Full length article| Volume 210, P231-235, March 2017

Download started.


Evaluation of the effectiveness of low-dose aspirin and omega 3 in treatment of asymmetrically intrauterine growth restriction: A randomized clinical trial

Published:January 03, 2017DOI:



      To test the effect of aspirin and omega 3 on fetal weight as well as feto-maternal blood flow in asymmetrical intrauterine growth restriction (IUGR).

      Study design

      This study is a clinically registered (NCT02696577), open, parallel, randomized controlled trial, conducted at Assiut Woman’s Health Hospital, Egypt including 80 pregnant women (28–30 weeks) with IUGR. They were randomized either to group I: aspirin or group II: aspirin plus omega 3. The primary outcome was the fetal weight after 6 weeks of treatment. Secondary outcomes included Doppler blood flow changes in both uterine and umbilical arteries, birth weight, time and method of delivery and admission to NICU. The outcome variables were analyzed using paired and unpaired t-test.


      The estimated fetal weight increased significant in group II more than group I (p = 0.00). The uterine and umbilical arteries blood flow increased significantly in group II (p < 0.05). The birth weight in group II was higher than that observed in group I (p < 0.05).


      The using of aspirin with omega 3 is more effective than using aspirin only in increasing fetal weight and improving utero-placental blood flow in IUGR.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


        • Royal College of Obstetricians and Gynaecologists
        The Investigation and Management of the Small-for-Gestational-Age. Green-top Guideline No. 31.
        RCOG, London2014
        • American College of Obstetricians and Gynecologists
        ACOG Practice bulletin no. 134: fetal growth restriction.
        Obstet Gynecol. 2013; 121: 1122-1133
        • Starčević M.
        • Predojević M.
        • Butorac D.
        • Tumbri J.
        • Konjevoda P.
        • Kadić A.S.
        Early functional and morphological brain disturbances in late-onset intrauterine growth restriction.
        Early Hum Dev. 2016; 93: 33-38
        • Sharma Deepak
        • Shastri Sweta
        • Sharma Pradeep
        Intrauterine growth restriction: antenatal and postnatal aspects.
        Clin Med Insights Pediatr. 2016; 10: 67-83
        • Vayssière C.
        • Sentilhes L.
        • Ego A.
        • Bernard C.
        • Cambourieu D.
        • Flamant C.
        • et al.
        Fetal growth restriction and intra-uterine growth restriction: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians.
        Eur J Obstet Gynecol Reprod Biol. 2015; 193: 10-18
        • Ureyen I.
        • Ozyuncu O.
        • Sahin Uysal N.
        • Kara O.
        • Basaran D.
        • Turgal M.
        • et al.
        Relationship of maternal mean platelet volume with fetal doppler parameters and neonatal complications in pregnancies with and without intrauterine growth restriction.
        J Matern Fetal Neonatal Med. 2016; 7: 1-19
        • Odibo A.O.
        • Francis A.
        • Cahill A.G.
        • Macones G.A.
        • Crane J.P.
        • Gardosi J.
        Association between pregnancy complications and small-for-gestational-age birth weight defined by customized fetal growth standards versus a population-based standard.
        J Matern Fetal Neonatal Med. 2011; 24: 411-417
        • Gutaj P.
        • Wender-Ozegowska E.
        Diagnosis and management of IUGR in pregnancy complicated by type 1 diabetes mellitus.
        Curr Diab Rep. 2016; 16: 39
        • Joshi S.R.
        • Mehendale S.S.
        • Dangat K.D.
        • Kilari A.S.
        • Yadav H.R.
        • Taralekar V.S.
        High maternal plasma antioxidant concentrations associated with preterm delivery.
        Ann Nutr Metab. 2008; 53: 276-282
        • Makrides M.
        • Gibson R.A.
        • McPhee A.J.
        • Yelland L.
        • Quinlivan J.
        • Ryan P.
        Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial.
        JAMA. 2010; 304: 1675-1683
        • Cohen Juliana F.W.
        • Rifas-Shiman Sheryl L.
        • Rimm Eric B.
        • Oken Emily
        • Gillman Matthew W.
        Maternal trans fatty acid intake and fetal growth.
        Am J Clin Nutr. 2011; 94: 1241-1247
        • Roje D.
        • Zekic Tomas S.
        • Capkun V.
        • Marusic J.
        • Resic J.
        • Kuzmic Prusac I.
        Asymmetrical fetal growth is not associated with altered trophoblast apoptotic activity in idiopathic intrauterine growth retardation.
        J Obstet Gynaecol Res. 2014; 40 (Epub 2013 Oct 7): 410-417
        • Maged A.M.
        • Hashem A.M.
        • Gad Allah S.H.
        • Mahy M.E.
        • Mostafa W.A.
        • Kotb A.
        The effect of loading dose of magnesium sulfate on uterine, umbilical, and fetal middle cerebral arteries Doppler in women with severe preeclampsia: a case control study.
        Hypertens Pregnancy. 2016; 24: 1-9
        • McCowan L.M.
        • Roberts C.T.
        • Dekker G.A.
        • Taylor R.S.
        • Chan E.H.
        • Kenny L.C.
        • et al.
        Risk factors for small-for-gestational-age infants by customised birth weight centiles: data from an international prospective cohort study.
        BJOG. 2010; 117: 1599-1607
        • Tasneem Nasira
        • Masood Humaira
        • Mahmud Ghazala
        The effect of low dose aspirin on fetal birth weight and fetal ponderal index in women with previous history of intrauterine growth restriction.
        Ann Pak Inst Med Sci. 2012; 8: 38-41
        • Jacobsson B.
        • Ahlin K.
        • Francis A.
        • Hagberg G.
        • Hagberg H.
        • Gardosi J.
        Cerebral palsy and restricted growth status at birth: population based case-control study.
        BJOG. 2008; 115: 1250-1255
        • Beaufils M.
        • Uzan S.
        • Donsimoni R.
        • Colau J.C.
        Prevention of pre-eclampsiaby early antiplatelet therapy.
        Lancet. 1985; 1: 840-842
        • Viinikka L.
        • Hartikainen-Sorri A.L.
        • Lumme R.
        • Hiilesmaa V.
        • Ylikorkala O.
        Low dose aspirinin hypertensive pregnant women: effect on pregnancy outcome andprostacyclin-thromboxanebalance in mother and newborn.
        Br J Obstet Gynaecol. 1993; 100: 809-815
        • Wang Z.
        • Li W.
        A prospective randomized placebo-controlled trial of low-dose aspirin for prevention of intra-uterine growth retardation.
        Chin Med J (Engl). 1996; 109: 238-242
        • Byaruhanga R.N.
        • Chipato T.
        • Rusakaniko S.
        A randomized controlledtrial of low-dose aspirin in women at risk from pre-eclampsia.
        Int J Gynaecol Obstet. 1998; 60: 129-135
        • Chiaffarino F.
        • Parazzini F.
        • Paladini D.
        • Acaia B.
        • Ossola W.
        • Marozio L.
        • et al.
        A small randomised trial of low-dose aspirin in women at high risk of pre-eclampsia.
        Eur J Obstet Gynecol Reprod Biol. 2004; 112: 142-144
        • Ayala D.E.
        • Ucieda R.
        • Hermida R.C.
        Chronotherapy with low-dose aspirin for prevention of complications in pregnancy.
        Chronobiol Int. 2013; 30: 260-279
        • Roberge S.
        • Nicolaides K.H.
        • Demers S.
        • Villa P.
        • Bujold E.
        Prevention of perinatal death and adverse perinatal outcome using low-dose aspirin: a metaanalysis.
        Ultrasound Obstet Gynecol. 2013; 41: 491-499
        • Bower S.J.
        • Harrington K.F.
        • Schuchter K.
        Prediction of preeclampsia by abnormal uterine Doppler ultrasound and modificationby aspirin.
        Br J Obstet Gynaecol. 1996; 103: 625-629
        • Posadas
        • Aires Buenos
        CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. CLASP(Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group.
        Lancet. 1994; 343: 619-629
        • Morris J.M.
        • Fay R.A.
        • Ellwood D.A.
        A randomized controlled trial of aspirin in patients with abnormal uterine artery blood flow.
        Obstet Gynecol. 1996; 87: 74-78
        • Rotchell Y.E.
        • Cruickshank J.K.
        • Gay M.P.
        Barbados Low Dose Aspirin Study in Pregnancy (BLASP): a randomised trial for the prevention of pre-eclampsia and its complications.
        Br J Obstet Gynaecol. 1998; 105: 286-292
        • Harrington K.
        • Kurdi W.
        • Aquilina J.
        A prospective management study of slow-release aspirin in the palliation of uteroplacental insufficiency predicted by uterine artery Doppler at 20 weeks.
        Ultrasound Obstet Gynecol. 2000; 15: 13-18
        • Ebrashy A.
        • Ibrahim M.
        • Marzook A.
        • Yousef D.
        Usefulness of aspirin therapy in high-risk pregnant women with abnormal uterine artery Doppler ultrasound at 14–16 weeks pregnancy: randomized controlled clinical trial.
        Croat Med J. 2005; 46: 826-3129
        • Kalinka J.
        • Sieroszewski P.
        • Hanke W.
        • Laudański T.
        • Suzin J.
        Evaluation of the effectiveness of a low-dose aspirin in the treatment of intrauterine growth retardation (IUGR).
        Ginekol Pol. 1999; 70: 126-134
        • Kalinka J.
        • Gottwald L.
        • Nowakowski M.
        • Lech W.
        • Zdziennicki A.
        • Laudanski T.
        The impact of low-dose aspirin therapy on umbilical and middle cerebral artery blood flow in pregnancy complicated by idiopathic intrauterine growth restriction.
        Ginekol Pol. 2004; 75: 254-260
        • McCowan L.M.
        • Harding J.
        • Roberts A.
        • Barker S.
        • Ford C.
        • Stewart A.
        Administration of low-dose aspirin to mothers with small for gestational age fetuses and abnormal umbilical Doppler studies to increase birth weight: a randomized double-blind controlled trial.
        Br J Obstet Gynaecol. 1999; 106: 647-651
        • Grab D.
        • Paulus W.E.
        • Erdmann M.
        • Terinde R.
        • Oberhoffer R.
        • Muche R.
        • et al.
        Effects of low-dose aspirin on uterine and fetal blood flow during pregnancy: results of a randomized, placebo-controlled, double-blind trial.
        Ultrasound Obstet Gynecol. 2000; 15: 19-27
        • Olsen S.F.
        • Olsen J.
        • Frische G.
        Does fish consumption during pregnancy increase fetal growth? A study of the size of the newborn, placental weight and gestational age in relation to fish consumption during pregnancy.
        Int J Epidemiol. 1990; 19: 971-977
        • Olsen S.F.
        • Grandjean P.
        • Weihe P.
        • Videro T.
        Frequency of seafood intake in pregnancy as a determinant of birth weight: evidence for a dose dependent relationship.
        J Epidemiol Community Health. 1993; 47: 436-440
        • Smuts C.M.
        • Huang M.
        • Mundy D.
        • Plasse T.
        • Major S.
        • Carlson S.E.
        A randomized trial of docosahexaenoic acid supplementation during the third trimester of pregnancy.
        Obstet Gynecol. 2003; 101: 469-479
        • Makrides M.
        • Duley L.
        • Olsen S.F.
        Marine oil, and other prostaglandin precursor, supplementation for pregnancy uncomplicated by pre-eclampsia or intrauterine growth restriction.
        Cochrane Database Syst Rev. 2006; 19: CD003402
        • Cohen J.F.
        • Rifas-Shiman S.L.
        • Rimm E.B.
        • Oken E.
        • Gillman M.W.
        Maternal trans fatty acid intake and fetal growth.
        Am J Clin Nutr. 2011; 94 (Epub 2011 Sep 14): 1241-1247
        • Ramakrishnan U.
        • Stein A.D.
        • Parra-Cabrera S.
        • Wang M.
        • Imhoff-Kunsch B.
        • Juárez-Márquez S.
        • et al.
        Effects of docosahexaenoic acid supplementation during pregnancy on gestational age and size at birth: randomized, double-blind, placebo-controlled trial in Mexico.
        Food Nutr Bull. 2010; 31: S108-S116
        • Bulstra-Ramakers M.T.E.W.
        • Huisjes H.J.
        • Visser G.H.A.
        The effects of 3 g eicosapentaenoic acid daily on recurrence of intrauterine growth retardation and pregnancy induced hypertension.
        BJOG. 1994; 102: 123-126
        • Onwude J.L.
        • Lilford R.J.
        • Hjartardottir H.
        • Staines A.
        • Tuffnell D.
        A randomized double blind placebo controlled trial of fish oil in high risk pregnancy.
        BJOG. 1995; 102: 95-100
        • Olsen S.F.
        • Secher N.J.
        • Tabor A.
        • Weber T.
        • Walker J.J.
        • Gluud C.
        Randomized clinical trials of fish oil supplementation in high risk pregnancies. Fish Oil Trials in pregnancy (FOTIP).
        BJOG. 2000; 107: 382-395