Evidence map›Paper›PMID 42563929›Full record

ReviewAnnals of the Child Neurology Society2026

Fetal Pain Perception:

William D Graf, Timothy M Crombleholme, Leon G Epstein, Dawn Gano, Phillip L Pearl, Timothy V Salomons, Mark S Scher, Elise Turk, Klaus-Peter Zimmer, Harvey B Sarnat

Abstract readReview
In one paragraph

Review in Annals of the Child Neurology Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

William D GrafDepartment of Pediatrics, Division of Neurology Connecticut Children's and The University of Connecticut Farmington Connecticut USA.ORCID https://orcid.org/0000-0003-0460-4605
Timothy M CrombleholmeDepartment of Surgery, UConn Health, Fetal Surgery Section Division of Pediatric General and Thoracic Surgery Farmington Connecticut USA.ORCID https://orcid.org/0000-0002-4752-9118
Leon G EpsteinDepartment of Pediatrics Northwestern University's Feinberg School of Medicine and The Ann & Robert H. Lurie Children's Hospital of Chicago, Pediatrics and Neurology Chicago Illinois USA.ORCID https://orcid.org/0000-0003-4264-3867
Dawn GanoDepartments of Neurology, UCSF School of Medicine University of California, San Francisco San Francisco California USA.ORCID https://orcid.org/0000-0003-4192-2362
Phillip L PearlDepartment of Neurology Boston Children's Hospital and Harvard Medical School Boston Massachusetts USA.ORCID https://orcid.org/0000-0002-6373-1068
Timothy V SalomonsDepartment of Psychology Queen's University Kingston Ontario Canada.ORCID https://orcid.org/0000-0002-1871-6969
Mark S ScherDepartment of Pediatrics and Neurology, Division of Pediatric Neurology, Fetal/Neonatal Neurology Program Case Western Reserve University School of Medicine Cleveland Ohio USA.ORCID https://orcid.org/0000-0003-3410-6797
Elise TurkDepartment of Neonatology, University Medical Center Utrecht Utrecht University Utrecht the Netherlands.ORCID https://orcid.org/0000-0002-4802-6774
Klaus-Peter ZimmerDepartment of Pediatrics, Division of Neonatology Justus-Liebig-University Giessen Giessen Germany.
Harvey B SarnatDepartments of Paediatrics, Pathology (Neuropathology) and Clinical Neurosciences University of Calgary Cumming School of Medicine, and Alberta Children's Hospital Research Institute (Owerko Centre) Calgary Alberta Canada.ORCID https://orcid.org/0000-0002-6953-2959

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Pain perception is a conscious experience, but neither pain nor consciousness is defined in the developing human fetus. Emergent consciousness may be regarded as a phenomenon that ultimately arises from an essential minimum of functional neuronal connectivity. Proposed U.S. federal legislation asserts that a functioning cerebral cortex is not necessary to experience pain. Methods: We assess the scientific premise of the 13 assertions in the "Pain-Capable Unborn Child Protection Act" with analysis and interpretation from a developmental neuroscience perspective. We review the biological requisites of fetal sentience, the emergence of involuntary spinal cord and brainstem reflexes, the early appearance of autonomic homeostatic stress reactions, and measures of synaptogenesis and neuronal connectivity through immunocytochemistry and fetal functional neuroimaging. Results: The formation of functional synapses can be demonstrated by synaptophysin immunoreactivity in the receptive sensory layers of fetal cerebral cortex at around 25 weeks' gestation, but immunoreactivity is not uniformly intense until after 35 weeks. In vivo, fetal functional magnetic resonance imaging confirms immunocytochemical results by showing complex, interconnected brain networks developing at similar gestational ages. Fetal magnetoencephalography detects magnetic fields from fetal brain activity and demonstrates second-order rule learning in fetuses over 35 weeks' gestation. The neural pathways required for the emotional and evaluative aspects of pain processing in the brain are still incomplete in term newborns. Conclusion: Given the limitations of reductionism to explain the subjective nature of consciousness, evidence from developmental neuroanatomy, neurophysiology, and functional neuroimaging infers that fetal pain perception requires the emergence of conscious cortical processing beginning with weak functional thalamocortical connectivity well after the age of fetal viability.

Indexed as

brainfetalneurodevelopmentpainsentience consciousness

Identifiers

PMID42563929
PMCPMC13359132

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.