Maternal Iron Supplementation Research Articles

Maternal arachidonic acid and iron supplementation improves performance in Morris Water Maze in 28‐day old offspring from diabetic rats – a pilot study

Maternal arachidonic acid and iron supplementation improves performance in Morris Water Maze in 28‐day old offspring from diabetic rats – a pilot study

Effects of Antenatal Micronutrient Supplementation on Cortisol and Erythropoietin in Pregnant Nepalese Women

Antenatal iron and multiple micronutrient supplementation improves birth weight. We examined whether this effect was mediated by reducing maternal stress and related factors that could compromise pregnancy outcomes. We examined late pregnancy serum erythropoietin (EPO) and cortisol in relation to maternal iron supplementation and iron status indicators (hemoglobin, Hb; ferritin, ferr; transferrin receptor, TfR) in 737 rural Nepalese women who participated in a 5-arm randomized, controlled micronutrient supplementation trial during pregnancy through 3 months postpartum. Women were randomized to receive vitamin A alone (as control), or with folic acid, folic acid+iron, folic acid+iron+zinc and a multiple micronutrient supplement (MN). EPO was ~0.5 mIu/ml lower (P<0.0001) in all groups receiving iron compared to the control group, with no difference in the folic acid only group. Cortisol was 1.3μg/dl lower (P=0.0422) in the MN group compared to the control group with no difference in other groups. Cortisol was associated with EPO (r = 0.20, P=0.008), TfR (r = 0.20, P=0.007), Ferr (−0.02, NS), and Hb (−0.15, p=0.053) in the control group. Hypoxia may elevate cortisol during iron deficiency. Reduction in mediators of maternal stress, including impaired erythropoeisis, is a likely mechanism by which iron and micronutrient supplementation may enhance birth weight. Support: USAID, Gates Foundation.

Maternal iron supplementation attenuates the impact of perinatal copper deficiency but does not eliminate hypotriiodothyroninemia nor impaired sensorimotor development

Copper, iron and iodine/thyroid hormone (TH) deficiencies disrupt brain development. Neonatal Cu deficiency causes Fe deficiency and may impact thyroidal status. One purpose of these studies was to determine the impact of improved iron status following Cu deficiency by supplementing the diet with iron. Cu deficiency was produced in pregnant Holtzman [Experiment 1 (Exp. 1)] or Sprague-Dawley [Experiment 2 (Exp. 2)] rats using two different diets. In Exp. 2, dietary Fe content was increased from 35 to 75 mg/kg according to NRC guidelines for reproduction. Cu-deficient (CuD) Postnatal Day 24 (P24) rats from both experiments demonstrated lower hemoglobin, serum Fe and serum triiodothyronine (T3) concentrations. However, brain Fe was lower only in CuD P24 rats in Exp. 1. Hemoglobin and serum Fe were higher in Cu adequate (CuA) P24 rats from Exp. 2 compared to Exp. 1. Cu- and TH-deficient rats from Exp. 2 exhibited a similar sensorimotor functional deficit following 3 months of repletion. Results suggest that Cu deficiency may impact TH status independent of its impact on iron biology. Further research is needed to clarify the individual roles for Cu, Fe and TH in brain development.

Maternal vitamin and iron supplementation and risk of infant leukaemia: a report from the Children's Oncology Group

Background:Prenatal supplementation has been inversely associated with childhood, but not with infant, leukaemia.Methods:Mothers of 443 cases of infant leukaemia diagnosed during 1996–2006 and 324 frequency-matched controls completed interviews. Associations were evaluated by unconditional logistic regression.Results:We observed no associations between prenatal vitamin (odds ratio (OR)=0.79, 95% confidence interval (CI): 0.44–1.42) or iron supplementation (OR=1.07, 95% CI: 0.75–1.52) and infant leukaemia after adjustment for race/ethnicity and income. Similar results were observed for leukaemia subtypes analysed separately.ConclusionThe observed null associations may be attributable to high supplementation rates and/or national fortification programmes.

Micronutrients, Birth Weight, and Survival

Maternal micronutrient requirements during pregnancy increase to meet the physiologic changes in gestation and fetal demands for growth and development. Maternal micronutrient deficiencies are high and coexist in many settings, likely influencing birth and newborn outcomes. The only recommendation for pregnancy currently exists for iron and folic acid use. Evidence is convincing that maternal iron supplementation will improve birth weight and perhaps gestational length. In one randomized trial, iron supplementation during pregnancy reduced child mortality in the offspring compared with the control group. Few other single micronutrients given antenatally, including vitamin A, zinc, and folic acid, have been systematically shown to confer such a benefit. A meta-analysis of 12 trials of multiple micronutrient supplementation compared with iron-folic acid reveals an overall 11% reduction in low birth weight but no effect on preterm birth and perinatal or neonatal survival. Currently, data are unconvincing for replacing supplementation of antenatal iron-folic acid with multiple micronutrients.

Prenatal Inflammation-Induced Hypoferremia Alters Dopamine Function in the Adult Offspring in Rat: Relevance for Schizophrenia

Maternal infection during pregnancy has been associated with increased incidence of schizophrenia in the adult offspring. Mechanistically, this has been partially attributed to neurodevelopmental disruption of the dopamine neurons, as a consequence of exacerbated maternal immunity. In the present study we sought to target hypoferremia, a cytokine-induced reduction of serum non-heme iron, which is common to all types of infections. Adequate iron supply to the fetus is fundamental for the development of the mesencephalic dopamine neurons and disruption of this following maternal infection can affect the offspring's dopamine function. Using a rat model of localized injury induced by turpentine, which triggers the innate immune response and inflammation, we investigated the effects of maternal iron supplementation on the offspring's dopamine function by assessing behavioral responses to acute and repeated administration of the dopamine indirect agonist, amphetamine. In addition we measured protein levels of tyrosine hydroxylase, and tissue levels of dopamine and its metabolites, in ventral tegmental area, susbtantia nigra, nucleus accumbens, dorsal striatum and medial prefrontal cortex. Offspring of turpentine-treated mothers exhibited greater responses to a single amphetamine injection and enhanced behavioral sensitization following repeated exposure to this drug, when compared to control offspring. These behavioral changes were accompanied by increased baseline levels of tyrosine hydroxylase, dopamine and its metabolites, selectively in the nucleus accumbens. Both, the behavioral and neurochemical changes were prevented by maternal iron supplementation. Localized prenatal inflammation induced a deregulation in iron homeostasis, which resulted in fundamental alterations in dopamine function and behavioral alterations in the adult offspring. These changes are characteristic of schizophrenia symptoms in humans.

The potential role of private pharmacies in maternal iron supplementation in rural Tanzania.

The reduction of maternal anemia is an agreed public health goal but one that has been very difficult to achieve. On Pemba Island, Tanzania, more than 90% of pregnant women are anemic, despite government efforts to identify and treat anemia during antenatal clinic visits. To investigate the potential of private pharmacies to be accessed for iron supplements for maternal anemia. We compared and contrasted the care given at private pharmacies and public clinics in terms of six characteristics: accuracy, affordability, availability, geographic accessibility, accommodation, and acceptability. We used data from in-depth interviews, surrogate customer encounters, governmental medicine record reviews, and participant observation. The accuracy of health care workers' advice about the treatment of anemia at private pharmacies and government clinics was similar. Supplements purchased at pharmacies were sometimes cheaper than the free supplements from the government, when the costs of transportation and time spent at the clinic were considered. Supplements at private pharmacies were always available, whereas the supply at government clinics was erratic. Private pharmacies were physically closer, socially less distant, and more accommodating than government clinics. Both clinics and private pharmacies were socially acceptable to pregnant women, although government clinics were typically not attended until later in pregnancy. The private sector probably has untapped potential for the reduction of maternal anemia in settings in which public health services fall short. Private pharmacies can contribute to the reduction of maternal anemia on Pemba Island and beyond.

Prenatal Diagnosis and Perinatal Management of Maternal—Fetal Congenital Parvovirus B19 Infection

In nonimmune pregnant woman, the primary infection with parvovirus B19 may lead to transplacental transmission to the fetus with variable outcomes, including congenital anemia, hydrops fetalis, fetal death or spontaneous resolution. The first case was of a 28-year-old woman, gravida 2, para 1, whose fetus was found to have left-sided pleural effusion on a sonogram at 29 weeks of gestation. A sample of aspirated pleural fluid was positive for parvovirus B19 by polymerase chain reaction. Cordocentesis showed fetal hemoglobin level of 5.0 g/dL. Intraperitoneal transfusion (IPT) was performed, because access to the fetal circulation was difficult. Thirty milliliters of group O, Rh-positive packed red cells were transfused into the peritoneal cavity. A non-hydropic baby weighing 2,680 g was delivered at 33 weeks of gestation. The neonates complete blood count examination showed a hemoglobin level of 16.3 g/dL. The newborn baby was discharged in stable condition. The second case was of a 31-year-old woman, gravida 2, para 1, whose fetus was found to have ascites, hypertrophic cardiomyopathy, and placentomegaly on a sonogram at 23 weeks of gestation. An amniotic fluid sample was positive for parvovirus B19 DNA by polymerase chain reaction. Fetal ascites and hypertrophic cardiomyopathy gradually resolved after maternal iron supplementation and 2 weeks of intrauterine digitalization therapy. A healthy infant weighing 3,198 g was delivered at 37 weeks of gestation. The neonates complete blood count examination showed a hemoglobin level of 10.3 g/dL. Termination of pregnancy is rarely indicated, because B19 virus is not teratogenic. Although intravascular transfusion offers obvious theoretical advantages, in some cases in which access to the fetal circulation is difficult or impossible, IPT should be performed combined with appropriate medical treatment. Thus, there is still a place for IPT in modern management of the severely anemic fetus, and this technique should not be neglected.

Reproductive Toxicity: Too Much of a Good Thing?

Vol. 114, No. 10 EnvironewsOpen AccessReproductive Toxicity: Too Much of a Good Thing? Valerie J. Brown Valerie J. Brown Search for more papers by this author Published:1 October 2006https://doi.org/10.1289/ehp.114-a578aAboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Pregnant women are famously exhorted to faithfully take their daily prenatal vitamins, which often contain iron and other minerals. But new research suggests that a weekly iron supplement coinciding with the renewal of the small intestine’s mucosal lining cells (where nutrient absorption occurs) works better than a daily supplement and prevents problems resulting from too much iron at the wrong times.Maternal iron deficiency and anemia early in gestation can result in premature birth and low birth weight. These, in turn, can trigger further problems ranging from slow physical growth and motor development to impaired emotional control. In severe cases, both maternal and fetal survival can be threatened at or near birth. Thus, there exists a near-global public health policy of maternal iron supplementation during pregnancy.The new study appears in the July 2006 issue of Archives of Medical Research. A team including nutritionist and epidemiologist Esther Casanueva of the National Institute of Perinatology Isidro Espinosa de los Reyes (INPerIER) in Mexico City and colleagues elsewhere in Mexico City and California studied 116 women receiving prenatal care at INPerIER. All had come to INPerIER for prenatal care by gestational week 20.None of the women were anemic at that point, but 66% had low levels of ferritin (the principal form of stored iron), suggesting low iron nutritional status. Half took 60 mg of iron as ferrous sulfate with 200 μg of folic acid and 1 μg of vitamin B12 once a day; the others took double this dose once a week. The researchers checked the women’s levels of hemoglobin (which transports oxygen) and ferritin every four weeks through the end of pregnancy.More of the women taking the weekly dose were mildly anemic (with hemoglobin levels shown not to carry any risk for mothers and infants) compared with the women taking the daily dose. However, by weeks 28 to 36, women taking the daily supplement had a significantly higher prevalence of hemoconcentration, a condition defined as hemoglobin levels above 145 g/L. Ironically, both early gestational iron-deficiency anemia and hemoconcentration later in pregnancy increase the risk of premature birth and low birth weight. Thus, the researchers suggest that excess iron supplementation can cause the same problems it is supposed to correct.Animal studies suggest that excess iron can also trigger formation of free radicals in the intestinal mucosa and other tissues, and that both iron deficiency and iron overload can damage nuclear DNA and mitochondrial DNA. This kind of damage has been implicated in cancer induction.The intestinal mucosa is renewed every 5 to 6 days and will absorb as much iron as necessary to maintain iron balance; however, mature cells will stop absorbing iron entirely if they are flooded with it, even if there is an iron deficit. “Maintaining a high iron environment in the intestine by ingesting significantly more iron than needed every day overwhelms this safety system,” says coauthor Fernando E. Viteri. A more subtly calibrated iron supplementation during pregnancy may be as effective as current public health recommendations, and perhaps safer.FiguresReferencesRelatedDetails Vol. 114, No. 10 October 2006Metrics About Article Metrics Publication History Originally published1 October 2006Published in print1 October 2006 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Cord serum ferritin levels, fetal iron status, and neurodevelopmental outcomes: Correlations and confounding variables

Cord serum ferritin levels, fetal iron status, and neurodevelopmental outcomes: Correlations and confounding variables

Anemia and iron deficiency: effects on pregnancy outcome

This article reviews current knowledge of the effects of maternal anemia and iron deficiency on pregnancy outcome. A considerable amount of information remains to be learned about the benefits of maternal iron supplementation on the health and iron status of the mother and her child during pregnancy and postpartum. Current knowledge indicates that iron deficiency anemia in pregnancy is a risk factor for preterm delivery and subsequent low birth weight, and possibly for inferior neonatal health. Data are inadequate to determine the extent to which maternal anemia might contribute to maternal mortality. Even for women who enter pregnancy with reasonable iron stores, iron supplements improve iron status during pregnancy and for a considerable length of time postpartum, thus providing some protection against iron deficiency in the subsequent pregnancy. Mounting evidence indicates that maternal iron deficiency in pregnancy reduces fetal iron stores, perhaps well into the first year of life. This deserves further exploration because of the tendency of infants to develop iron deficiency anemia and because of the documented adverse consequences of this condition on infant development. The weight of evidence supports the advisability of routine iron supplementation during pregnancy.

A maternal vegetarian diet in pregnancy is associated with hypospadias. The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.

To investigate the possible role of the maternal diet, particularly vegetarianism and consumption of phytoestrogens, in the origin of hypospadias, which is reported to be increasing in prevalence. Detailed information was obtained prospectively from mothers, including previous obstetric history, lifestyle and dietary practices, using structured self-completed questionnaires during pregnancy. Previously recognized associations with environmental and parental factors were examined, focusing particularly on the hypothesized hormonal link. Multivariate logistic regression was used to identify independent associations. Of 7928 boys born to mothers taking part in the Avon Longitudinal Study of Pregnancy and Childhood, 51 hypospadias cases were identified. There were no significant differences in the proportion of hypospadias cases among mothers who smoked, consumed alcohol or for any aspect of their previous reproductive history (including the number of previous pregnancies, number of miscarriages, use of the contraceptive pill, time to conception and age at menarche). Significant differences were detected for some aspects of the maternal diet, i.e. vegetarianism and iron supplementation in the first half of pregnancy. Mothers who were vegetarian in pregnancy had an adjusted odds ratio (OR) of 4.99 (95% confidence interval, CI, 2.10-11.88) of giving birth to a boy with hypospadias, compared with omnivores who did not supplement their diet with iron. Omnivores who supplemented their diet with iron had an adjusted OR of 2.07 (95% CI, 1.00-4.32). The only other statistically significant association for hypospadias was with influenza in the first 3 months of pregnancy (adjusted OR 3.19, 95% CI 1.50-6.78). As vegetarians have a greater exposure to phytoestrogens than do omnivores, these results support the possibility that phytoestrogens have a deleterious effect on the developing male reproductive system.

Decline in incidence of medulloblastoma in children

Medulloblastoma is one of the most common intracranial tumors in children. The perception that the incidence of this tumor has declined is reinforced by a decline in enrollment to international trials for the disease. A retrospective population-based study of children younger than 15 years whose brain tumors were reviewed histopathologically was performed in the county of Avon, in the southwest region of England from 1976 to 1991. Then, the incidence of medulloblastoma was studied in the noncontiguous southwest and northern regions of England, with a combined childhood population base of 20.0 million child years for the period 1976-1991. In Avon, 16 children with medulloblastoma presented in the period 1976-1984 and 2 in the period 1985-1991, representing a decrease in incidence from 9.6 per million per year to 1.7 per million per year. The incidence of medulloblastoma in the combined southwest and northern regions showed a significant (P = 0.006) decline from 5.5 per million per year in the period 1976-1984 to 2.8 in the period 1985-1991. Considered individually, the decline in the southwest (from 6.2 per million per year to 2.8 per million per year) was significant but that in the Northern region (from 4.7 to 2.7) was not. In this report, a decline in the incidence of medulloblastoma was shown. In a recent case control study, a protective effect of maternal folate, iron, and multivitamin supplementation against primitive neuroectodermal tumors, including medulloblastoma was found. The introduction of periconceptional multivitamin supplementation in the 1980s may have caused this significant decline in the incidence of medulloblastoma.

Effect of iron supplementation during lactation on human milk composition

There are no reports of studies specifically designed to test the effect of maternal iron supplementation on human milk composition. The purpose of this study was to evaluate the effect of moderate (40 mg Fe/day as FeSO 4) iron supplementation of nursing women for 3 months after delivery (non-supplemented, n = 14: supplemented, n = 14) on levels of iron, lactoferrin, total iron-ligands, and zinc in milk. Iron supplementation did not alter significantly iron and zinc levels in milk and the low iron to lactoferrin ratio was maintained, thus preserving the important functions of lactoferrin for the infant organism. However, iron supplementation increased total iron ligands in milk as measured by the total iron-binding capacity and increased the proportion of lactoferrin in total protein secreted. Also, lactoferrin levels tended (P = 0.059) to be higher in milk of the supplemented women. Our results suggest that the increase in total iron ligands and in the proportion of lactoferrin in total protein in milk after iron supplementation may be a response of the mammary gland to a higher plasma transferrin saturation. ( J. Nutr. Biochem. 5:331–337, 1994.)

Exclusive breast-feeding for 9 months: Risk of iron deficiency

Thirty-six infants who were exclusively breast-fed were observed for 9 months. Thirty-two infants who were completely weaned prior to age 3 1/2 months served as controls; these infants received iron supplementation in formula and solid foods. A great majority of exclusively breast-fed infants were able to maintain their iron status at the same level as that of the control infants. The mean concentration of hemoglobin was higher in breast-fed infants than in control infants at ages 4 and 6 months. However, six breast-fed infants required iron medication because they had laboratory evidence of iron deficiency, although none had anemia. Maternal iron supplementation during breast-feeding, even in large daily doses, did not have any effect on the infants' iron nutrition, nor prevent infants from developing some signs of iron deficiency. Our data indicate that it is safe in exclusively breast-fed infants to shift the starting age for introduction of iron to 6 months.

THE VALUE OF IRON SUPPLEMENTATION DURING PREGNANCY.

Summary: Haemoglobin and haematocrit values of 174 healthy primigravidae and secundigravidae on adequate diets were studied. Haemoglobin and haematocrit levels were unrelated to dietary iron intake. There was no significant difference in haemoglobin and haematocrit values of primigravidae and secundigravidae. None of the women developed anaemia (haemoglobin below 10 gm./100 ml.) The value of iron supplementation on maternal haemoglobin and haematocrit values could not be demonstrated, although the iron supplemented group had significantly higher haemoglobin values in the third trimester and on the fifth day after delivery than the unsupplemented group. This was no longer apparent six weeks and three months after delivery. Maternal iron supplementation had no effect on the cord haemoglobin levels and those of the offspring six weeks, three months, and six months post‐natally.