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. SoetomoGeneral 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 populationaccording 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 late-onset 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. Aterm 82 68,33%

2. Moderate preterm 26 21,67%

3. Very preterm 9 7,50%

4. Extremely preterm 3 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.

0

10

20

30

40

50

60

70

80

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.

Low birth weight

normal

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 - IUGR + Total

Onset

Early

(Percentage)

25

(20,83%)

6

(5,00%)

31

(25,83%)

Late

(Percentage)

76

(63,33%)

13

(10,83%)

89

(74,17%)

Total

(Percentage)

101

(84,17%)

19

(15,83%)

120

(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 perinataloutcome 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

Baby’s 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 late-onset severe preeclampsia.

3. The onset severe preeclampsia has no effect on the incidence of IUGR