Association Between Maternal Caffeine Consumption and Metabolism and Neonatal Anthropometry

Abstract

IMPORTANCE 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. OBJECTIVE To evaluate the association between maternal caffeine intake and neonatal anthropometry, testing effect modification by fast or slow caffeine metabolism genotype. DESIGN, SETTING, AND PARTICIPANTSA 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. EXPOSURES 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). MAIN OUTCOMES AND MEASURES 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. RESULTS 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 (Յ28 ng/mL), neonates of women in the fourth quartile (>659 ng/mL) had lower birth weight (β = −84.3 g; 95% CI, −145.9to −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) (continued) Key Points Question Is maternal caffeine intake associated with neonatal anthropometry? Findings In this cohort study of 2055 women from 12 clinical sites, measures of caffeine consumption (plasma caffeine and paraxanthine and selfreported consumption) were associated with neonatal size at birth. Increasing caffeine m...

Association of Maternal Caffeine Consumption During Pregnancy With Child Growth

“…We have previously observed similar results for both self-reported and measured caffeine and paraxanthine. 3 Thus, we have good confidence that measured first trimester caffeine and paraxanthine is an adequate proxy for habitual intake on a population level, without the limitations of self-reported intake. 35 A strength of our study is the use of 2 independent cohorts to evaluate associations: a contemporary cohort reflecting modern caffeine consumption trends in the US and a historical cohort with high consumption.…”

“…Maternal caffeine consumption during pregnancy, even in modest amounts (eg, 50 mg or one-half cup of coffee per day), is associated with lower birth weight and higher rates of birth weight below 2500 g. 1,2 These decreases in birth weight were attributed to shorter birth length and less lean tissue mass in the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies. 3 The potential mechanism is unclear, but caffeine is a neural stimulant not metabolized by the fetus that accumulates in fetal tissue. 4 Given that approximately 8 in 10 US pregnant women consume caffeine, 5 it is important to determine whether in utero caffeine exposure has long-term growth implications in offspring.…”

Beyond AOPs: A Mechanistic Evaluation of NAMs in DART Testing

“…Follow-up in vitro studies in differentiating cardiomyocytes and neuronal rosettes, which are expected to express adenosine receptors ( Headrick et al, 2013 ), were negative at caffeine exposure up to 100 μM, a concentration that is above the expected level in consumers (∼40–80 µM) and provide reassurance that these levels of activity may not be sufficient to adversely affect cardiac or neuronal development, at least in the periods covered by the assays. This conclusion is supported by the available epidemiology data, which suggest that the most sensitive adverse effect associated with oral caffeine exposure in pregnant women is intra-uterine growth retardation, and not specific malformations of the heart and brain ( Gleason et al, 2021 ).…”

“…We followed this framework for two hypothetical exposure scenarios, applying the PBK model approaches to estimate caffeine's internal maternal and foetal exposure, combined with the biological activity characterisation using the NAMS evaluated in the biological coverage section. Caffeine effects during pregnancy have been a topic of debate for many years, but safety agencies around the world agree that a daily consumption of 200 mg is unlikely to lead to significant adverse reproductive and developmental effects (USDA 2015;EFSA, 2015;FDA, 2018;ACOG, 2020;Gleason et al, 2021;James, 2021;NHS, 2020). Here we found that an oral dose below 20 mg/day and a dermal exposure with 0.1% caffeine would result in a maternal BER higher than one implying that this exposure would result in no in vivo biological activity.…”

Relationship between maternal caffeine and coffee intake and pregnancy loss: A grading of recommendations assessment, development, and evaluation-assessed, dose-response meta-analysis of observational studies

“…Hoyt et al reported that 82% of pregnant women in the United States consumed caffeine ( 9 ). In another study, the National Institute of Child Health and Human Development (NICHD) reported that 35% of participants consumed coffee and 41% drank soda daily ( 10 ). A safe dose of daily caffeine intake in pregnancy is not more than 200 mg (or two cups) of coffee ( 11 ).…”