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  • Review Article
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Impact of prenatal opioids on cardiac and autonomic development: systematic review and meta-analysis


Prenatal opioid exposure has recently risen four-fold with limited data on the developmental effects on neonatal physiology. The objective of this systematic review is to develop an association between prenatal opioid exposure and fetal and neonatal cardiac and autonomic development and function. The review was conducted in accordance with PRISMA Guidelines, and searches were conducted using PubMed, Embase, CINAHL, and Web of Science between May 25 and October 27, 2020. Twenty studies fit inclusion criteria, in four categories: (1) fetal cardiac outcomes, (2) neonatal cardiac outcomes, (3) noninvasive autonomic outcomes, and (4) clinical and behavioral measures. For the meta-analysis, three studies (total of 210 subjects) were included. Effect sizes were measured as the mean difference in fetal heart rate between opioid-exposed and non-exposed groups. Mothers with prenatal opioid use had a significantly lower fetal heart rate as compared to mothers without prenatal opioid use, requiring further studies to determine clinical significance.

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Fig. 1: PRISMA 2020 Flow Diagram.
Fig. 2: Pooled Estimates.

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Authors and Affiliations



MPH wrote the systematic review protocol, supervised the search and data abstraction, and assisted with analysis, preparation, and critical review of the final manuscript. CAW and MZR executed the PRISMA search, primarily conducted included study data abstraction, and assisted with preparation and critical review of the final manuscript. WMY assisted with execution of PRISMA search and data abstraction, preparation, and critical review of the final manuscript. LAW assisted with systematic review protocol, conduction and supervision of all included databases, preparation and critical review of the final manuscript. SSO assisted by conducting meta-analysis of included studies, preparation and critical review of the final manuscript. BB and SI assisted with data abstraction of rodent studies, preparation and critical review of the final manuscript. TRK assisted by providing critical review of all extracted data, preparation and critical review of the final manuscript. SC and KKG assisted with data abstraction of studies, analysis of data extracted from included studies, preparation and critical review of the final manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Meghan P. Howell.

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Howell, M.P., Wiseman, C.A., Rosen, M.Z. et al. Impact of prenatal opioids on cardiac and autonomic development: systematic review and meta-analysis. J Perinatol 43, 259–270 (2023).

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