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Advances in Preterm Delivery

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Obstetrics & Gynecology".

Deadline for manuscript submissions: closed (20 February 2022) | Viewed by 34560

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Prof. Dr. Eyal Sheiner

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Department of Obstetrics and Gynecology, Soroka University Medical Center, Beersheba, Israel
Interests: obstetrics; high risk pregnancy; clinical studies; placental abruption; placenta previa; pregnancy as a window of opportunity to detect long-term diseases; obesity in pregnancy; maternal-fetal medicine; perinatal outcome
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Dear colleagues,

Preterm delivery (PTD; <37 weeks’ gestation) complicates 5%–13% of deliveries worldwide depending on the geographical and demographical characteristics of the population tested. Based on data from 184 countries, the global average preterm birth rate in 2010 was 11.1%, giving a worldwide total of 14.9 million. It is the leading cause of perinatal morbidity and mortality, as well as maternal morbidity. In fact, prematurity has both short- and long-term consequences for affected offspring and can leave these individuals with lifelong disabilities, even after the available interventions are attempted. Morbidity and mortality increase in proportion to decreasing gestational age, and numbers are especially grave in those defined as “very” preterm (<32 weeks) and “extremely” preterm (<28 weeks).

Many factors can predispose to the development of preterm birth, but it is useful to categorize preterm birth into three general etiologic groups: spontaneous labor with intact membranes, preterm premature rupture of membranes (PPROM) leading to preterm birth, and labor induction due to maternal or fetal factors. While various risk factors for preterm birth are well recognized, the etiology for preterm birth is multifactorial. Preterm parturition is a syndrome resulting from premature activation of the common pathway of parturition, including: an increased myometrial contractility; cervical ripening/dilatation and effacement; and membrane/decidual activation. The activation of human parturition is the result of anatomical, physiological, biochemical, endocrinological, immunological, and clinical events that occur in the mother and/or fetus in both term and preterm labor. In most cases of spontaneous labor at term, there is synchronous activation of the common pathway. However, preterm parturition is the clinical presentation of different underlying mechanisms, including intrauterine infection, uteroplacental ischemia, uterine over-distention, cervical disease, allergic phenomena, and endocrine disorders.

Because the prevalence of preterm birth is so high, it is thought to put more financial, medical, and emotional stress on affected communities than any other perinatal issue. In past years, most of the research interest resulted in the prevention of preterm birth in order to alleviate the complications of prematurity. However, recent evidence suggests that the effect of preterm birth goes beyond the impact on the future health of both the mother and her offspring and the specific delivery in which preterm delivery has occurred.

We sincerely welcome your submission to the Journal of Clinical Medicine.

Prof. Dr. Eyal Sheiner
Guest Editor

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Keywords

Epidemiology of PTD
Risk factors
Symptoms
Classification
Pathophysiology
Genetics
Diagnosis
Ultrasound
Multiple gestations
Prevention
Intervention
Complications
Long-term consequences for the mother and child

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Published Papers (12 papers)

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Editorial

Jump to: Research, Review

4 pages, 216 KiB

Open AccessEditorial

“Advances in Preterm Delivery”—How Can We Advance Further?

by Tamar Wainstock and Eyal Sheiner

J. Clin. Med. 2022, 11(12), 3436; https://doi.org/10.3390/jcm11123436 - 15 Jun 2022

Viewed by 1293

Abstract

Preterm delivery (PTD: <37 gestational weeks) complicates 5–13% of deliveries worldwide [...] Full article

(This article belongs to the Special Issue Advances in Preterm Delivery)

Research

Jump to: Editorial, Review

14 pages, 603 KiB

Open AccessArticle

The Association between Gestational Age and Risk for Long Term Ophthalmic Morbidities among Offspring Delivered in Different Preterm Subgroups

by Erez Tsumi, Itai Hazan, Tamir Regev, Samuel Leeman, Chiya Barrett, Noa Fried Regev and Eyal Sheiner

J. Clin. Med. 2022, 11(9), 2562; https://doi.org/10.3390/jcm11092562 - 2 May 2022

Cited by 4 | Viewed by 1602

Abstract

Objective: To investigate whether there is a linear association between the degree of prematurity and the risk for long-term ophthalmic morbidity among preterm infants. Study design: A population-based, retrospective cohort study, which included all singleton deliveries occurring between 1991 and 2014 at a single tertiary medical center. All infants were divided into four groups according to gestational age categories: extremely preterm births, very preterm births, moderate to late preterm births and term deliveries (reference group). Hospitalizations of offspring up to 18 years of age involving ophthalmic morbidity were evaluated. Survival curves compared cumulative hospitalizations and regression models controlled for confounding variables. Results: During the study period, 243,363 deliveries met the inclusion criteria. Ophthalmic-related hospitalization rates were lower among children born at term (0.9%) as compared with extremely preterm (3.6%), very preterm (2%), and moderate to late preterm (1.4%) born offspring (p < 0.01; using the chi-square test for trends). The survival curve demonstrated significantly different hospitalization rates between the gestational ages (p < 0.001). The regression demonstrated an independent risk for ophthalmic morbidity among extremely preterm born offspring (adjusted hazard ratio 3.8, confidence interval 1.6–9.2, p < 0.01), as well as very preterm and moderate to late preterm (adjusted hazard ratio 2.2 and 1.5, respectively) as compared with term deliveries. Conclusions: The risk for long-term ophthalmic-related hospitalization of preterm offspring gradually decreases as the gestational age increases. Full article

(This article belongs to the Special Issue Advances in Preterm Delivery)

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9 pages, 494 KiB

Open AccessArticle

Low Five-Minute Apgar Score and Neurological Morbidities: Does Prematurity Modify the Association?

by Tamar Wainstock and Eyal Sheiner

J. Clin. Med. 2022, 11(7), 1922; https://doi.org/10.3390/jcm11071922 - 30 Mar 2022

Cited by 5 | Viewed by 3030

Abstract

(1) Background: We aimed to study whether a low 5 min Apgar score is associated with pediatric neurological morbidities throughout childhood. (2) Methods: A population-based retrospective cohort study was conducted. The exposed group was defined as offspring with a 5 min Apgar score <7, and the remaining offspring served as the comparison group. The primary outcome was defined as pediatric hospitalizations with any neurological morbidity. Multivariable survival models were used to evaluate the association between the exposure and outcome while adjusting for potential confounders. Additional models were used to study this association separately among term- and preterm-born offspring. (3) Results: The study population included 349,385 singletons born between the years 1991 and 2021, 0.6% (n = 2030) of whom had a 5 min Apgar score <7 (exposed). The cohort was followed for up to 18 years (median ~ 10.6). The incidence of neurological morbidity-related hospitalizations was higher among the exposed group versus the unexposed group (11.3% versus 7.5%, hazard ratio = 1.84; 95%CI 1.58–2.13). A low 5 min Apgar score remained a significant risk factor for neurological hospitalizations after adjusting for preterm delivery, maternal age, hypertension during pregnancy, gestational diabetes mellitus, chorioamnionitis, and delivery mode (adjusted hazard ratio = 1.61; 95%CI 1.39–1.87). However, after modeling term and preterm offspring separately, a low 5 min Apgar score was independently associated with neurological hospitalizations only among offspring born at term (adjusted hazard ratio = 1.16; 95%CI 0.87–1.55 and 1.70; 95%CI 1.42–2.02 for preterm and term offspring, respectively). (4) Conclusions: A low 5 min Apgar score is independently associated with childhood neurological morbidity, specifically among term-born offspring. Although not designed to identify risk for long-term health complications, Apgar scores may be a marker of risk for short- and long-term neurological morbidities among term newborns. Full article

(This article belongs to the Special Issue Advances in Preterm Delivery)

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13 pages, 1246 KiB

Open AccessArticle

Prematurity and Long-Term Respiratory Morbidity—What Is the Critical Gestational Age Threshold?

by Gil Gutvirtz, Tamar Wainstock, Eyal Sheiner and Gali Pariente

J. Clin. Med. 2022, 11(3), 751; https://doi.org/10.3390/jcm11030751 - 30 Jan 2022

Cited by 11 | Viewed by 2414

Abstract

Respiratory morbidity is a hallmark complication of prematurity. Children born preterm are exposed to both short- and long-term respiratory morbidity. This study aimed to investigate whether a critical gestational age threshold exists for significant long-term respiratory morbidity. A 23-year, population-based cohort analysis was performed comparing singleton deliveries at a single tertiary medical center. A comparison of four gestational age groups was performed according to the WHO classification: term (≥37.0 weeks, reference group), moderate to late preterm (32.0–36.6 weeks), very preterm (28.0–31.6 weeks) and extremely preterm (24.0–27.6 weeks). Hospitalizations of the offspring up to the age of 18 years involving respiratory morbidities were evaluated. A Kaplan–Meier survival curve was used to compare cumulative hospitalization incidence between the groups. A Cox proportional hazards model was used to control for confounders and time to event. Overall, 220,563 singleton deliveries were included: 93.6% term deliveries, 6% moderate to late preterm, 0.4% very preterm and 0.1% extremely preterm. Hospitalizations involving respiratory morbidity were significantly higher in children born preterm (12.7% in extremely preterm children, 11.7% in very preterm, 7.0% in late preterm vs. 4.7% in term, p < 0.001). The Kaplan–Meier survival curve demonstrated a significantly higher cumulative incidence of respiratory-related hospitalizations in the preterm groups (log-rank, p < 0.001). In the Cox regression model, delivery before 32 weeks had twice the risk of long-term respiratory morbidity. Searching for a specific gestational age threshold, the slope for hospitalization rate was attenuated beyond 30 weeks’ gestation. In our population, it seems that 30 weeks’ gestation may be the critical threshold for long-term respiratory morbidity of the offspring, as the risk for long-term respiratory-related hospitalization seems to be attenuated beyond this point until term. Full article

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10 pages, 535 KiB

Open AccessArticle

Benefits of a Single Dose of Betamethasone in Imminent Preterm Labour

by Natalia Saldaña-García, María Gracia Espinosa-Fernández, Celia Gómez-Robles, Antonio Javier Postigo-Jiménez, Nicholas Bello, Francisca Rius-Díaz and Tomás Sánchez-Tamayo

J. Clin. Med. 2022, 11(1), 20; https://doi.org/10.3390/jcm11010020 - 21 Dec 2021

Cited by 2 | Viewed by 3154

Abstract

Background: A complete course of prenatal corticosteroids reduces the possibility of morbimortality and neonatal respiratory distress syndrome (RDS). Occasionally, it is not possible to initiate or complete the maturation regimen, and the preterm neonate is born in a non-tertiary hospital. This study aimed to assess the effects of a single dose of betamethasone within 3 h before delivery on serious outcomes (mortality and serious sequelae) and RDS in preterm neonates born in tertiary vs. non-tertiary hospitals. Materials and methods: Preterm neonates who were <35 weeks and ≤1500 g, treated during a period of five years in a level IIIC NICU, were included in this retrospective cohort study. Participants were divided into groups as follows: NM, non-matured; PM, partial maturation (one dose of betamethasone up to 3 h antepartum). They were further divided based on their place of birth (NICU-IIIC vs. non-tertiary hospitals). The morbimortality rates and the severity of neonatal RDS were evaluated. Results: A total of 76 preterm neonates were included. A decrease in serious outcomes was found in the PM group in comparison to the NM group (OR = 0.2; 95%CI (0.07–0.9)), as well as reduced need for mechanical ventilation (54% vs. 68%). The mean time between maternal admission and birth was similar in both cohorts. The mean time from the administration of betamethasone to delivery was 1 h in the PM cohort. With regard to births in NICU-IIIC, the PM group performed better in terms of serious outcomes (32% vs. 45%) and the duration of mechanical ventilation (117.75 vs. 132.18 h) compared to the NM group. In neonates born in non-tertiary hospitals with PM in comparison to the NM group, a trend towards a reduced serious outcome (28.5% vs. 62.2%) and a decreased need for mechanical ventilation (OR = 0.09; 95%CI (0.01–0.8)) and maximum FiO₂ (p = 0.01) was observed. Conclusions: A single dose of betamethasone up to 3 h antepartum may reduce the rate of serious outcomes and the severity of neonatal RDS, especially in non-tertiary hospitals. Full article

(This article belongs to the Special Issue Advances in Preterm Delivery)

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22 pages, 4831 KiB

Open AccessArticle

Elastography and Metalloproteinases in Patients at High Risk of Preterm Labor

by Izabela Dymanowska-Dyjak, Aleksandra Stupak, Adrianna Kondracka, Tomasz Gęca, Arkadiusz Krzyżanowski and Anna Kwaśniewska

J. Clin. Med. 2021, 10(17), 3886; https://doi.org/10.3390/jcm10173886 - 29 Aug 2021

Cited by 7 | Viewed by 2008

Abstract

Preterm birth (PTB) is the leading cause of perinatal morbidity and mortality. Its etiopathology is multifactorial; therefore, many of the tests contain the assessment of the biochemical factors and ultrasound evaluation of the cervix in patients at risk of preterm delivery. The study aimed at evaluating the socioeconomic data, ultrasound examinations with elastography, plasma concentrations of MMP-8 and MMP-9 metalloproteinases, and vaginal secretions in the control group as well as patients with threatened preterm delivery (high-risk patients). The study included 88 patients hospitalized in the Department of Obstetrics and Pregnancy Pathology, SPSK 1, in Lublin. Patients were qualified to the study group (50) with a transvaginal ultrasonography of cervical length (CL) ≤ 25 mm. The control group (38) were patients with a physiological course of pregnancy with CL > 25 mm. In the study group, the median length of the cervix was 17.49 mm. Elastographic parameters: strain and ratio were 0.20 and 0.83. In the control group, the median length of the cervix was 34.73 mm, while the strain and ratio were 0.20 and 1.23. In the study group, the concentration of MMP-8 in the serum and secretions of the cervix was on average 74.17 and 155.46 ng/mL, but in the control group, it was significantly lower, on average 58.49 and 94.19 ng/mL. The concentration of MMP-9 in both groups was on the same level. Evaluation of the cervical length and measurement of MMP-8 concentration are the methods of predicting preterm delivery in high-risk patients. The use of static elastography did not meet the criteria of a PTB marker. Full article

(This article belongs to the Special Issue Advances in Preterm Delivery)

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8 pages, 420 KiB

Open AccessArticle

Maternal Systemic Lupus Erythematosus (SLE) High Risk for Preterm Delivery and Not for Long-Term Neurological Morbidity of the Offspring

by Dora Davidov, Eyal Sheiner, Tamar Wainstock, Shayna Miodownik and Gali Pariente

J. Clin. Med. 2021, 10(13), 2952; https://doi.org/10.3390/jcm10132952 - 30 Jun 2021

Cited by 11 | Viewed by 2243

Abstract

Objective: Pregnancies of women with systemic lupus erythematosus (SLE) are associated with preterm delivery. As preterm delivery is associated with long-term neurological morbidity, we opted to evaluate the long-term neurologic outcomes of offspring born to mothers with SLE regardless of gestational age. Methods: Perinatal outcomes and long-term neurological disease of children of women with and without SLE during pregnancy were evaluated. Children of women with and without SLE were followed until 18 years of age for neurological diseases. Generalized estimating equation (GEE) models were used to assess perinatal outcomes. To compare cumulative neurological morbidity incidence a Kaplan–Meier survival curve was used, and a Cox proportional hazards model was used to control for confounders. Result: A total of 243,682 deliveries were included, of which 100 (0.041%) were of women with SLE. Using a GEE model, maternal SLE was noted as an independent risk factor for preterm delivery. The cumulative incidence of long-term neurological disease was not found to be significantly higher when using the Kaplan Meier survival curves and maternal SLE was not found to be associated with long-term neurological disease of the offspring when a Cox model was used. Conclusion: Despite the association of SLE with preterm delivery, no difference in long-term neurological disease was found among children of women with or without SLE. Full article

(This article belongs to the Special Issue Advances in Preterm Delivery)

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11 pages, 1328 KiB

Open AccessArticle

Identifying the Critical Threshold for Long-Term Pediatric Neurological Hospitalizations of the Offspring in Preterm Delivery

by Shiran Zer, Tamar Wainstock, Eyal Sheiner, Shayna Miodownik and Gali Pariente

J. Clin. Med. 2021, 10(13), 2919; https://doi.org/10.3390/jcm10132919 - 29 Jun 2021

Cited by 7 | Viewed by 3897

Abstract

We opted to investigate whether a critical threshold exists for long-term pediatric neurological morbidity, and cerebral palsy (CP), in preterm delivery, via a population-based cohort analysis. Four study groups were classified according to their gestational age at birth: 24–27.6, 28–31.6, 32–36.6 weeks and term deliveries, evaluating the incidence of long-term hospitalizations of the offspring due to neurological morbidity. Cox proportional hazard models were performed to control for confounders. A Kaplan–Meier survival curve was used to compare the cumulative neurological morbidity incidence for each group. A total of 220,563 deliveries were included: 0.1% (118) occurred at 24–27.6 weeks of gestation, 0.4% (776) occurred at 28–31.6 weeks of gestation, 6% (13,308) occurred at 32–36.6 weeks of gestation and 93% (206,361) at term. In a Cox model, while adjusting for confounders, delivery before 25 weeks had a 3.9-fold risk for long-term neurological morbidity (adjusted HR (hazard ratio) = 3.9, 95% CI (confidence interval) 2.3–6.6; p < 0.001). The Kaplan–Meier survival curve demonstrated a linear association between long-term neurological morbidity and decreasing gestational age. In a second Cox model, adjusted for confounders, infants born before 25 weeks of gestation had increased rates of CP (adjusted HR = 62.495% CI 25.6–152.4; p < 0.001). In our population, the critical cut-off for long-term neurological complications is delivery before 25 weeks gestation. Full article

(This article belongs to the Special Issue Advances in Preterm Delivery)

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12 pages, 233 KiB

Open AccessArticle

Preterm Delivery; Who Is at Risk?

by Dvora Kluwgant, Tamar Wainstock, Eyal Sheiner and Gali Pariente

J. Clin. Med. 2021, 10(11), 2279; https://doi.org/10.3390/jcm10112279 - 24 May 2021

Cited by 7 | Viewed by 2108

Abstract

Preterm birth (PTB) is the leading cause of perinatal morbidity and mortality. Adverse effects of preterm birth have a direct correlation with the degree of prematurity, in which infants who are born extremely preterm (24–28 weeks gestation) have the worst outcomes. We sought to determine prominent risk factors for extreme PTB and whether these factors varied between various sub-populations with known risk factors such as previous PTB and multiple gestations. A population-based retrospective cohort study was conducted. Risk factors were examined in cases of extreme PTB in the general population, as well as various sub-groups: singleton and multiple gestations, women with a previous PTB, and women with indicated or induced PTB. A total of 334,415 deliveries were included, of which 1155 (0.35%) were in the extreme PTB group. Placenta previa (OR = 5.8, 95%CI 4.14–8.34, p < 0.001), multiple gestations (OR = 7.7, 95% CI 6.58–9.04, p < 0.001), and placental abruption (OR = 20.6, 95%CI 17.00–24.96, p < 0.001) were the strongest risk factors for extreme PTB. In sub-populations (multiple gestations, women with previous PTB and indicated PTBs), risk factors included placental abruption and previa, lack of prenatal care, and recurrent pregnancy loss. Singleton extreme PTB risk factors included nulliparity, lack of prenatal care, and placental abruption. Placental abruption was the strongest risk factor for extreme preterm birth in all groups, and risk factors did not differ significantly between sub-populations. Full article

(This article belongs to the Special Issue Advances in Preterm Delivery)

9 pages, 259 KiB

Open AccessFeature PaperArticle

Can We Predict Preterm Delivery Based on the Previous Pregnancy?

by Tamar Wainstock, Ruslan Sergienko and Eyal Sheiner

J. Clin. Med. 2021, 10(7), 1517; https://doi.org/10.3390/jcm10071517 - 5 Apr 2021

Cited by 3 | Viewed by 1963

Abstract

(1) Background: Preterm deliveries (PTD, <37 gestational weeks) which occur in 5–18% of deliveries across the world, are associated with immediate and long-term offspring morbidity, as well as high costs to health systems. Our aim was to identify risk factors during the first pregnancy ending at term for PTD in the subsequent pregnancy. (2) Methods: A retrospective population- based nested case−control study was conducted, including all women with two first singleton consecutive deliveries. Women with PTD in the first pregnancy were excluded. Characteristics and complications of the first pregnancy were compared among cases, defined as women with PTD in their second pregnancy, and the controls, defined as women delivering at term in their second pregnancy. A multivariable logistic regression model was used to study the association between pregnancy complications (in the first pregnancy) and PTD (in the subsequent pregnancy), while adjusting for maternal age and the interpregnancy interval. (3) Results: A total of 39,780 women were included in the study, 5.2% (n = 2088) had PTD in their second pregnancy. Women with PTD, as compared to controls (i.e., delivered at term in second pregnancy), were more likely to have the following complications in their first pregnancy: perinatal mortality (0.4% vs. 1.0%), small for gestational age (12.4% vs. 8.1%), and preeclampsia (7.6% vs. 5.7%). In the multivariable model, after adjusting for maternal age, interpregnancy interval and co-morbidities, having any one of these first pregnancy complications was independently associated with an increased risk for PTD (adjusted OR = 1.44; 95%CI 1.28–1.62), and the risk was greater if two or more complications were diagnosed (adjusted OR = 2.09; 95%CI 1.47–3.00). These complications were also risk factors for early PTD (<34 gestational weeks), PTD with a systematic infectious disease in the background, and possibly with spontaneous PTD. (4) Conclusions: First pregnancy complications are associated with an increased risk for PTD in the subsequent pregnancy. First pregnancy, although ending at term, may serve as a window of opportunity to identify women at risk for future PTD. Full article

(This article belongs to the Special Issue Advances in Preterm Delivery)

15 pages, 2083 KiB

Open AccessArticle

Identification of Vaginal Microbial Communities Associated with Extreme Cervical Shortening in Pregnant Women

by Monica Di Paola, Viola Seravalli, Sara Paccosi, Carlotta Linari, Astrid Parenti, Carlotta De Filippo, Michele Tanturli, Francesco Vitali, Maria Gabriella Torcia and Mariarosaria Di Tommaso

J. Clin. Med. 2020, 9(11), 3621; https://doi.org/10.3390/jcm9113621 - 10 Nov 2020

Cited by 13 | Viewed by 3578

Abstract

The vaginal microbiota plays a critical role in pregnancy. Bacteria from Lactobacillus spp. are thought to maintain immune homeostasis and modulate the inflammatory responses against pathogens implicated in cervical shortening, one of the risk factors for spontaneous preterm birth. We studied vaginal microbiota in 46 pregnant women of predominantly Caucasian ethnicity diagnosed with short cervix (<25 mm), and identified microbial communities associated with extreme cervical shortening (≤10 mm). Vaginal microbiota was defined by 16S rRNA gene sequencing and clustered into community state types (CSTs), based on dominance or depletion of Lactobacillus spp. No correlation between CSTs distribution and maternal age or gestational age was revealed. CST-IV, dominated by aerobic and anaerobic bacteria different than Lactobacilli, was associated with extreme cervical shortening (odds ratio (OR) = 15.0, 95% confidence interval (CI) = 1.56–14.21; p = 0.019). CST-III (L. iners-dominated) was also associated with extreme cervical shortening (OR = 6.4, 95% CI = 1.32–31.03; p = 0.02). Gestational diabetes mellitus (GDM) was diagnosed in 10/46 women. Bacterial richness was significantly higher in women experiencing this metabolic disorder, but no association with cervical shortening was revealed by statistical analysis. Our study confirms that Lactobacillus-depleted microbiota is significantly associated with an extremely short cervix in women of predominantly Caucasian ethnicity, and also suggests an association between L. iners-dominated microbiota (CST III) and cervical shortening. Full article

(This article belongs to the Special Issue Advances in Preterm Delivery)

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Review

Jump to: Editorial, Research

11 pages, 263 KiB

Open AccessReview

Prevention of Preterm Birth with Progesterone

by Gian Carlo Di Renzo, Valentina Tosto, Valentina Tsibizova and Eduardo Fonseca

J. Clin. Med. 2021, 10(19), 4511; https://doi.org/10.3390/jcm10194511 - 29 Sep 2021

Cited by 13 | Viewed by 5058

Abstract

Gestational age at birth is a critical factor for perinatal and adulthood outcomes, and even for transgenerational conditions’ effects. Preterm birth (PTB) (prematurity) is still the main determinant for infant mortality and morbidity leading cause of infant morbidity and mortality. Unfortunately, preterm birth (PTB) is a relevant public health issue worldwide and the global PTB rate is around 11%. The premature activation of labor is underlined by complex mechanisms, with a multifactorial origin influenced by numerous known and probably unknown triggers. The possible mechanisms involved in a too early labor activation have been partially explained, and involve chemokines, receptors, and imbalanced inflammatory paths. Strategies for the early detection and prevention of this obstetric condition were proposed in clinical settings with interesting results. Progesterone has been demonstrated to have a key role in PTB prevention, showing several positive effects, such as lower prostaglandin synthesis, the inhibition of cervical stromal degradation, modulating the inflammatory response, reducing gap junction formation, and decreasing myometrial activation. The available scientific knowledge, data and recommendations address multiple current areas of debate regarding the use of progesterone in multifetal gestation, including different formulations, doses and routes of administration and its safety profile in pregnancy. Full article

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