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, and Daniel Ciampi de Andrade, Grupo de Estudo da Dor Fetal (Fetal Pain Study Group)

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).

(A) Initial items from neonatal facial coding system and 2 supplementary items. 1. Brow lowering. 2. Eyes squeezed shut. 3. Deepening of the nasolabial furrow. 4. Open lips. 5. Horizontal mouth stretch. 6. Vertical mouth stretch. 7. Lip purse. 8. Taut tongue. 9. Tongue protrusion. 10. Chin quiver. 11. Neck deflection. 12. Yawning. (B) Final items from the Fetal-5 Scale. 1. Brow lowering. 2. Eyes squeezed shut. 3. Deepening of the nasolabial furrow. 4. Open lips. 5. Horizontal mouth stretch. 6. Vertical mouth stretch. 7. Neck deflection.

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.

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