervention for fetal well-being in 8 of 20 women (40%) with these risk factors. Only 2 of 94 patients (2%) without nephropathy or hypertension required delivery because of abnormal results of fetal testing (p less than 0.001). One fetal death occurred. No significant differences in the various glycemic parameters were found in women delivered for suspected fetal jeopardy versus the nonintervention group. CONCLUSION: Pregnancies complicated by vascular disease are at greatest risk for abnormal results of fetal testing that necessitate early delivery. Women without vascular complications and with maintenance of good glycemic control rarely have fetal compromise.     

Maternal-fetal status of copper,iron, molybdenum,selenium and zinc in insulin-dependent diabetic pregnancies

Objective The objective was to assess the status of essential trace elements such as copper, iron, molybdenum, selenium and zinc in insulin-dependent diabetic pregnancies at term and to compare the data with a control group. Fetal-maternal ratios of the elements and copper:zinc ratio were also computed in the control and study populations.Methodology Samples from maternal vein, umbilical artery and umbilical vein of diabetic and control women were collected at the time of spontaneous delivery or cesarean section and activities of trace elements evaluated by atomic absorption spectrophotometry.Results Cu, Fe, Mo, Se and Zn concentrations in maternal venous blood averaged 2,156, 2,020, 13, 102 and 656 g/l in control women (n=17) while in the diabetic group (n=14), the corresponding values for the trace elements averaged 3,135, 3,675, 15, 85 and 628 g/l respectively. Values for copper and molybdenum were significantly higher (p<0.05) in the study group compared to control while those of zinc, iron and selenium were not significantly different (p>0.05). Iron and molybdenum values were significantly higher (p<0.05) and that of zinc significantly lower (p<0.05) in umbilical arterial samples of diabetic group compared to controls. In the case of molybdenum, copper the values were significantly higher (p<0.05) in umbilical venous samples of diabetic group compared to that of control. Significant differences in Cu:Zn ratio of maternal venous and umbilical samples and fetal-maternal ratios of some elements were noted between control and study group as well.Conclusion We speculate that altered status of some essential trace elements and altered antioxidant mineral ratio observed in insulin dependent diabetic patients could have deleterious influences on the health of the mother as well as the fetus and newborn.     

Preeclampsia in diabetic pregnancies

Diabetic pregnancies complicated by preeclampsia are of concern because of poor perinatal outcome. However, with improved maternal and fetal surveillance the impact of preeclampsia in diabetic pregnancies is declining. This prospective controlled study compared the incidence of preeclampsia and maternal-fetal outcome in 334 diabetic pregnancies and 16,534 nondiabetic pregnancies. The incidence of preeclampsia was 9.9% (33/334) in diabetic pregnancies compared with 4.3% (716/16,534) in nondiabetic controls. The incidence of preeclampsia rose with increasing severity of diabetes by White classification, but was still 8.9% after exclusion of diabetic patients with nephropathy or chronic hypertension. The perinatal mortality rate per 1000 births was 60 for preeclamptic diabetic patients compared with 3.3 for normotensive diabetic patients. Parity, maternal age, and blood glucose control were similar in preeclamptic diabetic patients compared with normotensive diabetic patients. We conclude that preeclampsia is twice as common in diabetic pregnancies compared with normal controls.     

Stillbirth in diabetic pregnancies

Pregnancy in women with pregestational diabetes is associated with high perinatal morbidity and mortality. Stillbirth accounts for the majority of cases with perinatal death. Intrauterine growth restriction, pre-eclampsia, foetal hypoxia and congenital malformations may be contributing factors, but more than 50% of stillbirths are unexplained. Majority of stillbirths are characterised by suboptimal glycaemic control during pregnancy. Foetal hypoxia and cardiac dysfunction secondary to poor glycaemic control are probably the most important pathogenic factors in stillbirths among pregnant diabetic women. There is thus a need for new strategies for improving glycaemic control to near-normal levels throughout pregnancy and for preventing and treating hypertensive disorders in pregnancy. Antenatal surveillance tests including ultrasound examinations of the foetal growth rate, kick counting and non-stress testing of foetal cardiac function are widely used. However, future research should establish better antenatal surveillance tests to identify the infants susceptible to stillbirth before it happens.     

Complication of insulin-dependent diabetic pregnancies by preeclampsia and/or chronic hypertension: analysis of outcome

The significance of hypertensive complications of insulin-dependent diabetic pregnancies (IDDP) has not been well examined since the early reports of Pedersen, which demonstrated an increased risk of neonatal death in women with pregnancy induced hypertension (PIH). To assess the effect of both PIH and chronic hypertension (CH) on outcome of IDDP managed using contemporary obstetrical and diabetic management, we reviewed the records of all 199 IDDP delivered at our institution over a 7-year period. Patients were classified as having PIH (Group 1, n = 37), CH (Group 2, n = 18) or both (Group 3, n = 4) on the basis of standard clinical criteria. All other IDDP were placed in the control group (Group 4, n = 140). Comparing all groups, significant differences were found for maternal age (P less than .0001) and distribution among White's Classes (P less than .0001). There was no significant difference in estimated gestational age (EGA) at delivery, birthweight, Apgar scores, hypoglycemia, hyperbilirubinemia, or congenital anomalies. Intrauterine fetal death (IUFD) was no more common in Groups 1, 2 or 3 than in Group 4; however, IDDP with CH were significantly more likely to have had previous stillbirths than IDDP with PIH (P = .011) or control IDDP (P = .017). Contrary to common clinical belief, the "stress" of CH and PIH did not offer protection to the newborn in the development of RDS or HMD. In fact, Group 3 infants had a higher rate of HMD than control infants (P = .024).(ABSTRACT TRUNCATED AT 250 WORDS)     

High maternal levels of hemoglobin A1c associated with delayed fetal lung maturation in insulin-dependent diabetic pregnancies

Phosphatidylglycerol (PG) in 227 amniotic fluid specimens obtained by amniocentesis during the third trimester and hemoglobin A1c (Hb A1c) in 889 maternal blood specimens obtained between 6 and 39 gestational weeks were measured for 115 singleton insulin-dependent diabetic pregnancies without major fetal malformations or stillbirths. The fetuses of diabetics whose mean Hb A1c during pregnancy was 8.5% or more remained PG-negative more often than those in the pregnancies with the mean Hb A1c below 8.5% at 37 (4/7 vs. 8/68, chi 2 = 10.2, p less than 0.01) and 38 (2/7 vs. 2/84, chi 2 = 5.2, p less than 0.05) completed weeks of gestation. The fetuses of the patients with a mean Hb A1c 8.0% or more were more often PG-negative at 37 gestational weeks (7/15) than those in the pregnancies with a mean Hb A1c below 8.0% (5/60, chi 2 = 10.4, p less than 0.005). Because Hb A1c reflects long-term blood glucose levels, the results suggest that maternal hyperglycemia, or other metabolic disturbances associated with hyperglycemia, is the cause of delayed fetal lung maturation among insulin-dependent diabetics.     

Alterations of maternal metabolism in normal and diabetic pregnancies: differences in insulin-dependent, non-insulin-dependent, and gestational diabetes

In normal and diabetic pregnancies, the placenta functions as a complex endocrine gland that modulates all classes of maternal nutrients to the fetus. The metabolic alterations of normal pregnancy are diabetogenic and associated with modest resistance to endogenous insulin. Pregnant women with carbohydrate intolerance represent three metabolically heterogeneous groups: type I (insulin-dependent), type II (non-insulin-dependent), and gestational diabetes. Patients with type I diabetes are at risk for ketosis and require replacement therapy because of a deficient production of insulin. They have decreased 24-hour, around-the-clock levels of C-peptide and glucagon, and lower nocturnal cortisol values and higher 24-hour prolactin levels than those of women with type II diabetes. Type II pregnant diabetic patients are not prone to ketosis and are more resistant to endogenous and exogenous insulin. They have higher fasting and meal-stimulated levels of C-peptide, accentuated fasting hypertriglyceridemia, and significantly lower high-density lipoprotein cholesterol levels than those of normal or type I women. In gestational diabetes, the metabolic stress of pregnancy evokes reversible hyperglycemia which may be associated with either a surfeit or a deficiency of insulin. These metabolic differences among diabetic pregnant women could have implications for placental structure and function that might influence fetal growth.     

Placental weight in diabetic pregnancies

The placenta from 30 women with diabetes mellitus were examined and weighed at delivery. Nineteen of these were from women with overt and eleven from women with gestational diabetes. Eleven placentae from normal pregnancies served as controls. There was no difference between the mean +/- s.d. placental weight for the diabetic group and the control group (609 +/- 148 versus 591 +/- 93 g, NS). The mean placental weight ratios for the diabetic group and the control group were also similar (0.98 +/- 0.23 versus 0.89 +/- 0.15, NS). Moreover, there was no difference between the weights and weight ratios of placentae from women with overt (622 +/- 173 g, 1.02 +/- 0.27) and those with gestational diabetes (586 +/- 90 g, versus 0.90 +/- 0.13). Placental weights correlated with birthweights (r = 0.70, P less than 0.01) and with skinfold thickness measurements fo the infants (r = 0.40, P less than 0.05), but neither with gestational ages (r = 0.15, NS) nor with maternal glycosylated haemoglobin levels in the third trimester (r = 0.24, NS). Among the women with overt diabetes, placental weights were greater in those in White's class B and C than those in class D and R (689 +/- 143 versus 530 +/- 177 g; P less than 0.05). In general, placentae from well controlled diabetic patients were not heavier than those from normal pregnant women, although there was an increase in placental weight in White's class B and C, as compared with those in class D and R.     

Management of diabetic pregnancies in the United Kingdom.

The aim of this postal questionnaire survey was to identify facilities currently available for the care of pregnant diabetic women in the United Kingdom and determine how closely these reflect the standards recommended by The St Vincent Declaration Action Programme. A questionnaire was sent to a physician and an obstetrician in each of the 255 obstetric hospitals in the UK. Two hundred and forty-five (96.1%) hospitals replied, with most of these managing 20 or less insulin dependent diabetics per year. Of the hospitals, 58.4%, had a special combined diabetic antenatal clinic; 86.6% of the units had a single physician responsible for diabetic care, whilst more than one obstetrician was involved in 50.6% of the units. Prepregnancy counselling was provided in 87.4% of the hospitals. Home blood glucose monitoring was used in 97.9% of the units. Ideal mean pre- and postprandial blood glucose concentrations were 6.0 mmol/1 (SD 0.82) and 7.9 mmol/l (SD 0.91), respectively. Ultrasound was routinely used to assess fetal growth in 98.7% of the units. The mean gestational age for elective caesarean section was 38.2 weeks (SD 0.55), compared with 39.0 weeks (SD 0.35) for planned vaginal delivery. During labour, 98% of the units used a dextrose and insulin infusion, but only 53.7% of the units maintained an intrapartum maternal blood glucose of between 4 and 6 mmol/l. We conclude that there is widespread variation in the management of the pregnant diabetic patient, and much practice is suboptimal. Many of the recommendations of the St Vincent Declaration are not being met by current UK practice.