Apryl Susi

Association Between Use of Acid-Suppressive Medications and Antibiotics During Infancy and Allergic Diseases in Early Childhood

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 (H2RA), 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 H2RA, 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 H2RAs 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 (95% CI, 1.60-1.80) and 1.84 (95% CI, 1.56-2.17) for medication allergy, 1.51 (95% CI, 1.38-1.66) and 1.45 (95% CI, 1.22-1.73) for anaphylaxis, 1.50 (95% CI, 1.46-1.54) and 1.44 (95% CI, 1.36-1.52) for allergic rhinitis, and 1.25 (95% CI, 1.21-1.29) and 1.41 (95% CI, 1.31-1.52) for asthma. The aHRs after antibiotic prescription in the first 6 months of life were 2.09 (95% CI, 2.05-2.13) for asthma, 1.75 (95% CI, 1.72-1.78) for allergic rhinitis, 1.51 (95% CI, 1.38-1.66) for anaphylaxis, and 1.42 (95% CI, 1.34-1.50) for allergic conjunctivitis. Conclusions and Relevance This study found associations between the use of acid-suppressive medications and antibiotics during the first 6 months of infancy and subsequent development of allergic disease. Acid-suppressive medications and antibiotics should be used during infancy only in situations of clear clinical benefit.

Autism Spectrum Disorders and Metabolic Complications of Obesity

OBJECTIVES To assess for an increased risk of obesity, type 2 diabetes mellitus, hypertension, hyperlipidemia, and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis in children with autism spectrum disorders (ASD). Additionally, to determine the rates of prescribed treatment for obesity-related metabolic disorders and to determine whether treatment with psychotropic medications is associated with the development of obesity for children with ASD. STUDY DESIGN A retrospective 1:5 case-control study was performed by use of the Military Health System database from October 2000 to September 2013. For children with ASD and matched controls, International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes for obesity, type 2 diabetes mellitus, hypertension, hyperlipidemia, nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, and prescriptions were obtained. Conditional logistic regression determined ORs and 95% CIs. RESULTS A total of 48 762 individuals with ASD and 243 810 matched controls were identified. Children with ASD had significantly greater odds of having obesity (OR 1.85; 95% CI 1.78-1.92), having obesity-related disorders, and being prescribed a medication when they had these diseases. In children with ASD, mood stabilizers, antipsychotics, antiepileptic drugs, and selective serotonin reuptake inhibitors were associated with obesity. CONCLUSIONS Children with ASD have an increased risk of obesity and obesity-related metabolic disorders. They are more likely to be prescribed medications to treat these complications, suggesting they may have more severe disease. There is a significant association between the use of some psychotropic categories and a diagnosis of obesity, suggesting that obesity in children with ASD may be partially iatrogenic.

Prevalence of Diagnosed Sleep Disorders and Related Diagnostic and Surgical Procedures in Children with Autism Spectrum Disorders.

Objective: Sleep disorders are common and important comorbid conditions in children with autism spectrum disorder (ASD) and can contribute to cognitive and behavioral problems. Sleep-disordered breathing (SDB) is a diagnosable and treatable cause of behavioral problems in children. We aimed to quantify the relative risk for children with ASD versus controls of being diagnosed with sleep disorders including SDB and undergoing related diagnostic and surgical procedures. Method: This retrospective case-cohort study included 48,762 children with ASD aged 2 to 18 years enrolled in the military health system (MHS) from 2000 to 2013. Children with ASD were matched 1:5 by birthdate, sex, and enrollment time to children without an ASD diagnosis. The MHS database was queried for International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for sleep disorders or ICD-9-CM and Current Procedural Terminology codes for diagnostic and surgical procedures. Relative risks (RR) and 95% confidence intervals (CI) were determined with binary Poisson regression conditional on the match and adjusting for confounders. Results: Children with ASD were at higher risk of receiving any sleep disorder diagnosis (RR: 1.97 [95% CI, 1.91–2.02]) including SDB (RR: 1.96 [95% CI, 1.88–2.05]). Children with ASD also were at increased risk of undergoing polysomnography (RR: 3.74 [95% CI, 3.56–3.93]) and sleep disorder-related surgery (RR: 1.50 [95% CI, 1.46–1.54]). Conclusion: Children with ASD are more likely to be given a sleep disorder diagnosis including SDB and are more likely to undergo related diagnostic and surgical procedures compared with controls without ASD.

Otitis Media and Related Complications among Children with Autism Spectrum Disorders.

Acute otitis media (AOM) symptoms can be masked by communication deficits, common to children with autism spectrum disorders (ASD). We sought to evaluate the association between ASD and otitis media. Using ICD-9-CM diagnostic codes, we performed a retrospective case-cohort study comparing AOM, and otitis-related diagnoses among children with and without ASD. Children with ASD had a significantly increased rate of AOM, otitis media with effusion, otorrhea, and PE tube placement. Children with ASD were more than twice as likely to develop mastoiditis, and to undergo mastoidectomy and tympanoplasty. Children with ASD are more likely to have middle ear infections and otitis-related complications, highlighting the importance of routine middle ear examinations and close attention to hearing impairment in this population.

Feeding Disorders in Children With Autism Spectrum Disorders Are Associated With Eosinophilic Esophagitis

Objectives: Eosinophilic esophagitis (EoE) can present as food selectivity or feeding disorders in children. Children with autism spectrum disorders (ASDs) commonly demonstrate behavioral food selectivity in type and texture, which often leads to the diagnosis of feeding disorder. We sought to evaluate the association of ASD with EoE. Methods: A retrospective matched case-cohort study was performed using the Military Health System database from October 2008 to September 2013. We performed a 1:5 case-control match by age, sex, and enrollment timeframe. Feeding disorders, EoE, and atopic disorders were defined using diagnostic and procedure codes. Results: There were 45,286 children with ASD and 226,430 matched controls. EoE was more common in children with ASD (0.4%) compared with controls (0.1%). Feeding disorders were associated with EoE in both children with ASD and controls. Feeding disorders also had a higher odds ratio for EoE compared with other atopic conditions, among both children with ASD (7.17, 95% confidence interval [CI] 4.87–10.5) and controls (11.5, 95% CI 7.57–17.5). Compared with controls with a feeding disorder, children with ASD and a feeding disorder had no difference in the rate of diagnosed EoE (0.85, 0.95% CI 0.39–1.88). Conclusions: Children with ASD are more likely to be diagnosed with EoE compared with controls; however, among children with feeding disorders, there is no difference in the odds of EoE. A diagnosis of feeding disorder was strongly associated with EoE. Feeding disorders in children with ASD should not be assumed to be solely behavioral and an esophagogastroduodenoscopy should be performed to evaluate for EoE.

Prenatal, perinatal, and neonatal risk factors of autism spectrum disorder

BackgroundWe explored the association of 29 previously reported neonatal, perinatal, and prenatal conditions, and exposures with later diagnosis of autism spectrum disorder (ASD) in a large sample of children followed over multiple years.MethodsA retrospective case–cohort study was formed using the Military Health System database. Cases were identified by International Classification of Diseases, Ninth Revision codes for ASD between 2000 and 2013, and were matched 3:1 with controls on sex, date of birth, and enrollment time frame. Exposures included 29 conditions previously associated with ASD; 17 prenatal conditions and their pharmaceutical treatment, 5 perinatal conditions, and 6 neonatal conditions.ResultsA total of 8,760 children diagnosed with ASD between the ages of 2 and 18 years were matched with 26,280 controls. ASD is associated with maternal mental illness, epilepsy, obesity, hypertension, diabetes, polycystic ovary syndrome, infection, asthma, assisted fertility, hyperemesis, younger maternal age, labor complications, low birth weight, infant infection, epilepsy, birth asphyxia, and newborn complications. The greatest increased risk was associated with infant epilepsy (odds ratio (OR) 7.57 (5.68–10.07)), maternal mental health (OR 1.80 (1.65–1.96)), and epilepsy (OR 1.60 (1.02–2.50)) medications.ConclusionASD is associated with a range of prenatal, perinatal, and neonatal factors, with the highest magnitude associations with maternal medication use and neonatal seizure.

Suspected or known neonatal sepsis and neurodevelopmental delay by 5 years

ObjectiveEvaluate impact of known and suspected neonatal sepsis in the term and preterm infant on neurodevelopmental delay by 5 years.Study DesignIncluded infants were born in 2009–2010 and followed for 5 years. Diagnostic codes and at least 5 days of antibiotic use identified suspected sepsis. Laboratory results confirmed known sepsis. Diagnostic codes stratified developmental delay by sub-type. Logistic regression analysis determined odds of developmental delay for sepsis and suspected sepsis.ResultsOf 65,938 included infants, 190 had sepsis and 3449 had suspected sepsis. After adjustment for known developmental risk factors, sepsis and suspected sepsis were associated with increased risk for any developmental delay, (1.48 (1.05–2.09) and 1.09 (1.01–1.18)), respectively, and multiple developmental delay sub-types.ConclusionNeonatal sepsis and suspected sepsis are associated with neurodevelopmental delay by 5 years of age.

Association of Autism Spectrum Disorders and Inflammatory Bowel Disease

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.