New peer-reviewed article: Fetal Pain in the First Trimester
On December 6, 2021, The Linacre Quarterly published Dr. Bridget Thill’s dissertation “Fetal Pain in the First Trimester.” The article is written for a medical audience, with over 100 references to research in medical journals published from 1936 through 2021. If you can read the entire article, do, but for those who aren’t able to, here are some notes from my reading. I also link to some TikTok content at the end of this post.
External awareness of pain represents an unreflected experience of “being in pain,” such as a neonate who experiences, but will not remember, pain from a heel lance. In contrast, internal awareness represents a self-reflective experience of knowing that one is in pain, such as a 4-year-old who remembers and fears the pain of an immunization. Neurodevelopmentally, the self-reflective experience of pain does not emerge until cortical synapses develop during the first 2 years of postnatal life.
There is a lot of debate over what constitutes “feeling” pain, and one suggestion is that pain doesn’t really count (i.e. is not morally meaningful) unless the entity experiencing it is consciously aware they are experiencing it. I’m pretty skeptical that many people would find this definition persuasive even at face value, but if this were the definition, it would mean that even newborns don’t have morally meaningful pain, because newborns aren’t yet capable of self-reflection.
[Related reading – Personhood based on human cognitive abilities]
On the history of neonatal pain management
The assumption that newborns were insensitive to pain due to an undeveloped cortex was widely adopted by the scientific and medical communities until the late 1980s, despite dissenting views. Anesthesia, if administered to infants, was utilized for the benefit of the surgeon in order to suppress movement during surgical procedures, by means of paralytic medications. Analgesia was considered unnecessary during surgery due to lack of higher cortical function and the infant’s inability to remember the pain.
In other words, these children were given medications to paralyze them but not to manage pain. Pretty horrifying. In fairness there was also hesitation about using anesthesia because at the time there was no standard medical practice established and medical professionals weren’t certain if anesthesia could cause further harm to the fetus. (I note this concern doesn’t have an analog in the abortion debate, where the fetus who may receive anesthesia is about to be killed anyway.)
The paper goes on to explain this standard changed due to a combination of “humanitarian concerns and parental activism” (imagine being a parent to a baby going through this!) along with a revolutionary study in 1987. In the study, 16 preterm infants were paralyzed prior to cardiac surgery. Half were given the very strong pain medication fentanyl and half weren’t given pain medication. The half that had no pain meds during surgery had “substantial stress responses” and endured “significant intra- and post-operative morbidity” including hemorrhaging. Preterm infant pain seemed like a problem after all. And as the medical community started to recognize neonatal pain, it also started to recognize (previously disputed) pain in “preterm, term, cognitively impaired, and sedated neonates.” So that’s a relief. Now it is standard medical practice during invasive procedures to provide pain management even for preterm infants born as early as 21 weeks.
The paper addresses procedural memory and sensitization. In this case procedural memory involves the long-term neurophysiological effects of pain, regardless of whether the child consciously remembers the pain. Compared to infants with limited exposure to pain, infants with greater exposure have increased heart rate and oxygen saturation and stronger reaction to painful procedures months later (e.g. immunizations). They can also become sensitized to respond to even non-painful stimuli as if it were painful. Similarly, fetal exposure to pain raises significant concerns about resultant long-term health issues.
Since 1979, the International Association for the Study of Pain has noted that “Pain is always subjective.” My husband, a registered nurse, has explained that their RN training always emphasizes “Pain is whatever the patient says it is.” But when patients can’t communicate (as in the case for fetuses, preterm infants, neonates, and older patients with communication impairments), how do we determine whether they are in pain?
On the neuroanatomical evidence for fetal pain
Fetal pain perception requires that the pathways for pain signal transmission are present and functioning, at least at an immature level. The sensory systems for both tactile and nociceptive [painful] stimuli develop early in embryologic development, preceding the development of the olfactory, vestibular, auditory, and visual systems.
The paper posits that fetal pain perception involves impulses transmitted through the following stages:
- Peripheral free nerve endings
- Spinal cord
- Brainstem and thalamus
- Cortical structures (first cortical subplate, later actual cortex)
Much of the debate revolves around which of these stages an impulse must reach in order for the fetus to “experience” pain. Our current understanding is that the body can sense noxious (painful) stimuli in these and related regions around the following gestational ages:
- Peripheral free nerve endings:
- perioral area (around the mouth) – 7.5 weeks gestation
- hands – 10 weeks
- most other areas – 14 weeks
- Spinal cord: nerve fibers from peripheral receptors reach here starting at 7-8 weeks
- Brainstem and thalamus: projections from spinal cord reach here starting at 7 weeks
- Cortical structures:
- Nerve fibers from thalamus project to cortical subplate starting at 12-15 weeks
- These fibers “massively invade” the subplate between 15-26 weeks
- These fibers project fully to the cortex beginning at 23-24 weeks
This last fact is a major premise for the argument that fetuses can’t feel pain until at least 23-24 weeks. The idea is that their bodies may in some way be perceiving pain in these other areas (peripheral areas, spinal cord, etc), but that the fetus can’t process that pain in a way that would make the pain morally meaningful until nerve fibers reach the cortex. This is the “cortical necessity” hypothesis purported by the Royal College of Obstetricians and Gynaecologists (RCOG), American College of Obstetricians and Gynecologists (ACOG), and others. Proponents of the cortical necessity hypothesis sometimes claim there is scientific consensus on the question of fetal pain, and the consensus is that the cortex is necessary. But in fact there are at least four competing hypotheses:
- Pain isn’t possible at least until fibers project into the cortex at 23-24 weeks (the cortical necessity hypothesis)
- Pain is possible once the cortical subplate forms (around 12 weeks)
- Pain is possible when the brainstem and thalamus form (around 7-8 weeks)
- Pain is not possible until onset of fetal consciousness (varying estimates for the timing of this one)
Regarding Hypothesis 1: Cortical necessity (>24 weeks):
Proponents of the cortical necessity hypothesis view all fetal responses to noxious [painful] stimuli prior to 24 weeks gestation as unconscious, reflexive, subcortical reactions, not indicative of a pain experience. This is in contrast to comparable responses to noxious stimuli in extremely preterm infants and neonates, in which these same physiologic and behavioral reactions are viewed as signs of pain.
The paper gives examples of how the medical community accepts “facial actions” as indicators of pain in extremely preterm infants, and fetuses of the same gestational age have given those same facial actions during fetal surgery. Additionally, infants born without a cortex (anencephaly or hydranencephaly) demonstrate awareness of pain (crying, avoidance, withdrawal) and the ability to be soothed.
Regarding Hypothesis 2: Cortical subplate (>12 weeks)
This is the hypothesis put forth by Bockmann and Derbyshire in the 2020 Journal of Medical Ethics article “Reconsidering Fetal Pain” (currently the 5th most read article in JME’s history). Animal studies have shown the cortical subplate responds to stimuli before the cortex is functioning, lending credence to the idea that humans don’t need a functioning cortex in order to similarly respond to pain.
Regarding Hypothesis 3: Brainstem and thalmus (7-8 weeks)
The idea here is that the fetus may be able to sense pain once the minimum neuroanatomy develops: nerves connecting the brainstem and thalamus. This would be prior to nerve connections to the cortex and prior to forming the cortical subplate, so even earlier than Hypotheses 1 & 2. However, at this point researchers can’t really test Hypothesis 3; we don’t yet have the neuroimaging technology to assess thalamus function at this early gestational age.
Regarding Hypothesis 4: Consciousness
This hypothesis suggests the neuroanatomical (physical) structures alone aren’t enough for a fetus to experience pain; the fetus must also have a minimum state of consciousness to be aware that she is experiencing pain. Proponents of this view suggest that both (1) the intrauterine environment (environment in the womb) and (2) the fetus’s level of development will affect how conscious the fetus is.
1) Prior work has suggested neurochemicals in the womb could keep the fetus constantly unconscious, and thus unable to perceive pain. More recent work has discredited this idea. Basically there are neurochemicals that do have some sedative effect for the fetus, but the effect would have to be 10-20x stronger to actually block fetal pain perception. These chemicals aren’t that intense of a sedative.
2) There’s a lot of ambiguity around the definition of “consciousness,” so it’s hard to say which fetal behavior would suggest “consciousness.” One suggestion is that once the fetus can plan actions (as opposed to acting only on reflex) this action planning indicates a level of consciousness. There is evidence of action planning anywhere from 13 weeks through 22 weeks, all before the 24 week mark of cortical connections. For example:
Fetal movements in twin gestations were studied, utilizing 4-D ultrasound from 14 weeks gestation. The study noted action planning via purposeful movements of the fetuses toward the co-twin, as well as self-directed movements. The study also noted differentiation in the velocity of targeted fetal movements. Slower velocity of fetal movements was noted toward the co-twin as well as with self-directed movements toward the sensitive eye regions, when compared to non-targeted movements toward the uterine wall, for example. The presence of such action planning, learning, and social behavior raises consideration of fetal consciousness and awareness by 14 weeks gestation.
Other research has found that both humans and animals without cortexes (either by birth defect or, in the case of some animals, surgery for animal research) demonstrate the ability to perceive and respond to pain, calling into question the premise that cortex-dependent consciousness is a prerequisite to experiencing pain. Instead, Dr. Thill explains,
These studies suggest an emerging level of consciousness once the brainstem, including the thalamus (diencephalon), is present during fetal development, not as an all-or-none event occurring at a distinct gestational age. A useful analogy to consider is the post-operative patient emerging from general anesthesia who transitions through a spectrum of unconsciousness to increasing levels of consciousness until becoming fully awake, alert, aware, and responsive.
On physiologic (organ and system) and hormonal responses to pain
Responses to pain can be physiologic, hormonal, or behavioral. The American Academy of Pediatrics already accepts these markers as signs of pain in extremely preterm (22-27 week) infants. One of the major physiologic responses to pain for children and adults is increased blood flow to the brain. It is a “brain-sparing reaction to protect essential organs during threatened or ongoing tissue damage.” Fetal studies conducted as early as 16 weeks gestation have shown the same increased brain blood flow in response to painful stimuli. Similarly, noxious stimuli elevate levels of certain hormones (cortisol, adrenaline, and β-endorphins), but if the fetus is first given analgesics (pain relievers) they suppress the hormonal stress response.
On behavioral responses to pain
We know that fetuses will make characteristic facial expressions and withdraw from potentially painful stimulus. Part of the reason we know this is because of “ethically questionable” research conducted from the 1930s to 1960s:
University of Pittsburgh anatomists, Hooker and Humphrey, sought to determine fetal motor responses to tactile stimulation. Their research utilized more than 150 intact, living fetuses obtained from surgical abortions via hysterotomy (or less commonly through spontaneous preterm delivery) which were immediately suspended in saline solution. Fetal responses to repeated stimulation of the skin and musculature with monofilaments or bead-tipped glass rods were recorded, until demise occurred 8-20 min after placental separation.
Withdrawal reflexes begin first in the perioral area (around the mouth) by about 7.5 weeks gestation, extending to face, hands, feet, trunk, and limbs by 14 weeks. These observations, though, were for fetuses who had been separated from the placenta and were completely deprived of oxygen, which could subdue responses. If a similar experiment were possible for a fetus still connected to her mother and healthy, the responses may be more pronounced or appear earlier in gestation.
As far as facial reactions, compared to newborns, fetuses don’t have as much adipose tissue (fat) or neuromuscular development, so in general they aren’t yet physically capable of as many different facial expressions as a newborn would be. Still, some facial movements are observable via ultrasound by 20 weeks, and research has found fetuses make certain faces more often when receiving injections for fetal surgery compared to when not. Their expressions in response to these shots are similar to the expressions of infants in response to pain.
Since the 1960s, government regulations have stopped nontherapeutic research on living fetuses. Researchers may still observe fetal responses to pain during fetal surgery, but such surgery is uncommon before 15 weeks gestation. So today there’s limited data regarding responses to painful stimuli for fetuses that young or younger.
On abortion and feticide
Procedures performed in the second and third trimester involve either
- Causing cardiac asystole (flatline) by injection of a lethal agent (e.g. potassium chloride, lidocaine, or digoxin) either directly to the fetus or, less commonly, to the amniotic fluid;
- Causing hypoxia-induced cardiac arrest (insufficient oxygen causing heart attack) by stopping blood flow through the umbilical cord either through occlusion, radiofrequency ablation, or transection; or
- Dilation and evacuation (using grasping forceps to remove the fetus from the uterus in pieces)
Injecting potassium chloride causes pain. It’s used in death penalty lethal injections, but only after the person is given anesthesia. There’s good reason to believe heart attacks cause pain, of course, as does ripping limbs off of someone. Nevertheless, ACOG doesn’t recommend fetal analgesia prior to abortions because “fetal perception of pain may not occur until the third trimester.”
Conclusion
A few quotes to leave you with:
The integrity of the medical profession depends on informed consent, including a full and accurate disclosure regarding the fetus, fetal pain capacity, and the methodologies involved in abortion or feticide procedures. Medical ethics also imposes the requirement to avoid cruelty and unnecessary pain and suffering.
And:
Clinicians in fetal medicine are already voluntarily addressing these issues in developing standards of care for the use of analgesia and anesthesia during invasive fetal procedures. A dichotomy exists in the practice of medicine. Disparate treatment of two indistinguishable human fetuses occurs, in which one fetus is accorded patient status and humanity, to whom beneficence and nonmaleficence are owed, while for the other fetus, this status is withheld. This cognitive dissonance disturbs and causes significant tension within the practice of medicine in view of objective medical evidence as well as in light of the fundamental mission of medical professionals as healers.
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