Raised Plasma Homocysteine Concentration in Pregnancy as a Predictor of Preeclampsia Pandya B 1,2, Awan N 1, Shah S 2, Pande R 3, Prasad V 1, Myers M 3, Robertson I 3 1 University Hospital Aintree, Liverpool 2 University of Liverpool, Liverpool 3 Lancashire teaching Hospital, Preston To determine whether the plasma homocysteine concentration in pregnancy is a predictor of development of preeclampsia. To correlate variant MTHFR (methylene tetrahydrofolate reductase) gene with raised plasma homocysteine levels. The median plasma homocysteine level was 5.51 (mean 5.94, SD 2.25, range , IQR 2.08) in our population. Out of 203 women, 18 (8.9%) had developed preeclampsia. Analysis of the ROC curve (figure 1) showed that the Area Under the Curve (AUC) obtained was 54% and therefore suggests low accuracy of diagnostic ability of plasma homocysteine levels for preeclampsia. Optimal cut-off point for homo-cysteine levels = 5.51 (indicated by red dot), where Sensitivity = 61.11% (95% CI: – 82.7) and Specificity = 49.73% (95% CI: – 57.16). The Kruskal-Wallis test showed a statistically significant difference in the mean homocysteine level (α=5%) among the three genotypes (p- value = 0.024<0.05). Introduction Aims and Objectives Elevated plasma homocysteine levels have a role in placental vascular disease and are associated with preeclampsia. Raised levels during pregnancy can be associated with complicated maternal or foetal outcome with increased incidence of neural tube defects, placental abruption and infarction or intra-uterine growth retardation. Identified causes for hyperhomocysteinaemia are nutritional i.e. inadequate intake of vitamin B12, B6 and folate and mutations in the gene responsible for the enzyme MTHF. Normal plasma homocysteine levels are 5-15 μmol/L. MTHFR is one of the key enzymes in the metabolism of homocysteine. The mutation leads to substitution of valine with alanine. Individuals who have homozygous C677T mutation exhibit decreased specific activity and increased thermolability of this enzyme which leads to increased plasma level of homocysteine. Method A cohort of 300 pregnant women were recruited from antenatal clinic between 2004 and 2006, at the time of booking in, over the period of 3 years. Data from 203 individuals were included in the analysis. Preeclampsia was defined as raised blood pressure and leakage of protein through the kidneys from blood in urine. The symptoms are severe headache, excessive weight gain and swelling of the body due to extra fluid Results Figure 1 – ROC Curve The plasma homocysteine levels are comparatively low in pregnancy than in the general population. The study also suggests that plasma homocysteine levels could not predict the development of preeclampsia. There is a significant difference in homocysteine level among 3 genetic polymorphisms in our pregnant population. Conclusion References 1)Walker MC et al. Changes in homocysteine levels during normal pregnancy. Am J Obstet Gynecol. 1999;180: )Wald DS. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ. 2002;325: )Lewis SJ. Meta-analysis of MTHFR 677C→ T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate? BMJ. 2005;331: )Athyros VG et al. Homocysteine: An Emerging Cardiovascular Risk Factor that Never Really Made it. The Open Clinical Chemistry Journal. 2010;3: )Virtanen JK et al. Homocysteine as a risk factor for CVD mortality in men with other CVD risk factors: the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. J Intern Med. 2005;257(3): )Faeh D et al. Homocysteine as a risk factor for cardiovascular disease: should we (still) worry about it? SWISS MED WKLY. 2006;136:745–75. Those with a normal pregnancy were deemed to be controls. Samples were collected for plasma homocysteine, vitamin B12 and folate. Renal and liver function tests, serum urate levels and MTHFR genotype data were also gathered. ROC curves (figure 1) and 95% confidence intervals were obtained. A Kruskal-Wallis test was performed in order to assess whether the homocysteine level differed among the genotypes (heterozygous, homozygous and wildtype).