Association of glucose metabolism and blood pressure during pregnancy with subsequent maternal blood pressure.

The goal of this study was to examine associations of measures of maternal glucose metabolism and blood pressure during pregnancy with blood pressure at follow-up in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort. The HAPO Follow-Up Study included 4747 women who had a 75-g oral glucose tolerance test (OGTT) at ~28 weeks' gestation. Of these, 4572 women who did not have chronic hypertension during their pregnancy or other excluding factors, had blood pressure evaluation 10-14 years after the birth of their HAPO child. Primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension (SBP ≥ 140 and/or DBP ≥ 90 or treatment for hypertension) at follow-up. Blood pressure during pregnancy was associated with all blood pressure outcomes at follow-up independent of glucose and insulin sensitivity during pregnancy. The sum of glucose z-scores was associated with blood pressure outcomes at follow-up but associations were attenuated in models that included pregnancy blood pressure measures. Associations with SBP were significant in adjusted models, while associations with DBP and hypertension were not. Insulin sensitivity during pregnancy was associated with all blood pressure outcomes at follow-up, and although attenuated after adjustments, remained statistically significant (hypertension OR 0.79, 95%CI 0.68-0.92; SBP beta -0.91, 95% CI -1.34 to -0.49; DBP beta -0.50, 95% CI -0.81 to -0.19). In conclusion, maternal glucose values at the pregnancy OGTT were not independently associated with maternal blood pressure outcomes 10-14 years postpartum; however, insulin sensitivity during pregnancy was associated independently of blood pressure, BMI, and other covariates measured during pregnancy.

Racial and ethnic disparities in diabetes risk after gestational diabetes mellitus.

AIMS/HYPOTHESIS: To investigate racial/ethnic disparities in diabetes risk after gestational diabetes mellitus (GDM). METHODS: This is a retrospective cohort study of women enrolled in the Kaiser Permanente Southern California health plan from 1995 to 2009. GDM status was identified on the basis of plasma glucose levels during pregnancy. The incidence of diabetes after the first delivery complicated by GDM before 31 December 2009 (n = 12,998) was compared with the experience for women without GDM (n = 64,668) matched on maternal age at delivery, race/ethnicity and year of delivery (1:5 ratio). Matched Cox regression was used to compare the RRs of diabetes associated with GDM within and across racial/ethnic groups. RESULTS: Compared with the women without GDM, the HRs (95% CI) of diabetes for women after GDM were 6.5 (5.2, 8.0) in non-Hispanic white, 7.7 (6.8, 8.7) in Hispanic, 9.9 (7.5, 13.1) in black and 6.3 (5.0, 7.9) in Asian/Pacific Islanders after adjustment for parity, maternal education, comorbidity and number of outpatient visits before the index pregnancy. The HR of diabetes for black women was significantly higher than that for non-Hispanic white women (p = 0.032). Further adjustment for prepregnancy BMI reduced the diabetes risk association with GDM for each racial/ethnic group, but did not explain the risk differences across groups. CONCLUSIONS/INTERPRETATIONS: Racial/ethnic disparities exist in risk of diabetes after GDM. Black women with GDM had the highest risk of developing diabetes. This highlights the importance of developing an effective diabetes screening and prevention programme in women with GDM, particularly black women with GDM.

Pregnancy plasma glucose levels exceeding the American Diabetes Association thresholds, but below the National Diabetes Data Group thresholds for gestational diabetes mellitus, are related to the risk of neonatal macrosomia, hypoglycaemia and hyperbilirubinaemia.

AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is a risk factor for perinatal complications. In several countries, the criteria for the diagnosis of GDM have been in flux, the American Diabetes Association (ADA) thresholds recommended in 2000 being lower than those of the National Diabetes Data Group (NDDG) that have been in use since 1979. We sought to determine the extent to which infants of women meeting only the ADA criteria for GDM are at increased risk of neonatal complications. MATERIALS AND METHODS: In a multiethnic cohort of 45,245 women who did not meet the NDDG criteria and were not treated for GDM, we conducted nested case-control studies of three complications of GDM that occurred in their infants: macrosomia (birthweight >4,500 g, n = 494); hypoglycaemia (plasma glucose <2.2 mmo/l, n = 488); and hyperbilirubinaemia (serum bilirubin > or =342 micromol/l (20 mg/dl), n = 578). We compared prenatal glucose levels of the mothers of these infants and mothers of 884 control infants. RESULTS: Women with GDM by ADA criteria only (two or more glucose values exceeding the threshold) had an increased risk of having an infant with macrosomia (odds ratio OR = 3.40, 95% CI = 1.55-7.43), hypoglycaemia (OR = 2.61, 95% CI = 0.99-6.92) or hyperbilirubinaemia (OR = 2.22, 95% CI = 0.98-5.04). Glucose levels 1 h after the 100-g glucose challenge that exceeded the ADA threshold were particularly strongly associated with each complication. CONCLUSIONS/INTERPRETATION: These results lend support to the ADA recommendations and highlight the importance of the 1-h glucose measurement in a diagnostic test for GDM.

Managing type I diabetes in pregnancy: how near normal is necessary?

OBJECTIVE: This was a feasibility study to determine if pregnant women with type I diabetes managed with liberal target glucose values will have a decreased frequency of hypoglycemia with no differences in adverse outcomes compared with tightly controlled subjects. STUDY DESIGN: Twenty-two women who had type I diabetes were randomized in first trimester to 'rigid' and 'less rigid' groups. Participants recorded blood glucose results and symptoms of hypoglycemia on memory-based meters. RESULTS: Mean maternal glucose was significantly greater in first and second trimesters among patients in the 'less rigid' group. Both subjective and objective hypoglycemias were more frequent in the 'rigid' group. There were no differences between groups in cesarean deliveries, birth weights and neonatal glucose concentrations. CONCLUSIONS: Utilizing glucose targets higher than those conventionally recommended in pregnancies of women who have type I diabetes may decrease maternal hypoglycemia while not increasing maternal or perinatal morbidity. The findings of this study justify further investigation with a larger patient base.

Induction of labor versus conservative management of pregnant diabetic women.

Reasons for inducing labor at term in pregnancies complicated by diabetes include the avoidance of fetal demise and the prevention of excessive fetal growth and its concomitant conditions, shoulder dystocia and Cesarean delivery. Objectively evaluating the risks and benefits of labor induction is potentially confounded by the status of the cervix at the time of initiation of induction, early determination of an arrest disorder and physician bias toward Cesarean delivery for women who have diabetes. In non-diabetic women, incorporating estimates of fetal weight in deciding the route of delivery has not diminished the incidence of shoulder dystocia, and may have increased the incidence of Cesarean deliveries. Currently available evidence suggests that, while induction of labor for women who have diabetes may not carry much maternal or fetal risk, the benefit of this procedure is unclear.

The utility of a single test to identify women at risk for gestational diabetes.

A number of single tests have been proposed as both screening and definitive tests of glucose intolerance during pregnancy. Despite limitations imposed by a lack of uniformity in methodology and definitions of gestational diabetes mellitus, there appears to be an independent relationship between some single-test results and clinically meaningful outcomes. Further study is needed to identify those glucose values above which women and their babies who are at risk for glycemia-related adverse outcomes may be identified.

Estimating fetal weight in the management of macrosomia.

The purpose of this review is to examine the evidence that, including estimates of fetal macrosomia in patient care, will decrease adverse perinatal outcomes. A literature search for the years 1980 to 1999 was used. Shoulder dystocia and brachial plexus injuries occur more often in macrosomic than in non-macrosomic neonates. However, 26 to 58 percent of shoulder dystocias and 24 to 44 percent of brachial plexus injuries occur to babies weighing less than 4000 gm. Persistence of impairment is extremely rare. Neither historical nor clinical factors have strong positive predictive values for macrosomia. From 15 to 81 percent of the babies predicted to be macrosomic are confirmed by birth weight. Of babies determined to be macrosomic at birth, only 50 to 100 percent were successfully predicted. Shoulder dystocia and brachial plexus injuries are unpredictable events. Available evidence suggests that planned interventions based on estimates of fetal weight do not reduce the incidence of shoulder dystocia and do not decrease adverse outcomes attributable to fetal macrosomia.

When is fasting really fasting? The influence of time of day, interval after a meal, and maternal body mass on maternal glycemia in gestational diabetes.

OBJECTIVE: The object of the study was to determine whether time of day, interval after a standard meal, and maternal body mass influence plasma glucose concentrations in women with gestational diabetes mellitus. STUDY DESIGN: Identical mixed meals were administered on 2 separate occasions 1 week apart to 30 women with dietarily treated gestational diabetes and pregnancies between 28 and 38 weeks' gestation. One meal was administered at 7 AM (morning meal) and the other was administered at 9 PM (evening meal), each after a fast of >/=5 hours. The order of the meals (morning first versus evening first) was assigned randomly. Sixteen of the women had a body mass index >/=27 kg/m(2) (overweight) and 14 women had a body mass index <27 kg/m(2) (lean). Venous plasma concentrations of glucose, insulin, free fatty acids, beta-hydroxybutyrate, and bound and free cortisol were measured hourly for 9 hours after each of the test meals. RESULTS: When all women were considered together glucose concentrations after the morning meal were significantly greater at 1 hour, were not different at 2 hours, and were significantly lower from 3 through 9 hours postprandially than those at corresponding times after the evening meal. Plasma beta-hydroxybutyrate and free fatty acid concentrations were higher between 5 and 9 hours after the morning meal than at the same times after the evening meal. Total and free cortisol levels were higher for the first 7 hours after the morning feeding, reflecting known diurnal variation in cortisol concentrations. Overweight patients' glucose values were significantly greater than those of lean subjects during the last 4 hours of the overnight fast. CONCLUSIONS: Among women with dietarily treated gestational diabetes the glucose concentrations were significantly higher from 3 to 9 hours after an evening meal, whereas suppression of free fatty acids and beta-hydroxybutyrate was less sustained after a morning feeding. The mechanisms underlying these differences remain to be determined but may involve diurnal influences of counterregulatory hormones. The relationships between measurements of maternal glycemia and maternal and perinatal outcomes in pregnancies complicated by gestational diabetes may be clarified by establishing a uniform duration of a fast and by developing meal-specific preprandial and postprandial maternal glucose targets for these patients.

Should the same glucose values be targeted for type 1 as for type 2 diabetics in pregnancy?

OBJECTIVE: Our purpose was to determine whether the same maternal glycemic control is necessary to achieve similar perinatal outcomes for type 1 as for type 2 diabetics. STUDY DESIGN: The subjects were all women with pregestational diabetes mellitus delivered of live-born singletons. Glycemic control was achieved with diet and insulin. Self-monitoring of blood glucose was performed before meals and at bedtime. Target glucose values were 60 to 90 mg/dl fasting and 60 to 105 mg/dl at other times. RESULTS: Of 60,628 deliveries, 46 type 1 and 113 type 2 diabetic women met inclusion criteria. Respective differences were found between type 1 and type 2 diabetics in average daily glucose levels (112 mg/dl vs 97 mg/dl, p < 0.001), percent of values within target ranges (35% vs 57%, p < 0.001), and mean amplitude of glycemic excursion (48.1 mg/dl vs 24.9 mg/dl, p < 0.001). At least one daily glucose value was < 50 mg/dl during 19% of observation days for type 1 vs 2% of observation days for type 2 pregnancies (p < 0.001). There were no statistically significant differences between type 1 and type 2 diabetic pregnancies in neonatal macrosomia (30% vs 34%), proportion of cesarean deliveries during labor for arrest disorders (67% vs 69%), shoulder dystocia (2% vs 6%), and neonatal hypoglycemia (18% vs 26%). CONCLUSIONS: Less stringent maternal glycemic control may permit comparable maternal and neonatal outcomes for type 1 compared with type 2 diabetics. Higher target values for type 1 diabetics may decrease the frequency of maternal hypoglycemic episodes.

Toward universal criteria for gestational diabetes: the 75-gram glucose tolerance test in pregnancy.

OBJECTIVES: The purpose of this study was to determine the distribution of values for the 75 gm glucose tolerance test in pregnancy and to define glucose intolerance by the relationship between maternal glucose values and neonatal macrosomia. STUDY DESIGN: A total 3505 unselected pregnant women were given a 75 gm, 2-hour glucose tolerance test. Diet or insulin therapy was offered only to patients with a fasting plasma glucose level > or = 105 mg/dl or a 2-hour post-glucose-load value > or = 200 mg/dl. Birth weights of live-born singletons delivered from 36 to 42 weeks whose mothers had a fasting plasma glucose level < 105 mg/dl and 2-hour post-glucose-load value < 200 mg/dl were used to calculate relationships between glucose levels and birth weights. RESULTS: At 24 to 28 weeks' gestation the mean and SD plasma glucose values were fasting 83.6 (8.9) mg/dl, 1 hour 128.4 (32.9) mg/dl, and 2 hour 108.4 (24.8) mg/dl. In a multiple logistic regression model the factors found to be statistically significantly associated with macrosomia were maternal race, parity, prepregnancy body mass index, weight gain, gestational age at testing, fasting plasma glucose level, and 2-hour post-glucose-load value. A positive association was found between maternal glucose values and birth weight percentiles. No clinically meaningful glucose threshold values relative to birth weight or macrosomia were found. CONCLUSION: In the absence of a meaningful threshold relationship between glucose tolerance test values and clinical outcome, criteria defining gestational diabetes will probably be established by consensus.

Caring for the female Jehovah's Witness: balancing medicine, ethics, and the First Amendment.

Blood transfusion has been doctrinally forbidden for Jehovah's Witnesses since 1945. Despite serious theologic consequences for its violation, this proscription may not be observed universally by members of the denomination. When a patient declines a lifesaving transfusion, a conflict is generated between the physician's autonomy-based and beneficence-based obligations to the patient. This conflict is intensified when the patient is a woman who had minor dependent children, either in utero or already born. A spectrum of opinion exists regarding the resolution of this conflict. As one of society's repositories of moral and legal values, the court is the most appropriate forum in which religious, medical, and ethical viewpoints may receive a fair and impartial hearing.

Monocyte monolayer assay as a predictor of severity of hemolytic disease of the fetus and newborn.

The monocyte monolayer assay (MMA), an in vitro model of in vivo antibody-mediated red blood cell destruction, was previously reported to predict the severity of hemolytic disease of the fetus and newborn accurately when only Rh antibodies and antigen-positive babies were studied. We studied 33 women whose serum contained antibodies with the potential to cause erythroblastosis fetalis; 7 of the 33 women had antibodies other than Rh. None of the babies of the ten women who had consistently negative test results required intrauterine or neonatal transfusions. False-positive MMA results were sometimes found when the fetus was antigen negative. Although the predictive value of a negative MMA was 100%, the efficiency of the MMA was no better than that of the antibody titer. Because of the lack of advantage of the MMA as well as the time and expense it requires, we cannot recommend the general clinical application of this test at this time.

Fetal macrosomia and gestational diabetes: what's the problem?

OBJECTIVE: To review the definition of, morbidity attendant upon, and interventions designed to prevent fetal macrosomia in gestational diabetes. DATA SOURCES: Both MEDLINE and manual searches of the Index Medicus from 1980-1992 for articles pertaining to fetal macrosomia were employed. Macrosomia was also cross-referenced with pregnancy in diabetes. METHODS OF STUDY SELECTION: Seventy-nine articles that provided definitions, data, and opinions relevant to this topic were selected. DATA EXTRACTION AND SYNTHESIS: There is no universally accepted definition of fetal macrosomia. Potential associated morbidities include birth trauma, neonatal hypoglycemia, and childhood and adolescent obesity. Maternal glucose intolerance, age, parity, race and ethnicity, weight, weight gain, smoking status, and fetal gender may influence birth weight. Not all of these factors have been considered in analyses of the impact of interventions designed to prevent macrosomia. CONCLUSIONS: A consensus definition of fetal macrosomia is a necessary and attainable goal. Randomized trials are necessary in which all factors that influence fetal growth and development are uniformly analyzed to develop appropriate clinical interventions.

Could the fasting plasma glucose assay be used to screen for gestational diabetes?

The fasting plasma glucose assay was compared with the one-hour post-glucose test as a screening test for identification of gestational diabetes. Of 4,561 consecutive patients screened with a 50-g glucose test, 968 (21.2%) had results > or = 135 mg/dL; 141 (14.6%, or 3.1% of the total) were found to have diabetes. In the 968 patients, the area under the fasting plasma glucose receiver operating characteristic curve was greater than that under the glucose screening test curve, indicating greater discriminatory value of the former test. Of the 116 patients who had sequential glucose screening tests and fasting plasma glucose assays performed twice during pregnancy, a significant correlation was found for fasting plasma glucose values, but not for glucose screening test values. We conclude that the fasting plasma glucose assay may perform better than the one-hour post-glucose test as a screening test for gestational diabetes. Based on these data, a population-based prospective study seems justified.

Isoimmunization to Cromer antigen in pregnancy.

Pregnancy in a woman isoimmunized to Cromer antigen, a high-frequency antigen, is reported. Neither of her two Cromer antigen-positive infants was affected with hemolytic disease of the newborn. Autologous blood or that from a compatible Cromer antigen-negative relative may be frozen and stored for possible transfusion in a pregnant woman with anti-Cromer antigen antibodies.

Do the current standards for glucose tolerance testing in pregnancy represent a valid conversion of O'Sullivan's original criteria?

The venous plasma values for the 100 gm glucose tolerance test endorsed by the Second International Workshop-Conference on Gestational Diabetes represent an arbitrary conversion from O'Sullivan's original values. The latter were calculated from whole blood by means of the Somogyi-Nelson method. The factor used to convert the whole blood values to plasma glucose values was empirically derived in a population in whom pregnancy status was not stated. A conversion factor derived from a nonpregnant population may systematically overestimate plasma glucose concentration when applied to a pregnant population. Paired specimens obtained from 995 consecutive pregnant patients were analyzed by the Somogyi-Nelson method on whole blood and the glucose oxidase method on plasma. A conversion formula was derived and was used to estimate plasma glucose values and 95% confidence limits equivalent to whole blood values. Application of this formula yields plasma glucose oxidase glucose tolerance test values of fasting, 96 mg/dl; 1 hour, 172 mg/dl; 2 hours, 152 mg/dl, and 3 hours, 131 mg/dl. These values are all lower than those currently endorsed.

How reliable is the fifty-gram, one-hour glucose screening test?

The Second International Workshop-Conference on Gestational Diabetes recommended screening all pregnant women with a 1-hour 50 gm oral glucose screening test, given without regard to time of day or time elapsed from the last meal. This study was designed to evaluate the reproducibility of that test, given under those clinical conditions. Thirty women with gestational diabetes and 80 control volunteers between 24 and 28 weeks' gestation were tested at the same time of day on two successive days. Of the 30 women with diabetes, three (10%) had glucose screening test results below the 135 mg/dl threshold on both days and 10 (33%) had results that straddled the threshold on successive days. Test results of 11 control women also straddled the threshold. Among these 21 women with results that straddled the threshold, there was no difference in mean glucose screening test results in diabetic women compared with nondiabetic ones. We conclude that, as currently recommended, the 1-hour glucose screening test is moderately reproducible. Reliance should not be placed on a single normal test result, particularly among patients with risk factors.

Screening for gestational diabetes with the one-hour 50-g glucose test.

A one-year experience of screening for gestational diabetes is reported. Patients with any of seven risk factors were screened at the time of prenatal registration. Those without risk factors, and those not found to be diabetic by 24 weeks' gestation, were tested later in pregnancy. Of 4116 patients, 77% had at least one risk factor. The prevalence of diabetes in patients with risk factors was significantly greater than among those with no risk factors (P less than .001). Of 936 patients who had no risk factors, four were found to have diabetes. Multiple logistic regression analysis suggested that family history, obesity, and age over 25 years contributed significantly to the prediction of gestational diabetes. More than 10% of gestational diabetics had screening values between 135-139 mg/dL. Among patients whose early screening values were elevated and whose initial glucose tolerance tests were normal, the odds of being classified ultimately as a gestational diabetic were 7.3 times that of patients whose initial screening tests were normal. Selective screening based on risk factors including maternal age may enhance detection of diabetes early in gestation.