obstetrical pathology

One reasonable cause of unexplained and unexpected fetal death is occlusion of umbilical cord blood flow. Not all potential causes of umbilical cord occlusion would necessarily be evident at delivery. I submitted a study to NIH that aimed to discover the incidence in fetal death of two such “invisible” anatomic configurations. The two configurations are occult cord prolapse and functional short cord segment due to cord wrapping. 

The first is familiar from cases of fetal compromise in livebirths. The cord prolapse puts a loop of cord at two risks for occlusion: First is direct pressure between the presenting part and the uterine wall. The second is the risk of kinking if the loop becomes a “V”. The anatomy and physiology of this kinking is analogous to bending a straw or making a “V” in a soft hose to stop water flow.

The second configuration is less familiar but may account for the increased incidence of stillbirth with multiple cord wrappings. A medical student and I investigated this mechanism in vitro.  Based on our in vitro study, we found that the shorter the cord segment being twisted, the fewer degrees of twist (rotation) are needed to stop umbilical vein flow. A functional short segment occurs if a cord wrapping around the fetus begins close to the placental insertion. At least in vitro the cord wrapping around a pipe is sufficient to anchor the cord and prevent propagation of the twist along the wrapped portion, creating a functional short cord segment. Then that cord segment extending past the wrap is the critical length that determines the degree of torsion needed to stop flow in vitro. A rotation of as little as 180 degrees applied to a few centimeters of free cord will stop flow. In vivo, the rotation would be applied by the turning of the fetus. 

 Both a functional short segment and an occult cord prolapse might not be evident after the delivery. Multiple cord wrappings or tight nuchal cord may be indirect indicators of a risk of short fetal to placental segment. Placental evidence of obstructed fetal blood flow (fetal vascular malperfusion lesions) likewise may be indirect evidence of obstructed umbilical blood flow.

            The NIH reviewers of the grant did not have significant criticism of the hypothesis, per se, but rather to the fact that I had no preliminary data. The radiologist on the study confirmed that the equipment we had would be able to image the whole cord and its relationships. However, the at-risk cord configurations had not been demonstrated in an actual case. A further valid criticism was that I had been unable to find a collaborator in fetal maternal medicine. I did obtain IRB approval for the study. The study also had a questionnaire that would provide a more systematic clinical history of immediate postmortem events. The catch 22 is that to get preliminary data requires funding, but funding requires preliminary data. One possible strategy would be to order an MRI before delivery as an extension of the autopsy with minimal risk to the mother. I have no idea if medical insurance would cover the cost of the MRI. 

            I have retired and will not be pursuing this project. I want to offer this protocol to anyone who will pursue it. I think the PI on the study should be an obstetrician, not a pathologist. A careful clinical history and pathological study of the placenta and fetal autopsy are important, but not necessary components to gather the preliminary MRI data. A secondary benefit of the study is that the MRI would also provide a virtual postmortem exam of the fetus, which may show important quantifiable information about the redistribution of organ blood volumes, and heart dilatation. 

Note: references supporting this blog are in the NIH study protocol. The protocol is identified as SUMT (Stillbirth Umbilical cord MRI Tipping point study) in the list of pages on this site. (I can no longer add titles into the side boxes with my free version of WordPress)

 This is a brainstorming idea. I need criticism and more ideas. Like most brainstorming, it is a broad idea that needs to be narrowed and focused.

            As a pathologist who has performed over 1,000 autopsies on stillbirth infants, I am frustrated that at least one third of those autopsies do not reveal a convincing chain of causation accounting for the infant’s to death. As an obstetrical pathology medico-legal consultant reviewing more than 500 placentas from infants who meet the criteria for birth asphyxia and have subsequent brain damage, I am more often than not, unable to find a definitive explanation as to why the infant suffered such a tragic outcome. Every week, I look at several placentas sent for examination because of an unplanned Cesarean section that was required due to non-reassuring fetal heart rate tracings. In many cases, there is no clear explanation. In these examples, there may be some pathological lesions in the placenta, but these same lesions are present in infants without serious complications. 

            Of course, in some of the above situations, there is an explanation for the obstetrical complications that are understandable. These explanations include a wide range of pathologies such as large abruptions, tight umbilical cord knots, fetal to maternal hemorrhage, and infection with disease causing microorganisms. However, even with a discoverable anatomic cause of death, questions often remain. How large of a placental separation in abruption is lethal for a given infant? When and how did an umbilical cord knot tighten? How did a fetal hemorrhage occur and how rapid a blood loss is needed to produce death or brain damage?  The exact degree of compromise may vary for each placenta and fetus.

            These questions underly a research project that I proposed to find better explanations for stillbirth. The first part of the study simply provides an MRI before delivery of the infant which will show anatomic positions that might compromise fetal umbilical blood flow but would not be detectable after delivery. The second part was directed to the general question of cumulative factors that might lead to fetal death by tipping the fetus into a lethal feedback loop that would lead to death. For example, if a certain event led to a just enough decrease in oxygen level to produce fetal lactic acidosis, this acidosis could decrease cardiac contractility, hence causing the heart to pump less blood to the placenta, thus further reducing oxygen, creating a spiral to fetal death. The idea of a tipping point as a mechanism of stillbirth without one single cause seemed probable from the lack of definitive findings at autopsy in so many cases. The kinds of events we are asking about in the stillbirth study, such as supine sleeping or possible sleep apnea, would not normally cause a tipping point in themselves, unless other factors were also present such as a compromised umbilical cord, or a placenta that was not adapting fast enough to a growing fetus. This idea a tipping point forced me to think of stillbirth as a placental system failure. 

            This system includes all the components needed to provide oxygen for brain and heart survival, such as the functional placenta reserve for oxygen diffusion, fetal metabolic level, the fetal and maternal cardiac output, fetal and maternal hematocrit, maternal blood gases, etc, etc. Many of the individual components have been studied. The same idea of placental system failure in stillbirth, would also apply to birth asphyxia or non-reassuring fetal heart tones. The components that lead to failure in any individual case might be very different, but the final pathway would be the same. Within the feed forward loop to hypoxia, rescue might be possible if the onset of placental system failure were detected in time. Prediction of stillbirth or asphyxia during labor might might depend on different factors in the individual cases. Many current tests of fetal well-being as a result do not have high sensitivity and specificity.  A model using multiple inputs to the placental system could better predict the risk that each factor contributes. This broader understanding could help avoid catastrophic obstetrical complications, and improve specificity to avoid unnecessary emergency operative deliveries. 

            Because of the many relationships between the different factors, there is unlikely to be a simple solution to predicting placental system failure. This kind of system prediction, like a weather forecast, requires a model of the system components and their known interactions. This approach to the complexity of placental system failure views fetal survival states as attractor states in a complex chaotic system. There are recursive interactions between fetal blood pressure, fetal pH, fetal cardiac output, utero-placental blood flow, maternal oxygenation, etc. The inputs on some components can be measured before labor, such as measures of fetal metabolic requirement for oxygen (heart and brain size) or placental efficiency of oxygen transfer between contractions (placental functional volume, or even better functional MRI estimates). I think the anatomic degree of umbilical wrapping and kinking is also important. These measures change during the pregnancy, but they can be measured near term. Other measures that could be obtained during labor include uterine pressure tracings, heart rate tracings, and perhaps a continuous doppler measure of cardiac output (umbilical vein diameter in a good cross section times the flow rate). The outcome could include the umbilical artery and vein gases, the cord hematocrit, etc. The quantitative descriptions of the interactions of variables on fetal heart rate (includes carotid chemoreceptor, CNS vagal effects, cord occlusion effects, which include effects on cardiac dynamics, not just gas exchange), and on fetal acidosis such as metabolic needs (brain and heart size, inflammatory or anemic elevations of heart rate, etc. and on fetal cardiac output (pressures, ductal flow modulation, contractility based on substrate, oxygen and blood pH) have been studied individually, usually in sheep but some in humans and other primates. The goal is to build a model from all this data that will demonstrate what happens when different stresses (changes in the parameters) are put on the system, such as maternal supine position, prolonged contractions or close together contractions, or fetal stresses such as hemorrhage, or inflammation. The effects in the model can then be compared to patient results and eventually improve predictive value in patient care and ideally improve our ability to predict placental system failure. 

            I revised the autopsy protocol portion for the MRI Stillbirth study and posted it. 

The MRI Stillbirth study has three aims directly referring to three parts of the methods. Part 1 is the in vivo MRI of the umbilical cord. Part 2 is the close questioning of the parents about immediate events around the time of the stillbirth and Part 3 is gathering correlation from clinical risk factors, the autopsy and the placenta. The next method section that needs expanding is the placenta examination. I want to get beyond the cataloging of lesions to the calculation of the reserve of the placenta to survive either decreased fetal blood flow, decreased maternal blood flow or decreased maternal oxygenation. 

            To achieve this goal, I need to do some preliminary work. A first problem is estimating the volume of the placenta, as any histological measure of function will need to be multiplied by that volume. A crude estimate is to use either the placental weight or the surface area times an estimate of the thickness. Another approach is that the MRI could give an in vivo estimate of placenta volume. The MRI would measure the volume under normal (or possibly reduced) maternal inflow. Early in my career, I developed a simple approach to measuring placental volume.  I bought a second-hand meat slicer to cut even 1 cm placenta slices that could be photographed and traced to yield a volume. To my surprise, it worked. I probably would not take that kind of risk today with sharp rotating electric blades. The problem with simply putting the placenta into a fluid to measure displacement is that the intervillous space can absorb some of the fluid, and the volume of interest is the combined placenta substance and the intervillous space, or at least that portion of the intervillous space that does not collapse after delivery of the placenta.

            The quantity of capillary syncytial membranes (cap-syn membrane) is the most important element in determining the reserve for oxygen exchange. Mayhew’s group demonstrated oxygen diffusion varies by the inverse third power of the barrier thickness between the fetal and maternal red cells¹. Therefore, oxygen exchange depends almost entirely on the area of cap-syn membrane, analogous to alveolar capillary exchange in the lung. The problem is how to measure the surface area of these membranes over the whole placenta. One long standing approach first used by Harold Fox was to count the number of membranes per terminal villus on the microscope slide. This approach has two problems. The first is finding the total volume of terminal villi in a placenta which will be considered under sampling below. The second is that the estimate of the linear extent of cap-syn membranes along a villus likely depends on the extent of capillary distention which for whatever reason (perhaps cord clamping time) varies remarkably among placental samples that we see in practice. We might get around this by distending all placentas via the umbilical vein to the same pressure of saline, but this presents problems. Instead, I want to do a preliminary study of the relationship of the villous surface expansion to the capillary diameters by experimentally infusing a few chorionic veins at selected pressures. With luck the relationship will be simple and there will be a formula that will give the linear extent of cap syn membrane using the mean capillary width, and the villous area on the microscope slide.

            Maturation of the placenta, that is the increase in terminal villi with syncytial knots and cap-syn membranes appears directly related to maternal blood flow. That blood flow is not uniform because of the placentone effect, which is the perfusion volume of one spiral artery². In the very mature placenta, this effect may be visible on a single slide with two ends showing small villi with increased syncytial knots, and a central zone of less mature appearing villi. This pattern is a reflection of the spiral artery inflow as a fountain coming in through a basal orifice and flowing down the periphery, which was shown in Dr. Ramsey’s radiographic primate studies³. The phenomenon at the extreme can be seen grossly by ultrasound in the grade 4 placenta. A few random samples for histology may not consistently capture the effect of this difference in regional flow. In order to estimate the total volume of terminal villi for gas exchange, a different sampling approach may be needed.

            To understand the placentone concept, consider: The law of continuity (a variant of conservation of mass in a flowing system) requires that the velocity of flow times the perpendicular cross-sectional area must remain constant. This is why a nozzle increases the velocity or fluid from a down pointing faucet narrows. This concept gets complicated in the intervillous space, but as the blood in the fountain from the spiral artery comes back down from the fetal surface, it covers a wider intervillous volume and must slow down, which would improve the oxygen extraction. The immature villi that actively extract nutrients tend to be in the center of spiral artery inflow and the mature villi with oxygen extraction will be at the periphery of the fountain. The problem is how to account for the effect of the placentone on sampling and still have a reasonable number of samples to determine the anatomic capacity to extract oxygen. 

            I have considered sampling not in the usual vertical manner but taking horizontal sections in sequence. Not only will this put the sections in context of the spiral artery entrance, but it will give a better idea of the size of the placentone effect, a value that may be a proxy for maternal flow. Finally, stem villi do not correlate precisely with the spiral artery flow, so an approach that samples stem villi at the top, and spiral arteries and basal veins on the bottom can map a stem villous to placentone relationship. The method would first fix an area of placenta large enough to completely encompass one placentone. Then all corners would be color inked to maintain orientation of the horizontal sections to each other. This approach, which is tedious, would need to be evaluated to see if it really is a more accurate way to get a functional picture of the placenta. 

            A final complication to measuring total functional capacity of the placenta in a stillbirth is the effect of fetal death on the fetal vessels that mimics cessation of flow from local in vivo occlusions. One difference is that thrombi by definition do not form after death, but mapping loss of villi from fetal vascular malperfusion will require tracing vascular trees and correlating changes with other measures of postmortem retention. 

            The premortem fetal blood flow may be estimated from the umbilical vein diameter and thickness as in general the diameter of the vein will reflect flow and the thickness of the media pressure. As with capillary beds, we need to distend the vein at different pressure in vitro to see the relationship of wall thickness to diameter under pressure. The postpartum umbilical vein diameter and wall thickness also need to be correlated with in vivo Doppler studies. 

            A final preliminary study needs to look further at a study of CD15 staining to identify immature villi that was positive in stillbirth⁴. With acute abruption, the staining was similar to controls. Few details of the IUFD category were provided. Cases of infants with hydrops and with parvo infection were positive as well. This may be a very helpful marker of villous dysmaturity, but it needs more preliminary work with autopsy correlation. 

            Unlike the autopsy portion of methods, the placental examination is going to explore new approaches. My plan is to write a separate protocol for these that uses “waste tissue”, that is portions of placenta and cord not needed for diagnosis. That unfunded proposal should receive accelerated IRB approval, and provide some preliminary data by the time the MRI stillbirth protocol is submitted. The MRI Stillbirth study is a pilot, but I want to have better formed placental hypotheses to be further tested in the context of the study. 

1.         Mayhew TM, Jackson MR, Haas JD. Microscopical morphology of the human placenta and its effect on oxygen diffusion: a morphometric model. Placenta 1986;7:121-31.

2.         Schuhmann RA. Placentone structure of the human placenta. Biblthca anat 1982;22:26-57.

3.         Ramsey EM, Donner MW. Placental vasculature and circulation. Philadelphia: W. B. Saunders Company Ltd; 1980.

4.         Seidmann L, Suhan T, Kamyshanskiy Y, Nevmerzhitskaya A, Gerein V, Kirkpatrick CJ. CD15 – a new marker of pathological villous immaturity of the term placenta. Placenta 2014;35:925-31.

            I posted the autopsy manual on the brain today with the same complaints, e.g. that half the images I had in my database were never digitized. I did not even have on photo of holoprosencephaly or of CMV in the brain. Still, I think the autopsy manual sections that I have posted so far will allow me to justify the details of the autopsy protocol for the stillbirth study.

            I want for the study to be able to attempt to correlate physiologic changes of different duration and form, from different stresses on the fetus, with the clinical features and the placental findings. 

            Using the autopsy as a tool to understand lethal physiology is difficult because of differences in gestational age, length of intrauterine postmortem retention, and complex overlapping physiological change. The goal at this point is to develop reasonable techniques and ideas for testable hypotheses. The main difference between the usual autopsy and the study protocol will be the attempt to find reliable methods of quantitation from the gross and microscopic observations. 

For example:

            Does the duration of gasping change the lung volume, the amount of blood in the lung capillaries and the distribution of intrathoracic petechiae?

            Does a severe acute but then resuscitated asphyxial episode lead to detectable changes in the brain with neuronal necrosis or white matter gliosis, or with brain edema as measured by weight compared to gestation?

            Does subacute hypoxia lead to heart failure measured by the volume of effusions, the dilatation of the ventricles, or the loss of atrial or brain natriuretic peptide. 

            What features clinical and placental features lead to lipid accumulation in the adrenal and loss of thymic cortical lymphocytes?

            What events correlate with increased nucleated red cells in the circulation, with or without, an increase in erythropoiesis measured by volume % or synchrony in the liver?

            Was blood acutely shunted away from the kidneys, or other non-vital organs?

            Are changes in the ductal intima indicative of contraction and right ventricular strain and passive congestion in the liver or other organs.?

            Does mobilization of colloid in the thyroid, normally triggered by birth, occur in utero and under what conditions?

            Does insulin or somatostatin islet cell hypertrophy or hyperplasia occur in physiologic states other than maternal diabetes?

So before going to some other organ manuals like bone, skin and pituitary, I am going to start on the detailed autopsy protocol.

The latest post has my same complaints: I need a library to read or reread articles, and I lack many images that I had. The posted manuals are more like an outline that needs to be filled in.

The manual will be the basis for the stillbirth study, which I hope will be able to become multi-institutional. I have done over 2,000 perinatal autopsies in 40 years, 40 people doing 50 autopsies a year could achieve the same experience in a year if we pool information and images. With more careful protocols and insights gained in previous autopsies we have performed, and perhaps with more resources as part of a funded study, we will be able to provide even more meaningful information. Hope some of this will become reality. I am now Pittsburgh, to start work at Magee on Feb 1.

This page like others suffers from my inability to find some never digitized images, particularly in this case the gross photo of an enlarged thyroid in a stillborn infant of a mother with a history of Graves syndrome. I am moving to Pittsburgh this week if all goes well, so there will be a delay before the next blog.

            I have posted a new autopsy manual page on the spleen. It will need continued work, but I think it provides an atlas that will be useful in the stillbirth project. In relation to the physiologic mechanisms of death, I am interested in the weight and how it is affected by the balance of sinus congestion with possible decreased T lymphocyte population with stress induced cortisol. This would require an area measurement of the percentage of T cells times the spleen weight that could then be correlated with thymic weight, assuming a negligible difference in blood versus tissue density.

            Over the years, I have found rare lesions like hamartoma and HLH that I wish could have been evaluated genetically. Perhaps as such studies become less expensive, or even covered by maternal insurance, it will be possible to pursue such cases.

I have added one more organ to the manual. I am still frustrated by having discarded my copies of papers with notes, and images on film, but I think the manual provides a start. I have continued to work on the proposal for the study of stillbirth (see research menu), and this manual will provide a basis for the autopsy protocol for that study. As always, I hope the manual will be useful to residents and fellows.

I have added a page on the heart to the autopsy manual. I hope to expand this chapter with more references and examples as I resume work now at Magee Hospital. I spent more time on this page describing how I do the dissection than I have in other pages since it is more difficult with the small size and often soft texture of fetal hearts. As I hope this manual will be of value to residents of pathology, I would like someday to be able to create videos of the dissection technique, since I find learning this aspect of the autopsy to be difficult for novices.

This blog is a posting of the introduction section to Stillbirth, that I will publish as a page, but I wanted to have it on-line now, also as a useful introduction to the proposal for a study of stillbirth:

         A pathologist performing an autopsy is not looking for a single cause of death, but rather a chain of causation in which one event logically based on experimental and observational data links to another until a final cause of death is identified. Any terminology for the parts of that chain or overall classification system usually become tangled in these chains of causation. 

         Perhaps the most clearly defined term is the immediate or final cause of death. In utero this is relatively simple. Death is considered the irreversible cessation of the fetal heart pumping. The fetal-placenta-maternal system can keep the fetus alive despite absent function of many organ systems such as lungs, kidney, brain, etc. as is often demonstrated by infants born alive without those organs. The components needed for life are those needed for receiving oxygen, and for removing respiratory and metabolic acids. These systems include the blood, the heart pump, adequate patent vessels from fetus to umbilical cord to placenta, and a viable maternal circulation of the placenta. Anything that interferes with this system can cause death.

         We usually distinguish multiple mechanisms that are immediate causes of death, that is they stop cardiac function. These mechanisms are asphyxia, which is the interference with respiratory gases, shock which is the failure of adequate forward pumping of blood to support the needs of tissues, and heart failure in which the heart cannot fully empty, creating a back pressure which in utero is always elevates systemic venous pressure. These are useful concepts taught routinely to physicians, but clearly, they overlap, and even assigning such a mechanism as the immediate cause of death is not straight forward. For example, asphyxia causes hypoxia which increases systemic acidosis from anaerobic metabolism. The acidosis weakens cardiac contractions which then fails to pump blood forward, and develops failure with increasing umbilical venous pressure. The latter decreases umbilical venous flow and with failing cardiac forward flow increases hypoxia from decreased placental perfusion. Other starting points such a primary heart failure, for example from ventricular tachycardia, or hypovolemic shock, feed into the same final mechanisms as asphyxia. Assigning an immediate cause of death still requires a weighing of events. The pathologist, from the autopsy, is looking for anatomic evidence to clarify the order of events, the timing, and relative contribution of different factors that ended death, more than assigning an immediate cause of death*. 

         Another approach to classifying cause of death is to identify the initiating etiology. This can seem simple enough. Take the well-known example of Rh sensitization as a primary etiology. However, even in this straight-forward example, this etiology is not a complete description of all we would want to know about the fetal death. There is a complex chain of causation from sensitization to transfer of antibody to hemolysis of fetal Rh+ cells to timing of hypoxic heart failure and death. Understanding of each part of the chain has improved our therapies. The cause of death that matters depends on our objectives. If we want to look at failed prevention of Rh sensitization we may want to tabulate deaths from those who did not receive therapy because Rh was not screened for due to poverty or lack of medical resources, or those who were identified but did not receive therapeutic Rhogam on time, or we might want to look at those who became sensitized despite optimum prevention strategies, or we might want to look at infant who received in utero transfusion but died anyway or from complications of the procedure. The autopsy can provide some information on the extent of hemolysis, evidence of the severity of heart failure/hydrops, or identify therapeutic accidents. In some circumstances it may be important that the autopsy identify the cause of fetal hydrops as hemolysis from Rh sensitization.

         There are two points from this example. One is that the definition of cause may depend on the information needed to inform therapeutic practices or prevention practices, not just the biology. The second point is that the autopsy can identify some links in the chain of the autopsy from anatomy, but the investigation of death often requires a broader input.

In the case of Rh sensitization, the chain of causation is well understood. In many fetal deaths, understanding the chain is incomplete. 

         Another instructive example of a primary etiology of death is premature separation of the placenta, which may or may not be accompanied by a clinical placental abruption. The pathologist needs to evaluate the placental evidence in terms of how much placenta was acutely separated. If nearly complete, then the mechanism of death was primarily from asphyxia. If less of the placenta, but more than half, is separated of an otherwise normal placenta, then the mechanism of death is a progressive hypoxia/acidosis/ heart failure. The pathologist can estimate the timing of the separation by changes in the infarcted placental villi above the separation. If the separation is smaller than 50%, it could still be a contributing factor to immediate cause of death if the placenta already showed evidence of compromise of function, such as villous evidence of adaptation to utero-placental ischemia, of multiple placental infarctions, or severe loss of functioning perfused placentas. In such a situation, then the small separation may have caused sufficient hypoxia to be a final lethal asphyxia or to create a slower, progressive positive feedback of hypoxia/acidosis.

         Finding a placental separation and the chain of events leading to death is not the only goal of the autopsy. Discovering temporally proximal causes that initiated the placental separation are also important data. For example, evidence of fetal trauma and maternal history would point to mechanical forces separating the placenta, often an automobile accident. In other cases, there may be evidence clinically and pathologically in the placenta of preeclampsia/eclampsia in which case hemorrhage from spiral arteries is a suspected cause. There may be anatomic or clinical evidence of less well-established causes such as maternal coagulopathies, or vena caval compression. In some cases, placental separations have an increased recurrence risk unrelated to known causal factors, perhaps due to genetic differences in spiral artery remodeling or decidual trophoblast interactions. 

         Even looking for proximal causes does not completely define the chain of causation in premature placental separation. There are still many unanswered questions about the steps in pathogenesis of premature placental separation prior to and during the actual separation. If preeclampsia, coagulopathy, or recurrent/unexplained separation is present, are there anatomic predisposing reasons for the occurrence in the particular pregnancy with those risk factors. The pathologist looks for anatomic evidence of unusual changes in uninvolved basal or even parietal decidual spiral arteries that might explain a tendency to rupture and cause a hematoma that will separate the placenta. The fetal membranes are examined for venous engorgement that might indicate venous outflow obstruction. The autopsy also may yield other useful information such as the interval from the time of the separation, estimated from the timing of the overlying infarction, to the timing of intrauterine postmortem retention, to provide a estimate of the window of opportunity for rescuing the infant. The autopsy may show evidence for clues to the risk of separation, such as the presence of multiple placental infarctions. 

         I could present similar arguments for many topics including other maternal immune disease, fetal hemorrhage, maternal diabetes, etc., but these are all topics that I anticipate covering in other pages of this site. 

         My suggestion is, rather than look for classifications of stillbirth, to develop studies focused on questions about particular links in the chain of causation in fetal death. This would require many different studies and would require large multi-institution collaboration. The autopsy and placental examination can make a valuable contribution to such studies, but that the investigation of stillbirth, and of any death, requires a broad approach beyond pathological findings. The pathologist needs to be part of a team of obstetricians, radiologists, scientists and other care givers, to optimize investigations that will improve our understanding and prevention of stillbirth.  

         However, for epidemiologic purposes, investigators have sought classification schemes for perinatal death and more specifically for stillbirth. An innovative scheme was that provided by the NIH funded SCRU study¹. The published paper also has an excellent critical review of classification systems. The SCRU approach recorded detailed findings, both clinical and anatomic, in an attempt at standardization. What it does not do is attempt to quantify and link the various findings into a plausible chain of events leading to the fetal demise.

(For the purposes of gathering data for the project proposed on this web site, I think these data sheets would be useful, as well as point of comparison to the SCRU studies. I have not asked for permission to publish them on the web site or use them in the study, but that is the intent. I confirmed with the NIH that Dr. Reddy has not modified the forms. The stillbirth study I am proposing would still ask detailed questions about events around the time of fetal death relating to changes in fetal movements, how and where mother slept, her diet, her perception of any illness, activities, and any medications, prescribed or over the counter, that she was taking.)

*(Different rules may apply in classification of causes in forensic/legal cases)

1.      Dudley DJ, Goldenberg R, Conway D, et al. A new system for determining the causes of stillbirth. Obstet Gynecol 2010;116:254-60.