Prenatal exposure to beta-2 adrenergic receptor agonists in relation to autism/autism spectrum disorder: a case-control study 公开

Huh, Konny (2012)

Permanent URL: https://etd.library.emory.edu/concern/etds/vd66w031m?locale=zh
Published

Abstract

Background
Beta-2 adrenergic receptor (B2AR) agonists are a class of drugs that are administered to
mothers during pregnancy to treat various indications including preterm labor, asthma,
allergy and respiratory infection. B2AR agonists are able to cross the placenta and blood-
brain barrier of the fetus. Based on studies linking structural brain abnormalities to
autism/autism spectrum disorder (AU/ASD), the in utero period has been hypothesized as
an etiologically relevant risk period, and animal studies have shown an association between
exposure to B2AR agonist drugs in the prenatal period and subsequent neurodevelopmental
damage.

Methods
The CHildhood Autism Risks from Genetics and the Environment (CHARGE) Study is a
case-control study that enrolled 879 children and their caretakers from families with an index
child with AU/ASD, with a developmental delay but not AU/ASD, or from the general
population. AU/ASD diagnoses for the children were evaluated using the Autism Diagnostic
Observation Schedules (ADOS) and the Autism Diagnostic Interview-revised (ADI-R).
Maternal B2AR agonist drug use was based on a structured telephone interview with the
mother. All analyses used conditional logistic regression controlling for maternal birth place
and the matching factors: regional catchment center, child's sex and child's age at
enrollment. Sampling fractions were used to weight the analyses to represent the general
California population.

Results
Prenatal exposure to B2AR agonists is associated with a decreased odds of having a child
diagnosed with AU/ASD when taken: (1) at any time during the pregnancy period (adjusted
Odds Ratio (ORadj) 0.53; 95% Confidence Interval (CI) 0.46 - 0.61) or (2) in the third trimester
(ORadj 0.49; 95% CI 0.40 - 0.61).


Conclusions
Although prior studies have reported B2AR agonist use during pregnancy increases the risk
of AU/ASD, the results of this large study did not confirm these earlier findings.

Table of Contents

Table of Contents

Page

Chapter One ................................................................................................................... 1

1. Introduction and Background .......................................................................................... 1

Autism/Autism Spectrum Disorder (AU/ASD) .......................................................................... 1

Descriptive Epidemiology.....................................................................................................1

Possible Risk Factors..........................................................................................................1

Etiologically Relevant Window of Time ................................................................................. 3

2. Maternal Medications ................................................................................................... 4

B2AR agonists..................................................................................................................4

Biologic Plausibility.............................................................................................................5

Studies of Exposure to Terbutaline and AU/ASD .................................................................... 5

Studies with Other Developmental Disorder Outcomes ............................................................ 7


3. Contribution .............................................................................................................. 10

Chapter Two ................................................................................................................. 11

1. Methods ................................................................................................................... 13

Study Design..................................................................................................................13


Recruitment and Data Collection........................................................................................ 13

Data Analysis..................................................................................................................15


2. Results...................................................................................................................... 15

Population Characteristics.................................................................................................15


3. Discussion ................................................................................................................ 17

References ................................................................................................................... 21

Table 1 ........................................................................................................................ 26

Table 2 ........................................................................................................................ 28

Appendix A. IRB Letter of Approval ................................ ................................................... 29

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