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.

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.

Prevalence of anaemia, risk of haemoconcentration and risk factors during the three trimesters of pregnancy / Prevalencia de anemia y riesgo de hemoconcentración durante los 3 trimestres de embarazo y factores de riesgo

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 (AU)

Objetivo: valorar la prevalencia de anemia y de riesgo de hemoconcentración y sus factores de riesgo durante los 3 trimestres de embarazo en las mujeres de una zona mediterránea del sur de Europa. Material y métodos: estudio longitudinal con 11.259 mujeres que realizaron el seguimiento de su embarazo en centros de atención primaria entre el 2007 y 2012. A partir de la historia clínica informatizada se recogieron datos de hemoglobina (Hb) de cada trimestre de gestación, edad de la madre, bajo nivel socioeconómico, presencia de obesidad, hábito tabáquico, tipo de embarazo, número de embarazos y partos previos. Se definió anemia como Hb < 110 g/L para el 1er y 3er trimestre de gestación y como Hb < 105 g/L para el 2º trimestre. Se definió riesgo de hemoconcentración a Hb > 130 g/L en el 2º y 3er trimestre. Resultados: la prevalencia de anemia aumentó del 3.8% en el primer trimestre al 21.5% en el 3er trimestre. Alrededor de un 10% de las mujeres tuvieron Hb > 130 g/L en el 3er trimestre. Tener hijos previos y/o ser menor de 20 años predispone a tener anemia (adj. OR: 1.4; 95% CI: 1.1-1.9), pero tener más de 34 años predispone a Hb > 130 g/L (adj. OR: 1.3; 95% CI: 1.1-1.5). Conclusión: la elevada prevalencia de anemia supone un problema moderado de salud pública. El conocimiento de los factores que pueden influir en dichas prevalencias puede ayudar a adaptar mejor la pauta de suplementación con hierro (AU)

Haemoconcentration risk at the end of pregnancy: effects on neonatal behaviour.

OBJECTIVE: To determine the associations between haemoconcentration at the end of pregnancy (third trimester and delivery) and neonatal behaviour in healthy pregnant women supplemented with moderate doses of Fe. DESIGN: A prospective longitudinal study in which obstetric and clinical history, maternal toxic habits, maternal anxiety and Hb levels were recorded at the third trimester and delivery. Neonatal behaviour was assessed at 48-72 h of age using the Neonatal Behavioral Assessment Scale. SETTING: Unit of Obstetrics and Gynaecology of the Sant Joan University Hospital in Reus, Tarragona (Spain). SUBJECTS: A total of 210 healthy and well-nourished pregnant women and their full-term, normal-weight newborns. RESULTS: The results showed that, after adjusting for confounders, in the third trimester the risk of haemoconcentration (6·2 % of pregnant women) was related to decreased neonatal state regulation (B=-1·273, P=0·006) and alertness (B=-1·848, P=0·006) scores. In addition, the risk of haemoconcentration at delivery (12·0 % of pregnant women) was also related to decreased neonatal state regulation (B=-0·796, P=0·021) and poor robustness and endurance (B=-0·921, P=0·005) scores. CONCLUSIONS: Our results show that the risk of haemoconcentration at the end of pregnancy is related to the neonate's neurodevelopment (and self-regulation capabilities), suggesting that Fe supplementation patterns and maternal Fe status during pregnancy are important factors for neurodevelopment which may be carefully controlled.

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.

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.

Efectividad de la pauta de suplementación con hierro recomendada en España a embarazadas sin anemia al inicio de la gestación / Effectivity of the iron supplementation pattern recommended in Spain for pregnant women without anemia at the beginning of pregnancy

Fundamentos: Las autoridades sanitarias españolas aconsejan suplementar con 30 mg/día de hierro de forma temprana a las embarazadas no anémicas. Nuestro objetivo es analizar el porcentaje de éxito en la prevención del déficit de hierro al final del embarazo con la pauta de suplementación recomendada por el Ministerio de Sanidad y Consumo. Métodos: Estudio longitudinal realizado en 120 embarazadas sin anemia inicial, suplementadas con hierro (20-40 mg/día). Se valora: historia clínica y obstétrica. Durante los tres trimestres y parto se determinan: Hemoglobina, Ferritina sérica, Saturación de transferrina. Resultados: El estado en hierro evoluciona negativamente durante la gestación, recuperándose ligeramente al final del embarazo. El 17,9% de las embarazadas inicia la gestación sin reservas de hierro. En el momento del parto, un 53,4% presentó las reservas de hierro exhaustas y un 16,2%, anemia ferropénica. Conclusiones: La pauta de suplementación con hierro aconsejada en España a las mujeres embarazadas sin anemia inicial, no previene los estados carenciales en hierro al final de la gestación en un porcentaje elevado de mujeres de nuestra población. Son necesarias más evidencias que contribuyan a definir la pauta de suplementación con hierro más efectiva para prevenir la anemia en la mujer embarazada (AU)

Background: Health authorities in Spain recommended supplementing the initially non-anemic pregnant women with 30 mg of iron per day from early gestation. The aim of the study was to analyze the rate of success in preventing iron deficiency in late pregnancy with the supplementation pattern recommended by the Spanish Ministery of Health. Methods: Longitudinal study conducted in 120 pregnant women without initial anemia and taking iron supplementation (20-40 mg/day). Clinical and obstetric histories were collected. Blood haemoglobin, serum ferritin and transferrin saturation were measured in each trimester and at delivery. Results: Iron status decreases during pregnancy and recovers slightly in late pregnancy. A 17.9% of pregnant women start pregnancy without iron stores. At the time of delivery, 53.4% had exhausted iron stores and 16.2% presented iron deficiency anemia. Conclusions: The iron supplementation pattern recommended in Spain to pregnant women without initial anemia does not prevent iron-deficiency states at the end of gestation in a high percentage of women in our population. More evidence is needed to help to define the more effective pattern of iron supplementation in order to prevent anemia in pregnant women (AU)

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.