IMPORTANCE Allergic diseases are prevalent in childhood. Early exposure to medications that can alter the microbiome, including acid-suppressive medications and antibiotics, may influence the likelihood of allergy. OBJECTIVE To determine whether there is an association between the use of acid-suppressive medications or antibiotics in the first 6 months of infancy and development of allergic diseases in early childhood. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study was conducted in 792 130 children who were Department of Defense TRICARE beneficiaries with a birth medical record in the Military Health System database between October 1, 2001, and September 30, 2013, with continued enrollment from within 35 days of birth until at least age 1 year. Children who had an initial birth stay of greater than 7 days or were diagnosed with any of the outcome allergic conditions within the first 6 months of life were excluded from the study. Data analysis was performed from April 15, 2015, to January 4, 2018. EXPOSURES Exposures were defined as having any dispensed prescription for a histamine-2 receptor antagonist (H 2 RA), proton pump inhibitor (PPI), or antibiotic. MAIN OUTCOMES AND MEASURES The main outcome was allergic disease, defined as the presence of food allergy, anaphylaxis, asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, urticaria, contact dermatitis, medication allergy, or other allergy. RESULTS Of 792 130 children (395 215 [49.9%] girls) included for analysis, 60 209 (7.6%) were prescribed an H 2 RA, 13 687 (1.7%) were prescribed a PPI, and 131 708 (16.6%) were prescribed an antibiotic during the first 6 months of life. Data for each child were available for a median of 4.6 years. Adjusted hazard ratios (aHRs) in children prescribed H 2 RAs and PPIs, respectively, were 2.18 (95% CI, 2.04-2.33) and 2.59 (95% CI, 2.25-3.00) for food allergy, 1.70

ASD is associated with a range of prenatal, perinatal, and neonatal factors, with the highest magnitude associations with maternal medication use and neonatal seizure.

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ObjectiveGut microbiota alterations are associated with obesity. Early exposure to medications, including acid suppressants and antibiotics, can alter gut biota and may increase the likelihood of developing obesity. We investigated the association of antibiotic, histamine-2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) prescriptions during early childhood with a diagnosis of obesity.DesignWe performed a cohort study of US Department of Defense TRICARE beneficiaries born from October 2006 to September 2013. Exposures were defined as having any dispensed prescription for antibiotic, H2RA or PPI medications in the first 2 years of life. A single event analysis of obesity was performed using Cox proportional hazards regression.Results333 353 children met inclusion criteria, with 241 502 (72.4%) children prescribed an antibiotic, 39 488 (11.8%) an H2RA and 11 089 (3.3%) a PPI. Antibiotic prescriptions were associated with obesity (HR 1.26; 95% CI 1.23 to 1.28). This association persisted regardless of antibiotic class and strengthened with each additional class of antibiotic prescribed. H2RA and PPI prescriptions were also associated with obesity, with a stronger association for each 30-day supply prescribed. The HR increased commensurately with exposure to each additional medication group prescribed.ConclusionsAntibiotics, acid suppressants and the combination of multiple medications in the first 2 years of life are associated with a diagnosis of childhood obesity. Microbiota-altering medications administered in early childhood may influence weight gain.

BACKGROUND: Acid suppression therapy (AST), including proton pump inhibitors (PPIs) and histamine H 2 -receptor antagonists (H 2 RAs), is frequently prescribed to treat symptomatic gastroesophageal reflux in otherwise healthy infants. PPI use has been associated with increased fracture risk in older adults; 2 preliminary studies in children have conflicting results. METHODS:A retrospective cohort of children born 2001 to 2013 who were followed for $2 years was formed. Those with osteogenesis imperfecta, cholestasis, or child maltreatment were excluded. Prescription data were used to identify AST prescription before age 1 year. International Classification of Diseases, Ninth Revision, Clinical Modification codes identified fractures after age 1 year. A Cox proportional hazard analysis assessed fracture hazard and was adjusted for sex, prematurity, low birth weight, previous fracture, anti-epileptics, and overweight or obesity.RESULTS: Of 851 631 included children, 97 286 (11%) were prescribed AST in the first year of life; 7998 (0.9%) children were prescribed PPI, 71 578 (8%) were prescribed H 2 RA, and 17 710 (2%) were prescribed both a PPI and H 2 RA. Infants prescribed AST had an earlier median first fracture age (3.9 vs 4.5 years). After adjustment, increased fracture hazard was associated with PPI use (21%) and PPI and H 2 RA use (30%), but not H 2 RA use alone. Longer duration of AST treatment and earlier age of first AST use was associated with increased fracture hazard.CONCLUSIONS: Infant PPI use alone and together with H 2 RAs is associated with an increased childhood fracture hazard, which appears amplified by days of use and earlier initiation of ASTs. Use of AST in infants should be weighed carefully against possible fracture.WHAT'S KNOWN ON THIS SUBJECT: Proton pump inhibitors (PPIs) are used frequently in the treatment of symptomatic gastroesophageal reflux. Studies in adults have revealed an association between PPIs and increased fracture risk, but this has not been well studied in infants and children. WHAT THIS STUDY ADDS:This study included young children without known serious medical conditions prescribed acid suppression therapy during the first year of life, likely for symptomatic treatment of reflux. A positive association was found between PPI use and childhood fracture incidence.

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Autism spectrum disorders (ASD) and inflammatory bowel disease (IBD) both have multifactorial pathogenesis with an increasing number of studies demonstrating gut-brain associations. We aim to examine the association between ASD and IBD using strict classification criteria for IBD. We conducted a retrospective case-cohort study using records from the Military Health System database with IBD defined as having one encounter with an ICD-9-CM diagnostic code for IBD and at least one outpatient prescription dispensed for a medication to treat IBD. Children with ASD were more likely to meet criteria for Crohn's disease (CD) and Ulcerative colitis (UC) compared to controls. This higher prevalence of CD and UC in children with ASD compared to controls confirms the association of ASD with IBD.

OBJECTIVES: There has long been an association between congenital heart disease (CHD) and general neurodevelopmental delays. However, the association between CHD and autism spectrum disorders (AuSDs) is less well understood. Using administrative data, we sought to determine the association between CHD and AuSD and identify specific CHD lesions with higher odds of developing AuSD. METHODS: We performed a 1:3 case-control study of children enrolled in the US Military Health System from 2001 to 2013. Children with International Classification of Disease, Ninth Revision, Clinical Modification codes for AuSD were identified as cases and matched with controls on the basis of date of birth, sex, and enrollment time frame. Each child's records were reviewed for CHD lesions and associated procedures. Conditional logistic regression determined odds ratios (ORs) and 95% confidence intervals (CIs) for comparative associations. RESULTS: There were 8760 cases with AuSD and 26 280 controls included in the study. After adjustment for genetic syndrome, maternal age, gestational diabetes, short gestation, newborn epilepsy, birth asphyxia, and low birth weight, there were increased odds of AuSD in patients with CHD (OR 1.32; 95% CI 1.10-1.59). Specific lesions with significant OR included atrial septal defects (n = 82; OR 1.72; 95% CI 1.07-2.74) and ventricular septal defects (n = 193; OR 1.65; 95% CI 1.21-2.25). CONCLUSIONS: Children with CHD have increased odds of developing AuSD. Specific lesions associated with increased risk include atrial septal defects and ventricular septal defects. These findings will be useful for counseling parents of children with CHD.