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BACKGROUND Gestational iron-deficiency anaemia has adverse pregnancy outcomes. Antenatal iron supplementation can be beneficial in anaemic women, but the effects in non-anaemic women are controversial. This observational study assessed the relationship of maternal iron stores (depleted or non-depleted) at gestational Weeks 8-12 with birthweight, in non-anaemic pregnant women following the guidelines of the Ministry of Health of Spain. METHODS Healthy, non-anaemic pregnant women (n = 205) were studied. At the first antenatal visit, a general clinical assessment was conducted, and basal blood taken. Women were classified as having non-depleted or depleted iron stores [serum ferritin (SF) < 12 µg/l)]. Daily antenatal iron supplements (48 mg on average) were started at 17 (range: 16-18) weeks. Blood haemoglobin, SF and transferrin saturation (TS) were measured in each trimester. RESULTS Of the study sample, 20, 54 and 66% had SF < 12 µg/l in the first, second and third trimesters, respectively. The prevalence of iron-depletion (SF < 12 µg/l) and iron-deficiency (SF < 12 µg/l and TS < 16%) was greater during the entire pregnancy in women with initial iron depletion versus no depletion (81.6 and 73.7% versus 61.7 and 55.4%, respectively, in the third trimester, P < 0.05). Women with initial iron-depletion delivered babies weighing on average 192 g less than that with initial iron stores, after adjusting for confounding variables (P = 0.028). CONCLUSIONS Beginning pregnancy with non-depleted iron stores is beneficial for the maternal iron status during pregnancy and infant birthweight. These findings reaffirm the importance of health promotion to ensure that women have adequate iron stores prior to, or early in, pregnancy when supplemented with moderate daily iron doses.

The iron endowment at birth depends, in large part, on the newborn's birth weight and gestational age. These are determined by many factors, some of which are maternal characteristics, including the following: maternal iron stores at her own birth and during her own early life, maternal growth and development, maternal age at conception, intergenesic intervals, maternal body characteristics and iron status at conception and during early pregnancy, gestational body weight gain, and iron status throughout gestation, particularly at conception and early pregnancy, and gestational body weight gain. Although less studied, paternal influences on the initiation and progression of pregnancy and on maternal environmental exposures are also important. Even though tools for the quantitative evaluation of women's iron status are very well developed, the quantitative estimation of body iron in the newborn and young infant remains a challenge. This article describes the crucial role played by the placenta in protecting the embryo and the fetus. In addition, neonatal health, particularly early in pregnancy, is briefly addressed, as are some important aspects of antenatal nutritional interventions that include iron.

This article summarizes thirty years of intensive clinical metabolic and therapeutic studies of the consequences of severe protein deficiency relative to calories, which results in kwashiorkor, and of a balanced deficiency of protein and calories that results in marasmus. Evidence is provided that these are two different metabolic diseases, but kwashiorkor is usually superimposed on some degree of chronic marasmus and hence most cases studied were marasmic kwashiorkor. The value of the creatinine/height index to indicate the degree of lean body cell mass with any disease is demonstrated.

Mutations in the HFE gene result in iron overload and can produce hereditary hemochromatosis (HH), a disorder of iron metabolism characterized by increased intestinal iron absorption. Dietary quality, alcoholism and other life-style factors can increase the risk of iron overload, especially among genetically at risk populations. Polymorphisms of the HFE gene (C282Y, H63D and S65C) were measured together with serum ferritin (SF), transferrin saturation (TS) and hemoglobin, to measure iron status, in randomly-selected healthy subjects living in the Spanish Mediterranean coast (n = 815; 425 females, 390 males), 18 to 75 years of age. The intake of dietary components that affect iron absorption was calculated from 3-day dietary records. The presence of C282Y/H63D compound heterozygote that had a prevalence of 2.8% in males and 1.2% in females was associated with an elevated TS and SF. No subject was homozygous for C282Y or S65C. The C282Y heterozygote, H63D heterozygote and homozygote and H63D/S65C compound heterozygote genotypes were associated with increased TS relative to the wild type in the general population. These genotypes together with the alcohol and iron intake increase the indicators of iron status, while calcium intake decreases them. We did not observe any affect of the S65C heterozygote genotype on these levels. All the HFE genotypes except for the S65C heterozygote together with the alcohol, iron and calcium intake affect the indicators of iron status. The C282Y/H63D compound heterozygote genotype has the higher phenotypic expression in our Spanish Mediterranean population.

Micronutrient deficiencies (MNDs) contribute significantly to the world's disease and mortality burden. Global efforts addressing MNDs have achieved significant yet heterogeneous progress across and within regions and countries. For vitamin A and iodine interventions, enhancing achievements in coverage require further political and financial commitment and targeting of hard-to-reach populations. Anemia control must focus on prevention among preschoolers and adolescent women and on integrated public health programs. Current international guidelines on iron supplementation and cut-off values for anemia need revision. For zinc, advocacy to accelerate the application of revised diarrhea management guidelines is critical, as are efficacy studies on food-based interventions and preventive supplementation.

We undertook this study to compare the effectiveness and safety of antenatal daily and weekly supplementation with iron, folic acid, and vitamin B(12) in healthy, pregnant women who were not anemic at gestational week 20.Women with singleton pregnancies and blood hemoglobin (Hb)115 g/L at gestational week 20 (equivalent to 105 g/L at sea level) were randomly assigned to two groups, one consuming one tablet containing 60 mg iron, 200 mug folic acid and 1 mug vitamin B(12) daily (DS, n = 56); the other consuming two tablets once weekly (WS, n = 60). Blood Hb and serum ferritin concentrations were measured every 4 weeks from weeks 20 to 36, and pregnancy outcomes were evaluated.Mild anemia and hypoferritinemia throughout pregnancy occurred less frequently in DS than WS. None of the 116 women had Hb concentrations103 g/L at any evaluation point. In contrast, hemoconcentration (Hb145 g/L) from gestational week 28 onwards occurred in 11% in DS and 2% in WS. We observed ex post facto that hemoconcentration at gestational week 28 was associated with a significantly higher relative risk of low birth weight (RR 6.23, 95% CI 1.46-26.57) and premature delivery (RR 7.78, 95% CI 1.45-24.74).In women who were nonanemic at gestational week 20, both schemes (DS and WS) prevented the occurrence of Hb levels100 g/L. DS women had a higher incidence of hemoconcentration. Hemoconcentration was associated with increased risk of low birth weight and premature delivery.

The community mobilization and social marketing program promoting a preventive approach of weekly iron-folic acid supplementation in women of reproductive age improved iron status of non-pregnant women in Vietnam. Three to six months of weekly pre-pregnancy supplementation and regular weekly intake of supplements during pregnancy allowed women to achieve good iron and hemoglobin status during the two first trimesters of pregnancy. In the third trimester, iron deficiency and anemia were notably present but low birth weight prevalence was low. This demonstrates the effectiveness and safety of the preventive approach as implemented here to prevent and control iron deficiency and anemia in women of reproductive age before and during pregnancy.

Most women worldwide enter pregnancy without adequate iron reserves or are already iron deficient. Estimates of iron needs during pregnancy are markedly reduced when iron reserves are available. The needs of absorbed iron to correct mild to moderate anemia in the last two trimesters are estimated. Pre-pregnancy and prenatal weekly supplementation can improve iron reserves effectively and safely, preventing excess iron and favoring better pregnancy outcomes. We explain how the weekly supplementation idea was developed, why current hemoglobin norms may be inadequately high (especially in pregnancy), and why excess iron as recommended by many agencies for developing populations can be undesirable.

The adverse effects of micronutrient deficiencies and excesses in children up to reproductive age are presented. A summary of risks and adverse functional and health outcomes associated with deficient and excessive intakes and nutrition status of iron, iodine, zinc, vitamins A and D, folate, vitamin B12, and riboflavin is presented. Nutrient-nutrient interactions of micronutrients, age, gender, and other host and environmental conditions, such as pregnancy, genetic conditions, overall nutrition, force of infection, and social conditions are considered as covariates in trying to define causation and outcomes due to specific micronutrients. The outcomes analyzed focus on growth and development, mental and neuromotor performance, immunocompetence, physical working capacity, morbidity, and in the case of pregnancy, overall reproductive performance. The results presented include responses to specific and multiple "experimental" interventions. A brief analysis of possible public health programs is presented, with emphasis on prevention.

Numerous studies have shown that iron-loaded diets increase markers of lipid peroxidation in rats, but few have addressed the effects of oral iron supplements on these markers. We investigated the effects of daily and intermittent iron supplements on iron and vitamin E status, and lipid peroxidation. Iron supplements were administered in doses equivalent to those often given to pregnant women in the developing world. In Study 1, iron-deficient (D) and iron-normal (N) rats were fed either 0 or 8000 microgram of supplemental iron daily for 21 d. In Study 2, D rats were fed either the same supplements daily or once every 3 d (8 supplements total). Lipid peroxidation was assessed by breath ethane and pentane and by malondialdehyde (MDA) (using GC-MS). In Study 1, daily supplemented N and D rats had liver nonheme iron concentrations that were 1.8- and 2.7-fold higher, respectively, than those in unsupplemented N rats. Breath ethane levels were also higher in supplemented rats (P < 0.05), but MDA (in plasma, liver, kidney) and liver vitamin E did not differ. Unexpectedly, severely D, anemic rats had significant elevations in the levels of breath ethane, liver MDA and kidney MDA. In Study 2, liver iron and breath ethane decreased progressively (P < 0.05) from 1 d to 3 d after the last iron dose in intermittently supplemented rats. We conclude that iron deficiency results in lipid peroxidation, but that its correction with daily iron supplements results in abnormal iron accumulation and increased lipid peroxidation in rats. These effects are mitigated by intermittent iron supplementation.

The iron status of a national sample of adults living in France and participating in the SU.VI.MAX cohort, was assessed using serum ferritin and hemoglobin concentrations. Complete data were obtained for 6648 women 35-60 y old and for 3283 men 45-60 y old. Assessment of iron dietary intakes was realized on a subsample of 3111 women and 2337 men who reported six 24 h dietary records during a one-year period; 22.7% of menstruating women and 5.3% of post-menopausal women presented a total depletion of iron stores (serum ferritin < 15 microg/l). Iron-deficient anemias were found in, respectively, 4.4% and less than 1% of these women. Three-quarters of the anemias were related to iron deficiency in menstruating women. In men, iron depletion and iron deficiency anemia were very rare. Post-menopausal women had much higher serum ferritin levels than menstruating women. In menstruating women, those using intrauterine devices had significantly lower serum ferritin levels than those without contraception, and much lower than those using oral contraception. The frequency of iron depletion reached 28.1% in women using intrauterine devices, but only 13.6% in those using oral contraceptives. The mean iron intake was 16.7 +/- 5.7 mg/d in men and 12.3 +/- 3.4 mg/d in women. Heme iron represented respectively, 11.1 and 10.4% of iron intake. Ninety-three percent of menstruating women had dietary iron intakes lower than recommended dietary allowances (RDA); 52.6% consumed less than two thirds of these RDA. In post-menopausal women and men, respectively 27.7% and 3.6% had dietary intakes lower than RDA. Serum ferritin was positively correlated with meat, fish and total iron intake, and negatively correlated with dietary products consumption, calcium and fiber intake.

In China 246 healthy children 3-6 years old were assigned to 1 of 3 groups (group 1: a daily dose of iron 6 days/week; group 2: same dose twice/weekly every 3-4 days; and group 3: same dose once/weekly every 7 days) to test the hypothesis that intermittent iron supplementation is more efficient and causes fewer side effects than daily iron administration. The children were attending the kindergarten of Chang-ji Autonomous Prefecture in Xinjian province. The researchers also divided the children into anemic (hemoglobin [Hb] 110 g/l) groups based on their baseline data. Anemic children comprised 36%. The anemic children had a greater response to iron supplementation in every regimen than nonanemic children. At the end of the study no child had anemia. All children fell within a normal probability plot for normally distributed values. The increments in Hb level as a result of the 3 iron supplementation regimens were greater than 10 g Hb/l for all anemic children and 37% of nonanemic children for a total of 59%. These 59% who were responsive to iron were considered to be at least iron deficient. All 3 regimens also increased serum ferritin levels. The nonanemic children receiving the supplements daily or twice weekly had significantly lower serum ferritin levels than the anemic children though. Among the anemic children the daily iron supplementation regimen resulted in a higher serum ferritin level than the other regimens (55.2 vs. 48.1 mcg/l for twice weekly and 26.7 mcg/l for weekly; p < 0.05). Undesirable side effects were more common in children receiving a daily supplement than their counterparts (37% vs. 7% for twice weekly and 4% for weekly). No anemic child receiving weekly supplements had undesirable side effects. Side effects were experienced by both anemic and nonanemic children receiving daily and twice weekly supplements. These findings indicate that the weekly dose regimen was the most efficacious regimen since it achieved the same hematological response with 1/6 the daily dose and produced almost no side effects.

10.1007/s00394-012-0468-4 Propose: To assess the factors associated with risk of haemoconcentration at delivery, such as initial haemoglobin levels and alterations in the HFE gene, and its effect on low birth weight in pregnant women supplemented with moderate doses of iron. Methods: Case-control study nested in a longitudinal study conducted on 217 healthy pregnant women taking moderate iron supplementation and their newborns. Women were classified according to the risk of haemoconcentration at delivery, defined as Hb > 130 g/L. Each subject's obstetric and clinical history, smoking habit, and iron biochemical parameters (haemoglobin (Hb), serum ferritin and transferrin saturation) were recorded at 1st, 2nd and 3rd trimester and at delivery. Polymorphisms of the HFE gene (C282Y, H63D and S65C) were also measured. Results: The average of iron supplementation of all the women was 43.9 mg/dia (geometric mean, 95 % CI: 43.6-44.1). Higher levels of Hb at early gestation and the presence of HFE mutations were associated with greater risk of haemoconcentration at delivery, adjusted odds ratios of 1.14 (95 % CI: 1.05-1.25) and 5.35 (95 % CI: 1.6-17.8). Haemoconcentration at delivery was associated with a greater risk of low birth weight, adjusted odd ratio of 11.48 (95 % CI: 1.13-116.6). Conclusions: Moderate daily doses of supplementary iron may be harmful for foetal growth in women with alterations in HFE gene and who started pregnancy with good haemoglobin levels. Overall, this suggests the importance of determining a woman's iron status early in her pregnancy in order to establish a more appropriate pattern of supplementation.

Anemia is highly prevalent, especially in poorly nourished populations living in unsanitary conditions. Studies of the Central American population showed that iron was the predominant deficient hematopoyetic micronutrient and that correction of nutrient deficiencies led to hematological normality as defined by WHO. The bioavailability of diverse iron compounds added to the mostly vegetable diets of such populations showed the superior absorption of chelated iron (NaFeEDTA) and its strong effectiveness in correcting iron deficiency when added to sugar. The consequences on development and mental behavioral functions as well as on work capacity of iron deficiency and anemia in infants, children and adults, and the positive effects of their correction was demonstrated. In protein-energy malnourished (PEM) children, the deficit in active tissue mass (basal oxygen consumption) and in total hemoglobin content were closely related. This relationship persisted as the rates of active tissue mass repletion was modified by levels of protein intake. This demonstrated the strong adaptive nature of hemoglobin content in response to oxygen needs in PEM and during recovery.Gastrointestinal functions in PEM and in populations demonstrated the bacterial invasion of the upper GI tract and how this resulted in secondary bile acids that are toxic to the intestinal mucosal cells impairing their absorptive functions. Environmental hygiene in populations reversed gut bacterial migration and improved GI function.

Background Intake of supplements containing iron or a combination of iron and folic acid by pregnant women may improve maternal health and pregnancy outcomes. Recently, intermittent supplementation regimens have been proposed as alternatives to daily regimens. Objectives To assess the effectiveness and safety of daily and intermittent use of iron or iron+folic acid supplements by pregnant women. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (March 2009) and contacted relevant organisations for the identification of ongoing and unpublished studies. Selection criteria All randomised or quasi-randomised trials evaluating the effect of supplementation with iron or iron+folic acid during pregnancy. Data collection and analysis We assessed the methodological quality of trials using the standard Cochrane criteria. Two authors independently assessed which trials to include in the review and one author extracted data. Main results We included 49 trials, involving 23,200 pregnant women. Overall, the results showed significant heterogeneity across most prespecified outcomes and were analysed assuming random-effects. The trials provided limited information related to clinical maternal and infant outcomes. Overall, daily iron supplementation was associated with increased haemoglobin levels in maternal blood both before and after birth and reduced risk of anaemia at term. These effects did not differ significantly between women receiving intermittent or daily iron or iron+folic acid supplementation. Women who received daily prenatal iron supplementation with or without folic acid were less likely to have iron deficiency at term as defined by current cut-off values than those who received no treatment or placebo. Side effects and haemoconcentration (a haemoglobin level greater than 130 g/L) were more common among women who received daily iron or iron+folic acid supplementation than among those who received no treatment or placebo. The risk of haemoconcentration during the second and third trimester was higher among those on a daily regimen of iron supplementation. The clinical significance of haemoconcentration remains uncertain. Authors' conclusions Universal prenatal supplementation with iron or iron+folic acid provided either daily or weekly is effective to prevent anaemia and iron deficiency at term. We found no evidence, however, of the significant reduction in substantive maternal and neonatal adverse clinical outcomes (low birthweight, delayed development, preterm birth, infection, postpartum haemorrhage). Associated side effects and particularly haemoconcentration during pregnancy may suggest the need for revising iron doses and schemes of supplementation during pregnancy and adjust preventive iron supplementation recommendations.

BACKGROUND It has been suggested that routine intake of supplements containing iron or combination of iron and folic acid during pregnancy improves maternal health and pregnancy outcomes. OBJECTIVES To assess the efficacy, effectiveness and safety of routine antenatal daily or intermittent iron supplementation with or without folic acid during pregnancy on the health of mothers and newborns. SEARCH STRATEGY We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (June 2005). Additionally, we contacted relevant organizations for the identification of ongoing and unpublished studies. SELECTION CRITERIA All randomised or quasi-randomised trials evaluating the effect of routine supplementation with iron or combination of iron and folic acid during pregnancy. DATA COLLECTION AND ANALYSIS We assessed trials for methodological quality using the standard Cochrane criteria. Two authors independently assessed the trials for inclusion and one author extracted data. We collected information on randomisation method, allocation concealment, blinding and loss to follow up. The primary outcomes included maternal and infant clinical and laboratory outcomes. MAIN RESULTS Forty trials, involving 12706 women, were included in the review. Overall, the results showed significant heterogeneity across most prespecified outcomes. Heterogeneity could not be explained by standard sensitivity analyses including quality assessment; therefore, all results were analysed assuming random-effects. Very limited information related to clinical maternal and infant outcomes was available in the included trials. The data suggest that daily antenatal iron supplementation increases haemoglobin levels in maternal blood both antenatally and postnatally. It is difficult to quantify this increase due to significant heterogeneity between the studies. Women who receive daily antenatal iron supplementation are less likely to have iron deficiency and iron-deficiency anaemia at term as defined by current cut-off values. Side-effects and haemoconcentration are more common in women who receive daily iron supplementation. No differences were evident between daily and weekly supplementation with regards to gestational anaemia; haemoconcentration during pregnancy appears less frequent with the weekly regimen. The clinical significance of hemoconcentration defined as haemoglobin greater than 130 g/L remains uncertain. AUTHORS' CONCLUSIONS Further studies are needed to assess the effects of routine antenatal supplementation with iron or a combination of iron and folic acid on clinically important maternal and infant outcomes.

Little is known about the long-term evolution, nutrition status, growth, and eventual deficiencies of patients with short bowel syndrome (SBS) adapted to oral feeding after parenteral nutrition (PN). Because there are not absolute criteria for weaning from parenteral or enteral nutrition to oral feeding, new nutrient deficiencies may develop. Subtle nutrition deficits could induce subclinical immune deficiencies; therefore, we studied long-term growth, nutrition status, and the state of the immune system in 10 patients with SBS after weaning PN for at least 2 years.Ten children with SBS (3-12 years old; mean, 7.4 years) who had not received PN for at least 2 years were studied. Anthropometric measurements, hemoglobin values, and indicators of iron, zinc, copper, folate and vitamin B(12) nutrition status were evaluated, along with immunoglobulins, lymphocyte subpopulations, and polymorphonuclear candidicidal activity.Weight-for-height was normal in 8 children; height-for-age was low in 5 children whose SBS was established early in life. Fat body mass was also low in 5 subjects. Four children presented macrocytosis, 2 with anemia. Low serum levels of vitamin B(12) (1 child), folates (4 children), and ferritin (2 children) were observed. Diminished candidicidal activity (4 children) was the only remarkable immunological abnormality.Many biologic and growth deficiencies are frequently seen in patients with SBS, even in children adapted to enteral feeding. This finding and the existence of previously unreported decreased candidicidal activity in some patients with SBS deserve long-term clinical and biologic follow up.

Daily iron supplementation programs for pregnant women recommend amounts of iron that are considered by some to be excessive and either lower-dose or less frequent iron supplementation regimens have been proposed. A randomized placebo-controlled study was performed to assess and compare the relative effectiveness of a weekly (WS) or twice weekly (TW) iron supplementation schedule in maintaining or achieving hemoglobin (Hb) levels at term considered to carry minimal maternal and fetal risk (90–130 g/L). Pregnant women (n = 116) at wk 10–30 of gestation (63 WS and 53 TW) were enrolled in the study (52 in WS and 44 TW completed the study). Women were randomly allocated to receive a 120-mg oral dose of iron as ferrous sulfate and 0.5 mg of folic acid weekly (n = 52) or 60 mg iron and 0.25 mg folic acid and a placebo twice weekly (n = 44). Hb hematocrit serum ferritin and transferrin saturation were estimated at baseline and at 36–39 wk of gestation. Baseline dietary data and the presence and intensity of intestinal helminthic infections were assessed. The duration of supplementation was 14 ± 4 wk and the median level of adherence was 60.5%. Hb concentrations improved in women following the TW regimen and in women following WS who had low baseline Hb levels. About 89% of WS women and 95% of TW women maintained Hb levels at term (between 90 g/L and130 g/L) a range associated with optimal pregnancy outcomes. One woman in the TW group exhibited higher Hb levels that potentially carried perinatal risk (>130 g/L). Intermittent iron and folic acid supplementation may be a valid strategy when used as a preventive intervention in prenatal care settings. (authors)

Pregnancy, mostly because of the mitochondria-rich placenta, is a condition that favors oxidative stress. Transitional metals, especially iron, which is particularly abundant in the placenta, are important in the production of free radicals. Protective mechanisms against free radical generation and damage increase throughout pregnancy and protect the fetus, which, however, is subjected to a degree of oxidative stress. Oxidative stress peaks by the second trimester of pregnancy, ending what appears to be a vulnerable period for fetal health and gestational progress. Conditions restricted to pregnancy, such as gestational hypertension, insulin resistance and diabetes, exhibit exaggerated indications of free radical damage. Antioxidants as well as avoidance of iron excess ameliorate maternal and early fetal damage. In rats both iron deficiency and excess result in free radical mitochondrial damage. Estimates of gestational iron requirements and of the proportion of iron absorbed from different iron supplemental doses suggest that with present supplementation schemes the intestinal mucosal cells are constantly exposed to unabsorbed iron excess and oxidative stress. Unpublished work carried out in Mexico City with nonanemic women at midpregnancy indicates that 60 mg/d of iron increases the risk of hemoconcentration, low birth weight and premature birth and produces a progressive decline in plasma copper. These risks are not observed in women supplemented with 120 mg iron once or twice per week. Studies on the influence of iron supplementation schemes on oxidative stress are needed.

Approximately two billion people, mainly women and children, are iron deficient. Two studies examined the effects of iron deficiency and supplementation on rats. In study 1, mitochondrial functional parameters and mitochondrial DNA (mtDNA) damage were assayed in iron-deficient (≤5 μg/day) and iron-normal (800 μg/day) rats and in both groups after daily high-iron supplementation (8,000 μg/day) for 34 days. This dose is equivalent to the daily dose commonly given to iron-deficient humans. Iron-deficient rats had lower liver mitochondrial respiratory control ratios and increased levels of oxidants in polymorphonuclear-leukocytes, as assayed by dichlorofluorescein ( P < 0.05). Rhodamine 123 fluorescence of polymorphonuclear-leukocytes also increased ( P < 0.05). Lowered respiratory control ratios were found in daily high-iron-supplemented rats regardless of the previous iron status ( P < 0.05). mtDNA damage was observed in both iron-deficient rats and rats receiving daily high-iron supplementation, compared with iron-normal rats ( P < 0.05). Study 2 compared iron-deficient rats given high doses of iron (8,000 μg) either daily or every third day and found that rats given iron supplements every third day had less mtDNA damage on the second and third day after the last dose compared to daily high iron doses. Both inadequate and excessive iron (10 × nutritional need) cause significant mitochondrial malfunction. Although excess iron has been known to cause oxidative damage, the observation of oxidant-induced damage to mitochondria from iron deficiency has been unrecognized previously. Untreated iron deficiency, as well as excessive-iron supplementation, are deleterious and emphasize the importance of maintaining optimal iron intake.

This 7-mo double-blind study compared the efficacy of two iron supplementation schemes in improving iron nutrition among 116 healthy fertile-age women. They were randomly distributed in three groups, receiving: Group 1, iron + folate (60 mg and 250 microg, respectively) daily for 3 mo (currently recommended scheme), and folate (250 microg) weekly the subsequent 4 mo. Group 2, folate daily, and 60 mg iron only once weekly for 3 mo, and then weekly iron + folate for 4 mo. Group 3, folate daily for 3 mo and then weekly for 4 mo. At baseline, 16% had depleted stores (plasma ferritin

Iron supplementation, mostly with a therapeutic orientation, has been a key strategy for the short-term control of iron deficiency and ferropenic anemia. It has been used almost exclusively in antenatal clinics, but in spite of its confirmed efficacy in supervised trials, it has proven ineffective in practice in most developing countries. Poor effectiveness has been attributed to various factors including insufficient dose and time of supplementation and poor adherence. These problems have led to the administration of high iron doses, which have proven equally ineffective in practice. This paper introduces four concepts: (1) that iron supplementation targeted to pregnant women should cover the full reproductive cycle, from prepregnancy to at least the end of lactation instead of only the pregnant woman; (2) that entering pregnancy with iron deficiency contributes to the failure of antenatal iron supplementation and that prepregnancy iron reserves increase the effectiveness of antenatal supplementation; (3) that medium- to long-term weekly ingestion of proper iron-folate supplements, with a preventive aim and directed to all risk groups, should be community based rather than health service based but supervised by the latter (in this sense, preventive supplementation is equal to targeted iron fortification); and (4) that preventive supplementation, based on weekly dosing, has proven efficacious. Problem-oriented research to evaluate the sustainability and medium- to long-term efficacy of these concepts is called for. The bases for the concepts and suggestions are summarized in this paper.

AIM: To evaluate the anthropometric, iron, B12 Vitamin and folate nutritional condition in patients with short bowel syndrome (SBS) after suspending parenteral nutrition (PN) for no less than 2 years. PATIENTS AND METHODS: We studied 10 pediatric patients with SBS. Anthropometric parameters evaluated: weight, height, brachial perimeter, and width of subscapular, suprailiac, bicipital and tricipital cutaneous folds with Lange caliper. Waterlow′s classification of nutritional condition was used according to weight/height (W/H) and height/age (H/A) fitting percentages, usinge NCHS reference tables. Values, volume and concentration of hemoglobin were assessed, as well as those of ferritin, transferrin, ferremia and percent saturation of transferrin, folic acid, and B12 vitamin. A nutritional survey was also performed. RESULTS: The age range of the patients was 3.3 - 12.9 yrs. The mean of residual bowel was 46.3 cm (range:20–70), jejunum: 30.4 (10–60), ileum 17.9 cm (0–60). The average time of PN dependence was 378.5 days (range:70 – 900). W/H was normal in 8 patients, with a Score I deficit in 2 patients and a low percent of fatty and lean body mass in 1 patient. H/A was abnormally low in 5 patients: 3 Score 1, and 2 Score II. Height was already affected during the PN period The percent of adipose mass was low in 5 patients. Three patients presented anemia, two of which also developed macrocytosis. Such alteration in MCV was also found in two cases where anemia was absent. The levels of B12 vitamin (1 patient) and serum folates (4 patients) were low. The nutritional survey showed that the average daily intake of B12 vitamin and folic acid was adequate, while 50% of patients could not adapt to the intake of iron. Caloric and protein intakes were 110 (range: 67–238) and 326 (r:122–684), respectively. CONCLUSION: Malabsorption of macro and micronutrients can manifest subtly and late. Height in 50% of patients was affected since they were receiving PN. Despite the protein intake fitting percent was well above 100% in all patients, they would apparently not be able to develop a compensatory growth capacity in the post-PN period. Both nutritional control and long-term clinical-biological follow-up should be very strict in SBS patients after PN retrieval.

The mechanisms of the previously described competitive zinc:iron interaction were explored in healthy human volunteers, using the increment in plasma zinc concentration after an oral dose of 25 mg of zinc as zinc sulfate as the index of zinc absorption. Ferric iron in a 2:1 Fe/Zn ratio reduced the plasma uptake of zinc, but to a significantly lesser degree than ferrous iron; addition of 1 g of ascorbic acid increased the magnitude of the inhibitory effect of ferric iron to that seen with ferrous iron. An inverse relationship between some indices of iron status in adult women, or of parenteral iron administration in a child, and the magnitude of zinc:iron interaction was observed. Saturation of the intestinal mucosa with consecutive-day doses of therapeutic iron did not influence the uptake of zinc administered alone or in the context of a 2:1 ferrous iron:zinc ratio in solution. The results are most consistent with a combination of an intraluminal competition of the two minerals and an intracellular competition at a site "distal" to the regulatory step by which iron nutriture modulates the entry of iron into the body, but "proximal" to the site at which the daily administration of therapeutic doses of iron blocked the passage of dietary iron.

Duodenal aspirates from PCM patients and from children with diarrhea present quantitative and qualitative alterations in their content of bile acids, consisting mainly in decreased concentrations of conjugated bile acids (CBA) and increased amounts of primary and secondary free bile acids (FBA). In the absence of diarrhea, PCM was associated with relatively uniform decrements of CBA, increasing to normal levels with nutritional recovery; the amounts of primary and secondary FBA did not change significantly with recovery. The effect of diarrhea on the bile composition of the children varied depending on the patient's nutritional status: a) In recovered children with diarrhea, all CBA, especially the taurine conjugates, were decreased; the glycine/taurine (G/T) ratios were above 1:4 in most of these patients. Although all FBA increased with diarrhea, such an increase was most significant in cholic and lithocholic acids; these children also presented high FBA/CBA ratios. b) In PCM children, the degree of decrement of CBA during diarrhea was similar in taurine and glycine conjugates, the G/T ratio remaining within normal limits. The concentrations of primary and secondary FBA did not change significantly in PCM children with diarrhea when compared with the group without diarrhea. It is believed that the changes in bile acids observed in these children are due to the interaction of malnutrition, diarrhea, and an increased gastrointestinal flora. A theory of how the bile acid events described herein occur is also proposed. Am. J. C/in. Nutr. 27: 788-796, 1974.

The relationship between individual modernization and elevated arterial blood pressure was examined in a study in urban Brazil. We hypothesized that elevated blood pressure would result from the discrepancy between an individual's style of life and his or her economic resources; specifically, we suggested that when modern life-style acquisition exceeded economic resources, a circumstance referred to as “life-style stress,” blood pressure would be elevated. This factor was related to diastolic, but not systolic, blood pressure, independently of a variety of biologic, dietary, and sociocultural confounding factors. The perceived change associated with life events also predicted diastolic, but not systolic, blood pressure. Other predictors of diastolic blood pressure were calcium intake, fat intake, race, age, and the body mass index. We argue that sociocultural risk factors emerge in the modernization process as a result of social structural imbalances generated by economic development and represent independent risk factors for elevated arterial blood pressure.

A collaborative study of nutritional anemia in third trimester pregnancy was performed in seven Latin American countries. Laboratory measurements included hemoglobin level, mean corpuscular hemoglobin concentration (MCHC), serum iron and iron-binding capacity, serum folate, vitamin B12 and albumin. Iron deficiency (transferrin saturation below 15%) was found in 48% of pregnant women, as compared with 21% of nonpregnant females and 3% of male controls of comparable age. The prevalence of folate deficiency (serum folate below 3 ng/ml.) was 10%, 10% and 9% in these three groups, respectively. Vitamin B12 deficiency (serum level below 80 pg/ml.) was found in 15% of pregnant women, but in less than 1% of both control groups. Anemia, as defined by current WHO criteria, was found in 38.5% of pregnant women, 17.3% of nonpregnant women and 3.9% of men. Analysis of the frequency distribution for hemoglobin levels, based on a Gaussian distribution in normal subjects, suggested that a large portion of subjects considered anemic by WHO criteria were normal and that the true incidence of anemia in pregnant and nonpregnant females was 22 and 12% respectively. Correlation analysis indicated that iron deficiency was of major importance as a cause of anemia, while folate lack was contributory only in pregnancy; no relationship could be demonstrated between vitamin B12 deficiency and anemia.

NEvIN S. SCRIMSHAW, PII.D., M.D.� O NE of the consequences of the severe protein malnutrition underlying kwashiorkor is a decrease in the activity of various enzymes as measured in blood serum, tissues, and duodenal contents. ‘ Thompson and Trowell’ and G#{243}mez ci a!.’ have reported that the activities of lipase, trypsin, and amylase are reduced in the duodenab secretions of kwashiorkor patients. Of the three enzymes lipase appears to be the first to be affected, followed by trypsin.’ These biochemical findings are consistent with the histologic damage observed in the pancreas and intestine when the disease is severe.4’ A decrease in pancreatic bipase and in bile salts as well as functional alterations of the small intestine, are known to impair the absorption of vitamin A. In the course of studies in children with kwashiorkor in Central America6 very low serum levels of vitamin A have been found and ocular lesions suggestive of vitamin A deficiency are observed. From the Institute of Nutrition of Central America and Panama (INCAP), Guatemala, CA. This study was assisted by funds from the Nutrition Foundation, Inc. and National Institute of Arthritis and Metabolic Diseases of the National Institutes of Health (A-981), Public Health Service. Reported in part at the Annual Meeting of the American Institute of Nutrition

The creatinine height index (CHI), which consists of the following ratio: CHI: 24 hour creatinine excretion of subject 24 hour creatinine excretion of normal child of same height has been devised for estimating the relative muscle mass of children. Age is not considered because children of developing areas are very often retarded in height. The normal CHI is close to 1.0, both in well nourished children and in fully recovered malnourished ones, with heights ranging from 64.8 to 135 cm. Protein calorie malnourished (PCM) children of the edematous type (kwashiorkor and kwashiorkormarasmus) had CHI's ranging from 0.25 to 0.75, lower CHI's were observed in more severely malnourished children and vice versa. In clinically marasmic children (PCM without edema) the CHI ranged from 0.33 to 0.85, independent of the degree of weight deficit or the clinical severity of marasmus, indicating that severe caloric deficiency can occur with a wide range of muscle wasting. No creatinine retention was observed in any PCM children with adequate urine flows. Independent estimates of protein and calorie repletion were obtained during recovery by the use of CHI and weight for height. A significant negative correlation between CHI and N retention was found, indicating the physiological significance of the CHI in estimating protein nutrition.

The peak rise in breath hydrogen and the volume of excess pulmonary excretion of hydrogen in response to a 10 g dose of the non-absorbable disaccharide, lactulose, was significantly lower in children with active gastroenteritis and diarrhea than in non-diarrheal controls. Thus, despite the fact that the H2 breath test is a convenient, noninvasive technology for use in children, it cannot be recommended for measuring carbohydrate malabsorption in individuals with active, on-going episodes of diarrhea.

This paper selectively reviews the main findings of studies on the possible effects of iron deficiency on cognitive function among infants and preschool children published after 1976, and presents data from a study recently conducted in rural Guatemala. In comparison to infants without signs of sideropenia, infants with iron deficiency with and without anemia tend to score lower in the Bayley Scale of Mental Development; conversely, there is no evidence for an association between iron deficiency and delayed motor development. Iron repletion therapy implemented over a period of 7 to 10 days is likely to result in an improvement in mental development scale scores among infants with iron deficiency with or without anemia. In comparison with preschool children without sideropenia, preschool children with iron deficiency with or without anemia are less likely to pay attention to relevant cues in problem solving situations.

To assess the effects of iron therapy on developmental test scores in infants with iron deficiency anemia, 68 Guatemalan babies 6 to 24 months of age, with and without mild iron deficiency anemia, were tested with the Bayley Scales of Infant Development before and after one week of oral iron treatment. The two major findings of the study were developmental deficits in the anemic group prior to treatment, and lack of rapid improvement with short-term oral iron therapy. The mean pretreatment Mental Development Index of the anemic group was significantly lower than that of nonanemic infants. The anemic group's pretreatment Psychomotor Development Index was also lower than that of the nonanemic control group. In a double-blind randomized study, six to eight days of oral iron therapy did not reverse these deficits. Consequently, the deficits of the anemic group cannot be unequivocably attributed to iron lack. However, no significant differences were found between anemic and nonanemic groups in birth histories, socioeconomic level, or general nutritional status which might otherwise explain the lower developmental test scores of the anemic babies.

Publisher Summary This chapter discusses the clinical aspects of protein malnutrition. Protein malnutrition tends to be manifest primarily in young children and is a major factor in the high mortality rate of children in the 1–4 year age group, which in technically underdeveloped areas is 20 to 60 times greater than in the United States and Western Europe. Most of the excessive mortality of preschool children characterizing these areas is because of the interaction between protein malnutrition and infection. Very young children are less likely to suffer from protein deficiency because of the probability that they can be receiving breast milk when the parents cannot afford other food sources or cannot use them properly. The multiple factors responsible for protein malnutrition can be conveniently classified as those relating to the agent, the host, and the environment. A large majority of the preschool children in the areas where the acute protein malnutrition of kwashiorkor is prevalent go through a period of chronic protein deficiency.

In its severe form, protein malnutrition is most frequently seen today in young children. Under the name ofsindrome pluricarencial de la infancia(S. P. I.) in the Spanish-speaking countries, and kwashiorkor in most other parts of the world, a well-defined protein deficiency syndrome is common in children 1 to 5 years of age in most underdeveloped areas of the world. The condition begins to develop as soon as the quantity of protein contained in the mother's milk becomes inadequate for the needs of the growing child. The amount of protein obtained by the nursing infant becomes inadequate sometime after the 8th to 10th month. This inadequacy steadily increases until the time of weaning, when the child is likely to receive a diet containing a high proportion of carbohydrate and little or no protein of animal origin. During this period, the growth and maturation of the child are greatly slowed.

ministration of Lipomul#{174} IV. (Upjohn) in man have virtually disappeared, continuous multiple infusion therapy has been associated with a severe reaction, sometimes called the ‘ ‘over-loading syndrome, ‘ ‘ but better referred to as the long-term 3 The latter is characterized by the abrupt onset of fever, hepatosplenomegaly, anemia and hemorrhagic manifestations. It may develop at any time, even several days after completion of the series, but never before at least the twelfth infusion, and more frequently after sixteen or more. Although one or all the features of the syndrome may be present in any one patient, the anemia arid hemorrhagic complications are the most striking and lifethreatening. The incidence of these reactions is difficult to ascertain, since most investigators have been rightly unwilling to explore the regularity of occurrence for ethical reasons. Since a similar syndrome cannot be produced in animals with comparable dosage schedules, we may never know its true incidence. Nonetheless, it should be noted that many patients can be given extremely large quantities of the emulsion without ever having any serious complications. However, regardless of incidence, the threat of such a reaction precludes general acceptance of Lipomul IV. except for shortterm administration.

Children hospitalized for acute protein-calorie malnutrition in Guatemala City were not delayed in ossification status as compared with Guatemalan Indian children on their customary low-protein diets, but were markedly and often dramatically deficient in cortical bone.

Background: Iron deficiency and its consequent anemia constitute the commonest micronutrient deficiency in the world. Objective: We investigated whether long-term, weekly iron-folate supplements administered at school would improve hemoglobin and ferritin concentrations in adolescent girls, including those with mild-to-moderate anemia and hemoglobin concentrations indicating borderline anemia. Design: Subjects were 266 girls with hemoglobin concentrations of 80-119.9 g/L (group A) and 358 girls with hemoglobin concentrations of 120-130 g/L (group B) who were otherwise healthy. Two hundred sixty-six girls in group A and 268 girls in group B were randomly assigned to receive either 60 or 120 mg Fe plus 3.5 mg folic acid weekly for 22 wk. Ninety of the girls in group B wi:re randomly assigned to receive only 5 mg folic acid weekly. Capillary hemoglobin and plasma ferritin were measured at baseline and after 12 and 22 wk of supplementation. Results: By the end of the study, 2% of the girls had dropped out and >96% hart taken greater than or equal to 20 of the 22 tablets; side effects were minimal. Mean plasma ferritin increased significantly in all iron-supplemented groups, independently of initial hemoglobin values and iron doses. Ferritin concentrations decreased in the girls supplemented with folic acid only. As expected, hemoglobin responses to iron were higher in group A than in group B and increases were positively correlated with initial plasma ferritin. Hemoglobin failed to respond to folate supplementation if initial plasma ferritin concentrations were low. Mean hemoglobin increased significantly and consistently in relation to the length of treatment. Conclusion: Long-term, weekly iron-folate supplementation was found to be a practical, safe, effective, and inexpensive method for improving iron nutrition in adolescent schoolgirls.