The efficacy of omega-3 supplements in prevention of preeclampsia among pregnant women with high risk factors in Sulaymaniyah governorate

H ypertensive disorders of pregnancy, including preeclampsia, complicate up to 10% of pregnancies worldwide, constituting one of the greatest causes of maternal and perinatal morbidity and mortality worldwide. The aim of the current study is to evaluate the efficacy of omega-3 supplements in prevention of preeclampsia among women with high risk. This study was carried out at Shanroy Hospital in al – Sulaimanya city from January 2016 till December 2016.In a single blind clinical trial, a total of 100 pregnant women were divided into two groups, one group had received omega-3 1000 mg and another group receive capsule prefilled with glucose as placebo. Selection criteria include: primipara women, ages under than 20 and above 40 years, previous history of preeclampsia or positive family history, obesity, history of renal disease and hypertension. Demographic profile with pregnancy length and neonatal outcome were recorded. The result of this study showed there was significant difference in development of preeclampsia during current pregnancy between omega-3 and placebo groups and there was a significant relationship (p<0.05) between both groups when compare the preeclampsia in its all forms. In conclusion, omega-3 deems promising drug for prevention of preeclampsia in pregnant women with high risk.


Introduction
Hypertensive disorders of pregnancy, including preeclampsia, complicate up to 10%%of pregnancies worldwide,..constituting one of the greatest causes of maternal and perinatal morbidity and mortality worldwide [1].…Pathophysiology and aetiology of preeclampsia are not completely known and are still under investigation.The dominant hypothesis of preeclampsia is decreased placental uterine perfusion due to defective invasion of cytotrophoblast to uterine spiral arteries.Other hypotheses include intolerance...of mother's…immunity with fetalplacental tissues, incompatibility.ofmother with cardiovascular inflammatory changes during normal pregnancy, nutritional deficiencies and hereditary factors.Preeclampsia is known as the disease of theories and there is no cause, treatment, valid and cost-effective preventive and predictive methods for it yet [2].It's widely believed that defective trophoblast invasion results in relative under -perfusion of the placenta and that this releases a factor..(S) in to the maternal circulation that targets the vascular endothelium.The nature of this factor has not been identified, although numerous candidates have been proposed including a variety of growth factors, cytokines and products of oxidative stress caused by hypoxic-..reperfusion injury in the placenta.As the target cell of the disease process ,the vascular endothelial cell, is so ubiquitous ,preeclampsia is a truly multisystem disease, affecting multiple organ systems, often concurrently[ [3].Omega-3 FA, found primarily in fatty fish with high oil content, consists of both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) [4].Both fatty acids and EPA in particular, have close homology mode with arachidonic acid (AA), with EPA and AA differing only in the presence or absence of the omega-3 (n-3) double bond respectively [5].Research has shown increasing evidence for antiinflammatory, antithrombotic, antiarrhythmic and [[ antiatherogenic effects of fish oil.Fish oil is the most significant source of dietary omega-3 FA [4].The anti-inflammatory activity of EPA and DHA are due to inhibition the oxidation of arachidonic acid (AA) by the cyclooxygenase (COX) and lipoxygenase enzymes that are,,, pivotal in the production of the C20 oxylipids, known as eicosanoids (eicosa means twenty in Greek)..These mediators are important in regulating various homeostatic functions, including the gastric…mucosal integrity, vascular patency, homeostasis and inflammation [6].Sufficient supplementation of omega-3 fatty acids is vitally important during pregnancy as they are critical building blocks of fetal brain and retina.Omega-3 fatty acids are critical for fetal neurodevelopment and may be important for the timing of gestation and birth weight as well Omega-3 fatty acids may also play a role in determining the length of gestation and in preventing perinatal depression [7,8].The aim of the current study is to assess the influence of omega-3 fatty acids (EPA,DHA) on prevention of development of preeclampsia in pregnant women with high risk.….

Study design
This study was carried out at Shanroy Hospital in al -Sulaimanya city from January 2016 till December 2016.In a single-blind clinical trail 100 pregnanet women with risk of preeclampsia and gestational age of (18) weeks were participate in this study after receive a literal agreement.The sample was randomly divided in to two groups, one group take omega-3 1000 mg capsule daily and the second group take capsule prefilled with glucose as placebo.Omega-3 capsule was supplied by Adrien Gagnon, Canada.Whereas glucose was supplied by SDI, Samarra, Iraq.Demographic and obstetric data were recorded on special forms for each participant.Gestational age determination was based on precisely recalled menstrual dates as they were having regular menstrual cycles, and further confirmed by their first or early second trimester ultrasound.Selection criteria include:-primipara women, ages under than 20 and above 40 years, previous history f preeclampsia or a positive family history, twin pregnancy, obesity, history of renal disease and hypertension, history of diabetes mellitus.Pregnant women were visited monthly until the end of pregnancy and their health and possible side effects of drug and placebo were evaluated.Apgar score was assessed at 5 and 10 minutes at the time of delivery, delivery information and the presence of preeclampsia were investigated.The collected data have been transferred to the computer on the SPSS manager system (the statistical package for social sciences) version no.18,.Both descriptive and analytic statistics have been carried out and the relation between the variables by using Chi-square (χ2), and ANOVA (Analysis of Variance) was used to compare between means of numerical variables when we have multiple observation at each level.The level of statistical significance of P value was 0.05

Results
The study population consists of 100 pregnant women who having risk factors for development of preeclampsia.They divided in to two groups, group 1 consist of 50 pregnant women who received 1000 mg of omega-3capsule, and group 2 consist of 50 pregnant women who received placebo, from table (1) it was founded that mean age of omega-3 group ± standard deviation was (28.7±7.28)yr. and for placebo group was(29.26±6.4 ) yr.About parity it was found that primipara account 19 of omega-3 group (38%) and 12 (24%) from placebo group, while previous history of hypertension in its all form among omega-3 group were 47 (94%) and previous history of hypertension in its all form among placebo group were 44 (88%).Only 2 cases with diabetes mellitus and 5 cases with history of renal diseases while 19 cases with obesity were found among omega-3 group, while in placebo group only 2 cases of renal disease and 11 case of obesity were found.4) was shown the relationship between development of PE during current pregnancy among both omega-3 and placebo groups by using Chi-Square test, there was a significant relationship (p<0.05) between both groups when compare the PE in its all form while in comparing the severe form only it was no significant relationship (p>0.05) between both groups.The study showed that there was significant relationship between both study groups and mode of delivery by applying Chi-Square statistical test p-value less than 0.05 level of significant as showed in table (5).

Discussion
Omega-3 is a polyunsaturated fatty acid that may reduce blood pressure and brain and heart attacks affecting the production of prostaglandins and reducing unwanted fat, vasodilatation and platelet adhesion.In a study by Schiff et al.[.9],, they expressed that thromboxane A2 levels and the risk of preeclampsia is reduced after the daily administration of 1.6 g of omega-3 in the third quarter of pregnancy.The effect of treatment with omega-3 on prevention of preeclampsia in pregnant women with risk was investigated in this study.The result of this study showed there was significant difference in development of preeclampsia during current pregnancy between omega-3 and placebo groups.This result was consistent with a single blind clinical trial performed by Lalooha F.etal..which concluded that daily use of 1000mg of omega-3 supplements from the second trimester of pregnancy is effective in reducing the risk of preeclampsia and its severity [10].
Our study disagrees with study done by Shao J.etal which concluded that omega-3 supplementation in the second half of pregnancy has no effect on the risk of preeclampsia.[11]).Our study revealed that there was no effect on reduction of severity of preeclampsia which was inconsistent with Innis SM and Makrides M,et al [12,13]..In our study it was found that there was no significant difference between omega-3 and placebo groups regarding pregnancy out come by measuring Apgar's scores, which was disagree with the study done by Dirix et al which obtained a significant relationship between receiving omega-3 especially in early pregnancy and birth weight and Apgars scores at minute 5[14]...

Table ( 2) Risk development of current pregnancy among omega-3 and placebo groups Placebo n=50 Omega-3 n=50 Risk factor
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