Effect of Low-Dose Iron Supplementation on Early Development in Breastfed Infants: A Randomized Clinical Trial.

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. Trial Registration: ClinicalTrials.gov Identifier: NCT02242188.

Higher Parenteral Electrolyte Intakes in Preterm Infants During First Week of Life: Effects on Electrolyte Imbalances.

OBJECTIVES: This study aimed to investigate the effects of a higher intake of electrolytes from parenteral nutrition (PN) on plasma electrolyte concentrations in very low birth weight (VLBW, <1500 g) infants. METHODS: This was a single-center cohort study including all VLBW infants born before (n = 81) and after (n = 53) the implementation of a concentrated PN regimen. Daily nutritional intakes and plasma concentrations of sodium, chloride, potassium, phosphate, and calcium were collected from clinical charts. RESULTS: During the first postnatal week, electrolyte intakes were higher in infants who received concentrated PN compared with infants who received original PN. Infants who received concentrated PN had a lower incidence of hypokalemia (<3.5 mmol/L; 30% vs 76%, P < 0.001) and severe hypophosphatemia (<1.0 mmol/L; 2.2% vs 17%, P = 0.02). While the relatively high prevalence of severe hypophosphatemia in infants who received original PN can be explained by a phosphorus intake below the recommendation, the potassium intake during the first 3 postnatal days (mean ± SD: 0.7 ± 0.2 mmol/kg/d) was within the recommendation. The prevalence of early hypernatremia was not affected by the different sodium intake in the 2 groups. CONCLUSIONS: In VLBW infants, a sodium-containing PN solution (about 2.7 mmol/100 mL) does not cause hypernatremia during the first days of life. Furthermore, providing at least 1 mmol potassium/kg/d during the first 3 postnatal days might be necessary to prevent early hypokalemia.

Sodium supply from administered blood products was associated with severe intraventricular haemorrhage in extremely preterm infants.

AIM: The aim of this study was to investigate the associations between sodium supply, fluid volume, sodium imbalances and severe intraventricular haemorrhage (IVH) in extremely preterm (EPT) infants. METHODS: We used data from the EXtremely PREterm infants in Sweden Study (EXPRESS) cohort consisting of all infants born at 22 to 26 gestational weeks from 2004 to 2007 and conducted a nested case-control study. For every infant with severe IVH (grade 3 or peri-ventricular haemorrhagic infarction), one IVH-free control infant with the birthday closest to the case infant and matched for hospital, sex, gestational age and birth weight was selected (n = 70 case-control pairs). RESULTS: Total sodium supply and fluid volume were higher in infants with severe IVH compared with controls [daily total sodium supply until postnatal Day 2: mean ± SD (mmol/kg/day): 5.49 ± 2.53 vs. 3.95 ± 1.91, p = 0.009]. These differences were accounted for by sodium and fluid from transfused blood products. High plasma sodium concentrations or large sodium fluctuations were not associated with severe IVH. CONCLUSION: Our results suggest a relationship between sodium-rich transfusions of blood products and severe IVH in EPT infants. It is unclear whether this is an effect of sodium load, volume load or some other transfusion-related factor.

Use of Concentrated Parenteral Nutrition Solutions Is Associated With Improved Nutrient Intakes and Postnatal Growth in Very Low-Birth-Weight Infants.

BACKGROUND: Evidence showing the beneficial effects of enhanced parenteral nutrition (PN) to very low-birth-weight (VLBW, <1500 g) infants is accumulating. However, PN composition and its impact on growth outcomes are questioned. This study aimed to investigate the associations between administration of a concentrated PN regime and intakes of energy and macronutrients as well as postnatal growth in VLBW infants. METHODS: We compared 2 cohorts of VLBW infants born before (n = 74) and after (n = 44) a concentrated PN regime was introduced into clinical use. Daily nutrition and fluid intake during the first 28 postnatal days and all available growth measurements during hospitalization were retrospectively collected from clinical charts. RESULTS: Infants who received concentrated PN compared with original PN had higher parenteral intakes of energy (56 vs 45 kcal/kg/d, P < 0.001), protein (2.6 vs 2.2 g/kg/d, P = 0.008), and fat (1.5 vs 0.7 g/kg/d, P < 0.001) during the first postnatal week. Changes in standard deviation scores for weight and length from birth to postnatal day 28 were more positive in the concentrated PN group (mean [95% CI]; weight change: -0.77 [-1.02 to -0.52] vs -1.29 [-1.33 to -1.05], P = 0.005; length change: -1.01 [-1.36 to -0.65] vs -1.60 [-1.95 to -1.25], P = 0.025). There were no significant differences in fluid intake and infant morbidity between the groups. CONCLUSION: Our results suggest that concentrated PN is useful and seems to be safe for improving early nutrition and growth in VLBW infants.

Sodium supply influences plasma sodium concentration and the risks of hyper- and hyponatremia in extremely preterm infants.

BACKGROUND: Hyper- and hyponatremia occur frequently in extremely preterm infants. Our purpose was to investigate plasma sodium (P-Na) concentrations, the incidence of hyper- and hyponatremia, and the impact of possible predisposing factors in extremely preterm infants. METHODS: In this observational study, we analyzed data from the EXtremely PREterm (< 27 wk.) infants in Sweden Study (EXPRESS, n = 707). Detailed nutritional, laboratory, and weight data were collected retrospectively from patient records. RESULTS: Mean ± SD P-Na increased from 135.5 ± 3.0 at birth to 144.3 ± 6.1 mmol/l at a postnatal age of 3 d and decreased thereafter. Fifty percent of infants had hypernatremia (P-Na > 145 mmol/l) during the first week of life while 79% displayed hyponatremia (P-Na < 135 mmol/l) during week 2. Initially, the main sodium sources were blood products and saline injections/infusions, gradually shifting to parenteral and enteral nutrition towards the end of the first week. The major determinant of P-Na and the risks of hyper- and hyponatremia was sodium supply. Fluid volume provision was associated with postnatal weight change but not with P-Na. CONCLUSION: The supply of sodium, rather than fluid volume, is the major factor determining P-Na concentrations and the risks of hyper- and hyponatremia.