Lack of correlation between free erythrocyte porphyrin and serum ferritin values at birth and at 2 months of life in low birthweight infants.

Red cell free erythrocyte porphyrin and serum ferritin determinations were performed on capillary blood specimens from 63 healthy infants weighing 2500 g or less at birth, during the first week of life, and, from 44 of them, again at 8-10 weeks. Free erythrocyte porphyrin values were high both at 3-7 days (mean 156 microgram/100 ml RBC) and at 8-10 weeks (mean 128 microgram/100 ml RBC). The respective serum ferritin values were also high (mean 226 and 107 ng/ml), excluding a depletion in iron stores. In addition, no correlation was found between free erythrocyte porphyrin and serum ferritin values either at birth or at age 2 months. These findings are consistent with an earlier hypothesis that in the presence of iron stores, the rate of iron release from the stores in low birthweight infants may not be sufficient to maintain optimal erythropoiesis if the demand is accelerated.     

Medicinal iron to low birth weight infants

Serum ferritin concentrations were measured during the first 6 months of life in 28 low birth weight infants (mean birth weight 1820 g range 900-2460; mean gestational age 34 weeks range 29-37) fed a standard formula fortified with ferrous sulphate. Fifteen of the infants received supplementary medicinal iron (ferrous succinate) from 3 weeks of age, and 13 only from 2 months of age. All were given vitamin E from 10 days of age. The serum ferritin values did not differ between the groups at 1-2 days, 8-10 weeks or at 6 months. Furthermore, there were no signs of hyperhaemolysis at 8-10 weeks in the group receiving medicinal iron early. The data indicate that the iron content in the formula is sufficient until 2 months of age, but also that thereis no disadvantage in starting medicinal iron at 3 weeks of age, if the diet is sufficient in vitamin E.     

Free erythrocyte porphyrins in cord blood

Red cell free erythrocyte porphyrin determinations were performed on cord blood specimens from 236 term infants and on capillary blood specimens from 63 preterm infants weighing less than 1,500 gm, during the first week of life. These results were contrasted with those obtained from 398 normal infants and children ages 1 to 6 years. The mean FEP value for the infants was significantly higher than that observed in the normal control subjects. In 10.5% of the term infants and 15.9% of the preterm infants, values in excess of 120 microgram/dl RBCs, the highest value recorded in the normal subjects, were observed. Elevations in FEP values were not related to either blood lead concentration or hematocrit levels in the infants. Infants with elevated FEP values were found to have lower serum iron and transferrin saturation values than did infants with low FEP values. These findings suggest that elevations in cord blood FEP values may indicate a state of relative iron deficiency present at birth.     

Iron status at 9 months of infants with low iron stores at birth

OBJECTIVE: To determine the 9-month follow-up iron status of infants born with abnormally low serum ferritin concentrations.Study design: Ten infants of >34 weeks' gestation with cord serum ferritin concentrations <5th percentile at birth (<70 microg/L) and 12 control infants with cord serum ferritin concentrations >80 microg/L had follow-up serum ferritin concentrations measured at 9 +/- 1 month of age. The mean follow-up ferritins, incidences of iron deficiency and iron-deficiency anemia, and growth rates from 0 to 12 months were compared between the two groups. RESULTS: At follow-up, the low birth ferritin group had a lower mean ferritin than the control group (30 +/- 17 vs 57 +/- 33 microg/L; P =.03), but no infant in either group had iron deficiency (serum ferritin <10 microg/L) or iron-deficiency anemia. Both groups grew equally well, but more rapid growth rates were associated with lower follow-up ferritin concentrations only in the low birth ferritin group (r = -0.52; P =.05). Both groups were predominantly breast-fed without iron supplementation before 6 months. CONCLUSIONS: Infants born with serum ferritin concentrations <5th percentile continue to have significantly lower ferritin concentrations at 9 months of age compared with infants born with normal iron status, potentially conferring a greater risk of later onset iron deficiency in the second postnatal year.     

Abnormal iron distribution in infants of diabetic mothers: spectrum and maternal antecedents

Because chronic hypoxemia causes a redistribution of iron from serum and storage pools into an expanding erythrocyte mass, and because infants of diabetic mothers are often hypoxemic in utero and have a high prevalence of polycythemia at birth, we studied iron distribution in 43 term infants of diabetic mothers. Twenty-four infants were at an appropriate size for gestational age; 19 were large for gestational age. At birth, 28 infants (65%) had abnormal serum iron profiles; eight had decreased ferritin concentrations only (stage 1), nine had decreased ferritin and increased total iron-binding capacity values (stage 2), and 11 had these serum findings plus elevated free erythrocyte protoporphyrin concentrations (stage 3). The hypoglycemic infants who were large for gestational age (n = 14) had a higher prevalence of abnormal iron profiles than euglycemic infants who were appropriate in size for gestational age (n = 20; 93% vs 50%; p = 0.009). Progressively abnormal iron profiles were associated with higher glycosylated fetal hemoglobin values, greater degrees of macrosomia, increased hemoglobin and erythropoietin concentrations, and increased erythrocyte/storage iron ratios. Erythropoietin concentrations were inversely linearly correlated with serum iron values (n = 32, r = -0.54; p = 0.003). The combined erythrocyte and storage iron pools were significantly lower in infants with abnormal iron values whose mothers were diabetic, particularly in infants of women with confirmed diabetic vasculopathy. We speculate that these findings are likely due to (1) increased fetal iron utilization during compensatory hemoglobin synthesis in response to chronic hypoxemia and (2) reduced iron transfer during late gestation complicated by diabetes.     

Iron and the exclusively breast-fed infant from birth to six months

This study was designed to determine whether normal, full-term, exclusively breast-fed infants develop iron deficiency anemia, as defined by hemoglobin or red blood cell indices more than two standard deviations below the age-specific mean, or depletion of iron stores, as defined by an abnormally low serum ferritin level. Thirty-three breast-fed infants were followed from birth to 6 months. Maternal blood and cord blood at delivery, and venous blood from the infants at 2, 4, and 6 months were analyzed for anemia as defined above. At 6 months of age, the mean hemoglobin concentration of these infants was slightly higher than the normal mean; four of 33 infants (12%) had a mean corpuscular volume greater than 2 SD below the reported normal mean; and two of 33 infants (6%) had a serum ferritin level less than 12 ng protein/ml. These data suggest that the infant who is exclusively breast-fed for the first 6 months of life is not at high risk for the development of iron deficiency anemia or the depletion of iron stores during that time.     

Iron status of the preterm infant during the first year of life

The iron status of 49 preterm infants (mean gestational age 33.1 weeks) was assessed serially during the 1st year of life. Haemoglobin concentration, serum ferritin, serum transferrin, serum iron, and transferrin saturation were measured on nine occasions in each infant. In 16 infants of gestational age 28-32 weeks the haemoglobin concentration was significantly lower at 3, 6, and 9 weeks when compared to 33 infants of gestational age 33-36 weeks. For all other measures of iron status there were no significant differences between these gestational age groups. For the entire group of 49 infants the mean haemoglobin concentration reached a nadir of 11.2 g/dl at 9 weeks. Mean serum iron and transferrin saturation reached peaks of 24 mumol/l and 65%, respectively, at 3 weeks. The mean serum ferritin remained over 100 micrograms/l until after 18 weeks. 13 infants (26%) had iron deficiency defined as either serum ferritin less than 10 micrograms/1 (n = 10) or transferrin saturation less than 10% (n = 5) or both (n = 3).     

Iron supplementation in children after cardiopulmonary bypass for surgical repair of congenital heart disease

Summary A controlled study was carried out to evaluate the effects of postoperative iron therapy on iron status in anemic children after cardiopulmonary bypass. The patients were 8 boys and 9 girls (mean age 6.5 years) who underwent elective closure of atrial septal defect, secundum type. On postoperative day 9, patients were randomly assigned to either iron supplementation with iron sulfate 5mg/kg until day 56 or to a control group. Hemoglobin, reticulocytes, transferrin saturation, free erythrocyte protoporphyrin, and ferritin were measured, the final outcome measure being postoperative iron status on day 56. The treatment group showed higher transferrin saturations (33.5% versus 18.0%), smaller decreases in ferritin level (+3.0 versus –13.7ng/ml), and a lower incidence of depleted iron stores (0/8 versus 5/9) than the control group (all data:P<0.05). Anemic children after cardiopulmonary bypass for surgical repair of congenital heart disease thus benefit from iron supplementation within the first postoperative weeks.     

The role of erythrocyte protoporphyrin in the diagnosis of iron deficiency anemia of children

The values of erythrocyte protoporphyrin, ferritin and mean corpuscular volume (MCV) measurements in diagnosing iron deficiency anemia were investigated in 72 iron deficient and in 25 healthy control infants. Receiver operator curve, sensitivity and specificity of erythrocyte protoporphyrin, ferritin and mean corpuscular volume were compared between the study and control groups. In the study group mean corpuscular volume, hemoglobin and ferritin concentrations were significantly lower, and erythrocyte protoporphyrin was significantly higher when compared to the control group. In the iron deficient study group, erythrocyte protoporphyrin was the most sensitive test and ferritin was the most specific test, whereas ferritin was the most diagnostic test and mean corpuscular volume was the least diagnostic test. A significant correlation between erythrocyte protoporphyrin and hemoglobin values was determined. We conclude that erythrocyte protoporphyrin is a more sensitive but less specific test than ferritin, and it can be used as a first-line diagnostic test in the evaluation of iron deficiency and in diagnosing iron deficiency anemia in infants.     

Free erythrocyte protoporphyrin as an index of perinatal iron status

The relationship between free erythrocyte protoporphyrin and conventional indices of iron status was studied in 49 mothers and their infants. Maternal venous blood samples were collected at 34 weeks gestation and at delivery. The corresponding infant blood samples were collected from the umbilical cord and at age 6 weeks. In each case free erythrocyte protoporphyrin, serum iron, total iron binding capacity, and serum ferritin were determined. Cord free erythrocyte protoporphyrin was negatively correlated with maternal ferritin at 34 weeks gestation (p = 0.016) and at delivery (p = 0.014), and with transferrin saturation at delivery (p = 0.026). The infants' haemoglobin concentrations at 6 weeks were significantly negatively related to maternal free erythrocyte protoporphyrin at 34 weeks (p = 0.026) and at delivery (p = 0.026). Cord free erythrocyte protoporphyrin is an index of maternal iron status in the last trimester. Maternal free erythrocyte protoporphyrin in the last trimester predicts the magnitude of physiological anaemia of the infant at age 6 weeks.     

Serum ferritin in term and preterm infants

Serum ferritin levels were examined in maternal serum, In cord sera and at one, four, eight and twelve weeks in 19 term and 28 preterm infants. There was no correlation between maternal and cord ferritin levels. Mean serum ferritin concentration was lower in preterm infants, and both term and preterm Infants exhibited' an initial rise in serum ferritin concentration followed by a steady fall. Serum ferritin concentration showed a good correlation with calculated iron stores at twelve weeks of age suggesting that serum ferritin estimation is the method of choice for monitoring body iron stores in infants. No correlation was found between serum ferritin concentration and calculated iron intake at any age in either term or preterm infants. It is suggested that iron supplementation additional to that present in modified cow's milk is not necessary for the first twelve weeks of life in either term or preterm infants.     

Iron absorption from infant milk formula and the optimal level of iron supplementation

Thirty healthy infants, aged 11-13 months, were studied with regard to the iron absorption from proprietary milk formula. The infants were divided into three groups (I-III) depending on the concentration of iron in the formula: 0.8 (I), 6.8 (II), and 12.8 (III) mg/l, respectively. The calculated amount of iron absorbed per test dose of 50 ml of milk averaged 5 microgram (I), 32 microgram (II), and 43 microgram (III). Group I differed significantly from groups II and III. No correlation was found between iron absorption and hemoglobin, MCV, serum transferrin saturation or serum ferritin within the range of normal values. Our findings suggest that at least 7 mg of iron as ferrous sulphate per litre of formula is required to prevent iron deficiency.     

The relationship between decreased iron stores, serum iron and neonatal hypoglycemia in large-for-date newborn infants

We assessed the relationship between neonatal hypoglycemia and newborn iron status in 15 hypoglycemic, large-for-date newborn infants, 12 of whom were infants of diabetic mothers. These infants had significantly lower mean serum iron concentrations, ferritin concentrations, percent iron-binding saturation and calculated iron stores, and significantly higher mean transferrin concentrations, total iron-binding capacity concentrations and mid-arm circumference:head circumference ratios when compared with either 15 euglycemic large-for-date or 15 euglycemic appropriate-for-date control infants (p less than 0.001 for all comparisons). All hypoglycemic infants had ferritin concentrations below the 5th percentile as compared to 3% of controls (p less than 0.001), and 67% had transferrin concentrations above the 95th percentile (controls: 0%; p less than 0.001). Only the hypoglycemic infants demonstrated a significant negative linear correlation between ferritin and transferrin concentrations (r = -0.83; p less than 0.001). Decreased serum iron concentrations were associated with size at birth (r = -0.60; p = 0.01) and with increased red cell iron (r = -0.60; p = 0.01), implying a redistribution of iron dependent on the degree of fetal hyperglycemia and hyperinsulinemia. Infants with increased red cell iron had more profound neonatal hypoglycemia. These results show a significant association between decreased iron stores and neonatal hypoglycemia in macrosomic newborn infants associated with a significant shift of iron into red blood cells.     

Relationship between newborn and maternal iron status and haematological indices.

The haemoglobin, mean corpuscular volume, mean corpuscular haemoglobin, haematocrit, serum iron and total iron binding capacity, and serum ferritin concentrations in umbilical cord blood samples taken from 96 appropriate-for-gestational age infants delivered at term were measured and compared to the respective maternal values measured at 36 weeks' gestation. All the values were higher in cord blood. Only maternal mean corpuscular volume and mean corpuscular haemoglobin were correlated with cord serum iron. Cord blood haematological indices were not correlated with either gestation at delivery or birth weight. However, newborn serum ferritin was positively correlated with gestation at delivery, while the maternal:newborn ferritin ratio was inversely correlated with gestation and birth weight. The results suggest that maternal haematological and iron indices are not predictive of the haemoglobin or iron status of the newborn, and that the fetus continues to take up iron from the mother until delivery.     

Serum ferritin, iron levels and iron binding capacity in asymmetric SGA babies.

The concentration of serum ferritin reflects the extent of iron stores in premature infants. We aimed to determine serum ferritin levels and iron status in asymmetric small for gestational age (SGA) babies. This study was performed on 21 SGA babies and 19 appropriate for gestational age (AGA) babies. Hemoglobin, iron, iron binding capacity and ferritin levels were investigated in the first six hours after the birth. Hemoglobin levels in the SGA and control groups were 20.9 +/- 1.3 (19.4-23.4 g/dl) and 19.6 +/- 0.8 (18.5-21.5 g/dl), respectively (p = 0.001). Serum ferritin levels in the SGA and AGA groups were 58.36 +/- 20.1 ng/ml and 90.46 +/- 30.5 ng/ml, respectively. Ferritin levels were found lower in the SGA group (p < 0.001). In the SGA group, decreased serum iron and increased iron binding capacity were found but the difference was not significant (p > 0.05). Decreased ferritin levels may result from either impaired iron transport associated with uteroplacental vascular insufficiency or increased iron utilization during enhanced erythropoiesis in conditions characterized by chronic fetal hypoxia. Our results stress the significance of iron supplementation and careful anemia follow-up in term SGA babies. Because anemia progress early, beginning iron therapy as soon as possible is a necessity in SGA babies as in prematures.     

Early iron supplementation in very low birth weight infants – a randomized controlled trial

Aim: To evaluate if supplementing iron at 2 weeks of age improves serum ferritin and/or haematological parameters at 2 months of life in very low birth weight (VLBW) infants.
Methods: Preterm VLBW infants who received at least 100 mL/kg/day of oral feeds by day 14 of life were randomized to either 'early iron' (3–4 mg/kg/day orally from 2 weeks) or 'control' (no iron until 60 days) groups. Infants were followed up fortnightly and all morbidities were prospectively recorded. Serum ferritin was measured at 60 days by enzyme immunoassay method.
Results: Forty-six infants were included in the study; primary outcome was available for 42 infants. There was no difference in either serum ferritin (mean: 50.8 vs. 45.3 μg/L; adjusted difference in means: 5.8, 95% CI: −3.0, 14.6; p = 0.19) or haematocrit (32.5 ± 5.3 vs. 30.8 ± 6.3%; p = 0.35) at 60 days between the early iron and control groups. The magnitude of fall in serum ferritin from baseline to the end of study period was also not different between the groups (4.9 vs. 13.8 μg/L; difference in means: 8.8; 95% CI: −0.3, 17.9; p = 0.06). The requirement of blood transfusions (9.5 vs. 13%; p = 0.63) and a composite outcome of common neonatal morbidities (19% vs. 21.7%; p = 0.55) were also not different between the two groups.
Conclusion: Supplementing iron at 2 weeks of age in preterm VLBW infants did not improve either serum ferritin or the haematological parameters at 2 months when compared to the standard practice of starting iron from 8 weeks of age.     

Gender difference in cord serum ferritin concentrations.

We measured cord serum ferritin concentrations in a total of 255 infants (116 females and 139 males), and evaluated the association between these values and various neonatal as well as maternal characteristics. The mean ferritin concentration in females (166 +/- 110 microg/l) was significantly higher than that in male infants (123 +/- 77 microg/l). The gender differences in ferritin were significant within groups of infants with fetal growth restriction, those who weighed <3,000 g, those whose mothers were African Americans or <25 years old. Maternal serum ferritin concentrations at 36 weeks of gestation significantly correlated with cord serum ferritin of male infants (r = 0.32, p < 0.001), whereas the association was not significant for females (r = 0.09, p > 0.41). Although the mechanism of the gender difference is unknown, it may be important to consider the sex of neonates when evaluating their iron nutriture immediately after birth.     

Bioavailability of iron in soy-based formula and its effect on iron nutriture in infancy

Soy products have been reported to inhibit absorption of nonheme food iron and fortification iron. Iron bioavailability from a soy formula (Prosobee-PP 710) (iron added as ferrous sulfate: 12 mg/L; ascorbic acid: 54 mg/L) was examined in 16 adult women using the extrinsic radioactive tag method. The geometric mean absorption from the soy formula was only 1.7%. The effect of this formula on iron nutrition in infants was studied in 47 healthy term infants weaned spontaneously before 2 months of age and who received the formula ad libitum until 9 months of age. For control, 45 infants received a cow's milk formula fortified with ferrous sulfate (iron: 15 mg/L; ascorbic acid: 100 mg/L), which has been shown to be effective in preventing iron deficiency, and 49 additional breast-fed infants were also followed. All babies received solid foods (vegetables and meat) starting at 4 months of age. Iron nutritional status was determined at 9 months. Infants fed soy formula and iron-fortified cow's milk had similar mean values of hemoglobin, mean corpuscular volume, transferrin saturation, free erythrocyte protoporphyrin, and serum ferritin; both formula groups differed significantly (P less than .05) from the breast-fed group in all measurements except free erythrocyte protoporphyrin. Anemia (hemoglobin less than 11 g/dL) was present in only 4.3% and 2.2% of infants receiving the soy and the fortified formulas, respectively, v 27.3% in the breast-fed group. These results indicate that soy formula, in spite of the lower iron bioavailability when measured in adults, is essentially as effective as iron-fortified cow's milk in preventing iron deficiency in infants.     

Cord transferrin and ferritin values in newborn infants at risk for prenatal uteroplacental insufficiency and chronic hypoxia

We measured cord transferrin and ferritin levels in 50 newborn infants with fetal conditions associated with either uteroplacental vascular insufficiency or chronic hypoxia. Sixteen small for gestational age infants, 21 infants of mothers with preeclampsia, and 13 symptomatic infants of diabetic mothers had significantly higher transferrin levels and lower ferritin levels and calculated iron stores than did asymptomatic gestational age-matched control infants without these conditions. Cord ferritin levels and calculated iron stores were significantly lower in the infants of diabetic mothers than in any other group of infants. Cord transferrin levels were inversely correlated with ferritin levels (r = -0.59, P less than 0.001) and were unrelated to transthyretin levels and birth weight in the high-risk infants, but were positively correlated with ferritin levels (r = 0.50, P less than 0.001), transthyretin levels (r = 0.65, P less than 0.001), and birth weight (r = 0.75, P less than 0.001) in the control infants. We conclude that cord transferrin levels do not reflect protein-energy status in newborn infants with prenatal histories suggesting uteroplacental insufficiency or chronic hypoxia, and that when associated with decreased cord ferritin levels, indicate possible impaired iron stores in these infants.     

Relation of maternal and cord blood serum ferritin

Serum ferritin was measured in 51 term normal pregnant mothers and the corresponding cord blood samples. All of the mothers had received prophylactic oral iron and folate during pregnancy. The mean (+/-SD) maternal serum ferritin at the end of pregnancy was 58 +/- 42.9 microgram/l (range 16-201 microgram/l), compared to a mean of 183.2 +/- 61.2 microgram/l (range 62-313 microgram/l) in these newborns. No correlation was found between the serum ferritin of mothers and babies, nor between the serum ferritin and serum iron of mothers at the end of pregnancy or between these parameters in the newborn.