A trial of simple versus intensified dietary modification for prevention of progression to diabetes mellitus in women with impaired glucose tolerance.

Women with impaired glucose tolerance are at high risk of developing noninsulin dependent diabetes mellitus (NIDDM). The Mercy Hospital for Women has a long-term follow-up programme for women with gestational diabetes, which identifies many women with impaired glucose tolerance. Two hundred of these women were entered into a randomized controlled trial of intensive versus routine dietary advice. Seven women were lost to follow-up. The annual incidence rates of diabetes mellitus for the 2 groups were 6.1% (intervention) and 7.3% (control), an incident rate ratio of 0.83, 95% confidence interval 0.47-1.48, p = 0.50. Overall, there was a return to normal glucose tolerance in 44% of patients. Multivariate analysis showed that body mass index, fasting and 2-hour plasma glucose levels at trial entry were significantly associated with an increased risk of diabetes mellitus. Impaired glucose tolerance is an important condition that should be treated with advice about lifestyle modification (diet and/or exercise). We consider that future trials in the management of women with previous gestational diabetes who have impaired glucose tolerance should investigate the effect of pharmacological intervention in addition to diet and/or exercise, the latter providing a therapy that it would be unethical to exclude on the evidence presently available.

A follow-up program for women with previous gestational diabetes mellitus.

OBJECTIVE: To analyse the patterns of attendance in a gestational diabetes mellitus (GDM) follow-up program for detection of impaired glucose tolerance and diabetes mellitus. DESIGN: Retrospective cohort study using computerised data from the GDM follow-up program. PARTICIPANTS AND SETTING: All women with GDM who delivered at the Mercy Hospital for Women in Victoria between 1 January 1981 and 31 December 1995. OUTCOME MEASURES: Enrollment and maintenance in the follow-up program. Predictors of attendance analysed were attendance for the postnatal oral glucose tolerance test (OGTT), severity of GDM, insulin requirement in pregnancy, age at index pregnancy, country of birth, patient booking status and year of index pregnancy. RESULTS: There were 3524 women with GDM delivered during the study period. Attendance for postnatal OGTT was 71% and increased from 43.7% to 69.5% to 84.4% during the three five-year periods of the study (P < 0.00001). Entry into the follow-up program was 58% (1743 of 2986 eligible). A further 538 women (15.3%) were awaiting the postnatal OGTT or first follow-up OGTT. By December 1995, 45% of women who had entered the program had been lost to follow-up. Enrollment in the follow-up program was significantly predicted by insulin requirement in pregnancy (odds ratio [OR], 2.22; 95% confidence interval [95% CI], 1.57-3.13), attendance for postnatal OGTT (OR, 1.94; 95% CI, 1.64-2.29), private patient status (OR, 1.31; 95% CI, 1.12-1.54), severity of GDM (OR, 1.50; 95% CI, 1.24-1.82) and age 30 years or more (OR, 1.37; 95% CI, 1.17-1.60). Maintenance in the follow-up program was significantly associated with attendance for postnatal OGTT (OR, 2.67; 95% CI, 2.19-3.24), insulin requirement in pregnancy (OR, 2.56; 95% CI, 1.87-3.50), age 30 years or more (OR, 1.59; 95% CI, 1.34-1.88) and severity of GDM (OR, 1.55; 95% CI, 1.28-1.89). CONCLUSIONS: There are major difficulties with both recruiting women with GDM into a follow-up program and ensuring their continued attendance. However, a postnatal OGTT and consultation is the most important remediable factor for continuation in a follow-up program. The dedication of the follow-up team administrators rather than the clinical variables of the patients was probably the main determinant of compliance with the follow-up program.

Studies of postnatal diabetes mellitus in women who had gestational diabetes. Part 1. Estimation of the prevalence of unrecognized prepregnancy diabetes mellitus.

This study investigated the prevalence of undiagnosed diabetes in women in the reproductive age group in a Victorian population by analysis of the results of glucose tolerance testing in 57,563 pregnancies. Gestational diabetes (GD) was diagnosed in 4,243 pregnancies and in 2,957 (69.7%) of these, postnatal glucose tolerance testing was performed. Diabetes mellitus was diagnosed within 26 weeks of delivery in 59 women, 55 of whom were diagnosed by the postnatal glucose tolerance test (GTT). There were 4 women with GD who developed diabetic ketosis during pregnancy (3) or within 12 weeks of delivery (1). By consideration of the results of the antenatal and postnatal GTTs, it was deduced that 53% (31 of 59) of the women with diabetes diagnosed after delivery may have had unrecognized prepregnancy diabetes. Consideration of the entire glucose-tolerance tested population led to the conclusion that approximately 1 in 1,031 women in the reproductive age group in our community have unrecognized prepregnancy diabetes mellitus.

Studies of postnatal diabetes mellitus in women who had gestational diabetes. Part 2. Prevalence and predictors of diabetes mellitus after delivery.

An important part of the management of women with gestational diabetes (GD) is their subsequent follow-up after delivery. At this postnatal visit a glucose tolerance test (GTT) is essential. We have analysed the results of the postnatal GTT's in 2,957 women whose pregnancies were complicated by GD. Diabetes mellitus was diagnosed in 59 women (2.0%) in the first 6 months after delivery. As stated in Part 1 of this paper, 31 of these 59 women may have had unrecognized prepregnancy diabetes mellitus. The significant independent predictors of postnatal diabetes mellitus on logistic regression analysis in these women were severity of GD, Asian origin and the 1-hour plasma glucose level during the antenatal GTT.

Identification and treatment of women with hyperglycaemia diagnosed during pregnancy can significantly reduce perinatal mortality rates.

We wished to determine whether gestational diabetes was associated with an increased perinatal mortality rate, and to investigate the cause for the observed increase in the incidence of gestational diabetes. We therefore reviewed the results of glucose tolerance tests and pregnancy outcome in 116,303 pregnancies, 1971-1994, at the Mercy Hospital for Women. The main outcome measurements were the presence or absence of gestational diabetes, and perinatal mortality. Over the entire period of the study, gestational diabetes was associated with an increased risk of perinatal mortality (Mantel-Haenszel adjusted odds ratio 1.53, 95% CI 1.13-2.06, p = 0.0069). Women with gestational diabetes that was only diagnosed retrospectively had a higher perinatal mortality rate than their contemporaries with normal glucose tolerance (OR 2.31, 95% CI 1.37-3.91, p = 0.0025). Women in whom a glucose tolerance test was not performed continued to have a higher perinatal mortality rate than women who were tested (adjusted OR 2.21, 95% CI 1.56-3.12, p < 0.00001). There has been an increase in the prevalence of gestational diabetes from 2.9% to 8.8%. Some of this is due to changes in population characteristics (increases in maternal age, obesity and proportion from South-East Asia), but there was still an independent increase over time. We conclude that identification and treatment of women with gestational diabetes can reduce perinatal mortality rates. Similarly to diabetes mellitus in the total population, the prevalence of gestational diabetes has increased over time.

Comparison of the 50 g capillary plasma glucose tolerance test with the 75 g venous plasma glucose tolerance test in pregnancy.

OBJECTIVE: To compare the 50 g oral glucose tolerance test with capillary sampling used in the Mercy Hospital for Women, Melbourne with the 75 g test with venous sampling advocated by the Australasian Diabetes in Pregnancy Society. METHODS: Both the 50 g and 75 g glucose tolerance tests were performed on 60 women. Criteria for diagnosing gestational diabetes were the combination of a 1-hour capillary plasma glucose > or = 9 mmol/l and a 2-hour glucose > or = 7 mmol/l for the 50 g test and a fasting glucose > or = 5.5 mmol/l and/or a 2-hour venous plasma glucose > or = 8.0 mmol/l for the 75 g test. RESULTS: Twenty-eight of 60 women had gestational diabetes diagnosed with the 50 g test; 24 of these, and an additional 5 had gestational diabetes diagnosed on the 75 g test. Twenty-seven women had normal results on both tests. The kappa statistic was 0.70. The 1-hour glucose value was similar for both tests, but the 2-hour value was significantly higher for the 75 g test (mean difference 0.65 mmol/l, 95% confidence limits 0.24-1.01 mmol/l, p = 0.003). The area under the curve was similar for the 2 tests. CONCLUSIONS: The 2 tests diagnose similar women as having gestational diabetes. The combination of a 75 g load and venous sampling gives similar 1-hour but higher 2-hour values than a 50 g load and capillary sampling.

Effect of follow-up of women with gestational diabetes on the ratio of IDDM to NIDDM in pregnancy.

OBJECTIVE: We wished to test the hypothesis that the diagnosis of diabetes in women with previous gestational diabetes in our follow-up program had altered the ratio of IDDM to NIDDM in our pregnant population. RESEARCH DESIGN AND METHODS: We identified all pregnancies managed at the Mercy Hospital for Women in Melbourne, Australia, from 1971 to 1994 that were complicated by prepregnancy diabetes. In these 374 pregnancies, we identified those women who had previously been diagnosed with gestational diabetes mellitus (GDM). The changing prevalences over time of prepregnancy IDDM and NIDDM, as well as the contribution to both of these conditions made by women who had previously had GDM, were calculated. RESULTS: Over the period of the study, there was an increase in the prevalence of IDDM from 0.15 to 0.44% (chi 2 for trend, P < 0.00001) and NIDDM from 0.03 to 0.11% (chi 2 for trend, P = 0.0001). The proportion of all women with diabetes with NIDDM did not change significantly (16.7-20%). There was a progressive increase in the proportion of women with NIDDM who had had GDM (from 8.3 to 39.1%), but the trend was not statistically significant (P = 0.059). Women with NIDDM were more likely (20 of 64, 31.3%) to have had gestational diabetes in the past than women with IDDM (12 of 310, 3.9%, odds ratio 11.3, 95% CI 5.16-24.7, P < 0.0001). CONCLUSIONS: Despite finding relatively young women to have NIDDM, our GDM follow-up clinic has not yet altered significantly the ratio of IDDM to NIDDM in pregnancy.

Linea alba pigmentation and umbilical deviation in nulliparous pregnancy: the ligamentum teres sign.

OBJECTIVE: To determine the incidence and direction of umbilical deviation in pregnancy at term in nulliparas with linea alba pigmentation. METHODS: All women attending one prenatal clinic over a period of 19 months were available. Subjects studied were the 315 nulliparas whose pregnancies had reached at least 37 weeks' gestation. The presence of linea alba pigmentation, with or without umbilical flattening and/or deviation, was assessed with the woman lying symmetrically on her back on an examination couch. RESULTS: Forty-four of the 315 women (14%) had sufficient pigmentation for assessment; 27 of the 44 (61.4%) were born in Asia or the Indian subcontinent, although such women comprised only 13.5% of the clinic population. In 31 of the 44 women (70.5%), the umbilicus and supra- or infraumbilical linea nigra was deviated to the right side, and in 13 it remained in the midline; in none was there deviation to the left side. CONCLUSION: Displacement of the umbilicus and adjacent structures commonly occurs in term pregnancy; pressure of the uterus on the ligamentum teres and falciform ligament determines that displacement is invariably toward the right side.

Maternal serum triglyceride, glucose tolerance, and neonatal birth weight ratio in pregnancy.

OBJECTIVE: To determine the value of measuring serum triglyceride (TG) levels early in pregnancy for predicting late-gestation glucose tolerance and neonatal birth weight ratio (BWR) (birth weight corrected for gestational age). RESEARCH DESIGN AND METHODS: The relationships between morning nonfasting TG measured early in pregnancy (gestational age 12 +/- 6 weeks [mean +/- SD]) and glucose tolerance measured by a 3-h 50-g oral glucose tolerance test (OGTT) late in pregnancy (gestational age 30 +/- 3 weeks) and BWR were investigated in 388 women attending routine antenatal care. The data were analyzed for all women in addition to subgroups of Australian/Western European-born (n = 246) and Asian-born (n = 97) women. RESULTS: Morning nonfasting TG positively correlated with the OGTT glucose area under the curve (OGTT-GAUC) (r = 0.23, P < 0.0001) in all subjects. This correlation was stronger in the subset of subjects who had TG measured between 9 and 12 weeks of gestation (r = 0.35, P = 0.0001) and was particularly strong in Asian-born women who had TG measured within this period (r = 0.71, P < 0.0001). Mean TG and the 2- and 3-h OGTT values were higher in Asian-born subjects compared with Australian/Western European-born subjects (P = 0.004, P < 0.0001, and P = 0.02, respectively). TG correlated positively with BWR in all subjects (r = 0.12, P = 0.02), in Asian-born subjects (r = 0.23, P = 0.02), and in subjects with gestational diabetes mellitus (GDM) (r = 0.60, P = < 0.001). CONCLUSIONS: TG, if measured between 9 and 12 weeks of gestation, has moderate predictive value for subsequent glucose tolerance in pregnancy. TG is also predictive of BWR in GDM subjects. Further studies are warranted to investigate the role of early TG measurement in the screening and management of GDM. Metabolic heterogeneity exists between Asian-born and Australian/Western European-born women, the significance of which is still unclear and warrants further study.

Prevalence of antibodies to glutamic acid decarboxylase in women who have had gestational diabetes.

OBJECTIVES: Our purpose was to determine the prevalence of autoantibodies to glutamic acid decarboxylase in women who had had gestational diabetes, including those in whom insulin-requiring or non-insulin-requiring diabetes mellitus has since developed. STUDY DESIGN: The study group comprised 734 women with previous gestational diabetes who were consecutive attendees to a follow-up clinic. These women were tested for autoantibodies to glutamic acid decarboxylase with a radioimmunoprecipitation assay. We similarly tested 104 women in whom permanent diabetes mellitus developed after gestational diabetes, of whom 20 were using insulin and 84 were not. Those using insulin also had fasting C-peptide levels measured. RESULTS: Thirteen of the 734 (1.8%, 95% confidence interval 0.9% to 3.0%) women with previous gestational diabetes were positive for autoantibodies to glutamic acid decarboxylase. Of the 20 women with diabetes treated with insulin, 12 had insulin deficiency confirmed by low levels of C peptide; all 12 were positive for autoantibodies to glutamic acid decarboxylase. Of the 84 women with diabetes not requiring insulin, 6 (7.1%, 95% confidence interval 2.7% to 14.9%) were positive for autoantibodies to glutamic acid decarboxylase. CONCLUSIONS: The prevalence of autoantibodies to glutamic acid decarboxylase in women with previous gestational diabetes was 1.8%. Our data also showed that insulin-dependent diabetes mellitus will develop in 1.7% of women with gestational diabetes. A positive test for autoantibodies to glutamic acid decarboxylase may help in the early identification of insulin-dependent diabetes mellitus. Adult-onset insulin-dependent diabetes mellitus developed in only 5.2% (12/230) of women with previous gestational diabetes who later had diabetes mellitus.

Factors predictive of recurrent gestational diabetes diagnosed before 24 weeks' gestation.

The purpose of this study was to determine which patient and pregnancy characteristics in the first pregnancy complicated by gestational diabetes mellitus (GDM) were associated with the diagnosis of GDM before 24 weeks' gestation in a subsequent pregnancy--early recurrent GDM. The case notes of 180 women who previously had GDM diagnosed and who had glucose tolerance tests performed before 24 weeks' gestation in their next ongoing pregnancy were reviewed. Factors examined included severity of GDM, insulin requirement, racial origin, macrosomia, obesity, age, family history of diabetes, preeclampsia, and parity. Multivariate analysis showed that women with early recurrent GDM were more likely, in their first pregnancy with GDM, to have needed insulin (odds ratio [OR] 11.26; 95% confidence interval [CI] 2.02 to 62.65), to be more often of non-Northern European origin (OR, 5.53; 95% CI, 2.46 to 12.44), to have had a macrosomic infant (OR, 4.01; 95% CI, 1.40 to 11.49) or severe GDM (OR, 3.52; 95% CI, 1.60 to 7.76), and were more often 30 years or more of age (OR, 2.27; 95% CI, 1.05 to 4.90). Obesity, family history, fasting plasma glucose levels, and parity were not significant risk factors. However, even without any of the significant risk factors, logistic regression modeling suggested that a woman who has had GDM in a previous pregnancy has a 5.1% (95% CI, 2.2 to 11.6%) chance of having early recurrent GDM. We therefore continue to recommend that all women who have had GDM diagnosed previously should have glucose tolerance testing performed early (before 24 weeks' gestation) in any future pregnancies.

The biochemistry and clinical application of urinary oestriol measurement during late pregnancy in the 1990's.

Part 1. The present disillusionment with oestriol measurement as a test of fetoplacental function could be explained by the use of poor methodology and inappropriate normal ranges rather than that the test has lost its usefulness. We have updated the Lever method for measuring oestriol in urine, and examined the automatic TDX system supplied by Abbott Laboratories. The precision of the methods and consistency of results between methods have been determined and normal ranges have been established for both methods. The overall accuracy of collection of 24-hour urine specimens in a routine laboratory setting has also been calculated. The normal ranges suggested as a guide for the TDX method by Abbott were based on those derived from the original method of Brown and were found to be too low and therefore unsuitable for clinical use. This study reports appropriate lower limits of normal for both the updated Lever and the TDX methods. Part 2. The results obtained using the updated Lever method since its introduction in 1991 have been compared with those obtained by the original Brown method during the years 1971-1989. The new, user-friendly Lever method of oestriol assay measurement used in 1991-1993 gave results of equivalent clinical value to the Brown method used in 1971-1989, although the perinatal mortality rates in the tested populations fell from 0.95% to 0.37%. During 1971-1989, low oestriol excretion on 1 or more occasions was associated with a 5.6-fold increase in the perinatal mortality rate (0.66% to 3.67%), whereas in 1991-1993, the factor was 4.4 (0.27% to 1.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Value of cardiotocography in women with antepartum haemorrhage--is it too late for caesarean section when the cardiotocograph shows ominous features?

Caesarean section is thought to be indicated by an ominous antepartum cardiotocograph (CTG). However, the fear remains that infants delivered for this indication in the presence of antepartum haemorrhage, especially when premature, are destined to have severe hypoxic neurological damage. We therefore reviewed our experience of cardiotocography in women with antepartum haemorrhage (APH) from 1989 to 1992. There were 472 women with APH who had a CTG performed. Of them, 68 had abruptio placentae and 317 had an APH of undetermined cause. For the group with abruptio placentae, the perinatal mortality rate (PMR) was 230.7 per 1,000 when the CTG was abnormal, but only 18.2 per 1,000 if the CTG was normal (odds ratio 16.2, 95% confidence interval [CI] 1.53-171.9, p = 0.02). For APH of undetermined cause, the corresponding rates were 90.9 per 1,000 and 9.8 per 1,000 (odds ratio 10.1, 95% CI 0.96-105.8, p = 0.13). There were no perinatal losses in women with APH due to placenta praevia (87 cases). There were 6 cases of critical fetal reserve identified on a CTG in women with abruptio or APH of undetermined cause. All were delivered by Caesarean section, with 4 surviving infants, 3 with normal neurological outcome and 1 lost to follow-up. There were 3 cases of APH resulting in an infant with cerebral palsy, all of whom had had a normal antepartum CTG. Our data suggest that cardiotocography allows pregnancy to be safely prolonged in pregnancies complicated by abruptio placentae or APH of undetermined cause, and that Caesarean section is an appropriate form of delivery when the CTG becomes abnormal in these cases.