Serum progesterone, glycosylated hemoglobin and insulin levels with the risk of premature rupture of membranes in gestational diabetes mellitus.

OBJECTIVE: To discuss the correlation between serum progesterone, glycosylated Hemoglobin (HbA1c), and insulin levels in pregnant women with Gestational Diabetes Mellitus (GDM) and the risk of Premature Rupture of Membranes (PROM). METHODS: A retrospective analysis was conducted on 52 patients diagnosed with GDM who also presented with PROM (Observation group) and compared with 89 patients diagnosed with GDM but not complicated with PROM (Control group). Progesterone, insulin, and HbA1c were detected. Risk factors for PROM in GDM patients were analyzed. RESULTS: The observation group had higher HbA1c and fasting blood glucose levels. Poor blood glucose control and GWG are risk factors for PROM in GDM patients. PROM increases adverse pregnancy outcomes in GDM. HbA1c, insulin, and HOMA-IR can predict the risk of PROM in GDM. CONCLUSIONS: The effective prediction of preterm PROM can be achieved through the monitoring of serum HbA1c, insulin levels, and insulin resistance in patients with GDM.

Asociación entre el grado de severidad de la infección por COVID-19 durante el embarazo y la rotura prematura de membranas pretérmino en un hospital nivel III del Perú / Association between the degree of severity of COVID-19 infection during pregnancy and preterm premature rupture of membranes in a level III hospital in Peru

RESUMEN Objetivos. Determinar la asociación entre el grado de severidad de la infección por COVID-19 durante el embarazo y la rotura prematura de membranas pretérmino (RPMP) en un hospital nivel III de Perú. Materiales y Métodos. Estudio transversal, analítico y observacional en mujeres mayores de 18 años con diagnóstico de infección por COVID-19 en el embarazo durante el 2020-2022. Se recogieron variables clínicas y obstétricas. Para el análisis descriptivo se realizaron las pruebas de Chi Cuadrado y exacta de Fisher, y para el análisis multivariado, se calculó la razón de prevalencia mediante regresión de Poisson en modelos crudos y ajustados. Todas las pruebas estadísticas se realizaron considerando un valor de p<0,05 como significativo y con un nivel de confianza de 95%. Resultados. Se analizaron los datos de 163 gestantes con COVID-19, de las cuales el 9,2% tuvieron RPMP, todas fueron casos sintomáticos. Los casos leves de COVID-19 tuvieron 1,10 veces la probabilidad de presentar RPMP (RPa=1,10; IC95%: 1,02−1,18) y los casos moderados/severos tuvieron 1,64 veces esta probabilidad (RPa=1,64; IC95%: 1,43−1,87), en comparación con los casos asintomáticos. Conclusiones. Se identificó que un mayor grado de severidad de la infección por COVID-19 durante el embarazo se asoció a una mayor probabilidad de tener RPMP.

ABSTRACT Objectives. To determine the association between the degree of severity of COVID-19 infection during pregnancy and preterm premature rupture of membranes (PPROM) in a level III hospital in Peru. Materials and Methods. Cross-sectional, analytical and observational study in women older than 18 years diagnosed with COVID-19 infection during pregnancy, between the years 2020 and 2022. Clinical and obstetric variables were collected. The chi-square and Fisher's exact tests were used for the descriptive analysis. For the multivariate analysis, we calculated the prevalence ratio by using Poisson regression in crude and adjusted models. All statistical tests were performed considering a value of p<0.05 as significant and with a confidence level of 95%. Results. We analyzed data from 163 pregnant women with COVID-19, of which 9.2% had PPROM; all were symptomatic cases. Mild COVID-19 cases were 1.10 times more likely to have PPROM (RPa=1.10; 95%CI: 1.02-1.18) and moderate/severe cases were 1.64 times more likely (RPa=1.64; 95%CI: 1.43-1.87), compared to asymptomatic cases. Conclusions. We identified that a higher degree of severity of COVID-19 infection during pregnancy was associated with a higher probability of having PPROM.

Residential greenspace counteracts PM2.5 on the risks of preterm birth subtypes: A multicenter study.

BACKGROUND: The association between residential greenspace and preterm birth (PTB) risk remained inconclusive. The PTB subtypes have been ignored and the effect of co-exposure of PM2.5 on PTB risk is still unclear. OBJECTIVE: To investigate the independent, interactive, and mixed effects of residential greenspace and PM2.5 on the risk of PTB subtypes. METHODS: A total of 19,900 singleton births from 20 hospitals in Shanghai, China, from 2015 to 2017 were included. The Normalized Difference Vegetation Index (NDVI) within 500 m and 1000 m buffers of the maternal residence and a combined geoscience-statistical model-derived PM2.5 and its six components were used as the exposure measures. PTB (<37 completed weeks of gestation) were divided into early PTB (24-33 weeks) vs. late PTB (34-36 weeks) and into spontaneous PTB (sPTB), preterm premature rupture of the fetal membranes (PPROM), and iatrogenic PTB. Multivariable logistic regression models were applied to assess the independent and interactive effects of NDVI and PM2.5 on PTB in each trimester. The quantile g-computation approach was employed to explore the mixture effect of PM2.5 components and greenspace across the pregnancy and to determine the main contributors. RESULTS: Levels of PM2.5 and greenspace were associated with increased [aOR (95%CI) ranging from 1.18 (1.07, 1.30) to 3.36 (2.45, 4.64)] and decreased risks [aORs (95%CI) ranging from 0.64 (0.53, 0.78) to 0.86 (0.73, 0.99)] of PTB subtypes, respectively. At the same PM2.5 level, higher residential greenspace was associated with lower risks, and vice versa. All these associations were more pronounced in late pregnancy. Early PTB and PPROM were the main affected subtypes, and the main drivers in PM2.5 were black carbon and ammonium. CONCLUSIONS: Residential greenspace may mitigate the PTB risks due to PM2.5 exposure during pregnancy.

The role of neutrophils in chorioamnionitis.

Chorioamnionitis, commonly referred to as intrauterine infection or inflammation, is pathologically defined by neutrophil infiltration and inflammation at the maternal-fetal interface. Chorioamnionitis is the common complication during late pregnancy, which lead to a series of serious consequences, such as preterm labor, preterm premature rupture of the fetal membranes, and fetal inflammatory response syndrome. During infection, a large number of neutrophils migrate to the chorio-decidua in response to chemokines. Although neutrophils, a crucial part of innate immune cells, have strong anti-inflammatory properties, over-activating them can harm the body while also eliminating pathogens. This review concentrated on the latest studies on chorioamnionitis-related consequences as well as the function and malfunction of neutrophils. The release of neutrophil extracellular traps, production of reactive oxygen species, and degranulation from neutrophils during intrauterine infection, as well as their pathological roles in complications related to chorioamnionitis, were discussed in detail, offering fresh perspectives on the treatment of chorioamnionitis.

The possibility of diagnosing intrauterine infection by the content of nitrite and non-thiolate nitroso compounds in maternal blood plasma.

The aim of the study is to develop a method for early diagnosis of intrauterine infection (IUI). A study of markers of inflammation in the venous blood of 60 pregnant women was conducted. The study was followed by a retrospective assessment of the outcomes of pregnancies and childbirth. Of these, 33 patients with a gestation period of more than 37 weeks (full-term pregnancy) and, accordingly, 27 patients from whom the blood sample was taken at a period of less than 37 weeks - patients with the threat of premature birth (PB). PB is the main factor contributing to the development of IUI. 27 patients were diagnosed with premature rupture of the membranes (PROM). Of these, 15 are with the threat of PB. 8 of them had a diagnosed IUI. In all cases of diagnosed PROM, including those with IUI, the concentration of nitrite and nontiolate nitroso compounds (NO2-+RNO) in the mother's blood plasma was 2.3±1.2 µM, while normally it does not exceed 0.1 µM (p<0.001). Regardless of the duration of pregnancy. The use of antibiotics in the case of PROM contributed to the normalization of the concentration (NO2-+RNO). Therefore, increasing of this indicator is result of bacterial infection. Indications of other markers of inflammation: the number of leukocytes in venous blood and in a smear of vaginal contents, the level of C-RB did not significantly change in both PROM and IUI (p>0.1). Since the concentration index (NO2-+RNO) increased in almost all cases of PREM, unlike all other clinical and biochemical indicators used in modern medicine, there is an obvious sense of its use for the current monitoring of the health of pregnant women. But it is still impossible to say unequivocally about the possibility of monitoring the fetal health by concentration (NO2-+RNO) in the mother's blood.

Potential Serum Biomarkers Associated with Premature Rupture of Fetal Membranes in the First Trimester.

Premature rupture of the fetal membranes (PROM) is a common and important obstetric complication with increased risk of adverse consequences for both mothers and fetuses. An accurate and timely method to predict the occurrence of PROM is needed for ensuring maternal and fetal safety. Untargeted metabolomics was applied to characterize metabolite profiles related to PROM in early pregnancy. 41 serum samples from pregnant women who developed PROM later in gestation and 106 from healthy pregnant women as a control group, were analyzed. Logistic regression analysis was adjusted to analyze a PROM prediction model in the first trimester. A WISH amniotic cell viability assay was applied to explore the underlying mechanisms involved in PROM, mediated by C8-dihydroceramide used to mimic a potential biomarker (Cer 40:0; O2). Compared with healthy controls, 13 serum metabolites were identified. The prediction model comprising four compounds (Cer 40:0; O2, sphingosine, isohexanal and PC O-38:4) had moderate accuracy to predict PROM events with the maximum area under the curve of a receiver operating characteristics curve of approximately 0.70. Of these four compounds, Cer 40:0; O2 with an 1.81-fold change between PROM and healthy control serum samples was defined as a potential biomarker and inhibited the viability of WISH cells. This study sheds light on predicting PROM in early pregnancy and on understanding the underlying mechanism of PROM. Trial Registration: This study protocol has been registered at www.ClinicalTrials.gov, CT03651934, on 29 August 2018 (prior to recruitment).

Perinatal and neonatal outcomes of women with very early preterm premature rupture of membranes treated via serial transabdominal amnioinfusion and expectant management: Experience of a tertiary referral center in Turkey.

AIM: We compared the outcomes of serial transabdominal amnioinfusion and expectant management on the perinatal and neonatal outcomes of pregnancies complicated with very early preterm premature rupture of membranes (PPROM). METHODS: We retrospectively reviewed the records of patients with very early PPROM admitted to the University of Inonu School of Medicine from 2014 to 2019. All such patients received comprehensive counseling on the possible prognoses; all were offered pregnancy termination, expectant management, and serial transabdominal infusion. RESULTS: Sixty-three women met the inclusion criteria; 36 were assigned to the expectant management group and 27 were assigned to the amnioinfusion group. The median delivery latency and the gestational age at delivery were significantly higher in the amnioinfusion than the expectant management group [35 (11-90), 14 (7-48), p < 0.001; 27.6 (22.1-34.0), 22.3 (19.0-26.5), p < 0.001, respectively]. Serial transabdominal amnioinfusion was associated with significantly less neonatal mortality than expectant management (29.6 vs 83.3%, p < 0.001). Multivariate binary logistic regression showed that the odds of neonatal mortality were 6.12 times higher among neonates in the expectant management group compared to that of the serial transabdominal amnioinfusion group after adjusting for potential confounders. Severe neonatal morbidities were significantly more common in the expectant management group than in the amnioinfusion group (p = 0.011). CONCLUSION: The present study has demonstrated a significant positive effect of serial transabdominal amnioinfusion procedure on latency period and neonatal morbidity and mortality in pregnant women complicated with very early PPROM.

Interleukin-6 bedside test in detecting chorioamnionitis in women with preterm premature rupture of fetal membranes.

OBJECTIVES: About 30-80% of preterm deliveries following preterm premature rupture of fetal membranes (PPROM) are complicated by histological chorioamnionitis. To evaluate the accuracy of Interleukin-6 (IL-6) bedside test in detecting chorioamnionitis in women with PPROM. MATERIAL AND METHODS: One hundred and ten (110) pregnant women with PPROM > 24 and < 34 weeks' gestation, admitted for conservative management were included in this study. Participants were examined on admission using sterile speculum examination for assessment of IL-6 in the cervico-vaginal secretions using the IL-6 bedside test. The IL-6 bedside test was repeated for all participants once termination of pregnancy (TOP) decided. After TOP, placenta, umbilical cord, and fetal membranes samples were examined for histologic detection of chorioamnionitis (gold standard). The histological results were compared with IL-6 bedside test results to evaluate the accuracy of IL-6 bedside test in detecting chorioamnionitis in women with PPROM. RESULTS: The IL-6 bedside test had 98.6% sensitivity, 94.7% specificity, 97.3% positive predictive value (PPV), 97.3% negative predictive value (NPV) and 97.3% overall accuracy in detecting chorioamnionitis. The sensitivity, specificity, NPV and overall accuracy of IL-6 bedside test (98.6%, 94.7%, 97.3%, and 97.3%; respectively) were significantly higher than the clinical and laboratory parameters of chorioamnionitis (65.3%, 57.9%, 46.8%, and 62.7%; respectively) (p = 0.04, 0.02, 0.001 and 0.03; respectively). CONCLUSIONS: The IL-6 bedside test is an accurate, non-invasive bedside test with 98.6% sensitivity, 94.7% specificity, 97.3% PPV, 97.3% NPV, and 97.3% overall accuracy in detecting chorioamnionitis. The IL-6 bedside test had significantly higher sensitivity, specificity, NPV, and overall accuracy than the clinical and laboratory parameters of chorioamnionitis.

Novel regulatory roles of small leucine-rich proteoglycans in remodeling of the uterine cervix in pregnancy.

The cervix undergoes rapid and dramatic shifts in collagen and elastic fiber structure to achieve its disparate physiological roles of competence during pregnancy and compliance during birth. An understanding of the structure-function relationships of collagen and elastic fibers to maintain extracellular matrix (ECM) homeostasis requires an understanding of the mechanisms executed by non-structural ECM molecules. Small-leucine rich proteoglycans (SLRPs) play key functions in biology by affecting collagen fibrillogenesis and regulating enzyme and growth factor bioactivities. In the current study, we evaluated collagen and elastic fiber structure-function relationships in mouse cervices using mice with genetic ablation of decorin and/or biglycan genes as representative of Class I SLRPs, and lumican gene representative of Class II SLRP. We identified structural defects in collagen fibril and elastic fiber organization in nonpregnant mice lacking decorin, or biglycan or lumican with variable resolution of defects noted during pregnancy. The severity of collagen and elastic fiber defects was greater in nonpregnant mice lacking both decorin and biglycan and defects were maintained throughout pregnancy. Loss of biglycan alone reduced tissue extensibility in nonpregnant mice while loss of both decorin and biglycan manifested in decreased rupture stretch in late pregnancy. Collagen cross-link density was similar in the Class I SLRP null mice as compared to wild-type nonpregnant and pregnant controls. A broader range in collagen fibril diameter along with an increase in mean fibril spacing was observed in the mutant mice compared to wild-type controls. Collectively, these findings uncover functional redundancy and hierarchical roles of Class I and Class II SLRPs as key regulators of cervical ECM remodeling in pregnancy. These results expand our understating of the critical role SLRPs play to maintain ECM homeostasis in the cervix.

Home management by remote self-monitoring in intermediate- and high-risk pregnancies: A retrospective study of 400 consecutive women.

INTRODUCTION: Home management in general is considered to improve patient well-being, patient involvement and cost-effectiveness, for obstetric patients as well. But concerns regarding inclusion of intermediate- and high-risk pregnant women are an issue and a limitation for clinical implementation. This retrospective study evaluated the outcome and safety of extended remote self-monitoring of maternal and fetal health in intermediate- and high-risk pregnancies. MATERIAL AND METHODS: The study reports on 400 singleton pregnancies complicated by preterm premature rupture of membranes (PPROM), fetal growth restriction, preeclampsia, gestational diabetes mellitus, high-risk of preeclampsia, or a history of previous fetal or neonatal loss. Remote self-monitoring was performed by pregnant women and included C-reactive protein, non-stress test by cardiotocography, temperature, blood pressure, heart rate, and a questionnaire concerning maternal and fetal wellbeing. Data were transferred to the hospital using a mobile device platform and evaluated by healthcare professionals. In case of non-reassuring registrations, the pregnant women were invited for assessment at the hospital. Primary outcome was perinatal death. Secondary outcomes were other maternal and perinatal complications. RESULTS: No severe maternal complications were observed. Nine fetal or neonatal deaths occurred, all secondary to malformations, severe fetal growth restriction, extreme prematurity or lung hypoplasia in cases of PPROM before 24 weeks. Even in the latter group, fetal and neonatal survival was 78% (18/23) and rose to 97% (60/62) when PPROM occurred after a gestational age 23+6 weeks. None of the fetal or neonatal deaths were attributable to the home-management setting. CONCLUSIONS: Home-monitoring including remote self-monitoring of fetal and maternal well-being in intermediate- and high-risk pregnancies seems to be a safe alternative to inpatient or frequent outpatient care, which sets the stage for a new way of thinking of hospital care. The implementation process included staff training workshops and development of patient enrollment practice with clarification of expectations and responsibilities, which can be crucial to the results.

Can vitamin C and interleukin 6 levels predict preterm premature rupture of membranes: evaluating possibilities in North Indian population.

OBJECTIVE: We aimed to evaluate the relation between plasma ascorbic acid levels and the occurrence of preterm premature rupture of membranes (PPROM) and whether patients with ascorbic acid deficiency have predisposition to microbial invasion, as revealed by serum interleukin-6 (IL-6) levels and confirmed by placental culture sensitivity evaluation. METHODS: This controlled study involved 50 women with PPROM at gestational age between 28 and 36.6 weeks. Fifty patients with uncomplicated pregnancy and intact membranes were observed as control group. Serum ascorbic acid and IL-6 levels were evaluated for PPROM group subjects and controls, matched by their gestational age and body mass index. Repeat samples for IL-6 were taken after 48 hours of admission in PROM group subjects and at the onset of labor in controls. Placental membranes were sent for culture sensitivity evaluation after delivery. RESULTS: The mean plasma level of ascorbic acid was 0.60±0.35 mg/dL and 1.18±0.43 mg/dL in the PPROM and control groups, respectively, showing significant difference. Plasma IL-6 level rose from 18.18±5.94 pg/mL to 34.32±7.31 pg/mL after 48 hours of admission in the PPROM group (P=0.000). Plasma IL-6 level in controls rose from 5.59±4.36 pg/mL at admission to 7.36±3.67 pg/mL at the onset of labor. Membrane culture test results were positive in a total of 40 samples, of which 37 samples were from the PPROM group subjects. CONCLUSION: Vitamin C deficiency, when complemented with elevated serum IL-6 level, can predict susceptibility to PPROM in the third trimester; the risk increases in women with prior history of similar pathology.

Preventing Early-Onset Group B Streptococcus neonatal infection and reducing antibiotic exposure using a rapid PCR test in term prelabour rupture of membranes.

BACKGROUND: How best to target intrapartum antibiotic prophylaxis (IAP) to minimise both Early-Onset Group B Streptococcus (EOGBS) neonatal infection and maternal/fetal antibiotic exposure is uncertain, with both routine-screening and risk-factor approaches available. AIMS: This retrospective cohort study was undertaken to examine the outcomes of a hybrid risk-and-screen approach to EOGBS prevention using GBS polymerase chain reaction (PCR). The target population was women with term prelabour rupture of membranes (TermPROM) having the risk factor of prolonged rupture of membranes (ROM) ≥18 h. MATERIALS AND METHODS: Non-labouring TermPROM women had rapid GBS PCR testing at presentation. GBS screen-positive women proceeded to induction of labour and received IAP. GBS screen-negative women were allowed home to await spontaneous labour and not given IAP regardless of duration of ROM, unless other risk factors developed. For all other women, the risk-factor approach was followed. RESULTS: From 2009 to 2018, there were 20 cases of culture-positive EOGBS, a rate of 0.36/1000 live births (95% CI 0.22-0.56/1000), comparable to other recent reports. Over 2010-2018 when laboratory data were available, 1120 TermPROM women with ROM ≥18 h avoided antibiotics because they were GBS PCR-negative (2.3% of all births, 3.6% of vaginal births) while 338 TermPROM women with ROM <18 h received targeted antibiotics for being GBS-positive. No cases of EOGBS occurred in TermPROM women, those with ROM ≥18 h, or due to protocol-compliance failure. CONCLUSIONS: A hybrid approach involving risk-factor-based IAP and intrapartum GBS PCR screening of non-labouring TermPROM women delivers acceptably low rates of EOGBS while minimising and better targeting antibiotic exposure.

A Comprehensive Integrative Review of the Factors Associated with Spontaneous Preterm Birth, Its Prevention and Prediction, Including Metabolomic Markers / Uma revisão integrativa abrangente dos fatores associados ao parto prematuro espontâneo, sua prevenção e predição, incluindo marcadores metabolômicos

Abstract Pretermbirth is amajormaternal complication that has a great impact on perinatal and neonatal health, with consequences suffered during childhood and adulthood. Little is known about its etiology and development, resulting in poor screening, prediction and preventive methods. The present integrative review discusses the current knowledge regarding some risk factors for preterm birth, the differences between screening and prediction methods, the limitations of some current preventive interventions, the importance of applying standardized concepts for exposures and outcomes, and why it is important to develop more accurate and reproducible methods to predict preterm birth. In addition, the authors introduce the concept of metabolomics and the technology involved in this technique, and discuss about how it has become a promising approach to identify biomarkers for spontaneous preterm birth.

Resumo Parto prematuro é uma complicação obstétrica de grande impacto para saúde perinatal e neonatal, tendo consequências tambémpara a infância e a vida adulta. Pouco se sabe sobre sua etiologia e fatores determinantes, o que limita osmétodos de rastreamento, predição e prevenção. Esta revisão integrativa traz a discussão sobre o conhecimento atual sobre fatores de risco para parto prematuro espontâneo, as diferenças entre métodos de rastreamento e predição, as limitações das atuais intervenções preventivas, a importância de se aplicar conceitos padronizados para exposição e desfecho na investigação de parto prematuro espontâneo, e porque é importante desenvolver métodos precisos e reprodutíveis para predizer o parto prematuro. Por fim, introduzimos o conceito demetabolômica e da tecnologia envolvida nessa técnica, e discutimos como ela tem se mostrado uma abordagem prosmissora para identificar biomarcadores associados ao parto prematuro espontâneo.

Cytokine Changes in Maternal Peripheral Blood Correlate With Time-to-Delivery in Pregnancies Complicated by Premature Prelabor Rupture of the Membranes.

Premature prelabor rupture of the membranes (PPROM) causes one-third of preterm births worldwide and is most likely caused by subclinical intrauterine infection and/or inflammation. We proposed that women with systemic inflammation at the time of PPROM would have shorter latency. Peripheral blood samples were collected from 20 singleton pregnant women with PPROM between 23 ± 1 and 33 ± 6 weeks. The first sample was drawn within 48 hours of admission, followed by weekly blood draws until delivery. Pregnancies complicated with acute chorioamnionitis, preeclampsia, intrauterine growth restriction, obesity, substance abuse, and chronic maternal disease were excluded. Twenty uncomplicated, gestational age-matched pregnancies served as controls. Plasma concentration of 39 cytokines was measured longitudinally using Luminex assays to investigate their value as predictive biomarkers of latency. Women with PPROM exhibited significantly lower plasma concentration of interferon-γ-inducible protein 10-Chemokine (c-x-c motif; IP10/CXCL10), Chemokine (c-x-c motif) Ligand 9 (MIG/CXCL9), Platelet-derived growth factor BB (PDGFbb), and cutaneous T cell-attracting chemokine, also known as CCL27/CCL27 than controls at admission but significantly elevated interleukin (IL)1RA, tumor necrosis factor α, monocyte chemotactic protein-1/CCL2 at delivery compared to admission. Women with PPROM who delivered within 7 days had significantly lower plasma concentration of anti-inflammatory cytokine IL1RA than those with latency periods >7 days. The IL1RA and endotoxin activity in conjunction with clinical parameters results in excellent prediction of latency to delivery (area under the receiver-operating characteristic curve = 0.91). We concluded that higher levels of anti-inflammatory cytokines in women with PPROM were associated with increased latency until delivery, likely due to counterbalancing of proinflammatory load. When used in conjunction with other predictive characteristics of time until delivery, cytokines may further assist clinical decision-making and optimize pregnancy outcomes in women with PPROM.

Biallelic variants in VARS in a family with two siblings with intellectual disability and microcephaly: case report and review of the literature.

Two male siblings ages 15 and 10 yr old had similar features of intellectual disability, developmental delay, severe speech impairment, microcephaly, prematurity, and transient elevation of liver enzymes in infancy. Exome sequencing revealed one novel (c.65C>A; p.Ala22Asp) and one ultra-rare (c.3214T>C; p.Phe1072Leu) predicted damaging missense variant in trans in the gene encoding cytoplasmic valyl-tRNA synthetase (VARS). Biallelic variants in VARS have previously been associated with a neurodevelopmental disorder characterized by microcephaly, seizures, and cortical atrophy (NDMSCA; MIM #617802). Although our patients have no history of seizures or cortical atrophy, we suggest that the biallelic variants in VARS p.Ala22Asp and p.Phe1072Leu in this family are likely pathogenic and associated with NDMSCA, expanding the clinical phenotype of the condition.

Does the use of probiotics in pregnant women with premature rupture of membranes improve the maternal and perinatal outcome? A systematic review / O uso de probióticos em gestantes com rotura prematura de membranas ovulares melhora o desfecho materno e perinatal? Uma revisão sistemática

Introduction: Premature rupture of membranes (PROM) is a condition that affects 8­10% of all pregnancies, and contributes with 20­40% of preterm deliveries. Evidence shows that changes in the vaginal microbiota may also have a favorable impact on the decrease in the prevalence of PROM, and that expectant treatment may be an appropriate approach to reduce morbidity in these cases. Objective: To investigate whether the use of probiotics in pregnant women with premature rupture of ovary membranes improves the maternal and perinatal outcome. Methods: This is a systematic review, developed from articles published between January 2001 and August 2018, which justify the use of probiotics in pregnant women with PROMto improve maternal and perinatal outcome. Results: Some studies have shown a potential role of probiotics in modulating vaginal bacterial communities, reducing rates of cesarean section and PROM, and increasing the latency and weight of newborns in pregnant women with PROM. However, in other studies, there was no confirmation of changes in the vaginal microbiota from the use of oral probiotics. Conclusion: There are benefits in the administration of probiotics to the mother-fetus binomial. However, there are still doubts about routes of administration, choice of strains and period of use. More studies are necessary to settle them.

Introdução: A rotura prematura de membranas ovulares é uma condição que afeta 8­10% de todas as gestações e contribui com 20­40% dos partos prematuros. Evidências mostram que mudanças na microbiota vaginal podem ter impacto favorável na diminuição de sua prevalência, e o tratamento expectante pode ser uma abordagem adequada para reduzir a morbidade nesses casos. Objetivo: Investigar se o uso de probióticos em gestantes com rotura prematura de membranas ovulares melhora o desfecho materno e perinatal. Métodos: Trata-se de uma revisão sistemática desenvolvida com base em artigos publicados no período de janeiro de 2001 a agosto de 2018, que justificam o uso de probióticos em gestantes com rotura prematura de membranas ovulares para melhorar o desfecho materno e perinatal. Resultados: Alguns estudos mostraram potencial atuação dos probióticos em modular comunidades bacterianas vaginais, em reduzir taxas de cesarianas e rotura prematura de membranas ovulares, além de aumentar o período de latência e peso do recém-nascido de gestantes com esse quadro. Porém, em outros trabalhos, não houve confirmação de mudanças na microbiota vaginal pelo uso de probióticos orais. Conclusão: Há benefícios na administração dos probióticos sobre o binômio mãe-feto, contudo ainda há dúvidas sobre vias de administração, sobre escolha das cepas e sobre tempo de uso. Mais estudos precisam ser realizados para dirimi-las.

Visualisation of the insertion of a membrane for the treatment of preterm rupture of fetal membranes using a synthetic model of a pregnant uterus.

Preterm premature rupture of fetal membranes is a leading cause of preterm delivery. Preterm labour can compromise fetal survival, and even if a pregnancy affected by preterm premature rupture of fetal membrane continues, major complications associated with leakage of amniotic fluid and risk of infection can affect the normal development and survival of the baby. There are limited management options for preterm premature rupture of fetal membrane other than delivery of the baby if ascending infection (chorioamnionitis) is suspected. We have previously reported the development and characterisation of an implantable membrane with the aim of using it to occlude the internal os of the cervix, in order to prevent amniotic fluid loss, allow fluid reaccumulation and reduce the risk of chorioamnionitis. For this, an electrospun biocompatible and distensible bilayer membrane was designed with mechanical properties similar to the human amniotic membrane. In this study, we consider the effects of sterilization on the membrane, how to insert the membrane and visualise it using routine clinical methods. To do this, we used e-beam sterilisation and examined the ability of the membrane to adhere to ex vivo human cervical tissues. We also studied its insertion into a custom-synthesised model of a 20-week pregnant uterus and imaged the membrane using ultrasound. Sterilisation produced minor effects on physical and mechanical properties, but these did not affect the capacity of the membrane to be sutured or to provide a fluid barrier. We demonstrated that fibrin glue can successfully adhere the bilayer membrane to cervical tissues. Finally, we demonstrated that the membrane can be inserted through the cervix as well as visualized in place using ultrasound imaging and an endoscope. In summary, we suggest this membrane is a candidate for further development in an appropriate animal model, supported by appropriate imaging, to precede possible future human studies if judged to demonstrate satisfactory safety and efficacy profiles.

Factores maternos que inciden en amenaza de parto pretérmino en adolescentesgestantes del cantón San Jacinto de Yaguachi / Maternal factors that affect thethreat of preterm delivery in pregnantadolescents of San Jacinto deYaguachi canton

Introducción:La amenaza de parto pre término consiste en la presencia de contracciones regulares después de las 20 y antes de las 37 semanas de gestación Objetivo: Determinar los factores maternos que inciden la amenaza de parto pretérmino en las mujeres gestantes que acuden al Hospital Básico de Yaguachi.Métodos:Sé realizo un Estudio cuantitativo, descriptivo, y transversal en el Hospital Básico "Dr. José Cevallos Ruiz", con una muestra de 20 adolescentes de sexo femenino, con el diagnostico amenaza de parto pretérmino, a las que se les aplicó una encuesta que constó con 5 preguntas entre ellas: Edad, educación, domicilio, controles prenatales y patología asociada a su embarazo.Resultados:Predominó el grupo de adolescentes correspondiente a los 17-19 años con un65%, instrucción secundaria el 55%, el 80% de las gestantes residía en la zona rural. En cuanto a los controles prenatales el 60% de las adolescentes asistieron de 1 a 4 controles, y el 50% de las adolescentes presentaron como factor de riesgo para la amenaza de parto pretérmino, la rotura prematura de membranas como patología asociada a su embarazo. Conclusiones:El factor materno que predominó fue la rotura prematura de membranas, sin embargo la infección de vías urinarias y los trastornos hipertensivosdel embarazo, también se encontraron presentes y por ello, la educación prenatal debe ser tomada en gran consideración

Introduction:The threat of preterm birth consists in the presence of regular contractions after 20 and before 37 weeks of gestation. Objective: To determine the maternal factors that affect the threat of preterm delivery in pregnant women who come to the Basic Hospital of YaguachiMethods:Aquantitative, descriptive, and transversal study in the Basic Hospital "Dr. José Cevallos Ruiz ", with a sample of 20 female adolescents, with the diagnostic threat of preterm delivery, to which a survey was applied that consisted of 5 questions including: Age, education, home, prenatal check-ups and associated pathology to your pregnancy.Results:The group of adolescents corresponding to 17-19 years old predominated with 65%, secondary instruction 55%, 80% of pregnant women resided in the rural area. Regarding the prenatal controls, 60% of the adolescents attended from 1 to 4 controls, and 50% of the adolescents presented as a risk factor for the threat of preterm delivery, the premature rupture of the membranes as a pathology associated with their pregnancy.Conclusions:The maternal factor that predominated was the premature rupture of membranes, nevertheless the infection of urinary tract and the hypertensive disorders of pregnancy, were also present and therefore, prenatal education should be taken into great consideration

An extremely rare case of hand prolapse with preterm premature rupture in the membrane of one twin.

The latency in preterm premature rupture of membranes (PPROM) can last for weeks. We describe an extremely rare case of hand prolapse with PPROM that was exposed for 23 days before delivery. The patient had spontaneous PPROM of twin A at 21.4 weeks of gestation with shoulder presentation. The right arm of the fetus eventually protruded out the vagina and the hand was exposed for extended period of time of 23 days until delivery. Daily dressing by applying collagen to dry skin and silicone to keep moisture was done to the protruding hand to prevent dehydration and desquamation of the skin. Prophylactic antibiotics were used and the patient underwent emergent cesarean section due to uncontrolled preterm labor at 25.2 weeks. To the best of our knowledge, this is the first case of hand prolapse of one twin with extended period of latency before delivery.

An extremely rare case of hand prolapse with preterm premature rupture in the membrane of one twin

The latency in preterm premature rupture of membranes (PPROM) can last for weeks. We describe an extremely rare case of hand prolapse with PPROM that was exposed for 23 days before delivery. The patient had spontaneous PPROM of twin A at 21.4 weeks of gestation with shoulder presentation. The right arm of the fetus eventually protruded out the vagina and the hand was exposed for extended period of time of 23 days until delivery. Daily dressing by applying collagen to dry skin and silicone to keep moisture was done to the protruding hand to prevent dehydration and desquamation of the skin. Prophylactic antibiotics were used and the patient underwent emergent cesarean section due to uncontrolled preterm labor at 25.2 weeks. To the best of our knowledge, this is the first case of hand prolapse of one twin with extended period of latency before delivery.