Nuclear magnetic resonance (NMR) metabolic profiling quantifies a large number of metabolites. From adolescence, specific metabolites are influenced by age, sex and body mass index; data on early-life metabolic profiles are limited. We investigated associations between sex, birth weight, weight and adiposity with NMR metabolic profile at age 12 months.
The plasma NMR metabolic profile was quantified in infants (n = 485) from the Barwon Infant Study. Associations between 74 metabolites and sex, birth weight z-score and 12-month measures (weight z-score, skinfold thickness, weight-for-length z-score) were examined using linear regression models.
Several cholesterol and fatty acid measures were higher (0.2–0.3 SD) in girls than in boys; we observed modest sex-specific associations of birth weight z-scores and 12-month sum of skinfold thicknesses with metabolites. The pattern of associations between weight z-score and weight-for-length z-score with metabolites at 12 months was more pronounced in girls, particularly for fatty acid ratios.
We identified sex differences in the infant metabolic profile. Sex-specific patterns observed differ from those reported in older children and adults. We also identified modest cross-sectional associations between anthropometric and adiposity measures and metabolites, some of which were sex specific.
Subscribe to Journal
Get full journal access for 1 year
only $64.85 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Baird, J. et al. Developmental origins of health and disease: a lifecourse approach to the prevention of non-communicable diseases. Healthcare (Basel) 5, E14 (2017).
Johnson, C. H., Ivanisevic, J. & Siuzdak, G. Metabolomics: beyond biomarkers and towards mechanisms. Nat. Rev. Mol. Cell Biol. 17, 451–459 (2016).
Yu, Z. et al. Human serum metabolic profiles are age dependent. Aging Cell 11, 960–967 (2012).
Saito, K. et al. Gender- and age-associated differences in serum metabolite profiles among Japanese populations. Biol. Pharm. Bull. 39, 1179–1186 (2016).
Kettunen, J. et al. Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA. Nat. Commun. 7, 11122 (2016).
Dunn, W. B. et al. Molecular phenotyping of a UK population: defining the human serum metabolome. Metabolomics 11, 9–26 (2015).
Mittelstrass, K. et al. Discovery of sexual dimorphisms in metabolic and genetic biomarkers. PLoS Genet. 7, e1002215 (2011).
Krumsiek, J. et al. Gender-specific pathway differences in the human serum metabolome. Metabolomics 11, 1815–1833 (2015).
Ellul, S. et al. Metabolomics: population epidemiology and concordance in Australian children aged 11–12 years and their parents. BMJ Open 9, 106 (2019).
Davis, C. E. et al. Sex difference in high density lipoprotein cholesterol in six countries. Am. J. Epidemiol. 143, 1100–1106 (1996).
Michaliszyn, S. F. et al. Metabolomic profiling of amino acids and beta-cell function relative to insulin sensitivity in youth. J. Clin. Endocrinol. Metab. 97, E2119–E2124 (2012).
Mihalik, S. J. et al. Metabolomic profiling of fatty acid and amino acid metabolism in youth with obesity and type 2 diabetes: evidence for enhanced mitochondrial oxidation. Diabetes Care 35, 605–611 (2012).
Wang, T. J. et al. Metabolite profiles and the risk of developing diabetes. Nat. Med. 17, 448–453 (2011).
McCormack, S. E. et al. Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents. Pediatr. Obes. 8, 52–61 (2013).
Ruoppolo, M. et al. Female and male human babies have distinct blood metabolomic patterns. Mol. Biosyst. 11, 2483–2492 (2015).
Vuillermin, P. et al. Cohort profile: The Barwon Infant Study. Int. J. Epidemiol. 44, 1148–1160 (2015).
Pink, B. Socio-economic Indexes for Areas (SEIFA). Technical Paper (Australian Bureau of Statistics, 2011).
Vidmar, S. I., Cole, T. J. & Pan, H. Standardizing anthropometric measures in children and adolescents with functions for egen: update. Stata J. 13, 366–378 (2013).
Soininen, P. et al. High-throughput serum NMR metabonomics for cost-effective holistic studies on systemic metabolism. Analyst 134, 1781–1785 (2009).
Wurtz, P. et al. Quantitative serum NMR metabolomics in large-scale epidemiology: a primer on -omic technology. Am. J. Epidemiol. 186, 1084–1096 (2017).
Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B (Methodol.) 57, 289–300 (1995).
Lawlor, D. A. et al. Sex differences in the association between birth weight and total cholesterol. A meta-analysis. Ann. Epidemiol. 16, 19–25 (2006).
Thorand, B. et al. Sex differences in the relation of body composition to markers of inflammation. Atherosclerosis 184, 216–224 (2006).
Team RC. R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, Vienna, 2018).
Wasserstein, R. L., Schirm, A. L. & Lazar, N. A. Moving to a world beyond “p < 0.05”. Am. Stat. 73, 1–19 (2019).
Gillman Matthew, W. Primordial prevention of cardiovascular disease. Circulation 131, 599–601 (2015).
Uekert, S. J. et al. Sex-related differences in immune development and the expression of atopy in early childhood. J. Allergy Clin. Immunol. 118, 1375–1381 (2006).
Klein, S. L. & Flanagan, K. L. Sex differences in immune responses. Nat. Rev. Immunol. 16, 626 (2016).
Würtz, P. et al. Metabolic signatures of adiposity in young adults: mendelian randomization analysis and effects of weight change. PLoS Med. 11, e1001765 (2014).
Perng, W. et al. Associations of cord blood metabolites with perinatal characteristics, newborn anthropometry, and cord blood hormones in project viva. Metab. Clin. Exp. 76, 11–22 (2017).
Perng, W., Rifas-Shiman, S. L., Hivert, M.-F., Chavarro, J. E. & Oken, E. Branched chain amino acids, androgen hormones, and metabolic risk across early adolescence: a prospective study in Project Viva. Obesity (Silver Spring) 26, 916–926 (2018).
Perng, W. et al. Metabolomic profiles and childhood obesity. Obesity (Silver Spring) 22, 2570–2578 (2014).
Butte, N. F. et al. Global metabolomic profiling targeting childhood obesity in the Hispanic population. Am. J. Clin. Nutr. 102, 256–267 (2015).
Kadakia, R. et al. Cord blood metabolomics: association with newborn anthropometrics and c-peptide across ancestries. J. Clin. Endocrinol. Metab. 104, 4459–4472 (2019).
Kadakia, R. et al. Cord blood metabolites associated with newborn adiposity and hyperinsulinemia. J. Pediatr. 203, 144–149.e141 (2018).
Walford, G. A. et al. Metabolite profiles of diabetes incidence and intervention response in the Diabetes Prevention Program. Diabetes 65, 1424–1433 (2016).
Merino, J. et al. Metabolomics insights into early type 2 diabetes pathogenesis and detection in individuals with normal fasting glucose. Diabetologia 61, 1315–1324 (2018).
Reusch, J. E. B., Kumar, T. R., Regensteiner, J. G., Zeitler, P. S. & Conference, P. Identifying the critical gaps in research on sex differences in metabolism across the life span. Endocrinology 159, 9–19 (2018).
Lau, A., West, L. & Tullius, S. G. The impact of sex on alloimmunity. Trends Immunol. 39, 407–418 (2018).
Colafella, K. M. M. & Denton, K. M. Sex-specific differences in hypertension and associated cardiovascular disease. Nat. Rev. Nephrol. 14, 185–201 (2018).
We thank the BIS participants for the generous contribution they have made to this project. We also thank current and past staff for their efforts in recruiting and maintaining the cohort and in obtaining and processing the data and biospecimens. The establishment work and infrastructure for the BIS was provided by the Murdoch Children’s Research Institute, Deakin University and Barwon Health. Subsequent funding was secured from the National Health and Medical Research Council of Australia, The Jack Brockhoff Foundation, the Scobie Trust, the Shane O’Brien Memorial Asthma Foundation, the Our Women’s Our Children’s Fund Raising Committee Barwon Health, The Shepherd Foundation, the Rotary Club of Geelong, the Ilhan Food Allergy Foundation, GMHBA Limited and the Percy Baxter Charitable Trust, Perpetual Trustees. In-kind support was provided by the Cotton On Foundation and CreativeForce. Research at Murdoch Children’s Research Institute is supported by the Victorian Government’s Operational Infrastructure Support Program. This work was also supported by NHMRC Senior Research Fellowships (APP1008396 to A.-L.P.; APP1064629 to D.B.; APP1045161 to R.S.).
The authors declare no competing interests.
The BIS protocol was approved by the Barwon Health Human Research Ethics Committee (HREC 10/24).
Written informed consent was obtained from all participating families in the study.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Members of the Barwon Infant Study Investigator Team are listed at the end of the paper.
About this article
Cite this article
Ellul, S., Ponsonby, A., Carlin, J.B. et al. Sex differences in infant blood metabolite profile in association with weight and adiposity measures. Pediatr Res (2020). https://doi.org/10.1038/s41390-020-0762-4