Iron deficiency of liver, heart, and brain in newborn infants of diabetic mothers.

Infants of diabetic mothers frequently have polycythemia, elevated serum erythropoietin concentrations, and decreased serum iron and ferritin concentrations, likely representing a redistribution of fetal iron into erythrocytes to support augmented fetal hemoglobin synthesis. We hypothesized that fetal liver, heart, and brain iron concentrations are also reduced in these infants. After obtaining autopsy tissue from infants who had died before 7 days of age, we measured liver, heart, and brain iron concentrations using atomic absorption spectrophotometry. Seven infants of diabetic mothers and seven gestational age-matched control infants were studied. All infants of diabetic mothers had pancreatic islet cell hyperplasia, indicating fetal hyperglycemia and hyperinsulinemia. Liver iron concentrations in the infants of diabetic mothers were 6.6% of control values (489.0 +/- 154.4 vs 7379.7 +/- 1473.8 micrograms/gm dry tissue weight (mean +/- SEM); p less than 0.001), heart iron concentrations were 43.9% of control values (124.7 +/- 20.5 vs 284.1 +/- 34.8 micrograms/gm dry tissue weight; p less than 0.002), and brain iron concentrations were 60.6% of control values (106.1 +/- 13.7 vs 175.2 +/- 10.7 micrograms/gm dry tissue weight; p less than 0.003). Heart and brain iron concentrations were directly correlated with liver iron concentrations (r = 0.80 for both; p less than 0.001) and indicated that hepatic iron was greater than 75% depleted before heart and brain iron reduction. We conclude that severely affected infants of diabetic mothers have reduced liver, heart, and brain iron concentrations. The role of tissue iron deficiency in the genesis of the abnormal clinical findings in these infants deserves further consideration.     

Iron status in low-birth-weight infants, small and appropriate for gestational age. A follow-up study

Iron nutrition was measured in 84 low-birth-weight infants. At birth, they were assigned to three groups: preterm infants appropriate for gestational age (n = 29); preterm infants small for gestational age (n = 17); and full-term infants small for gestational age (n = 38). A sub-sample of infants was supplemented with iron 3 mg/kg from two to four months of age. At birth, preterm appropriate-for-gestational-age infants had a lower hemoglobin concentration than full-term small-for-gestational-age infants (p < 0.01) and a higher serum ferritin than preterm small-for-gestational-age infants (p < 0.05). In the non-supplemented group, full-term small-for-gestational-age infants had significantly higher hemoglobin concentrations at four months of age. At this age, iron-supplemented preterm infants appropriate or small for gestational age had significantly higher hemoglobin levels than non-supplemented subjects, while iron supplementation did not have an effect on final hemoglobin concentration in full-term small-for-gestational-age infants. We conclude that preterm infants, irrespective of their adequacy for gestational age, show evidence of iron deficiency before four months of age. Full-term infants do not develop iron deficiency up to this age.     

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.     

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.     

The Relationship between Decreased Iron Stores, Serum Iron and Neonatal Hypoglycemia in Large-for-Date Newborn Infants

ABSTRACT. 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 < 0.001 for all comparisons). All hypoglycemic infants had ferritin concentrations below the 5th percentile as compared to 3 % of controls ( p < 0.001), and 67 % had transferrin concentrations above the 95th percentile (controls: 0 %; p < 0.001). Only the hypoglycemic infants demonstrated a significant negative linear correlation between ferritin and transferrin concentrations ( r =−0.83; p < 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.     

极低出生体重儿血清铁蛋白水平及影响因素

目的 分析极低出生体重儿(very low birth weight infants,VLBWI)的铁营养状况及影响其变化的因素.方法 收集2014年1月至12月我院收治的115例VLBWI,检测其基础血清铁蛋白及出院前末次血清铁蛋白水平,并对可能的影响因素如胎龄、出生体重、基础血红蛋白、住院期间累积输血量、累积失血量,孕母糖尿病、高血压及贫血等临床资料进行分析.结果 115例VLBWI的基础血清铁蛋白为100.8 ～210.3 μg/L,平均(140.32±13.21) μg/L;不同胎龄的VLBWI基础血清铁蛋白水平比较差异有统计学意义(F=14.367,P=0.000),胎龄＜32周的LBWI其基础血清铁蛋白最低[(124.5±31.3) g/L].母亲贫血程度越重,婴儿基础血清铁蛋白越低[无贫血:(230.9±68.7) μg/L,轻度贫血:(189.5 ±75.3) μtg/L,中度贫血:(133.5 ±88.1) μg/L,重度贫血:(122.2 ±56.8) μg/L;P ＜0.05].VLBWI基础血红蛋白水平越低,其基础血清铁蛋白水平越低(P＜0.05).同时VLBWI住院期间末次血清铁蛋白水平受累积输血量的影响差异有统计学意义(P＜0.05).结论 提高VLBWI基础血红蛋白水平对增加VLBWI体内铁储备是有益的,定期监测住院期间甚至出院后血清铁蛋白以指导VLBWI补铁治疗十分必要.     

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.     

Does maternal iron supplementation during the lactation period affect iron status of exclusively breast-fed infants?

Iron deficiency anemia (IDA) causes growth and developmental retardation in infants. Iron supplementation from the 4th month of age may prevent IDA, but side effects of oral iron supplementation limit its usage. The aim of this study was to investigate the effect of maternal iron supplementation on the iron status of mothers and their exclusively breast-fed infants. In a prospective, placebo-controlled, double-blinded randomized study, healthy mothers (Hb > or = 11 g/dl) and their 10-20-day-old healthy term infants who were admitted to Hacettepe University for neonatal screening were enrolled. The mothers who were intending to exclusively breast-feed at least up to four months were included. Iron supplementation (n = 82, 80 mg elementary iron) and placebo (n = 86) were given to the mothers randomly for four months. The anthropometrical measurements of infants were recorded monthly. Of all, 69 mothers and their infants in the iron group and 63 in the placebo group completed the study. At the end of the study period, blood samples (complete blood count, serum iron, iron binding capacity and serum ferritin) were drawn from the mothers and their infants. After adjustment for baseline hemoglobin value, the mean levels of hemoglobin, serum iron and ferritin were similar in the two groups at the end of the study; however, serum iron binding capacity was significantly lower in the iron group than in the placebo group. Giving maternal iron supplementation during the first four months of the lactation period had no effect on the serum iron and ferritin levels of mothers and infants. This could be due to the relatively short duration of the follow-up period. A longer follow-up period is recommended to detect the effect of the maternal iron supplementation during lactation.     

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.     

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).     

Smoking during pregnancy--hematological observations in the newborn

Hematological values were measured in 28 newborn infants of mothers smoking 10-20 cigarettes daily during pregnancy, and in 25 infants of non-smokers. Higher hematocrit levels were found on the 1st day of life in infants of smoking mothers (60.8 +/- 5.0%, mean +/- S.D.) compared to controls (57.5 +/- 4.8%) (p less than 0.05). The hematocrit levels correlated positively with the maternal smoking level (r = 0.318, p less than 0.05) and the maternal serum thiocyanate concentrations at delivery (r = 0.389, p less than 0.01). Cord serum values for erythropoietin, serum-iron, transferrin and ferritin showed no statistically significant difference between the two groups. A significant inverse correlation was found between the hematocrit value on the 1st day of life and the cord serum ferritin concentration (r = -0.495, p less than 0.005). The present results suggest that maternal smoking stimulates fetal erythropoiesis, probably through a hypoxic effect on the fetus, dose related to the maternal smoking level. Increased erythropoiesis may cause increased iron incorporation into erythrocytes at expense of iron storage in the bone marrow and reticuloendothelial system.     

Plasma ferritin in the assessment of iron status of Indian infants

In order to assess the iron nutritional status of infants, plasma ferritin levels were measured in the infants and children at different time intervals till two years of age from two different socio economic groups. While ferritin levels at 3-4 months age were significantly higher in upper income group infants, levels were almost similar in the subsequent infancy between the two income groups. A close correlation was seen between ferritin levels of mothers and infants at 1-3 months of age (p less than 0.001). Prenatal iron supplements (oral or parenteral) resulted in higher ferritin levels at 4-6 months age as compared to placebo group. While the infants born to mothers receiving parenteral iron did not show any evidence of iron deficiency (serum ferritin levels less than 12 ng/ml), 23.5 and 25.0% of infants in oral iron and placebo group had evidence of iron deficiency between 6-12 months. Thus it would appear that improving the iron status of mothers during pregnancy will have significant impact on the iron status of breast fed infants till 6 months.     

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.     

Reduced hemoglobin values in children and young adults with hemophilia

Mild leukopenia and thrombocytopenia are common in multitransfused hemophiliacs. Because little attention has previously been directed to measurements of erythropoiesis in these patients, we prospectively examined hemoglobin concentration and RBC indices in 94 children and young adults with hemophilia during comprehensive clinic visits. Additional studies performed in many included serum transferrin saturation, ferritin, haptoglobin, and free erythrocyte protoporphyrin measurements. Hemoglobin concentrations were recorded as age-related percentile values. Hemophiliacs of all ages and degrees of severity often had lower than average values for hemoglobin; 31% had values less than the third percentile, 46% less than the tenth percentile, and 83% less than the mean value. Reduced hemoglobin percentile values were unrelated to age, severity of disease, or human immunodeficiency virus antibody status. Only five patients had an obvious cause for anemia. Serum ferritin, transferrin saturation, and erythrocyte protoporphyrin values were usually normal, indicating that iron deficiency and anemia of chronic disease were uncommon. Although serum haptoglobin was reduced in 44% of the patients, reticulocyte count was infrequently increased. We conclude that hemoglobin values are frequently less than the mean normal values for age in hemophiliacs. Although frank anemia is common, it is usually mild and without obvious cause. Hemophiliac individuals with slightly reduced hemoglobin values probably do not routinely require detailed investigation for occult blood loss, iron deficiency, or inflammation.     

Iron status with different infant feeding regimens: relevance to screening and prevention of iron deficiency

The objective of this study was to evaluate the benefit of screening for anemia in infants in relation to their previous diet. The iron status of 854 nine-month-old infants on three different feeding regimens and on a regimen including iron dextran injection was determined by analysis of hemoglobin, serum ferritin, and erythrocyte protoporphyrin levels and of serum transferrin saturation. Infants were categorized as having iron deficiency if two or three of the three biochemical test results were abnormal and as having iron deficiency anemia if, in addition, the hemoglobin level was less than 110 gm/L. The prevalence of iron deficiency was highest in infants fed cow milk formula without added iron (37.5%), intermediate in the group fed human milk (26.5%), much lower in those fed cow milk formula with added iron (8.0%), and virtually absent in those injected with iron dextran (1.3%). The corresponding values for iron deficiency anemia were 20.2%, 14.7%, 0.6%, and 0%, respectively. The use of iron supplements is therefore justified in infants fed cow milk formula without added iron, even when there is no biochemical evidence of iron deficiency. The low prevalence of iron deficiency in the group fed iron-fortified formula appears to make it unnecessary to screen routinely for anemia in such infants. These results also support the recommendation that infants who are exclusively fed human milk for 9 months need an additional source of iron after about 6 months of age.     

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.     

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.     

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.     

The diagnosis of iron deficiency by erythrocyte protoporphyrin and serum ferritin analyses

Free erythrocyte protoporphyrin (FEP) and serum ferritin have been determined in 57 healthy children and in 25 children with varying degrees of iron deficiency. FEP was found to be inversely correlated to the concentration of hemoglobin (r = -0.80) as well as to serum ferritin (r=-0.64). Elevated FEP was found in children with hemoglobin less than 12.5 g/dl, or serum ferritin less than 8 microgram/l. In a group of apparently hematologically normal children between the age of 10--14 years (hemoglobin greater than 12.5 g/dl), a 2-month-trial of iron medication resulted in an increase in hemoglobin and ferritin, and a decrease in FEP, indicating suboptimal supply of iron for hemoglobin synthesis before iron medication. In a patient with iron deficiency (FEP 15.3 mumole/l, hemoglobin 5.2 g/dl), iron therapy was followed by a rapid fall in FEP before any changes in hemoglobin, serum iron transferrin saturation and ferritin could be detected. The rapid fall in FEP during start of treatment in iron deficiency makes FEP a sensitive biochemical parameter on iron homeostasis in iron deficiency anemia.     

Hepatic iron storage in very low birthweight infants after multiple blood transfusions

OBJECTIVE: To investigate the effect of multiple blood transfusions on hepatic iron storage in preterm, very low birthweight (VLBW) infants. METHODS: Seventeen VLBW infants who died within the first six months of life and underwent postmortem examination were studied. Serum ferritin, iron, and total iron binding capacity were measured within the week before the infants' death. Liver iron concentration was quantitatively determined by atomic absorption spectrophotometry and semiquantitatively assessed by histochemical liver iron grading. The clinical characteristics and the iron results were compared between infants receiving < 100 ml of blood (group A) and those receiving >/= 100 ml (group B). Spearman's correlation coefficient was used to evaluate the relation between the volume of blood transfused and serum/liver iron concentrations. Statistically significant variables associated with liver iron concentration were further subjected to multivariate stepwise regression analysis. RESULTS: Infants in group B had significantly higher serum iron (p < 0.01), serum ferritin (p < 0.01), and liver iron concentration (p < 0.01) than those in group A. The total and net volume of blood transfused were significantly associated with liver iron concentration (p < 0.001, r = 0.86; p < 0.001, r = 0.71 respectively), semiquantitative histochemical liver iron grading (p < 0.001, r = 0.80; p < 0.005, r = 0.71 respectively), and serum ferritin (p < 0.001, r = 0.84; p < 0.01, r = 0.69 respectively). In addition, both liver iron concentration and liver iron grading were found to be significantly associated with serum ferritin (p < 0.001, r = 0.76; p < 0.005, r = 0.68 respectively). Multivariate stepwise regression analysis indicated that the (log) liver iron concentration was significantly associated with the (log) volume of blood transfusion (p < 0.001; regression coefficient 0.39, SE 0.09), after adjustment for gestational age (R(2) = 0.84). CONCLUSIONS: This study showed a significant positive relation between the volume of blood transfused and the liver iron concentration in preterm VLBW infants. Although the transfusional blood volume correlated closely with the amount of iron deposited in hepatic tissues, clinical manifestations of iron overload were not observed. Carers should be aware of this potential harmful effect before prescribing blood or routine iron supplement to vulnerable preterm infants.