There’s a bill currently in the house and senate addressing the issue of fetal pain, and what doctors should say to mothers that need abortions for fetuses beyond 22 weeks gestational age. Naturally, given the subject matter, it’s controversial. A week ago, a review was published in the prominent medical journal JAMA, which surveyed the medical and scientific field and found the bill wanting. It made the news. A day later, it was revealed that 1 of 5 authors had a prior connection to the pro-choice movement, one performed abortions. They were accused of bias; they disagreed. It also made the news. In all of this, the review it self was hard to obtain, so most of the disagreement and conflict occurred without direct reference to the meat of the paper. If there’s one call for action from this mess, it’s this: open the access to this and similar papers. It’s simply atrocious that as arguments progress in this area few will go through the trouble that I did to obtain the paper – signing up, providing personal information, and paying twelve dollars.
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But back to the bill, back to the science. The proposed legislation, the fetal pain bill, would require doctors to tell mothers needing abortions for fetuses of 22 weeks gestational age (20 weeks post-fertilization age) that fetuses feel pain. The bill includes a script that the doctor must use, which includes this: “The Congress of the United States has determined that at this stage of development, an unborn child has the physical structures necessary to experience pain.” The bill also requires doctors to suggest the use of fetal anesthetics.
Can we believe the accuracy of what “the Congress of the United States has determined”? The review article recently published in JAMA – “Fetal Pain: A systematic multidisciplinary review of the evidence” – does not. The authors, Lee et al from UCSF, state that what evidence there is on fetal pain suggests it occurs only after 29 weeks, gestational age – not the 22 weeks of the bill. The paper also summarizes the literature on fetal anesthetic procedures and tell us that fetal anesthetics and analgesics are currently used not to reduce pain, but to extend mortality of fetuses or neonates (for example, it helps immobilize them during surgical procedures, in this way making the surgeries more effective, and the chance of survival post-surgery, greater) Instead, there’s ample evidence that these fetal anesthetics reduce the chances of the mothers survival.
For a complex issue, and one characterized primarily by sparse information, the review assesses evidence on the multiple fronts necessary to understand what kind of legislation if any should be passed – pain for the fetus, survival for the mother, and the current state of fetal anesthetics.
The response to the papers content, both as expressed in the press and on right-to-life websites, has focused on the issue of pain – for the fetus. Dissenters point to evidence that pain is felt by the fetus at 22 weeks – fetuses at this age will show reactions to touch. At 23-24 weeks, according to the one scientist most prominently quoted, neonates will ‘cry’ when blood is drawn. These reactions are similar to our immediate physical reactions to touch, a cut or burn, etc. No one’s disagreed (yet) on the existence of these reactions and the fetal age at which they occur. The disagreement lies in interpretation. Some scientists (at least one) pro-life activists and the authors of the bill seem to think that this is an obvious marker of pain. Other scientists, and I will add pretty standard neuroscience, believe that nociception (stimulation of receptors of ‘pain’ on our skin), and reflexive reactions are distinct from perceived pain. Distinct to the extent that pain can occur without physical stimulus or reactions – for example pain can be felt in anticipation of a learned scenario, and also most strikingly from phantom limbs in adults, where there’s actually no physical stimulus at the time of the perception. It’s also generally agreed that to feel pain requires a functioning cortex.
So, do fetuses have cortexes at 22 weeks? Sort of, it’s developing. But what’s also only just developing at this time are the nerves that carry information from the periphery, feet, hands, legs and body – to the cortex. These nerves first grow to the thalamus, and then nerves from the thalamus grow towards and synapse onto the cortex. Here the evidence (not disputed as far as I can tell) is that thalamic neurons develop and reach the cortical plate at 23-24 weeks. Perhaps these are the ‘structures required to feel pain’ to which the bill refers – although this is still later than the 22 weeks mentioned. However, these ‘structures’ are just that – physical structures, the conduits for future communications. The nerves from the thalamus grow into the cortical plate by 23-24 weeks (undisputed) but once there, do they do anything? Again, standard development neuroscience fare is that there’s a lag between development of physical synapses and any functioning electrophysiology. Standard, only because all the evidence across species, development stage, and experiment-type reveal this two-staged activation of synapses. So as physical structures, the synapses between the rest of our body and our cortex, get cemented by 23-24 weeks, but do they fire up immediately? From Lee et al, the earliest signs of a ‘proper’ evoked electric potential (activate a neuron near the skin and see if the cortical neurons fires in response) or EEGs that look like sleep-wake cycles occur at 29-30 weeks. Therefore, say Lee et al, the earliest evidence for perceived pain in the fetus is at 29 weeks gestation age. Prior to this time, the nerves in the body that are receiving information about potential pain can’t even convey the information to the cortex. No cortical connection, no pain.
In my mind, there are wrinkles to the fetal pain story from Lee et al’s review. For something as complex as connecting our knowledge of the human fetus with our understanding of the neuroscience behind the cognitive percept of pain, it’s to be expected. Here are my questions: There’s a cortical subplate to which thalamic neurons make connections in gestation weeks 20-22. The subplate is a transient structure, but its thought to help the growth of thalamic neurons into the cortex. But are subplate neurons themselves making connections to the cortex earlier than 29 weeks, and as such proxying for thalamic-cortical connections? I couldn’t tell from the review. The EEG data in my mind is full of questions just because, as Lee et al themselves describe, neonatal baseline EEGs are different from adult baseline EEGs. This makes assessing the first ‘normal’ occurrence of an evoked potential in the fetus or neonate a little tenuous. Finally, I’d want to know more about the various hormonal responses that do occur in fetuses at 20 weeks or younger. Although here too, hormonal reactions are not in and of themselves predictors of pain – or a functioning cortex.
Others’ critiques of the JAMA review, and/or supporters of the bill focus only on the fetal pain issue rather than other aspects of the paper. The power of the review, though is not just its summary of the evidence on fetal pain, but in its review of the balance of evidence on pain, anesthetics, and mortality for both mother and fetus. That’s why it’s the sum total of the review that Lee et al present that’s key in informing the debate on the fetal pain bill. After all, the bill is not just about getting doctors to present seemingly factual information that may or may not be accurate about the percept of pain. Instead, it’s about providing information and suggestions that can negatively impact a mothers life.
But wait. Is the review it self believable? A day after the review was published came another sort of reaction. One of the authors worked with NARAL pro-choice America, the other performs abortions. The criticism: the authors should have revealed these potential sources of bias.
I absolutely agree. They should have, certainly for the NARAL connection. It’s a little less clear with the doctor performing abortions, but it wouldn’t have hurt. Given such an obviously charged arena, with an obvious political and legislative context that the authors themselves use to frame the paper, it’s disingenuous of those fingered for conflict of interest or potential bias to say that it’s not an issue.
That the authors didn’t bring up their personal politics shouldn’t be surprising to anyone. As a start, conflicts of interest are narrowly defined in scientific publishing as ‘financial connections’. The several paragraphs in JAMA’s disclosure rules focus on financial interests, of which the authors have none, nor are they accused of having any. Although there’s a phrase in the disclosure requirements on ‘personal relationships’ the meaning of which is left ambiguous – for example, personal relationships to what, and when? And beyond this, there is a deep cultural issue in science of assuming objectivity even in the face of obvious sources of conscious – or unconscious potential bias. The methodology of science is solid and powerful, but scientists are still human beings. Scientists choose questions, frame issues, and can miss things – because of default assumptions and inherent biases. If the potential for bias is acknowledged in a broad sense in the medical and scientific communities, then across the board we would have won one small battle in improving our quest for truth. But that’s another war. Here, the critiques brought up about the authors are not about the culture of science in general, or the nature of bias, but just about implications for this one paper.
So what can we pull out of the paper it self as being problematic? I haven’t heard about anything disagreed with in content – other than the one major interpretative difference on reflexes and pain. I read the review, and it seems transparent in methodology, as much as can be in a review. If there were only a couple of authors on the review, I might consider it more likely that in framing and emphasis we’d see more obvious impact of individual authors bias. But there were a total of five authors. Given this I rest mostly easy until I can find the evidence for bias having influenced method and results. In fact, one of the powers of the review is the diversity of (medical) background of the authors, bringing overlapping but distinct expertise to the review. And beyond the five authors, the article was peer-reviewed prior to publication by additional scientists. Not bullet-proof, but not too shabby.
So, back to the bill. As the prelude to the bill, some ‘findings’ are referenced. These, I presume, form the ‘factual’ basis for the rest of the bill. I’ve selected four from the seven findings:
(1) At least 20 weeks after fertilization, an unborn child has the physical structures necessary to experience pain.
(2) There is substantial evidence that by 20 weeks after fertilization, unborn children draw away from certain stimuli in a manner which in an infant or an adult would be interpreted as a response to pain.
(3) Anesthesia is routinely administered to unborn children who have developed 20 weeks or more past fertilization who undergo prenatal surgery.
(6) Medical science is capable of reducing such pain through the administration of anesthesia or other pain-reducing drugs directly to the unborn child.
Lee et al show through a consideration of others’ work, that the physical structures necessary to experience pain do not exist for a fetus 20 weeks after fertilization, unless one believes that reflexive actions imply the perception of pain. Drawing away from a stimulus is not interpreted as a response to pain in adults. It’s interpreted as existence of the appropriate nociceptive reflex. We learned this very early on in neuroscience graduate school, in fact it was drilled into us. Anesthesia is administered to neonates, but not for the purpose of reducing pain, instead, to make it more likely that a neonate can survive surgical procedures. And finally, there is no evidence that medical science is currently capable of reducing fetal ‘pain’, were it to exist. Instead there is ample evidence that administering these anesthetics to the fetus can harm the mother, to the extent of killing her.
Epilogue: Derivative Ping Pong
Now for the real pain. You may or may not agree with my review and analysis of the JAMA paper. But at least you should know that I *did* read the paper. I also read one other paper referenced on pro-life sites, and of course I read the articles in USA Today, LA times, NY Times, Forbes, the International Herald Tribune, CNN, SF Chronicle and more. But getting to the original JAMA article, on a subject clearly pertinent to me and my decisions (I want to have children) was certainly not easy. The article wasn’t available freely on-line, not as in beer, and not as in speech. I had to find the article on JAMA’s web-site, sign up for an account, and pay 12 dollars to actually read what others were derivatively going back and forth on.
If ever there were an argument for open access to medical publishing, it’s this article. How can we hope to get beyond superficial debate if we don’t even have access to the primary material? I’m putting a call out right now, that if JAMA has any moral sense of duty as per its medical mission, they should make the article freely available and easily accessible. This way people can actually read what they subsequently argue about.
You may disagree with me, but if you don’t have the article in front of you, it would be hard to have an even-handed discussion of points. We’d have lost before we’d begun. Even I wouldn’t enjoy that argument.
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My disclosures: I got my Ph.D. in neuroscience from UCSF. I believe it’s very important to keep pushing the boundaries of knowledge on the status of a fetus. I also believe that there’s a historical bias in our society towards undervaluing the life of a mother and the freedom of a woman.
A note on ages: Gestational age, used in the JAMA review, is age from fertilization + 2 weeks. The bill mentions fetal age 20 weeks from fertilization, which I’ve converted to 22 weeks gestational age. I’ve tried to be consistent and refer to all ages as gestational age.
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