Department of Population, Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
Departments of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Int J Obes (Lond). 2019 Oct;43(10):1967-1977. doi: 10.1038/s41366-019-0417-x. Epub 2019 Jul 22.
BACKGROUND/OBJECTIVES: 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.
SUBJECTS/METHODS: 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/m 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.
背景/目的：酰基辅酶 A 是脂肪酸氧化的中间产物，已知与肥胖和胰岛素抵抗有关。由于母亲孕前超重或肥胖（OWO）是公认的子女 OWO 的主要危险因素，我们假设母体血浆酰基辅酶 A 可能在代际 OWO 中发挥作用。
研究对象/方法：本研究纳入了 1998 年至 2013 年期间在波士顿医疗中心出生的 1402 对母婴（1043 例足月，359 例早产），并前瞻性随访至 18 岁。主要结局是定义为 BMI≥年龄和性别第 85 百分位的儿童 OWO。主要暴露是母亲孕前 OWO，定义为 BMI≥25kg/m2，采用液相色谱-串联质谱法（LC-MS）在产后即刻采集血浆样本，以靶向方式测量母体酰基辅酶 A 水平。
研究中约有 40%的儿童在 5 岁时超重。母亲 OWO 与足月和早产出生的儿童 OWO 均有显著相关性。在调整了潜在混杂因素和多次比较后，β-羟丁酸酰基辅酶 A（C4-OH）水平与足月出生的儿童 OWO 呈显著正相关。C4-OH 水平处于最高三分位的 OWO 母亲所生的儿童超重的风险最高：与 C4-OH 水平处于最低三分位的非 OWO 母亲所生的儿童相比，OR=3.78（95%CI：2.47，5.79）（P 交互作用=0.035）。在中介/交互分析的四分位分解中，我们估计 C4-OH 水平解释了代际 OWO 风险的约 27%（se=0.08）（P=0.001）。相比之下，这些关联在早产中并未观察到。
在这项美国城市低收入出生队列研究中，我们提供了 OWO 代际关联的进一步证据，并揭示了 C4-OH 在解释足月和早产之间代际肥胖中的差异作用。需要进一步研究以更好地理解和预防 OWO 的代际传播。
