Early amniocentesis and fetal nuchal translucency in women requesting karyotyping for advanced maternal age.

Fetal nuchal translucency was measured at 11-14 weeks' gestation in 97 pregnancies referred for early amniocentesis for advanced maternal age. The nuchal translucency was abnormal in 11 fetuses and the fetal karyotype was abnormal in five of these 11 cases. The karyotype was normal in 86 cases with normal nuchal translucency. The culture failure and miscarriage rates associated with early amniocentesis were 3.3 per cent and 2.2 per cent respectively. Amniotic fluid leakage occurred in 6 per cent of cases. In women requesting fetal karyotyping for advanced maternal age without additional biochemical screening, fetal nuchal translucency should be measured at 11-14 weeks. If the nuchal thickness is > or = 3 mm, a first-trimester diagnostic procedure is indicated; however, if it is < 3 mm, amniocentesis should be delayed until 16 weeks' gestation.

Effect of delivery on fetal erythropoietin and blood gases in pregnancies with maternal diabetes mellitus.

In 29 pregnancies complicated by maternal diabetes mellitus paired samples of umbilical venous blood were obtained at cordocentesis and delivery to investigate the effect of delivery on indices of fetal oxygenation. After delivery by elective Caesarean section the median umbilical venous blood pH was significantly lower than predelivery, however, there was no significant change in the median umbilical venous blood pO2 or plasma erythropoietin concentration. In those delivered after labour the median umbilical venous blood pH and pO2 were significantly lower and the median plasma erythropoietin concentration was significantly higher than predelivery. The data of this study demonstrate that umbilical venous blood pH and pO2 and plasma erythropoietin are influenced by the mode of delivery and results obtained at delivery may not accurately reflect in utero homeostasis.

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 facial defects: associated malformations and chromosomal abnormalities.

During an 8-year period, facial defects were observed in 146 (7%) of the 2,086 fetuses that underwent karyotyping in our unit because of fetal malformations and/or growth retardation. Chromosomal abnormalities were detected in 37 of 56 (66%) fetuses with micrognathia, in 10 of 13 (77%) with macroglossia, in 31 of 64 (48%) with cleft lip and palate, in 5 of 11 (45%) with severe hypotelorism or cyclops, and in 6 of 19 (32%) with nasal hypoplasia, proboscis or single nostril. Macroglossia was mainly associated with trisomy 21, micrognathia with trisomy 18 and triploidy, facial cleft with trisomies 13 and 18, and ocular or nasal defects with trisomy 13. In all chromosomally abnormal fetuses with facial defects, there were additional multisystem defects, and the pattern of these malformations was compatible with the type of the underlying chromosomal abnormality. In the total series of 2,086 fetuses with malformations and/or growth retardation, there were 31 with trisomy 13, 83 with trisomy 18 and 69 with trisomy 21; facial defects were found in 71, 36 and 14% of these fetuses, respectively.

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.

Fetal plasma erythropoietin concentration in red blood cell-isoimmunized pregnancies.

OBJECTIVE: The aim of this study was to investigate the relationship between fetal anemia, plasma erythropoietin concentration, and erythroblastosis in red blood cell-isoimmunized pregnancies. STUDY DESIGN: Fetal plasma erythropoietin concentration in umbilical venous blood samples from 68 red blood cell-isoimmunized pregnancies at 18 to 35 weeks' gestation was measured. Measurements were compared with the appropriate reference range with gestation, and associations with blood pH, erythroblast count, and hemoglobin concentration were examined. RESULTS: The mean fetal plasma erythropoietin concentration and erythroblast count in red blood cell-isoimmunized pregnancies were significantly increased only in severe fetal anemia (hemoglobin deficit > 7 gm/dl). Furthermore, some severely anemic fetuses were hydropic and acidemic. The degree of increase in plasma erythropoietin was significantly associated with both fetal acidemia and, more strongly, fetal erythroblastosis. CONCLUSION: These findings suggest that in fetuses from red blood cell-isoimmunized pregnancies the ability to prevent tissue hypoxia is present until anemia becomes severe, presumably by an increase in cardiac output and tissue perfusion. In severe anemia tissue hypoxia occurs, and the data indicate that fetuses respond by increasing erythropoietin production from at least 20 weeks' gestation. Furthermore, more accurate assessment of tissue oxygenation may be obtained by measuring the erythroblast count rather than the blood pH.

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 polycythemia and thrombocytopenia in pregnancies complicated by maternal diabetes mellitus.

In 40 pregnancies complicated by maternal diabetes mellitus umbilical venous blood was obtained by cordocentesis within 24 hours of elective delivery at 36 to 40 weeks' gestation. The mean fetal hematocrit was significantly higher and the mean platelet count significantly lower than the corresponding values of our reference ranges. Furthermore, blood gas analysis demonstrated these fetuses to be normoxemic but acidemic. The degree of fetal acidemia was significantly associated with both maternal and fetal blood glucose concentrations. The fetal hematologic indices were significantly related to the maternal glycosylated hemoglobin percentage but not to the degree of fetal acidemia or to the maternal or fetal blood glucose concentration at the time of cordocentesis. Fetal acidemia, polycythemia, and thrombocytopenia may contribute to the increased incidence of late unexplained intrauterine deaths in pregnancies complicated by maternal diabetes mellitus.

Strawberry-shaped skull in fetal trisomy 18.

During an 8-year period, a strawberry-shaped skull (flattening of the occiput with pointing of the frontal bones), was observed in 54 (3%) of the 2,086 fetuses that underwent karyotyping in our unit because of fetal malformations and/or growth retardation. In all 54 cases with a strawberry-shaped skull, there were other fetal malformations; in 43 (80%) fetuses, there was trisomy 18 and in 1 triploidy. Therefore, the ultrasonographic finding of a strawberry-shaped skull should initiate a diligent search for the presence of other markers of trisomy 18 and is a strong indication for fetal karyotyping. However, in the total series of 2,086 fetuses with malformations and/or growth retardation, there were another 40 fetuses with trisomy 18 and 41 with triploidy who did not have a strawberry-shaped skull.