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Epidemiology and population health

Associations of prenatal metabolomics profiles with early childhood growth trajectories and obesity risk in African Americans: the CANDLE study

International Journal of Obesity volume 45, pages 1439–1447 (2021)Cite this article

Subjects

Abstract

Objective

Prenatal metabolomics profiles, providing measures of in utero nutritional and environmental exposures, may improve the prediction of childhood outcomes. We aimed to identify prenatal plasma metabolites associated with early childhood body mass index (BMI) trajectories and overweight/obesity risk in offspring.

Methods

This study included 450 African American mother-child pairs from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood Study. An untargeted metabolomics analysis was performed on the mothers’ plasma samples collected during the second trimester. The children’s BMI-z-score trajectories from birth to age 4 [rising-high- (9.8%), moderate- (68.2%), and low-BMI (22.0%)] and overweight/obesity status at age 4 were the main outcomes. The least absolute shrinkage and selection operator (LASSO) was used to select the prenatal metabolites associated with childhood outcomes.

Results

The mothers were 24.5 years old on average at recruitment, 76.4% having education less than 12 years and 80.0% with Medicaid or Medicare. In LASSO, seven and five prenatal metabolites were associated with the BMI-z-score trajectories and overweight/obese at age 4, respectively. These metabolites are mainly from/relevant to the pathways of steroid biosynthesis, amino acid metabolism, vitamin B complex, and xenobiotics metabolism (e.g., caffeine and nicotine). The odds ratios (95% CI) associated with a one SD increase in the prenatal metabolite risk scores (MRSs) constructed from the LASSO-selected metabolites were 2.97 (1.95–4.54) and 2.03 (1.54–2.67) for children being in the rising-high-BMI trajectory group and overweight/obesity at age 4, respectively. The MRSs significantly improved the risk prediction for childhood outcomes beyond traditional prenatal risk factors. The increase (95% CI) in the area under the receiver operating characteristic curves were 0.10 (0.03–0.18) and 0.07 (0.02–0.12) for the rising-high-BMI trajectory (P = 0.005) and overweight/obesity at age 4 (P = 0.007), respectively.

Conclusions

Prenatal metabolomics profiles advanced prediction of early childhood growth trajectories and obesity risk in offspring.

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Fig. 1: BMI-z-score trajectories of the studied children.
Fig. 2: The classification of the childhood growth trajectory groups and weight groups at age 4 using PLS-DA.
Fig. 3: ROC curves of predictive models.

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Acknowledgements

We thank all the participants of the CANDLE study. This study was supported by the startup fund of QZ from the University of Tennessee Heath Science Center. The CANDLE study was supported by the Urban Child Institute, the University of Tennessee Heath Science Center, and the National Institutes of Health grants (1R01HL109977, 1UG3OD023271-01, and 5R01HL109977-05). QZ was also supported by the grant R01AG061917 from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Preventive Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA

    Qi Zhao, Zunsong Hu, Mehmet Kocak, Jay H. Fowke, W. Alex Mason & Frances A. Tylavsky

  2. Medicinal Chemistry Core, Office of Research, University of Tennessee Health Science Center, Memphis, TN, USA

    Jiawang Liu

  3. Department of Pharmaceutical Science, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA

    Jiawang Liu

  4. Departments of Pediatrics and Physiology, University of Tennessee Health Science Center, and Children’s Foundation Research Institute, Le Bonheur Children’s Hospital, Memphis, TN, USA

    Joan C. Han

  5. Proteomics and Metabolomics Core, Office of Research, University of Tennessee Health Science Center, Memphis, TN, USA

    David Kakhniashvili

  6. Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA

    Kaja Z. Lewinn

  7. Departments of Pediatrics and Psychiatry, University of California San Francisco, San Francisco, CA, USA

    Nicole R. Bush

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  1. Qi Zhao
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Contributions

QZ and FAT—designed research; QZ, JL, DK, and FAT—conducted metabolomics data collection; QZ, ZH, and MH—conducted data analysis; KZL, NRB, WAM, and FAT—collected clinical data and biosamples and management of the CANDLE study; QZ and FAT—drafted the manuscript; JHF, JCH, and KZL—provided critical review and revisions of the manuscript; QZ—had primary responsibility for final content; and all authors: reviewed and approved the final version of the manuscript.

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Correspondence to Qi Zhao.

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Zhao, Q., Hu, Z., Kocak, M. et al. Associations of prenatal metabolomics profiles with early childhood growth trajectories and obesity risk in African Americans: the CANDLE study. Int J Obes 45, 1439–1447 (2021). https://doi.org/10.1038/s41366-021-00808-3

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