This document summarizes a dissertation that compares the effects of daily versus intermittent oral iron therapy on hemoglobin levels in non-anemic pregnant women. The study aims to enroll 120 pregnant women between 14-20 weeks gestation and randomly assign them to a daily iron tablet group or weekly double-dose iron tablet group. Hemoglobin levels will be measured and compared between the two groups over the course of 1 month to assess differences in hemoglobin changes and side effect profiles between daily and intermittent iron supplementation regimens. The results of this study could help determine the most effective dosing schedule for iron supplementation during pregnancy.

1. SYNOPSIS OF DISSERTATION
BY DR.SHAIKKHUBRA
1ST YEARPG,MSOBG
GUIDE – DR.SUMALATHA RYALI
ASSOCIATE PROFESSOR , DEPT OF OBG

2. EFFECT OF DAILY VERSUS INTERMITTENT ORAL
IRON THERAPY ON HAEMOGLOBIN LEVELS IN
NON
ANAEMIC PREGNANT WOMEN
Title of the study

3. • Anemia is the most common nutritional deficiency
disorder in pregnancy, worldwide1. The
• World Health Organization (WHO) has estimated
that the global prevalence of anemia to be ~24.8%.
In India, approximately 62–88% of pregnant women
are anemic2. Pregnancy is a time in which the risk
for developing iron deficiency anemia is highest,
because iron requirements are substantially greater
than average absorbable iron intakes3.
Introduction

4. • Iron requirements increase during pregnancy. And
this requirement may lead to anemia in pregnant
women4. Lower hemoglobin cut off is 11.0 g/dL in
the first and last trimester and 10.5 g/dL in the
second trimester. Therefore, any level below 10.5
g/dL should be considered as anemia5.
• Strong evidence shows that iron deficiency in the
first trimester of pregnancy results in significant
decrements in fetal growth, whereas iron
deficiency anemia in the second and third
trimesters has little effect on fetal growth

5. • Supplementation programs have been
implemented since 1971 in India, and the dose of
supplementation has been increased up to 100 mg
of elemental iron per day, yet the magnitude of the
problem remains unchanged.
• It is recognized that one of the major problems of
daily supplementation schedule is lack of
compliance because of the high incidence of
gastrointestinal side effects. And the probable
cause is the effect of oxidative stress of high doses
of iron3.

6. • As gut mucosal turnover rates are about three days,
administering iron during these days may lead to
lower iron absorption. Periodic iron
supplementation may let the mucosa to heal and
gets better iron absorption.
• Previous studies reported, continuous
administration of oral iron impairs the absorption
of a subsequent iron dose.
• Significant equality and reduced side effects have
been reported in several epidemiological studies in
comparing the weekly prescription of iron with
daily supplementation

7. • The hypothesis behind intermittent iron
supplementation has been based on “mucosal
block” theory of iron absorption6.
• The gut has a mechanism to prevent entry of excess
iron in the body. The mucosal cells absorb iron on
the basis of iron requirement of the body. The iron
reaching inside the mucosal cell is either
transported to plasma or oxidized to ferric form
and complexed with apoferritin to form ferritin.
• The controversy over the so-called “mucosal block”
theory in iron supplementation is not yet resolved7.
It was hypothesized that a first dose of iron would
load the mucosa with iron and block subsequent
doses from absorption

8. • By reducing the dose frequency to once per week,
matching the mucosal turnover, iron from each
tablet would be better absorbed, and consequently
a lower amount of iron would be required.
• Studies in small animal support the hypothesis but
studies in humans showed only a small reduction in
absorption due to previous administration of iron.
This suggests that mucosal block effect is not
pronounced in humans.
• Some of the community-based trials testing the
mucosal block theory in practice showed that daily
supplementation had a greater effect than did
weekly supplementation.

9. Need for the study:
• Although many studies were previously done on
daily and intermittent iron supplementation
regimens in pregnancy, they lack proper results so
this present study is being done to further evaluate.

10. Objectives of the study:
• 1. To compare outcome on hemoglobin levels
between daily regimen and intermittent regimen of
oral iron therapy in non-anemic pregnant women.
• 2. To assess the side effects profile and compliance
of patients in both groups.

11. Review of the Literature:
Kumar Agrawal et al3 study 2020: A prospective
randomized clinical trial on Effect of daily versus
intermittent iron therapy in pregnant women,
hematological and pregnancy outcome .141 healthy
pregnant women between 14 -20 weeks of
gestational age were studied to compare daily iron
supplementation and intermittent iron
supplementation in preventing anemia. Study
concluded that daily or weekly iron supplementation
is equally effective for healthy pregnant women
without anemia.

12.  Lata Rajoria et al6 study 2018: A randomized
control trial on Comparative study of daily vs
intermittent iron supplementation in pregnant women.
Study concluded that Prophylactic oral iron supplements
when given intermittently were not effective in
preventing iron deficiency anaemia in 92 pregnant
women. In non-anemic pregnant women, a weekly
regimen is an effective alternative to a daily regimen for
antenatal oral iron and folate supplementation for
preventing anemia and iron deficiency during the third
trimester.
Review of the Literature:

13.  A Cochrane data base systemic review 20128:
Randomized control trial of Intermittent oral iron
supplementation during pregnancy in total 4072
women from 13 different countries. It concluded that
intermittent iron and folic acid regimen produced
similar maternal and infant outcomes at birth but
with fewer side effects
Review of the Literature:

14.  Mukhopadhyaya et al9 study 2004: A
randomized control trial on Impact of daily versus
intermittent oral iron supplemnentation in pregnant
women in total of 111 women. Study concluded that
weekly iron supplementation is an effective option
for prophylaxis in non anaemic pregnant women but
has less than optimal benefit in anaemic women.
Review of the Literature:

15.  Sunil Gomber et al10 study 2002: A randomized
control trial on Impact of daily versus weekly hematinic
supplementation on Anemia in 80 pregnant women.
Study concluded that Weekly iron supplementation is an
effective mode of treating anemia among pregnant
women and maternal anemia during pregnancy is
adversely associated with fetal growth.
 Endi Ridwan E et al14 study 1996: A study
conducted.on The effect of weekly iron supplementation
in pregnant women in Indonesia women were
compared to that of daily supplementation in total of
139 women in Indonesia. The study concluded that there
was no significant difference between groups for changes
in haemoglobin but serum ferritin levels did not show
any significant concentration.
Review of the Literature:

16. Materials & Methods
1. Study design: Single blinded randomized control study
2. Study setting: PESIMSR Hospital, Obstetrics and Gynaecology .
3. Study period: 18 months (Jan 2021-Jun 2022)
4. Study population: Pregnant women between 14 – 20 weeks of
gestational age attending obstetrics and gynecology out patient
department in PESIMSR hospital.
5. Sampling method: Purposive sampling technique.
a. Sample size: 120 (60 in each group)
Based on study by Kumar Agrawal et al3, where the significance of
the difference between the daily and weekly supplemented groups
was assessed by the student’s t-test for unpaired values and the
chi-square test for non-parametric variables. The significance level
was set at p<0.05.
b. calculated using, formula:

17. Inclusion Criteria:
• Pregnant women between 14 and 20 weeks of
gestation.
• Pregnant women with a hemoglobin level above
10.5 gm/dl
• Singleton pregnancy.
• Age between 18-40 years.

18. Exclusion Criteria:
• Women with medical problems known to affect
iron metabolism or homeostasis • Women with
existing anaemia (pre pregnancy or during the
pregnancy (Hb < 10.5gm/dl)
• Underlying malabsorption disease.
• women taking drugs e.g. antiepileptics, NSAIDs,
antithyroid; the history of prior blood transfusion.
• History of chronic illness e.g. liver, renal and heart
diseases
• Multiple gestation.

19. Tools to be used in the study:
1. Informed consent
2. Proforma
3. Automated hematology cell analyzer
4. Iron blister packets
5. Book

20. Procedure for data collection:
• This study will be done to compare changes in
haemoglobin percentage with intermittent vs daily
oral supplementation of iron, which is well
tolerated and effective in non-anemic pregnant
women.
• A total of 120 pregnant women will be randomly
selected, who fulfill the inclusion criteria and
exclusion criteria.
• After obtaining written informed consent, data will
be recorded by using a separate proforma for every
study subject.

21. • These 120 pregnant women, between 14 and 20
weeks of gestation will be divided into two odd and
even number groups.
• Tablets used in this study are Hemobest XT which
contain ferrous ascorbate equivalent to 100mg
elemental iron.

22. • Group I (odd): Women in group I (n=60) will be
instructed to take one tablet daily and supplied 3
blister packets (total of 30 tablets) for 1 month.
• Group II (even): Women in group II (n=60) will be
supplied one blister packet (10 tablets) to cover
one month. They will be instructed to choose Any
day of the week and take two tablets on that day –
one before lunch and the other before dinner total
200 mg elemental iron/week). No tablets will be
given for the rest of the week and the regimen is
repeated weekly.

23. • All women will be instructed to take their iron
tablets before their meals (30minutes approx.) and
not to take them with tea, coffee, or milk.
• Patients will be advised to bring back their blister
packets at each ANC visit. The number of days for
which the drugs consumed will be recorded. An
attempt will be made to verbally verify compliance,
and by checking the used blister packets.
• Patients are ensured to take iron tablets without
missing by keeping alarms and documentation in a
book while taking iron tablets

24. • Patients will be informed about the usual side
effect of iron preparations and told to report
nausea, vomiting, bowel disturbances, or any other
complications. They will also to report if severe
intolerance caused them to stop taking
supplements.
• Serum hemoglobin levels will be measured for all
pregnant women who attended the antenatal
clinics between the 14 and 20 week of gestation.

25. • Haemoglobin percentage will be checked by
automated haematology cell analyzer at entry into
the study, repeated at 1 month and 3 months after
starting supplementation. Final hemoglobin
estimation will be done at 32-34 weeks period of
gestation.
• If the patient is diagnosed as anemic they will be
treated according to standard protocol of the
institute.
• Subsequently side effects will be noted and
corrective measures will be taken.

26. Statistical Analysis of data:
• The data will be entered into MS excel 2010 version
and further analyzed using SPSS version 21.
• Descriptive statistics will be analyzed as follows:
• The categorical data will be analyzed using
percentages and the continuous data will be
analyzed using mean and standard deviation.
• Inferential statistics will be analyzed as follows:
• Chi-square test, ‘t’ test etc will be used. A
probability value of <0.05 will be considered as
statistically significant.

27. • After obtaining informed consent , data will be
recorded by using a separate proforma for every
study subject.
• Proforma includes details regarding obstetric
history , past history , clinical examination will be
collected, investigations and outcome.

28. • Ethical clearance will be obtained from the
Institutional Human Ethics Committee , PESIMSR.
ETHICAL CLEARANCE

29. OUTCOME
• To know the most suitable iron prophylaxis regimen
which is best suited in non-anemic pregnant
women with respect to
• a. prevent anemia
• b. with low side effect profile and
• c. better compliance

30. IMPACT OF THE STUDY
• We can choose the better oral iron regimen which
is best suited for pregnant women.
• And if the results are fruitful large field studies can
be done on the basis of this study

31. DISTRIBUTION OF STUDY GROUPS
GROUP NUMBER %
DAILY 100 50
WEEKLY 100 50

32. MEAN AGE DISTRIBUTION
GROUP A GROUP B T value P value
MEAN +/-SD MEAN+/-SD
AGE IN YEARS 25.42+/-3.25 25.30+/-3.60 0.175 0.861

33. GRAPH 1 MEAN AGE OF
DISTRIBUTION
25.42 25.3
0
5
10
15
20
25
30
Group A Group B
Mean
age
in
years
Axis Title
Series 1
Table shows the age distribution details. Both the groups were matched for maternal age on
the entry in the study

34. occupation Group A Group B Total P value
Agriculture 4 3 7
8.0% 6.0% 7.0%
Doctor 1 2 3
2.0% 4.0% 3.0%
Housewife 42 43 85 0.78
84% 86% 85%
Lecturer 2 0 2
4.0% 0.0% 2.0%
s/n 1 2 3
2.0% 4.0% 3.0%
Total 50 50 100
100.0% 100.0% 100.0%
TABLE – 2 : OCCUPATION

35. GRAPH 2 : OCCUPATION
0
5
10
15
20
25
30
35
40
45
50
Agriculture Doctor Housewife Lecturer s/n
No
of
patients
Occupation
Chart Title
Series 1 Series 2
There was p value <0.728 which is not statistically significant, so there was no statistically
significant difference between the two groups with regards to occupation. Both the groups
were compared using chi-square test

36. Religion Group A Group B Total
Hindu
46 45 91
92.0% 90.0% 91.0%
Muslim
4 5 9
8.0% 10.0% 9.0%
Total 50 50 100
100% 100% 100%
0.574
P value
TABLE 3 - RELIGION

37. GRAPH 3 - RELIGION
0
5
10
15
20
25
30
35
40
45
50
Hindu Category 2
No
of
patients
Religion
Chart Title
Series 1 Series 2
There was p value <0.574 which is not statistically significant, so there was no statistically
significant difference between the two groups with regards to religion. Both the groups were
compared using chi-square test

38. TABLE 4 SOCIOECONOMIC STATUS
SES GROUP A GROUP B TOTAL P VALUE
II
30 34 64
60.0% 68.0% 64.0%
III
20 16 36 0.405
40.0% 32.0% 36.0%
TOTAL
50 50 100
100.0% 100.0% 100.0%

39. 0
5
10
15
20
25
30
35
40
II III
NO
OF
PATIENTS
SES
Chart Title
Series 1 Series 2
GRAPH 4 SOCIOECONOMIC
STATUS
There was p value <0.405 which is not statistically significant, so there was no statistically
significant difference between the two groups with regards to socioeconomic status. Both the
groups were compared using chi-square test

40. TABLE 5 OBSTETRIC HISTORY
OBSTETRIC
HISTORY
GROUP A GROUP B TOTAL P VALUE
PRIMI 30 29 59
60.0% 58.0% 59.0%
MULTI 20 21 41 0.839
40.0% 42.0% 41.0%
TOTAL 50 50 100
100.0% 100.0% 100.0%

41. 0
5
10
15
20
25
30
35
PRIMI MULTI
NO
OF
PATIENTS
OBSTETRIC HISTORY
Chart Title
Series 1 Series 2
GRAPH 5 OBSTETRIC HISTORY
There was p value <0.839 which is not statistically significant, so there was no statistically
significant difference between the two groups with regards to Obstetric history. Both the
groups were compared using chi-square test

42. TABLE -6 HAEMOGLOBIN
TIME GROUP A GROUP B t VALUE P VALUE
VISIT 1 10.96±0.68 11.08±0.92 -0.718 0.474
VISIT 2 11.31±0.73 11.40±0.72 -0.572 0.569
VISIT 3 11.90±0.83 11.69±0.80 1.308 0.194

43. GRAPH -6
HAEMOGLOBIN
10.96
11.31
11.9
11.08
11.4
11.69
10.4
10.6
10.8
11
11.2
11.4
11.6
11.8
12
VISIT 1 VISIT 2 VISIT 3
MEAN
HAEMOLOBIN
Chart Title

44. TABLE -7 NAUSEA
NAUSEA GROUP A GROUP B TOTAL P VALUE
PRESENT
22 7 29
44.0% 14.0% 29.0%
ABSENT
28 43 71
0.001
56.0% 86.0% 71.0%
TOTAL
50 50 100
100.0% 100.0% 100.0%

45. 0
5
10
15
20
25
30
35
40
45
50
PRESENT ABSENT
NO
OF
PATIENTS
NAUSEA
Chart Title
GROUP A GROUP B
GRAPH -7 NAUSEA
A very highly statistically significant difference was found between the two groups for side
effects of nausea

46. TABLE – 8 VOMITING
VOMITING GROUP A GROUP B TOTAL P VALUE
PRESENT 19 4 23
38.0% 8.0% 23.0%
ABSENT 31 46 77 0.000
62.0% 92.0% 77.0%
TOTAL 50 50 100
100.0% 100.0% 100.0%

47. 0
5
10
15
20
25
30
35
40
45
50
PRESENT ABSENT
No
of
patients
vomiting
Chart Title
Series 1 Series 2
GRAPH – 8 VOMITING
A very highly statistically significant difference was found between the two groups for
side effects of vomiting.

48. TABLE -9 GASTRITIS
METALLIC
TEST
GROUP A GROUP B TOTAL P VALUE
PRESENT
6 1 7
12.0% 2.0% 7.0%
ABSENT
44 49 93 0.050
88.0% 98.0% 93.0%
TOTAL
50 50 100
100.0% 100.0% 100.0%

49. 0
10
20
30
40
50
60
PRESENT ABSENT
NO
OF
PATIENTS
GASTRITIS
Chart Title
GRAPH -9 GASTRITIS
A very highly statistically significant difference was found between the two groups for
side effects of Gastritis

50. TABLE -10 CONSTIPATION
CONSTIPATION GROUP A GROUP B TOTAL P VALUE
PRESENT
9 4 13
18% 8.0% 13.0%
ABSENT
41 46 87
0.137
82.0% 92.0% 87.0%
TOTAL
50 50 50
100.0% 100.0% 100.0%

51. 0
5
10
15
20
25
30
35
40
45
50
PRESENT ABSENT
NO
OF
PATIENTS
CONSTIPATION
Chart Title
GRAPH -10 CONSTIPATION
A very highly statistically significant difference was found between the two groups for
side effects of Constipation

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55. THANK YOU