BREASTFEEDING MEDICINE Volume 13, Number 6, 2018 ABM Protocol ª Mary Ann Liebert, Inc. DOI: 10.1089/bfm.2018.29095.snt ABM Clinical Protocol #29: Iron, Zinc, and Vitamin D Supplementation During Breastfeeding Sarah N. Taylor and The Academy of Breastfeeding Medicine A central goal of The Academy of Breastfeeding Medicine is the development of clinical protocols, free from commercial interest or influence, for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient. uman milk is designed to deliver comprehensive improved outcomes and, therefore, is not recommended. Hnutrition through the first 6 months of age and com- (LOE IB) plementary nutrition through the early years. However, micronutrient supplementation may be appropriate, espe- Vitamin D cially when a mother is deficient or an infant has special needs such as prematurity. In contemporary high- and low- The breastfeeding infant should receive vitamin D sup- resource settings, concern has been raised regarding iron, plementation shortly after birth in doses of 10–20 lg/day zinc, and vitamin D status of human milk-fed infants. This (400–800 IU/day) (LOE IB). This supplement should be protocol reviews the available evidence regarding iron, zinc, cholecalciferol, vitamin D3, because of superior absorption and vitamin D supplementation of the breastfeeding dyad. unless a vegetable source such as ergocaliferol vitamin D2,is Quality of evidence (levels of evidence [LOE] IA, IB, IIA, desired (LOE IIA). Randomized trials demonstrate that safe IIB, III, and IV) is provided and based on levels of evidence vitamin D supplementation may be provided to a nursing used for the National Guidelines Clearing House.1 From mother to achieve healthy vitamin D status in her breast- currently available evidence, recommendations are provided feeding infant, when there is objection or contraindication to and areas for future study are identified. A brief summary of direct infant supplementation. A maternal dose of 160 lg/day recommendations is presented first, followed by more in- (6,400 IU/day) is suggested. depth discussion of the three micronutrients. Iron Recommendations Downloaded by 192.31.255.3 from www.liebertpub.com at 02/28/19. For personal use only. Background section Iron Iron is a mineral critical to infant somatic growth and Iron supplementation is not required for the non-anemic neurodevelopment. It is most commonly recognized for its breastfeeding mother. Iron supplementation to the 4-month- role in iron-deficiency anemia, but it importantly has direct old full-term, exclusively breastfed infant is associated with effects on brain maturation. Iron deficiency during infancy is improved hematological indices. However, the long-term associated with poor cognitive and behavioral outcomes that benefit of improved hematologic indices at 4–6 months is not may persist after iron repletion. Therefore, ensuring adequate known. If iron supplementation is given before 6 months, it iron stores in infancy is essential. should be given as a 1 mg/kg/day distinct iron supplement Infants born at term have transplacentally acquired hepatic until iron-fortified cereals (7–7.5 mg ferrous sulfate/day) or iron stores that are mobilized and utilized over the first 4–6 other iron-rich foods such as meat, tofu, beans, and others are months. Preterm infants, term infants born growth-restricted, initiated at 6 months of age with other complementary foods. and infants born to mothers with iron deficiency during (LOE IB) pregnancy may have smaller iron stores. The iron in human milk has high bioavailability (*50%) to complement the Zinc infant’s iron stores.2 Research has investigated whether these Zinc supplementation, above dietary intake, to the lactat- two sources, fetal accretion and human milk iron concen- ing mother or breastfeeding infant is not associated with tration, provide adequate supply and for how long this supply Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut. 398 ABM PROTOCOL 399 alone is adequate. Studies have also examined the role of Large randomized controlled trials have examined iron iron-containing or fortified complementary foods in pro- supplementation at 4–9 months of age. Some studies have tecting iron stores, especially in the second half of the first specifically compared iron initiation at 4 or 6 months. Others year when the fetal supply is diminished. have compared iron drops and iron-fortified foods. In one Iron is a pro-oxidant and some studies have shown sup- study of 609 infants in Thailand, both iron and zinc supple- plemental iron to negatively affect immune function. In fact, mentation were evaluated with initiation at 4–6 months. In- iron may mitigate the antipathogenic actions of human fants receiving 10 mg iron as iron sulfate (with or without milk.3–5 zinc) exhibited significantly higher hemoglobin and ferritin Iron-deficiency anemia is diagnosed by abnormal hema- concentrations at 6 months of therapy compared with infants tological values. Studies of iron supplementation in infants receiving only zinc or placebo. When controlling for gender have used serum iron, ferritin, iron binding capacity, mean and birth weight, infants receiving iron had significantly corpuscular volume (MCV), and hemoglobin as indicators of higher Ponderal weight growth and weight-for-length z-score sufficient iron to avoid the risk of anemia. Other potential (LOE IB).9 markers of adequate iron supplementation include anthro- One double-blinded randomized placebo-controlled pemetric growth and neurodevelopment. Randomized con- trial, occurring in Honduras and Sweden, evaluated iron trolled trials (LOE IB) of iron supplementation to the supplementation alone. In this study, 232 near-exclusive or lactating mother or to the infant have included serum and exclusively breastfeeding infants at 4 months of age were milk iron concentrations, ferritin and iron binding capacity, randomized to receive (1) placebo until 9 months of age, hematologic indices, growth, and neurodevelopment as out- (2) placebo for 4–6 months followed by iron (1 mg/kg/day) comes. for 6–9 months, or (3) iron (1 mg/kg/day) until at least There are few studies investigating iron supplementation 9 months.10,11 The primary aim, to detect a difference in directly to the breastfeeding mother to support infant iron hemoglobin, was demonstrated for the infants receiving iron status. One study recruited 168 healthy, nonanemic mothers supplementation starting at 4 months. When iron supple- in the first 10–20 postnatal days if they planned to exclusively mentation started at 6 months, the infants in Honduras breastfeed for at least 4 months. These mothers were ran- demonstrated significantly higher hemoglobin while the domized to receive 80 mg elemental iron daily or placebo. No Swedish infants did not (LOE IB).11 In evaluation of growth, difference was seen in maternal or infant iron studies, rate of the Swedish infants supplemented with iron had significantly iron-deficiency anemia, or infant growth. In the intervention lower length and head circumference gains than those infants group, both mother and infant had significantly increased receiving placebo from 4 to 9 months (LOE IB).10 In Hon- serum iron binding capacity but the significance of this single duras, a negative effect on linear growth was evident at 4–6 difference is not known (LOE IB).6 months only among iron-sufficient infants (with an initial Hb When evaluating the evidence of direct infant supplemen- ‡110 g/L). In addition, in both sites, iron supplementation tation, it is necessary to consider the age at which supple- increased the likelihood of diarrhea among iron-sufficient mentation occurred—in the first 4 months, starting at 4–6 infants. months, or starting at 6 months of age. Two small randomized The question as to whether iron should be provided as a controlled trials have evaluated iron supplementation initi- daily or weekly dose has been evaluated by one randomized ated before 4 months of age. The first study included 77 term trial without study blinding. No difference in iron deficiency breastfed infants who were randomized to receive either 7.5 mg or iron-deficiency anemia was observed with ferrous sulfate elemental iron as ferrous sulfate or placebo from 1 to 6 months suspension dosed at 1 mg/kg daily, 7 mg/kg weekly, versus of age (LOE IB).7 At 6 months, the supplemented group had no supplement provided to breastfeeding infants at 4–10 significantly higher hemoglobin (124 versus 116 g/L) and months of age (n = 79) (LOE IB).12 MCV (81 versus 77 fL). Forty-six of the 77 study subjects had Studies of whether iron should be provided as a distinct Downloaded by 192.31.255.3 from www.liebertpub.com at 02/28/19. For personal use only. neurodevelopmental assessment at 12–18 months; the inter- dose or instead through fortified cereal are open-label studies. vention group exhibited higher Bayley psychomotor develop- In 2004 in Honduras, 4-month-old, exclusively breastfeeding ment indexes and visual acuity. No significant differences were infants were randomized to iron-fortified cereal or no cereal seen in mental development indices. until 6 months of age (LOE IB).13 In this study, infants who A second study of early iron supplementation specifically exhibited anemia at study initiation (58% of the iron-fortified focused on the term low birth weight (<2,500 g) infant. group and 47% of exclusively breastfeeding group) also re- Healthy infants (n = 62) who were predominantly breastfed ceived iron drops. Of the infants who were not anemic at study at 50–80 days were randomized to iron 3 mg/kg/day (25 mg initiation, those receiving iron-fortified cereal had signifi- Fe/mL ferric ammonia citrate) or placebo for 8 weeks (LOE cantly higher hemoglobin and lower prevalence of anemia IB).8 Infant hemoglobin levels were significantly higher in than those exclusively breastfed.