RAJIVGANDHIUNIVERSITY OF HEALTHSCIENCES, KARNATKA, BANGLORE

Annexure– II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

(To be submitted in duplicate)

Name of candidate: DR URVASHI

Address: Department of OBG

M.S.RamaiahMedicalCollege

Bangalore- 54.

Name of Institution: M.S.RamaiahMedicalCollege,

Bangalore-54.

Course of study and subject: MS (OBG)

Date of admission to course: 02-06-2007

Title: Comparison of carbonyl iron

and ferrousSULPHATE

PREPARATION in term of

efficacy, tolerability and

complianceduring pregnancy.

6. Brief resume of the intended work

6.1 The need for study:

There is high prevalence of iron depletion –anemia and iron deficiency without overt

decrease in hemoglobin among Indian population.Anemia is one of the leading cause of maternal mortality.Increased demand during pregnancy and depleted stores prior to pregnancy, calls for iron supplementation to be given to every pregnant woman.

Various iron salts comprising of the cheaper ferrous sulphate and the newer expensive carbonyl preparations are available, claiming superiority over the former.The carbonyl preparation would not be affordable to the lower socioeconomic strata of our population.Hencethe need to study their efficacy of the two different preparations in improving the iron store and preventinganemia.

The role of prophylactic iron supplementation during pregnancy is to maintain iron stores during the time of increased physiological demand.

Carbonyl iron consists of elemental iron in the form of sub microscopic crystals of less than 5µm diameter. It has lesser side effects and more elemental iron as compared to ferrous preparation.

The study attempts to compare the efficacy, compliance and tolerability and improvement of iron stores to meet the increased demands during third trimester of pregnancy when fetal erythropoisis increases and placenta accumulates iron.

6.2 Review of literature:

Indeveloping countries, incidence of anemia and iron deficiency is high and many women enter the pregnancy who are either anemic or who have grossly depleted iron stores. High proportion of women in their reproductive years lack stored iron.Greatnumber of vegetarians among Asian population will not have sufficient iron stores to meet the needs of pregnancy1

WHO defines anemia as hemoglobin concentration of <11gm during pregnancy2.Cut off point suggested by Centre for Disease Control and Prevention 1990is 10.5g% in II trimester and 11g%in I and III trimester.3

Average prevalence of anemia is 56% in non-industrializedcountries. In non-industrialized countries anemia is responsible for 40-60% of maternal deaths. For most women the non-industrialized countries where diets are low in iron bioavailability, sufficient iron is not supplied by diet alone.Deficiencyof essential hematinics arisesusually from increased requirement and inadequate intake. Iron deficiency is most common hematinic deficiency during pregnancy4

In those not taking iron, progressing drop in hemoglobin concentration occurs, lowest level being reached at 32 weeks of gestation and may take >1year after delivery before the pre pregnancy hemoglobin levels are reached.Anemia by WHO standards is found in 13%Asian women in 1st trimester, 28%and 47% in 2nd and 3rd trimester respectively, but iron efficiency (Serum Ferritin <12ηg/ml) is found to be far greater -35%in 1sttrimester 86%in 3rd trimester1. Daily iron requirement in pregnancy is approximately 4mg/day. Absorption of iron is less than 10% so average 40mg dietary iron is required daily.As iron deficiency develops,Serum Ferritin level decreases first then Serum Iron, reduction in hemoglobin concentration is late development. In iron deficiency, Serum Ferritin level will be lower than normal and it will correlate with depletion of marrow iron4

Classical morphological evidence of iron deficiency anemia erythrocytic hypochromasia and microcytosis is less prominent in pregnancy when compared to that in non-pregnant women as increased drive to erythropoisis results in higher proportion of young large RBCs mask the effect of iron deficiency on MCV in pregnancy even when anemia is established1

Initial evaluation of pregnant women with moderate iron deficiency should include measurement of

Hemoglobin

PCV

RBC Indices-MCV,MCH,MCHC

Peripheral smear

Serum Iron

Serum TIBC

Serum Ferritin

In the development of iron deficiency, a low Serum Ferritin is first abnormal lab test result.3

The goal of prophylactic iron administration during pregnancy is to maintain maternal iron stores during the time of increased physiological demand4

The government of India, Ministry of health, recommends 100mg elemental iron and 0.5mg folic acid for prophylaxis. The commonly used iron preparations are ferrous sulphate (available free of cost in most ofIndian Hospitals), ferrous fumarate, ferrous gluconate and latest being carbonyl iron.

Carbonyl iron consists of elemental iron in the form of submicroscopic crystals of <5µm diameter. It has lesser side effects and more elemental iron as compared to ferrous preparation. It is safe and effective for the treatment of iron deficiency anemia and it is associated with tolerable side effects. There is also no renal, hepatic or hematological toxicity with doses of carbonyl iron which is 5-15 times the usual recommended doses of ferrous sulphate5.

It is also seen that short term course of carbonyl iron can correct anemia and may atleast partially rebuild iron stores in patients with mild iron deficiency anemia.

6.3 Objectives of study:-

  1. To compare the efficacy of ferrous salt and carbonyl iron in pregnant women.
  2. To evaluate compliance and tolerability with each preparation.

7. Materials and Methods:-

7.1 Source of data: Blood samples will be collected from pregnant women in II trimester (between 14-20 weeks period of gestation)attending antenatal clinic in MSRMTH & MHHospital from January 1st 2008.

There subjects will then be assigned to two groups of 36 subjects each.

The sample size was determined based on the study ‘Carbonyl Iron in Iron Deficiency Anemia’ in which Mean +/- SD was 15.7+/- 1.8. The precision considered

a)clinically significant difference as 50% i.e. 0.023

b)5% α error.

7.2 Method of collection of data:-

  • Compliance will be determined by counting the number of pills consumed at each antenatal visit.
  • Tolerability and side effects will be determined by questionnaire at every antenatal visit.

Followinginvestigations will be done on the samples collected from study subjects

Hemoglobin

Peripheral smear

PCV

MCV

MCH

MCHC

Urine

Albumin

Sugar

Microscopy

Stool

Ova

Cyst

Occult blood

RBS

Serum Iron

Serum TIBC

Serum Ferritin

A comparative study will then be conducted for above parameters in following two groups

Group1: Pregnant women given oral iron supplementation in the form of ferrous sulphate for a period of 12 weeks.

Group 2: Pregnant women given oral iron supplementation in the form of carbonyl iron for a period of 12 weeks.

Re estimation of following lab investigation will be done in all subjects after a period of 12 weeks supplementation.

-Hemoglobin -SerumFerritin

-Peripheral smear -Serum TIBC

-MCV -Serum Iron

-MCH

-MCHC

Inclusion Criteria:-

  1. Pregnant women >14 weeks of gestation including primigravidae and multigravidae
  2. Pregnant women on oral iron supplementation with ferrous sulphate and carbonyl iron

Exclusion criteria:-

  1. Pregnancy <14weeks gestation
  2. Anemia due to causes other than iron deficiency
  3. Pregnancy with other medical illnesses /intercurrent infections
  4. Pregnant women not on oral iron supplementation
  5. Pregnant women on iron supplementation other than ferrous sulphate and carbonyl iron
  6. Miscarriage during the course of study
  7. Multiple pregnancy

Statistical Analysis:-

Independent ‘t’ test will be used to compare the Serum Ferritin levels between the two groups who are supplemented with ferrous Sulphate and carbonyl iron respectively, thereby determining the improvement in iron stores and helping to establish therapeutic efficiency of each of the two preparations.

7.3Does the study require any investigations or interventions to be conducted on patients or to the humans or animals? It so describe briefly>

Yes, it will be doing investigations and supplementing ferrous sulphate or carbonyl iron to the study subjects.

7.4Has ethical clearance been obtained from your institution in case of 7.3?

8. LIST OF REFERENCES:

  1. Michael de Swiet (2002).Medical Disorders in Obstetric Practice, Fourth Edition, Blackwell Publication.Blood Volume Hematinics,Anemia., page no 35-36.
  1. Saha L et al (2007). Comparison of Efficacy, Tolerability and Cost of Iron Polymaltose Complex With Ferrous Sulphate in the Treatment of Iron eficiency Anemia in Pregnant Women, MedGenMed, Volume 9(1): 1.
  1. F. Gary Cunningham et al(2005).Williams Obstetrics, twenty second edition, MWGraw Hill Medical Publishing Division..Hematological Disorders;1144-1145.
  1. High Risk Pregnancy Management Options, Third Edition, D. K. James et al, Elsevier Publications, page no 868.
  1. Victor R. et. al(1986) . Carbonyl Iron Therapy for Iron Deficiency Anemia, Volume 67, No 3, pg 745-752
  1. Signature of the candidate :
  2. Remarks of the guide :
  3. Name and designation of

Guide : Dr SUJANI B. K.

Professor

Department of OBG

M.S.RamaiahMedicalCollege

Bangalore

Signature :

Co guide DR NANDINI

Associate Professor

Department of OBG

M.S.RamaiahMedicalCollege

Bangalore

Signature:

Head of the Department: Dr UMA DEVI

Professor and HeadDepartment of OBG

M.S.RamaiahMedicalCollege

Bangalore

Signature:

Remarks of Chairman

and Principal:

Signature: