after my third miscarriage dr h did a basic blood panel and discovered that i have an elevated titer of anticardiolipin antibodies. he put me on baby aspirin for my next pregnancy.

but i pprom-d with earl and lost her, so dr h sent me to a rhematologist (dr r) to see if he’d missed something. dr r did a workup and said no. this was both relieving and baffling. clearly there is something wrong with some part of my system, and someone, dammitalltohell, should be able to find it.

later, after i pprom-d with ruby, dr l thought i should consult with a perinatologist who suggested a) we should get me checked out for ehlers-danlos and/or marfan syndrome(s) and b) we should get the dr r’s report to see what tests he did to see whether we need to look harder and further.

three weeks, four phone calls and two faxes later the dr r’s report (back from 2005) is finally in my hands. and everything is negative. the report even includes the comment that i have no apparent connective tissue diseases, which i am assuming is shorthand for eds and marfan’s.

so that’s good, right? right?

except that i don’t know whether dr r looked for “everything” — what the hell is “everything” anyway? — so maybe it’s neither good nor right. and it’s all getting a little scary, since, oh, the zero trimester could be ending any day now.

“Midtrimester amniotic fluid matrix metalloproteinase-8 (MMP-8) levels above the 90th percentile are a marker for subsequent preterm premature rupture of membranes.”

Abstract: Objective: We sought to determine whether midtrimester amniotic fluid levels of matrix metalloproteinase-8 were associated with subsequent preterm premature rupture of membranes.Study design: We conducted a case-control study examining 57 asymptomatic women who underwent genetic amniocentesis from 14 to 21 weeks’ gestation and subsequently had preterm premature rupture of membranes (<35 wk) and 58 women with subsequent term delivery. Measurement of total matrix metalloproteinase-8 level in amniotic fluid was conducted using a commercially available enzyme-linked immunosorbent assay and association with preterm birth due to preterm premature rupture of membranes was assessed. Results: The overall distribution of matrix metalloproteinase-8 concentrations was similar in women who had preterm premature rupture of membranes and term controls (median 2.39 ng/mL, 25th to 75th percentile 1.1-10.1 vs 2.37 ng/mL, 25th to 75th percentile 1.5-4.7, P=.94). However, 26% of women who had preterm premature rupture of membranes had a matrix metalloproteinase-8 concentration above the 90th percentile (8.7 ng/mL), compared with only 10% of term controls (odds ratio 3.1, 95% CI 1.1-8.7; P=.03). Elevated matrix metalloproteinase-8 remained associated with preterm premature rupture of membranes after adjustment for maternal age, race, parity, gestational age, and year of amniocentesis (odds ratio 3.4, 95% CI 1.2-9.9; P=.03). Conclusions: The overall distribution of midtrimester amniotic fluid matrix metalloproteinase-8 levels did not differ between women who had preterm premature rupture of membranes and those delivered at term. However, marked elevations of midtrimester amniotic fluid matrix metalloproteinase-8 were highly associated with subsequent preterm premature rupture of membranes, suggesting that the pathophysiologic processes that contribute to preterm premature rupture of membranes may begin in early pregnancy.

and this:

Human neutrophil collagenase (matrix metalloproteinase 8 ) in parturition, premature rupture of the membranes, and intrauterine infection

MAYMON E.; ROMERO R.; PACORA P.; GOMEZ R.; ATHAYDE N.; EDWIN S.; YOON B. H.

Perinatology Research Branch, National Institute of Child Health and Human Development, ETATS-UNIS
Department of Obstetrics and Gynecology, Wayne State University/Hutzel Hospital, ETATS-UNIS
Department of Obstetrics and Gynecology, Seoul National University, COREE, REPUBLIQUE DE

OBJECTIVES: The mechanisms by which microbial invasion of the amniotic cavity leads to membrane weakening and rupture are poorly understood. Recently, endogenous host enzymes have been implicated in this process. Matrix metalloproteinases are a family of potent enzymes that degrade components of the extracellular matrix. Collagen type I provides the main tensile strength of the fetal membranes. Matrix metalloproteinase 8 (MMP-8), or neutrophil collagenase, degrades interstitial collagens, acting preferentially on collagen type I. This study was undertaken (1) to determine whether MMP-8 is present in amniotic fluid and whether its concentrations are changed in preterm and term labor and membrane rupture with and without intra-amniotic infection and (2) to determine whether the amniotic fluid concentrations of MMP-8 in labor at term are different in the lower and upper uterine compartments. STUDY DESIGN: A cross-sectional study was conducted and transabdominal amniocentesis was performed in women in the following categories: (1) midtrimester (n = 25), (2) preterm labor in the presence and absence of microbial invasion of the amniotic cavity (n = 86), (3) preterm premature rupture of the membranes in the presence and absence of microbial invasion of the amniotic cavity (n = 51), (4) term patients in labor and not in labor (n = 51), and (5) term premature rupture of membranes (n = 20). Additional paired samples of amniotic fluid were retrieved by transabdominal amniocentesis (upper compartment) and transvaginal amniocentesis (lower or forebag compartment) from 14 term patients (28 samples) in spontaneous labor with intact membranes. Amniotic fluid MMP-8 concentrations were determined with a sensitive and specific immunoassay. RESULTS: MMP-8 was detected in 95.4% (249/261) of all samples. (1) Spontaneous human parturition was associated with a significant increase in amniotic fluid concentrations of MMP-8 in both term and preterm gestation. Term (no labor median, 3.3 ng/mL; range, <0.06-38.6 ng/mL; vs labor median, 16.6 ng/mL; range, 0.33-1650 ng/mL; P <.05). Patients with preterm labor who delivered preterm (in the absence of microbial invasion of the amniotic cavity) had a significantly higher median amniotic fluid MMP-8 concentration than those with preterm labor who delivered at term (preterm labor, term delivery median, 3.1 ng/mL; range, <0.06-415.1 ng/mL; vs preterm labor, preterm delivery median, 32.5 ng/mL; range, <0.06-6006.6 ng/mL; P <.003). (2) Spontaneous rupture of membranes in preterm gestation but not in term gestation was associated with elevated amniotic fluid concentrations of MMP-8. Preterm gestation (preterm labor, intact membranes median, 3.1 ng/mL; range, <0.06-415.1 ng/mL; vs preterm premature rupture of membranes median, 35.1 ng/mL; range, 0.71-1184.1 ng/mL; P <.05). Term gestation (intact membranes median, 3.3 ng/mL; range, 0.24-38.6 ng/mL; vs rupture of membranes median, 5.6 ng/mL range, 0.22-19.8 ng/mL; P =.9). (3) Microbial invasion of the amniotic cavity was associated with a significant increase in amniotic fluid MMP-8 concentration in patients with preterm labor and intact membranes, as well as in patients with preterm premature rupture of membranes. Preterm labor (no microbial invasion of the amniotic cavity, preterm delivery median, 32.5 ng/mL; range, <0.06-6006.6 ng/mL; vs microbial invasion of the amniotic cavity median, 208.1 ng/mL; range, 4.2-14,600 ng/mL; P<.001).

American journal of obstetrics and gynecology (Am. j. obstet. gynecol.) ISSN 0002-9378 CODEN AJOGAH

and a bit of help from wikipedia, on “metalloproteinase”:

The collagenases are capable of degrading triple-helical fibrillar collagens into distinctive 3/4 and 1/4 fragments. These collagens are the major components of bone and cartilage, and MMPs are the only known mammalian enzymes capable of degrading them. Traditionally, the collagenases are #1, #8, #13, and #18. In addition, #14 has also been shown to cleave fibrillar collagen, and more controversially there is evidence that #2 is capable of collagenolysis. In MeSH, the current list of collegenases includes #1, #2, #8, #9, and #13. #14 is present in MeSH but not listed as a collegenase, while #18 is absent from MeSH.

so now i know that there may be a genetic factor (mthfr) and/or a physiological factor (the proteinases are enzymes) at work. the genetic factor can be tackled by folic acid. but the enzymes? no idea. must ask more about collagen structure and ways to strengthen it. and about enzyme testing — if such a thing exists and/or is possible — and at what stage.

the most interesting tidbit i gleaned while reading is that amniotic fluid is typically without white blood cells, so any response to infection (maybe only if the sac hasn’t broken? that makes sense, but i don’t actually know) comes from the baby. it’s such an interesting glimpse  into the mother/baby relationship during gestation.

encouraged by blog-o-comments everywhere reminding women to ASK THEIR DOCTORS THEIR QUESTIONS! i am going to see dr. l tomorrow. turns out his receptionist thought an in-office convo would be better than one over the phone. i agree, and am a little surprised they’ll give me an appointment when i don’t have an apparent complaint.

so i get to ask my folic acid questions: should i be taking more than 1 mg? how much is too much? and should i have the test for mthfr you know, just in case?

and my vitamin c questions: that 2005 study from mexico documents that 100 mg of c correlated with decreased rates of prom. should i be taking c now, in preparation? how much? is linus pauling really crazy, or can i take up to 44,000 mg? (i can’t wait to see his face with that one.)

and my c & e questions: i’ve read several studies that open with the vague statement that prom has been linked to collagen weakness and oxidative stress (so why is it that docs say they’re not sure what causes it?) so if i supplement to build strong collagen and dope up on antioxidants that’s a good thing, right? so what, and how much of it, should i take?

and my luteal phase defect question. can i get day 3 bloodwork again? you know, just to see if anything has changed? ’cause maybe i don’t need the prometrium after all…?

and the million dollar question. i know you said it’s best to wait 3 cycles but i’m going crazy with the wait and my body has rebounded and i really really want to be pregnant and i really really want to be done having kids (not getting any younger here) and i’d like to get knocked up now but s says i have to ask you if it’s ok so this is me asking whether one cycle is enough to wait, and this is me being prepared to compromise and wait for a second period but i don’t wait to wait for the third and isn’t that really ok…?

all the while trying to convince him that i’m enthusiastic, not, you know, desperate….

many women in situations like mine — all of the various situations that can be considered “like mine” — find themselves glued to keyboards and screens looking for answers. and it’s wonderful, and it’s hard, because the beauty of having so much information at your fingertips is countered by the sheer ugly bulk of too-much-mis-information popping up in the search engine. but we keep at it. at least i do. (it’s part of the addictive personality, i guess.)

my latest forays have left me wondering whether i have the homozygous MTHFR mutation.

now, like most of my self-diagnoses, this one is lousy and uninformed. but i cling to anything that looks like a reason for recurrent pprom, and if i find anything that resonates with my experiences, well, then, i hang on all the tighter.

the one that gets me about this possibility is something my last ob said (before we moved out of state and so had to change docs). it went something like this:

“you know, i was at a conference recently and heard a talk about a genetic mutation that can cause prom. it’s expensive to test for, but the treatment is a megadose of folic acid. and since folate is good for you while pregnant anyway, why don’t you dose yourself up. take 1 mg a day.”

well, i thought this was a big deal, since 1mg is so much more than the 400 mcg typically recommended (even though many prenatals have higher doses). and i really thought it was a big deal when i went to buy 1mg pills and found out that that is considered a prescription strength. (i got around that by buying 400 mcg tablets and cutting a bunch of them in half.) and i took those extra pills faithfully, every damn day i was pregnant with mairin. and voila.

when slim came along and i met my new doctor, i gave him my shorthand version of my old ob’s prescription. new doc (dr. l) told me that 1mg isn’t really that much of a megadose, but sure, i could go ahead and take it. stupid me — i read into this that it wasn’t that essential. so sure, i took my folic acid like a good little mommy-to-be, but i didn’t go out of my way to dose myself up.

one of the sickest aspects of grieving is guilt. and guilt i’ve got by the gulletsful over this one. if i’d taken all that extra folic acid would ruby still be with us? i’ll never know. but i thought mr. google might be able to help me find out.

so it is that after many searches and links and related hits i ended up learning about mthfr.

like all my medical knowledge, i know about mthfr only enough to be a danger to myself. most interesting to me, though, is that some women who are prescribed folic acid for it take up to 4 mg a day. that’s a whole lotta folate. is there a toxicity level? what happens to a non-mthfr woman who takes this much? and even without the mthfr mutation, could such a high level help prevent pprom?

and the $10,000 question: how do i muster the courage to call dr. l and say, yet again, “so, i’ve been reading, and have this really wacky idea…”?