Associations of Prenatal and Childhood Antibiotic Exposure With Obesity at Age 4 Years

Leong, Karen S. W.; McLay, Jessica; Derraik, José G. B.; Gibb, Sheree; Shackleton, Nichola; Taylor, Rachael W.; Glover, Marewa; Audas, Rick; Taylor, Barry; Milne, Barry; Cutfield, Wayne S.

doi:10.1001/jamanetworkopen.2019.19681

Cited by 44 publications

(48 citation statements)

References 30 publications

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“…In this study, it was clear that antibiotic treatment dramatically altered the intestinal microbiota composition immediately, but the effects induced by a shortterm therapeutic dose of ceftriaxone on intestinal microbiota at least at the phylum level did not appear to continue to adulthood. Recently, research has explored the relationship between obesity and antibiotic treatment, especially in infancy or childhood, but the results lacked consistency [46][47][48]. In our study, antibiotic use induced the dysbiosis of the intestinal microbiota during early life, although this effect did not continue to adulthood.…”

Section: Discussionmentioning

confidence: 57%

Dysbiosis of intestinal microbiota in early life aggravates high-fat diet induced dysmetabolism in adult mice

et al. 2021

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Background Accumulating evidence have shown that the intestinal microbiota plays an important role in prevention of host obesity and metabolism disorders. Recent studies also demonstrate that early life is the key time for the colonization of intestinal microbes in host. However, there are few studies focusing on possible association between intestinal microbiota in the early life and metabolism in adulthood. Therefore the present study was conducted to examine whether the short term antibiotic and/or probiotic exposure in early life could affect intestinal microbes and their possible long term effects on host metabolism. Results A high-fat diet resulted in glucose and lipid metabolism disorders with higher levels of visceral fat rate, insulin-resistance indices, and leptin. Exposure to ceftriaxone in early life aggravated the negative influences of a high-fat diet on mouse physiology. Orally fed TMC3115 protected mice, especially those who had received treatment throughout the whole study, from damage due to a high-fat diet, such as increases in levels of fasting blood glucose and serum levels of insulin, leptin, and IR indices. Exposure to ceftriaxone during the first 2 weeks of life was linked to dysbiosis of the fecal microbiota with a significant decrease in the species richness and diversity. However, the influence of orally fed ceftriaxone on the fecal microbiota was limited to 12 weeks after the termination of treatment. Of note, at week 12 there were still some differences in the composition of intestinal microbiota between mice provided with high fat diet and antibiotic exposure and those only fed a high fat diet. Conclusions These results indicated that exposure to antibiotics, such as ceftriaxone, in early life may aggravate the negative influences of a high-fat diet on the physiology of the host animal. These results also suggest that the crosstalk between the host and their intestinal microbiota in early life may be more important than that in adulthood, even though the same intestinal microbes are present in adulthood.

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Section: Discussionmentioning

confidence: 57%

Dysbiosis of intestinal microbiota in early life aggravates high-fat diet induced dysmetabolism in adult mice

et al. 2021

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“…Our findings must be interpreted in the light of a recent cross-sectional study 42 of 284,211 participants that included siblings and twins in New Zealand and that analyzed prenatal and early infancy antibiotic exposure (first two years) and its association with obesity at 4 years. The study found that both prenatal and early infancy exposure to antibiotics were independently associated with obesity at 4 years in a dose dependent manner.…”

Section: Discussionmentioning

confidence: 92%

Early and frequent exposure to antibiotics in children and the risk of obesity: systematic review and meta-analysis of observational studies

et al. 2020

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Background: This study aimed to systematically evaluate the available evidence on prenatal and early infancy antibiotic exposure and the association with overweight and obesity in later childhood. Methods: We conducted a comprehensive search of Embase, MEDLINE, and Web of Science for observational studies assessing prenatal and early antibiotic exposure on the risk of overweight and obesity. We independently assessed the risk of bias using the ROBINS instrument and the overall quality of evidence using the GRADE approach. Results: Our search identified thirteen observational studies including 554,983 participants; most studies were at moderate risk of bias. We found a statistically significant impact of early antibiotic exposure and the risk of being overweight later in childhood (OR 1.18; 95% CI 1.05 to 1.34) (very low quality evidence). We also found that early childhood antibiotic exposure was associated with the risk for childhood obesity (OR 1.14; 95% CI 1.04 to 1.24) (very low quality evidence). Conclusions: Very low quality evidence suggests that exposure to antibiotics early in life may be associated with an increased risk of being overweight and obese in later childhood. However, very low quality evidence raises serious questions about the plausibility of prenatal and early infancy antibiotic exposure being causally related to weight in children. PROSPERO registration: CRD42016050011 (14/12/2016)

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“…Observational studies in high resource settings have shown an association between antibiotic consumption and increased child growth, leading to concerns about antibiotic consumption and childhood obesity [ 22 , 23 ]. Potential biases including unmeasured confounding limit the ability to draw causal conclusions from these studies [ 24 ]. Randomized controlled trial evidence has generally shown increased growth among children with known acute or chronic illness following antibiotic administration in lower resource settings [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Single-dose azithromycin for child growth in Burkina Faso: a randomized controlled trial

et al. 2021

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Background In lower resource settings, previous randomized controlled trials have demonstrated evidence of increased weight gain following antibiotic administration in children with acute illness. We conducted an individually randomized trial to assess whether single dose azithromycin treatment causes weight gain in a general population sample of children in Burkina Faso. Methods Children aged 8 days to 59 months were enrolled in November 2019 and followed through June 2020 in Nouna Town, Burkina Faso. Participants were randomly assigned to a single oral dose of azithromycin (20 mg/kg) or matching placebo. Anthropometric measurements were collected at baseline and 14 days and 6 months after enrollment. The primary anthropometric outcome was weight gain velocity in g/kg/day from baseline to 14 days and 6 months in separate linear regression models. Results Of 450 enrolled children, 230 were randomly assigned to azithromycin and 220 to placebo. Median age was 26 months (IQR 16 to 38 months) and 51% were female. At 14 days, children in the azithromycin arm gained a mean difference of 0.9 g/kg/day (95% CI 0.2 to 1.6 g/kg/day, P = 0.01) more than children in the placebo arm. There was no difference in weight gain velocity in children receiving azithromycin compared to placebo at 6 months (mean difference 0.04 g/kg/day, 95% CI − 0.05 to 0.13 g/kg/day, P = 0.46). There were no significant differences in other anthropometric outcomes. Conclusions Transient increases in weight gain were observed after oral azithromycin treatment, which may provide short-term benefits. Clinical trials registration ClinicalTrials.gov NCT03676751. Registered 19/09/2018.

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Associations of Prenatal and Childhood Antibiotic Exposure With Obesity at Age 4 Years

Cited by 44 publications

References 30 publications

Dysbiosis of intestinal microbiota in early life aggravates high-fat diet induced dysmetabolism in adult mice

Dysbiosis of intestinal microbiota in early life aggravates high-fat diet induced dysmetabolism in adult mice

Early and frequent exposure to antibiotics in children and the risk of obesity: systematic review and meta-analysis of observational studies

Single-dose azithromycin for child growth in Burkina Faso: a randomized controlled trial

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