Abstract
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. 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. 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. 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. 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). 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.
Highlights
Prenatal opioid exposure (POE) is a fast-growing health problem, with at least 1 in 5 pregnant women in high-income countries known to have used some form of opioid during pregnancy.[1]
Motor outcomes were compared for 688 children with POE and 1500 nonexposed children up to age 6 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)
Summary
Prenatal opioid exposure (POE) is a fast-growing health problem, with at least 1 in 5 pregnant women in high-income countries known to have used some form of opioid during pregnancy.[1] This incidence has been reported to be associated with increases in the risk of perinatal problems, including neonatal abstinence syndrome (NAS), prematurity, and low birth weight.[2] Neonatal abstinence syndrome affects 75% to 90% of all infants with POE1 and is considered a major global public health issue. The number of babies affected by NAS has increased by more than 400% in the past 2 decades,[3] resulting in consumption of health care and social resources. Opioid-using mothers often have poorer educational attainment,[10] an increased risk of psychiatric comorbidity,[11] and poorer physical health[12] that, together with other problems (eg, poverty, inadequate nutrition, and social chaos), may impair their ability to nurture their children
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