Outcome of pregnancy in patients with insulin-dependent diabetes mellitus and nephropathy with moderate renal impairment.

This study examines the effect of pregnancy on fetal outcome and maternal renal function in 17 women with Type 1 diabetes mellitus and nephropathy attending a joint diabetic-antenatal clinic between 1985 and 1993. There were 7 successful pregnancies in 6 women with moderate renal impairment, mean pre-pregnancy serum creatinine 165 mumol l-1 (Group 1), and 12 in 11 women with proteinuria and preserved renal function (Group 2). Median gestation of pregnancy was 31 + 3 weeks in Group 1 and 36 + 4 weeks in Group 2 (p < 0.05). All babies in Group 1 required neonatal intensive care for a median of 19 days (range 8-271) as compared to only 5 of 13 in Group 2 whose median stay was 13 (7-17) days (p < 0.05). There was one late death in Group 1. Longitudinal creatinine data in those with moderate renal impairment suggest no systematic adverse long-term effect of pregnancy on maternal renal function, although differing changes in renal function were observed during pregnancy. The generally favourable outcome achieved relied heavily upon neonatal care expertise.

Fetal pancreatic beta-cell function in pregnancies complicated by maternal diabetes mellitus: relationship to fetal acidemia and macrosomia.

OBJECTIVE: Our purpose was to investigate the relationship between fetal pancreatic beta-cell function and fetal acidemia and macrosomia in pregnancies complicated by maternal diabetes mellitus. STUDY DESIGN: A cross-sectional study at the Harris Birthright Research Centre for Fetal Medicine, London, was performed. In 32 pregnancies complicated by maternal diabetes mellitus cordocentesis was performed at 36 to 39 weeks' gestation for the measurement of umbilical venous blood pH, PO2, PCO2, lactate, and glucose concentration; plasma insulin immunoreactivity; and insulin/glucose ratio. A reference range for plasma insulin and insulin/glucose ratio was constructed by studying fetal blood samples from 80 women who did not have diabetes mellitus. RESULTS: Mean umbilical venous blood pH was significantly lower and plasma insulin immunoreactivity and insulin/glucose ratio were significantly higher than the appropriate normal mean for gestation. There were significant associations between (1) maternal and fetal blood glucose concentrations (r = 0.95, p < 0.0001), (2) fetal blood glucose and plasma insulin immunoreactivity (r = 0.57, p < 0.01), (3) fetal plasma insulin immunoreactivity and blood pH (r = -0.39, p < 0.05), and (4) fetal insulin/glucose ratio and degree of macrosomia (r = 0.76, p < 0.0001). CONCLUSION: Fetal pancreatic beta-cell hyperplasia is implicated in the pathogenesis of both fetal acidemia and macrosomia.

Prediction of fetal acidaemia in pregnancies complicated by maternal diabetes mellitus by biophysical profile scoring and fetal heart rate monitoring.

OBJECTIVE: To determine whether computer assisted fetal heart rate analysis or the biophysical profile score can provide noninvasive prediction of fetal acidaemia. DESIGN: Cross sectional study. SETTING: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital School of Medicine, London. SUBJECTS: Forty-one women with pregnancies complicated by diabetes mellitus. INTERVENTIONS: Fetal heart rate (FHR) monitoring with computer assisted analysis, biophysical profile score (BPS) and cordocentesis for measurement of umbilical venous blood glucose concentration and blood gases, up to 24 h before delivery at 27 to 39 weeks gestation. RESULTS: The mean umbilical venous blood pH was significantly lower than the normal mean for gestation, and was below the 5th centile in 18 pregnancies, including all six cases where the mother had nephropathy and hypertension. The mean pO2 was not significantly different from the normal mean for gestation. There were significant associations between fetal acidaemia and both the BPS (r = 0.46, P < 0.01) and FHR variation (r = 0.42, P < 0.01). However, of the 12 acidaemic fetuses of non-nephropathic mothers, nine had normal BPS and six had normal FHR variation. CONCLUSIONS: In pregnancies complicated by maternal diabetes mellitus, BPS and FHR variation are of limited value in the prediction of fetal blood pH.

Placental and fetal Doppler velocimetry in pregnancies complicated by maternal diabetes mellitus.

OBJECTIVE: Our purpose was to investigate placental and fetal circulation in pregnancies complicated by maternal diabetes mellitus and to relate any changes to fetal blood pH, Po2, and hematocrit. STUDY DESIGN: Doppler measurements of both uterine arteries, one umbilical artery, the fetal descending thoracic aorta, and one fetal middle cerebral artery were performed in 65 well-controlled diabetic pregnancies in a cross-sectional study at the Harris Birthright Research Centre for Fetal Medicine, London. In 41 cases cordocentesis was also performed for the measurement of umbilical venous blood pH, Po2, and hematocrit. RESULTS: The mean umbilical venous blood pH was significantly lower and the hematocrit significantly higher than the appropriate normal mean for gestation. However, the Doppler indices of the placental and fetal circulations were essentially normal, except in some of the cases complicated by preeclampsia or intrauterine growth retardation. CONCLUSIONS: Maternal diabetes mellitus is not associated with abnormalities in Doppler indexes of the placental or fetal circulations.

Fetal plasma erythropoietin in pregnancies complicated by maternal diabetes mellitus.

OBJECTIVE: Our purpose was to investigate the relationship between fetal plasma erythropoietin concentration and measures of short-term and long-term glycemic control and fetal oxygenation in pregnancies complicated by maternal diabetes mellitus. STUDY DESIGN: A cross-sectional study was performed at The Harris Birthright Research Centre for Fetal Medicine, London. Cordocentesis was performed in 31 diabetic pregnancies for the measurement of umbilical venous blood pH, PO2, PCO2, lactate and glucose concentration, erythroblast count, hemoglobin, and plasma erythropoietin concentrations. RESULTS: The mean pH was significantly lower and the PCO2, lactate, erythropoietin, hemoglobin, and erythroblast counts were significantly higher than the appropriate normal mean for gestation. There were significant associations between (1) fetal erythropoietin and erythroblast count, (2) fetal erythroblast count and hemoglobin, (3) fetal hemoglobin and maternal glycosylated hemoglobin, and (4) maternal glucose and fetal glucose, pH, and lactate. CONCLUSIONS: We postulate that maternal hyperglycemia causes fetal hyperglycemia and acidemia. Increased erythropoietin may be caused by tissue hypoxia or hyperinsulinemia. The increase in fetal hemoglobin may be the consequence of increased erythropoiesis, mediated by either erythropoietin or hyperinsulinemia.

Doppler velocimetry and fetal heart rate studies in nephropathic diabetics.

OBJECTIVES: Our objectives were to determine in pregnancies complicated by diabetic nephropathy (1) if impedance to flow in the uterine and umbilical arteries is normal and (2) if these fetuses are hypoxemic and acidemic and if they have decreased fetal heart rate variation and Doppler blood flow redistribution. STUDY DESIGN: In a cross-sectional study at the Harris Birthright Research Centre for Fetal Medicine, London, serial assessment of fetal heart rate variation and Doppler velocimetry of the placental and fetal circulations was undertaken in six pregnancies complicated by diabetic nephropathy. In all cases cordocentesis was performed within 24 hours before delivery for the measurement of umbilical venous blood gases. RESULTS: Cordocentesis demonstrated these fetuses to be hypoxemic and acidemic. The fetal heart rate variation was decreased; however, impedance to flow in the uterine artery was normal, and increased impedance to flow in the umbilical artery with evidence of blood flow redistribution was observed in only one case. CONCLUSIONS: Fetal hypoxemia and acidemia in pregnancies complicated by diabetic nephropathy is not a consequence of impaired placental perfusion, and the degree of metabolic derangement may be obscured by the apparent normal growth and failure of these fetuses to demonstrate blood flow redistribution.

Fetal acidosis and hyperlacticaemia diagnosed by cordocentesis in pregnancies complicated by maternal diabetes mellitus.

Fetal blood samples were obtained by cordocentesis (ultrasound guided needle aspiration) from 28 pregnant Type 1 diabetic women between 20 and 40 weeks' gestation. Analysis of the deviations from normal values of blood pH and plasma lactate showed significant acidosis (p less than 0.001) and hyperlacticaemia (p less than 0.01) in the third trimester, but not in the second trimester. Blood PO2 and PCO2 levels did not differ significantly from normal values. The pH showed significant correlations with PO2 (r = 0.54; p less than 0.01) PCO2 (r = -0.70; p less than 0.001), lactate (r = -0.46; p less than 0.05), fetal glycosylated haemoglobin (r = -0.53; p less than 0.01), and maternal glycosylated haemoglobin (r = -0.57; p less than 0.01). Plasma lactate showed significant correlations with PO2 (r = -0.54; p less than 0.01), PCO2 (r = 0.50; p less than 0.05), and pH (r = -0.46; p less than 0.05). Neither pH nor lactate showed significant correlations with birthweight. These observations suggest that some fetuses of diabetic women are significantly acidotic and hyperlacticaemic in the third trimester. This may provide a possible explanation for the phenomenon of late intrauterine fetal death in pregnancies complicated by maternal diabetes mellitus.

Pregnancy in diabetic women who have proteinuria.

Pregnancy in diabetic women known to have proteinuria is thought to have a poor outcome. We report 22 pregnancies in 20 women with proteinuria in or before the first trimester culled from 396 diabetic pregnancies between 1974 to 1984. Despite a poor obstetric history all the present pregnancies were successful. Half were delivered before 37 weeks compared with 20 per cent of pregnancies in diabetic women without proteinuria. Hypertension precipitated two-thirds of the premature deliveries. The babies were small for dates with 65 per cent below the 50th centile, compared with 36 per cent in those without proteinuria. Serum creatinine levels were raised (greater than 150 mumol/l) in four of 19 patients in the third trimester. Since delivery one patient has died from renal failure, three have serum creatinine levels of 150 to 440 mumol/l, 11 have normal creatinine levels, and five have been lost to the study. The poor long-term maternal prognosis is an important reason for discouraging such pregnancies despite the good short-term results.

Diabetic pregnancy following renal transplantation.

Renal transplantation for diabetic nephropathy prolongs survival and the return of fertility makes pregnancy possible. We describe a successful pregnancy in a 38-year-old diabetic renal transplant recipient despite blindness, gangrenous toes, cardiac impairment, and both sensory and autonomic neuropathy. Renal function remained stable throughout the pregnancy which was complicated by supine hypertension, postural hypotension and increasing proteinuria. Fetal distress and increasing proteinuria precipitated delivery by Caesarean section at 29 weeks of a female infant weighting 1.1 kg. Following delivery, hypertension improved, gangrene resolved, proteinuria decreased, and renal function remained stable. Pregnancy in long-standing diabetic patients with renal transplants, although hazardous, may be successful yet the maternal morbidity and mortality makes them inadvisable.

Acute liver disease with encephalopathy and renal failure in late pregnancy and the early puerperium -- a study of fourteen patients.

Fourteen patients, aged 18 to 38 years, presented in the last trimester of pregnancy, or immediately post partum, with severe acute hepatic dysfunction. Liver biopsy confirmed the presence of acute fatty liver in six patients; the cause of hepatic dysfunction was presumed viral hepatitis in five patients, pre-eclampsia in two, and gram-negative septicaemia in one. There was one set of twins and the perinatal mortality was 33 per cent; there were three maternal deaths (21 per cent). Two survivors with acute fatty liver subsequently had successful pregnancies without evidence of hepatic dysfunction.

Management of the pregnant diabetic: home or hospital, with or without glucose meters?

Thirteen pregnant insulin-dependent diabetic patients were allocated to blood-glucose self-monitoring (meter) or conventionally treated (non-meter) groups at 30--31 weeks. A day-profile of blood-glucose and intermediary metabolite levels was obtained 2 weeks later at home and after routine admission to hospital at 35--36 weeks. Metabolic profiles were also obtained in eight normal pregnant women of equivalent gestational ages admitted to hospital for study. The mean blood-glucose and metabolite concentrations in both the meter and non-meter groups were similar to those obtained in the non-diabetic pregnant women (mean diurnal blood-glucose 4.6 +/- 1.1 mmol/l, meter group; 5.3 +/- 1.5 non-meter group; 4.8 +/- 0.8 controls). The diabetic control achieved at home was not improved by the use of a meter or admission to hospital (mean glucose at home 5.0 +/- 1.3 and 6.3 +/- 1.6 mmol/l in hospital). Both the use of a meter and admission to hospital may be valuable in some patients. Neither, however, is essential for the good control of blood-glucose in all pregnant diabetics.

Use by general practitioners of obstetric beds in a consultant unit: a further report.

Of 1,700 women booked for delivery by general practitioner obstetricians in a consultant unit, 1,399 had uncomplicated deliveries and the co-operation between practitioner and consultant was an obvious advantage for the 257 who were transferred completely to consultant care during pregnancy, labour, or puerperium. The scheme, which started in 1964, has enabled general practitioners to continue to give complete obstetric care to their patients. The number of participating practitioners has, however, declined from 80 to 16 indicating that many preferred to concentrate on antenatal work.