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Iron requirements in the first 2 years of life

Posted: Nov 20, 2019

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Principal author(s)

Sharon L. Unger, Tanis R. Fenton, Radha Jetty, Jeff N. Critch, Deborah L. O’Connor; Canadian Paediatric Society, Nutrition and Gastroenterology Committee

Paediatr Child Health 2019 24(8):555. (Abstract)

Abstract

Iron is an essential micronutrient required for hemoglobin synthesis, central nervous system development, and protection from infection. Early childhood is a time of vulnerability as iron deficiency in this period is associated with impaired neurodevelopment. Low socio-economic status, preterm birth, and suboptimal diet are risk factors for iron deficiency. Due to a lack of iron excretory mechanism, the possibility of iron excess also exists. Appropriate iron intake in the first 2 years of life is critical.

Keywords: Anemia; Complementary feeding; Infant nutrition; Iron deficiency; Iron requirements

Iron physiology

Iron, a key element in human metabolism, is involved in oxygen and electron transport, and DNA synthesis [1]. Iron is also essential to the carefully regulated process of hematopoiesis, which maintains red blood cells within a narrow range. Sixty-five percent of body iron is in hemoglobin, with the remaining stored in splenic and hepatic macrophages, myoglobin, cytochromes, and other ferroproteins [2].

Iron absorption largely depends on iron status. Because the human body has limited ability to excrete excess iron, stores are regulated at the level of intestinal absorption by hepatically synthesized hepcidin [3]. Iron absorption decreases when the body is iron-replete, and increases when the body is deficient. Losses occur from sloughing of skin, intestinal, and urinary cells, and from bleeding. Iron as heme (animal source) and non-heme is absorbed at the brush border and transported in plasma by transferrin. Serum ferritin, a major iron storage protein, is the best measure of iron stores, although serum ferritin levels may become elevated in inflammation [4]. Iron absorption from human milk is assumed to be 20% to 50%, depending on an infant’s age and iron status, compared with 10% to 20% from infant formulas [5][6]. Infant formulas typically contain higher iron levels than human milk.

Iron deficiency/Excess

A child may be iron sufficient or have one of three progressive stages of iron deficiency. Depleted iron stores (low serum ferritin), then decreased iron transport (low transferrin saturation) are the first two stages of deficiency and, for clarity, may be termed ‘non-anemic iron deficiency’ or NAID. The third stage of iron deficiency presents with anemia, termed ‘iron deficiency anemia’ or IDA. Iron deficiency is the most common micronutrient deficiency world-wide [7][8]. Globally, approximately 40% of preschool children are anemic, mostly secondary to iron deficiency [9]. The current Canadian prevalence of iron deficiency in infants is unknown. In the mid-1990s, IDA in middle-class infants and toddlers in Canada was reported to be 4.3% [10]. The Canadian Paediatric Surveillance Program (CPSP) identified 195 cases of severe IDA (hemoglobin <80 g/L) from 2009 to 2011 [11]. Dietary factors played a role in most cases. Known risk factors for iron deficiency before 2 years of age include preterm delivery or birth weight <2500 g [1], low socio-economic status [12], infants born to mothers with anemia [13] or obesity [14], early umbilical cord clamping [15], male sex [16], exclusive breastfeeding for longer than 6 months [17], high cow’s milk intake [18], prolonged bottle use [19], chronic infection [20], lead exposure [21], and a low dietary intake of iron-rich complementary foods. The last risk factor should be particularly considered in infants with decreased intake of iron-rich foods secondary to neuro-impairment [22]. Infants and toddlers are particularly vulnerable to iron deficiency as their needs increase during this period of rapid growth, especially if they have low iron stores at birth.

The prevalence of IDA in Indigenous communities may be up to ten times higher than in the rest of Canada, with estimates of 36% in infants 4 to 18 months old [23] to 58% in infants 9 to 14 months old [24], due to poverty, food insecurity, and other factors. Diminishing access to traditional iron-rich foods and increasing access to low-iron ‘convenience’ foods contribute to reduced iron intake and bioavailability.

NAID and IDA have been associated with lower neurodevelopmental scores [25]-[27] and compromised immune response [28]. Toddlers with IDA have shown lower cognitive and motor function compared with non-anemic controls [26][29][30], effects which appear to persist beyond childhood [26][31]. Animal studies and human observational studies have both suggested that suboptimal neurodevelopment associated with iron deficiency may not be completely reversible with iron supplementation [32][33], highlighting the importance of preventing  iron deficiency, starting before birth.

Not having an efficient iron excretory mechanism as part of the normal human physiology makes the   risk of excessive iron intake possible, either from over-supplementation or a genetic predisposition to absorb and store excess iron (e.g. hemochromatosis). Along with iron overload in tissues, increased iron may be available to pathogenic bacteria in the intestines [22].

Early iron requirements

Rapid growth during infancy and early childhood increases iron requirements per kilogram more than at any other developmental stage. This elevation is balanced by the young child’s ability to absorb iron from the gastrointestinal tract slightly more than usual during times of increased requirement [34]. Iron stores at birth are related to birth weight [35]. Most healthy term infants of normal birth weight are born with sufficient stores to meet their iron requirements, including hemoglobin synthesis, until they are 6 months old. At about this time, iron stores become depleted and breast milk alone cannot meet iron requirements beyond 6 months.

Health Canada supports using the National Academy of Medicine Dietary Reference Intakes. For infants 7 to 12 months of age, 11 mg/day of elemental iron (Table 1) is the Recommended Dietary Allowance [36]. Due to slower growth rates after the first year, iron recommendations decrease to 7 mg/day for children 1 to 3 years old, then increase to 10 mg/day for children 4 to 8 years old [36].

In 1995, the Canadian Paediatric Society (CPS) recommended routine iron supplementation for preterm infants for the first year [37]. In 2012, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee on Nutrition recommended 2 to 3 mg/kg/day of iron for the first year for preterm infants born weighing <2000 g [5]. For term and preterm infants weighing 2000 g to 2500 g, they recommended 1 to 2 mg/kg/day, beginning at 2 to 6 weeks of age, until 6 months. Recent systematic reviews of iron supplementation for LBW infants have found that those who were given iron supplements of 2 to 3 mg/kg/day had slightly higher hemoglobin levels, improved iron stores, and a lower risk for developing IDA, compared with infants who did not receive supplements. There was no apparent hematological benefit from higher doses [38]. The timing recommended for starting iron supplementation in LBW infants is at 2 to 3 weeks postnatal age, compared with 4 weeks postnatal age for infants in the normal range [39].

Table 1. Dietary Reference Intakes for iron in infants and toddlers
Recommended iron intake Typical estimates of iron intake

Health Canada/CPS [40]

AAP [43][47]

ESPGHAN [5][48]

National Academy of Medicine [36]

Exclusively breastfed

Exclusively formula-fed
Term infants, 0 to 6 months

Exclusive breastfeeding is sufficient to meet iron requirements until 6 months of age

Formula-fed infants: Iron- fortified formula

Exclusive breastfeeding is sufficient until 4 months of age

Exclusively or >50% breastfed infants:

1 mg/kg/day iron supplement from 4 to 6 months

Formula-fed infants: Formula containing 4 mg/L to 12 mg/L of iron

Exclusive breastfeeding is sufficient to meet iron requirements until 4 to 6 months of age

Formula-fed infants: Formula containing 4 mg/L  to 8 mg/L iron

0.27 mg/day from breast milk alone, if iron stores are adequate

0.05-0.07 mg/kg/day

1-2 mg/kg/day
Term infants, 7 to 12 months

Continued breastfeeding with the introduction of iron-rich complementary foods at about 6 months

Delay cow’s milk until 9 to12 months of age (then limit to 750 mL/day)

11 mg/day

0.9 to 1.3 mg/kg/day

Delay cow’s milk until 12 months of age (then limit to 500 mL/day)

11 mg/day

 

 
Note: All references in this table refer to elemental iron.
AAP – American Academy of Pediatrics CPS –  Canadian Paediatric Society ESPGHAN –  European Society for Paediatric Gastroenterology, Hepatology and Nutrition
 

Preventing iron deficiency

The ESPGHAN Committee on Nutrition [5] reported on the most effective measures to reduce iron deficiency, including:

  • Delayed cord clamping
  • If formula feeding, providing iron-fortified formula
  • Feeding iron-rich complementary foods from age 6 months
  • Not using cow’s milk as the main milk source until infants are a year old, and limiting cow’s milk intake to 500 mL/day thereafter.

Health Canada’s joint document entitled  “Nutrition for Healthy Term Infants: Recommendations from Six to 24 months” recommends delaying introduction of cow’s milk until 9 to 12 months, limiting intake to 750 mL/day, then offering 500 mL/day of cow’s milk to children 1 to 2 years old [40]. In Canada at the present time, infant formulas for term infants typically contain iron in the range of 6.5 mg/L to 13 mg/L, which is not always sufficient to meet the needs of formula-fed infants at risk for iron deficiency [40][41]. Health Canada further recommends that the first complementary foods introduced at about 6 months should be iron-rich (e.g., meat, meat alternatives, and iron-fortified cereals). There is little evidence that iron-fortified formulas and cereals or iron-rich foods cause adverse gastro-intestinal effects, such as constipation, in infants or toddlers [27].

Iron therapy

Several reviews of the literature have concluded that neither universal screening for iron deficiency nor routine supplementation with iron is required for healthy term infants who do not have a risk factor for IDA [27][42]. By contrast, in 2010 the American Academy of Pediatrics recommended universal screening for anemia at 12 months of age using a risk factor assessment and a determination of hemoglobin [43]. They further stated that infants who are predominantly breastfed (i.e., greater than 50% of intake) should receive iron supplements, starting at 4 months of age and continuing until iron-rich complementary foods are well established [43]. This last point especially has been much debated [44].

Treatment for infants and toddlers deemed to have IDA due to insufficient iron intake includes oral supplements, at a dosage of 2 mg/kg/day to 6 mg/kg/day of elemental iron in divided doses [45][46]. Absorption improves when iron is ingested with a source of vitamin C. Supplements should be continued for a minimum of 3 months, followed by a reassessment of iron status including CBC and serum ferritin.

Recommendations (all dosage recommendations refer to elemental iron)

  1. Exclusive breastfeeding is recommended for the first 6 months.
  2. If normal birth weight infants are not breastfed, they should receive formula containing 6.5 mg/L to 13 mg/L of iron (which is the typical concentration in standard cow’s milk-based formulas in Canada) for the first 9 to 12 months. Formula-fed infants who may be at higher risk for iron deficiency (e.g., due to low socio-economic status, maternal anemia, low intake of iron-rich complementary foods, or living in an Indigenous community that may be challenged by poverty, food insecurity, high consumption of evaporated milk or cow’s milk, and a high burden of H pylori infection) should receive formula with a higher iron content (13 mg/L of iron).
  3. For the healthy term infant, iron-rich complementary foods, such as meat, meat alternatives, and iron-fortified infant cereals, should be introduced at about 6 months. Access to traditional iron-rich foods should be encouraged and facilitated in Indigenous communities. In populations with higher risk for IDA, case-selecting infants for testing may be one approach to assess the benefit from receiving supplementation with oral iron drops before 6 months. If an infant is developmentally ready, introducing iron-rich complementary foods between 4 to 6 months could also be considered when there is high risk for IDA.
  4. At each well child visit in the first 2 years, assess for risk of iron deficiency, with particular attention to high-risk individuals (e.g., those living with chronic illness, low socio-economic status, suboptimal intake of iron-rich foods, or prolonged bottle feeding), and screen (CBC, serum ferritin) appropriately. When anemia is identified, screen further to identify the etiology.
  5. There is insufficient evidence to recommend routine iron supplementation or laboratory screening for iron deficiency in healthy term infants with no risk factors who are exclusively breastfed for 6 months.
  6. For well infants, formula feeding is not required beyond 12 months of age, when whole cow’s milk can be introduced. Formulas designed for toddlers beyond 12 months are not necessary.
  7. For low birth weight infants (birth weight less than 2.5 kg) who are predominantly breastfed (i.e., greater than 50% of intake), iron supplementation is routinely recommended.
    • Infants with a birth weight of 2.0 kg to 2.5 kg, should receive an iron supplement of 1-2 mg/kg/day for the first 6 months of age.
    • Infants with a birth weight less than 2.0 kg, should receive an iron supplement of 2-3 mg/kg/day for the first year of age.
  8. For low birth weight infants (birth weight less than 2.5 kg) who are predominantly  formula-fed (i.e., greater than 50% of intake), iron supplementation is not required when the formula used is high in iron.
    • Infants with a birth weight of 2.0 kg to 2.5 kg: formula provides 1-2 mg/kg/day of elemental iron (typically provided with formula containing 10 mg/L to 12 mg/L of iron)
    • Infants with a birth weight less than 2.0 kg: formula provides 2-3 mg/kg/day of elemental iron (typically provided with formulas containing 10 mg/L to 14 mg/L of iron, i.e., formulas specifically designated for preterm infants).

Acknowledgements

This practice point was reviewed by the Community Paediatrics, Fetus and Newborn, and First Nations, Inuit and Métis Health Committees of the Canadian Paediatric Society. It was also reviewed by Patricia D’Onghia and Deborah Hayward, on behalf of Health Canada. The authors wish to especially acknowledge Becky Blair, RD, of the Dietitians of Canada, for her valuable assistance in editing this practice point.

CANADIAN PAEDIATRIC SOCIETY NUTRITION AND GASTROENTEROLOGY COMMITTEE

Members: Dana L. Boctor MD (past member), Linda M. Casey MD, Jeffrey N. Critch MD (past Chair), Manjula Gowrishankar MD (past member), Eddy Lau MD (Board Representative), Catherine M. Pound MD (Chair), Ana M. Sant’Anna MD, Pushpa Sathya MD, Christopher Tomlinson MB, ChB, PhD, Sharon L. Unger MD (past member)
Liaisons: Becky Blair MSc RD, Dietitians of Canada; Patricia D’Onghia MPH RD, Health Canada; Tanis R. Fenton PhD RD, Dietitians of Canada; Laura Haiek, Breastfeeding Committee for Canada; Deborah Hayward, Bureau of Nutritional Sciences, Health Canada; Sarah Lawrence MD, Canadian Pediatric Endocrine Group
Principal authors: Sharon L. Unger MD FCRP, Tanis R. Fenton PhD RD, Radha Jetty MD FCRP, Jeff N. Critch MD FRCP, Deborah L. O’Connor PhD RD

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Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.

Last updated: Feb 7, 2024

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