A Prospective Birth Cohort Study on Intra-Uterine Inflammation and Developmental Disabilities Including Autism Among Preterm- and Term- Born Children

Friday, May 13, 2016: 5:30 PM-7:00 PM
Hall A (Baltimore Convention Center)
M. Li1, M. D. Fallin2, R. Landa3, L. K. Hironaka4, L. Sices4, T. Stivers4, D. M. Caruso5, J. L. Kaczaniuk1, C. Pearson4, B. Zuckerman4 and X. Wang6, (1)Wendy Klag Center for Autism and Developmental Disabilities and Center on Early Life Origins of Disease, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, (2)Wendy Klag Center for Autism and Developmental Disabilities, JHBSPH, Baltimore, MD, (3)The Kennedy Krieger Institute, Baltimore, MD, (4)The Boston University Medical Center, Boston, MA, (5)Center on the Early Life Origins of Disease, Department of Population, Family, Reproductive Health, JHBSPH, Baltimore, MD, (6)Center on Early Life Origins of Disease, Department of Population, Family, Reproductive Health, JHBSPH, Baltimore, MD
Background: Maternal intra-uterine inflammation (IUI) is suspected to play a role in the development of autism spectrum disorder (ASD); limited epidemiologic evidence has linked indirect markers of IUI such as maternal infection and inflammatory cytokines with risk of ASD. However, the effect of IUI may not be specific to ASD, but general to any neurodevelopmental disorder. Studies on IUI and neurodevelopmental disorders mostly included children born extremely preterm; the effect of IUI among children born with longer gestation is unknown.

Objectives: Using a prospective birth cohort enriched by preterm birth, we sought to examine the effect of IUI, measured by clinical chorioamnionitis (CA), in combination with a range of gestational ages, in the development of ASD. We also included analyses on other developmental disorders (DD) in parallel to examine if the effects are specific to ASD or common across various DDs.

Methods: This study included 2359 children (87 ASD cases) with clinical CA data, a subset of the Boston Birth Cohort who completed at least one postnatal study visit at Boston Medical Center between 1998 and 2014. Cases of ASD, intellectual disabilities (ID), attention-deficit hyperactive disorder (ADHD) and other DD were identified based on ICD9 codes of physician diagnoses in electronic medical records. Gestational age was defined by an algorithm based on prenatal ultrasound before 20 weeks of gestation and date of last menstrual period. CA was identified if the mother and the child had at least two of the clinical signs and symptoms of CA. Using Cox proportional hazard regression model controlling for potential confounders, risk of each type of DD was compared among children with different gestational age and CA status. 

Results: Controlling for gestational age, CA was associated with increased risk of ASD (Hazard Ratio: 1.9 [95% confidence interval: 1.0-3.6]) and ID (Hazard Ratio: 3.7 [95% confidence interval 2.1-6.4]), but not ADHD or other DD in children. Jointly, early preterm birth (less than 34 weeks of gestation) without and with CA were both associated with greatly increased risks of ASD (Hazard Ratio: 4.6 and 6.3) and ID (Hazard Ratio: 3.2 and 8.5), and moderately increased risks of ADHD (Hazard Ratio: 2.1 and 2.7) and other DD (Hazard Ratio: 1.7 and 3.0). Term birth with CA and late preterm birth (34 to 36 weeks of gestation) without CA were also significantly associated with increased risk of ID (Hazard ratio: 4.7 and 1.9), while late preterm birth with CA was significantly associated with increased risk of other DD (Hazard ratio 2.1).

Conclusions: This is the first prospective study on the effect of IUI on DDs across gestational ages. We found IUI to have heterogeneous associations with DDs independent of preterm birth: it is a risk factor for ASD and ID, but not ADHD and other DD. We also found IUI to be a risk factor for ID among term children.

See more of: Epidemiology
See more of: Epidemiology