0.01 percentile

In October, shortly after I found out the diagnosis of maternal floor infarction/massive perivillous fibrin deposition (basically, huge clots formed around the villi, the little fingerlike placental protusions that delivered nutrients to Luke, making them unable to function), I connected with the folks over at the Star Legacy Foundation, the only national U.S. organization dedicated to stillbirth awareness. They responded quickly and kindly and put me in touch with experts who answered a few questions; they also let me know about Dr. Harvey Kliman, a Yale University placental pathologist who consults on stillbirth cases.

We soon began working with the hospital to have slides from my placenta sent to Dr. Kliman’s office. On Dec. 22, I received Dr. Kliman’s report. (This is probably a post for another time, one in which I recount all the ways people suck, but the report was dated Dec. 2 and sent directly to my doctor, who never bothered to contact me; I only got the report after following up with Kliman’s office. My doctor has always been really nice and kind to me and that’s why I’m still with her, but I’m incredibly pissed about this. I had even taken the time to give her a heads up that the report would be coming.)

The gist of the report, and the finding that was new and shocking to us, is that my placenta was EXTREMELY small; Dr. Kliman even used all caps in his report, as shown below. It actually weighed less than the 0.01 percentile for his gestational age of 37 weeks. For those of you who have all but forgotten about your SAT scores, this means that 99.99 percent of placentas of the same gestational age, statistically speaking, are larger than mine was. Given this fact, it seems astonishing that Luke survived to 37 weeks, and indeed Dr. Kliman notes in his report that “the survival of this fetus to 37 weeks [was] remarkable.”

To me this seems to suggest that the placental clots must have formed rapidly, because there was no indication of this problem at Luke’s 32-week growth scan, and in fact at that time he measured large for his age. So some time between 32 weeks and 37 weeks something went very wrong. Unless the ultrasound technician royally screwed up—and there was a substitute working that day, a technician from a different office who wasn’t used to the machine—but I’m inclined to think that wasn’t the case, because at birth Luke weighed 5 pounds 6 ounces, which while small, to me doesn’t indicate that he’d had a super tiny, infintesimal placenta for very long. He was also quite the kicker and squirmer until the end.

Zack and I will be traveling to Yale on Tuesday to meet with Dr. Kliman, ask him all of our questions, and hear about his recommendations for a future pregnancy. Except that I don’t really have any concrete questions at this point, just a swirling hot mass of confusion and despair. I have a stack of printouts about MFI/MPFD that I made right after we received the diagnosis, but I haven’t been able to read through them because they are so technical and dire. It’s something I’ll have to bring myself to do in the next few days, but I’m not looking forward to it, as what little research I have done shows there’s not a lot of global consensus on how to treat these conditions—and everything depends on what the insurance companies will pay for anyway.

Speaking of which, Dr. Kliman in his report recommends for a future pregnancy a technique called estimated placental volume. It seems like a simple process in which the health care provider regularly measures the width, height, and thickness of the placenta. Because I’m now extremely cynical about everything, I’m not holding out much hope that I’d be able to persuade the doctors to do this, even the high-risk doctor I’d be seeing for regular ultrasounds. I’m sure it’s not approved by the American College of Obstetricians and Gynecologists, and I’m sure that without ACOG sanctioning, insurance companies won’t pay for it, even though it seems like it would be simple enough to grab those measurements while they’re already in there poking around.

I’m not even sure that ACOG has published standards for what size the placenta should be; I know they haven’t for the umbilical cord. Similar to Dr. Kliman’s EPV technique (and I’m just assuming at this point that it’s not ACOG-approved), a dedicated and courageous umbilical cord researcher named Dr. Jason Collins came up with a technique and equipment for monitoring babies in utero so that moms could be alerted right away when their babies are in distress, but he never got the doctors and insurance companies on board, and he could never find the funding to mass-produce the equipment, so it’s not even available anymore.

Anyway, I digress. The only small upside to Dr. Kliman’s report is that he doesn’t seem to think it was villitis of unknown etiology, as another expert suggested, which is somewhat more dire because it can’t be treated (it seems not even with anti-clotting agents, though I’m not entirely sure) and can worsen with subsequent pregnancies. However, the MFI/MPFD diagnosis suggests I may have an autoimmune disease, which is odd since I’ve never had any other kind of symptoms—and Zoe was born on time, with no growth restrictions. So one of the next steps, I’m sure, is to figure out what the fuck is up with all of that.

(From the report:)

This placenta was EXTREMELY small, weighing less than the 0.01 %ile for gestational age. There are three major causes for such a small placenta: decreased maternal perfusion of placenta, chronic maternal immunologic rejection or an intrinsic genetic abnormality. In this case there was a combination of decreased maternal perfusion, immunologic rejection, and massive intervillous fibrin deposition (as a consequence of the first two issues). Not only was this placenta extremely small in weight, only about 10-20% of the villi were functional, making the survival of this fetus to 37 weeks remarkable. The pathologic progression of this process can be seen in the images, with the top image showing evidence of intervillositis with monocytes, macrophages and lymphocytes. This progressed to total trapping of the villi in the middle image, followed by death of the villi in the bottom image. There was no evidence of genetic abnormality seen, nor evidence of an intraamniotic fluid infection. This condition can recur.

It would be useful in subsequent pregnancies to follow the placental volume using the Estimated Placental Volume (EPV) technique (see http://klimanlabs.yale.edu/placenta/epv/index.aspx) and if this recurs to deliver by section as early as is prudent for the fetus.

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Maternal floor infarction

On Thursday, Oct. 15, my doctor called with the results of my clotting disorder tests and Luke’s autopsy (clotting disorders such as a Factor V or Factor II mutation are one cause of stillbirths).

First, she said, all my labs came back normal except one. I have the xx mutation of the MTHFR gene, involved in metabolizing folic acid. It’s a common mutation, she said: “80 percent of the female population has it.” I would need to take baby aspirin throughout a subsequent pregnancy.

Next, the autopsy. “The baby was fine,” she said. “There was nothing wrong with him. It was the placenta.”

The cause, she continued, was determined to be an extremely rare placental disorder known as maternal floor infarction (MFI). (The condition may also be known as massive perivillous fibrin deposition, or MPFD, although at least one journal abstract I found seems to suggest that they are different conditions on a spectrum.) In any case, what happened was that a clot formed, resulting in placenta insufficiency: a placenta unable to sustain Luke. In the scientific language, fibrin (a clotting protein) built up in the spaces between the placental villi, the small fingerlike projections that we all learned about in health class. The placenta was actually 75 percent “infarcted.”

From the autopsy report: Massive perivillous fibrin deposition is a condition characterized by enmeshment of chorionic villi in a fibrinoid material and in placental insufficiency of various degrees. The perivillous fibrin deposition essentially strangles the chorionic villi. This in turn leads to a marked reduction of fetal blood flow in the affected villi and secondary stromal fibrosis. Thus, functional villi are reduced in number, and if the process is sufficiently large, placental function is compromised. The consequences include a significant risk of intrauterine growth restriction, intrauterine death, and preterm delivery.

“We do not know what causes it,” my doctor said, “and the downside is that it has a high risk of recurrence.” Around 30-32 weeks of a subsequent pregnancy, she said, I would be monitored more closely, with twice-weekly ultrasounds, and would be induced at 37 weeks (which was the plan anyway, before we knew the cause). “The ultrasound can show some things, but not everything,” she said; I would also have to be hyper-vigilant about kick counts, but in the end, we would have to leave things up to a certain amount of chance.

I reeled from shock. I had always figured the autopsy would come back inconclusive, or with some kind of freak cord accident. I knew the chance of having two stillbirths was incredibly rare, much more rare than the risk of having one (I think it’s like 2 percent of all stillbirth moms go on to have a second stillbirth), and it never occurred to me that a subsequent pregnancy would really, truly be high risk and that my rainbow baby could be just a fleeting dream. Suddenly I was launched into the grieving process all over again, and now trying to figure out how we could decide whether to try to have another child.

After digesting this information for a few days, I contacted the Star Legacy Foundation for Stillbirth Awareness. In online searches for both maternal floor infarction and massive perivillous fibrin deposition, I had found mostly technical journal abstracts, nothing much written from the lay perspective or by other mothers in the same situation. I asked the foundation if they had any information on the condition(s) written for a lay audience. To my surprise and eternal gratitude, they responded within hours and forwarded my inquiry to two members of their board.

The first, placental pathologist Dr. Mana Parast of the University of California, responded with a recommendation that I be screened for autoimmune conditions such as lupus and antiphospholipid antibody syndrome (a clotting disorder). She said if an autoimmune condition is indicated, she has known women treated with low molecular weight heparin or other treatments during subsequent pregnancies who delivered healthy babies (and normal-looking placentas).

Then she mentioned that she might question whether the cause was MFI, and not instead a condition that can mimic MFI called villitis of unknown etiology (VUE), in which the mother’s immune system attacks paternal antigens on placental cells. It can also be associated with fibrin deposition in the placenta. The recurrence rate is high, just as for MFI (up to 50 percent in subsequent pregnancies), but there is no treatment.

Since I had a normal pregnancy with Zoe, she questions the MFI diagnosis, unless Zoe had undetected fetal growth restriction or I developed an autoimmune disease after that pregnancy. On the other hand, VUE, she noted, gets worse with subsequent pregnancies (i.e., “mom’s immune system is now alerted to the paternal antigens, so she’ll fight them back faster”).

We are in the process of sending samples of my placenta to a Yale pathologist, Dr. Harvey Kliman, also recommended by the Star Legacy Foundation. Hopefully Dr. Kliman will be able to give us a definitive answer as to MFI/MPFD or VUE, and we can go from there.

Star Legacy also connected me with Dr. Alexander Heazell of the UK’s University of Manchester, who has created “rainbow clinics” to work closely with parents to plan and deliver subsequent pregnancies. Dr. Heazell was in a radiology residency program when his child was stillborn, and he changed his focus to OB/GYN, dedicating his career to finding answers. He didn’t have much to add to what I already knew, but it gave me hope to hear that his clinics have yet to lose a rainbow pregnancy.

In the meantime, I have a number of questions swirling around my head—ones I can’t seem to find many answers to because a) I don’t want to shell out hundreds of bucks for a journal subscription, and b) the disorder is so rare and so poorly understood that there aren’t many journal articles on it to begin with. Among my questions:

1. MFI is associated with central nervous system (CNS) injuries and “adverse neurodevelopment outcomes” such as cerebral palsy. What impact does treatment (aspirin, heparin) have on the risk of such outcomes?
2. Is VUE also associated with such outcomes?
3. Are MFI and MPFD truly on a spectrum? What does that mean for my situation? Where am I on the spectrum?
4. In the case of MFI, does treatment eliminate or merely reduce the risk of another stillbirth?
5. What exactly is the risk of recurrence with MFI?
6. Does my MTHFR mutation have anything to do with MFI? I’ve seen other women with MFI say they were prescribed extra folic acid (not sure if they meant folate) in subsequent pregnancies; is this because the MTHFR mutation is somehow related?
7. Is MFI/MPFD related to a clotting disorder, an autoimmune disorder, or both?
8. I’ve heard that some women develop clotting disorders only in pregnancy—so even if I came back negative for Factor V now, maybe I would have it during pregnancy?
9. Exactly which autoimmune diseases should I be screened for?
10. Why the fuck is this happening to me?

Thanks to the kind folks at Star Legacy, I have some of these questions out to the placental pathologists and hope to hear more answers soon—and hopefully Dr. Kliman will also be able to clear a lot of this up for us. All I can do now is focus on the next step.

Autopsy report, part 2

I talked to the state’s social worker on Monday about finding out the status of Luke’s autopsy report and whether we could get a written copy instead of just a phone call. I hadn’t heard back, so I emailed her for an update. She called back and said that an autopsy had been declined because my daughter’s death at 38 weeks had been considered natural.

Zack and I lost it.

We requested an autopsy, I told her. I signed paperwork authorizing it. I had a son, not a daughter. And I was 37 weeks, not 38. Are you sure you even pulled the right case, I asked her? I’m freaking out right now, I said.

She apologized and said I should speak directly to her organization’s executive director. She gave me the phone number. I called right away and left a message explaining the situation and telling her that I was highly distraught. Within a few minutes, the woman called back. She asked me a few questions and then explained that it was the state medical examiner’s office that didn’t do an autopsy, that they defer to local hospitals in such cases, and that the hospital would have conducted the autopsy. She said the hospital is probably still waiting for lab tests to come back and that is the likely reason for the delay.

Well, Jesus. I wish the social worker had been better informed of how these things work. Isn’t that her job? She could have bypassed the medical examiner’s office and gone straight to the hospital to begin with—preventing us all this heartache in the meantime.

The executive director then offered to make some calls on Monday and try to find out more about the status. She kept getting the name of the hospital wrong, but we finally squared it away. (Franklin Square Hospital? Frederick Square Hospital? Oh, Frederick Memorial Hospital? Got it).

So, that’s where we are now.

Autopsy report

We’ve gotten a couple voicemails from a social worker who works for the state of Maryland. I hadn’t called her back because in one message she referred to Luke as “her” and in another she said she’d called on Aug. 17. Since we didn’t find out Luke was dead until Aug. 20, I thought that was interesting.

Anyway, the hospital didn’t send us home with anything about the autopsy—when to expect results, what to expect, who to call with questions. It’s been 4.5 weeks and we haven’t heard a peep. So I decided to call the social worker this morning and ask her what she knows.

She said she’d call the University of Maryland Center for Infant and Child Loss and find out what they know about the status of the autopsy. She said it usually takes 8-12 weeks. Will something be mailed to us? I asked. Usually it’s just a phone call, she replied. I told her we’d want a copy of any written documentation. I can’t imagine there wouldn’t be anything written. It seems crazy that your full-term baby can die inside of you, and all you get is a phone call.

So that’s where it stands now. She’s going to see if she can find out the status and let them know we want a copy of anything written.