Modest and Severe Maternal Iron Deficiency in Pregnancy are Associated with Fetal Anaemia and Organ-Specific Hypoxia in Rats.

Prenatal iron-deficiency (ID) is known to alter fetal developmental trajectories, which predisposes the offspring to chronic disease in later life, although the underlying mechanisms remain unclear. Here, we sought to determine whether varying degrees of maternal anaemia could induce organ-specific patterns of hypoxia in the fetuses. Pregnant female Sprague Dawley rats were fed iron-restricted or iron-replete diets to induce a state of moderate (M-ID) or severe ID (S-ID) alongside respective controls. Ultrasound biomicroscopy was performed on gestational day (GD)20 to assess uterine and umbilical artery blood flow patterns. On GD21, tissues were collected and assessed for hypoxia using pimonidazole staining. Compared to controls, maternal haemoglobin (Hb) in M- and S-ID were reduced 17% (P < 0.01) and 48% (P < 0.001), corresponding to 39% (P < 0.001) and 65% (P < 0.001) decreases in fetal Hb. Prenatal ID caused asymmetric fetal growth restriction, which was most pronounced in S-ID. In both severities of ID, umbilical artery resistive index was increased (P < 0.01), while pulsatility index only increased in S-ID (P < 0.05). In both M-and S-ID, fetal kidneys and livers showed evidence of hypoxia (P < 0.01 vs. controls), whereas fetal brains and placentae remained normoxic. These findings indicate prenatal ID causes organ-specific fetal hypoxia, even in the absence of severe maternal anaemia.

Pregnancy and maternal iron deficiency stimulate hepatic CRBPII expression in rats.

Iron deficiency impairs vitamin A (VA) metabolism in the rat but the mechanisms involved are unknown and the effect during development has not been investigated. We investigated the effect of pregnancy and maternal iron deficiency on VA metabolism in the mother and fetus. 54 rats were fed either a control or iron deficient diet for 2weeks prior to mating and throughout pregnancy. Another 15 female rats followed the same diet and were used as non-pregnant controls. Maternal liver, placenta and fetal liver were collected at d21 for total VA, retinol and retinyl ester (RE) measurement and VA metabolic gene expression analysis. Iron deficiency increased maternal hepatic RE (P<.05) and total VA (P<.0001), fetal liver RE (P<.05), and decreased placenta total VA (P<.05). Pregnancy increased Cellular Retinol Binding Protein (CRBP)-II gene expression by 7 fold (P=.001), decreased VA levels (P=.0004) and VA metabolic gene expression (P<.0001) in the liver. Iron deficiency increased hepatic CRBPII expression by a further 2 fold (P=.044) and RBP4 by~20% (P=.005), increased RBPR2 and decreased CRBPII, LRAT, and TTR in fetal liver, while it had no effect on VA metabolic gene expression in the placenta. Hepatic CRBPII expression is increased by pregnancy and further increased by iron deficiency, which may play an important role in VA metabolism and homeostasis. Maternal iron deficiency also alters VA metabolism in the fetus, which is likely to have consequences for development.

Quantitative proteomic analyses of cerebrospinal fluid using iTRAQ in a primate model of iron deficiency anemia.

Iron deficiency affects nearly 2 billion people worldwide, with pregnant women and young children being most severely impacted. Sustained anemia during the first year of life can cause cognitive, attention and motor deficits, which may persist despite iron supplementation. We conducted iTRAQ analyses on cerebrospinal fluid (CSF) from infant monkeys (Macaca mulatta) to identify differential protein expression associated with early iron deficiency. CSF was collected from 5 iron-sufficient and 8 iron-deficient anemic monkeys at weaning age (6-7 months) and again at 12-14 months. Despite consumption of iron-fortified food after weaning, which restored hematological indices into the normal range, expression of 5 proteins in the CSF remained altered. Most of the proteins identified are involved in neurite outgrowth, migration or synapse formation. The results reveal novel ways in which iron deficiency undermines brain growth and results in aberrant neuronal migration and connections. Taken together with gene expression data from rodent models of iron deficiency, we conclude that significant alterations in neuroconnectivity occur in the iron-deficient brain, which may persist even after resolution of the hematological anemia. The compromised brain infrastructure could account for observations of behavioral deficits in children during and after the period of anemia.

Iron in pregnancy: How do we secure an appropriate iron status in the mother and child?

Iron deficiency and iron deficiency anemia (IDA) during pregnancy are risk factors for preterm delivery, prematurity, and small for gestational age birth weight. Iron deficiency has a negative effect on intelligence and behavioral development in the infant. It is essential to prevent iron deficiency in the fetus by preventing iron deficiency in the pregnant woman. The requirements for absorbed iron increase during pregnancy from ∼1.0 mg/day in the first trimester to 7.5 mg/day in the third trimester. More than 90% of Scandinavian women of reproductive age have a dietary iron intake below the recommended 15 mg/day. Among nonpregnant women of reproductive age, ∼40% have plasma ferritin ≤30 µg/l, i.e. an unfavorable iron status with respect to pregnancy. An adequate iron status during pregnancy implies body iron reserves ≥500 mg at conception, but only 15-20% of women have iron reserves of such a magnitude. Iron supplements during pregnancy reduce the prevalence of IDA. In Europe, IDA can be prevented by a general low-dose iron prophylaxis of 30-40 mg ferrous iron taken between meals from early pregnancy to delivery. In affluent societies, individual iron prophylaxis tailored by the ferritin concentration should be preferred to general prophylaxis. Suggested guidelines are: ferritin >70 µg/l, no iron supplements; ferritin 31-70 µg/l, 30-40 mg ferrous iron per day, and ferritin ≤30 µg/l, 60-80 mg ferrous iron per day. In women with ferritin <15 µg/l, i.e. depleted iron reserves and possible IDA, therapeutic doses of 100 mg ferrous iron per day should be advised.

Evaluación de la fracción de reticulocitos inmaduros como parámetro de ferropenia en el embarazo / Evaluation of the fraction of immature reticulocytes as a parameter of iron deficiency in pregnancy

Las embarazadas constituyen un grupo susceptible de desarrollar anemia ferropénica, la cual produce una alteración de la hematopoyesis, con aumento de reticulocitos principalmente a expensas de la fracción de reticulocitos inmaduros (IRF). El objetivo de este trabajo ha sido evaluar la sensibilidad (S) y especificidad (E) del IRF para el diagnóstico temprano de la deficiencia de hierro en el embarazo. Se obtuvieron muestras de sangre de 99 embarazadas que concurrieron al laboratorio del Hospital Vélez Sarsfield para su control prenatal. Se realizó el hemograma y el recuento reticulocitario en un autoanalizador hematológico, y se determinaron el hierro sérico y la ferritina. Se halló una sensibilidad de 76,1% y una especificidad de 53,1% por medio del análisis de la curva ROC (receiver- operating characteristic curve) para un valor de IRF de 0,35. La comparación de parámetros hematológicos y bioquímicos de las muestras con IRF menor o mayor a 0,35 muestran diferencias significativas (p<0,05). Por estos datos se podría recomendar esta prueba para el diagnóstico precoz de la deficiencia de hierro.

Pregnant women constitute a group capable of developing iron deficiency anemia, which causes a disturbance of hematopoiesis, with increased reticulocyte mainly at the expense of the immature reticulocyte fraction (IRF). The aim of this work was to assess IRF sensitivity (S) and specificity (E for its name in Spanish) for early diagnosis of iron deficiency in pregnancy. Blood samples from 99 pregnant women who attended Vélez Sarsfield Hospital Laboratory for prenatal care. Complete blood cells and reticulocyte automated counts were performed and serum iron and ferritin were analyzed. A 0.35 IRF cutoff was taken when the ROC curve (receiver-operating characteristic curve) was evaluated and a 76.1% sensitivity and 53.1%. specificity were found. Comparison of hematological and biochemical parameters of the samples with IRF lower and higher than 0.35 shows significant differences (p<0.05). These results make it possible to recommend this test for early diagnosis of iron deficiency.

[The effect of benzine and formaldehyde on the prenatal development of rats with induced iron trace-element disorder]. / O vliianii benzina i formal'degida na prenatal'noe razvitie krys s indutsirovannym mikroélementozom zheleza.

Iron-deficiency anemia induced in the maternal organism markedly enhances embryotoxic and teratogenic effects of the studied pollutants: gasoline and formaldehyde. The prenatal effects of these drugs against the background of iron-deficiency state in pregnant females leads to development of the main feature of the tissue hypoxia, decompensated metabolic acidosis, in both the maternal organism and 20-day embryos.