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Philippine Obstetrical and

Gynecological Society (POGS), Foundation, Inc.

!
CLINICAL PRACTICE GUIDELINES
on
IRON DEFICIENCY ANEMIA
!

November 2009

Task Force on Clinical Practice Guideline

In the Management of Iron Deficiency Anemia
 Philippine Obstetrical and
Gynecological Society (POGS),
Foundation, Inc.

CLINICAL PRACTICE GUIDELINES

on
NORMAL LABOR and DELIVERY

November 2009

Task Force on Clinical Practice Guidelines

In the Management of
Iron Deficiency Anemia
 FOREWORD!

!
LOURDES B. CAPITO, MD
President
Philippine Obstetrical and Gynecological Society (Foundation), Inc. (POGS), 2009

I have envisioned and have implemented to completion the publication of a

series of Clinical Practice Guidelines on the major procedures and topics of Obstetrics
and Gynecology. This is in consonance with the theme of my Presidency, “Babae,
Kalusugan Mo, Katungkulan Natin”. This is the Clinical Practice Guidelines on Iron
Deficiency Anemia and is the First Edition of this Publication, 2009.

In the role of the POGS to provide its members with updates, current and
standard practice recommendations and guidelines, this publication will fulfill the
objective of continuing education and implementation of refinements in Obstetrics and
Gynecology. In keeping with the highest standards of care, the Level and Grades of
Clinical Practice/Recommendation have been adopted for every recommendation that is
completed and decided.

In the process of the formulation of the guideline/recommendation, the entire

membership of the POGS was consulted. I take special effort to thank the AdHoc
Committee on Clinical Practice Guidelines, headed by its Chair, Dr. Efren J. Domingo for
the unceasing tireless effort to complete this publication. I also gratefully acknowledge
the Chairs and Training Officers of the Residency-Accredited Hospitals, the Technical
Working Group, and the CME Committee.

It becomes easy, dignified and scientific to conduct the practice of Obstetrics and
Gynecology specifically on Iron Deficiency Anemia. Now, the Clinical Practice Guidelines
on Iron Deficiency Anemia will hope to update and make the practice current and
responsive to world-class standards and make the patients under our care deserving of
the trust and confidence that we, Obstetricians, impart with utmost care and
compassion.

LOURDES BLANCO-CAPITO, MD
 INTRODUCTION!

EFREN J. DOMINGO, MD, PhD

Chair, AdHoc Committee on the Clinical Practice Guidelines, 2009

The Clinical Practice Guidelines on Irone Deficiency is the First Edition of this
Publication, 2009. The Philippine Obstetrical and Gynecological Society, (Foundation),
Inc. (POGS), through the AdHoc Committee on Clinical Practice Guidelines initiated and
led to completion the publication of this manual in plenary consultation with the
Residency Accredited Training Hospitals’ Chairs and Training Officers, The Regional
Board of Directors, The Board of Trustees, The Task Force on the Management of Iron
Deficiency Anemia and the Committee on Continuing Medical Education.

This publication represents the collective effort of the POGS in updating the
clinical practice of Obstetrics and Gynecology, specifically on Iron Deficiency Anemia,
and making it responsive to the most current and acceptable standard in this procedure.
A greater part of the inputs incorporated in this edition are the contributions originating
from the day-to-day academic interactions from the faculty of the different Residency-
Accredited Hospitals in Obstetrics and Gynecology in the country.

This Clinical Practice Guideline on Iron Deficiency Anemia is envisioned to

become the handy companion of the Obstetrician-Gynecologist in his/her day-to-day
rendition of quality care and decision making in managing the Obstetric patient. This is
also envisioned to provide the academic institutions in the country and in Southeast Asia
updated information and Iron Deficiency Anemia treatments being practiced in the
Philippines.

Profound gratitude is extended to all the members of the POGS, the Chairs and
Training Officers of the Residency-Training Accredited Institutions, the Regional
Directors, The Task Force on Iron Deficiency Anemia Reviewers/Contributors, The CME
Committee members, and the 2009 POGS Board of Trustees.

EFREN J. DOMINGO, MD, PhD

BOARD OF TRUSTEES 2009

OFFICERS

Lourdes B. Capito, MD
President

Regta L. Pichay, MD
Vice President

Ma. Carmen H. Quevedo, MD

Secretary

Ditas Christina D. Decena, MD

Treasurer

Christia S. Padolina, MD
Public Relations Officer

BOARD OF TRUSTEES
Mayumi S. Bismarck, MD
Virgilio B. Castro, MD
Efren J. Domingo, MD, PhD
Gil S. Gonzales, MD
Diosdado V. Mariano, MD
Ma. Socorro M. Solis, MD
 ADHOC COMMITTEE ON CLINICAL PRACTICE GUIDELINES ON
IRON DEFICIENCY ANEMIA

Efren J. Domingo, MD, PhD

Chair

MEMBERS
Jennifer T. Co, MD Lisa Teresa P. Jabson, MD
Jericho Thaddeus P. Luna, MD Noel E. Raymundo, MD
Josephine M. Lumitao, MD Elisa O. Tiu, MD

FELLOWS
Rachelle U. delos Reyes, MD Ana Victoria V. Dy Echo, MD
May Nueva-Hipolito, MD Michelle R. Ong, MD
Renee Vina G. Sicam, MD

TECHNICAL STAFF ASSISTANTS

Ms. Emiliana C. Enriquez
Ms. Jhasmin G. De Guzman

TASK FORCE ON IRON DEFICIENCY ANEMIA

Virginia Abalos, MD Rogelio P. Mendiola, MD

Lourdes B. Capito, MD Rudie B. Mendiola, MD
Irene Castillo, MD Marissa Nualla, MD
Ditas Christina D. Decena, MD Judith Sison, MD
Angelina Gapay, MD

TASK FORCE REVIEWERS AND PLENARY REVIEWERS

Rainerio S. Abad, MD Rommel Z. Dueñas, MD Patria P. Punsalan, MD

Imelda O. Andres, MD
Cecilia Joyce M. Bascarra, MD
Mayumi S. Bismark, MD
Ricardo R. Braganza, MD
Sylvia A. Carnero, MD
Virgilio B. Castro, MD
Lyra Ruth Clemente-Chua, MD
Maria Lourdes B. Coloma, MD
Godofreda V. Dalmacion, MD
Ditas Cristina D. Decena, MD
Santiago A. del Rosario, MD
Rey H. Delos Reyes, MD
Virginia R. de Jesus, MD
Arcangel N. Diamante, MD
Joseline A. Ferrolino, MD
Ma. Corazon N. Gamilla, MD
Erlinda G. Germar, MD
Ma. Antonia E. Habana, MD
Myrna R. Habaña, MD
Bernardita B. Javier, MD
Milagros T. Jocson, MD
Lilia P. Luna, MD
Augusto M. Manalo, MD
Diosdado V. Mariano, MD
Jocelyn Z. Mariano, MD
Christia S. Padolina, MD
Mildred N. Pareja, MD
Wilhelmina Pineda, MD
Ma. Carmen H. Quevedo, MD
Rebecca M. Ramos, MD
Cristina C. Raymundo, MD
Rosendo R. Roque, MD
Marilyn D. Ruaro, MD
Ma. Socorro M. Solis, MD
Sherri Ann L. Suplido, MD
Walfrido W. Sumpaico, MD
Carmencita B. Tongco, MD
Ma. Victoria Torres, MD
Milagros P. Torres, MD
Ma. Trinidad R. Vera, MD
Ma. Guadalupe N. Villanueva, MD

Regional Directors
Ellen A. Manzano, MD (Region 1)
Melchor C. dela Cruz, MD (Region 2)
Concepcion P. Aronza, MD (Region 3)
Ernesto S. Naval, MD (Region 4)
Rowena M. Auxillos, MD (Region 4A)
Cecilia Valdes-Neptuno, MD (Region 5)
Evelyn R. Lacson, MD (Region 6)
Belinda N. Pañares, MD (Region 7)
Realino G. Molina, MD (Region 8)
Suzette S. Montuno, MD (Region 9)
Jana Joy R. Tusalem, MD (Region 10)
Amelia A. Vega, MD (Region 11)
 DISCLAIMER, RELEASE AND WAIVER OF RESPONSIBILITY

• This is the Clinical Practice Guidelines (CPG) on Iron Deficiency Anemia, First Edition,
November 2009.
• This is the publication of the Philippine Obstetrical and Gynecological Society, (Foundation),
Inc. (POGS).
• This is the ownership of the POGS, its officers, and its entire membership.
• The obstetrician-gynecologist, the general practitioner, the patient, the student, the allied
medical practitioner, or for that matter, any capacity of the person or individual who may
read, quote, cite, refer to, or acknowledge, any, or part, or the entirety of any topic, subject
matter, diagnostic condition or idea/s willfully release and waive all the liabilities and
responsibilities of the POGS, its officers and general membership, as well as the AdHoc
Commiittee on the Clinical Practice Guidelines and its Editorial Staff in any or all clinical or
other disputes, disagreements, conference audits/controversies, case discussions/critiquing.
• The reader is encouraged to deal with each clinical case as a distinct and unique clinical
condition which will never fit into an exact location if reference is made into any or all part/s
of this CPG.
• The intention and objective of this CPG is to serve as a guide, to clarify, to make clear the
distinction. It is not the intention or objective of this CPG to serve as the exact and precise
answer, solution and treatment for clinical conditions and situations. It is always encouraged
to refer to the individual clinical case as the one and only answer to the case in question, not
this CPG.
• It is hoped that with the CPG at hand, the clinician will find a handy guide that leads to a
clue, to a valauable pathway that leads to the discovery of clinical tests leading to clinical
treatments and eventually recovery.
• In behalf of the POGS, its Board of Trustees, the Adhoc Committee on The Clinical Practice
Guidelines, 2009, this CPG is meant to make each one of us a perfect image of Christ, the
Healer.

!
 CPG ON IRON DEFICIENCY ANEMIA
TABLE OF CONTENTS!

I. Burden of Disease, Rationale and Objectives ……………………….... 1

II. Definition ……………………………………………………………… 2
III. Diagnosis ……………………………………………………………….
IV. Management
a. Oral …………………………………………………………….
b. Parenteral ………………………………………………………
c. Blood transfusion ………………………………………………
d. Supportive Measures …………………………………………..
V. Prevention
a. Nutrition/Diet …………………………………………………
b. Antihelminthics ……………………………………………….
V. Appendix ……………………………………………………………..
 BURDEN OF DISEASE, RATIONALE AND OBJECTIVES

Anemia is a major global problem that affects women in all countries. The
prevalence, however, is highest in developing countries, where malnutrition is a major
concern.
A deficiency of biologically available iron in food intake is one of the most
frequent aspects of malnutrition. In developing countries, the Philippines included, iron
deficiency is often due to malnutrition and infectious diseases like hookworm anemia.
Oftentimes, there is also deficiency in some of the micronutrients (e.g., zinc, iodine,
vitamins A, B12, folic acid) and proteins.
Individual lifestyles can also lead to iron deficiency, such as slimming diets,
vegetarian diets, and intensive physical training.
Iron deficiency occurs as a result of a prolonged negative iron balance due to
reduced iron intake, increased demand as in growing children and pregnancy, excessive
loss, as in cases of hemorrhage, and malabsorption syndromes.
The general prevalence of iron deficiency in developing countries is estimated to
be 40%.1 It is even higher in the two high risk groups of menstruating women and small
children by as much as 70%.2 Worldwide, more than 1.5-1.8 billion people suffer from
iron deficiency anemia.3 Estimates by the Center for Human Nutrition at Johns Hopkins
University in Baltimore (USA) suggest that as many as 3.5 billion people worldwide
suffer from an anemia that is at least in part due to iron deficiency.4
This Clinical Practice Guideline (CPG) is an attempt to define iron deficiency and
how it causes iron deficiency anemia, its pathophysiology, prevention and treatment.
Discussion is based on the best evidence available. Studies and journal articles used as
resource materials were reviewed and evaluated for quality according to the method
outlined by the US Preventive Task Force. (See Appendix A)

References

1. Yeung and Kwan, 2002.

2. Ramakrishnan and Yip, 2002.
3. Who, 1998.
4. Caballero, 2002.
 DEFINITION

Anemia is the most common hematologic problem during pregnancy.1

Physiologic anemia can occur during pregnancy as a result of a dilutional process
secondary to an increase in plasma volume. The physiologic changes that occur during
pregnancy make it difficult to define normal hematologic values for pregnant women.
But recently the World Health Organization (WHO) and the US Center for Disease
Control (CDC) have defined the criteria for anemia in pregnancy, as seen in Table 1.

Table 1
Stage of Pregnancy Anemic if less than (g/dl)
1st trimester: 0-12 weeks 11.0
2nd trimester: 13-28 weeks 10.5
3rd trimester: 29 weeks to term 11.0

Likewise, the WHO stratified the severity of anemia depending on the

hemoglobin levels:

Table 2: Severity of Anemia

Category Anemia Severity Hemoglobin Level (g/dl)
1 Mild 9.5-10.5
2 Moderate 8.0-9.4
3 Severe 6.9-7.9
4 Very severe < 6.9

Iron Deficiency Anemia (IDA) in Pregnancy

There are various causes of anemia during pregnancy such as nutritional

deficiencies, hemolysis and other diseases that can cause significant anemia affecting
both mother and fetus (see Appendix B). But of all the causes of anemia, IDA is the most
common among pregnant women.2 This is due to the increased diversion of iron to the
growing fetus, the placenta, and the increased maternal red cell mass. Likewise
contributing to the iron deficiency is the blood loss at delivery and iron loss in breast
milk. It is estimated that the average iron lost from transfer to fetus, blood loss during
delivery, and iron loss in breast milk is about 900 to 1000 mg, nearly equivalent to a loss
of more than 2 L of blood. The risk of iron deficiency during pregnancy is higher in
women with a history of previous pregnancies, heavy menses or poor diet which all result
in poor iron reserves.

References

1. Wheby MS (Ed) Anemia. Med Clin North Am 1992;76:631-645.

2. Schwartz WS, Thurman GR. Iron deficiency anemia in pregnancy. Clin Obstet Gynecol 1995;38:
443-454.
 DIAGNOSIS

The diagnosis of iron deficiency anemia (IDA) is suggested by the following

features:
• Low hemoglobin (Hgb), hematocrit (Hct)
• Suggestive features on peripheral smear:
Hypochromia
Microcytosis, anisocytosis, poikilocytosis
Pencil-shaped red blood cells (RBCs)
Low MCV, MCHC, MCH *
High RDW

However, the definitive diagnosis of IDA is made through documentation of the

patient’s iron status. Definitions of iron status are based on the criteria determined by the
Center for Disease Control (CDC) and the Center for Disease Prevention as summarized
in Table 3.

Table 3: Definitions of iron status for women during pregnancy and the post-
partum period!
Iron deficiency Iron deficiency
Iron sufficiency
without anemia anemia
Pregnancy:
Hgb ! 110 g/L Hgb ! 110 g/L Hgb < 110 g/L
20 weeks to
Ferritin ! 12 "gL Ferritin < 12 "gL Ferritin < 12 "gL
delivery
Postpartum: Hgb ! 120 g/L Hgb ! 120 g/L Hgb < 120 g/L
6 mos. Ferritin ! 15 "gL Ferritin < 15 "gL Ferritin < 15 "gL
#The more conservative cutoffs reflect the physiologic hemodilution that occurs
in pregnancy.

Additionally, the following parameters can be used for the diagnosis of IDA:
• Reduced serum iron (<30 umol/L)
• Increased total iron binding capacity (TIBC) (>80 umol/L)
• Reduced transferrin saturation (<15%), computed as serum iron/TIBC

Therapeutic Trial of Oral Iron

In the final analysis, the response to iron therapy is the proof of correctness in
diagnosis of IDA. Furthermore, some physicians or patients may not have access to all
the tests described for diagnosis of IDA. In this event, the patient’s response to therapy
may become a primary diagnostic measure. Iron administration in such a therapeutic trial
should usually be by the oral route only. A therapeutic trial under any circumstance
should be followed carefully. If the cause of anemia is iron deficiency, adequate iron
therapy should result in reticulocytosis with a peak occurring after 1 to 2 weeks of
therapy, although if anemia is mild, the reticulocyte response may be minimal. A
significant increase in the hemoglobin concentration of the blood should be evident 3 to 4
weeks later, and the hemoglobin concentration should attain a normal value within 2 to 4
months of adequate oral iron treatment. Unless there is evidence of continued substantial
blood loss, a malabsorption syndrome, or evidence of H. pylori infection, the absence of
these changes must be taken as evidence that iron deficiency is not the cause of anemia.3
Iron therapy should be discontinued and referral for hematologic consultation should be
sought.

References

1. Wheby MS (Ed) Anemia. Med Clin North Am 1992;76:631-645.

2. Schwartz WS, Thurman GR. Iron deficiency anemia in pregnancy. Clin Obstet Gynecol 1995;38:
443-454.
3. Lichtman MA, et. al. (Ed) Williams Hematology 7th Edition. McGraw-Hill. 2006.
 MANAGEMENT

A. Oral Therapy

Preventive Iron Supplementation

1. Routine (universal) low dose (30 mg) iron supplementation beginning at the
first prenatal visit decreases the prevalence of maternal anemia at delivery.
There is no evidence to advise against this policy of routine iron
supplementation in pregnancy.1,2,3,6,7,16 (Level II-2, Grade A)

2. The recommended daily dietary allowance of ferrous iron during pregnancy

is 27 mg, which is present in most prenatal vitamins, and 9-10 mg during
lactation.6 The high physiological requirement for iron in pregnancy is
difficult to meet even with nutritious diets which provide only about 12-14
mg of iron.6,7 (Level II-3, Grade B)

3. There is little evidence that iron supplementation results in morbidity beyond

gastrointestinal symptoms, except in patients with hemochromatosis or
certain other genetic disorders.16 (Level III, Grade C)

4. There was no discernible difference between supplemented and placebo

patients in maternal health status upon delivery despite the differences in
iron status during pregnancy.16 (Level II-2, Grade A)

5. Iron supplementation results in significantly longer gestation durations and

increased infant birth weight but did not reduce the risk of preterm
delivery.18 (Level I, Grade A)

6. Randomized controlled trials (RCT) have been inconclusive on the effect of

universal iron supplementation in pregnancy versus adverse maternal and
fetal outcomes. 8 (Level III, Grade B)

Iron Therapy

1. All pregnant women should be screened for iron deficiency anemia (IDA).2,15
(Level III, Grade B)

2. All pregnant women with IDA should be treated with supplemental iron, in
addition to prenatal vitamins.2,3,6 (Level III, Grade C)

3. Pregnant women with IDA should receive 60-120 mg iron plus 400 "g folic
acid daily up to three months postpartum and should continue preventive
supplementation regimen.7,8 (Level III, Grade C)
4. Ferrous sulfate is recommended over newer iron preparations as first-line
therapy of iron deficiency. If ferrous sulfate is not tolerated, alternative
formulations may be tried.19 (Level I, Grade B)

5. There are no significant differences in tolerability or efficacy between

different formulations of oral iron salts. Controlled-release iron preparations
may cause fewer gastrointestinal side effects, but discontinuation rates are
similar and efficacy is comparable.19 (Level I, Grade B)

6. Anemia with hemoglobin levels less than 6 g/dl is associated with poor
pregnancy outcome like prematurity, spontaneous abortions, low birth
weight, and fetal deaths.2,13,14,15 (Level III, Grade B)

7. Severe anemia with maternal hemoglobin levels less than 6 g/dL has been
associated with abnormal fetal oxygenation resulting in nonreassuring fetal
heart rate patterns, reduced amniotic fluid volume, fetal cerebral
vasodilatation, and fetal death.2,17 (Level III, Grade B)

8. IDA during pregnancy has been associated with an increased risk of

postpartum depression; with poor results in mental and psychomotor
performance testing in offspring.2 (Level III, Grade B)

9. Empiric iron therapy may be initiated in patients without evidence of causes

of anemia other than iron deficiency, without first obtaining iron test results.
(Level III, Grade C)

10. Iron requirement is 1.8 times higher for vegetarians because of the lower
intestinal absorption of nonheme iron in plant foods. Vegetarians should
consider consuming nonheme iron sources together with a good source of
vitamin C, such as citrus fruits, to improve the absorption of nonheme iron.6
(Level III, Grade C)

11. Iron requirement may also be higher in some developing countries where
access to a variety of foods is limited.6 (Level II-2, Grade B)

12. Failure to respond to iron therapy should prompt further investigation and
may suggest an incorrect diagnosis, coexisting disease, malabsorption
(sometimes caused by the use of enteric-coated tablets or concomitant use of
antacids), noncompliance, or blood loss.2 (Level II-3, Grade B)

Practical Issues about Iron Therapy

1. Oral iron supplements must dissolve rapidly in the stomach so that the iron
can be absorbed in the duodenum and upper jejunum. Enteric-coated or
 delayed-release preparations may have fewer side-effects but are not as well
absorbed, and may be less effective since they do not dissolve in the stomach.
They are not usually recommended.2,9,10 (Level II, Grade B)

2. Daily iron supplementation should be divided in two or three equally spaced

doses since the amount of iron absorbed decreases as the doses get larger.3,10
(Level II, Grade C)

3. Iron supplements are absorbed better if taken an hour before meals.9 (Level
II, Grade C)

4. Iron is better taken with vitamin C or orange juice as Vitamin C increases

the absorption of iron.6,10 (Level III, Grade C)

5. Iron should not be taken together with milk, caffeine, tea, wine, legumes,
whole grains, antacids, H-2 receptor blockers, proton pump inhibitors and
calcium supplements as they decrease iron absorption.6,9,10 (Level II, Grade C)

6. In cases of gastrointestinal upset, start with half the recommended dose and
gradually increase to the full dose to minimize these side effects.9,10 (Level III,
Grade C)

7. A stool softener such as docusate sodium may be along with your iron if
constipation is a problem.9 (Level III, Grade C)

Follow-Up of Treatment

1. Evaluate the hemoglobin concentration at subsequent prenatal visits within 2

to 3 weeks of starting iron supplementation when hemoglobin usually
increases. If there has been no response to iron supplementation, refer for
additional medical evaluation. If the hemoglobin concentration is normal for
that stage of pregnancy, lower the supplemental iron dose to 30 mg of iron
per day.8 (Level II-3, Grade B)

2. Adequate iron replacement has typically occurred when the serum ferritin
level reaches 50 "g per L (8.9 "mol per L).11 (Level II-2, Grade B)

References

1. Pena-Rosas JP, Viteri FE. Effects of routine oral iron supplementation with or without folic acid
for women during pregnancy. Cochrane Database Syst Re 2006,Issue 3.
2. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 95: anemia in
pregnancy. Obstet Gynecol 2008;112(1):201-7.
3. Centers for Disease Control and Prevention. Recommendations to Prevent and Control Iron
Deficiency in the United States. MMWR Recomm Rep 1998;47(RR-3):1–29.
 4. Scholl TO. Iron status during pregnancy: setting the stage for mother and infant. Am J Clin Nutr
2005;81:1218S–22S.
5. Rasmussen K. Is there a causal relationship between iron deficiency or iron-deficiency anemia and
weight at birth, length of gestation and perinatal mortality? J Nutr 2001;131:590S,601S;
discussion 601S–603S.
6. Institute of Medicine (US). Dietary reference intakes for vitamin A, vitamin K, arsenic, boron,
chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc.
Washington, DC: National Academy Press 2002.
7. Stoltzfus R, Dreyfuss. Guidelines for the use of iron supplements to prevent and treat iron
deficiency anemia. International Nutritional Anemia Consultative Group. Washington DC: ILSI
Press 1998.
8. Institute of Medicine. Recommended Guidelines For Preventing And Treating Iron Deficiency
Anemia In Pregnant Women. In: Iron Deficiency Anemia: Recommended Guidelines for the
Prevention, Detection, and Management Among U.S. Children and Women of Childbearing Age.
National Academy Press 1993.
9. National Anemia Action Council. www.anemia.org. April 2009
10. National Institute of Health. Office of Dietary Supplements. Dietary Supplement Fact Sheet: Iron.
August 2007.
11. Frewin R, Henson A, Provan D. ABC of clinical haematology. Iron deficiency anemia. BMJ 1997;
314:360-3.
12. Little, David R. Ambulatory management of common forms of anemia. Am Fam Physician 1999.
13. Sifakis S, Pharmakides G. Anemia in pregnancy. Ann N Y Acad Sci. 900:125-136.
14. Brabin BJ, et. al. An analysis of anemia and pregnancy-related maternal mortality. J Nutr.
2001;131:604S-615S.
15. Helfand M, Freeman M, Nygren P, Walker M. Screening for iron deficiency anemia in childhood
and pregnancy: Update of 1996 USPSTF Review. Evidence Synthesis No. 43 Rockville, MD:
Agency for Healthcare Research and Quality. April 2006
16. Meier PR. Prevention of iron deficiency anemia in adolescent and adult pregnancies. Clin Med Res
2003;1(1):29-36.
17. Allen LH. Biological mechanisms that might underlie iron’s effects on fetal growth and preterm
birth. J Nutr 2001;131:581S–9S.
18. Cogswell ME, Parvanta I, Ickes L, Yip R, Brittenham. Iron supplementation during pregnancy,
anemia, and birth weight: a randomized controlled trial. Am J Clin Nutr 2003;78:773–81.
19. Zumberg MS, et. al. Evidence-based Hematology. Ed. Crowther MA, et. al. Blackwell Publishing.
2008.

B. Parenteral Iron Therapy in Pregnancy and Puerperium

Parenteral iron is the best alternative to oral iron preparation in moderate to

severe anemia. It appears to be the treatment of choice with less serious side effects
indicated in the rapid correction of anemia in pregnancy or restoring maternal iron
stores, especially because the total dose can be administered over a shorter period of
time. This treatment will certainly help reduce the risk of homologous blood
transfusions during the peripartum period if timely given.

1. There are numerous indications for using parenteral iron in the treatment of
iron deficiency anemia in pregnancy. (Level I, Grade A)

Indications for parenteral iron infusion are the following:

a. Severe intestinal malabsorption1
b. Poor or non-compliance1
 c. Failure in response to oral iron therapy1
d. Severe intolerance to oral iron therapy1
e. Refuses blood transfusion or with contraindications to blood transfusion1
f. Functional or absolute iron deficiency with erythropoetin therapy 1
g. Hemoglobin level 7-10.5 g/dL2
h. Need for rapid efficacy2

2. Parenteral iron therapy has advantages over oral therapy and blood
transfusion. (Level III, Grade C)

Iron by the oral route is the treatment of choice for correction of IDA
because of its low cost, and easy to prescribe and use. However, the efficacy of
iron administered orally is low and its bioavailability is only 10-15 % of the
administered dose. The efficacy of oral iron treatment over a period of as little as
seven days is obviously low.
With parenteral iron therapy, there’s less risk of transmission of infections
like human immunodeficiency virus (HIV,) hepatitis B and C, malaria,
cytomegalovirus (CMV), and other undetectable infections. It is not associated
with blood transfusion reactions (hemolytic and non hemolytic) causing urticaria,
fever, rash, tachycardia and hypotension. It is also available in unlimited
quantities, is not group specific, has long shelf half-life and is much easier to store
close to the point of use.
Blood transfusion is expensive compared with intravenous iron. The
procurement costs of blood maybe seven times greater than intravenous iron when
based on the iron content.3

3. Iron sucrose is more stable compared to iron dextran and sodium ferric
gluconate. (Level I, Grade A)

There are three types of parenteral iron preparation available. Iron dextran
comes in the form of high (> 100,000 dalton) and low molecular weight iron
dextran. The half-life of iron dextran elimination from plasma is 3-4 days. The
iron binds to transferrin and some reenters the plasma, from where it is
transported to the bone marrow and utilize for hemoglobin synthesis. However,
because the complexes have a very high molecular mass, they cause severe
allergic reactions. Iron sucrose has a molecular weight of 30-100,000 dalton with
a maximum plasma concentration reached as early as 10 minute following bolus
administration of 30 mg/L. Its half-life is 5.5 hours. The substance maybe rated
as very safe for clinical use since anaphylactic reactions are extremely rare.
Sodium ferric gluconate are composed of unstable, labile complexes with
molecular weights of < 50,000 dalton. Because of their low stability compared
with iron dextran and iron sucrose complexes, they show less binding to transport
proteins, with greater quantities of free iron being released in the short term. They
are comparable to the iron sucroses with regard to allergic or anaphylactic
reaction, thus have a better side effect profile than the iron dextrans.1
4. Timing, dose and interval treatment are important considerations in
administering parenteral iron therapy. (Level I, Grade A)

It should be used during pregnancy if clearly needed, and should not be

started before 21 weeks gestation.4
Iron deficiency may be computed using the formula: Weight kg x (target
Hgb – actual Hgb) x 0.24 + 500 mg.5 The number of ampoules of iron sucrose
which may be needed may be computed using the formula: Target Hgb – Actual
Hgb x 2.5 = # ampoules (100 mg).6
Dosing schedule is as follows: 2 ampoules (200 mg) dissolved in 100 ml
0.9% normal saline solution, infused over 1 hour (2 ampoules of iron sucrose
results in an increase in hemoglobin level which is equivalent to one unit of
blood). The same dose (with or without dilution of 100 ml NSS) can also be
administered as a slow bolus injection over 10 minutes.7 Maximum cumulative
doses were 800 mg postpartum (200 mg/day for 4 days) and 1600 mg in
pregnancy (200 mg twice per week to a target Hgb of 110 g/l or for a maximum
of 4 weeks), administered over 30 minutes for short infusions (in-patients) and
over 5-10 minutes for bolus injections (outpatients). 8
Dose of IV dextran may be computed following the formula: Fe mg =
0.66 x wt in kg x 14 – patient Hgb in g/dl + 500 mg.9
If the hemoglobin level is below 10 g/dl, IV iron therapy is indicated. For
this, 200 mg iron sucrose 1-2 x/week is administered. If hemoglobin level is less
than 9 g/dl, IV sucrose is given 200 mg 2x/week.7
To avoid overloading the iron transport system, oral and parenteral iron
supplementation should not be combined (interval of at least 5 days).1

5. There is no risk of iron overload with intravenous iron therapy. (Level III,
Grade C)

The iron in intravenous preparations such as iron sucrose does not bind to
the hepatocytes but to Kupffer cells, thus, there is no evidence of developing
parenchymal lesion from iron overload. Furthermore, if serum ferritin exceeds the
upper limit during intravenous iron therapy, the levels will rapidly decrease after
discontinuation of parenteral iron.10,11

6. There are no significant adverse effects with iron sucrose compared with iron
dextran. (Level II, Grade A)

Studies have shown that there are less anaphylactic reactions (<0.4%) and
adverse side effects with iron sucrose as compared to iron dextran.4 No fatal
anaphylactic events were reported with iron sucrose compared to iron dextran
(0.61%) and iron gluconate (0.04%). But in the absence of head-to-head
comparative clinical trials it cannot be stated with confidence that iron sucrose or
any other parenteral iron formulation is clearly safer than iron dextran.12
 7. Iron sucrose plus recombinant erythropoietin is more effective in correcting
pregnancy anemia than iron sucrose alone. (Level I, Grade A)

If an adequate hemoglobin level is still not achieved, erythropoietin

therapy (10,000 U) maybe considered; this can be started as primary therapy in
combination with iron sucrose in cases of severe iron deficiency anemia.7 Its
effectivity can be seen in the increases in reticulocyte count, hematocrit and
hemoglobin level.4,13,14,15,16

8. The administration of a test dose is prudent before giving the therapeutic

dose. (Level I, Grade A)

It is not possible to predict which patient will suffer an anaphylactic

reaction. Even with a “negative test dose” and after many well tolerated
administrations, an anaphylactic reaction can still occur. Thus before
administering a therapeutic dose to a new patient, a test dose should be given.4,17
0.5 ml test dose of iron sucrose (10 mg) at room temperature may be
injected while the patient is observed and asked about side effects for 2-3 minutes.
In the absence of abnormal reaction, the remainder of the dose may be injected.4

Treatment of Iron Deficiency Anemia in Pregnancy

Target Hgb 11.0 g/dl

Get Hemoglobin level

10-11 g/dl 9 - 9.9 g/dl < 9 g/dl <8.5g/dl $7g/dl

Oral Iron Iron Sucrose Iron sucrose rHEPO with Blood
Iron Sucrose Transfusion
200 mg /day 200 mg 1-2x /wk 200 mg 2x/wk
Treatment of Iron Deficiency Anemia in the Immediate Post Partum Period19

Target Hgb 11.0 g/dl

Get Hemoglobin level

9.6 - 11 g/dl 8.5 - 9.5 g/dl < 8.5 g/dl < 8.5 g/dl $7g/dl
Oral Iron Iron Sucrose Iron sucrose rHEPO with Blood Transfusion
200 mg /day 200 mg 1-2x /wk 200 mg 2x/wk Iron Sucrose

References

1. Huch R, Breymann C. Anemia in pregnancy and the puerperium. 2nd Edition, 2008.
2. Al-Momen, et. al. Intravenous iron sucrose complex in the treatment of iron deficiency anemia
during pregnancy. Eur J Obstet Gynecol Reprod Biol 1996;69:121-124.
3. Murphy MF, et. al. Guidelines of the clinical use of red cell transfusions. British committee for
standards in hematology, blood transfusion task force. Br J Hematol 2001;113:24-31.
4. Breymann C, et. al. Efficacy and safety of intravenously administered iron sucrose with and
without adjuvant recombinant human erythropoietin for the treatment of resistant iron-deficiency
anemia during pregnancy. Am J Obstet Gynecol 2000;184(4):662-667.
5. Bayoumeu F, et. al. Iron therapy in iron deficiency anemia in pregnancy: IV route versus oral
route. Am J Obstet Gynecol 2002;186:518-22.
6. Breymann C. European congress of obstetrics and gynaecology, Athens, 2004.
7. Huch R, Schaefer R. Iron deficiency and iron deficiency anemia, 2006.
8. Perewusnyk G, Huch R, Huch A, Breymann C. Parenteral iron therapy in obstetrics: 8 years
experience with iron-sucrose complex. Br J Nutr 2002;88,3-10.
9. Clinical Practice Guidelines, The management of anemia in pregnancy and chronic kidney disease.
Academy of Medicine, Malaysia 2007.
10. Locatelli F. et. al. Revised european best practice guidelines for the management of anemia in
patients with chronic renal failure. Nephrol Dial Transplant 2004;19 Suppl 2: ii 1-47.
11. Iron Therapy Focus Organization, March 2008 (www.irontherapy.org )
12. Fishbane S. Safety in iron management. Am J Kidney Dis 2003;41(5 Suppl):18-26.
13. Vora M, Gruslin A. Erythropoietin in obstetrics. Obstet Gynecol Surv 1998;53:736.
14. Makrydimas G, et. al. Recombinant human erythropoietin treatment of postpartum anemia.
Preliminary results. Eur J Obstet Gynecol Reprod Biol 1998;81:27-31.
15. Braga J. Maternal and perinatal implications of the use of human recombinant erythropoietin. Acta
Obstet Gynecol Scan 1996;755:449-53.
16. Harris SA, et. al. Erythropoietin treatment of erythropoietin-deficient anemia without renal disease
during pregnancy. Obstet Gynecol 1996;87(5 Pt 2):812-4.
17. Junca J, Eur J Hematol 1995;55:277-8.
18. NKF-K/DOQI Clinical practice guidelines for anemia of chronic kidney disease. New York:
National Kidney Foundation, 2001.
19. Eisenbrief 2005 (Modified)
C. Blood Transfusion

Red cell transfusion rapidly improves the oxygen carrying capacity of blood
but does not correct the cause of the anemia.

1. The decision to transfuse blood should not be based on severity of anemia or

hemoglobin levels alone but also on the patient’s critical need.1 (Level III,
Grade C)

The following factors must be taken into account in deciding for

transfusion of the pregnant patient:
• Age of gestation
• Co-existing cardiovascular disease
• Presence of infection: e.g. pneumonia, malaria
• Obstetric history
• Anticipated blood loss during delivery
• Duration of the anemia

In general, clinicians transfuse if the hemoglobin falls below 6 g/dl and

rarely consider transfusion when it exceeds 10 g/dl.2 The intervals between these
values is the area of controversy.

2. A hemoglobin level of < 7 gm/dl is an indication for blood transfusion

especially in the symptomatic and the pregnant patient.3 (Level III, Grade C)

Packed red cells are the usual component of choice for the treatment of all
patients who require transfusion because of a red cell mass deficit.

3. Packed red blood cells and balanced salt solutions appear to be as effective as
whole blood in correcting blood loss that occurs after surgery.2 (Level I,
Grade A)

Adverse effects of Blood Transfusion

Blood transfusion therapy carries a significant risk of adverse reactions.

These are categorized into immunologic and non-immunologic risks, hemolytic and
non-hemolytic, acute and delayed.
Immunologic complications are usually those that are thought of as
transfusion reactions and frequently occur at the beginning or during transfusion.
Some of them are enumerated as follows:
• Fever, chills, urticaria
• Hemolytic transfusion reaction
• Fatal hemolytic transfusion reaction
• Graft vs Host disease
• Transfusion-associated lung injury
 1. If an acute transfusion reaction is suspected, transfusion should be stopped
immediately, the blood bank should be notified immediately, appropriate
samples collected and the patient monitored closely. (Level I, Grade A)

For urticarial reactions, antihistaminics maybe given. If a febrile

hemolytic transfusion reaction is suspected, intravenous access should be
maintained with physiologic saline, and measures instituted to correct shock,
maintain renal circulation, and correct bleeding diathesis.4,5
Nonimmunologic complications are usually due to the physical effects of
the blood component or to transmission of disease. These are often the delayed
adverse effects of blood transfusion. Examples are:
• Iron overload
• Circulatory overload
• Transmission of Hepatits, HIV, CMV, malaria
• Bacterial sepsis caused by contaminated components

References

1. WHO. Blood transfusion safety. The Clinical Use of Blood Handbook. 2002.
2. Stehling L. (Chair) Practice guidelines for blood component therapy: A report by the American
Society of Anesthesiologists Task Force on blood component therapy. Anesthesiology 1996;
84(3): 734-747.
3. POGS. Consensus statement made during the presentation of clinical practice guidelines on iron
deficiency anemia. August 13, 2009. Pasig City.
4. Lichtman MA, et. al. (Ed) Williams Hematology 7th Edition. McGraw-Hill. 2006.
5. Rodgers GP, Young NS (Ed). Bethesda Hand Book of Clinical Hematolgy. Lippincott Williams &
Wilkins, 2005.

D. Supportive Measures: Maintenance of intravascular homeostasis

A major cause of anemia in the peripartal period is acute hemorrhage from

various causes whether antepartum, intrapartum or postpartum. The physiologic
anemia of pregnancy and increased blood volume may initially confuse the signs and
symptoms of blood loss. The physiologic anemia and tachycardia of pregnancy may
be mistaken for hemorrhage. Increased blood volume may allow significant
hemorrhage to occur before traditional signs of hypovolemia are apparent.

1. A healthy patient only requires transfusion if hemoglobin is less than 7 g/dL.

(Level II-1, Grade B)

The decision to transfuse an individual patient depends on medical

judgement, taking into account not only the hemoglobin concentration, but also
the physical status of the patient (his/her physiological reserve), the clinical
conditions (ongoing blood loss, sepsis, etc), the duration of anemia, anticipated
 blood loss, the intravascular volume and the presence of cardiovascular or
cerebrovascular disease and available monitoring.1,2

2. Hypovolemia due predominantly to blood loss should be treated with either a

balanced crystalloid solution or a suitable colloid until packed red cells are
available. (Level I, Grade A)

Early volume replacement is more important than the type of fluid given,
although colloids and blood products should be given early consideration. Women
who experience postpartum hemorrhage ranging from 550-1100 ml have
diminished reserve to compensate for any additional blood loss, and they require
immediate measures to avoid further deterioration.3,4

3. Fluid shifting to the entire extracellular space should be minimized by using

crystalloids only to replace urine production and insensible perspiration and
by using iso-oncotic colloids for substitution of acute blood loss. (Level I,
Grade A)

Isotonic crystalloids are distributed within the whole extracellular

compartment, i.e. 4/5 leave the vasculature, whereas, iso-oncotic colloids have
been designed to remain within the circulatory space. Consequently, the primary
indication of crystalloids is replacement of fluid losses via (1) insensible
perspiration and (2) urinary output. Colloids, by contrast, are indicated to replace
plasma deficits due to (1) acute blood loss or (2) protein-rich fluid shifts toward
the interstitial space (pathologic type 2 shift). Despite its being recommended and
still being widely performed, there is no rationale to substitute the first 1,000 ml
of blood loss with a 3-4 fold dose of isotonic crystalloids. Nor is there evidence to
increase crystalloid infusion rate when patient seem to be clinically hypovolemic
during surgery, despite intact extracellular fluid balance.
Due to the risk of inducing hyperchloremic acidosis in routine practice,
when crystalloid resuscitation or replacement is indicated, balanced salt solutions,
e.g. Ringer’s lactate/acetate or Hartmann’s solution should replace 0.9% saline,
except in cases of hypochloremia, e.g. from vomiting or gastric drainage.
Volume-resuscitation therapy should focus not only on correcting
systemic hemodynamics, but also on improving microcirculatory perfusion and
oxygenation. Colloids are more effective in resuscitation with lower volume and
rarely cause peripheral edema. Colloids are a more efficient regimen to ensure
adequate microcirculatory flow than crystalloids.5,6,7

4. The use of dextrans must be considered with caution in patients with pre-
existing hemostatic deficit or treated with antiplatelet drugs or
anticoagulants. (Level I, Grade A)

Dextrans may induce abnormal bleeding due to their effects on primary

hemostasis and on the fibrinolytic system while gelatins and in vivo low-
molecular weight Hydroxyethyl starch probably may not.8
 5. Maintain perioperative normothermia to reduce blood loss and transfusion
requirements. (Level I, Grade A)

Anesthetic-induced hypothermia is known to reduce platelet function and

impair enzymes of the coagulation cascade. Even mild hypothermia (<1 °C)
increases blood loss by approximately 16% (4-26%) and increases the relative
risk for transfusion by approximately 22% (3-37%).9

References

1. American Society of Anesthesiologists Task Force on Blood Component Therapy. Practice

guidelines for blood component therapy. Anesthesiology 1996;84:732-47.
2. P. Van der Linden. Acute normovolemic anemia: physiological and practical concerns. Jurnalul
de Chirurgie 2007;3(3).
3. Wali MS, Suresh A, Greg R. Antepartum hemorrhage in anesthetic and obstetric management of
high-risk pregnancy (ed), 3rd edition. Mosby-Year Book Inc, 2004.
4. Hahn RG, Prough DS, Svensen C. Fluid management in obstetrics, in perioperative fluid therapy.
CRC Press, 2006.
5. Chappel D, Jacob M, Hofman-Kiefer K, Conzen P, Rehm M. A rational approach to perioperative
fluid management. Anesthesiology 2008;109:723-40.
6. British Consensus Guidelines on IV Fluid Therapy for Adult Surgical Patients.
7. Lang K, Boldt J, Suttner S, Haisch G. Colloid versus crystalloids and tissue oxygen tension in
patients undergoing major abdominal surgery. Anesth Analg 2001;93:405-9.
8. Van der Linden, et. al. Effects of colloids on hemostasis. Can J Anaesth 2006;53(6):S30-S39.
9. Rajagopalan S, Mascha E, Na J, Sessler DI. Anesthesiology 2008;108(1):71-77.
 PREVENTION STRATEGIES

A survey of current literature showed that the approaches to the prevention of iron
deficiency anemia includes the following:

• Food-based approaches
o Dietary improvement
o Food Fortification1
• Iron Supplementation9,10

A. Food-based approaches

Food-based approaches represent the most desirable and sustainable method of

preventing micronutrient malnutrition particularly iron deficiency. Such
approaches are designed to increase micronutrient intake through the diet.1
(Level III, Grade C)

Food-based approaches should therefore include strategies to:

• improve the year-round availability of micronutrient-rich foods
• ensure the access of households, especially those at risk, to these foods
• change feeding practices with respect to these foods6

1.a. Dietary Improvement

The primary cause of iron deficiency anemia (IDA) is inadequate dietary

iron intake. Hence, the key to prevention of IDA is a healthy iron-rich diet. The
recommended nutrient intakes of iron for the pregnant women are the following:
27 mg/day (1st trimester), 34 mg/day (2nd trimester) and 38 mg/day (3rd trimester).
The recommended nutrient intakes of iron for lactating women are 27 mg/day
(amenorrheic) and 30 mg/day (lactating women).2
Applied to iron deficiency, the primary goal of dietary modification is to
improve and maintain the iron status of a population through changes in behavior,
leading to an increase consumption of iron-containing foods and a meal pattern
favorable to increase bioavailability.6
Iron is present in a variety of foods of both animal and plant. Liver and
glandular organs are the richest sources of iron. Among the plant foods, the
legume family, green leafy vegetables, seaweeds and dried foods such as prunes
are the best iron sources.3
Dietary iron exists in food, primarily as heme and non-heme iron. Heme
is a constituent of hemoglobin and myoglobin and therefore, present in animal
products. It has high bioavailability because its absorption is relatively unaffected
by the composition of the meal and only slightly affected by the individual’s iron
status. The alkaline pH of the small intestines favors heme absorption.4
 Non-heme iron, which is found in plant foods, is less bioavailable
because its absorption is strongly influenced by its solubility. Non-heme
iron bound to components of food are enzymatically liberated by gastric
secretions of the stomach as ferric (Fe+3) and absorption is favored by the acidic
environment. Majority of the absorbed ferric is reduced to ferrous (Fe+2).
However, alkaline pH of the small intestine will cause the ferric to be oxidized to
ferric iron and forms insoluble iron complexes making iron less available for
absorption.4

Below is a food pyramid showing Filipino foods rich in iron. (Fig. 1)

Fig. 1 Iron Rich Filipino Foods

A table showing list of Filipino foods rich in iron in terms of milligrams of iron
per 100 grams of edible food is given in the appendix.11

Remember: Iron from raw food is absorbed better.

Vegetarian Diet

A diet that is typically plant-based with high fiber, phytate and polyphenol
content results in low bioavailability of dietary iron. A major characteristic of
the vegetarian diet is the replacement of meat by soya beans. However, consumed
to excess, soy has many potential anti-nutrient effects.6,5,7
Bioavailability of food iron is strongly influenced by enhancers and
inhibitors in the diet.
Presently, there is no satisfactory in vitro method for predicting the
bioavailability of iron in a meal.
Iron absorption can vary from 1% to 40%, depending on the mix of
enhancers and inhibitors in the meal. Therefore, the adequacy, i.e. bioavailability
of iron in usual diets can be improved by altering meal patterns to favor
enhancers, lower inhibitors, or both.4
 Enhancers of iron absorption include:
• heme iron, present in meat, poultry, fish, and seafood
• ascorbic acid or vitamin C, present in fruits, juices, potatoes and some other
tubers and green leafy vegetables such as green leaves, cauliflower, and
cabbage
• fermented or germinated food and condiments,such as sauerkraut and soy
sauce (note that cooking,fermentation, or germination of food reduces the
amount of phytates).6,13

Heme iron present in meat, poultry, fish, and seafood enhances absorption
of non-heme iron. Vitamin C along with citric, lactic and tartaric acids acts as a
reducing agent and forms a chelate with non-heme ferric iron at an acid pH
improving intestinal absorption of noh-heme iron.4 This happens only when
Vitamin C is taken with meals.8

Inhibitors of iron absorption include:

• phytates, present in cereal bran, cereal grains, high-extraction flour, legumes,
nuts, and seeds
• food with high inositol content
• iron-binding phenolic compounds (tannins); foods that contain the most
potent inhibitors resistant to the influence of enhancers include tea, coffee,
cocoa, herbal infusions in general, certain spices (e.g. oregano), and some
vegetables
• calcium, particularly from milk and milk products 6
Inhibitors are those dietary constituents which bind with iron to form
insoluble complexes hence decreasing its bioavailability.

Examples of simple but effective alterations in meal patterns that

enhance iron absorption might include:
• separate tea drinking from mealtime - one or two hours later, the tea will not
inhibit iron absorption because most of the food will have left the stomach
• include in the meal fruit juices such as orange juice, or another source of
ascorbic acid such as tubers, cabbage, carrots, or cauliflower
• consume milk, cheese, and other dairy products as a between-meal snack,
rather than at mealtime
• consume foods containing inhibitors at meals lowest in iron content, e.g. a
breakfast of a low-iron cereal (bread or corn tortilla) consumed with tea or
milk products. This meal pattern can provide adequate calcium without
hampering iron nutrition.6

1.b. Food Fortification

Adding of nutrient during the processing of food is an effective long-term

approach to improving the iron status of populations.6 (Level III, Grade C)
 Several iron fortificants have been used successfully in a variety of
national programs particulary in rice, flour, cereals and milk products. A complete
list of Iron-Fortified Food Products “Sangkap Pinoy” under the Philippine Food
Fortification Program has been approved and released by DOH and BFAD.
Dietary iron is not sufficient to meet the needs of pregnant women. Hence,
food based approaches should be integrated with iron supplementation and other
interventions throughout pregnancy.6

B. Iron supplementation

1. Iron supplementation is the most common strategy currently used to prevent

and correct iron deficiency.6 (Level I, Grade A)

It is important to differentiate between supplementation that aims at

preventing anemia by correcting iron deficiency before iron deficiency anemia is
manifested while therapeutic supplementation, which aims at correcting
established iron deficiency anemia.

Dosage schedule for iron supplementation to prevent iron deficiency anemia6

Age Group Indication for Dosage schedule Duration
Supplementation
Women of Where anemia Iron: 60 mg/day 3 months
childbearing age prevalence is above 40% Folic acid: 400 mcg/day
Pregnant women Universal Iron: 60 mg/day ASAP after gestation.
supplementation Folic acid: 400 mcg/day Starts no later than 3rd
month and continuing
for the rest of
pregnancy
Lactating women Where anemia Iron: 60 mg/day 3 months postpartum
prevalence is above 40% Folic acid: 400 mcg/day

2. Iron supplementation during pregnancy is recommended universally to meet

the increased demand for iron during the second and third trimesters. (Level
III, Grade C)

During the second trimester, iron requirements begin to increase and

continue to do so throughout the remainder of pregnancy. As pregnancy
progresses, iron requirement for fetal and placental development steadily rises
from 4-5 mg/day during the second trimester up to > 6 mg daily during the third
trimester. In determining the iron requirements during pregnancy, the amount of
blood loss during parturition should be taken into consideration.14 In developing
countries it is recommended to give 60 mg elemental iron per day starting second
trimester and 120 mg elemental iron per day if supplementation is not started at
the beginning of the second trimester.15
 3. Weekly supplementation is an alternative to daily iron supplementation in
non-anemic pregnant women. (Level I, Grade A)

Randomized controlled studies show that a once weekly dose of 100-120

mg of elemental iron given as supplement to non-anemic pregnant women starting
20 weeks age of gestation or an average of 17 weeks is comparable to a once daily
dose of 60-100 mg elemental iron.16,17
Intake of iron rich and iron fortified foods and the use of iron supplements
if necessary for all women even before pregnancy, is highly recommended in
order to build up iron stores.6

References

1. Bothwell TH. Iron requirements in pregnancy and strategies to meet them. Am J Clin Nutr
2000;72:257S-64S
2. Food and Agriculture Organization 2002. Iron. Report on Recommended Energy and Nutrition
Intake.
3. Food and Nutrition Research Institute. Department of Science and Technology (FNRI-DOST).
2001. “ Mga Pagkaing Yaman sa Yero” FNRI Publication, Manila.
4. Groff JL and Gropper SS. 1999. Iron. Advanced Nutrition and Human Metabolism:
Microminerals. 3rd Edition Wadsworth Thomson Learning. 401-420.
5. Hallberg L. Wheat fiber, phytates and iron absorption. Scand J Gastroenterol Suppl. 1987;129:
73-9.PMID: 2820048
6. Iron Deficiency Anemia Assessment, Prevention and Control WHO/NHD/01.3
7. Lynch SR, et. al. Inhibitory effect of a soybean-protein-related moiety on iron absorption in
humans. Am J Clin Nutr 1994;60(4):567-72. PMID:8092092
8. Lynch SR. Interaction of iron with other nutrients. Nutr Rev 1997;55(4):102-110.
9. Mary EC, et. al. Iron supplementation during pregnancy, anemia and birth weight: a randomized
controlled trial. Am J Clin Nutr 2003;78:773-81.
10. Mahomed K. Routine iron supplementation during pregnancy. Cochrane Library Syst Rev 2005;
Issue 2.Oxford.
11. The Philippine Food Composition Tables 1997, Food Nutrition Research Institute.
12. Philippine Food Fortification Program. DOH-BFAD January 2008.
13. Teucher B, et. al. Enhancers of iron absorption: ascorbic acid and other organic acids. Int J Vitam
Nutr Res 2004;74(6):403-19. PMID: 15743017.
14. Bothwell TH. Iron requirements in pregnancy and strategies to meet them. Am J Clin Nutr
2000;72(suppl):257S-64S.
15. Stoltzfus RJ, Dreyfus ML. Guidelines for the use of iron supplements to prevent and treat iron
deficiency anemia. INACG/WHO/UNICEF. Washington, DC: ILSI Press, 1998.
16. Casanueva E, Viteri FE, Mares-Galindo M, Meza-Camacho C, Loría A, Schnaas L, Valdés-
Ramos R. Weekly iron as a safe alternative to daily supplementation for nonanemic pregnant
women. Arch Med Res 2006;37(5):674-82.
17. Mukhopadhyay A, Bhatla N, Kriplani A, Pandey RM, Saxena R. Daily versus intermittent iron
supplementation in pregnant women: hematological and pregnancy outcome. J Obstet Gynaecol
Res 2004;30(6):409-17.

.
Antihelminthics

1. Pregnant women residing in endemic areas should be screened for malaria,

hookworm and other parasitic infections. (Level I, Grade A)

A meta-analysis reviewing the association between hookworm infection and

hemoglobin levels involving thirteen observational studies done in Africa, Asia and
Latin America showed that increasing hookworm infection intensity is linked to
lower hemoglobin levels in pregnant women.1 Malaria and Schistosomiasis were also
associated with iron deficiency anemia in pregnant women.2

2. Antihelminthics together with iron supplementation should be given to pregnant

women residing in hookworm-endemic areas. (Level I, Grade A)

Several studies have shown the benefit derived from deworming pregnant
women residing in hookworm-endemic areas. Mebendazole given in combination
with iron supplementation showed a significantly lower proportion of very low
birthweight as compared to iron supplementation alone (P<0.007).3 No severe adverse
events were reported in the women given Mebendazole nor Albendazole during the
second trimester and during breastfeeding. Single dose of Albendazole 400 mg and
Mebendazole 500 mg may be given. All provided evidence favorable to deworming,
in terms of both maternal and infant outcomes.4

3. Iron supplementation, food fortification and deworming coupled with health and
nutritional education programs should be implemented to effectively lower the
rates of anemia. (Level I, Grade A)

A combination of different approaches has been found to be successful in

reducing the prevalence of anemia.5 Weekly iron-folic supplementation, family life
education and deworming were successful in lowering the prevalence of anemia in
adolescent girls from 73.3% to 25.4%.6 Iron fortification of food is regarded as the
most effective method in reducing the prevalence of nutritional iron deficiency
anemia. New interventions and innovations to dietary fortification that ensure the
delivery of the right amount of bioavailable iron have demonstrated that food
fortification can be an effective and implementable strategy for controlling nutritional
iron deficiency in non-industrialized countries.7

References

1. Brooker S, Hotez PJ, Bundy DAP. Hookworm-related anaemia among pregnant women: A
systematic review. PLoS Negl Trop Dis 2008;2(9): e291.doi:10.1371/journal.pntd.0000291.
2. Van den Broek NR, Letsky EA. Etiology of anaemia in pregnancy in south Malawi. Am J Clin
Nutr 2000;72:247S–256S.
3. Larocque R, Casapia M, Gotuzzo E, MacLean JD, Soto JC, et. al. Adouble-blind randomized
controlled trial of antenatal mebendazole to reduce low birthweight in a hookworm-endemic area
of Peru. Trop Med Int Health 2006;11:1485–1495.
4. Gyorkos TW, Larocque R, Casapia M, Gotuzzo E. Lack of risk of adverse birth outcomes after
 deworming in pregnant women. Pediatr Infect Dis J 2006;25:791–794.
5. Rivera JA, Sotres-Alvarez D, Habicht JP, Shamah T, Villalpando S. Impact of the mexican
program for education, health, and nutrition (Progresa) on rates of growth and anemia in infants
and young children a randomized effectiveness study. JAMA 2004;291:2563-2570.
6. Vir SC, Singh N, Nigam AK, Jain R. Weekly iron and folic acid supplementation with counseling
reduces anemia in adolescent girls: a large-scale effectiveness study in Uttar Pradesh, India. Food
Nutr Bull 2008;29(3):186-94.
7. Lynch SR. The impact of iron fortification on nutritional anaemia. Best Pract Res Clin Hematol
2005 Jun;18(2):333-46.
 APPENDIX

I
LEVELS OF EVIDENCE AND GRADES OF RECOMMENDATION

LEVEL DEFINITION
I Evidence obtained from at least one properly randomized controlled trial
Evidence obtained from well-designed controlled trials without
II-1
randomization
Evidence obtained from well-designed cohort or case-control analytic
II-2
studies, preferably from more than one center or research group
Evidence obtained from multiple time series with or without the
II-3
intervention.
Opinions of respected authorities, based on clinical experience; descriptive
III
studies and case reports or reports of expert committees.

GRADE DEFINITION
There is good evidence to support the recommendation of the practice in
A
iron deficiency anemia.
There is fair evidence to support the recommendation of the practice in
B
iron deficiency anemia.
There is insufficient evidence to recommend for or against the inclusion of
C
the practice in iron deficiency anemia.
There is fair evidence to support the recommendation that the practice be
D
excluded in iron deficiency anemia.
There is good evidence to support the recommendation that the practice be
E
excluded in iron deficiency anemia.
A good practice point (GPP) is a recommendation for best practice based on the
GPP experience of the Task Force.

.
 II
Causes of Anemia in Pregnancy

Nutritional
• Iron deficiency
• Megaloblastic anemia
Folate deficiency
Cobalamin deficiency

Anemia Due to Marrow Suppression

• Aplastic
• Secondary to chronic systemic disease

Hemolytic
• Acquired
Associated with pre-eclampsia (HELLP Syndrome)
Autoimmune
• Congenital
Thalassemias
Sickle cell anemia and related hemoglobinopathies

Secondary to Blood Loss

 III
Normal Complete Blood Count Values for Adult Females

Old SI
Hemoglobin 11.5-15.5 g/dl 110-155 g/L
Hematocrit 36-48% 0.36-0.48
RBC Count 3.9-5.6 x 1012 /L 3.9-5.6 x 1012/L
MCV 80-95 fl
MCH 27-34 pg
MCHC 30-35 g/dl 300-350 g/L
RDW 11.6-14.6%
WBC
Total 4000-10000 cells/mm3 4.0-11.0 x109 /L
Differential
Neutrophils 55-65%
Lymphocytes 25-35%
Monocytes 2-6%
Eosinophils 2-4%
Basophils 0-1%
Platelets 150000-400000/mm3 150-400 x109 /L

IV
Commonly Used Oral Iron Preparations and Elemental iron content
Iron Compound Elemental iron
Preparation Percent Iron %
mg/tab mg/tab
Ferrous sulfate 325 20 65
Ferrous sulfate, dessicated 200 30 60
Ferrous gluconate 325 12 36
Ferrous fumarate 325 33 106

References

1. Red book. Montvale, N.J.: Medical Economics Data, 1999

2. Fishbane S, et al. Kidney Int Suppl. 1999 Mar
 V
List of Filipino foods rich in iron in terms of milligrams of iron per 100 grams of
edible food
Reference: The Philippine Food Composition Tables 1997, Food Nutrition Research Institute
Sources of Heme-Iron Milligrams of Iron per
100 grams of food
Pork liver 32
Anchovy dried ( dilis ) 31
Duck liver 22
Theraponid silvery 21.4
( ayungin )
Beef liver 12.2
Clams 8.7
( halaan , paros )
Oysters ( talaba ) 5.9
Egg yolk chicken 4.6
Shrimp head ( sugpo ) 3.5
Chicken liver 3.5

Sources of Milligrams of Iron per

Non-Heme Iron 100 grams of food
Legumes
Soy bean
Cheese (tahure) 9.2
Curd (tausi) 6.2
Curd (tofu) 3.2
Green Leafy Vegetables
Gabi leaves 38.5
Chinese Celery (kinchay) 14.4
Corchorus olitorius Jute 11.6
(saluyot)
Amaranthus gracilis (kulitis) 8.3
Allium odoratum Leek (kutsay) 7.2
Horseradish tree leaves 5.9
(malunggay)
Seaweeds
Hydroclathrus clathratus 44.5
(balbalulang)
Porphyra denticulate (gamet) 31.6
Caulerpa recemosa (lato) 18
Laurencia okamurae (kulot) 6.1
Others
Sardines (tawilis and tuyo) 18.8
Dried prunes 5.3