Does the fortified milk with high iron dose improve the neurodevelopment of healthy infants? Randomized controlled trial.

BACKGROUND: Since iron plays an important role in several physiological processes, its deficiency but also overload may harm the development of children. The aim was to assess the effect of iron-fortified milk on the iron biochemical status and the neurodevelopment of children at 12 months of age. METHODS: Randomized controlled trial conducted in 133 Spanish children, allocated in two groups to receive formula milk fortified with 1.2 or 0.4 mg/100 mL of iron between 6 and 12 months of age. Psychomotor (PDI) and Mental (MDI) Development Index were assessed by the Bayley Scales before and after the intervention. Maternal obstetrical and psychosocial variables were recorded. The biochemical iron status of children was measured and data about breastfeeding, anthropometry and infections during the first year of life were registered. RESULTS: Children fortified with 1.2 mg/100 mL of iron, compared with 0.4 mg/100 mL, showed higher serum ferritin (21.5 vs 19.1 µg/L) and lower percentage of both iron deficiency (1.1 to 5.9% vs 3.8 to 16.7%, respectively, from 6 to 12 months) and iron deficiency anemia (4.3 to 1.1% vs 0 to 4.2%, respectively, from 6 to 12 months) at the end of the intervention. No significant differences were found on neurodevelopment from 6 to 12 months between children who received high dose of Fe compared with those who received low dose. CONCLUSION: Despite differences on the iron status were observed, there were no effects on neurodevelopment of well-nourished children in a developed country after iron supplementation with doses within dietary recommendations. Follow-up studies are needed to test for long-term neurodevelopmental improvement. TRIAL REGISTRATION: Retrospectively registered in ClinicalTrials.gov with the ID: NCT02690675.

[Consumption of free sugars and excess weight in infants. A longitudinal study]. / Ingesta de azúcares libres y exceso de peso en edades tempranas. Estudio longitudinal.

INTRODUCTION: The consumption of free sugars has been related to excess weight, with the WHO recommending an intake of <10% of total energy. The aim of this study is to assess the association between the consumption of free sugars at 12 months and the risk of excess weight at 30 months in healthy children. MATERIAL AND METHODS: A longitudinal study was conducted on 81 children followed-up from birth to 30 months. A record was made of the clinical history and anthropometry, at birth, and at 12 and 30 months. Weight status was classified as with or without excess weight, according to WHO values. At 12 months, the intake of energy and nutrients was analysed by differentiating the intake of free and natural sugars. Multivariate analyses adjusted for the main confounding variables were performed. RESULTS: Free sugars were consumed by 40.4% of the 12-month-old children, being higher than that recommended, and being significantly higher in children with excess weight at 30 months (60.9%). The higher intake of free sugars at 12 months is associated with an increased risk of excess weight at 30 months (OR: 1.130, 95% CI: 1.032-1.238). CONCLUSIONS: The consumption of free sugars is much higher than that recommended in 12-month-old infants. This high intake could be a risk factor for excess weight, even at early ages.

Prevalence of anaemia, risk of haemoconcentration and risk factors during the three trimesters of pregnancy.

OBJECTIVE: To evaluate the prevalence of anaemia and the risk of haemoconcentration and its risk factors during all 3 trimesters of pregnancy in women in a Mediterranean area in the south of Europe. MATERIAL AND METHODS: Longitudinal study of 11,259 women whose pregnancies were monitored at primary care centres between 2007 and 2012. The computerised clinical histories of all the pregnancies were used to collect haemoglobin (Hb) data for each trimester. The histories also provided information on the age of the mother, her socioeconomic status, the presence of obesity, tobacco use, type of pregnancy, and number of previous pregnancies and births. Anaemia was defined as Hb < 110 g/L in the 1st and 3rd trimesters of pregnancy and Hb < 105 g/L in the second. The risk of haemoconcentration was defined as Hb > 130 g/L in the 2nd and 3rd trimesters of pregnancy. RESULTS: The prevalence of anaemia increased from 3.8% in the first trimester to 21.5% in the 3rd trimester. Around 10% of the women had Hb > 130 g/L during the 3rd trimester. Having children previously and/or being younger than 20 increased the chances of anaemia (Adj. OR: 1.4; 95% CI: 1.1-1.9), but being older than 34 increased the chances of Hb > 130 g/L (Adj. OR: 1.3; 95% CI: 1.1-1.5). CONCLUSION: The increased prevalence of anaemia is a moderate public health problem. Understanding the factors that influence these problems may help improve the guidelines regarding the use of iron supplements.

Elevated iron status and risk of gestational diabetes mellitus: A systematic review and meta-analysis.

The aim of this systematic review and meta-analysis of observational studies was to assess the relationship between elevated iron status, measured as hemoglobin and ferritin levels, and the risk of gestational diabetes mellitus (GDM). The present study was recorded in PROSPERO (2013:CRD42013005717). The selected studies were identified through a systematic review of scientific literature published in The Cochrane Library and PubMed/MEDLINE databases from their inception until March 10, 2016, in addition to citation tracking and hand-searches. The search strategy of original articles combined several terms for hemoglobin, ferritin, pregnancy, and GDM. OR and 95% CI of the selected studies were used to identify associations between hemoglobin and/or ferritin levels with the risk of GDM. Summary estimates were calculated by combining inverse-variance using fixed-effects model. 2468 abstracts were initially found during the search. Of these, 11 with hemoglobin and/or ferritin data were selected for the meta-analyses. We observed that high hemoglobin (OR = 1.52; 95% CI: 1.23-1.88), as well as ferritin (OR = 2.09; 95% CI: 1.48-2.96) levels were linked to an increased risk of GDM. Low heterogeneity was observed in hemoglobin (I2  = 33.3%, P = 0.151) and ferritin (I2  = 0.7%, P = 0.418) meta-analyses, respectively. Publication bias was not appreciated. High hemoglobin or ferritin levels increase the risk of GDM by more than 50% and more than double, respectively, in the first and third trimester. Therefore, determining of hemoglobin or ferritin concentration in early pregnancy might be a useful tool for recognizing pregnant women at risk of GDM.

Adapting iron dose supplementation in pregnancy for greater effectiveness on mother and child health: protocol of the ECLIPSES randomized clinical trial.

BACKGROUND: Currently, there is no consensus regarding iron supplementation dose that is most beneficial for maternal and offspring health during gestation. Recommended iron supplementation dose does not preempt anemia in around 20% of the pregnancies, nor the risk of hemoconcentration in 15%. This deficit, or excess, of iron prejudices the mother-child wellbeing. Therefore the aims of the study are to determine the highest level of effectiveness of iron supplementation adapted to hemoglobin (Hb) levels in early pregnancy, which would be optimum for mother-child health. DESIGN: Randomized Clinical Trial (RCT) triple-blindedSetting: 10 Primary Care Centers from Catalunya (Spain)Study subjects: 878 non-anemic pregnant women at early gestation stage, and their subsequent newborns METHODS: The study is structured as a RCT with 2 strata, depending on the Hb levels before week 12 of gestation. Stratum #1: If Hb from 110 to 130 g/L, randomly assigned at week 12 to receive iron supplement of 40 or 80 mg/d. Stratum #2: If Hb >130 g/L, randomly assigned at week 12 to receive iron supplement of 40 or 20 mg/d. MEASUREMENTS: In the mother: socio-economic data, clinical history, food item frequency, lifestyle and emotional state, and adherence to iron supplement prescription. Biochemical measurements include: Hb, serum ferritin, C reactive protein, cortisol, and alterations in the HFE gene (C282Y, H63D). In children: ultrasound fetal biometry, anthropometric measurements, and temperament development.Statistical analyses, using the SPSS program for Windows, will include bivariate and multivariate analyses adjusted for variables associated with the relationship under study. DISCUSSION: Should conclusive outcomes be reached, the study would indicate the optimal iron supplementation dose required to promote maternal and infant health. These results would contribute towards developing guidelines for good clinical practice.

[Effects of tobacco habit, second-hand smoking and smoking cessation during pregnancy on newborn's health]. / Impacto del tabaquismo, la exposición pasiva al tabaco y el dejar de fumar sobre la salud del recien nacido.

BACKGROUND AND OBJECTIVE: Tobacco during pregnancy affects the health of the newborn. The aim was to assess the effect of maternal exposure to active and passive tobacco and of smoking cessation on the risk of preterm deliveries and birth weight, taking into account other risk factors. PATIENTS AND METHOD: Longitudinal study conducted in 282 healthy pregnant women. General, obstetrical and hematological data were collected as it was the smoking habit during pregnancy. Pregnant women were classified as "exposed to smoke" (active smoker and passive smoker) and "unexposed to smoke" (non-smokers and women who quitted smoking during pregnancy). RESULTS: A percentage of 59.2 were non-smokers, 18.4% active smokers, 8.5% second-hand smokers and 13.8% had stopped smoking. Unexposed pregnant women who stopped smoking had the same risk of premature deliveries and children with similar birth weight as non-smoker women. Active and second-hand smokers were at higher risk of preterm deliveries than non-smokers (odds ratio [OR] 6.5, 95% confidence interval [95% CI] 1.4-30.8 and OR 6.2, 95% CI 1.0-38.9, respectively); however, higher levels of hemoglobin in the 1st and 3rd trimester exerted a protective effect (OR 0.9, 95% CI 0.8-0.9). Active and second-hand smokers had babies weighing less than non-smokers (around 129 and 178g less, respectively). CONCLUSIONS: Active or passive exposure to smoke during pregnancy and lower hemoglobin levels are associated with an increased risk of premature deliveries and lower birth weight. Stopping smoking during pregnancy prevents these detrimental effects.

Diet, iron biomarkers and oxidative stress in a representative sample of Mediterranean population.

BACKGROUND: The consumption pattern characterized by high consumption of vegetables, fruit, fish, olive oil and red wine has been associated with improvements in the total antioxidant capacity of individuals and reduced incidence of diseases related to oxidation. Also, high body iron levels may contribute to increase the oxidative stress by the generation of reactive oxygen species. The objective of this study is to analyze the relationship between antioxidant and pro-oxidant factors obtained from the diet and iron biomarkers on lipoprotein oxidation and total antioxidant capacity in a representative sample of the Mediterranean population. METHODS: Cross-sectional prospective study, carried out with 815 randomly selected subjects (425 women and 390 men). Dietary assessment (3-day food records), iron biomarkers (serum ferritin, serum iron and transferrin saturation), biochemical markers of lipoperoxidation (TBARS), antioxidant capacity (ORAC) and CRP (C-Reactive Protein) were determined. Multiple Linear Regression (MLR) models were applied to analyze the association between diet factors and iron biomarkers on TBARS and ORAC levels. RESULTS: We observed that lipoperoxidation measured by TBARS increased by age but no differences were observed by sex. Antioxidant capacity measured by ORAC is independent of age and sex. In general, increasing age, tobacco, heme iron intake from meat and fish and transferrin saturation were independently and positively associated with TBARS, while non-heme iron was negatively associated. Vegetables, vitamin C intake and serum ferritin were positively associated with ORAC, whereas saturated fatty acids and meat intake were negatively associated. CONCLUSIONS: In our general population, we observed that oxidative stress is related to aging, but antioxidant capacity is not. The highest intake of dietary non-heme iron, vegetables and vitamin C intake exerts a protective effect against oxidation while the highest intake of dietary heme iron from meat and fish and saturated fatty acids are associated with increased oxidative stress. High levels of circulating iron measured by transferrin saturation are associated with increased oxidative stress in women however its association with the higher levels of serum ferritin is controversial.

Prevalence of iron deficiency states and risk of haemoconcentration during pregnancy according to initial iron stores and iron supplementation.

OBJECTIVE: To describe the prevalence of iron depletion (ID), iron-deficiency anaemia (IDA) and risk of haemoconcentration during pregnancy and at delivery and to assess the influence of initial Fe stores and Fe supplementation on that prevalence. DESIGN: Longitudinal study. SETTING: Hospital Universitari Sant Joan de Reus (Catalonia, Spain). SUBJECTS: Two hundred and eighty-five pregnant women. Serum ferritin and Hb were measured in the first, second and third trimesters and at delivery. Women were classified according to initial Fe stores as ID or no ID (serum ferritin $12mg/l) and according to Fe supplement use as supplemented or nonsupplemented. RESULTS: Initial ID was 16.2%. At delivery, 45.7% had ID, 13.5% IDA and 13.3% had risk of haemoconcentration. Initial ID and non-supplemented groups had significantly higher prevalences of ID and IDA and lower risk of haemoconcentration at delivery than the other groups. In the multiple logistic models, no initial ID and Fe supplementation exerted a protective effect against ID at delivery (adjusted OR50.28; 95% CI 0.13, 0.58 and adjusted OR50.39; 95% CI 0.22, 0.69, respectively). Moderate Fe supplementation did not seem to clearly prevent IDA (adjusted OR50.91; 95% CI 0.42, 1.96) or to enhance the haemoconcentration (adjusted OR51.42; 95% CI 0.58, 3.50). CONCLUSIONS: The prevalence of ID and IDA was high in late pregnancy in healthy pregnant women, particularly in those with initial ID and/or those not taking supplements. Starting pregnancy with no ID and/or taking moderate Fe supplementation decreased the likelihood of ID at delivery. The risk of haemoconcentration was high at delivery, but did not seem to be promoted by Fe supplementation. Further research is necessary to determine the most appropriate nutritional advice for pregnant women.

Effect of different doses of iron supplementation during pregnancy on maternal and infant health.

Currently, there is no consensus regarding the optimum iron supplementation during pregnancy. The aim of this study is to evaluate the effect of different iron supplementation doses (including no supplementation) during pregnancy on the iron status of the mother and on the health of the neonate. A longitudinal study was conducted involving 358 pregnant women and their newborns. Mothers were classified as non-supplemented, low iron supplemented (<60 mg/day), moderate iron supplemented (between 60 and 100 mg/day) or high iron supplemented (>100 mg/day). General clinical and obstetric histories, haemoglobin (Hb), serum ferritin (SF) and transferrin saturation were evaluated in the first, second, third trimesters, and at partum. SF and Hb decreased less sharply in the iron-supplemented groups compared to the non-supplemented group. The higher the doses of iron supplementation, the lower the percentages of iron depletion at partum (p < 0.001), iron deficiency anaemia (p < 0.001) and preterm deliveries (p = 0.009) as well as a higher birth weight of the newborn. However, the group with high supplementation had a greater percentage (27.6 %) of women at risk of haemoconcentration at partum. Our Mediterranean women began gestation with iron stores close to deficit (SF, 28.1 µg/L; 95 % CI 27.9-28.4). With these iron stores, supplementation with iron at daily doses of between 60 and 100 mg appears to be the most beneficial for the health of mother and child. These findings need to be confirmed in further randomised clinical trials.

Pre-pregnancy iron reserves, iron supplementation during pregnancy, and birth weight.

BACKGROUND: Early iron supplementation in women with sufficient reserves could provoke iron excess resulting in haemoconcentration and low infant birth weight (IBW). AIM: To clarify the influence of early iron supplementation on maternal iron status and the IBW, taking into account pre-pregnancy iron deposits. STUDY DESIGN: Longitudinal, prospective study. SUBJECTS: Healthy women volunteers (n=82) intending to become pregnant. OUTCOME MEASURES: Women were grouped as a function of their pre-pregnancy (low or present) iron stores (serum ferritin (SF)

Effects of iron deficiency on neonatal behavior at different stages of pregnancy.

Animal and human studies have shown that prenatal and postnatal iron deficiency is a risk factor for behavioral, emotional and cognitive development. The aim of this study was to determine the associations between iron status of pregnant women and the behavior of their newborn, taking into account the timing in which the deficit occurs. This study was conducted in Spain (developed country) where: the general population is well-nourished; during pregnancy routine obstetrical checks are carried out; and pregnant women are systematically iron supplemented. A total of 216 healthy and well-nourished pregnant women and their term, normal weight newborn participated in this study. The neonatal behavior was assessed by the Neonatal Behavior Assessment Scale (NBAS). The results showed that in the first and second trimesters of pregnancy, iron deficiency was a weak and significant predictor of the NBAS autonomous nervous system cluster score, and in the third trimester, this condition predicted the NBAS motor and state organization clusters score and the NBAS robustness and endurance supplementary item. In conclusion, iron deficiency during pregnancy is related to the neonate's general autonomous response, motor performance and self regulation capabilities.