Which Of The Quadrants In The Service Process Matrix Has High Labor Intensity And Low Customization?

Review

. 2014 Aug 15;345(6198):760-5.

doi: 10.1126/science.1251816. Epub 2014 Aug 14.

Preterm labor: one syndrome, many causes

Affiliations

PMID: 25124429
PMCID: PMC4191866
DOI: 10.1126/science.1251816

Free PMC article

Review

Preterm labor: one syndrome, many causes

Roberto Romero et al. Science. 2014 .

Free PMC article

Abstract

Preterm birth is associated with 5 to 18% of pregnancies and is a leading cause of infant morbidity and mortality. Spontaneous preterm labor, a syndrome caused by multiple pathologic processes, leads to 70% of preterm births. The prevention and the treatment of preterm labor have been long-standing challenges. We summarize the current understanding of the mechanisms of disease implicated in this condition and review advances relevant to intra-amniotic infection, decidual senescence, and breakdown of maternal-fetal tolerance. The success of progestogen treatment to prevent preterm birth in a subset of patients at risk is a cause for optimism. Solving the mystery of preterm labor, which compromises the health of future generations, is a formidable scientific challenge worthy of investment.

Figures

**Figure 1**
Labor (term and preterm) is characterized by increased myometrial contractility, cervical dilatation, and rupture of the chorioamniotic membranes. Collectively, these events have been referred to as the "common pathway of parturition." The switch of the **myometrium** from a quiescent to a contractile state is associated with a change in nuclear progesterone receptor isoforms and an increase in the expression of the miR-200 family, as well as an increase in estrogen receptor α signaling. **Cervical** ripening is mediated by changes in extracellular matrix proteins, as well as changes in epithelial barrier and immune surveillance properties. **Decidual/membrane** activation, in close proximity to the cervix, occurs in preparation for membrane rupture, and to facilitate separation of the chorioamniotic membranes and placenta from the uterus. E: epithelium; M: mucus; Os: cervical os.

**Figure 2**
Proposed mechanisms of disease implicated in spontaneous preterm labor. Genetic and environmental factors are likely contributors to each mechanism.

**Figure 3**
Mechanisms of microbial-induced preterm labor. (A) Bacteria from the lower genital tract gain access to the amniotic cavity and stimulate the production of chemokines and cytokines (IL-1α, TNFα), as well as inflammatory mediators (prostaglandins and reactive oxygen radicals) and proteases. These products can initiate myometrial contractility and induce membrane rupture. (B, upper left) Amniotic fluid containing bacteria that was retrieved by amniocentesis from a patient with preterm labor. Bacteria and nuclei stain with DAPI (blue). (upper middle) Bacteria identified with a probe against 16S rRNA using fluorescent *in situ* hybridization (FISH). (B, lower left and middle) Bacteria invading the amnion epithelium. Note the absence of bacteria in the subepithelial part of the amnion, suggesting that the pathway of microbial invasion is ascending into the amniotic cavity. (C) Chorioamniotic membranes without evidence of inflammation. Amnion and chorion are identified. (D) A similar membrane section as C from a patient with intramniotic infection. Inflammatory cells from the mother infiltrate the chorion and amnion.

**Figure 4**
A subset of patients with preterm labor has placental vascular lesions, including failure of physiologic transformation of the uterine spiral arteries. (A) Schematic drawing of the maternal-fetal interface in normal pregnancy. A physiologically transformed uterine spiral artery with a wide lumen delivers blood to the intervillous space of the placenta to supply blood to villi. (B) A spiral artery with an expanded ostium that normally enables adequate perfusion of the intervillous space. (C) Ostium of a narrow spiral artery with failure of physiologic transformation in a patient with spontaneous preterm labor. (D) PAS staining of a histological section of the maternal-fetal interface in normal pregnancy shows a spiral artery transformed by cytokeratin 7-positive cytotrophoblasts (brown) that line the lumen (200x). (E) Failure of physiologic transformation of a spiral artery in a patient with preterm labor. The lumen is narrow and cytotrophoblasts have not invaded the muscular wall (200×).

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