Study of Uterine Artery Perfusion and Total Antioxidant Capacity in Second Trimester

Study of Uterine Artery Perfusion and Total Antioxidant Capacity in Second Trimester Pregnancies

6.1 Need for the Study

Pre-eclampsia accounts for a major part of perinatal and maternal morbidity worldwide.

Despite extensive research, the pathophysiology and etiology of this pregnancy disorder is still unknown. One hypothesis favours oxidative stress as a relevant pathophysiological factor.

Doppler ultrasound measurement of uterine perfusion in second trimester of pregnancy is a feasible, non-invasive method to identify pregnant woman at risk for both Pre-eclampsia and Intra Uterine Growth Restriction (IUGR). Although sensitivity and predictive value are limited at present, there is no better method available for early risk assessment.

Thus additional parameters are needed to improve the prediction of an abnormal pregnancy outcome. The aim of the present study is to investigate whether pathological uterine perfusion is characterized by altered plasma antioxidant capacity and to investigate whether measurement of total antioxidant capacity has possible diagnostic pathophysiologic therapeutic and prognostic implications in pre-eclampsia.

6.2Review of Literature

Pre-eclampsia and Intrauterine growth restriction are characterized by a shallow endovascular trophoblast invasion and especially pre-eclampsia is linked to maternal endothelial cell dysfunction and damage1.

The etiology of these pregnancy disorders is still unknown. One hypothesis favours oxidative stress as a relevant pathophysiological factor. Oxidative stress as an imbalance between free radicals and capacity of of protective antioxidant systems is thought to be a potent promoter of maternal vascular dysfunction and endothelial damage2.

Doppler ultrasound measurement of uterine perfusion in 2nd trimester is a feasible , noninvasive method to identify pregnant women at risk for both pre-eclampsia and Intrauterine growth restriction3.

A study done by Thaler et.al in 1992 shows that the presence of a notch in uterine artery flow velocity waveform is a better predictor of poor pregnancy outcome4. But the sensitivity and predictive value of Doppler ultrasound for early risk assessment are limited5. Not all patients with with disturbed uterine perfusion develop these pregnancy complications. Thus additional parameters are needed to improve the prediction of an abnormal pregnancy outcome.

A study done by H.Stepan et.al shows 2nd trimester pregnancies with pathological uterine perfusion are characterized by a decreased antioxidant capacity in maternal plasma6.

6.3Objectives of Study

To examine whether pathological uterine perfusion in second trimester is associated with altered plasma antioxidant capacity.

To investigate whether altered total antioxidant capacity in maternal plasma is related to adverse pregnancy outcome like pre-eclampsia and IUGR.

7 Materials and Methods

7.1 Source of Data :- All pregnant women in second trimeseter attending the Obstetric and Gynaecology department in M.S Ramaiah Teaching Hospital and M.SRamaiahMemorialHospital.

Study Period:- November 2011 to April 2013

Study Design:- Prospective Cohort Study

Sample Size:- It has been reported in the study carried out by H Stepan that the Plasma total antioxidant capacity (TAC) of pregnant women with pathological uterine perfusion is 227.3 +/- 4.0 micro-mol/L as compared to normal uterine perfusion of 275.2 +/- 10.5 micro-mol/L.

The above findings have been utilized for estimating the sample size for present study at a power of 95% and alpha error of 1%. It is estimated that 25 cases in each group are required for satisfactory statistical analysis.

Statistical Analysis:- All the quantitative variables such as age, TAC and gestational age will be described in terms of mean value, standard deviation and standard error of mean. Statistical comparison will be carried out by ‘t’ test / Mann – Whitney test. Association between qualitative variables will be assessed through chi-square test of significance.

7.2 Methods of Data Collection

All pregnant women in second trimester between 20 weeks to 24 weeks of gestation period undergoing ultrasound will be routinely offered a Color Doppler ultrasound examination for assessment of uterine perfusion. The uterine perfusion will be defined as pathological if there is uterine artery notching.

25pregnant women with normal uterine perfusion and 25 pregnant women with

abnormal uterine perfusion will be evaluated for TAC.

After 8-10 hours of fasting, 5 ml of venous blood will be collected in yellow vacutainer tube devoid of any anticoagulants and subjected to centrifugation. Clear serum obtained after centrifugation will be used for measurement of Total Antioxidant Capacity.

TAC is measured by Ferric Reducing Antioxidant Power (FRAP) assay according to the method of Benzie F.F and Strain JJ7.

The patients will be followed up till their delivery to know the outcome.

Inclusion Criteria:- All pregnant women between 18 to 35 years with gestational age range of 20 to 24 weeks.

Exclusion Criteria:- Women with history of chronic hypertension, diabetes mellitus, multiple gestation, anemia, major illness, history of taking vitamin A,E and C supplements which may affect the antioxidant status.

7.3 Does the study require any investigations or interventions to be conducted on patients or other humans or animals?

Yes, Obstetric Doppler of pregnant women and relevant blood investigation.

7.4 Has ethical clearance been obtained from your institution?

8 List of References:

DekkerGA, Sibai BM, Etiology and pathogenesis of preeclamplsia: current concepts.

Am J ObstetGynecol 1998; 179: 1359 – 1375.

Bowen RS, Moodley J, Dutton MF, Theron AJ. Oxidative stress in preeclampsia.

Acta Obstet Gynecol Scand 2001; 80: 719 – 725.

Chien PF, Arnott N, Gordon A, Owen, P, KhanKS. How useful is uterine artery Doppler flow velocimetry in the prediction of preeclampsia, intrauterine growth retardation and perinatal death? An overview. BJOG 2000; 107: 196 – 208.

Thaler I, Weiner Z, Itskovitis J, “ Systolic or diastolic notch in uterine artery blood flow velocity

waveforms in hypertensive pregnant patients: relationship to outcome”.

Obstet Gynaecol 1992;80:277-282

Albaiges G, Missfelder-Lobos H, Lees C, Parra M, Nicolaides KH. One stage screening for pregnancy complications by color Doppler assessment of uterine arteries at 23 weeks gestation.

Obstet Gynecol 2000; 96: 559 – 564.

6. H.Stepan, A.Heinhoff-Klose and R.Faber -

Reduced antioxidant capacityin 2nd trimester pregnancies with pathological

uterine perfusion.

Ultrasound Obstretics Gynaecology 2004;23:579-583

7. Benzie FF, Strain JJ - The ferric reducing ability of plasma (FRAP) as a

measure of anti-oxidant power

The FRAP assay, Analytical Biochemistry 1996.239:70-76