Incidence Of Spontaneous Preterm Birth Research Articles

The relationship between active/passive smoking and spontaneous preterm birth: Data from a multicenter study.

Prematurity is considered to be the leading cause of death in children under 5 years of age, with one child dying every 2 s. Smoking is known to be one of the factors associated with prematurity, with both immediate and late consequences. However, it is difficult to obtain concrete data on the relationship between smoking and spontaneous preterm birth. The aim of this study was to evaluate the influence of active and passive smoking on spontaneous preterm birth. This was a multicenter, cross-sectional complementary study that included data on preterm births in 20 maternity hospitals in Brazil between 2011 and 2012. The relationship between smoking category (people who smoke [PWS]; people who smoke indirectly [PWSI]; and people who do not smoke [PWDNS]) and sociodemographic characteristics, birth, and neonatal data was assessed. Statistical analysis was performed using frequencies, percentages, the χ2 test, and stepwise comparisons, with a significance level of 5%. The original study included 5295 pregnant participants and their preterm infants. There were 1491 spontaneous preterm births (SPBs); 1191 preterm rupture of membranes; 1468 therapeutic preterm births; and 1146 term births. The proportion of women who were PWS during pregnancy was 13.5%, and 31.6% were PWSI. Pregnant individuals who smoked and who smoked indirectly had a higher incidence of SPBs (61.2%) compared with PWDNS (48.4%; P < 0.0001); however, multivariate analysis did not confirm causality. This study did not confirm that smoking during pregnancy increases the risk of SPB. PWSI also did not have an increased incidence of spontaneous preterm birth or adverse neonatal outcomes.

Primary prevention with vaginal chlorhexidine before 16 weeks reduces the incidence of preterm birth: results of the Preterm Labor Prevention Using Vaginal Antiseptics study

Preterm labor is one of the leading causes of perinatal death and is currently considered a syndrome with many causes. One of the most important causes of preterm birth is ascending infection from bacterial vaginosis. Chlorhexidine has proven to be effective against bacterial vaginosis and against bacterial biofilms without affecting gestation. We aimed to evaluate the effectiveness of a universal primary prevention strategy for preterm birth using intravaginal chlorhexidine applied before 16 weeks (Preterm Labor Prevention Using Vaginal Antiseptics study). We performed a prospective observational study with 2 cohorts of pregnant women that were assigned either to prevention of preterm birth by means of intravaginal chlorhexidine (Cum Laude Chlorhexidine, chlorhexidine digluconate 0.2%) before 16 weeks (n=413), or to no treatment following the usual hospital protocol (n=704). Primary outcomes were the incidence of spontaneous preterm birth before 34 and 37 weeks; the incidence of preterm birth before 34 and 37 weeks, including inductions for premature rupture of membranes; and the incidence of preterm birth before 34 and 37 weeks, including any indication for termination of pregnancy. Both cohorts were compared using Mann-Whitney and Fisher tests. Finally, a multivariable analysis, including the odds ratio was performed, adjusting for clinical parameters, to evaluate the importance of the different determinants in the prediction of preterm birth. In pregnancies treated with chlorhexidine, the incidences of spontaneous preterm birth; preterm birth, including induction for premature rupture of membranas; and preterm birth, including any indication for termination of pregnancy were at 34 and 37 weeks: 0% and 0%, 0.24% and 1.69, and 2.90% and 3.15%, respectively; whereas in nontreated pregnancies, these incidences were 9% and 11%, 12% and 23%, and 35% and 43%, respectively. According to the multivariable analysis, the incidence of preterm birth among women treated with chlorhexidine before 16 weeks was halved (Odds ratio, 0.52; P<.05). Universal treatment with vaginal chlorhexidine before 16 weeks reduces the incidence of preterm birth, especially before 34 weeks.

Comparison of transvaginal cervical cerclage versus laparoscopic abdominal cervical cerclage in cervical insufficiency: a retrospective study from a single centre

BackgroundCervical cerclage has been proposed as an effective treatment for cervical insufficiency, but there has been controversy regarding the surgical options of cervical cerclage in singleton and twin pregnancies. This study aimed to compare the pregnancy outcomes between transvaginal cervical cerclage (TVC) and laparoscopic abdominal cervical cerclage (LAC) in patients with cervical insufficiency. We also aimed to evaluate the efficacy and safety, and provide more evidence to support the application of cervical cerclage in twin pregnancies.MethodsA retrospective study was carried out from January 2015 to December 2021. The primary outcomes were the incidence of spontaneous preterm birth (sPTB) < 24 weeks, < 28, < 32, < 34 weeks, and < 37weeks, gestational age at delivery, and the incidence of admission for threatened abortion or preterm birth after cervical cerclage. The secondary outcomes included admission to the Neonatal Intensive Care Unit, adverse neonatal outcomes and neonatal death. We also analysed the pregnancy outcomes of twin pregnancies after cervical cerclage.ResultsA total of 289 patients were identified as eligible for inclusion. The LAC group (n = 56) had a very low incidence of sPTB ˂ 34 weeks, and it was associated with a significant decrease in sPTB < 28 weeks, ˂32 weeks, ˂34 and < 37 weeks, and admission to the hospital during pregnancy for threatened abortion or preterm birth after cervical cerclage (0 vs.27%; 1.8% vs. 40.3%; 7.1% vs. 46.8%; 14% vs. 63.5%, 8.9% vs. 62.2%, respectively; P < 0.001), and high in gestational age at delivery compared with the TVC group (n = 233) (38.3 weeks vs.34.4 weeks,P < 0.001). Neonatal outcomes in the LAC group were significantly better than those in the TVC group. The mean gestational age at delivery was 34.3 ± 1.8 weeks, with a total foetal survival rate of 100% without serious neonatal complications in twin pregnancies with LAC.ConclusionIn patients with cervical insufficiency, LAC appears to have better pregnancy outcomes than TVC. For some patients, LAC is a recommended option and may be selected as the first choice. Even in twin pregnancies, cervical cerclage can improve pregnancy outcomes with a longer latency period, especially in the LAC group.

Role of Cervical Length in Predicting the Premature Labour: A Prospective Observational Study

Background: Over the last decade, little progress has been made in understanding and preventing preterm birth, and the incidence of spontaneous preterm birth has continued to rise, even in low risk women. One of the key predictors of premature birth is cervical length. Methods: This was a hospital based prospective study conducted at the postgraduate department of obstetrics and gynecology, Government Lalla Ded Hospital, Srinagar for a period of one and a half year (2019-2021). Out of the 140 women, 36 were removed from the research owing to rescue or emergency cerclage, and 22 women were lost to follow-up. For the 82 remaining women, the association between cervical length between the 16th and 24th week of pregnancy and premature birth was examined. Results: We observed that 2.5 cm cervical length was the ideal cut-off with sensitivity, specificity, positive predictive, negative predictive, and accuracy values of (68.7%), (75.7%), (77.5%), (66.7%), and (71.9%), respectively. The average cervical length of patients with gestational age at delivery fewer than 37 weeks was significantly smaller compared to those with gestational age more than 37 weeks at delivery (2.75 vs 3.92, p-value &lt; 0.001). Conclusion: We concluded that a short cervical length of &lt;2.5cm is a risk factor for development of spontaneous preterm labour and that ≤ 2.5mm is an optimum threshold for it. Our findings imply that the cervix's length is a reliable predictor of its competence and should be seen as a continuous rather than a binary characteristic. Preterm birth is more likely to occur if the cervix is shorter than normal. The length of the cervix strongly correlates with the length of pregnancy. Keywords: Cervical length, Preterm, Pregnancy

Developing a risk profile for spontaneous preterm birth and short interval to delivery among patients with threatened preterm labor

Threatened preterm birth is the most common reason for antepartum hospitalization in the United States, accounting for approximately 50% of these admissions. However, fewer than 10% of patients with inpatient evaluation for signs or symptoms of preterm labor ultimately deliver before term. This study aimed to generate predictive models to assess the risk of preterm delivery and time to delivery based on clinical signs and symptoms of patients evaluated in our institution for preterm labor concerns. This was a retrospective cohort study of singleton pregnancies evaluated for signs and/or symptoms of preterm labor, including contractions, abdominal pain, vaginal bleeding, and short cervix, between 22 0/7 and 33 6/7 weeks of gestation. Inpatient evaluations were classified by patient presentation: (1) symptomatic with cervical findings (transvaginal cervical length of <2.5 cm or cervical dilation of ≥2.0 cm), (2) asymptomatic with cervical findings, and (3) symptomatic without cervical findings. The primary outcomes included incidence of spontaneous preterm birth and interval from presentation to delivery, compared between groups. The risk of preterm delivery was evaluated using log-binomial regression, and presentation to delivery timing was assessed by survival analysis and Cox proportional hazards modeling. Of 631 patients with preterm labor concerns, 96 (16%) were symptomatic with cervical findings on evaluation, 51 (8%) were asymptomatic with cervical findings, and 466 (76%) were symptomatic without cervical findings. The occurrence of preterm birth was significantly higher among symptomatic patients with cervical findings (49%) than among those with cervical findings alone (31%) or symptoms alone (11%) (P<.0001). In addition, symptomatic patients with cervical findings were significantly more likely to deliver within 48 hours (20%), 1 week (30%), 2 weeks (33%), and 1 month (43%) of presentation than patients with cervical findings alone (2%, 2%, 6%, and 10%, respectively) or symptoms alone (0.4%, 1%, 1.5%, and 5%, respectively) (P value for trend<.0001). Adjusted for gestational age at presentation and previous preterm birth, the overall risk of preterm delivery was significantly higher among patients with symptoms and cervical findings than among patients with cervical findings alone (relative risk, 2.81; 95% confidence interval, 1.74-4.54) or symptoms alone (relative risk, 4.39; 95% confidence interval, 3.16-6.09). Adjusted for the same variables, symptomatic patients with cervical findings were also at higher risk of delivery over time after assessment than patients with cervical findings alone (hazard ratio, 2.06; 95% confidence interval, 1.47-2.90) or symptoms alone (hazard ratio, 2.16; 95% confidence interval, 1.74-2.70). The negative predictive value of these models suggested that only 1% of patients with isolated symptoms or cervical findings are at risk of preterm delivery within 1 week of initial presentation. Symptomatic patients with cervical findings suggestive of preterm labor were at the greatest risk of preterm birth and a shorter interval from presentation to delivery. The study findings supported a risk profile that may facilitate the selection of patients most appropriate for admission and targeted management. Nonetheless, as nearly 50% of patients meeting this risk profile subsequently deliver at term, future research is needed to identify which of these patients will require intervention.

Relationship between unremoved cervical polyp in pregnancy and spontaneous preterm birth

Cervical polyps removed during pregnancy have been reported to be associated with preterm birth; however, the association between unremoved cervical polyps and preterm birth has not been elucidated. This study aimed to clarify the relationship between cervical polyps detected before 12 weeks of gestation managed expectantly and spontaneous preterm birth. This retrospective cohort study included pregnant women who visited a tertiary perinatal center before 12 weeks of gestation between January 2015 and December 2019. The exclusion criteria were as follows: multiple gestations, loss or termination of pregnancy before 12 weeks of gestation, major fetal anomalies, fetal chromosomal abnormalities, fetal demise, having undergone removal of cervical polyps before the first visit to our hospital, and moving to other hospitals before delivery. A vaginal speculum examination was routinely performed during a prenatal visit before 12 weeks of gestation. When a cervical polyp was detected on speculum examination, it was managed expectantly, unless gynecologic malignancy was suspected. Relationships between cervical polyps and spontaneous preterm birth before 34 weeks of gestation were evaluated using logistic regression analysis and Cox proportional-hazards analysis adjusted for known confounders for spontaneous preterm birth. A total of 4172 pregnant women were included, of whom 92 (2.2%) had a cervical polyp detected before 12 weeks of gestation. None of the women underwent polypectomy during pregnancy. The incidence of spontaneous preterm birth before 34 weeks of gestation was higher in pregnant women with cervical polyps than in those without them (5.4% vs 0.7%; P<.01). Logistic regression analysis revealed that cervical polyps were an independent risk factor for spontaneous preterm birth before 34 weeks of gestation (adjusted odds ratio, 4.09; 95% confidence interval, 1.70-9.81; P<.01). The adjusted hazard ratio for spontaneous preterm birth before 34 weeks of gestation among women with vs without cervical polyps was 2.95 (95% confidence interval, 1.32-6.62; P<.01). Cervical polyps detected before 12 weeks of gestation managed expectantly are a significant risk factor for spontaneous preterm birth before 34 weeks of gestation.

Comparison of two stitches versus one stitch for emergency cervical cerclage to prevent preterm birth in singleton pregnancies.

To compare the efficacy of two stitches versus one stitch in women with emergency cervical cerclage. A retrospective case-control study of 26 women with singleton pregnancies who underwent emergency cervical cerclage before 26 weeks. A comparison was made between patients with two stitches versus one stitch at the time of cervical cerclage placement. The primary outcome was gestational age (GA) at delivery and preterm birth (PTB) before 37, 34, 32, 28, and 24 weeks. Average GA at delivery in the two-stitches group was significantly greater than in the one-stitch group (32.71 ± 5.54 weeks vs 27.99 ± 4.70 weeks, P= 0.028). There were significant decreases in the incidence of spontaneous PTB at <34 weeks and less than 32 weeks in the two-stitches group (P= 0.034; P= 0.013, respectively). The neonatal intensive care unit (NICU) admissions rate and length of stay in the NICU in the two-stitches group were significantly reduced (P= 0.035 and P= 0.018, respectively). However, there was no significant difference in neonatal mortality between the two groups. Compared with emergency cervical cerclage placement with one stitch, the procedure with two stitches can prolong the pregnancy and improve the neonatal prognosis more effectively.

Maternal LINE-1 DNA Methylation in Early Spontaneous Preterm Birth.

Despite considerable effort aimed at decreasing the incidence of spontaneous preterm birth (SPTB), it remains the leading cause of infant mortality and morbidity. The aim of this study was to evaluate maternal LINE-1 DNA methylation (DNAm), along with DNMT polymorphisms and factors proposed to modulate DNAm, in patients who delivered early preterm. This case-control study included women who delivered spontaneously early preterm (23-336/7 weeks of gestation), and control women. DNAm was analyzed in peripheral blood lymphocytes by quantification of LINE-1 DNAm using the MethyLight method. There was no significant difference in LINE-1 DNAm between patients with early PTB and controls. Among the investigated predictors, only the history of previous PTB was significantly associated with LINE-1 DNAm in PTB patients (β = -0.407; R2 = 0.131; p = 0.011). The regression analysis showed the effect of DNMT3B rs1569686 TT+TG genotypes on LINE-1 DNAm in patients with familial PTB (β = -0.524; R2 = 0.275; p = 0.037). Our findings suggest novel associations of maternal LINE-1 DNA hypomethylation with DNMT3B rs1569686 T allele. These results also contribute to the understanding of a complex (epi)genetic and environmental relationship underlying the early PTB.

The Predictive Value of Cervical Length During the Second Trimester for Non-Medically Induced Preterm Birth.

ObjectiveThe aim of the present study was to investigate the predictive value of transvaginal ultrasonography measurement of cervical length (CL) during the second trimester for spontaneous preterm birth.MethodsData from 1222 women with a single fetus pregnancy, who delivered at our hospital between March 2019 and May 2020, were retrospectively analyzed. CL was measured during the second trimester, with a length of <25 mm regarded as cervical shortening. The relationship between CL, cervical shortening, and pregnancy outcome was analyzed.ResultsThe incidence of spontaneous preterm birth and cervical shortening in the 1222 women was 7.3% (89/1222) and 0.33% (4/1222), respectively. The average CL during the second trimester was 37.9 ± 5.7 mm for the spontaneous preterm birth group and 39.3 ± 3.8 mm for those who gave birth at full term. Three of the four cases of cervical shortening resulted in a spontaneous preterm birth. This showed a predictive sensitivity of 3.33% and a specificity of 99.9%.ConclusionCL measurement during the second trimester can be used as a routine test to predict spontaneous preterm birth. During the second trimester, the distribution of CL in women with single fetus pregnancies in China is different compared with other countries. Reducing the threshold of CL may improve the predictive value for preterm birth.

The contemporary value of dedicated preterm birth clinics for high-risk singleton pregnancies: 15-year outcomes from a leading maternal centre.

Preterm birth clinics provide dedicated obstetric care to women athigh risk of spontaneous preterm birth (SPTB). There remains a lack of conclusive evidence to support the overall utility of such clinics, attributable to a paucity and heterogeneity of primary data. This study audits Australia's largest and oldest dedicated preterm birth clinic with the aim to add primary data to the area and offer opportunities for similar clinics to align practice. A retrospective audit of referrals to the Preterm Labour Clinic at the Royal Women's Hospital, Melbourne, Australia, between 2004 and 2018 was conducted. 1,405 singleton pregnancies met inclusion criteria. The clinic's key outcomes, demographics, predictive tests and interventions were analysed. The primary outcomes were SPTB before 37, 34 and 30weeks' gestation. The overall incidence of SPTB in the clinic was 21.2% (n=294). Linear regression showed reductions in the adjusted rates of overall SPTB and pre-viable SPTB (delivery <24weeks) from 2004 (108%; 8%) to 2018 (65%; 2% respectively). Neonatal morbidity and post-delivery intensive care admission concurrently declined (p=0.02; 0.006 respectively). Rates of short cervix (cervical length <25mm) increased over time (2018: 30.9%) with greater uptake of vaginal progesterone for treatment. Fetal fibronectin, mid-trimester short cervix, and serum alkaline phosphatase were associated with SPTB on logistic regression. Dedicated preterm birth clinics can reduce rates of SPTB, particularly deliveries before 24weeks' gestation, and improve short-term neonatal outcomes in pregnant women at risk of preterm birth.

What is driving the decreased incidence of preterm birth during the coronavirus disease 2019 pandemic?

Institutions across the world have observed a decrease in the incidence of preterm births during the coronavirus disease 2019 pandemic. The reason for this reduction remains unknown. We sought to explore potential causes for the decrease in preterm births by exploring the following 3 hypotheses: (1) do women who are more likely to be able to work from home incur less physical/or emotional stress resulting in longer gestation? (2) Does the effect of the coronavirus disease 2019 pandemic on the incidence of preterm births vary by race? (3) Is this change provider driven? Using a retrospective cohort of all singleton deliveries at a single tertiary care center, we compared the deliveries for the period before the coronavirus disease 2019 pandemic (January 1, 2018-January 31, 2020) with those occurring during the pandemic (April 1, 2020-October 27, 2020). Comparisons between the period before and during the pandemic were made using Pearson chi-square or t tests as appropriate. The overall incidence of preterm birth, defined as delivery at <37 weeks' gestation, was analyzed and then further classified into spontaneous or indicated preterm births. The population was then stratified by the following categories: (1) insurance type and neighborhood disadvantage; (2) race; and (3) provider type. The provider type was classified as delivery occurring within an outpatient care facility, a clinic that provides prenatal care to those eligible for medical assistance, or a nonoutpatient care facility. In a population of 17,687 pre-coronavirus disease 2019 deliveries, and 5396 deliveries occurring during the coronavirus disease 2019 pandemic, there was a significant decrease in the overall incidence of preterm births (11.1 vs 10.1%; P=.039). Both spontaneous and indicated preterm deliveries decreased across the entire population. When stratified, decreases in the incidence of spontaneous preterm birth before vs during the coronavirus disease 2019 pandemic were limited to deliveries to women from more advantaged neighborhoods (most advantaged, 4.4 vs 3.8%; least advantaged, 7.2 vs 7.4%), white mothers (white, 5.6 vs 4.7%; black, 6.6 vs 7.1%), and those receiving care from nonoutpatient care providers (nonoutpatient care providers, 5.5 vs 4.8%; outpatient care providers, 6.3 vs 6.7%). The incidence of preterm births has decreased during the coronavirus disease 2019 pandemic. Decreases in the rate of spontaneous preterm births were limited to deliveries to white women, living in more advantaged neighborhoods, and deliveries at nonoutpatient care facilities. The coronavirus disease 2019 response regulations may have benefited women with more indicators of advantage disproportionately more.

Physical examination-indicated cerclage in twin pregnancy: a retrospective cohort study.

This study aimed to evaluate the efficacy of physical examination-indicated cerclage in twin pregnancies and compare it with those that received conservative management. We used a retrospective cohort study design of asymptomatic twin pregnancies identified with physical examination indications at 14-26weeks from 2015 through 2019 at Fujian Maternity and Child Health Hospital. The primary outcomes were gestational age (GA) at delivery and the incidence of spontaneous preterm birth (SPTB) at < 34weeks, < 32weeks, < 28weeks, and < 24weeks. The main secondary outcomes were latency period from diagnosis to delivery, composite neonatal adverse outcome and neonatal survival at discharge. Thirty-one women with twin pregnancies were managed with physical examination-indicated cerclage, and another 31 received expectant management. The demographic characteristics of the two groups were not significantly different. GA at delivery was significantly later in the cerclage group than in the controls: 32.53 ± 4.78 vs. 27.53 ± 4.15weeks, with a mean difference of 5.00weeks [95% confidence interval (CI), 2.73-7.28]. There were significant decreases in the incidence of spontaneous preterm birth (SPTB) at < 34weeks, < 32weeks, < 28weeks, and < 24weeks in the cerclage group. The interval from diagnosis to delivery was increased with cerclage by a mean difference of 4.37weeks (95% CI, 1.96-7.06). Regarding neonatal outcome, the perinatal mortality rate in the cerclage group was significantly reduced compared to that in the control group [8/62 (12.9%) vs. 26/62 (41.9%); P < 0001]. Likewise, the neonatal intensive care unit (NICU) admissions, length of stay in the NICU, and composite adverse neonatal outcome in the cerclage group were significantly reduced. Physical examination-indicated cerclage was associated with significantly later GA at delivery, longer latency period from diagnosis to delivery, decreased incidence of SPTB at any given GA, and improved perinatal outcome compared with the corresponding measures in controls treated conservatively.

Early vaginal progesterone versus placebo in twin pregnancies for the prevention of spontaneous preterm birth: a randomized, double-blind trial

In women with a singleton pregnancy and sonographic short cervix in midgestation, vaginal administration of progesterone reduces the risk of early preterm birth and improves neonatal outcomes without any demonstrable deleterious effects on childhood neurodevelopment. In women with twin pregnancies, the rate of spontaneous early preterm birth is 10 times higher than that in singletons, and in this respect, all twins are at an increased risk of preterm birth. However, 6 trials in unselected twin pregnancies reported that vaginal administration of progesterone from midgestation had no significant effect on the incidence of early preterm birth. Such apparent lack of effectiveness of progesterone in twins may be due to inadequate dosage or treatment that is started too late in pregnancy. The early vaginal progesterone for the prevention of spontaneous preterm birth in twins, a randomized, placebo-controlled, double-blind trial, was designed to test the hypothesis that among women with twin pregnancies, vaginal progesterone at a dose of 600 mg per day from 11 to 14 until 34 weeks' gestation, as compared with placebo, would result in a significant reduction in the incidence of spontaneous preterm birth between 24+0 and 33+6 weeks. The trial was conducted at 22 hospitals in England, Spain, Bulgaria, Italy, Belgium, and France. Women were randomly assigned in a 1:1 ratio to receive either progesterone or placebo, and in the random-sequence generation, there was stratification according to the participating center. The primary outcome was spontaneous birth between 24+0 and 33+6 weeks' gestation. Statistical analyses were performed on an intention-to-treat basis. Logistic regression analysis was used to determine the significance of difference in the incidence of spontaneous birth between 24+0 and 33+6 weeks' gestation between the progesterone and placebo groups, adjusting for the effect of participating center, chorionicity, parity, and method of conception. Prespecified tests of treatment interaction effects with chorionicity, parity, method of conception, compliance, and cervical length at recruitment were performed. A post hoc analysis using mixed-effects Cox regression was used for further exploration of the effect of progesterone on preterm birth. We recruited 1194 women between May 2017 and April 2019; 21 withdrew consent and 4 were lost to follow-up, which left 582 in the progesterone group and 587 in the placebo group. Adherence was good, with reported intake of ≥80% of the required number of capsules in 81.4% of the participants. After excluding births before 24 weeks and indicated deliveries before 34 weeks, spontaneous birth between 24+0 and 33+6 weeks occurred in 10.4% (56/541) of participants in the progesterone group and in 8.2% (44/538) in the placebo group (odds ratio in the progesterone group, adjusting for the effect of participating center, chorionicity, parity, and method of conception, 1.35; 95% confidence interval, 0.88-2.05; P=.17). There was no evidence of interaction between the effects of treatment and chorionicity (P=.28), parity (P=.35), method of conception (P=.56), and adherence (P=.34); however, there was weak evidence of an interaction with cervical length (P=.08) suggestive of harm to those with a cervical length of ≥30 mm (odds ratio, 1.61; 95% confidence interval, 1.01-2.59) and potential benefit for those with a cervical length of <30 mm (odds ratio, 0.56; 95% confidence interval, 0.20-1.60). There was no evidence of difference between the 2 treatment groups for stillbirth or neonatal death, neonatal complications, neonatal therapy, and poor fetal growth. In the progesterone group, 1.4% (8/582) of women and 1.9% (22/1164) of fetuses experienced at least 1 serious adverse event; the respective numbers for the placebo group were 1.2% (7/587) and 3.2% (37/1174) (P=.80 and P=.06, respectively). In the post hoc time-to-event analysis, miscarriage or spontaneous preterm birth between randomization and 31+6 weeks' gestation was reduced in the progesterone group relative to the placebo group (hazard ratio, 0.23; 95% confidence interval, 0.08-0.69). In women with twin pregnancies, universal treatment with vaginal progesterone did not reduce the incidence of spontaneous birth between 24+0 and 33+6 weeks' gestation. Post hoc time-to-event analysis led to the suggestion that progesterone may reduce the risk of spontaneous birth before 32 weeks' gestation in women with a cervical length of <30 mm, and it may increase the risk for those with a cervical length of ≥30 mm.

In vitro selenium supplementation suppresses key mediators involved in myometrial activation and rupture of fetal membranes.

Spontaneous preterm birth, which can affect up to 20% of all pregnancies, is the greatest contributor to perinatal morbidity and mortality. Infection is the leading pathological cause of spontaneous preterm birth. Infection activates the maternal immune system, resulting in the upregulation of pro-inflammatory and pro-labor mediators that activate myometrial contractions and rupture of fetal membranes. Anti-inflammatory agents therefore have the potential for the prevention of spontaneous preterm birth. Selenium, an essential micronutrient, has been shown to be a potent anti-inflammatory regulator. Notably, clinical and epidemiological studies have suggested a link between selenium and preterm birth. Thus, the aim of this study was to assess the effect of selenite (an inorganic form of selenium) on the expression of pro-inflammatory and pro-labor mediators in human gestational tissues. Human fetal membranes and myometrium were pre-incubated with or without selenite before incubation with the bacterial product lipopolysaccharide (LPS) to stimulate inflammation associated with preterm birth. Selenite blocked LPS-induced expression of pro-inflammatory cytokines and chemokines and enzymes involved in remodelling of myometrium and degradation of fetal membranes. Of note, selenite also suppressed myometrial activation induced by inflammation as evidenced by a decrease in LPS-induced prostaglandin signalling and myometrial cell contractility. These effects of selenite were mediated by the MAPK protein ERK as selenite blunted LPS induced activation of ERK. In conclusion, selenite suppresses key mediators involved in inflammation induced activation of mediators involved in active labor in human fetal membranes and myometrium. These findings support recent clinical studies demonstrating selenium supplementation is associated with decreased incidence of spontaneous preterm birth.

Clinical Characteristics and Incidence of Spontaneous Preterm Birth in Symptomatic COVID-19 Pregnant Women: An Observational Study

Background: There is limited data regarding COVID-19 and preterm birth. Most published studies do not exclude induced preterm deliveries or women at higher risk for preterm birth. Objective (s): To determine the incidence of spontaneous preterm delivery in pregnancies complicated by maternal COVID-19 infection with no other independent risk factors for preterm birth. Study design: This was an observational study of symptomatic women diagnosed with COVID-19 during the third trimester of pregnancy who delivered at Flushing Hospital Medical Center in Queens, New York between March 1 and May 1, 2020. IRB approval was obtained. Charts of symptomatic women who were confirmed COVID-19 positive by RT-PCR in the third trimester were reviewed. Patient information collected included gestational age at diagnosis of COVID-19, obstetrical history, comorbidities, x-ray findings, and blood work. Women with a history of preterm birth, short cervix in current pregnancy, and multiple gestations were excluded. Statistical evaluation for normally distributed continuous variables was done using a student’s t-test, and for dichotomous variables, a Chi-square analysis or Fisher’s exact test was used. A multiple regression analysis model was used to correlate the relationship of clinical variables to the gestational age at delivery. Results: 24 pregnant women met initial criteria, 17 of which delivered in the time period stated. Preterm delivery rate in our sample size was 29% (n=5). Our institution’s preterm delivery rate for a similar time-period in 2019, using the same exclusion and inclusion criteria, was 2.7%. When comparing COVID-19 positive women that delivered preterm to COVID-19 positive women who delivered at term, the gestational age on admission was lower in the preterm cohort (weeks 34.1 ± 1.5 weeks versus 38.0 ± 1.7; p<0.001). Multiple regression analysis showed the following variables correlated with the gestational age at birth: gestational age on admission (Coefficient 0.95, (95% CI 0.86 - 1.03; p<0.001), white blood count (Coefficient 0.142, 95% CI 0.07 - 0.22; p=0.002), and lymphocyte percentage (Coefficient 0.038, 95% CI 0.01 - 0.06; p=0.008). Conclusion (s): Symptomatic COVID-19 infection seems to be a significant risk factor for spontaneous preterm delivery, especially if the gestational age on admission is below 37 weeks, the white blood cell count is low, or the lymphocyte percentage is decreased.

Weight gain and pregnancy outcomes in overweight or obese women with twin gestations

Background While adequate weight gain in twin pregnancies with normal prepregnancy BMI has been associated with improved pregnancy outcomes, it remains unclear whether adequate weight gain in patients with overweight or obese prepregnancy BMI is associated with similarly improved pregnancy outcomes, and whether this comes at the expense of maternal health risks such as increased risk for gestational diabetes or hypertension. Objective To estimate the association between adherence to weight gain recommendations and pregnancy outcomes in overweight and obese women with twin pregnancies. Methods This is a retrospective cohort study of women with overweight (BMI 25.0–29.9 kg/m2) and obese prepregnancy BMI (≥30.0 kg/m2) and twin pregnancies delivered >24 weeks by a single MFM practice between 2005 and 2017. Baseline characteristics, weight gain patterns, and pregnancy outcomes were compared between women who met or exceeded, and who did not meet gestational weight gain requirements, as recommended by the Institute of Medicine (IOM) in 2009. Since total weight gain is also dependent on gestational age at delivery, we used weight gain per week to define adequate weight gain for overweight (0.85 lb/week) and obese (0.68 lb/week) women. Results A total of 252 overweight and obese women with twin pregnancies met inclusion criteria, 171 (67.9%) of whom met or exceeded weight gain requirements and 81 (32.1%) of whom did not. There were no differences in baseline clinical and demographic characteristics between the two groups. Women with inadequate weight gain had significantly less weight gain in each trimester, as well as less total weight gain for the whole pregnancy. Women with inadequate average gestational weight gain had significantly lower birthweights of the larger twin (2440 versus 2675 g, p = .001) and the smaller twin (2212 versus 2398 g, p = .005), higher incidence of spontaneous preterm birth <37 weeks (33.3 versus 21.1%, p = .03), higher incidence of premature rupture of membranes (24.7 versus 11.7%, p = .008), and greater likelihood of any twin birthweight < 10th percentile for gestational age (51.9 versus 35.5%, p = .01). There were no differences in the likelihood of cesarean delivery, preeclampsia, or gestational diabetes between the two groups. These results did not differ after excluding the 24 women in the cohort with excessive weight gain. Conclusions For overweight and obese women with twin gestations, meeting the IOM recommendations for weight gain in pregnancy is associated with improved pregnancy outcomes. Condensation Women with overweight or obese prepregnancy BMI in twin gestations who gain the recommended amount of weight in pregnancy have improved pregnancy outcomes.

Antibiotic treatment for patients with amniotic fluid "sludge" to prevent spontaneous preterm birth: A historically controlled observational study.

Amniotic fluid "sludge" has been associated with an increased rate of spontaneous preterm delivery before 35weeks, a higher frequency of clinical and histologic chorioamnionitis in a high-risk population. Only one study evaluating the use of antibiotics in the presence of amniotic fluid "sludge" showed reduced rates of spontaneous preterm birth at <34weeks. The objective of this study was to evaluate routine antibiotic treatment in the presence of amniotic fluid "sludge" for prevention of preterm delivery. A historically controlled observational study was performed between October 2010 and January 2015, including a total of 86 pregnant women with singleton pregnancies and the presence of amniotic fluid "sludge" at ultrasound. Women admitted from October 2010 to September 2012 received no treatment with antibiotics, whereas those admitted from October 2012 to January 2015, received routinely clindamycin and first-generation cephalosporin. The groups were compared considering the incidence of spontaneous preterm delivery. The effect of antimicrobials was also compared in the subgroup of women at high risk for spontaneous preterm birth (ie, cervical length≤25mm, history of spontaneous preterm birth, previous spontaneous loss in the second trimester, Mullerian malformations or cervical conization). Antibiotic therapy reduced the incidence of spontaneous preterm birth at <34weeks (13.2% vs 38.5%, P=0.047) in women at high-risk for preterm birth, with an odds ratio of 0.24 (95% confidence interval [CI] 0.06-0.99). Birthweight was significantly different between the study groups (2961±705 vs. 2554±819g, respectively; P=0.028), with no statistical significance for others variables. This study suggests that antibiotic treatment in high-risk pregnant women with amniotic fluid "sludge" can be effective in the reduction of the frequency of spontaneous preterm delivery and can increase the birthweight.

330: Weight gain and pregnancy outcomes in overweight or obese women with twin gestations

To estimate the association between adherence to weight gain recommendations and pregnancy outcomes in overweight and obese women with twin pregnancies. This is a retrospective cohort study of women with overweight (BMI 25.0 – 29.9 kg/m2) and obese pre- pregnancy BMI (> 30.0 kg/m2) and twin pregnancies delivered > 24 weeks by a single MFM practice between 2005- 2017. Baseline characteristics, weight gain patterns and pregnancy outcomes were compared between women who did and did not meet or exceed gestational weight gain requirements, as recommended by the Institute of Medicine in 2009. Since total weight gain is also dependent on gestational age at delivery, we used weight gain per week to define adequate weight gain for women with overweight (0.85 lb/week) and obese (0.68 lb/week) pre- pregnancy BMI. A total of 252 overweight and obese women with twin pregnancies met inclusion criteria, 171 (67.9%) of whom met or exceeded weight gain requirements and 81 (32.1%) of whom did not. There were no differences in baseline clinical and demographic characteristics between the two groups. Women with inadequate weight gain had significantly less weight gain in each trimester, as well as less total weight gain for the whole pregnancy. Women with inadequate average gestational weight gain had significantly lower birthweights of the larger twin (2440g vs. 2675g, p=0.001) and the smaller twin (2212g vs. 2398g, p=0.005), higher incidence of spontaneous preterm birth <37 weeks (33.3% vs. 21.1%, p=0.03), higher incidence of premature rupture of membranes (24.7% vs. 11.7%, p=0.008), and greater likelihood of any twin birthweight <10th percentile for gestational age (51.9% vs. 35.5%, p=0.01). There were no differences in the likelihood of cesarean delivery, preeclampsia, or gestational diabetes between the two groups. For overweight and obese women with twin gestations, meeting the IOM recommendations for weight gain in pregnancy is associated with improved pregnancy outcomes.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

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To compare the mean transvaginal ultrasound (TVU) cervical length (CL) at midtrimester screening for spontaneous preterm birth in asymptomatic monochorionic diamniotic versus dichorionic diamniotic twin pregnanciesThis was a multicenter retrospective cohort study. Study subjects were identified at the time of a routine second trimester fetal ultrasound exam at 18 0/7–23 6/7 weeks gestation. We excluded women that received progesterone, pessary, or cerclage. Distribution of CL was determined and normality was examined. Mean of TVU CL were compared between monochorionic diamniotic and dichorionic diamniotic pregnancies. The relationship of TVU CL with gestational age (GA) at delivery and incidence of spontaneous preterm birth (SPTB) at different TVU CL cut offs were assessed. Incidence of short TVU CL, defined as TVU CL ≤30 mm, was also calculated in the two groups.580 women with diamniotic twin pregnancies underwent TVU CL screening between 18 0/6 and 23 6/7 weeks. 175 (30.2%) were monochorionic diamniotic pregnancies, and 405 (69.8%) were dichorionic pregnancies. The demographic characteristics were similar on both groups. The mean GA at TVU CL was about 20 week in both groups. The mean TVU CL was significantly lower in the monochorionic diamniotic (32.8 ± 10.1) compared to the dichorionic (34.9 ± 8.6) group (MD −2.10 mm, 95% CI −3.91 to −0.29). TVU CL ≤30 mm was 16.6% (29/175) in the monochorionic group, and 11.9% (48/405) in the dichorionic group (aOR 1.48, 95% CI 1.03–2.43). Twins with a monochorionic diamniotic pregnancy had a significantly higher incidence of SPTB (53.1% vs 44.9%; aOR 1.22, 95% CI 1.22–1.79). For any given CL measured between 18 0–7 and 23 6/7 weeks, gestational age at delivery for monochorionic diamniotic pregnancies was about 2 weeks earlier compared to dichorionic pregnancies (MD -2.1 weeks; ANCOVA P < 0.001).Monochorionic diamniotic twin pregnancies had a higher rate of spontaneous preterm birth than dichorionic diamniotic pregnancies. The higher rate of spontaneous preterm delivery in monochorionic pregnancies is associated with lower midtrimester TVU CL when compared to dichorionic pregnancies.

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To compare the mean transvaginal ultrasound (TVU) cervical length (CL) at midtrimester screening for spontaneous preterm birth in asymptomatic monochorionic diamniotic versus dichorionic diamniotic twin pregnanciesThis was a multicenter retrospective cohort study. Study subjects were identified at the time of a routine second trimester fetal ultrasound exam at 18 0/7–23 6/7 weeks gestation. We excluded women that received progesterone, pessary, or cerclage. Distribution of CL was determined and normality was examined. Mean of TVU CL were compared between monochorionic diamniotic and dichorionic diamniotic pregnancies. The relationship of TVU CL with gestational age (GA) at delivery and incidence of spontaneous preterm birth (SPTB) at different TVU CL cut offs were assessed. Incidence of short TVU CL, defined as TVU CL ≤30 mm, was also calculated in the two groups.580 women with diamniotic twin pregnancies underwent TVU CL screening between 18 0/6 and 23 6/7 weeks. 175 (30.2%) were monochorionic diamniotic pregnancies, and 405 (69.8%) were dichorionic pregnancies. The demographic characteristics were similar on both groups. The mean GA at TVU CL was about 20 week in both groups. The mean TVU CL was significantly lower in the monochorionic diamniotic (32.8 ± 10.1) compared to the dichorionic (34.9 ± 8.6) group (MD −2.10 mm, 95% CI −3.91 to −0.29). TVU CL ≤30 mm was 16.6% (29/175) in the monochorionic group, and 11.9% (48/405) in the dichorionic group (aOR 1.48, 95% CI 1.03–2.43). Twins with a monochorionic diamniotic pregnancy had a significantly higher incidence of SPTB (53.1% vs 44.9%; aOR 1.22, 95% CI 1.22–1.79). For any given CL measured between 18 0–7 and 23 6/7 weeks, gestational age at delivery for monochorionic diamniotic pregnancies was about 2 weeks earlier compared to dichorionic pregnancies (MD -2.1 weeks; ANCOVA P < 0.001).Monochorionic diamniotic twin pregnancies had a higher rate of spontaneous preterm birth than dichorionic diamniotic pregnancies. The higher rate of spontaneous preterm delivery in monochorionic pregnancies is associated with lower midtrimester TVU CL when compared to dichorionic pregnancies.