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Progressive uterorenal denervation may contribute to both placental and cardiovascular syndromes?

Published:December 19, 2016DOI:https://doi.org/10.1016/j.ajog.2016.12.010
      To the Editors:
      Cain et al
      • Cain M.A.
      • Salemi J.L.
      • Tanner J.P.
      • Kirby R.S.
      • Salihu H.M.
      • Louis J.M.
      Pregnancy as a window to future health: maternal placental syndromes and short-term cardiovascular outcomes.
      find that women experiencing “placental syndromes” are at increased risk of serious cardiovascular disease within 5 years. We believe they have a common source of injury, namely, progressive autonomic denervation. Both uterus and kidneys receive sympathetic nerves from the same thoracic segments (T10-12). Persistent physical efforts during defecation are a common source of progressive autonomic injury in Western populations where they complicate 20-30% of Western bowel movements.
      • Heaton K.W.
      • Cripps H.A.
      Straining at stool and laxative taking in an English population.
      With the introduction of Western fast foods and removal of squat toilets over the past 25 years, it is becoming a major source of recent, cardiovascular morbidity in China.
      • Li Y.
      • Wang D.D.
      • Ley S.H.
      • et al.
      Potential impact of time trend of life-style factors on cardiovascular disease burden in China.
      In terms of the obstetrics syndromes, stretching injured, intrauterine vasomotor nerves (Figure) may activate uterorenal nerves to create a renal corticomedullary shunt leading to preeclampsia with, or without, intrauterine growth restriction.
      • Quinn M.J.
      The etiology of narrowed uterine arterioles in obstetric and gynecological syndromes.
      Disruption of narrowed uterine arterioles may cause placental abruption and denervation anywhere in the lower genital tract may increase the risk of opportunist infection and preterm birth, although this may be a less specific outcome compared to early-onset preeclampsia.
      • Quinn M.J.
      The etiology of narrowed uterine arterioles in obstetric and gynecological syndromes.
      Hypertension is a common antecedent to the listed, cardiovascular syndromes.
      • Cain M.A.
      • Salemi J.L.
      • Tanner J.P.
      • Kirby R.S.
      • Salihu H.M.
      • Louis J.M.
      Pregnancy as a window to future health: maternal placental syndromes and short-term cardiovascular outcomes.
      The histological hallmark of “resistant” hypertension is renal arteriolar sclerosis that has strikingly similar features to the uterine lesion (Figure, A). Resistant renal hypertension may result from similar mechanisms, namely injury to renal nerves caused by downward displacement of the kidney through persistent physical efforts during defecation, though clearly, there may be many other contributory factors to hypertension including increased body mass index, persistent hyperglycemia, and type 2 diabetes. By excluding preterm labor and intrauterine growth retardation from their definition of the placental syndromes, Cain et al
      • Cain M.A.
      • Salemi J.L.
      • Tanner J.P.
      • Kirby R.S.
      • Salihu H.M.
      • Louis J.M.
      Pregnancy as a window to future health: maternal placental syndromes and short-term cardiovascular outcomes.
      may trade some sensitivity for specificity. Nevertheless, they present a compelling argument for short-term follow-up of women with placental syndromes in their population. These women may also be at risk of gynecological problems and other Western diseases associated with injuries at different levels of the branches of the sympathetic chains that have longer latent periods between neural injury and clinical presentation.
      • Quinn M.J.
      Autonomic denervation and Western diseases.
      Figure thumbnail gr1
      FigureNeurovascular etiology of many obstetric and gynecological syndromes
      A, Gynecological lesion demonstrates halo of injured nerves around circumference of injured arteriole with irregular hyperplasia of vessel wall. This lesion occurs in many painful, premenstrual gynecological syndromes. Injuries to vasomotor nerves result in release of cytokines with regeneration of injured nerves and hyperplasia of now-denervated vessel walls. B, Obstetric lesion demonstrates halo of hyalinization around circumference of narrowed arteriole with irregular hyperplasia of tunica media and intima. Injured nerves cannot extend to placental bed during pregnancy. This lesion bears close resemblance to renal arteriolar hyperplasia where displacement of kidney by up to 2 vertebral bodies about its neurovascular pedicle may lead to similar injuries and appearances.
      Quinn. Am J Obstet Gynecol 2017.

      References

        • Cain M.A.
        • Salemi J.L.
        • Tanner J.P.
        • Kirby R.S.
        • Salihu H.M.
        • Louis J.M.
        Pregnancy as a window to future health: maternal placental syndromes and short-term cardiovascular outcomes.
        Am J Obstet Gynecol. 2016; 215: 484.e1-484.e14
        • Heaton K.W.
        • Cripps H.A.
        Straining at stool and laxative taking in an English population.
        Dig Dis Sci. 1993; 38: 1004-1008
        • Li Y.
        • Wang D.D.
        • Ley S.H.
        • et al.
        Potential impact of time trend of life-style factors on cardiovascular disease burden in China.
        J Am Coll Cardiol. 2016; 68: 818-833
        • Quinn M.J.
        The etiology of narrowed uterine arterioles in obstetric and gynecological syndromes.
        Placenta. 2016; 44: 114
        • Quinn M.J.
        Autonomic denervation and Western diseases.
        Am J Med. 2014; 127: 3-4

      Linked Article

      • Pregnancy as a window to future health: maternal placental syndromes and short-term cardiovascular outcomes
        American Journal of Obstetrics & GynecologyVol. 215Issue 4
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          Cardiovascular disease is the leading cause of death among women. Identifying risk factors for future cardiovascular disease may lead to earlier lifestyle modifications and disease prevention. Additionally, interpregnancy development of cardiovascular disease can lead to increased perinatal morbidity in subsequent pregnancies. Identification and implementation of interventions in the short term (within 5 years of first pregnancy) may decrease morbidity in subsequent pregnancies.
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        American Journal of Obstetrics & GynecologyVol. 216Issue 4
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          The authors thank Quinn for comments regarding our article titled “Pregnancy as a window to future health: maternal placental syndromes and short-term cardiovascular outcomes.”1 The article presented the short-term risk of cardiovascular disease among nulliparous women experiencing placental syndromes. We then further evaluated this risk when the women experienced placental syndromes in conjunction with a preterm delivery or delivery of a small-for-gestational-age (SGA) infant. A statewide, multiyear maternal-infant database in the state of Florida provided data for our study.
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