A Longitudinal Study of Nifedipine Versus Labetalol in Hypertension in Pregnancy at A Teritiary Hospital

Dr. Swetha Bobba¹, Dr. Bharathi Rao *²

1. Junior Resident, Department of Obstetrics and Gynaecology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education.

2. Professor, Department of Obstetrics and Gynaecology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education.

Corresponding Author: Dr. Bharathi Rao, Professor, Department of Obstetrics and Gynaecology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education.

Copy Right: © 2023 Dr. Bharathi Rao, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received Date: May 11, 2023

Published Date: June 01, 2023

DOI: 10.1027/margy.2023.0226

Abbreviations

ACOG -           American College of Obstetrics and Gynaecology

sFlt-1   -           Soluble Fms-Like Tyrosine kinase-1

VEGF  -           Vascular Endothelial Growth Factor

PlGF    -           Placental Growth Factor

ET-1    -           Endothelin-1

ROS    -           Reactive Oxygen Species

NO      -           Nitric Oxide

RBF     -          Renal Blood Flow

GFR    -         Glomerular Filtration Rate

DIC     -         Disseminated Intravascular Coagulation

FGR    -         Fetal Growth Restriction

NICE   -         National Institute for Health and Care Excellence

MTHFR          - Methylenetetrahydrofolate reductase

CNS    -        Central Nervous System

FDA    -        Food and Drug Administration

IUGR  -        Intrauterine Growth Restriction

A-V     -       Arterio-Venous

SA       -       Sinoatrial

AV      -       Atrioventricular

COPD  -       Chronic Obstructive Pulmonary Disease

NICU  -       Neonatal Intensive Care Unit

PRES   -      Posterior reversible encephalopathy syndrome

ICU     -      Intensive Care Unit

Introduction

Pregnancy is complicated by hypertensive disorders to up to 5-10% [1]. Preeclampsia is seen in 3.9% of pregnant women [1]. It forms a lethal triad along with infection and haemorrhage, contributing to rise in rate of morbidity and mortality. Most commonly used medications for hypertension in pregnancy are oral labetalol and oral nifedipine [2]. Insufficient data on the efficacy of routinely used antihypertensive drugs may result in subpar treatment of hypertension in pregnancy [3].

Etiopathogenesis includes Primigravida women exposed to significant number of chorionic villi, pre-existing conditions like vascular disease and a genetic predisposition.

In pre-eclampsia there is deficient endothelial nitric oxide synthase activity, which causes cell    permeability   to    increase    and    thereby   causing   damage    to    endothelium. In some cases there may be endangering thrombocytopenia caused by platelet activation and coagulopathy.

Antihypertensive therapy should ideally be initiated only when blood pressure is more than or equal to 140/90mmHg. The optimal blood pressure antenatally should be 135/85 mm Hg. Cardiovascular disorders later in life maybe a result of having a history of hypertension in pregnancy.

According to the National Institute for health and care excellence guidelines (2010) Labetalol is the first line treatment, followed by Nifedipine [4]

Aim and Objectives

Aim:

To assess the efficacy of Labetalol and Nifedipine in hypertension in pregnancy

Objectives

1. To study the efficacy of Labetalol and Nifedipine in the controlling blood pressure in hypertension in pregnancy
2. To study the effects of Labetalol and Nifedipine on proteinuria
3. To study the maternal and foetal outcomes of pregnant women treated with anti-hypertensive drugs Labetalol and Nifedipine

Methodology

a) Study settings: Govt. Lady Goshen Hospital and KMC Hospital, Attavar.

b) Study design: Comparative prospective longitudinal study

c) Study participants: Antenatal women diagnosed with hypertension more than 20 weeks of gestation requiring Nifedipine and Labetalol drug therapy

d) Inclusion criteria:

All antenatal women diagnosed with hypertension more than 20 weeks period of gestation requiring the above-mentioned drugs. Patients will be followed up till date of discharge.

e) Exclusion criteria:

1. Patients on other hypertensive drugs other than the above-mentioned drugs
2. Patients who are a known case of Bronchial asthma/COPD
3. Cardiac failure
4. Chronic hypertension

f): Study duration: One and half year after ethical committee clearance

g) Sample size:

               p2- proportion of 2^nd sample    q2= 100-p2

With 95% CL and 88% power with respect to Thakur et al; the sample size comes to be 200

h) Sampling method:

Universal sampling

i) Outcome variables:

A proforma, excel sheet, patient information sheet, informed and written consent was taken. Patients diagnosed with hypertension more than 20 weeks of gestation was followed up till delivery. The patients were categorised into Group A & Group B. Group A being individuals prescribed Tablet Nifedipine 30–120 mg/day orally of a slow- release preparation. Group B consisting of individuals were started on Tab. Labetalol 200–2,400 mg/day orally in 2-3 divided doses. Patients were sub grouped into: Number of individuals needing additional antihypertensives, number individuals needing intravenous antihypertensive, number of individuals needing Capsule Nifedipine. Blood pressures were monitored at intervals based on severity of blood pressure.

Blood pressures post treatment, Number of days of antihypertensives, dose of antihypertensives and the use of monotherapy or combined therapy were observed.

Maternal outcomes:

• Spontaneous labour/ Induced labour,
• Mode of delivery: Vaginal delivery or Caesarean section
• Eclampsia
• HELLP syndrome
• ICU admission – PPH

Fetal outcomes:

• Term/Preterm baby
• Birth weight
• NICU admission

i) Data analysis:

We used SPSS version 17.0 to do the analysis.  If P<0.05 will be considered to be significant.

Chi square test will be done. A master excel sheet will be plotted and the data will be analyzed using various statistical methods:

1. For observational data: results will be indicated in percentages.
2. For categorical data: chi square test/ odds ratio will be used to prove significance.
3. For interval data: mean/ student T test/Z test will be used to prove significance.

j) Data collection tool:

Collecting data after taking consent from study participants using Performa.

Results

The total number of individuals studied was 200. 100 individuals from group Nifedipine and 100 individuals from group labetalol were studied. Factors studied include, age distribution, body mass index, parity, complications, mode of delivery, neonatal intensive care admission.

More than half of the sample size were young women aged 21-25 (Table no1). No significance noted. Table 2

Just over half of the patients were Primigravida in both drug groups. Nifedipine group attributed to 52 % and Labetalol, 51%. The rest of the sample was multigravida.

Front both drug groups, BMI was found be in the overweight range, no significance was noted.

Just over half of the diagnosis was at term gestation seen in both drug groups (Table 3). Majority of the diagnosis at delivery was at term; 76 % were taking oral labetalol and 82%, were taking Nifedipine.

Mean arterial pressure in the first 6 hours after initiation of medication was 126.46 in group labetalol and 135.09 in group nifedipine. Labetalol was found to be statistically significant at 12, 24 and 48 hours after onset of medication depicted in the line diagram (Figure 4).

Proteinuria was noted in 57% of cases in Nifedipine group and 66% in Labetalol group. More number was noted in the Labetalol group than Nifedipine which not statistically significant (Table 6, Figure 5)

Additional antihypertensive drugs

12 patients part of group Labetalol required additional Nifedipine. 8 patients from group Nifedipine group required Labetalol. 9 patients from group labetalol were given Intravenous labetalol for severe hypertension. 5 patients were given capsule Nifedipine. 6 patients from group Nifedipine were given Intravenous labetalol and 4 patients were given Capsule Nifedipine for the control of severe hypertension.

Hypertension related complications

4 patients had Eclampsia- 2 from group Labetalol, 1 from the Nifedipine group and 1 from the combined group. 3 patients had abruptio placenta, 2 of which were on both antihypertensive drugs. 1 patient was from the Nifedipine group. 3 patients developed HELLP syndrome. 2 patients on Labetalol and 1 patient on Nifedipine. 2 patients developed PRES syndrome both on Labetalol, one patient required ICU care for ionotropic support was on both antihypertensive therapies.

Elective LSCS was found to be 15% in Nifedipine group and 11 % in group labetalol. 58% of individuals were induced from the Nifedipine group and 61% form group labetalol. More number of individuals were found to be induced as compared to spontaneous labour.. (Table 7, Figure 6)

Total number of LSCS in was 30% in both drug groups (Table 9, Figure 7).   Total number of vaginal delivery attributed to 68% in Nifedipine group and 66% in the Labetalol group (excluding forceps vaginal delivery).

Most common side effects were headache and palpitations noticed predominantly in group Nifedipine which was statistically significant. (P value= 0.02)

Additional antihypertensive drugs

12 patients part of group Labetalol required additional Nifedipine. 8 patients from group Nifedipine group required Labetalol. 9 patients from group labetalol were given Intravenous labetalol for severe hypertension. 5 patients were given capsule Nifedipine. 6 patients from group Nifedipine were given Intravenous labetalol and 4 patients were given Capsule Nifedipine for the control of severe hypertension.

Hypertension related complications

4 patients had Eclampsia- 2 from group Labetalol, 1 from the Nifedipine group and 1 from the combined group. 3 patients had abruptio placenta, 2 of which were on both antihypertensive drugs. 1 patient was from the Nifedipine group. 3 patients developed HELLP syndrome. 2 patients on Labetalol and 1 patient on Nifedipine. 2 patients developed PRES syndrome both on oral Labetalol, one patient required ICU care for ionotropic support was on both antihypertensive therapies.

9 neonates from the Labetalol group had Fetal growth restriction, out of which 2 neonates had fetal bradycardia. 6 babies in the Nifedipine group had FGR. 3 babies developed cardiac anomalies. Out of 26 neonates in NICU, 15 were admitted due to extreme prematurity.

Discussion

The management in hypertensive disorders complicating pregnancy is recommended to reduce maternal and fetal complications. Labetalol and Nifedipine are known to be used for management of hypertension in pregnancy. Nifedipine is cheaper and readily available in tertiary care hospitals. We therefore wanted to collate the potency of the two drugs, Nifedipine retard and Labetalol in the management of hypertensive disorders in pregnancy. The mean maternal age in the present study was 24 -25 years which was similar to T Easterling et al, Thakur et al and Nilesh et al [20,7,32]

Body mass index was not statistically significant, though most of the sample size was overweight. T Easterling et al included multiple pregnancy in their study as opposed to the present study. Primigravida was predominant in both drug groups (almost half) which was comparable to Thakur et al where it is attributed to 24-48% in both drugs groups.   Additional hypertensive drugs were required up to 12% in Labetalol group and 8% in the Nifedipine group, which was more than Easterling et al and Thakur et al.

A Meta-analysis constructed by Liu Q et al included the assessment of the potency, adverse effects and perinatal outcomes of nifedipine versus other antihypertensive drugs(5). Compared with other antihypertensives, nifedipine contributed greater efficacy in controlling blood pressure contrary to the present study

Stefano R. Giannubilo et al concluded that there was a higher occurrence of fetal growth restriction amid women treated with labetalol as opposed to the nifedipine group (38.8 vs.

15.5 %) [6]. In the present study, 9 neonates from the Labetalol group had Fetal growth restriction, out of which 2 neonates had fetal bradycardia (NICU admission).

More number of caesarean sections (64%) were observed in Easterling et al study which was contrary to the present study (30%). There was no statistical significance in maternal complications such as Abruptio placenta, Eclampsia and ICU admission. Dhali B et al, found higher incidence of eclampsia in the labetalol group [33]

Thakur et al [7] found that Labetalol, Nifedipine and Methyldopa were effective in Pregnancy induced hypertension; where Labetalol was more effective in reducing albuminuria.

Sivaranjani et al have seen that nifedipine has many pros like cheaper than other drugs, immediate action along with longer duration of action and can be taken orally. [8] Despite many advantages, it is known to cause maternal hypotension, foetal distress due to the placental hypoperfusion, palpitations and progressive neuromuscular weakness when used along with magnesium sulphate. Our study was conducted in a tertiary hospital; hence it can be concluded Nifedipine can be used as it is more versatile and cost effective.

Conclusion

Labetalol was shown to be more efficacious in the first 48 hours after initiation of treatment. Nifedipine was proven to be equally efficacious after 72 hours of medication. Side effects such as headache and palpitations were found in group Nifedipine which not detrimental to patient health. Hence it can be concluded that Nifedipine can be used in low resource settings as it is readily available and cost effective. There was was no disparity in proteinuria as well as other maternal and neonatal outcomes in both drug groups. More number of ICU admission was noted in the combined drug group.

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