New page added, An invitation to study stillbirth

18 Oct

            10/15/20 I am back to writing the blog. I have accepted a position at Magee Woman’s Hospital as a placenta/perinatal pathologist to start Feb 1. I am very excited about the potential to accomplish some cherished research projects at Magee. For my interview seminar, I presented the stillbirth project I had proposed on this blog. The main novelty of the project is to obtain an MRI of the infant in the uterus after death, but before delivery, in order to look at umbilical cord configurations. The other novelty is to ask questions about immediate events surrounding the presumed time of death, such as changes in fetal movements, sleep positions, eating and gastrointestinal issues etc. that have bearing on the theory that stillbirth may be due to multiple contributing factors. The idea is that partial hypoxia/acidosis can reach a tipping point in which hypoxic/acidotic cardiac failure leads to a positive feedback loop with decreasing placental perfusion leading to decreasing cardiac output, eventually leading to death. I have posted an edited version of this talk as a new page on the blog “Invitation to a study of stillbirth”

            I did not try to write the methods for the study. Instead the proposal acknowledges the need to first find a group of people who have multiple different knowledge bases. The project will need commitment from radiologists, and obstetrical caregivers, but it would also benefit from the input of basic scientists, parents of stillborn infants, bioengineers, behavioral scientists etc. The proposal needs to be hashed out by a group that would want to participate in developing the study. I plan to pilot the study at Magee, but I don’t think it is too early to find support at other institutions. I think the arguments in the talk make a reasonable case for cord accidents as a cause of stillbirth. I still have to accept that I could be wrong, and that the pilot MRIs do not find an explanation of stillbirth. The problem of the high incidence of the stillbirth remains, and the research would continue.

            As part of the project that will improve our understanding of stillbirth, I want to collaborate with other pathologists to develop autopsy protocols that are very specific to understanding the mechanisms of stillbirth by identifying and quantifying the evidence of the physiology leading to death. I have already posted on the blog some of my autopsy protocols for gestational age determination, postmortem retention and measurements. Below is a preliminary draft of an approach to the autopsy for this study. I would be grateful for any input.  A stillbirth specific placenta protocol will also be needed to quantify the placental contribution to fetal hypoxia or other mechanisms of death.

Draft of an stillbirth specific autopsy protocol:

            Stress: adrenergic/corticosteroid elevation:

                        Adrenal weights, adrenocytomegaly, thickeness fetal to adult cortex.

                        Thymic weights, histology how to measure cortical v medulla, eosinophils

                        Islet somatostatin

            Heart failure:

                        Measure thoracic cavity effusions

                        ? measure on skin, radiology, weight after blanket

                        Pulmonary weight to body or brain

                        Measures of cardiac dilatation, muscle cell morphology

                        Liver weight: brain weight, spleen weight

            Gasping:

                        Intrathoracic petechia

                        Asp amniotic squames

                        Asp mec or blood\      

                        Airway configuration/expansion

                        Diaphragm?

            Previous asphyxia:

                        Pap muscle heart, necrosis or calci, other endocardial necrosis

                        Brain lesions any destructive, necrotic lesions, white or gray, various nuclei (basal ganglia, lateral geniculate, acrcuate and, hypothalamic), , hippocampus, and multiple samples of neocortex 

            Shock

                        Adrenal hemorrhage

                        Diffuse petechiae and small hemorrhages

                        Vasodilation

                        Liver sinusoidal thrombi

            Blood loss

                        Pallor, how to measure

                        Color loss from postmortem hemoglobin diffusion

                        Erythropoetic expansion

                        Nrbcs in blood

                        Hemosiderin in spleen

                        Internal hemorrhages esp cranial, abdominal from liver, tumor

            Infection

                        Spleen B cells

                        Histological organisms

                        Pmns in lung, gut

                        Microorganism identification, incl STDs

            Nutritional loss

                        Brain body weight

                        Adipose thickness skin, over kidney

                        Muscle fiber diameter

                        Growth plate lines

            Ductal closure

            Hyperthyroidism

                        Size

                        Histology

            Thrombophilia

                        Thrombi in major and large vessels

                        Infarcts esp brain

            IDM

                        Adipose

                        Isler hypertrophy/ insulin

                        nrbcs

                        Muscle diameter

            Cytotoxic

                        Lack of liver EMH

                        Cortical thickness

                        ? Gi tract

            Reliability of histology v Genest

            Organ weight changes with retention

            Fluid shifts with retention

            Tests other than histology, lung culture, radiograph, how to save, such as blood smear, H1ac, DNA, most other biochemistry must deal the 98.6F autolysis, when is it regular enough to extrapolate.

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