Iron Salts and Breastfeeding

Summary of use during lactation

Iron is a normal component in human milk. Daily oral iron intake from prenatal vitamins or other multimineral supplements does not affect milk iron levels. Higher daily oral iron dosing has a minimal effect on milk iron levels and is not expected to cause harm to the breastfed infant if needed to treat the mother’s anemia, but it is not an adequate substitute for direct infant iron supplementation to prevent or treat infant anemia.

Drug levels in milk and infant serum

Iron is normally present in human breastmilk, with higher concentrations in hindmilk.[1] One-third of milk iron is found in the fat fraction bound to metalloproteins in the outer membrane of fat globules. Most of the remainder is in the whey fraction bound mostly to lactoferrin, but also to other proteins such as transferrin and to smaller ligands. About 10% of milk iron is bound to casein.[2] Quantities are highest in colostrum, and they decrease as lactation progresses. Reported average milk iron levels in the first postpartum week are about 1 mg/L, decreasing to a range of 0.4 to 0.9 mg/L during the first postpartum month, then 0.2 to 0.4 mg/L from 1 to 3 months, and 0.1 to 0.3 mg/L from 3 to 6 months.[1-4] Mammary epithelial trace element active transporters regulate milk iron content and are believed to be responsible for insulating milk iron levels from changes in maternal iron status.[5] However, severe maternal malnutrition and anemia can lead to lower milk iron levels. Maternal Levels. In a study of 75 postpartum women in India, the average milk iron level at 12 to 18 days postpartum was 0.69 mg/L in women with severe anemia, defined as a hemoglobin level ≤6 grams/dL during the third trimester, compared to 0.74 to 0.79 mg/L in those with less severe anemia, and 0.83 mg/L in those with hemoglobin ≥ 11grams/dL.[6] A similar study in Cairo, Egypt reported an average milk level of 0.29 mg/L in malnourished, severely anemic mothers compared to 0.78 mg/L and 1.6 mg/L in mildly anemic and non-anemic mothers, respectively.[7] A study of 212 non-malnourished and mostly non-anemic mothers in West Java, Indonesia identified a 1.9% and 0.4% change in milk iron concentration for every 1 gram/L change in maternal hemoglobin and 1 mcg/L change in serum ferritin, respectively, but milk iron levels were not associated with maternal dietary iron intake.[8] A lack of correlation between milk levels and maternal dietary iron intake has also been reported in similar studies.[9-11] In 62 healthy and well-nourished, lactating mothers from Valencia, Italy taking 0 to 160 mg of supplemental elemental iron daily (exact doses not given), average milk iron levels were 0.57 mg/L and 0.5 mg/L on day 3 and day 15 postpartum, respectively. There was no linear relationship between iron dose and milk iron level.[1] Forty-seven non-anemic, lactating mothers in Ankara, Türkiye randomly received 80 mg elemental iron daily as ferrous sulfate or placebo beginning 10 to 20 days postpartum and continued for 4 months. Average milk iron levels changed from 0.58 mg/L at baseline to 0.37 mg/L at 4 months in the iron supplemented group, compared to 0.51 mg/L and 0.39 mg/L, respectively, in the placebo group. The difference in percent change from baseline between the two groups was not significant.[12] Twenty-eight breastfeeding women in Rio de Janeiro, Brazil with normal baseline iron status who received oral iron supplements during pregnancy as part of their routine prenatal care were randomized to receive 40 mg elemental iron as ferrous sulfate or no iron, once daily beginning at 1 or 2 days postpartum and continuing for 3 months. Milk iron levels were approximately 1 mg/L in both groups at baseline. At 30 to 40 days postpartum, average milk iron levels were approximately 0.7 mg/L in both groups. At 90 to 100 days, milk levels were 0.7 mg/L in the supplemented group and 0.55 mg/L in the nonsupplemented group, but were not significantly different. However, the percentage of milk protein as lactoferrin was significantly higher in the supplemented group.[13] High milk lactoferrin has also been reported in populations with high dietary iron intake.[2] The clinical relevance of this observation is not established. Among 145 healthy women between 20 and 60 days postpartum in Marilia, Brazil who donated breastmilk to a milk bank, those who reported taking an iron supplement during lactation had average milk iron levels of 0.3 mg/L compared to 0.4 mg/L in those who did not take an iron supplement. The exact doses of those in the iron group were not given.[14] Thirty-two exclusively breastfeeding and well-nourished women in Warsaw, Poland who were 4 to 6 weeks postpartum provided 4 milk samples in a single day in addition to completing an extensive dietary history. Almost half of the participants reported taking a dietary supplement that contained a low dose of iron, around 30 mg or less daily. The average milk iron level in the entire group was 0.39 mg/L. Milk iron level was not correlated with the maternal supplemental iron dose, but was correlated with the total iron intake from food and supplement.[15] Nineteen well-nourished but mildly anemic lactating mothers from Trujillo, Peru were given 100 mg elemental iron as ferrous sulfate once daily beginning on postpartum day 2. Average milk iron level was 0.90 mg/L at baseline and 0.38 mg/L at 30 days postpartum, compared to 0.8 mg/L and 0.35 mg/L, respectively in 10 other non-anemic lactating mothers who did not receive supplementation. Because no anemic control group was included in the study it is not clear if iron supplementation made a difference, although milk levels in the anemic group were not significantly different from the non-anemic group at 30 days which would indicate such an intervention is at least safe.[16] Sixty-five healthy women in Copenhagen, Denmark with postpartum hemorrhage within 48 hours of delivery were randomized to receive oral or intravenous iron to improve hematopoietic recovery. Women randomized to the oral group received an average of 45 mg elemental iron daily (salt form not stated) in the first three days of the study as they transitioned from their prenatal vitamins to high-dose oral supplementation, and then 90 mg daily from day 4 to day 8. Milk was collected 2 to 4 days after iron initiation and again at 6 to 8 days. Average milk levels were 0.4 mg/L and 0.44 mg/L, respectively.[17] In a U.S. study of 63 postpartum, lactating, mostly white, women taking a daily prenatal or multivitamin, those on a vegan or vegetarian diet had similar milk iron levels to those on an omnivore diet.[18] Infant Levels. One-hundred thirty-one non-anemic, lactating mothers in Ankara, Türkiye randomly received 80 mg elemental iron daily as ferrous sulfate or placebo beginning 10 to 20 days postpartum and continued for 4 months. Average serum iron levels in the iron group infants at 4 months was 0.4 mg/L compared to 0.46 mg/L in the placebo group.[19] In a study of 1066 breastfeeding infants born to mothers living in rural Bangladesh who randomly received 30 mg or 60 mg elemental iron as ferrous fumarate once daily beginning during their second trimester and continuing postpartum, there were no differences in the frequency of infant anemia, or blood iron indices, at 6 months postpartum between the groups.[20] Although iron levels are lower in milk than infant formula (<1 mg/L vs 10 to 15 mg/L), human milk iron is more bioavailable. Infant iron stores are similar in breastfed and formula-fed term infants born to non-anemic mothers who took an iron-containing prenatal vitamin during pregnancy.[21]

Effects in breastfed infants

One-hundred thirty-one non-anemic, lactating mothers in Ankara, Türkiye randomly received 80 mg elemental iron as ferrous sulfate daily or placebo beginning 10 to 20 days postpartum and continued for 4 months. Hematological indices and biochemical iron status values were no different between the two groups of infants at the end of the study.[19]

Effects on lactation and breastmilk

Iron-enriched human milk fortifier intended for preterm hospitalized infants increases milk microbial growth compared to iron-free fortifier under in vitro experimental conditions.[22] The clinical consequences of these findings have not been evaluated. Such studies tested milk iron concentrations in the range of 13 to 14 mg/L which were common for fortifiers in the countries where the studies were conducted. Currently available U.S. premature infant milk fortifier provides a much lower iron supplemental dose resulting in a milk iron level of 3 mg/L above the mother’s underlying milk level.

Alternative drugs to consider

Ferric Carboxymaltose, Ferric Derisomaltose, Iron Sucrose

References

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