Labetalol in Comparison to Methyl Dopa in Treatment of Gestational Hyperten- sion, A Randomized Trial

Volume 4 | Issue 1 Labetalol in Comparison to Methyl Dopa in Treatment of Gestational Hypertension, A Randomized Trial Mahmoud Alalfy*1, E.Eltaieb2 and Mahmoud.Soliman3 1Assistant Researcher, Reproductive Health and Family Planning Department, National Research Centre, Egypt, Specialist of Obstetrics and Gynecology at Aljazeerah Hospital, Egypt 2Lecturer in Obstetrics and Gynecology, Ain Shams University, Egypt 3Lecturer, Obstetrics and Gynecology Department, Kasralainy Faculty of Medicine, Cairo University, Egypt *Corresponding author: Mahmoud Alalfy, Assistant Researcher, Department of Reproductive Health and Family Planning, National research Centre, Egypt, Tel: +2 1002611058, E-mail: mahmoudalalfy@ymail.com Citation: Mahmoud Alalfy, E.Eltaieb, Mahmoud.Soliman (2018) Labetalol in Comparison to Methyl Dopa in Treatment of Gestational Hypertension, A Randomized Trial. J Gynecol Res 4(1): 101. doi: 10.15744/2454-3284.4.101


Introduction
Hypertension is the most frequent disorder that happens in gestation [1]. Hypertensive problems comprise around ten percent of pregnancy and are one of the chief factors that can cause death to mothers and fetuses [2].
Conclusion: Labetalol is more safe, has lesser side effects on the mother and the neonate has a more rapid action in obtaining enough control of pressure with significant lengthening of the period of pregnancy if it is used in treatment of pregnancy complicated with hypertension.
Results: A labetalol is very effective in controlling blood pressure and has earlier onset of action than methyldopa. Labetalol is very efficient in managing blood pressure, avoiding preeclampsia and eclampsia with statistically significant values in reducing Blood pressure in comparison to methyldopa with s P value less than 0.05 and increasing the length of pregnancy to reach fetal maturity. Labetalol has lower side effects than methyldopa. There is no difference in the 2 drugs as regard obstetric interference. Both drugs are safe for the neonate.
Pressure. There are no available data that indicate any hazardous effect on the off springs in the Methyldopa treated patients. When methyldopa is given in high doses, the sedative and depressant effects of methyldopa are noted. Methyldopa should not be used if there is a risk of maternal depression where a beta-blocking drug or calcium channel blocker can be more appropriate. Labetalol has a better treating efficiency in controlling blood pressure when compared to other anti-hypertensive drugs [12].
Labetalol is a mixed alpha and beta-blocking medication and has the advantage over other beta blockers as it has an extra arteriolar vasodilating effect that helps to decrease peripheral vascular resistance with a slight or no decrease in cardiac output.
Advantage of labetalol is its availability in an injectable and oral form and the time to start its action is earlier than methyldopa [12].
However now, it is known that b-blockers cross the placental barrier and may cause a decrease in fetal heart rate.
Experimental evidence also suggests that β-blocking drugs decrease fetal affordability to hypoxic stress [12].

Patients and Methods
A Double blinded randomized controlled trial superiority with allocation ratio 1:1.

Study design
Study Settings was carried out in multicentres at Ain Shams University maternity hospital in collaboration with kasralainy maternity hospital and National research centre, Egypt and Aljazeerah hospital, Egypt.
The study was conducted in the period from 5 January 2017 till 10 december 2017.

Study duration
Inclusion and exclusion criteria.

Eligibility criteria
Inclusion criteria: 1. Pregnant women aged 22-40 years. 2. Gestational age between 24 and 34 weeks. 3. Blood pressure greater than or equal to 140 mm Hg systolic or greater than or equal to 90 mm Hg diastolic or more after blood pressure measurement on 2 occasions with 4 hours apart in a previously normal blood pressure. 4. Patients were kept in house with regular follow up visits.
Exclusion Criteria: 1. Pregnant women with underlying chronic hypertension, history of antihypertensive medication before 20 week gestation and secondary hypertension. 2. Patients with molar pregnancies, multiple pregnancy, placenta previa. 3. Pregnant women with renal disease, hematological disease, heart disease.

Intervention
Randomized in to 2 groups. Group A will receive labetalol and group B will receive alpha methyldopa then measure BP.

Subjects
Study group: 264 women attending Ain Shams University maternity hospital. Patients were distributed in two groups randomly. After randomization group A received labetalol 100 mg tid and group B received methyldopa 250 mg tid as starting dose. Mean Arterial pressure (MAP) was calculated.
Patients were kept in house and they were asked to come for regular follow up in the antenatal clinic in a fixed visits where Patients were monitored in the antenatal clinic after 48hrs from taking the drug and dose was assessed to control BP When there was no fall in BP even after 48 hours of drug therapy, dose of the drug was doubled. Then monitored in the antenatal clinic weekly for two weeks. Then every 2 weeks till delivery.

Measurement of BP
Auscultatory measurement with the sphygmomanometer is the most widespread method for indirect BP determination, having a high concordance level with the direct intra-arterial method.

Methods
Randomization: Randomization of cases was done by computer method. 264 women with pregnancy induced hypertension were enrolled in the study and were distributed in two groups:group A and group B. The randomization allocation was 1:1.The two groups are randomly selected.
Allocation and Concealment: 264 opaque envelopes were numbered serially and in each envelope the corresponding letter which donate the allocated group was put according to randomization table then all envelops were closed and put in one box. When the first patient arrives the first envelope was opened and the women were allocated according to the letter inside.

Sample size: Sample Size Calculation
The required sample size has been calculated using the G*Power Software (Universität Düsseldorf, Germany). The primary outcome measure is the proportion of patients with adequate control of blood pressure at 48 hours from starting treatment, defined as systolic blood pressure <140 mmHg and diastolic blood pressure <90 mmHg. The secondary outcome measure is the proportion of patients that would undergo spontaneous onset of labor. There is at present no adequate information regarding the expected difference in the outcome measures between labetalol and methyldopa in patients with gestational hypertension. So, the present study tries to target an effective size that would be clinically relevant.
The study was conducted after approval of the ethical committee of Ain Shams University Maternity Hospital. Patients signed an informed consent to participate in the study.      Table 3: Comparison between systolic blood pressure measurements starting before treatment (baseline) overtime till delivery in methyldopa group    Table 5: Comparison between diastolic blood pressure measurements starting before treatment (baseline) overtime till delivery in methyldopa group   Table 7: Comparison between mean arterial blood pressure measurements starting before treatment (baseline) overtime till delivery in methyldopa group

Discussion
PIH is a major cause of fetal and maternal morbidity and mortality and protection from its development is not always possible as its pathology is not completely predictable .Various medications are used in controlling hypertensive abnormalities during pregnancy [13].
In a Study made by Verma et al. denoted that adverse outcome was evidently less in the labetalol treated pregnant women compared to the methyldopa group [10].
In the present study, there is a decrease in the systolic blood pressure readings starting from a baseline which was the blood pressure before intake of the antihypertensive treatment and the measurements after 48 hours, 1, 3, 5, 7, 9 weeks after drug intake and at time of delivery in the methyldopa and labetalol group.
Verma et al. made a study and mentioned the age distribution which showed maximum patients between 19-24 years in both groups (64.44% in methyldopa group and 57.77% in labetalol group) and there was no significant difference in age distribution in both groups [13].
In the present study, there was a decrease in the diastolic blood pressure readings starting from a baseline which was the blood pressure before intake of the antihypertensive treatment and the measurements after 48 hours, 1, 3, 5, 7, 9 weeks after drug intake and at time of delivery in the methyldopa and labetalol group.
Most common age group is in contrast to the data obtained from a large database study indicate a linear relationship between age and incidence of PIH [15].
In the present study, there was a decrease in the mean arterial blood pressure readings starting from a baseline which was the blood pressure before intake of the antihypertensive treatment and the measurements after 48 hours, 1, 3, 5, 7, 9 weeks after drug intake and at time of delivery in the methyldopa and labetalol group.
In the present study, our results show a statistically significant difference in control of blood pressure with values of systolic, diastolic and mean arterial blood pressure measurements are less in labetalol group than in methyldopa group after 48 hours, 1, 3, 5, 7, 9 weeks post drug therapy and at time of delivery with P value < 0.001 indicating a better control of blood pressure.
Labetalol is an effective antihypertensive drug which decreases both systolic and diastolic BP in pregnancy induced hypertension. About 55% of the methyldopa group received nifedepine and phenobarbitonewhere as only 22.5% of labetalol group received injections of labetalol and phenobarbitone showed that methyl dopa requires additional drugs to decrease BP than labetalol [18].
In a study made by Dharwadkar MN et al. about 32.5 percent of the pregnant ladies in Methyldopa group and 37.5% in Labetalol group were primigravidae. The rest of the patients were multigravidae. However the percentage of primigravidae is greater in most other studies where the prevalence of primigravidae was 50% or above [16,17,22].
In a previous study demonstrated that labetalol is an efficient drug in decreasing blood pressure of the patients and then maintain optimal BP levels [22]. Volume 4 | Issue 1

Journal of Gynecology Research
Marked decrease of both systolic and diastolic pressure within 24 and 48 hours from the onset of using methyldopa was observed by Hans and Kopelman [21].
Also in the present study, there was a considerable difference in pregnant women who developed proteinuria after the same dose of treatment by both drugs, as in the group of women received methyldopa there was 8 ladies developed proteinuria checked at time of delivery while in labetalol there was only one lady who had proteinuria at time of delivery with P value of 0.036 ,indicate a statistically significant value that denotes better control of arterial blood pressure and prevention of progression to preeclampsia with labetalol than with methyldopa treatment.
Future researches can be made on a larger number of pregnant women to compare various drugs used in treatment of hypertension.

Conclusion
The present study confirms that labetalol is an effective and safe drug for use and is more rapid in achieving adequate control of blood pressure in PIH. With a low chance of fetomaternal side-effects and this makes it appropriate to be used in PIH. Labetalol gives good control of blood pressure than methyldopa and decreases the liability for proteinuria and for progression to preeclampsia.
Labetalol has the advantage of decreasing peripheral vascular resistance with no decrease in cardiac output of the mother and heart rate and so better uteroplacental perfusion than methyldopa.