Preterm Birth In Twins Research Articles

Analysis of risk factors for very early preterm and early preterm birth in twins following invitro fertilization and intracytoplasmic sperm injection-assisted pregnancy: Aretrospective study.

To investigate the risk factors influencing very early preterm and early preterm births in twin pregnancies after invitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). This retrospective study analyzed 2042 twin pregnancies that underwent embryo transfer via IVF/ICSI at the Reproductive Center of Sir Run Run Shaw Hospital between January 2019 and December 2022. Spontaneous very early, early preterm, and provider-initiated preterm births were examined separately. Based on gestational age, participants were categorized into three groups: very early preterm birth (<28 weeks), early preterm birth (≥28 to <34 weeks), and ongoing pregnancy (≥34 weeks). Univariate analysis was conducted to assess general conditions, among the three groups. Multiple logistic regression analysis was performed to identify independent risk factors for very early and early spontaneous preterm birth in twin pregnancies. A total of 2042 twin pregnancies were included in the study, with birth rates of 4.36% (89 of 2042) <28 weeks, 12.14% (248 of 2042) ≥28 to <34 weeks, and 83.50% (1705 of 2042) ≥34 weeks. The primary cause of provider-initiated preterm birth <28 weeks was placental factors, while hypertensive disorders of pregnancy (31.11%) were the predominant cause for preterm births ≥28 to <34 weeks. Multiple logistic regression analysis identified the independent risk factors for births <28 weeks (P < 0.05) as cervical cerclage, history of late miscarriage or premature birth, uterine adhesions, primary infertility of polycystic ovary syndrome (PCOS), monochorionic pregnancies, history of cervical surgery, uterine malformations, body mass index ≥25 kg/m2, and uterine longitudinal axis lengths <3.6 cm. Cervical cerclage, main factors of infertility (PCOS), adenomyosis, and uterine longitudinal axis lengths <3.6 cm were identified as independent risk factors for ≥28 to 34 weeks (P < 0.05). It is crucial to consider risk factors during IVF/ICSI treatment because of the high incidence of very early and early preterm twin pregnancies, which can be identified early and properly managed.

Cervical cerclage for prevention of preterm birth and adverse perinatal outcome in twin pregnancies with short cervical length or cervical dilatation: A systematic review and meta-analysis.

The optimal approach to prevent preterm birth (PTB) in twins has not been fully established yet. Recent evidence suggests that placement of cervical cerclage in twin pregnancies with short cervical length at ultrasound or cervical dilatation at physical examination might be associated with a reduced risk of PTB. However, such evidence is based mainly on small studies thus questioning the robustness of these findings. The aim of this systematic review was to determine the role of cervical cerclage in preventing PTB and adverse maternal or perinatal outcomes in twin pregnancies. Key databases searched and date of last search: MEDLINE, Embase, and CINAHL were searched electronically on 20 April 2023. Eligibility criteria: Inclusion criteria were observational studies assessing the risk of PTB among twin pregnancies undergoing cerclage versus no cerclage and randomized trials in which twin pregnancies were allocated to cerclage for the prevention of PTB or to a control group (e.g., placebo or treatment as usual). The primary outcome was PTB <34 weeks of gestation. The secondary outcomes were PTB <37, 32, 28, 24 weeks of gestation, gestational age at birth, the interval between diagnosis and birth, preterm prelabor rupture of the membranes (pPROM), chorioamnionitis, perinatal loss, and perinatal morbidity. Subgroup analyses according to the indication for cerclage (short cervical length or cervical dilatation) were also performed. Risk of bias assessment: The risk of bias of the included randomized controlled trials (RCTs) was assessed using the Revised Cochrane risk-of-bias tool for randomized trials, while that of the observational studies using the Newcastle-Ottawa scale (NOS). Statistical analysis: Summary risk ratios (RRs) of the likelihood of detecting each categorical outcome in exposed versus unexposed women, and (b) summary mean differences (MDs) between exposed and unexposed women (for each continuous outcome), with their 95% confidence intervals (CIs) were computed using head-to-head meta-analyses. Synthesis of the results: Eighteen studies (1,465 twin pregnancies) were included. Placement of cervical cerclage in women with a twin pregnancy with a short cervix at ultrasound or cervical dilatation at physical examination was associated with a reduced risk of PTB <34 weeks of gestation (RR: 0.73, 95% CI [0.59, 0.91], p = 0.005 corresponding to a 16% difference in the absolute risk, AR), <32 (RR: 0.69, 95% CI [0.57, 0.84], p < 0.001; AR: 16.92%), <28 (RR: 0.54, 95% [CI 0.43, 0.67], 0.001; AR: 18.29%), and <24 (RR: 0.48, 95% CI [0.23, 0.97], p = 0.04; AR: 15.57%) weeks of gestation and a prolonged gestational age at birth (MD: 2.32 weeks, 95% [CI 0.99, 3.66], p < 0.001). Cerclage in twin pregnancy with short cervical length or cervical dilatation was also associated with a reduced risk of perinatal loss (RR: 0.38, 95% CI [0.25, 0.60], p < 0.001; AR: 19.62%) and composite adverse outcome (RR: 0.69, 95% CI [0.53, 0.90], p = 0.007; AR: 11.75%). Cervical cerclage was associated with a reduced risk of PTB <34 weeks both in women with cervical length <15 mm (RR: 0.74, 95% CI [0.58, 0.95], p = 0.02; AR: 29.17%) and in those with cervical dilatation (RR: 0.68, 95% CI [0.57, 0.80], p < 0.001; AR: 35.02%). The association between cerclage and prevention of PTB and adverse perinatal outcomes was exclusively due to the inclusion of observational studies. The quality of retrieved evidence at GRADE assessment was low. Emergency cerclage for cervical dilation or short cervical length <15 mm may be potentially associated with a reduction in PTB and improved perinatal outcomes. However, these findings are mainly based upon observational studies and require confirmation in large and adequately powered RCTs.

Gestational weight gain and neonatal outcomes in different zygosity twins: a cohort study in Wuhan, China

ObjectiveTo evaluate whether twin zygosity influences the association between neonatal outcomes and gestational weight gain (GWG) based on the Chinese guidelines in twin-pregnancy women.DesignA retrospective cohort study. And it is...

Highlights from the International Twins Congress 2021

Highlights from the International Twins Congress 2021

The effectiveness of the Dr. Arabin cervical pessary in the prevention of extreme preterm birth and very preterm birth in twins

BACKGROUND: Multiple pregnancy remains a serious obstetrical problem, as it is a high risk factor for miscarriage/preterm birth at any gestational age. On average, in 54% of patients with twins, pregnancy ends in preterm birth, regardless of the economic situation and the level of perinatal care in the state, and is characterized by high childhood morbidity and mortality.&#x0D; AIM: The aim of this study was to identify risk factors for spontaneous preterm birth and to evaluate the effectiveness of a cervical pessary in pregnant women with twins and a short cervix.&#x0D; MATERIALS AND METHODS: This prospective, open, randomized cohort study included 91 women with twins, a short cervix (25 according to the L.J. Salomon scale) and a threatened miscarriage / preterm birth in the second and third trimesters of pregnancy, who received the Dr. Arabin cervical pessary. We analyzed pregnancy outcomes and identified risk factors for spontaneous preterm birth.&#x0D; RESULTS: Based on the pregnancy outcomes, all patients were categorized into two main groups after 16 pregnant women with induced preterm birth were excluded from further study. The study was continued by 75 pregnant women, with term birth in 40 (53.3%) women in group I and spontaneous preterm birth in 35 (46.7%) women in group II.&#x0D; The average period of pregnancy prolongation was statistically different between groups II and I (8.86 4.86 and 12.32 4.38 weeks, p 0.01). The average gestational age of labor initiation was 37.73 0.62 weeks in group I and 34.24 2.08 weeks in group II (p 0.001). We found no extreme preterm birth (22-27 6/7 weeks) in group II, the perinatal mortality of newborns being the highest at this gestational age. Labor at a gestational age of 28-33 6/7 weeks was in 14 (18.67%) women and of 34-36 6/7 weeks in 21 (28.00%) women. The detailed analysis of the course and outcomes of pregnancy and labor in high-risk groups identified two factors that affect the occurrence of spontaneous preterm birth in twin pregnancies: the Bishop score 5 points (p = 0.03579; odds ratio 4.93, 95% confidence interval 1.2319.74) and cervical length on bimanual vaginal examination 20 mm (p = 0.014; odds ratio 4.67, 95% confidence interval 1.4714.82).&#x0D; CONCLUSIONS: The use of a cervical pessary in the group of pregnant women with twins and at a high risk of spontaneous preterm birth not only allows for prolonging pregnancy and excluding the birth of extremely premature babies, but also reduces the number of spontaneous extreme and very preterm births.

The amniotic cavity is sterile before the onset of parturition in early preterm twins

The microbial invasion of the amniotic cavity is the leading cause of early preterm birth in twins as well as singletons. Ureaplasma species are the microorganisms most frequently isolated from amniotic fluid of twin pregnancies with early preterm birth. Gastric fluid (GF) of newborns contains swallowed amniotic fluid and presence of bacteria in GF is suggestive of the microbial invasion of the amniotic cavity. The purpose of this study was to evaluate a difference in the rate of positive GF culture for ureaplasmas according to the etiology of preterm birth and birth order.

Racial and sociodemographic disparities associated with twin preterm births are increased in earlier gestational ages

Several racial and sociodemographic have been characterized as independent risk factors for preterm birth (PTB) in twin gestations. We aimed to evaluate whether the association of racial/ethnic minority groups, lower educational attainment, and Medicaid insurance with PTB changes based on the gestational age at delivery.

Risk of spontaneous preterm birth in asymptomatic twins with a short cervix in early viability

Risk of spontaneous preterm birth in asymptomatic twins with a short cervix in early viability

Cervical Cerclage in Twin Pregnancies: An Updated Systematic Review and Meta-analysis

(Abstracted from Eur J Obstet Gynecol Reprod Biol 2021;260:137–149) Preventing preterm birth (PTB) in twins is important because the risk is significantly higher compared with singleton pregnancies. The effectiveness of cervical cerclage as an option to prevent PTB in twin pregnancies is unclear.

Performance of the cervical shortening for prediction of spontaneous preterm birth in uncomplicated twins

Objective There is a lack of consensus about the management of twins with significant cervical length (CL) shortening, especially if CL is above 25 mm. Therefore, it is important to define “abnormal” CL change over time, and to compare the performance of different strategies. The aim of this study was twofold, to describe the performance of the cervical shortening and that of an integrated strategy that includes both the cervical shortening and a fixed CL cutoff <25 mm in any measurement as predictor of spontaneous PTB (sPTB) < 34 weeks in uncomplicated twin pregnancies. Material and methods Retrospective cohort study of twins followed in our Twins Clinic at Hospital Italiano de Buenos Aires from 2013 to 2017. Inclusion criteria were dichorionic or monochorionic diamniotic twins with CL measurement between 18 and 33 + 6 weeks with available data of the delivery. Exclusion criteria included any of the following complications: iatrogenic preterm delivery <34 weeks, cerclage, fetal growth restriction, fetal death, structural anomalies, polyhydramnios, twin–twin transfusion syndrome, selective fetal growth restriction, twin anemia–polycythemia sequence, and twin reversed arterial perfusion sequence. Spontaneous preterm birth was defined as spontaneous delivery <34 weeks. Cervical shortening was analyzed in the following periods: 20–24 weeks, 20–28 weeks, 24–28 weeks, 24–32 weeks and 28–32 weeks. Cervical changes were analyzed as velocity of shortening over time (mm/week) and as the ratio of shortening over time (%/week). ROC curves for each period were constructed and two different cutoffs were used to classify changes of the CL as positive or negative screening: a) the shortening of CL associated to the highest value of the Youden Index and b) fixing a 10% false positive rate (FPR). For the second objective, we analyzed an integrated strategy considering a fixed cutoff of 25 mm at any GA and/or a significant shortening. The screening was considered positive if any CL measurement was <25 mm at any GA or there was a shortening of the CL ≥ the cutoff obtained for each period. We report sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio and area under the ROC curve. Results We included 378 patients and 1417 measurements, 284 (75%) dichorionic and 94 (25%) monochorionic. Between 20 and 28 weeks, with a change in CL cutoff = 1.6 mm/week or 4.1%/week the detection rate was 54.2% (32.8–74.4%) and the specificity 80.5% (75.1–85.1%) and 83.5% (78.5–87.8%) respectively. In the integrated strategy, the detection rate was 65.7% (47.8–80.9%) and the specificity 69 (63.7–74). All the ROC curves of the periods studied showed an AUC < 0.7. In the group of patients that delivered preterm the initial mean CL was shorter than in the term group, 39 (±12) mm vs. 43 (± 7.7) mm (p = .02) and the most important change in CL was at 20–24 weeks both in the velocity and in the ratio of shortening over time. Conversely, patients that delivered at term showed a higher change in CL in the third trimester. Conclusion The performance of all the strategies analyzed as a predictor of sPTB <34 weeks was moderate. The period 20–28 weeks detected half of the patients at risk with a FPR around 10–20% and the integrated strategy increased the sensitivity up to a detection of two thirds of the patients at risk but with a FPR of ∼30%. Future analyses need to explore other strategies to improve the performance and to really identify the patients at higher risk.

Trends in Spontaneous and Medically Indicated Preterm Birth in Twins versus Singletons: A California Cohort 2007 to 2011.

The study aimed to describe preterm birth (PTB) rates, subtypes, and risk factors in twins compared with singletons to better understand reasons for the decline in PTB rate between 2007 and 2011. This was a retrospective population-based analysis using the California linked birth certificates and maternal-infant hospital discharge records from 2007 to 2011. The main outcomes were overall, spontaneous (following spontaneous labor or preterm premature rupture of membranes), and medically indicated PTB at various gestational age categories: <37, <32, and 34 to 36 weeks in twins and singletons. Among the 2,290,973 singletons and 28,937 twin live births pairs included, overall PTB <37 weeks decreased by 8.46% (6.77-6.20%) in singletons and 7.17% (55.31-51.35%) in twins during the study period. In singletons, this was primarily due to a 24.91% decrease in medically indicated PTB with almost no change in spontaneous PTB, whereas in twins indicated PTB declined 7.02% and spontaneous PTB by 7.39%. Recent declines in PTB in singletons appear to be largely due to declines in indicated PTB, whereas both spontaneous and indicated PTB declined in twins. · The declines in PTB noted between 2006 and 2014 occurred in both singleton and twins.. · Declines were mostly in medically indicated PTB.. · Interventions proposed as causing the declines in singletons would not apply to twins..

Perinatal conditions of late preterm twins versus early term twins

OBJECTIVE To study the perinatal complications of late preterm twins (LPTs) versus early term twins (ETTs). METHODS A retrospective analysis was performed for the complications of 246 LPTs, 496 ETTs, and their mothers. The risk factors for late preterm birth were analyzed. According to gestational age, the twins were divided into five groups: 34-34+6 weeks (n=44), 35-35+6 weeks (n=70), 36-36+6 weeks (n=132), 37-37+6 weeks (n=390), and 38-38+6 weeks (n=106). The perinatal complications were compared between groups. RESULTS Maternal hypertension, maternal thrombocytopenia, placenta previa, and premature rupture of membranes were independent risk factors for late preterm birth in twins (P < 0.05). The LPT group had higher incidence rates of respiratory diseases, feeding intolerance, and hypoglycemia than the ETT group (P < 0.05). The 34-34+6 weeks group had a higher incidence rate of neonatal asphyxia than the 37-37+6 weeks and 38-38+6 weeks groups; and had a higher incidence rate of septicemia than 36-36+6 weeks group (P < 0.0045). The 34-34+6 weeks and 35-35+6 weeks groups had higher incidence rates of neonatal respiratory distress syndrome, neonatal apnea, and anemia than the other three groups; and had higher incidence rates of neonatal pneumonia, hypoglycemia and septicemia than the 37-37+6 weeks and 38-38+6 weeks groups (P < 0.0045). The 35-35+6 weeks group had a higher incidence rate of feeding intolerance than the 36-36+6 weeks, 37-37+6 weeks, and 38-38+6 weeks groups (P < 0.0045). The 36-36+6 weeks group had a lower incidence rate of hypoglycemia than the 34-34+6 weeks group and a higher incidence rate of hypoglycemia than the 37-37+6 weeks group (P < 0.0045). CONCLUSIONS Compared with ETTs, LPTs have an increased incidence of perinatal complications. The incidence of perinatal complications is associated with gestational ages in the LPTs and ETTs.

744 Clinical factors associated with gestational latency in women with twins undergoing physical exam-indicated cerclage

A randomized trial demonstrated that, compared to expectant management, physical exam-indicated cerclage (PEIC) reduced preterm birth in twins with advanced cervical dilation < 24 weeks gestational age (GA). However, data are limited to personalize the expected gestational latency after PEIC placement. Thus, we assessed clinical factors associated with gestational latency among pregnant women with twin gestations undergoing PEIC. This single-site retrospective cohort study included all women with a twin gestation who underwent a PEIC and delivered between 2009 and 2018. PEIC was performed in the setting of painless cervical dilation ≥ 1 cm between 16 0/7 and 23 6/7 weeks GA. The primary outcome was gestational latency ≥ 28 days. Generalized linear models using a Poisson error distribution with robust error variances were created. A priori covariates included a history of preterm birth and use of perioperative antibiotics and indomethacin. Other clinical covariates were included based on statistical significance of p < 0.10 on bivariable analyses. Effect modification between clinical variables associated with gestational latency was evaluated using interaction variables. Subgroup analyses were performed for interaction variables significant on multivariable analysis at p < 0.05. 130 women were included. Women who achieved a gestational latency ≥ 28 days had a lower frequency of prolapsing membranes (36.6% v 64.9%, p = 0.003) and cervical dilation ≥ 2 cm (32.3% v. 62.2%, p = 0.002) when compared to those who did not (Table 1). On multivariable analysis, the interaction between prolapsing membranes and cervical dilation was significant (p=0.004). Women with cervical dilation ≥ 2 cm and prolapsing membranes had a lower risk of achieving a gestational latency ≥ 28 days than women with cervical dilation < 2 cm and no prolapsing membranes (aRR 0.51, 95% CI 0.32-0.80, Table 2). Both cervical dilation and prolapsing membranes are associated with gestational latency after PEIC in twin gestations and can be used to counsel women on anticipated clinical outcomes.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Cervical-length as a screening for spontaneous preterm birth in uncomplicated twins: one vs. serial measurements

Objective While cervical length (CL) provides an effective screening tool for spontaneous preterm birth in singletons, the performance in twins is still controversial. Our aim was twofold. First, to compare the performance of a single CL measurement at mid-gestation (∼20 weeks) versus serial measurements as a predictor of spontaneous preterm birth < 34 weeks in uncomplicated twin pregnancies. Second, to describe the performance of a single CL at ∼24, ∼28 and ∼32 weeks. Material and methods cohort study of twins followed at Hospital Italiano de Buenos Aires from 2013 to 2017. Inclusion criteria were dichorionic or monochorionic diamniotic twins with CL measurement between 18 and 33 + 6 weeks with available data of the delivery. Exclusion criteria included any of the following complications: iatrogenic preterm delivery <34 weeks, cerclage, fetal growth restriction, fetal death, structural anomalies, polyhydramnios, twin–twin transfusion syndrome, selective fetal growth restriction, twin anemia–polycythemia sequence, and twin reversed arterial perfusion sequence. Spontaneous preterm birth was defined as spontaneous delivery < 34 weeks. Two different cutoffs were used to classify CL as short (positive screening) or normal (negative screening): (a) a fixed cutoff of 25 mm at any gestational age (GA). The screening was considered positive if any CL measurement was <25 mm; and (b) a GA adjusted cutoff to a 10% false positive rate (FPR). The 10% FPR for each GA was calculated and the screening was considered positive if any of the CL measurements were below this 10% FPR cutoff. We report sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratio and area under the ROC curve. Results Among 777 twins followed in our Unit, 381 met exclusion criteria and 18 were excluded due to incomplete follow-up. We included 378 patients, 284 (75%) dichorionic and 94 (25%) monochorionic. The performance of one CL at 20 weeks showed a sensitivity ≤ 20% with an area under the ROC curve of 0.58 (95% CI, 0.45–0.70), while the performance of serial measurements showed a sensitivity of 58.8% (95% CI, 40.7–75.4) with an area under the ROC curve of 0.70 (95% CI, 0.61–0.79) (p < .001). The analyses of the performance of a single CL at ∼24, ∼28 and ∼32 weeks showed similar AUC than the serial measurements and, for a FPR = 10%, the performance of one measurement at 24 and 32 weeks showed a sensitivity of 30% (95% CI, 14.7–49.4) and 31.6% (95% CI, (12.6–56.6), while the measurement at 28 weeks showed a sensitivity of 48.3% (95% CI, (29.4–67.5). Conclusion Serial measurements showed a better performance than a single one in mid-gestation. Moreover, among single measurements the CL in mid-gestation showed the poorest performance, while the 28 weeks assessment detected half of the preterm deliveries. However, all the strategies showed modest performances.

Current Practice of Maternal-Fetal Medicine Specialists Regarding the Prevention and Management of Preterm Birth in Twin Gestations.

To investigate the current practices of maternal-fetal medicine (MFM) specialists regarding the prevention and management of preterm birth (PTB) in twin pregnancies. This was a cross-sectional study of Canadian MFM specialists. Participants responded to an anonymous survey regarding the prevention and management of PTB in twins, including lifestyle and gestational weight gain recommendations, cervical length screening, PTB prevention, and labour and delivery practices. Of 137 MFM specialists surveyed, 95 (69%) responded. Most MFM specialists recommend against activity restriction (77.9%), avoidance of sexual activity (96.7%), routine progesterone (97.8%), routine prophylactic cerclage (98.9%), and routine administration of antenatal corticosteroids (95.6%). There were considerable inconsistencies with respect to gestational weight gain management. Despite lack of support by guidelines, most MFM specialists reported using routine cervical length screening (97.8%) and progesterone for short cervix (92.3%). Over half (52.7%) of MFM specialists recommend cervical cerclage when the cervix is <15mm. In cases of PTB, most MFM specialists recommend vaginal delivery when twins are in vertex presentation (63%-75%). MFM specialists are less likely to recommend vaginal delivery when twin B is non-vertex (35%-41%). There is a considerable variation among MFM specialists regarding the prevention and management of PTB in twins, and the practice of many MFM specialists differs from that recommended by professional societies' guidelines. These findings underscore the necessity for high-quality studies and up-to-date recommendations.

Two-stage nomogram models in mid-gestation for predicting the risk of spontaneous preterm birth in twin pregnancy.

This study aimed to develop two-stage nomogram models to predict individual risk of preterm birth at < 34weeks of gestation in twin pregnancies by incorporating clinical characteristics at mid-gestation. We used a case-control study design of women with twin pregnancies followed up in a tertiary medical centre from January 2018 to March 2019. Maternal demographic characteristics and transvaginal cervical length data were extracted. The nomogram models were constructed with independent variables determined by multivariate logistic regression analyses. The risk score was calculated based on the nomogram models. In total, 65 twin preterm birth cases (< 34weeks) and 244 controls met the inclusion criteria. Based on univariate and multivariate logistic regression analyses, we built two-stage nomogram prediction models with satisfactory discrimination and calibration when applied to the validation sets (first-stage [22-24weeks] prediction model, C-index: 0.805 and 0.870, respectively; second-stage [26-28weeks] prediction model, C-index: 0.847 and 0.908, respectively). Restricted cubic splines graphically showed the risk of preterm birth among individuals with increased risk scores. Moreover, the decision curve analysis indicated that both prediction models show positive clinical benefit. We developed and validated two-stage nomogram models at mid-gestation to predict the individual probability of preterm birth at < 34weeks in twin pregnancy.

Impact of mode of delivery on perinatal outcome in moderately and late preterm twin birth.

To examine the impact of the mode of delivery on neonatal and maternal outcomes in moderately and late preterm twin birth. This single-center cohort study included 275 live diamniotic moderately and late preterm twin deliveries at 32+0 -36+6 weeks of gestation. These twin deliveries were divided into two groups according to the planned mode of delivery: trial of labor (TOL) (N=199, 72.4%) and planned cesarean section (CS) (N=76, 27.6%). The primary outcome was neonatal morbidity. Maternal outcome and the effects of gestational age and chorionicity on neonatal outcome were also studied. Of the women in the TOL group, 170 (85.4%) delivered vaginally. Both for the first and second twin, and for dichorionic or monochorionic deliveries, there were no differences between the TOL and CS groups in composite neonatal morbidity or in other neonatal outcomes. No significant differences were found between the TOL and CS groups when the moderately and late preterm gestational age cohorts were studied separately. Mothers in the planned CS group more often had puerperal infection and surgical complications in comparison with mothers in the TOL group. Among 275 moderately and late preterm twin deliveries, planned mode of delivery did not affect neonatal outcome.

VP52.08: Mid‐trimester cervical consistency index, uterocervical angle and cervical texture analysis to predict spontaneous preterm birth in twins

VP52.08: Mid‐trimester cervical consistency index, uterocervical angle and cervical texture analysis to predict spontaneous preterm birth in twins

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.

The effect of early administration of rectal progesterone in IVF/ICSI twin pregnancies on the preterm birth rate: a randomized trial

BackgroundThe rate of multiple pregnancies in IVF/ICSI ranges from 20 to 30%. The incidence of preterm birth in multiple pregnancies is as high as 60% and is even higher in pregnancies conceived after IVF & ICSI. The effect of progesterone on prevention of preterm birth in twins is controversial. Our group has proven a positive effect in reduction of preterm birth, by starting progesterone from the mid-trimester, in exclusively IVF/ICSI singleton pregnancies but not twins. The purpose of our current study was to explore the effect of earlier administration of natural progesterone, in IVF/ICSI twin pregnancies starting at 11–14 weeks for prevention of preterm birth.MethodsThis is a double-blind, placebo controlled, single center, randomized clinical trial. Women with dichorionic twin gestations, having an IVF/ICSI trial were randomized to receive natural rectal progesterone (800 mg daily) vs placebo, starting early from 11 to 14 weeks. They also received oral and vaginal antimicrobial agents as part of our routine treatment for vaginitis and urinary tract infection. They were randomized regardless of cervical length and had no previous history of preterm birth or known Mullerian anomalies. The primary outcome was spontaneous preterm birth rate before 37 weeks. The secondary outcome was; spontaneous preterm birth before 34, 32, 28 weeks and neonatal outcome.ResultsA total of 203 women were randomized to both groups, final analysis included 199 women as 4 were lost to follow up. The base line characteristics as well as gestational age at delivery were not significantly different between the study and the placebo group (34.7 ± 3.6 vs 34.5 ± 4.5, P = 0.626). Progesterone administration was not associated with a significant decrease in the spontaneous preterm birth rates before 37 weeks (73.5% vs 68%, P = 0.551), before 34 (20.6% vs 21.6%, P = 0.649), before 32 (8.8% vs 12.4%, P = 0.46) & before 28 (4.9% vs 3.1%, P = 0.555) weeks.ConclusionsRectal natural progesterone starting from the first trimester in IVF/ICSI twin pregnancies did not reduce spontaneous preterm birth.Trial registrationThe trial was registered on 31 January 2014 at www.ISRCTN.com, number 69810120.