Is maternal caffeine consumption associated with child growth and are there such associations in low consumption groups?

Is maternal caffeine consumption associated with child growth and are there such associations in low consumption groups?

Today, caffeine consumption most commonly takes place in the form of tea, coffee and caffeinated soft drinks. With coffee's stimulating effects, most people find it difficult to limit it despite concerns about its health effects. A new paper published in JAMA network opened discusses the connection between caffeine consumption during pregnancy and the future growth of the offspring.

Lernen: Assoziation des mütterlichen Koffeinkonsums während der Schwangerschaft mit dem Wachstum des Kindes. Bildnachweis: Galina Zhigalova/Shutterstock

introduction

About 80% of American women drink coffee during their pregnancy. Caffeine is a brain-stimulating compound and accumulates in fetal tissue due to a lack of metabolic pathways during this phase of life.

Previous research, such as that conducted by the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies, suggested an adverse effect of caffeine consumption during pregnancy, even at levels as low as 50 mg, the amount in half a cup of coffee per day, depending on the size and weight of the baby at birth. The proportion of babies born with a birth weight of less than 2.5 kg or babies with low birth weight (LBW) was higher after caffeine consumption, mainly due to reduced birth length and a reduction in lean tissue mass.

Conversely, other studies have shown increases in infant weight gain, infant body mass index (BMI), and childhood obesity with increasing caffeine consumption. The goal of the current study, called the Environmental Influences on Child Health Outcomes (ECHO-FGS) study, was to follow up on previous research conducted in a subset of the NICHD Fetal Growth Studies-Singletons offspring cohort.

The ECHO-FGS study was conducted from 2017 to 2019 at ten sites with over a thousand mother-infant dyads from the NICHD Fetal Growth Studies Singletons cohort. Both obese and normal weight mothers were included along with their children aged 4 to 8 years. The women came from different backgrounds.

The researchers also conducted a high caffeine exposure study. This was the Collaborative Perinatal Project (CPP) at 12 sites on pregnant women and their offspring.

For both groups of participants, age- and sex-normalized BMI was calculated along with z-scores for BMI, weight, and height in relation to the approximate differences in standardized weight and height at seven years, which was the time of a visit to the CPP and the mean measurement age for the ECHO-FGS.

Caffeine is rapidly metabolized in the body, primarily to paraxanthine. In the first trimester this occurs within three hours, but can last up to ten hours in late pregnancy. Therefore, the researchers decided to measure both caffeine and paraxanthine levels to see a connection to the child's growth.

What did the study show?

In the ECHO-FGS study, the lowest caffeine concentrations were in women from black backgrounds, typically younger and not pregnant, unmarried or without a partner, with lower social and educational backgrounds and lower income levels. The children were on average about seven years old at the time of the study, with about a quarter being above the BMI criterion for normal.

The mean concentration for caffeine was ~170 ng/ml and for paraxanthin ~74 ng/ml, corresponding to caffeine consumption of less than 50 mg per day. Height Z-scores decreased by more than a fifth in the fourth quartile of consumption compared to the first between four and eight years, corresponding to a shortening of about 1.5 cm at age seven.

Breath Biopsy®: The Complete Manual eBook

Introduction to breath biopsy, including biomarkers, technology, applications, and case studies. Download a free copy

Comparing the third quartile to the first, weight in the previous cohort fell by over a quarter, meaning the children were on average 1.1kg lighter at age seven. Similar findings were available for paraxanthin.

No difference was observed in BMI, fat mass, or fat percentage, ruling out an increase in the risk of obesity or overweight for both caffeine and paraxanthine.

In the CPP study, mean concentrations for caffeine and paraxanthine were much higher at 625 and 296 ng/mL, respectively, equivalent to two cups of coffee per day. When analyzed by quintile, children born to those in the lowest consumption quintile were taller than those whose mothers fell in the highest consumption quintile.

The height difference increased by the end of the study at eight years of age, from 16% at four years of age to 37% at eight years of age. At this point in time, the children in the lowest-consuming quintile were 0.7 to 2.2 cm taller than those in the highest-consuming quintile. However, there was no significant difference in weight between quintiles.

BMI was higher in women in the second and third quintiles at ages seven and eight years. In both studies, child gender had no influence on these associations.

What are the effects?

The results that both caffeine and paraxanthine concentrations in maternal blood were associated with smaller child height by age eight in two different cohorts with different patterns of caffeine consumption are significant. The reduction is similar to maternal smoking during pregnancy.

Aside from height reduction, children's weight was reduced with increasing consumption, but only in the third quartile and third quintile in the ECHO-FGS and CPP studies.

It is concerning that "maternal caffeine consumption is associated with long-term decline in infant height, even when maternal consumption is below current recommendations of 200 mg per day."

Previous studies have shown that a lack of weight gain is usually associated with a higher risk of heart and metabolic diseases, as well as obesity and diabetes in adults. The mechanism could be via direct effects of caffeine and paraxanthine on the fetus, as both cross the placenta but cannot be metabolized by the fetus. Increased maternal glucocorticoid secretion due to caffeine with inhibition of fetal glucocorticoid catabolic pathways could also play a role in the accumulation of caffeine and its metabolites in the fetus.

This could influence the endocrine regulation of fetal growth via the hypothalamic-pituitary-adrenal axis or by enhancing insulin action in the fetus due to glucocorticoid-induced insulin sensitivity. This supports the developmental paradigm of health and disease mediated by metabolic disturbances in fetal life.

In the study that preceded the current one, the same researchers reported a potential for such metabolic dysregulation in the form of intact fat mass but reduced lean mass upon caffeine exposure.

Some researchers have found that weight increases over time with higher caffeine consumption, compared to a decrease over time with low consumption. It is noteworthy that no such risk of obesity or overweight was found among the children in this study. This could suggest that up to a certain threshold, maternal caffeine consumption may not have a positive effect on child weight, but may be associated with lower weight.

Future research on caffeine consumption during pregnancy should follow the child's growth through puberty and beyond to determine whether height differences continue to widen into adulthood and whether smaller height associated with maternal caffeine consumption confers a greater risk of cardiometabolic dysfunction.

Reference:

• Gleason, J. et al. (2022) „Assoziation des mütterlichen Koffeinkonsums während der Schwangerschaft mit dem Wachstum des Kindes“, JAMA Network Open, 5(10), p. e2239609. doi: 10.1001/jamanetworkopen.2022.39609.

.