From the Pediatric Literature

Do Risk Factors During Infancy Predict Eosinophilic Esophagitis

Do Risk Factors During Infancy Predict Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus involving eosinophils and leading to esophageal damage, including fibrosis. EoE is increasing in prevalence, and although it is thought that food allergies may play a role in its pathogenesis, it is unknown if early infant exposures increase the risk of EoE. The authors of this study developed a case-control study using the United States military health system database (TRICARE Management Activity’s Military Health System) which contains medical data on all service members and their families.

All included patients with EoE were born between 2001 and 2014, and the diagnosis of EoE was determined by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Such patients with EoE required a complete birth and maternal record, had to be in the military health system since birth, and needed EoE to be diagnosed after 6 months of age. Patient controls were matched by sex and date of birth at a ratio of 2:1 to patients with EoE. Early infant risk factors were defined as occurring prior to 6 months of age and included prematurity, Cesarean section delivery, chorioamnionitis, prolonged rupture of membranes, eczema, seborrheic dermatitis, erythema toxicum neonatorum, milk protein allergy, hematochezia, asthma, gastroesophageal reflux, feeding problems, infant colic, oral candidiasis, and medication exposure (specifically outpatient antibiotics, histamine-2 receptor antagonists (H2RAs), and proton pump inhibitors (PPIs)). Univariate and multivariable conditional logistic regression modeling was performed to determine unadjusted and adjusted odds ratios.

In total, 1410 children with EoE were compared with 2820 patient controls. Median age of EoE diagnosis was 4.2 years (range 0.5 – 13.7 years), and 68.7% were boys. Adjusted conditional logistic regression demonstrated an increased risk of developing EoE if patients were exposed to antibiotics, H2RAs, or PPIs in the first 6 months of life. Other risk factors for EoE included prematurity, milk protein allergy, hematochezia, eczema, seborrheic dermatitis, erythema toxicum neonatorum, gastroesophageal reflux, and feeding problems.

This study demonstrates that potential exposuresin the first 6 months of life may increase the risk of EoE long-term. Exposures such as prematurity, antibiotics, and acid suppression medication use suggest that changes in the microbiome during early infancy may predispose to EoE. Judicious use of antibiotics and acid suppression medication in early infancy is encouraged.

Witmer C., Susi A., Min S., Nylund C. Early infant risk factors for pediatric eosinophilic esophagitis. Journal of Pediatric Gastroenterology and Nutrition 2018; 67: 610-615.

Infant Colic and Long-Term Outcomes

Infant colic is typically defined as excessive amounts of crying in the first 3 months of life. Many infants with colic are referred to pediatric gastroenterology as parents and providers often have concerns that there is a gastrointestinal cause for this condition although the potential association between gastrointestinal disorders and colic is debatable. It is also unclear as to the long-term outcome of infants with colic.

The authors of this study evaluated data from two prior studies. The Baby Biotics study was a randomized, controlled trial evaluating the effect of a probiotic (Lactobacillus reuteri DSM 17938) in infants with colic who were both breast feeding and formula fed. The Baby Business study was a randomized controlled trial that consisted of a parental education program to improve infant sleep. All infants were recruited prior to 3 months of age, and follow up data existed between 2 to 3 years of age for the Baby Biotics trial and 2 years of age for the Baby Business study. Long-term outcome data was obtained on these children using the validated Child Behavior Checklist.

Long-term data was available for 627 infants (124 from the Baby Biotics study and 503 from the Baby Business study). There were 99 infants in the Baby Biotics study who were defined as a “true colic cohort” (colic symptoms at recruitment but no symptoms at 6 months of age). Additionally, there were 182 infants in the Baby Business study who were defined as a “no colic cohort” (no colic at recruitment and had no colic throughout the study). The “true colic cohort” was thus compared to the “no colic cohort”. Demographic data on these two groups were similar except that patient age at follow up was significantly greater in the true colic group (34 months versus 25 months, P<0.01) and fewer mothers had higher education backgrounds in the true colic group (61.5% vs. 76.4%, P<0.01). Long-term follow up demonstrated that there was no difference between groups in regards to internalizing behavioral problems as well as parental perceptions of crying, feeding, sleeping, and family function.

This study appears to demonstrate that infant colic does not lead to long-term behavioral difficulties and suggests that probiotic use during infancy has no benefit in later childhood behavior.

Bell G., Hiscock H., Tobin S., Cook F., Sung V. Behavioral outcomes of infant colic in toddlerhood: a longitudinal study. Journal of Pediatrics 2018; 201: 154-159.

John Pohl, M.D., Book Editor, is on the Editorial Board of Practical Gastroenterology