Dhatrilauha: Right choice for iron deficiency anemia in pregnancy.

BACKGROUND: Anemia in pregnancy is multi-factorial. Iron deficiency anemia (IDA) is the most common one. Major cause is increased demand of iron during pregnancy. In Ayurveda, under Pandu-Roga the features of anemia are described. It is characterized by Vaivarnyata or Varnanasha (change/destruction in normal color of the body), a disorder of Pitta vitiation. Ayurvedic management is an effective way of curing anemia in general by a large number of Lauha preparations of which Dhatrilauha has been used widely for centuries. AIM: To evaluate the effect of Dhatrilauha in the management of IDA based on the scientific parameters among pregnant patients.
MATERIALS AND METHODS: A total of 58 cases were selected by simple randomized sampling method as per inclusion criteria of pregnant women between 4(th) and 7(th) months of pregnancy with a clinical diagnosis and laboratory confirmation of IDA. Dhatrilauha 500 mg in two divided doses after food with normal potable water were given for 45 days with three follow-ups, each of 15 days intervals. Final assessment was done after completion of 45 days and results were statistically analyzed by using Cochran's Q-test and Student's t-test.
RESULTS: Dhatrilauha showed statistically significant (P < 0.01) improvement in the majority of sign-symptoms and objective parameters such as weakness, fatigue, palpitation, effort intolerance, breathlessness, heartburn, pallor, constipation, hemoglobin, red blood cells (RBC), hematocrit, mean corpuscular volume, mean corpuscular hemoglobin concentration, RBC distribution width, mean platelet volume, serum iron, and total iron binding capacity.
CONCLUSION: Dhatrilauha possesses many fold effectiveness in anemia (IDA), which was evidenced with the significant results obtained in the majority of parameters in this study.

Introduction

Anemia is a qualitative or quantitative deficiency of hemoglobin (Hb) or red blood cells (RBC) in circulation leading to reduced oxygen (O2) - carrying capacity of blood to organs and tissues. According to Indian Council of Medical Research, anemia is defined as Hb level of <11 g/dl, mild with Hb of 10–10.9 g/dl, moderate with Hb of 7–10 g/dl and severe with Hb of <7 g/dl.[1] Nutritional anemia is the most common due to increased demand of iron during pregnancy.[2] In healthy, iron-sufficient women, Hb concentrations change dramatically during pregnancy to accommodate the increasing maternal blood volume and the iron needs of the fetus.[3] It is one of the most commonly encountered medical disorders during pregnancy.[4] It is responsible for various adverse obstetric outcomes due to inability to cope with the stress of child birth.[1] Ranging from cardiac failure, puerperal sepsis, decreased lactation, preterm baby and low birth weight baby, etc.[5] National Anemia Prophylaxis Program revealed that the majority of women were not taking iron folic acid (IFA).[6] National Family Health Survey (3) showed that IFA coverage as only 57.60% of all pregnant women with 32% in Uttar Pradesh. Lack of effective implementation mechanisms and poor compliance due to ignorance or side-effects are the main impediments in effectiveness of iron supplementation during pregnancy.[6]

In Ayurveda, Garbhini-Pandu (anemia in pregnancy) has not been referred so far, but at one place Kashyapa stated that if a pregnant woman become weak and white complexioned, her fetus gets troubled.[7] This condition may simulate to anemia in pregnancy and its complication. In general, under Pandu Roga the features of anemia may be kept. The disease Pandu Roga is called so because of the prominence of pallor in skin.[89] It has been vividly described with etiopathogenesis, clinical features, management, etc., in the ancient texts.[1011] The Pitta predominant Doshas are vitiated in Dhatus and as a result of morbidity of Dosha and Dushya (those affected by Dosha), complexion, strength, unctuousness, and other properties of Ojas (Rakta, i.e. blood or Ojas, i.e. immunity itself get diminished[12]). Thus, it is affected with Alparakta (deficiency of blood), Alpamedas (deficiency of fat), Nihsara (diminished Ojas), Shithilendriya (looseness of body parts) and Vaivarnya (abnormality of complexion)[13] or vitiation of Rakta leads to paleness of skin.[14] Hridya-Spandana (palpitation), Raukshya (dryness of skin), Sweda-Abhawa (absence of sweat) and Shrama (exhaustion) are striking clinical presentations.[15] The ancient commentator stated that though Pitta and Rakta are similar in nature, aggravation of the Pitta does not lead to increase of Rakta, rather it is decreased because of depletion of the nutrient Rasa by Pitta. Similarly, Pitta responsible for complexion produces abnormal color when get vitiated.[16] In Garbhini (pregnant woman), the nutrient Rasa takes three courses - nourishment of her own body, for lactation and for growth of the fetus.[1718] Thus, a Garbhini is more prone to suffer from Pandu, especially due to Anuloma-Kshaya of Rasa Dhatu. It also opined that in all types of Pandu, Pitta is the root cause.[19] The disorders of the pregnant woman should be treated with diet and drugs consisting of Mridu Virya (mild potency), Madhura (sweet), Sheeta (cold), etc., properties and which are non-contrary to fetus.[2021] This implies that proper nutrition (Poshya Rasa) along with Pitta pacifying measures are the main stream of management in Ayurveda, a key to treat iron deficiency anemia (IDA) as in modern parlance too. Thus, Ayurvedic management with Dhatrilauha, which consisting of all the above-mentioned properties may be considered as an effective way of curing IDA in pregnancy.

Aim and objective

To evaluate the effect of Dhatrilauha in the management of IDA based on the scientific parameters among pregnant patients.

Materials and Methods

Selection of cases

Simple randomized allocation of the 58 pregnant patients selected on the basis of inclusion criteria after the ethical clearance of the research ethical committee of the Institute of Medical Sciences (IMS), Banaras Hindu University (BHU). The patients were selected from the outpatient department of Prasuti Tantra, Faculty of Ayurveda, Sir Sundarlal Hospital, IMS, BHU, Varanasi, Uttar Pradesh, India.

Selection of the test drug

Ayurvedic management is an effective way of curing anemia in general by a large number of Lauha preparations of which Dhatrilauha has been used widely for centuries.[2223] Dhatrilauha was selected for two reasons in this study, firstly its classical indication in Pandu Roga, Pitta-Roga and secondly its ingredients which are nutritional, Rasayana (rejuvenating) and Pitta Shamaka (pacifying Pitta) in property. It consists of Dhatri (Amalaki – Emblica officinalis Gaertn.), Yasthimadhu (Glycyrrhiza glabra Linn.), Guduchi (Tinospora cordifolia (Willd) Miers. ex Hook. f. and Thoms.) and Lauha Bhasma (oxide of iron). All ingredients are having Rasayana property. Dhatri is Tridoshahara, specially Pitta Shamaka;[2425] Yasthimadhu is Madhura, promotes strength and complexion, pacifies Pitta, Rakta[26] and mild purgative;[27] Guduchi is having Tridoshahara (pacifies Vata, Pitta and Kapha), Balya (strength promoting), Pandu Nashaka (cures anemia),[28] Deepana (appetizer), Pachana (digestive), Krimighna (anthelmintic) and Rakta Vardhaka (hematinic) properties.[29] Lauha Bhasma (Lauha Rajas) is said to be best Pandu Roga Nashaka,[30] Tridoshahara, found in many formulations for the treatment of Pandu and Pitta Roga.[313233] Presence of ascorbic acid (vitamin C) in Amalaki has a significant effect on iron bioavailability from cereals and pulses in vitro.[34] Lauha Bhasma also has a significant hematinic and cytoprotective activity,[35] hemoglobin regeneration efficacy.[36]

Preparation of the test drug

Among the ingredients of the test drug Amalaki, Yasthimadhu and Guduchi in raw form were purchased from Goladinanath (local) Market, Varanasi. Lauha Bhasma was purchased from Dhootpapeshwar Pvt., Ltd., Mumbai. The test drug was prepared referring to Bhaishajya Ratnawali in the Ayurvedic Pharmacy, Department of Rasashastra, IMS; BHU, Varanasi, following standard operating procedure with due permission from the department concern.

Dose selection and drug schedule

The therapeutic dose in this study was calculated to 500 mg[37] in two divided doses after food with normal potable water were given for 45 days with three follow-ups, each of 15 days intervals. Final assessment was done after completion of 45 days and results were statistically analyzed.

Inclusion criteria

Pregnant women between 4th and 7th month of pregnancy with a clinical diagnosis and laboratory confirmation of IDA, but Hb level is not <7 g/dl

Hematological investigations suggestive of Hb level ≤10 g/dl. Peripheral blood picture showing microcytic, normocytic, and hypochromic type of erythrocytes.

Exclusion criteria

Patients having Hb level ≤7 g/dl

Patients with a history of anemia due to any bleeding conditions as bleeding piles, menorrhagia (excessive cyclic vaginal bleeding either in amount or duration), gastric ulcers etc

Patients having bleeding disorders as coagulation defects, thalassemia, etc

Presence of any other comorbid disease such as renal insufficiency, coronary heart disease, hypertension, tuberculosis, diabetes mellitus, etc.

Investigation

Complete blood count

General blood picture for RBC morphology

Serum iron

Total iron binding capacity (TIBC)

Stool – ova and cyst.

Assessment of result

The patient was assessed after each follow-up statistically by using Cochran's Q-test and Student's t-test as required of the following parameters:

The sign and symptoms (weakness, fatigue, palpitation, effort intolerance, breathlessness, heartburn, pallor, and constipation) were assessed before and after treatment with scoring pattern[37] depending on the severities

The objective parameters (Laboratory investigations as Hb, RBC, Hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), RBC distribution width [RDW], rat parvovirus (RPV), serum iron, TIBC).

Scoring pattern on the sign and symptoms in IDA

I. Weakness (Daurbalya)

No feeling of weakness during the daily activit - 0

Sometimes feeling of weakness, but performs daily activity - 1

Often feels weakness, but hampers daily activity - 2

Always feels weakness, unable to perform daily activity even routine postural movements - 3

II. Fatigue (Shrama)

No fatigue except hard work - 0

Fatigue after moderate work for a certain period of time - 1

Fatigue after light work for a certain period of time - 2

Fatigue after routine work for a certain period of time - 3

(Hard work - weight lifting, excess work at the workplace or at home without rest, etc.; Moderate work - washing clothes and utensils, brooming, climbing stairs, cooking, etc.; Light work - walking, bathing, feeding, etc.)

III. Breathlessness (Shwasa)

No breathlessness - 0

Breathlessness after heavy work, relieved soon, tolerable - 1

Breathlessness after moderate work, relieved later, tolerable - 2

Breathlessness after light work, relieved later, intolerable - 3

IV. Pallor - Skin, face, sclera, nails (Pandu Varna Twak etc.)

Pallor absent in all these region - 0

Pallor present in any two region - 1

Pallor present in any three region - 2

Pallor present in these entire region - 3

Overall assessment of result

Overall effect on the sign - symptoms and objective parameters were calculated after the completion of 45 days therapy by the percentage of relief as shown below:

Complete remission of sign - symptoms: 100% relief

Marked improvement in sign - symptoms: ≥75–<100% relief

Moderate improvement in sign - symptoms: ≥50–<75% relief

Mild improvement in sign - symptoms: ≥25–<50% relief

No improvement in sign - symptoms: <25% relief.

Good improvement Hb percentage ≥ 1 g% gain.

Mild improvement Hb percentage ≥ 0.5–<1 g% gain.

No improvement Hb percentage ≤0.5 g% gain.

Observations

In the present clinical study, 13.8% of the patients were from the age group of 22 and 25 years, 69% were from the semi-urban area, 82.8% were housewife, 50% from lower socioeconomic condition, 84.5% literate, 34.5% were having a family member of 05, 27.6% had last delivery 2 years back. About 77.6% had a chief complaint of which 58.6% had duration of chief complain more than 6 month. 69% had regular bowel habit [Table 1]. In this study, 39.7% of patients were having Pitta predominant Tridoshaja Prakriti [Table 2].

Table 1

Baseline features of the pregnant patients shown as highest percentage in that variable

Table 2

The Prakriti (body constituents) wise distribution of 58 patients with iron deficiency anemia in pregnancy

Results

Dhatrilauha was found statistically significant in reducing the majority of sign-symptoms - weakness (Q = 124.6, P < 0.001), fatigue (Q = 105.0, P < 0.001), palpitation (Q = 70.94, P < 0.001), effort intolerance (Q = 95.54, P < 0.001), breathlessness (Q = 92.35, P < 0.001), swelling feet (Q = 52.45, P < 0.001), heartburn (Q = 32.28, P < 0.001), pallor (Q = 143.2, P < 0.001), and constipation (Q = 46.6, P < 0.001) [Table 3].

Table 3

Effect of Dhatrilauha on sign and symptoms of iron deficiency anemia in pregnancy

On diagnostic parameters, it was found statistically highly significant in Hb (t = 10.22, P < 0.001), RBC (t = 5.14, P < 0.001), HCT (t = 9.64, P < 0.001), MCV (t = 10.05, P < 0.001), MCHC (t = 6.30, P < 0.001), RDW (t = 5.34, P < 0.001), mean platelet volume (MPV) (t = 4.96, P < 0.001), serum iron (t = 48.20, P < 0.001), TIBC (t = 19.10, P < 0.001). MCH (t = 0.088, P = 0.930) was found statistically insignificant [Table 4].

Table 4

Effects on objective parameters of the test drug

Overall therapeutic effect of the test drug [Figure 1] apart from Hb (g%) improvement was found that, out of 19 patients complaining of heartburn, 16 patients got relief and of 26 patients having constipation 24 patients got relief which were found statistically significant.

Figure 1

Graphical representation of overall improvement after treatment (F3)

Discussion

Anemia in pregnancy is defined as a Hb concentration of <11 g/dL. However, in India and most of the other developing countries a lower limit of 10 g/dL is often accepted. It is considered to be the most commonly encountered medical disorder during pregnancy and is responsible for various adverse obstetric outcomes. Ineffective implementation, ignorance or side-effects of conventional iron are the main obstacles in effectiveness of iron supplementation.

Maximum patients were from the age group of 22 and 25 years, the age for the Pitta predominance. Prevalence of the condition among the lower socioeconomic group and in housewife may be due to the devotion only toward the family, no time for self-care, negligence and less education also unawareness toward self.

In Ayurveda, the fertile period of a female is considered normally Pitta predominant. Indulgence of Pitta Vardhaka Ahara (Pitta aggravating diets) such as Amla (sour), Lavana (salt), Katu (pungent), etc., by the pregnant female for fulfillment of Dauhrid (desirous intake) is further vulnerable to vitiate Dhatus by aggravated Pitta. Improper nourishment by Ahara Rasa to the Garbhini is also an important factor. Thus, prevalence of Pandu increases during pregnancy if proper care not taken of especially in relation to diets. In the present study, out of the 58 patients (39.7%) had Pitta predominant Tridoshaja Prakriti (constituents). Therefore, on the basis of observation and etiopathogenesis of Pandu in pregnancy, it could be said that IDA in pregnancy is more close to Pitta predominant Tridoshaja Pandu. In the pathogenesis, the involvement of Dhatus, especially depletion of the nutrient Rasa by vitiated Pitta predominant Doshas and subsequent malnourishment to successive Dhatus have a greater impact on the Ojas as stated in Ayurveda. The Ojas here taken either as blood or the immunity in general by the commentator of Charaka Samhita, Chakrapani. Thus, the principle depends on the two essential strategies namely the drugs those pacify Pitta and diets those nourishes Rasa Dhatu. Both components had been fulfilled by Dhatrilauha in this study.

All the ingredient of Dhatrilauha having Tridoshhara, Rasayana and Rasa-Poshaka (nutritional) properties may be considered the best to maintain the aggravated Pitta.[26272829303132333435363738] Amalaki, due to Madhura Rasa (sweet taste) and Sheeta Virya (cold potency) reduces Pitta[2627] and thus breaks down the main factor in the pathogenesis of Pandu Roga. Further, it contains richest source of vitamin-C, which helps in the absorption of iron thus increases its bioavailability.[36] Yasthimadhu, due to Varnya (complexion promoting) and Pitta pacifying property[2829] maintains the normal color of the skin. Guduchi being Tikta Rasa (bitter taste) increases appetite, Krimighna (anti helmentic) and effective against many infections.[3031] Lauha Bhasma, the oxide of iron has a direct impact on bodily iron.[32333435363738] Thus, the double fold increase in the Pitta aggravation (due to fertile age and Dauhrid) in pregnancy, Dhatrilauha possesses many fold effectiveness in anemia (IDA). This is evidenced with the significant results obtained in the majority of parameters in this study.

The Dhatrilauha was found statistically significant in increasing the Hb level, serum iron and reducing the value of TIBC. Totally 19 patients having complained of acidity, heartburn-related to the gastrointestinal system, of which 16 got relief. A total of 26 patients having constipation, and 24 were relieved from the symptom, may be considered as few advantages over the conventional iron therapy. It showed good tolerability with high acceptance to the pregnant patient without any reported untoward effect.

This work was aimed at providing a new dimension for future large population and multicenter study in the cases of pregnancy anemia so as to utilize this excellent classical drug as a part of National anemia control program to benefit the nation and also to avoid the untoward effect of contemporary iron preparations.

Conclusion

Iron deficiency anemia in pregnancy may be considered under the preview of Pitta Pradhana Pandu Roga in Ayurveda. In this study, a total of 58 pregnant patients were studied with Dhatrilauha and found effective in relieving the majority of sign-symptoms and objective parameters Hb, RBC, HCT, MCV, MCHC, RDW, MPV, serum iron, TIBC. The drug showed good tolerability with high acceptance to the pregnant patient without any reported adverse drug reaction.