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To evaluate the effect of iron supplementation on serum copper and zinc levels.
In a randomized, double-blind, placebo-controlled trial, 66 pregnant women with hemoglobin 13.2 g/dL or greater between the 13th and 18th week of pregnancy were randomized into case and control groups. From the 20th week until the end of pregnancy the case group received one ferrous sulfate tablet containing 50 mg elemental iron daily, while the control group received placebo. Hemoglobin, ferritin, copper, and zinc levels at 24-28 and 32-36 weeks of pregnancy were measured and compared.
In the case group, serum copper levels in the second and third trimester were significantly lower than the control group (P<0.01 and P<0.001, respectively). Serum zinc levels in the case group in the second and third trimester were also significantly lower than the control group (P<0.001).
Iron supplementation in pregnant women with hemoglobin greater than 13.2 g/dL reduces serum levels of copper and zinc.
To read the full-text of this research, you can request a copy directly from the authors.
... Sodium intake among people with normal and high blood pressure was studied in Ajani . The e ects of iron supplementation on serum copper and zinc levels in pregnant women with high-normal hemoglobin was investigated in . Association between parity and breastfeeding with maternal high blood pressure was discovered in . ...
... The last term is obtained by the equalities (8) and (20). The following lemma that may be obtain with a straightforward calculation can be used to compute the mathematical expectation of the random variable Va with pdf (20). ...
... The last term is obtained by the equalities (8) and (20). The following lemma that may be obtain with a straightforward calculation can be used to compute the mathematical expectation of the random variable Va with pdf (20). ...
In the statistical literature, truncated distributions can be used for modeling real data. Due to error
of measurement in truncated continuous data, choosing a crisp trimmed point caucuses a fault inference, so
using fuzzy sets to define a threshold pointmay leads us more efficient results with respect to crisp thresholds.
Arellano-Valle et al.  defined a selection distribution for analysis of truncated data with crisp threshold. In
this paper, we define fuzzy multivariate selection distribution that is an extension of the selection distributions
using fuzzy threshold. A practical data set with a fuzzy threshold point is considered to investigate the
relationship between high blood pressure and BMI.
... The presence of appreciable amount of folic acid and vitamins has been reported to be essential for normal embryogenesis (1)(2)(3). There is reliable evidence indicating that maternal micronutrient status contributes to pregnancy outcome (4)(5)(6)(7)(8)(9). A possible link has been suggested between nutrient deficiencies and reproductive risk factors. ...
... Interest has focused mainly on the risk of malformations. An association between intake of micronutrients, such as folic acid and zinc, magnesium and iron, and pregnancy outcome has been investigated (1)(2)(3)(4)(5)(6)(7)(8)(9). ...
Spontaneous abortion is the most common adverse pregnancy outcome. We aimed to investigate a possible link between nutrient deficiencies and the risk of spontaneous abortion.
Materials and Methods
This case-control study included the case group (n=331) experiencing a spontaneous abortion before 14 weeks of pregnancy and the control group (n=331) who were healthy pregnant women over 14 weeks of pregnancy. The participants filled out Food Frequency Questionnaire (FFQ), in which they reported their frequency of consumption for a given serving of each food item during the past three months, on a daily, weekly or monthly basis. The reported frequency for each food item was converted to a daily intake. Then, consumption of nutrients was compared between the two groups.
There are significant differences between the two groups regarding consumed servings/day of vegetables, bread and cereal, meat, poultry, fish, eggs, beans, fats, oils and dairy products (P=0.012, P<0.001, P=0.004, P<0.001, P=0.019, respectively). There are significant differences between the two groups in all micronutrient including folic acid, iron, vitamin C, vitamin B6, vitamin B12 and zinc (P<0.001).
Poor nutrientions may be correlated with increased risk of spontaneous abortion.
... Thus, in the recently published guidelines by the WHO, 30 -60 mg of elemental iron supplementation is advised for all pregnant women (4). However, excessive iron consumption might lead to an increase in Hb levels and blood viscosity (5)(6)(7)(8)(9)(10). This condition results in poor placental blood transfusion and adversely affects birth outcome such as preterm delivery, low birth weight (LBW), intra-uterine growth retardation (IUGR), postnatal growth retardation, low fetal head circumfer-ence, preeclampsia, and maternal hypertension, as well as fetal and early neonatal death, neurological and skeletal abnormalities, abnormal lung development, and even prenatal mortality (5,6,(9)(10)(11)(12). ...
... However, excessive iron consumption might lead to an increase in Hb levels and blood viscosity (5)(6)(7)(8)(9)(10). This condition results in poor placental blood transfusion and adversely affects birth outcome such as preterm delivery, low birth weight (LBW), intra-uterine growth retardation (IUGR), postnatal growth retardation, low fetal head circumfer-ence, preeclampsia, and maternal hypertension, as well as fetal and early neonatal death, neurological and skeletal abnormalities, abnormal lung development, and even prenatal mortality (5,6,(9)(10)(11)(12). Moreover, it is clear that oral iron consumption may be unpleasant due to increasing gastrointestinal complications such as nausea, vomiting, abdominal pain. ...
Iron supplementation is a chief component in prenatal care, with the aim of preventing anemia; however, extreme maternal iron status may adversely affect the birth outcome. Given the negative consequences of high maternal iron concentrations on pregnancy outcomes, it seems that iron supplementation in women with high hemoglobin (Hb) should be limited.
The aim of this study was to examine the effect of iron supplementation on iron status markers in pregnant women with high Hb.
Patients and methods:
In a randomized, double-blind, placebo-controlled trial, 86 pregnant women with Hb > 13.2 g/dL and ferritin > 15 μg/l in the 16th - 20th week of pregnancy were randomized into experimental and control groups. From the 20th week until the end of pregnancy, the experimental group received one ferrous sulfate tablet containing 50 mg of elemental iron daily, while the control group received a placebo. Hb and ferritin levels at 37 - 39 weeks of pregnancy were evaluated and compared. In addition, after delivery the birth weight was measured in two groups and compared.
There were statistically significant differences between the two groups in Hb (p = 0/03) and ferritin (p = 0/04) levels at the end of pregnancy, but the incidence of anemia exhibited no difference in either group (p < 0/001). In addition, the mean of birth weight in experimental group and control group were 3391/56 ± 422, 3314/06 ± 341, respectively and it was not significant difference (p = 0.2).
Not using iron supplementation did not cause of anemia in women with Hb concentrations greater than 13.2 g/dL during pregnancy; thus, the systematic care and control of iron status markers without iron supplementation is recommended for these women.
... Women in the first trimester of pregnancy who additionally received multivitamin preparations containing 60-65 mg of Fe showed a reduction in Zn absorption compared to women receiving less than 30 mg Fe/day . Ziaei et al.  estimated that HgB greater than 13.2 g/dL in pregnant women reduces serum Zn levels. Andersen et al.  suggested that Cu deficiency has not only a direct effect on the concentration of Fe, but also an indirect effect through regulation of Fe transporters, which, inter alia, affects the delivery of Fe to the fetus. ...
Iron (Fe), copper (Cu), and zinc (Zn) are microelements essential for the proper functioning of living organisms. These elements participatein many processes, including cellular metabolism and antioxidant and anti-inflammatory defenses, and also influence enzyme activity, regulate gene expression, and take part in protein synthesis. Fe, Cu, and Zn have a significant impact on the health of pregnant women and in the development of the fetus, as well as on the health of the newborn. A proper concentration of these elements in the body of women during pregnancy reduces the risk of complications such as anemia, induced hypertension, low birth weight, preeclampsia, and postnatal complications. The interactions between Fe, Cu, and Zn influence their availability due to their similar physicochemical properties. This most often occurs during intestinal absorption, where metal ions compete for binding sites with transport compounds. Additionally, the relationships between these ions have a great influence on the course of reactions in the tissues, as well as on their excretion, which can be stimulated or delayed. This review aims to summarize reports on the influence of Fe, Cu, and Zn on the course of single and multiple pregnancies, and to discuss the interdependencies and mechanisms occurring between Fe, Cu, and Zn.
... High Fe intakes (another commonly used mineral supplement), particularly if coupled with low dietary Cu intake, can also lower Cu status. Recent evidence shows that supplementation of Fe to pregnant women who have good Fe status can reduce serum Cu, increase the risk for hypertension in the mother, and increase the incidence of small-forgestational age in the offspring, arguing against indiscriminate Fe supplementation during pregnancy [25,26]. Fe supplements can also reduce indices of Cu status in breastfed infants  and increase morbidity . ...
Copper (Cu) is an essential nutrient whose requirement is increased during pregnancy and lactation. These represent times of critical growth and development, and the fetus and neonate are particularly vulnerable to deficiencies of this nutrient. Genetic mutations that predispose the offspring to inadequate stores of Cu can be life threatening as is observed in children with Menkes disease. During the last decade, severe Cu deficiency, once thought to be a rare condition, has been reported in the literature at an increasing frequency. Secondary Cu deficiencies can be induced by a variety of ways such as excessive zinc or iron intake, certain drugs, and bariatric surgery. Premature and low birth weight infants can be born with low Cu stores. A number of mechanisms can contribute to the teratogenicity of Cu including decreased activity of select cuproenzymes, increased oxidative stress, decreased nitric oxide availability, altered iron metabolism, abnormal extracellular matrix protein crosslinking, decreased angiogenesis and altered cell signaling among others. The brain, heart, and vessels as well as tissues such as lung, skin and hair, and systems including the skeletal, immune, and blood systems, are negatively affected by suboptimal Cu during development. Additionally, persistent structural, biochemical, and functional adverse effects in the offspring are noted even when Cu supplementation is initiated after birth, supporting the concept that adequate Cu nutriture during pregnancy and lactation is critical for normal development. Although Cu-containing IUDs are an effective method for increasing intrauterine Cu concentrations and for reducing the risk of pregnancy, high amounts of dietary Cu are not thought to represent a direct developmental risk.
... Similarly, a randomized placebo-controlled trial has shown that women receiving high doses of ferrous sulfate [150 g tablet, containing 50 mg of elemental iron) had higher rates of SGA neonates (15.7 %) compared to placebo groups (10.3 %) . Excess iron intake may lead to increased blood viscosity with impaired poor placental perfusion and increased oxidative stress , as well as negative influence on the absorption of other minerals . Epidemiological studies have shown that excess iron intake in pregnancy may be associated with increased risk for preeclampsia, gestational diabetes mellitus , and infant convulsions . ...
We examined whether high doses of folic acid and iron supplementation in early-to-mid pregnancy affect the risk of preterm birth, low birth weight, and small for gestational age neonates, in the mother–child cohort in Crete, Greece (Rhea study).
We included 1,279 women with singleton pregnancies with complete data on supplements use in early-to-mid pregnancy and birth outcomes. Anthropometric measurements at birth were obtained from medical records. Red blood cell folate concentrations in cord blood were measured in a subsample of the study population (n = 58).
Sixty-six percent of the study participants reported high doses of supplemental folic acid use (5 mg/day), while 21 % reported excessive doses of folic acid use (>5 mg/day) in early-to-mid pregnancy. Daily intake of 5-mg supplemental folic acid was associated with a 31 % decrease in the risk of preterm birth (RR, 0.69; 95 % CI, 0.44, 0.99), 60 % decrease in the risk of delivering a low birth weight neonate (RR, 0.40; 95 % CI, 0.21, 0.76), and 66 % decrease in the risk of delivering a small for gestational age (SGA) neonate (RR, 0.34; 95 % CI, 0.16, 0.73). Daily doses of iron supplementation more than 100 mg were associated with a twofold increased risk for SGA neonates (RR, 2.14; 95 % CI, 0.99, 5.97).
These findings suggest that high daily doses of supplementary folic acid in early-to-mid pregnancy may be protective for preterm birth, low birth weight, and small for gestational age neonates, while high daily doses of supplementary iron may be harmful for fetal growth.
... in blood estrogens and decreased biliary excretion which is common in pregnancy. [8,35] The relationship between copper and iron has been a subject for debate. It has been shown that iron supplementation in pregnant women (with hemoglobin greater that 13.2 g/ dL) significantly reduced serum copper concentrations in both second and third trimesters.  Furthermore, Ghosh et al.  reported higher serum copper concentration in anemic pregnant women than in non-anemic ones in both second and third trimesters. This supported the view that iron has the potency of inducing negative copper concentrations or limiting its bioavailability in pregnancy. This phenomenon should be taken into co ...
Copper and selenium are important trace elements in man. They function as antioxidants and play roles in oxido-reductase reactions. Several imported multivitamin preparations are given to our women during pregnancy and lactation to correct possible deficiencies.
The aim of the study is to determine the serum level of these micronutrients (selenium and copper) in a cross section of pregnant women in Enugu, southeastern Nigeria.
A cross section of 130 healthy pregnant women at different trimesters of pregnancy and 30 non-pregnant controls were selected from two health facilities in Enugu, southeastern Nigeria. Serum from the samples collected was assayed for copper and selenium using atomic absorption spectrophotometer.
The mean copper level increased (P = 0.018), while the selenium level decreased (P < 0.0001) as pregnancy advanced.
High copper levels indicate that supplementation should not be undertaken during normal pregnancy. Dietary intake should be modified to ensure optimal selenium levels during pregnancy.
... According to Takagi et al., the level of oxidative stress and redox-related molecules was higher in the placenta in preeclampsia and IUGR than in normal pregnancy . Secondly, previous studies have reported that iron supplements could interrupt the absorption of zinc and copper in pregnant women with Hb ≥132 g/L [37,38] or with normal Hb levels [39,40]; the reason being competitive absorption of iron, zinc, and copper from the small intestine via divalent metal transporter. Moreover, a high dose of iron supplements (>30 mg/day) can frequently lead to gastrointestinal problems such as constipation , diarrhea, nausea and vomiting . ...
Iron supplementation is a common recommendation for pregnant women to prevent iron deficiency during pregnancy. There is an increasing concern about excessive iron consumption as a general iron prophylaxis by pregnant women without any due consideration about their dietary iron intake or iron status. Our present study investigated the association between total iron intake from diet and supplements and fetal growth in 337 pregnant women at mid-pregnancy in South Korea.
Iron intake from diet and supplements was examined by a 24-hour recall method. Subjects were divided into three groups based on tertiles of total iron intake levels. Fetal biometry was assessed by ultrasonography at mid-pregnancy.
About 99% of the non-supplement users had iron intake below the recommended nutrient intake (RNI) for pregnant women (24 mg), whereas 64.9% of supplement users had iron intake above the upper level (UL) (45 mg). In the babies of mothers in the third tertile of iron intake (>17.04 mg), biparietal diameter, abdominal circumference, and femur length were lower by 0.41 cm (P =0.019), 0.41 cm (P = 0.027), and 0.07 cm (P = 0.051), respectively, than the babies of mothers in the second tertile of iron intake (11.49 ~ 17.04 mg).
These results suggest that excessive maternal iron intake at mid-pregnancy is associated with reduced fetal growth. Iron supplementation for pregnant women should be individualized according to their iron status. Appropriate diet education is needed for pregnant women so that they can consume adequate amounts of iron from food and supplements.
... Chez des femmes enceintes de la région Rhône-Alpes, nous avons observé un déficit biologique dès la 14 e semaine de gestation (c'est-à-dire avant même l'hémodilution) chez 54 % d'entre elles (Zn < 10,7 µmol/l), et 76 % présentaient un taux en dessous du seuil des valeurs normales (Zn < 11 µmol/l)  , alors que, parallèlement, une anémie était présente chez seulement 4 % d'entre elles. Les déficits en zinc de la femme enceinte pourraient être aggravés en cas de supplémentation martiale  , fréquemment prescrite pendant la grossesse, et il conviendrait donc, dans ce cas, de veiller à augmenter les apports en zinc. Chez les nourrissons de faible poids de naissance et allaités par des laits artificiels  , les risques de carences sont plus fréquents. ...
Le chrome trivalent joue un rôle clé dans l'homéostasie glucidique via un effet potentialisateur de l'insuline. En France, les apports recommandés (60 µg/j) sont rarement atteints. Maintenir un statut adéquat en chrome est nécessaire dans les groupes de population présentant une sensibilité à l'insuline diminuée tels que les sujets âgés, les sujets en syndrome métabolique, les sujets en surpoids, et les diabétiques de type 2. Le risque de déficit en zinc conduit à une baisse de l'immunité, à des troubles de la croissance et de la cognition, et à un risque oxydatif plus élevé. Il se corrige en apportant par voie orale des doses de 10 à 30 mg de zinc par jour. La supplémentation systématique ne se justifie pas, mais une attention toute particulière doit être accordée aux femmes enceintes et allaitantes et aux sujets âgés en institution. Les doses pharmacologiques de zinc sont à éviter. Le sélénium a des propriétés antioxydantes et immunomodulatrices. Une carence modérée en sélénium pourrait favoriser l'apparition de certains cancers, le déclin des fonctions cognitives, ainsi que la survenue ou la progression d'infections virales comme l'infection au virus de l'immunodéficience humaine (VIH). Chez les sujets âgés, le maintien des apports par la nutrition ou par les compléments alimentaires à doses nutritionnelle (50 à 100 µg/j) est essentiel. Une supplémentation à dose supranutritionnelle (200 µg/j) serait efficace dans la prévention des cancers, cancers de la prostate en particulier, mais le risque de toxicité doit également être évalué pour ces doses élevées. Les déficits en fer ont des retentissements hématologiques, mais entraînent également un déclin immunitaire. La prévalence des anémies est peu fréquente, à l'exclusion de groupes particuliers devant faire face à des besoins de croissance élevéss (femmes enceintes, enfants, adolescents). Paradoxalement, l'excès de fer peut être impliqué dans le diabète, les maladies cardiovasculaires, les maladies neurodégénératives et certains cancers. Il convient donc d'éviter toute supplémentation systématique en dehors d'une justification biologique de déficit.
...  In addition, in a study by Ziaei et al., iron supplementation in pregnant women with hemoglobin > 13.2 g/dl reduces serum levels of copper and zinc.  O'Brien et al. observed similar findings, too.  In contrast, Harvey and his colleagues' findings showed no reduction in serum zinc of pregnant women after iron supplementation. ...
Iron supplementation can decrease the absorption of zinc and influence other antioxidants levels such as vitamin C. This study aimed to investigate the effect of iron supplements alone and in combination with vitamin C on zinc and vitamin C status in iron deficient female students.
In a double-blind randomized clinical trail, 60 iron deficient students were selected from 289 volunteers residing in dormitory. After matching, subjects were randomly assigned into two groups: Group I (50 mg elemental iron supplements) and Group II (50 mg elemental iron + 500 mg ascorbic acid). Serum ferritin, iron, serum zinc, and plasma vitamin C concentrations were measured by using enzyme-linked immunosorbent assay, spectrophotometer, atomic absorption spectrometer, and colorimeter, respectively after 6 and 12 weeks supplementation. Student's t-test and repeated measures analysis of variance were applied to analyze the data using SPSS software.
Serum zinc levels had no significant differences between 2 groups at the baseline; however, its concentration decreased from 80.9 ± 4.2-68.9 ± 2.7 μg/dl to 81.2 ± 4.5-66.1 ± 2.9 μg/dl (P < 0.001) in Groups I and II, respectively after 6 weeks of supplementation. Continuous supplementation increased serum zinc concentration to baseline levels (79.0 ± 2.9 μg/dl; P < 0.01) in Group I and 70.5 ± 3.1 μg/dl in Group II following 12 weeks of supplementation. Plasma vitamin C increased from 3 ± 0/1-3.3 ± 0.2 mg/dl to 2.7 ± 0. 1-4.2 ± 0.2 mg/dl (P < 0.01) in Groups I and II, respectively. At the end of study, plasma vitamin C significantly increased from 3.3 ± 0.3-4.7 ± 0.3 (P < 0.01) to 4.2 ± 0.2-7.1 ± 0.2 (P < 0.001) in Groups I and II, respectively.
Iron supplementation with and without vitamin C led to reduction in serum Zn in iron-deficient female students after 6 weeks. However, the decreasing trend stops after repletion of iron stores and Zn levels returned to the approximately baseline values after 12 weeks.
... It can suggest the need to pay attention to the copper-zinc balance in women in early pregnancy or planning pregnancy. It is generally known that zinc and copper compete during absorption , and GWAS studies (genome-wide association study) have shown that there is a link between Cu and Zn metabolic pathways . ...
Early identification of women at risk of developing pregnancy-induced hypertension (PIH) is very important. The involvement of copper (Cu) and zinc (Zn) in the oxidative balance suggests the possibility of their association with this disease, in which oxidative stress plays a key role. However, it has not been established so far whether the microelement levels in early pregnancy may be risk markers of the disease, as prospective studies are limited in number. In our innovative single-center study, we identified from a prospective cohort of healthy women in the 10–14th week of a single pregnancy: women subsequently developing pregnancy-induced hypertension (n = 121) and matched women remaining normotensive (n = 363). We measured the concentrations of microelements in the serum from 10–14 week, using the inductively coupled plasma mass spectrometry (ICP-MS). The odds ratios of the disease (and 95% confidence intervals) were assessed in logistic regression. In the whole cohort, the odds ratio (OR) of PIH was 1.52 (p = 0.174) for women in the lowest (Q1) quartile of Cu (≤1540.58 µg/L) compared with women in the highest (Q4) quartile (>1937.46 µg/L), but adjusted odds ratio (AOR) was 2.17 (p = 0.019) after adjusted for pre-pregnancy body mass index (BMI) and gestational age at recruitment. The higher levels of Cu in the subgroup of BMI ≥ 25 kg/m2 compared to normal BMI were found (1847.64 vs. 1673.36 µg/L; p < 0.0001). In the subgroup of women with the normal pre-pregnancy BMI, the adjusted odds ratio of PIH was AOR = 2.95 (p = 0.040) for Q1 vs. Q4 quartile. Our results suggest that lower Cu levels in early pregnancy may be connected with higher risk of PIH, but BMI affected estimated odds ratios. Zinc levels had no effect on the risk.
... Extreme maternal iron status may increase Hb level and adversely affect birth outcomes (4). However, some have doubted the necessity of iron supplementation and challenged its value (10,11). Associations between Hb concentrations and birth outcomes have not been well characterized in adolescents despite the fact that this group is at a higher risk of early childbearing. ...
Studies on the association between maternal hemoglobin (Hb) concentration and adverse pregnancy outcome have been inconsistent. Many studies have shown the impact of Hb concentration on pregnancy outcomes in adult women; however, it is not revealed in adolescent pregnant women.
The aim of this study was to examine the effect of Hb concentration on birth outcomes in pregnant adolescents as a high-risk group.
Patients and methods:
In this cross-sectional study, 312 healthy and nonsmoker adolescent pregnant women with gestational age (GA) of 37-40 weeks were chosen by random sampling, and were followed until delivery. A complete history was obtained from women. In addition, clinical examination and Hb test were performed. After birth, the associations between Hb concentration during pregnancy and birth outcomes were investigated. Statistical analyses were performed using SPSS software by t-test, chi-square and ANOVA.
In total, about 23.2 % were anemic, 58% had normal level of Hb (11-13.2 g/dL) and 18.8% had Hb > 13.2 g/dL. The mean birth weight was 3197.8 ± 398.25 grams and it was more in mothers with Hb = 10.5-12.5 g/dL than others (Hb < 10.5 or Hb > 12.5 g/dL) (P < 0.001). The lowest mean birth weight was found in mothers with Hb < 10.5 (3033.33 ± 422). Moreover, the mean birth weight of male newborns was more than females (P = 0.001). Eight percent of neonates had Apgar score less than eight. Low Apgar score in anemic group and mothers with high Hb concentration (Hb > 12.5 g/dL) was more than others.
Abnormal Hb concentrations increase the risk of adverse birth outcomes such as low birth weight (LBW) and low Apgar scores in pregnant adolescents, so intensive care is recommended for this group of pregnant women.
... Impaired metabolism of trace elements, such as copper and iron, has been reported in diabetes (2). Cu is the third most abundant trace element in the human body; it is an essential element in the structure of many metalloenzymes that are involved in the oxidation and reduction processes, and provide a major portion of the energy required for metabolism (3). Cu is known as the cause of many diseases and plays an important role in the peroxidation mechanisms. ...
Diabetes mellitus is one of the most common metabolic diseases in humans. The blood concentrations of various trace elements, such as copper (Cu) and molybdenum (Mo), are altered in diabetes mellitus, which may have a significant role in the pathogenesis and progress of this disease. This study was aimed to evaluate the levels of copper and molybdenum concentrations in diabetic patients and healthy subjects. A total of 87 patients with type 2 diabetes and 45 participants with normal blood glucose were included in this study. The blood levels of Cu and Mo concentrations were measured by graphite furnace atomic absorption spectroscopy (GF-AAS). Statistical analyses were performed using SPSS 19.0 software. Biochemical factors were compared using student’s t-test, Mann-Whitney test and Pearson correlation coefficient. The results showed a significant increase in mean Cu level in diabetic patients (394.11 ± 10.08) compared to healthy subjects (134.34 ± 3.66), however a significant decrease was found in mean Mo level in diabetic patients (8.41 ± 0.141) compared to healthy subjects (16.45 ± 0.72). Statistical analysis showed a significant positive correlation between the concentrations of each element with diabetes. The study indicates that type 2 diabetes can alter the blood levels of copper and molybdenum. The results of this study confirmed that the level of copper in diabetic patients is higher than healthy subjects, and that the level of molybdenum in diabetic patients is lower than that of healthy subjects. In addition, increasing or decreasing the copper concentration has no significant effect on the concentration of molybdenum in diabetic patients, meaning that there is no significant correlation between the two variables in diabetic patients.
... There were some residual confounding factors which were not considered, such as dietary habit, Cu supplement, and other factor interactions, although we have adjusted iron and multivitamin supplementation during pregnancy. Some studies have suggested that high iron supplementation, particularly coupling with low dietary Cu intake, could lead to lower Cu status [6,48]. Also, vitamin supplementation could also affect maternal Cu concentrations . ...
Our study aimed to assess the distribution of copper (Cu) in umbilical cord serum and estimated the association between umbilical serum Cu status and neonatal birth outcomes in a Chinese population. Through the Ma’anShan Birth Cohort Study, 2689 maternal-singleton pairs with detailed birth records and available serum samples were identified. The tertile levels of ln-transformed Cu were used to define low, medium, and high levels for serum Cu. The median for umbilical cord serum Cu was 298.2 μg/L with a range of 123.1–699.6 μg/L in this study population. Our study found a positive association between the concentration of serum Cu in the umbilical cord and the duration of gestation. Compared with medium Cu levels, we found that infants with low Cu levels had a significant higher risk of preterm birth (OR = 5.06, 95% CI 2.74, 9.34) and early-term birth (OR = 1.36, 95% CI 1.10, 1.69) in the crude model. We also found that infants with high Cu levels had a significant higher risk of late- or post-term birth (OR = 1.47, 95% CI 1.11, 1.95). A significant higher risk of preterm, early-term, and late- or post-term birth still remained, even after adjustment for potential confounding factors. Our findings suggested that both Cu deficiency and Cu overload had an adverse effect on neonatal birth outcomes.
... Third, iron overload may impair the systemic response to inflammation and infection (1), which could be associated with adverse birth outcomes (50,51). Finally, there is also the potential for excess iron to alter the maternal gut microbiome (52) as well as increase the risk of copper and zinc deficiency (53), which may have implications for birth outcomes (54,55). ...
Both iron deficiency (ID) and excess can lead to impaired health status. There is substantial evidence of a U-shaped curve between the risk of adverse birth outcomes and maternal hemoglobin concentrations during pregnancy; however, it is unclear whether those relations are attributable to conditions of low and high iron status or to other mechanisms. We summarized current evidence from human studies regarding the association between birth outcomes and maternal hemoglobin concentrations or iron status. We also reviewed effects of iron supplementation on birth outcomes among women at low risk of ID and the potential mechanisms for adverse effects of high iron status during pregnancy. Overall, we confirmed a U-shaped curve for the risk of adverse birth outcomes with maternal hemoglobin concentrations, but the relations differ by trimester. For low hemoglobin concentrations, the link with adverse outcomes is more evident when hemoglobin concentrations are measured in early pregnancy. These relations generally became weaker or nonexistent when hemoglobin concentrations are measured in the second or third trimesters. Associations between high hemoglobin concentration and adverse birth outcomes are evident in all 3 trimesters but evidence is mixed. There is less evidence for the associations between maternal iron status and adverse birth outcomes. Most studies used serum ferritin (SF) concentrations as the indicator of iron status, which makes the interpretation of results challenging because SF concentrations increase in response to inflammation or infection. The effect of iron supplementation during pregnancy may depend on initial iron status. There are several mechanisms through which high iron status during pregnancy may have adverse effects on birth outcomes, including oxidative stress, increased blood viscosity, and impaired systemic response to inflammation and infection. Research is needed to understand the biological processes that underlie the U-shaped curves seen in observational studies. Reevaluation of cutoffs for hemoglobin concentrations and indicators of iron status during pregnancy is also needed.
... • Excess iron may impair the maternal systemic response to inflammation and infection leading to adverse birth outcome . • Lastly, excess iron may alter the maternal gut microbiome  and/or increase the risk of copper and zinc deficiency [86,87], which in turn may culminate in adverse pregnancy outcomes. ...
Iron is an essential element for the survival of most organisms, including humans. Demand for iron increases significantly during pregnancy to support growth and development of the fetus. Paradoxically, epidemiologic studies have shown that excessive iron intake and/or high iron status can be detrimental to pregnancy and is associated with reproductive disorders ranging from endometriosis to preeclampsia. Reproductive complications resulting from iron deficiency have been reviewed elsewhere. Here, we focus on reproductive disorders associated with iron overload and the contribution of ferroptosis—programmed cell death mediated by iron-dependent lipid peroxidation within cell membranes—using preeclampsia as a model system. We propose that the clinical expressions of many reproductive disorders and pregnancy complications may be due to an underlying ferroptopathy (elemental iron-associated disease), characterized by a dysregulation in iron homeostasis leading to excessive ferroptosis.
To summarise evidence on the associations of maternal anaemia and prenatal iron use with maternal haematological and adverse pregnancy outcomes; and to evaluate potential exposure-response relations of dose of iron, duration of use, and haemoglobin concentration in prenatal period with pregnancy outcomes.
Systematic review and meta-analysis
Searches of PubMed and Embase for studies published up to May 2012 and references of review articles.
Randomised trials of prenatal iron use and prospective cohort studies of prenatal anaemia; cross sectional and case-control studies were excluded.
48 randomised trials (17 793 women) and 44 cohort studies (1 851 682 women) were included. Iron use increased maternal mean haemoglobin concentration by 4.59 (95% confidence interval 3.72 to 5.46) g/L compared with controls and significantly reduced the risk of anaemia (relative risk 0.50, 0.42 to 0.59), iron deficiency (0.59, 0.46 to 0.79), iron deficiency anaemia (0.40, 0.26 to 0.60), and low birth weight (0.81, 0.71 to 0.93). The effect of iron on preterm birth was not significant (relative risk 0.84, 0.68 to 1.03). Analysis of cohort studies showed a significantly higher risk of low birth weight (adjusted odds ratio 1.29, 1.09 to 1.53) and preterm birth (1.21, 1.13 to 1.30) with anaemia in the first or second trimester. Exposure-response analysis indicated that for every 10 mg increase in iron dose/day, up to 66 mg/day, the relative risk of maternal anaemia was 0.88 (0.84 to 0.92) (P for linear trend<0.001). Birth weight increased by 15.1 (6.0 to 24.2) g (P for linear trend=0.005) and risk of low birth weight decreased by 3% (relative risk 0.97, 0.95 to 0.98) for every 10 mg increase in dose/day (P for linear trend<0.001). Duration of use was not significantly associated with the outcomes after adjustment for dose. Furthermore, for each 1 g/L increase in mean haemoglobin, birth weight increased by 14.0 (6.8 to 21.8) g (P for linear trend=0.002); however, mean haemoglobin was not associated with the risk of low birth weight and preterm birth. No evidence of a significant effect on duration of gestation, small for gestational age births, and birth length was noted.
Daily prenatal use of iron substantially improved birth weight in a linear dose-response fashion, probably leading to a reduction in risk of low birth weight. An improvement in prenatal mean haemoglobin concentration linearly increased birth weight.
Iron and folic acid supplementation has been the preferred intervention to improve iron stores and prevent anaemia among pregnant women, and it may also improve other maternal and birth outcomes.
To assess the effects of daily oral iron supplements for pregnant women, either alone or in conjunction with folic acid, or with other vitamins and minerals as a public health intervention.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (2 July 2012). We also searched the WHO International Clinical Trials Registry Platform (ICTRP) (2 July 2012) and contacted relevant organisations for the identification of ongoing and unpublished studies.
Randomised or quasi-randomised trials evaluating the effects of oral preventive supplementation with daily iron, iron + folic acid or iron + other vitamins and minerals during pregnancy.
We assessed the methodological quality of trials using standard Cochrane criteria. Two review authors independently assessed trial eligibility, extracted data and conducted checks for accuracy.
We included 60 trials. Forty-three trials, involving more than 27,402 women, contributed data and compared the effects of daily oral supplements containing iron versus no iron or placebo.Overall, women taking iron supplements were less likely to have low birthweight newborns (below 2500 g) compared with controls (8.4% versus 10.2%, average risk ratio (RR) 0.81; 95% confidence interval (CI) 0.68 to 0.97, 11 trials, 8480 women) and mean birthweight was 30.81 g greater for those infants whose mothers received iron during pregnancy (average mean difference (MD) 30.81; 95% CI 5.94 to 55.68, 14 trials, 9385 women). Preventive iron supplementation reduced the risk of maternal anaemia at term by 70% (RR 0.30; 95% CI 0.19 to 0.46, 14 trials, 2199 women) and iron deficiency at term by 57% (RR 0.43; 95% CI 0.27 to 0.66, seven trials, 1256 women). Although the difference between groups did not reach statistical significance, women who received iron supplements were more likely than controls to report side effects (25.3% versus 9.91%) (RR 2.36; 95% CI 0.96 to 5.82, 11 trials, 4418 women), particularly at doses 60 mg of elemental iron or higher. Women receiving iron were on average more likely to have higher haemoglobin (Hb) concentrations at term and in the postpartum period, but were at increased risk of Hb concentrations greater than 130g/L during pregnancy and at term. Twenty-three studies were conducted in countries that in 2011 had some malaria risk in parts of the country. In some of these countries/territories, malaria is present only in certain areas or up to a particular altitude. Only two of these reported malaria outcomes. There is no evidence that iron supplementation increases placental malaria. For some outcomes heterogeneity was higher than 50%.
Prenatal supplementation with daily iron are effective to reduce the risk of low birthweight, and to prevent maternal anaemia and iron deficiency in pregnancy. Associated maternal side effects and particularly high Hb concentrations during pregnancy at currently used doses suggest the need to update recommendations on doses and regimens for routine iron supplementation.
Anaemia is a frequent condition during pregnancy, particularly among women from developing countries who have insufficient iron intake to meet increased iron needs of both the mother and the fetus.Traditionally, gestational anaemia has been prevented with the provision of daily iron supplements throughout pregnancy, but adherence to this regimen due to side effects, interrupted supply of the supplements, and concerns about safety among women with an adequate iron intake, have limited the use of this intervention. Intermittent (i.e. one, two or three times a week on non-consecutive days) supplementation with iron alone or in combination with folic acid or other vitamins and minerals has recently been proposed as an alternative to daily supplementation.
To assess the benefits and harms of intermittent supplementation with iron alone or in combination with folic acid or other vitamins and minerals to pregnant women on neonatal and pregnancy outcomes.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (23 March 2012). We also searched the WHO International Clinical Trials Registry Platform (ICTRP) for ongoing studies and contacted relevant organisations for the identification of ongoing and unpublished studies (23 March 2012).
Randomised or quasi-randomised trials.
We assessed the methodological quality of trials using standard Cochrane criteria. Two review authors independently assessed trial eligibility, extracted data and conducted checks for accuracy.
This review includes 21 trials from 13 different countries, but only 18 trials (with 4072 women) reported on our outcomes of interest and contributed data to the review. All of these studies compared daily versus intermittent iron supplementation.Three studies provided iron alone, 12 iron+folic acid and three more iron plus multiple vitamins and minerals. Their methodological quality was mixed and most had high levels of attrition. Overall, there was no clear evidence of differences between groups for infant primary outcomes: low birthweight (average risk ratio (RR) 0.96; 95% confidence interval (CI) 0.61 to 1.52, seven studies), infant birthweight (mean difference MD -8.62 g; 95% CI -52.76 g to 35.52 g, eight studies), premature birth (average RR 1.82; 95% CI 0.75 to 4.40, four studies). None of the studies reported neonatal deaths or congenital anomalies.For maternal outcomes, there was no clear evidence of differences between groups for anaemia at term (average RR 1.22; 95% CI 0.84 to 1.80, four studies) and women receiving intermittent supplementation had less side effects (average RR 0.56; 95% CI 0.37 to 0.84, 11 studies) than those receiving daily supplements. Women receiving intermittent supplements were also at lower risk of having high haemoglobin (Hb) concentrations (greater than 130 g/L) during the second or third trimester of pregnancy (average RR 0.48; 95% CI 0.35 to 0.67, 13 studies). There were no significant differences in iron-deficiency anaemia between women receiving intermittent or daily iron+folic acid supplementation (average RR 0.71; 95% CI 0.08 to 6.63, 1 study). There were no maternal deaths (six studies) or women with severe anaemia in pregnancy (six studies). None of the studies reported on iron deficiency at term or infections during pregnancy.Where sufficient data were available for primary outcomes, we set up subgroups to look for possible differences between studies in terms of earlier or later supplementation; women's anaemia status at the start of supplementation; higher and lower weekly doses of iron; and the malarial status of the region in which the trials were conducted. There was no clear effect of these variables on the results of the review.
The present systematic review is the most comprehensive summary of the evidence assessing the benefits and harms of intermittent iron supplementation regimens in pregnant women on haematological and pregnancy outcomes. The findings suggest that intermittent iron+folic acid regimens produce similar maternal and infant outcomes at birth as daily supplementation but are associated with fewer side effects. Women receiving daily supplements had increased risk of developing high levels of Hb in mid and late pregnancy but were less likely to present mild anaemia near term. Although the evidence is limited and the quality of the trials was low or very low, intermittent may be a feasible alternative to daily iron supplementation among those pregnant women who are not anaemic and have adequate antenatal care.
Introduction: Prescribing routine Iron supplementation during pregnancy has been done regardless of their need for many years. Considering the possibility of adverse pregnancy outcomes with unnecessary consumption of iron supplementation in pregnant women, this study was performed with aim to assess the effect of iron supplementation in pregnant women with high hemoglobin on neonatal jaundice.
Methods: This double-blind controlled randomized clinical trial was performed on 140 nonsmoker healthy pregnant women with gestational age of 14-18weeks and singleton pregnancy with Hb > 13.2 g/dL and ferritin > 15 μg/l in Ardabil during 2016-17. Mothers were randomly assigned to 50 mg ferrous sulfate and placebo groups from 20th weeks of pregnancy. Also, 24 hour after delivery, the neonates were assessed in terms of bilirubin level (by photometric method using BT3500 device) and jaundice. Data were analyzed by SPSS software (version 16) and independent t-test, Chi-square, and exact fisher test. P < 0.05 was considered statistically significant.
Results: There was significant difference between two groups in Hb (P = 0.03) and ferritin (P = 0.04) levels after the intervention, but no significant difference was found between two groups in the incidence of anemia (Hb<11 g/dl) (P < 0.001). In addition, the incidence of neonatal jaundice was more in interventional group than placebo (P=0.005). The incidence of neonatal jaundice was associated with first-trimester ferritin (P=0.01).
Conclusion: Iron supplementation in pregnant women with Hb > 13.2 g/dl is associated with increased risk of neonatal jaundice; therefore, routine prescribing of iron supplementation should be done with caution in pregnancy.
Ferrous sulfate; Hemoglobin; Neonatal Jaundice; Pregnancy
The potential adverse effects associated with some of the more common oral vitamin supplements--vitamins A, D, and E and niacin (forms include nicotinic acid and nicotinamide), and mineral supplements--zinc, copper, and iron, used in dermatology are manifold. Although the dermatologist may be familiar with adverse effects of vitamins A and D, less well-known adverse effects, such as hematologic and neurologic effects from zinc, are presented.
Background & Aims: Prescribing routine Iron supplementation during pregnancy regardless of the maternal hemodynamic condition that may be accompanied with pregnancy and delivery complications. This study conducted to assessing the effect of iron supplementation in pregnant women with high hemoglobin on delivery type and newborn’s Apgar score.
Material & Methods: The randomized double-blind clinical trial performed on 140 healthy pregnant women, 18-35years old, normal BMI, nonsmoker, in the 14th - 18th weeks of singleton pregnancy with Hb> 13.2 g/dL and ferritin > 15 μg/l. Mothers were randomly assigned to experimental and control groups from the 20th week of pregnancy, the experimental group received one ferrous sulfate tablet (50 mg) daily, while the control group received a placebo. Both of them were followed up to delivery and the type of birth and newborn’s Apgar were evaluated and compared.
Results: There was significant differences between the two groups in Hb (P = 0.03) and ferritin (P=0.04) levels after intervention, but the incidence of anemia exhibited no difference between them (P = 0.1). In addition there was no different between the two groups in birth weight (P=0/2), but the incidence of cesarean section (P=0/01) and low birth Apgar score (less than 8) (P=0/02) in drug group more than other group.
Conclusion: Iron supplementation increased the risk of cesarean section and low Apgar score in pregnant women with Hb concentrations greater than 13.2 g/dl; therefore, it should be done with caution in pregnancy.
Keywords: Ferrous sulfate, Pregnancy, Hemoglobin, Apgar score, cesarean
Anaemia is a widespread problem in many parts of the world especially in tropic areas. Among pregnant women, it has negative consequences on maternal and perinatal outcomes. A cross-sectional study was conducted to investigate the prevalence of anaemia, iron, zinc and copper deficiencies among pregnant women in Wad Medani hospital, central Sudan and to examine the relationship of these micronutrients with haemoglobin (Hb) levels. One hundred four (52.5%) out of 200 pregnant women had anaemia (Hb < 11 gm/dl) and 3 (1.5) % had severe anaemia (Hb < 7 gm/dl). Iron deficiency (S-ferritin < 15 µg/l), iron deficiency anaemia (<11 gm/dl and S-ferritin < 15 µg/l) were prevalent in 25 (12.5%) and 13 (6.5%) of these women, respectively. Ninety (45.0%) and eight (4.0%) of these women had zinc (<80 µg/ml) and copper (<80 µg/ml) deficiency, respectively. In 24 (12.0%) of these women, there were ≥2 deficiencies of these elements. S-copper was not [corrected] significantly lower in patients with anaemia. While age, parity, gestational age, ferritin, zinc and copper were not predictors for anaemia, women who practiced pica were at higher risk for anaemia (OR = 3.4, 95% CI = 1.4-7.9, P = 0.004). Gestational age was significantly inversely correlated with haemoglobin (r = 0.161, P = 0.03), S-ferritin (r = 0.285, P = 0.001) and S-zinc (r = 0.166, P = 0.02). Thus, dietary and supplement interventions are required to prevent and control anaemia in this setting. Further research is needed.
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.
To assess the effectiveness and safety of daily and intermittent use of iron or iron+folic acid supplements by pregnant women.
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.
All randomised or quasi-randomised trials evaluating the effect of supplementation with iron or iron+folic acid during pregnancy.
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.
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.
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.
The effect of iron-folate supplementation on maternal serum copper concentration in late pregnancy (33 to 35 weeks gestation) was examined. In the 30 women who had taken daily iron-folate supplements since the start of the second trimester (11 to 15 weeks gestation), the median serum copper concentration was lower than that in the 27 women who had taken no supplements (p < 0.005). However, in the supplemented women the median values for serum iron concentration and blood hemoglobin concentration were higher, and the median value for serum transferrin concentration was lower, than the corresponding median values in the unsupplemented women (p < 0.001, p < 0.02 and p < 0.001, respectively). Further work is needed to determine whether the difference between the median values for serum copper concentration is due to a reduction in values in the women who took iron-folate, perhaps as a result of an interaction between iron and copper, or is due to an increase in values in the unsupplemented women secondary to their apparently reduced iron status.
Objective: To examine the association of maternal hemoglobin during pregnancy with preterm birth and small for gestational age (SGA). Methods: We performed a retrospective cohort analysis of hemoglobin and birth outcome among 173,031 pregnant women who attended publicly funded health programs in ten states and delivered a liveborn infant at 26–42 weeks' gestation. We defined preterm as less than 37 weeks' gestation and SGA as less than the tenth percentile of a US fetal growth reference. Results: Risk of preterm birth was increased in women with low hemoglobin level in the first and second trimester. The odds ratio (OR) for preterm birth with moderate-to-severe anemia during the first trimester (more than three standard deviations [SD] below reference median hemoglobin, equivalent to less than 95 g/L at 12 weeks' gestation) was 1.68 (95% confidence interval [CI] 1.29, 2.21). Anemia was not associated with SGA. High hemoglobin level during the first and second trimester was associated with SGA but not preterm birth. The ORs for SGA in women with very high hemoglobin level during the first and second trimester (more than three SDs above reference median hemoglobin, equivalent to greater than 149 g/L at 12 weeks' gestation and greater than 144 g/L at 18 weeks') were 1.27 (95% CI 1.02, 1.58) and 1.79 (95% CI 1.49, 2.15), respectively. Conclusion: These data highlight the importance of considering anemia and high hemoglobin level as indicators for adverse pregnancy outcome. An elevated hemoglobin level (greater than 144 g/L) is an indicator for possible pregnancy complications associated with poor plasma volume expansion, and should not be mistaken for good iron status. During the past three decades, the high prevalence of anemia has persisted among low-income pregnant women attending public health nutrition programs in the United States. Defined as a hemoglobin level below the fifth percentile of a trimester-specific hemoglobin reference level in iron-supplemented pregnant women, the prevalence of anemia among women participating in public health nutrition programs is approximately 8% in the first trimester, 12% in the second trimester, and 29% in the third trimester.1 Observational studies in the United States and Europe have produced conflicting results concerning the clinical relevance of maternal anemia during pregnancy.2–13 Although several researchers have reported an association between anemia and low birth weight (LBW), preterm birth, or both,4–8,10,13 others have not found such an association.9,11,12 One study indicated that anemia due to iron deficiency but not other causes was associated with both LBW and preterm delivery.12 Past studies differ in the criteria used to define anemia and adjustment for factors associated with LBW and preterm birth.14,15 Study limitations complicate the interpretation of study results and have led the United States Preventive Services Task Force to question the indications for iron supplementation of pregnant women.2,3 In addition to anemia, several studies have found an association between elevated maternal hemoglobin and adverse birth outcome, including LBW, preterm birth, and small-for-gestational-age (SGA) birth.4,6,11,13 However, because a high maternal hemoglobin level is sometimes mistakenly equated with good iron status, its effect on pregnancy outcome has not received the same attention as anemia. We used data from the Centers for Disease Control and Prevention (CDC) Pregnancy Nutrition Surveillance System to examine the association between maternal hemoglobin level during pregnancy and preterm birth and SGA birth. We were specifically interested in effects associated with low and high maternal hemoglobin levels.
High intakes of Fe may impair Cu status, but the underlying mechanism is not known. Male rats, aged 7 weeks, were given purified diets adequate in Cu (8 mg Cu/kg) and containing either 7, 40 or 389 mg Fe/kg. After 6 weeks the concentrations of Fe in liver and spleen were positively related with dietary Fe level and those of Cu were negatively related with dietary Fe level. Increasing Fe intakes reduced apparent absorption and biliary excretion of Cu in a dose-dependent fashion. In individual rats, biliary Cu excretion showed a significant, positive correlation with liver Cu concentration. It is concluded that increased Fe intakes depress Cu absorption which produces a decrease in plasma and organ Cu concentrations. As a result, biliary Cu excretion is lowered which contributes to achieving Cu balance at high Fe intakes. Because the concentrations of Cu in plasma and bile, and also plasma ceruloplasmin (EC 220.127.116.11) activities, showed much greater percentage reductions with increasing Fe intake than did the concentrations of Cu in organs, it is possible that increased Fe status interferes with the mobilization of Cu stores.
Prenatal iron supplements may adversely influence zinc absorption during pregnancy. To examine the impact of prenatal iron supplements on supplemental zinc absorption, fractional zinc absorption was measured in 47 pregnant Peruvian women during the third trimester of pregnancy (33 +/- 1 wk gestation). Of these 47 women, 30 received daily prenatal supplements from wk 10-24 of pregnancy until delivery. Supplements contained 60 mg of Fe and 250 microg of folate without [iron group (Fe), n = 16] or with [iron and zinc supplemented group (Fe + Zn), n = 14] 15 mg of Zn. The remaining 17 women [unsupplemented control group (C)] received no prenatal supplementation. Zinc concentrations were measured in plasma, urine and cord blood and percentage zinc absorption was determined following dosing with oral ((67)Zn) and intravenous ((70)Zn) stable zinc isotopes. Percentage zinc absorption was significantly lower than controls in fasting women receiving iron- containing prenatal supplements (20.5 +/- 6.4 vs. 20.2 +/- 4.6 vs. 47.0 +/- 12.6%, Fe, Fe + Zn and C groups, respectively, P: < 0.0001, n = 40). Plasma zinc concentrations were also significantly lower in the Fe group compared to the C group (8.2 +/- 2.2 vs. 9.2 +/- 2.2 vs. 10.9 +/- 1. 8 micromol/L, Fe, Fe + Zn and C groups, respectively, P: = 0.002), and cord zinc concentrations were significantly related to maternal plasma Zn levels (y = 6.383 + 0.555x, r = 0.486, P: = 0.002). The inclusion of zinc in prenatal supplements may reduce the potential for iron supplements to adversely influence zinc status in populations at risk for deficiency of both these nutrients.
The World Health Organization estimates that 58% of pregnant women in developing countries are anemic. In spite of the fact that most ministries of health in developing countries have policies to provide pregnant women with iron in a supplement form, maternal anemia prevalence has not declined significantly where large-scale programs have been evaluated. During the period 1991–98, the MotherCare Project and its partners conducted qualitative research to determine the major barriers and facilitators of iron supplementation programs for pregnant women in eight developing countries. Research results were used to develop pilot program strategies and interventions to reduce maternal anemia.
Iron requirements are greater in pregnancy than in the nonpregnant state. Although iron requirements are reduced in the first trimester because of the absence of menstruation, they rise steadily thereafter; the total requirement of a 55-kg woman is ≈1000 mg. Translated into daily needs, the requirement is ≈0.8 mg Fe in the first trimester, between 4 and 5 mg in the second trimester, and >6 mg in the third trimester. Absorptive behavior changes accordingly: a reduction in iron absorption in the first trimester is followed by a progressive rise in absorption throughout the remainder of pregnancy. The amounts that can be absorbed from even an optimal diet, however, are less than the iron requirements in later pregnancy and a woman must enter pregnancy with iron stores of ≥300 mg if she is to meet her requirements fully. This is more than most women possess, especially in developing countries. Results of controlled studies indicate that the deficit can be met by supplementation, but inadequacies in health care delivery systems have limited the effectiveness of larger-scale interventions. Attempts to improve compliance include the use of a supplement of ferrous sulfate in a hydrocolloid matrix (gastric delivery system, or GDS) and the use of intermittent supplementation. Another approach is intermittent, preventive supplementation aimed at improving the iron status of all women of childbearing age. Like all supplementation strategies, however, this approach has the drawback of depending on delivery systems and good compliance. On a long-term basis, iron fortification offers the most cost-effective option for the future.
The main purpose of this article is to review the studies describing the relationship between zinc nutriture and pregnancy outcome in humans and animals. In addition, we have included a brief description of our recent findings from a randomized trial on the positive effect of zinc supplementation during pregnancy on birth weight and head circumference of infants. In human studies, the findings in the literature are mostly inconclusive because of inconsistent study conditions, insufficient sample size, or the lack of specific and sensitive test(s) to accurately assess zinc nutriture. Many unanswered questions which require further investigation relating to maternal zinc nutriture and pregnancy outcome are discussed.
The relation between haemoglobin (Hb) concentrations at antenatal booking and subsequent outcome was examined in 54 382 singleton pregnancies. Both high (greater than 13.2 g/dl) and low (less than 10.4 g/dl) Hb values were associated with an adverse outcome. Mothers with a booking Hb in the intermediate range (10.4-13.2 g/dl) fared best. Significant differences emerged in perinatal mortality between those with high and those with intermediate Hb levels at 13-19 weeks' gestation. The frequencies of perinatal death, low birthweight, and preterm delivery were greater with high than with intermediate Hb. There was a striking relation between booking Hb values and the subsequent frequency of hypertension (p less than 0.001). In primiparas, the frequency of subsequent hypertension ranged from 7% at Hb values under 10.5 g/dl to 42% at Hb concentrations over 14.5 g/dl.
The effect of zinc supplementation on concentrations of zinc in hair and serum of 213 pregnant Hispanic women attending a clinic in Los Angeles was assessed using a random, double-blind experiment. Both the treatment (T) and control (C) groups received similar vitamin and mineral supplements except that 20 mg zinc was added to the supplements for the treatment group. Nutrient intakes were calculated from 24-h recalls. The initial mean dietary zinc intake of both groups was about 50% of the Recommended Dietary Allowance (9 +/- 5 mg). Initially there were no significant differences between the two groups in mean zinc levels in serum (66 +/- 11 micrograms/dl, C, and 65 +/- 12 micrograms/dl, T) or in hair (184 +/- 41 micrograms/g, C, and 175 +/- 38 micrograms/g, T). Zinc supplementation did not alter mean zinc levels in serum or hair but significantly (p less than 0.05) reduced the number of low serum zinc values (less than or equal to 53.3 micrograms/dl) toward the end of pregnancy. Although serum zinc levels do decline in pregnancy, our results suggest that severely depressed levels (less than or equal to 50 to 55 micrograms/dl) indicate inadequate zinc status.
Iron requirements are greater in pregnancy than in the nonpregnant state. Although iron requirements are reduced in the first trimester because of the absence of menstruation, they rise steadily thereafter; the total requirement of a 55-kg woman is approximately 1000 mg. Translated into daily needs, the requirement is approximately 0.8 mg Fe in the first trimester, between 4 and 5 mg in the second trimester, and >6 mg in the third trimester. Absorptive behavior changes accordingly: a reduction in iron absorption in the first trimester is followed by a progressive rise in absorption throughout the remainder of pregnancy. The amounts that can be absorbed from even an optimal diet, however, are less than the iron requirements in later pregnancy and a woman must enter pregnancy with iron stores of >/=300 mg if she is to meet her requirements fully. This is more than most women possess, especially in developing countries. Results of controlled studies indicate that the deficit can be met by supplementation, but inadequacies in health care delivery systems have limited the effectiveness of larger-scale interventions. Attempts to improve compliance include the use of a supplement of ferrous sulfate in a hydrocolloid matrix (gastric delivery system, or GDS) and the use of intermittent supplementation. Another approach is intermittent, preventive supplementation aimed at improving the iron status of all women of childbearing age. Like all supplementation strategies, however, this approach has the drawback of depending on delivery systems and good compliance. On a long-term basis, iron fortification offers the most cost-effective option for the future.
To examine the association of maternal hemoglobin during pregnancy with preterm birth and small for gestational age (SGA).
We performed a retrospective cohort analysis of hemoglobin and birth outcome among 173,031 pregnant women who attended publicly funded health programs in ten states and delivered a liveborn infant at 26-42 weeks' gestation. We defined preterm as less than 37 weeks' gestation and SGA as less than the tenth percentile of a US fetal growth reference.
Risk of preterm birth was increased in women with low hemoglobin level in the first and second trimester. The odds ratio (OR) for preterm birth with moderate-to-severe anemia during the first trimester (more than three standard deviations [SD] below reference median hemoglobin, equivalent to less than 95 g/L at 12 weeks' gestation) was 1.68 (95% confidence interval [CI] 1.29, 2. 21). Anemia was not associated with SGA. High hemoglobin level during the first and second trimester was associated with SGA but not preterm birth. The ORs for SGA in women with very high hemoglobin level during the first and second trimester (more than three SDs above reference median hemoglobin, equivalent to greater than 149 g/L at 12 weeks' gestation and greater than 144 g/L at 18 weeks') were 1.27 (95% CI 1.02, 1.58) and 1.79 (95% CI 1.49, 2.15), respectively.
These data highlight the importance of considering anemia and high hemoglobin level as indicators for adverse pregnancy outcome. An elevated hemoglobin level (greater than 144 g/L) is an indicator for possible pregnancy complications associated with poor plasma volume expansion, and should not be mistaken for good iron status.
High and low maternal hemoglobin concentrations during pregnancy have been reported to increase risk of small-for-gestational-age (SGA) birth, which is a predictor of stillbirth. The relationship between hemoglobin concentration during pregnancy and risk of stillbirth is unclear.
To study the associations among hemoglobin concentration at first measurement during antenatal care, change in hemoglobin concentration during pregnancy, and risk of stillbirth.
Population-based, matched case-control study of births from 1987 through 1996 in Sweden including 702 primiparous women with stillbirths occurring at 28 weeks' gestation or later and 702 primiparous women with live births.
Risk of stillbirth, classified as malformed or nonmalformed, antepartum or intrapartum, preterm or term, and SGA or non-SGA, compared by maternal hemoglobin concentration at first antenatal measurement and weekly changes in hemoglobin concentration during pregnancy, adjusted for maternal age, body mass index, height, smoking, socioeconomic status, and week of first hemoglobin measurement.
In multivariate analyses, compared with women with hemoglobin concentrations of 126 to 135 g/L at first antenatal measurement, women with concentrations of 146 g/L or higher were at increased risk of stillbirth (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.0-3.3). This risk was slightly increased when the analysis was restricted to antepartum stillbirths without malformations (OR, 2.0; 95% CI, 1.1-3.8). When we further restricted the analyses to preterm and SGA antepartum nonmalformed stillbirths, the ORs increased to 2.7 (95% CI, 1.1-6.4) and 4.2 (95% CI, 1.3-13. 9), respectively. Excluding women with preeclampsia and eclampsia further increased these risks. Average weekly change in hemoglobin concentration during early or late pregnancy was not significantly associated with risk of stillbirth, although a larger decrease in concentration tended to be protective. Anemia (hemoglobin concentration <110 g/L) was not significantly associated with risk of stillbirth in multivariate analyses (OR, 1.2; 95% CI, 0.5-2.7).
High hemoglobin concentration at first measurement during antenatal care appears to be associated with increased risk of stillbirth, especially preterm and SGA antepartum stillbirths. JAMA. 2000;284:2611-2617.
To study the relationship between zinc, insulin-like growth factor (IGF-I), osteocalcin and perinatal growth.
Anthropometric variables, serum levels of IGF-I, osteocalcin and zinc were measured in preterm (PT) appropriate for gestational age (AGA), full term (FT) small for gestational age (SGA) and FT AGA newborns at birth (n=52), at first week (n=38) and at third week (n=38) of postnatal age.
At birth, the FT SGA had lower levels of IGF-I. At the first week after birth, both FT SGA and PT AGA infants had less deposits of subcutaneous fat; FT SGA infants also showed significantly lower osteocalcin and zinc levels. At 3 weeks of postnatal life, FT SGA infants continued to show significantly lower zinc levels. They had increased their fat deposits so that differences between groups in skinfold measurements failed to be significant. The highest levels of osteocalcin were found in PT AGA infants at the third week after birth.
Perinatal nutrition influences the IGF-I levels. The low concentration of osteocalcin found in SGA infants at first week of life probably reflects decreased bone turnover. During the first weeks of life, there is a progressive decrease in the serum levels of zinc, accentuated in the FT SGA group.
More than 9 million neonatal deaths occur each year, 98% of them in developing countries. Neonatal deaths account for two-thirds of deaths in infancy and 40% of deaths before age 5 y. The major direct causes of neonatal death are infections, preterm delivery and asphyxia. Important indirect causes include low birth weight and hypothermia. The present body of work on multiple micronutrient interventions is not sufficient for us to draw conclusions on their effects on neonatal well-being. Because studies have generally concentrated on single micronutrients and a range of outcomes, this paper reviews the findings for individual nutrients and then summarizes the situation. The evidence for the contribution of micronutrient deficiencies to perinatal mortality and duration of gestation is limited, and the evidence base for individual micronutrient effects on neonatal mortality and morbidity is patchy. To translate knowledge into policy, community evaluations of effect and an expanded evidence base that includes affordability, acceptability and scalability are also required. A balance between supply-side and demand-side interventions must be struck, with an emphasis on effect and sustainability. Among the key requirements are randomized, controlled community effectiveness trials of the effect of micronutrient supplementation in pregnancy on perinatal mortality and neurodevelopment, studies on improving adherence and studies on the relation between micronutrient deficiencies and sepsis and neonatal encephalopathy. It would also be helpful to look at mechanisms for bringing the periconceptional period within the ambit of trials.
Micronutrients may have a role in enhancing reproductive health of women living in the developing world. Two illustrative micronutrients, zinc and vitamin A, have received some attention in this regard. Numerous animal experiments and observational studies suggest the potential role of zinc deficiency in labor and delivery-related complications such as premature rupture of membrane, placental abruption, preterm labor and inefficient uterine contraction. These associations have not been confirmed in supplementation studies. Zinc does not appear to be a limiting factor in intrauterine growth in the developing world, contrary to some evidence of its suggested benefit among women residing in industrialized countries. One study in Nepal found that maternal vitamin A or beta-carotene supplementation reduces pregnancy-related mortality but not infant mortality. These findings are corroborated by observations of the significantly higher risk of mortality among night-blind women compared to non-night-blind women long after the termination of pregnancy and the resolution of night blindness. Maternal multiple micronutrient supplementation needs more careful evaluation before its use in large-scale programs. Two recent trials indicated that a prenatal multiple micronutrient supplement provides no added advantage over iron and folate in reducing outcomes such as low birth weight and probably no survival benefit. Data are also suggestive that adding zinc may negate the beneficial effect of iron and folic acid on birth weight. Research is needed to further our understanding of nutrient-nutrient interactions.
Deficient or excessive levels of blood trace elements can be an adverse factor in human and animal pregnancy. The aim of this study was to investigate possible differences in the levels of serum magnesium, calcium, copper, and zinc in preeclamptic and healthy pregnant women. Samples were collected from 30 preeclamptic (PE) and 30 healthy pregnant (HP) women. The serum copper concentration was significantly lower in the PE group by 68% (p<0.0001) when compared to the healthy controls. The serum zinc and calcium were 43% and 10% lower in the PE women, respectively (both with p<0.0001), whereas the magnesium concentration showed nonsignificant differences between the two groups. Measurement of these elements may be useful for the early diagnosis of a preeclamptic condition.
Zinc and copper deficiency is associated with anaemia or iron deficiency and affects fetus growth and pregnant women during pregnancy. To examine iron, zinc and copper status of Chinese pregnant women with and without anaemia in the third trimester, 1185 subjects were enrolled for measurements of Hb, ferritin, transferrin, soluble transferrin receptor (sTfR), and serum iron, zinc and copper. The results showed that there were lower levels of ferritin (14.1 microg/L) and transferrin (3.33 g/L) in subjects with Hb<or=100g/L as compared with subjects with Hb>or=101 g/L. sTfR levels in subjects with Hb<or=100g/L were significantly higher than those in subjects with Hb>or=120 g/L (38.5 nmol/L vs. 25.04 nmol/L, P<0.001). Serum iron was lower in subjects with Hb<or=100 g/L than those with Hb>or=120 g/L (871 microg/L vs. 990 microg/L, P<0.01). Lower levels of serum iron and zinc were also found in anaemic (Hb<110 g/L) as compared with non-anaemic women (Hb>or=110 g/L). Frequencies of marginal deficiencies in serum iron and zinc were 41.58% and 51.05% respectively higher in anaemic than in non-anaemic subjects. Distribution of serum zinc and iron showed a decreasing trend as Hb decreased. Few anaemic as well as non-anaemic subjects had copper deficiency although copper and Hb levels were found inversely correlated and the ratio of copper/iron was higher in anaemic than in non-anaemic group. In conclusion, a lower level of serum zinc in anaemic pregnant women might be related to anaemia and iron deficiency during pregnancy. Therefore, combined zinc and iron supplementation should be recommended to Chinese pregnant women, especially those with anaemia.
Trace element deficiencies have been documented to play an important role in determination of the fetal outcome. Pregnant women in developing countries have been reported to consume diets with a lower density of minerals and vitamins. Deficiencies of trace elements like zinc, copper and magnesium have been implicated in various reproductive events like infertility, pregnancy wastage, congenital anomalies, pregnancy induced hypertension, placental abruption, premature rupture of membranes, still births and low birth weight. The present review article highlights the important of role played by zinc, copper and magnesium during pregnancy and its outcome. The role of individual trace elements and in combination with other trace elements has not been completely documented. There is a need to undertake further studies in this field.
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Burits CA, Ashwoods ER, Aldrich JE, Tietz NW. Tietz Funda-mentals of Clinical Chemistry, fifth Edn., vol. 973. United State of America: W.B. Saunders; 2001. p. 1018.