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Notizen: Objective To assess the reports that maternal phosphoglucomutase-1 (PGM 1) phenotype is highly related to macrosomia in diabetic pregnancy. This could be either a direct metabolic phenomenon, or the PGM1 locus could be a marker for a tightly linked gene involved in the maternal control of fetal growth.Design A comparative biochemical genetic study.Setting A large diabetic pregnancy clinic.Subject One hundred and fifty-two women who had diabetes during pregnancy, 136 being insulin dependent before pregnancy. Two hundred and thirty-six women without pre-existing medical or pregnancy complications who functioned as a control group.Measures PGM1 phenotype was assessed by conventional electrophoresis and subgroups were examined using iso-electric focusing.Outcome Standardised birthweight was corrected for sex, maternal parity and gestation confirmed in every case by early pregnancy ultrasound. Maternal diabetes control was assessed by glycosylated haemoglobin.Results No differences were found in the observed phenotype frequencies for diabetics and control pregnant women. No association between PGM1 phenotype and macrosomia in diabetic pregnancy was found. PGM1 did not make a significant contribution to birthweight, standardised birthweight, length or ponderal index of the baby as assessed by multiple regression.Conclusions Our study of a larger number of insulin dependent diabetics in Scotland makes the claim that macrosomia in diabetic pregnancy is associated with PGM1 phenotype unlikely to be of general significance.

Notizen: Objective To assess the effect on obstetric practice of clinician access to umbilical artery Doppler ultrasound results.Design Randomised controlled trial.Setting A large teaching hospital.Subjects Two thousand two hundred and eighty-nine pregnancies defined as being at risk by referral for Doppler or fetal monitoring.Interventions Continuous wave Doppler studies of umbilical artery. Results immediately available to clinicians.Main outcome measures Fetal outcome: perinatal mortality, Apgar score and admission to the neonatal unit. Obstetric intervention: admission to hospital, induction of labour and caesarean section. Use of tests of fetal well being: cardiotocography, biophysical profile and ultrasound biometry.Results The treatment and control groups were comparable in age, parity, gestation at point of entry and risk features. There were no overall differences in perinatal outcome, obstetric intervention or use of fetal monitoring. Examination of a subset recruited only because of hypertension or suspected intrauterine growth retardation (n = 754) similarly showed no difference attributable to group randomisation. Comparison of only those pregnancies retrospectively defined as low risk and high risk showed more use of cardiotocography in the high risk group with access to Doppler (P= 0.007) but no difference in the low risk group.Conclusion Doppler umbilical artery recording has been shown to perform well in prediction power of antenatal fetal compromise. What has been examined in this study is the response of clinicians to the test. The results suggest that obstetricians do not use the test to modify their risk assessment, and, therefore, the need for fetal monitoring in particular pregnancies. There is a real need for accumulation of information from very large data sets, particularly in the prediction power of Doppler for antenatal fetal compromise from apparently chronic utero-placental cause to guide use of monitoring resources. If simply added to existing fetal monitoring techniques in a hospital where these are widely used, then umbilical artery Doppler recordings may at present simply involve extra resources of staff and expenses, without benefit.

Notizen: Objective To determine the concentrations of the metabolites of prostaglandin E2 (PGEM) and of prosta-glandin F2α (PGFM) prior to the onset of labour and during spontaneous labour, and to correlate the changes in concentrations of these metabolites with labour outcome.Design Longitudinal study throughout labour.Setting Labour ward of a large maternity unit.Subjects Seven primigravid and 11 parous women in the late third trimester with no signs of labour, and 17 primigravid and 11 parous women in spontaneous labour.Interventions Six of the primigravid women required augmentation with oxytocin because of dysfunctional labour.Results Before labour, parous women had significantly higher concentrations of both PGEM (P〈0.007) and PGFM (P〈0.006) compared with primigravid women. During labour, PGFM concentrations were significantly higher in both primigravid (P〈0.0002) and parous (P〈0.0001) women compared with the concentrations of these metabolites in women not in labour; the same was true for PGEM in primigravid (P〈0.003) but not in parous (P= 0.1) women. There was a small but significant increase (P〈0.02) in PGEM as labour progressed in both the normal groups. Amniotomy was associated with a significant increase in PGFM in primigravid and parous women (P〈0.002 and P〈0.009, respectively). The concentration of PGFM one hour following amniotomy correlated inversely with the amniotomy to delivery interval in both the normal primigravid (r=−0.624; P= 0.04) and the parous (r= 0.745; P= 0.021) groups. Women with dysfunctional labour showed no significant rise in PGEM or PGFM. Their PGFM concentrations were significantly lower than those seen in normal labour (P〈0.05). The concentration of PGFM in cord blood was significantly higher (P〈0.0001) in the parous women who laboured than in women delivered by elective caesarean section. There was no difference in the corresponding concentrations of PGEM (P= 0.9).Conclusions These data show that spontaneous labour is associated with increased concentrations of prostaglandin metabolites in the maternal plasma, and are consistent with PGF2α being an important stimulator of uterine contractility, with a relative deficiency of PGF2α being associated with dysfunctional labour.

Notizen: Objective To assess the elaboration of placental stem villous vessels from pregnancies complicated by intrauterine growth restriction (IUGR) with absent end–diastolic flow velocity detected prior to delivery in the umbilical artery.Design Comparison between IUGR and control groups of the distribution, in 15 pm increments of 600 randomly chosen stem vessel profiles (post-fixation diameter 10-160 pm) identified by immunohistochemical localisation of a-smooth muscle actin in the vessel media.Setting Clinical teaching hospital and university anatomy department.Subjects Paraffin-fixed blocks obtained from placentas of eight pregnancies complicated by IUGR and eight gestational age-matched controls.Results The distribution of the stem villous vessels in the IUGR placentas, as assessed by the mean vessel diameter in each case, did not differ from the controls (mean vessel diameter 31.8 μm [SD 2.41 vs 29.6 pm [2.3]; P= 0.13). In five IUGR cases a-smooth muscle actin positive cells (myofibroblasts) were identified within the stroma of nonmuscularised peripheral (mature intermediate and terminal) villi, but in none of the controls.Conclusions Our data do not support the theory that IUGR with absent end-diastolic flow velocity in the umbilical artery is due to a selective loss of small stem villous vessels. The increased impedance in this condition may be conferred more distally within the nonmuscularised capillaries of the peripheral villi.

Notizen: Objective To determine whether circulating levels of cell adhesion molecules, markers of endothelial damage and leucocyte activation, were increased in pre-eclampsia.Design Serum was prepared from peripheral venous blood and stored at –70°C. The cell adhesion molecules, VCAM-1, E-Selectin and ICAM-1, were measured by ELISA.Setting Department of Obstetrics and Gynaecology, Royal Infirmary, Glasgow.Subjects Sixteen primigravid women with pre-eclampsia were recruited for the study. The pre-eclampsia group were compared with 18 healthy primigravid women with uncomplicated pregnancies.Results The pre-eclamptic group had significantly higher serum levels of the cell adhesion molecule VCAM-1 (t= 3.673; P 〈 0.001). There were no significant differences in the adhesion molecules ICAM-1 or E-Selectin.Conclusions Endothelial damage and dysfunction are common to all the pathological features of pre-eclampsia. This study shows that concentrations of cell adhesion molecules, which indicate leucocyte-endothelial attachment and activation, are elevated in the serum of patients with pre-eclampsia. Such increases in soluble circulating cell adhesion molecules may reflect increased expression of these molecules on the endothelium and thereby explain the mechanism for leucocyte activation in pre-eclampsia.

Notizen: Objective To assess the effect of uncomplicated diabetes on umbilical artery flow velocity waveforms (FVWs); to investigate the relation between glycaemic control and FVWs and the predictive value of umbilical artery FVWs for antenatal fetal compromise.Design Prospective descriptive study.Setting A large diabetic pregnancy clinic in a teaching hospital.Subjects 128 pregnancies complicated by diabetes mellitus. 170 non diabetic women with no pre-existing or pregnancy complications.Interventions In diabetic pregnancies, umbilical artery resistance index (RI) Doppler recordings and glycosylated haemoglobin were measured every 2 weeks from 28 weeks.Main outcome measures Umbilical artery RI and antenatal fetal compromise defined as a non reactive, decelerative cardiotocograph and/or a biophysical profile score persistently 〈6 and leading to immediate caesarean section.Results Uncomplicated diabetic pregnancies had FVW values similar to those in the non-diabetic range. Glycaemic control was unrelated to umbilical artery FVW values. Abnormal umbilical artery RI was found in nine pregnancies, these were more likely to show evidence of fetal compromise and to be associated with birth weights of 〈50th centile. In seven pregnancies there was evidence of fetal compromise, but only three of these pregnancies had abnormal FVW values.Conclusions The non-diabetic range of umbilical artery RI values is appropriate for diabetic pregnancies. Long-term glycaemic control, within the range in this study, does not seem to affect umbilical artery RI. Abnormal umbilical artery RI is a significant predictor of fetal compromise in diabetic pregnancy, but fetal compromise can occur in association with normal RI values. Undue reliance should not be placed on normal FVW values in diabetic pregnancies.

Notizen: Whether booking body mass index (BMI) in the UK is increasing is unknown but is of clinical interest since overweight or obese pregnant women face far greater risks of pregnancy complications including pre-eclampsia and gestational diabetes. We examined booking BMI in 1990 and 2002/2004, of women with singleton pregnancies. Our analyses indicate an increase of 1 U in mean BMI over this period despite lower parity in recent years. When the model was adjusted for maternal age, parity, smoking status and deprivation category the mean BMI was 1.37 U higher in 2002/2004 than in 1990. More striking was the significant increase in the proportion of women who were obese (BMI ≥ 30 kg/m2) at booking—more than twofold higher in unadjusted analysis (18.9%vs 9.4%) rising to greater than threefold higher in multivariate analysis. These findings suggest that obesity-related pregnancy complications are likely to increase with implications for both mother and child.