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Children whose mothers consumed caffeine-containing products at rates well above average while pregnant with them ended up shorter than offspring of women with the lowest caffeine intake, researchers found.

In two prospectively followed cohorts, with some 2,400 children in total, children of women with the highest intake averaged 1.5 to 2.2 cm shorter (0.6-0.9 inches) at ages 7 to 8, reported Jessica L. Gleason, PhD, MPH, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Maryland, and colleagues.

There was also an inverse but weaker relationship involving children's weight, they , and no clear link to body mass index (BMI) values.

Gleason and colleagues cautioned against jumping to the conclusion that moms-to-be should cut out the morning coffee. "The clinical implication of this height difference is unclear and warrants future investigation," they wrote, and the study did not corroborate earlier suggestions that fetal exposure to caffeine increases risk of subsequent obesity.

At the same time, however, the researchers noted that the "approximately 2-cm height difference" is similar to that found in earlier studies of maternal smoking in pregnancy, which is (albeit for many reasons, not just for effects on children's growth).

The two cohorts analyzed in the study were an offshoot of the Fetal Growth Studies project, called Environmental Influences on Child Health Outcomes (ECHO-FGS), and the Collaborative Perinatal Project (CPP). The first involved nonsmoking women giving birth to single infants, 788 in all; the second had 1,622 women and offspring. Only a handful of mothers in ECHO-FGS were smokers and their results were adjusted for levels of plasma cotinine (a nicotine metabolite) to account for primary and second-hand smoke exposure.

Importantly, maternal caffeine intake in both cohorts was measured via blood tests for caffeine and its metabolite paraxanthine -- a key strength of the study insofar as it did not rely on women's self-reports of caffeine-containing beverage intake. For statistical analysis, caffeine levels were stratified into quartiles for ECHO-FGS and quintiles for CPP.

Children's outcomes for height, weight, and BMI were measured periodically. Gleason and colleagues reported them primarily as normalized "z scores" to adjust for children's expected age-related growth.

In the ECHO-FGS group, the association between caffeine intake and children's z score for height was β = -0.21 for the fourth quartile versus the first (95% CI -0.41 to -0.02) across ages 4 to 8. "At age 7, this difference in z score translated to an approximate 1.5-cm difference," the researchers noted.

The CPP cohort showed a similar relationship when the fifth quintile was compared to the first, "with a widening gap through age 8 years," they added. At age 4, the β value was -0.16 (95% CI -0.31 to -0.01); by age 8, it had reached -0.37 (95% CI -0.57 to -0.16). In terms of height, these differences equated to 0.7 to 2.2 cm.

Trends toward lower weight with increased caffeine exposure were seen in most comparisons. These reached statistical significance only in ECHO-FGS and only for the third caffeine quartile, not the fourth.

Previous studies had also pointed to reduced child height and weight with maternal caffeine drinking, with the height deficit being greater. That led to concerns that offspring might actually be more inclined to overweight and obesity. But in the new study, the ECHO-FGS contingent showed "no evidence of overweight or obesity in any quartile"; CPP did have some increase in overweight/obesity in the two highest quintiles but they fell short of significance.

Whether an average height deficit of less than 1 inch at ages 7 to 8 is clinically significant is open to question. (Of course, assuming a normal distribution, that is, a symmetrical bell curve, it would be substantially greater for some.) In terms of physical health outcomes, it's probably not, insofar as there was no clear effect on BMI in these data. But height is very important from a social and cultural perspective. If the deficit continues to grow through puberty, then it could have a major impact, and perhaps risks of obesity would grow as well, hence, the researchers' call for further investigation.

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