Can glucose tolerance test predict fetal hyperinsulinism?

Objective To establish cut off levels for oral glucose tolerance test in pregnancy using fetal hyperinsulinism as a clinical endpoint.
Design Capillary blood glucose levels at 0, 1, and 2 hours after the ingestion of either 1 g/kg or 75 g glucose, at 28 (SD 5) weeks of gestation were analysed in 220 women with elevated amniotic fluid insulin levels [≥ 42 pmol/L (≥ 7 μU/mL)] after a mean (SD) of 31 weeks (3) and in 220 nondiabetic controls.
Results In women with elevated amniotic fluid insulin levels the mean (SD) capillary blood glucose values at 0, 1, and 2 hours were 5.2 mmol/L (1.0) [94 mg/dL (18)], 10.5 mmol/L (1.4) [189 mg/dL (25)] and 8.2 mmol/L (2.0) [147 mg/dL (36)], respectively. The one-hour value had the highest sensitivity to predict elevated amniotic fluid insulin levels. The 5th centile of the one-hour blood glucose levels representing a detection rate of 95% was 8.9 mmol/L (160 mg/dL).
Conclusion Glucose cut off levels in most established oral glucose tolerance test criteria are too high, to accurately predict amniotic fluid hyperinsulinism. A one-hour test may be sufficient for detecting amniotic fluid hyperinsulinism. Since different loads (1 g/kg, 75 g or 100 g) and blood fractions (venous plasma or capillary blood) have minimal impact on oral glucose tolerance test results, a single one-hour cut off of 8.9 mmol/L (160 mg/dL), independent of the sampling method, may be appropriate for the diagnosis of gestational diabetes mellitus severe enough to cause amniotic fluid hyperinsulinism.     

Serum fructosamine and amniotic fluid insulin levels in patients with gestational diabetes and healthy control subjects

Gestational diabetic pregnancies with fetal hyperinsulinism should be identified because these cases require insulin therapy. To determine the relationship between the serum fructosamine and amniotic fluid insulin concentrations, these substances were measured in 87 pregnant women with impaired glucose tolerance. Fructosamine was also measured in 678 healthy pregnant control subjects, in 113 of whom amniotic fluid insulin levels were available. Fetal hyperinsulinism was rare at serum fructosamine levels of less than 2.6 mmol/L. These results suggest that when both the oral glucose tolerance test and fructosamine level are used, only 30% of women with gestational diabetes need to undergo amniocentesis to assess fetal insulin homeostasis.     

Gestational diabetes and screening during pregnancy

The oral glucose tolerance test is an unreliable test in screening for diabetogenic fetal disease. In diabetogenic fetopathy due to gestational diabetes (White class A diabetes), the insulin content in the umbilical cord blood as well as in the fetal urine is considerably raised. As increased amounts of insulin pass into the amniotic fluid via the fetal urine, the fetal disease can be diagnosed from the amniotic fluid insulin content. In 75 pregnant women with potential diabetes, the blood sugar value was below 160 mg/dL at maximum under glucose loading in 28 patients; it was over 200 mg/dL in 25 patients. However, diabetogenic fetopathy was present in only 14 patients. The endangered and the healthy fetus could be distinguished in each case by amniotic fluid insulin content. The mean amniotic fluid insulin values in diabetogenic fetopathy were about seven times the normal.     

Fructosamine in relation to maternofetal glucose and insulin homeostasis in gestational diabetes

Summary The problem in screening for gestational diabetes is recognizing fetuses endangered by hyperinsulinism. 21.8% of patients with gestational diabetes (defined as a glucose peak exceeding 160 mg/dl after an oral glucose load of 1 g per kg body weight) develop fetal hyperinsulinism. Thus, is indicated by an elevated amniotic fluid insulin (AFI) concentration and requires insulin treatment. Since fetal hyperinsulinism can be neither predicted nor ruled out by single parameters of materal metabolism, every patient with gestational diabetes had to undergo amniocentesis for amniotic fluid analysis. In 110 gestational diabetics and 822 controls, fetal hyperinsulinism was predicted by the combination of the oGTT (≥160 mg/dl) and maternal serum fructosamine (≥2.6 mmol/l) with a sensitivity of 95.8% and a specificity of 91.8%. Thus, 73% of gestational diabetics need not undergo amniocentesis. With a sensitivity of 20.8%, the combination of the oGTT and HbA1c is not useful in identifying hyperinsulinemic fetuses.     

Diagnosis and treatment of gestational diabetes according to amniotic fluid insulin levels

In spite of dietary treatment, the infants of pregnant patients with abnormal glucose tolerance have hyperinsulinism and diabetogenic fetopathy in 10 to 36% of cases. Those patients, who require insulin to prevent from fetopathy cannot be reliably selected by maternal parameters such as blood glucose and glycosylated hemoglobin values. We recommend the measurement of amniotic fluid insulin between the 28 and 32 weeks of pregnancy to differentiate whether the fetus is compromised or not. Subjects with values above the 97th centile require insulin therapy. Inadequate insulin dosage or delayed fetal hyperinsulinism can be discovered by checking the amniotic fluid insulin level at 33 to 36 weeks. In a total of 88 gestational diabetic patients 19 had raised amniotic fluid insulin levels indicating the onset of diabetic fetopathy at an early stage. Diabetic patients with raised amniotic fluid insulin levels needed large doses of insulin, namely 64.6 +/- 29.5 (Mean +/- SD) U/24 h. This treatment reduced mean blood glucose levels from 98 +/- 9 (Mean +/- SD) mg/dl to 82 +/- 10 mg/dl and was sufficient to prevent from diabetic fetopathy.     

Effect of the 100-g oral glucose tolerance test on fetal acid-base balance

OBJECTIVE: Previous studies have shown that maternal hyperglycemia may lead to fetal hypoxia and acidosis. The aim of the present study was to examine the impact of an oral 100-g glucose tolerance test on the fetal acid-base balance at mid-gestation. METHODS: The study was conducted in healthy women who were scheduled for termination of pregnancy. The study group (n = 18) received an oral solution containing 100-g glucose and the control group (n = 18) received only water 1 h prior to termination of pregnancy. Termination of pregnancy was performed by fetal intracardiac injection of potassium chloride (KCl) and intraamniotic instillation of PGF2alpha. Acid-base variables were evaluated in the fetal blood and the amniotic fluid. RESULTS: The glucose levels differed significantly between the study group and the control group with regard to maternal blood (127 +/- 28 versus 69 +/- 11 mg/dL, p < 0.001), fetal blood (128 +/- 24 versus 71 +/- 17 mg/dL, p < 0.001) and amniotic fluid (39 +/- 13 versus 28 +/- 5 mg/dL, p < 0.006). A linear relationship was found between maternal, fetal and amniotic fluid levels of glucose after maternal glucose ingestion. No significant changes were observed in the acid-base balance variables (pH, base excess, bicarbonate, lactate) in the fetal blood and the amniotic fluid of the study and control groups. CONCLUSION: The 100-g oral glucose tolerance test has no adverse effect on the fetal acid-base balance when glucose levels reach a peak 1 h after the test in normal pregnancies.     

Amniotic Fluid Insulin Values in Women with Gestational Diabetes as a Predictor of Emerging Diabetes Mellitus

Summary: Amniotic fluid insulin levels were estimated in 30 women with insulin-dependent diabetes, 216 with gestational diabetes and 27 with normal glucose tolerance. Results were correlated with birth-weight, incidences of fetal macrosomia and neonatal hypoglycaemia, and the risk of the mothers with gestational diabetes developing diabetes mellitus on follow-up.
The women with prepregnaney diabetes had significantly higher amniotic fluid insulin values and showed a significant correlation between raised liquor insulin values (>97th percentile) and hypoglycaemia in the infant (p = 0.039).
In the gestational diabetic pregnancies there were highly significant associations between elevated liquor insulin values and macrosomia (p <0.0045) and birth-weight (p <0.00004), and a weak correlation with neonatal blood glucose levels (p = 0.042).
Women with gestational diabetes who later developed permanent diabetes mellitus had higher mean amniotic fluid insulin levels than those whose glucose tolerance remained normal on follow-up (p ≤0.0072) and more of them had a level greater than the 97th percentile than those whose glucose tolerance remained normal (odds ratio 6.48, 95% confidence interval 1.51–27.8, p = 0.0094). However a high amniotic fluid insulin level was of less clinical value for detection of women destined to develop diabetes (7 of 25, 28%) than was the need for insulin therapy during pregnancy (18 of 39, 46%) .     

Correlation between amniotic fluid glucose concentration and amniotic fluid volume in pregnancy complicated by diabetes

OBJECTIVE: Pregnancies complicated by diabetes are frequently characterized by an increased volume of amniotic fluid, and the pathophysiologic mechanism of this increase is not known. Our goal was to evaluate the relationship between amniotic fluid glucose concentration and the amniotic fluid index in pregnancies complicated by insulin-treated diabetes and to compare it with that seen in normal pregnancies. STUDY DESIGN: Amniotic fluid index and amniotic fluid glucose levels were measured before elective repeated cesarean delivery in 41 women with insulin-treated diabetes and in 35 women without diabetes. Only singleton gestations without anomalous fetuses were included. Women with diabetes were hospitalized for approximately 4 weeks before delivery, during which time glycemic control was optimized. Amniotic fluid index and amniotic fluid glucose concentration were correlated with each other and were compared between the groups with and without diabetes. RESULTS: The mean amniotic fluid index was significantly increased in the diabetes group (16.6 +/- 5.0 cm in the diabetes group vs 13.4 +/- 3.5 cm in the control group; P =.002). The amniotic fluid glucose concentration was also significantly greater in the diabetes group than in the control group (39 +/- 17 mg/dL in the diabetes group vs 24 +/- 11 mg/dL in the control group; P <.001). Among women with diabetes the amniotic fluid glucose concentration was significantly correlated with the amniotic fluid index (r = 0.32; P =.04), a correlation not found among the control women. The mean fasting blood glucose concentration among the women with diabetes for the week before amniocentesis was 82 +/- 11 mg/dL. CONCLUSION: The amniotic fluid index parallels the amniotic fluid glucose level among women with diabetes. This finding raises the possibility that the hydramnios associated with diabetes is a result of increased amniotic fluid glucose concentration.     

Decreased plasma adiponectin concentrations in women with gestational diabetes mellitus

OBJECTIVE: Adiponectin is an adipocyte-specific protein that has been found to be associated with insulin sensitivity and obesity. Because gestational diabetes mellitus is associated with obesity and decreased insulin sensitivity, we have analyzed plasma adiponectin levels in women with gestational diabetes mellitus. STUDY DESIGN: Twenty women with gestational diabetes mellitus and 21 unaffected women were included in the study. Plasma adiponectin levels were analyzed with the use of enzyme-linked immunosorbent assay. RESULTS: Women with gestational diabetes mellitus were significantly older (34.3 years vs 29.4 years; P < .001) than unaffected women. Adiponectin plasma levels were significantly lower in women with gestational diabetes mellitus when compared with women without gestational diabetes mellitus (5827 +/- 1988 ng/mL vs 8085 +/- 3816 ng/mL; P = .02). Adiponectin plasma levels were correlated negatively with plasma glucose concentrations of the oral glucose tolerance test ( r > -0.38; P < .04) and correlated positively with gestational age ( r = 0.36; P = .03). CONCLUSION: Our data show that decreased plasma adiponectin levels were found in women with gestational diabetes mellitus compared with unaffected women.     

Impaired glucose tolerance associated with adverse pregnancy outcome: a population-based study in southern Sweden

OBJECTIVE: We conducted a population-based study of maternal and neonatal characteristics and delivery complications in relation to the outcome of a 75-g, 2-hour oral glucose tolerance test at 25 to 30 weeks' gestation. STUDY DESIGN: An oral glucose tolerance test was offered to pregnant women in a geographically defined population. Pregnancy outcome was analyzed according to the test result. RESULTS: Among women delivered at Lund Hospital, we identified 4526 women with an oral glucose tolerance value of <7.8 mmol/L (<140 mg/dL), 131 women with a value of 7.8 to 8.9 mmol/L (140-162 mg/dL), and 116 women with gestational diabetes (> or =9.0 mmol/L [> or =162 mg/dL]). A further 28 cases of gestational diabetes were identified, giving a prevalence of 1.2%. An increased rate of cesarean delivery and infant macrosomia was observed in the group with a glucose tolerance value of 7.8 to 8.9 mmol/L (140-162 mg/dL) and in the gestational diabetes group. Advanced maternal age and high body mass index were risk factors for increased oral glucose tolerance values in 12,657 screened women in the area. CONCLUSION: The study stresses the significance of moderately increased oral glucose tolerance values.     

A comparison of amniotic fluid fetal pulmonary phospholipids in normal and diabetic pregnancy

OBJECTIVE: Our purpose was to determine whether there are differences in the timing of the appearance of various amniotic fluid fetal pulmonary phospholipids in normal and diabetic pregnancy. STUDY DESIGN: A case-control study of 295 subjects with diabetes and 590 control subjects was performed by use of gestational age-matched amniocentesis specimens analyzed for lecithin/sphingomyelin (L/S) ratio, phosphatidylinositol (PI), and phosphatidylglycerol (PG) composition. Diabetic subjects were stratified according to type of diabetes, degree of blood glucose control, and birth percentile of the neonate. RESULTS: There was no difference in L/S ratios over gestational age by type of diabetes or quality of glycemic control. Women with preexisting diabetes had significantly higher PI levels at 33 to 35 weeks' gestation, which became similar to levels of control subjects after 36 weeks, whereas patients with gestational diabetes mellitus and control subjects had similar PI levels throughout. In diabetic subjects, the onset of production of PG was delayed from 35.9 +/- 1.1 weeks (controls) to 38.7 +/- 0.9 weeks (overt diabetics) and 37.3 +/- 1.0 weeks for gestational diabetes mellitus (P <.001). The delay in PG synthesis was not related to infant sex, level of maternal glucose control, or fetal macrosomia. CONCLUSIONS: Fetal pulmonary maturation, as evidenced by the onset of PG production in the amniotic fluid, is delayed in diabetic pregnancy by 1 to 1.5 weeks. This delay appears to be associated with an early and sustained elevation in amniotic fluid PI levels at 32 to 34 weeks.     

Does insulin secretion in patients with one abnormal glucose tolerance test value mimic gestational diabetes mellitus?

OBJECTIVE: The purpose of this study was to investigate the insulin response to a 3-hour oral glucose tolerance test and to compare the insulin levels in the gestational diabetes mellitus and single abnormal test value groups with a nondiabetic control group. STUDY DESIGN: One hundred ten Turkish women with uncomplicated pregnancy participated in this prospective controlled study between 24 to 28 weeks of gestation. A 100-g 3-hour oral glucose tolerance test was given, and glucose and insulin plasma levels were assayed. The subjects were classified according to established criteria. Early-phase insulin secretion was assessed by the insulinogenic index. Total insulin secretion was assessed by mean insulin level during the oral glucose tolerance test; insulin resistance was assessed by fasting insulin concentration and by the use of the homeostasis model. Data were analyzed by the Student t test and 1-way analysis of variance, with posthoc Bonferroni correction. RESULTS: The fasting insulin levels of patients with normal oral glucose tolerance test results were significantly lower than those of patients with gestational diabetes mellitus and a single value abnormality (P <.001 and P <.005, respectively). The insulinogenic index as a marker of early-phase insulin secretion was significantly lower in gestational diabetes mellitus, compared with that of patients with normal oral glucose tolerance test results (P <.05). The worsening of glycemic profile from normal oral glucose tolerance test results to gestational diabetes mellitus was associated with an increase in the homeostasis model; no significant difference was found between gestational diabetes mellitus and a single value abnormality group in terms of both the homeostasis model and the insulinogenic index. Values for total insulin secretion were highest in gestational diabetes mellitus, followed by the single value abnormality group, both significantly differing from the values of patients with normal oral glucose tolerance test results (P <.001 and P <.005, respectively). CONCLUSION: In this prospective study of Turkish subjects, we found a striking similarity in terms of patient characteristics between the gestational diabetes mellitus group and the single value abnormality group. Additionally, when we used fasting insulin level and insulin resistance as 2 separate criteria of analysis, patients with single value abnormality were indistinguishable from patients with gestational diabetes mellitus; both groups were significantly different from the normal oral glucose tolerance test group. Our findings suggest that a single abnormal test value on an oral glucose tolerance test should be regarded as a pathologic finding and that the patient with a single abnormal test value may be treated similarly to the patient with gestational diabetes mellitus.     

Fetal hyperinsulinism and maternal one-hour postload plasma glucose level

OBJECTIVE: Fetal insulin concentrations reflect the intrauterine glucose load given the fetus by the mother. In this study, we assessed the association between maternal glucose levels during oral glucose tolerance testing and fetal cord insulin. METHODS: Pregnant women with an oral glucose tolerance test (OGTT) result were included in this prospective study. The patients were divided into 3 groups according to their 1-hour OGTT glucose concentration: up to 160 mg/dL (control, group I), 160-179 mg/dL (intermediate, group II), and gestational diabetes mellitus (GDM, group III). Patients with GDM were assigned to insulin therapy if blood glucose levels were not in the preferable range. RESULTS: Of the 930 patients who entered the study, 570 (61.3%) were assigned to group I, 76 (8.2%) to group II, and 284 (30.5%) to group III. The cord blood insulin value was significantly (P < .001, Mann-Whitney test) higher in group II (median, 12.8 microU/mL; range, 3-130 microU/mL) than in group I (median, 7.25 microU/mL; range, < 3-98 microU/mL). Cord blood insulin values were higher, albeit not significantly (P = .100, Mann-Whitney test), in group II than in group III (median, 9.9 microU/mL; range, < 3-61 microU/mL). CONCLUSION: Children whose mothers had a 1-hour value between 160 and 179 mg/dL had significantly higher cord blood insulin values than offspring of women with a 1-hour value below 160 mg/dL.     

Accelerated starvation in late pregnancy: a comparison between obese women with and without gestational diabetes mellitus

We compared the glucose, insulin, free fatty acid, and 3-hydroxybutyrate responses to a briefly extended overnight fast during the third trimester of pregnancy between two groups: obese women with normal glucose tolerance (n = 10) and age- and weight-matched women with gestational diabetes mellitus (n = 10). After a 12-hour overnight fast, plasma glucose (95 +/- 4 vs. 78 +/- 2 mg/dl; p less than 0.01), insulin (32 +/- 5 vs. 17 +/- 2 microU/ml; p less than 0.02), and free fatty acid (860 +/- 63 vs. 639 +/- 79 mmol/L; p less than 0.05) levels were higher in the patients with gestational diabetes mellitus. 3-Hydroxybutyrate levels were similar in the two groups at that time (0.23 +/- 0.04 vs. 0.18 +/- 0.03 mmol/L; p greater than 0.3). When the fast was extended to 18 hours by having the patients skip breakfast, glucose levels fell more rapidly in the group with gestational diabetes mellitus but remained elevated compared with the nondiabetic women. Insulin levels declined at a similar rate in the two groups. Free fatty acid levels did not increase significantly in the group with gestational diabetes mellitus during the extended fast. In contrast, free fatty acid levels increased by 44% in the normal pregnant women, reaching the level observed in the group with gestational diabetes mellitus after 18 hours. 3-Hydroxybutyrate levels remained virtually identical in the two groups throughout the brief fast. Thus, compared with that of normal pregnant women, the response of obese women with gestational diabetes mellitus to brief caloric deprivation during late pregnancy was characterized by a greater fall in plasma glucose values without a greater propensity to ketosis. Our findings may have important implications for the dietary management of obese patients with gestational diabetes mellitus.     

Clinical predictors for a high risk for the development of diabetes mellitus in the early puerperium in women with recent gestational diabetes mellitus

OBJECTIVE: The purpose of this study was to identify which maternal, antepartum, or neonatal clinical parameters were predictive for a high risk of diabetes mellitus in the puerperium in women with recent gestational diabetes mellitus and to calculate the associated diabetes mellitus rates and odds ratios. STUDY DESIGN: One thousand six hundred thirty-six women underwent an oral glucose tolerance test within 1 to 4 months of delivery. Demographic, historic, and antenatal glycemic parameters and neonatal outcome parameters were tested by univariate and multivariate logistic regression for risk of postpartum diabetes mellitus. Continuous variables were divided into quartiles that compared the upper to lower quartile adjusted odds ratio and prevalence of diabetes mellitus. RESULTS: Postpartum diabetes mellitus was diagnosed in 230 women (14.1%) according to the American Diabetes Association criteria (1997). No maternal demographic or neonatal parameters were significantly associated with diabetes mellitus. The final model of independent predictors in decreasing significance included the highest fasting plasma glucose level during pregnancy, any fasting plasma glucose level of > or = 105 mg/dL (class A(2)), the area under the curve of pregnancy oral glucose tolerance test, gestational age at diagnosis, previous gestational diabetes mellitus history, and 50-g glucose challenge test results. The fasting plasma glucose level was the best discriminator, with a 21-fold (95% CI, 4.6-96.3) increased odds ratio comparing the 4th quartile (fasting plasma glucose level, >121 mg/dL; diabetes mellitus rate, 36.7%) to 1st quartile (fasting plasma glucose level, < 95 mg/dL; diabetes mellitus rate, 0.5%). The presence of previous gestational diabetes mellitus or current class A(2) gestational diabetes mellitus approximately doubled the odds ratio for diabetes mellitus. The odds ratio increased 3- to 4-fold when the area under the curve was > or = 33.36 min small middle dot g/dL (4th quartile) or the glucose challenge test was > or = 155 mg/dL (2nd-4th quartiles) and decreased > 50% if gestational diabetes mellitus was diagnosed at > 27 weeks (3rd-4th quartile). CONCLUSION: During pregnancy, the highest fasting glucose level, followed by the severity of glucose intolerance, and earlier gestational diabetes mellitus diagnosis were the best predictors for postpartum diabetes mellitus. Diabetic education should begin during pregnancy, especially for women who are identified to be at a high risk when they are highly motivated and under medical care.     

C-peptide and insulin levels at 24-30 weeks' gestation: an increased risk of adverse pregnancy outcomes?

OBJECTIVE: The hypothesis was that fasting C-peptide and insulin values, during an oral glucose tolerance test (OGTT), might allow an estimation of the increased risk for gestational hypertension (GH) and fetal macrosomia. STUDY DESIGN: Two-hundred and six consecutive patients were submitted to an OGTT. Thirty-five developed gestational hypertension and 29 delivered large-for-gestational-age (LGA) newborns. Plasma glucose levels (mg/dl) and insulin levels (microU/ml) were measured fasting and after 60, 120 and 180 min C-peptide fasting levels (ng/ml) were also measured. RESULTS: Twenty-five patients were excluded, 181 were enrolled. According to the OGTT, 143 patients were classified as normal, 26 were found affected by gestational diabetes (GD) mellitus, and 12 had impaired gestational glucose tolerance (IGGT). Hypertensive women exhibited higher 60 and 120 min insulin values than the normotensive group (128.3+/-69.9 microU/ml versus 86.2+/-58.3 microU/ml, P<0.05; 104.9+/-66.4 microU/ml versus 78.7+/-56.5 microU/ml, P<0.05).C-peptide cut-off at 2.9 ng/ml resulted predictive for patients delivering large-for-gestational-age newborns (OR=3.42, 95% CI=1.59-7.39). CONCLUSIONS: C-peptide and insulin may be used as indicators of risk for the development of complications in late pregnancy.     

Patterns of congenital anomalies and relationship to initial maternal fasting glucose levels in pregnancies complicated by type 2 and gestational diabetes

OBJECTIVES: We sought to determine the types of congenital anomalies affecting infants of women with gestational diabetes mellitus or type 2 diabetes and to examine the relationship between those malformation types and measures of initial glycemia of women at entry into prenatal care with type 2 diabetes or at time of diagnosis in women with gestational diabetes mellitus. STUDY DESIGN: A total of 4,180 pregnancies complicated by gestational diabetes mellitus (n = 3764) or type 2 diabetes (n = 416) that were delivered after 20 weeks of gestation were reviewed for the presence of congenital malformations diagnosed before hospital discharge. Anomalies were categorized as being absent, minor, major, genetic syndromes, or aneuploidies. Major anomalies were further categorized by the number and type of affected organ systems. In addition to maternal clinical and historical parameters, the initial fasting serum glucose either from the diagnostic glucose tolerance test (gestational diabetes mellitus) or at entry to prenatal care (type 2 diabetes) and the initial glycosylated hemoglobin before insulin therapy were examined for a relationship to anomalies. RESULTS: The initial fasting serum glucose and glycosylated hemoglobin levels were significantly higher in pregnancies with major (n = 143) and minor (n = 112) anomalies and genetic syndromes (n = 9) compared with pregnancies with no anomalies (n = 3895). Of those pregnancies with major anomalies, the most commonly affected organ systems were the cardiac (37.6%), musculoskeletal (14.7%), and central nervous systems (9.8%) and anomalies involving multiple organ systems (16%). There was no increased predominance of any specific organ system involvement seen with increasing fasting serum glucose levels in pregnancies with major congenital anomalies. Pregnancies with major anomalies affecting multiple organ systems had significantly higher initial fasting serum glucose levels (166 +/- 64 mg/dL) compared with pregnancies in which one organ system was affected (141 +/- 55 mg/dL, P <.04) or no organ systems were affected (115 +/- 38 mg/dL, P <.0001). CONCLUSION: Congenital anomalies in offspring of women with gestational and type 2 diabetes affect the same organ systems that have been previously described in pregnancies complicated by type 1 diabetes. Increasing hyperglycemia at diagnosis or presentation for care was associated with an increasing risk of anomalies in general and with anomalies involving multiple organ systems without a preferential increase in involvement of specific organ system.     

Isolated polyhydramnios in the third trimester: is a gestational diabetes evaluation of value?*

We evaluated implications of testing for gestational diabetes mellitus (GDM) in pregnancies complicated by third trimester isolated polyhydramnios with previous negative diabetes screening test. In this retrospective cohort study of 104 pregnant women with polyhydramnios between 2005 and 2013, all had normal first trimester fasting glucose and normal glucose challenge test (GCT?p?=?0.38) or fasting glucose values (82 vs. 86?mg/dL, p?=?0.29) between women in the polyhydramnios group with and without late GDM diagnosis. Moreover, no significant difference was found in relation to the mode of delivery or birth weight between the studied groups (3437?±?611 vs. 3331?±?515?g, p?=?0.63). Diagnosis of third trimester polyhydramnios was not associated with increased risk for GDM or neonatal complications.     

Placental transfer of indomethacin in the human pregnancy

Little is known about the placental transfer of indomethacin in the human pregnancy. Twenty-six pregnant patients (gestational age, 29.4 +/- 0.5 weeks) were given a 50 mg oral dose of indomethacin 6.08 +/- 0.07 hours before 42 cordocenteses undertaken for standard indications. Maternal serum, fetal serum, and amniotic fluid levels were measured at the time of each procedure. Maternal indomethacin levels were not significantly different from corresponding fetal levels (218 +/- 21 vs 219 +/- 13 ng/ml). The maternal/fetal serum ratio (0.97 +/- 0.07) was not found to vary with gestational age (R = -0.07, p = 0.66). Fetal serum levels were significantly higher than corresponding amniotic fluid levels (219 +/- 16 vs. 21 +/- 2 ng/ml; p less than 0.001). The fetal/amniotic fluid ratio (10.0 +/- 1.2) did not vary with gestational age (R = 0.33, p = 0.11). Indomethacin crosses the human placenta easily throughout gestation; only small amounts of the unchanged drug are found in the amniotic fluid.     

Maternal serum fructosamine and maternofetal glucose and insulin homeostasis in normal pregnancy

Summary Well-defined normal values are necessary to identify pregnancies complicated by gestational diabetes (GD) and thus further reduce perinatal morbidity and mortality from this condition. The present study defined the range for the oral glucose tolerance test (oGTT) in 2578 pregnancies. After exclusion of abnormal results 822 randomized patients were used to define normal values for fructosamine, HbA1c, insulin, glucose and C-peptide in the maternal serum; insulin, glucose and fructosamine in the amniotic fluid; and insulin, glucose, C-peptide and fructosamine in the cord blood.