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JAMA Netw Open. 2019 Jul 3;2(7):e197025. doi: 10.1001/jamanetworkopen.2019.7025.

Cognitive and Motor Outcomes of Children With Prenatal Opioid Exposure: A Systematic Review and Meta-analysis.

Yeoh SL1, Eastwood J1,2,3,4,5, Wright IM6,7, Morton R8, Melhuish E7,9,10, Ward M1,10, Oei JL1,11.

Author information

Medical student, University of New South Wales, Sydney, New South Wales, Australia.
Sydney Local Health District, Croydon, New South Wales, Australia.
Ingham Institute of Applied Medical Research, Liverpool, New South Wales, Australia.
Sydney Medical School, Faculty of Medicine and Health, Sydney University, Sydney, New South Wales, Australia.
Sydney Institute for Women, Children and Their Families, Camperdown, Sydney, New South Wales, Australia.
Early Start Research Institute, University of Wollongong, Wollongong, New South Wales, Australia.
University of Queensland Centre for Clinical Research, Herston, Queensland, Australia.
NHMRC Clinical Trials Centre, Faculty of Medicine and Health, University of Sydney, Camperdown, New South Wales, Australia.
Department of Education, University of Oxford, Oxford, United Kingdom.
Birkbeck, University of London, London, United Kingdom.
Department of Newborn Care, Royal Hospital for Women, Sydney, Australia.



Prenatal opioid exposure (POE) is one of the fastest-growing global health problems, but its association with long-term neurologic and physical development remains unknown.


To assess the association between POE and cognitive and motor development in children from age 6 months to 18 years.

Data Sources:

Key search terms included prenatal opioid exposure, neonatal abstinence syndrome, and neurocognitive development. Studies were searched using PubMed and Embase, with no publication date restriction, through August 20, 2018.

Study Selection:

Only published cohort studies comparing the results of age-appropriate standardized cognitive and/or motor tests between children with any POE (aged 0-18 years) with drug-free controls were included. Data that were not convertible to means and SDs were excluded.

Data Extraction and Synthesis:

This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Data were pooled using a random-effects model.

Main Outcomes and Measures:

Standardized mean difference of cognitive and motor tests between POE and nonexposed children.


Twenty-six peer-reviewed cohort studies were included. Cognitive outcomes were compared for a total of 1455 children with POE and 2982 nonexposed children across 3 age groups (mean [SE] age at cognitive testing was 13 [1.58] months for the toddler group; 4.5 [0.38] years for the preschool group; and 13 [2.36] years for the school-aged group). Motor outcomes were compared for 688 children with POE and 1500 nonexposed children up to age 6 years (mean [SD] age at motor testing, 2 [0.45] years). Standardized mean difference was lower in cognitive tests for children with POE at 0 to 2 years (d = -0.52; 95% CI, -0.74 to -0.31; P < .001) and 3 to 6 years (d = -0.38; 95% CI, -0.69 to -0.07; P < .001); the difference was not significant for those aged 7 to 18 years (d = -0.44; 95% CI, -1.16 to 0.28; P = .23). Motor scores were lower in children with POE (d = 0.49; 95% CI, 0.23-0.74; P < .001).

Conclusions and Relevance:

Prenatal opioid exposure appeared to be negatively associated with neurocognitive and physical development from age 6 months, and this association persisted until adolescence. The cause and association of this with POE or other factors (eg, withdrawal treatment) are uncertain but suggest that POE necessitates long-term support and intervention.

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