The First Ache
- By ANNIE MURPHY PAUL Published: February 10, 2008
Twenty-five years ago, when Kanwaljeet Anand was a medical resident in a neonatal intensive care unit, his tiny patients, many of them preterm infants, were often wheeled out of the ward and into an operating room. He soon learned what to expect on their return. The babies came back in terrible shape: their skin was gray, their breathing shallow, their pulses weak. Anand spent hours stabilizing their vital signs, increasing their oxygen supply and administering insulin to balance their blood sugar.
"What's going on in there to make these babies so stressed?" Anand wondered. Breaking with hospital practice, he wrangled permission to follow his patients into the O.R. "That's when I discovered that the babies were not getting anesthesia," he recalled recently. Infants undergoing major surgery were receiving only a paralytic to keep them still. Anand's encounter with this practice occurred at John Radcliffe Hospital in Oxford, England, but it was common almost everywhere. Doctors were convinced that newborns' nervous systems were too immature to sense pain, and that the dangers of anesthesia exceeded any potential benefits.
Anand resolved to find out if this was true. In a series of clinical trials, he demonstrated that operations performed under minimal or no anesthesia produced a "massive stress response" in newborn babies, releasing a flood of fight-or-flight hormones like adrenaline and cortisol. Potent anesthesia, he found, could significantly reduce this reaction. Babies who were put under during an operation had lower stress-hormone levels, more stable breathing and blood-sugar readings and fewer postoperative complications. Anesthesia even made them more likely to survive. Anand showed that when pain relief was provided during and after heart operations on newborns, the mortality rate dropped from around 25 percent to less than 10 percent. These were extraordinary results, and they helped change the way medicine is practiced. Today, adequate pain relief for even the youngest infants is the standard of care, and the treatment that so concerned Anand two decades ago would now be considered a violation of medical ethics.
But Anand was not through with making observations. As NICU technology improved, the preterm infants he cared for grew younger and younger — with gestational ages of 24 weeks, 23, 22 — and he noticed that even the most premature babies grimaced when pricked by a needle. "So I said to myself, Could it be that this pain system is developed and functional before the baby is born?" he told me in the fall. It was not an abstract question: fetuses as well as newborns may now go under the knife. Once highly experimental, fetal surgery — to remove lung tumors, clear blocked urinary tracts, repair malformed diaphragms — is a frequent occurrence at a half-dozen fetal treatment centers around the country, and could soon become standard care for some conditions diagnosed prenatally like spina bifida. Whether the fetus feels pain is a question that matters to the doctor wielding the scalpel.
And it matters, of course, for the practice of abortion. Over the past four years, anti-abortion groups have turned fetal pain into a new front in their battle to restrict or ban abortion. Anti-abortion politicians have drafted laws requiring doctors to tell patients seeking abortions that a fetus can feel pain and to offer the fetus anesthesia; such legislation has already passed in five states. Anand says he does not oppose abortion in all circumstances but says decisions should be made on a case-by-case basis. Nonetheless, much of the activists' and lawmakers' most powerful rhetoric on fetal pain is borrowed from Anand himself.
Known to all as Sunny, Anand is a soft-spoken man who wears the turban and beard of his Sikh faith. Now a professor at the University of Arkansas for Medical Sciences and a pediatrician at the Arkansas Children's Hospital in Little Rock, he emphasizes that he approaches the question of fetal pain as a scientist: "I eat my best hypotheses for breakfast," he says, referring to the promising leads he has discarded when research failed to bear them out. New evidence, however, has persuaded him that fetuses can feel pain by 20 weeks gestation (that is, halfway through a full-term pregnancy) and possibly earlier. As Anand raised awareness about pain in infants, he is now bringing attention to what he calls "signals from the beginnings of pain."
But these signals are more ambiguous than those he spotted in newborn babies and far more controversial in their implications. Even as some research suggests that fetuses can feel pain as preterm babies do, other evidence indicates that they are anatomically, biochemically and psychologically distinct from babies in ways that make the experience of pain unlikely. The truth about fetal pain can seem as murky as an image on an ultrasound screen, a glimpse of a creature at once recognizably human and uncomfortably strange.
IF THE NOTION that newborns are incapable of feeling pain was once widespread among doctors, a comparable assumption about fetuses was even more entrenched. Nicholas Fisk is a fetal-medicine specialist and director of the University of Queensland Center for Clinical Research in Australia. For years, he says, "I would be doing a procedure to a fetus, and the mother would ask me, 'Does my baby feel pain?' The traditional, knee-jerk reaction was, 'No, of course not.' " But research in Fisk's laboratory (then at Imperial College in London) was making him uneasy about that answer. It showed that fetuses as young as 18 weeks react to an invasive procedure with a spike in stress hormones and a shunting of blood flow toward the brain — a strategy, also seen in infants and adults, to protect a vital organ from threat. Then Fisk carried out a study that closely resembled Anand's pioneering research, using fetuses rather than newborns as his subjects. He selected 45 fetuses that required a potentially painful blood transfusion, giving one-third of them an injection of the potent painkiller fentanyl. As with Anand's experiments, the results were striking: in fetuses that received the analgesic, the production of stress hormones was halved, and the pattern of blood flow remained normal.
Fisk says he believes that his findings provide suggestive evidence of fetal pain — perhaps the best evidence we'll get. Pain, he notes, is a subjective phenomenon; in adults and older children, doctors measure it by asking patients to describe what they feel. ("On a scale of 0 to 10, how would you rate your current level of pain?") To be certain that his fetal patients feel pain, Fisk says, "I would need one of them to come up to me at the age of 6 or 7 and say, 'Excuse me, Doctor, that bloody hurt, what you did to me!' " In the absence of such first-person testimony, he concludes, it's "better to err on the safe side" and assume that the fetus can feel pain starting around 20 to 24 weeks.
Blood transfusions are actually among the least invasive medical procedures performed on fetuses. More intrusive is endoscopic fetal surgery, in which surgeons manipulate a joystick-like instrument while watching the fetus on an ultrasound screen. Most invasive of all is open fetal surgery, in which a pregnant woman's uterus is cut open and the fetus exposed. Ray Paschall, an anesthesiologist at Vanderbilt Medical Center in Nashville, remembers one of the first times he provided anesthesia to the mother and minimally to the fetus in an open fetal operation, more than 10 years ago. When the surgeon lowered his scalpel to the 25-week-old fetus, Paschall saw the tiny figure recoil in what looked to him like pain. A few months later, he watched another fetus, this one 23 weeks old, flinch at the touch of the instrument. That was enough for Paschall. In consultation with the hospital's pediatric pain specialist, "I tremendously upped the dose of anesthetic to make sure that wouldn't happen again," he says. In the more than 200 operations he has assisted in since then, not a single fetus has drawn back from the knife. "I don't care how primitive the reaction is, it's still a human reaction," Paschall says. "And I don't believe it's right. I don't want them to feel pain."
But whether pain is being felt is open to question. Mark Rosen was the anesthesiologist at the very first open fetal operation, performed in 1981 at the University of California, San Francisco, Medical Center, and the fetal anesthesia protocols he pioneered are now followed by his peers all over the world. Indeed, Rosen may have done more to prevent fetal pain than anyone else alive — except that he doesn't believe that fetal pain exists. Research has persuaded him that before a point relatively late in pregnancy, the fetus is unable to perceive pain.
Rosen provides anesthesia for a number of other important reasons, he explains, including rendering the pregnant woman unconscious and preventing her uterus from contracting and setting off dangerous bleeding or early labor. Another purpose of anesthesia is to immobilize the fetus during surgery, and indeed, the drugs Rosen supplies to the pregnant woman do cross the placenta to reach the fetus. Relief of fetal pain, however, is not among his objectives. "I have every reason to want to believe that the fetus feels pain, that I've been treating pain all these years," says Rosen, who is intense and a bit prickly. "But if you look at the evidence, it's hard to conclude that that's true."
Rosen's own hard look at the evidence came a few years ago, when he and a handful of other doctors at U.C.S.F. pulled together more than 2,000 articles from medical journals, weighing the accumulated evidence for and against fetal pain. They published the results in The Journal of the American Medical Association in 2005. "Pain perception probably does not function before the third trimester," concluded Rosen, the review's senior author. The capacity to feel pain, he proposed, emerges around 29 to 30 weeks gestational age, or about two and a half months before a full-term baby is born. Before that time, he asserted, the fetus's higher pain pathways are not yet fully developed and functional.
What about a fetus that draws back at the touch of a scalpel? Rosen says that, at least early on, this movement is a reflex, like a leg that jerks when tapped by a doctor's rubber mallet. Likewise, the release of stress hormones doesn't necessarily indicate the experience of pain; stress hormones are also elevated, for example, in the bodies of brain-dead patients during organ harvesting. In order for pain to be felt, he maintains, the pain signal must be able to travel from receptors located all over the body, to the spinal cord, up through the brain's thalamus and finally into the cerebral cortex. The last leap to the cortex is crucial, because this wrinkly top layer of the brain is believed to be the organ of consciousness, the generator of awareness of ourselves and things not ourselves (like a surgeon's knife). Before nerve fibers extending from the thalamus have penetrated the cortex — connections that are not made until the beginning of the third trimester — there can be no consciousness and therefore no experience of pain.
Sunny Anand reacted strongly, even angrily, to the article's conclusions. Rosen and his colleagues have "stuck their hands into a hornet's nest," Anand said at the time. "This is going to inflame a lot of scientists who are very, very concerned and are far more knowledgeable in this area than the authors appear to be. This is not the last word — definitely not." Anand acknowledges that the cerebral cortex is not fully developed in the fetus until late in gestation. What is up and running, he points out, is a structure called the subplate zone, which some scientists believe may be capable of processing pain signals. A kind of holding station for developing nerve cells, which eventually melds into the mature brain, the subplate zone becomes operational at about 17 weeks. The fetus's undeveloped state, in other words, may not preclude it from feeling pain. In fact, its immature physiology may well make it more sensitive to pain, not less: the body's mechanisms for inhibiting pain and making it more bearable do not become active until after birth.
The fetus is not a "little adult," Anand says, and we shouldn't expect it to look or act like one. Rather, it's a singular being with a life of the senses that is different, but no less real, than our own.
THE SAME MIGHT be said of the five children who were captured on video by a Swedish neuroscientist named Bjorn Merker on a trip to Disney World a few years ago. The youngsters, ages 1 to 5, are shown smiling, laughing, fussing, crying; they appear alert and aware of what is going on around them. Yet each of these children was born essentially without a cerebral cortex. The condition is called hydranencephaly, in which the brain stem is preserved but the upper hemispheres are largely missing and replaced by fluid.
Merker (who has held positions at universities in Sweden and the United States but is currently unaffiliated) became interested in these children as the living embodiment of a scientific puzzle: where consciousness originates. He joined an online self-help group for the parents of children with hydranencephaly and read through thousands of e-mail messages, saving many that described incidents in which the children seemed to demonstrate awareness. In October 2004, he accompanied the five on the trip to Disney World, part of an annual get-together for families affected by the condition. Merker included his observations of these children in an article, published last year in the journal Behavioral and Brain Sciences, proposing that the brain stem is capable of supporting a preliminary kind of awareness on its own. "The tacit consensus concerning the cerebral cortex as the 'organ of consciousness,' " Merker wrote, may "have been reached prematurely, and may in fact be seriously in error."
Merker's much-discussed article was accompanied by more than two dozen commentaries by prominent researchers. Many noted that if Merker is correct, it could alter our understanding of how normal brains work and could change our treatment of those who are now believed to be insensible to pain because of an absent or damaged cortex. For example, the decision to end the life of a patient in a persistent vegetative state might be carried out with a fast-acting drug, suggested Marshall Devor, a biologist at the Center for Research on Pain at Hebrew University in Jerusalem. Devor wrote that such a course would be more humane than the weeks of potentially painful starvation that follows the disconnection of a feeding tube (though as a form of active euthanasia it would be illegal in the United States and most other countries). The possibility of consciousness without a cortex may also influence our opinion of what a fetus can feel. Like the subplate zone, the brain stem is active in the fetus far earlier than the cerebral cortex is, and if it can support consciousness, it can support the experience of pain. While Mark Rosen is skeptical, Anand praises Merker's work as a "missing link" that could complete the case for fetal pain.
But anatomy is not the whole story. In the fetus, especially, we can't deduce the presence or absence of consciousness from its anatomical development alone; we must also consider the peculiar environment in which fetuses live. David Mellor, the founding director of the Animal Welfare Science and Bioethics Center at Massey University in New Zealand, says he was prompted to consider the role of fetal surroundings in graduate school. "Have you ever wondered," one visiting professor asked, "why a colt doesn't get up and gallop around inside the mare?" After all, a horse only minutes old is already able to hobble around the barnyard. The answer, as Mellor reported in an influential review published in 2005, is that biochemicals produced by the placenta and fetus have a sedating and even an anesthetizing effect on the fetus (both equine and human). This fetal cocktail includes adenosine, which suppresses brain activity; pregnanolone, which relieves pain; and prostaglandin D2, which induces sleep — "pretty potent stuff," he says.
Combined with the warmth and buoyancy of the womb, this brew lulls the fetus into a near-continuous slumber, rendering it effectively unconscious no matter what the state of its anatomy. Even the starts and kicks felt by a pregnant woman, he says, are reflex movements that go on in a fetus's sleep. While we don't know if the intense stimulation of surgery would wake it up, Mellor notes that when faced with other potential threats, like an acute shortage of oxygen, the fetus does not rouse itself but rather shuts down more completely in an attempt to conserve energy and promote survival. This is markedly different from the reaction of an infant, who will thrash about in an effort to dislodge whatever is blocking its airway. "A fetus," Mellor says, "is not a baby who just hasn't been born yet."
Even birth may not inaugurate the ability to feel pain, according to Stuart Derbyshire, a psychologist at the University of Birmingham in Britain. Derbyshire is a prolific commentator on the subject and an energetic provocateur. In milder moods, he has described the notion of fetal pain as a "fallacy"; when goaded by his critics' "lazy" thinking, he has pronounced it a "moral blunder" and "a shoddy, sentimental argument."
For all his vehemence in print, Derbyshire is affable in conversation, explaining that his laboratory research on the neurological basis of pain in adults led him to the matter of what fetuses feel: "For me, it's an interesting test case of what we know about pain. It's a great application of theory, basically." The theory, in this case, is that the experience of pain has to be learned — and the fetus, lacking language or interactions with caregivers, has no chance of learning it. In place of distinct emotions, it experiences a blur of sensations, a condition Derbyshire has likened to looking at "a vast TV screen with all of the world's information upon it from a distance of one inch; a great buzzing mass of meaningless information," he writes. "Before a symbolic system such as language, an individual will not know that something in front of them is large or small, hot or cold, red or green" — or, Derbyshire argues, painful or pleasant.
He finds "outrageous" the suggestion that the fetus feels anything like the pain that an older child or an adult experiences. "A fetus is biologically human, of course," he says. "It isn't a cow. But it's not yet psychologically human." That is a status not bestowed at conception but earned with each connection made and word spoken. Following this logic to its conclusion, Derbyshire has declared that babies cannot feel pain until they are 1 year old. His claim has become notorious in pain-research circles, and even Derbyshire says he thinks he may have overstepped. "I sometimes regret that I pushed it out quite that far," he concedes. "But really, who knows when the light finally switches on?"
IN FACT, "THERE may not be a single moment when consciousness, or the potential to experience pain, is turned on," Nicholas Fisk wrote with Vivette Glover, a colleague at Imperial College, in a volume on early pain edited by Anand. "It may come on gradually, like a dimmer switch." It appears that this slow dawning begins in the womb and continues even after birth. So where do we draw the line? When does a release of stress hormones turn into a grimace of genuine pain?
Recent research provides a potentially urgent reason to ask this question. It shows that pain may leave a lasting, even lifelong, imprint on the developing nervous system. For adults, pain is usually a passing sensation, to be waited out or medicated away. Infants, and perhaps fetuses, may do something different with pain: some research suggests they take it into their bodies, making it part of their fast-branching neural networks, part of their flesh and blood.
Anna Taddio, a pain specialist at the Hospital for Sick Children in Toronto, noticed more than a decade ago that the male infants she treated seemed more sensitive to pain than their female counterparts. This discrepancy, she reasoned, could be due to sex hormones, to anatomical differences — or to a painful event experienced by many boys: circumcision. In a study of 87 baby boys, Taddio found that those who had been circumcised soon after birth reacted more strongly and cried for longer than uncircumcised boys when they received a vaccination shot four to six months later. Among the circumcised boys, those who had received an analgesic cream at the time of the surgery cried less while getting the immunization than those circumcised without pain relief.
Taddio concluded that a single painful event could produce effects lasting for months, and perhaps much longer. "When we do something to a baby that is not an expected part of its normal development, especially at a very early stage, we may actually change the way the nervous system is wired," she says. Early encounters with pain may alter the threshold at which pain is felt later on, making a child hypersensitive to pain — or, alternatively, dangerously indifferent to it. Lasting effects might also include emotional and behavioral problems like anxiety and depression, even learning disabilities (though these findings are far more tentative).
Do such long-term effects apply to fetuses? They may well, especially since pain experienced in the womb would be even more anomalous than pain encountered soon after birth. Moreover, the ability to feel pain may not need to be present in order for "noxious stimulation" — like a surgeon's incision — to do harm to the fetal nervous system. This possibility has led some to venture an early end to the debate over fetal pain. Marc Van de Velde, an anesthesiologist and pain expert at University Hospitals Gasthuisberg in Leuven, Belgium, says: "We know that the fetus experiences a stress reaction, and we know that this stress reaction may have long-term consequences — so we need to treat the reaction as well as we can. Whether or not we call it pain is, to me, irrelevant."
BUT THE QUESTION of fetal pain is not irrelevant when applied to abortion. On April 4, 2004, Sunny Anand took the stand in a courtroom in Lincoln, Neb., to testify as an expert witness in the case of Carhart v. Ashcroft. This was one of three federal trials held to determine the constitutionality of the ban on a procedure called intact dilation and extraction by doctors and partial-birth abortion by anti-abortion groups. Anand was asked whether a fetus would feel pain during such a procedure. "If the fetus is beyond 20 weeks of gestation, I would assume that there will be pain caused to the fetus," he said. "And I believe it will be severe and excruciating pain."
After listening to Anand's testimony and that of doctors opposing the law, Judge Richard G. Kopf declared in his opinion that it was impossible for him to decide whether a "fetus suffers pain as humans suffer pain." He ruled the law unconstitutional on other grounds. But the ban was ultimately upheld by the U.S. Supreme Court, and Anand's statements, which he repeated at the two other trials, helped clear the way for legislation aimed specifically at fetal pain. The following month, Sam Brownback, Republican of Kansas, presented to the Senate the Unborn Child Pain Awareness Act, requiring doctors to tell women seeking abortions at 20 weeks or later that their fetuses can feel pain and to offer anesthesia "administered directly to the pain-capable unborn child." The bill did not pass, but Brownback continues to introduce it each year. Anand's testimony also inspired efforts at the state level. Over the past two years, similar bills have been introduced in 25 states, and in 5 — Arkansas, Georgia, Louisiana, Minnesota and Oklahoma — they have become law. In addition, state-issued abortion-counseling materials in Alaska, South Dakota and Texas now make mention of fetal pain.
In the push to pass fetal-pain legislation, Anand's name has been invoked at every turn; he has become a favorite expert of the anti-abortion movement precisely because of his credentials. "This Oxford- and Harvard-trained neonatal pediatrician had some jarring testimony about the subject of fetal pain," announced the Republican congressman Mike Pence to the House of Representatives in 2004, "and it is truly made more astonishing when one considers the fact that Dr. Anand is not a stereotypical Bible-thumping pro-lifer." Anand maintains that doctors performing abortions at 20 weeks or later should take steps to prevent or relieve fetal pain. But it is clear that many of the anti-abortion activists who quote him have something more sweeping in mind: changing perceptions of the fetus. In several states, for example, information about fetal pain is provided to all women seeking abortions, including those whose fetuses are so immature that there is no evidence of the existence of even a stress response. "By personifying the fetus, they're trying to steer the woman's decision away from abortion," says Elizabeth Nash, a public-policy associate at the Guttmacher Institute, a reproductive-rights group.
Another, perhaps intended, effect of fetal-pain laws may be to make abortions harder to obtain. Laura Myers, an anesthesia researcher at Children's Hospital Boston and Harvard Medical School who analyzed the Unborn Child Protection Act for the abortion-rights organization Physicians for Reproductive Choice and Health, concluded that abortion clinics do not have the equipment or expertise to supply fetal anesthesia. "The handful of centers that perform fetal surgery are the only ones with any experience delivering anesthesia directly to the fetus," Myers says. "The bill makes a promise that the medical community can't fulfill." Even these specialized centers have no experience providing fetal anesthesia during an abortion; such a procedure would be experimental and would inevitably carry risks for the woman, including infection and uncontrolled bleeding.
In his speeches about fetal pain, Senator Brownback often asks why a fetus undergoing surgery receives anesthesia but not a fetus "who is undergoing the life-terminating surgery of an abortion." Mark Rosen rejects the analogy. "Fetal surgery is a different circumstance than abortion," he says, pointing out that none of the objectives of anesthesia for fetal surgery — relaxing the uterus, for example — apply to the termination of pregnancy. That includes an objective identified just recently: preventing possible long-term damage. For the fetus that is to be aborted, there is no long term. And if there is no pain, as Rosen maintains, then there is no cause to put the woman's health at risk.
Rosen sees no contradiction in his position, only a necessary complexity. When he was in medical school, he says, he worked for a time at an abortion clinic in the morning and a fertility clinic in the afternoon — an experience that showed him "the amazing incongruities of life." In the three decades since then, he says he has come to believe that "there's a time for fetal anesthesia, and maybe there's a time not."
In their use of pain to make the fetus seem more fully human, anti-abortion forces draw on a deep tradition. Pain has long played a special role in how society determines who is like us or not like us ("us" being those with the power to make and enforce such distinctions). The capacity to feel pain has often been put forth as proof of a common humanity. Think of Shylock's monologue in "The Merchant of Venice": Are not Jews "hurt with the same weapons" as Christians, he demands. "If you prick us, do we not bleed?" Likewise, a presumed insensitivity to pain has been used to exclude some from humanity's privileges and protections. Many 19th-century doctors believed blacks were indifferent to pain and performed surgery on them without even that era's rudimentary anesthesia. Over time, the charmed circle of those considered alive to pain, and therefore fully human, has widened to include members of other religions and races, the poor, the criminal, the mentally ill — and, thanks to the work of Sunny Anand and others, the very young. Should the circle enlarge once more, to admit those not yet born? Should fetuses be added to what Martin Pernick, a historian of the use of anesthesia, has called "the great chain of feeling"? Anand maintains that they should.
For others, it's a harder call. When it comes to the way adults feel pain, science has borne out the optimistic belief that we are all the same under the skin. As research is now revealing, the same may not be true for fetuses; even Anand calls the fetus "a unique organism." Exhibiting his flair for the startling but apt expression, Stuart Derbyshire warns against "anthropomorphizing" the fetus, investing it with human qualities it has yet to develop. To do so, he suggests, would subtract some measure of our own humanity. And to concern ourselves only with the welfare of the fetus is to neglect the humanity of the pregnant woman, Mark Rosen notes. When considering whether to provide fetal anesthesia during an abortion, he says, it's not "erring on the safe side" to endanger a woman's health in order to prevent fetal pain that may not exist.
Indeed, the question remains just how far we would take the notion that the fetus is entitled to protection from pain. Would we be willing, for example, to supply a continuous flow of drugs to a fetus that is found to have a painful medical condition? For that matter, what about the pain of being born? Two years ago, a Swiftian satire of the Unborn Child Pain Awareness Act appeared on the progressive Web site AlterNet.org. Written by Lynn Paltrow, the executive director of the National Advocates for Pregnant Women, it urged the bill's authors to extend its provisions to those fetuses "subjected to repeated, violent maternal uterine contraction and then forced through the unimaginably narrow vaginal canal."
She continued: "Imagine the pain a fetus experiences with a forceps delivery, suffering extensive bruising during and after! Shouldn't these fetuses also be entitled to their own painkillers?" And in fact, both Nicholas Fisk and Marc Van de Velde have raised the possibility of administering pain relief to fetuses undergoing difficult deliveries. Obstetricians have yet to embrace the proposal. But Sunny Anand, for one, says the idea may have merit. Though he has "misgivings about messing with a process that has worked for thousands of years," he can envision an injection of local anesthetic into the fetus's scalp where it is grasped by the forceps or vacuum device. "Let's try and work out what's best for the baby," he says.
Annie Murphy Paul is at work on a book about the lasting effects of early experience.
http://www.nytimes.com/2008/02/10/magazine/10Fetal-t.html?ref=magazine&pagewanted=all
