Plasma Acylcarnitines during Pregnancy and Neonatal Anthropometry: A Longitudinal Study in a Multiracial Cohort.

Yiqing Song,Susanna D Mitro,Ming Li,Mohammad L Rahman,Yeyi Zhu,Cuilin Zhang,Chen Lyu,Liwei Chen,Michael Y Tsai,Stefanie N Hinkle,Zhen Chen,Ling-Jun Li,Natalie L Weir

doi:10.3390/metabo11120885

Abstract

As surrogate readouts reflecting mitochondrial dysfunction, elevated levels of plasma acylcarnitines have been associated with cardiometabolic disorders, such as obesity, gestational diabetes, and type 2 diabetes. This study aimed to examine prospective associations of acylcarnitine profiles across gestation with neonatal anthropometry, including birthweight, birthweight z score, body length, sum of skinfolds, and sum of body circumferences. We quantified 28 acylcarnitines using electrospray ionization tandem mass spectrometry in plasma collected at gestational weeks 10–14, 15–26, 23–31, and 33–39 among 321 pregnant women from the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons. A latent-class trajectory approach was applied to identify trajectories of acylcarnitines across gestation. We examined the associations of individual acylcarnitines and distinct trajectory groups with neonatal anthropometry using weighted generalized linear models adjusting for maternal age, race/ethnicity, education, parity, gestational age at blood collection, and pre-pregnancy body mass index (BMI). We identified three distinct trajectory groups in C2, C3, and C4 and two trajectory groups in C5, C10, C5–DC, C8:1, C10:1, and C12, respectively. Women with nonlinear decreasing C12 levels across gestation (5.7%) had offspring with significantly lower birthweight (−475 g; 95% CI, −942, −6.79), birthweight z score (−0.39, −0.71, −0.06), and birth length (−1.38 cm, −2.49, −0.27) than those with persistently stable C12 levels (94.3%) (all nominal p value < 0.05). Women with consistently higher levels of C10 (6.1%) had offspring with thicker sum of skinfolds (4.91 mm, 0.85, 8.98) than did women with lower levels (93.9%) during pregnancy, whereas women with lower C10:1 levels (12.6%) had offspring with thicker sum of skinfolds (3.23 mm, 0.19, 6.27) than did women with abruptly increasing levels (87.4%) (p < 0.05). In conclusion, this study suggests that distinctive trajectories of C10, C10:1, and C12 acylcarnitine levels throughout pregnancy were significantly associated with neonatal anthropometry.

Highlights

Pregnant women undergo systemic and dynamic physiological adaptations to meet the nutritional and metabolic demands of both the mother and developing fetus [1]
In the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons, we examined the longitudinal and prospective association of acylcarnitines throughout pregnancy with neonatal anthropometrics, including birthweight, birthweight z score, birth length, sum of skinfolds, and sum of body circumferences
Individual acylcarnitines can directly activate classical proinflammatory signaling pathways [20], inducing placental mitochondrial dysfunction related to adverse pregnancy complications

Summary

Introduction

Pregnant women undergo systemic and dynamic physiological adaptations to meet the nutritional and metabolic demands of both the mother and developing fetus [1]. Emerging evidence suggests that maintenance of healthy mitochondrial function is essential to ensure adequate fetal nutrient and energy supply for growth and development, since mitochondria utilize a variety of substrates, including fatty acids, carbohydrates, ketones, and certain amino acids [2,3,4]. Acylcarnitines are detectable in plasma, and their levels vary as a function of various metabolic pathways related to biosynthesis, turnover, and transport, as well as renal handling [6,9,10]. Elevated circulatory acylcarnitines have been identified as surrogates of mitochondrial dysfunction, reflective of inefficient coordination across FAO, the tricarboxylic acid cycle, and the electron transport chain in both animal models and human studies [5,8,11]. Acylcarnitine profiling analysis using plasma or other biospecimens, especially long-chain acylcarnitines, has a clinical application in neonatal screening to identify inborn genetic defects of mitochondrial

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