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

by deprimita_patro3 min read19th Jan 201623 comments

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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.

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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.

I think this is probably the best answer so far.

deprimita_patro: Family history would be another factor. If you or your wife have living mothers or grandmothers it might be worth asking them if they've ever suffered stillbirths. If the total is large then edge that 1/40 estimate up a little. If it's zero you might be able to edge it down a little.

Sorry for your loss.

If it helps I know a few people who had stillbirths and subsequently had perfectly healthy babies.

The base rate is about 1/160 to 1/200 births.

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

Yep. This is the information needed.

Starting from here, since all known predictable causes were ruled out (presumably the more likely repeat failures), I think the probability is somewhere between 1/40 and 1/160.

Maybe you could get base rate variation based on age. And country.

The cooccurrence rate looks like good news to me. Or at least good news if you want to try again. I don't know that the difference between 0.5% and 2.5% would even register in my brain. If someone had told me that the base rate was 2.5%, it wouldn't deter me from wanting a child.

I've done some of my family tree. The sad thing about looking back at cemetery records is how many times you see children under 1 and 2 dying just 100, 150 years ago.

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.

LW should make this unique thread widely known. Many couples facing similar decisions can be helped.

I am sorry for your loss.

EDIT: This association to your post won't leave me alone, so here it is: APACHE II software gives the odds of an adult leaving an ICU alive. Perhaps there is, or will soon be, an intrauterine version of this using blood values & other metrics that can prompt preventive measures early in a pregnancy.

I am sorry for your loss.

My condolences on your loss.

I think what you're most interested in is P(B3=stillborn | B1=toterm, B2=stillborn). You're looking at the joint distribution of trials.

At the most basic level of analysis, I'd want to estimate the cooccurence statistic above. Probably you can't get exactly that. But there certainly should be P(B1=stillborn), hopefully somewhere P(B2=stillborn2| B1=stillborn), maybe P(B2=stillborn|B1=toterm). With those, I think you can get the maxent estimate for your desired distribution above.

With that, you could start to do the adjustments based on particular causes that can be ruled out (for not having the problem SNP, for example), but I'd think those are more second order effects compared to base rate issues.

Ugh ugh ugh. That's awful for you and I wish you well in recovering from it.

I am not a medical professional or anything like one; I would just like to give further emphasis to the following things others have already said:

  • waveman says: base rate is 1/200 to 1/60, probability given a history of stillbirths is 1/40.
    • I remark (but maybe this is already taken into account somehow) that a couple with a history of stillbirths, just like a couple with a history of live births, is statistically going to be older than average; if, as I guess, older means more stillbirth risk, then this may mean that the difference between the "base" and "history of stillbirths" condition is really less than these figures suggest.
  • Elo says: the most obvious causes, including ones giving obvious reason to expect higher risk in a future pregnancy, seem improbable given what your doctors have found. It looks like you're in that "Undetermined" category.

Most likely you will never know what the problem was. It seems like Pr(next child stillborn) is probably no worse than about 2%, and in particular not drastically worse than the probabilities anyone else faces.

I repeat that I am not offering any new analysis (aside from the remark about ages), just picking out what look to me like the key points of other people's.

If you (very understandably) want a probability estimate from an actual obstetrician, you might try explicitly looking for an obstetrician willing to give probability estimates. That is, contact some local obstetricians and ask not "Can I consult you about this?" but "Are you willing to give me your best estimate of probabilities?". You may of course find that they all say no, or that they have no actual understanding of probability.

If you (very understandably) want a probability estimate from an actual obstetrician, you might try explicitly looking for an obstetrician willing to give probability estimates. That is, contact some local obstetricians and ask not "Can I consult you about this?" but "Are you willing to give me your best estimate of probabilities?". You may of course find that they all say no, or that they have no actual understanding of probability.

From my experience sitting on the other side of those conversations, I'm never going to give a number. First, producing the number is very resource intensive, likely more difficult that figuring out the correct things to do for the client.

Similarly, I'm not confident that I know (or remember) all the relevant facts about your situation that would effect my professional opinion. In particular, I've always found there were facts I was told and forgot or could have discovered but didn't. Even though I can perform quality work, failure to keep all those facts in mind during this estimate is not providing an opinion to a reasonable degree of professional certainty.

Third, my clients are human, and like all humans, are bad at probability. If I tell a client they have a 60% chance of winning and we lose, the client will be mad at me. That by itself is reason to give qualitative estimates, not quantitative ones.

Yup, that sounds very plausible. Would your unwillingness to give a number be changed if your client said -- as I think the OP here would -- something like this? "I understand that any probability you give me may be wrong in ways it's prohibitively hard to prevent, and I promise that I am not looking for perfection or anything like it. I understand that providing a probability may mean extra work, and I am happy to pay for that extra work. And I assure you that my own understanding of probability is extremely good and I will not do silly things like assuming that if you say something's unlikely and it happens then you're incompetent."

No, my answer would not change.

First, I don't believe the assertion. Second, the kind of work to generate this kind of answer is different from providing service for the client. I enjoy advocating for clients, not meta-level analysis of advocacy. Think medical care vs. MetaMed.

Fair enough. (In so far as you're typical, it sounds like the OP is unlikely to get any further benefit from talking to more medical professionals.)

Third, my clients are human, and like all humans, are bad at probability. If I tell a client they have a 60% chance of winning and we lose, the client will be mad at me. That by itself is reason to give qualitative estimates, not quantitative ones.

This is a huge meta-level problem with trying to be rational as a human being, surrounded by other human beings who are not rational.

Organisations with access to quantitative information have every incentive to hide it from you because the average human is a f**king idiot who will make a total pig's breakfast of the decision theory and probability theory, and then try to use the legal system to punish the giver-of-information.

(there is a lot here and might take some time to reply to)

Suggest the early contractions were braxton hicks contractions http://www.babycenter.com/0_braxton-hicks-contractions_156.bc (from some brief reading) aka nothing unusual.

Consider if still possible other DNA tests of the fetus to determine if there are any other genetic abnormalities that could have caused this event. if you could get a full sequence you could rule out a whole lot more, but it might be expensive to do.

I am pretty unfamiliar with prenatal development to suggest what happens around week 30, so I can be no help there.

What might be worth thinking about is how this might have unfolded 100 years ago (or more). The loss of one child; while tragic and very real to you right here and now; 100 years ago would have to have been taken into your stride. A lot more was unexplained and a lot less could have been done about it; such events would have been less comfortable and more raw. I by no means want to play down your suffering, but in understanding that this sort of thing would be the norm for back then, maybe you can help yourselves realise the value and benefits of continuing to try to have another child.

Given that you were already intending to have another child; I wouldn't be about to let this stop you.

I would also mention the benefits of having several children (they get the sibling benefits).

What is the most likely cause of death? How likely is that cause?

I believe that undetermined is the large remaining factor. given that no other data is strong, I suspect all conclusions will lead here.

Given that cause, if we choose to have another child, then how likely is it to survive its birth?

Very likely live birth; Given that all known common (or uncommon) causes of death are well known and well documented. if you consider that maybe 99.9% (estimated number) of all causes of death and complications are known, have been documented and are understood now; you happened to have something strange and unknown go wrong. If there was something strange relating to the pair between you and your wife; it would be something genetic (able to be tested for), or specifically environmental (likely not going to happen again). Given that all known common causes don't very well pattern match to this case; the odds of it happening again are very very low.

Are there any other ways I could reduce uncertainty (additional tests, etc...) that I haven't listed here?

Genetic testing that is available. regular ultrasounds. I wonder if USB ultrasound devices are available yet...

Why won't doctors give probabilities?

Doctors can't give good probabilities because medicine is a soft science still. and half the time they can't understand statistics for themselves. I wouldn't blame doctors for this; it's just the way it is for now.

hope this helps; and I hope you choose to try to have more children.

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

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

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.

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.

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?

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.

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.

Thanks for this.