Biomedical subjects

Valerie A Holmes

Publications and source records attributed to Valerie A Holmes.

4 recordsLinked to original sources

PubMed2005

Could antioxidant supplementation prevent pre-eclampsia?

Pre-eclampsia is a disorder characterised by pregnancy-induced hypertension and new-onset proteinuria occurring in the second half of pregnancy. Worldwide, approximately 2-3% of all pregnant women develop pre-eclampsia. The condition is a major cause of maternal and fetal morbidity and mortality. Abnormal placentation is an important predisposing factor for pre-eclampsia, while endothelial activation appears to be central to the pathophysiological changes, possibly indicative of a two-stage disorder characterised by reduced placental perfusion and a maternal syndrome. There is increasing evidence that pre-eclampsia is associated with both increased oxidative stress and reduced antioxidant defences, which has led to the hypothesis that oxidative stress may play an important role in the pathogenesis of pre-eclampsia, perhaps acting as the link in a two-stage model of pre-eclampsia. In support of this hypothesis a small, but important, preliminary study has shown a highly significant (P=0.02) reduction in the incidence of pre-eclampsia in women at risk who were taking a supplement of vitamins C and E from mid-pregnancy. Furthermore, these findings support the hypothesis that oxidative stress is at least partly responsible for the endothelial dysfunction of pre-eclampsia. Several larger multicentre trials are currently underway to evaluate the efficacy, safety and cost benefits of antioxidant supplementation during pregnancy for the prevention of pre-eclampsia in both low- and high-risk women, including women with diabetes. The results of these trials are awaited with interest.

Antioxidants↗

PubMed2004

Homocysteine is lower in the third trimester of pregnancy in women with enhanced folate status from continued folic acid supplementation.

BACKGROUND: In many countries, current recommendations are that women take a daily 400-mug folic acid supplement from before conception until the end of the 12th week of gestation for the prevention of neural tube defects. Low folate status is associated with an increased concentration of plasma total homocysteine (tHcy), a risk factor associated with pregnancy complications such as preeclampsia. METHODS: In a longitudinal study, we determined tHcy and corresponding folate status in 101 pregnant women at 12, 20, and 35 weeks of gestation, in 35 nonpregnant controls sampled concurrently, and in a subgroup (n = 21 pregnant women and 19 nonpregnant controls) at 3 days postpartum. RESULTS: Plasma tHcy was significantly lower throughout pregnancy compared with nonpregnant controls, with values lowest in the second trimester before increasing toward nonpregnant values in the third trimester. Importantly, mean tHcy concentrations were lower in pregnant women taking folic acid supplements than in those not, an effect that reached significance in the third trimester (5.45 vs 7.40 micromol/L; P <0.05). During the third trimester, tHcy concentrations were significantly higher in pregnant women with a history of miscarriage than in women with no previous history (8.15 vs 6.38 micromol/L; P <0.01). CONCLUSIONS: This is the first longitudinal study to show that homocysteine concentrations increase in late pregnancy toward nonpregnant values; an increase that can be limited by enhancing folate status through continued folic acid supplementation. These results indicate a potential role for continued folic acid supplementation in reducing pregnancy complications associated with hyperhomocysteinemia.

Adolescent↗

PubMed2003

Changes in haemostasis during normal pregnancy: does homocysteine play a role in maintaining homeostasis?

Homocysteine, derived from the demethylation of the amino acid methionine, is either further catabolised by trans-sulfuration to cysteine or remethylated to methionine. Remethylation to methionine requires the cofactors, folate and vitamin B12. Folate is an effective homocysteine-lowering agent and, thus, homocysteine and folate status are inversely related. Hyperhomocysteinaemia is a strong independent risk factor for venous thromboembolism (VTE) and is associated with adverse pregnancy outcomes such as pre-eclampsia, placental abruption, early pregnancy loss and neural-tube defects. Pregnancy is a risk factor for VTE as a result of prothrombotic changes in levels of haemostatic factors. However, despite this hypercoagulable state, the incidence of pregnancy-associated VTE is relatively low. Hyperhomocysteinaemia is associated with abnormalities in markers of coagulation activation, and recent research suggests that folic acid supplementation, as well as lowering homocysteine, lowers markers of coagulation activation and increases levels of coagulation inhibitors. Tissue factor (TF) is the initiator of blood coagulation in vivo, and homocysteine induces TF expression in vitro. During pregnancy, monocyte TF expression is lower than that in the non-pregnant state, and this lowering of TF may act to counterbalance increases in coagulation activation. Furthermore, despite a high folate requirement, several studies have reported that homocysteine is lower in normal pregnancy than in the non-pregnant state. Although the exact mechanism of homocysteine lowering during pregnancy is unclear, one possible outcome of lower homocysteine may be the protection of women from pregnancy complications and VTE, and thus lower homocysteine may contribute to maintaining homeostasis in haemostasis.

Female↗

PubMed2002

Tissue factor expression on monocyte subpopulations during normal pregnancy.

Pregnancy is often referred to as a hypercoagulable state due to changes in the haemostatic system. Tissue factor (TF) is the initiator of blood clotting in vivo. The effect of pregnancy on monocyte TF expression was determined in a longitudinal case control study (89 pregnant, 39 non-pregnant). Using whole blood flow cytometry and CD14 as a monocyte marker, TF expression was measured on all CD14 positive, CD14Bright and CD14Dim cells. TF expression was significantly lower in pregnant women than in non-pregnant control subjects, on all CD14 positive cells at 20 and 35 weeks, on CD14Bright cells at 12 and 35 weeks and on CD14Dim cells at 20 weeks. Additionally, we report that a higher percentage of CD14Dim than CD14Bright cells express TF. These results suggest that, in order to maintain homeostasis in haemostasis in an otherwise hypercoagulable state, monocyte TF expression is reduced during normal pregnancy.

Adult↗