Michael R. N. Darling

Accelerated folate breakdown in pregnancy

During pregnancy there is an increased requirement for folate. We studied pregnant women to determine whether the increased requirement might be due to enhanced catabolism of the vitamin. Six normal pregnant women provided 24 h urine samples during each trimester and postpartum while taking a defined diet. The urines were assayed for the folate breakdown products p-amino-benzoylglutamate (pABGlu) and its acetylated derivative p-acetamidobenzoylglutamate (apBGlu) by high-pressure liquid chromatography. Mean concentration of excreted apABGlu rose significantly in the second trimester but returned to baseline postpartum. This increased rate of folate catabolism produces an extra demand for dietary folate of about 200-300 micrograms per day in pregnant women, a considerably greater value than recent recommendations.

Haemostatic, fibrinolytic and endothelial variables in normal pregnancies and pre‐eclampsia

Objective To determine the behaviour of the coagulation variables antithrombin III (ATIII), protein C, thrombin/antithrombin III (TATIII); fibrinolytic activity, tissue plasminogen activator antigen (t‐PA), plasminogen activator inhibitors (PAI) 1 and 2, and endothelial involvement by fibronectin assay in normal and pre‐eclamptic pregnancies.

Nitric oxide in the uteroplacental, fetoplacental, and peripheral circulations in preeclampsia

OBJECTIVE Altered production of nitric oxide by the vascular endothelium may influence the pathogenesis of preeclampsia. The aim of this study was to measure circulating levels of nitric oxide metabolites (nitrites) in the uteroplacental, fetoplacental, and peripheral circulation of preeclamptic pregnancies compared with normotensive controls. METHODS Fifteen women with preeclampsia were compared with 16 women with normotensive pregnancies. At cesarean, blood samples were taken from the uterine vein draining the placental site, the umbilical vein, and the antecubital vein after delivery of the baby but before delivery of the placenta. Plasma nitrites were measured using the Greiss reaction after conversion of plasma nitrates to nitrites using nitrate reductase. RESULTS Nitric oxide metabolites were higher in the uteroplacental (P < .01), fetoplacental (P < .001), and peripheral (P < .02) circulations in samples from preeclamptic pregnancies compared with control pregnancies. In samples from the fetoplacental circulation only, nitric oxide metabolite levels were negatively correlated with gestational age (r = -.489, P < .01) and birth weight (r = -.544, P < .004). Nitric oxide metabolite levels were not significantly correlated with blood pressure, placental weight, or maternal age. CONCLUSION In established preeclampsia, production of nitric oxide was higher in the uteroplacental, fetoplacental, and peripheral circulation than in normotensive pregnancies. This increase may be part of a compensatory mechanism to offset the pathologic effects of preeclampsia.

Can 24-hour ambulatory blood pressure measurement predict the development of hypertension in primigravidae?

Objective To assess the role of 24‐hour ambulatory blood pressure measurement in the mid‐second trimester as a predictive test for the development of hypertension in pregnancy.

Hemostasis in the uteroplacental and peripheral circulations in normotensive and pre-eclamptic pregnancies

OBJECTIVE Our purpose was to determine the hemostatic changes in the uteroplacental and peripheral circulations in normotensive and pre-eclamptic pregnancies. STUDY DESIGN This prospective, observational study involved 2 patient groups. Group 1 consisted of 30 normotensive women and 22 women with pre-eclampsia who were followed up longitudinally through pregnancy and post partum. Group 2 consisted of 20 women with established pre-eclampsia and 19 normotensive control subjects, all undergoing cesarean section. Plasma levels of thrombin-antithrombin III complex, soluble fibrin, plasmin-alpha2-antiplasmin complex, and fibrin-degradation product (D-dimer) were measured in blood drawn from the antecubital vein (group 1) and from both the antecubital and uterine veins (group 2). Data were analyzed by analysis of variance. RESULTS In group 1 levels of thrombin-antithrombin III complex, soluble fibrin, and fibrin-degradation product were significantly higher during normal pregnancy than at 6 weeks post partum. Plasmin-alpha2-antiplasmin complex levels did not change. No differences between the pre-eclamptic and normotensive pregnancy groups were found for any of the hemostatic markers. In group 2 normotensive women undergoing cesarean section, thrombin-antithrombin III complex and soluble fibrin levels were significantly higher in the uterine vein than in the antecubital vein. In group 2 women with pre-eclampsia, thrombin-antithrombin III complex and fibrin-degradation product levels were significantly higher in the uterine vein than in the antecubital vein. In addition, plasmin-alpha2-antiplasmin complex and fibrin-degradation product levels were higher and soluble fibrin levels were lower in the uterine vein in the pre-eclamptic group than in the normotensive group. CONCLUSION Both the coagulation and fibrinolytic systems are activated during normal pregnancy. Activation of these systems is more marked in the uteroplacental circulation than in the systemic circulation in both normotensive and pre-eclamptic pregnancies. An abnormal pattern of hemostasis occurs in the uteroplacental circulation in pre-eclampsia.

Circulating vascular cell adhesion molecule–1 in pre-eclampsia, gestational hypertension, and normal pregnancy: Evidence of selective dysregulation of vascular cell adhesion molecule–1 homeostasis in pre-eclampsia

OBJECTIVE Our purpose was to investigate circulating levels of vascular cell adhesion molecule-1 in the peripheral and uteroplacental circulations during normotensive and hypertensive pregnancies. STUDY DESIGN This prospective observational study involved 2 patient groups. Group 1 consisted of 22 women with pre-eclampsia and 30 normotensive women followed up longitudinally through pregnancy and post partum. There were an additional 13 women with established gestational hypertension. Group 2 consisted of 20 women with established pre-eclampsia and 19 normotensive control subjects undergoing cesarean delivery. Plasma levels of vascular cell adhesion molecule-1 were measured in blood drawn from the antecubital vein (group 1) and from both the antecubital and uterine veins (group 2). Data were analyzed by analysis of variance. RESULTS In group 1 vascular cell adhesion molecule-1 levels did not change significantly throughout normal pregnancy and post partum. Women with established pre-eclampsia had increased vascular cell adhesion molecule-1 levels compared with the normotensive pregnancy group (P = .01). Vascular cell adhesion molecule-1 levels were not elevated in women with established gestational hypertension. In group 2 significantly higher levels of vascular cell adhesion molecule-1 were detected in the uteroplacental (P < .0001) and peripheral (P < .0001) circulations of pre-eclamptic women by comparison with normotensive women. In the pre-eclamptic group there was a tendency toward higher vascular cell adhesion molecule-1 levels in the peripheral circulation than in the uteroplacental circulation (P = .06). In contrast to vascular cell adhesion molecule-1, circulating levels of E-selectin and intercellular adhesion molecule-1, other major leukocyte adhesion molecules expressed by the endothelium, were not different in pre-eclamptic and normotensive pregnancies. CONCLUSION Established pre-eclampsia is characterized by selective dysregulation of vascular cell adhesion molecule-1 homeostasis. This event is not an early preclinical feature of pre-eclampsia, does not persist post partum, is not a feature of nonproteinuric gestational hypertension, and is not observed with other major leukocyte adhesion molecules. Induction of vascular cell adhesion molecule-1 expression in pre-eclampsia may contribute to leukocyte-mediated tissue injury in this condition or may reflect perturbation of other, previously unrecognized, functions of this molecule in pregnancy.

The relationship between increased folate catabolism and the increased requirement for folate in pregnancy

Objectives To estimate the rate of folate catabolism in pregnant and nonpregnant women and to derive the recommended dietary allowance for folate.

Maternal and neonatal hyponatraemia: a comparison of Hartmanns solution with 5% dextrose for the delivery of oxytocin in labour.

We performed a randomised controlled trial to compare the effect on neonatal and maternal serum sodium of using oxytocin in Hartmanns solution compared to the standard 5% Dextrose regimen for induction or augmentation in labour. We found significantly decreased maternal and neonatal serum sodium concentrations in the 5% Dextrose group compared to the Hartmanns group.

The Effect of Pre-eclampsia on Coagulation and Fibrinolytic Activation in the Neonate

brin-degradation products in the uteroplacental circulation of pregnancies complicated by preeclampsia [9], suggesting an activation of both the

Previous caesarean section: a risk factor for major obstetric haemorrhage?

SummaryHaemorrhage associated with childbirth continues to be a significant cause of morbidity and mortality. Despite recommendations in the Report on Confidential Enquiries into Maternal Deaths, obstetric haemorrhage ranks in the top three leading causes of death and is associated with many of the other fatalities studied in these reports. The aim of this study was to look for risk factors that are associated with significant obstetric haemorrhage. The case notes and blood transfusion records of all women delivering after 25 completed weeks gestation who suffered obstetric haemorrhage and required at least 6 units of blood to be transfused were identified and then studied in detail. Over the six year period January 1984 to December 1989, there were 38 480 deliveries at the hospital of which 34 446 were considered as part of this study cohort. The incidence of major obstetric haemorrhage in this population was 1:931 deliveries. Most obstetric units can therefore expect to see at least two or three cases p...