Diabetes mellitus is a common chronic disease in Singapore. Its occurrence in pregnant women was 1.3% in a previous report. In a survey of 145 consecutive pregnant women registered at Alexandra Hospital the incidence of gestational diabetes was 13.1% when a total screen with 75 gm oral glucose challenge was used. The mean age of this sample was 27 years and the mean gestation at screening 33 weeks. There was an excess of Malay and Indian patients. Fifty percent had traditional risk factors tor gestational diabetes. Whether this higher incidence is a result of more stringent screening and/or increased occurrence remains to be confirmed.
A prospective study was carried out in the Maternity Hospital, Kuala Lumpur in 1989 to determine the morbidity and mortality of infants of diabetic mothers. Out of 24,856 neonates born during the study period, 54 neonates (2.2 per 1000 livebirths) were born to mothers who were diagnosed to have diabetes mellitus before the current pregnancy or who had impaired glucose tolerance test during the current pregnancy. Almost a third (29.6 percent) of these infants of diabetic mothers had birthweight of 4000 grams and above, and 37.0 percent of the 54 babies were large-for-gestational age. Hypoglycemia occurred in 9/54 (16.7 percent) of the neonates, respiratory distress syndrome in 5/54 (9.3 percent), shoulder dystocia in 7/54 (13.0 percent), and congenital abnormalities in 4/54 (7.4 percent). Three (5.6 percent) neonates died during the neonatal period. The results of this study suggest a need to intensify control of maternal diabetes mellitus during pregnancy in order to reduce the rates of morbidity and mortality of their infants.
The pregnancy outcome of 33 women with gestational diabetes who were treated with glibenclamide and changed to insulin if glibenclamide failed, were compared with the pregnancy outcome of 21 women with gestational diabetes treated conventionally with insulin. The pregnancy outcome, with regard to the overall glycaemic control, rates of preterm labour, neonatal hypoglycaemia, fetal macrosomia, perinatal morbidity and mortality, were not statistically different between the two treatment groups. The limited number of women studied, and the non-random allocation of these women to each treatment group however, could have influenced these results. There were a few observed differences in the pregnancy outcome between the two treatment groups, which although were not statistically significant, caused some concern. In particular we noted an increased rate of fetal macrosomia in the glibenclamide treated group, which in theory could have been drug mediated.
OBJECTIVES: To assess the prevalence and association of frequently used screening risk factors for gestational diabetes mellitus (GDM) and to compare the validity and cost of universal screening with risk factor screening.
METHOD: A cross-sectional survey of 768 pregnant women at > or = 24 weeks' gestation who were attending the antenatal clinic at the Hospital Universiti Kebangsaan Malaysia (HUKM) was made. Risk factors were determined using a questionnaire. An abnormal oral glucose tolerance test was defined as a 2-h post-prandial blood sugar level of > or = 7.8 mmol/l.
RESULTS: A total of 191 pregnant mothers (24.9%) had GDM. The most commonly identified screening factors were positive family history of diabetes mellitus (31.4%), history of spontaneous abortion (17.8%), vaginal discharge and pruritus vulvae in current pregnancy (16.0%), and maternal age greater than 35 years (14.7%). Five hundred and thirteen mothers (66.8%) had at least one risk factor. All screening risk factors, except past history of diabetes mellitus in previous pregnancy and maternal age, were not significantly associated with abnormal glucose tolerance (GT). Risk factor screening gave a sensitivity of 72.2% and a specificity of 35.0%. Universal screening would cost RM 12.06 while traditional risk factor screening would cost RM 11.15 per identified case and will have missed 53 of the 191 cases.
CONCLUSIONS: Risk factor screening scored poorly in predicting GDM. Cost analysis of universal compared with traditional risk factor screening showed a negligible difference. Thus universal screening appears to be the most reliable method of diagnosing GDM.
AIMS: To determine the role of serum insulin-like growth factor I (IGF-I) in predicting the occurrence of septal hypertrophic cardiomyopathy in infants of mothers with diabetes.
METHODS/MATERIALS: In this prospective study, 100 pregnant women (50 with diabetes and 50 controls), matched for age and race, were studied. One intrapartum blood sample was taken at 28 weeks of gestation from both groups of mothers and another sample at delivery. All samples were analysed for maternal IGF-I by an enzyme linked immunosorbent assay method. A chest radiograph and an electrocardiogram were performed on the babies of the mothers with diabetes within the first 24 hours of life. An echocardiogram was performed in the first 3 days of life to look for septal hypertrophy and to measure the myocardial thickness.
RESULTS: In the six cases of neonatal septal hypertrophic cardiomyopathy, all the mothers had greatly raised IGF-I concentrations of more than 400 ng/ml at the time of delivery compared with a mean (SD) of 302 (25) ng/ml in control mothers.
CONCLUSIONS: In the present study a crude analysis revealed that increased IGF-I concentrations correlate with neonatal septal hypertrophic cardiomyopathy.
Study site: Obstetric and gynaecology clinic, Pusat Perubatan Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
Aim: To determine the incidence of an abnormal umbilical artery resistance index (UARI) in diabetic pregnancies and the relation to fetal outcome and the development of neonatal septal hypertrophic cardiomyopathy.
Methods: A case-control study with subjects comprising 50 randomly selected diabetic mothers and a matched control group of 50 non-diabetic pregnancies. Doppler studies of the UARI were carried out at least once per week, beginning from 36 weeks' gestation for both groups. Within 48 h post delivery, echocardiograms were carried out on the newborn infants to identify those with hypertrophic cardiomyopathy, particularly asymmetrical septal hypertrophy.
Results: The numbers of patients with abnormal UARI were similar in both the diabetic and control groups. A higher proportion of operative deliveries for intrapartum fetal distress was seen in patients with an abnormal UARI in the diabetic group. However, the groups did not differ in the numbers of infants who were small for gestational age, who had low Apgar scores or umbilical artery acidosis, and who required admission to the special care nursery. Six infants of diabetic mothers (12%) had septal hypertrophy, but none of these were associated with abnormal antenatal UARI.
Conclusion: Diabetic pregnancy is not associated with a significantly higher incidence of abnormal UARI on Doppler study than non-diabetic pregnancy. UARI is not a useful single indicator by which to predict subsequent fetal outcome or the development of neonatal septal hypertrophic cardiomyopathy in diabetic pregnancies.
AIM: To determine the relationships between maternal and fetal outcomes and gestational diabetes mellitus (GDM), impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), respectively.
METHODS: A retrospective cohort study design was used with 149 patients with abnormal oral glucose tolerance test (OGTT) and 149 normal patients. Statistical analysis used was the chi-squared test, Fisher's exact test or the Student's t-test, as appropriate. P < 0.05 was considered significant.
RESULTS: The level of hyperglycemia according to the OGTT (World Health Organization criteria) was associated with pre-eclampsia, polyhydramnios and macrosomia in GDM patients. There was no increase in the complications of preterm labor and premature rupture of membranes, despite the increased risk of polyhydramnios. Although treated with insulin, macrosomia still occurred in patients with GDM, but there was no shoulder dystocia as there was an increase in the incidence of cesarean section (CS). The IGT group was not associated with adverse fetal or maternal outcomes, but there was an increase in intervention and the incidence of CS. The IFG group was associated with a significantly increased risk of pre-eclampsia and macrosomia. These findings challenge the concept of IFG being a lesser pathology than GDM. Further prospective studies with a larger number of patients are needed to ascertain the significance of these findings.
CONCLUSION: There was an increased risk of pre-eclampsia and macrosomia in both the GDM and IFG patients, but IGT was not associated with adverse fetal or maternal outcomes.
Study site: Maternity Hospital Kuala Lumpur (MHKL), Kuala Lumpur, Malaysia
BACKGROUND: Septal hypertrophic cardiomyopathy (sHCM) is a characteristic anomaly of the infant of diabetic mother (IDM). Insulin-like growth factor-1 (IGF-1) has been identified as a mediator of tissue overgrowth and we have previously shown that maternal IGF-1 levels were significantly elevated among neonates with asymmetrical sHCM. IGF-1 does not cross the placenta; it exerts physiologic action through binding to the IGF-1 receptor (IGF-1R). Localisation and expression of IGF-1R in term diabetic pregnancies are largely unclear. We have studied IGF-1R in the placentae of diabetic and normal pregnancies and this receptor expression in association with neonates with sHCM.
METHODS: IGF-1R localization and expression in the placentae of six diabetic pregnancies associated with neonatal sHCM were compared with six each of randomly selected diabetic and normal pregnancies without neonatal sHCM by immunohistochemistry. The staining for IGF-1R in the deciduas, cytotrophoblasts, syncytiotrophoblasts and villous endothelium for these 18 samples were assessed and scored by two pathologists who were blinded to the respective diagnoses.
RESULTS: Placental IGF-1R staining was negative in the villous endothelium for all three groups. IGF-1R staining was present in deciduas, cytotrophoblasts and syncytiotrophoblasts but the staining was weaker in the entire group of infants with sHCM compared to those without sHCM.
CONCLUSIONS: IGF-1R is localized in all cell types of the placenta except in villous endothelium. Weaker placental IGF-1R staining in the placentae of diabetic pregnancies associated with sHCM suggests reduced expression of IGF-1R. This may be a down-regulatory response to elevated maternal IGF with neonatal sHCM outcome.
Background: The best method of screening for gestational diabetes (GDM) remains unsettled. The 50-g glucose challenge test (GCT) is used in a two-stage screening process but its best threshold value can vary according to population.
Aims: To evaluate the role of risk factors in conjunction with GCT and to determine an appropriate threshold for the one-hour venous plasma glucose with the GCT.
Method: In a prospective study, 1600 women at antenatal booking without a history of diabetes mellitus or GDM filled a form on risk factors before GCT. Women who had GCT >or= 7.2 mmol/L underwent the 75-g oral glucose tolerance test (OGTT). GDM was diagnosed according to WHO (1999) criteria.
Result: Thirty-five per cent had GCT >or= 7.2 mmol/L, 32.6% underwent OGTT and 34.5% of OGTT confirmed GDM. The GDM rate in our population was at least 11.4%. Examination of the receiver operator characteristic curve suggested that the best threshold value for the GCT in our population was >or= 7.6 mmol/L. Multivariable logistic regression demonstrated that only GCT >or= 7.6 mmol/L was an independent predictor for GDM (adjusted odds ratio 3.7: P < 0.001). After GCT, maternal age and anthropometry, OGTT during the third trimester, family history, obstetric history and glycosuria were not independent predictors of GDM.
Conclusions: Risk factors were not independent predictors of GDM in women with GCT >or= 7.2 mmol/L. GCT threshold value >or= 7.6 mmol is appropriate for the Malaysian population at high risk of GDM.
AIM:
To evaluate the relationship between gamma-glutamyltransferase (GGT) level in pregnant women at oral glucose tolerance test (OGTT) and the diagnosis of gestational diabetes (GDM).
METHODS:
Blood was taken for analyzing GGT level from women at high risk of GDM at the time of their scheduled OGTT. GDM was diagnosed according to World Health Organization 1999 criteria.
RESULTS:
GGT level correlated positively with the 2-hour glucose level (Spearman's rho = 0.112: P < 0.05). GGT values that were stratified into quartiles demonstrated a significant trend with diagnosis of GDM (chi(2) for trend; P = 0.03). Multivariable logistic regression analysis taking into account maternal age, gestational age at OGTT, body mass index and a positive 50-g glucose challenge test (GCT) indicated that high GGT was an independent risk factor for GDM (adjusted odds ratio [AOR] 2.1 95% CI 1.2-3.8: P = 0.01). In the subset of women identified by a positive GCT, on multivariable logistic regression analysis, only high GGT was an independent risk factor for GDM (AOR 2.3 95% CI 1.3-4.2: P = 0.007).
CONCLUSION:
Raised GGT level is an independent risk factor for GDM in high risk pregnant women undergoing OGTT.
OBJECTIVE:
To evaluate the 50-g glucose challenge test (GCT) on pregnancy outcome in a multiethnic Asian population at high risk for gestational diabetes (GDM).
METHODS:
GCT was positive if the 1-hour plasma glucose level was >or=7.2 mmol/L. GDM was diagnosed by a 75-g glucose tolerance test using WHO (1999) criteria. Of the 1368 women enrolled in the study, 892 were GCT negative, 308 were GCT false-positive, and 168 had GDM. Pregnancy outcomes were extracted from hospital records. Multivariable logistic regression analysis was performed with GCT negative women as the reference group.
RESULTS:
GCT false-positive status was associated with preterm birth (adjusted odds ratio [AOR] 2.1; 95% CI, 1.2-3.7) and postpartum hemorrhage (AOR 1.7; 95% CI, 1.0-2.7). GDM was associated with labor induction (AOR 5.0; 95% CI, 3.3-7.5), cesarean delivery (AOR 2.2; 95% CI, 1.6-3.2), postpartum hemorrhage (AOR 2.1; 95% CI, 1.2-3.7), and neonatal macrosomia (AOR 2.5; 95% CI, 1.0-6.0).
CONCLUSION:
GCT false-positive women had an increased likelihood of an adverse pregnancy outcome. The role and threshold of the GCT needs re-evaluation.
To establish baseline levels of maternal plasma soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) among normotensive Malaysian mothers and to compare the marker levels between normotensives and mothers with gestational hypertension (GH).
To compare the efficacy of two screenings methods for gestational diabetes mellitus, namely the universal screening using 50g Glucose Challenge Test to that of selective screening based on risk factors.
Gestational diabetes mellitus (GDM), defined as carbohydrate intolerance diagnosed for the first time during pregnancy, affects both maternal and fetal health. Possession of a specific genetic polymorphism can be a predisposing factor for susceptibility to some diseases. The aim of this study was to investigate the association between single nucleotide polymorphisms (SNP) in the promoter gene of interleukin-10 (IL-10) as well as tumor necrosis factor-alpha (TNF alpha) with the development of GDM. Two hundred and twelve consecutive series of eligible normal pregnant women (controls) and gestational diabetes mellitus women were selected based on the study's inclusion and exclusion criteria. DNA was extracted from blood and genotyped for IL-10 at three positions and TNF alpha for gene polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Plasma levels of IL-10 and TNF alpha at different gestational periods as well as postpartum were quantified using enzyme linked immunosorbent assay (ELISA). The results of the study showed that the difference in the frequency of SNP at position -597 in the promoter of the human IL-10 gene between the control and GDM groups was statistically significant (p < 0.05). In contrast, there was no significant difference in the frequency of SNP at the other two sites in the promoter region of the human IL-10 gene (-824 and -1082) as well as position -308 in the promoter of the human TNF-alpha (p > 0.05). In addition, there was no significant difference between the two groups in terms of plasma levels of IL-10 as well as TNF alpha in different stages of pregnancy. SNP at position -597 was significantly associated with the development of GDM and shows potential for use as a predictive marker for GDM.
OBJECTIVE: The aim of this study is to investigate if an association exists between single nucleotide polymorphism (SNP) in the tumor necrosis factor-alpha (TNF-alpha) and TNF-beta genes.
METHODS: The DNA was extracted and SNP in the human TNF-alpha and TNF-beta genes at positions -308 (G/A) and 252 (A/G), respectively, was analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Plasma levels of TNF-alpha in different stages of pregnancy were quantified using enzyme linked immunosorbent assay (ELISA).
RESULTS: There was no significant difference in genotype and allele frequency of SNP at position -308 (G/A) in the promoter region of the human TNF-alpha gene as well as the SNP at position 252 (A/G) in the human TNF-beta gene between the GDM and control subjects. Using the logistic regression model, it was found that the SNP in the TNF-alpha as well as TNF-beta were not associated with development of GDM. In addition, the TNF-alpha levels in the plasma of GDM and control mothers were not significantly different.
CONCLUSIONS: In the population studied, the SNP in position -308 (G/A) of the human TNF-alpha or in position 252 (A/G) of the human TNF-beta gene is not an independent risk factor or a predictor for GDM.
AIM: To evaluate the safety and tolerability of once or twice daily neutral protamine hagedorn (NPH) insulin in fasting pregnant diabetics during Ramadan.
METHODS: This was a prospective cohort study conducted during Ramadan 2006 and 2007. Twenty four pregnant diabetic women were given NPH insulin once at 5 pm or twice daily at 5 pm and 5 am. Demographic data, blood glucose control, insulin requirement, days of fasting and hypoglycemic episodes were analyzed.
RESULTS: Most women were parity 1 (37.5%) in their second trimester (54.2%) and worked during the daytime (87.5%). Fourteen women (58.3%) had gestational diabetes mellitus, nine women (37.5%) had type 2 and one (4.2%) had type 1 diabetes mellitus. There were significant reductions in mean fasting blood glucose (6.16 mmol/L versus 5.34 mmol/L, P = 0.001), glycosylated hemoglobin (HbA1c) (6.70% ± 0.91 versus 6.64% ± 0.96, P = 0.001) and serum fructosamine (232.4 mmol/L ± 24.0 versus 217.0 mmol/L ± 24.3, P = 0.001) after Ramadan compared to before Ramadan. Throughout the four weeks of Ramadan, home blood glucose monitoring showed a reducing trend and was within the acceptable limits. Insulin requirement was increased from the first to the fourth week with a reduction in insulin dose noted after (38.5 U/day) compared to before the start of Ramadan (40 U/day). Most women (79.2%) were able to fast for more than 15 days without any hypoglycemia or fetal demise.
CONCLUSION: Once or twice daily NPH insulin is a safe and tolerable option for pregnant diabetics who wish to fast during Ramadan.
We investigated the usefulness of a single value of maternal HbA1c in late pregnancy as a predictor for neonatal hypoglycaemia and secondly, to find the appropriate threshold value. A prospective analysis of the HbA1c concentration between 36 to 38 weeks of gestation in 150 pregnant mothers with either pre-existing or gestational diabetes was performed. At delivery, glucose levels in the cord blood were analysed. Neonatal hypoglycaemia was defined as a blood sugar level of < 2.6 mmol/l. Receiver operator characteristic curve was constructed to evaluate the value of HbA1c concentration in predicting hypoglycaemia. There were 16 foetuses who were hypoglycaemic at delivery. The area under the ROC curve for predicting neonatal hypoglycaemia was 0.997 with a 95% confidence interval of 0.992 to 1, a very good prediction rate. The optimal threshold value for HbA1c in predicting hypoglycaemia in the foetus was 6.8% (51 mmol/mol). HbA1c level in late pregnancy is a good predictor for hypoglycaemia in the newborn.