Caffeine in Preterm Infants and its Effect on Neonatal Sleep: A Systematic Review

Authors

• Kristina Denisova, Division of Math and Natural Sciences, Department of Psychology, Autism Origins Lab, City University of New York, Queens College and Graduate Center, New York, NY, USA.
• Nicholas Diamandis, Division of Math and Natural Sciences, Department of Psychology, Autism Origins Lab, City University of New York, Queens College and Graduate Center, New York, NY, USA.
• Jean Ee Tang, Biobehavioral Sciences Department, Teachers College, Columbia University, New York, NY, USA.
• Mia Eng-Kohn, Department of Neuroscience and Behavior, Barnard College, New York, NY, USA.
• Gloria Willson, The Levy Library, Mount Sinai Icahn School of Medicine, New York, NY, USA.
• Bikash Shrestha, Division of Math and Natural Sciences, Department of Psychology, Autism Origins Lab, City University of New York, Queens College and Graduate Center, New York, NY, USA.
• Alyssa DeStefano, Division of Math and Natural Sciences, Department of Psychology, Autism Origins Lab, City University of New York, Queens College and Graduate Center, New York, NY, USA.
• Jane Lee, Division of Math and Natural Sciences, Department of Psychology, Autism Origins Lab, City University of New York, Queens College and Graduate Center, New York, NY, USA.
• Jacob Merrin, Department of Psychiatry, PGSP-Stanford Consortium, Palo Alto University and Stanford University Medical School, Palo Alto, CA, USA.
• Zhichun Lin, Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL, USA.
• Neli Kotlyar, Division of Math and Natural Sciences, Department of Psychology, Autism Origins Lab, City University of New York, Queens College and Graduate Center, New York, NY, USA.
• Amanda Kessler, Department of Neurology, Cognitive Neurology, and Neuropsychology, Johns Hopkins University Medical School, MD, USA.
• Ryan Dosumu-Johnson, NY Presbyterian Weill Cornell University Hospital of Columbia and Cornell, New York, NY, USA.
• Kirwan Walsh, Division of Math and Natural Sciences, Department of Psychology, Autism Origins Lab, City University of New York, Queens College and Graduate Center, New York, NY, USA.
• Yidan Lou, Department of Social, Behavioral, and Population Sciences, Tulane University, New Orleans, LA, USA.
• Jeremy Payano, George Washington University, Washington, DC, USA.
• John N. van den Anker, Division of Clinical Pharmacology, Children's National Hospital, Washington, DC, USA.

Document Type

Journal Article

Publication Date

2-1-2026

Journal

Journal of clinical pharmacology

Volume

66

Issue

2

DOI

10.1002/jcph.70096

Keywords

caffeine; central nervous system stimulants; early postnatal period; infant; neonatal intensive care units; neonatal sleep; neonatology; premature; sensorimotor function; systematic review; wakefulness

Abstract

The development of good-quality sleep is very important in early life. Sleep promotion programs aim to increase preterm infants' sleep quality because preterm infants in the neonatal intensive care unit (NICU) have poor sleep. Interestingly, the majority of preterm infants are treated with caffeine, a nervous system stimulant. The primary objective of this systematic review was therefore to appraise the current evidence concerning potentially sleep-disruptive effects of caffeine in preterm infants within the first month of life. We performed a search (PROSPERO protocol CRD42022273596) according to PRISMA guidelines in PubMed, Embase, Scopus, and PsycInfo (as well as CENTRAL). We looked for studies involving preterm infants (<37 weeks of gestational age) treated with caffeine in the NICU, with sleep measures acquired within the first month of life. Eight studies met the eligibility criteria. Underlying effect sizes for main outcomes are represented using albatross plots. Among studies reporting on wakefulness (N = 213), 83.33% detected significant disruptions (P <  .05). Among studies reporting on sensorimotor functioning (N = 80), 100% detected significant reductions (P <  .05). Moreover, significant reductions (P <  .05) in sleep states were detected. Available evidence suggests that caffeine exposure in preterm infants may produce alterations in sleep-wake and sensorimotor functioning, and related processes during the first month of life. The overall evidence is mixed, with some studies reporting no effect of caffeine exposure on neonatal sleep. Additional research is needed to understand how caffeine alters the quality of neonatal sleep in preterm infants and whether the effects may differ among infant subgroups. There is a continued need to investigate and support sleep quality in preterm infants during their NICU stay.

APA Citation

Denisova, Kristina; Diamandis, Nicholas; Tang, Jean Ee; Eng-Kohn, Mia; Willson, Gloria; Shrestha, Bikash; DeStefano, Alyssa; Lee, Jane; Merrin, Jacob; Lin, Zhichun; Kotlyar, Neli; Kessler, Amanda; Dosumu-Johnson, Ryan; Walsh, Kirwan; Lou, Yidan; Payano, Jeremy; and van den Anker, John N., "Caffeine in Preterm Infants and its Effect on Neonatal Sleep: A Systematic Review" (2026). GW Authored Works. Paper 8791.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/8791

Department

Pharmacology and Physiology