A 10-year retrospective analysis of pregnancy outcome in pregestational Type 2 diabetes: comparison of insulin and oral glucose-lowering agents.

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.

A double-blind randomised controlled trial of continuous oxygen therapy for compromised fetuses.

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.

Maternal diabetes and neonatal outcome.

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.

A randomised controlled trial of intravenous magnesium sulphate versus placebo in the management of women with severe pre-eclampsia.

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.

Growth of the fetal biparietal diameter in urban Cape coloured families.

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.

The campomelic syndrome--prenatal ultrasound investigations. A case report.

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.

Ultrasound examination before amniocentesis and success of culture in genetic referrals. Six years' experience in Cape Town.

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.

The management of non-insulin-dependent diabetes during pregnancy.

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.

Oral hypoglycaemics in the first trimester and fetal outcome.

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.

Pregnancy in insulin-dependent diabetics. A 5 1/2-year study at Groote Schuur Hospital.

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.

Ultrasound examination before amniocentesis. Its effect on cell culture for cytogenetic studies.

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.

Pregnancy in established non-insulin-dependent diabetics. A five-and-a-half year study at Groote Schuur Hospital.

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.