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SHARON SCOTT MOREY

CDC Issues Guidelines for Prevention, Detection and Treatment of Iron Deficiency

The Centers for Disease Control and Prevention (CDC), in collaboration with experts on iron deficiency, has developed recommendations for the prevention, detection and treatment of iron deficiency. The recommendations, published in the April 3, 1998, issue of Morbidity and Mortality Weekly Report, include discussions on iron metabolism, manifestations of iron deficiency, the prevalence and risk of iron deficiency and tests for assessing iron status. The report also includes a discussion of the justifications for the recommendations.

According to the CDC, these recommendations differ in two major areas from the guidelines published by the U.S. Preventive Services Task Force. First, the Preventive Services Task Force recommends screening for anemia only among infants at high risk for anemia and among pregnant women. In contrast, the CDC recommends periodic screening for anemia among high-risk populations of infants and preschool children, among pregnant women and among women of childbearing age. Second, the Preventive Services Task Force recommendations state that evidence is insufficient to recommend for or against iron supplementation during pregnancy. The CDC, however, recommends universal iron supplementation to meet the iron requirements of pregnancy, similar to the guidelines issued by the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists.

The following, excerpted from MMWR, summarizes the recommendations for prevention, detection and treatment of iron deficiency.

Prevention in Infants and Preschool Children

The recommendations for primary prevention in infants and preschool children are as follows:

• Encourage breast feeding of infants.
• Encourage exclusive breast feeding of infants (without supplementary liquid, formula or food) for four to six months after birth.
• When exclusive breast feeding is stopped, encourage use of an additional source of iron (approximately 1 mg per kg per day of iron), preferably from supplementary foods.
• For infants younger than 12 months of age who are not breast fed or who are partially breast fed, recommend only iron-fortified formula as a substitute for breast milk.
• For breast-fed infants who by age six months receive insufficient iron (i.e., less than 1 mg per kg per day) from supplementary foods, suggest 1 mg per kg per day of iron drops.
• Encourage use of only breast milk or iron-fortified infant formula for any milk-based part of the diet (e.g., in infant cereal) and discourage use of milk low in iron (e.g., cow's milk, goat's milk and soy milk) until age 12 months.
• Suggest that children aged one to five years consume no more than 24 oz of cow's milk, goat's milk and soy milk each day.
• At age four to six months or when the extrusion reflex disappears, recommend that infants be introduced to plain, iron-fortified infant cereal. Two or more servings per day of iron-fortified infant cereal can meet an infant's requirements for iron at this age.
• By approximately six months of age, encourage one feeding per day of foods rich in vitamin C (e.g., fruits, vegetables and juice) to improve iron absorption, preferably with meals.
• Suggest introducing plain, pureed meats after age six months or when the infant is developmentally ready to consume such food.

The recommendations for secondary prevention in infants and preschool children are as follows:

• In populations of infants and preschool children at high risk for iron deficiency anemia (e.g., children from low-income families, children eligible for the Special Supplemental Nutrition Program for Women, Infants and Children, migrant children and recently arrived refugees), screen all children for anemia between the ages of nine and 12 months, six months later, and then annually from ages two to five years.
• In populations of infants and preschool children not at high risk for iron deficiency anemia, screen only those children who have known risk factors.
• Consider anemia screening before age six months for preterm infants and low-birth-weight infants who are not fed iron-fortified formula.
• Annually evaluate children two to five years of age for risk factors of iron deficiency anemia (e.g., a low-iron diet, limited access to food because of poverty or neglect, and special health care needs). Screen these children if they have any of the risk factors.
• At ages nine to 12 months and then six months later, assess infants and young children for risk factors for anemia. Screen the following children: preterm and low-birth-weight infants; infants fed a diet of non­iron-fortified infant formula for more than two months; infants introduced to cow's milk before age 12 months; breast-fed infants who do not consume a diet adequate in iron after age six months; children who consume more than 24 oz of cow's milk daily; and children who have special health care needs.

Diagnosis and Treatment in Infants and Preschool Children

• Check a positive anemia screening result by obtaining a repeat hemoglobin concentration or hematocrit test. If the tests agree and the child is not ill, a presumptive diagnosis of iron deficiency anemia can be made and treatment begun.
• Treat presumptive iron deficiency anemia by prescribing 3 mg per kg per day of iron drops, to be administered between meals. Counsel parents or guardians about adequate diet to correct the underlying problem of low iron intake.
• Repeat anemia screening in four weeks. An increase in the hemoglobin concentration of 1 g per dL (10 g per L) or more, or an increase in the hematocrit of 3 percent (0.03) or more, confirms the diagnosis of iron deficiency anemia. If iron deficiency is confirmed, reinforce dietary counseling, continue iron treatment for two more months and then recheck hemoglobin concentration. Reassess hemoglobin or hematocrit approximately six months after successful treatment is completed.
• If after four weeks anemia does not respond to iron treatment despite compliance and the absence of acute illness, further evaluate the anemia by using other laboratory tests, including mean cell volume (MCV), red blood cell distribution width (RDW) and serum ferritin concentration.

Children Ages Five to 12 Years and Adolescent Boys

Only children and adolescent boys who have a history of iron deficiency anemia, special health care needs or low iron intake should be screened for anemia.

Treatment for iron deficiency anemia includes one 60-mg iron tablet each day for school-age children and two 60-mg iron tablets each day for adolescent boys. Counseling about dietary intake of iron should be carried out. Follow-up and laboratory evaluation are the same for this age group as they are for infants and preschool children.

Prevention in Adolescent Girls and Women of Childbearing Age

The recommendations for primary prevention in adolescent girls and women of childbearing age are as follows:

• Most adolescent girls and women do not require iron supplements, but encourage them to eat iron-rich foods and foods that enhance iron absorption.
• Women who have low-iron diets are at additional risk for iron deficiency anemia; guide these women in optimizing their dietary iron intake.

The recommendations for secondary prevention are as follows:

• Starting in adolescence, screen all nonpregnant women for anemia every five to 10 years throughout their childbearing years during routine health examinations.
• Annually screen for anemia in women who have risk factors for iron deficiency (e.g., extensive menstrual or other blood loss, low iron intake, previous diagnosis of iron deficiency anemia).

Diagnosis and Treatment in Adolescent Girls and Women of Childbearing Age

• Confirm a positive anemia screening result by performing a repeat hemoglobin concentration or hematocrit test. If the adolescent girl or woman is not ill, a presumptive diagnosis of iron deficiency anemia can be made and treatment begun.
• Treat adolescent girls and women who have anemia by prescribing 60 to 120 mg per day of iron. Counsel these patients about correcting iron deficiency through diet.
• Follow-up of adolescent girls and women of childbearing age is the same as that for infants and preschool children. For a confirmed case of iron deficiency anemia, continue iron treatment for two to three more months.
• If after four weeks the anemia does not respond to iron treatment despite compliance with iron supplementation and the absence of acute illness, further evaluate the anemia by using other laboratory tests, including MCV, RDW and serum ferritin concentration. In women of African, Mediterranean or Southeast Asia ancestry, mild anemia unresponsive to iron therapy may be due to thalassemia minor or sickle cell trait.

Prevention in Pregnancy

The recommendations for primary prevention in pregnant women are as follows:

• Start oral low-dose (30 mg per day) supplements of iron at the first prenatal visit.
• Encourage pregnant women to eat iron-rich foods and foods that enhance iron absorption.
• Pregnant women whose diets are low in iron are at additional risk for iron deficiency anemia; guide these women in optimizing their dietary iron intake.

The recommendation for secondary prevention in pregnant women is as follows:

• Screen for anemia at the first prenatal visit.

Diagnosis and Treatment in Pregnancy

• Confirm a positive anemia screening result by performing a repeat hemoglobin concentration or hematocrit test. If the pregnant woman is not ill, a presumptive diagnosis of iron deficiency anemia can be made and treatment begun.
• If the hemoglobin concentration is less than 9.0 g per dL (90 g per L) or the hematocrit is less than 27 percent (0.27), refer the patient to a physician familiar with anemia during pregnancy for further medical evaluation.
• Treat anemia by prescribing an oral dose of 60 to 120 mg per day of iron. Counsel about correcting iron deficiency anemia through diet.
• If after four weeks the anemia does not respond to iron treatment despite compliance and absence of illness, further evaluate the anemia by using other tests, including MCV, RDW and serum ferritin concentration.
• When hemoglobin concentration or hematocrit becomes normal for the stage of gestation, decrease the iron dosage to 30 mg per day.
• During the second and third trimesters, if the hemoglobin concentration is more than 15.0 g per dL (150 g per L) or the hematocrit is more than 45 percent (0.45), evaluate the woman for potential pregnancy complications related to poor blood volume expansion.

ACOG Releases Report on Antimicrobial Therapy in Pregnancy

The Committee on Educational Bulletins of the American College of Obstetricians and Gynecologists (ACOG) has released a report titled "Antimicrobial Therapy for Obstetric Patients" (Educational Bulletin No. 245). The report summarizes current information on the use of antimicrobial therapy for intra-amniotic infection, endometritis, bacterial endocarditis, sexually transmitted diseases (chlamydial infection, gonorrhea, syphilis, vaginal trichomoniasis, bacterial vaginosis and herpes) and urinary tract infections. The following highlights information from the report.

General Guidelines

Commonly Used Antibiotics The rightsholder did not grant rights to reproduce this item in electronic media. For the missing item, see the original print version of this publication.

The table summarizes the maternal and fetal effects of commonly used antibiotics. The report states that dosage modification may be needed during pregnancy because of the expanded maternal blood volume, increased glomerular filtration rate, increased hepatic metabolism and sequestration of the drug in the fetal compartment. According to the report, drug levels are generally 10 to 50 percent lower in women in late pregnancy and in the immediate postpartum period than in women who are not pregnant. When drugs are excreted primarily by the kidneys, dosages at the upper end of the recommended range may be needed.

Passage of antimicrobial agents across the placenta and into fetal circulation is affected by the duration of the pregnancy and the protein-binding capacity of the drug. The report states that greater transfer occurs with advancing gestation and with agents that are minimally protein bound. For example, ampicillin, which is 20 percent protein bound, attains high levels in the fetus, whereas dicloxacillin, which is 98 percent protein bound, does not.

The report acknowledges that clinical trials of antibiotic therapy in pregnancy are insufficient to determine the safety of these agents with certainty. For agents such as azithromycin, acyclovir and the newer cephalosporins, no known or theoretic risks to the fetus exist. For other drugs, a theoretic risk exists but no untoward effects have been reported in humans. Sulfonamides have not been reported to cause neonatal kernicterus as a result of fetal exposure at any gestational age. Gentamicin and tobramycin have not been associated with hearing loss in neonates, but hearing loss has been reported in association with kanamycin and streptomycin. Fetal exposure to nitrofurantoin has not been reported to cause hemolytic anemia in the newborn, and metronidazole has not been associated with an increase in birth defects or subsequent cancer. The report states that use of these agents may be reasonable when they offer specific advantages over other agents.

All quinolone antibiotics are contraindicated in pregnancy because of reports of arthropathy in young animals receiving these agents. The report also mentions that information is scant on the use of newer extended-spectrum penicillins and second-, third-, and fourth-generation cephalosporins in pregnancy, but it is likely that these antibiotics are safe to use in pregnant women.

Infections Related to Pregnancy

The report states that most pelvic infections in women are caused by a mixture of aerobic and anaerobic organisms. Aerobic organisms include groups A, B and D streptococci, enterococci, Escherichia coli, Klebsiella species, Proteus species, Staphyloccus aureus and Gardnerella vaginalis. Anaerobic pathogens include Peptostreptococcus species, Prevotella bivia, Prevotella disiens, Bacteroides fragilis, Porphyromonas asaccharolyticus, Fusobacterium species, Clostridium species and Mobiluncus species. Other organisms include genital mycoplasmas, Chlamydia trachomatis and Neisseria gonorrhoeae.

• Intra-amniotic Infection. According to ACOG, the most extensively studied regimen for amniotic infection is a combination of ampicillin, 2 g intravenously every four to six hours, or penicillin, 5 million U every four to six hours, plus an aminoglycoside such as gentimicin, 1.5 mg per kg intravenously every eight hours. This combination has excellent activity against group B streptococci and E. coli.

If cesarean delivery is required in a patient who has received ampicillin and gentamicin, the addition of clindamycin, 900 mg intravenously every eight hours, or metronidazole, 500 mg every 12 hours, is recommended immediately after the cord is clamped. As an alternative, newer agents such as cefotetan, ampicillin-sulbactam, ticarcillin with or without clavulanic acid, piperacillin with or without tazobactam and ceftizoxime provide good coverage and can be continued following cesarean delivery. Therapy should continue postoperatively until the patient has been afebrile and asymptomatic for 24 to 48 hours. After vaginal delivery, therapy may be discontinued soon after delivery.

• Prophylaxis Against Postpartum Endometritis. The ACOG report states that the preferred agent for prophylaxis against postpartum endometritis is a first-generation cephalosporin such as cefazolin, 1 g intravenously, or ampicillin, 1 to 2 g intravenously. Cefazolin is noted to have the advantage of a longer half-life and less of a risk of allergic reactions, but it may more likely allow the emergence of enterococci in cases in which prophylactic therapy has failed. If an infection subsequently develops, the agent used in prophylaxis should not be used to treat the infection. Thus, the report states, extended-spectrum agents should not be used for prophylaxis but, instead, should be reserved for the treatment of endometritis.
• Treatment of Postpartum Endometritis. The traditional regimen of a penicillin plus an aminoglycoside is usually effective when endometritis develops after vaginal delivery. Compared with endometritis after cesarean delivery, endometritis following vaginal delivery is much more likely to be caused by a single pathogen, such as streptococci. With cesarean delivery, the report notes that no regimen has been found to be superior to the standard regimen of gentamicin, 1.5 mg per kg, admixed with clindamycin, 900 mg, in the same intravenous solution, administered every eight hours. The addition of ampicillin may be warranted in specific circumstances, such as in patients with evidence of septic shock or when enterococcal infection is suspected.
• Bacterial Endocarditis. Prophylaxis against bacterial endocarditis is not routinely recommended by the American Heart Association for patients with structural cardiac defects who undergo cesarean or vaginal delivery. It may be an option in high-risk patients. The recommended regimen is ampicillin, 2 g intramuscularly or intravenously, and gentamicin, 1.5 mg per kg (not to exceed 120 mg) within 30 minutes of delivery, followed in six hours by ampicillin, 1 g intramuscularly or intravenously, or amoxicillin, 1 g orally.

Common Infections in Pregnant Patients

• Sexually Transmitted Diseases. For chlamydial infection, pregnant patients may receive one of the following treatments: erythromycin base, 500 mg, or erythromycin ethylsuccinate, 800 mg, orally four times daily for seven days; amoxicillin, 500 mg orally three times daily for seven days; or azithromycin, 1 g orally as one dose.

For gonorrhea, recommended treatment regimens include one of the following: ceftriaxone, 125 mg intramuscularly in a single dose; cefixime, 400 mg orally in a single dose; or spectinomycin, 2 g intramuscularly in a single dose (for patients who cannot tolerate a cephalosporin). In addition, treatment for chlamydial infection should be instituted because of the likelihood of coinfection.

For syphilis, a penicillin regimen appropriate for the stage of syphilis should be instituted. Patients with early syphilis should receive benzathine penicillin G, 2.4 million U intramuscularly. For late-stage syphilis, 2.4 million U intramuscularly should be administered once a week for three consecutive weeks.

Patients with vaginal trichomoniasis may be treated with 2 g of metronidazole orally in a single dose. Metronidazole is not recommended in the first trimester.

The ACOG report notes that recent studies suggest that treatment of bacterial vaginosis may reduce the rate of preterm delivery in certain high-risk patients. In the first trimester, symptomatic bacterial vaginosis can be treated with 2 percent clindamycin cream, one full applicator (5 g) intravaginally at bedtime for seven days, or oral clindamycin, 300 mg twice daily. Clindamycin cream is recommended instead of oral therapy because of the limited fetal exposure with vaginal administration. After the first trimester, metronidazole, 250 mg orally three times a day or 500 mg orally twice a day for seven days, may be used. Alternative therapy includes 2 g of oral metronidazole in a single dose or 300 mg of oral clindamycin twice daily for seven days.

The report states that little progress has been made in knowledge of the use of acyclovir for genital herpes infection in pregnancy. The decision to use acyclovir in a pregnant patient must be made on the basis of an individual's risk and benefit of therapy. Information is also insufficient on the use of acyclovir for recurrent episodes or for suppression throughout pregnancy. The agent has been used near term to prevent the need of cesarean delivery after a first episode of genital herpes.

• Urinary Tract Infections. Treatment of asymptomatic bacteriuria should be considered when a urine specimen reveals 25,000 to 100,000 colony-forming units of a single organism per mL. A three-day course of antibiotic therapy, such as trimethoprim-sulfamethoxazole, nitrofurantoin or cephalexin, is sufficient for most women. Similarly, symptomatic cystitis can be treated with a three-day course of antibiotic therapy.

Effective regimens for acute pyelonephritis include one of the following: ampicillin, 1 to 2 g every six hours, plus gentamicin, 1.5 mg per kg every eight hours; ceftriaxone, 1 to 2 g every 24 hours; or trimethoprim-sulfamethoxazole, 160/800 mg every 12 hours. Intravenous therapy is continued until the patient is afebrile and is then followed by oral therapy to complete a 10-day course of therapy.

The report notes that women who develop pyelonephritis during pregnancy require antibiotic suppression and periodic screening for the remainder of the pregnancy. Women with other types of urinary tract infections likewise require periodic screening for infection with cultures or urine dipstick for nitrites or leukocyte esterase. If infection recurs, treatment should be initiated and the patient should receive suppressive therapy.

For more information on ACOG educational bulletins and committee opinions, contact ACOG at 409 12th St., S.W., P.O. Box 96920, Washington, D.C. 20090-6920; telephone: 800-762-2264.

Copyright © 1998 by the American Academy of Family Physicians.
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