Pregnant women who consumed the caffeine equivalent of as little as half a cup of coffee a day on average had slightly smaller babies than pregnant women who did not consume caffeinated beverages, according to a study by researchers at the US National Institutes of Health. The researchers found corresponding reductions in size and lean body mass for infants whose mothers consumed below the 200 milligrams of caffeine per day – about two cups of coffee – believed to increase risks to the foetus. Smaller birth size can place infants at higher risk of obesity, heart disease and diabetes later in life.
The researchers were led by Dr Katherine L Grantz, of the division of intramural population health research at NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development.
"Until we learn more, our results suggest it might be prudent to limit or forego caffeine-containing beverages during pregnancy," Grantz said. "It's also a good idea for women to consult their physicians about caffeine consumption during pregnancy."
Previous studies have linked high caffeine consumption (more than 200 milligrams of caffeine per day) during pregnancy to infants being small for their gestational age (stage of pregnancy) or at risk for intrauterine growth restriction – being in the lowest 10th percentile for infants of the same gestational age. However, studies on moderate daily caffeine consumption (200 milligrams or less) during pregnancy have produced mixed results. Some have found similar elevated risks for low birth weight and other poor birth outcomes, while others have found no such links. The current study authors noted that many of the earlier studies did not account for other factors that could influence infant birth size, such as variation in caffeine content of different beverages and maternal smoking during pregnancy.
For their study, the authors analysed data on more than 2,000 racially and ethnically diverse women at 12 clinical sites who were enrolled from 8 to 13 weeks of pregnancy. The women were non-smokers and did not have any health problems before pregnancy. From weeks 10 to 13 of pregnancy, the women provided a blood sample that was later analysed for caffeine and paraxanthine, a compound produced when caffeine is broken down in the body. The women also reported their daily consumption of caffeinated beverages (coffee, tea, soda and energy drinks) for the past week – once when they enrolled and periodically throughout their pregnancies.
Compared to infants born to women with no or minimal blood levels of caffeine, infants born to women who had the highest blood levels of caffeine at enrolment were an average of 84 grams lighter at birth (about 3 ounces), were .44 centimetres shorter (about .17 inches), and had head circumferences .28 centimetres smaller (about .11 inches).
Based on the women's own estimates of the beverages they drank, women who consumed about 50 milligrams of caffeine a day (equivalent to a half cup of coffee) had infants 66 grams (about 2.3 ounces) lighter than infants born to non-caffeine consumers. Similarly, infants born to the caffeine consumers also had thigh circumferences .32 centimetres smaller (about .13 inches).
The researchers noted that caffeine is believed to cause blood vessels in the uterus and placenta to constrict, which could reduce the blood supply to the foetus and inhibit growth. Similarly, researchers believe caffeine could potentially disrupt foetal stress hormones, putting infants at risk for rapid weight gain after birth and for later life obesity, heart disease and diabetes.
The authors concluded that their findings suggest that even moderate caffeine consumption may be associated with decreased growth of the foetus.
Association Between Maternal Caffeine Consumption and Metabolism and Neonatal Anthropometry
Jessica L. Gleason; Fasil Tekola-Ayele; Rajeshwari Sundaram; Stefanie N Hinkle; Yassaman Vafai; Germaine M Buck Louis; Nicole Gerlanc; Melissa Amyx; Alaina M Bever; Melissa M Smarr; Morgan Robinson; Kurunthachalam Kannan; Katherine L Grantz
Published in JAMA Network Open on 25 March 2021
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).
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.
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.
Conclusions and Relevance
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.
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