Full-Term Infants

Most healthy term infants have sufficient iron stores to last until 4 to 6 months of age, largely because of relatively high hemoglobin (Hb) concentration and blood volume relative to body weight. Both decline during the first months after birth, with iron recycled, diminishing the early requirement for iron and likely accounts for human milk iron content evolving to be relatively low-on average, 0.35 mg/L. The iron concentration of human milk varies between days and between individuals. The NAM used the average iron content of human milk and an average intake of human milk (0.78 L/day) to determine the AI of 0.27 mg/day for full-term healthy breastfed infants through 6 months of age (see Table 18.1 and Appendix D). The NAM recommendations, however, do not take into account the at-risk infants born with a lower-than-usual iron endowment, listed in Table 18.2.^31,32,33 It is important to identify those with low fetal iron status because infants born with low iron endowment and breastfed exclusively until 4 months of age were at much higher risk for developing ID before 6 months.³⁴

In addition to other benefits, the AAP and American Heart Association (AHA) Neonatal Resuscitation Program, and American College of Obstetricians and Gynecologists³⁵ recommend delayed cord clamping or placental transfusion at nearly all births to improve erythrocyte iron endowment and thus both short- and long-term iron status in infancy.³⁶ Delaying cord clamping may also improve neurocognitive development at school age.³⁷ A number of studies have shown that exclusively breastfed infants supplemented with iron before 6 months of age exhibit higher Hb concentrations compared to unsupplemented infants at 6 months of age.^38,39 Iron supplementation also resulted in improved visual acuity and higher Bayley psychomotor developmental indices by 13 months of age.³⁸ Infant iron supplementation between 6 and 9 months improved 9-month motor scores more than maternal iron supplementation during pregnancy alone.⁴⁰ Such findings support the AAP recommendation that all exclusively breastfed term infants receive iron supplementation of 1 mg/kg/day elemental iron starting at 4 to 6 months of age using either iron drops or iron-containing multivitamin drops that also provide vitamin D.⁴ Supplementation should continue until appropriate iron-containing complementary foods are introduced.⁴ For partially breastfed infants, if more than one-half their daily feedings are human milk, and no iron-containing complementary foods are fed, the AAP suggests 1 mg/kg/day of supplemental iron be started at 4 to 6 months of age to help prevent breastfeeding infants from developing ID (see AAP text box).³¹

For infants 7 to 12 months of age, the RDA for iron is 11 mg/day (see Table 18.1 and Appendix D), as determined by a factorial approach that calculated iron losses, iron requirements for growth (increased blood volume, tissue mass), and storage iron. The disjuncture that occurs when contrasting to 0.27 mg/day to 11 mg/day by 6 months of age results from the very different methods of determining these values (see Table 18.1). Other recommendations in resource-rich countries ranged from 6.9 to 11 mg/day, based on different levels of iron bioavailability.⁴¹ Infants in the second 6 months after birth do not need iron supplementation if receiving adequate amounts of iron from iron-containing formula, iron-fortified cereals, or appropriate amounts of iron-rich complementary foods (see Appendix E and AAP text box).³¹ Meats containing heme iron should be encouraged, given its better bioavailability and improved enteral absorption (20% to 35% of intake) than iron in fruits and vegetables.

Healthy full-term, formula-fed infants do not need additional iron. For the last 20 years, most standard infant formulas in the United States have contained 12 mg of iron/L, higher than in other countries and above the maximum amount allowed in Europe by EFSA. This amount was estimated to supply all the exogenous iron requirements of a normal formula-fed full-term infant for the first year after birth. Because a normal infant has iron sources other than formula (especially cereal and meats), the 12 mg/L iron formula appears to supply more iron than is necessary.⁴ Concerns have been expressed that this amount of iron may have associated risks; however, the AAP has concluded that infant formula containing 12 mg of elemental iron/L is safe for its intended use.³¹ Although some concerns are expressed about linear growth in iron-replete infants receiving additional iron, no published studies have convincingly documented decreased linear growth in iron-replete infants receiving formulas containing high amounts of iron.⁴² Evidence is also insufficient to associate formulas containing 12 mg of iron/L with gastrointestinal tract symptoms. Several studies found no adverse effects.^43,44,45,46 In 2022, related to the infant formula shortages, the United States began allowing imported formulas that generally contained 4 to 8 mg/L of iron, consistent with European standards, and some US formulas also began lowering the iron intake to around 8 mg/L. This value may not be adequate for all full-term infants.

After 12 months of age, cow milk can begin, but intake should be a maximum of 24 ounces/day, although lower volumes (16-20 ounces or less per day), preferably given in a cup in lieu of a bottle, may be optimal. Intake of iron-fortified infant cereals substantially improves daily iron intake above those not normally consuming cereal.⁴⁷ Iron contained in wet packed iron-fruit cereals was equally as well absorbed as medicinal iron in infants.⁴⁸ Early introduction of meat is also a valuable way of providing highly bioavailable iron for infants.

Preterm Infants

Accretion of iron occurs predominantly in the last 3 months of intrauterine life; therefore, preterm infants lack sufficient iron. This iron deficit is more severe with earlier gestational age. Late preterm or low birth weight infants also lack the full fetal iron endowment. In addition to preterm birth, factors that further impede iron endowment at birth include intrauterine growth restriction, maternal anemia, hypertension, obesity, and diabetes, common diagnoses in mothers of preterm infants. Postnatal events can also affect an infant's iron status. These include frequent blood sampling that can further deplete body iron. The use of erythropoietin or erythrocyte stimulating agents to avoid transfusions can also dramatically increase the need for exogenous iron. On the other hand, sick preterm infants frequently receive multiple blood transfusions, an excellent source of iron. Delaying umbilical cord clamping or placental transfusion when possible in these children to improves physiology and iron status.⁴⁹ Delaying umbilical cord clamping in preterm infants may decrease the numbers of postnatal transfusions in the neonatal intensive care unit (NICU; see Chapter 5: Nutritional Needs of the Preterm Infant).^50,51 Identifying which preterm infants are at-risk for ID, how much and how the iron should be supplied in the NICU or postdischarge is challenging, due to the individual variations in iron requirements of preterm infants. This makes establishing recommendations difficult. The AAP and European Society for Pediatric Gastroenterology, Hepatology and Nutrition have recommended that all preterm infants be provided an intake of 2 to 3 mg/kg/day iron through 12 months of age, which is generally the amount of iron supplied by iron-fortified formulas.^31,52 Early iron supplementation in prematurity resulted in improved iron indices and did not interfere with linear growth.⁵³ Although neurocognitive sequelae of ID is of concern, a meta-analysis of 15 studies in low birth weight infants included only 2 reporting neurocognitive outcomes, and no difference in these outcomes was found.⁵³ Despite limited data, iron supplementation with screening of these at-risk infants may be considered a component of a neuroprotective strategy. Published quality improvement projects found 16% were iron deficient when screened at 1 month of age, despite delayed clamping of the cord at birth and NICU protocols starting iron supplementation by 2 weeks.^54,55 Despite feedings with iron-containing formula, 14% of moderately preterm infants developed ID between 4 and 8 months of age.⁵⁶ One study screened and found that 32% of very preterm infants had ID at 4 to 6 months of age, although 2.7% had IDA.⁵⁷ Preterm infants fed human milk should receive an iron supplement of 2 mg/kg/day by 2 weeks of age, and this should be continued until infants are weaned to iron-fortified formula or consume complementary foods that supply 2 to 3 mg/kg/day of iron. A potential exception may be those iron loaded from multiple transfusions during their hospitalization.³¹ Clinicians may withhold iron after a transfusion to avoid iron overload. Because of this, preterm infants may benefit from a personalized approach as part of a neuroprotection strategy, especially with human milk feedings.

Toddlers 1 Through 3 Years of Age

Toddlers 1 through 3 years of age should have an intake of iron of 7 mg/day (see Table 18.1 and Appendix D). Toddlers go through many dietary changes that affect their iron status. In their transition from "infant food" to more adult-like food, they leave behind iron-fortified formula and cereal, but they potentially gain a variety of iron-containing foods, such as meats and some vegetables, which should be encouraged (see Appendix E). Fruits containing vitamin C augment iron absorption and cellular processing and should also be encouraged. Toddlers are picky eaters, and their food choices may select against iron-rich foods. Given the diet variability within this age group, the iron status of toddlers is often difficult to predict. Historical, medical, and dietary risk factors, as well as certain clinical presentations should be considered in decisions to evaluate (see Table 18.2).³¹ For example, pica, an intense craving to eat, lick, or chew nonfood items (ie, dirt, rocks, paper, baby wipes, or cardboard), is highly associated with ID. The AAP recommends universal screening of toddlers for ID at 9 to 12 months of age. Toddlers who were primarily formula fed during the first year after birth but subsequently transitioned to cow milk may be at risk for developing ID after this screening, specifically if excessive cow milk intake is present.³¹ Additional screening may be warranted in older toddlers with such risk factors. All children with ID or IDA should have appropriate dietary counseling, treatment with oral iron and followed at 1 and 3 months, continuing until resolution of ID or IDA (see AAP text box).³¹ A study examining barriers to effective treatment in infants and toddlers found that emphasizing the health benefits of iron and avoidance of invasive treatments may improve parental adherence to therapy.⁵⁸

ID and lead poisoning are associated morbidities in this age group (see Table 18.2). Children with IDA have enhanced lead absorption because lead substitutes for iron in the duodenal divalent metal transporter and also poorer physiological lead chelation in the gut. Correction of ID limits lead absorption and restores the response to chelation. Thus, primary ID prevention could reduce the risk of lead intoxication as well as neurotoxicity.⁵⁹ For toddlers not receiving the recommended 7 mg/day of iron or who are at increased risk of ID, liquid iron supplements or multivitamins with iron are suitable for children 12 to 36 months of age, and chewable vitamins for children 3 years and older).³¹ It is important to note, however, that many gummy or jelly vitamins do not contain iron; therefore, it is important to read labels. In gummy or jelly multivitamins containing iron, the risk for accidental iron overdose is high and care should be taken to ensure child-safe storage.

School-Aged: 4 to 8 Years of Age

In young school-age children, iron-containing foods (see Appendix E) as part of a well-balanced diet, should be promoted by providers and caregivers with the goal of obtaining an iron intake of 10 mg per day. Prevalence of ID and IDA is significantly less in this age group compared with young children but is more common in combination with certain historical, medical or dietary risk factors (see Table 18.2). Therefore, children in this age group who develop ID or IDA warrant not only a full dietary review but also assessment of overall growth, illnesses, and potential gastrointestinal blood loss. If anemia or ID is suspected, screening for both ID and IDA should be performed (see section Screening for ID and IDA). In addition to addressing the underlying etiology (diet versus blood loss), ID should be treated with therapeutic iron supplementation and followed at 1 and 3 months until resolution.

School-Aged: 9 to 13 Years of Age

Older school-aged children and adolescents have increasing discretion in food selection and may consume over half of their food outside of the home (ie, snacks and meals at school or extracurricular activities as well as meals on the go). These factors result in decreased supervision of meal content and quality, thereby increasing the risk of restricted diets and poorer nutritional choices (see Chapter 8: Adolescent Nutrition). Iron needs in this group are heterogeneous because of variability in growth spurts, which result in increased Hb and muscle mass, as well as menstrual blood loss in girls with the onset of menarche. In general, children aged 9 to 13 years should receive approximately 8 mg per day of iron (see Table 18.1), and foods with high iron content should be encouraged (see Appendix E).

Increased iron demands may exceed dietary iron availability and deplete iron stores. Therefore, any adolescent with a history of a low-iron diet, restricted dietary behaviors, or pica (ie, paper, starch, ice), are at increased risk for ID. Children who follow a vegetarian or vegan diet should be counseled to include nonheme iron-rich foods into their diet consistently. Age-specific historical, medical, and dietary risks should be considered (see Table 18.2) and etiology addressed. For any child identified to be iron deficient, with or without anemia, dietary modifications should be initiated in addition to oral iron therapy. All children should be followed at 1 and 3 months, until resolution of IDA, including normalization of iron stores.

Adolescents: 14 to 18 Years of Age

As in preadolescence, iron needs in older adolescents must account for basal losses, increased Hb and muscle mass, and menstrual blood loss in girls. Lifestyle and variations in food preferences, including alternative diets or missed meals, may also occur (see Chapter 8: Adolescent Nutrition). Recommended iron intake for this age group is 11 mg for males and 15 mg for females (see Table 18.1). Nutritious diets with regular meals including iron-rich foods should be encouraged (see Appendix E). Any adolescent with a restricted diet, inconsistent eating patterns or symptoms of pica should be screened for ID and IDA. Young women with heavy menstrual bleeding or abnormal uterine bleeding, particularly within the first 2 years of menarche are at increased risk for the development of ID and IDA. Consideration should be given to following the American College of Obstetrics and Gynecology (ACOG) recommendations that adolescent girls who present with heavy menstrual bleeding should be assessed for anemia from blood loss, including serum ferritin, the presence of an endocrine disorder leading to anovulation, and an evaluation for the presence of a bleeding disorder.⁶⁰ Other age-specific historical, medical and dietary risks should be considered in this assessment as well (see Table 18.2). If identified, the underlying etiology for the IDA should be addressed and iron replacement therapy initiated and followed until resolution. For girls with excessive menstrual blood loss resulting in ID or IDA, hormonal therapy may be considered to minimize future blood loss and enhance iron replacement therapy.⁶⁰ Screening for an underlying bleeding disorder should also be considered in these patients.⁶⁰

In addition to poor concentration and fatigue, several other neurologic and sleep conditions have been associated with ID, particularly in the adolescent age group. Pediatric restless leg syndrome (RLS), a disorder that results in the urge to move the legs, typically accompanied by uncomfortable and unpleasant sensations, has been strongly associated with ID.^12,61 Likewise, periodic limb movement disorder (PLMD), which is characterized by repetitive, stereotyped movements involving the lower limbs resulting in sleep disturbance, is associated with ID. Patients with both RLS and PLMD receiving iron therapy have reported subsequent improved symptom management but may need higher serum ferritin levels for iron efficacy.^62,63 Both RLS and PLMD can have a family predominance, and such, genome-wide association studies found a total of 4 single-nucleotide polymorphisms that conferred increased risk for RLS or PLMD, one of which on chromosome 6 also confers greater risk for developing ID. At least 1 study has found that children with neurally mediated syncope (ie, simple faint), the most common type of syncope in pediatric populations, had a higher prevalence of ID compared with children with other forms of syncope.⁶⁴ Adolescents with postural tachycardia syndrome, an autonomic disorder of orthostatic tolerance, also have higher prevalence of ID and anemia compared with the normal US pediatric population and may have symptomatic improvement with iron therapy.⁶⁵