Prenatal iron supplementation adjusted to maternal iron stores reduces behavioural problems in 4-year-old children.

Prenatal iron supplementation improves children's health and cognitive performance, but few studies explore behavioural development. This study assessed the effects of adjusting prenatal iron supplementation to maternal iron stores during early pregnancy on children's behavioural problems. Randomized controlled trial conducted in Tarragona (Spain) involving 230 nonanaemic pregnant women and their children after a 4-year follow-up. Based on haemoglobin (Hb) levels before gestational week (GW) 12, women receive different iron doses: those with Hb = 110-130 g/L were randomized to receive 80 or 40 mg/day and those with Hb > 130 g/L were randomized to receive 20 or 40 mg/day. Maternal iron stores at GW12 were classified using serum ferritin (SF) as low (SF < 15 µg/L), normal (SF = 15-65 µg/L), and normal-high (SF > 65 µg/L). Children's behaviour was assessed by parents using the Child Behaviour Checklist for ages 1.5-5 years and the Behaviour Rating Inventory of Executive Function-Preschool Version, and by teachers using the Teacher's Report Form for ages 1.5-5 years. Multivariable regression models were performed. Taking 80 mg/day of iron improved child behaviour when women had low iron stores but worsened it when mothers had normal-high iron stores, except for depressive and attention/hyperactivity problems. Taking 20 mg/day of iron improved behaviour only in those children whose mothers had SF > 65 µg/L in early pregnancy. Additionally, executive functioning improved at high doses of prenatal iron when maternal baseline SF < 15 µg/L. Adjusting prenatal iron supplementation to both maternal baseline Hb levels and iron stores reduces behavioural problems in 4-year-old children.

Importance of Maternal Iron Status on the Improvement of Cognitive Function in Children After Prenatal Iron Supplementation.

INTRODUCTION: The effectiveness of prenatal iron supplementation improves maternal hematological outcomes, but little research has focused on child outcomes. The objective of this study was to assess whether prenatal iron supplementation adjusted to maternal needs improves children's cognitive functioning. METHODS: The analyses included a subsample of nonanemic pregnant women recruited in early pregnancy and their children aged 4 years (n=295). Data were collected between 2013 and 2017 in Tarragona (Spain). On the basis of hemoglobin levels before the 12th gestational week, women receive different iron doses: 80 vs 40 mg/d if hemoglobin is 110-130 g/L and 20 vs 40 mg/d if hemoglobin >130 g/L. Children's cognitive functioning was assessed using the Wechsler Preschool and Primary Scale of Intelligence-IV and Developmental Neuropsychological Assessment-II tests. The analyses were carried out in 2022 after the completion of the study. Multivariate regression models were performed for assessing the association between different doses of prenatal iron supplementation and children's cognitive functioning. RESULTS: Taking 80 mg/d of iron was positively associated with all the scales of the Wechsler Preschool and Primary Scale of Intelligence-IV and Neuropsychological Assessment-II when mothers had initial serum ferritin <15 µg/L, but it was negatively associated with Verbal Comprehension Index, Working Memory Index, Processing Speed Index, and Vocabulary Acquisition Index from Wechsler Preschool and Primary Scale of Intelligence-IV and verbal fluency index from Neuropsychological Assessment-II when mothers showed initial serum ferritin >65 µg/L. In the other group, taking 20 mg/d of iron was positively associated with Working Memory Index, Intelligence Quotient, verbal fluency, and emotion recognition indices when women had initial serum ferritin >65 µg/L. CONCLUSIONS: Prenatal iron supplementation adjusted to the maternal hemoglobin levels and baseline iron stores improves cognitive functioning in children aged 4 years.

Adapting prenatal iron supplementation to maternal needs results in optimal child neurodevelopment: a follow-up of the ECLIPSES Study.

BACKGROUND: Prenatal prescription of standard iron supplements to prevent iron deficiency appears not to be appropriate for all women and their children, as some women may be at risk of iron deficiency and others at risk of iron excess early in pregnancy. The present study aimed to assess whether prenatal iron supplementation adapted to the needs of each pregnant woman affects their child's neurodevelopment. METHODS: Follow-up of a community-based RCT involving 503 mother-child pairs. Non-anaemic pregnant women recruited in Tarragona (Spain) early in pregnancy were prescribed a daily iron dose based on their initial haemoglobin levels: Stratum 1 (Hb = 110-130 g/L, 80 or 40 mg/d of iron) and Stratum 2 (Hb > 130 g/L, 40 or 20 mg/d of iron). Women receiving 40 mg/d were considered the control group in each Strata. The child's neurodevelopment was assessed at 40 days of age using the Bayley Scales of Infant Development-III (BSID-III). Adjusted multiple regression models were used. RESULTS: Multiple regression analyses showed no association between the intervention and control group within each Strata on the BSID-III scores on any of the developmental scales in children, including cognitive, language, and motor development: Stratum 1 (ß 1.46, 95%CI -2.15, 5.07; ß 1.30, 95%CI -1.99, 4.59; and ß 2.04, 95%CI -3.88, 7.96, respectively) and Stratum 2 (ß -4.04, 95%CI -7.27, 0.80; ß -0.36, 95%CI -3.47, 2.75; and ß -3.76, 95%CI -9.30, 1.78, respectively). CONCLUSIONS: In non-anaemic women in early pregnancy, no differences were found in the cognitive, language and motor development of children at 40 days of age between the dose of iron tested in each case -adjusted to initial Hb levels- compared to the dose of the control group. Further studies are guaranteed to confirm our findings. TRIAL REGISTRATION: The ECLIPSES study was registered at www.clinicaltrialsregister.eu as EudraCT number 2012-005,480-28.

[Prevention of eating disorders in primary education]. / Prevención de los trastornos de la conducta alimentaria en educación primaria.

Introduction: Eating disorders are infrequent in school age, being predominant in the female sex. The main predictive factors at this age are similar to those of other age groups, the influence of body changes being particularly important, especially in girls. Despite preventive programs in this age group are scarce, those focused mainly on the acceptance of body image, internalization of the ideal of appearance and media literacy have shown some effectiveness. However, new research is needed to confirm the approaches with the best results.

Introducción: Los trastornos de la alimentación son poco frecuentes en las edades de la etapa escolar, siendo predominantes en el sexo femenino. Los principales factores predictivos en esta edad son similares a los de otros grupos de edad, siendo particularmente importante la influencia de los cambios corporales, sobre todo en las niñas. Aunque los programas preventivos en este grupo de edad son escasos, los centrados principalmente en la aceptación de la imagen corporal, la internalización del ideal de apariencia y la alfabetización mediática han observado cierta eficacia. No obstante, son necesarias nuevas investigaciones que confirmen los enfoques con mejores resultados.

The effect of prenatal smoke exposure on child neuropsychological function: a prospective mother-child cohort study.

Objective: To study prospectively the effect of prenatal smoke exposure (PSE) on child neuropsychological function and intelligence quotient (IQ).Background: PSE has been associated with adverse effects on child neurodevelopment. However, some studies reported that these associations disappear after adjustment for potential confounders.Methods: A cohortof 248 mothers-child dyad was followed from the first trimester of pregnancy until children were 7.5 years old. PSE was recorded during pregnancy by questionnaire and plasma cotinine. The Wechsler Intelligence Scale for Children, the Neuropsychological Assessment of Executive Functions for Children (ENFEN) and the School Neuropsychological Maturity Questionnaire were administered at 7.5 years of age. The effect of PSE on child IQ and neuropsychological function was assessed with ANCOVA, adjusting for obstetric, neonatal and sociodemographic factors.Results: Children whose mothers smoked throughout pregnancy scored lower in interference (ENFEN) compared to unexposed children (F = 4.1; p = .008). The results showed no differences in other executive functions, verbal and visual memory and IQ between the PSE groups.Conclusion: PSE had little effect on child neuropsychological outcome and was limited to mental flexibility. Nevertheless, these findings support further efforts aimed at encouraging mothers to quit smoking in pregnancy.

Association of Iron Status and Intake During Pregnancy with Neuropsychological Outcomes in Children Aged 7 Years: The Prospective Birth Cohort Infancia y Medio Ambiente (INMA) Study.

Early iron status plays an important role in prenatal neurodevelopment. Iron deficiency and high iron status have been related to alterations in child cognitive development; however, there are no data about iron intake during pregnancy with other environmental factors in relation to long term cognitive functioning of children. The aim of this study is to assess the relationship between maternal iron status and iron intake during pregnancy and child neuropsychological outcomes at 7 years of age. We used data from the INMA Cohort population-based study. Iron status during pregnancy was assessed according to serum ferritin levels, and iron intake was assessed with food frequency questionnaires. Working memory, attention, and executive function were assessed in children at 7 years old with the N-Back task, Attention Network Task, and the Trail Making Test, respectively. The results show that, after controlling for potential confounders, normal maternal serum ferritin levels (from 12 mg/L to 60 mg/L) and iron intake (from 14.5 mg/day to 30.0 mg/day), respectively, were related to better scores in working memory and executive functioning in offspring. Since these functions have been associated with better academic performance and adaptation to the environment, maintaining a good state of maternal iron from the beginning of pregnancy could be a valuable strategy for the community.

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.

Influence of breastfeeding and iron status on mental and psychomotor development during the first year of life.

Breastfeeding (BF) confers numerous benefits on the developing infant in both the short and the long term including psychological development, but there are multiple other factors that must be taken into account when these relationships are studied. To analyse how breastfeeding during the first 4 months of life affects infant mental and psychomotor development (MPD) at 6 and 12 months in a group of healthy infants from a Mediterranean Spanish city considering many important potential confounds. This is a longitudinal study conducted on infants from birth until the age of 12 months. A total of 154 healthy infants were evaluated by Paediatric Unit of Sant Joan University Hospital in Reus, Spain. Type of feeding, clinical history, anthropometry, iron status and mental and psychomotor development were assessed and analysed. At 4 months, 24% of infants received BF and 26% received mixed feeding (MF). Multiple Linear Regression models were applied adjusting for potential prenatal, perinatal and postnatal confounds showing that infants who received BF for at least four months presented higher psychomotor development index (PDI) at 6 and at 12 months of age. Also, gestational age and BMI at 6m were associated positively with PDI at 6 m, and haemoglobin levels at 12m and birth height were associated with PDI and MDI at 12m (respectively). In conclusion, after the adjustment of important potential confounds, BF during at least four months and adequate infant iron status are related to better psychomotor development during the first year. No associations were found between BF and mental development.

Effects of prenatal iron status on child neurodevelopment and behavior: A systematic review.

Iron deficiency and iron-deficiency anemia are the main worldwide nutritional disorders. A good level of prenatal iron is essential for the correct child neurodevelopment but this association has been poorly investigated. To gather the scientific evidence on the relation between prenatal iron status and child neurodevelopment. To emphasize the importance of personalize the dose and type of supplementation. Wide search strategy was performed in electronic databases for English language articles with no limitations as regards the language or date of publication. Additional studies were selected by hand search. The inclusion criteria were pregnant women without high-risk pregnancy and their children as study population and neurodevelopment as the main outcome. Six RCTs and 13 observational studies were included. The majority concluded that deficit or excess iron during pregnancy injures the mental and psychomotor development of child. Other authors found no association of low iron level with troubles in neurodevelopment, recommended multi-micronutrients instead of iron alone and/or showed inconsistent results. Both iron deficiency as its excess are harmful for the child neurodevelopment. The prenatal iron supplementation should be adjusted for each woman, taking into account the iron stores, some genetic mutation and other health habits.

Are there early inflammatory biomarkers that affect neurodevelopment in infancy?

Few studies have investigated the relationship between post-natal inflammatory biomarkers at early age and child neurodevelopment outcomes. The main aim of this study was to examine the relationship between IL-6, IL-1ß, IL-4 cytokines, as well as cortisol at 6 and 12months of age, and neurodevelopment and psychological problems at 30months of age. The study was conducted on a sample of 51 full-term newborns who were followed up at 6, 12, and 30months of age. Infant neurodevelopment was assessed using the Bayley Scales of Infant Development-II, psychological problems were assessed with the Child Behavior Checklist 1.5-5 (CBCL 1.5-5) and the mother's emotional symptoms were assessed with the General Health Questionnaire-28. When the infants were 6 and 12months old, IL-6, IL-1ß, IL-4 cytokines, and cortisol were measured in blood samples. The results showed that higher IL-6 at 12months predicted higher scores in internalizing (emotionally reactive, anxious/depressed, withdrawn and attention problems) and externalizing problems (aggressive behavior) at 30months. By contrast, high levels of IL-1ß at 6months were related to worse motor skills. Inflammatory biomarkers were not related to mental performance. IL-6 and IL-1ß could be early markers of later psychological problems and psychomotor disabilities.

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.

Prevalencia de la sintomatología del Síndrome de Asperger y variables asociadas en preescolares españoles / Prevalence of Asperger Syndrome symptomatology and associated variables in Spanish preschoolers

El Síndrome de Asperger (AS) forma parte del espectro de trastornos autistas, su estudio es reciente para el caso de edades tempranas. El objetivo de esta investigación es determinar la prevalencia de los síntomas del AS en población preescolar general, rural y urbana en preescolares de España. Además, analizamos las áreas de desarrollo y síntomas de ansiedad asociados a la presencia de sintomatología del AS. La muestra de este estudio se conforma de 1104 preescolares de 3 a 6 años de edad. La presencia de síntomas del AS se evaluó con base en el reporte de padres y maestros, mediante un instrumento de detección de desórdenes psiquiátricos. La prevalencia informada por padres fue de 11,7%, mientras que para los maestros fue de 8,1%. La presencia de sintomatología del AS se asoció a retrasos en el desarrollo de la comprensión del lenguaje, la coordinación motora, las habilidades de autoayuda y la práctica de juegos. Además, nuestros resultados indican que el AS tiene una fuerte relación con síntomas de fobia específica y tics. Concluimos que es posible hacer una detección temprana de la sintomatología del AS, ya que encontramos prevalencias similares a otras descritas en investigaciones recientes. Dada la afectación asociada al AS, su detección es altamente recomendable.

Asperger's Syndrome (AS) forms part of the whole spectrum of autistic disorders. Until recently it has not been studied in early ages. The aim of this study is to determine the AS's prevalence of symptoms in general preschool, rural and urban population. In addition, the association of the development areas and symptoms of anxiety and the presence of symptoms of AS was analized. The sample of this study consisted in 1104 preschool children between 3-6 years old. The presence of AS's symptoms was evaluated by a screening tool for psychiatric disorders. This tool was applied to both, preschooler's parents and their teachers. The prevalence of symptoms of AS for parents and teachers was 11.7% and 8.1%, respectively. The presence of AS's symptoms was associated with language compression delays, general and fine motor coordination, self-help skills and impairment in game activities. In addition, our results showed that the AS has a strong association with specific phobia symptoms and tics. We conclude that an early detection of AS's symptoms is possible since we found similar prevalence described in other recent researches. Given the impairment associated with AS, its detection is highly recommended.

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.