The lesser-known health risks of antibiotics in children explained.
Although antibiotics use has decreased overall since the early 2000s, it is not the case for respiratory diseases. In the US, it is estimated that antibiotics were prescribed to one-fifth of children’s medical visits, of which 50% were broad-spectrum (usually macrolide), and over 70% were for respiratory diseases.
Antibiotics only kill bacteria, not viruses. Yet both bacteria and viruses can cause respiratory illness. So, about 29% of antibiotics given for respiratory disease in children are unnecessary, which comprises over 10 million visits per year in the US. “Broad-spectrum antibiotic prescribing in ambulatory pediatrics is extremely common and frequently inappropriate,” said a 2011 national study in the US. In 2016, the CDC reports that one in three antibiotics were given needlessly.
Unnecessary antibiotics are not only improper in the context of superbugs pandemics but come with health risks as well, especially in children. The gut microbiota is undergoing rapid changes in infancy and childhood. Antibiotics, especially broad-spectrum ones, tend to wipe out beneficial gut microbes. Not to mention that children’s brains and physique are also experiencing sensitive growth phases.
Antibiotics and Weight Gain
In a 2019 study of 586 children, 33.79% received 1–2 courses, and 5.63% received >3 courses of antibiotics within the first year of life. When these children turned six years old, those that took antibiotics had a dose-dependent increase in both excess weight and risk of future obesity. Results remained significant after adjusting for maternal age, BMI, race, marital status, income, education, smoking, diabetes, and breastfeeding. Statistically speaking, children that took 1–2 and >3 courses of antibiotics had a 0.17 and 0.42 increase in BMI z-score, respectively.
(The WHO classifies BMI z-score of < −2.0, > 1.0, > 2.0, and > 3.0 as wasted, at-risk-for-overweight, overweight, and obese, respectively, in children of 0–5 years old. Scientists use this BMI z-score method to standardized weight in light of the child’s increasing height.)
Weight gain is particularly prominent with broad-spectrum antibiotics like cephalosporins and macrolides. Narrow-spectrum antibiotics, in contrast, had little-to-no impact on weight gain unless taken for 5–7 courses.
In a 2015 Finland study of 12,062 children under two years old, those exposed to 2–3 and >4 courses of antibiotics had a 0.10 and 0.18 higher BMI z-score, respectively, than those never exposed. And this number is 0.23 and 0.28 — indicating overweight to near obesity — in girls and boys, respectively, under six months old that took macrolide, a common broad-spectrum antibiotic.
Other massive cohort studies in the US — in 2014 (65,480 children), 2015 (163,820 children), and 2017 (8,793 children) — all found a dose-response effect of antibiotics on weight gain. All results were also adjusted for possible confounding factors. The weight gain is particularly prominent with broad-spectrum antibiotics like cephalosporins and macrolides. Narrow-spectrum antibiotics, in contrast, had little-to-no impact on weight gain unless taken for 5–7 courses.
Boys appear to be more susceptible to weight gain from antibiotics than girls.
As the Finland study and other research have noticed, boys appear to be more susceptible to weight gain from antibiotics than girls.
- A Canadian study in 2014 of 616 children reported that antibiotics exposure in the first year of life presented a five-fold increased odds of being overweight at 12 years old in boys but not girls.
- In another 2014 study involving 74,946 children from 18 countries, early antibiotics exposure was an independent risk factor for future weight gain in boys only.
- Even in chickens and older adults, males tended to gain more weight from antibiotics exposure compared to females.
While reasons are still uncertain, scientists of the 2014 multinational study speculated that: “Our finding of the BMI-promoting effects of antibiotics being confined to boys might be explained by sex-specific differences in intestinal adaptation to early-life antibiotic exposure or to how antibiotic drugs are metabolized.”
Antibiotics and Neurodevelopment
It was first shown in a 2017 study that early life antibiotics exposure may pose unfavorable neurodevelopment consequences. In New Zealand, researchers followed 871 children from birth. They learned that those with antibiotics use within the first year of life had an elevated risk of behavioral issues and symptoms of depression and ADHD at 3.5 and 11 years of age. These did not happen in children that never took or took antibiotics after age one.
The earlier the antibiotics intake, the worse the neurodevelopmental outcomes.
Later in a 2019 study, the same research team in New Zealand sought to see if their 2017 results could be replicated with another cohort of 473 children. After adjusting for confounders, children that took antibiotics within the first two years of life had lower IQ and verbal comprehension at 11 years old. The earlier the antibiotics intake, the worse the neurodevelopmental outcomes as well. Children under six months old that took antibiotics had more problems with cognition, impulsivity, working memory, ADHD, and anxiety at 11 years old than children unexposed or exposed to antibiotics at later ages.
Lastly, a nationwide Finland study in 2019 tracked 990,098 births over time. Antibiotics exposure, especially broad-spectrum ones, within the first two years of life lead to a 12–53% increased risk of “childhood development of sleep disorders, ADHD, conduct disorder, mood and anxiety disorders, and other behavioral and emotional disorders,” the academics concluded. “Given the high occurrence of early-life antibiotic exposure, and the substantial prevalence of childhood- and adolescent-onset psychopathology, modest associations among these phenomena are of public health relevance.”
Infant gut microbiota disturbance might underlie the detrimental effects of antibiotics on neurodevelopment.
While these studies did not analyze the gut microbiota, they posited that infant gut microbiota disturbance might underlie the detrimental effects of antibiotics on neurodevelopment. One research in 2018 has shown, for the first time, that infant gut microbiota profile was associated with future cognitive outcomes in children.
More robust evidence of causation can be derived from animal experimentations. Studies in 2016 and 2020 by two independent research groups presented strikingly similar results: Antibiotics disrupted the gut microbiota and memory of mice, which was followed by abnormalities in brain biochemistry related to brain-derived neurotrophic factor (BDNF) and socioemotional neuropeptide systems.
One in three antibiotic prescriptions (including in children) is not justified. Not only do they hasten superbugs pandemics but pose health consequences too. Antibiotics exposure in early life (1–2 years old) is an independent risk factor for future weight gain and poor neurodevelopmental outcomes, probably as a result of gut microbiota disruption. These effects are stronger with broad-spectrum antibiotics. And boys appeared to be more susceptible than girls to antibiotics-induced weight gain. So, it is best to avoid antibiotics when it is not mandatory. Lastly, an article in JAMA Pediatrics by Professor Megan Moreno, MD, is useful in helping a parent decide “When Your Child Does Not Need Antibiotics.”
This article was previously published in Microbial Instincts with minor changes.
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