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.

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Preterm labor: One syndrome, many causes

The preterm parturition syndrome

The "Great Obstetrical Syndromes" are associated with disorders of deep placentation.

Rheological and Physiological Consequences of Conversion of the Maternal Spiral Arteries for Uteroplacental Blood Flow during Human Pregnancy

Pre-eclampsia is characterized by new-onset hypertension and proteinuria at ≥20 weeks of gestation. In the absence of proteinuria, hypertension together with evidence of systemic disease (such as thrombocytopenia or elevated levels of liver transaminases) is required for diagnosis. This multisystemic disorder targets several organs, including the kidneys, liver and brain, and is a leading cause of maternal and perinatal morbidity and mortality. Glomeruloendotheliosis is considered to be a characteristic lesion of pre-eclampsia, but can also occur in healthy pregnant women. The placenta has an essential role in development of this disorder. Pathogenetic mechanisms implicated in pre-eclampsia include defective deep placentation, oxidative and endoplasmic reticulum stress, autoantibodies to type-1 angiotensin II receptor, platelet and thrombin activation, intravascular inflammation, endothelial dysfunction and the presence of an antiangiogenic state, among which an imbalance of angiogenesis has emerged as one of the most important factors. However, this imbalance is not specific to pre-eclampsia, as it also occurs in intrauterine growth restriction, fetal death, spontaneous preterm labour and maternal floor infarction (massive perivillous fibrin deposition). The severity and timing of the angiogenic imbalance, together with maternal susceptibility, might determine the clinical presentation of pre-eclampsia. This Review discusses the diagnosis, classification, clinical manifestations and putative pathogenetic mechanisms of pre-eclampsia.

Pre-eclampsia part 1: current understanding of its pathophysiology

Failure of physiologic transformation of the spiral arteries in patients with preterm labor and intact membranes

Failure of physiologic transformation of the spiral arteries in the placental bed in preterm premature rupture of membranes

OBJECTIVE
Intraamniotic inflammation/infection is the only mechanism of disease with persuasive evidence of causality for spontaneous preterm labor/delivery. Previous studies about the behavior of cytokines in preterm labor have been largely based on the analysis of the behavior of each protein independently. Emerging evidence indicates that the study of biologic networks can provide insight into the pathobiology of disease and improve biomarker discovery. The goal of this study was to characterize the inflammatory-related protein network in the amniotic fluid of patients with preterm labor.


STUDY DESIGN
A retrospective cohort study was conducted that included women with singleton pregnancies who had spontaneous preterm labor and intact membranes (n = 135). These patients were classified according to the results of amniotic fluid culture, broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry, and amniotic fluid concentration of interleukin (IL)-6 into the following groups: (1) those without intraamniotic inflammation (n = 85), (2) those with microbial-associated intraamniotic inflammation (n = 15), and (3) those with intraamniotic inflammation without detectable bacteria (n = 35). Amniotic fluid concentrations of 33 inflammatory-related proteins were determined with the use of a multiplex bead array assay.


RESULTS
Patients with preterm labor and intact membranes who had microbial-associated intraamniotic inflammation had a higher amniotic fluid inflammatory-related protein concentration correlation than those without intraamniotic inflammation (113 perturbed correlations). IL-1β, IL-6, macrophage inflammatory protein (MIP)-1α, and IL-1α were the most connected nodes (highest degree) in this differential correlation network (degrees of 20, 16, 12, and 12, respectively). Patients with sterile intraamniotic inflammation had correlation patterns of inflammatory-related proteins, both increased and decreased, when compared to those without intraamniotic inflammation (50 perturbed correlations). IL-1α, MIP-1α, and IL-1β were the most connected nodes in this differential correlation network (degrees of 12, 10, and 7, respectively). There were more coordinated inflammatory-related protein concentrations in the amniotic fluid of women with microbial-associated intraamniotic inflammation than in those with sterile intraamniotic inflammation (60 perturbed correlations), with IL-4 and IL-33 having the largest number of perturbed correlations (degrees of 15 and 13, respectively).


CONCLUSIONS
We report for the first time an analysis of the inflammatory-related protein network in spontaneous preterm labor. Patients with preterm labor and microbial-associated intraamniotic inflammation had more coordinated amniotic fluid inflammatory-related proteins than either those with sterile intraamniotic inflammation or those without intraamniotic inflammation. The correlations were also stronger in patients with sterile intraamniotic inflammation than in those without intraamniotic inflammation. The findings herein could be of value in the development of biomarkers of preterm labor.

Iconographies supplémentaires de l'article : Evidence of perturbations of the cytokine network in preterm labor

Iconographies supplémentaires de l'article : A short cervix in women with preterm labor and intact membranes: A risk factor for microbial invasion of the amniotic cavity

OBJECTIVE
The purpose of this study was to examine the diagnostic performance of ultrasonographic measurement of the cervical length and vaginal fetal fibronectin determination in the prediction of preterm delivery in patients with preterm uterine contractions and intact membranes.


STUDY DESIGN
Ultrasound examination of the cervical length and fetal fibronectin determination in vaginal secretions were performed in 215 patients admitted with preterm uterine contractions (22-35 weeks) and cervical dilatation of </=3 cm. Outcome variables were the occurrence of preterm delivery within 48 hours, 7 days, and 14 days of admission, delivery </=32 and </=35 weeks, as well as the admission-to-delivery interval. Statistical analysis included chi-square test, receiver-operator characteristic (ROC) curve analysis, logistic regression, and survival analysis.


RESULTS
The overall prevalence of preterm delivery </=35 weeks was 20% (43/215). The prevalence of spontaneous preterm delivery within 48 hours, 7 days, and 14 days of admission, and delivery </=32 and </=35 weeks were 7.9% (17/215), 13.0% (28/215), 15.8% (34/215), 8.9% (9/101), and 15.8% (34/215), respectively. ROC curve analysis and contingency tables showed a significant relationship between the occurrence of preterm delivery and both cervical length and fetal fibronectin results ( P < .01 for each). Both tests performed comparably in the prediction of spontaneous preterm delivery. However, when fetal fibronectin results were added to those of cervical length (<30 mm), a significant improvement in the prediction of preterm delivery was achieved.


CONCLUSION
Fetal fibronectin adds prognostic information to that provided by sonographic measurement of the cervical length in patients with preterm uterine contractions and intact membranes.

Iconographies supplémentaires de l'article : Cervicovaginal fibronectin improves the prediction of preterm delivery based on sonographic cervical length in patients with preterm uterine contractions and intact membranes

Tinnakorn Chaiworapongsa

Papers

Failure of physiologic transformation of the spiral arteries in patients with preterm labor and intact membranes

Failure of physiologic transformation of the spiral arteries in the placental bed in preterm premature rupture of membranes

Iconographies supplémentaires de l'article : Evidence of perturbations of the cytokine network in preterm labor

Iconographies supplémentaires de l'article : A short cervix in women with preterm labor and intact membranes: A risk factor for microbial invasion of the amniotic cavity

Iconographies supplémentaires de l'article : Cervicovaginal fibronectin improves the prediction of preterm delivery based on sonographic cervical length in patients with preterm uterine contractions and intact membranes