RELATIONSHIP BETWEEN SEVERE

PREECLAMPSIA ONSET WITH IUGR

INCIDENCE AT DR. SOETOMO
GENERAL HOSPITAL IN 2012

Ryan Enast Intan1, Budi Utomo2, Budi

Wicaksono3

Medical Faculty of Airlangga University

Surabaya, Jawa Timur, Indonesia

ABSTRACT
Intra Uterine Growth Restriction can be a serious problem in neonates because
it is associated with increased morbidity and mortality and long-term sequel in
the future. One of the main maternal risk factors of IUGR is severe
preeclampsia in pregnancy. This study analyzed the relationship between the
onset of severe preeclampsia and the incidence of IUGR in Dr. Soetomo
General Hospital. The aim of this study was to prove whether early onset
severe preeclampsia is a risk factor for IUGR compared with late-onset severe
preeclampsia. This was an analytic observational cross-sectional study.
Sampling technique in this study was random sampling. The data in this study
were taken from the medical records at the Department of Obstetrics and
Gynecology Dr. Soetomo General Hospital Surabaya in 2012. Data analysis
was used cross tabulation and chi-square test with level of significance of 95 %
( p < 0.05 ). There were 120 patients in this study. Results showed that
prevalence rate of IUGR in early-onset severe preeclampsia was 1.32 times
higher compared with late-onset severe preeclampsia,. However, there was no
statistically significant association between early-onset preeclampsia and the
incidence of IUGR. ( p = 0.53; PR = 0.71 ; 95 % CI = 0.25 to 2.07 ).Late-onset
severe preeclampsia also had no effect on the incidence of IUGR ( p = 0.53;
PR = 1.40 ; 95 % CI = 0.48 to 4.08 ). It can be concluded that the onset severe
preeclampsia had no effect on the incidence of IUGR .

Introduction
Intrauterine Growth Restriction (IUGR) is infant with birth
weight below the 10th percentile of a reference population
according to gestational age.
IUGR is associated with increased morbidity and
mortality, asphyxia, meconium aspiration, hypoglycemia, and
abnormal neurological growth, as well as the sequel to the
disease in the future
Based on the onset, preeclampsia can be classified into
two, namely early-onset preeclampsia ( 34 weeks) and lateonset preeclampsia (> 34 weeks)
IUGR can be influenced by many factors, both environmental
factors, fetal and maternal factors. One of the main causes of
maternal factors IUGR is preeclampsia in pregnancy.

Prevalence
One-third of all cases of infants weighing
under 2500 grams had IUGR and 6-30%
of babies born with IUGR. It is estimated
that 30 infants born annually in
developing countries experiencing
IUGR, where the incidence rate is 6 times
higher than in developed countries. IUGR
prevalence is highest in developing
countries in Asia which reached 75%.

IUGR and Preeclampsia

Xiong et al., 2001, concluded that women with
a history of preeclampsia only at risk of having
babies with low birth weight in premature
birth, whereas at normal gestational age, birth
weight was not different with a normal birth
weight infants. Statistically, association of
early onset preeclampsia with IUGR is seen
when compared with normal pregnancy, but
whether early onset preeclampsia is a risk
factor that determine the incidence of IUGR
compared with late-onset preeclampsia is still
unclear and has not been investigated in
Indonesia.

Main Problem
Is there a relationship between the
onset of severe preeclampsia with
IUGR incidence in Dr. Soetomo
General Hospital in 2012 ?

Objective
General objective
Trying to determine whether there is a
relation between the onset of severe
preeclampsia with IUGR incidence in
hospitals Soetomo 2012.
Spesifict objective
The purpose of this study was to prove
whether early onset severe
preeclampsia is a risk factor for IUGR
compared with late-onset severe
preeclampsia.

Conceptual Mapping

Legend :
independent
variable
Dependent
variable

Early Hypothesis
There is a relation between the onset
of severe preeclampsia with IUGR
incidence in hospitals Soetomo 2012.
Early onset severe preeclampsia is a
risk factor for IUGR compared with
late-onset severe preeclampsia.

METHODS
This was an analytic observational
cross-sectional study.
The data in this study were taken
from the medical records at the
Department of Obstetrics and
Gynecology Dr. Soetomo General
Hospital Surabaya in 2012
Sampling technique in this study was
random sampling.

Data
Data in this study include : gestational
age, preeclampsia onset, sex, birth
weight, and IUGR incidence.
Onset of severe preeclampsia were divided
into two categories: early onset ( 34 weeks)
and late onset (> 34 weeks).
The instrument which used to determine the
incidence of IUGR is intra-uterine
Lubchenco curves according to gender.
IUGR neonates includes newborn with birth
weight below 10% percentile of the weight
curve for gestational age with birth weight
2500 grams.

Sample
The sample in this study were women
with severe preeclampsia in Space
VK Maternity Hospital Emergency
Room Dr. Soetomo period of January
1, 2012 to December 31, 2012

 Inclusion criteria
Preeclampsia patients which have a
complete medical record data
Exclusion criteria
patients with chronic
hypertension, gestational
diabetes, anemia, chronic energy
malnutrition, placenta previa, and
multiple pregnancy

 Independent variable
onset of severe preeclampsia ( early
or late onset)
Dependent variable
neonates with IUGR

Flowchart
procedure

Data analysis
Data analysis was performed in two stages, the
univariate and bivariate analysis.
univariate analysis
we made distribution of frequencies of each variable.
bivariate analysis
data analysis were performed descriptively, presented
in the form of cross-tabulation and percentage.
Analytical analysis performed using chi-square test
with a significant level of 95% (p <0.05) to determine
the relationship between the independent variable on
the dependent variable and use prevalence ratio to
determine the risk estimates of the causes of IUGR.

Result
Based on the data in the medical
record, Dr. Soetomo General Hospital was
known to have a total of 508 patients with
severe preeclampsia during 2012. From
these data, we make a random sampling to
find 120 medical records which meets
inclusion criteria. Descriptive data are
presented in the form of distribution birth
weight, gestational age, and the onset of
preeclampsia.

Table 1. Gestational age patients with severe preeclampsia referral

hospitals Soetomo 2012
Num.

Gestational Age

Number

Percentage

1.
2.
3.
4.

Aterm
Moderate preterm
Very preterm
Extremely preterm

82
26
9
3

68,33%
21,67%
7,50%
2,50%

Total

120

100%

Table 1 above shows that the majority of patient referrals for severe
preeclampsia in Dr. Soetomo General Hospital in 2012 could achieved
term pregnancy. The highest gestational age was 42 weeks and the
lowest gestational age was 26 weeks.

Table 2 Distribution of birth weight of the patient referral

severe preeclampsia dr. Soetomo in 2012
Num Birth Weight Group Total

Percentage

1.

2500 gram

81

67,50%

2.

<2500 gram

39

32,50%

Total

120

100%

The table above shows that the birth weight of the patient referral of
severe preeclampsia in Dr. Soetomo in 2012 the majority has
reached a sufficient weight, ie 2500 grams with the heaviest weight
of 4300 grams and about one-third of total with low birth weight
(LBW) with the lightest weight of 500 grams.

80
70
60
50
40

Low birth weight

30

normal

20

10
0

Aterm

Moderate
preterm

Very
preterm

Extremely
preterm

Figure 5.1 Bar graph of birth weight distribution from severe preeclampsia mother
according to gestational age

From the graph above, we see that the majority of infants with term gestational age have
weight 2500 g . These results indicate that at term gestational age, most babies can
achieve optimal weight like normal baby. Infants who born below 37 weeks gestation
have similar pattern. The number of low birth weight babies are higher than normal
weight babies for the category of moderately preterm , very preterm , and extremely
preterm , with the greatest incidence of low birth weight are at moderate preterm
gestational age.

Table 3 onset severe preeclampsia patient referrals in

dr. Soetomo in 2012
Num

Total

Percentage

1.

Early onset preeclampsia

31

25,83%

2.

Late onset preeclampsia

89

74,17%

Total

120

100,00%

Table 3 shows that the number of patients with late-onset

preeclampsia is much more than patients with early onset
preeclampsia with onset average reached 36.28 weeks. The most
onset occurred in 39 weeks gestation. Range of onset severe
preeclampsia in Dr Soetomo General Hospital in 2012 was also very
wide with the earliest onset at 26 weeks gestation and the latest
onset at 41 weeks gestation.

Table 4 Distribution of onset of preeclampsia on the

occurrence of IUGR in neonates
IUGR Onset

IUGR +

Early
25
6
(Percentage) (20,83%) (5,00%)

Total
31
(25,83%)

Late
76
13
89
(Percentage) (63,33%) (10,83%) (74,17%)
Total
(Percentage)

101
19
120
(84,17%) (15,83%) (100,00%)

Results of cross tabulation about influence of preeclampsia onset on the

occurrence of IUGR neonates showed that women who had early onset
preeclampsia have IUGR infant outcomes as much as 6 out of 31 infants
(prevalence rate = 19.35%), whereas the late onset preeclampsia patients
have IUGR infant outcomes as much 13 of 89 infants (prevalence rate =
14.60%). The result of this study shows that the outcome of IUGR infants of
mothers who experience early onset preeclampsia have a prevalence rate
1.32 times higher than women with late-onset preeclampsia.

 The results of descriptive analytic using chi-square

and prevalence ratio for early-onset preeclampsia
showed early onset severe preeclampsia had no effect
on the incidence of IUGR (p = 0.53; PR = 0.71; 95%
CI = 0.25 to 2.07 ).
The same results are shown in the calculation of the
late-onset preeclampsia as a risk factor. Late onset
severe preeclampsia also had no effect on the
incidence of IUGR risk factor (p = 0.53; PR = 1.40;
95% CI = 0.48 to 4.08).
Based on the results, we conclude that the onset of
preeclampsia has no effect on the incidence of IUGR.

Discussion

Kaufman and Sibai said that the theory of abnormal placental implantation allows
preeclampsia and IUGR has the same root of pathogenesis , but have different
clinical manifestations. Early onset preeclampsia is generally associated with
IUGR, abnormal uterine and also adverse maternal and neonatal outcomes. In
contrast, slow-onset preeclampsia is often associated with a mild maternal
disorders, fetal lesser influence, and better perinatal outcomes. This is possible
because it considers placenta insufficiency as a single cause that resulted
preeclampsia and IUGR, so the earlier the onset of preeclampsia, the higher the
chances of IUGR incidence. Meanwhile at late onset preeclampsia, babies tend to
grow normally.

Previous statistical studies regarding the outcome of preeclampsia provide results

that have a very large range variety. Sibai and Barton conduct a review of the many
reports from the early 1990s on the management of severe preeclampsia.The results
showed that early onset preeclampsia cases which have the same range of
gestational age , have a variety of IUGR outcomes incidence, with the lowest value
reach 22% and the highest value reached 94%. This suggests that the perinatal
outcome of early-onset severe preeclampsia may show different results and do not
have a certain relation to the incidence of IUGR, so it can not be concluded yet
whether preeclampsia onset is a risk factor of the incidence of IUGR

The results of this study showed that prevalence rates of IUGR

resulted from early onset preeclampsia by 19.35%. These
results are consistent with research from Xiong et al., because
prevalence rate of IUGR in early-onset preeclampsia is 1.32
times higher than late-onset preeclampsia IUGR. But the result
of the descriptive analysis using prevalence ratio show that the
early onset preeclampsia or late onset preeclampsia is not
associated with the incidence of IUGR. Chi-square analysis
results also lead to the conclusion that preeclampsia onset is not
a risk factor for the incidence of IUGR. Thus, there are several
theories that allow this to happen:

1. Preeclamspia and IUGR are not based on a single

pathophysiology, but a combination of several factors.
If the terms of the theory of placental insufficiency as a single
pathophysiological cause of preeclampsia and IUGR, then
theoretically it is supposed that the earlier onset of
preeclampsia, the incidence of IUGR will be even greater. But in
fact, preeclampsia and IUGR is also influenced by other factors.
One of the factors that influence the preeclampsia and IUGR are
genetic factors and nutritional factors [8,9]. The influence and
the combined pathophysiology apart from ischemic theory
placenta, causing IUGR incidence of severe preeclampsia in
women may occur at any onset, is not limited to the early
onset, because it can cause overlap and influence each
other, so that the onset of preeclampsia is not a risk factor the
occurrence of IUGR, especially in developing countries such as
Indonesia, nutritional adequacy rate for pregnant women on
average still low. In addition, the influence of genetic factors will
also affect the outcome of IUGR of preeclampsia, so it does not
depend on the onset of preeclampsia

2. Preeclampsia and IUGR share the same basic

cause, but it has different development and disease
manifestations, so-called independent correlated.

This theory explains that both fetal

growth restriction and preeclampsia is
a two-stage disorder. The hypothesis
of this theory says there is a spectrum
or stages recognize the occurrence of
preeclampsia. According to
Redman, stage 1 is caused by an error
endovascular trophoblast remodeling
resulting in ischemic placenta and
subsequent phase 2, namely placental
oxidative stress. Increased oxidative
stress and anti oxidative defense
mechanisms may contribute to the
disease process either preeclampsia
or IUGR. Of stage 2 is then appeared
different manifestation, whether
leading to IUGR, preeclampsia, or
both. Pathophysiology process can be
seen in the image beside.

The big difference in developmental pathways of the disease

process is also supported by other studies. Granovsky et al., said
that although the pathophysiology of preeclampsia and IUGR
share maternal and placental, but they have different phenotypes
and biological profiles. Preeclampsia is a systemic maternal
disease, which in some cases, but not always, associated with
fetal growth restriction / IUGR, while IUGR are primarily fetal
abnormalities. Another factor that supports the possibility of
mechanical differences between the development of preeclampsia
and IUGR are differences in risk factors between the two
processes. Diabetes, obesity, and chronic hypertension
associated with preeclampsia, whereas IUGR is more commonly
found in women who have a low BMI

Through the above description it is likely that the onset of

preeclampsia, especially early-onset preeclampsia is not a risk
factor for the incidence of IUGR due the different pathways of
process leading to IUGR and preeclampsia syndrome and both of
these cases also has different etiology and risk factors.

3. Preeclampsia early onset and late onset has

different basic pathophysiology and etiology

Birth weight percentiles less than the third, less than the fifth, and
less than the 10th percentiles for gestational age were each
significantly associated with preeclampsia at an earlier gestational
age (P < .001). Similarly, birth weight greater than the 90th
percentile was significantly increased at 37 weeks or longer (P <
.001. Early-onset preeclampsia and late onset share the same
etiology appearance, but differ in terms of risk factors, and lead to a
different outcome. Existing data now supports that the difference in
vascular adaptation in early and late onset preeclampsia may
indicate differences in pathophysiology, so early onset preeclampsia
and late onset preeclampsia should be viewed as a different kind, in
terms of etiological, prognostic, and pathophysiology .

Because early-onset preeclampsia and late onset preeclampsia are

two different entities, the possibility of a lack of correlation between
the onset of preeclampsia risk factors and the incidence of IUGR is
also possible.

Limitation of the study

1. The number of samples is too few.
This examination is using data from medical records. Too few amount of samples
can cause cross-sectional analytical results have the value of 1 in it, so it can
cause biased result. One of the obstacles faced by researchers is the lack of
medical records that met the inclusion criteria, which is severe preeclampsia
patients who had complete medical record data. We found some medical records
that do not have complete data, such as data of gestational age when diagnosed
as preeclampsia and data of birth weight.

2. Data taken are sourced from secondary data source

Babys weight that recorded in medical record is data of birth weight and
preeclampsia diagnosis is established when the first symptoms of hypertension
and proteinuria appears. In association with IUGR, these data are based on
final point of fetal growth, therefore could not reflect the process of the disease
and the rate of growth of the fetus. With this method, the fetus who failed to
grow in optimal potential size, but still above percentile 10 of birth weight, could
not be identified. In addition, in this study, criteria used of IUGR is birth weight
below the 10th percentile included in birth weight curve according to gestational
age, which is the same definition as SGA (Small for Gestational Age).
Therefore SGA infants who did not experience growth restriction could be
misunderstood as IUGR.

3. There is no standard curve of baby weight by gestational age for

infants in Indonesia

Lubchenco curve which is used as the reference point in

determining the intra-uterine fetal growth percentiles, was
based on previous research to standard infants in USA.
Indonesia does not have their own standard, therefore this
will have an effect because there shall be a difference on
average between the infants weight in Indonesia and infants
weight in USA for the same gestational age.
Theoretically, average weight of infants in Indonesia should
be lower than infants in the USA because the nutritional
adequacy for pregnant women in developing countries is still
not so good as developed countries.

CONCLUSION
1. Prevalence rate of IUGR in early
onset severe preeclampsia is higher
than the prevalence rate of IUGR in
late-onset severe preeclampsia.
2. The early onset severe preeclampsia
has no effect on the incidence of risk
factors for IUGR compared with lateonset severe preeclampsia.
3. The onset severe preeclampsia has
no effect on the incidence of IUGR