Left ventricular remodeling in twin pregnancy, noninvasively assessed using hemodynamic forces and pressure-volume relation analysis: prospective, cohort study.

This study was designed to prospectively investigate the pattern of intraventricular hemodynamic forces (HDFs) associated with left ventricular (LV) function and remodeling in women with uncomplicated twin pregnancy. Transthoracic echocardiography was performed on 35 women (aged 35.9 ± 4.7-yr old) during gestation (T1, <14 wk; T2, 14-27 wk; T3, >28 wk) and 6-7 mo after delivery (T0). LV HDFs were computed from echocardiography long-axis data sets using a novel technique based on endocardial boundary tracking, both in apex-base (A-B) and latero-septal (L-S) directions. HDF distribution was evaluated by L-S over A-B HDF ratio (L-S:A-B HDF ratio). At T1, L-S:A-B HDF ratio was higher than in T0 (P < 0.05) indicating HDF misalignment. At T2, a slight impairment of cardiac function was then recorded with a reduction of global longitudinal strain (GLS) and left ventricular end-systolic elastance (Ees) at pressure-volume relationship analysis versus T1 (both P < 0.05). Finally, at T3, when HDF misalignment and LV contractility reduction (GLS and Ees) were all restored, a rightward shift of the end-diastolic pressure-volume relationship (EDPVR) with an increase of ventricular capacitance was documented. In twin pregnancy, HDF misalignment in the first trimester precedes the slight temporary decrease in left ventricular systolic function in the second trimester; at the third trimester, a rightward shift of the EDPVR was associated with a realignment of HDF and normalization of ventricular contractility indexes. These coordinated changes that occur in the maternal heart during twin pregnancy suggest the role of HDFs in cardiac remodeling.NEW & NOTEWORTHY These changes indicate that 1) the misalignment of hemodynamic forces (HDFs) precedes a mild reduction in systolic function in twin pregnancy and 2) the positive left ventricular (LV) response to hemodynamic stress is mainly due to an improved diastolic function with enhanced LV cavity compliance.

Changes in cytokine and sequestosome-1 levels during twin pregnancy progression: Association with outcome.

BACKGROUND: Twin pregnancies are associated with complications and adverse outcomes. The number of twin pregnancies has increased in the last decades, due to the use of assisted reproductive techniques and delayed childbearing. Analysis of changes that occur during twin pregnancy progression and their association with outcome will lead to improved clinical interventions. OBJECTIVE: We evaluated if the plasma concentration of select cytokines and the level of sequestosome-1 (p62) in peripheral blood mononuclear cells (PBMCs) during each trimester of twin gestations was predictive of pregnancy outcome. STUDY DESIGN: This prospective, observational study was conducted at Careggi University Hospital, Florence, Italy. Plasma from 82 women with twin pregnancies was collected in each trimester for measurement of interleukin (IL)-1ß, IL-6, IL-10, IL-12 and tumor necrosis factor (TNF)-α. The intracellular PBMC concentration of p62, a protein involved in autophagy, kinase activity and cell differentiation, was also determined. RESULTS: IL-1ß (p < 0.001), IL-6 (p < 0.001), TNF-α (p < 0.001) and p62 (p < 0.05) increased from the 1st to the 2nd to the 3rd trimester. The TNF-α level was correlated with the IL-1ß concentration in the 1st and 3rd trimesters p < 0.01) and with the IL-6 concentration in each of the three trimesters (p < 0.01). The intracellular p62 level in PBMCs was negatively correlated with the concentration of IL-1ß in the 2nd trimester (p < 0.05) and negatively correlated with the IL-6 level in the 3rd trimester (p < 0.05). The TNF-α level was significantly higher in the 2nd (p < 0.05) and 3rd (p < 0.001) trimester in women with a spontaneous preterm delivery. The TNF-α concentrations in the 2nd (p < 0.05) and 3rd (p < 0.01) trimester, respectively, and 3rd trimester IL-6 (p < 0.01), were negatively associated with gestational age at delivery. The concentration of IL-6 was highest in the 2nd (p < 0.05) and 3rd (p < 0.05) trimesters in women who utilized assisted reproductive technologies. An elevated IL-1ß level in the 3rd trimester was associated with gestational diabetes mellitus (p < 0.05). CONCLUSION: Variations in cytokine levels between individual women during the three trimesters of twin gestations are predictive of spontaneous preterm delivery and the onset of gestational diabetes.

Late selective termination in dichorionic twins: comparing late second and third trimester procedures.

RESEARCH QUESTION: Do perinatal outcomes of selective termination performed in the late second versus third trimester differ and what risk factors are associated with subsequent preterm birth? DESIGN: This is a retrospective cohort study of late selective terminations performed in dichorionic twins between 2009 and 2021. Perinatal outcomes were compared between two groups: group A, late second trimester (20.2 to 24.2 weeks, n = 26), and group B, third trimester (≥28.2 weeks, n = 55) selective terminations. Univariate and multivariate analyses were conducted to identify factors associated with post-procedure preterm birth. RESULTS: In total, 81 dichorionic twin pregnancies were included. There were no pregnancy losses but 16% (13/81) of cases experienced complications. Group A had a higher median birthweight centile (36.5th versus 15th centile, P = 0.002) and lower rates of intrauterine growth restriction (IUGR) and Caesarean delivery (11.5% versus 32.7%, P = 0.04; and 26.9% versus 61.8%, P = 0.003) than group B. Preterm birth rates were similar (46.2% versus 63.6%, P = 0.15). Multiple regression revealed that reduction of the presenting twin and cervical length ≤35 mm were independently associated with post-procedure preterm birth (odds ratio [OR] 8.7, P = 0.001, 95% confidence interval [CI] 2.5-29.8; OR 3.8, P = 0.015, 95% CI 1.3-11). CONCLUSIONS: Late second trimester selective termination is associated with a higher birthweight centile and lower rates of IUGR and Caesarean delivery, compared with third trimester selective termination. Cervical length 35 mm or less and reduction of the presenting twin are independent risk factors for post-procedural preterm birth. These findings may help determine the optimal time to perform a late selective termination.

Greater risk of type 2 diabetes progression in multifetal gestations with gestational diabetes: the impact of obesity.

BACKGROUND: The relationship between gestational diabetes mellitus and adverse outcomes in multifetal pregnancies is complex and controversial. Moreover, limited research has focused on the risk of gestational diabetes mellitus progression to type 2 diabetes mellitus specifically in multifetal pregnancies, resulting in conflicting results from existing studies. OBJECTIVE: This study aimed to assess the risk of gestational diabetes mellitus progression to type 2 diabetes mellitus between singleton and multifetal pregnancies in a large cohort of parturients with a 5-year follow-up. STUDY DESIGN: A retrospective study was conducted on a prospective cohort of pregnant individuals with pregnancies between January 1, 2017, and December 31, 2020, followed up to 5 years after delivery. Glucose levels during pregnancy were obtained from the Meuhedet Health Maintenance Organization laboratory system and cross-linked with the Israeli National Diabetes Registry. The cohort was divided into 4 groups: singleton pregnancy without gestational diabetes mellitus, singleton pregnancy with gestational diabetes mellitus, multifetal pregnancy without gestational diabetes mellitus, and multifetal pregnancy with gestational diabetes mellitus. Gestational diabetes mellitus was defined according to the American Diabetes Association criteria using the 2-step strategy. Univariate analyses, followed by survival analysis that included Kaplan-Meier hazard curves and Cox proportional-hazards models, were used to assess differences between groups and calculate the adjusted hazard ratios with 95% confidence intervals for progression to type 2 diabetes mellitus. RESULTS: Among 88,611 parturients, 61,891 cases met the inclusion criteria. The prevalence of type 2 diabetes mellitus was 6.5% in the singleton pregnancy with gestational diabetes mellitus group and 9.4% in the multifetal pregnancy with gestational diabetes mellitus group. Parturients with gestational diabetes mellitus, regardless of plurality, were older and had higher fasting plasma glucose levels in the first trimester of pregnancy. The rates of increased body mass index, hypertension, and earlier gestational age at delivery were significantly higher in the gestational diabetes mellitus group among patients with singleton pregnancies but not among patients with multifetal pregnancies. Survival analysis demonstrated that gestational diabetes mellitus was associated with adjusted hazard ratios of type 2 diabetes mellitus of 4.62 (95% confidence interval, 3.69-5.78) in singleton pregnancies and 9.26 (95% confidence interval, 2.67-32.01) in multifetal pregnancies (P<.001 for both). Stratified analysis based on obesity status revealed that, in parturients without obesity, gestational diabetes mellitus in singleton pregnancies increased the risk of type 2 diabetes mellitus by 10.24 (95% confidence interval, 6.79-15.44; P<.001) compared with a nonsignificant risk in multifetal pregnancies (adjusted hazard ratio, 9.15; 95% confidence interval, 0.92-90.22; P=.059). Among parturients with obesity, gestational diabetes mellitus was associated with an increased risk of type 2 diabetes mellitus for both singleton and multifetal pregnancies (adjusted hazard ratio, 3.66; [95% confidence interval, 2.81-4.67; P<.001] and 9.31 [95% confidence interval, 2.12-40.76; P=.003], respectively). CONCLUSION: Compared with gestational diabetes mellitus in singleton pregnancies, gestational diabetes mellitus in multifetal pregnancies doubles the risk of progression to type 2 diabetes mellitus. This effect is primarily observed in patients with obesity. Our findings underscore the importance of providing special attention and postpartum follow-up for patients with multifetal pregnancies and gestational diabetes mellitus, especially those with obesity, to enable early diagnosis and intervention for type 2 diabetes mellitus.

Longitudinal evaluation of cervical length and shear wave elastography in women with spontaneous preterm birth.

OBJECTIVE: To evaluate longitudinal changes in cervical length (CL) and mean cervical shear wave elastography (CSWE) score in women with a singleton or twin pregnancy who undergo spontaneous preterm birth (sPTB) compared with those who deliver at term. METHODS: This was a prospective longitudinal study of unselected women with a singleton or twin pregnancy attending a dedicated research clinic for screening for sPTB at four timepoints during pregnancy: 11 + 0 to 15 + 6 weeks, 16 + 0 to 20 + 6 weeks, 21 + 0 to 24 + 6 weeks and 28 + 0 to 32 + 6 weeks. At each visit, a transvaginal ultrasound scan was conducted to measure the CL and the CSWE scores in six regions of interest (ROI) (inner, middle and external parts of anterior and posterior cervical lips). The mean CSWE score from the six ROIs was calculated for analysis. Log10 transformation was applied to data to produce a Gaussian distribution prior to statistical analysis. A multilevel mixed-effects analysis was performed to compare longitudinally CL and CSWE between the sPTB and term-delivery groups. RESULTS: The final cohort consisted of 1264 women, including 1143 singleton pregnancies, of which 57 (5.0%) were complicated by sPTB, and 121 twin pregnancies, of which 33 (27.3%) were complicated by sPTB. Compared to those who delivered at term, women with sPTB had a lower CL across gestation when controlling for history of cervical surgery, number of fetuses, gestational age (GA) at cervical assessment and the interaction between GA at cervical assessment and sPTB (P < 0.001). Specifically, CL in the sPTB group was significantly lower at 21 + 0 to 24 + 6 weeks (P = 0.039) and 28 + 0 to 32 + 6 weeks (P < 0.001). Twin pregnancies had significantly greater CL throughout pregnancy compared with singleton pregnancies (regression coefficient, 0.01864; P < 0.001). After adjusting for maternal age, weight, height, body mass index and GA at cervical assessment, CSWE score in the sPTB group was significantly lower compared with that in the term-delivery group across gestation (P = 0.013). However, on analysis of individual visits, CSWE score in the sPTB group was significantly lower than that in the term-delivery group only at 11 + 0 to 15 + 6 weeks (P = 0.036). There was no difference in CSWE score between singleton and twin pregnancies throughout gestation (regression coefficient, -0.00128; P = 0.937). CONCLUSIONS: Women with sPTB have a shorter and softer cervix across gestation compared with those who deliver at term. A shorter cervix in the sPTB group is observed from the late second trimester onwards, while lower cervical stiffness in the sPTB group is observed primarily in the first trimester. CL is significantly lower in singleton pregnancies compared with twin pregnancies, while cervical stiffness does not differ between the two. Our findings indicate that the cervix tends to undergo a softening process prior to shortening in sPTB cases. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prevalence and adverse outcomes of twin pregnancy in Eastern Africa: a systematic review and meta-analysis.

INTRODUCTION: Multiple pregnancies are much more common today than they were in the past. Twin pregnancies occur in about 4% of pregnancies in Africa. Adverse pregnancy outcome was more common in twin pregnancy than in singleton pregnancy. There is no pooled evidence on the burden and adverse pregnancy outcome of twin pregnancy in eastern Africa. Thus, this systematic review and meta-analysis were conducted to assess the prevalence and adverse pregnancy outcomes of twin pregnancies. METHODS: This systematic review and meta-analysis covers published and unpublished studies searched from different databases (PubMed, CINAHL (EBSCO), EMBASE, DOAJ, Web of Sciences, MEDLINE, Cochrane Library, SCOPUS, Google Scholar, and Google search). Finally, 34 studies were included in this systematic review and meta-analysis. JBI checklist was used to assess the quality of included papers. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. Data synthesis and statistical analysis were conducted using STATA Version 14 software. Heterogeneity and publication bias were assessed. A forest plot was used to present the pooled prevalence using the random effect model. RESULTS: The prevalence of twin pregnancy in eastern Africa was 3% [95% CI: 2, 3]. The adverse pregnancy outcomes like neonatal intensive care unit admission (78%), low birth weight (44%), low APGAR score (33%), prematurity (32%), stillbirth (30%), neonatal mortality (12%) and maternal complications like hypertensive disorder of pregnancy (25%), postpartum hemorrhage (7%), Cesarean section (37%), premature rupture of membrane (12%) and maternal mortality are more common among twin pregnancy than singleton pregnancy. CONCLUSION: One in every 33 children born a twin in east Africa; admission to neonatal intensive care unit, low birth weight, low APGAR score, prematurity, stillbirth, neonatal mortality and maternal complications are its associated adverse birth outcomes. Since twin pregnancy is a high-risk pregnancy, special care is needed during pregnancy, labor and delivery to reduce adverse pregnancy outcomes.

Emergency cervical cerclage in delayed-interval delivery of twin pregnancies: a scoping review.

BACKGROUND: The protocol for delayed-interval delivery of the second twin in twin pregnancies has not been standardized. Cervical cerclage is often performed, but its use is debated. To conduct a scoping review on cervical cerclage for prolonging the intertwin delivery interval and improving second twin survival and maternal outcomes after preterm delivery or spontaneous abortion of the first twin in twin pregnancies. METHODS: Seven Chinese and English language databases were searched from inception to March 1, 2023, including PubMed, The Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP Chinese Science Journal Database, and Sinomed. Relevant observational studies that assessed the effectiveness of the use of cervical cerclage in delayed-interval delivery of twins were screened and selected, and raw data were extracted, and descriptive statistics and chi-square analysis were performed. RESULTS: A total of 102 articles were retrieved. After screening and exclusion of duplicate and irrelevant articles, 22 articles meeting the inclusion criteria were obtained. Studies in which cerclage was performed reported longer intertwin delivery intervals than those that did not perform cerclage, and the difference was statistically significant. The cerclage group also tended to have lower rates of chorioamnionitis and maternal complications, but the difference between the two groups was not statistically significant. CONCLUSION: After excluding patients with contraindications, emergency cervical cerclage can be considered in cases of spontaneous abortion of the first twin in twin pregnancies to prolong the gestation and improve the prognosis of the remaining fetus until it becomes viable and increases its birth weight.

Prognosis of remaining fetus in twin pregnancy after demise of one fetus according to its location.

BACKGROUND: To investigate the prognosis of the remaining fetus in twin pregnancy after experiencing one fetal demise in the first trimester according to the location of the demised fetus. METHODS: This was a retrospective study of twin pregnancies with one fetal demise after the first trimester (14 weeks of gestation) delivered between September 2004 and September 2022. The study population was divided into two groups based on the location of the demised fetus as determined by the last recorded ultrasonography results: Group 1 included twin pregnancies where the presenting fetus was demised (n = 36) and Group 2 included twin pregnancies where the non-presenting fetus was demised (n = 44). The obstetric and neonatal outcomes were also reviewed. RESULTS: A total of 80 pregnant women were included. The median gestational age for the diagnosis of fetal demise was 24.1 weeks. The gestational age of the demised fetus was not different between Groups 1 and 2; however, the gestational age of the remaining fetus at delivery was significantly earlier in Group 1 than it was in Group 2 (33.8 vs. 37.3 weeks, P = .004). The rate of preterm birth before 28 weeks was almost five times higher in Group 1 than in Group 2 (22.2% vs. 4.5%, P = .037). Regression analysis demonstrated significant differences between Groups 1 and 2. Respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus, retinopathy of prematurity, and jaundice were more common in Group 1 than in Group 2; however, the association was not significant after adjusting for gestational age at delivery. CONCLUSIONS: When the presenting fetus is demised in a twin pregnancy, the remaining fetus tends to be delivered earlier than when the non-presenting fetus is demised.

Serum lipid reference values recommended during a twin pregnancy and evaluating its association with perinatal outcomes.

BACKGROUND: Maternal lipid metabolism fluctuations have been shown to increase the risk of adverse pregnancy outcomes. However, there is no consensus over what constitutes normal maternal lipid values during twin pregnancy. Therefore, the aim of this study was to establish a serum lipid reference range for a twin pregnancy. METHODS: A retrospective survey was conducted, from 2011 to 2021, at the Peking University Third Hospital. A total of 881 twin pregnancies, with lipid data from early and middle pregnancies, were included. After excluding those with adverse pregnancy outcomes, we performed a descriptive analysis of total cholesterol (TC), triglycerides (TG), high-density lipid cholesterol (HDL-C), and low-density lipid cholesterol (LDL-C) levels, using the mean and standard deviation to determine appropriate percentiles. We later determined the lipid reference range in early and middle pregnancy based on the initial results. We evaluated Inappropriate lipid levels associations with pregnancy outcomes, including gestational diabetes, pregnancy-induced hypertension, small for gestational age. RESULTS: (1) Serum levels of TC, TG, LDL-C, and HDL-C increased significantly from early to late pregnancy, where the greatest increase was observed in TG. (2) Based on the results, we recommend that TC, TG, and LDL-C serum reference values during early and middle pregnancy should be less than the 95th percentile. On the other hand, HDL-C should be greater than the 5th percentile. During early pregnancy, the values recommended are TC < 5.31 mmol/L, TG < 2.25 mmol/L, HDL > 1.02 mmol/L and LDL < 3.27 mmol/L, and those during middle pregnancy are TC < 8.74 mmol/L, TG < 4.89 mmol/L, HDL > 1.25 mmol/L and LDL < 5.49 mmol/L, while the values during late pregnancy are TC < 9.11 mmol/L, TG < 6.70 mmol/L, HDL > 1.10 mmol/L and LDL < 5.81 mmol/L. Higher levels of blood lipids were associated with GDM, PE, SGA. CONCLUSIONS: We suggested a reference ranges for blood lipids during the twin pregnancy in a Chinese population. The reference ranges recommended by this study can be used to identify women with twin pregnancies using unfavorable lipid values. Higher levels of blood lipids were associated with adverse pregnancy outcomes.

Predictive value of maternal serum placental growth factor levels for discordant fetal growth in twins: a retrospective cohort study.

BACKGROUND: Accurate prenatal recognition of discordant fetal growth in twins is critical for deciding suitable management strategies. We explored the predictive value of the level of maternal second-trimester placental growth factor (PLGF) as a novel indicator of discordant fetal growth. METHODS: A total of 860 women pregnant with twins were enrolled, including 168 women with monochorionic twins (31 cases of discordant fetal growth and 137 without) and 692 with dichorionic twins (79 cases of discordant fetal growth and 613 without). Maternal second-trimester PLGF concentrations were measured via immunofluorescence. RESULTS: Maternal second-trimester PLGF levels were significantly lower in women pregnant with twins who subsequently developed discordant fetal growth than in those who did not (monochorionic twin pregnancy: P < 0.001; dichorionic twin pregnancy: P < 0.001). A 3-4 fold difference in median PLGF concentrations was detected between the two groups with both monochorionic and dichorionic twin pregnancies. Maternal second-trimester PLGF levels were significantly correlated with birth weight differences (monochorionic twin pregnancy: r = - 0.331, P < 0.001; dichorionic twin pregnancy: r = - 0.234, P < 0.001). A receiver operating characteristic curve was used to evaluate the predictive efficiency. In monochorionic twin pregnancies, the area under the curve (AUC) was 0.751 (95% confidence interval [CI]: 0.649-0.852), and the cutoff value was 187.5 pg/mL with a sensitivity of 77.4% and specificity of 71.0%. In dichorionic twin pregnancies, the AUC was 0.716 (95% CI; 0.655-0.777), and the cutoff value was 252.5 pg/mL with a sensitivity of 65.1% and specificity of 69.6%. Based on the above cutoff values, univariate and multivariate logistic regression analyses were performed to calculate the odds ratios (OR) for the PLGF levels. After adjustment for potential confounding factors, low PLGF concentrations still significantly increased the risk of discordant fetal growth (monochorionic twin pregnancy: adjusted OR: 7.039, 95% CI: 2.798-17.710, P < 0.001; dichorionic twin pregnancy: adjusted OR: 4.279, 95% CI: 2.572-7.120, P < 0.001). CONCLUSIONS: A low maternal second-trimester PLGF level is considered a remarkable risk factor and potential predictor of discordant fetal growth. This finding provides a complementary screening strategy for the prediction of discordant fetal growth and offers a unique perspective for the subsequent research in this field.

Selective feticide in dichorionic diamniotic (DCDA) twins complicated with previable premature rupture of membrane before 24 weeks may be a safe therapeutic alternative to ongoing pregnancy.

BACKGROUND: To date, there are no clinical guidelines for dichorionic diamniotic (DCDA) twins complicated with previable premature rupture of membrane (PV-ROM) before 24 weeks of gestation. The typical management options including expectant management and/or pregnant termination, induce the risks of fetal mortality and morbidity. OBJECTIVE: To explore the feasibility selective feticide in DCDA twins complicated with PV-ROM. STUDY DESIGN: A Retrospective cohort study, enrolling 28 DCDA twins suffering from PV-ROM in a tertiary medical center from Jan 01 2012 to Jan 01 2022. The obstetric outcome was compared between selective feticide group and expectant management group. RESULTS: There were 12 cases managed expectantly and 16 underwent selective feticide. More cases suffered from oligohydramnios in expectant management group compared to selective feticide group (P = 0.008). Among 13 cases with ROM of upper sac, the mean gestational age at delivery was (33.9 ± 4.9) weeks in the selective feticide group, which was significantly higher than that in the expectant management (P = 0.038). Five fetuses (83.3%) with selective feticide delivered after 32 weeks, whereas only one (14.3%) case in expectant management group (P = 0.029). However, in the subgroup with ROM of lower sac, no significant difference of the mean gestation age at delivery between groups and none of cases delivered after 32 weeks. CONCLUSION: There was a trend towards an increase in latency interval in DCDA twins with PV-ROM following selective feticide, compared to that with expectant management. Furthermore, selective feticide in cases with PV-ROM of upper sac has a favorable outcome.

Effectiveness and pregnancy outcomes of ultrasound-indicated and physical examination-indicated cervical cerclage: a retrospective study from a single centre.

OBJECTIVE: Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality worldwide, and cervical incompetence (CIC) is a significant contribution. Cervical cerclage (CC) is an effective obstetric intervention. However, many clinical factors affect the success rate of surgery. The objective was to investigate and compare the pregnancy and neonatal outcomes of patients who underwent ultrasound- and physical examination-indicated cervical cerclage and to explore the influencing factors of preterm delivery before 34 weeks. METHODS: The sociodemographic characteristics and clinical data of patients with a diagnosis of cervical incompetence who underwent ultrasound- and physical examination-indicated transvaginal cervical cerclage at Nanjing Maternal and Child Health Hospital from January 2020 to December 2022 were retrospectively analyzed. The pregnancy and neonatal outcomes of the patients were evaluated. Continuous variables were compared using Student's t test (for normally distributed data) or the Mann-Whitney U test (for nonnormally distributed data). Categorical variables were analysed using the chi-square test or Fisher's exact test. Additionally, logistic regression analyses and receiver operating characteristic curves were used to evaluate the associations of inflammatory markers with maternal and neonatal outcomes. RESULTS: This study included 141 participants who underwent cervical cerclage, including 71 with ultrasound-indicated cerclage and 70 with physical examination-indicated cerclage. Compared to those in the ultrasound-indicated cerclage group, the duration from cerclage to delivery, birth weight, and APGAR score in the physical examination-indicated cerclage group were significantly lower, and the rates of delivery at < 28 weeks, < 32 weeks, < 34 weeks, and < 37 weeks of gestation and neonatal mortality were significantly higher (all P < 0.05). Compared to those in the physical ultrasound-indicated cerclage group, in the physical examination-indicated cerclage group, maternal blood inflammatory markers, such as C-reactive protein (CRP), the systemic immune-inflammation index (SII) and the systemic inflammation response index (SIRI) were significantly higher (P < 0.05). Additionally, maternal blood inflammatory markers, such as the CRP, white blood cell count, platelet to lymphocyte ratio (PLR), SII, and SIRI were significantly higher in the group with delivery before 34 weeks of gestation. Furthermore, the results demonstrated that twin pregnancy had the highest OR for preterm delivery before 34 weeks of gestation (OR = 3.829; 95% CI 1.413-10.373; P = 0.008), as well as the following: the SII level (OR = 1.001; 95% CI 1.000-1.002; P = 0.003) and CRP level (OR = 1.083; 95% CI 1.038-1.131; P = 0.022). The risk factors for preterm delivery before 34 weeks of gestation were twin gestation, an increased SII level and an increased CRP level, which had good combined predictive value. CONCLUSION: In patients with cervical insufficiency, ultrasound-indicated cervical cerclage appears to lead to better pregnancy outcomes than physical examination-indicated cerclage. Twin pregnancy and maternal blood inflammatory markers, such as the CRP level and the SII, are associated with preterm delivery before 34 weeks of gestation.

Cushing's disease with twin pregnancy and diabetes mellitus: a case report and literature review.

A 38-year-old Japanese woman with a history of abnormal thyroid function of non-autoimmune origin, pituitary endocrine tumor, and untreated diabetes mellitus was referred to our outpatient clinic when she became pregnant with twins. Physical findings consistent with Cushing's syndrome (CS) were absent at the time of presentation. Although baseline plasma adrenocorticotropic hormone, serum cortisol, and 24-hour urinary free cortisol excretion levels were above the upper limits of normal non-pregnant reference ranges, we could not exclude a physiological increase associated with pregnancy. No medical or surgical intervention for hypercortisolism was performed during pregnancy. Spontaneous vaginal delivery resulted in the normal delivery of live twins. A diagnosis of Cushing's disease (CD) was established when papery skin developed postpartum. Transsphenoidal surgery was performed and the hypercortisolism partially resolved post-operatively. The patient's abnormal thyroid function also resolved. Pregnancy in women with endogenous CS is rare, with less than 300 cases reported. Most reported cases of CS during pregnancy are of adrenal origin. Only two cases of twin pregnancies with CD have been reported. Therefore, we reported the third case of CD in a twin pregnancy and reviewed the diagnostic and therapeutic challenges associated with CD during pregnancy.

Neonatal respiratory complications in twins at 36-38 weeks of gestation.

BACKGROUND: Twin pregnancies are associated with a high risk of perinatal mortality and morbidity. Late preterm or early term delivery is frequently performed to avoid unexpected fetal death in uncomplicated twin pregnancies. Nonetheless, delivery before full term is associated with neonatal respiratory complications. This study aimed to evaluate perinatal respiratory complications in twins delivered between 36 and 38 weeks of gestation. METHODS: A retrospective cohort study was conducted on twins delivered between 36 and 38 weeks of gestation from January 2008 to June 2020. The primary outcomes were the incidence of composite neonatal respiratory morbidity, which included respiratory distress syndrome, transient tachypnea of the newborn, meconium aspiration syndrome, mechanical ventilation or continuous positive airway pressure according to gestational age at delivery, and chorionicity. The relationship between gestational age at delivery and composite neonatal respiratory morbidity was evaluated using multivariate logistic regression analysis adjusted for potential confounders. RESULTS: This study included 1608 twins (614 monochorionic diamniotic twins, 994 dichorionic diamniotic twins). At 36, 37, and 38 weeks of gestation, the frequencies of composite neonatal respiratory morbidity were 19.4%, 10.7%, and 9.2% in dichorionic diamniotic twins and 13.6%, 8.7%, and 9.4% in monochorionic diamniotic twins, respectively. In dichorionic diamniotic twins, the composite neonatal respiratory morbidity rate was higher for twins delivered at 36 weeks of gestation than for those delivered at 37 weeks. No significant differences between monochorionic diamniotic twins were detected. CONCLUSIONS: In uncomplicated dichorionic diamniotic twin pregnancies, delivery should be considered after 37 weeks of gestation to reduce neonatal respiratory complications.

The prognostic role of CRL discordance in first trimester ultrasound.

OBJECTIVES: In the first trimester, intertwin crown-rump length (CRL) discordance has emerged as a notable factor linked to adverse perinatal health effects. It is frequently employed as a basis for counseling parents regarding potential adverse pregnancy outcomes. Despite its established association with adverse outcomes, the significance of CRL discordance in substantially predicting pregnancy problems and its efficacy in pregnancy screening remain subjects of ongoing discussion. The aim of this manuscript is to present current knowledge on CRL discordance. METHODS: PubMed was searched for related articles with terms "Crown-Rump length", "Prenatal Screening", "Twin pregnancy", "Discordance". RESULTS: Twenty-two studies were included in our study with six reporting data on monochorionic and 16 assessing the correlation between CRL discordance and adverse pregnancy outcomes. Fetal loss at the 20th and 24th week of the pregnancy, SGA neonates, pre-term delivery (32 weeks), perinatal death (24 weeks) are all reported adverse outcomes associated with CRL discordance. The reported cut-off for increased risk of adverse perinatal outcomes is a discordance of at least 10% or more. CONCLUSIONS: Increased CRL (>10 %) discordance is linked to a higher risk of sFGR in both monochorionic and dichorionic pregnancies, fetal loss, and preterm delivery.

Cervical length as a screening tool for preterm birth in twin pregnancies: a systematic review and critical evaluation of quality clinical practice guidelines.

OBJECTIVES: Twin pregnancies are at increased risk of preterm birth (PTB) compared to singletons. Evaluation of cervical length (CL) represents the optimal tool to screen PTB in singleton. Conversely, there is less evidence on the use of CL in twins. Our aim was to evaluate the methodological quality and clinical heterogeneity of clinical practice guidelines (CPGs) on the CL application in twins using AGREE II methodology. METHODS: MEDLINE, Scopus, and websites of the main scientific societies were examined. The following aspects were evaluated: diagnostic accuracy of CL, optimal gestational age at assessment and interventions in twin pregnancies with reduced CL. The quality of the published CPGs was carried out using "The Appraisal of Guidelines for REsearch and Evaluation (AGREE II)" tool. The quality of guideline was rated using a scoring system. Each considered item was evaluated by the reviewers on a seven-point scale that ranges from 1 (strongly disagree) to 7 (strongly agree). A cut-off >60 % identifies a CPGs as recommended. RESULTS: The AGREE II standardized domain scores for the first overall assessment had a mean of 74 %. The score was more than 60 % in the 66.6 % of CPGs analyzed indicating an agreement between the reviewers on recommending the use of these CPGs. A significant heterogeneity was found; there was no specific recommendation on CL assessment in about half of the published CPGs. There was also significant heterogeneity on the CL cut-off to prompt intervention. CONCLUSIONS: Despite the fact that the AGREE II analysis showed that the majority of the included guidelines are of good quality, there was a significant heterogeneity among CPGs as regard as the indication, timing, and cut-off of CL in twins as well as in the indication of interventions.

Association between first-trimester uterine artery Doppler and crown-rump length with growth discordance: does it make a difference.

OBJECTIVES: The purpose of this study was to investigate the association between first-trimester uterine artery pulsatility index (UtA-PI) and crown-rump length discordance (CRLD) with growth discordance (GD) in twins and analyze the influence of chorionicity in these parameters. METHODS: This retrospective analysis integrated data from the twin pregnancy database of Centro Hospitalar São João (2019-2023), including 184 fetuses, with 19 monochorionic and 73 dichorionic gestations. To determine the association between UtA-PI and CRLD with GD, correlation analyses were computed and linear regression models were carried out. Separate analyses were conducted for each type of placentation. Logistic regression analysis was carried out to determine the association of mean UtA-PI and CRLD with severe GD, defined as discordance ≥25 %. RESULTS: GD≥25 % was detected in 9.80 % of pregnancies. A statistically significant difference between monochorionic and dichorionic gestations was found in crown-rump length (p=0.009), CRLD (p<0.001) and birth weight (p=0.025), but not in mean UtA-PI (p=0.853) or GD (p=0.556). Mean UtA-PI was significantly higher in discordant than in concordant pairs (p<0.001), but that association was not seen in CRLD (p=0.931). Mean UtA-PI and GD were correlated by the regression line "GD=3.844 × UtA-PI + 6.638", with R2 0.027. CRLD and GD were correlated by the regression line "GD=0.280 × CRLD + 10.79", with R2 0.010. Mean UtA-PI, but not CRLD, was significantly associated with severe GD (odds ratio, 22.753; p=0.002). CONCLUSIONS: Mean UtA-PI, but not CRLD, is associated with GD. The prevalence of severe GD increases significantly with increasing mean UtA-PI.

Prevention of preterm birth in twin-to-twin transfusion syndrome: a systematic review and network meta-analysis.

OBJECTIVES: We aimed to perform a systematic review and network meta-analysis to evaluate the preventive strategies for preterm birth in twin-to-twin transfusion syndrome. METHODS: PubMed, Embase and Cochrane Central were searched from inception to December 2023 with no filters. Additionally, the reference lists of the included studies were manually examined to identify any supplementary studies. We selected randomized controlled trials and cohorts comparing interventions to prevent preterm birth in twin pregnancies complicated by twin-to-twin transfusion syndrome. A random-effects frequentist network meta-analysis was performed using RStudio version 4.3.1. Randomized controlled trials and cohorts were assessed respectively using the Risk of Bias in Non-randomized Studies of interventions tool and Cochrane Collaboration's tool for assessing risk of bias in randomized trials. RESULTS: In this systematic review and meta-analysis, we included eight studies comprising a total of 719 patients. Compared with expectant management, cerclage stood out as the only intervention associated with an increase in the survival of at least one twin (risk ratio 1.12; 95 % confidence interval 1.01-1.23). Our subgroup analysis based on different thresholds for short cervix demonstrated a significant reduction in the risk of preterm birth before 32 weeks with ultrasound-indicated cerclage using a 15 mm criterion (risk ratio 0.65; 95 % confidence interval 0.47-0.92). CONCLUSIONS: Our study suggests the potential benefit of cerclage as a preventive strategy for preterm birth in pregnancies complicated by twin-to-twin transfusion syndrome. These findings highlight the necessity for further investigation to corroborate our results and address the optimal threshold for ultrasound-indicated cerclage.

Association between aneuploidy screening analytes and adverse outcomes in twin gestations.

OBJECTIVES: To evaluate associations between serum analytes used for genetic screening and obstetric complications among twin pregnancies. METHODS: This cohort included twins delivered at a tertiary care hospital from 2009 to 2017. Abnormal levels of pregnancy associated plasma protein (PAPP-A), first and second trimester human chorionic gonadotropin (hCG), alpha fetoprotein (AFP), estriol, and inhibin, reported as multiples of the median (MoM), were defined as <5 %ile or >95 %ile for our cohort. Associations between abnormal analytes and preterm delivery, small for gestational age, and pregnancy-associated hypertension were calculated using Fisher's exact test. RESULTS: A total of 357 dichorionic/diamniotic and 123 monochorionic/diamniotic twins were included. Among dichorionic/diamniotic twins, elevated AFP (>3.70 MoM) was associated with increased preterm delivery <34 weeks (44.4 vs. 16.5 %, p=0.007), while elevated inhibin (>4.95 MoM) was associated with increased preterm delivery<37 weeks (94.1 vs. 58.8 %, p=0.004). For monochorionic/diamniotic twins, elevated inhibin (>6.34 MoM) was associated increased preterm delivery <34 weeks (66.7 vs. 24.8 %, p=0.04) and hypertension (66.7 vs. 21.4 %, p=0.03). CONCLUSIONS: Selected abnormal analyte levels were associated with increased rates of adverse outcomes in twin pregnancies, which differed by chorionicity. Our findings assist providers in interpreting abnormal analyte levels in twin pregnancies and may help to identify those at increased risk for adverse outcomes.

Hepatic arterial buffer response in monochorionic twins with selective fetal growth restriction.

OBJECTIVES: Monochorionic twins (MC) have higher risk of perinatal morbi-mortality compared to singletons and dichorionic twins (DC). Selective fetal growth restriction (sFGR) increases the chances of adverse outcome. Hepatic arterial buffer response (HABR) is an important mechanism for maintaining liver perfusion. We hypothesised that HABR is active in monochorionic diamniotic twins (MCDA) with sFGR where restricted fetus may have liver hypoperfusion. The objective of this study is to test whether the HAV-ratio is diminished in pregnancies affected by selective fetal growth restriction pointing to activation of HABR in the growth-restricted fetus. METHODS: sFGR was defined according to a consensus definition. Hepatic artery (HA) peak systolic velocity (PSV) was measured and its correlation with fetal Dopplers and pregnancy characteristics were determined. A ratio using HA-PSV (HAV-ratio) was calculated and its association with sFGR was established. Further analysis of HA-PSV was performed comparing z-scores between normal and growth restricted fetuses. RESULTS: We included 202 MCDA pregnancies, 160 (79 %) normal and 42 (21 %) with sFGR. HAV-ratio was significant different between groups. The mean HAV-ratio was 1.01 (±0.20) for normal twins and 0.77 (±0.25) for sFGR. Furthermore, HA-PSV z-scores was significant increased in in growth-restricted fetus (0.94±1.45), while in normal fetuses was -0.16 (±0.97). CONCLUSIONS: Our findings demonstrate that, in pregnancies with sFGR, HAV-ratio is significantly lower than in normal MCDA pregnancies. The lower HAV-ratio is due to an increase in HA PSV in the growth restricted fetus. This observation indicates an activation of HABR in the small fetus.