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Objective: To determine the reproducibility of the oral glucose tolerance test (OGTT)., Design: A retrospective study of 205 women who underwent screening for gestational diabetes., Setting: A university teaching hospital in a South African city., Sample: Women who had an abnormal OGTT had the test repeated during the same pregnancy without any diabetic or dietary advice given in the intervening time period., Methods: Women with two OGTTs in the same pregnancy had a proforma completed at the time. Completed proformas were filed and reviewed for the purpose of this study., Main Outcome Measure: The κ statistic was used for estimating the agreement between repeated tests using the same nominal or dichotomous scale., Results: The OGTT was repeated during the index pregnancy in 205 women and in a subset of 76 women within 17 days. The κ statistic was 0.269 for 205 women and 0.212 for 76 women for the fasting glucose value (fair strength of agreement). The κ statistic for the 2-h glucose value was 0.157 for 205 patients and 0.174 for 76 patients (slight strength of agreement). The overall OGGT classification produced κ statistics of 0.167 and 0.150 for the whole group and the 76 patients, respectively., Conclusion: The reproducibility was better with the fasting glucose and less with the 2-h result and the overall OGGT classification. Caution needs to be exercised when interpreting the single positive result of an OGTT in pregnant women.

The problem of screening and treating diabetes in pregnancy in a resource-poor country is explored. Although the burden of disease is high, diabetes contributes to higher perinatal mortality and morbidity and ultimately can lead to metabolic diseases when the offspring reaches adulthood. The mother is also more likely to develop full blown diabetes in later life with resulting diabetic morbidity and even mortality. Cheaper options for screening, including task shifting, are essential. In type 2 diabetes and gestational diabetes there are cheaper alternatives to insulin for treatment, such as diet, exercise, and oral glucose lowering agents such as metformin and glibenclamide.

Aims: To review the use of oral glucose-lowering agents (OGLA) in pregnant women with Type 2 diabetes mellitus., Methods: Retrospective analysis of outcomes and their predictors in singleton pregnancies > or = 24 weeks managed at Groote Schuur hospital, Cape Town, South Africa from 1991 to 2000. There were 379 pregnancies, subdivided into three groups according to therapy: OGLA alone, converted from OGLA to insulin, insulin alone or converted from diet alone to insulin. The OGLA used were metformin and glibenclamide., Results: Mean glycated haemoglobin (HbA(1c)) was similar at booking and throughout pregnancy in all groups. In the OGLA alone, converted from OGLA to insulin and insulin alone/converted from diet alone to insulin groups, fetal anomaly rates were comparable: 5.7%, 2.0% and 0.0%, P = 0.2, respectively; whereas perinatal mortality rates (per 1000 births) were: 125, 28, 33, P = 0.003, respectively. Booking HbA(1c) was independently associated with fetal anomaly [odds ratio (OR) 1.48; 95% confidence interval (CI) 1.11, 1.97; P = 0.006]. The specific OGLA used in the first trimester was not associated with the occurrence of fetal anomaly. Last HbA(1c) (OR 1.65; 95% CI 1.16, 2.42; P = 0.005) and fetal anomaly (OR 15.18; 95% CI 2.43, 93.37; P = 0.005) were independently associated with perinatal mortality. Conversion from OGLA to insulin was protective for perinatal mortality compared with OGLA alone treatment (OR 0.220; 95% CI 0.061, 0.756; P = 0.024). No perinatal mortality was observed in women on metformin alone., Conclusions: These data suggest that metformin and glibenclamide are not teratogenic but that it is advisable to replace OGLA, in particular glibenclamide, with insulin when women book for pregnancy care to reduce perinatal mortality rates.

Objective: To investigate the effect of chronic oxygen therapy in fetuses with absent end diastolic flow in the umbilical artery assessed by doppler analysis at 24-30 weeks of gestation., Design: A double-blind, randomised control trial was performed with patients blindly allocated to receive humidified oxygen or humidified air., Setting: A tertiary referral hospital in South Africa., Participants: Thirty-two women who presented between 24 and 30 weeks of gestation with a confirmed finding of absent end diastolic flow in the umbilical artery., Methods: After randomisation patients were allocated to receive a 40% mixture of humidified oxygen or humidified air from uniform coloured gas cylinders which were marked either 'a' or 'b' All women received betamethasone from 27 weeks of gestation on a weekly basis. Cardiotocographs were used from 28 weeks of gestation; after 28 weeks of gestation an amniocentesis was considered to confirm fetal maturity. Women were expected to breath the allocated gas continuously apart from meals and visits to the toilet., Main Outcome Measures: Survival of the fetus was the main outcome measure with secondary outcome measures documenting improvement in the fetal condition in utero., Results: There were 16 women randomised to receive oxygen and 16 to receive air. There were nine survivors in the oxygen group (56.3%) and six in the air group (37.5%) (relative risk 1.5, 95% confidence interval 0.7-3.2). There was a nonsignificant increase in mean birthweight in the oxygen group (858.3 grammes vs 774.4 grammes) and a nonsignificant increase in mean duration of treatment in the oxygen group (12.8 days vs 10.4 days)., Conclusion: This study did not demonstrate that chronic oxygen therapy provides any benefits to compromised fetuses between 24 and 30 weeks of gestation. Larger studies with sufficient power are necessary to assess whether oxygen therapy can reduce perinatal mortality by a clinically useful amount in this group of patients.

The new definitions and classification of diabetes is discussed. An electronic literature search was done especially for randomized trials in management of maternal diabetes. However, because of the paucity of such trials the modern management we propose is still based on evaluative and retrospective evidence. Problems of type 2 diabetes specifically in the developing world are highlighted. Although the goals of the St Vincent declaration are attainable; in a practical setting (even in excellent centres) we fall far short of achieving perinatal mortality and fetal anomaly rates equivalent to the non-diabetic pregnant population. This is mainly due to lack of excellent pre-conceptional care for the future diabetic mother., (Copyright 2000 Harcourt Publishers Ltd.)

Objective: To determine whether the administration of prophylactic intravenous magnesium sulphate reduces the occurrence of eclampsia in women with severe pre-eclampsia., Design: Randomised controlled trial., Setting: A tertiary referral obstetric unit., Population: Eight hundred and twenty-two women with severe pre-eclampsia requiring termination of pregnancy by induction of labour or caesarean section., Methods: The women were randomised to receive either placebo (saline) or magnesium sulphate intravenously. The investigators were blinded to the contents of the pre-mixed solutions., Main Outcome Measure: The occurrence of eclampsia in the two groups., Results: The data of 699 women were evaluated. Fourteen were withdrawn after randomisation. The overall incidence of eclampsia was 1.8%. Of 345 women who received magnesium sulphate, one developed eclampsia (0.3%); in the placebo group, 11/340 women (3.2%) developed eclampsia (relative risk 0.09; 95% confidence interval 0.01-0.69; P = 0.003)., Conclusion: The use of intravenous magnesium sulphate in the management of women with severe pre-eclampsia significantly reduced the development of eclampsia.

The campomelic syndrome is a skeletal dysplasia of unknown aetiology which is apparent at birth and is characterized by bilateral bowing of the tibiae, clubfoot and other multiple congenital abnormalities. Up to 50% of cases are either stillborn or die within 24 hours of birth in respiratory distress. With a few exceptions, the remainder die within 10 months. The patient in this report demonstrated characteristic features of the syndrome which were detected antenatally by ultrasound and confirmed after delivery. The apparently female infant died 2 hours postpartum in respiratory distress, but was subsequently found to have a 46,XY chromosome constitution. Autopsy and postmortem radiographs revealed multiple congenital abnormalities consistent with the campomelic syndrome. The findings in this case are discussed and the possibility of antenatal diagnosis is raised.

A prospective series of 307 patients who underwent laparoscopic sterilization on a day-case basis is presented. Of these, 196 patients attended for the 6-month and 117 for the 1-year follow-up visit. There were 5 Blacks, 197 Coloureds and 105 Whites. Sterilization was done by means of tubal cauterization (137), Hulka-Clemens clips (34) and Falope rings (136). Although 18% of patients were under 30 years old, 16% were 40 years of age or older. A marked tendency to low parity was evident, 43% of Coloureds and 90% of Whites being para 3 or less. The main operative problem was uterine perforation. Of the patients 17% were not discharged on the day of operation. By the 5th postoperative day 86% had returned to normal working activities. Significantly more postoperative abdominal pain was reported in the clip and ring groups. Seven pregnancies occurred in the series, 6 after tubal cauterization and 1 after the application of Falope rings. On patient was probably pregnant at the time of the operation. Most patients reported no change in libido at the 1-year follow-up visit, and in 20% libido was increased Mild pelvic infection was the only significant finding at the 6-month and 1-year follow-up visits. Apart from the disturbingly high pregnancy rate and the relatively large number of patients who were not discharged on the day of operaton, the sterilization programme has been most acceptable.

The birth weight, length, head circumference and body proportions of infants born to women with well-controlled diabetes were compared with those of infants born to poorly controlled diabetics. The latter infants were significantly heavier, with a greater weight/length ratio and a smaller head circumference/weight ratio, while their length, and head circumference/length ratio were appropriate for age. The size and body proportions of infants born to well-controlled diabetics were normal. Hairiness of the pinna was observed in infants born to both well- and poorly controlled diabetics, and may prove to be a useful clinical sign in identifying the infant of a diabetic mother.

Ultrasonic measurements of biparietal diameter (BPD) between the 12th week of menstrual age (MA) and delivery were taken longitudinally on a group of 98 Cape Coloured employees of Groote Schuur Hospital. The socio-economic situation of subjects was above average for the community; this was reflected in their larger body size and the increased birth weight of observed fetuses. A growth chart showing MA as a function of BPD has been constructed for clinical use. This chart can be regarded as representing a 'norm' closer to the ideal than to the average in the population.

During a 5 1/2-year period we have seen 171 pregnant women with established insulin-independent diabetes. Eleven of them booked late and received virtually no treatment. The remaining 160 patients were managed primarily by regulating diet; when this failed metformin or glibenclamide therapy was instituted. Insulin was used when diet and oral drugs failed. Diabetic control was considered adequate if fasting blood glucose levels remained below 5,5 mmol/l and post-prandial levels were below 6,7 mmol/l. Twenty-five per cent of patients were well controlled on diet only during the duration of their pregnancies, with 1 perinatal death. Glibenclamide and metformin appear to be safe drugs during pregnancy when properly used. The overall perinatal mortality rate was 78/1 000; 42/1 000 since January 1978, as compared with 364/1 000 in the 'untreated' group. Only 18 babies were large (> 4 000 g), respiratory distress rarely occurred and hyaline membrane disease was virtually absent. Hypoglycaemia of the neonate was seldom a problem, but was most frequently related to the use of glibenclamide. Neonatal hypoglycaemia may be abolished if patients receiving tablets or insulin are given continuous, intravenous low-dose insulin 24 hours before planned delivery. The prevalence of major abnormalities was as least double that among infants of non-diabetic mothers.

In order to obtain metaphases plates from amniotic fluid cells for chromosome analysis, amniocentesis is performed on patients who are at risk of carrying a fetus with genetic disorders. Ultrasound examination is routinely done before amniocentesis as an aid to the latter procedure and to obtain clinical data concerning the fetus. Speculation that ultrasound examination would reduce the number of blood-stained taps obtained at amniocentesis and maybe also inhibit the growth of amniotic fluid cells in culture is discussed, based on findings in this laboratory over a 3-year period.

Two hundred and sixteen patients were selected for laparoscopic sterilization on a day-case basis. Patients were sterilized by electrocautery, by applying Silastic bands (Falope rings), and by means of Hulka-Clemens clips. Three patients required laparotomy and 35 patients were discharged the day after the operation. By the 3rd day 146 (69%) and by the 5th day 184 (86%) patients had returned to their routine work. From the technical and immediate postoperative point of view, there appears to be relatively little difference between the three techniques. There may be slightly more risk of thermal complications with bipolar cauterization, a slightly highly incidence of postoperative abdominal pain with the Silastic band applicator, and slightly more difficulty in applying the Hulka-Clemens clip. These problems are all reduced by experience and proper training of the operator, which is essential. Our experience confirms that laparoscopic sterilization is safe, efficient, and feasible as a day-case procedure, and that it has major advantages in terms of patient convenience and acceptability as well as reduction in hospitalization costs.

Sixty pregnant "maturity-onset" (insulin-independent), established and gestational, diabetics were treated with Metformin in the second and third trimester after dietary treatment had failed. The incidence of Metformin failure was 53.8% in the established diabetics and 28.6% in the "gestational" diabetics. The 27 Metformin failures were transferred to other therapy, leaving for further analysis 33 patients who received Metformin up till delivery. Two neonatal deaths occurred in this group (1 congenital abnormality and 1 preterm infant) giving a perinatal mortality of 61/1000. This compares with a perinatal mortality of 103/1000 in the Metformin failure group and 105/1000 in a group of insulin-dependent diabetics treated during the same period. Apart from a high incidence of neonatal jaundice requiring phototherapy the infant morbidity in the Metformin group was low. The mothers of 3 infants with congenital abnormalities had received Metformin only during the last trimester of their pregnancy.

During a 5 1/2-year period we have seen only 39 pregnant women with insulin-dependent diabetes, as opposed to 171 with established insulin-independent diabetes. Tight control with two injections of mixed insulins per day was attempted, but satisfactory blood glucose values were obtained in only 16 cases. Nevertheless the overall perinatal mortality rate was 77/1000; of the 3 infants which died 2 had lethal congenital abnormalities and 1 was born to a mother whom we had been seeing for only 4 weeks. Perinatal morbidity was similar to that in other series, except that few of our infants were oversized, hyaline membrane disease was uncommon, and only 2 had a low Apgar score. Fourteen infants weighed less than 2500 g. Hypoglycaemia in the newborn appears to be much reduced by the use of continuous low-dose intravenous insulin infusion during labour or caesarean section. To reduce perinatal mortality further, we conclude that exact blood glucose control should be attained before conception.

During a 5 1/2-year period we saw 171 pregnant women with established non-insulin-dependent diabetes; 78 patients received oral hypoglycaemic drugs during the 1st trimester and 93 did not. The outcome of pregnancy in these two groups is compared. Only two major congenital anomalies were seen in the tablet-taking group and the number of abortions (4) was not excessive. The perinatal mortality (PNM) rate was initially high after large doses of chlorpropamide or metformin had been given during the 1st trimester, but this was clearly related to inadequate diabetic control in later pregnancy. Among the last 50 of the total of 75 viable infants whose mothers received oral drugs early in pregnancy, the PNM rate was 40/1 000. We conclude that modern oral hypoglycaemic drugs are safe and useful, not only during later pregnancy but also during the 1st trimester, provided excellent control of blood glucose levels is achieved.

Early morning ketonuria, as judged by Ketostix testing, occurred in 19% of urine samples from insulin-independent diabetic pregnant women eating 1000 calorie diets, in 14% from diabetics on higher calorie diets, and in 7% of urines from nondiabetic pregnant women. Ketostix test was never found to be positive in blood, even when it was 2+ in urine samples, and acetoacetate levels were always below 1 mmol/L. Enzymatic estimations of acetoacetate (AA) and beta-hydroxybutyrate (BB) in urine and plasma samples revealed (1) no significant differences in range or mean between the groups receiving different restricted diets or full diets, the highest value observed for plasma AA being 0.34 mmol/L; (2) that Ketostix became positive at a concentration of AA above 1 mmol/L and that such a value in urine corresponded to plasma levels of between 0.06 and 0.1 mmol/L, i.e., double the normal; and (3) a 50-100-fold increase in urine AA when blood levels exceeded 0.08 mmol/L. Neonates born to diabetic mothers with ketonuria had no fetal distress or asphyxia neonatorum. The lowest Apgar score at 5 min was 8; 80% of neonates had a score of 10. Hence, positive Ketostix tests in urine samples do not indicate toxic levels in the blood, and a 1000 calorie diet for obese pregnant diabetics appears to be safe as regards neonatal outcome.

Our experience in Cape Town shows that ultrasound examination is of great benefit when amniocentesis is performed to obtain amniotic fluid cells for metaphase plates from patients at risk of carrying a fetus with a genetic disorder. Data taken over a period of 6 years show that the number of blood-contaminated fluid specimens decreases significantly when patients are scanned before amniocentesis is performed. The presence of blood in the fluid increases the possibility that cells will not grow in culture. There was no evidence to suggest that ultrasound examination inhibited amniotic fluid cell growth in culture.

Two hundred and two patients were referred to the ultrasound department for evaluation of a pelvic mass during 1977, and of these only 120 underwent an operation enabling a definitive diagnosis to be made. The diagnostic accuracy of ultrasound was compared with the final operative diagnosis. The great majority (98%) of pelvic masses could be detected, and ultrasound was accurate in predicting the antatomical site of a pelvic lesion in 88% of cases. Uterine lesions were precisely diagnosed in 87% of cases, but only 30% of adnexal conditions could be specifically recognized. Numerous situations in which ultrasound provided additional information of great clinical value were noted.

We propose a rational regimen for management of non-insulin-dependent pregnant diabetics (NIDD), using appropriately constituted calorie-restricted diets with the oral agents metformin and glibenclamide as may be necessary, with rapid recourse to insulin if the latter do not produce excellent control of blood glucose. Using this regimen between June 1974 and December 1983 we have managed 423 new diabetics (ND, diagnosed during pregnancy) with a perinatal mortality (PNM) of 14 per 1000 and 268 established diabetics (known diabetics, KD) with a PNM of 70/1000 (57/1000 since 1978). A further 80 NIDDs were 'untreated', i.e., not seen by us until near term; these suffered a PNM of 313/1000. Side-effects of the drugs have been few and mild, they are not teratogenic; 'starvation ketosis' does not occur; neonatal hypoglycaemia is preventable by using continuous insulin infusion during delivery. We suggest that the regimen outlined here is acceptable to the patients, is safe, gives excellent results and furthermore teaches the diabetic mother proper dietary control and combats lifelong obesity. It should be useful especially in developing countries in which pregnant, overweight NIDDs are common. Precise control of the blood glucose is essential.

Over a period of 5 years, 434 women at risk of having abnormal babies have had antenatal daignostic tests carried out during the first half of their pregnancy by the laboratories of the Department of Human Genetics, University of Cape Town. From these investigations, it was predicted that 13 fetuses had chromosomal abnormalities, 6 had severe central nervous system defects and 4 had autosomal recessive metabolic disorders. In addition, 4 cases with X-linked recessive traits were monitored and 3 male fetuses were recognized. Affected pregnancies were terminated except for 1 with a fetal sex-linked disorder where the parents revoked their original decision. The diagnosis was confirmed by fetal autopsies in all cases except 4 (2 spontaneous abortions and 2 out-of-town terminations). There was only 1 case where culture failed and the pregnancy went to term with the birth of a baby with Down syndrome. Antenatal diagnosis is now an important part of normal clinical practice. The fact that the fetal abnormalities were recognized in 6% of pregnancies is justification for the use of this procedure.

The indications for and results of all glucose tolerance tests (GTTs) performed at the Antenatal Clinic, Groote Schuur Hospital, Cape Town, over a period of 1 year, and the indications for a GTT in the first 80 newly diagnosed diabetics over a 4-year period are analysed. Out of 558 GTTs, only 17 tentative diagnoses of 'gestational diabetes' were made. The most rewarding single indication for a GTT was repeated glycosuria, which was an indication in 61 out of the 80 newly diagnosed diabetics. A combination of two indications in the same patient was related to twice as many abnormal GTTs as a single indication, while reported previous diabetes or hyperglycaemia certainly merited confirmation. Reasons for repeating GTTs are discussed, as well as the management of 'borderline' and 'potential' diabetics. It is emphasized that 'diabetes' or 'hyperglycaemia' diagnosed during pregnancy is not equivalent to a definite diagnosis of diabetes in the non-pregnant state.

Degenerative diseases of the cerebral white matter are rare, but have severe consequences. The diagnosis of one such disorder, Krabbe's disease, may be made by biochemical analysis of cultured fibroblasts. As the disease is inherited as an autosomal recessive trait, there is a high risk of affected children being born to a heterozygote couple. A description is given of an infant with Krabbe's disease and of the monitoring of the mother's second pregnancy in which an affected fetus was found.

As a result of active screening for gestational diabetes of the population attending various antenatal clinics in the Cape Peninsula, 127 patients with a repeatedly diabetic glucose tolerance test (GTT) were discovered; in many the GTT was grossly abnormal. The most useful screening factor was repeated glycosuria. Because they had booked late, 22 patients received virtually no treatment, and 1 patient aborted. Treatment of the remaining 104 patients was achieved principally by regulating diet, but when this failed metformin or glibenclamide therapy was instituted. Insulin was used when diet and oral drugs failed. Diabetic control was considered adequate if fasting blood glucose levels remained below 5,5 mmol/l and if postprandial levels were below 7 mmol/l. Most patients (67) were well controlled on a strict dietary regimen, and there were no perinatal deaths in this group. Glibenclamide and metformin, judging from this small series, appear to be safe for use in gestational diabetics. The overall perinatal mortality in treated patients was 10/1 000 as compared with an effective perinatal mortality of 145/1 000 in the 'untreated' group. Neonatal morbidity was similar to that in other reported series. Hypoglycaemia was seldom a problem and 79% of birth weights were between the 10th and the 90th percentiles.