Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Department of Nutritional Sciences, School of Health Professions, Rutgers University, Newark, NJ, USA.
Int J Obes (Lond). 2019 Jul;43(7):1422-1434. doi: 10.1038/s41366-018-0255-2. Epub 2018 Nov 21.
BACKGROUND/OBJECTIVES: Maternal obesity impacts fetal growth as early as second trimester of pregnancy, yet little is known about the molecular mechanisms involved. We aimed to examine associations between maternal adipokines throughout pregnancy and neonatal size by prepregnancy obesity status.
In a prospective cohort of 2802 U.S. pregnant women from the NICHD Fetal Growth Studies-Singleton Cohort (2009-2013), biospecimens were analyzed in a matched case-control subset of 321 women. Blood was collected at 10-14, 15-26 (fasting), 23-31, and 33-39 gestational weeks. Plasma leptin and soluble leptin receptor (sOB-R) and total and high-molecular-weight (HMW)-adiponectin were measured. Free leptin was calculated as leptin/sOB-R. Birthweight was abstracted from medical records. Neonatal length and skinfolds were measured.
Leptin and sOB-R in late pregnancy tended to be positively and negatively associated with neonatal length, respectively, while free leptin throughout pregnancy tended to be positively associated with length. Free leptin associations with neonatal length were differential by obesity (i.e., inversely among women without obesity and positively among women with obesity). A per unit increase in free leptin at 33-39 weeks was associated with a shorter neonatal length by -0.55 cm (95%CI, -0.83, -0.28) in women without obesity and longer length by 0.49 cm (95%CI, 0.34, 0.65) in women with obesity. HMW-adiponectin at 33-39 weeks was inversely associated with neonatal length (β = -1.29 cm; 95%CI, -1.74, -0.85) and skinfold thickness (β = -1.46 mm; 95%CI, -1.58, -0.56) among women with obesity. Free leptin across pregnancy tended to be negatively associated with neonatal skinfold thickness among women without obesity, while free leptin in early pregnancy was positively associated with skinfold thickness.
Maternal adipokines were associated with multiple pathways that influence neonatal size including length and adiposity, which differed in timing across pregnancy and by prepregnancy obesity. These findings provide new potential insights into mechanisms and timing by which maternal obesity may impact fetal growth.
背景/目的:肥胖的母亲会影响胎儿在妊娠中期的生长,但目前对于涉及的分子机制知之甚少。我们的目的是检查整个孕期母亲脂联素与新生儿大小之间的关联,按孕前肥胖状态进行分层。
在 2009-2013 年 NICHD 胎儿生长研究-单胎队列的 2802 名美国孕妇的前瞻性队列中,对 321 名妇女的匹配病例对照亚组进行了生物样本分析。在 10-14、15-26 周(空腹)、23-31 周和 33-39 周时采集血样。检测血浆瘦素和可溶性瘦素受体(sOB-R)、总和高分子量(HMW)-脂联素。通过瘦素/sOB-R 计算游离瘦素。从病历中提取出生体重。测量新生儿的长度和皮褶厚度。
妊娠晚期的瘦素和 sOB-R 与新生儿长度呈正相关和负相关,而整个孕期的游离瘦素与长度呈正相关。游离瘦素与新生儿长度的相关性因肥胖而不同(即,在无肥胖的女性中呈负相关,在肥胖的女性中呈正相关)。在无肥胖的女性中,33-39 周时游离瘦素每增加一个单位,新生儿长度减少 0.55cm(95%CI,-0.83,-0.28),肥胖的女性中增加 0.49cm(95%CI,0.34,0.65)。33-39 周时 HMW-脂联素与肥胖女性的新生儿长度(β=-1.29cm;95%CI,-1.74,-0.85)和皮褶厚度(β=-1.46mm;95%CI,-1.58,-0.56)呈负相关。整个孕期游离瘦素与无肥胖女性的新生儿皮褶厚度呈负相关,而妊娠早期游离瘦素与皮褶厚度呈正相关。
母亲的脂联素与影响新生儿大小的多个途径有关,包括长度和肥胖,这些途径在整个孕期的时间和孕前肥胖状态方面存在差异。这些发现为母体肥胖可能影响胎儿生长的机制和时间提供了新的潜在见解。