Demographic Characteristics in Preeclamptic Women in Macedonia

Background: Worldwide, pre-eclampsia and eclampsia contribute to the death of a pregnant woman every three minutes. Aim: To determine the demographic risk factors and values of blood pressure to predict preeclampsia. Material and Methods: Demographic and clinical features of 300 normotensive pregnant women aged 28 ± 5 years and 100 preeclamptic women aged 28 ± 6 years, were assessed. Women with multiple pregnancies were excluded from the study. Results: Women with less educational attainment had a higher risk of mild and severe preeclampsia. Weight gain during pregnancy in control and pre eclamptic women were 14 ± 3 and 20 ± 5 kg, respectively (p < 0.01). Women with severe preeclampsia had high signifi cantly shorter gestations then the other two patient groups (p < 0.01). Compared to nor-motensive women, at 6 to 12 weeks of gestation, pre eclamptic women had higher systolic (102 ± 7 and 113 ± 9 mmHg respectively), diastolic (64 ± 5 and 74 ± 10 mmHg respectively) and mean arterial pressure (77 ± 5 and 87 ± 8.01 mmHg respectively). Conclusions: Women with basic education or illiterate have a higher risk of developing preeclampsia. During the fi rst or second trimester of pregnancy, mean arterial pressure is the best predictor for preeclampsia.

W orldwide, pre-eclampsia and eclampsia contribute to the death of a pregnant woman every 3 minutes.The management of pregnancies complicated by hypertension has not changed signifi cantly for many years, possibly as result of little progress being made in our understanding of the condition 1 .
Preeclampsia (PE) is one of the most common medical problems in perinatology.PE is a multisystem disorder, of unknown etiology, usually associated with raised blood pressure and proteinuria 2 .
Several authors associate PE with obesity during pregnancy.Optimal weight gain should be 11-12,5 kg for single and 6-20 kg for multiple pregnancies.However, the estimate has to be individualized because it depends on the characteristics of the future mother (age, body weight before pregnancy, habits, ethnicity, etc) 8 .Eating habits are closely connected with excessive weight gain during pregnancy.Hypercaloric food, especially high in carbohydrate and fat, and low in proteins could cause a metabolic misbalance leading to PE 6,8,9 .
While some authors consider that there is a connection between PE and smoking, others disagree 10 .Smoking during pregnancy reduces baby weight by 150-300 grams.Quitting smoking before the third trimester improves fetus health and weight.Smoking increases the concentration of carbohemoglobin in the maternal and fetal blood, which leads to relative fetal hypoxemia.Smoking also causes a release of adrenalin and noradrenalin, which can induce a spasm in uterine blood vessels and reduce their blood fl ow.The endothelium of fetal blood vessels of smoking mothers has lower amounts of prostacyclin (PGI2), also reducing fetal blood circulation 11,12 .
A large number of pregnancies with PE, especially the severe form, lacked an adequate antenatal surveillance.Active protection is very important in the prevention of preeclampsia and does not require special or expensive equipment.It is ne-cessary to treat every pregnancy as a potential PE at the beginning.Attention should be paid mainly to the high risk groups.
The aim of this research was to identify risk groups of pregnant women for PE and to identify risk factors for the condition.

Study population
The research was conducted in the Clinical Hospital "Dr Trifun Panovski" in Bitola, Macedonia, Department of Gynaecology and Obstetrics.Patients studied were admitted between May 1st 2008 to August 1st 2009 The Ethics Committee of School of Medicine University of Belgrade, Serbia, approved the experimental study protocol.The participants were included in the study after written informed consent was obtained.The fi nal study included 400 previously healthy women aged 15 to 43 years, (300 normotensive and 100 with PE), with no history of any chronic disease, with singleton pregnancies, without chromosomal or congenital abnormalities, with a known date of the last menstrual period and regular previous menstrual periods.
The criteria to determine the exact pregnancy stage was based on anamnestic data, obstetrical and ultrasound examinations, which means that the information of the last period was in concordance with the results from obstetrical and ultrasound examinations.The fi rst assessment was performed at 6 to12 weeks of gestation (wg).

Defi nition of study variables
Age, education, nationality, parity, smoking status, week of PE onset, duration of PE, duration of pregnancy, birth weight and length, and birth weight in percentiles, were assessed.Smoking status and level of education were determined by self-report.
All subjects were followed until delivery.The gestational age at delivery, obstetric complications if any, and neonatal outcome were recorded.For those subjects who subsequently delivered in another hospital, the obstetric information was obtained telephoning the subject or contacting the staff in the other hospital.Birth weight (to the nearest gram) was classifi ed into fi ve categories: very low birth weight (< 5th percentile), low (5 -9,9), normal (10-89.9),high (90-94.9)and very high (> 95).
Prepregnancy BMI was determined based on measured height and maternal weight at the initial visit (6-12 w.g.) and maternal self report of prepregnancy weight.Height was measured by using a portable stadiometer, accurate to 1 mm.Weight was determined by using the average of two measurements, with the woman lightly clothed.A scale accurate to 0.2 kg was used.Pre-pregnancy BMI was categorized as: underweight (< 19.9), normal (20.0-24.9),overweight (25.0-29.9)or obese (> 30.0) 13 .Total maternal weight gain during pregnancy was recorded on admission to delivery ward.
Blood pressure measurements at all clinic sites were taken according to a standardized published protocol, and all urine specimens were assessed for protein using dipsticks.
Mild preeclampsia was defi ned by the occurrence of two or more systolic blood pressure readings  140 mmHg and/or diastolic pressure  90 mmHg, with the fi rst elevated blood pressure occurring after 20 weeks of gestation up to 24 hours after delivery, combined with proteinuria of at least 0.3g or "1+ protein" per 24 hours 14,15 .
Severe preeclampsia was defi ned as a systolic blood pressure of 160 mmHg or greater and a diastolic blood pressure of 110 mmHg or greater on at least two occasions at least 4 hours apart or on one occasion if antihypertensive therapy was administered.Severe proteinuria was defi ned with a 24-hour urine sample containing  3.5 g of protein or two urine samples of "3+ protein" or greater, taken at least 4 hours apart.The syndrome of haemolysis, elevated liver enzymes, and low platelets and eclampsia was also categorized as severe PE 14,15 .

Statistical analysis
Quantitative data are presented as mean ± standard deviation and relative number of subjects in each category Student's t test, chi-square test and Spearman correlation coeffi cient, were used to evaluate the statistical signifi cance of differences between normal and preeclamptic patients.For all comparisons, two-tailed tests were accepted as signifi cant when p < 0.05.

Results
Table 1 shows the demographic and clinical characteristics of the women studied.Normo-tensive and preeclamptic women had similar age and parity.
There was a decreased risk of mild and severe preeclampsia among women who smoked during pregnancy.The impact of smoking on preterm delivery and/or lower birth weight was not analyzed.
Women who developed preeclampsia had higher rates of overweight prior to pregnancy and gained more weight during pregnancy.Mean weight gain during pregnancy in control and preeclamptic women was 13.9 ± 3.1 and 19.8 ± 5.2 kg, respectively (p < 0.01).
Women with preeclampsia had signifi cantly shorter gestations than their controls (p < 0.01) and their offspring had a lower weight and length at birth.
Blood pressure values, especially diastolic and mean pressure had a direct correlation with the severity of preeclampsia.

Discussion
Preeclampsia is a major cause of maternal and neonatal morbidity and mortality worldwide, although the etiology of preeclampsia is still unclear.Some studies concluded that the major phenotype of PE, hypertension and proteinuria, may be due to an excess of circulating antiangiogenic growth factors, most notably soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng) 10,16 .The main focus of PE and its symptomatology is arterial hypertension.Diastolic blood pressure, related to arteriolar spasm, causes a permanent damage of blood circulation and has a primary infl uence in the disease.Recommendations adopted by the WHO state that systolic pressure is more variable than diastolic pressure and that itdoes not make any contribution toward the diagnostic or prognostic signifi cance of the hypertensive disorders of pregnancy.There is little evidence to support this asseveration 17 .
The importance of blood pressure measurements during pregnancy has been recognized for more than a century (Seligman, 1987) and is a fundamental part of antenatal care.For many women their pregnancy will be the fi rst point of medical contact and they may have been unaware of any pre-existing hypertension up to this point 18 .By design, the groups in our study did not differ by age.The percentage of nulliparous women was signifi cantly higher among those with PE.Women with less educational attainment had a higher risk of PE.Macedonian women had a lower risks of PE, compared to Muslims (Albanians and Turks).However, Muslim women had also a lower degree of education; twenty fi ve of 31 were housewives and 23 had less than 8 years of education.
According to previous publications, PE is more common in patients who during were performing heavy physical activities pregnancy and in profes-Características demográficas de pacientes con pre eclampsia -E.Jasovic-Siveska et al Rev Med Chile 2011; 139: 748-754 sional workers, which may be related to stressful situations 11,12 .In our study, PE developed more often in housewives.Moreover, a lower level of education increased the risk of developing PE.
It is well known that smoking is a strong and common risk factor for low birth weight.Smoking seems to be negatively associated with PE.Thus, adjusting for smoking would increase rather than decrease the effect of PE in infants' weight 14 .
Women who developed preeclampsia had higher rates of overweight prior to pregnancy and gained more weight during pregnancy.These fi ndings confi rm previous fi ndings that prepregnancy BMI is a strong independent risk factor for preeclampsia.Infl ammation and lipids levels at fi rst and second trimesters may be important mediators of the BMI-preeclampsia association.
In the present study, PE was associated with lighter, shorter and leaner newborns, compared to newborns from normal pregnancies.These results are similar to previous reports in the literature 19,20 .
We found marked differences in blood pressure between groups.However it must be emphasized that these differences were present even before the onset of PE (before 20 weeks of gestation).
Cnossen SJ et al (2008), reviewed 34 studies including 60,599 women, among which 3,341 had preeclampsia.They focused their review on diastolic and mean blood pressure but not on systolic pressure.They concluded that a diastolic blood pressure over 75mmHg in the period of 13-20 wg, had predictive importance.They also concluded that in the same period, mean arterial pressure values over 85-90 mmHg also had predictive importance for the development of PE, which was also the case in our research 21 .
After childbirth, blood pressure between groups did not differ.This proves that delivery is the only real cure for pre-eclampsia.
Early diagnosis of hypertension has important implications for the management and prognosis of both the mother and the fetus.It is dependent on the accurate measurement of blood pressure, as hypertension is often the only early sign of impending PE.It is not, however, necessarily indicative of PE or eclampsia 21 .
Our study has limitations.We did not assess the combined effects of smoking and weight among women developing preeclampsia.We did not investigate and analyze the effect of diet, physical activity and the use of vitamin supplements during pregnancy.
Based on our results we stress that preeclampsia develops more frequently in primiparas.Housewives, illiterate women and women with lower education levels have the higher risk.The development of PE is preceded by obesity.The measurement of blood pressure can be used to predict the development of PE since there are differences between hypertensive and normotensive groups even before the onset of PE.To reduce the level of perinatal morbidity and mortality in PE, a regular and organized surveillance of every pregnancy is necessary.With better antenatal protection, we can infl uence perinatal morbidity and mortality.

Table 2 .
Average values of systolic blood pressure (mmHg)

Table 3 .
Average values of diastolic blood pressure (mmHg) † Student's t test.