Real-time ultrasound demonstration of uterine isthmus contractions during pregnancy.

BACKGROUND: Asymptomatic isthmic contractions are a frequent physiological phenomenon in pregnancy, sometimes triggered by bladder voiding. They can interfere with proper cervical length assessment and may lead to false images of placenta previa. However, there is limited research on the prevalence and characteristics of these contractions. OBJECTIVE: This study aimed to determine the prevalence and characteristics of isthmic contractions after bladder voiding in the second trimester of pregnancy, to evaluate their effect on cervical length assessment, and to propose a new method for the objective assessment of the presence and intensity of isthmic contractions. STUDY DESIGN: In this prospective observational study, long videos of the uterine cervix were recorded in 30 singleton pregnancies during the second trimester of pregnancy after bladder voiding. Isthmic length and cervicoisthmic length changes were assessed over time. The isthmic length was measured using a new approach, which involved calculating the distance from the base of the cervix to the internal os, including the isthmus. RESULTS: Isthmic contractions were observed in 43% of pregnant women (95% confidence interval, 26%-62%) after bladder voiding. The median time for complete isthmus relaxation was 19.7 minutes (95% confidence interval, 15.0 to not available). No substantial differences in maternal characteristics were found between individuals with and without contractions. The proposed method for measuring isthmic length provided an objective assessment of the presence and intensity of isthmic contractions. A cutoff of 18 mm in isthmic length allowed for the distinction of pregnant women presenting a contraction. In addition, the study identified a characteristic undulatory pattern in the relaxation of the isthmus in half of the cases with contractions. CONCLUSION: Isthmic contractions are a common occurrence after bladder voiding in the second trimester of pregnancy and may interfere with proper cervical length assessment. We recommend performing cervical assessment at least 20 minutes after bladder voiding to reduce the risk of bias in cervical length measurement and to avoid false images of placenta previa. The new method for measuring isthmic length provides an objective way to assess the presence and intensity of isthmic contractions. Further research is needed to understand the role of isthmic contractions in the physiology of pregnancy and birth.

Progestogen only contraception in women with congenital heart disease.

BACKGROUND: There is little information of progestogen-only contraceptives in patients with congenital heart disease (CHD) on the long-term. OBJECTIVE: To evaluate the use of contraception in patients with CHD. We studied both short-acting reversible contraceptives (SARCs), oral progestin-only pills (POPs) and long-acting reversible contraceptives (LARCs): intrauterine devices (IUD-IPs) and subdermal implants both impregnated with progestogens (SI-IPs). STUDY DESIGN: Retrospective study of all women attending the preconception clinic. Contraceptive methods were classified in three TIERs of effectiveness before and after consultation. ESC classification regarding pregnancy risk, WHOMEC classification for combined oral contraceptive safety was collected. RESULTS: Six hundred and fifty-three patients. A significant proportion of them switched from TIER 3 to TIER 2 or 1 (p < .001) after consultation. One hundred and ninety-nine patients used POPs, 53 underwent IUD-IPs implantation and 36 SI-IPs, mean duration was 58 ± 8, 59 ± 8 and 53 ± 38 months, respectively. CONCLUSIONS: Because of their safety and efficacy, IUD-IPs and SI-IPs should be considered as first-line contraception in patients with CHD.

We looked at the use of progestogen-only contraceptives in women with congenital heart disease (CHD) over a long period and determine how safe and effective these contraceptives are for such patients. We considered two types of contraceptives: short-acting ones like progestin-only pills (POPs) and long-acting ones like intrauterine devices and subdermal implants that release progestogens.We gathered information from 653 women and assessed how women's contraceptive choices changed before and after they had a consultation with us.After consulting with our clinic, a significant number of women switched from less effective contraceptives to more effective ones. Among the women who used POPs, most of them followed the prescribed regimen quite well. Additionally, 89 women used long-acting contraceptives, without failure of method.In conclusion, our findings suggest that long-acting progestogen-only contraceptives are safe and effective choices for contraception in women with CHD. Therefore, these options should be considered as the first choice.

Reference values for interleukin-6 in the amniotic fluid of asymptomatic pregnant women.

INTRODUCTION: Nowadays, proinflammatory factors are considered to play an important role in the pathophysiology of threatened preterm labor or chorioamnionitis. The aim of this study was to establish the normal reference range for interleukin-6 (IL-6) levels in the amniotic fluid and to identify factors which may alter this value. MATERIAL AND METHODS: Prospective study in a tertiary-level center including asymptomatic pregnant women undergoing amniocentesis for genetic studies from October 2016 to September 2019. IL-6 measurements in amniotic fluid were performed using a fluorescence immunoassay with microfluidic technology (ELLA Proteinsimple, Bio Techne). Maternal history and pregnancy data were also recorded. RESULTS: This study included 140 pregnant women. Of those, women who underwent termination of pregnancy were excluded. Therefore, a total of 98 pregnancies were included in the final statistical analysis. The mean gestational age was 21.86 weeks (range: 15-38.7) at the time of amniocentesis, and 38.6 weeks (range: 30.9-41.4) at delivery. No cases of chorioamnionitis were reported. The log10 IL-6 values follow a normal distribution (W = 0.990, p = 0.692). The median, and the 5th, 10th, 90th, and 95th percentiles for IL-6 levels were 573, 105, 130, 1645, and 2260 pg/mL, respectively. The log10 IL-6 values were not affected by gestational age (p = 0.395), maternal age (p = 0.376), body mass index (p = 0.551), ethnicity (p = 0.467), smoking status (p = 0.933), parity (p = 0.557), method of conception (p = 0.322), or diabetes mellitus (p = 0.381). CONCLUSIONS: The log10 IL-6 values follow a normal distribution. IL-6 values are independent of gestational age, maternal age, body mass index, ethnicity, smoking status, parity and method of conception. Our study provides a normal reference range for IL-6 levels in the amniotic fluid that can be used in future studies. We also observed that normal IL-6 values were higher in the amniotic fluid than in serum.

Addition of intermittently scanned continuous glucose monitoring to standard care in a cohort of pregnant women with type 1 diabetes: effect on glycaemic control and pregnancy outcomes.

AIMS/HYPOTHESIS: The aim of this study was to assess whether the addition of intermittently scanned continuous glucose monitoring (isCGM) to standard care (self-monitoring of blood glucose [SMBG] alone) improves glycaemic control and pregnancy outcomes in women with type 1 diabetes and multiple daily injections. METHODS: This was a multicentre observational cohort study of 300 pregnant women with type 1 diabetes in Spain, including 168 women using SMBG (standard care) and 132 women using isCGM in addition to standard care. In addition to HbA1c, the time in range (TIR), time below range (TBR) and time above range (TAR) with regard to the pregnancy glucose target range (3.5-7.8 mmol/l) were also evaluated in women using isCGM. Logistic regression models were performed for adverse pregnancy outcomes adjusted for baseline maternal characteristics and centre. RESULTS: The isCGM group had a lower median HbA1c in the second trimester than the SMBG group (41.0 [IQR 35.5-46.4] vs 43.2 [IQR 37.7-47.5] mmol/mol, 5.9% [IQR 5.4-6.4%] vs 6.1% [IQR 5.6-6.5%]; p=0.034), with no differences between the groups in the other trimesters (SMBG vs isCGM: first trimester 47.5 [IQR 42.1-54.1] vs 45.9 [IQR 39.9-51.9] mmol/mol, 6.5% [IQR 6.0-7.1%] vs 6.4% [IQR 5.8-6.9%]; third trimester 43.2 [IQR 39.9-47.5] vs 43.2 [IQR 39.9-47.5] mmol/mol, 6.1% [IQR 5.8-6.5%] vs 6.1% [IQR 5.7-6.5%]). The whole cohort showed a slight increase in HbA1c from the second to the third trimester, with a significantly higher rise in the isCGM group than in the SMBG group (median difference 2.2 vs 1.1 mmol/mol [0.2% vs 0.1%]; p=0.033). Regarding neonatal outcomes, newborns of women using isCGM were more likely to have neonatal hypoglycaemia than newborns of non-sensor users (27.4% vs 19.1%; ORadjusted 2.20 [95% CI 1.14, 4.30]), whereas there were no differences between the groups in large-for-gestational-age (LGA) infants (40.6% vs 45.1%; ORadjusted 0.73 [95% CI 0.42, 1.25]), Caesarean section (57.6% vs 48.8%; ORadjusted 1.33 [95% CI 0.78, 2.27]) or prematurity (27.3% vs 24.8%; ORadjusted 1.05 [95% CI 0.55, 1.99]) in the adjusted models. A sensitivity analysis in pregnancies without LGA infants or prematurity also showed that the use of isCGM was associated with a higher risk of neonatal hypoglycaemia (non-LGA: ORadjusted 2.63 [95% CI 1.01, 6.91]; non-prematurity: ORadjusted 2.52 [95% CI 1.12, 5.67]). For isCGM users, the risk of delivering an LGA infant was associated with TIR, TAR and TBR in the second trimester in the logistic regression analysis. CONCLUSIONS/INTERPRETATION: isCGM use provided an initial improvement in glycaemic control that was not sustained. Furthermore, offspring of isCGM users were more likely to have neonatal hypoglycaemia, with similar rates of macrosomia and prematurity to those of women receiving standard care.

Cervical pessary and cerclage placement for preterm birth prevention and cervicovaginal microbiome changes.

INTRODUCTION: Our objective was to compare the vaginal microbiome in low-risk and high-risk pregnant women and to explore a potential association between vaginal microbiome and preterm birth. MATERIAL AND METHODS: A pilot, consecutive, longitudinal, multicenter study was conducted in pregnant women at 18-22 weeks of gestation. Participants were assigned to one of three groups: control (normal cervix), pessary (cervical length ≤25 mm) and cerclage (cervical length ≤25 mm or history of preterm birth). Analysis and comparison of vaginal microbiota as a primary outcome was performed at inclusion and at 30 weeks of gestation, along with a follow-up of pregnancy and perinatal outcomes. We assessed the vaginal microbiome of pregnant women presenting a short cervix with that of pregnant women having a normal cervix, and compared the vaginal microbiome of women with a short cervix before and after placement of a cervical pessary or a cervical cerclage. RESULTS: The microbiome of our control cohort was dominated by Lactobacillus crispatus and inners. Five community state types were identified and microbiome diversity did not change significantly over 10 weeks in controls. On the other hand, a short cervix was associated with a lower microbial load and higher microbial richness, and was not correlated with Lactobacillus relative abundance. After intervention, the cerclage group (n = 19) had a significant increase in microbial richness and a shift towards community state types driven by various bacterial species, including Lactobacillus mulieris, unidentified Bifidobacterium or Enterococcus. These changes were not significantly observed in the pessary (n = 26) and control (n = 35) groups. The cerclage group had more threatened preterm labor episodes and poorer outcomes than the control and pessary groups. CONCLUSIONS: These findings indicate that a short cervix is associated with an altered vaginal microbiome community structure. The use of a cerclage for preterm birth prevention, as compared with a pessary, was associated with a microbial community harboring a relatively low abundance of Lactobacillus, with more threatened preterm labor episodes, and with poorer clinical outcomes.

The Overlooked Impact of Lower Uterine Segment Contractions on Second Trimester Cervical Assessment.

INTRODUCTION: Asymptomatic contractions in the lower uterine segment (LUS) may affect uterocervical angle and cervical length (CL); however, this has never been investigated. Therefore, the aim of this study was to evaluate the effect of LUS contractions on uterocervical angle, CL, and LUS thickness. MATERIALS AND METHODS: This was a prospective, observational, single-cohort study conducted on 102 asymptomatic singleton pregnancies between 19.0 and 22.6 weeks of gestation. Uterocervical angle and CL were measured by transvaginal ultrasound at two different time points with an interval of at least 20 min. LUS thickness was also measured as an indirect marker of myometrial contraction. A linear and curvilinear regression were performed to explore a potential association between LUS contractions, measured as increments in LUS thickness, and changes in CL and uterocervical angle. RESULTS: The linear regression between changes in LUS thickness and changes in CL showed that LUS contractions impact CL; for every 1-mm increase in LUS thickness, CL increased by 0.909 mm, when the isthmus was included in the CL measurement (R2 = 0.358; ß = 0.909; p < 0.001). By contrast, when the isthmus was not included in the measurement, a curvilinear relation between changes in LUS thickness and changes in CL was found (R2 = 0.077; ß1 = 0.575, ß2 = 0.038; p = 0.018). The relation between changes in uterocervical angle and changes in LUS thickness was not significant. DISCUSSION/CONCLUSION: LUS contractions can be observed in many asymptomatic women during the second trimester of pregnancy. LUS contractions lead to an increase in CL and LUS thickness, thus impacting ultrasound cervical assessments. These contractions do not affect the uterocervical angle.

Prospective evaluation of the uterocervical angle as a predictor of spontaneous preterm birth.

INTRODUCTION: The uterocervical angle has been proposed as an ultrasound marker to predict spontaneous preterm birth; however, the studies that provided this evidence were retrospective and their results heterogeneous. This study aimed to assess the ability of the uterocervical angle to predict spontaneous preterm birth before 34 and 37 weeks of gestation. MATERIAL AND METHODS: A prospective cohort study with singleton pregnancies between 19.0 and 22.6 weeks of gestation. Uterocervical angle and cervical length were measured by transvaginal ultrasound. Maternal history and pregnancy data were recorded. Delivery data were subsequently collected. RESULTS: The final analysis included 1453 singleton pregnancies. Spontaneous preterm birth before 37 weeks occurred in 52 cases (3.6%) and before 34 weeks in 17 (1.2%). For the prediction of spontaneous preterm birth before 34 weeks, the area under the curve for the uterocervical angle was 0.67 (95% CI 0.54-0.79) and the detection rates were 5.9% and 23.5% for fixed false-positive rates of 5% and 10%, respectively. For the prediction of spontaneous preterm birth before 37 weeks, the area under the curve was 0.58 (95% CI 0.50-0.67) and the detection rates were 5.8% and 18% for fixed false-positive rates of 5% and 10%, respectively. Combined predictive models were studied. To predict spontaneous preterm birth before 34 weeks, the best model was provided by a combination of uterocervical angle and cervical length (area under the curve 0.72; 95% CI 0.58-0.86). The detection rates of this model were 35.3% and 41.2% for fixed false-positive rates of 5% and 10%, respectively. To predict spontaneous preterm birth before 37 weeks of gestation, the best model was provided by a combination of uterocervical angle, cervical length, and previous history of spontaneous preterm birth (area under the curve 0.64; 95% CI 0.55-0.72). The detection rates of this model were 15.4% and 30.8% for fixed false-positive rates of 5% and 10%, respectively. Obese women and those with a history of cesarean section had a wider uterocervical angle. CONCLUSIONS: The uterocervical angle, measured mid-trimester, is a poor predictor of spontaneous preterm birth.

[Validation of the Ocular Surface Disease Index Questionnaire for Chilean patients]. / Adaptación cultural y validación del cuestionario Ocular Surface Disease Index en una población chilena.

BACKGROUND: Ocular Surface Disease Index (OSDI) is the most commonly used questionnaire worldwide to detect dry eye disease. Although it is massively used in clinical practice in Chile, its use has not been validated yet in the country. AIM: To develop a cultural adaptation and to validate the OSDI questionnaire for the Chilean population. MATERIAL AND METHODS: For cultural adaptation, a translation, retro-translation and an expert panel review was carried out. The resulting questionnaire was applied to a pilot group of twelve participants and their comments were considered for the final questionnaire version. The final questionnaire was applied to a non-random sample of 200 patients aged 53 ± 17 years (75% women). Internal consistency and construct validity were evaluated by Cronbach's alpha and exploratory factor analysis respectively. RESULTS: According to the OSDI score, 81% of respondents had dry eye (55% severe). Reliability was 0.91 and factor analysis resulted in three factors explaining 75.4% of the total variance. CONCLUSIONS: The OSDI questionnaire version obtained in this study demonstrated excellent internal consistency values and adequate construct validity making it applicable to clinical practice and dry eye research.

Cervical pessary for preventing preterm birth in twin pregnancies with maternal short cervix after an episode of threatened preterm labor: randomised controlled trial.

BACKGROUND: No intervention has proved effective to date in reducing the spontaneous preterm birth rate in twin pregnancies following an episode of threatened preterm labor and with a short cervix remaining. This study was designed to ascertain whether cervical pessaries are useful in preventing spontaneous preterm birth in women with twin pregnancies and a short cervix remaining after a threatened preterm labor episode. STUDY DESIGN: This open, randomized, controlled trial was conducted in 132 pregnant women who had not delivered 48 hours after a threatened preterm labor episode and had a short cervix remaining (≤20 mm between 240 and 296 weeks and ≤10 mm between 300 and 336 weeks). Patients were randomly assigned to cervical pessary (n = 67) or routine management (n = 65). The primary outcome was the spontaneous preterm birth rate before 34 weeks. Spontaneous preterm birth before 28 and 37 weeks and neonatal morbidity and mortality were also evaluated in an intention-to-treat analysis. RESULTS: Significant differences were observed in the spontaneous preterm birth rate before 34 weeks between the pessary and routine management groups (11 of 67 [16.4%] in the pessary group vs 21 of 65 [32.3%] in the control group; relative risk, 0.51 [confidence interval, 0.27-0.97]; P = .03). No significant differences were observed in the preterm birth rate < 28 weeks or < 37 weeks between groups. The pessary group less frequently required readmission for new threatened preterm labor episodes (4 of 67 [5.6%] vs 14 of 65 [21.5%]; relative risk, 0.28 [confidence interval, 0.10-0.80]; P = .009). Significant reduction was observed in the number of neonates weighing less than 2500 g (17.9% [24 of 134] vs 70.8% [92 of 130]; relative risk, 0.25 [confidence interval, 0.15-0.43]; P < .0001). CONCLUSION: Pessary use did significantly lower the spontaneous preterm birth rate before 34 weeks in twin pregnancies with maternal short cervix remaining after a threatened preterm labor episode. Pessary use also reduced the threatened preterm labor recurrence and neonates' weight less than 2500 g.

Cervical modifications after pessary placement in singleton pregnancies with maternal short cervical length: 2D and 3D ultrasound evaluation.

INTRODUCTION: The use of a pessary proved to prevent preterm birth in asymptomatic women with mid-trimester short cervical length (CL); however, the precise mechanisms by which the pessary confers its benefit remain unclear. The aim of this study was to evaluate multiple cervical characteristics assessed by 2-dimensional and 3-dimensional ultrasound before and after placement of a cervical pessary to ascertain its mechanism of action. MATERIAL AND METHODS: In this prospective cohort study, we assessed the cervical characteristics in singleton pregnancies with maternal short CL and compared them with matched reference women with normal CL. The variables evaluated were: CL, uterocervical angles, cervical consistency indices (cervical consistency index and CL consistency index), cervical volume and vascular indices. All variables were re-assessed immediately after pessary placement and 4-6 weeks later in all participants. Mann-Whitney U test was used to assess differences between groups and paired samples t test for comparisons in two different examinations in the same women. The aim of this study was to evaluate multiple cervical ultrasound variables before and after the placement of a cervical pessary and compare the evolution of these variables with a reference group with normal CL to better understand the device's mechanism of action. RESULTS: Thirty-three women with short CL and 24 reference women with normal CL were enrolled. At the time of enrollment, gestational age and maternal baseline characteristics did not differ between groups. Immediately after pessary placement, CL increased, uterocervical angles were narrower and cervical consistency increased significantly. When the magnitude of change in cervical variables was compared over time between the reference group and the study group, median CL had increased in the study group (1.47 mm) but it had shortened in the reference group (-2.56 mm). These inverse trends were statistically significant (P = 0.006). CONCLUSIONS: Cervical pessary reduces both uterocervical angles and corrects cervical angulation by pushing the cervix up toward the uterus. Maintaining the cervix aligned to the uterine axis leads to reduced cervical tissue stretch, so avoiding further cervical shortening. All these changes were present after pessary placement; however, the clinical implications of these findings remain unknown.

Circadian rhythms identified in Caenorhabditis elegans by in vivo long-term monitoring of a bioluminescent reporter.

Circadian rhythms are based on endogenous clocks that allow organisms to adjust their physiology and behavior by entrainment to the solar day and, in turn, to select the optimal times for most biological variables. Diverse model systems-including mice, flies, fungi, plants, and bacteria-have provided important insights into the mechanisms of circadian rhythmicity. However, the general principles that govern the circadian clock of Caenorhabditis elegans have remained largely elusive. Here we report robust molecular circadian rhythms in C elegans recorded with a bioluminescence assay in vivo and demonstrate the main features of the circadian system of the nematode. By constructing a luciferase-based reporter coupled to the promoter of the suppressor of activated let-60 Ras (sur-5) gene, we show in both population and single-nematode assays that C elegans expresses ∼24-h rhythms that can be entrained by light/dark and temperature cycles. We provide evidence that these rhythms are temperature-compensated and can be re-entrained after phase changes of the synchronizing agents. In addition, we demonstrate that light and temperature sensing requires the photoreceptors LITE and GUR-3, and the cyclic nucleotide-gated channel subunit TAX-2. Our results shed light on C elegans circadian biology and demonstrate evolutionarily conserved features in the circadian system of the nematode.

Prevention of spontaneous preterm birth.

BACKGROUND: It is estimated that globally, approximately 13 million preterm infants are born annually and a much higher number of pregnancies are characterized by threatening preterm birth. FINDINGS: A proportional inverse correlation between gestational age at delivery and neonatal mortality has been observed which is more prevalent in countries without high standard neonatal care. The socioeconomic burden of preterm birth is enormous, as preterm neonates are particularly prone to severe morbidity that may expand up to adulthood. Several strategies have been proposed for the prevention of preterm birth which can be sub-stratified as primary (when these apply to the general population), secondary (when they target women at risk), and tertiary (optimizing neonatal outcomes when preterm birth cannot any longer be prevented). The aim of this review is to summarize the most important strategies.

Cervical pessary to reduce preterm birth <34 weeks of gestation after an episode of preterm labor and a short cervix: a randomized controlled trial.

BACKGROUND: To date, no intervention has proved effective in reducing the spontaneous preterm birth rate in singleton pregnancies following an episode of threatened preterm labor and short cervix remaining. OBJECTIVE: This study was designed to ascertain whether cervical pessaries could be useful in preventing spontaneous preterm birth in women with singleton pregnancies and a short cervix after a threatened preterm labor episode. STUDY DESIGN: This open randomized controlled trial was conducted in 357 pregnant women (between 240-336 weeks) who had not delivered 48 hours after a threatened preterm labor episode and had a short cervix remaining (≤25 mm at 240-296 weeks; ≤15 mm at 300-336 weeks). Patients were randomly assigned to cervical pessary (179) or routine management (178). The primary outcome was the spontaneous preterm birth rate <34 weeks. Spontaneous preterm birth <28 and 37 weeks and neonatal morbidity and mortality were also evaluated in an intention-to-treat analysis. RESULTS: No significant differences between the pessary and routine management groups were observed in the spontaneous preterm birth rate <34 weeks (19/177 [10.7%] in the pessary group vs 24/175 [13.7%] in the control group; relative risk, 0.78; 95% confidence interval, 0.45-1.38). Spontaneous preterm birth <37 weeks occurred less frequently in the pessary group (26/175 [14.7%] vs 44/175 [25.1%]; relative risk, 0.58; 95% confidence interval, 0.38-0.90; P = .01). Preterm premature rupture of membranes rate was significantly lower in pessary carriers (4/177 [2.3%] vs 14/175 [8.0%]; relative risk, 0.28; 95% confidence interval, 0.09-0.84; P = .01). The pessary group less frequently required readmission for new threatened preterm labor episodes (8/177 [4.5%] vs 35/175 [20.0%]; relative risk, 0.23; 95% confidence interval, 0.11-0.47; P < .0001). No serious adverse maternal events occurred; neonatal morbidity and mortality were similar in both groups. CONCLUSION: Pessary use did not significantly lower the spontaneous preterm birth rate <34 weeks in women with a short cervix remaining after a threatened preterm labor episode but did significantly reduce the spontaneous preterm birth rate <37 weeks, threatened preterm labor recurrence, and the preterm premature rupture of membranes rate.

Cervical pessary to prevent preterm birth in women with twin gestation and sonographic short cervix: a multicenter randomized controlled trial (PECEP-Twins).

BACKGROUND: Spontaneous preterm birth (SPB) is the leading cause of perinatal morbidity and mortality. In twins, the rate of preterm birth is higher than in singletons; interventions to prevent preterm birth are needed in this high-risk population. OBJECTIVE: We sought to test whether a cervical pessary reduces the preterm birth rate in twin pregnancies with sonographic short cervix. STUDY DESIGN: A prospective, open-label, multicenter, randomized clinical trial was conducted in 5 hospitals in Spain. The ethics committees of all participating hospitals approved the protocol. The trial was registered as ClinicalTrials.gov, number NCT01242410. Eligible women were scanned in Spain. The primary outcome was SPB <34 weeks of gestation. Neonatal morbidity and mortality were also evaluated. RESULTS: Cervical length was measured in 2287 women; 137 pregnant women with a sonographic cervical length ≤25 mm (of 154 detected with a short cervix) were randomly assigned to receive a cervical pessary or expectant management (1:1 ratio). SPB <34 weeks of gestation was significantly less frequent in the pessary group than in the expectant management group (11/68 [16.2%] vs 26/66 [39.4%]; relative risk, 0.41; 95% confidence interval, 0.22-0.76). Pessary use was associated with a significant reduction in the rate of birthweight <2500 g (P = .01). No significant differences were observed in composite neonatal morbidity outcome (8/136 [5.9%] vs 12/130 [9.1%]; relative risk, 0.64; 95% confidence interval, 0.27-1.50) or neonatal mortality (none) between the groups. No serious adverse effects associated with the use of a cervical pessary were observed. CONCLUSION: The insertion of a cervical pessary was associated with a significant reduction in the SPB rate. We propose the use of a cervical pessary for preventing preterm birth in twin pregnancies of mothers with a short cervix.

Maternal and foetal angiogenic imbalance in congenital heart defects.

AIMS: Animal models showed that angiogenesis is related to abnormal heart development. Our objectives were to ascertain whether a relationship exists between congenital heart defects (CHDs) and angiogenic/anti-angiogenic imbalance in maternal and foetal blood and study the expression of angiogenic factors in the foetal heart. METHODS AND RESULTS: Maternal and cord blood placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) were compared in 65 cases of CHD and 204 normal controls. Angiogenic factor expression and markers of hypoxia were measured in heart tissue from 23 CHD foetuses and 8 controls. In the CHD group, compared with controls, plasma PlGF levels were significantly lower (367 ± 33 vs. 566 ± 26 pg/mL; P < 0.0001) and sFlt-1 significantly higher (2726 ± 450 vs. 1971 ± 130 pg/mL, P = 0.0438). Foetuses with CHD had higher cord plasma sFlt-1 (442 ± 76 vs. 274 ± 26 pg/mL; P = 0.0285) and sEng (6.76 ± 0.42 vs. 4.99 ± 0.49 ng/mL, P = 0.0041) levels. Expression of vascular endothelial growth factor (VEGF), sFlt-1, markers of chronic hypoxia, and antioxidant activity were significantly higher in heart tissue from CHD foetuses compared with normal hearts (VEGF, 1.59-fold; sFlt-1, 1.92-fold; hypoxia inducible factor (HIF)-2α, 1.45-fold; HO-1, 1.62-fold; SOD1, 1.31-fold). CONCLUSION: An intrinsically angiogenic impairment exists in CHD that appears to be present in both the maternal and foetal circulation and foetal heart. Our data suggest that an imbalance of angiogenic-antiangiogenic factors is associated with developmental defects of the human heart.

Risk factors of early spontaneous preterm birth despite carrying a cervical pessary in singleton pregnancies with a short cervix: Development of a risk prediction model.

Introduction: We aimed to identify the incidence and risk factors of spontaneous preterm birth in pessary carriers with singleton pregnancies and a short cervix in the mid-trimester of pregnancy. Material and Methods: Patient data were obtained from the PECEP Trial. We analyzed singleton pregnancies in pessary carriers with a short cervix (≤25 mm) between 18 and 22 gestational weeks. Demographics and obstetric history were compared to identify risk factors for spontaneous preterm birth < 34 gestational weeks. Each demographic and obstetric variable was compared between spontaneous preterm birth < 34 and ≥ 34 weeks of gestation.Regression analysis was used to identify risk factors. A risk score model was generated using the odds ratio for significant factors. The risk score model and spontaneous preterm birth risk were assessed using the receiver operating characteristic curve. Perinatal outcomes were compared by risk score. Results: Among 190 pregnant individuals, 12 (6.3%) had spontaneous preterm birth < 34 gestational weeks. In the bivariate analysis, statistically significant differences between those with and without spontaneous preterm birth were only observed for mean cervical length at diagnosis and mean cervical length after pessary placement. By multiple logistic regression analysis, maternal age (OR 0.818; 95% CI 0.69-0.97; P 0.020), cervical length at diagnosis (OR 0.560; 95% CI 0.43-0.73; P < 0.001) and smoking status (OR 7.276; 95% CI 1.02-51.80; P 0.048) remained significantly associated with spontaneous preterm birth.The ROC curve from the multiple logistic regression analysis, including cervical length, maternal age and smoking status, had an area under the curve (AUC) of 0.952 (P < 0.001). The ROC curve for the risk score model incorporating all three variables had an AUC of 0.864 (95% CI 0.77-0.96; P < 0.001). A high-risk score was predictive of spontaneous preterm birth with a sensitivity of 75%, specificity of 84%, positive predictive value of 24%, and negative predictive value of 98%.Women with a high-risk score had a significantly reduced latency to delivery and poorer neonatal outcomes than those with a low-risk score. Conclusions: Patients at a high risk for spontaneous preterm birth despite pessary therapy may be identified using cervical length at diagnosis added to maternal age and smoking status.

Real-World Evidence of Off-Label Use of Commercially Automated Insulin Delivery Systems Compared to Multiple Daily Insulin Injections in Pregnancies Complicated by Type 1 Diabetes.

Aims: To compare glycemic control and maternal-fetal outcomes of women with type 1 diabetes (T1D) using hybrid closed loop (HCL) versus multiple daily insulin injections (MDI) plus continuous glucose monitoring. Methods: Multicenter prospective cohort study of pregnant women with T1D in Spain. We evaluated HbA1c and time spent within (TIR), below (TBR), and above (TAR) the pregnancy-specific glucose range of 3.5-7.8 mmol/L. Adjusted models were performed for adverse pregnancy outcomes, including baseline maternal characteristics and center. Results: One hundred twelve women were included (HCL n = 59). Women in the HCL group had a longer duration of diabetes and higher rates of prepregnancy care. There was no between-group difference in HbA1c in any trimester. However, in the second trimester, MDI users had a greater decrease in HbA1c (-6.12 ± 9.06 vs. -2.16 ± 7.42 mmol/mol, P = 0.031). No difference in TIR (3.5-7.8 mmol/L) and TAR was observed between HCL and MDI users, but with a higher total insulin dose in the second trimester [+0.13 IU/kg·day)]. HCL therapy was associated with increased maternal weight gain during pregnancy (ßadjusted = 3.20 kg, 95% confidence interval [CI] 0.90-5.50). Regarding neonatal outcomes, newborns of HCL users were more likely to have higher birthweight (ßadjusted = 279.0 g, 95% CI 39.5-518.5) and macrosomia (ORadjusted = 3.18, 95% CI 1.05-9.67) compared to MDI users. These associations disappeared when maternal weight gain or third trimester HbA1c was included in the models. Conclusions: In a real-world setting, HCL users gained more weight during pregnancy and had larger newborns than MDI users, while achieving similar glycemic control in terms of HbA1c and TIR.

Cervical pessary in pregnant women with a short cervix (PECEP): an open-label randomised controlled trial.

BACKGROUND: Most previous studies of the use of cervical pessaries were either retrospective or case controlled and their results showed that this intervention might be a preventive strategy for women at risk of preterm birth; no randomised controlled trials have been undertaken. We therefore undertook a randomised, controlled trial to investigate whether the insertion of a cervical pessary in women with a short cervix identified by use of routine transvaginal scanning at 20-23 weeks of gestation reduces the rate of early preterm delivery. METHODS: The Pesario Cervical para Evitar Prematuridad (PECEP) trial was undertaken in five hospitals in Spain. Pregnant women (aged 18-43 years) with a cervical length of 25 mm or less were randomly assigned according to a computer-generated allocation sequence by use of central telephone in a 1:1 ratio to the cervical pessary or expectant management (without a cervical pessary) group. Because of the nature of the intervention, this study was not masked. The primary outcome was spontaneous delivery before 34 weeks of gestation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00706264. FINDINGS: 385 pregnant women with a short cervix were assigned to the pessary (n=192) and expectant management groups (n=193), and 190 were analysed in each group. Spontaneous delivery before 34 weeks of gestation was significantly less frequent in the pessary group than in the expectant management group (12 [6%] vs 51 [27%], odds ratio 0·18, 95% CI 0·08-0·37; p<0·0001). No serious adverse effects associated with the use of a cervical pessary were reported. INTERPRETATION: Cervical pessary use could prevent preterm birth in a population of appropriately selected at-risk women previously screened for cervical length assessment at the midtrimester scan. FUNDING: Instituto Carlos III.