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Effect of Prenatal Iron Supplementation Adapted to Hemoglobin Levels in Early Pregnancy on Fetal and Neonatal Growth-ECLIPSES Study.
Díaz-Torres, S, Díaz-López, A, Arija, V
Nutrients. 2024;(3)
Abstract
In this randomized clinical trial, we evaluated the effects of prenatal iron supplementation adapted to pregnant women's initial hemoglobin (Hb) levels on fetal growth parameters until birth in women from the Mediterranean coast of northern Spain. All (n = 791) women were iron-supplemented during pregnancy according to Hb levels at the 12th gestational week: stratum 1 (Hb: 110-130 g/L) received 40 or 80 mg iron daily; stratum 2 (Hb > 130 g/L) received 40 or 20 mg iron daily. Fetal biometric and anthropometric measurements were evaluated in the three trimesters and at birth, respectively. In stratum 1, using 80 mg/d instead of 40 mg/d increased the risk of fetal head circumference > 90th percentile (OR = 2.49, p = 0.015) at the second trimester and fetal weight (OR = 2.36, p = 0.011) and femur length (OR = 2.50, p = 0.018) < 10th percentile at the third trimester. For stratum 2, using 40 mg/d instead of 20 mg/d increased the risk of fetal head circumference > 90th percentile (OR = 3.19, p = 0.039) at the third trimester. A higher risk of delivering an LGA baby (OR = 2.35, p = 0.015) for birthweight was also observed in stratum 1 women receiving 80 mg/d. It is crucial to adjust the prenatal iron supplementation to each pregnant woman's needs, i.e., adapted to their initial Hb levels, to achieve optimal fetal development, since excessive iron doses appear to adversely influence fetal growth.
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Prenatal iron supplementation adjusted to maternal iron stores reduces behavioural problems in 4-year-old children.
Iglesias-Vázquez, L, Canals, J, Hernández-Martínez, C, Voltas, N, Arija, V
Maternal & child nutrition. 2024;(1):e13595
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Abstract
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.
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Prenatal Exposure to Air Pollutants and Attentional Deficit Hyperactivity Disorder Development in Children: A Systematic Review.
Kaur, S, Morales-Hidalgo, P, Arija, V, Canals, J
International journal of environmental research and public health. 2023;(8)
Abstract
Up to 9.5% of the world's population is diagnosed with attention deficit/hyperactivity disorder (ADHD), making it one of the most common childhood disorders. Air pollutants could be considered an environmental risk condition for ADHD, but few studies have specifically investigated the effect of prenatal exposure. The current paper reviews the studies conducted on the association between prenatal air pollutants (PM, NOx, SO2, O3, CO and PAH) and ADHD development in children. From the 890 studies searched through PubMed, Google Scholar, Scopus, and Web of Science, 15 cohort studies met the inclusion criteria. NOS and WHO guidelines were used for quality and risk of bias assessment. The accumulative sample was 589,400 of children aged 3-15 years. Most studies reported an association between ADHD symptoms and prenatal PAH and PM exposure. Data available on NO2 and SO2 were inconsistent, whereas the effect of CO/O3 is barely investigated. We observed heterogeneity through an odd ratio forest plot, and discrepancies in methodologies across the studies. Eight of the fifteen studies were judged to be of moderate risk of bias in the outcome measurement. In a nutshell, future studies should aim to minimize heterogeneity and reduce bias by ensuring a more representative sample, standardizing exposure and outcome assessments.
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Maternal factors associated with iron deficiency without anaemia in early pregnancy: ECLIPSES study.
Iglesias-Vázquez, L, Gimeno, M, Coronel, P, Caspersen, IH, Basora, J, Arija, V
Annals of hematology. 2023;(4):741-748
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Abstract
Several population-specific genetic, sociodemographic, and maternal lifestyle factors are related to iron status in early pregnancy, and their identification would allow preventive actions to be taken. The study aimed to identify maternal factors associated with iron deficiency (ID) in early pregnancy in non-anaemic pregnant women from a European Mediterranean country. Cross-sectional study using the initial population of the ECLIPSES study performed in non-anaemic pregnant women before gestational week 12. Serum ferritin (SF) and haemoglobin concentrations were measured to evaluate iron status, and ID was defined as SF < 15 µg/L. Several sociodemographic and lifestyle data were recorded and used as covariates in the multivariate-adjusted regression models. Out of the 791 participants, 13.9% had ID in early pregnancy. Underweight (OR 3.70, 95%CI 1.22, 15.53) and parity (1 child: OR 2.03, 95%CI 1.06, 3.88; ≥ 2 children: OR 6.96, 95%CI 3.09, 15.69) increased the odds of ID, while a high intake of total meat (≥ 108.57 g/day: OR 0.37, 95%CI 0.15, 0.87), red/processed meat (≥ 74.29 g/day: OR 0.70, 95%CI 0.35, 0.98), protein (≥ 65.05 g/day: OR 0.85, 95%CI 0.30, 0.99), and dietary iron (≥ 8.58 mg/day: OR 0.58, 95%CI 0.35, 0.94) protected against it. Smoking was also associated with a reduction in ID odds (OR 0.34, 95%CI 0.12, 0.99). Baseline BMI, parity, smoking, and diet are associated with ID in early pregnancy in non-anaemic women. Pregnancy planning policies should focus on women at higher risk of ID, such as those who are underweight, multiparous, or following vegetarian diets. This clinical trial was registered at www.clinicaltrialsregister.eu as EudraCT number 2012-005,480-28 and at www.clinicaltrials.gov with identification number NCT03196882.
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Effect of walnut consumption on neuropsychological development in healthy adolescents: a multi-school randomised controlled trial.
Pinar-Martí, A, Gignac, F, Fernández-Barrés, S, Romaguera, D, Sala-Vila, A, Lázaro, I, Ranzani, OT, Persavento, C, Delgado, A, Carol, A, et al
EClinicalMedicine. 2023;:101954
Abstract
BACKGROUND Omega-3 fatty acids are critical for neuropsychological functioning. Adolescence is increasingly believed to entail brain vulnerability to dietary intake. The potential benefit on adolescent neurodevelopment of consuming walnuts, a source of omega-3 alpha-linolenic acid (ALA), remains unclear. METHODS We conducted a 6-month multi-school-based randomised controlled nutrition intervention trial to assess whether walnut consumption has beneficial effects on the neuropsychological and behavioural development of adolescents. The study took place between 04/01/2016 and 06/30/2017 in twelve different high schools in Barcelona, Spain (ClinicalTrials.gov Identifier: NCT02590848). A total of 771 healthy teenagers aged 11-16 years were randomised into two equal groups (intervention or control). The intervention group received 30 g/day of raw walnut kernels to be incorporated into their diet for 6 months. Multiple primary endpoints concerning neuropsychological (working memory, attention, fluid intelligence, and executive function) and behavioural (socio-emotional and attention deficit hyperactivity disorder [ADHD] symptoms) development were assessed at baseline and after intervention. Red blood cell (RBC) ALA status was determined at baseline and 6 months as a measure of compliance. Main analyses were based on intention-to-treat using a linear mixed-effects model. A per-protocol effect of the intervention was analysed using inverse-probability weighting to account for post-randomisation prognostic factors (including adherence) using generalised estimating equations. FINDINGS In intention-to-treat analyses, at 6 months there were no statistically significant changes between the intervention and control groups for all primary endpoints. RBC ALA (%) significantly increased only in the intervention group, coefficient = 0.04 (95% Confidence Interval (CI) = 0.03, 0.06; p < 0.0001). The per-protocol (adherence-adjusted) effect on improvement in attention score (hit reaction time variability) was -11.26 ms (95% CI = -19.92, -2.60; p = 0.011) for the intervention group as compared to the control group, improvement in fluid intelligence score was 1.78 (95% CI = 0.90, 2.67; p < 0.0001), and reduction of ADHD symptom score was -2.18 (95% CI = -3.70, -0.67; p = 0.0050). INTERPRETATION Our study suggested that being prescribed eating walnuts for 6 months did not improve the neuropsychological function of healthy adolescents. However, improved sustained attention, fluid intelligence, and ADHD symptoms were observed in participants who better complied with the walnut intervention. This study provides a foundation for further clinical and epidemiological research on the effect of walnuts and ALA on neurodevelopment in adolescents. FUNDING This study was supported by Instituto de Salud Carlos III through the projects 'CP14/00108, PI16/00261, PI21/00266' (co-funded by European Union Regional Development Fund 'A way to make Europe'). The California Walnut Commission (CWC) has given support by supplying the walnuts for free for the Walnuts Smart Snack Dietary Intervention Trial.
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Supplementation of Infant Formula and Neurodevelopmental Outcomes: a Systematic Review.
Arija, V, Jardí, C, Bedmar, C, Díaz, A, Iglesias, L, Canals, J
Current nutrition reports. 2022;(2):283-300
Abstract
PURPOSE OF THE REVIEW The aim is to examine data from clinical trials and prospective longitudinal studies that evaluate the effect of infant formula supplements on the cognitive function of children. RECENT FINDINGS A total of 300 articles from 2000 to 2021 were selected. The most researched IF supplements were initially long-chain polyunsaturated fatty acids (LC-PUFA), some proteins and, recently, milk fat globule membrane (MFGM). Supplementation of IF with LC-PUFA led to some positive effects on specific cognitive functions or no effect; however, there was no consistent benefit for cognitive function. Modifying the amount of proteins did not affect the children's neuropsychological tests. Supplementation of IF with MFGM and its components had beneficial effects on child cognitive development in the short term, but no effect was observed in the long term. Further studies are needed to confirm the safety of supplementation on the development of cognitive function in children fed with infant formula.
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Omega-3 Fatty Acid Intake during Pregnancy and Child Neuropsychological Development: A Multi-Centre Population-Based Birth Cohort Study in Spain.
Tahaei, H, Gignac, F, Pinar, A, Fernandez-Barrés, S, Romaguera, D, Vioque, J, Santa-Marina, L, Subiza-Pérez, M, Llop, S, Soler-Blasco, R, et al
Nutrients. 2022;(3)
Abstract
Background: There are few studies that look at the intake of all types of omega-3 polyunsaturated fatty acids (n-3 PUFAs) during the different stages of pregnancy along with a long-term neuropsychological follow-up of the child. This study aims to explore the association between maternal n-3 PUFA intake during two periods of pregnancy and the child’s neuropsychological scores at different ages. Methods: Prospective data were obtained for 2644 pregnant women recruited between 2004 and 2008 in population-based birth cohorts in Spain. Maternal n-3 PUFA intake during the first and third trimester of pregnancy was estimated using validated food frequency questionnaires. Child neuropsychological functions were assessed using Bayley Scales of Infant Development version one (BSID) at 1 year old, the McCarthy Scale of Children’s Abilities (MSCA) at 4 years old, and the Attention Network Test (ANT) at 7 years old. Data were analysed using multivariate linear regression models and adjusted for potential covariates, such as maternal social class, education, cohort location, alcohol consumption, smoking, breastfeeding duration, and energy intake. Results: Compared to participants in the lowest quartile (<1.262 g/day) of n-3 PUFA consumption during the first trimester, those in the highest quartile (>1.657 g/day) had a 2.26 points (95% confidence interval (CI): 0.41, 4.11) higher MSCA general cognitive score, a 2.48 points (95% CI: 0.53, 4.43) higher MSCA verbal score, and a 2.06 points (95% CI: 0.166, 3.95) higher MSCA executive function score, and a 11.52 milliseconds (95% CI: −22.95, −0.09) lower ANT hit reaction time standard error. In the third pregnancy trimester, the associations were weaker. Conclusions: Positive associations between n-3 PUFA intake during early pregnancy and child neuropsychological functions at 4 and 7 years of age were found, and further clinical research is needed to confirm these findings.
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Perinatal emotional states: a comparative study between two cohorts recruited in a Mediterranean environment.
Voltas, N, Arija, V, Hernández-Martínez, C, Nappi, L, Cibelli, G, Basora, J, Canals, J
Women & health. 2021;(3):221-234
Abstract
Experiencing negative emotional states during pregnancy has been linked to adverse outcomes for mother and offspring. Our study aims were to compare the perinatal emotional states and obstetrical variables between pregnant women recruited in Spain (n = 202) and Italy (n = 103), and to investigate prenatal anxiety related factors. The study had two phases. In the 1st phase (3rd trimester of pregnancy), prenatal anxiety was assessed using the State-Trait Anxiety Inventory (STAI); other prenatal and sociodemographic variables were also collected. In the 2nd phase (40 days postpartum), the STAI and the Edinburgh Postnatal Depression Scale were administered. Compared to the Spanish sample, the Italian sample presented higher STAI state and STAI factor 1 mean scores (22.5 vs. 18.6 and 10.0 vs. 7.2), shorter gestations (mean gestation weeks: 39.1 vs. 39.8), more unplanned pregnancies (31.1% vs. 16.4%), and more cesareans deliveries (42.5% vs. 16.0%). Low socioeconomic levels, younger ages, previous miscarriages and unplanned pregnancies were related to prenatal anxiety. Postpartum depression rates was 31.3% and there were no differences between countries. Our results suggested that it may be interesting in both countries to create a prenatal monitoring protocol that attaches more importance to emotional wellbeing both during pregnancy and in the long term.
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Walnuts, Long-Chain Polyunsaturated Fatty Acids, and Adolescent Brain Development: Protocol for the Walnuts Smart Snack Dietary Intervention Trial.
Julvez, J, Gignac, F, Fernández-Barrés, S, Romaguera, D, Sala-Vila, A, Ranzani, OT, Persavento, C, Delgado, A, Carol, A, Torrent, J, et al
Frontiers in pediatrics. 2021;:593847
Abstract
Background: Adolescence, when the most complex behaviors are refined to adult sophistication, represents a major window of opportunity and vulnerability for neuropsychological development. To support and protect this complex and active brain growth, different nutritional components considered essential need to be acquired from the diet. For instance, omega-3 fatty acids are mainly obtained from seafood, seeds, and walnuts. Known for their rich lipid profile, walnuts contain sizable amounts of an essential fatty acid, alpha-linolenic acid (ALA), the vegetable omega-3 fatty acid that is the precursor of two longer-chain omega-3 polyunsaturated fatty acids (omega-3 PUFA): docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids. While there is growing evidence of neuropsychological improvements in the young developing brain associated with omega-3 PUFA intake, few studies have examined whether consuming walnuts during adolescence entails similar beneficial effects. There is a need to further explore the ways in which walnuts influence youthful brain function, particularly for the long-term. Thus, we designed the WALNUTs study (WSS), a population-based randomized controlled trial conducted in adolescents in Barcelona, Spain. We hypothesize that walnut intake will increase omega-3 PUFA tissue availability (particularly ALA) to a level that enhances the neuropsychological development during adolescence. Methodology/Design: We conducted a 6-month population-based randomized controlled trial in teenagers (n = 800) and we aimed to determine the effectiveness of the intervention (four walnuts per day, or 30 kernel g, ~1.5g of ALA) in enhancing brain neuropsychological and socio-emotional development compared to a control group with no walnut intervention. Before randomization, different neuropsychological tests were recorded for all participants, and blood samples (in a subsample of participants) were collected to measure omega-3 PUFA levels at baseline, and all again, after randomization and the intervention. The data is now collected and we will conduct linear regression models to assess the effect of the intervention. Discussion: The WALNUTs (WSS) study results will allow us to better understand the role of plant-based omega-3 PUFA intake from regular walnut consumption on neuropsychological development during adolescence. Results could be translated into nutritional public health recommendations targeting teenagers. Trial Registration: ClinicalTrials.gov, U.S. National Library of Medicine, National Institutes of Health # NCT02590848. Retrospectively registered 29/10/2015.
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Changes in fatty acid levels (saturated, monounsaturated and polyunsaturated) during pregnancy.
Aparicio, E, Martín-Grau, C, Hernández-Martinez, C, Voltas, N, Canals, J, Arija, V
BMC pregnancy and childbirth. 2021;(1):778
Abstract
BACKGROUND During pregnancy a high amount of fatty acids (FA) is necessary to meet foetus demands, which vary during gestation. The present study describes the changes in maternal fatty acid concentrations during pregnancy in a sample of pregnant women. METHODS This is a longitudinal study of 479 pregnant women who were monitored from the first trimester to third trimester of pregnancy. Data on maternal characteristics were recorded and a serum sample was collected in each trimester. The fatty acid profile (saturated (SFA: total, lauric acid, myristic acid, palmitic acid, stearic acid), monounsaturated (MUFA: total, palmitoleic acid, oleic acid) and polyunsaturated fatty acids (PUFA: total omega-6 (n-6), linoleic acid, dihomo-γ-linolenic acid, arachidonic acid (AA), total omega-3 (n-3), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)) was analysed with a gas chromatography-mass spectrometry combination. RESULTS From the first trimester to third trimester of pregnancy, a significant increase in total SFA, total MUFA and total n-6 PUFA was found. (p < 0.001). Nevertheless, the serum concentration of arachidonic acid (AA), eicosapentaenoic acid (EPA) and total n-3 PUFA decreased during gestation (p < 0.001). A statistically non-significant result was observed for the docosahexaenoic acid (DHA) serum concentration between the first and third trimesters of pregnancy. Significant correlations were observed between each total fatty acid concentrations of the first and third trimesters. CONCLUSION The circulating serum concentration of SFA, MUFA and n-6 PUFA increases during pregnancy, whereas essential fatty acids such as AA and EPA decrease, and DHA remains unchanged. Further research is necessary to understand the role played by FA throughout gestation.