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Prenatal Infection and Child Neurodevelopment

Wed, April 7, 11:35am to 1:05pm EDT (11:35am to 1:05pm EDT), Virtual

Abstract

Introduction
The hypothesis that early – including prenatal – experiences and exposures may have lasting influences on child and adult health has a long history. One line of research considers prenatal maternal immune alterations and inflammation as an organizing framework for the study of early environmental influences and child health outcomes. We have developed a program of research on this topic because a) pregnancy is an immune-challenged state; b) many targeted prenatal exposures associated with child health (stress, environmental chemicals, obesity) imply alterations in prenatal immunity; and c) there is considerable animal and some human evidence linking prenatal inflammation to significant neurodevelopmental disturbance in the offspring. We draw from data from two studies to advance research in this area.

Hypotheses
Prenatal inflammation, derived from reports of infection (study 1) or measured proinflammatory cytokines (study 2), will be associated with poorer neurodevelopment in children, after adjusting for covariates.

Study Population and Methods
Study 1: Data are based on the Avon Longitudinal Study of Parents and Children (ALSPAC), an ongoing population-based study designed to investigate the effects of a wide range of influences on the health and development of children. We included those children who were born less than 2,500g or before 37 weeks gestation (n=7,042). Prenatal infection covering the period from late first through second trimester was based on maternal report. We subsequently classified these conditions, on an a priori basis, according to the likelihood of active systemic infection; we calculated a sum of reported infections and a dichotomous index of presence/absence of any infection. Child neurodevelopment assessed at age 8 years was based on standard in-person IQ testing using the Wechsler Intelligence Scale for Children and the Social and Communication Disorders Checklist (SCDC) which assesses social and communication problems associated with autism.

Study 2: Data for study 2 are based on a complementary cohort study of 328 women recruited in Rochester NY who are part of the Environmental influences on Child Health Outcomes (ECHO) program. Psychological, socio-demographic, and health data as well as a blood sample were collected at each trimester. Maternal blood samples were analyzed for a panel of chemokines and cytokines. In-person assessment of child neurodevelopment was based on cognitive assessment (Bayley Scales of Infant Development) and executive function measures from 6 months through 2 years. The sampling strategy over-sampled low-income, high-stress women and included approximately 40% minority participation.

Results
Findings from study 1, provided in Figure 1, show a dose-response pattern between prenatal infection and severity of social and communication disorder symptoms; additional analyses (not shown) also indicate that prenatal infection predicted symptoms of inattention/hyperactivity. These effects are independent of covariates, including general IQ.
Findings from study 2, based on a preliminary sample of 50 so far analyzed, indicate that prenatal inflammation predicted lower Bayley scores at 12 month (for IL-6, r= -.32*; for IL-1b, r=-.19+). Analyses provide some of the first evidence for early-onset effects of prenatal immune activation on child neurodevelopment.

Authors