Sorting pain out of salience: assessment of pain facial expressions in the human fetus

Lisandra S Bernardes; Mariana A Carvalho; Simone B Harnik; Manoel J Teixeira; Juliana Ottolia; Daniella Castro; Adriano Velloso; Rossana Francisco; Clarice Listik; Ricardo Galhardoni; Valquiria Aparecida da Silva; Larissa I Moreira; Antonio G de Amorim Filho; Ana M Fernandes; Daniel Ciampi de Andrade

doi:10.1097/PR9.0000000000000882

Sorting pain out of salience: assessment of pain facial expressions in the human fetus

Pain Rep. 2021 Jan 27;6(1):e882. doi: 10.1097/PR9.0000000000000882. eCollection 2021 Jan-Feb.

Authors

Lisandra S Bernardes^{1

2

3}, Mariana A Carvalho¹, Simone B Harnik⁴, Manoel J Teixeira⁵, Juliana Ottolia¹, Daniella Castro⁶, Adriano Velloso⁶, Rossana Francisco¹, Clarice Listik⁵, Ricardo Galhardoni⁵, Valquiria Aparecida da Silva⁵, Larissa I Moreira⁵, Antonio G de Amorim Filho¹, Ana M Fernandes^{1

5}, Daniel Ciampi de Andrade^{5

7}

Affiliations

¹ Disciplina de Obstetrícia, Departamento de Obstetrícia e Ginecologia, Faculdade de Medicina da FMUSP, Universidade de São Paulo, São Paulo, Brazil.
² School of Medicine, Faculdade Israelita de Ciências da Saúde Albert Einstein, São Paulo, Brazil.
³ Hospital e Maternidade SEPACO, São Paulo, Brazil.
⁴ Instituto de Matemática e Estatística da Universidade de São Paulo, São Paulo, Brazil.
⁵ Pain Center, LIM-62, Department of Neurology, University of São Paulo, São Paulo, Brazil.
⁶ Computational Science Department Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
⁷ Pain Center, Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira, University of São Paulo, São Paulo, Brazil.

Abstract

Introduction: The question of whether the human fetus experiences pain has received substantial attention in recent times. With the advent of high-definition 4-dimensional ultrasound (4D-US), it is possible to record fetal body and facial expressions.

Objective: To determine whether human fetuses demonstrate discriminative acute behavioral responses to nociceptive input.

Methods: This cross-sectional study included 5 fetuses with diaphragmatic hernia with indication of intrauterine surgery (fetoscopic endoluminal tracheal occlusion) and 8 healthy fetuses, who were scanned with 4D-US in 1 of 3 conditions: (1) acute pain group: Fetuses undergoing intrauterine surgery were assessed in the preoperative period during the anesthetic injection into the thigh; (2) control group at rest: Facial expressions at rest were recorded during scheduled ultrasound examinations; and (3) control group acoustic startle: Fetal facial expressions were recorded during acoustic stimulus (500-4000 Hz; 60-115 dB).

Results: Raters blinded to the fetuses' groups scored 65 pictures of fetal facial expressions based on the presence of 12 items (facial movements). Analyses of redundancy and usefulness excluded 5 items for being of low discrimination capacity (P>0.2). The final version of the pain assessment tool consisted of a total of 7 items: brow lowering/eyes squeezed shut/deepening of the nasolabial furrow/open lips/horizontal mouth stretch/vertical mouth stretch/neck deflection. Odd ratios for a facial expression to be detected in acute pain compared with control conditions ranged from 11 (neck deflection) to 1,400 (horizontal mouth stretch). Using the seven-item final tool, we showed that 5 is the cutoff value discriminating pain from nonpainful startle and rest.

Conclusions: This study inaugurates the possibility to study pain responses during the intrauterine life, which may have implications for the postoperative management of pain after intrauterine surgical interventions.

Keywords: Fetal; Pain; Ultrasound.