Comment author: Strangeattractor 25 January 2016 11:55:35PM 2 points [-]

Tests for infectious diseases, in general, are incomplete. Even if the antibodies to that particular virus were not high enough that the doctors think of it as a cause, it is possible that there was another infection that didn't show up on the tests, because the particular strain wasn't tested for, or because the test wasn't sufficiently accurate. Some infectious diseases are difficult to test for.

So I wouldn't rule that explanation out.

One thing you could do is do more wide ranging tests for infectious diseases by testing for their antibodies, and also you could test for cytokines (eg. interleukins) which are markers of inflammation in the body. If some of the cytokines are high then that would be an indication of an undiagnosed infection, or another cause of inflammation. Then you could look into it more, and potentially treat the infection before starting to seek another pregnancy.

Garth Nicholson, a professor and a founder of an institute has recommendations for which labs have good tests: http://www.immed.org/clinical%20testing/ClinicalTesting2015.pdf

As of 2015, he is recommending

Clongen Laboratories http://www.clongen.com

Igenex http://www.igenex.com

for infectious diseases.

He used to recommend RedLab for cytokines, but they went out of business. I'm not sure who is doing high quality cytokine testing these days. And there aren't very many people around who would be helpful in interpreting the results, since cytokines are relatively new as biomarkers. But cytokine testing can indicate problems that other tests miss.

Nicholson's perspective on chronic diseases is not shared by many doctors, so you'd have to evaluate his ideas for yourself, but I have respect for him. He has a PhD in Biochemistry, and has published hundreds of scientific papers.

An infection may not have been the cause of the problem at all, but if you want to explore it more, that's what I would suggest.

Comment author: deprimita_patro 06 February 2016 12:59:05AM 0 points [-]

Thanks for this.

Comment author: PipFoweraker 19 January 2016 09:32:37PM *  3 points [-]

It may be worthwhile to cast a wider net in order to glean more professional opinions and sources of data while reducing any emotional response. Consider spending a useful amount of time exploring mailing lists, forums, and professional bodies. Google indicates there are tons of professional bodies in both the US and overseas that will have members who have dealt with similar experience and questions before. Some have membership requirements which a determined person can get around without too many problems, PM me if you get stuck. You may also consider asking a similar question on the various 'Ask a question' websites, but obviously the responses to a shotgun approach will vary wildly.

In doing so, you may be able to filter for more considered reactions if you phrase it as a hypothetical exam question or another form that encourages people to provide clear reasoning behind their answers. Focusing on the 'undetermined' section may lead to suggestions of non-obvious tests or papers that are obscure enough to have not appeared in initial searches.

Editing this page with useful summaries of more detailed information gleaned may boost its search ranking in the future. If it does, you may want to provide an easy way for someone to contact you without creating a LW account in case of the useful but lazy passerby.

If you have boldness, why not contact the writers of the textbook and ask them?

Comment author: deprimita_patro 20 January 2016 05:37:11AM 1 point [-]

You may also consider asking a similar question on the various 'Ask a question' websites, but obviously the responses to a shotgun approach will vary wildly.

Thank you for this idea. I submitted a variant of my post to Health Stack Exchange.

...you may want to provide an easy way for someone to contact you without creating a LW account in case of the useful but lazy passerby.

I've edited my post to include contact information.

If you have boldness, why not contact the writers of the textbook and ask them?

I will contact them tomorrow, but I don't expect much from cold-emailing researchers.

Comment author: Elo 19 January 2016 01:05:59PM 3 points [-]

Have you considered family history? It was not mentioned above is all.

Comment author: deprimita_patro 20 January 2016 05:11:52AM 1 point [-]

I edited the post the include what I know about our family history.

Comment author: waveman 19 January 2016 09:20:18AM *  31 points [-]

My sympathies to you.

This is a pretty common situation in medicine - you have a problem and you have little idea what the numbers are and insight is very hard to come by. It is incredibly frustrating. There may be studies but they only report the risks for a small number of factors or even just one (eg risk of stillbirth by age of mother or given a prior stillbirth). The raw numbers from studies are usually not available to "lay people" to allow them to do their own analysis for their own circumstances which would provide a much better insight.

When you go and look at the studies you see results that differ by a factor of 5 or worse. Does low Testosterone halve (one study), or triple (another study) your chance of getting prostate cancer? Is the risk of death within 15 years from prostate cancer at stage T1C with Gleason score 6 without surgery or radiotherapy 3% (one study) or 20% (another)? What is the incidence of impotence after prostate removal (pick a number, any number between 20% and 80%)?

You are asking "what is the likely cause?" however it is fairly likely you will never know this. Most stillbirths are never explained. There are probably thousands of things it could have been. Human reproduction is a fallible process with many points of failure. I suggest you may have to move past this question at some point.

I guess what you really need to know is "what is the risk of another stillbirth given you have had one already?".

The base rate is about 1/160 to 1/200 births. I see nothing in your report that indicates an elevated risk. I assume you have looked at the risk factors including possible family history, and found nothing.

Acording to this meta-analysis http://www.bmj.com/content/350/bmj.h3080 the chance of a second stillbirth given a history of stilbirth is about 2.5% or 1/40. This is a lot higher than the base of ~1/200 but it is still pretty unlikely.

Sorry that's the best I can offer.

I have no medical qualifications but due to various health issues I have been reading medical books and papers and learning statistics for several decades.

Comment author: deprimita_patro 20 January 2016 04:55:53AM *  1 point [-]

I assume you have looked at the risk factors including possible family history, and found nothing.

Sorry, not including this in the post was a huge oversight on my part. L has a cousin who has had two miscarriages, and I have an aunt who had several stillbirths followed by 3 live births of healthy children. We don't know the cause of any of these. We know of no other family members that have had similar misfortunes. I updated the post to reflect this.

Comment author: AstraSequi 19 January 2016 12:00:07PM *  4 points [-]

My sympathies for your loss.

In the tradition of "making up numbers and doing Fermi estimation is better than making up answers," I would focus on the history. The frequency of past outcomes is always a good place to start (I think that's in the Sequences somewhere) since there's no need to consider causality, only frequency and genetic distance. An example:

Simplify and assume the cause is genetic (which will overestimate the probability; environmental or shared genetic-environmental has more randomness and will have occurrence closer to the population average). What is the total number of siblings for yourself and your spouse, including both of you, and how many stillbirths were there? Add your children to the number, including the one stillbirth, and weight those double because they're the generation you want to know about. Calculate the percentage, then increase it by 5-10% as a crude correction for the assumption of a genetic cause. This is my estimate before you start thinking about causality.

Other things: If V is your son from a different relationship, his genetic distance is further so I would give him normal weight instead of double, but if L has other children I would still double them since the mother's genetics are probably more important. Optionally add any of your siblings' children, but weight them by half due to greater genetic distance. Check what percentage of stillbirths are genetic vs environmental, which could be used that to make a better correction than 5-10%. To avoid the multiple comparisons problem, make these choices before doing the analysis and commit not to change them.

Disclaimers: I am not a doctor or genetic counselor, and this is not medical advice. This is a superficial analysis written at 5am with the first few ideas I thought of, based on my unreliable intuitions about what sort of estimates might work. This sort of estimate is a lot weaker than direct evidence like the BMJ meta-analysis. I take no responsibility for any decisions that anyone makes...etc.

PS: you should probably assume the disclaimers apply to anything you read here. Also, I think another reason doctors avoid giving probabilities is that there can be legal consequences, especially if they're misinterpreted.

Comment author: deprimita_patro 19 January 2016 05:32:42PM 1 point [-]

If V is your son from a different relationship, his genetic distance is further so I would give him normal weight instead of double, but if L has other children I would still double them since the mother's genetics are probably more important.

Both V and J are genetically related to L and I. Neither of us have had any other children. I've updated the post to make this more clear. Thank you.

How did my baby die and what is the probability that my next one will?

22 deprimita_patro 19 January 2016 06:24AM

Summary: My son was stillborn and I don't know why. My wife and I would like to have another child, but would very much not like to try if the probability of this occurring again is above a certain threshold (of which we have already settled on one). All 3 doctors I have consulted were unable to give a definitive cause of death, nor were any willing to give a numerical estimate of the probability (whether for reasons of legal risk, or something else) that our next baby will be stillborn. I am likely too mind-killed to properly evaluate my situation and would very much appreciate an independent (from mine) probability estimate of what caused my son to die, and given that cause, what is the recurrence risk?

Background: V (L and my only biologically related living son) had no complications during birth, nor has he showed any signs of poor health whatsoever. L has a cousin who has had two miscarriages, and I have an aunt who had several stillbirths followed by 3 live births of healthy children. We know of no other family members that have had similar misfortunes.

J (my deceased son) was the product of a 31 week gestation. L (my wife and J's mother) is 28 years old, gravida 2, para 1. L presented to the physicians office for routine prenatal care and noted that she had not felt any fetal movement for the last five to six days. No fetal heart tones were identified. It was determined that there was an intrauterine fetal demise. L was admitted on 11/05/2015 for induction and was delivered of a nonviable, normal appearing, male fetus at approximately 1:30 on 11/06/2015.

Pro-Con Reasoning: According to a leading obstetrics textbook1, causes of stillbirth are commonly classified into 8 categories: obstetrical complications, placental abnormalities, fetal malformations, infection, umbilical cord abnormalities, hypertensive disorders, medical complications, and undetermined. Below, I'll list the percentage of stillbirths in each category (which may be used as prior probabilities) along with some reasons for or against.

Obstetrical complications (29%)

  • Against: No abruption detected. No multifetal gestation. No ruptured preterm membranes at 20-24 weeks.

Placental abnormalities (24%)

  • For: Excessive fibrin deposition (as concluded in the surgical pathology report). Early acute chorioamnionitis (as conclused in the surgical pathology report, but Dr. M claimed this was caused by the baby's death, not conversely). L has gene variants associated with deep vein thrombosis (AG on rs2227589 per 23andme raw data).
  • Against: No factor V Leiden mutation (GG on rs6025 per 23andme raw data and confirmed via independent lab test). No prothrombin gene mutation (GG on l3002432 per 23andme raw data and confirmed via independent lab test). L was negative for prothrombin G20210A mutation (as determined by lab test). Anti-thrombin III activity results were within normal reference ranges (as determined by lab test). Protein C activity results were withing normal reference ranges (as determined by lab test). Protein S activity results were within normal reference ranges (as determined by lab test). Protein S antigen (free and total) results were within normal references ranges (as determined by lab test).

Infection (13%)

  • For: L visited a nurse's home during the last week of August that works in a hospital we now know had frequent cases of CMV infection. CMV antibody IgH, CMV IgG, and Parvovirus B-19 Antibody IgG values were outside of normal reference ranges.
  • Against: Dr. M discounted the viral test results as the cause of death, since the levels suggested the infection had occurred years ago, and therefore could not have caused J's death. Dr. F confirmed Dr. M's assessment.

Fetal malformations (14%)

  • Against: No major structural abnormalities. No genetic abnormalities detected (CombiSNP Array for Pregnancy Loss results showed a normal male micro array profile).

Umbilical cord abnormalities (10%)

  • Against: No prolapse. No stricture. No thrombosis.

Hypertensive disorder (9%)

  • Against: No preeclampsia. No chronic hypertension.

Medical complications (8%)

  • For: L experienced 2 nights of very painful abdominal pains that could have been contractions on 10/28 and 10/29. L remembers waking up on her back a few nights between 10/20 and 11/05 (it is unclear if this belongs in this category or somewhere else).
  • Against: No antiphospholipid antibody syndrome detected (determined via Beta-2 Glycoprotein I Antibodies [IgG, IgA, IgM] test). No maternal diabetes detected (determined via glucose test on 10/20).

Undetermined (24%)

What is the most likely cause of death? How likely is that cause? Given that cause, if we choose to have another child, then how likely is it to survive its birth? Are there any other ways I could reduce uncertainty (additional tests, etc...) that I haven't listed here? Are there any other forums where these questions are more likely to get good answers? Why won't doctors give probabilities? Help with any of these questions would be greatly appreciated. Thank you.

If your advice to me is to consult another expert (in addition to the 2 obstetricians and 1 high-risk obstetrician I already have consulted), please also provide concrete tactics as to how to find such an expert and validate their expertise.

Contact Information: If you would like to contact me, but don't want to create an account here, you can do so at deprimita.patro@gmail.com.

[1] Cunningham, F. (2014). Williams obstetrics. New York: McGraw-Hill Medical.

EDIT 1: Updated to make clear that both V and J are mine and L's biological sons.

EDIT 2: Updated to add information on family history.

EDIT 3: On PipFoweraker's advice, I added contact info.

EDIT 4: I've cross-posted this on Health Stack Exchange.

EDIT 5: I've emailed the list of authors of the most recent meta-analysis concerning causes of stillbirth. Don't expect much.

Comment author: deprimita_patro 04 January 2016 09:06:13PM *  28 points [-]

Thank you.