Vol3,No1

January2015

Malondialdehydeinthreatenedabortion11

Research Article

Serum Malondialdehyde Level as a Risk Factor for Threatened Abortion

Kadar Malondialdehid Serum sebagai FaktorRisiko Terjadinya AbortusIminens
GustiNSutama,IGedePSurya
DepartmentofObstetricsandGynecology
FacultyofMedicineUniversityofUdayana/
SanglahGeneralHospital
Denpasar
Abstract

Abstrak

Objective:Todeterminetheroleofserummalondialdehydelevelas
ariskfactorforthreatenedabortion.

Tujuan:Untukmengetahuiperanankadarmalondialdehidpadase
rumsebagaifaktorrisikoterjadinyaabortusiminens.
Metode: Penelitian ini dilakukan dengan metode kasuskontrol. Se
banyak60ibuhamildiikutsertakansebagaisubjek,30orangdengan
abortusiminensdalamkelompokkasusdan30orangdengankeha
milannormalsebagaikelompokkontrol.Pemeriksaankadarmalon
dialdehid serum dikerjakan di Laboratorium Biokimia Fakultas Ke
dokteran Universitas Gadjah Mada Yogyakarta. Uji normalitas data
yang terkumpul dilakukan dengan uji KolmogorovSmirnov, dan di
lakukananalisadatadenganttestuntuksampelindependen.Untuk
menentukanrisikoterjadinyaabortusiminenspadakadarmalondial
dehidyangtinggidigunakanujiChiSquare.
Hasil:Padapenelitianinididapatkanreratakadarmalondialdehidse
rum pada kelompok abortus iminens adalah 1,33K0,11 nmol/ml dan
reratakadarmalondialdehidserumpadakehamilannormaladalah
1,03K0,10 nmol/ml. Analisa ttest independen menunjukkan bahwa
rerata kadar serum malondialdehid pada kedua kelompok tersebut
berbeda secara bermakna (p=0,001). Berdasarkan nilai batas 1,12
nmol/ml,didapatkanbahwakadarserummalondialdehidyangtinggi
meningkatkanrisikoterjadinyaabortusiminenssebesar29,57kali(IK
95%=6,85127,64,p=0,001).
Kesimpulan:Kadarmalondialdehidserumpadaabortusiminensme
miliki perbedaan yang bermakna jika dibandingkan dengan kadar
malondialdehidserumpadakehamilannormal,dantingginyakadar
malondialdehid serum merupakan faktor risiko terjadinya abortus
iminens.
[MajObstetGinekolIndones2015;1:1114]
Katakunci:abortusiminens,kehamilannormal,malondialdehid

Method:Ourstudywasacasecontrolstudy.Weexamined60preg
nantwomenasoursubject,30subjectswiththreatenedabortionas
casesand30subjectswithnormalpregnancyascontrolgroup.Se
rumlevelsofmalondialdehydeofeachwomanwasexaminedinthe
BiochemistryLaboratoryFacultyofMedicineGadjahMadaUniver
sityinYogyakarta.WetestedthenormalityofourdatausingKolmo
gorovSmirnov test, and analysis was then performed using inde
pendentsamplettest.Todeterminetherelationshipofserumma
londialdehydewiththreatenedabortion,ChiSquaretestwasused.
Result:Fromthisstudywefoundthattheaverageserummalondial
dehydelevelinthreatenedabortionwas1.33K0.11nmol/ml,while
the average level of serum malondialdehyde in normal pregnancy
was 1.03K0.10 nmol/ml. The analysis using independent ttest
shows that the average serum malondialdehyde level on the two
groups was significantly different (p=0.001). Based on the cutoff
valueof1.12nmol/ml,wefoundthattherelativeriskofthreatened
abortion is 29.57 times (95% CI=6.85127.64, p=0.001) in those
withahighlevelofserummalondialdehyde.
Conclusion:Theserummalondialdehydelevelinthreatenedabor
tion was significantly different compared to normal pregnancy. A
highlevelofserummalondialdehydeinpregnancywasariskfactor
forthreatenedabortion.
[IndonesJObstetGynecol2015;1:1114]
Keywords:malondialdehyde,normalpregnancy,threatenedabor
tion

Correspondence:GustiNSutama,DepartmentofObstetricsandGynecology,FacultyofMedicineUniversityofUdayana/
SanglahGeneralHospital,Denpasar,Bali.Mobile:081337497507,email:gosmansutama@gmail.com

INTRODUCTION
Abortionisacommonlyfoundobstetriccomplica
tion in early pregnancy, mostly presenting with
vaginalbleeding.Threatenedabortionisasituation
of threatened pregnancy termination before 20
weeks gestational age or fetal weight reaches 500
grams.1Recently,manyresearchesbeganstudying
theroleofoxidativestressinabortionpathogene
sis.Oxidativestressitselfistheimbalancebetween
levelsofprooxidativeagents(freeradical)andan
tioxidants.2,3Oxidativestressmayleadtodisorders

in placentation. One possible complication result

ing from placentation disorder is abortion. It has
beenhypothesizedthattheincreasingincidenceof
placentationdisorderiscorrelatedwithimbalance
offreeradicallevels,whichaffectsplacentaldeve
lopmentandeventuallythefetus.4,5
Abortioniscausedbyinadequatetrophoblastin
vasion, followed by trophoblastic oxidative stress,
which finally leads to inadequate supply of fetal
oxygen and nutrient requirements from the spiral
arteries.Aspregnancydevelops,itisphysiological

IndonesJ
ObstetGynecol

12SutamaandSurya
that there is increasing energy needs to maintain
maternalbodilyfunctionsandfetalgrowthandde
velopment, which in the end leads to increasing
oxygenneeds.Althoughoxygenisessentiallyneed
ed in cellular function, a drastic surge in oxygen
metabolism will result in toxic substance produc
tion known as reactive oxygen species (ROS). The
increasing levels of the toxic ROS will bring about
cell damage. In order to prevent cellular damage
caused by ROS, cells enhance an antioxidant sys
tem. When an increase in ROS production causes
an imbalance in homeostasis, oxidative stress will
leadtoimpairedcellfunctionor,intheworsecase,
cellular death.35 An increase in oxidative stress
without increasing antioxidant enzyme levels (Su
peroxide dismutase, gluthatione peroxidase, kata
lase)cellmembranedamagewilloccur,formingco
valent bonds of free radicals and lipid on the cell
membrane(peroxidativelipid).Lipidperoxidation
isaprocesswherefreeradicalsinteractwithpoly
unsaturated fatty acids (PUFA) on the cell mem
brane and lipoproteins in the cytoplasm. Malon
dialdehyde acts as a marker of peroxidative lipid
production.6Theexaminationofserummalondial
dehydeasthemarkeroflipidperoxidationprocess
isapotentialpredictivetestforabortion.Thisstu
dy aimed to understand the role of serum malon
dialdehydelevelasariskfactorofthreatenedabor
tion.Intheend,weexpectthestudytobeableto
explainthepathophysiologyofabortionandeven
tuallyfindapreventivesolution.

METHODS
Wecarriedoutacasecontrolstudy.Sixtypregnant
women were recruited as samples in this study.
Each groups were comprised of 30 women, those
with threatened abortion in the case group and
thosewithnormalpregnancyinthecontrolgroup.
Theinclusioncriteriaappliedforcaseswaswo
men with normal pregnancy who experienced a
threatenedabortionat814weeksgestationalage.
Whereaswomenwithnormalpregnancywhocar
ried to term were included as controls. Subjects
wereexcludediftheyhadhydatidiformmole,ute
rineanatomyanomalies,uterinemyoma,andahis
toryofinducedabortion.
Serum malondialdehyde level was assessed in
BiochemistryLaboratoryoftheMedicalFacultyof
Gadjah Mada University, Yogyakarta. The normal
ity of the collected data was assessed using Kol
mogorovSmirnovtest,andthedifferencebetween
both groups was analyzed with independentsam
plettest.Chisquarewasusedtocalculatetherisk
of threatened abortion in women with a high ma
londialdehydelevel.

RESULTS
This study involved 60 women as samples. Thirty
womenwiththreatenedabortionwereincludedin
thecasegroupandtheother30womenwithnor
malpregnancywereincludedinthecontrolgroup.
The baseline characteristics of our sample is pre
sentedinTable1.

Table1. BaselineCharacteristicsandAverageSerumMalondialdehydeLevel.
Group

Variable

Case

Control

Age(years)

27.73K3.91

26.53K4.42

0.270

Parity

1.00K0.83

0.90K0.92

0.661

Gestationalage(weeks)

9.43K1.41

9.87K1.66

0.279

Malondialdehydelevel(nmol/ml)

1.33K0.11

1.03K0.10

0.001

Vol3,No1
January2015

Malondialdehydeinthreatenedabortion13

Table2. RiskofThreatenedAbortioninWomenwithHighSerumMalondialdehydeLevel

Serum
MalondialdehydeLevel

Case

Control

High

27

Normal

23

As shown in Table 1, there was no difference

betweenthetwogroupsintermsofage,parity,and
gestational age at the time of recruitment. Mean
serum malondialdehyde level in the case group
was1.33K0.11nmol/ml,whileinthecontrolgroup
was1.03K0.10nmol/ml.Furthermore,theaverage
serummalondialdehydelevelswasfoundtobesig
nificantly different in the two groups of samples
(p=0.001).
Chisquare was used to investigate the role of
serum malondialdehyde on threatened abortion.
AccordingtotheROCcurve,thecutoffpointused
for serum malondialdehyde is 1.12 nmol/ml with
sensitivity of 96.7% and specificity of 80%. The
analysisresultsarepresentedinTable2.
Table2showsthathighserummalondialdehyde
level is a risk factor for threatened abortion, with
risksincreasingasmuchas29.57timesinwomen
with serum malondialdehyde levels higher than
1.12nmol/mlcomparedtowomenwithlowerse
rummalondialdehyde(OR=29.57,95%CI=6.85
127.64,p=0.001).

DISCUSSION
The analysis results showed that high serum ma
londialdehyde level is a risk factor for threatened
abortion, with increase in risk as much as 29.57
times with a higher level of serum malondialde
hyde (p=0.001). It is because serum malondialde
hyde is formed by lipid peroxidation produced in
oxidativestress.68Ahighlevelofmalondialdehyde
indicates the occurrence of cell membrane oxida
tion and oxidative stress in threatened abortion.
Oxidative stress will in turn lead to impaired pla
centation. The effect of impaired placentation be
gins as blood flow disruption in the intervillous
area and progresses to pregnancy termination.
Abortionitselfhappensastheresultofinadequate
trophoblastinvasion,andtheresultinginadequate
supplyfromthespiralarteries.4,5
Measuring the level of free radicals directly is

OR

95%CI

29.57

6.85127.64

0.001

difficult as it is highly reactive. Furthermore, the

difficultyofperformingdirectanalysisoffreeradi
cals is caused by its instability and its inclination
toobtainelectronsfromothersubstancesinorder
to stabilize itself. This process occurs in a short
time,makingitdifficulttomeasurefreeradicalsin
its true form. The formation of peroxidative lipid,
however, can be used as indirect measurement of
free radicals. This is applicable through measure
ment of peroxidative lipid products marker, such
asmalondialdehyde.Malondialdehydeisadecom
position product of PUFA peroxidation.6,7 Analy
zingmalondialdehydemeansindirectlymeasuring
free radicals and therefore provides an easy me
thodtodeterminefreeradicallevels.Malondialde
hyde provides detection of free radicals in exces
sivelypathologicalconditions.4,911Asaresult,ma
londialdehyde is the substance mostly examined
since it is believed as a good in vivo peroxidative
lipid marker, both in human or animals, which is
significantly more accurate and stable then the
other markers. Nowadays, malondialdehyde has
beenusedwidelyasaclinicalmarkeroflipidper
oxidation.6,8,12,13 The reasons why malondialde
hyde is a good oxydative stress biomarker are its
formationalongsideoxidativestressspecificallyli
pid peroxidation, the ability to measure its serum
levels accurately using available methods, its sta
bility in isolated body fluid samples, not being in
fluencedbydiurnalvariationanddietaryfatintake,
andthepresenceofdetectableamountsinallbody
tissues and biological body fluid to determine the
referenceinterval.9Lipidperoxidationisincreasing
inabortionandpregnancytermination.
Patil reported serum malondialdehyde level in
nonpregnant women was 1.19K0.09 nmol/ml
whilst in pregnant women were 1.42K0.13 nmol/
ml,1.64K0.14nmol/ml,1.79K0.14nmol/ml(inthe
1st,2nd,3rdtrimester).InTurkey,Ozkayareported
that serum malondialdehyde level in women who
suffered spontaneous abortion was higher (66.4K
13.7 nmol/ml) than those in normal pregnancy
(40.3K16.1nmol/ml)inthesamegestationalage.14

14SutamaandSurya

CONCLUSION
The serum malondialdehyde level in threatened
abortionissignificantlydifferentthanthoseinnor
malpregnancy.Ahigherlevelofserummalondial
dehydewasfoundtobeariskfactorforthreatened
abortion.

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