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Author(s): Jorgensen, Josh M; Young, Rebecca; Ashorn, Per; Ashorn, Ulla; Chaima, David; Davis, Jasmine CC; Goonatilleke, Elisha; Kumwenda, Chiza; Lebrilla, Carlito B; Maleta, Kenneth; Prado, Elizabeth L; Sadalaki, John; Totten, Sarah M; Wu, Lauren D; Zivkovic, Angela M; Dewey, Kathryn G | Abstract: BackgroundHuman milk oligosaccharides (HMOs) and bioactive breast milk proteins have many beneficial properties. Information is sparse regarding associations between these milk constituents and infant growth and development in lower-income countries.ObjectivesWe aimed to examine associations of milk content of HMOs and bioactive proteins at 6 mo postpartum with infant growth and motor and cognitive development. These are secondary analyses of a randomized controlled trial in rural Malawi.MethodsBreast milk samples were analyzed at 6 mo (nn=n659) for general categories of HMOs (total HMOs, fucosylated HMOs, and sialylated HMOs), 51 individual HMOs, and 6 bioactive proteins (lactalbumin, lactoferrin, lysozyme, antitrypsin, IgA, and osteopontin). We examined associations of the relative abundances of HMOs and concentrations of bioactive proteins with infant growth from 6 to 12 mo [change in length-for-age (ΔLAZ), weight-for-age, weight-for-length, and head circumference z-scores] as well as ability to stand or walk alone at 12 mo, and motor and language skills, socioemotional development, executive function, and working memory at 18 mo. Analyses were adjusted for covariates and multiple hypothesis testing.ResultsAmong all participants, there were inverse associations of IgA and lactoferrin concentrations with motor skills (Pn=n0.018 and P =n0.044), and a positive association of lactalbumin concentration with motor skills (Pn=n0.038). Among secretors only [fucosyltransferase 2 gene (FUT2) positive], there were positive associations of absolute abundance of HMOs with ΔLAZ (Pn=n0.035), and relative abundance of fucosylated and sialylated HMOs with language at 18 mo (Pnln0.001 and Pn=n0.033, respectively), and inverse associations of osteopontin with standing and walking at 12 mo (Pn=n0.007 and 0.002, respectively). Relative abundances of several individual HMOs were associated with growth and development, mostly among secretors.ConclusionsCertain bioactive breast milk proteins and HMOs are associated with infant growth and motor and cognitive development. Further studies are needed to determine if a causal relation exists.This trial was registered at clinicaltrials.gov as NCT01239693.

Author(s): Kamng'ona, Arox W; Young, Rebecca; Arnold, Charles D; Patson, Noel; Jorgensen, Josh M; Kortekangas, Emma; Chaima, David; Malamba, Chikondi; Ashorn, Ulla; Cheung, Yin B; Ashorn, Per; Maleta, Kenneth; Dewey, Kathryn G | Abstract: BACKGROUND:Diet may alter the configuration of gut microbiota, but the impact of prenatal and postnatal nutritional interventions on infant gut microbiota has not been investigated. OBJECTIVE:We evaluated whether providing lipid-based nutrient supplements (LNSs) to mother-infant dyads promotes a more diverse and mature infant gut microbiota, compared to maternal supplementation with multiple micronutrients (MMN) or iron and folic acid (IFA). METHODS:We enrolled 869 pregnant women in a randomized trial in Malawi. There were 3 study groups, with women receiving 1 MMN capsule daily during pregnancy and 6nmo postpartum, or 1 LNS sachet (20 g) daily during pregnancy and 6nmo postpartum, or 1 IFA capsule daily (during pregnancy) then a placebo daily (postpartum). Infants in the LNS group received LNS from 6 to 18nmo; infants in the other groups did not receive supplements. The infants' fecal microbiota were characterized by PCR amplification and sequencing of the bacterial 16S rRNA gene (variable region 4). The primary outcomes were microbiota α diversity and maturation [as microbiota-for-age z score (MAZ)]. Specific associations of taxa with intervention were established with indicator species analysis (ISA). RESULTS:Primary outcomes did not differ between IFA and MMN groups, so these groups were combined (IFAn+nMMN). Meann±nSD α diversity was higher in the LNS group at 18nmo for Shannon index [3.01n±n0.57 (LNS) compared with 2.91n±n0.60 (IFAn+nMMN), Pn=n0.032] and Pielou's evenness index [0.61n±n0.08 (LNS) compared with 0.60n±n0.09 (IFAn+nMMN), Pn=n0.043]; no significant differences were observed at 1, 6, 12, or 30nmo. MAZ and β diversity did not differ at any age. We found 10 and 3 operational taxonomic units (OTUs) positively associated with LNS and IFAn+nMMN, respectively; however, these associations became nonsignificant following false discovery rate correction at 10%. CONCLUSIONS:Prenatal and postnatal LNS intake promoted infant gut microbiota diversity at 18nmo, after 12nmo of child supplementation, but did not alter microbiota maturation. This trial was registered at clinicaltrials.gov as NCT01239693.

Objective:We aimed to identify factors (child diet, physical activity; maternal BMI) associated with body composition of Ghanaian pre-school children.Design:Longitudinal analysis of the International Lipid-Based Nutrient Supplements (iLiNS)-DYAD-Ghana randomized trial, which enrolled 1320 pregnant women at ≤20 weeks’ gestation and followed them and their infants until 6 and 18 months postpartum, respectively. At follow-up, child age 4–6 years, we collected data on body composition (by2H dilution), physical activity and diet, extracted dietary patterns using factor analysis, and examined the association of children’s percentage body fat with maternal and child factors by regression analysis.Setting:Eastern Region, Ghana.Participants:Children 4–6 years of age.Results:The analysis included 889 children with percentage body fat and dietary data at follow-up. We identified two major dietary patterns, a snacking and a cooked foods pattern. Percentage body fat was positively associated (standardizedβ(se)) with maternal BMI at follow-up (0·10 (0·03);P= 0·003) and negatively associated with physical activity (−0·15 (0·05);P= 0·003, unadjusted for child gender), but not associated with the snacking (0·06 (0·03);P= 0·103) or cooked foods (−0·05 (0·07);P= 0·474) pattern. Boys were more active than girls (1470v.1314 mean vector magnitude counts/min;P< 0·0001) and had lower percentage body fat (13·8v.16·9 %;P< 0·0001).Conclusions:In this population, maternal overweight and child physical activity, especially among girls, may be key factors for addressing child overweight/obesity. We did not demonstrate a relationship between the dietary patterns and body fatness, which may be related to limitations of the dietary data available.

It is important to identify the periods during childhood when exposure to environmental risk factors results in long-term neurodevelopmental deficits. Stunting and anaemia may be sensitive indicators of exposure to such risks. In a prospective cohort enrolled before birth, we investigated the association of developmental scores at 4-6years with (a) birth length and linear growth during three postnatal periods and (2) haemoglobin (Hb) concentration at three time points. Children were participants in a follow-up study of a randomized controlled trial of nutritional supplementation in Ghana. At 4-6years, cognitive, motor, and social-emotional developments were assessed using standard tests adapted for this population. We estimated the associations of length-for-age z-score (LAZ) at birth and postnatal linear growth (n=710) and Hb (n=617) with developmental scores in regression models, using multistage least squares analysis to calculate uncorrelated residuals for postnatal growth. Cognitive development at 4-6years was significantly associated with LAZ at birth (β=0.12, 95% CI=0.05, 0.19), ΔLAZ from 6 to 18months (β=0.16, 95% CI=0.04, 0.28), and Hb at 18months (β=0.13, 95% CI=0.06, 0.20), but not with ΔLAZ during 0-6months, ΔLAZ from 18months to 4-6years, Hb at 6months, or Hb at 4-6years. No evidence of associations with motor or social-emotional development were found. These results suggest that in similar contexts, the earlier periods prior to birth and up to 18months are more sensitive to risk factors for long-term cognitive development associated with LAZ and Hb compared with later childhood. This may inform the optimal timing of interventions targeting improved cognitive development.