Sugar-Containing Beverages in Infancy and Liver Fat Accumulation at School Age

By Rakesh Calton, MD

Associate Professor, Clinical Foundations, Ross University School of Medicine, Barbados, West Indies

Summary Points

• To the assess association between sugar-containing beverage intake in infancy, and nonalcoholic fatty liver disease (NAFLD) among school aged-children, the authors conducted a population-based prospective study in a cohort of 1,940 infants.
• Liver fat was measured at 10 years of age by conducting magnetic resonance imaging studies. Four samples of at least 4 cm² from the central portion of liver volume were used to measure liver fat fraction. NAFLD was defined as liver fat of > 5 %.
• According to the study data, the median sugar-containing beverage intake in infancy was 0.9 servings/day (95% confidence interval [CI], 0.0-3.7). The median liver fat fraction at 10 years of age was 2.0% (95% CI, 1.2-4.6) for low sugar-containing beverage intake during infancy, 1.9% (95% CI; range, 1.2-4.3) for medium sugar-containing beverage intake during infancy, and 2.0% (95% CI; range, 1.2-6.1) for high sugar-containing beverage intake during infancy.
• Children in whom liver fat measurement wasn’t performed were mostly of non-European ethnicity and had higher daily energy intake during infancy.

SYNOPSIS: In this observational study, the authors examine the associations between sugar-containing beverage intake in infancy and liver fat accumulation and nonalcoholic fatty liver disease among school-aged children.

SOURCE: Geurtsen ML, Santos S, Gaillard R, et al. Associations between intake of sugar-containing beverages in infancy with liver fat accumulation at school age. Hepatology 2021;73:560-570.

High intake of sugar-containing beverages is associated with obesity across all age groups. Geurtsen et al cited several studies that show a strong correlation between a high intake of sugar-containing beverages among infants and a high body mass index (BMI) in adulthood, as well as adiposity among children. It also is evident that high sugar consumption leads to increased liver fat accumulation. These changes are variable and may include fatty changes, inflammatory response, fibrosis, cirrhosis, or end-stage liver disease.

To assess the association between sugar-containing beverage intake in infancy and nonalcoholic fatty liver disease (NAFLD) among school-aged children, the authors conducted a population-based prospective study of 1,940 infants.

The data for this study were obtained from Generation R study.¹ All the participants in this study were born between April 2002 and January 2006. A total of 5,088 mothers were given the infant Food Frequency Questionnaire (FFQ), which 3,643 completed. Using this FFQ, 3,614 infants were assessed by 1 year of age. Of that group, 1,940 children were subjected to a magnetic resonance imaging (MRI) screening at 10 years of age.

The FFQ was designed based on a preexisting validated FFQ and contained 221 items.² The FFQ was modified and included foods that are frequently consumed during early life. Based on a validation study, the interclass correlation coefficient for sugar-containing beverages was calculated as 0.76.³ Various sugar-containing beverages included fruit juices, fruit concentrates, lemonades, and soft drinks. Authors converted the intake of these beverages into a number of servings per day (each serving being equal to 150 g) as per the Dutch Food Composition Table.⁴ The consumption of sugar was categorized into several groups: mild (< 1 serving/day), moderate (1 to 2 servings/day), and high (> 3 servings/day).

Liver fat was measured at 10 years of age by conducting MRI studies. Four samples of at least 4 cm² from the central portion of liver volume were used to measure liver fat fraction. NAFLD was defined as liver fat of > 5%.

Various covariates studied were maternal age and parity, mother’s education, history of smoking, and household income. Height, weight, and prepregnancy BMI were measured. Other parameters obtained for the children were age, gender, birth weight, and ethnicity of parents.

The statistical analysis began with a nonresponse analysis conducted among infants having a valid FFQ, comparing children with and without liver MRI scans using Student t-test, Mann-Whitney U tests, and chi-square tests. The association between sugar-containing beverages and liver fat accumulation was determined using linear regression. Meanwhile, a logistic regression model was used to assess the association between sugar-containing beverage intake and the odds of developing NAFLD.

These models were adjusted to account for confounding variables as well as for mediators. The basic model adjusted for child at 10 years of age, sex, and total energy intake. Meanwhile, the confounder model adjusted for maternal prepregnancy BMI, education, net household income, child ethnicity, physical activity, and screen time. Finally, the mediator model adjusted for sugar-containing beverage intake at 8 years of age and BMI at 10 years of age.

Results

According to the study data, the median sugar-containing beverage intake in infancy was 0.9 servings/day (95% confidence interval [CI], 0.0-3.7). The median liver fat fraction at 10 years of age was 2.0% (95% CI, 1.2-4.6) for low sugar-containing beverage intake during infancy, 1.9% (95% CI; range, 1.2-4.3) for medium sugar-containing beverage intake during infancy, and 2.0% (95% CI range, 1.2-6.1) for high sugar-containing beverage intake during infancy. Children in whom liver fat measurement wasn’t performed were mostly of non-European ethnicity and had higher daily energy intake during infancy.

The distribution of liver fat fraction at 10 years of age was categorized into categories of < 2.0%, 2.0% to 2.9%, 3.0% to 3.9%, 4.0% to 4.9%, and ≥ 5.0%. The percentage of children with a liver fat fraction of ≥ 5.0% increased in the high sugar-containing beverage intake group (4.0%, n = 14 of 353; P < 0.01) compared to the low sugar-containing beverages intake group (1.4%, n = 14 of 1,015). Higher odds for developing NAFLD were observed in the higher sugar-containing beverage intake group as well (odds ratio [OR], 1.34; 95% CI, 1.06-1.69; P < 0.05).

According to the data, less-educated mothers tended to give higher sugar-containing beverages to their children during infancy, which resulted in an increased fat fraction in these children as demonstrated on MRI conducted at age 10 years (standard deviation 0.09; 95% CI, 0.03-0.16, per one-serving-per-day increase in sugar-containing beverage intake). Meanwhile, highly educated mothers tended to give fewer high sugar-containing beverages to their children during infancy.

The odds of NAFLD were found to be stronger among children of mothers with a lower or medium level of education (OR, 1.48; 95% CI, 1.12-1.97) compared to the children of mothers with a higher level of education. The odds of NAFLD were found to be higher among children who were overweight or obese (OR, 1.47; 95% CI, 1.05-2.07) compared to the children with normal body weights.

The association of development of NAFLD and intake of high sugar containing beverages was only seen in the beverages that were sweetened. However, according to the authors, this association was not seen in the children who were given beverages categorized as fruit juices, soft drinks, and lemonade. No difference in results was observed between confounder and basic models after adjustment for sugar-containing beverage intake at 8 years of age and BMI at 10 years of age (P = 0.13).

COMMENTARY

In this well-designed population-based prospective study, the authors studied the relationship between intake of sugar-containing beverages and the odds of developing an elevated liver fat fraction or NAFLD. A large sample size (1,940 infants assessed with MRI at 10 years of age) obtained from a prospective longitudinal study is the main strength of this study. The authors built a logical case as they introduced the topic and provided sound context for the problem statement that is clear, concise, and well-articulated. The conceptual framework is explicit, and constructs under investigation were clearly identified and presented. The literature review was adequate and up to date. The data were obtained from the Generation R study, and the research design adequately handled the internal validity and confounding variables. Data analysis measures were well-defined and addressed various biases to ensure trustworthiness.

The authors concluded that there is a direct relationship between higher sugar-containing beverage intake in infancy with development of NAFLD in school-aged children. This association only is seen with sweetened beverages and not with fruit juices, soft drinks, and lemonades. This association is stronger among children of mothers with a lower level of education and among overweight or obese children. These observations were consistent with Chhimwal et al, who observed that the ingestion of sugar-rich beverages causes a metabolic burden and raises the risk of NAFLD.⁵ This observation is further supported by a systematic review and dose-response meta-analysis that showed 1.39-fold increased odds of NAFLD (95% CI, 1.29-1.50; P < 0.00001) among those who consumed sugar-sweetened beverages.⁶

Practicing physicians should adopt preventive strategies that are focused on reducing the intake of sugar-containing beverages from infancy onward. Practicing physicians may adopt motivational interviewing techniques, especially among mothers with low levels of education, encouraging them to avoid high sugar-containing beverage intake in their children during infancy.

REFERENCES

1. Kooijman MN, Kruithof CJ, van Duijn CM, et al. The Generation R study: Design and cohort update 2017. Eur J Epidemiol 2016;31:1243-1264.
2. Feunekes GI, Van Staveren WA, De Vries JH, et al. Relative and biomarker-based validity of a food-frequency questionnaire estimating intake of fats and cholesterol. Am J Clinical Nutr 1993;58:489-496.
3. Leermakers ETM, Felix JF, Erler NS, et al. Sugar-containing beverage intake in toddlers and body composition up to age 6 years: The Generation R study. Eur J Clin Nutr 2015;69:314-321.
4. National Institute for Public Health and the Environment. Comparison of salt, saturated fat, and sugar content in foods between 2011 and 2016. [Vergelijking van zout-, verzadigd vet- en suikergehalten in voedingsmiddelen tussen 2011 en 2016]. Published 2017. https://rivm.openrepository.com/bitstream/handle/10029/620837/2017-0011.pdf?sequence=1
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