Fetal Pain—ReplyFetal Pain—Reply

In Reply: We agree with Dr Myers and colleagues that fetuses and preterm neonates undergoing surgery or other invasive procedures should receive appropriate anesthesia or analgesia. As the article stated, “Despite ongoing debate regarding fetal capacity for pain, fetal anesthesia and analgesia are still warranted for surgical procedures undertaken to promote fetal health.” Furthermore, one author (Dr Rosen) is a founding member of the Fetal Treatment Center at UCSF Children's Hospital, staffed by a multidisciplinary team that pioneered the field of fetal surgery and has advocated for, and provided, fetal anesthesia for more than 25 years.^{1 - 2}

Myers et al are in error in their “first and foremost” concern that none of the authors routinely care for preterm infants. Another author (Dr Partridge) is a neonatal intensive care specialist who has provided care to preterm infants for more than 20 years and has lectured widely and written about neonatal ethics and pain management.^{3 - 4}

Review articles in JAMA have citation limitations that precluded referencing all secondary sources (including textbooks) addressing fetal pain. However, numerous review articles and non–peer-reviewed textbooks were carefully searched for original research (primary sources), which we reviewed and cited in our article if relevant. Myers et al note 2 primary sources that we reviewed but did not cite.^{5 - 6} Both are studies of hemodynamic and neuroendocrine changes in fetuses undergoing stressful procedures that do not constitute evidence of fetal pain. The autonomic nervous system and hypothalamic-pituitary-adrenal axis mediate stress responses without conscious cortical processing. Although we confined ourselves to the medical literature and did not consider nonmedical databases as pointed out by Dr Lyman, we subsequently performed a PsycINFO search that did not yield research that would have met inclusion criteria.

Myers et al and Dr Sites raise questions about the initial appearance of neural connections between the thalamus and somatosensory cortex, which are necessary for pain perception. We agree that the available neuroanatomical evidence only permits reporting developmental age ranges, as we have done. Nonetheless, the growth of thalamocortical axons into the cortical plate occurs after 26 weeks,⁷ and parvalbumin, a marker for thalamocortical axons, first appears in layer 4 (the layer of termination of thalamocortical afferent axons) of the human somatosensory cortex at 38 weeks.⁸ It can reasonably be concluded that the neural circuitry that is necessary for pain perception does not yet exist until at least the sixth month of development, and perhaps later, contrary to the 21 to 30 weeks' gestational age speculated by Sites.

Care must be taken to avoid conflating analgesia/anesthesia administered to a preterm neonate or fetus during a surgical procedure undertaken to promote its long-term health and experimental analgesia/anesthesia administered to a fetus during abortion. For fetal or neonatal surgery, analgesia/anesthesia is indicated because long-term fetal and neonatal well-being is the primary objective. We cited multiple studies demonstrating beneficial outcomes of treatment of stress in neonates. However, just as the principle of beneficence requires the neonatologist to act in the best interests of the preterm neonate, the principles of beneficence and nonmaleficence apply to the woman undergoing an abortion procedure: every effort should be made to minimize or prevent short- or long-term harm to her. Fetal anesthesia for abortion procedures remains experimental, and the possible but unknown fetal benefit must be balanced with inevitable and potentially unacceptable risk to the woman. Providing fetal anesthesia for abortion procedures is not necessarily “err[ing] on the safe side,” as suggested by Myers et al.