Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Biostatistics Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
JAMA Netw Open. 2021 Mar 1;4(3):e213238. doi: 10.1001/jamanetworkopen.2021.3238.
Higher caffeine consumption during pregnancy has been associated with lower birth weight. However, associations of caffeine consumption, based on both plasma concentrations of caffeine and its metabolites, and self-reported caffeinated beverage intake, with multiple measures of neonatal anthropometry, have yet to be examined.
To evaluate the association between maternal caffeine intake and neonatal anthropometry, testing effect modification by fast or slow caffeine metabolism genotype.
DESIGN, SETTING, AND PARTICIPANTS: A longitudinal cohort study, the National Institute of Child Health and Human Development Fetal Growth Studies-Singletons, enrolled 2055 nonsmoking women at low risk for fetal growth abnormalities with complete information on caffeine consumption from 12 US clinical sites between 2009 and 2013. Secondary analysis was completed in 2020.
Caffeine was evaluated by both plasma concentrations of caffeine and paraxanthine and self-reported caffeinated beverage consumption measured/reported at 10-13 weeks gestation. Caffeine metabolism defined as fast or slow using genotype information from the single nucleotide variant rs762551 (CYP1A2*1F).
Neonatal anthropometric measures, including birth weight, length, and head, abdominal, arm, and thigh circumferences, skin fold and fat mass measures. The β coefficients represent the change in neonatal anthropometric measure per SD change in exposure.
A total of 2055 participants had a mean (SD) age of 28.3 (5.5) years, mean (SD) body mass index of 23.6 (3.0), and 580 (28.2%) were Hispanic, 562 (27.4%) were White, 518 (25.2%) were Black, and 395 (19.2%) were Asian/Pacific Islander. Delivery occurred at a mean (SD) of 39.2 (1.7) gestational weeks. Compared with the first quartile of plasma caffeine level (≤28 ng/mL), neonates of women in the fourth quartile (>659 ng/mL) had lower birth weight (β = -84.3 g; 95% CI, -145.9 to -22.6 g; P = .04 for trend), length (β = -0.44 cm; 95% CI, -0.78 to -0.12 cm; P = .04 for trend), and head (β = -0.28 cm; 95% CI, -0.47 to -0.09 cm; P < .001 for trend), arm (β = -0.25 cm; 95% CI, -0.41 to -0.09 cm: P = .02 for trend), and thigh (β = -0.29 cm; 95% CI, -0.58 to -0.04 cm; P = .07 for trend) circumference. Similar reductions were observed for paraxanthine quartiles, and for continuous measures of caffeine and paraxanthine concentrations. Compared with women who reported drinking no caffeinated beverages, women who consumed approximately 50 mg per day (~ 1/2 cup of coffee) had neonates with lower birth weight (β = -66 g; 95% CI, -121 to -10 g), smaller arm (β = -0.17 cm; 95% CI, -0.31 to -0.02 cm) and thigh (β = -0.32 cm; 95% CI, -0.55 to -0.09 cm) circumference, and smaller anterior flank skin fold (β = -0.24 mm; 95% CI, -0.47 to -0.01 mm). Results did not differ by fast or slow caffeine metabolism genotype.
In this cohort study, small reductions in neonatal anthropometric measurements with increasing caffeine consumption were observed. Findings suggest that caffeine consumption during pregnancy, even at levels much lower than the recommended 200 mg per day of caffeine, are associated with decreased fetal growth.
重要性：怀孕期间摄入较高的咖啡因与较低的出生体重有关。然而，基于咖啡因的血浆浓度及其代谢产物以及自我报告的含咖啡因饮料摄入量的咖啡因摄入与新生儿多项人体测量学指标的关联尚未得到检验。
目的：评估母体咖啡因摄入量与新生儿人体测量学指标之间的关联，并检验咖啡因代谢快速或慢速基因型的修饰作用。
设计、地点和参与者：这是一项纵向队列研究，即国家儿童健康与人类发展研究所胎儿生长研究-单胎，纳入了 2055 名在美国 12 个临床地点于 2009 年至 2013 年间完成的无吸烟、低胎儿生长异常风险且咖啡因摄入量完整信息的低风险女性。次要分析于 2020 年完成。
暴露因素：咖啡因通过血浆咖啡因和对黄嘌呤浓度以及 10-13 周妊娠时自我报告的含咖啡因饮料摄入量进行评估。咖啡因代谢通过单核苷酸变异 rs762551（CYP1A2*1F）的基因型信息定义为快速或慢速。
主要结果和措施：新生儿人体测量学指标包括出生体重、身长、头围、腹围、臂围和大腿围、皮褶和脂肪量。β系数表示每暴露因素标准差变化时新生儿人体测量学指标的变化。
结果：共有 2055 名参与者的平均（标准差）年龄为 28.3（5.5）岁，平均（标准差）体重指数为 23.6（3.0），580 名（28.2%）为西班牙裔，562 名（27.4%）为白人，518 名（25.2%）为黑人，395 名（19.2%）为亚洲/太平洋岛民。分娩发生在平均（标准差）39.2（1.7）孕周。与血浆咖啡因水平第一四分位数（≤28ng/mL）相比，第四四分位数（>659ng/mL）的孕妇新生儿出生体重较低（β=-84.3g；95%CI，-145.9 至-22.6g；趋势 P=0.04）、身长（β=-0.44cm；95%CI，-0.78 至-0.12cm；趋势 P=0.04）、头围（β=-0.28cm；95%CI，-0.47 至-0.09cm；趋势 P<0.001）、臂围（β=-0.25cm；95%CI，-0.41 至-0.09cm；趋势 P=0.02）和大腿围（β=-0.29cm；95%CI，-0.58 至-0.04cm；趋势 P=0.07）。对黄嘌呤四分位数和咖啡因和黄嘌呤浓度的连续测量也观察到类似的降低。与不饮用含咖啡因饮料的女性相比，每天饮用约 50mg 咖啡因（约 1/2 杯咖啡）的女性新生儿出生体重较低（β=-66g；95%CI，-121 至-10g）、臂围（β=-0.17cm；95%CI，-0.31 至-0.02cm）和大腿围（β=-0.32cm；95%CI，-0.55 至-0.09cm）较小，前侧肋皮褶厚度（β=-0.24mm；95%CI，-0.47 至-0.01mm）较小。结果不因咖啡因代谢快速或慢速基因型而异。
结论：在这项队列研究中，随着咖啡因摄入量的增加，新生儿人体测量学指标的小幅度降低。这些发现表明，即使在低于推荐的每日 200mg 咖啡因摄入量的情况下，妊娠期间摄入咖啡因仍与胎儿生长减少有关。
