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Breastfeeding, infant hyperbilirubinemia, statistical graphics, and modern medicine

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So by now the cat is out of the bag, so to speak. My son Nicolas was born Tues May 4, 2010, so I am going to add a new topic to the blog to do with science and medicine related to Pediatric care. I am very interested in the transition that medicine is undergoing from a purely model driven art to an evidence and model driven science. You might think that this would have happened say in the 1940's or so at the dawn of modern medicine (development of vaccines and antibiotics) but it really hasn't even now become a hard science based endeavor. This is in part due to the difficulty of ethical experimentation on humans.

For now, what I want to talk about is related to our experience in the local hospital (to remain anonymous). After arriving in Maternity my wife was on some IV opiate painkiller and recovering from the opiates used in the spinal anesthesia. Unsurprisingly after many many hours of labor followed by C-Section and soforth, she was asleep for quite a few hours, perhaps from 11 AM to 5 PM. The baby, also tired from the whole process, and swaddled by the nurses, slept the whole time as well. Nicolas was born at about 3.5 kg and full term, with 8-9 Apgar score (indicating excellent health) so we were not concerned at this point, we were primarily tired.

Now my wife is exclusively breastfeeding our child, which means that the child's intake of fluids is limited to whatever early colostrum is available. That was counter to the main experience at this hospital. Most people seem to exclusively bottle feed and infants have a very high fluid intake immediately. The hospital room had an HVAC vent running continuously providing perhaps 20% humidity air, acting as an excellent dessicator and a staff of nurses whose primary experiences are with bottle-fed formula babies and many of the nurses spoke English as a second language. We spent much of our waking hours begging for drinking water which was only available behind a locked kitchen door. As an infant, the surface area to volume ratio is much higher, so infants dehydrate even faster than adults. This, together with a total lack of early explanation about the nurses expectations led to a lot of concern on the part of the nurses that the child would become unhealthy through dehydration and starvation. I believe at this point that the nurses dropped the ball in terms of communication, and the ball would stay dropped until the day nurse on Thursday who spoke with a very understandable accent and who clearly cared about communication and was more on board with the breastfeeding experience.

In any case, Wed morning at about 24 hours of age, the nurse came to take a bilirubin screening. This is done with some kind of photometry directly through the skin via a contact probe. Based on the measurement levels from the screening (8 to 10 mg/dL) they decided to do a heel-stick and get a quantitative blood total serum bilirubin level. This came back at about 7.5 mg/dL (if I remember correctly). Based on this reading the nurse station had a chart provided by the AAP (American Academy of Pediatrics) which looks like this:

Bilirubin Risk Chart from AAP

Bilirubin Risk Chart Used by Nurse Station

As you can see from the chart, at 24 hours a 7.5 mg/dL reading would plot in the "high intermediate risk zone". What does that mean? It is my belief that it turns out that no-one really knows what this nomograph means. If you go to the AAP guidelines article (linked above) it appears that this nomograph is designed to help decide whether or not the infant needs bilirubin monitoring (and of course the parents would need jaundice education), it is not an indicator of the need for treatment. An infant that falls in the low risk zone can pretty much be ignored, an infant in higher categories has a risk of developing hyperbilirubinemia requiring treament. The word risk does not refer at this point to the babies health, but rather that there is a probability that phototherapy and other treatment will eventually be required. However, this technical use of the term risk causes potentially quite high stress levels in both nurses and doctors, and then through them to the parents. These stress levels themselves interfere with frequent breastfeeding, which is of course the primary treatment that would be recommended for an otherwise healthy infant since bilirubin is excreted into the gastrointestinal tract and the urine.

Why such a fuss about bilirubin? It's a common issue that babies experience some amount of jaundice. This can be caused by a variety of factors which you can read about elsewhere. However the wikipedia article points out that in infants, especially pre-term infants, the blood-brain barrier is not well established, and therefore bilirubin can enter the brain where it can cause brain damage if it remains high enough.

The AAP guidelines go on beyond this initial nomograph to figures 3 and 4 which are the guidelines for starting phototherapy, and then for initiating an exchange transfusion, a highly invasive operation in which the baby's blood is replaced with donor blood to prevent Kernicterus, a kind of permanent brain damage. These graphs look like this:

For Initiation of Phototherapy:

Phototherapy initiation chart (AAP)

Chart published by AAP for initiation of phototherapy

For Transfusion:

AAP chart for initiation of exchange transfusion

AAP chart for initiation of exchange transfusion

Back to the Story:

After reading off the initial "High Intermediate Risk Zone" measurement, the Pediatrician was notified.

In the meantime, my wife had an intensive 2 hour one on one session with a lactation consultant who seemed underemployed at this hospital but was extremely helpful and respectful. The net result was that we discovered the main difficulty of getting little Nicolas to eat was his strong sleep response to the warm conditions of swaddling by the somewhat old-fashioned tues evening and wednesday morning nurses.

Throughout the day tues and wed we were asked to keep a record of breastfeeding (time and duration for each breast) and diaper changes (time and color and fluid content), and of course this log was mis-used by the nurses to misinterpret our infrequency of breastfeeding. The form is fairly rigid requiring you to fill in certain boxes for start time, and duration and soforth. There was no way to put in for example a description of the 2 hour lactation consultation in which the baby suckled for say 3 minutes at a time every 15 minutes continuously for 2 hours. Also it was impossible to say that we tried for 1/2 hour on each breast in order to get say 10 mins of total suckling time. At this point I began to keep a more free form journal of the same information but with more extensive comments.

By the afternoon the Pediatrician had ordered continuous dual phototherapy and a second morning heelstick early Thurs to get total serum bilirubin levels after a full night of phototherapy. Practically speaking this means two different lights were to be on him at all times when he was not being breastfed. This pediatrician seemed to be somewhat dismissive of our concerns that this was overkill and would interfere with proper bonding and breastfeeding. She informed us that he was almost in a high risk category (which she clearly interpreted as high risk to his health) and that she wanted us to breastfeed as often as possible and to have the continuous therapy to prevent any danger. Since then, having had plenty of time to carefully read through the guidelines and things I now know what went wrong, and I blame the AAP and their choice of communications methodology. Edward Tufte would not be amused. More on that below.

A plastic temperature controlled incubator was brought into the room, and a combination of a blue/UV fluorescent light and a halogen bulb were trained on him for the duration of the night. To protect his eyes he would wear a so called "Biliband" which is a sort of velcro fastened eye-mask. For the next 12 hours or so (from about 9 PM to 9 AM) he would stay in the incubator (held at 32 degrees C) with these lights shining on him continuously. The UV fluorescent clearly produced ozone in the room which we could smell, and was potentially damaging to our eyes and lungs. The plastic of the incubator most likely protected Nicolas from the UV content but when we asked the nurses they weren't sure what we were talking about, even the NICU nurse who helped set up the incubator. Apparently the blue spectrum of the light is relatively more active at converting bilirubin in the skin into a water soluble form that can be easily excreted. However, the warm temperature of the incubator of course compounded Nicolas' sleepiness and made getting him to suckle more difficult. So while the bilirubin was being solubilized by the light, the heat was preventing us from giving him the food and moisture he needed to excrete it.

Luckily we had brought a copy of the Merk Manual where we could look up some information about bilirubin, and we found that the general levels at which phototherapy were recommended were much higher than the ones quoted to us from the heel stick, so our level of stress over the bilirubin itself was reduced, however the new stress became the frequency with which Nicolas would claw the biliband off his eyes and over his nose, and his resulting breathing distress. Throughout the night she breastfed him at between 1.5 and 3 hour intervals and we constantly had to adjust the band and calm him from struggling in the clearly uncomfortable and scary plastic box.

By Thursday morning the bilirubin level was at 10 mg/dL leaving him in the middle of the low and high intermediate risk zone on their first chart (an inappropriate chart for the use they were putting it to).  We were lucky enough to get a really first rate day nurse (mentioned above) who switched us to in-arm holding of the baby while using a single halogen light and removed the incubator. When the pediatrician returned, she approved the new setup but required a second halogen light. So for the next 12  hours or so Nicolas got breastfeedings while blindfolded and intensively irradiated by halogen lights with his mother and I wearing our sunglasses continuously. This continued throughout the day and next night, until the next morning's heelstick which came back in the low risk zone (again on the first chart). The doctor ordered a final heelstick that afternoon at 4:30 and discharged us after it too came back low risk.

What went wrong? A case of bad statistical communication

Decision making:

Knowing the basic biochemistry of bilirubin toxicity, and the fact that many infants have jaundice and the variety of causes for onset of jaundice is very different from being able to come up with guidelines for treatment. That is why the AAP has put together a specific study group on this problem and they have published the guidelines article above (one version in 1994 and an updated version in 2004). It would surprise me if the Pediatrician had never read the guidelines at all, but it would not surprise me if she were confused. Basically the article is confusing and especially the graphical displays. Contrast the 3 different charts and an associated flow chart for decision making with the following chart developed using the AAP 1994 recommendations at a Kaiser hospital in Colorado:

Mehl's comprehensive chart

Mehl 2004 comprehensive chart based on AAP's guidelines

This comprehensive chart attempts to be a full graphical communication of the essential decision making content of the AAP guidelines. For a given age (in days, x axis) and bilirubin content (presumably mg/dL vertical axis though the lack of a units label is inexcusable) the color zone keys you to a right hand group where the summary of the recommendation from the AAP guidelines (1994) is given. This chart completely ignores the so called "risk type" chart (the first chart from the AAP) which is totally unhelpful for clinical practice since it has nothing to say about actions to take. Instead this chart focuses on the recommendations for treatment. A 3500 g baby presenting with bilirubin levels of 7.5 mg/dL at 1 day age doesn't even qualify for considering phototherapy, even if he were as small as 1500 g less than half his actual size he would not qualify. And yet the first chart above puts such an infant into the "high intermediate risk zone" which no-one actually understands but everyone thinks they understand... in a manner totally devoid of consideration of the size of the infant.

Bilirubin is measured as concentration, which means for a larger infant, at the same concentration, there is more bilirubin, so it might at first seem to be irrelevant what size the infant is. However the toxicity of bilirubin is controlled in part by the undeveloped nature of the blood-brain barrier and other organs such as the liver and gut, so I interpret the AAP recommendations as implying that larger, more mature infants must have healthier organs and blood brain barriers and hence can tolerate more bilirubin.

Treatment:

Suppose for a moment that the guidelines did justify the start of phototherapy, or that the doctor wished to be more cautious due to the presence of the overenthusiastic HVAC or the greater difficulty that a mother with a C-Section delivery might experience in breastfeeding. Does science support the type and degree of phototherapy used?

First of all, what is known about how phototherapy works? We know that bilirubin in the skin is photo-isomerized into a more water soluble form, and then can be excreted more easily. How long does this transformation take? What are the kinetics of this reaction? Is it necessary to irradiate continuously or is it just as good to do intermittent irradiation? How about turning to get all of the skin evenly irradiated? These questions are of significant practical importance, since for the non-critical child, the parents will be caring for and feeding the child during the therapy, and any interference with the feeding and bonding can compound the child's problems.

I found that intermittent treatment is a somewhat controversial subject. This paper from 1984 used a small randomized trial and suggested that intermittent treatment about 1 hour out of 4 was just as good as continuous treatment. More recently, this paper on position changing (turning over) suggested that perhaps changing positions to irradiate more of the skin was actually counterproductive. The idea is that after the bilirubin in the skin has been thoroughly bleached out (about 150 minutes) the light can penetrate into the blood supply below the skin and directly convert a large amount of bilirubin in the blood. So from a practical perspective, perhaps the best method would be to do something like 3 hours at a time (180 mins) every 6 hours which is compatible with the usual breastfeeding schedule of every 2 or 3 hours.

Conclusion:

I'm not a doctor, and this is not to be considered medical advice, but I am a competent reader and interpreter of biological, scientific, and technical articles, and have worked with research biologists both casually and professionally. My reading of these things suggests the following summary:

  • Hyperbilirubinemia is a serious condition, requiring alertness and proper care when present.
  • The AAP has comprehensive clinical guidelines for treatment.
  • The AAP has done a terrible job of communicating their clinical guidelines. Especially graphically.
  • Most doctors and nurses may be unaware of the correct method for using the AAP provided statistical graphics, and standard chart packets may not even include the proper decision making graphs (no-one from the hospital showed me the other two charts at any point in time).
  • Breastfed babies are likely to have higher bilirubin but unless this level reaches action levels suggested by AAP, it is not an unexpected problem, and mothers should just be cautioned to try feedings frequently, and babies should be kept in a not-too-dry climate controlled room.
  • Except in cases of truly high bilirubin heading towards transfusion, intermittent phototherapy would seem to be much preferable due to its lower stress inducement and higher compatibility with parental bonding and breastfeeding. The truth is that the child will probably be on intermittently anyway, so the parents should not be made to feel as if they are compromising treatment.
  • Turning is apparently counterproductive. I think it makes sense to have the child breastfed while lying on his side with his back irradiated by halogen type light, but I could also see intermittent feeding followed by face-up irradiation of the stomach as a good alternative. (Elsewhere you can read about why babies should not sleep on their stomach due to SIDS risk).

I hope this article helps some doctors and nurses somewhere to improve their practice of care for breastfed infants, or helps the parents of newborns to better understand what the clinical reality vs. recommendations are. I also hope this article helps the AAP and doctors in general to improve their communications and to take the practice of statistical decision theory seriously, and consult with statisticians and visualization experts in developing their risk analysis and decision tools. Gone are the days when doctors have the luxury of spending a significant amount of time wading through multiple poorly designed charts and graphs to get to a practical decision. I applaud Mehl for making a strong effort to do a better job of summarizing the clinical guidelines in graphical form.


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