Progestogens for maintenance tocolysis in symptomatic women. A systematic review and meta-analysis.

OBJECTIVE: Prevention of preterm birth (PTB) with progestogens after an episode of threatened preterm labour is still controversial. As different progestogens have distinct molecular structures and biological effects, we conducted a systematic review and pairwise meta-analysis to investigate the individual role played by 17-alpha-hydroxyprogesterone caproate (17-HP), vaginal progesterone (Vaginal P) and oral progesterone (Oral P). METHODS: The search was performed in MEDLINE, ClinicalTrials.gov and the Cochrane Central Register of Controlled Trials (CENTRAL) up to 31 October 2021. Published RCTs comparing progestogens to placebo or no treatment for maintenance tocolysis were considered. We included women with singleton gestations, excluding quasi-randomized trials, studies on women with preterm premature rupture of membrane, or receiving maintenance tocolysis with other drugs. Primary outcomes were preterm birth (PTB) < 37 weeks' and < 34 weeks'. We assessed risk of bias and evaluated certainty of evidence with the GRADE approach. RESULTS: Seventeen RCTs including 2152 women with singleton gestations were included. Twelve studies tested vaginal P, five 17-HP, and only 1 oral P. PTB < 34 weeks' did not differ among women receiving vaginal P (RR 1.21, 95%CI 0.91 to 1.61, 1077 participants, moderate certainty of evidence), or oral P (RR 0.89, 95%CI 0.38 to 2.10, 90 participants, low certainty of evidence) as opposed to placebo. Instead, 17-HP significantly reduced the outcome (RR 0.72, 95% CI 0.54 to 0.95, 450 participants, moderate certainty of evidence). PTB < 37 weeks' did not differ among women receiving vaginal P (RR 0.95, 95%CI 0.72 to 1.26, 8 studies, 1231 participants, moderate certainty of evidence) or 17-HP (RR 0.86, 95%CI 0.60 to 1.21, 450 participants, low certainty of evidence) when compared to placebo/no treatment. Instead, oral P significantly reduced the outcome (RR 0.58, 95% CI 0.36 to 0.93, 90 participants, low certainty of evidence). CONCLUSIONS: With a moderate certainty of evidence, 17-HP prevents PTB < 34 weeks' gestation among women that remained undelivered after an episode of threatened preterm labour. However, data are insufficient to generate recommendations in clinical practice. In the same women, both 17-HP and vaginal P are ineffective in the prevention of PTB < 37 weeks'.

Supplementation of Probiotics in Pregnant Women Targeting Group B Streptococcus Colonization: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aimed to determine if probiotic supplementation in pregnancy reduced maternal Group B streptococcus (GBS) recto-vaginal colonization in pregnant women at 35-37 weeks of gestation. Electronic databases (i.e., PubMed, MEDLINE, ClinicalTrials.gov, ScienceDirect, and the Cochrane Library) were searched from inception up to February 2022. We included RCTs assessing the effects of probiotic supplementation in pregnancy on GBS recto-vaginal colonization. The primary outcome was GBS-positive recto-vaginal cultures performed at 35-37 weeks of gestation. Secondarily, we evaluated obstetric and short-term neonatal outcomes. A total of 132 publications were identified; 9 full-length articles were reviewed to finally include 5 studies. Probiotic supplementation reduced vaginal GBS colonization: the GBS positive culture rate was estimated at 31.9% (96/301) in the intervention group compared to 38.6% (109/282) in the control group (OR = 0.62, 95% CI 0.40-0.94, I2 4.8%, p = 0.38). The treatment started after 30 weeks of gestation and was more effective in reducing GBS colonization (OR 0.41, 95% CI 0.21-0.78, I2 0%, p = 0.55). Probiotic administration during pregnancy, namely in the third trimester, was associated with a reduced GBS recto-vaginal colonization at 35-37 weeks and a safe perinatal profile. Whether this new strategy could reduce the exposition of pregnant women to significant doses of antibiotics in labor needs to be evaluated in other trials.

Complete hydatidiform mole in higher-order multiple pregnancies.

Molar degeneration of the trophoblast is a rare, yet possible, complication of pregnancies. Complete hydatidiform mole is the most common histological type among all trophoblastic tumors and it is the result of the fertilization of an empty oocyte from two sperms or by one sperm that then duplicates. Complete mole is characterized by hydropic degeneration of abnormal chorionic villi, diffused trophoblast hyperplasia and the absence of identifiable embryonic or fetal tissue; the hyperplastic trophoblast justifies the common finding of high serum beta HCG levels. Twin molar pregnancy is an uncommon obstetric event, and even less frequent are triplet/quadruplet molar pregnancies. We hereby report a case of a complete hydatidiform mole with two coexistent fetuses in a triplet pregnancy after in vitro fertilization procedure; the pregnancy ended with a therapeutic abortion. During the follow-up, the serum beta human chorionic gonadotropin concentration started to rise, and the diagnosis of post-molar gestational trophoblastic neoplasia was made and consequently methotrexate treatment was started. Due to the rarity of this condition, there are no specific guidelines for the management of multiple pregnancies complicated by complete hydatidiform mole. We therefore performed a review of the literature including all reported cases of triplets/quadruplets pregnancies complicated by complete mole of a fetus focusing on ultrasound diagnosis, treatment and outcomes of this rare and life-threatening condition.

Perinatal outcomes in twin late preterm pregnancies: results from an Italian area-based, prospective cohort study.

BACKGROUND: Multiple gestations represent a considerable proportion of pregnancies delivering in the late preterm (LP) period. Only 30% of LP twins are due to spontaneous preterm labor and 70% are medically indicated; among this literature described that 16-50% of indicated LP twin deliveries are non-evidence based. As non-evidence-based delivery indications account for iatrogenic morbidity that could be prevented, the objective of our observational study is to investigate first neonatal outcomes of LP twin pregnancies according to gestational age at delivery, chorionicity and delivery indication, then non evidence-based delivery indications. METHODS: Prospective cohort study among twins infants born between 34 + 0 and 36 + 6 weeks, in Emilia Romagna, Italy, during 2013-2015. The primary outcome was a composite of adverse perinatal outcomes. RESULTS: Among 346 LP twins, 84 (23.4%) were monochorionic and 262 (75.7%) were dichorionic; spontaneous preterm labor accounted for 85 (24.6%) deliveries, preterm prelabor rupture of membranes for 66 (19.1%), evidence based indicated deliveries were 117 (33.8%), while non-evidence-based indications were 78 (22.5%). When compared to spontaneous preterm labor or preterm prelabor rupture of membranes, pregnancies delivered due to maternal and/or fetal indications were associated with higher maternal age (p <  0.01), higher gestational age at delivery (p <  0.01), Caucasian race (p 0.04), ART use (p <  0.01), gestational diabetes (p <  0.01), vaginal bleeding (p <  0.01), antenatal corticosteroids (p <  0.01), diagnosis of fetal growth restriction (FGR) (p <  0.01), and monochorionic (p <  0.01). Two hundred twenty-six pregnancies (65.3%) had at least one fetus experiencing one composite of adverse perinatal outcome. Multivariate analysis confirmed that delivery indication did not affect the composite of adverse perinatal outcomes; the only characteristic that affect the outcome after controlling for confounding was gestational age at delivery (p <  0.01). Moreover, there was at least one adverse neonatal outcome for 94% of babies born at 34 weeks, for 73% of those born at 35 weeks and for 46% of those born at 36 weeks (p <  0.01). CONCLUSION: Our study suggests that the decision to deliver or not twins in LP period should consider gestational age at delivery as the main determinant infants' prognosis. Delivery indications should be accurately considered, to avoid iatrogenic early birth responsible of preventable complications.

Delivery indication matters for perinatal outcomes in late preterm newborns.

BACKGROUND: The late preterm (LP) rate in Western countries is 3-6% of all births, accounting for about two-thirds of the entire preterm population. However, all LP babies are not the same. AIMS: To identify pregnancies at risk for adverse outcomes in the LP period, we investigated how gestational age (GA) at delivery, delivery indication and prenatal risk factors may affect neonatal outcomes. STUDY DESIGN: Prospective cohort study among singleton infants born between 34 + 0 and 36 + 6 weeks, in Emilia Romagna, Italy, during 2013-2015. OUTCOMES MEASURES: The primary outcome was a composite of adverse perinatal outcomes. Multivariate logistic regression models were used to, respectively, investigate the effects of GA at delivery, circumstances at parturition and prenatal risk factors, on study outcomes after controlling for confounding variable. RESULTS: Among 1867 births, 302, 504, and 1061 infants were born at 34, 35, and 36 weeks, respectively. There were no neonatal deaths. An increased risk of composite neonatal outcome was observed among 34 and 35 weeks deliveries compared with 36 weeks, and among indicated deliveries compared with spontaneous. When studying prenatal risk factors, neonatal morbidity was associated with pre gestational diabetes, preterm premature rupture of membranes (pPROM), maternal obesity, bleeding and polyhydramnios; instead, preeclampsia had a protective effect. CONCLUSION: LP with indicated deliveries at 34 or 35 weeks, or with specific prenatal risk factors have worse neonatal outcome when compared to 36. Such differences should be considered when counseling patients and planning interventions such as timing of delivery in LP period.

Prevalence of uterine rupture among women with one prior low transverse cesarean and women with unscarred uterus undergoing labor induction with PGE2: A systematic review and meta-analysis.

BACKGROUND: As uterine rupture may affect as many as 11/1000 women with 1 prior cesarean birth and 5/10.000 women with unscarred uterus undergoing labor induction, we intended to estimate the prevalence of such rare outcome when PGE2 is used for cervical ripening and labor induction. METHODS: We searched MEDLINE, ClinicalTrials.gov and the Cochrane library up to September 1st 2020. Retrospective and prospective cohort studies, as well as randomized controlled trials (RCTs) on singleton viable pregnancies receiving PGE2 for cervical ripening and labor induction were reviewed. Prevalence of uterine rupture was meta-analyzed with Freeman-Tukey double arcsine transformation among women with 1 prior low transverse cesarean section and women with unscarred uterus. RESULTS: We reviewed 956 full text articles to include 69 studies. The pooled prevalence rate of uterine rupture is estimated to range between 2 and 9 out of 1000 women with 1 prior low transverse cesarean (5/1000; 95%CI 2-9/1000, 122/9000). The prevalence of uterine rupture among women with unscarred uterus is extremely low, reaching at most 0.7/100.000 (<1/100.000.000; 95%CI <1/100.000.000-0.7/100.000, 8/17.684). CONCLUSIONS: Uterine rupture is a rare event during cervical ripening and labor induction with PGE2.

Neonatal outcomes and risk of neonatal sepsis in an expectantly managed cohort of late preterm prelabor rupture of membranes.

OBJECTIVE: Expectant management in patients with prelabor preterm rupture of membranes between between 340/7 and 36 6/7 weeks (late preterm pPROM or LpPROM) has been shown to decrease the burden of prematurity, when compared to immediate delivery. As the severity of prematurity depends on gestational age (GA) at PROM, and PROM to delivery interval, we first investigated how such variables affect neonatal outcomes (NO). Second, we assessed the risk of neonatal sepsis. STUDY DESIGN: retrospective cohort study on neonatal morbidity among singleton infants born to expectantly managed mothers with LpPROM in five hospitals affiliated with three Italian academic institutions. The primary NO was a composite of neonatal death, non-invasive (cPAP) or invasive (mechanical ventilation) respiratory support, hypoglycemia (< 44 mg/dl needing therapy), newborn sepsis, confirmed seizures, stroke, intraventricular hemorrhage (IVH), basal nuclei anomalies, cardiopulmonary resuscitation, umbilical-cord-blood arterial pH < 7.0 or base excess < -12.5, and prolonged hospitalization (≥ 5 days). Univariate analysis described differences in the population according to GA at delivery. Multivariate logistic regression was then used to investigate the effects of GA at PROM, and PROM to delivery interval on the NO. RESULTS: 258/606 (42.6 %) women with LpPROM were expectantly managed, as they did not deliver within the first 24 h. The median latency duration was 2 (95 %CI 1-3) days, having no effect on neonatal morbidity on multivariate analysis. Multivariate analysis also showed increased risks of adverse NO among PROM at 34 (OR 2.3 95 %CI 1.03-5.1) but not at 35 weeks when compared to 36 weeks, and among women receiving antenatal corticosteroids (OR 3.6 95 %CI 1.3-9.7), while antibiotic treatment showed a non-significant protective effect (OR 0.2 95 %CI 0.04-1.02). Prevalence of neonatal sepsis was 0.8 % (2/258) CONCLUSION: Expectant management of LpPROM should be encouraged especially between 34+0 and 34+6 weeks', when the burden of prematurity is the greatest. Antibiotics may have beneficial effects, while careful consideration should be given to antenatal corticosteroids until future studies specifically address LpPROM.

Adenocarcinoma in situ of the uterine cervix: Clinical practice guidelines from the Italian society of colposcopy and cervical pathology (SICPCV).

OBJECTIVE: to provide a practical tool for the evidenced-based management of adenocarcinoma in situ (AIS) of the uterine cervix, a challenging diagnosis encountered by colposcopists in their daily practice. METHODS: the proposed recommendations were drafted by the Italian Society of Colposcopy and Cervical Pathology (SICPCV) based on comprehensive reviews of previous guidelines, large uncontrolled studies, metanalysis, and sytematic reviews. The quality Level and the strength of the recommendations were graded and respectively expressed in Roman numbers (I-VI) and letters (A-E). RESULTS: Women with all subcategories of abnormal glandular cells and AIS on cervical citology should be offered colposcopy with endocervical sampling (Strength of recommendation: A). In women with cytological AIS and negative colposcopy or endocervical curettage, an excisional treatment under colposcopic guidance is recommended (Strength of recommendation: A). If immediate post-conization endocervical sampling is positive, further conization is indicated (Strength of recommendation: C). In women who desire to preserve fertility with positive cone margins, further conization should be performed (Strength of recommendation: B). If colposcopy is adequate, a cylindrical excision that includes the whole transformation zone and at least 1-1.5 cm of endocervix beyond the squamous-columnar junction should be performed (Strength of recommendation: B). If colposcopy is inadequate, it is recommended that conization includes the whole transformation zone with a depth of 20-25 mm (Strength of recommendation: B). Hysterectomy is the standard definitive treatment for AIS in women who do not wish to preserve fertility (Strength of recommendation: B). CONCLUSION: the proposed recommendations should enable clinicians to correctly diagnose, treat and follow AIS patients, avoiding mismanagement.

Increasing BMI is associated with both endometrioid and serous histotypes among endometrial rather than ovarian cancers: a case-to-case study.

AIM: Although obesity has been associated with endometrioid (type I) and, to a lesser extent, with serous (type II) endometrial cancer (EC), the association with the same histotypes of ovarian cancer (OC) remains unclear. Therefore, we intended to compare the role of BMI in carcinogenesis of endometrioid and the serous malignancies, at both ovarian and endometrial level. METHODS: A retrospective case-to-case study was performed in the University Hospital of Bologna (Italy), through the review of primary EC matched with the corresponding OC cases in the same period (1988-2017). RESULTS: We included 1052 women diagnosed with EC (n = 897 endometrioid, n = 52 serous) and 955 women affected by OC (n = 132 endometrioid, n = 627 serous). EC patients had higher median BMI than women diagnosed with OC (27.3 [23.4-31.9] vs 24.9 [21.7-27.5], p < 0.01). After controlling for confounding, 1 unit increase in BMI was associated with a 5% higher odds of endometrial as opposed to ovarian cancer (OR for ovarian as opposed to endometrial cancer 0.95; 95% CI 0.91-0.98, p = 0.004). CONCLUSIONS: Increasing BMI is associated with endometrial rather than ovarian cancer, among both serous and endometrioid histotypes.

Multimodal Pain Management for Cesarean Delivery: A Double-Blinded, Placebo-Controlled, Randomized Clinical Trial.

OBJECTIVE: Our objective was to evaluate the efficacy of perioperative multimodal pain management in reducing opioid use after elective cesarean delivery (CD). STUDY DESIGN: A single-center, double-blinded, placebo-controlled randomized trial of women undergoing elective CD. Participants were allocated 1:1 to receive the multimodal protocol or matching placebos. The multimodal protocol consisted of a preoperative dose of intravenous acetaminophen, preincision injection of subcutaneous bupivacaine, and intraoperative injection of intramuscular ketorolac. Primary outcome was total opioid intake at 48 hours postoperatively. Secondary outcomes were pain scores, time to first opioid intake, neonatal outcomes, and total outpatient opioid intake on postoperative day (POD) 7. Data were analyzed using parametric and nonparametric tests and quantile regression as appropriate. RESULTS: A total of 242 women were screened with 120 randomized, 60 to the multimodal group and 60 to control group. There was no significant difference in the primary outcome of opioid use nor in the secondary outcomes. Smokers and patients with a history of drug use had higher median postoperative opiate use and earlier administration. On POD 7, only 40% of prescribed opioids had been used, and there was no difference between the groups. CONCLUSION: This perioperative multimodal pain regimen did not reduce opioid use in 48 hours after CD. Patients who smoke or with a history of drug use required more opioids in the postoperative period. Providers significantly overprescribed opioids after CD.

Effects of medication intake in early pregnancy on the fetal fraction of cell-free DNA testing.

OBJECTIVES: To determine the association between medications intake in early pregnancy and variation in the fetal fraction (FF) in pregnant women undergoing cell-free DNA (cfDNA) testing. METHODS: We performed a retrospective cohort study of women (n = 1051) undergoing cfDNA testing at an academic center. The exposed group included women taking medications (n = 400; 38.1%), while the nonexposed group consisted of women taking no medications (n = 651; 61.9%). Our primary outcome was FF. We performed univariate and multivariate analyses as appropriate. RESULTS: The FFs were 8.8% (6.6-12.1), 8.7% (6.3-11.6), and 7.7% (5.1-9.3) among women taking 0, 1, and two or more medications, respectively (P < 0.01). Using multivariable linear mixed effects model, the mean FF was significantly lower among those taking two or more medications compared with the nonexposed group. FF was directly correlated with gestational age at the time of cfDNA testing and inversely correlated with maternal obesity. Exposure to metformin was associated with 1.8% (0.2-3.4) lower mean FF when compared with the nonexposed group (P = 0.02). Obesity and intake of two or more medications were associated with higher hazard ratio of having a low FF less than 4%. CONCLUSIONS: Exposure to metformin or two or more medications was associated with decreased FF, and obesity is associated with delay in achieving adequate FF percentage. These findings should be considered while counseling patients on test limitations.

Reference intervals for hemoglobin and hematocrit in a low-risk pregnancy cohort: implications of racial differences.

Objective: As anemia in pregnancy is associated with adverse perinatal outcomes, we sought to define the mean and the fifth percentile of Hb and Ht using a contemporary multiethnic large cohort of low-risk pregnancies, and assess potential racial differences. Methods: We conducted a retrospective cohort study on women who delivered between 1 January 2008 and 31 December 2013 in Reggio Emilia County, Italy. Linear mixed effects models were used to describe changes in mean Hb and Ht, while quantile regression with matrix-design bootstrap defined changes in the fifth percentile of Hb and Ht, controlling for race, maternal age, smoking, and pregnancy number. Results: We analyzed 23,657 hemograms from 7318 pregnancies and 6870 women. Multivariate analysis showed that when compared to Caucasians', African women's mean Hb and Ht were respectively 0.24 (95%CI 0.3-0.17) g/dl and 0.7 (95%CI 0.8-0.5) % lower, while Asian mothers' were 0.11 (95%CI 0.19-0.03) g/dl and 0.3 (95%CI 0.5-0.1) % inferior. Similarly, both African and Asian women had lower fifth Ht percentiles (-1, 95%CI -1.3 to -0.6, and -0.4, 95%CI -0.7 to -0.04) than Caucasians, while African mothers also had lower fifth Hb percentile (0.3, 95%CI 0.5-0.1). The fifth percentile for Hb and Ht were, respectively, 11.3 (95%CI 11-11.5) g/dl and 32.8 (95%CI 32.3-33.4) % in the first trimester, 10.4 (95%CI 10.1-10.6) g/dl and 30.2 (95%CI 29.6-30.8) % in the second trimester, 10.1 (95%CI 9.8-10.3) g/dl and 30.6 (95%CI 30-31.1) % in the third trimester. Conclusions: We provided contemporary references to define anemia in pregnancy, and we confirmed that even in pregnancy, African and Asian women have lower Hb and Ht than Caucasian. Racial and population-specific references may have significant clinical and public health implication for more accurate disease diagnosis and appropriate treatment.

Maternal obesity is associated with chorioamnionitis and earlier indicated preterm delivery among expectantly managed women with preterm premature rupture of membranes.

OBJECTIVE: To determine the association between maternal obesity and delivery due to chorioamnionitis prior to labor onset, among expectantly managed women with preterm premature rupture of membranes (pPROM). METHODS: This was a secondary analysis of a multicenter randomized trial of magnesium sulfate versus placebo to prevent cerebral palsy or death among offspring of women with anticipated delivery at 24-31-week gestation. After univariable analysis, Cox proportional hazard evaluated the association between maternal obesity and chorioamnionitis, while Laplace regression investigated how obesity affects the gestational age at delivery of the first 20% of women developing the outcome of interest. RESULTS: A total of 164 of the 1942 women with pPROM developed chorioamnionitis prior to labor onset. Obese women had a 60% increased hazard of developing such complication (adjusted HR 1.6, 95%CI 1.1-2.1, p = .008), prompting delivery 1.5 weeks earlier, as the 20th survival percentile was 27.2-week gestation (95%CI 26-28.6) among obese as opposed to 28.8 weeks (95%CI 27.4-30.1) (p = .002) among nonobese women. CONCLUSIONS: Maternal obesity is a risk factor for chorioamnionitis prior to labor onset. Future studies will determine if obesity is important enough to change the management of latency after pPROM according to maternal BMI.

Using Cervical Length Measurement for Lower Spontaneous Preterm Birth Rates Among Women With Threatened Preterm Labor.

Spontaneous preterm birth is a leading cause of perinatal morbidity and mortality; however, accurate identification of women who will deliver prematurely after the onset of uterine contractions is still challenging, because less than 10% actually give birth within 7 days of presentation. Risk stratification in women with preterm contractions would allow targeting of interventions such as corticosteroids, magnesium sulfate, and maternal transfer to a perinatal center to those who will indeed deliver preterm. Moreover, unnecessary treatments associated with potential complications could be avoided in symptomatic women who are unlikely to deliver preterm. Fetal fibronectin testing and cervical length measurement are the most used methods to assess the risk of preterm birth among symptomatic women. Interventional studies in singleton gestations suggest that assessment of cervical length, unlike fetal fibronectin testing, improves diagnostic accuracy and leads to better perinatal outcomes.

Effect of maternal age, height, BMI and ethnicity on birth weight: an Italian multicenter study.

AIM: To assess the effect of maternal age, height, early pregnancy body mass index (BMI) and ethnicity on birth weight. SUBJECTS AND METHODS: A cross-sectional study was conducted on more than 42,000 newborns. Ethnicity was defined by maternal country of birth or, when missing (<0.6% of records), by citizenship. The effect of maternal characteristics on birth weight was evaluated with general linear models. RESULTS: Maternal height and BMI, although not age, significantly affected birth weight. Among Italian babies, 4.7% of newborns were classified as appropriate-for-gestational age (AGA) (birth weight between the 10th and the 90th centile) according to the country-specific Italian Neonatal Study (INeS) charts and were re-classified as either large-(LGA) (birth weight >90th centile) or small-(SGA) (birth weight <10th centile) for gestational age (GA) after adjustment for maternal characteristics. On the contrary, 1.6% of Italian newborns were classified as SGA or LGA according to the INeS charts and re-classified as AGA after adjustment. Maternal ethnicity had a significant impact on birth weight. Specifically, babies born to Senegalese mothers were the lightest, whilst babies born to Chinese mothers were the heaviest. CONCLUSIONS: Maternal height and early pregnancy BMI, should be considered in the evaluation of birth weight. The effect of ethnicity suggests the appropriateness of ethnic-specific charts. Further studies are necessary to determine if changes in birth weight classification, may translate into improved detection of subjects at risk of adverse outcomes.

Tranexamic Acid for the Management of Obstetric Hemorrhage.

Obstetric hemorrhage remains the most common cause of maternal mortality worldwide. It is believed that increased fibrinolytic activity, secondary to release and activation of endothelial tissue plasminogen activator, is involved in its pathogenesis. Tranexamic acid (TXA), an antifibrinolytic agent, has been shown to be beneficial in trauma patients if used within 3 hours of injury. A recent large randomized controlled trial showed that TXA given to hemorrhaging women within 3 hours after delivery was associated with decreased risk of death resulting from bleeding with no increase in thromboembolic complications. Limited evidence suggests that prophylactic TXA reduces blood loss at the time of delivery and decreases transfusion rates in the obstetric population. Tranexamic acid appears to be a safe and effective option in the treatment of obstetric hemorrhage. In addition, the limited available evidence supports the need for a well-designed adequately powered clinical trial to test its benefit as a prophylactic agent.

Uterus-targeted liposomes for preterm labor management: studies in pregnant mice.

Preterm labor caused by uterine contractions is a major contributor to neonatal morbidity and mortality. Treatment intended to reduce uterine contractions include tocolytic agents, such as indomethacin. Unfortunately, clinically used tocolytics are frequently inefficient and cross the placenta causing fetal side effects. Here we show for the first time in obstetrics the use of a targeted nanoparticle directed to the pregnant uterus and loaded with a tocolytic for reducing its placental passage and sustaining its efficacy. Nanoliposomes encapsulating indomethacin and decorated with clinically used oxytocin receptor antagonist were designed and evaluated in-vitro, ex-vivo and in-vivo. The proposed approach resulted in targeting uterine cells in-vitro, inhibiting uterine contractions ex-vivo, while doubling uterine drug concentration, decreasing fetal levels, and maintaining the preterm birth rate in vivo in a pregnant mouse model. This promising approach opens new horizons for drug development in obstetrics that could greatly impact preterm birth, which currently has no successful treatments.