A systematic study on prenatal opioid exposure: a review of neurodevelopmental consequences Restricted; Files Only

Abstract

Illegal uses of opiates and synthetic opioids are of concern among pregnant women,

prompting concerns for not only the mothers but also the infant population prenatally exposed

to opioid. This systematic review was conducted to explore the identity of opioid as a teratogen.

Conducted according to guidelines of PRISMA, this review identified studies from the

Web of Science database based on a preliminary search strategy. Quality assessment was

conducted according to GRADE system. After applying exclusion criteria to the identified

collection of studies, eighty-six studies were included in this review. Results were grouped into

one neuroimaging domain and five neurobehavioral function domains: executive, cognitive,

motor, neurosensory, and socioemotional. The meta-analysis of the pooled results across the

studies in each domain all yielded statistically significant differences between the exposed and

unexposed groups, indicating neurodevelopmental impairments in children prenatally exposed

to opioid. After statistical adjustments to pooled estimates following Egger's test results, effect

size (Hedge's g) was largest in socioemotional domain (-1.14, -1.61 to -0.66, 95% CI) and smallest

in cognitive domain (-0.44, -0.70 to -0.18, 95% CI). Neuroimaging studies on prenatal exposure

to opioid were limited and varied in the techniques and topographical focus in their approaches,

resulting in a heterogenous body of literature.

The observed neurodevelopmental impairments in children prenatally exposed to opioid

can be due to factors that are widespread among this population of mothers using substances

during pregnancy. For that reason, opioid uses during a pregnancy can still serve as a biomarker

that flags the need for future interventions in the development of that child. The public health

implications of this systematic review can inform the need for future policies in prioritizing the

children population at-risk for impaired neurodevelopmental growth indicated by mothers using

opioid during pregnancy.

Table of Contents

Introduction.........................................................................................................................................1

Methods..............................................................................................................................................3

Search Strategy.......................................................................................................................3

Figure 1: Search terms...............................................................................................3

Exclusion Criteria....................................................................................................................4

Study Quality Assessment......................................................................................................4

Data Extraction and Synthesis................................................................................................5

Results.................................................................................................................................................6

Figure 2: PRISMA flow diagram.............................................................................................6

Dichotomous Outcomes.........................................................................................................7

Table 1: Risk differences..............................................................................................8

Study Quality...........................................................................................................................8

Figure 3: Histograms of study quality distribution......................................................9

Effect Sizes...............................................................................................................................9

Figure 4: Hedge's g forest plots.................................................................................10

Positive Result Bias and Heterogeneity.................................................................................14

Figure 5: Funnel plots and Egger's values.................................................................14

Neuroimaging.......................................................................................................................16

Table 2: Neuroimaging studies..................................................................................16

Discussion..........................................................................................................................................18

Limitation.............................................................................................................................19

Citation..............................................................................................................................................21

Index.................................................................................................................................................40

Supplementary 1: Table of GRADE system............................................................................40

Supplementary 2: Table of assessment types.......................................................................41

Supplementary 3: Table of included studies.........................................................................42

Supplementary 4: Figure of relative risk forest plots.............................................................44

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Health Sciences, Toxicology Health Sciences, Public Health Health Sciences, Human Development
Keyword	prenatal opioid maternal
Committee Chair / Thesis Advisor	Kable, Julie, Emory University
Committee Members	Dilks, Daniel, Emory University Jacob, Nitya, Emory University

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