| Abstract|| |
In view of continuous controversies regarding hypertension in pregnancy and lack of reports on this subject in Saudi Arabia, we retrospectively studied 135 episodes of hypertension in pregnancy in 123 patients over a 9-years period. Fifty-one (37.8%) were primiparas, the remaining were multiparas from 2 nd up to 14 11 pregnancy. Of the multiparas, 44% had a history of pregnancy induced hypertension, 26% of chronic hypertension, and 13% of diabetes mellitus. " HELLP"-syndrome occurred in nine and eclampsia in four pregnancies. There were 10 foetal deaths, eight of them presented on admission. Chronic hypertension and diabetes mellitus approached significance as risk factors for foetal death (logistic regression analysis). For the whole group, the time of delivery was the only factor with significant impact on the Apgar score (multiple regression analysis), with an additional negative influence of diabetes mellitus and intravenous hydralazine in the multiparas. When the patients with chronic hypertension and diabetes mellitus were not included, hydralazine lost its significance. The finding suggests that intravenous hydralazine should be given in multiparas with caution, particularly in the presence of chronic hypertension and diabetes mellitus. There was a significant relation of the birth weight to the time of delivery, the serum levels of total protein and, especially in multiparas, of uric acid, confirming the importance of these factors as markers of the severity of pregnancy induced hypertension. The hypertension persisted in patients not known to have chronic hypertension in 9.6% of pregnancies during a follow-up ranging from 2 months up to 9 years.
Keywords: Preeclampsia, Antihypertensive agents, Foetal outcome, Hydralazine, Apgar score.
|How to cite this article:|
Hussein MM, Mooij JM, Roujouleh H. Hypertension in Pregnancy: Presentation, Management and Outcome - A Retrospective Analysis of 135 Cases. Saudi J Kidney Dis Transpl 1998;9:416-24
|How to cite this URL:|
Hussein MM, Mooij JM, Roujouleh H. Hypertension in Pregnancy: Presentation, Management and Outcome - A Retrospective Analysis of 135 Cases. Saudi J Kidney Dis Transpl [serial online] 1998 [cited 2020 May 29];9:416-24. Available from: http://www.sjkdt.org/text.asp?1998/9/4/416/39099
| Introduction|| |
Preeclampsia is one of the major causes of maternal and foetal morbidity and mortality worldwide and develops in 5-10% of all pregnancies.  Although extensive research has been done, the pathogenesis of preeclampsia remains unclear. Current theories include utero-placental ischemia, imbalance in the production of vasodilating and vasoconstricting prostaglandins, deficiency of nitric oxide, sympathetic overactivity and vascular endothelial dysfunction, while immunological factors and coagulation abnormalities are also implicated ,,,,,, .
There is also still discussion about its definition. While the American College of Obstetricians defined 3 rd trimester pregnancy induced hypertension as a blood pressure of 140/85 mm Hg or above, sustained over a period of 4-6 hours  , the International Society of the Study of Hypertension in Pregnancy in 1988 classified it as two consecutive measurements of DBP of 90 mm Hg or above after the 20 th week of pregnancy.  Redman and Jefferies in 1988 defined criteria for preeclampsia as the combination of a first diastolic pressure (in the first half of pregnancy) below 90 mm Hg and a subsequent increase of at least 25 mm Hg.  Pregnancy induced hypertension is defined as a blood pressure of 140/90 mm Hg or greater after the 20 th week of pregnancy. 
The management of hypertension in pregnant women also continues to raise controversy.  In view of these controversies and because of lack of reports about the spectrum of pregnancy induced hypertension in the Kingdom of Saudi Arabia; we decided to study our own experience with this condition in a single center over a nine-year period.
| Methods|| |
The medical records of all in-patients with the diagnosis of hypertension in pregnancy from 1988 up to the end of 1996 were reviewed. There were 123 evaluable patients. The patients were included in the study if the diastolic blood pressure recorded during pregnancy, labor, or puerperium was on more than one occasion 90 mm Hg or above. ,
The following parameters were studied, for the whole group of patients as well as for primiparas and multiparas separately: age of the patient, the number (primipara, multipara) and type of pregnancy (cephalic, breech presentation, twins, etc.), history of chronic hypertension, diabetes mellitus, preeclampsia in the past. The time of presentation of preeclampsia, the systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the time of presentation of preeclampsia, and the maximum SBP and DBP recorded during the follow-up.
The laboratory parameters studied were: serum creatinine and uric acid level, platelets count, liver function tests (serum aspartate and alanine aminotransferases; SGOT and SGPT), serum total protein and albumin level, urine protein (dipstick, and if positive, the 24-hours urine protein excretion).
Antihypertensive treatment was in general aimed for a blood pressure of 140/90 mm Hg. The antihypertensive medication given to reach that goal was reviewed. If the pregnancy was near term, delivery was indicated. In earlier stages an expectant policy was followed. However, if the blood pressure could not be controlled within 24-48 hrs or in cases of severe foetal distress, or if there were other clinical indications, termination of the pregnancy was considered. Patients did not routinely receive low-dose aspirin.
The time and the type of the delivery (spontaneous delivery, caesarean section, etc.) were recorded as well as the foetal outcome (birth-weight and Apgar score at one and five min). In the cases of twin or triplets pregnancy, the mean values of birthweights and Apgar scores of the neonates were recorded. We also followed up the mothers post delivery for persistence of hypertension. Persistent hypertension was defined as hypertension, which continued for more than two months after delivery in patients not known to have chronic hypertension prior to the delivery? 
Primiparas and multiparas were compared regarding the above parameters using one way analysis of variance for groups of factors, and Mann-Whitney-U-test and chi-square analysis for individual parameter.
The correlation of the following factors: age, number of pregnancy, presence of chronic hypertension or diabetes mellitus, preeclampsia in the history, time of presentation of preeclampsia and delivery, presence of proteinuria, the minimum platelet count, total serum protein and albumin level, the maximum level of serum creatinine, uric acid and SGOT, the maximum recorded SBP and DBP, and the antihypertensive treatment, to the outcome foetal death was analyzed with step wise-forward logistic regression analysis, and to the Apgar score (at 1 and 5 minutes) and to birth-weight with multiple regression analysis. This was done for the whole group of patients, as well as for primiparas and multiparas, separately.
The maximum SBP and DBP among the different treatment groups (nifedipine, methyldopa, intravenous (i. v.) hydralazine, atenolol and labetalol) were compared using a simple factorial analysis of variance followed by least-significant difference (SPSSPC 6.0; 1993; SPSS Inc, Chicago, 111. USA).
| Statistical Methods|| |
Values are given as mean ± standard deviation (SD). The level of significance was set at p < 0.05. Mann-Whitney and chisquare tests, besides simple factorial analysis of variance followed by least-significant difference, were used where appropriate.
| Results|| |
One hundred thirty-five pregnancies with episodes of hypertension in 123 patients were reviewed. Eight of the patients had preeclampsia in two pregnancies and two patients in three pregnancies.
Values for the whole group of patients as well as for primi- and multiparas separately are given in [Table l]a, b. Fifty one episodes (37.8%) were seen in primiparas, the remaining presenting in multiparas, from 2 nd up to 14 th pregnancy. The age at presentation ranged from 16-51 year with the highest frequency found in the 25-29 five year age cohort (n = 37; 27%). The age of the multiparas was expectedly significantly higher than that of the primiparas. The time of presentation ranged from 21-42 weeks with the median at 37 weeks. One hundred and twenty-two pregnancies (90.4%) had a normal (cephalic, singleton) type of pregnancy, with twin and breech presentations in five pregnancies (3.7%) each. There were single pregnancies of triplets, transverse and footling presentation.
In 23 pregnancies (17%) there was a previous history of chronic hypertension, and in 14 pregnancies (10.4%) of diabetes mellitus. The number of multiparas with known chronic hypertension was significantly higher compared to the primiparas. Thirtyseven of the 84 multiparas patients with preeclampsia (44%) had a history of preeclampsia in previous pregnancies.
The SBP at the time of presentation ranged from 110 - 224 mm Hg with a mean of 153 ± 24 mm Hg and DBP at presentation from 70-140 mm Hg with a mean of 99 ± 13 mm Hg. The maximum SBP during the hospital stay ranged from 120 - 250 mm Hg with a mean of 173 ± 25 mm Hg and the maximum DBP from 90 - 140 mm Hg with a mean of 110 ± 13 mm Hg.
Dipstick for proteinuria was done in 121 cases and was found to be positive in 103 (85.1%). In 50 pregnancies, a quantitative measurement was done: the excretion of protein ranged from 0.1 to 18.5 gm per 24 hours with a mean of 2.70 ±3.16 gm. Oedema was present in 39 pregnancies (28.9%) and absent in 38 pregnancies (28.1%). It was not recorded in 58 pregnancies (43%).
Platelets count was performed in 111 pregnancies. Low platelets count (less than 100 x 10 9 /I) was found in five pregnancies (range 37-76 x 10 9 /l) at presentation and in eight more pregnancies during the followup, making the total number 13 or 11.7% of the patients who had platelets measured. Liver function tests (SGOT and SGPT) were measured in 84 patients. Increased values (SGOT and SGPT more than twice the normal level or > 60 IU/1) were found in 13 pregnancies (15.5% of the patients with measured liver function tests) with the maximum levels being 82-1380 IU/1 and 89-582 IU/1, respectively. Nine pregnancies (7%) presented with the so-called "HELLP"syndrome.
The total protein and albumin concentrations were measured in 88 patients and ranged from 38 to 74 g/1 and 19 to 43 g/1, respectively, with the mean value of total protein: 56 ± 8 g/1 and of albumin: 30 ± 5 g/1. The serum total protein and albumin levels were lower in the primiparas compared to the multiparas.
The maximum uric acid concentration ranged from 0.20 to 0.75 mmol/l with a mean of 0.38 ± 0.10 mmol/L. Four patients (3%) developed eclampsia. The antihypertensive medication the patients received (single treatment or in combination) is shown in [Table - 2]. Primiparas and multiparas did not differ in the medication given (chi-square tests). Twenty-seven patients (20%) received in addition to the regular treatment, one single dose of nifedipine (10 mg) sublingually. No significant difference in antihypertensive treatment between primiand multiparas (chi-square test).
In the majority of the patients (n=74; 55%) delivery was performed by caesarean section, with normal, spontaneous delivery in 45 cases (33.3%). There was no difference in the number of caesarean sections performed in primi- and multiparas [Table l]a and b. In 11 patients (8.1%) vacuum extraction was done, and in five patients delivery was with forceps (3.7%).
The time of delivery ranged from 21-42 weeks with the median at 38 weeks. The birth-weight ranged from 610-4500 gm with a mean of 2,260 ±913 gm.
There were 10 cases (7.4%) of perinatal death occurring in nine mothers. Eight of them presented with foetal death on admission (all of them multiparas) and two cases died of perinatal distress during hospital stay (both primiparas).
None of the cases with the "HELLP"syndrome resulted in perinatal death. There was one case of maternal death, which was due to late presentation and hypoxia whilst the patient was being prepared for caesarean section.
There was follow-up for more than two months after delivery in 116 patients. Ninetyeight of these patients were not known to have chronic hypertension and in 13 of them (13.3%) the hypertension persisted after the delivery (nine in multiparas and four in primiparas).
Factors Influencing Foetal Death
When the influence of the factors: age, number of pregnancy, presence of chronic hypertension or diabetes mellitus, preeclampsia in the history, time of presentation of preeclampsia and delivery, presence of proteinuria, the minimum platelet count, minimal total serum protein and albumin level, the maximum level of uric acid and SGOT, the maximum recorded SBP and DBP, and the antihypertensive treatment, on the occurrence of foetal death was analyzed with (stepwise forward) logistic regression analysis, only the factor "history of chronic hypertension" approached significance: p=0.0647. In the multiparas separately, diabetes mellitus approached significance: p=0.0664.
Factors Influencing Apgar Score
When the influence of the same factors on the Apgar score at 1 and 5 minutes was analyzed with (stepwise) multiple regression analysis, only the factor: time of delivery (p=0.0007 and p=0.0018, respectively) had a significant (positive) influence. This held true for both primiparas and multiparas, separately. In multiparas the factors diabetes mellitus and i. v. hydralazine had an additional significant and negative influence, both for the Apgar score at one and at five minutes (for diabetes mellitus: p=0.0031, p=0.0018, and for i. v. hydralazine: p=0.0180 and p0.0436, for Apgar one and Apgar five, respectively).
When in the multiparas group the patients with history of chronic hypertension and diabetes mellitus were deleted, hydralazine lost its significance.
Factors Influencing Birth-weight
In the whole group of patients, the multiple regression analysis revealed a positive correlation of the birth-weight with the time of delivery (p=0.0000) and with the serum total protein concentration (p=0.022), and a negative correlation with the serum level of uric acid (p^0.0368). In the primiparas separately, only the factor time of delivery had a significant impact on the birthweight.
In the multiparas group, the negative impact of the uric acid level was more pronounced (p=0.0003) compared to the whole group of patients.
Comparison of maximum SBP and DBP among different treatment groups
In the primiparas, no difference was found in the SBP and DBP between the patients receiving five different medications.
In the multiparas, the maximum SBP did not differ among different treatment groups. However, the mean maximum DBP was highest in the patients receiving i. v. hydralazine and nifedipine p.o., with significantly lower DBP levels in the methyldopa, atenolol and labetalol group [Table - 3].
| Discussion|| |
We reviewed 135 cases of hypertension in pregnancy encountered over a nine-year period. Of this total number, 37.8% occurred in primiparas and 62.2% in multiparas (up to the 14 th pregnancy). Some experts claim that "pure" preeclampsia' is essentially a disease of primiparas and that preeclampsia in multiparas is in fact chronic hypertension, with or without superimposed preeclampsia.  In our study group, 74% of the multi-paras with preeclampsia had no known history of chronic hypertension and in 86.3% of them the blood pressure returned to normal after delivery, which suggests that the hypertension was "pregnancy-induced" in a majority of multiparas.
Confirming previous report  , a positive history of preeclampsia in previous pregnancies was found to be an important risk factor for the development of preeclampsia, as this was observed in 44% of our multiparas.
The course of preeclampsia in multiparas might be quite serious, as seven of the nine patients who presented with "Hellp"-syndrome, were multiparas, see [Table - 1]. Eclampsia was, however, more prevalent in primiparas (three of the four cases of preeclampsia were primiparas).
If the blood pressure was not controlled within 24-48 hrs after admission, and with other clinical indications, termination of the pregnancy was considered, which resulted in caesarean section performed in 54.8% of the cases.
Of the ten cases of foetal death, eight presented on admission and only two occurred during hospitalization. The patients who presented with foetal death on admission were all multiparas, of whom seven were found to have a history of chronic hypertension. This seems to confirm previous findings reporting a high risk for the foetus in gravidas with a history of chronic hypertension, , although in our study the correlation of foetal death with chronic hypertension did not reach significance in the logistic regression analysis. Superimposition of diabetes mellitus and preeclampsia in multiparas with chronic hypertension significantly worsened the foetal prognosis, as four out of the eight foetal death that occurred in multiparas, were in this group of patients. Poor control of the hypertension and/or diabetes mellitus in the patients, who presented with foetal death on admission, cannot be excluded.
As would be expected, the duration of pregnancy before the delivery was the most important parameter influencing the Apgar scores. However, in the multiparas, the presence of diabetes mellitus and the administration of i.v. hydralazine had both an additional negative impact. This effect of i.v. hydralazine was not seen in primiparas and with the other antihypertensive agents studied: labetalol, methyldopa, nifedipine, and atenolol. A possible explanation for the negative effect on the Apgar score in patients on i. v. hydralazine might be that the preeclampsia in these patients was more severe, which by itself could be the reason of the increased foetal distress. As seen in [Table - 3], the maximum DBP in the patients on i.v. hydralazine was higher than in those receiving methyldopa, atenolol and labetalol. However, there was no significant difference in DBP between the patients on i.v. hydralazine and nifedipine, and the multi-regression analysis did not show a negative effect of nifedipine on the Apgar score. In addition, the maximum DBP was included in the multi-regression analysis and, unlike i.v. hydralazine, failed to show a significant correlation with the Apgar score. These findings suggest that the factor i.v. hydralazine probably has an independent (and negative) impact on the foetal outcome in multiparas.
Intravenous hydralazine is generally recommended as the first line of treatment for severe preeclampsia. , However, this is based on studies comprising primiparas and multiparas together. As mentioned in [Table - 1], primiparas and multiparas differed, besides in age, in the presence of chronic hypertension and diabetes mellitus, suggesting that the incidence of vascular disease in multiparas is higher. In multiparas, the uterine-placenta circulation might therefore be more sensitive to the blood pressure lowering effects of i.v. hydralazine. In one prospective study comparing nifedipine  and i.v. hydralazine, acute foetal distress was found in 11 of 25 patients treated with hydralazine compared to only in one out of 24 patients given nifedipine.  Also Walker mentions the reduced placental blood flow and foetal distress associated with acute administration of i.v. hydralazine.  The continuous infusion of hydralazine has been found to cause a high incidence of foetal distress.  Our finding seems to indicate that i.v. hydralazine should be given with caution in multiparas, especially in patients having chronic hypertension or diabetes mellitus. However, as our study is a retrospective one with a relatively small number of patients, it should be confirmed in a larger study with prospective design.
The main factor influencing the birthweight was, as expected, the duration of pregnancy. However, there was also a positive correlation between birth-weight and the serum level of total protein, and a negative correlation between birth-weight and the serum uric acid, especially in multiparas. The serum level of uric acid is known to be an indicator of the seventy of preeclampsial"3'5 and intra-uterine foetal growth retardation is one of the main complications of preeclampsia. The strongly negative correlation between uric acid and birth-weight in multiparas seems to indicate that in multiparas the serum uric acid level is more sensitive as a preeclampsia marker than in primiparas.
The correlation of birth-weight with serum total protein concentration is probably a reflection of the correlation between foetal outcome and proteinuria. Friedman and Neff, studying over 32,000 pregnancies, reported an increase in perinatal mortality and intra-uterine growth retardation associated with proteinuria.
In the patients not known to have preexistent hypertension and who were followed for more than two months after delivery, persistent hypertension was found in 13.3% of the cases. Reports in the literature give conflicting figures. In a study from Sweden, 37% of patients with a history of preeclampsia developed chronic hypertension at a follow-up of seven years, compared with 2% in patients after a normotensive pregnancy. 
In the Samoan population in the Pacific's, however, with a high incidence of preeclampsia, non-insulin diabetes mellitus and cardiovascular events, hypertension persisted in 40% after preeclampsia, and in 2% in a control group.  In a recent prospective study from Italy, only six out of 100 patients with preeclampsia who underwent a later blood pressure measurement showed abnormal values of diastolic blood pressure.  The difference in these findings might be explained by the period of follow-up: which was seven years in the Swedish study, while in the Italian report the patients were followed for only 90-180 days. In our study the follow-up ranged from two months to nine years.
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Magdi M Hussein
Department of Nephrology, AI Hada Armed Forces Hospital, P.O. Box 1347, Taif
[Table - 1], [Table - 2], [Table - 3]