http://old.ssmu.ru/ofice/f6/ginfuv/information/rodi/f4.pdf

Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and neonatal morbidity: a systematic review and metaanalysis of individual patient data

Labor resembles an inflammatory response that includes secretion of cytokines/chemokines by resident and infiltrating immune cells into reproductive tissues and the maternal/fetal interface. Untimely activation of these inflammatory pathways leads to preterm labor, which can result in preterm birth. Preterm birth is a major determinant of neonatal mortality and morbidity; therefore, the elucidation of the process of labor at a cellular and molecular level is essential for understanding the pathophysiology of preterm labor. Here, we summarize the role of innate and adaptive immune cells in the physiological or pathological activation of labor. We review published literature regarding the role of innate and adaptive immune cells in the cervix, myometrium, fetal membranes, decidua and the fetus in late pregnancy and labor at term and preterm. Accumulating evidence suggests that innate immune cells (neutrophils, macrophages and mast cells) mediate the process of labor by releasing pro-inflammatory factors such as cytokines, chemokines and matrix metalloproteinases. Adaptive immune cells (T-cell subsets and B cells) participate in the maintenance of fetomaternal tolerance during pregnancy, and an alteration in their function or abundance may lead to labor at term or preterm. Also, immune cells that bridge the innate and adaptive immune systems (natural killer T (NKT) cells and dendritic cells (DCs)) seem to participate in the pathophysiology of preterm labor. In conclusion, a balance between innate and adaptive immune cells is required in order to sustain pregnancy; an alteration of this balance will lead to labor at term or preterm.

/pdf/immune-cells-in-term-and-preterm-labor-2g468h0vbp.pdf

Immune cells in term and preterm labor

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(16)00350-0.pdf

Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial

Vaginal Progesterone for Preventing Preterm Birth and Adverse Perinatal Outcomes in Singleton Gestations with a Short Cervix: A Meta-Analysis of Individual Patient Data

Background
Preterm birth is a major complication of pregnancy associated with perinatal mortality and morbidity. Progesterone for the prevention of preterm labour has been advocated.

Objectives
To assess the benefits and harms of progesterone for the prevention of preterm birth for women considered to be at increased risk of preterm birth and their infants.

Search methods
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (14 January 2013) and reviewed the reference list of all articles.

Selection criteria
Randomised controlled trials, in which progesterone was given for preventing preterm birth.

Data collection and analysis
Two review authors independently evaluated trials for methodological quality and extracted data.

Main results
Thirty-six randomised controlled trials (8523 women and 12,515 infants) were included.

Progesterone versus placebo for women with a past history of spontaneous preterm birth
Progesterone was associated with a statistically significant reduction in the risk of perinatal mortality (six studies; 1453 women; risk ratio (RR) 0.50, 95% confidence interval (CI) 0.33 to 0.75), preterm birth less than 34 weeks (five studies; 602 women; average RR 0.31, 95% CI 0.14 to 0.69), infant birthweight less than 2500 g (four studies; 692 infants; RR 0.58, 95% CI 0.42 to 0.79), use of assisted ventilation (three studies; 633 women; RR 0.40, 95% CI 0.18 to 0.90), necrotising enterocolitis (three studies; 1170 women; RR 0.30, 95% CI 0.10 to 0.89), neonatal death (six studies; 1453 women; RR 0.45, 95% CI 0.27 to 0.76), admission to neonatal intensive care unit (three studies; 389 women; RR 0.24, 95% CI 0.14 to 0.40), preterm birth less than 37 weeks (10 studies; 1750 women; average RR 0.55, 95% CI 0.42 to 0.74) and a statistically significant increase in pregnancy prolongation in weeks (one study; 148 women; mean difference (MD) 4.47, 95% CI 2.15 to 6.79). No differential effects in terms of route of administration, time of commencing therapy and dose of progesterone were observed for the majority of outcomes examined.

Progesterone versus placebo for women with a short cervix identified on ultrasound
Progesterone was associated with a statistically significant reduction in the risk of preterm birth less than 34 weeks (two studies; 438 women; RR 0.64, 95% CI 0.45 to 0.90), preterm birth at less than 28 weeks' gestation (two studies; 1115 women; RR 0.59, 95% CI 0.37 to 0.93) and increased risk of urticaria in women when compared with placebo (one study; 654 women; RR 5.03, 95% CI 1.11 to 22.78). It was not possible to assess the effect of route of progesterone administration, gestational age at commencing therapy, or total cumulative dose of medication.

Progesterone versus placebo for women with a multiple pregnancy
Progesterone was associated with no statistically significant differences for the reported outcomes.

Progesterone versus no treatment/placebo for women following presentation with threatened preterm labour
Progesterone, was associated with a statistically significant reduction in the risk of infant birthweight less than 2500 g (one study; 70 infants; RR 0.52, 95% CI 0.28 to 0.98).

Progesterone versus placebo for women with 'other' risk factors for preterm birth
Progesterone, was associated with a statistically significant reduction in the risk of infant birthweight less than 2500 g (three studies; 482 infants; RR 0.48, 95% CI 0.25 to 0.91).

Authors' conclusions
The use of progesterone is associated with benefits in infant health following administration in women considered to be at increased risk of preterm birth due either to a prior preterm birth or where a short cervix has been identified on ultrasound examination. However, there is limited information available relating to longer-term infant and childhood outcomes, the assessment of which remains a priority.

Further trials are required to assess the optimal timing, mode of administration and dose of administration of progesterone therapy when given to women considered to be at increased risk of early birth.

Prenatal administration of progesterone for preventing preterm birth in women considered to be at risk of preterm birth

Objectives Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery. This study was undertaken to determine the efficacy and safety of using micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix. Methods This was a multicenter, randomized, doubleblind, placebo-controlled trial that enrolled asymptomatic

/pdf/vaginal-progesterone-reduces-the-rate-of-preterm-birth-in-1hde1v1zef.pdf

Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial

Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: A multicenter, randomized, double-blind, placebo-controlled trial

W. Kinzler

Papers

Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial

Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: A multicenter, randomized, double-blind, placebo-controlled trial