Maternal caffeine intake tied to reduced foetal growth

Consuming caffeinated beverages* during pregnancy – even at levels below the ACOG**-recommended daily dose of 200 mg – may lead to small reductions in neonatal anthropometric measurements, according to a secondary analysis of the NICHD*** Foetal Growth Studies-Singletons.

“[Our findings show that] increasing caffeine measures were significantly associated with lower birth weight, shorter length, and smaller head, arm, and thigh circumferences,” said the researchers.

The longitudinal analysis comprised 2,055 non-smoking women (mean age 28.3 years) at low risk for foetal growth abnormalities. Plasma concentrations of caffeine (≤28 and >659 ng/mL for first and fourth quartiles, respectively) and paraxanthine (≤14.8 and >232.9 ng/mL, respectively) were evaluated, as well as self-reported caffeinated beverage intake reported or measured at 10–13 weeks gestation. [JAMA Network Open 2021;doi:10.1001/jamanetworkopen.2021.3238]

About half (42 percent) of the participants reported consuming no caffeinated beverages during the first trimester of their pregnancy. Thirty-six percent consumed at least 50 mg, while 23 percent had >50 mg/day. Primary caffeine sources were coffee (35 percent) and soda (41 percent).

Compared with the first quartile of plasma caffeine level, neonates of women in the fourth quartile had lower birth weight (β=−84.3 g; p_trend=0.04), shorter length (β=−0.44 cm; p_trend=0.04), and smaller circumferential measurements of the head (β=−0.28 cm; p_trend=0.001) and mid-upper arm (β=−0.25 cm; p_trend=0.02) and thigh (β=−0.29 cm; p_trend=0.07).

A similar trend across the above-noted anthropometric parameters was observed when looking at the paraxanthine quartiles (β=–83.7 g; p_trend=0.03, β=−0.45 cm; p_trend=0.03, β=−0.28 cm; p_trend<0.001, β=–0.23 cm; p_trend=0.02, and β=−0.31 cm; p_trend=0.09, respectively).

Compared with women who had no caffeinated beverage intake, those who consumed >50 mg/day had neonates with lower birth weight (β=−66 g), smaller mid-upper arm (β=−0.17 cm) and thigh (β=−0.32 cm) circumferences, and smaller anterior flank skin fold (β=−0.24 mm). Smaller subscapular skin folds (β=−0.14 mm) were observed among neonates of women who consumed at least 50 mg/day of caffeine.

Even little amounts count

Despite the different parameters and types of caffeinated beverages used to explore caffeine intake in this population, as well as the various anthropometric measurements, the correlations obtained from self-reported consumption were low, perhaps due to differences in caffeine content in each beverage type, metabolism, and timing of intake, noted the researchers.

“[Nonetheless, the findings] indicate that even small increases in caffeine consumption in the first trimester … and its major metabolite paraxanthine, were associated with lower birth weight, finding that smaller size was manifested by shorter length, and smaller head, arm, and thigh circumferences at birth,” they said. “The decreases in bone and muscle measures, but not skin folds and fat mass, may indicate decreases in lean tissue as caffeine consumption increases.”

Long-term effect

Caffeine reportedly affects foetal growth by disrupting neuroendocrine processes that trigger uteroplacental vasoconstriction, delay organ development, and modify stress response. [Toxicology 2014;325:74-84] Maternal caffeine intake may also modify fat deposition, consequently amplifying the risk for excess growth in infancy, overweight in early childhood, and the development of cardiometabolic disorders later in life among children of caffeine consumers. [BMJ Open 2018;8:e018895; Pediatr Obes 2020;15:e12607]

“[These suggest that] in the long term, these disruptions may put offspring at higher risk for rapid weight gain after birth, childhood obesity, and chronic disease,” said the researchers.

Further investigation is thus warranted to ascertain the validity of the results. “[Moreover, while] measuring caffeine in the first trimester may be a good proxy of consumption throughout pregnancy … evaluation of caffeine biomarker changes across trimesters may be warranted in future studies,” they added.