Accepted Manuscript

Preventing preterm pre-eclampsia

Yang Yang Li, MD, Qian Ru Gu, MD, Guo Rong Chen, MD, M.J. Quinn, MD, LLM

PII: S0002-9378(18)30686-0
DOI: 10.1016/j.ajog.2018.08.027
Reference: YMOB 12306

To appear in: American Journal of Obstetrics and Gynecology

Received Date: 16 March 2018

Accepted Date: 16 August 2018

Please cite this article as: Li YY, Gu QR, Chen GR, Quinn MJ, Preventing preterm pre-eclampsia,
American Journal of Obstetrics and Gynecology (2018), doi: 10.1016/j.ajog.2018.08.027.

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 ACCEPTED MANUSCRIPT

Preventing preterm pre-eclampsia

Yang Yang Li, MD

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Qian Ru Gu, MD
Guo Rong Chen, MD
M.J. Quinn, MD, LLM

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Department of Histopathology, First Affiliated Hospital, Medical University of Wenzhou,
Wenzhou, Zhejiang, China

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All authors report no conflict of interest
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Correspondence:
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MJ Quinn, MD, LLM, First Affiliated Hospital,

38, Harwood Road, Medical University of Wenzhou
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Fulham, Ouhai, Wenzhou, Zhejiang,

London, SW6 4PH. CHINA, PR 325000
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mjquinn001@icloud.com 0044 7710-288477

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In their extensive meta-analysis, Professor Nicolaides and colleagues describe a reduction of

preterm (<37 weeks), though not term (37-42 weeks), preeclampsia with a daily dose of more
than 100mgs aspirin starting before 16 weeks gestation (1). We offer some recent observations
from an entirely different source that tend to support their conclusions.

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In recent histologic studies, we find purinergic, (P2X3) "stretch" receptors in the walls of
denervated uterine arterioles, and, myometrium in pregnancy hysterectomy specimens (Fig. 1a-

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d). Increases in uterine blood flow in the second half of pregnancy may stretch these injured
arterioles resulting in viscero-visceral reflexes between the uterus and kidney redistributing renal

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blood flow from the cortex to the medulla, activating the renin-angiotensin system and causing
“early-onset”, (<37 weeks) pre-eclampsia (2-4). Stretching myometrial, P2X3 receptors may

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cause “late-onset”, (37-42 weeks) preeclampsia (2). In the uterus, injuries to vasomotor nerves
with release of cytokines and medial hyperplasia in denervated arteriolar walls, result from
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straining during defecation, medical and surgical procedures to evacuate the uterus,
hypertension, and difficult first labors (5).
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In this clinical framework, Professor Nicolaides’ results may be demonstrating the benefits of
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aspirin in women with injured, uterine arterioles in “early-onset” (<37 weeks) preeclampsia (Fig.
1c). Women with myometrial, P2X3, “stretch” receptors will not benefit in the same way (Fig.
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1d). I cannot improve on the selection criteria for preeclampsia at 16 weeks since both straining
during defecation, and, evacuation of the uterus are relatively common, non-specific, sources of
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injuries to uterine vasomotor nerves and arterioles at any time between birth and first pregnancy.
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References

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(1) Roberge S, Bujold E, Nicolaides, KH.
Aspirin for the prevention of preterm and term preeclampsia; systematic review and
meta-analysis. Am J Obstet Gynecol. 2018 March; 217(3):287-293

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(2) Wu XQ, Cai YY, Xia WT, Quinn MJ.

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The aetiology of pre-eclampsia 1945-1953.
BJOG. 2016 Dec;123(13):2130. doi: 10.1111/1471-0528.14297

(3) Sophian GJ.

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The aetiology of preeclampsia.
Lancet 1957; May 18; 272(6977):1044-5
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(4) Trueta J.
Studies of the renal circulation.
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Blackwells, Oxford, 1947.

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(5) Wu XQ, Xu XX, Zhou ZY, Quinn MJ.

The arteriolar injury in pre-eclampsia.
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BJOG. 2018 Mar;125(4):511-512.

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Figure Legend

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Injuries to arterioles in pregnant and non-pregnant uterus.

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(A) Symmetric “halo of injured nerves” in a non-pregnant uterus from a woman with chronic
pelvic pain (x100, stained with anti-S100, nerves are brown). There is a “halo” of

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injured nerves around a narrowed arteriole with hyperplasia of the tunica media
(B) Symmetric “halo of hyalinised cells” around a narrowed arteriole from the placental bed

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of a woman with preterm preeclampsia (x100, stained with hematoxylin and eosin).
Injured arterioles can extend to the placental bed in pregnancy though injured nerves
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cannot; leaving the “halo of hyalinisation” as a marker for proximal neural injury.
(C) Symmetric halo of P2X3 “stretch” receptors in a narrowed uterine arteriole from a
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pregnancy hysterectomy specimen (x200, stained with anti-P2X3, brown. Denervation

induces the development of P2X3 receptors in smooth muscle.
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(D) Arteriolar and myometrial P2X3 receptors from a pregnancy hysterectomy specimen
(x200, stained with anti-P2X3, brown).
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