April 1, 2021

A study has found that caffeine consumption during pregnancy, even in amounts less than the recommended 200 mg per day, is linked to smaller neonatal anthropometric measurements.

The longitudinal cohort study in JAMA Network Open concluded that compared to women who drank no, or very little caffeine, women who drank the most caffeine (a plasma caffeine level of ≤ 28 ng/mL) had neonates who weighed 84 g less, were 0.44 cm shorter in length, a 0.28 cm smaller head circumference, a 0.25 cm smaller arm circumference, and a 0.29 cm smaller thigh circumference.

“Most of the research on caffeine and neonatal size at birth focuses on birthweight and length, while relying on self-reported measures of caffeine consumption.,” said senior author Katherine Grantz, MD, an investigator in the Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, in Bethesda, Maryland.

The current study analyzed data from the NICHD Fetal Growth Studies–Singletons, which enrolled 2,055 nonsmoking women at low risk for fetal growth abnormalities with complete information on caffeine consumption from 12 U.S. clinical sites between 2009 and 2013.

“In the NICHD Fetal Growth Studies, we have rich data on multiple measures of neonatal anthropometry to more specifically characterize neonatal size, as well as objective measures of plasma concentrations of caffeine and its primary metabolite, paraxanthine,” Grantz told Contemporary OB/GYN.

The two main sources of caffeine were coffee and soda, which accounted for 35% and 41% of caffeine intake, respectively.

Caffeine was evaluated by both plasma concentrations of caffeine and paraxanthine and self-reported caffeinated beverage consumption measured/reported at 10 to 13 weeks gestation.

Caffeine metabolism was defined as fast or slow, based on genotype information from the single nucleotide variant rs762551.

“Prior caffeine studies have observed lower birthweight after consumption of higher amounts of caffeine -- usually 200 to 300 mg, or 2 to 3 cups of coffee, daily,” said Grantz, who served as a co-principal investigator of the NICHD Fetal Growth Studies.

Before starting their analyses, the current authors knew that the average consumption in the sample was much lower, about 35 mg/day, and only 16 women reported drinking more than 200 mg/day.

Because of this low consumption, we were uncertain we would see any significant results, so it was surprising that we still found that increasing caffeine consumption, even at low levels, was associated with some smaller anthropometric measures in the offspring,” Grantz said. “Also, the finding that the decreases in birthweight were manifested by decreases in bone and muscle measures, but not skin folds and fat mass, were unexpected. These findings may indicate decreases in lean tissue as caffeine consumption increases.”

The clinical implications of the study are unknown, considering there were only small reductions in some neonatal anthropometric measures, Grantz said. “Other evidence suggests that even small amounts of caffeine intake during pregnancy (50 mg/day) could be associated with a higher risk of excess growth in infancy and childhood that could put children at higher risk of later cardiometabolic disease,” she said. “Therefore, our results could indicate some disruption in normal fetal growth patterns, but will require more research to confirm.”

Although the study authors are unable to make recommendations based on the results of their single study, “we encourage pregnant women to talk to their providers about caffeine consumption, and suggest that caution may be warranted,” Grantz said.

The next step for the investigators is to evaluate the serial ultrasounds and fetal volumes conducted throughout pregnancy by the NICHD Fetal Growth Studies to determine when changes begin in fetal growth in relation to caffeine measures, and how these changes may be manifested in fetal volumes.

Disclosure

Grantz reports no relevant financial disclosures.

Reference

Gleason JL, Tekola-Ayele F, Sundaram R, et al. Association between maternal caffeine consumption and metabolism and neonatal anthropometry: a secondary analysis of the NICHD Fetal Growth Studies–Singletons. JAMA Network Open. Published online March 25, 2021. doi:10.1001/jamanetworkopen.2021.3238