Background: Complications of hypertension are the third leading cause of pregnancy relaed deaths, superseded only by hemorrhage and embolism. Pre-eclampsia is associated with increased potential risks of placental abruption, acute renal failure, cerebrovascular and cardiovascular complications, disseminated intravascular complication and maternal death. Consequently, early diagnosis of pre-eclampsia and close observation and timely drug intervention is needed. Labetalol is generally considered to be more effective than methyldopa for treating pre-eclampsia and pregnancy-induced hypertension (PIH) and Labetalol is quicker and more effective at controlling blood pressure and causes fewer side effects than methyldopa. Drowsiness is a common side effect of methyldopa. And also, Labetalol has a beneficial effect on renal function, ripening effect on the uterine cervix, decreases proteinuria/preeclampsia and decreases fetal/newborn death compared with methyldopa.1 Methyldopa is the medicine of choice for hypertensive conditions in pregnancy in several countries. Despite this, there is little proof of its safety in early pregnancy. So far, most methyldopa safety studies have focused on therapy during the second and third trimesters2,3,4. Thus this study was planned to know the efficacy of the two commonly used drugs comparatively in our set up. Research Question: What is the efficacy of the drugs Labetalol Vs Methyldopa on obstetric outcome in women with pre-eclampsia? The setting of the study was at department of Obstetrics and Gynaecology, Government Medical College, Machilipatnam. A one year observational study was conducted during the period from March ,2023 to February, 2024 on about 200 Pre-eclampsia patients admitted during the above period in the department of Obstetrics and Gynaecology by studying their socio-demographic profiles, type of hypertensive disorders, mode of delivery & preterm or term delivery, maternal complications and evaluation of efficacy of the drugs Labetalol and Methyl Dopa comparatively etc ; Results: The disease was more among the pregnant women between 21-25 years of age group (49.5%) and the Mean age was 52 years and very few about 3% was observed among >31 years of age group. And most of them are primigravidae. And also, majority of the study subjects were belonging to low socioeconomic group & early marriages (adolescent marriages) were also high in number. There was a significant reduction of Blood Pressure noticed by both the drugs but the more significant reduction was seen among those treated by Labetalol. And also, significantly (P<0.05), about 32% of spontaneous vaginal deliveries happened with Labetalol users when compared to 20% among Methyldopa users & 25% induced deliveries with Labetalol as against 21% with Methyldopa and also significantly 43% LSCS with Labetalol as against 59% LSCS with Methyldopa but totally among both the groups LSCS was little bit more happened among the study subjects. Further it was observed that Preterm deliveries were only 23% with Labetalol as against 40% with Methyldopa which was highly significant (P >0.001). With reference to Birth weight LBW babies were more among Methyldopa users (55%) when compared Labetalol users (50%).
It is known that pre-eclampsia, which occurs most often after 20 weeks of gestation and frequently near term, is one of the most severe complications of pregnancy and a leading cause of maternal and perinatal morbidity and mortality5. Worldwide, an estimated 4 million women are being diagnosed with pre-eclampsia (previously called toxaemia) each year, causing the deaths of >70,000 women and 500,000 babies5,6 Women who survive from pre-eclampsia have reduced life expectancy with increased risks of stroke, cardiovascular disease and diabetes5,7,8, while babies from a pre-eclamptic pregnancy have increased risks of preterm birth, perinatal death, neurodevelopmental delay, and cardiovascular and metabolic disease later in life5,7. Worldwide, >300 million women and children are estimated to be at increased risk of chronic health problems due to previous exposure to pre-eclampsia9. And Pre-eclampsia is associated with complications such as eclampsia (seizures), haemorrhagic stroke, haemolysis, elevated liver enzymes and low platelet count (HELLP)syndrome, placental abruption, renal failure, and pulmonary oedema10,11. Pre-eclampsia may be related to problems with the placenta early in the pregnancy.12 Such problems pose risks to the fetus, including:Lack of oxygen and nutrients which can impair fetal growth. Preterm birth and Stillbirth happened if placental abruption leads to heavy bleeding in the mother. Infant death13 and Stillbirths are more likely to occur when the mother has a more severe form of preeclampsia, including HELLP syndrome. Consequently early diagnosis of pre-eclampsia followed by close observation and timely drug intervention is needed. Labetalol is generally considered to be more effective than methyldopa for treating pre-eclampsia and pregnancy-induced hypertension (PIH) and Labetalol is quicker and more effective at controlling blood pressure and causes fewer side effects than methyldopa. Drowsiness is a common side effect of methyldopa. And also Labetalol has a beneficial effect on renal function, ripening effect on the uterine cervix, decreases proteinuria/preeclampsia and decreases fetal/newborn death compared with methyldopa.1 MEthyldopa is the medicine of choice for hypertensive conditions in pregnancy in several countries. Despite this, there is little proof of its safety in early pregnancy. So far, most methyldopa safety studies have focused on therapy during the second and third trimesters 2,3,4. Thus this study was planned to know the efficacy of the two commonly used drugs comparitively in our set up.
The setting of the study was at department of Obstetrics and Gynaecology, Government Medical College, Mavhilipatnam. A one year observational study was conducted during the period from March, 2023 to February, 2024. A total of 200 patients diagnosed as Pre-eclampsia or Gestational Hypertension clinically with blood pressure level >140/100 mm Hg were included in the study who visited the OBG OPD during the above period and the patients were devided into two groups as Group-A treated by oral Labetalol & Group-B treated by oral Methyldopa by following the `Matching` criteria. All the cases of pre-eclampsia clinically diagnosed and as per the the standard case definitions admitted in the ward during the above period up to reach the required sample size was included in the study after duly following the inclusion and exclusion criteria as indicated below. Inclusion criteria: 1. Pre-eclampsia with BP > 140/100 mm of Hg and urine albumin >1+dips stick 2. Gestational hypertension with BP >140/100 mm of Hg. 3.Primi and multigravida having above problem 4. Gestational age of the study subjects >28 weeks. Exclusion criteria: 1. Patients having Asthma, Diabetes, h/o congestive heart failure, heart block, severe liver disease and periferal vascular disease. 2.Patients with h/o eclampsia.3.Patients with chronic hypertension due to secondary causes.Objectives:1.To know the socio-demographic profiles of the study subjects 2. To study and compare the efficacy of Labetalol Vs Methyldopa in women with pre-eclampsia interms of degree of control of hypertension, meternal and fetal outcome. After receiving the Ethical committee clearance from the institution the study was began and the required data was collected by using a pretested proforma pertaining to their socio-demographic profiles,type of hypertensive disorders, mode of delivery & preterm or term delivery, maternal complications along with fetal outcome and there by evaluation of efficacy of the drugs Labetalol Vs Methyl Dopa comparatively etc; All the patients were initially admitted for evaluation. General physical examination, other systemic and per abdomenal examination and investigations including obstetic scan are done as shown in the proforma. Investigations like complete blood picture, renal function tests, liver function tests, non stress test, amniotic fluid index were repeated twice weekly. Fundoscopy and 24 hour urinary protein were done once in a week. The patients were counselled about the imminent signs and were asked to report immidiaetly. The patients with mild pre-eclampsia whose blood pressure is under control are sent home & reviewed to antenatal O.P every week or report immidiately to labor room if patient develops imminent symptoms, draining, bleeding per vagina, labor pains or decreased perception of fetal movements. Blood pressure was recorded initially, after 4hrs, 8hrs, 12hrs, 16hrs after starting the drug every 4th hourly. The patients were enquired daily for imminent symptoms & fetal kick count. Per abdomen examination is done for assessment of liquor, estimated fetal weight & fetal heart rate. Bed side clotting test & urine albumin is done daily. Obstretic scan is done to look for AFI, presentation, growth and placental location.
If blood pressure was more than 140/100mmHg even with antihypertensive, dose was increased accordingly. Maximum dose of labetalol given was 600mg per day in this study. For patients with methyldopa maximum dose given was 1500mg per day. Maternal complications like imminent signs, abruption, pulmonary oedema, oliguria, renal failure, HELLP syndrome were looked for but most of the patients delivered at term spontaneously while some needed induction. APGAR score and birth weight, signs of prematurity and IUGR of all babies were noted and all the cases (study subjects) of the study were managed and followed until discharge.
Finally the collected data was analyzed by using appropriate statistical tools like percentages, proportions, measures of central tendency, measures of dispersion, standard error of mean , and tests of significance etc; with the help of SPSS version 21computer software. The study results were compared and discussed in the light of published material of various similar studies belongs to different authors and there by conclusions and recommendations was framed.
Table-1 Age wise distribution of Hypertensive disorders among study subjects
S.No |
Age Group |
Hypertension Disorders |
Total |
|||
Labetalol |
Methyldopa |
|||||
GH |
Pre-Eclampsia |
GH |
Pre-Eclampsia |
|||
1. |
≤ 20 Yrs |
8 |
15 |
10 |
14 |
47 (23.5%) |
2. |
21-25 Yrs |
15 |
32 |
18 |
34 |
99 (49.5%) |
3. |
26-30 Yrs |
9 |
18 |
9 |
12 |
48 (24%) |
4. |
> 31 Yrs |
2 |
1 |
1 |
2 |
6 (3%) |
|
Total |
34 |
66 |
38 |
62 |
200(100%) |
Mean ± SD = 23.35 ±6.32= 19 – 31.67, P < 0.01
It was observed that the burden of the disease was more among the pregnant women between 21-25 years of age group (49.5%) and the Mean age was 52 years and very few about 3% was observed among >31 years of age group. And most of them were primi gravida. And also majority of the study subjects were belongs to low socioeconomic group & early marriages (adolescent marriages) were also high in number as observed.
S.NO |
Drug |
Initial Mean SBP/DBP |
4TH Hour Mean SBP/DBP |
8TH Hour Mean SBP/DBP |
12TH Hour Mean SBP/DBP |
16th Hour Mean SBP/DBP |
1. |
Labetalol |
151.2/103.2 |
145.6/88.4 |
136.5/88.4 |
130/83 |
128.9/83 |
2. |
Methyldopa |
148.5/101.8 |
147.5/101.5 |
147.6/101 |
136/88.6 |
134.9/85.1 |
Table-2 Efficacy of treatment by Labetalol Vs Methyldopa
P>0.05
Table-3 Distribution of Mode of delivery and Preterm & Term delivery
S.NO |
Mode of delivery |
|
Labetalol |
Methyldopa |
Total |
P-value |
|
||
n |
n |
n |
n |
N |
|
|
|||
1. |
Vaginal Delivery |
Spontaneous |
32 |
57 |
20 |
41 |
98 (49%) |
|
|
Induced |
25 |
21 |
P < 0.05 |
|
|||||
2. |
L S C S |
Elective |
13 |
43 |
20 |
59 |
102 (52.5%) |
|
|
Emergency |
30 |
39 |
|
||||||
3. |
PreTerm |
Delivery |
23 |
|
40 |
|
63 (31.5%) |
P < 0.05 |
|
4. |
Term |
Delivery |
77 |
|
60 |
|
137 (68.5%) |
|
|
Table-4 Distribution of Birth weight of Newborn babies of study subjects
S.NO |
Birth Weight in Kg |
Labetalol |
Methyldopa |
Total |
1. |
≤ 2 Kg |
26 |
21 |
47 (23.5%) |
2. |
2.1-2.4 Kg |
24 |
34 |
58 (29%) |
3. |
2.5-2.9 Kg |
25 |
19 |
44 (22%) |
4. |
3 Kg |
25 |
26 |
51 (25.5%) |
5. |
Total |
100 |
100 |
200 (100%) |
With reference to Birth weight LBW babies were more among Methyldopa users (55%) when compared Labetalol users (50%).
In this present study it was observed that the burden of the disease was more among the pregnant women between 21-25 years of age group (49.5%) and the Mean age was 23.35 years and very few about 3% was observed among >31 years of age group and majority were primi garavida as disease was more common among them only which was tiein with the studies of Jinturkar A et al14,Dharwadkar MN et al15, and Pentareddy MR etal16. And also majority of the study subjects were belongs to low socioeconomic group & early marriages (adolescent marriages) were also high in number as observed which intern leads to early conception and associated with more pregnancy relaed complications. In our study, need of additional antihypertensives in patients treated with Labetalol was only 6% when compared to 21% with Methyldopa patients which correlates with the Cochrane database review2 and Abulos et al 17 study. There was a significant reduction of Blood Pressure noticed by both the drugs but the more significant reduction was seen among those treated by Labetalol when compared to Methyldopa which was on a par with the studies of Lamming et al18,Elatrous et al19, el-Qarmalawi AM et a20, Lamming GD et al8,Gurjar BG et a21, Qasim A et al22 and Wallin JD etal23etc;
It was observed that significantly, about 32% of spontsneous vaginal deliveries happened with Labetalol users when compared to 20% among Methyldopa users & 25% induced deliveries with Labetalol as against 21% with Methyldopa and also significantly 43% LSCS with Labetalol as against 59% LSCS with Methyldopa but totally among both the groups LSCS was little bit more happened among the study subjects which corresponds to Sibai et al24, Lamming GD et al18 and el-Qarmalawi AM et al 20 studies.
Further it was observed that Preterm deliveries were only 23% with Labetalol as against 40% with Methyldopa which was highly significant (P >0.001). Similar findings were observed by studies of el-Qarmalai AM eta20 and Thulesius et al25 etc; With reference to Birth weight in the present study LBW babies were more among Methyldopa users (55%) when compared Labetalol users (50%) but the studies like Sibai et al24 and Laming GD et al18 reported that there was no difference between these two groups in this regard. Regarding the meternal complications, about 2 patients had imminent eclampsia in Labetalol group as against 8 patients in Methyldopa group and one patient developed HELLP in Methyldopa group but none in Labetalol group. And coming to fetal outcome in this study, 7% had IUGR foetuses in Labetalol group where as 10% in Methyldopa group which was similar to the reports of Redman et al26 study but Laming GD et al has reported no detrimental effects on fetuses. In addition to this Labetalol group has 5% of NICU admissions as against 8% in Methyldopa group probably due to Labetalol has direct beneficial effect on lung meturation there by significant reduction on Respiratory distress syndrome happened.
LIMITATIONS
The study was a hospital based and conducted in a small group of patients and lack of field level followup was observed.
As the distribution of the health problem was observed more among the adolescents and bteween 20 - 24 years of age group pregnant women, it is necessary to take measures to control child, adolescent and early marriages by means of proper implimentation of legislations & guidelines of proper age at marriage and creating awareness among the general public by utilizing print, electronic and social media. And not only this , involvement of local leaders of village & community level, perepheral health care workers, Anganwadis and Dwacra & self help groups etc; to reduce the problem at a large.
And also early registration of the pregnancies & regular antenatal check-ups will enable to identify the problem early and there by allow us to start intervention early to reduce the maternal and fetal complications.
Further our study proved that Labetalol was generally considered to be more effective drug than methyldopa for treating pre-eclampsia and pregnancy-induced hypertension interms of rapid ruction of hypertension, prolongation of pregnancy (term deliveries), reduction of LBW babies and overall better in prevention and control of maternal & fetal complications when compared to Methyldopa.