Plasma zinc concentrations in iron supplemented low birthweight infants.

We investigated the effect of prolonged iron supplementation of low birthweight infants on plasma zinc concentrations. Thirty infants (neonatal weight 820-2000 g) were examined at 6 or 12 months of life to assess their iron state and plasma zinc concentration. All of them were feeding on iron fortified formulas, which supply about 1 mg/kg/day of iron. In addition, 14 of them had been receiving 2 mg/kg/day of medicinal ferrous salts for at least five months. The other 16 were not given medicinal iron supplementation. Whereas iron state significantly differed in the two groups, plasma zinc concentrations were similar. Moreover, no zinc values below 75 micrograms/100 ml were found in any case. The results suggest that long term iron supplementation of low birthweight infants, at the recommended doses, does not influence zinc plasma concentrations unfavourably.     

Oral iron supplementation in preterm infants treated with erythropoietin

BACKGROUND: It is not known whether a moderate dose of oral iron supplementation would further enhance erythropoiesis in recombinant human erythropoietin (EPO)-treated very low-birthweight (VLBW) infants. METHODS: In total, 24 preterm infants with birthweights 750-1499 g were enrolled at the age of 14-28 days to receive 400 IU/kg per week EPO subcutaneously for 8 weeks. The infants were randomly allocated either to receive oral iron supplementation 4 mg/kg per day or to serve as controls. RESULTS: Hemoglobin and the absolute reticulocyte count in the iron supplementation and the control groups remained identical throughout the study period, whereas serum ferritin was significantly lower in the control group at study exit and follow up. Rates of treatment success (no need for transfusion and hemoglobin never below 8 g/dL) also did not differ between the groups. CONCLUSIONS: In this study we did not find a clear advantage in a moderate dose of oral iron supplementation on erythropoiesis in EPO-treated VLBW infants. Whether a higher dose would lead to enhanced erythropoiesis remains to be answered.     

Iron availability from an infant formula supplemented with bovine lactoferrin

Iron balance studies were performed in 16 term infants from their 3rd until their 17th week of life. The balance studies were performed at home and comprised five periods with an interval of 3 to 4 weeks, each consisting of three 24-hour collections of milk and stool samples. Seven infants were fed an adapted infant formula supplemented with bovine lactoferrin (100 mg/100 ml) and nine received the same formula without lactoferrin. The lactoferrin supplemented group received 169 micrograms iron/kg b.w. x day and retained 63 micrograms/kg b.w. x day. The mean iron intake of infants fed with the adapted formula without supplementation of lactoferrin was 118 micrograms/kg b.w. x day. The retention of iron was 43 micrograms/kg b.w. x day. Mean percentage retention of iron in the supplemented group was 36%, in the non-supplemented group 28%.     

Comparison of 2 iron doses in infants receiving recombinant human erythropoietin therapy

OBJECTIVE: To compare iron sufficiency in premature infants receiving high-dose recombinant human erythropoietin (r-HuEPO), 1200 IU/kg per week, supplemented with 6 or 12 mg/kg per day of enteral iron. DESIGN: We conducted a prospective, double-blind, controlled study of premature infants receiving r-HuEPO therapy, randomly assigned to receive 2 different doses of iron. Measurements of ferritin, iron, total iron-binding capacity, reticulocyte count, hemoglobin level, and hematocrit were obtained at baseline, 4, and 6 weeks. Transferrin saturation was calculated; the number of blood transfusions and the incidences of sepsis were recorded. SETTING: This study was performed in the neonatal intensive care unit at Loma Linda University Children's Hospital, Loma Linda, Calif. SUBJECTS: Infants with a gestational age of 32 weeks or younger, older than 7 days, and receiving r-HuEPO therapy from March 1, 1997, to June 30, 1998, were eligible for the study. Infants were randomly assigned to receive 6 mg/kg per day or 12 mg/kg per day of enteral iron during a course of r-HuEPO therapy for 4 to 6 weeks. RESULTS: Sixty-four infants were enrolled in the study. Twelve infants did not complete the study; 52 completed 4 weeks and 41 completed 6 weeks of the study. While ferritin levels and transferrin saturation decreased in both groups over the study period, there were no differences between the 2 study groups. CONCLUSIONS: Infants receiving high-dose r-HuEPO therapy (1200 IU/kg per week) decrease their ferritin levels (measure of iron stores) even when receiving high enteral iron supplementation. Given that the ferritin levels were similar between the 2 groups, we speculate that the additional iron either was not absorbed or was not stored.     

Iron Availability from an Infant Formula Supplemented with Bovine Lactoferrin

ABSTRACT. Iron balance studies were performed in 16 term infants from their 3rd until their 17th week of life. The balance studies were performed at home and comprised five periods with an interval of 3 to 4 weeks, each consisting of three 24-hour collections of milk and stool samples. Seven infants were fed an adapted infant formula supplemented with bovine lactoferrin (100 mg/100 ml) and nine received the same formula without lactoferrin. The lactoferrin supplemented group received 169 μg iron/kg b.w. × day and retained 63 μg/kg b.w. × day. The mean iron intake of infants fed with the adapted formula without supplementation of lactoferrin was 118 μg/kg b.w. × day. The retention of iron was 43 μg/kg b.w. × day. Mean percentage retention of iron in the supplemented group was 36%, in the non-supplemented group 28%.     

Effect of low and moderate doses of recombinant human erythropoietin on the haematological response in premature infants on a high protein and iron intake

There is no consensus regarding protein intake and the doses of recombinant human erythropoietin (r-HuEpo) and iron in the treatment of anaemia of prematurity (AOP). This open, randomized study has compared the effectiveness of 50 IU r-HuEpo/kg with that of 100 IU/kg, both given subcutaneously thrice weekly. In addition, two different protein supplements have been compared; lyophilized human milk protein and a commercial cow’s milk product. Total protein intake was 3 g/kg per day. Daily iron dose was 18–36 mg. “Healthy” preterm infants (n = 32, birth weight: 800–1400 g, gestational age ≤ 31 weeks) were studied from age 3 to 8 weeks. The two protein regimens yielded no differences in body growth, reticulocyte count or Hb concentration. In both r-HuEpo dose groups increased number of reticulocytes followed start of treatment; higher levels were, however, found in the group receiving 100 IU/kg. Mean Hb concentration plateaued at 12 g/dl for infants receiving 100 IU/kg, at 11 g/dl in the 50 IU/kg group. Even though serum levels of ferritin and transferrin saturation indicated no iron deficiency, soluble transferrin receptor increased in both groups, more rapidly and to higher levels in the 100 IU/kg group. In addition, the number of infants having more than 8% hypochromic red cells increased in both groups. Conclusions Commercial cow’s milk protein added to human milk was as good as human milk protein supplementation in supporting growth and erythropoiesis. Fifty IU/kg r-HuEpo thrice weekly during AOP stimulated erythropoiesis significantly, but less so than 100 IU/kg. Even when using high oral doses of iron to preterms receiving r-HuEpo, our data suggested a certain degree of iron deficient erythropoiesis.     

Effect of low and moderate doses of recombinant human erythropoietin on the haematological response in premature infants on a high protein and iron intake

There is no consensus regarding protein intake and the doses of recombinant human erythropoietin (r-HuEpo) and iron in the treatment of anaemia of prematurity (AOP). This open, randomized study has compared the effectiveness of 50 IU r-HuEpo/kg with that of 100 IU/kg, both given subcutaneously thrice weekly. In addition, two different protein supplements have been compared; lyophilized human milk protein and a commercial cow’s milk product. Total protein intake was 3 g/kg per day. Daily iron dose was 18–36 mg. “Healthy” preterm infants (n = 32, birth weight: 800–1400 g, gestational age ≤ 31 weeks) were studied from age 3 to 8 weeks. The two protein regimens yielded no differences in body growth, reticulocyte count or Hb concentration. In both r-HuEpo dose groups increased number of reticulocytes followed start of treatment; higher levels were, however, found in the group receiving 100 IU/kg. Mean Hb concentration plateaued at 12 g/dl for infants receiving 100 IU/kg, at 11 g/dl in the 50 IU/kg group. Even though serum levels of ferritin and transferrin saturation indicated no iron deficiency, soluble transferrin receptor increased in both groups, more rapidly and to higher levels in the 100 IU/kg group. In addition, the number of infants having more than 8% hypochromic red cells increased in both groups. Conclusions Commercial cow’s milk protein added to human milk was as good as human milk protein supplementation in supporting growth and erythropoiesis. Fifty IU/kg r-HuEpo thrice weekly during AOP stimulated erythropoiesis significantly, but less so than 100 IU/kg. Even when using high oral doses of iron to preterms receiving r-HuEpo, our data suggested a certain degree of iron deficient erythropoiesis. Received: 20 January 1996 / Accepted: 2 February 1996     

Haematological effect of iron supplementation in breast fed term low birth weight infants

Aims: To determine the haematological effects of iron supplementation in predominantly breast fed term low birth weight (LBW) infants. Methods: Seventy three healthy term LBW (<2500 g), predominantly breast fed infants aged 50–80 days were randomised into two groups to receive either iron (3 mg/kg/day) (iron supplemented (IS) group; n = 37) or placebo drops (placebo (P) group; n = 36). Haematological parameters and anthropometry were measured at baseline and repeated after four and eight weeks. Results: A total of 62 subjects (32 in the IS group and 30 in the P group) came for the first follow up and 26 (13 in the IS group and 13 in the P group) reported for the second visit. There were no significant differences in serum ferritin and anthropometry. However, covariates (infant age, haemoglobin, and ferritin, and maternal haemoglobin) adjusted haemoglobin change was significantly higher in the IS group after four weeks (4.6 g/l; 95% CI 0.5 to 8.8) and eight weeks (8.6 g/l; 95% CI 1.8 to 15.4). Conclusions: Iron supplementation in a therapeutic dose in term breast fed LBW infants results in a marginal increase in haemoglobin. The functional benefit of this haemoglobin rise requires further evaluation.     

Haematological effect of iron supplementation in breast fed term low birth weight infants.

AIMS: To determine the haematological effects of iron supplementation in predominantly breast fed term low birth weight (LBW) infants. METHODS: Seventy three healthy term LBW (<2500 g), predominantly breast fed infants aged 50-80 days were randomised into two groups to receive either iron (3 mg/kg/day) (iron supplemented (IS) group; n = 37) or placebo drops (placebo (P) group; n = 36). Haematological parameters and anthropometry were measured at baseline and repeated after four and eight weeks. RESULTS: A total of 62 subjects (32 in the IS group and 30 in the P group) came for the first follow up and 26 (13 in the IS group and 13 in the P group) reported for the second visit. There were no significant differences in serum ferritin and anthropometry. However, covariates (infant age, haemoglobin, and ferritin, and maternal haemoglobin) adjusted haemoglobin change was significantly higher in the IS group after four weeks (4.6 g/l; 95% CI 0.5 to 8.8) and eight weeks (8.6 g/l; 95% CI 1.8 to 15.4). CONCLUSIONS: Iron supplementation in a therapeutic dose in term breast fed LBW infants results in a marginal increase in haemoglobin. The functional benefit of this haemoglobin rise requires further evaluation.     

Vitamin E status in preterm infants fed human milk or infant formula

Vitamin E status was assessed in 36 infants with birth weights less than 1500 gm who were assigned randomly to receive one of three sources of nutrition: milk obtained from mothers of preterm infants (preterm milk), mature human milk, or infant formula. Infants in each dietary group were further assigned randomly to receive iron supplementation (2 mg/kg/day) beginning at 2 weeks or to receive no iron supplementation. All infants received a standard multivitamin, providing 4.1 mg alpha-tocopherol daily. Serum vitamin E concentrations at 6 weeks were significantly related both to type of milk (P less than 0.0001) and to iron supplementation (P less than 0.05). Infants fed preterm milk had significantly higher serum vitamin E levels than did infants fed mature human milk, and both groups had significantly higher levels than did those fed formula. Ratios of serum vitamin E/total lipid were also significantly greater for infants fed human milks than for those fed formula. The addition of iron to all three diets resulted in significantly lower serum vitamin E levels at 6 weeks (P less than 0.05); however, only in the group fed formula was there evidence of vitamin E deficiency. Preterm milk with routine multivitamin supplementation uniformly resulted in vitamin E sufficiency in VLBW infants whether or not iron was administered.     

Neonatal iron nutrition

Preterm infants are prone to iron deficiency. Their total body iron content at birth is low and gets further depleted by clinical practices such as uncompensated phlebotomy losses and exogenous erythropoietin administration during the neonatal period. Early iron deficiency appears to adversely affect cognitive development in human infants. To maintain iron sufficiency and meet the iron demands of catch-up postnatal growth, iron supplementation is prudent in preterm infants. A dose of 2–4 mg/kg/day is recommended for preterm infants who are fed exclusively human milk. A dose of 6 mg/kg/day or more is needed with the use of exogenous erythropoietin or to correct preexisting iron deficiency. However, due to the poor antioxidant capabilities of preterm infants and the potential role of iron in several oxidant-related perinatal disorders, indiscriminate iron supplementation should be avoided.     

提高缺铁动物对铁补充效应的实验研究

用大鼠血红蛋白恢复试验及铁补充与整体铁存留直线回归分析研究了缺铁大鼠每３日或每日连续补铁的生物利用效率。首先，用无铁基础饲料复制大鼠的缺铁性贫血（ＩＤＡ）模型，然后分别进行两周每间隔３日或每日连续补铁（８ｍｇ）试验。以０．８ｍｇ／日铁喂饲建立铁正常大鼠为对照。结果：铁正常对照，ＩＤＡ每３日或每日补铁三组大鼠血红蛋白转换效率分别为９．２１％，６．９％及２．８％，后两组相对生物利用率（ＲＢＡ）为７４．９％及３１．６％。铁补充与动物整体铁存留直线回归分析显示整体动物的ＲＢＡ分别为４２．８％及１７．７％。两种铁补充效应的评价均表明，每３日间隔补铁的ＲＢＡ为每日连续补铁的２．４倍，血液、骨骼等组织器官的铁生物利用为１．８～１．９倍。     

VITAMIN E REQUIREMENTS OF PRETERM INFANTS

ABSTRACT. Differences between feeding practices in earlier investigations prompted the present study of iron and vitamin E supplementation in breast milk fed preterm infants. A new and highly sensitive technique for quantitation of alpha-tocopherol in serum was used. Studies on 34 infants with a birth weight below 2000 g or gestational age ≤35 weeks showed that supplementation with 16.5 mg tocopheryl acetate/day from 10 days of age resulted in a significantly higher haemoglobin concentration and lower reticulocyte count at 8–10 weeks than supplementation with 1.5 mg/day (p<0.05). Studies on 23 infants with a birth weight of 2000–2499 g revealed subnormal alpha-tocopherol levels in 2 of the infants given 1.5 mg tocopheryl acetate/day but there was no effect on the haemoglobin concentration at 8–10 weeks. There were no untoward effects of an early iron supplementation with 2–3 mg Fe⁺⁺ (as ferrous succinate)/kg/day. It is concluded that extra supplementation with vitamin E is advisable also in breast milk fed preterm infants. A low dosage iron supplementation from 3 weeks of age is safe.     

Oral iron is sufficient for erythropoietin treatment of very low birth-weight infants

The aim of this study was to compare two different doses and means of administration of iron in recombinant human erythropoietin (rHuEPO)-treated very low birth-weight (VLBW) infants. VLBW infants (n = 41) were randomized to one of three groups. Fourteen infants were treated with rHuEPO (300 IU/kg three times a week s.c.) and oral iron (ferrofumarate, 6 mg of iron/kg per day). Another 14 infants received the same erythropoietin dose and intramuscular iron (ferroxypolymaltose, once 12 mg of iron/kg weekly). Thirteen infants were treated with the same dose of intramuscular iron but did not receive rHuEPO. After the 3-week study period, haemoglobin concentrations and reticulocyte counts were similar in the rHuEPO-treated groups and both were higher than in the group not receiving rHuEPO (P < 0.001). In both rHuEPO-treated groups the transferrin receptor concentration increased from 6.8–7.2 mg/l to 10.5–11.3 mg/l. Conclusion In erythropoietin-treated very low birth weight infants the iron need for erythropoiesis can be met by oral administration of iron. Received: 17 November 1997 and in revised form: 6 March 1998 / Accepted: 30 April 1998     

Preventive management of hypoglycemia in very low-birthweight infants following indomethacin therapy for patent ductus arteriosus

BACKGROUND: To evaluate the effects of an increase in glucose infusion rate of 2 mg/kg per min from the basal infusion rate on the prevention of hypoglycemia in very low-birthweight (VLBW) infants, following indomethacin therapy for patent ductus arteriosus (PDA). METHODS: Forty VLBW infants with PDA were given indomethacin 0.2 mg/kg intravenously up to three doses. In 15 of the 40 infants (supplemented group: between April 1995 and March 1996) the glucose infusion rate was increased in 2 mg/kg per min increments from the basal rate just before the initial indomethacin administration, compared with 25 historical control infants who received a fixed glucose infusion rate during the first 12 h after the initial dose. We evaluated the changes in blood glucose levels and glucose infusion rates in both groups. RESULTS: In the control group 11 of 25 (44%) infants had a blood glucose value below 40 mg/dL between 12 and 60 h (mean 32.7 h). In contrast only two out of 15 infants in the supplemented group reached the glucose level below 40 mg/dL between 72 and 96 h but both two were light-for-dates infants (defined as birthweight below the 10th percentile for gestational age on the standard intrauterine growth curve). Blood glucose values in the supplemented group were significantly higher than those in the control group between 12 and 96 h. However, glucose infusion rates were similar before and between 72 and 96 h. CONCLUSIONS: This retrospective study shows that an increase in glucose infusion rate of 2 mg/kg per min, in addition to the pre-existing stable maintenance glucose intake, might prevent against the occurrence of unexpected hypoglycemia in VLBW infants following indomethacin therapy.     

Effects of calcium and phosphorus supplementation on calcium retention and fat absorption in preterm infants fed pooled human milk

Fat, phosphorus, and calcium balance studies were performed in normal very low birth weight infants (BW less than or equal to 1,500 g) fed either normal or calcium- and phosphorus-supplemented pooled pasteurized human milk. Calcium and phosphorus supplements were 27 mg/dl and 24.5 mg/dl, respectively, throughout the study. Measured calcium and phosphorus intake in the supplemented group averaged 90 +/- 6 mg/kg/day and 62 mg/kg/day, respectively, compared to 47 +/- 7 mg/kg/day and 24 +/- 6 mg/kg/day in the nonsupplemented group. The percent of fat, calcium, and phosphorus absorption was similar in the two groups: respectively, 71 +/- 23%, 73 +/- 13%, and 93 +/- 2% in the supplemented group compared to 75 +/- 11%, 71 +/- 14%, and 92 +/- 4% in the nonsupplemented group. Calcium and phosphorus retention reached 62 +/- 12 mg/kg/day and 53 +/- 4 mg/kg/day in the supplemented group against 21 +/- 10 mg/kg/day and 21 +/- 5 mg/kg/day in the nonsupplemented group. These data support the notion that calcium, in addition to phosphorus supplementation in pooled human breast milk, improves both calcium and phosphorus retention in preterm infants.     

不同剂量氨茶碱在极低出生体重儿中的药代动力学及药效学研究

目的 探索不同剂量氨茶碱在不同校正胎龄、体重及日龄的极低出生体重儿中药代动力学和药效学特点。方法 选取发生呼吸暂停的极低出生体重儿40例,予以负荷剂量(5 mg/kg)氨茶碱静脉注射后随机分为两组,分别给予不同维持剂量(1 mg/kg及2 mg/kg,每8 h给药一次)。在治疗后8 h、3 d、7 d监测血药浓度及肝肾功能,记录呼吸暂停发作情况,比较两组药代动力学数据。结果 2 mg/kg组的稳态血药浓度、血浆清除率明显高于1 mg/kg组,半衰期低于1 mg/kg组(P<0.05)。2 mg/kg组患儿生后7 d内呼吸暂停发作天数明显较1 mg/kg组少(P<0.05)。两组患儿的氨茶碱血浆清除率与生后日龄及校正胎龄呈正相关(P<0.05)。结论 极低出生体重儿中不同维持剂量氨茶碱药代动力学及药效学参数具有差异,2 mg/kg氨茶碱治疗呼吸暂停效果优于1 mg/kg;临床上对氨茶碱进行剂量调整时应考虑患儿校正胎龄及生后日龄,同时进行常规血药浓度监测。     

Addition of metolazone to overcome tolerance to furosemide in infants with bronchopulmonary dysplasia.

A decreased response to the loop diuretic furosemide develops within a few doses in young infants. We tested the hypothesis that the use of the thiazide-like diuretic metolazone, in combination with furosemide, would inhibit water and electrolyte reabsorption and overcome pharmacologic tolerance to furosemide alone. Infants with bronchopulmonary dysplasia of similar gestational and postnatal ages were randomly assigned to one of three groups. Group 1 (n = 6) received furosemide (1 mg/kg per dose) intravenously every 24 hours for a total of five doses. Group 2 (n = 8) received the same treatment as group 1, but in addition metolazone (0.2 mg/kg per dose) was given enterally with doses 3 and 4 of furosemide. Group 3 (n = 8) received metolazone (0.2 mg/kg per dose) enterally every 24 hours for five doses. Urine was collected before the first diuretic dose and throughout the study for determination of the urine flow rate; urinary excretion of sodium, chloride, and potassium; and creatinine clearance. Urinary flow rate and urinary sodium and chloride excretion increased after the first dose in all groups. In the infants treated with either furosemide or metolazone, urinary flow rate and urinary and chloride excretion returned to baseline values after the last three doses. In contrast, when furosemide was administered with metolazone, urinary flow rate and urinary excretion of sodium, chloride, and potassium were greater than the values for baseline and for the previous dose, as well as for the corresponding doses of furosemide in group 1 and metolazone in group 3. Tolerance to furosemide (group 1) and metolazone (group 3) appeared to be explained by compensatory increased sodium and chloride reabsorption without changes in creatinine clearance. We conclude that the administration of metolazone with furosemide enhances diuresis, natriuresis, and chloruresis and overcomes the rapid development of tolerance to furosemide in infants with bronchopulmonary dysplasia by blocking the compensatory increase in renal sodium and chloride absorption.     

Randomized, placebo-controlled trial of iron supplementation in infants with low hemoglobin levels fed iron-fortified formula

In spite of the declining prevalence of iron-deficiency anemia, a large proportion of low-income infants have "low-normal" (11-11.5 g/dL) and "low" (less than 11 g/dL) hemoglobin (Hgb) values. Because most of these infants are fed iron-fortified formulas, it was of interest whether additional iron supplementation would enhance Hgb values. A cohort of 334 healthy, inner-city, minority, 6-month-old infants, fed iron-fortified formulas, with Hgb values ranging from 9 to 11.5 g/dL, participated in a double-blind, randomized, placebo-controlled trial of supplemental iron at 0, 3, and 6 mg/kg per day for 3 months. Hemoglobin values increased significantly with age, regardless of assignment to placebo or supplemental iron (means for the entire cohort: 6 months 10.9 g/dL, 8 months 11.2, 10 months 11.3, and 12 months 11.4). The proportion of "responders" (Hgb level increased greater than or equal to 1 g/dL) was 34% and did not differ significantly by placebo or iron dose. There were no significant differences in mean corpuscular volume or levels of erythrocyte porphyrins or serum ferritin between treatment groups. The implications of this clinical trial are twofold: (1) screening healthy infants fed iron-fortified formula at the age of 6 months is not justified, regardless of socioeconomic status; (2) the clinical practice of routinely treating low-income, "low-Hgb" infants with iron supplementation, without regard to dietary considerations, is unwarranted.     

Effect of high doses of human recombinant erythropoietin on the need for blood transfusions in preterm infants.

To determine whether prophylactic treatment with recombinant human erythropoietin (rHuEPO) and iron would reduce the need for blood transfusions, we randomly assigned 22 premature infants with gestational ages less than or equal to 32 weeks and birth weights less than or equal to 1.75 kg to receive rHuEPO, 400 IU/kg three times a week, plus iron, 20 mg/wk intravenously, from the second day of life (11 infants), or no rHuEPO and no iron (11 infants). The two groups had similar birth weights and clinical variables. The treated infants required fewer blood transfusions (0.8 +/- 1.5 vs 3.1 +/- 2.1; p = 0.01) and less volume of packed erythrocytes (14.2 +/- 25.9 vs 48.4 +/- 34.0 ml/kg; p = 0.02). The amounts of blood sampled were not different (19.5 +/- 21.1 vs 27.8 +/- 19.1 ml/kg; p = 0.35). Reticulocyte and hematocrit values were higher in the treated group (4.46% +/- 0.8% vs 1.49% +/- 1.1% (p = 0.0001) and 48.1% +/- 7.3% vs 43.8% +/- 4.7% (p = 0.004), respectively). No side effects of either rHuEPO or intravenously administered iron were noted. These data indicate that rHuEPO, in combination with iron supplementation, is effective in reducing the need for blood transfusions in the premature infant. More information is needed on dosage, timing, and iron and vitamin supplementation.