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Breastfed infants are particularly vulnerable to iron deficiency, which is associated with impaired neurodevelopment. Iron supplementation reduces behavioral problems in certain risk groups, but effects in healthy infants are uncertain. This randomized, double-blind, placebo-controlled trial evaluated whether daily low-dose iron supplementation (7, 10, or 15 mg micronized microencapsulated ferric pyrophosphate, approximating 1 mg/kg, from 4 to 9 months of age) affects behavioral outcomes at 3 years. The study was conducted in Warsaw, Poland and Umeå, Sweden and included full-term, healthy, predominantly breastfed infants who were non-anemic at baseline. Behavioral problems were assessed using the Child Behavior Checklist (CBCL) at 3 years as a pre-specified secondary outcome. Of the 221 participants randomized, 133 (60%) completed the CBCL. Iron supplementation compared to placebo significantly reduced CBCL externalizing T-scores (mean [SD], 45.6 [8.5] vs. 48.6 [8.9], adjusted P =.006). Lower scores were also observed for aggressive behaviors (adjusted P =.0329). This pre-specified secondary outcome analysis found that low-dose iron supplementation in predominantly breastfed healthy infants between 4 and 9 months of age may contribute to fewer behavioral problems at 3 years of age. These findings suggest a potential beneficial effect, though cautious interpretation is warranted until replicated in future studies.

Trial registration: clinicaltrials.gov; identifying number: NCT02242188; URL: http://www.clinicaltrials.gov/study/NCT02242188; Date of registration: 2014-09-14.

Aim: The aim of this study was to investigate the annual prevalence and characteristics of Paediatric Feeding Disorder (PFD) in Västerbotten county, Sweden, during the years 2012–2022.

Methods: In this retrospective study, medical records of patients attending paediatric clinics with possible feeding problems were identified by applying pre-defined diagnostic and procedure codes. Diagnostic criteria of PFD were verified. Additional data including nutritional status and enteral feeding tube placement were retrieved.

Results: Annual prevalence of PFD increased from 1.2 (95% CI, 0.9–1.5) per 1000 children in 2012 to 5.0 (95% CI, 4.4–5.6) per 1000 children in 2022. In 2022, the prevalence in children < 5 years of age was 10.2 (95% CI, 8.7–12.0) per 1000. Of those, 28% had thinness grades 2 or 3 (moderate or severe thinness), and 31% were fed via nasogastric tube or gastrostomy.

Conclusion: Prevalence of PFD has increased in the last decade, most notably for children under the age of five. High rates of malnutrition and enteral feeding in our study population indicate that we identified only the most severe cases of PFD. Given the rising prevalence of PFD, further research on the condition is of high priority.

PURPOSE OF REVIEW: Iron deficiency (ID) affects one in five children before they reach preschool age. Existing evidence on ID contributing to suboptimal development and neurodevelopmental disorders come mostly from mechanistic and observational studies. Recommendations for screening and treatment are diverging, emphasizing the knowledge gap. The purpose of this review is to summarize recent evidence on ID in infants and children, its possible role in developmental disorders, and effects of iron supplementation.

RECENT FINDINGS: Recent well powered randomized controlled trials showed no effect of early iron supplementation on psychomotor development in infants, neither in populations at high nor low risk of ID. Treatment of nonanemic ID in children 1-3 years did not improve their cognitive scores. Evidence from observational and imaging studies suggests association of brain ID and attention deficit hyperactivity disorder in children (ADHD).

SUMMARY: Universal prophylactic iron supplementation in infants is not supported by current evidence. Whether non anemic ID needs to be treated is uncertain and so is the legitimacy and timing of screening for ID and anemia. The role of ID and iron availability for the brain in pathogenesis of neurodevelopmental conditions such as ADHD requires further studies.

Background: Non-communicable diseases (NCDs) are a global health issue, posing a substantial burden on the individual, community, and public health. The risk of developing NCDs is influenced by a complex interplay between genetic, epigenetic, and environmental factors.

Methods: The NorthPop Birth Cohort Study (NorthPop) constitutes an infrastructure enabling cutting-edge research on the foundational pathways to NCDs in childhood, including allergic diseases and asthma, overweight/obesity, cognitive and neurodevelopmental dysfunction, gastrointestinal disorders, and caries. NorthPop aims at recruiting 10,000 families. Pregnant women and their partners residing in Västerbotten County, Sweden are eligible. Recruitment started in 2016 and is anticipated to end in 2025. Extensive data on parental, fetal and child health outcomes, lifestyle, diet, and environmental exposures are prospectively collected using web-based questionnaires in pregnancy and childhood until the children turn 7 years old. Urine samples are collected from the pregnant woman at gestational age 14–24 weeks. Blood samples are collected at gestational age 28 weeks. Placenta and cord blood are collected at birth. A breast milk sample is collected 1 month postpartum. Blood samples from the children are collected at 18 months and 7 years of age. Oral swabs and fecal samples are collected from the children within 48 h of birth, at 1, 9 and 18 months, 3 and 7 years of age. At age 7 years, children are invited to a follow-up visit, including measurements of weight, height, blood pressure, pulse, hand grip strength, working memory, skin prick test and saliva sampling. Additional measurements, such as sleep–wake and light exposure, and additional biological samples are collected in sub-cohorts. Permission for linkage to medical records and national registers e.g., the Swedish Pregnancy Register, the National Patient Register, the Longitudinal Integration Database for Health insurance and Labor market studies and the Swedish Prescribed Drug Register has been granted.

Discussion: Our multidisciplinary approach allows us to study how early life exposures, as well as parental health and lifestyle, influence future health in the offspring. Our results are anticipated to contribute to the understanding of disease risk and may inform future strategies aimed at risk reduction, highly significant for public health.

Trial registration: Retrospectively registered at Researchweb 11 November 2024 (project number 279272).

This position paper by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Special Interest Group on Coeliac Disease (SIG-CD) presents an update to the 2016 recommendations concerning early diet and the risk of coeliac disease (CD). This update adheres to the policy that mandates reviewing guidelines every 5 years, particularly when new data emerge. The 2024 statements and recommendations are essentially similar to the 2016 recommendations. Breastfeeding, whether any amount, exclusive, or of any duration, does not reduce the risk of developing CD. Introducing gluten into an infant's diet at any time between completed 4 months (≥17 weeks) and 12 months of age does not affect the cumulative incidence of CD, although earlier introduction may lead to earlier seroconversion and CD. In observational studies involving cohorts with a known risk for CD, consuming a high amount of gluten compared to a low amount during weaning and in the subsequent childhood years—specifically the first 2–3 years, and even up to 5 years in some studies—was associated with an increased risk for CD. However, the specific optimal amounts of gluten consumption remain undetermined due to insufficient evidence on safe thresholds, and the impact of restricting gluten in the diet of healthy children of unknown risk for CD is unknown. Thus, any recommendation on the gluten amount is currently unjustifiable for the general population and infants with known HLA risk types. There is no specific guidance on the type of gluten-containing foods to be introduced at weaning.

Importance: Breastfed infants are at risk of iron deficiency, which is associated with suboptimal development. There is a paucity of evidence on the effects of iron supplementation on child development, and current guidelines are divergent.

Objective: To assess whether daily iron supplementation, 1 mg/kg, between 4 and 9 months in exclusively or predominantly breastfed infants improves psychomotor development at 12 months.

Design, Setting, and Participants: This was a randomized, double-blind, placebo-controlled trial conducted between December 2015 and May 2020 with follow-up through May 2023 in an outpatient setting in Poland and Sweden. Participants were healthy singleton infants born at term with birth weight greater than 2500 g who were exclusively or predominantly breastfed (>50%) and did not have anemia (hemoglobin >10.5 g/dL) at age 4 months. Exclusion criteria included major illness, congenital anomaly, food allergy, and difficulty communicating with caregivers.

Interventions: Iron (micronized microencapsulated ferric pyrophosphate), 1 mg/kg, or placebo (maltodextrin) once daily from age 4 to 9 months.

Main Outcomes and Measures: The primary outcome was psychomotor development assessed by motor score of Bayley Scales of Infant and Toddler Development III at 12 months, adjusted for gestational age, sex, and maternal education. Secondary outcomes included cognitive and language scores at 12 months; motor, cognitive, and language scores at 24 and 36 months; iron deficiency (serum ferritin <12 ng/mL), and iron deficiency anemia (iron deficiency and hemoglobin <10.5 g/dL) at 12 months.

Results: Of 221 randomized infants (111 female), 200 (90%) were included in the intention-to-treat analysis (mean [SD] age, 12.4 [0.8] months). Iron supplementation (n = 104) compared to placebo (n = 96) had no effect on psychomotor development (mean difference [MD] for motor score, -1.07 points; 95% CI, -4.69 to 2.55), cognitive score (MD, -1.14; 95% CI, -4.26 to 1.99), or language score (MD, 0.75; 95% CI, -2.31 to 3.82) at 12 months. There were no significant differences at 24 and 36 months. The intervention did not reduce the risk for iron deficiency (relative risk [RR], 0.46; 95% CI, 0.16 to 1.30) or iron deficiency anemia (RR, 0.78; 95% CI, 0.05 to 12.46) at 12 months.

Conclusion and Relevance: No benefit was found with daily low-dose iron supplementation between 4 and 9 months with respect to psychomotor development, risk of iron deficiency, or iron deficiency anemia among breastfed infants in a setting of low risk of anemia.

Human milk is recommended for very low birth weight infants. Their nutritional needs are high, and the fortification of human milk is a standard procedure to optimize growth. Targeted fortification accounts for the variability in human milk composition. It has been a promising alternative to standard fixed-dose fortification, potentially improving short-term growth. In this trial, preterm infants (≤32 weeks of gestation) were randomized to receive human milk after standard fortification (HMF, Nutricia) or tailored fortification with modular components of proteins (Bebilon Bialko, Nutricia), carbohydrates (Polycal, Nutricia), and lipids (Calogen, Nutricia). The intervention started when preterms reached 80 mL/kg/day enteral feeds. Of the target number of 220 newborns, 39 were randomized. The trial was interrupted due to serious intolerance in five cases. There was no significant difference in velocity of weight gain during the supplementation period (primary outcome) in the tailored vs. standard fortification group: 27.01 ± 10.19 g/d vs. 25.84 ± 13.45 g/d, p = 0.0776. Length and head circumference were not significantly different between the groups. We found the feasibility of targeted fortification to be limited in neonatal intensive care unit practice. The trial was registered at clinicaltrials.gov NCT:03775785.

Background: Erythroferrone (ERFE) has been identified as a hepcidin-regulating hormone synthetized by erythroblasts correlating to the erythropoietic activity and the needs for iron substrate in bone marrow of adults. The present study aimed to assess the ERFE serum concentrations and its predictors in infants.

Methods: ERFE was explored at 4 time points during the first year of life in 45 healthy, breastfed, normal birth weight (NBW) infants, and 136 marginally low birth weight infants (LBW, 2000–2500 g) receiving iron (N = 58) or placebo (N = 78) between 6 weeks and 6 months of age.

Results: ERFE concentrations were low at birth, increasing gradually during the first year of life. In NBW infants, reference ranges (5th to 95th percentile) were at 6 weeks <0.005–0.99 ng/mL and at 12 months <0.005–33.7 ng/mL. ERFE was higher in LBW infants at 6 weeks but lower at 12 months compared to NBW and minimally affected by iron supplementation among LBW infants. Correlations of ERFE with erythropoietic and iron status markers were weak and inconsistent.

Conclusions: The role of ERFE in the crosstalk of erythropoiesis and iron homeostasis remains unclear in infants and further studies on ERFE in infants and older children are warranted within the framework of the erythropoietin–ERFE–hepcidin axis.

Impact: Normal range of erythroferrone in healthy infants is described for the first time. Erythroferrone in infants lacks correlation to iron status and markers of erythropoiesis. The findings indicate differences in infant regulation of iron homeostasis as compared to adults. The findings point to a need to study infant erythropoiesis separately from its adult counterpart. The findings may have clinical impact on management strategies of iron-loading anemia in infancy.

Introduction and objective: Human milk contains all the nutrients and bioactive components required for the optimal growth and development of newborns. It is also an optimal source of nutrition in premature infants, however it does not fully meet their nutritional demands. Studies have shown that infants fed exclusively human milk have better enteral nutrition tolerance, lower risk of necrotising enterocolitis, and improved neurodevelopmental outcomes. The aim of the study was to analyse preterm content of human milk collected from women as part of a randomised controlled trial assessing tailored nutrition.

Materials and methods: We studied 726 samples from 39 mothers of premature infants during their first postnatal four weeks. Infants were assigned to standard or tailored enteral nutrition, but all mothers were asked to pool milk samples from full breast expression at each feed across a 24-hour period twice a week. Glucose, fat, protein, and energy levels were measured using the Miris Human Milk Analyser and compared to published values. We assessed the relationship between postnatal week and human milk content.

Results: Protein content decreased over time. Median protein at four weeks of postnatal age was 1.37 and 1.32 per 100 mL (tailored vs. standard group, respectively). Lipid content increased over time. Median lipid content at four weeks of postnatal age was 4.06 and 3.82 per 100 mL (tailored vs. standard group). Glucose remained stable. Energy content increased over time only in the tailored group. Median energy at four weeks of postnatal age was 73.35 per 100 mL.

Conclusions: Variations in human milk content exist between populations and should be considered when prescribing enteral nutrition in preterm infants.