Inter-generational link of obesity in term and preterm births: role of maternal plasma acylcarnitines



Acylcarnitines, intermediates of fatty acid oxidation, are known to be involved in obesity and insulin resistance. Since maternal prepregnancy overweight or obesity (OWO) is a recognized major risk factor for offspring OWO, we hypothesized that maternal plasma acylcarnitines may play a role in inter-generational OWO.


This study included 1402 mother–child pairs (1043 term, 359 preterm) recruited at birth from 1998–2013 and followed prospectively up to age 18 years at the Boston Medical Center. The primary outcomes were child OWO defined as BMI ≥ 85th percentile for age and sex. The primary exposures were maternal prepregnancy OWO defined as BMI ≥ 25 kg/m2 and maternal acylcarnitine levels measured in plasma samples collected soon after delivery using liquid chromatography–tandem mass spectrometry (LC–MS) in a targeted manner.


Approximately 40% of the children in this study were OWO by age 5. Maternal OWO had a significant association with childhood OWO, both in term and preterm births. β-hydroxybutyryl-carnitine (C4-OH) levels were significantly and positively associated with child OWO among term births after adjustment for potential confounders and multiple-comparisons. Children born to OWO mothers in the top tertile C4-OH levels were at the highest risk of OWO: OR = 3.78 (95%CI: 2.47, 5.79) as compared with those born to non-OWO mothers in the lowest tertile (P for interaction of maternal OWO and C4-OH = 0.035). In a four-way decomposition of mediation/interaction analysis, we estimated that C4-OH levels explained about 27% (se = 0.08) of inter-generational OWO risk (P = 0.001). In contrast, these associations were not observed in preterm births.


In this U.S. urban low-income birth cohort, we provide further evidence of the inter-generational link of OWO and reveal the differential role of C4-OH in explaining the inter-generational obesity between term and preterm births. Further investigations are warranted to better understand and prevent the inter-generational transmission of OWO.

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This study is supported in part by the National Institutes of Health (NIH) grants (R01HD086013 and 2R01HD041702). The Boston Birth Cohort (the parent study) is supported in part by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) under grant number R40MC27443 and UJ2MC31074. XH is partially supported by Hopkins Population Center (NICHD R24HD042854). CZ is supported by the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The funders had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the article; or the decision to submit the article for publication. The content and conclusions contained in this article are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by, HRSA, HHS, or the US Government. XW is the principal investigator of the Boston Birth Cohort, and has full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Correspondence to Frank B. Hu or Xiaobin Wang.

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