This study included 14,572 children (7026 girls and 7546 boys), of whom 70% (10,220) received at least 1 antibiotic prescription during the first 2 years of life.
Early antibiotic exposure was associated with an increased risk of childhood-onset asthma, allergic rhinitis, atopic dermatitis, celiac disease, overweight, obesity, and attention deficit hyperactivity disorder: hazard ratios ranging from 1.20 to 2.89.
Children exposed to antibiotics had a higher probability of having combinations of conditions, particularly when given multiple prescriptions.
Significant associations exist between early life antibiotic exposure and several distinct health conditions with childhood onset.
The development of drug-resistant bacteria exemplifies unintended consequences of antibiotic overuse.
The increasing prevalence of health conditions with childhood onset, including asthma, food allergies, obesity, and attention deficit/hyperactivity disorder (ADHD), has triggered concern about antibiotic exposures during key developmental periods because of their impact on the microbiome.
The bacterial communities colonizing the human body play essential roles in the development of host immunity, metabolism, and behavior.
The transfer of bacterial communities begins at birth and is occurs through social interaction, diet, and environmental factors.
Cesarean section delivery, formula feeding, and pre- and postnatal antibiotic exposure negatively affect the microbiome and may compromise childhood health.
Disruption of early life microbiome is implicated in the development of multiple disorders.
The present study included 14,572 children (7026 girls and 7546 boys) with a median follow-up of 8.8 years.
Between birth and 2 years of age, 10,220 children (70%) were prescribed at least 1 antibiotic, with most receiving multiple antibiotics
Penicillins, cephalosporins, and macrolides were most often prescribed.
Nitrofurantoin, quinolones, and other antibiotics accounted for less than 1% of prescriptions.
Most prescriptions were for oral antibiotics (99%).
Both girls and boys prescribed at least 1 course of antibiotics had a higher cumulative incidence of asthma, allergic rhinitis, overweight, and ADHD.
Girls exposed to antibiotics are uniquely more susceptible to atopic dermatitis and celiac disease, whereas boys were uniquely more susceptible to obesity.
Among children who received 1 or 2 prescriptions, only girls were at a significantly higher risk of developing asthma and celiac disease than those unexposed.
Receiving 3 to 4 prescriptions was associated with a higher incidence of asthma, atopic dermatitis, and overweight in both sexes; ADHD and celiac disease in girls; and obesity in boys.
Both girls and boys who received 5 or more prescriptions had a significantly higher risk of developing asthma, allergic rhinitis, overweight, obesity, and ADHD, and girls also were at a higher risk of celiac disease.
Rxposure to cephalosporins was associated with an increased risk of the highest number of conditions and, uniquely, autism and food allergies.
Penicillins are associated with an increased risk of asthma and overweight in both sexes, celiac disease and ADHD in girls, and obesity in boys, whereas they were associated with a reduced risk of autism in girls.
Sulfonamides only increased the risk of overweight in boys.
Macrolides were associated with an increased risk of asthma and overweight in both sexes and allergic rhinitis and obesity in boys
Macrolides are associated with a reduced risk of atopic dermatitis in girls and learning disability in boys.
Antibiotics prescribed before 6 months of age were significantly associated with the risk of atopic dermatitis, overweight, and ADHD in both sexes; asthma, allergic rhinitis, and obesity in girls; and food allergy in boys.
Antibiotics prescribed between 6 and 12 months were most strongly associated with the incidence of asthma, allergic rhinitis, overweight, and obesity in both sexes.
Antibiotics prescribed from 12 to 24 months were associated with a significantly increased risk of asthma and overweight in both sexes, ADHD in girls, and allergic rhinitis in boys.
Male sex was associated with a significantly increased risk of asthma, allergic rhinitis, food allergy, overweight, obesity, ADHD, autism, and learning disability
Delivery by cesarean section was associated with an increased risk of allergic rhinitis, atopic dermatitis, overweight, obesity, and ADHD.
Higher birth weight was associated with an increased risk of overweight, obesity, and celiac disease, but a reduced risk of asthma and learning disability.
Maternal exposure to antibiotics is associated with an increased risk of asthma, allergic rhinitis, overweight, obesity, ADHD, and learning disability in their children.
Maternal smoking was associated with an increased risk of asthma, overweight, obesity, ADHD, and learning disability in their children.
Older maternal age was associated with an increased risk of allergic rhinitis, food allergy, and autism, but a reduced risk of asthma, overweight, obesity, and ADHD.
Maternal post high school education appeared to mitigate the risk of childhood asthma, overweight, obesity, ADHD, and learning disability, but was associated with an increased risk of food allergy in children.
After adjustment for male sex, ethnicity, delivery by cesarean section, and maternal age, education, smoking, and antibiotic exposure during pregnancy, antibiotic-associated risks remained significant for childhood onset of asthma, allergic rhinitis, atopic dermatitis, celiac disease, overweight, obesity, ADHD, and learning disability.
Children exposed to antibiotics during the first 2 years of life are more likely to develop multiple health conditions.
Obesity, asthma, and allergic rhinitis was the most common disease triad in both exposed and unexposed children, whereas combinations of asthma, obesity, and either atopic dermatitis or ADHD were more frequently observed in children exposed to antibiotics.
The prevalent use of antibiotics in infants and reveals associations between exposure to antibiotics and distinct immunological, metabolic, and neurobehavioral health processes during childhood.
The microbiome’s interactions contribute to the proper development of the immune system.
Because antibiotics markedly affect microbial composition, an even transient perturbation during critical developmental periods may compromise both immune tolerance and inflammatory responses.
With immature intestinal microbiota and low abundance of specific bacterial taxa may have increased asthma susceptibility.
Children exposed in the first 2 years of life to the most commonly prescribed antibiotic classes, penicillins, cephalosporins, and macrolides, are more likely to develop asthma and allergic rhinitis.
The risk of atopic dermatitis is increased, particularly in children receiving antibiotics early, in multiple doses, or, specifically, cephalosporins.
Antibiotic exposure is associated with food allergy risk, in both sexes with cephalosporins, and with exposure to any antibiotic before 6 months.
Associations of early life exposure to antibiotics with food allergies, with effects specific to cow’s milk and eggs have been identified.
Overall, findings suggest associations between early antibiotic exposure and later development of asthma, allergic diseases, and autoimmune conditions.
It is postulated the antibiotics have a causal role in the pathogenesis of childhood immune disorders by disrupting the microbiome during critical developmental periods.
The microbiome is known to shape host immunity, affect body composition and systemic metabolism.
Multiple antibiotic prescriptions during infancy significantly increased the risk of overweight and obesity.
The microbiome may affect neural development, and it is suggested
compromising the establishment of microbial communities with antibiotics may affect the risk of neurobehavioral disorders.
There is a significant association between antibiotic prescriptions in the first 2 years of life and ADHD in both sexes.
There is a significantly increased risk of autism and learning disabilities after exposure to cephalosporins.
A Danish study found an association between any treated infection and several childhood and adolescent neurobehavioral conditions.
Antibiotic exposure in the first 2 years of life is associated with an increased risk of several immunological, metabolic, and neurobehavioral childhood-onset health conditions.
The early life microbiome composition is a critical health determinant and that perturbations during key developmental periods can have long-term consequences.