Obstetric and perinatal outcomes in women with multiple pregnancy in Altai region

Overall, for women with a multiple pregnancy, the administration of progesterone (either IM or vaginal) does not appear to be associated with a reduction in risk of preterm birth or improved neonatal outcomes.Future research could focus on a comprehensive individual participant data meta-analysis including all of the available data relating to both IM and vaginal progesterone administration in women with a multiple pregnancy, before considering the need to conduct trials in subgroups of high-risk women (for example, women with a multiple pregnancy and a short cervical length identified on ultrasound).

Prenatal administration of progestogens for preventing spontaneous preterm birth in women with a multiple pregnancy.

Cervical cerclage, cervical pessary, and vaginal progesterone have each been shown to reduce preterm birth (PTB) in high-risk women, but to our knowledge, there has been no randomised comparison of the 3 interventions. The SuPPoRT "Stitch, Pessary, or Progesterone Randomised Trial" was designed to compare the rate of PTB <37 weeks between each intervention in women who develop a short cervix in pregnancy. SuPPoRT was a multicentre, open label 3-arm randomised controlled trial designed to demonstrate equivalence (equivalence margin 20%) conducted from 1 July 2015 to 1 July 2021 in 19 obstetric units in the United Kingdom. Asymptomatic women with singleton pregnancies with transvaginal ultrasound cervical lengths measuring <25 mm between 14+0 and 23+6 weeks' gestation were eligible for randomisation (1:1:1) to receive either vaginal cervical cerclage (n = 128), cervical pessary (n = 126), or vaginal progesterone (n = 132). Minimisation variables were gestation at recruitment, body mass index (BMI), and risk factor for PTB. The primary outcome was PTB <37 weeks' gestation. Secondary outcomes included PTB <34 weeks', <30 weeks', and adverse perinatal outcome. Analysis was by intention to treat. A total of 386 pregnant women between 14+0 and 23+6 weeks' gestation with a cervical length <25 mm were randomised to one of the 3 interventions. Of these women, 67% were of white ethnicity, 18% black ethnicity, and 7.5% Asian ethnicity. Mean BMI was 25.6. Over 85% of women had prior risk factors for PTB; 39.1% had experienced a spontaneous PTB or midtrimester loss (>14 weeks gestation); and 45.8% had prior cervical surgery. Data from 381 women were available for outcome analysis. Using binary regression, randomised therapies (cerclage versus pessary versus vaginal progesterone) were found to have similar effects on the primary outcome PTB <37 weeks (39/127 versus 38/122 versus 32/132, p = 0.4, cerclage versus pessary risk difference (RD) -0.7% [-12.1 to 10.7], cerclage versus progesterone RD 6.2% [-5.0 to 17.0], and progesterone versus pessary RD -6.9% [-17.9 to 4.1]). Similarly, no difference was seen for PTB <34 and 30 weeks, nor adverse perinatal outcome. There were some differences in the mild side effect profile between interventions (vaginal discharge and bleeding) and women randomised to progesterone reported more severe abdominal pain. A small proportion of women did not receive the intervention as per protocol; however, per-protocol and as-treated analyses showed similar results. The main study limitation was that the trial was underpowered for neonatal outcomes and was stopped early due to the COVID-19 pandemic. In this study, we found that for women who develop a short cervix, cerclage, pessary, and vaginal progesterone were equally efficacious at preventing PTB, as judged with a 20% equivalence margin. Commencing with any of the therapies would be reasonable clinical management. These results can be used as a counselling tool for clinicians when managing women with a short cervix. EU Clinical Trials register. EudraCT Number: 2015-000456-15, clinicaltrialsregister.eu., ISRCTN Registry: ISRCTN13364447, isrctn.com.

BackgroundCervical cerclage, cervical pessary, and vaginal progesterone have each been shown to reduce preterm birth (PTB) in high-risk women, but to our knowledge, there has been no randomised comparison of the 3 interventions. The SuPPoRT “Stitch, Pessary, or Progesterone Randomised Trial” was designed to compare the rate of PTB <37 weeks between each intervention in women who develop a short cervix in pregnancy.Methods and findingsSuPPoRT was a multicentre, open label 3-arm randomised controlled trial designed to demonstrate equivalence (equivalence margin 20%) conducted from 1 July 2015 to 1 July 2021 in 19 obstetric units in the United Kingdom. Asymptomatic women with singleton pregnancies with transvaginal ultrasound cervical lengths measuring <25 mm between 14+0 and 23+6 weeks’ gestation were eligible for randomisation (1:1:1) to receive either vaginal cervical cerclage (n = 128), cervical pessary (n = 126), or vaginal progesterone (n = 132). Minimisation variables were gestation at recruitment, body mass index (BMI), and risk factor for PTB. The primary outcome was PTB <37 weeks’ gestation. Secondary outcomes included PTB <34 weeks’, <30 weeks’, and adverse perinatal outcome. Analysis was by intention to treat.A total of 386 pregnant women between 14+0 and 23+6 weeks’ gestation with a cervical length <25 mm were randomised to one of the 3 interventions. Of these women, 67% were of white ethnicity, 18% black ethnicity, and 7.5% Asian ethnicity. Mean BMI was 25.6. Over 85% of women had prior risk factors for PTB; 39.1% had experienced a spontaneous PTB or midtrimester loss (>14 weeks gestation); and 45.8% had prior cervical surgery. Data from 381 women were available for outcome analysis. Using binary regression, randomised therapies (cerclage versus pessary versus vaginal progesterone) were found to have similar effects on the primary outcome PTB <37 weeks (39/127 versus 38/122 versus 32/132, p = 0.4, cerclage versus pessary risk difference (RD) −0.7% [−12.1 to 10.7], cerclage versus progesterone RD 6.2% [−5.0 to 17.0], and progesterone versus pessary RD −6.9% [−17.9 to 4.1]). Similarly, no difference was seen for PTB <34 and 30 weeks, nor adverse perinatal outcome. There were some differences in the mild side effect profile between interventions (vaginal discharge and bleeding) and women randomised to progesterone reported more severe abdominal pain.A small proportion of women did not receive the intervention as per protocol; however, per-protocol and as-treated analyses showed similar results. The main study limitation was that the trial was underpowered for neonatal outcomes and was stopped early due to the COVID-19 pandemic.ConclusionsIn this study, we found that for women who develop a short cervix, cerclage, pessary, and vaginal progesterone were equally efficacious at preventing PTB, as judged with a 20% equivalence margin. Commencing with any of the therapies would be reasonable clinical management. These results can be used as a counselling tool for clinicians when managing women with a short cervix.Trial registrationEU Clinical Trials register. EudraCT Number: 2015-000456-15, clinicaltrialsregister.eu., ISRCTN Registry: ISRCTN13364447, isrctn.com.

Vaginal progesterone or cerclage to prevent recurrent preterm birth?

BackgroundPreterm birth is the most important cause of neonatal morbidity and mortality. Clinical guidelines recommend assessment of risk of preterm birth and implementation of interventions to reduce preterm birth risk through dedicated preterm birth clinics. We hypothesized that a two-tier preterm birth clinic pathway can safely manage women at the highest risk of preterm birth while reducing intervention for women at moderate risk of preterm birth. We aimed to test this hypothesis by evaluating risk factors, management, and outcomes of women attending a two-tier preterm birth prevention service.MethodsWe conducted a retrospective cohort study of women who gave birth between January and June 2021 at a tertiary hospital in Oxford, UK. We included two cohorts: women attending a Cervical Screening Clinic and women attending a Preterm Birth Clinic, and we also reviewed all cases of births before 34 weeks over that time period. At the initial midwife appointment at 8–10 weeks’ gestation, risk factors for preterm birth were assessed. Pregnant women with moderate risk factors (previous preterm birth at 32+ 0 − 33+ 6 weeks, previous preterm prelabour rupture of membranes (PPROM) at 32+ 0 − 33+ 6 weeks, previous LLETZ / cone biopsy, known abnormal uterus, previous caesarean section at 10 cm dilatation, and multiple pregnancy) were referred to the Cervical Screening Clinic for a cervical length scan by a sonographer. Pregnant women with major risk factors (previous preterm birth at 16+ 0 − 31+ 6 weeks, previous PPROM at less than 32+ 0 weeks, radical trachelectomy, previous cervical cerclage) as well as those with a cervix < 25 mm at any scan were referred to the Preterm Birth Clinic for a cervical length scan and counselling by a specialist obstetrician. Detailed information on risk factors, management, and perinatal outcomes were collected from case notes and analysed.Results189 women attended the Cervical Screening Clinic: 79.1% had a moderate risk factor for preterm birth, 100% had a cervical length scan, 7% had a short cervix and 4.2% received an intervention. All 196 infants were live born, with overall preterm birth rates of 14.8% at < 37 weeks, 3.1% at < 32 weeks, and 0% at < 28 weeks. The spontaneous live preterm birth rates were 9.7% at < 37 weeks, 2.6% at < 32 weeks and 0% at < 28 weeks. 79 women attended the Preterm Birth Clinic: 87.3% had a major risk factor for preterm birth, 100% had ≥ 1 cervical length scan, 41.3% had a short cervix, 78.1% received vaginal progesterone, and 39% had a cervical cerclage. Overall preterm birth rates were 33.8% at < 37 weeks, 10.3% at < 32 weeks and 4.4% at < 28 weeks. Spontaneous live preterm birth rates were 22.1% at < 37 weeks, 7.4% at < 32 weeks, and 2.9% at < 28 weeks. 115 women gave birth to 130 babies before 34 weeks: 80% had no major risk factor for preterm birth, 29% had a cervical length scan and less than 15% had an intervention. Over 90% had a live birth, but the neonatal death rate was high (8.5%).ConclusionWomen with moderate risk factors for preterm birth seen in the Cervical Screening Clinic had low rates of intervention and good perinatal outcomes. Most women with major risk factors were appropriately referred and managed by the Preterm Birth Clinic. This two-tier preterm birth prevention service therefore appears safe and effective.

The rising preterm birth rate in China: a cause for concern

Objective: To evaluate for the presence of risk factors (RFs) for preterm birth (PTB) in women without prior PTB having second trimester cervical length (CL) screening, and to estimate the utility of RF screening.Methods: “Low-risk” singletons were prospectively screened with midtrimester transvaginal ultrasound CL. Prior PTB, intrauterine fetal demise and lethal anomalies were excluded. Women were analyzed based on second trimester CL (<25 mm versus ≥25 mm) and the presence of RFs for PTB. A p-value of < 0.05 was considered significant.Results: A total of 639 women were screened; 8% had CL <25 mm. Ninety-eight percent of women with CL <25 mm and 95% of women with CL ≥25 mm had RFs for PTB. Five percent of women with a CL ≥25 mm delivered preterm as compared to 18% with CL <25 mm (p < 0.01). Treatment of cervical dysplasia, drug use during the pregnancy and unmarried status were significantly more common in women with CL <25 mm than CL ≥25 mm. When data were analyzed by CL, the presence of additional RFs did not add to the prediction of PTB <37 weeks.Discussion: Over 95% of singleton gestations without prior PTB have ≥1 other RF for PTB. In women without prior PTB, assessment of other PTB RFs does not add to prediction of PTB provided by CL alone.

ObjectiveMultiple pregnancies carry an increased risk of maternal and perinatal complications, notably prematurity. Few studies have evaluated the risk factors for preterm births in multiple pregnancies within the Thai population. This study aims to ascertain maternal and perinatal outcomes and identify factors linked to preterm births in multiple pregnancies.MethodsThis study was carried out at Khon Kaen University, Faculty of Medicine, Department of Obstetrics and Gynecology in Thailand. We reviewed the medical records of women with multiple pregnancies who delivered at a gestational age of more than 20 weeks between January 1, 2012 and December 31, 2021. We excluded patients with incomplete data or those for whom data were missing.ResultsOut of 21,400 pregnancies, 427 were multiple pregnancies, constituting approximately 1.99%. Over the ten-year period, 269 multiple pregnancies (65.1%) resulted in preterm births. Of these, 173 (64.3%) were monochorionic twins, and 96 (35.7%) were dichorionic twins. Monochorionic twins had a notably higher rate of preterm delivery (AOR, 2.06; 95%CI 1.29—3.30). Vaginal delivery was observed in 7.9% of the cases, while cesarean sections were performed for both twins in 91.5% of cases. In 0.5% of the cases, only the second twin was delivered by cesarean section. In terms of neonatal outcomes, 160 infants (19.4%) weighed less than 1,500 g at birth, and there were 78 perinatal deaths (9.4%). Birth asphyxia was noted in 97 cases (20.2%) among monochorionic twins and in 28 cases (8.1%) for dichorionic twins.ConclusionThe prevalence of multiple pregnancies was 1.99%, with 65.1% resulting in preterm births. Neonatal complications were notably more frequent in monochorionic twins. Monochorionic placenta and antepartum complications emerged as significant risk factors for preterm birth.

Prior uterine evacuation and risk for preterm birth

To examine the relationship between preterm birth and socioeconomic factors, past history, cervical length, cervical interleukin-8, bacterial vaginosis, underlying diseases, use of medication, employment status, sex of the fetus and multiple pregnancy. In a multicenter, prospective, observational study, 1810 Japanese women registering their future delivery were enrolled at 8⁺⁰ to 12⁺⁶ weeks of gestation. Data on cervical length and delivery were obtained from 1365 pregnant women. Multivariate logistic regression analysis was performed. Short cervical length, steroid use, multiple pregnancy and male fetus were risk factors for preterm birth before 34 weeks of gestation. Multiple pregnancy, low educational level, short cervical length and part-timer were risk factors for preterm birth before 37 weeks of gestation. Multiple pregnancy and cervical shortening at 20-24 weeks of gestation was a stronger risk factor for preterm birth. Any pregnant woman being part-time employee or low educational level, having a male fetus and requiring steroid treatment should be watched for the development of preterm birth.

BackgroundAdenomyosis is thought to be associated with adverse perinatal outcomes. This study aimed to assess the relationship between pre-pregnancy uterine volume and preterm birth in singleton gravid women with adenomyosis.MethodsWe conducted a retrospective cohort study of 586 pregnant women with a singleton pregnancy between January 2014 and December 2022 who had a pre-pregnancy diagnosis of adenomyosis in Shanghai First Maternity and Infant Hospital. Multivariate logistic models were adopted to analyze the association between pre-pregnancy uterine volume and pregnancy outcomes in adenomyosis patients, including primary outcome (preterm birth) and secondary outcomes (pregnancy complications). The logistic model was performed for subgroup analysis as a sensitivity test.ResultsThe preterm birth (PTB) rate was 15.19% (89/586). The median uterine volume in preterm birth group 108.9 cm3 (interquartile range, 91.9-119.2) was larger than that in term birth group 85.3 cm3 (interquartile range, 67.0-101.3) (P < 0.001). The incidence of pre-eclampsia or eclampsia (13.5% vs. 5.2%, P = 0.004), placental malposition (32.6% vs. 8.9%, P < 0.001), and preterm premature rupture of membrane (PPROM) (28.1% vs. 14.3%, P = 0.001) was significantly higher in the PTB group than that in the term birth group. Multivariate logistic analysis revealed that, the pre-pregnancy uterine volume of gravid women with adenomyosis was associated with preterm birth in Model I (odds ratio [OR] adj = 1.37, per 10 cm3 increase, 95% confidence interval [CI]: 1.25–1.51, P < 0.001), Model II (OR adj = 1.40, per 10 cm3 increase, 95% CI: 1.27–1.55, P < 0.001) and Model III (OR adj = 1.36, per 10 cm3 increase, 95% CI: 1.25–1.48, P < 0.001). The inflection point of the uterine volume was 89.34 cm3. Pregnant women with focal adenomyosis exhibited distinct OR compared to those with diffuse adenomyosis between uterine volume and preterm birth (OR = 1.43; 95% CI: 1.29–1.58 vs. OR = 1.10; 95% CI: 0.91–1.33, respectively; p for interaction = 0.021).ConclusionsIncreased pre-pregnancy uterine volume may be a potential risk factor for preterm birth in women with adenomyosis. It may provide a target for future monitoring and intervention to reduce the risk of preterm birth in women with adenomyosis.

Objective: Electrohysterography (EHG) has been shown to provide valuable information for assessing preterm birth risk. However, few studies have focused on multiple gestations (MG), a well-known risk factor for preterm birth. This study aimed to comprehensively characterize and compare uterine EHG signals between singleton (SG) and MG pregnancies during the third trimester. Method: This prospective cohort study analyzed 383 EHG recordings from 61 SG and 92 MG women during the third trimester. A whole-window approach was used to extract four key EHG features: peak-to-peak amplitude (PPA), Kurtosis of the Hilbert Envelope (KHE), median frequency (MDF) and sample entropy (SampEn). Generalized additive models (GAM) were applied to evaluate temporal trends across gestational age (GA) and gestation type (SG and MG). Results: In SG pregnancies, PPA and KHE progressively increased, with a significant rise in KHE at labour. MDF remained stable until labour, while SampEn gradually declined, especially at term. MG pregnancies showed similar but less pronounced trends: MG exhibited a notably earlier activation of uterine activity than SG before 32 weeks of gestation (WoG), and a slowing-down electrophysiological progression beyond 32 WoG, resulting in similar characteristics with no significant differences. Conclusion: These findings provide electrophysiological evidence suggesting that MG pregnancies may enter a labour-preparatory state earlier, potentially increasing the PTB risk, while the later convergence of EHG features may indicate compensatory mechanisms to delay labour. This work integrates EHG signal analysis with clinical obstetric care, offering valuable insights for clinical management and early PTB risk assessment in MG pregnancies.

Screening of pregnant women for preterm birth, based on their obstetric history and sonographic measurement of the cervical length, can identify greater than 50% of those at risk. Administration of progesterone to at-risk women with a singleton pregnancy can significantly reduce rates of preterm birth. However, effects of this agent on the actual perinatal and long-term consequences of prematurity are difficult to assess. Existing randomized controlled trials (RCTs) and systematic reviews have focused mainly on the primary outcome of reduction of preterm birth rates. The aim of this meta-analysis was to systematically review published evidence and pool data on the perinatal outcome in women treated with progesterone for the prevention of preterm birth. MEDLINE and SCOPUS databases were searched for clinical trials in which progesterone was given to prevent preterm birth in pregnant women at risk compared with placebo. Randomized controlled trials that compared progesterone versus placebo in women with singleton or multiple pregnancies at risk for preterm birth based on previous history or short cervix were selected. The CONSORT statement was used to address the reporting quality of the RCTs. The risk of bias in the RCTs was assessed with the “risk-of-bias” tool from the Cochrane Collaboration. The primary outcomes were the rates of neonatal and perinatal mortality. Secondary outcomes were the rates of perinatal complications, including respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH) grade 3–4, sepsis, necrotizing enterocolitis (NEC), sepsis, retinopathy, and admission to the neonatal intensive care unit (NICU); a composite adverse outcome was also determined and defined as the presence of any perinatal morbidity or mortality. Of 628 retrieved items, 16 RCTs reporting on the use of progesterone in asymptomatic women to prevent preterm birth were included in the meta-analysis. Pooled data indicated that progesterone administration in these women significantly decreased the risk for composite adverse outcome (RR, 0.576; 95% confidence interval [CI], 0.373–0.891), neonatal death (relative risk, 0.487; 95% CI, 0.290–0.818), RDS (RR, 0.677; 95% CI, 0.490–0.935), and admission to the NICU (RR, 0.410; 95% CI, 0.204–0.823). No significant differences were found in rates of perinatal death, grade 3–4 IVH, NEC, retinopathy, or sepsis. Pooled data from 3 studies that used vaginal progesterone in women with a short cervix showed that progesterone significantly decreased the rate of composite adverse outcome (RR, 0.576; 95% CI, 0.373–0.891) and RDS (RR, 0.464; 95% CI, 0.275–0.786), but results did not reach statistical significance for rates of neonatal death, perinatal death, grade 3–4 IVH, NEC, sepsis, or admission to the NICU. Three studies tested systemic progesterone in women with a singleton pregnancy and a history of preterm birth; pooled results found that progesterone significantly decreased rates of neonatal death (RR, 0.412; 95% CI, 0.201–0.842) and NICU admission (RR, 0.277; 95% CI, 0.160–0.479). In 7 RCTs reporting on women with twin pregnancies, progesterone administration did not significantly affect the rates of neonatal death, grade 3–4 IVH, NEC, retinopathy, sepsis, or NICU admission. Progesterone significantly increased the rates of composite adverse outcome (RR, 1.211; 95% CI, 1.029–1.425), perinatal death (RR, 1.551; 95% CI, 1.014–2.372), and RDS (RR, 1.218; 95% CI, 1.038–1.428). The pooled data from 2 RCTs on women with triplets did not show significant differences in the rates of composite adverse outcome, neonatal death, RDS, grade 3–4 IVH, NEC, or sepsis. Preterm birth is a major cause of perinatal mortality and morbidity with long-term consequences. Results of this meta-analysis indicate that prophylactic progesterone administration in singleton pregnancies at risk can lower the rates of neonatal mortality, RDS, admission to the NICU, and a composite adverse outcome. Data, however, also indicate that use of progesterone in multiple pregnancies may lead to increased rates of perinatal death, RDS, and a composite adverse outcome.

Multiple pregnancy and a mid-gestation short cervix are known risk factors for spontaneous preterm birth (sPTB). We aimed to compare the effectiveness of cervical pessary and vaginal progesterone in multiples without a previous sPTB < 34 weeks of gestation and with a short cervix for the improvement of perinatal outcome through prevention of PTB. We performed an open-label multi-centre randomised clinical trial in 20 hospitals in the Netherlands (EUCTR2013-002884-24-NL). Asymptomatic individuals with a multiple (twin or triplet) pregnancy without previous sPTB < 34 weeks and with a mid-gestation cervical length < 38mm were randomised in a 1:1 ratio to receive either an Arabin cervical pessary or vaginal progesterone 200mg daily. Primary outcome was a composite of adverse perinatal outcomes. Secondary outcomes were rates of (s)PTB < 24, 28, 32, 34 and 37 weeks. Treatment effect was expressed as relative risk (RR) and 95% confidence intervals (CI). The sample size was set at 332 women and analysis was by intention-to-treat. The study was halted for futility based on the results of 237 participants at the 4th interim analyses. Between October 2014 and August 2023, we randomised 277 multiples, including 7 triplets, (pessary N = 138, progesterone N = 139) with 531 neonates (pessary N = 267, progesterone N = 264). The composite adverse perinatal outcome occurred in 19.5% of neonates in the pessary group versus 13.3% of neonates in the progesterone group (crude RR 1.6; 95% CI 0.99 – 2.5). The rates of (s)PTB were not significantly different between groups. In the predefined subgroup of cervical length ≤ 25mm, the composite perinatal outcome was equally frequent in the pessary and progesterone group (43.6% vs 34.0%, RR 1.5; 95% CI 0.68 – 3.3). In multiples without a history of previous sPTB < 34 weeks and with a mid-gestation cervical length < 38mm or ≤ 25mm, treatment with a pessary or progesterone did not result in statistically significant differences in the prevention of a composite adverse perinatal outcomes.