The JAMA Pediatrics report found children who had had four or more courses by the age of two were at a 10% higher risk of being obese.
However, scientists warn this does not show antibiotics cause obesity directly and recommend children continue using them.
Many more studies are needed to explain the reasons behind the link, they say.
Researchers from the University of Pennsylvania and Bloomberg School of Public Health reviewed the health records of more than 64,500 American children between 2001 and 2013.
The children were followed up until they reached five years of age.
Almost 70% of them had been prescribed two courses of antibiotics by the time they were 24 months old.
But those who had four or more courses in this time were at a 10% higher risk of being obese at the age of five than children who had been given fewer drugs.
And the type of antibiotics they were prescribed appeared to make a difference too – those given drugs targeted at a particular bug were less likely to put on weight.
But those given a broad-spectrum antibiotic – that can kill several types of bacteria indiscriminately – were more likely to have a higher body mass.
Prof. Charles Bailey at the University of Pennsylvania, said: “We think after antibiotics some of the normal bacteria in our gut that are more efficient at nudging our weight in the right direction may be killed off and bacteria that nudge the metabolism in the wrong direction may be more active.”
And researchers say the study highlights that over prescribing inappropriate antibiotics could have a negative impact on child growth.
Meanwhile in a separate study, scientists reporting in the journal of the American Society for Microbiology found that a species of gut bacteria – called Clostridium ramosum – could promote weight gain in mice.
Mice with these bacteria present in their guts became obese when fed a high-fat diet, while those that did not have the bacteria put on less weight despite being given high-calorie meals.
The scientists, from the German Institute of Human Nutrition, in Nuthetal, are now trying to understand how the bacteria interact with digestion.
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