Supplementation of Infant Formula and Neurodevelopmental Outcomes: a Systematic Review.

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.

Prenatal folic acid supplementation and folate status in early pregnancy: ECLIPSES study.

This research evaluates the prevalence of inadequate folate status in early pregnancy, the pattern of prenatal folic acid (FA) supplementation and associated factors in Spanish pregnant women from the ECLIPSES study, which included 791 participants prior gestational week 12. A cross-sectional evaluation of erythrocyte folate levels was performed at recruitment and used to calculate the prevalence of folate deficiency (erythrocyte folate < 340 nmol/l) and insufficiency (erythrocyte folate < 906 nmol/l). Sociodemographic and lifestyle data as well as information on prenatal FA supplementation were recorded. Descriptive and multivariate statistical analyses were performed. The prevalence of folate deficiency and insufficiency were 9·6 % and 86·5 %, respectively. Most of women used prenatal FA supplements, but only 6·3 % did so as recommended. Supplementation with FA during the periconceptional period abolished folate deficiency and reduced folate insufficiency. Prenatal FA supplementation with ≥1000 µg/d in periconceptional time and pregnancy planning increased erythrocyte folate levels. The main risk factor for folate insufficiency in early pregnancy was getting prenatal FA supplementation out of the periconceptional time (OR 3·32, 95 % CI 1·02, 15·36), while for folate deficiency they were young age (OR 2·02, 95 % CI 1·05, 3·99), and smoking (OR 2·39, 95 % CI 1·30, 4·37). In addition, social and ethnic differences according to folate status were also identified. As conclusion, periconceptional FA use is crucial for achieving optimal folate levels in early pregnancy. Pregnancy planning should focus on young women, smokers, those with low consumption of folate-rich foods, low socio-economic status or from ethnic minorities.

Maternal Factors Associated with Levels of Fatty Acids, Specifically n-3 PUFA during Pregnancy: ECLIPSES Study.

An optimal fatty acid (FA) profile during pregnancy, especially docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), is essential for the health of the mother and child. Our aim was to identify the socioeconomic and maternal lifestyle factors associated with serum FA concentration in pregnant women. A longitudinal study was conducted on 479 pregnant women, who were assessed during the first (T1) and third (T3) trimesters of pregnancy. Data on maternal characteristics, food consumption, and lifestyle were collected. Serum FA concentrations were analysed by a gas chromatography-mass spectrometry combination. The multiple linear regression showed that high educational level and older age were significantly associated with higher EPA and DHA concentrations and lower values of n-6/n-3 and arachidonic acid (AA)/EPA in T1 and/or T3. Regarding diet-fish and seafood consumption increased EPA concentration and reduced n-6/n-3 and AA/EPA values in both trimesters, whereas its consumption increased DHA concentration only in T1. Smoking was associated with lower DHA concentration in T1 and higher values of n-6/n-3 ratio in both trimester. Overweight and obesity were associated with higher values of n-6/n-3 ratio and AA/EPA ratio in T1. A statistically non-significant association was observed with saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA). In conclusion, high educational levels, older age, fish, seafood consumption, and/or non-smoking, are factors that influence better omega-3 polyunsaturated fatty acid (n-3 PUFA) profile in both trimesters of pregnancy. Further research is needed to go in-depth into these findings and their health consequences.

Nutrient Intake during Pregnancy and Post-Partum: ECLIPSES Study.

Pregnancy and post-partum are critical periods in which nutritional intake is essential to maternal and child health. Our aim was to describe dietary intake during pregnancy and post-partum and assess its adequacy. A longitudinal study was conducted on 793 pregnant women. Data about maternal characteristics, health, diet and lifestyle were assessed. Energy and nutritional intake were compared to the Recommended Dietary Allowances (RDA). The results showed that the intake of energy (82.6%), protein (80.6%) and carbohydrate (99.5%) was adequate (above 80% of RDA) during pregnancy, as were vitamins C, B2 and B12; but vitamin D, iron and folate intake were a long way from RDA (below 35%). Similar results were observed for the post-partum period although fiber, and vitamins E and C decreased compared to intake during pregnancy. In conclusion, although nutritional requirements increase during gestation, pregnant women did not increase their energy and nutritional intake during pregnancy and postpartum and they had a high risk of deficient intake of vitamin D, iron and folates during pregnancy, and therefore, of developing an unfavorable nutritional status, contrary to health recommendations. These findings underscore the necessity of intensive nutrition programs during and after pregnancy.

Food Consumption during Pregnancy and Post-Partum. ECLIPSES Study.

Inadequate maternal diet can adversely affect mother and child. Our aim was to assess adherence to the Spanish dietary guidelines and to the Mediterranean diet, to analyze changes in diet during pregnancy and post-partum, and to identify maternal factors associated with food consumption. A total of 793 healthy pregnant women were recruited during the first prenatal visit and followed until the post-partum period. Data from the clinical history, anthropometric measurements, and lifestyle habits were collected. Food consumption was evaluated using a food frequency questionnaire. The results show that in pregnant women the consumption of healthy foods did not meet recommendations, whereas consumption of red and processed meat and sweet food exceeded recommendations. The results also show a medium adherence to the Mediterranean diet that remained unchanged throughout pregnancy. A significant decrease was observed in the consumption of fruits, followed by vegetables and then salted and sweet cereals from pregnancy to post-partum. A better adherence to the Mediterranean diet has been reported by pregnant women that are older, of higher social class, and higher education level, and who do not smoke nor drink (p < 0.005). In conclusion, the diet of pregnant women from Spain departs from recommendations, medium adherence to the Mediterranean diet was maintained throughout the pregnancy and post-partum, and a decreasing consumption of healthy food from the first trimester to the post-partum period was observed. Maternal factors such as age, social class, education, and smoking influence diet quality.

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.

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

Introducción: El consumo de azúcares libres se ha relacionado con el exceso de peso, recomendando la OMS una ingesta < 10% de la energía total. El objetivo fue valorar la asociación entre el consumo de azúcares libres a los 12 meses y el riesgo de exceso de peso a los 30 meses en niños sanos. Material y métodos: Estudio longitudinal en 81 niños seguidos desde el nacimiento hasta los 30 meses. Se registró: historia clínica y antropometría al nacer, a los 12 y 30 meses. Se clasificó el estado ponderal en con y sin exceso de peso, según los valores de la OMS. A los 12 meses se analizó la ingesta de energía y nutrientes diferenciando la ingesta de azúcares libres y azúcares naturales. Se realizaron análisis multivariantes ajustados por las principales variables confusoras. Resultados: Un 40,4% de los niños de 12 meses realizaron ingestas de azúcares libres superiores a las recomendadas, siendo significativamente mayores en los niños con exceso de peso a los 30 meses (60,9%). La mayor ingesta de azúcares libres a los 12 meses se asocia a un mayor riesgo de exceso de peso a los 30 meses (OR: 1,136; IC 95%: 1,033-1,248). Conclusiones: Los lactantes de 12 meses realizan una ingesta de azúcares libres muy superior a la recomendada. Esta ingesta elevada podría ser un factor de riesgo de exceso de peso ya en edades tempranas

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

Excess nutritional risk in infants and toddlers in a Spanish city.

Adequate dietary intake is vital for infants' growth and development. The aim was to analyse food consumption and energy and nutrient intakes in a group of healthy Spanish infants and toddlers. Cross-sectional study. 154 infants were assessed at 6 months, and followed at 12 and 30 months. Clinical history, anthropometry, type of feeding, food consumption and energy and nutrient intakes (24-hours recall) were estimated. Advice about food consumed, estimated average requirements, the prevalence of inadequate intakes and percentage of adequacy of the recommended dietary allowance were applied. Toddlers had an excessive daily consumption of meat (>51.3g/day), milk (>545g/day), fish (>20.8g/day) and free-sugar foods (>30.5g/day). This consumption was related to a very high intake of proteins (>18%) and free sugars (>10%), at 12 and 30 months, as a percentage of daily energy intake. The mean prevalence of inadequacy intakes was above 48% for iron at 6 months, and 68% and 87% for vitamin D at 12 and 30 months, respectively. At 6 months, infants who were breastfed had greater adequacy in energy and nutrients to recommended dietary, while infants fed infant formula had a higher intake (>120% compared with RDA) in vitamins E, C, B1, B2, pantothenic acid, B6, B12 and folic acid. The contribution of micronutrients in infant formula should be reviewed, appropriate protein and free sugars should be provided during complementary feeding, as well as strategies to avoid vitamin D deficiency since childhood; and continue with the promotion of breastfeeding.

[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.

Serum hepcidin levels, iron status, and HFE gene alterations during the first year of life in healthy Spanish infants.

The aims of this study were to describe hepcidin levels and to assess their associations with iron status and the main variants in the HFE gene in healthy and full-term newborns during the first year of life, as a longitudinal study conducted on 140 infants. Anthropometric and biochemical parameters, hepcidin, hemoglobin (Hb), serum ferritin (SF), transferrin saturation (TS), mean corpuscular volume (MCV), and C-reactive protein (CRP), were assessed in 6- and 12-month-olds. Infants were genotyped for the three main HFE variants: C282Y, H63D, and S65C. Hepcidin levels increased from 6 to 12 months of age (43.7 ± 1.5 to 52.0 ± 1.5 ng/mL; p < 0.001), showing higher levels in infants with better iron status compared to those with iron deficiency (ID) (44.8 ± 1.5 vs 37.9 ± 1.3 ng/mL, p < 0.018, and 54.3 ± 1.5 vs 44.0 ± 1.4 ng/mL, p < 0.038, in 6- and 12-month-olds, respectively). In multivariate linear regression models, iron status was found to be associated with hepcidin levels in infants with wild-type HFE gene (p = 0.046 and p = 0.048 in 6- and 12-month-olds, respectively). However, this association was not found in HFE-alteration-carrying infants. Hepcidin levels increased in healthy infants during the first year of life and were positively associated with iron levels only in infants with wild-type HFE gene, a situation that requires further investigation.

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.