I wonder if there's a way to administer nicotine while blocking the addictive effects, which are probably the biggest concern ethically... though as Catherine points out it also mucks with bone growth and a bunch of other cascades. Though maybe blocking that pathway would imply blocking this cholinergic pathway and then you wouldn't get the benefit.

No, wouldn't get through ethics / IRB. I suppose I was just wondering if there was a safer delivery system; I'm not going to try it personally though.

Well, the trick there is that we know that nicotine causes other significant pregnancy problems, so it isn't an easy thing to trial. It does interfere with this particular cascade, but it's a player in all sorts of other stuff too. And smokers still get PE -- just at a lower rate -- so even though it interferes in this pathway it doesn't always do so effectively, for reasons not yet known. (Dose-response maybe.)

I just realized that I didn't explain the relevance of this very well at all. Both soluble FLT (or sFlt-1) and soluble endoglin (or sEng) are implicated in the onset of PE/HELLP symptoms. One is a VEGF antagonist and seems to cause proteinuria and hypertension while inhibiting placental growth. The other inhibits the TGB-beta cascade, which is a fancy way of saying that it breaks a lot of stuff. There's more about these particular proteins in the links in my .sig, and I'll pop the critical studies up later today.

Has anyone considering trying Nicotine Replacement Therapies during pregnancy? ... As a research trial I mean?

Nicotine is also recognized to inhibit bone repair... so not everything grows better under its influence.

Nicotine significantly facilitated endothelial migration and tube formation. By contrast, soluble fms-like tyrosine kinase 1 and/or soluble endoglin suppressed these endothelial functions. Nicotine restored these soluble fms-like tyrosine kinase 1 and/or soluble endoglin-reduced endothelial functions. Placental growth factor, but not transforming growth factor-beta1, production was significantly stimulated by the presence of nicotine...

http://www.ncbi.nlm.nih.gov/pubmed/20223446

Well, that's probably why smokers have a lower incidence. I wonder if that's why we invented smoking. (DO NOT START SMOKING. Yes, it is incredibly frustrating that doing everything right makes it more likely that you'll get preeclampsia, but drugs and cigarettes are still really, really bad for you.)

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