Documento de consenso de la Sociedad Española de Obstetricia y Ginecologia (SEGO)y el Comité Español Interdisciplinario para la Prevención Vascular (CEIPV). Ventanade oportunidad: prevención del riesgo vascular en la mujer. Resultados adversos delembarazo y riesgo de enfermedad vascular* / Consensus document from the Spanish Society of Obstetrics and Gynecology (SEGO) and the Spanish Interdisciplinary Committee for Vascular Prevention (CEIPV). Window of opportunity: vascular risk prevention in women. Adverse pregnancy outcomes and risk of vascular diseas

Este documento resume la evidencia que existe entre los resultados adversos del embarazo (RAE) y el riesgo que tiene una persona gestante de desarrollar factores de riesgo vascular (RV) que pueden terminar provocando enfermedad vascular (EV) futura. Asimismo, este documento destaca la importancia de saber reconocer los RAE cuando se evalúa el RV en mujeres. Un antecedente de RAE es un indicador suficiente para hacer una prevención primaria de EV. De hecho, adoptar una dieta saludable y aumentar la actividad física entre las mujeres con RAE, de inicio en el embarazo o en el posparto y manteniéndolas a lo largo de la vida, son intervenciones importantes que permiten disminuir el RV. Por otro lado, la lactancia materna también puede disminuir el RV posterior de la mujer, incluyendo menos riesgo de mortalidad. Estudios futuros que evalúen el uso del ácido acetilsalicílico, las estatinas y la metformina, entre otros, en las mujeres con antecedentes de RAE podrían reforzar las recomendaciones sobre el uso de la farmacoterapia en la prevención primaria de la EV entre estas pacientes. Existen diferentes opciones dentro de los sistemas de salud para mejorar la transición de la atención de las mujeres con RAE entre los diferentes profesionales e implementar estrategias para reducir su RV a largo plazo. Una posible estrategia podría ser la incorporación del concepto del cuarto trimestre en las recomendaciones clínicas y las políticas de atención de la salud.(AU)

This document summarises the evidence regarding the association between adverse pregnancy outcomes (APOs),such as hypertensive disorders, preterm birth, gestational diabetes, fetal growth defects (small for gestational ageand/or fetal growth restriction), placental abruption, fetal loss, and the risk that a pregnant individual in developingvascular risk factors (VR) that may lead to future vascular disease (VD): coronary heart disease, stroke, peripheralvascular disease, and heart failure. Furthermore, this document emphasises the importance of recognising APOswhen assessing VR in women. A history of APOs serves as a sufficient indicator for primary prevention of VD. In fact,adopting a healthy diet and increasing physical activity among women with APOs, starting during pregnancy and/or postpartum, and maintaining it throughout life are significant interventions that can reduce VR. On the otherhand, breastfeeding can also reduce the future VR of women, including a lower risk of mortality. Future studies evaluating the use of aspirin, statins, and metformin, among others, in women with a history of APOscould strengthen recommendations regarding pharmacotherapy for primary prevention of VD in these patients.Various healthcare system options exist to improve the transition of care for women with APOs between differenthealthcare professionals and implement long-term VR reduction strategies. One potential process could involveincorporating the fourth-trimester concept into clinical recommendations and healthcare policies.(AU)

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.

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.

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) vs. multiple daily insulin injections (MDI) plus continuous glucose monitoring (CGM). 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 3.5-7.8 mmol/L. Adjusted models were performed for adverse pregnancy outcomes including baseline maternal characteristics and center. RESULTS: 112 women were included (HCL n=59). Women in the HCL group had a longer duration of diabetes and higher rates of prepregnancy care. There were no between-group differences 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 differences in TIR (3.5-7.8 mmol/L) and TAR were observed between HCL and MDI users, but with a higher total insulin dose in the second trimester (+0.13 IU/Kg/d). HCL therapy was associated with increased maternal weight gain during pregnancy (ßadjusted 3.20 kg, 95%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 were 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.

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.

Reference ranges of thyroid hormones during the first trimester in Catalan women using the Atellica® IM Solution Immunoassay Analyzer.

BACKGROUND: Gestational hypothyroidism has been shown to be associated with adverse pregnancy outcomes as well as adverse outcomes for the child. Thyroid hormones concentrations change in gestation, especially within the first trimester, so the results of thyroid function test often are outside non-pregnant reference ranges. The objective of this study was to establish the first trimester reference ranges for thyroid stimulating hormone (TSH) and free thyroxine (FT4) for pregnant women in Barcelona (Spain). METHODS: It was a prospective study in which 673 women were recruited during their first trimester of gestation (8-13 weeks). Serum TSH, FT4 and antithyroid peroxidase antibodies (TPOAb) were measured with Atellica® IM 1600 (Siemens Healthineers). After excluding 418 women, the reference ranges for TSH and FT4 were calculated by the 2.5th and 97.5th percentiles. Potential variables examined in this study were age, body mass index (BMI), ethnicity, iodine supplementation and smoking habit. RESULTS: The reference ranges established on the Atellica® IM 1600 for the first trimester pregnancy in our population were 0.111 to 4.291 mIU/L for TSH and 11.45 to 17.76 pmol/L for FT4. No significant differences were found in thyroid hormones concentrations regarding maternal age (≤30 years vs >30 years) (p = .117), iodine supplementation (p = .683) and smoking habit (p = .363). The prevalence of TPOAb was estimated at 10.0%. CONCLUSIONS: We found that in our local population, the optimal TSH upper reference limit in the first trimester of gestation was 4.3 mIU/L, similar to that proposed by de ATA-2017 guideline (4.0 mIU/L).

[Documento de consenso de la Sociedad Española de Obstetricia y Ginecologia (SEGO) y el Comité Español Interdisciplinario para la Prevención Vascular (CEIPV). Ventana de oportunidad: prevención del riesgo vascular en la mujer. Resultados adversos del embarazo y riesgo de enfermedad vascular.] / Consensus document of the Spanish Society of Obstetrics and Gynecology (SEGO) and the Spanish Interdisciplinary Committee for Vascular Prevention (CEIPV). Opportunity window: vascular risk prevention in women. Adverse pregnancy outcomes and risk of vascular disease.

This document summarises the evidence regarding the association between adverse pregnancy outcomes (APOs), such as hypertensive disorders, preterm birth, gestational diabetes, fetal growth defects (small for gestational age and/or fetal growth restriction), placental abruption, fetal loss, and the risk that a pregnant individual in developing vascular risk factors (VR) that may lead to future vascular disease (VD): coronary heart disease, stroke, peripheral vascular disease, and heart failure. Furthermore, this document emphasises the importance of recognising APOs when assessing VR in women. A history of APOs serves as a sufficient indicator for primary prevention of VD. In fact, adopting a healthy diet and increasing physical activity among women with APOs, starting during pregnancy and/or postpartum, and maintaining it throughout life are significant interventions that can reduce VR. On the other hand, breastfeeding can also reduce the future VR of women, including a lower risk of mortality. Future studies evaluating the use of aspirin, statins, and metformin, among others, in women with a history of APOs could strengthen recommendations regarding pharmacotherapy for primary prevention of VD in these patients. Various healthcare system options exist to improve the transition of care for women with APOs between different healthcare professionals and implement long-term VR reduction strategies. One potential process could involve incorporating the fourth-trimester concept into clinical recommendations and healthcare policies.

Este documento resume la evidencia que existe entre los resultados adversos del embarazo (RAE), tales como son los trastornos hipertensivos, el parto pretérmino, la diabetes gestacional, los defectos en el crecimiento fetal (feto pequeño para la edad gestacional y/o restricción del crecimiento), el desprendimiento de placenta y la pérdida fetal, y el riesgo que tiene una persona gestante de desarrollar factores de riesgo vascular (RV) que pueden terminar provocando enfermedad vascular (EV) futura: cardiopatía coronaria, accidente cerebrovascular, enfermedad vascular periférica e insuficiencia cardíaca. Asimismo, este documento destaca la importancia de saber reconocer los RAE cuando se evalúa el RV en mujeres. Un antecedente de RAE es un indicador suficiente para hacer una prevención primaria de EV. De hecho, adoptar una dieta saludable y aumentar la actividad física entre las mujeres con RAE, de inicio en el embarazo y/o postparto y manteniéndolo a lo largo de la vida, son intervenciones importantes que permiten disminuir el RV. Por otro lado, la lactancia materna también puede disminuir el RV posterior de la mujer, incluyendo menos riesgo de mortalidad. Estudios futuros que evalúen el uso del ácido acetilsalicílico, las estatinas y la metformina, entre otros, en las mujeres con antecedentes de RAE podrían reforzar las recomendaciones sobre el uso de la farmacoterapia en la prevención primaria de la EV entre estas pacientes. Existen diferentes opciones dentro de los sistemas de salud para mejorar la transición de la atención de las mujeres con RAE entre los diferentes profesionales e implementar estrategias para reducir su RV a largo plazo. Una posible estrategia podría ser la incorporación del concepto del cuarto trimestre en las recomendaciones clínicas y las políticas de atención de la salud.

Documento de consenso de la Sociedad Española de Obstetricia y Ginecologia (SEGO) y el Comité Español Interdisciplinario para la Prevención Vascular (CEIPV). Ventana de oportunidad: prevención del riesgo vascular en la mujer. Resultados adversos del embarazo y riesgo de enfermedad vascular / Consensus document of the Spanish Society of Obstetrics and Gynecology (SEGO) and the Spanish Interdisciplinary Committee for Vascular Prevention (CEIPV). Opportunity window: vascular risk prevention in women. Adverse pregnancy outcomes and risk of vascular disease

Este documento resume la evidencia que existe entre los resultados adversos del embarazo (RAE), tales como son los trastornos hipertensivos, el parto pretérmino, la diabetes gestacional, los defectos en el crecimiento fetal (feto pequeño para la edad gestacional y/o restricción del crecimiento), el desprendimiento de placenta y la pérdida fetal, y el riesgo que tiene una persona gestante de desarrollar factores de riesgo vascular (RV) que pueden terminar provocando enfermedad vascular (EV) futura: cardiopatía coronaria, accidente cerebrovascular, enfermedad vascular periférica e insuficiencia cardíaca. Asimismo, este documento destaca la importancia de saber reconocer los RAE cuando se evalúa el RV en mujeres. Un antecedente de RAE es un indicador suficiente para hacer una prevención primaria de EV. De hecho, adoptar una dieta saludable y aumentar la actividad física entre las mujeres con RAE, de inicio en el embarazo y/o postparto y manteniéndolo a lo largo de la vida, son intervenciones importantes que permiten disminuir el RV. Por otro lado, la lactancia materna también puede disminuir el RV posterior de la mujer, incluyendo menos riesgo de mortalidad. Estudios futuros que evalúen el uso del ácido acetilsalicílico, las estatinas y la metformina, entre otros, en las mujeres con antecedentes de RAE podrían reforzar las recomendaciones sobre el uso de la farmacoterapia en la prevención primaria de la EV entre estas pacientes. Existen diferentes opciones dentro de los sistemas de salud para mejorar la transición de la atención de las mujeres con RAE entre los diferentes profesionales e implementar estrategias para reducir su RV a largo plazo. Una posible estrategia podría ser la incorporación del concepto delcuarto trimestre en las recomendaciones clínicas y las políticas de atención de la salud.(AU)

This document summarises the evidence regarding the association between adverse pregnancy outcomes (APOs), such as hypertensive disorders, preterm birth, gestational diabetes, fetal growth defects (small for gestational age and/or fetal growth restriction), placental abruption, fetal loss, and the risk that a pregnant individual in developing vascular risk factors (VR) that may lead to future vascular disease (VD): coronary heart disease, stroke, peripheral vascular disease, and heart failure. Furthermore, this document emphasises the importance of recognising APOs when assessing VR in women. A history of APOs serves as a sufficient indicator for primary prevention of VD. In fact, adopting a healthy diet and increasing physical activity among women with APOs, starting during pregnancy and/or postpartum, and maintaining it throughout life are significant interventions that can reduce VR. On the other hand, breastfeeding can also reduce the future VR of women, including a lower risk of mortality.Future studies evaluating the use of aspirin, statins, and metformin, among others, in women with a history of APOs could strengthen recommendations regarding pharmacotherapy for primary prevention of VD in these patients. Various healthcare system options exist to improve the transition of care for women with APOs between different healthcare professionals and implement longterm VR reduction strategies. One potential process could involve incorporating the fourth-trimester concept into clinical recommendations and healthcare policies.(AU)

Pregnancy-related aortic complications in women with bicuspid aortic valve.

OBJECTIVES: To describe the aortic-related risks associated with pregnancy in women with bicuspid aortic valve (BAV) and to evaluate changes in aortic diameter in pregnancy. METHODS: Prospective observational study of patients with BAV from a single-site registry of pregnant women with structural heart disease between 2013 and 2020. Cardiac, obstetric and neonatal outcomes were studied. An assessment of aortic dimensions was performed during pregnancy by two-dimensional echocardiography. Aortic diameters were measured at the annulus, root, sinotubular junction and maximum ascending aorta diameter, and the largest diameter was used. Measurements of the aorta were made using the end-diastolic leading edge-to-leading edge convention. RESULTS: Forty-three women (32.9 years, IQR 29.6-35.3) with BAV were included: 9 (20.9%) had repaired aortic coarctation; 23 (53.5%) had moderate or severe aortic valve disease; 5 (11.6%) had a bioprosthetic aortic valve; and 2 (4.7%) had a mechanical prosthetic aortic valve. Twenty (47.0%) were nulliparous. The mean aortic diameter in the first trimester was 38.5 (SD 4.9) mm, and that in the third trimester was 38.4 (SD 4.8) mm. Forty (93.0%) women had an aortic diameter of <45 mm; 3 (7.0%) had 45-50 mm; and none had >50 mm. Three women (6.9%) with BAV presented cardiovascular complications during pregnancy or the postpartum period (two prosthetic thrombosis and one heart failure). No aortic complications were reported. There was a small but significant increase in aortic diameter during pregnancy (third trimester vs first trimester, 0.52 (SD 1.08) mm; p=0.03). Obstetric complications appeared in seven (16.3%) of pregnancies, and there were no maternal deaths. Vaginal non-instrumental delivery was performed in 21 (51.2%) out of 41 cases. There were no neonatal deaths, and the mean newborn weight was 3130 g (95% CI 2652 to 3380). CONCLUSIONS: Pregnancy in BAV women had a low rate of cardiac complications with no aortic complications observed in a small study group. Neither aortic dissection nor need for aortic surgery was reported. A low but significant aortic growth was observed during pregnancy. Although requiring follow-up, the risk of aortic complications in pregnant women with BAV and aortic diameters of <45 mm at baseline is low.

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.

Abnormal Maternal Body Mass Index and Customized Fetal Weight Charts: Improving the Identification of Small for Gestational Age Fetuses and Newborns.

BACKGROUND: Obesity and thinness are serious diseases, but cases with abnormal maternal weight have not been excluded from the calculations in the construction of customized fetal growth curves (CCs). METHOD: To determine if the new CCs, built excluding mothers with an abnormal weight, are better than standard CCs at identifying SGA. A total of 16,122 neonates were identified as SGA, LGA, or AGA, using the two models. Logistic regression and analysis of covariance were used to calculate the OR and CI for adverse outcomes by group. Gestational age was considered as a covariable. RESULTS: The SGA rates by the new CCs and by the standard CCs were 11.8% and 9.7%, respectively. The SGA rate only by the new CCs was 18% and the SGA rate only by the standard CCs was 0.01%. Compared to AGA by both models, SGA by the new CCs had increased rates of cesarean section, (OR 1.53 (95% CI 1.19, 1.96)), prematurity (OR 2.84 (95% CI 2.09, 3.85)), NICU admission (OR 5.41 (95% CI 3.47, 8.43), and adverse outcomes (OR 1.76 (95% CI 1.06, 2.60). The strength of these associations decreased with gestational age. CONCLUSION: The use of the new CCs allowed for a more accurate identification of SGA at risk of adverse perinatal outcomes as compared to the standard CCs.

Caenorhabditis elegans as a Promising Model Organism in Chronobiology.

Circadian rhythms represent an adaptive feature, ubiquitously found in nature, which grants living beings the ability to anticipate daily variations in their environment. They have been found in a multitude of organisms, ranging from bacteria to fungi, plants, and animals. Circadian rhythms are generated by endogenous clocks that can be entrained daily by environmental cycles such as light and temperature. The molecular machinery of circadian clocks includes a transcriptional-translational feedback loop that takes approximately 24 h to complete. Drosophila melanogaster has been a model organism of choice to understand the molecular basis of circadian clocks. However, alternative animal models are also being adopted, each offering their respective experimental advantages. The nematode Caenorhabditis elegans provides an excellent model for genetics and neuro-behavioral studies, which thanks to its ease of use and manipulation, as well as availability of genetic data and mutant strains, is currently used as a novel model for circadian research. Here, we aim to evaluate C. elegans as a model for chronobiological studies, focusing on its strengths and weaknesses while reviewing the available literature. Possible zeitgebers (including light and temperature) are also discussed. Determining the molecular bases and the neural circuitry involved in the central pacemaker of the C. elegans' clock will contribute to the understanding of its circadian system, becoming a novel model organism for the study of diseases due to alterations of the circadian cycle.

Executive summary of the SEEN (Sociedad Española de Endocrinología y Nutrición[Spanish Society of Endocrinology and Nutrition])-SEGO (Sociedad Española deGinecología y Obstetricia [Spanish Society of Gynaecology and Obstetrics]) consensusdocument on the management of thyroid dysfunction during pregnancy.

During pregnancy, thyroid function disorders are associated with multiple complications, both maternal and foetal. In recent years, numerous Clinical Practice Guidelines have been developed to facilitate the identification and correct management of thyroid disease in pregnant women. However, this proliferation of guidelines has led to confusion by proposing different cut-off points for reference values and different recommendations for similar situations. For this reason, the Sociedad Española de Endocrinología y Nutrición and the Sociedad Española de Ginecología y Obstetricia have prepared this Consensus Document, with the aim of creating a framework for joint action to unify criteria for the diagnosis and treatment of thyroid dysfunction in these patients. The document is structured to answer the most frequently asked questions in clinical practice, grouped into five sections: 1/Reference values for thyroid function tests and screening during pregnancy 2/Iodine nutrition 3/Hypothyroidism and pregnancy 4/Hyperthyroidism and pregnancy 5/ Thyroid autoimmunity.

Implications of training for pessary placement and accuracy of cervical length measurements after pessary placement: A prospective, double-blind, randomized clinical trial.

BACKGROUND: Cervical pessary placement as an intervention for preterm birth prevention in women with a short cervix is a simple, painless procedure with few complications and a reasonable cost. Its efficacy depends on the expertise of the obstetrician performing the procedure. Therefore, it is reasonable to assume that untrained obstetricians with no expertise in pessary placement are more likely to insert the pessary incorrectly, thereby reducing its efficacy. Nevertheless, the impact of pessary placement expertise and training, as well as the accuracy of cervival length measurements, has never been evaluated. OBJECTIVE: To evaluate the impact of providing training for pessary placement to obstetricians with no expertise in this intervention. To this end, the percentage of correct pessary placements and accuracy of cervical length measurements after pessary placement achieved by obstetricians who received such training was compared with the results achieved by obstetricians who did not receive any training. METHODS: This prospective, double-blind, randomized clinical trial included 91 pregnant women requiring a cervical pessary due to a short cervix. Patients were assigned at random to a group treated by untrained obstetricians with no expertise in pessary placement (untrained group, n = 45) or to a group treated by trained obstetricians with no expertise in pessary placement (trained group, n = 46). The primary outcomes were the quality of pessary placement and the accuracy of cervical length measurements after pessary placement. RESULTS: Obstetricians in the trained group achieved a significantly higher percentage of correct pessary placements than obstetricians in the untrained group (97.8 % and 65.2 %, respectively; p < 0.001). No significant differences were observed between groups in terms of the accuracy of cervical length measurements after pessary placement (p = 0.661), and both groups showed moderate to good agreement with the expert's measurements (intraclass correlation coefficient 0.840 and 0.749, respectively). No differences in pregnancy outcomes were observed between groups. CONCLUSION: This study showed that providing training in pessary placement to obstetricians with no expertise in this procedure increases the quality of pessary placement. Furthermore, the inconsistent results found in pessary studies may be explained, in part, by a lack of training in pessary placement.

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.

Timing of Delivery for Twins With Growth Discordance and Growth Restriction: An Individual Participant Data Meta-analysis.

OBJECTIVE: First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies. DATA SOURCES: A search of MEDLINE, EMBASE, ClinicalTrials.gov, and Ovid between 2015 and 2018 was performed of cohort studies reporting risks of stillbirth and neonatal death in twin pregnancies from 32 to 41 weeks of gestation. Studies from a previous meta-analysis using a similar search strategy (from inception to 2015) were combined. Women with monoamniotic twin pregnancies were excluded. METHODS OF STUDY SELECTION: Overall, of 57 eligible studies, 20 cohort studies that contributed original data reporting on 7,474 dichorionic and 2,281 monochorionic twin pairs. TABULATION, INTEGRATION, AND RESULTS: We performed an individual participant data meta-analysis to calculate the risk of perinatal death (risk difference between prospective stillbirth and neonatal death) per gestational week. Analyses were stratified by chorionicity, levels of growth discordance, and presence of SGA in one or both twins. For both dichorionic and monochorionic twins, the absolute risks of stillbirth and neonatal death were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance and birth weight, perinatal risk balanced between 36 0/7-6/7 and 37 0/7-6/7 weeks of gestation in both dichorionic and monochorionic twin pregnancies, with likely higher risk of stillbirth than neonatal death from 37 0/7-6/7 weeks onward. CONCLUSION: Growth discordance or SGA is associated with higher absolute risks of stillbirth and neonatal death. However, balancing these two risks, we did not find evidence that the optimal timing of delivery is changed by the presence of growth disorders alone. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018090866.

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.