A randomized trial of two levels of iron supplementation and developmental outcome in low birth weight infants.

OBJECTIVES: To investigate the effect of increased iron intakes on hematologic status and cognition in low birth weight infants. STUDY DESIGN: We randomly assigned 58 infants to receive formula with 13.4 mg iron/L (normal iron) or 20.7 mg iron/L (high iron). At baseline, discharge, and at 3, 6, 9, and 12 months' corrected age, we assessed anthropometry; infections; red blood cell hemoglobin, catalase, glutathione peroxidase, red blood cell fragility (hydrogen peroxide test), and superoxide dismutase values; plasma malondialdehyde, ferritin, iron, transferrin, zinc and copper levels; and diet intake. Griffiths' Development Assessment was done at 3, 6, 9, and 12 months only. RESULTS: No statistical differences (P <.05) were noted for weight, catalase or malondialdehyde levels, red blood cell fragility, or Griffith's Development Assessment. Iron intakes were greater in the high iron group except at 12 months. Hemoglobin (high iron, 123 +/- 9; normal iron, 118 +/- 8) was not different at 3 months (P =.07). Plasma zinc levels (high iron, 70 +/- 14; normal iron, 89 +/- 27) and copper levels (high iron, 115 +/- 26; normal iron, 132 +/- 27; P =.06) at 12 months suggested inhibition of absorption by high iron formula. Glutathione peroxidase levels were higher in the high iron group. The total number of respiratory tract infections was greater in the high iron group (3.3 +/- 0.9) than in the normal iron group (2.5 +/- 0.9). CONCLUSION: In terms of cognitive outcome, there is no advantage associated with elevated iron intake for low birth weight infants.

Eighteen-month follow-up of infants fed evaporated milk formula.

In parts of Canada including Newfoundland and Labrador and among Aboriginal peoples, infants still consume evaporated milk (EM) formulas for cultural and economic reasons. At 3 and 6 months, full-term infants fed EM (n = 30) received low intakes of iron, thiamine, selenium and had higher weight velocity than breastfed (BF, n = 29) infants. EM infants had greater anemia, lowered transketolase activity (thiamine) and lowered glutathione peroxidase (selenium) activity (p < 0.05). To determine the later effect of early feeding deficit on nutritional status, we examined these same infants at 18 months of age. At that time, there were no differences in dietary intakes of energy, protein, zinc, copper, selenium and iron, nor in plasma levels of zinc, copper, vitamin C, nor in red blood cell activity levels of glutathione reductase (riboflavin), transketolase, glutathione peroxidase, nor in superoxide dismutase. However, EM infants weighed more and were more likely to visit a physician, have anemia, and have iron depletion than were BF infants. We conclude that infants consuming evaporated milk formulas should receive iron supplements throughout infancy.

Molybdenum requirements in low-birth-weight infants receiving parenteral and enteral nutrition.

BACKGROUND: Molybdenum (Mo) is an essential trace element required by three enzymatic systems, yet there are no reports of Mo deficiency in infants. Low-birth-weight infants (LBW) might be at risk for Mo deficiency because they are born before adequate stores for Mo can be acquired, they have rapid growth requiring increased intakes, and they frequently receive supplemental parenteral nutrition (SPN) and total parenteral nutrition (TPN) unsupplemented with molybdenum. METHODS: To investigate Mo requirements of LBW infants (n = 16; birth weight, 1336+/-351 g; gestational age, 29.8+/-2.5 weeks; M+/-SD), the authors collected all feeds, urine, and feces prior to TPN (baseline, n = 16, collections = 16), during TPN (n = 9, collections = 19), during SPN (n = 13, collections = 17), and after one week of full oral feeds (FOFs) of formula or human milk (FOF, n = 16, collections = 16). RESULTS: Infant weights at collection times were: 1.3+/-0.3 g, 1.27+/-0.4 g, 1.4+/-0.3 g, and 1.7+/-0.5 g, respectively. Mo intake was 0.03+/-0.1 microg/d, 0.34+/-0.1 microg/d, 1.25+/-1.7 microg/d, and 6.1+/-2.5 microg/d. Mo output was 0.64+/-0.6, 0.34+/-0.5, 0.68+/-0.8, and 4.1+/-2.5 microg/d. Mo balance at these times was -0.60+/-0.5, -0.001+/-0.5, 0.57+/-1.9, and 2.0+/-2.9 microg/d. Mo balance increased with time, yet some infants were always in negative balance, even though Mo intakes exceeded recommendations. CONCLUSIONS: The authors speculate that an intravenous intake of 1 microg/kg/d (10 nmol/kg/d) and an oral intake of 4-6 microg/kg/d (40-60 nmol/kg/d) would be adequate for the LBW infant.

Elemental composition of human milk from mothers of premature and full-term infants during the first 3 months of lactation.

To examine longitudinal and gestational effects of mineral content in human milk, we analyzed human milk from lactating mothers of premature (PRT, n = 24, < 2000 g birth weight, < 37 wk gestation) and full-term (FT, n = 19, > 2500 g, 39-41 wk gestation), living in Newfoundland, Canada. Samples were collected once a week for 8 wk with one final sample collected at 3 mo. Milk samples collected in acid-washed containers were wet ashed with concentrated HNO3, and barium, cadmium, calcium, cesium, cobalt, copper, cerium, lanthanum, magnesium, manganese, molybdenum, nickel, lead, rubidium, tin, strontium, and zinc were measured using inductively coupled plasma-mass spectrometry. Data were analyzed using standard multiple-regression procedures with correlated data analyses to take account of the relationship between successive weeks. Results indicated lower Ca and Pb in PRT milk. Calcium was the only nutritionally significant element to differ between groups. Molybdenum in both PRT and FT milk showed a definite decrease with time, suggesting that the Mo content in milk is homeostatically regulated. However, Ce, La, Ba, and Sn did not display any pattern indicative of biological regulation and potential human requirement.

Elevated intakes of zinc in infant formulas don not interfere with iron absorption in premature infants.

BACKGROUND: Zinc and iron may share common pathways for absorption and compete for uptake into mucosal cells. We determined whether elevated ratios of zinc to iron would interfere with erythrocyte incorporation of iron in premature infants both during and between feeds. METHODS: In the first experiment, five premature infants (<2500 g birth weight) were enrolled, once receiving full oral feeds by nasogastric tube. They received either high (1200 microg/kg, ratio 4:1) or low (300 microg/kg, ratio 1:1) doses of oral zinc sulfate, together with 300 microg/kg oral 58Fe as chloride in saline with 10 mg/kg vitamin C, between designated feeding periods. Each infant served as its own control and randomly received either high or low doses of zinc or iron and then the alternate dose after 2 weeks. In the second experiment, nine additional premature infants were assigned to the same zinc:iron intake protocol except zinc and iron were given with usual oral feeds (premature formula or human milk) equilibrated before feeding. Iron absorption was measured by the erythrocyte incorporation of 58Fe. RESULTS: High doses of zinc given between feeds significantly inhibited erythrocyte incorporation of iron. 58Fe incorporation (%) with the 1:1 ratio of zinc:iron intake was 7.5 (5.7, 10; geometric mean, -I SD, +1 SD). The percentage of 58Fe incorporation on the 4:1 ratio of zinc:iron intake was 3.6 (2.6, 5.1). Given with feeds, the percentage of 58Fe incorporation on low zinc:iron intake was 7.0 (2.6, 19). Finally, the percentage of 58Fe incorporation on high zinc:iron intake was 6.7 (2.5, 19). CONCLUSION: Elevated intakes of zinc do not interfere with erythrocyte incorporation of iron in premature formulas.

Evaluation of full-term infants fed an evaporated milk formula.

The objective of this prospective, cohort study was to compare the nutritional status of full-term infants who were fed human milk (BF, n = 29), formula (FF, n = 30) or evaporated milk formulae (EM, n = 30) for at least 3 months. Infants were seen at enrollment, 3 and 6 months, at which times a blood sample, diet record and anthropometric data were collected. Infants in the EM group received solids earlier (12 +/- 5 weeks) than did FF infants (15 +/- 4 weeks), and both were earlier than BF infants (19 +/- 4 weeks). Only 26% of the EM fed group received iron supplements as ferrous sulphate drops. Seven BF, 12 FF and 20 EM had abnormal ferritin values (< 10 ng ml-1) at 6 months. Copper intake was lower in the EM infants at 3 and 6 months. However, plasma copper and erythrocyte copper zinc superoxide dismutase (ZnCuSOD) levels did not differ between groups. Selenium intake was lower in the EM group (5 +/- 1 and 10 +/- 5 micrograms d-1; 3 and 6 months) than in the FF infants (13 +/- 4 and 19 +/- 7 micrograms d-1; 3 and 6 months). Erythrocyte SeGHSPx levels in EM infants were lower at 6 months (EM, 33.2 +/- 3.4; FF. 35.2 +/- 3.9: BF, 36.1 +/- 3.8 mU mg Hb-1). Thiamin intake (0.99 +/- 0.08 and 1.24 +/- 0.32; 3 and 6 months, mg 1000 kcal-1) was higher in the FF group than in EM infants (0.38 +/- 0.39 and 0.66 +/- 0.38; 3 and 6 months). There were more (13%) abnormal thiamin assays in the EM group at 6 months than in the BF and FF infants (0%). In conclusion, infants fed evaporated milk formula receive adequate copper but may not receive enough thiamin or selenium. Unless supplemented from birth with medicinal iron, intakes of iron will be inadequate.

Laboratory gloves as a source of trace element contamination.

Contamination in a trace element laboratory can come from a variety of sources, including laboratory gloves. Therefore, vinyl and latex gloves were obtained from as many manufacturers as would supply gloves. These gloves were either prepared for acid-washing and subsequent soaking in an acid solution, or immersed in an acid solution for a duration of either 1 min or 1 h. Incubation washes were analyzed for a variety of trace elements by flame atomic absorption spectroscopy (AAS) or inductively coupled mass spectrometry (ICP-MS). Results indicated that only three brands of vinyl gloves were acceptable for use in a trace element laboratory, whereas others had contamination of different elements. Latex gloves contained such high levels of biologically important elements that they were not considered suitable for routine trace element work. Vinyl gloves of choice should be routinely acid-washed before use in a trace element laboratory.

Thiamine, riboflavin, folate, and vitamin B12 status of infants with low birth Weights receiving enteral nutrition.

The purpose of the present study was to monitor the vitamin status of 14 low-birth-weight (LBW) infants (< 1,750 g birth weight) at 2 weeks and an additional four infants at 3 weeks who were receiving an enteral formula providing 247 micrograms/100 kcal thiamine, 617 micrograms/100 kcal riboflavin, 37 micrograms/100 kcal folate, and 0.55 micrograms/100 kcal vitamin B12. The mean birth weight of the 18 infants was 1,100 +/- 259 g, and mean gestational age was 29 +/- 2 weeks. Weekly blood, 24-h urine collections, and dietary intake data were obtained. For thiamine, red blood cell (RBC) transketolase activity was within the normal range for all infants. For riboflavin, RBC glutathione reductase activity was normal for all infants except one. We calculated from intake and urinary excretion data that these infants require 225 micrograms/100 kcal thiamine and 370 micrograms/100 kcal riboflavin, respectively. Mean plasma folate levels were 21 +/- 11 ng/ml at 2 weeks and 18 +/- 5 ng/ml at 3 weeks. RBC folate levels were 455 +/- 280 ng/ml at 2 weeks and 391 +/- 168 ng/ml at 3 weeks. All folate blood values were normal, except for one subject with an elevated level (59 ng/ml). Vitamin B12 plasma values were 737 +/- 394 pg/ml at 2 weeks and 768 +/- 350 pg/ml at 3 weeks, and all values were normal except for three infants with elevated values. In conclusion, appropriate vitamin status was maintained during this short observational period, during administration of this enteral formula; however, riboflavin concentrations in the enteral feed may be excessive.

Zinc absorption in premature infants: comparison of two isotopic methods.

The fractional absorption of an oral dose of zinc can be measured in adults when given simultaneously with an intravenous dose and subsequently measuring the ratio of the double isotopic enrichment of urine. To test this method in very-low-birth-weight (VLBW) premature infants [n=5 females and 7 males, 1160 +/- 290 g (chi +/- SD) birth weight, 29 +/- 4 wk gestational age], an oral dose of either 300 or 1200 micrograms 68Zn.kg(-1).d(-1) was equilibrated with formula or human milk and administered simultaneously with either 50 or 100 micrograms 70Zn.kg(-1).d(-1) given intravenously 35 +/- 3 wk postconception. Urine and fecal samples were collected for 3-6 d and analyzed by inductively coupled plasma mass spectrometry. Endogenous fecal zinc (EFZ) was determined from isotopic enrichment, whereas net absorption and retention were calculated by traditional methods. The mean fractional absorption calculated from urine was 0.22 +/- 0.09 and from feces it was 0.25 +/- 0.07. Zinc intake averaged 1821 +/- 330, fecal excretion 1637 +/- 419, and urinary excretion 67 +/- 30 micrograms.kg(-1).d(-1). EFZ averaged 390 +/- 270 micrograms.kg(-1).d(-1) and ranged from 48 to 889 micrograms.kg(-1).d(-1). Net absorption was 220 +/- 316 micrograms.kg(-1).d(-1) and net retention was 131 +/- 334 micrograms.kg(-1).d(-1). True absorption was 373 +/- 161 micrograms.kg(-1).d(-1). Fecal collection is difficult, tedious, and often incomplete, and may be replaced by urine collection for the fractional absorption of zinc in groups of premature infants.

Intravenous iron administration to very-low-birth-weight newborns receiving total and partial parenteral nutrition.

BACKGROUND: Intravenous iron supplements are not routinely administered to very-low-birth-weight newborns receiving total parenteral nutrition because of the possible increased risk of infection and because iron needs may be met with blood transfusions. METHODS: To assess the benefits of a prudent IV iron supplement (200 to 250 micrograms/kg/d), 26 very-low-birth-weight newborns (birth weight, 1005 +/- 302 g; gestational age, 28 +/- 2.3 weeks; mean +/- SD) were randomly allocated to receive total parenteral nutrition without iron (No-Iron) or with iron supplied as iron dextran (Iron). These newborns were followed at baseline (2 to 3 days after birth) and at weeks 1 to 4 thereafter. At each sampling time, urine samples, fecal samples (rarely), unused total parenteral nutrition solutions, blood products, and a blood sample (1 mL) were collected. RESULTS: There were no differences between the two groups in anthropometric measurements, hematologic or biochemical parameters, number or amount of blood transfusions (2.3 +/- 1.9), amount of blood removed for diagnostic purposes (44 +/- 16 mL), or number of septic events (n = 16). There was no difference between the groups for the total iron excreted; however, the Iron group retained more iron. Iron balance was negative for all but 10 newborns (No-Iron, 3; Iron, 7) throughout the study. CONCLUSIONS: A total iron intake of 400 micrograms/kg/d, half of which was provided by IV iron, is not sufficient to maintain iron balance or to meet fetal accretion rates (1000 micrograms/kg/d) in very-low-birth-weight newborns receiving total parenteral nutrition. Furthermore, endogenous iron from blood transfusions does not provide an adequate supply of iron.

Zinc requirement of premature infants.

Premature infants require adequate amounts of zinc to foster growth and cognitive development. Zinc given during TPN (450-500 micrograms.kg-1.day-1) is the only way to meet in utero accretion rates before 36 wk postconceptional age because of extensive resecretion into the gut of oral zinc. After that time, infants should be consuming formulas supplemented with 12 mg/L zinc for the whole of infancy.

Selenium status of very low birth weight infants.

The selenium (Se) intake and status of 82 very low birth weight infants (birth weight 1110 +/- 286 g, gestational age 29.2 +/- 3 wk, mean +/- SD) was assessed at 36.3 +/- 3 postconceptional wk, at 40.1 +/- 4 wk (hospital discharge), and at 3, 6, 9, and 12 +/- 0.75 mo corrected for gestational age. Infants were fed formula containing 0.13 mumol/L (10 micrograms/L) Se. Se-dependent glutathione peroxidase activity in red blood cells declined corresponding to low Se intakes (micrograms/kd/d) for the first 6 mo. With increased consumption of solid foods, intakes of dietary Se and Se-dependent glutathione peroxidase activity increased at 9 mo, suggesting that the earlier supply of Se was suboptimal. Se-dependent glutathione peroxidase activity and intakes of Se were lower in males than in females (p < 0.05). We suggest that infant formulas should probably contain 0.26-0.33 mumol/L (20-25 micrograms/L) Se, particularly those formulas consumed by very low birth weight infants.

Zinc supplementation in very-low-birth-weight infants.

Inadequate zinc intake may lead to poor growth and developmental outcome in very-low-birth-weight (VLBW; < 1,500 g) infants. Fifty-two infants (mean birth weight, 1,117 +/- 287 g; mean gestational age, 29 +/- 2.9 weeks) were randomly allocated to two groups. SUPP infants received a regular term formula plus zinc supplements (4.4 mg/L; final content, 11 mg/L); PLAC infants received the same formula plus placebo (final content, 6.7 mg/L). Infants started their formula at 1,853 +/- 109 g and consumed the formula for 6 months. All subjects were evaluated at 3, 6, 9, and 12 +/- 0.75 months corrected-for-gestational-age. At each evaluation, weight, length, and head circumference were measured, a Griffiths developmental assessment was performed, and a blood sample was taken. Higher plasma zinc levels (p < 0.05) were found in the SUPP group at 1 and 3 months, and improved linear growth velocity was found in the SUPP group over the study period for the whole group as well as for girls alone. Maximum motor development scores were higher (p = 0.018) in the SUPP (98 +/- 10) than the PLAC (90 +/- 8) group, indicating that increased zinc intake in early infancy may be beneficial to VLBW infants.

Thiamine, riboflavin, folate, and vitamin B12 status of low birth weight infants receiving parenteral and enteral nutrition.

Thirty infants were randomly assigned to receive either 3 mL of MVI-Pediatric supplement (PAR3 group, parenterally fed) or 2 mL (PAR2 group, parenterally fed). For the first week, 100% received total parenteral nutrition (TPN), 50% by the second, and less than 33% by the third. Eighteen control infants received enteral feeds of infant formula. Baseline (before TPN) and subsequent weekly blood samples, dietary data, and 24-hour urine collections were obtained. The adequacies of thiamine and riboflavin were assessed by the thiamine pyrophosphate effect and erythrocyte glutathione reductase activity, respectively. Urinary thiamine and riboflavin levels were measured by fluorometry. Plasma folate, red blood cell folate, urinary folate, and plasma vitamin B12 concentrations were determined by radioassay. No differences between groups were observed in thiamine pyrophosphate effect, erythrocyte glutathione reductase activity, urinary B1 or B2, or red blood cell folate levels at any time. Plasma folate differed (p less than .05) among the PAR3 group (24 +/- 7 ng/mL), and both the PAR2 (13 +/- 5 ng/mL) and enterally fed (ENT) groups (16 +/- 3 ng/mL) before the initiation of feeds, at week 1 (PAR3 = 32 +/- 15 ng/mL; PAR2 = 18 +/- 4 ng/mL; ENT = 19 +/- 9, ng/mL) and between the PAR3 (30 +/- 16 ng/mL) and PAR2 (16 +/- 4 ng/mL) infants at week 2. Plasma vitamin B12 levels differed among the ENT groups (551 +/- 287 pg/mL) and both the parenteral groups (PAR2 = 841 +/- 405 pg/mL; PAR3 = 924 +/- 424 pg/mL) at week 1 and between the ENT (530 +/- 238 pg/mL) and PAR3 (999 +/- 425 pg/mL) groups at week 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Holoprosencephaly as a possible embryonic alcohol effect.

Three mothers of infants with holoprosencephaly consumed alcohol heavily in pregnancy. We postulate that early alcohol exposure is a possible cause of their malformation. The 3 mothers consumed alcohol only in the first trimester but the first mother continued to take chlordiazepoxide and imipramine throughout the pregnancy. Her infant had an alobar holoprosencephaly associated with a median cleft lip, ocular hypotelorism, and a flat nose. The other infants had semilobar holoprosencephaly and hydrocephalus. These latter 2 infants did not show the characteristic facies of the fetal alcohol syndrome. G-band chromosome studies were normal in all 3 infants. The association of holoprosencephaly with alcohol exposure during pregnancy in humans has been mentioned only briefly, although this malformation has been induced by alcohol in animals. These 3 infants may support the hypothesis that acute or subacute heavy alcohol exposure early in pregnancy could lead to holoprosencephaly without the necessity of a chronic alcohol exposure and without necessarily causing the typical facial findings of the fetal alcohol syndrome.

Iron status of very-low-birth-weight infants during the first 15 months of infancy.

The adequacy of iron stores in infants of very low birth weight (defined as less than 1500 g) in Canada is unknown. We monitored the iron status of 81 such infants at 3, 6, 9, 12 and 15 months of age. All of the infants were fed formula fortified with iron (13 mg/L) for at least 6 months, starting at 2 months of age. The plasma ferritin level decreased after the formula was no longer used. Although 90% of the infants were given cereal fortified with iron (30 mg of iron per 100 g) by 9 months of age, the plasma ferritin level continued to decrease. The level was less than 10 micrograms/L in 54% of the infants at 12 months of age and in 74% at 15 months; this indicated depleted iron stores. Because of delayed development very-low-birth-weight infants eat small amounts of cereal and therefore require iron-fortified formula throughout infancy.

Trace elements in meconium from preterm and full-term infants.

Meconium samples from 23 preterm infants (birth weight = 1,097 +/- 359 g; gestational age 29 +/- 3 weeks, mean +/- SD) and 27 full-term infants (3,453 +/- 476 g; 39.5 +/- 1 weeks) were analyzed for zinc, copper, manganese, chromium and iron by atomic absorption spectrometry. Compared to meconium from preterm infants, full-term infants had an elevated (p less than 0.05) total excretion (microgram) of zinc (957 +/- 545 vs. 503 +/- 506), copper (245 +/- 256 vs. 128 +/- 94) and manganese (62 +/- 55 vs. 29 +/- 29), but not iron (190 +/- 147 vs. 332 +/- 532) or chromium (0.4 +/- 0.19 vs. 0.75 +/- 1.0). Two preterm infants had high losses (1.5 and 2 mg) of iron in their meconium. Zinc, copper and manganese losses into meconium appear to increase with gestation, whereas iron and chromium losses occur early in gestation and may be reabsorbed by term.

Zinc, copper, manganese, and iron balance of parenterally fed very low birth weight preterm infants receiving a trace element supplement.

To evaluate a pediatric trace element supplement (Ped-El, Pharmacia) 18 metabolic balance studies were completed in 13 infants (mean birth weight 909 +/- 67 g, x +/- SEM; mean gestational age 27.2 +/- 1 weeks) who received total parenteral nutrition. The supplement supplied 40 micrograms/kg/day of zinc resulting in negative retention of 226 micrograms/kg/day. Copper infused at 20 micrograms/kg/day led to a positive retention of 8 micrograms/kg/day and an increase in serum Cu (p less than 0.05) not related to Cu intakes. Manganese infused at 40 micrograms/kg/day was nearly all retained (88 +/- 16% retention). Iron infused at 120 micrograms/kg/day led to a positive retention of 93 micrograms/kg/day. Although plasma ferritin and percent transferrin saturation were elevated, only plasma Fe values were correlated with Fe intake. This trace element supplement does not appear suitable for very low birth weight preterm infants.

Neonatal renal candidiasis: sonographic diagnosis.

With improved survival of very-low-birth-weight infants, the incidence of neonatal renal candidiasis is increasing. The clinical and sonographic features of four premature infants with renal candidiasis are presented. Both parenchymal and intrapelvic renal lesions, with or without hydronephrosis, were detected. Abdominal sonography is a useful noninvasive technique for the diagnosis and follow-up management of renal candidiasis. Early diagnosis allows prompt intervention with antifungal therapy and should increase survival.