Background: Five of the most abundant human milk oligosaccharides (HMOs) in human milk are 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL). Methods: A randomized, double-blind, controlled parallel feeding trial evaluated growth in healthy term infants fed a control milk-based formula (CF; n = 129), experimental milk-based formula (EF; n = 130) containing five HMOs (5.75 g/L; 2′-FL, 3-FL, LNT, 3′-SL and 6′-SL) or human milk (HM; n = 104). Results: No significant differences (all p ≥ 0.337, protocol evaluable cohort) were observed among the three groups for weight gain per day from 14 to 119 days (D) of age, irrespective of COVID-19 or combined non-COVID-19 and COVID-19 periods. There were no differences (p ≥ 0.05) among the three groups for gains in weight and length from D14 to D119. Compared to the CF group, the EF group had more stools that were soft, frequent and yellow and were similar to the HM group. Serious and non-serious adverse events were not different among groups, but more CF-fed infants were seen by health care professionals for illness from study entry to D56 (p = 0.044) and D84 (p = 0.028) compared to EF-fed infants. Conclusions: The study demonstrated that the EF containing five HMOs supported normal growth, gastrointestinal (GI) tolerance and safe use in healthy term infants.

Lactose, the major carbohydrate in human milk and standard milk—based formulas, provides energy for growth in infants. The use of lactose-free milk protein—based infant formulas has increased in the United States. However, clinical studies of their impact on growth, safety, and gastrointestinal tolerance in infants are limited. Thus, a prospective, blinded, randomized clinical trial was conducted in healthy, normal-term infants fed an experimental lactose-free milk protein—based formula (NoLAC; n = 63) versus a standard commercial lactose-containing milk-based formula (LAC; n = 65) for 112 days. Growth (weight, length, and head circumference) was similar and normal in both groups (weight gain: NoLAC = 31.1 ± 0.9 g/day, LAC = 29.4 ± 0.9 g/day, mean ± SEM; P = .895). Serum biochemistries for both groups were within infants’ normal reference ranges. Both groups had comparable tolerance but the NoLAC group had softer stools and lower spit-ups. Thus, the study suggests that absence of lactose in milk-based formula does not adversely affect normal growth in term infants.

Maternal nutrition is an important factor for infant neurodevelopment. However, prior magnetic resonance imaging (MRI) studies on maternal nutrients and infant brain have focused mostly on preterm infants or on few specific nutrients and few specific brain regions. We present a first study in term-born infants, comprehensively correlating 73 maternal nutrients with infant brain morphometry at the regional (61 regions) and voxel (over 300 000 voxel) levels. Both maternal nutrition intake diaries and infant MRI were collected at 1 month of life (0.9 ± 0.5 months) for 92 term-born infants (among them, 54 infants were purely breastfed and 19 were breastfed most of the time). Intake of nutrients was assessed via standardized food frequency questionnaire. No nutrient was significantly correlated with any of the volumes of the 61 autosegmented brain regions. However, increased volumes within subregions of the frontal cortex and corpus callosum at the voxel level were positively correlated with maternal intake of omega-3 fatty acids, retinol (vitamin A) and vitamin B12, both with and without correction for postmenstrual age and sex (P < 0.05, q < 0.05 after false discovery rate correction). Omega-3 fatty acids remained significantly correlated with infant brain volumes after subsetting to the 54 infants who were exclusively breastfed, but retinol and vitamin B12 did not. This provides an impetus for future larger studies to better characterize the effect size of dietary variation and correlation with neurodevelopmental outcomes, which can lead to improved nutritional guidance during pregnancy and lactation.

Background: Effects of palm olein (POL) on calcium and fat metabolic balance and gastrointestinal (GI) tolerance have been clinically evaluated but its use in combination with palm kernel oil (PKO), and canola oil has not been similarly assessed in infants.Methods: Calcium and fat balance and GI tolerance were evaluated in 33 healthy term infants (age = 68-159d) in a randomized, double-blinded, 14d crossover trial at a day care center in Salvador, Brazil; followed by a 4d hospital ward metabolic balance study in 17 of the male subjects. The study compared two commercially available milk-based powdered formulas in Brazil; one containing POL (44% of total fat), PKO (21.7%) and canola oil (18.5%) as predominant fats (PALM), and the other containing none (NoPALM). Occasional human milk (HM) supplementation was allowed at home.Results: Formula and HM intakes, and growth were not different (p > 0.05). Calcium absorption (%) for infants fed NoPALM (58.8 ± 16.7%; means ± SD) was higher (p = 0.023) than those fed PALM (42.1 ± 19.2%), but was not significant (p = 0.104) when calcium intake was used as a covariate. Calcium intake was higher (p < 0.001) in NoPALM versus PALM fed infants. However, calcium retention (%) was higher in infants fed NoPALM compared to PALM with (p = 0.024) or without (p = 0.015) calcium intake as a covariate. Fat absorption (%) for NoPALM was greater than PALM fed infants (NoPALM = 96.9 ± 1.2 > PALM = 95.1 ± 1.5; p = 0.020 in Study Period I). Mean rank stool consistency was softer in infants fed NoPALM versus PALM (p < 0.001; metabolic period). Adverse events, spit-up/vomit, fussiness and gassiness were not different (p > 0.05). Formula acceptability was high and comparable for both formula feedings, regardless of HM supplementation.Conclusions: Term infants fed PALM based formula (containing palm olein, palm kernel and canola oils) demonstrated lower calcium retention and fat absorption, and less softer stool consistency versus infants fed NoPALM based formula. Study suggested formula fat differences may affect GI function in infants.Clinical trial registration: Clinical Trial.Gov # (http://www.clinicaltrials.gov):NCT00941564.

Palm oil/olein (PO/POL) is used in infant formulas to imitate the fatty acid profile of human milk (HM) and achieve similar levels of palmitic acid (PA). However, the positions of fatty acids on the triacylglyceride differ between PO/POL and HM, which affect fat absorption and produce unintended physiological consequences. Recent papers have reviewed evidence for physiological benefits of PO/POL and beta-palmitate (sn-2-palmitate) in infant formulas. The aim of the present review is to supplement the assessment of available clinical evidence on the physiological effects of PO/POL formulas in healthy infants. We intend to focus on PO/POL and not on sn-2-palmitate, since the latter was recently extensively reviewed. Clinical evidence supports that PO/POL in infant formulas leads to a lower fat, DHA, palmitate and calcium absorption, and bone mineralization; soft stools; and growth (weight accretion) compared to formulas without PO/POL. Consequently, it seems prudent to be considerate and cautious when adding PO/POL to infant formulas. While HM is the gold standard for infant nutrition, the development of infant formula should be based on achieving positive physiological outcomes, rather than just replicating HM nutrient composition.

Palm olein is used in infant formula fat blends in order to match the fatty acid profile of human milk. While the effects on fatty acid balance have been evaluated, the use of palm olein in combination with palm kernel oil and supplementation with docosahexaenoic acid (DHA) and arachidonic acid (ARA) has not been similarly assessed in infants. This study evaluated the effects of infant formulas containing different fat compositions on the balance of fat, fatty acids, and calcium. In this randomized, crossover, double-blinded study, 33 healthy term infants (68–159 ± 3 days of age at enrollment) were fed two formulas for 14 days in a tolerance period, followed by a 4-day metabolic balance period in 17 of the male subjects. The study compared two commercially available milk-based powdered formulas in Brazil; the PALM formula contained palm olein (44%), kernel palm oil (21.7%), and canola oil (18.5%) as the predominant fats, whereas the NoPALM formula contained other fat sources. Fat absorption (%) was greater for NoPALM versus PALM-fed infants (96.55 and 95.50%, respectively; p = 0.023). The absorption percentage of palmitic acid (C16:0) did not differ significantly between formulas (p > 0.05), but this acid was excreted at significantly higher concentrations in the PALM (29.42 mg/kg/day) than in the NoPALM (12.28 mg/kg/day) formula groups. DHA and ARA absorption percentages were also higher in NoPALM-fed infants. Calcium absorption was higher in NoPALM-fed infants (58.00%) compared to those fed PALM (40.90%), but the difference was not significant (p = 0.104) when calcium intake was used as a covariate. However, calcium retention was higher in NoPALM-fed infants compared to that in PALM-fed infants with or without calcium intake as a covariate. Adverse events did not differ between groups (p > 0.05). The absorption of essential fatty acids was similar for both formulas; however, long-chain polyunsaturated fatty acids (DHA and ARA) were better absorbed from the NoPALM formula. Fat absorption and calcium retention were lower in term infants fed the PALM-based formula. Clinicaltrial.gov # NCT00941564 .