Anyone willing to make absolute statements regarding fetal, infant or adult neural development and processing is a brave person. The complexities of the brain defy absolute explanation. —Dr. Ray Paschall
The baby blankets had elephants, giraffes and clowns. The nurses wore colorful scrubs. But the attempts at cheer in a sterile NICU room awash in the bluish light used to treat jaundice struck the parents as oddly macabre, and the efforts were certainly lost on the tiny patients.
Ian Puente spent three months with his wife, Melissa, at the Kaiser Permanente Neonatal Intensive Care Unit in Woodland Hills, Calif., coaxing their twins, Caleb and Julian, through premature birth and major surgeries. Caleb had a heart ligation to close a valve just a week after birth, a common preemie procedure. Julian had his cecum removed two weeks later, a much more invasive step.
"The hospital tried to create a warm environment, but it didn't really work," Ian said.
Not that they weren't happy to be there. A generation ago, they would not have been alive at all. The Puente twins were born at 26 weeks and 5 days of gestation. The date is exact because the twins were conceived in vitro.
Back in 1972 the Supreme Court in Roe v. Wade ruled that a state could regulate abortion only after a child could survive outside the womb. The court held that point of "viability" to be 28 weeks, which at the time was about right.
Since then, technology has steadily eroded the foundations of Roe v. Wade, beginning with viability outside the womb. By 1992, the Court simply acknowledged reality when it bumped the limit down from 28 to 24 weeks. But survival outside the womb was only part of the story.
Advances in fetal surgery were making it possible to address serious problems in the womb, often weeks before the infant could survive outside of it. Fetal surgery made possible new ways of thinking about life within the womb, altering politics and shaping new research agendas.
Then came the question of pain. Anesthesia is now routine for both neonatal and fetal surgery, but a generation ago newborns were thought to not perceive pain, and they routinely underwent surgery without anesthesia.
"It gives me chills to think of newborns in surgery without anesthesia," Ian said, after witnessing the struggles of his own sons.
Today newborn and fetal anesthesia are routine, but the logic behind the latter is hotly disputed.
The Puente twins were thus born into a scientific, ethical and legislative no-man's land, the front edge of abortion politics where doctors dispute whether a developing child can feel pain, while legislatures reshape law on the assumption they can. This summer, Texas became the 13th state to rely on fetal pain theory to ban abortion after 20 weeks.
Both sides are very aware that abortion politics and policy turn on how the humanity of the fetus is perceived by science and, thence, by the general public.
"Fundamentally, I'm a scientist," said Maureen Condic, a neurobiologist at the University of Utah Medical School, who has recently taken a prominent role arguing for the reality of fetal pain. "And whatever views I hold, if the scientific evidence were to contradict them, the other views would fall."
What does the science say? That depends on who you ask — and how you phrase the question.
For the Puentes, there is no doubt that their twins felt pain at birth.
At birth, they didn't have the strength to cry or squirm or even grimace, Melissa said. But she soon came to recognize signs of discomfort in their facial muscles, especially in the eyelids. When they were at ease, she said, "their eyelids are smooth and facial muscles are relaxed." But after surgery their muscles tightened and their eyelids appeared stressed. "It was obvious he was in pain," she said of one son.
The pain markers went well beyond facial cues. Even routine blood draws or IV insertions could cause measurable reactions.
"You saw a spike in blood pressure and heart rate, and a drop in blood stats and oxygen stats," Ian said.
The Puentes' observations of facial expressions and stress measures mirror techniques used by medical professionals to judge pain in premature infants and fetuses in the womb. These "surrogate measures" are needed since a newborn preemie or an unborn fetus cannot express itself, cannot even vocalize or even squirm.
But these surrogate measures are also controversial. Some experts argue they are not reflections of perceived pain at all, but rather a kind of biological reflex.
"Those surrogate measures in the fetus and in the premature newborn are imperfect at best," said Dr. F. Sessions Cole, director of the Division of Newborn Medicine the Washington University School of Medicine in St. Louis, "so there are always debates about whether a given measure of what a fetus or baby is feeling is accurate or not."
From newborns to unborns
The Puente twins would have been treated quite differently a generation ago, when newborns were thought incapable of pain and routinely underwent surgery without anesthesia.
In the early 1980s Dr. Kawaljeet Anand, then an intern at a British hospital, noticed many of his neonatal patients exhibiting stress and dying after surgery. This sparked research that led to a landmark 1987 piece published in the New England Journal of Medicine that outlined the evidence of neonatal pain, including a litany of stress and hormonal responses, key "surrogate measures" of pain. Neonatal surgery would never be the same after Anand got done with it.
Anand proved that newborns not only perceived pain, but that they were literally dying from it. In one of his studies, mortality dropped from 25 to 10 percent just through using anesthesia. By the turn of the 21st century, thanks largely to Anand, newborn anesthesia was standard. By the time the Puente twins came along, it was not even a question.
That challenge conquered, Anand's research moved on to premature infants like the Puente twins and from there to the pre-viable fetus. It is on the latter point, of course, that the controversy really takes life.
Now with an endowed chair at the University of Tennessee Health Science Center in Memphis, the pioneering pain researcher finds himself at the center of the national abortion debate, often castigated for his insistence that the fetus and premature newborn feel pain. As ever, the politics of abortion lurk directly behind the question of fetal pain.
Anand has, in fact, argued that a fetus or premature newborn may actually feel pain more intensely than an older newborn. He asserted in 2007 congressional testimony on fetal pain legislation that "a fetus at 20 to 32 weeks of gestation would experience a much more intense pain than older infants or children or adults" because certain pain mechanisms are in play much earlier, while "fibers which dampen and modulate the experience of pain" are delayed until between 32-34 weeks.
The JAMA article
The most widely known rejoinder to Anand is a 2005 coauthored article published in the prestigious Journal of the American Medical Association. The lead author is Dr. Mark Rosen, a prominent researcher at the University of California, San Francisco, and, oddly enough, one of the pioneers of fetal anesthesia.
The article reviews the evidence on both sides, concluding that "pain perception requires conscious awareness and recognition," which in turn requires a functional link between the thalamus (which records sensory data) and the cortex (which makes sense of it), a link not firmly established until 29 or 30 weeks.
The JAMA article is probably the central pillar of the argument against the fetal pain position. On one level, the authors do seem to discount fetal pain. But on closer inspection, the article uses very careful phrasing suggesting significant uncertainty. The article refers repeatedly to "pain perception" rather than simply to "pain," and it clearly allows that pain may harm a fetus that cannot consciously "perceive" it.
For example, the authors argue that fetal anesthesia in pre-birth surgery is justified not to dull pain perception in the fetus, but rather to (1) keep the fetus still, (2) relax the uterus, (3) prevent "hormonal stress responses associated with poor surgical outcomes in neonates," and (4) to "prevent possible adverse effects on long-term neurodevelopment and behavioral responses to pain."
In short, Rosen and his coauthors allow that fetal anesthesia may prevent long-term harm, though they add that, if the fetus is being aborted anyway, there is no long term. And yet, the mere fact of the dialog casts a long shadow over the abortion debate. If fetal anesthesia can reduce long-term harm, then the contested personhood of the fetus suddenly becomes much more tangible, and thus politically charged.
An anesthesiology professor at Vanderbilt University Medical Center, Dr. Ray Paschall is a pioneer in the field of fetal anesthesia since 1997 and has done anesthesia for more fetal surgeries than anyone in the world.
"It's not even close," he said "I've personally done around 260 now."
Paschall was part of a team that developed fetal surgery for myelomeningocele, a type of spina bifida where the spine fails to close correctly, leaving it exposed to corrosive amniotic fluid. The result is severe nerve damage, partial paralysis and hydrocephalus, or water on the brain.
Pre-birth intervention has been found to significantly improve outcomes. The target age for these surgeries, Paschall said, is between 21 and 25 weeks of gestational age, which happens to be precisely the age targeted in fetal pain abortion legislation.
These fetuses are not viable outside the womb. But they do, Paschall firmly believes, feel pain. They thus are right in the target zone of fetal pain legislation.
In one of their early surgeries, Paschall says he saw, and Dr. Noel Tullipan felt, a fetus move in response to pain. Paschall said he is "absolutely convinced, 100 percent more than I was even back in 2000, that that was a purposeful movement away from a neurosurgeon's knife."
In response, Paschall upped the doses of anesthesia for the fetus, and he has not seen one move in 200 surgeries since. "I would never go back and do less. I might do more."
Paschall's experience butts up against another theory offered by fetal pain skeptics, who argue that the unborn fetus is immersed in a mix of fluids that chemically induce sleep, meaning that even if the brain wiring were in place, the fetus will still be oblivious. Paschall, obviously, doubts this.
"Anyone willing to make absolute statements regarding fetal, infant or adult neural development and processing is a brave person," Paschall said, adding that "the complexities of the brain defy absolute explanation."
Those who doubt that the fetus perceives pain have focused on the link between the thalamus and the cortex, two key parts of the brain which don't fully connect until relatively late in fetal development. The thalamus is the key sensor of pain, the cortex the primary seat of conscious awareness.
Skeptics hold that without that connection the fetus cannot be aware of pain. And they widely hold that this connection doesn't happen until 29 weeks or later.
But not all experts agree.
Anand believes the fetus feels pain through the "subplate," a temporary structure that matures around 18 weeks and recedes after 30 weeks. The subplate provides a possible pathway for pain signals from the thalamus to the cortex. The JAMA article does not dismiss Anand's subplate theory, but it does treat it as unproven.
But pain wiring is, in any case, much more complex and multifaceted than suggested in the simple model of thalamus to cortex signaling, argues Maureen Condic, a neurobiology researcher at the University of Utah Medical School.
Condic argues that the thalamus plays a fairly central role in pain perception even in the adult organism — meaning, if she is right, that the focus on much later development of wiring to the cortex simply misses the point.
In fact, Condic argues that the cortex plays a limited role in pain perception, citing numerous studies that have yet to find any significant portion of the cortex that responds to painful stimuli. "You can map out what the brain is doing," Condic said, and in studies, "thousands upon thousands of cortical sites have been stimulated without finding any place in the cortex where people report pain."
Condic is equally dismissive on the timing of brain wiring. "The brain develops over a very long period of time," she said. "The earliest stage of brain development is probably 20 days post-fertilization, but the brain continues to develop until roughly the mid-20s. So young adults do not have a fully developed brain."
"I sometimes tell my teenagers that they are not fully human because their cortex isn't fully wired," Condic said.
Perception and awareness
Condic sees the “perception” debate as a philosophical dispute, not a scientific one.
"One camp gives a fundamentally psychological definition of pain perception," she said. "They say that to experience pain you must have conscious awareness. That, they argue, requires life experience to put sensations in context."
On the other side are those who, like Condic, see pain mainly as a biological reaction to trauma, one easily centered in the thalamus long before (and long after) the cortex is involved.
This expansive view of early pain builds on Anand's early research, which demonstrated that anesthesia could reduce neonatal mortality at a time when newborns were thought not to feel pain.
Condic points to studies where an animal's cortex was removed but the animal still responded to pain. She also points to research on hydranencephaly, in which the cortex simply does not develop and the space is filled with fluid instead. That research indicates that such children are conscious and respond to pleasure and pain despite not having a cortex at all, Condic said.
In short, Condic argues for a complex view of pain and consciousness in which pathways to the cortex are not the be-all and end-all.
The notion that pain hinges on conscious experience rather than on brain development is taken to extremes by some experts that, in some cases, push pain and personhood well beyond birth itself.
A 2011 article in the Journal of Medical Ethics, entitled "After-birth abortion: why should the baby live?" argues that both a fetus and a newborn are "potential persons," not "actual persons," and thus "abortion" should be legal even after birth.
"If a behavioral and neural reaction" to a noxious stimulus is considered sufficient for pain," the authors write, "then pain is possible from 24 weeks and probably much earlier. If a conceptual subjectivity is considered necessary for pain, however, then pain is not possible at any gestational age."
"Regardless of how pain is defined, it is clear that pain for conceptual beings is qualitatively different than pain for non-conceptual beings. It is therefore a mistake to draw an equivalence between fetal pain and pain in the older infant or adult," the authors conclude.
Stuart Derbyshire, a British psychologist and one of the most outspoken fetal pain skeptics, takes a similar stance in a widely-cited 2006 British Medical Journal piece, arguing that "psychological processes" center on "people, objects and symbols" that are "outside the brain."
"If pain also depends on content derived from outside the brain," Derbyshire concludes, "then fetal pain cannot be possible, regardless of neural development."
Not even a complete link between the cortex and thalamus would thus satisfy Derbyshire, who insists that pain requires experience only gained with time. Even a full-term newborn fails that test.
Back in St. Louis, Cole says no one really knows if a fetus feels pain. Cole does not himself stake a position on the fetal pain question, nor on the abortion policy implications.
"There is not a definitive source of knowledge about this," he said. "It is very hard to measure these things. Today, I'm not sure we have any reliable or defensible methods for measuring fetal response to pain."
Cole said that he definitely sees early preemies, like the Puente twins, showing strong responses to heal pricks and other intrusions. The surrogate measure like heart rate, hormonal responses and grimacing are all real, Cole acknowledges, but he can't say for sure what they mean.
"If you want to anchor legislation in science, you are going to have a hard time right now," Cole said.
Cole thus steers a middle ground. On the one side are experts, like Anand and Paschall, who argue emphatically for what they have observed. On the other side are the "perception and awareness" advocates like Derbyshire, who argue that only social awareness after birth counts for pain perception.
The question then becomes which side benefits from ambiguity.
Does the legislative and judicial default in U.S. law stick with the viability standard laid down in Roe v. Wade?
Or does medical ambiguity around fetal pain nudge public opinion toward earlier abortion regulation, more in line with European countries, where abortion limits after 12 weeks of gestation quite common?
Maureen Condic accepts that there is unclarity on the "psychological experience of pain," but holds on a biological level things are much more clear.
Condic accepts that there is no clarity on the "psychological experience of pain," but holds that on a biological level things are much more clear. "This is not so much a medical ambiguity," she said, "as it is an opportunity for us to consider what kind of society we want to be. And I think there is sufficient uncertainty to warrant giving the fetus the benefit of the doubt."
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