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.     

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.     

The influence of gestational age, size for dates, and prenatal steroids on cord transferrin levels in newborn infants

Serum transferrin levels assess protein status in older children and adults. To generate standards for its use in newborn infants, we measured umbilical cord serum transferrin levels in 161 appropriate (AGA), 25 large (LGA) and 16 small (SGA) for gestational age infants between 25 and 43 weeks' gestation. We also assessed the effects of intrauterine growth, exposure to prenatal steroids, and presence of pulmonary maturity on neonatal transferrin levels. Cord transferrin levels in AGA infants were significantly correlated with increasing gestational age (r = 0.60; p less than 0.001). Infants born before 37 weeks' gestation had significantly lower transferrin levels, when compared with those born at term (p less than 0.001). LGA infants had significantly higher levels than age-matched AGA infants (253 +/- 75 vs. 214 +/- 53 mg/dl; p less than 0.025). Despite significantly lower mean birth weights (p less than 0.001), SGA infants also had significantly higher levels than gestational age-matched AGA controls (227 +/- 63 vs. 167 +/- 40 mg/dl; p less than 0.005). For infants less than 35 weeks' gestation, neither the 20 preterm infants with exposure to prenatal steroids (maternal betamethasone), nor the 26 infants with pulmonary maturity had significantly elevated transferrin levels, when compared with gestational age-matched control infants. Newborn transferrin levels correlate well with gestational age and are significantly affected by size for dates, but not by a brief course of prenatal steroids or by pulmonary maturity.     

Cord prealbumin values in newborn infants: effect of prenatal steroids, pulmonary maturity, and size for dates

We assessed cord prealbumin concentrations in 214 appropriate for gestational age newborn infants, 21 small for gestational age infants, and 27 large for gestational age infants to establish normal values and to assess the effect of intrauterine growth, prenatal steroids, and pulmonary maturity on prealbumin levels. Cord prealbumin values were significantly correlated with increasing gestational age (r = 0.33; P less than 0.001) and birth weight (r = 0.40, P less than 0.001) in the AGA neonates. Neonates born before 37 weeks gestation had significantly lower prealbumin levels than those born at term (P less than 0.001). The SGA infants had significantly lower levels than age-matched AGA controls (P less than 0.01), and LGA infants had significantly higher levels than age-matched AGA controls (P less than 0.001). In preterm infants, those with exposure to prenatal steroids (betamethasone or premature rupture of membranes) had significantly higher prealbumin values than control infants of comparable age and weight (P less than 0.001). Infants without respiratory distress syndrome had higher levels than those of comparable age and weight with hyaline membrane disease (P less than 0.05). This study demonstrates that a correlation of gestational age and birth weight exists with cord prealbumin levels, and that the large variability at each gestational age may be accounted for in part by appropriateness of size for dates, prenatal steroid exposure, and pulmonary maturity.     

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.     

The effect of antenatal betamethasone on cord blood concentrations of retinol-binding protein, transthyretin, transferrin, retinol, and vitamin E

We assessed the effect of short-term (less than or equal to 1 week) and prolonged (greater than 1 week) exposure to antenatal betamethasone on umbilical cord serum concentrations of retinol-binding protein (serum t 1/2 = 12 h), transthyretin (t 1/2 = 2 days), transferrin (t 1/2 = 8 days), retinol (vitamin A), and vitamin E in appropriate-for-gestational-age preterm newborn infants of less than 36 weeks' gestation. A group of 30 infants whose mothers received a single course of betamethasone less than or equal to 1 week prior to delivery had significantly elevated mean retinol-binding protein and transthyretin but not transferrin concentrations when compared with a group of 30 gestational age- and birth weight-matched infants with no exposure to antenatal betamethasone. A group of eight infants whose mothers received multiple (more than two) weekly courses of betamethasone prior to delivery had significantly elevated mean serum concentrations of all three proteins when compared with eight gestational age- and weight-matched control infants with no betamethasone exposure. Serum retinol and vitamin E concentrations were measured in a group of 21 infants exposed to short-term prenatal betamethasone and were significantly greater than in a group of 21 control infants without steroid exposure. We conclude that antenatal steroids increase the umbilical cord serum concentrations of retinol-binding protein, transthyretin, transferrin, retinol, and vitamin E. The effect on the various serum proteins is dependent on the duration of exposure to steroids.     

Relationship of maternal and newborn (cord) serum ferritin concentrations measured by immunoradiometry

Serum ferritin concentration was determined by immunoradiometry in venous blood samples of 45 pregnant women at term, in their babies' cord blood samples, and blood specimens obtained from 43 infants aged 3-12 months. The concentration of ferritin was higher in cord serum than in respective maternal samples and infant specimens. Low values were found in more than half of the maternal venous samples. Iron stores of newborns delivered by mothers with low serum ferritin concentration were lower than in newborns of mothers having normal ferritin levels. Serum ferritin measurement is a sensitive method to determine iron deficiency in pregnancy.     

Serum transferrin levels in the longitudinal assessment of protein-energy status in preterm infants

We prospectively measured serum transferrin levels weekly from birth until discharge in 33 preterm newborn infants hospitalized on the newborn intensive care unit (n = 130 weeks) to study whether transferrin levels accurately reflect recent nutritional intakes and predict subsequent changes in anthropometric measurements and serum protein levels. Mean daily protein and caloric intakes were no greater during weeks when transferrin levels increased than when levels decreased. There were weak but statistically significant linear relationships between protein intake and transferrin levels (r = 0.24, p less than 0.01), caloric intake and transferrin levels (r = 0.27, p less than 0.01), and magnitudes of weekly changes in protein intake and transferrin levels (r = 0.31, p less than 0.001), and magnitudes of weekly changes in caloric intake and transferrin levels (r = 0.27, p less than 0.01). Transferrin levels did not reflect same-week weight or midarm circumference (MAC) gains, nor did they predict the following week's gains. Mean anthropometric measurement gains were similar following weeks when transferrin levels increased or decreased. There were no positive linear relationships between the magnitudes of changes in transferrin levels and same-week weight gain (r = -0.35), same-week MAC gain (r = -0.27), or following-week MAC gain (r = 0.01). Weak correlations were found with following-week albumin levels (r = 0.32, p less than 0.001) and with same-week transthyretin levels (r = 0.44, p less than 0.001). Weekly serum transferrin levels are not useful for longitudinal surveillance of protein-energy status in preterm infants.     

Study of maternal influences on fetal iron status at term using cord blood transferrin receptors

AIMS: To determine effects of maternal iron depletion and smoking on iron status of term babies using serum transferrin receptors (STfR) and their ratio to ferritin (TfR-F index) in cord blood. METHODS: Iron, ferritin, STfR, and haemoglobin (Hb) concentration were measured and TfR-F index calculated in 67 cord /maternal blood pairs. Twenty six mothers were iron depleted (ferritin <10 microg/l) and 28 were smokers. RESULTS: Maternal iron depletion was associated with decreased cord ferritin (113 v 171 microg/l) and Hb (156 v 168 g/l) but no change in STfR or TfR-F index. Smoking was associated with increased cord Hb (168 v 157 g/l) and TfR-F index (4.1 v 3.4), and decreased ferritin (123 v 190 microg/l). Cord TfR-F index and Hb were positively correlated (r = 0.48). CONCLUSIONS: Maternal iron depletion is associated with reduced fetal iron stores but no change in free iron availability. Smoking is associated with increased fetal iron requirements for erythropoiesis.     

CORD BLOOD HAEMOGLOBIN, IRON AND FERRITIN STATUS IN MATERNAL ANAEMIA

ABSTRACT. Maternal and cord blood haemoglobin, serum iron, transferrin saturation and ferritin were studied in sets of 30 anaemic (haemoglobin <110 g/l) and 21 nonanaemic (haemoglobin ≧110 g/l) mothers. The cord serum iron, transferrin saturation and ferritin concentrations had significant correlation with maternal haemoglobin. The significant low levels of these parameters suggested that maternal anaemia adversely affected the iron status including iron stores of the newborns. The cord serum iron of 15.2±4.35 μmol/l and ferritin of 29.7±10.93 ng/ml seem to be effective to maintain cord haemoglobin levels. Thus, anaemic mothers with reasonably maintained ferritin and trasferrin saturation levels provide sufficient iron for maintenance of cord haemoglobin, although foetal iron stores are likely to be depleted.     

Serum transferrin receptor levels in the evaluation of iron deficiency in the neonate

Iron deficiency anemia (IDA) is a major global problem. Early onset of iron deficiency in developing countries makes it imperative to identify iron deficiency in neonates. Most conventional laboratory parameters of iron status fail to distinguish neonates with iron deficient erythropoiesis. Serum transferrin receptor (STFR) levels are a recent sensitive measure of iron deficiency and the present study was carried out to evaluate the usefulness of cord serum transferrin receptors in identifying iron deficient erythropoiesis in neonates. A complete hemogram, red cell indices, iron profile: serum iron (SI), percent transferrin saturation (TS%) and serum ferritin (SF) was carried out in 100 full-term neonates and their mothers at parturition. Cord and maternal STFR levels were estimated using a sensitive enzyme-linked immunosorbent assay (ELISA) technique. Anemic women had a significantly lower SI, their TS% and high STFR levels suggesting that iron deficiency was responsible for the anemia. In the neonates of iron deficient mothers, cord SI, TS% and cord ferritin were not significantly different from those of neonates born to non-anemic mothers. Cord STFR level correlated well with hemoglobin (Hb) and laboratory parameters of iron status, and its level was significantly higher in neonates born to anemic mothers than in those bom to non-anemic mothers. It was the only laboratory parameter to differentiate between neonates bom to anemic and non-anemic mothers. Therefore, STFR is a sensitive index of iron status in neonates and identifies neonates with iron deficient erythropoiesis.     

早产儿和足月儿脐血及母亲静脉血硒含量的比较

目的：硒是一种人体必需的微量元素,在细胞抗氧化防御系统中发挥着主要的作用。在早期早产儿中,低水平的硒会增加诸如慢性新生儿肺疾病、早产儿视网膜病等并发症的发生。该研究旨在检测并比较早产儿和足月儿脐血及母亲静脉血硒含量。方法：选取2008年3~7月间30个足月儿（胎龄>37 周）和30个早产儿（胎龄< 34 周）及他们的母亲作为研究对象。用原子吸收光谱法测定脐血和母亲静脉血的硒含量。结果：足月儿的脐血硒平均含量高于早产儿,差异有非常显著性(124.80± 13.72 μg/L vs 100.30 ± 11.72 μg/L, P=0.0001) 。 足月儿母亲与早产儿母亲的的平均硒含量差异无显著性 (117.03±17.15 μg/L vs 110.56±17.49 μg/L, P=0.15)。将所有婴儿的资料一起分析时,发现脐血硒含量与胎龄和出生体重显著正相关(r=0.66, P<0.0001;r=0.59, P<0.0001)。60例婴儿母亲中,无一例的血硒含量低于正常参考值的下限（70.0 μg/L）。将所有婴儿及其母亲的资料一起分析时,发现母亲血硒含量与其婴儿脐血硒含量呈显著正相关 (r=0.40, P<0.001)。结论：在伊斯法罕地区,孕母的血硒水平处于一个良好的状态,血硒水平不是早产的预测指标。足月儿的脐血硒含量高于早产儿,但足月儿和早产儿的脐血硒含量均在正常参考范围。［中国当代儿科杂志,2009,11（7）：513-516］     

Prolactin in umbilical cord blood and the respiratory distress syndrome.

Prolactin was measured in umbilical cord serum obtained from 77 newborn infants of gestational age 28 to 40 weeks. A positive correlation with gestational age was demonstrated. Between 30 and 36 weeks of gestation the elevation of the regression line of the concentration of cord PRL versus gestation age was significantly lower (P less than 0.05) for those infants who developed respiratory distress syndrome compared to the regression line for infants who did not develop RDS. Between 32 and 33.5 weeks, the mean +/- SEM cord PRL concentration in infants who developed RDS (101.7 +/- 9.5 ng/ml) was significantly less (P less than 0.025) than the PRL concentration in those who did not develop RDS (161.8 +/- 18.9 ng/ml). Cord PRL did not correlate with cord cortisol or dehydroepiandrosterone sulfate concentrations. Cord growth hormone concentrations did not show any relationship to the occurrence of RDS. Serum PRL was not suppressed in a further 114 infants whose mothers were treated prenatally with betamethasone. These findings raise the possibility of a role of PRL in fetal lung maturation.     

Selected trace elements and proteins in serum of apparently healthy newborn infants of mothers who smoked during pregnancy

The serum concentrations of selected trace elements and proteins in cord blood from 17 newborn infants whose mothers were habitual smokers were compared with values from 22 infants of non-smoking mothers. All the mothers were healthy with normal pregnancies and deliveries. Cigarette smoke exposure was verified by determinations of nicotine, cotinine and thiocyanate concentrations in cord blood. Infants of smoking mothers had a slightly lower mean birth weight (3490 +/- 430 g) than control infants (3780 +/- 460 g). Infants of smokers had lower serum iron (p = 0.05) and prealbumin (p less than 0.05), but higher serum copper (p less than 0.05) and ceruloplasmin (p less than 0.01) levels than the controls. Infants of smoking mothers tended to have higher levels of the acute-phase reactants alpha-2-macroglobulin and orosomucoid, but lower levels of albumin, transferrin and retinol-binding-protein, although differences were not statistically significant.     

Cord plasma vasopressin, erythropoietin, and hypoxanthine as indices of asphyxia at birth

To assess the value of cord plasma arginine vasopressin (AVP), erythropoietin (EP), and hypoxanthine (HX) as indices of asphyxia, we studied 62 infants of mothers with preeclampsia, 34 acutely asphyxiated infants, with 5-min Apgar score less than or equal to 6 and/or umbilical arterial pH less than or equal to 7.05, and 38 control infants. Umbilical arterial AVP in the asphyxia group (geometric mean; 95% confidence interval: 180; 92-350 pg/ml) was higher than in the control group (23; 8-66, p = 0.002) and correlated with umbilical arterial pH (r = -0.447, p = 0.028). AVP levels in the preeclampsia group did not differ from controls. Cord venous EP was higher in infants delivered by elective cesarean section from women with severe preeclampsia (115; 75-177 mU/ml, p less than 0.001) than in control infants (23; 18-27); in the whole group EP correlated with pH (r = -0.493, p less than 0.001). EP in the asphyxia group was similar (46; 35-65) to controls (40; 33-47) and did not correlate with pH. Cord arterial HX in the preeclampsia group was similar to controls (12.3; 9.5-16.0 mumol/liter), but elevated in the asphyxia group (23.7; 17.6-31.8, p = 0.001), in which HX correlated with pH (r = 0.558, p = 0.008) and AVP (r = 0.588, p = 0.005). EP did not correlate with AVP or HX in any group, nor did any of the variables correlate with the Apgar score. We conclude that cord plasma AVP and HX reflect acute asphyxia, whereas EP is elevated after more prolonged hypoxia.     

Iron status in the first year of life

The iron status of babies of different race born at term to mothers in an inner city area was studied at birth and during the first year of life and related to maternal iron status. Haemoglobin and ferritin were measured in the mother at term (n = 81) and in the baby in cord blood (n = 81), at 6 months (n = 55), and at 1 year (n = 51). No relationship was found between the iron status of mothers and their babies at birth. However, iron stores at birth did affect later iron status, cord ferritin being significantly related to ferritin at 6 months (r = 0.42, p less than 0.01) and 1 year (r = 0.55, p less than 0.01) but not to haemoglobin at these ages. No relationship was found between haemoglobin iron at birth and subsequent iron status. Introduction of full cow's milk before the age of 6 months was associated with iron deficiency at this age and at 1 year. By the age of 1 year, iron deficiency was also associated with feeding greater than 900 ml whole cow's milk a day, inadequate feeding with solids, and higher weight gain. No stool parasites were found at the age of 1 year, and the presence of occult blood in stools did not significantly affect iron status at this age. At 1 year of age, 49% of these infants had low iron stores, including 20% with iron deficiency anaemia. Considerable improvement could result from simple changes in dietary practices.     

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).     

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.     

PLASMA FERRITIN CONCENTRATIONS IN PRETERM INFANTS IN CORD BLOOD AND DURING THE EARLY ANAEMIA OF PREMATURITY

Abstract. Hågå, P. (Department of Paediatrics and Paediatric Research Institute, National Hospital of Norway, and Department of Paediatrics, Oslo City Hospital, Ullevål, Oslo, Norway). Plasma ferritin concentrations in preterm infants in cord blood and during the early anaemia of prematurity. Acta Paediatr Scand, 69: 637, 1980.—Ferritin concentrations in cord blood were determined in 22 normal term and 32 preterm infants (birth weights 600–2000 g). Eight of the preterms were SGA infants. AGA preterm infants had significantly lower concentrations than term infants, and the SGA preterm newborn had even lower levels. Plasma ferritin in cord blood of the term and AGA preterm infants correlated positively with plasma iron and transferrin saturations, but not with the transferrin level, while plasma iron and transferrin concentrations correlated positively. In a longitudinal study, 17 AGA preterm infants (birth wights 850–1500 g) were followed during the early anaemia of prematurity. Iron was supplemented from 4 weeks of age. Plasma ferritin rose rapidly during the first days after birth, peak levels being reached at 1–4 weeks. Thereafter linear falls (semilog) occurred with similar slopes in different infants. Transferrin concentrations showed a slow progressive increase from 0–8 weeks. Plasma ferritin, after reaching the peak value, correlated negatively with weight gain. No infant had low ferritin values indicating iron deficiency during the early anaemia.