Maternal genetics is a key determinant of human milk oligosaccharide (HMO) composition in human milk. Beyond genetic status, other factors influencing the HMO profile are poorly defined. Thus, we aimed to review the existing evidence on the associations between nongenetic maternal and infant factors and HMO composition. A systematic search was performed on PubMed and Web of Science (without a time restriction) to identify any relevant studies published. In total, 1056 results were obtained, of which 29 articles were selected to be included in this review. The range of factors investigated include lactation stage, maternal pre-pregnancy BMI (ppBMI), maternal age, parity, maternal diet, mode of delivery, infant gestational age, and infant sex. The data suggest that, beyond maternal genetics, HMO composition seems to be influenced by all these factors, but the underlining mechanisms remain speculative. The published evidence is discussed in this review, along with potential implications for infant growth and development. For example, 2'-fucosyllactose, which was reportedly increased in mothers with higher ppBMIs, was also associated with increased infant weight and height. In addition, greater levels of sialylated HMOs after preterm birth may support brain development in these infants.

Atopic disorders (AD), often coexistent with food allergy (FA), start developing in early life and have lifelong health consequences. Breastfeeding is thought to be protective against AD and FA, but the data are controversial, and mechanisms are not well understood. Human milk oligosaccharides (HMOs) are complex carbohydrates that are abundant in human milk. These are thought to contribute to the development of the infant immune system by (i) promoting healthy microbiome, (ii) inhibiting pathogen binding to gut mucosa and (iii) modulating the immune system. Differences in microbiome composition between allergic and healthy infants have been observed, regardless of breastfeeding history. To date, limited studies have examined the preventive effects of HMOs on AD and FA in infants and current data relies on observation studies as trials of varying HMO intake through randomising individuals to breastfeeding are unethical. There is evidence for beneficial effects of breastfeeding on lowering the risks of FA, eczema and asthma but there are inconsistencies amongst studies in the duration of breastfeeding, diagnostic criteria for AD and the age at which the outcome was assessed. Furthermore, current analytical methods primarily used today only allow detection of 16–20 major HMOs while more than 100 types have been identified. More large-scale longitudinal studies are required to investigate the role of HMO composition and the impact of changes over the lactation period in preventing AD and FA later in life.

Optimal maternal vitamin status during pregnancy and lactation is essential to support maternal and infant health. For instance, vitamin D₃ is involved in infant bone development, and B-vitamins are involved in various metabolic processes, including energy production. Through a double-blind randomised controlled trial, we investigated the effects of maternal supplementation from preconception throughout pregnancy until birth on human milk (HM) concentrations of vitamin D₃ and B-vitamins. In addition, we aimed to characterise longitudinal changes in milk concentrations of these vitamins. Both control and intervention supplements contained calcium, iodine, iron, β-carotene, and folic acid, while the intervention also contained zinc, vitamins B₂, B₆, B₁₂, and D₃, probiotics, and myo-inositol. HM samples were collected across 4 time points from 1 week to 3 months post-delivery from 158 mothers in Singapore, and 7 time points from 1 week to 12 months from 180 mothers in New Zealand. HM vitamin D was quantified using supercritical fluid chromatography and B-vitamins with mass spectrometry. Potential intervention effects on HM vitamins D₃, B₂, B₆, and B₉, as well as other B-vitamin (B₁ and B₃) concentrations were assessed using linear mixed models with a repeated measures design. Over the first 3 months of lactation, HM 25-hydroxyvitamin D₃ concentrations were 20% (95% CI 8%, 33%, P = 0.001) higher in the intervention group, with more marked effects in New Zealand. There were no observed intervention effects on HM concentrations of vitamins B₁, B₂, B₃, B₆, and B₉. In New Zealand mothers, longitudinally, vitamin D₃ concentrations gradually increased from early lactation up to 12 months, while vitamins B₁ and B₂ peaked at 6 weeks, B₃ at 3 weeks, and B₆ and B₉ at 3 months. Maternal supplementation during preconception and pregnancy increased HM vitamin D, but not B-vitamin concentrations in lactation. Further studies are required to examine the discrete benefits of vitamin D supplementation starting preconception vs during pregnancy, and to further characterise the effects of supplementation on later offspring health outcomes. Registered at ClinicalTrials.gov on the 16 July 2015 (identifier NCT02509988); Universal Trial Number U1111-1171-8056. This study was academic-led by the EpiGen Global Research Consortium.

Multivitamin and mineral (MVM) supplements are frequently used amongst older populations to improve adequacy of micronutrients, including B-vitamins, but evidence for improved health outcomes are limited and deficiencies remain prevalent. Although this may indicate poor efficacy of supplements, this could also suggest the possibility for altered B-vitamin bioavailability and metabolism in older people. This open-label, single-arm acute parallel study, conducted at the Liggins Institute Clinical Research Unit in Auckland, compared circulatory and urinary B-vitamer responses to MVM supplementation in older (70.1 ± 2.7 y, n = 10 male, n = 10 female) compared to younger (24.2 ± 2.8 y, n = 10 male, n = 10 female) participants for 4 h after the ingestion of a single dose of a commercial MVM supplement and standardized breakfast. Older adults had a lower area under the curve (AUC) of postprandial plasma pyridoxine (p = 0.02) and pyridoxal-5′phosphate (p = 0.03) forms of vitamin B₆ but greater 4-pyridoxic acid AUC (p = 0.009). Urinary pyridoxine and pyridoxal excretion were higher in younger females than in older females (time × age × sex interaction, p < 0.05). Older adults had a greater AUC increase in plasma thiamine (p = 0.01), riboflavin (p = 0.009), and pantothenic acid (p = 0.027). In older adults, there was decreased plasma responsiveness of the ingested (pyridoxine) and active (pyridoxal-5′phosphate) forms of vitamin B₆, which indicated a previously undescribed alteration in either absorption or subsequent metabolic interconversion. While these findings cannot determine whether acute B₆ responsiveness is adequate, this difference may have potential implications for B₆ function in older adults. Although this may imply higher B vitamin substrate requirements for older people, further work is required to understand the implications of postprandial differences in availability.

Background: Nutritional intervention preconception and throughout pregnancy has been proposed as an approach to promoting healthy postnatal weight gain in the offspring but few randomised trials have examined this. Methods: Measurements of weight and length were obtained at multiple time points from birth to 2 years among 576 offspring of women randomised to receive preconception and antenatally either a supplement containing myo-inositol, probiotics, and additional micronutrients (intervention) or a standard micronutrient supplement (control). We examined the influence on age- and sex-standardised BMI at 2 years (WHO standards, adjusting for study site, sex, maternal parity, smoking and pre-pregnancy BMI, and gestational age), together with the change in weight, length, BMI from birth, and weight gain trajectories using latent class growth analysis. Results: At 2 years, there was a trend towards lower mean BMI among intervention offspring (adjusted mean difference [aMD] − 0.14 SD [95% CI 0.30, 0.02], p = 0.09), and fewer had a BMI > 95th percentile (i.e. > 1.65 SD, 9.2% vs 18.0%, adjusted risk ratio [aRR] 0.51 [95% CI 0.31, 0.82], p = 0.006). Longitudinal data revealed that intervention offspring had a 24% reduced risk of experiencing rapid weight gain > 0.67 SD in the first year of life (21.9% vs 31.1%, aRR 0.76 [95% CI 0.58, 1.00], p = 0.047). The risk was likewise decreased for sustained weight gain > 1.34 SD in the first 2 years of life (7.7% vs 17.1%, aRR 0.55 [95% CI 0.34, 0.88], p = 0.014). From five weight gain trajectories identified, there were more intervention offspring in the “normal” weight gain trajectory characterised by stable weight SDS around 0 SD from birth to 2 years (38.8% vs 30.1%, RR 1.29 [95% CI 1.03, 1.62], p = 0.029). Conclusions: Supplementation with myo-inositol, probiotics, and additional micronutrients preconception and in pregnancy reduced the incidence of rapid weight gain and obesity at 2 years among offspring. Previous reports suggest these effects will likely translate to health benefits, but longer-term follow-up is needed to evaluate this. Trial registration: ClinicalTrials.gov, NCT02509988 (Universal Trial Number U1111-1171–8056). Registered on 16 July 2015.

Background: In a multinational randomized controlled trial, we previously showed that maternal supplementation with myo-inositol, probiotics, and micronutrients was associated with reduced incidence of rapid infant weight gain and high body mass index (BMI) at two years among offspring. It was unclear whether these differences in weight gain and body mass were due to reduced adiposity. Therefore, we aimed to determine whether there were any differences in body composition. Methods: Body composition was measured using bioelectrical impedance spectroscopy at six weeks, six months, one year, and two years among offspring born to mothers who received a nutritional intervention (n = 268) or control (n = 264) supplement preconception and during pregnancy. Results: There were no group-level differences in body composition, except at two years, when fat-free mass was greater among control offspring [adjusted mean difference (aMD) 0.14 kg, 95% confidence interval (CI) 0.03, 0.25, P = 0.012]. However, there were no differences in mean percentage fat mass (%FM) at any time. In both groups, rapid weight gain [Δ weight > 0.67 standard deviation (SD) from birth to one year] was associated with greater %FM (aMD 2.0% at six months, 2.0% at one year, 1.4% at two years) compared with those who did not have rapid weight gain. Likewise, high BMI (≥ 95 percentile) at two years was associated with greater %FM (aMD 2.5%). Conclusions: A maternal nutritional intervention did not lead to differences in average offspring body composition in the first two years of life. However, fewer offspring from the supplemented group experienced rapid weight gain and high BMI, characterized by greater %FM. Graphical