Clinical application of amino-terminal pro-brain natriuretic peptide concentration in amniotic fluid for the prediction of preterm birth in symptomatic women.

BACKGROUND: Preterm birth accounts for 60% to 80% of neonatal mortality. Approximately one-third of preterm births are caused by the spontaneous onset of preterm labor. Nevertheless, 70% to 90% of women diagnosed with preterm labor will not deliver within 7 days. Thus, many women will be unnecessarily treated by preterm labor with risk medications. Better tools are needed to categorize women in preterm labor into high or low risk of preterm delivery. OBJECTIVE: This study aimed to evaluate the amino-terminal pro-brain natriuretic peptide concentration in the amniotic fluid as a prognostic test to predict the risk of delivery within 48 hours or 7 days and before 34 0/7 or 37 0/7 weeks of gestation in women in preterm labor. STUDY DESIGN: A total of 102 pregnant women presenting signs and symptoms of spontaneous preterm birth (22 0/7 to 34 0/7 weeks of gestation) were included. Amniotic fluid was obtained by amniocentesis, and amino-terminal pro-brain natriuretic peptide concentration was measured. Below normal concentration was defined as <0.5 multiples of the median of the standard curve according to gestational age. The risk of preterm delivery was estimated according to normal or lower-than-normal amino-terminal pro-brain natriuretic peptide concentrations. The predictive capacity of the test (below normal amino-terminal pro-brain natriuretic peptide concentration) was evaluated to identify spontaneous preterm birth at 48 hours or 7 days from amniocentesis and less than 34 0/7 or 37 0/7 weeks at delivery. RESULTS: For the outcome delivery within 48 hours, lower-than-normal amino-terminal pro-brain natriuretic peptide concentration had 94.6% sensitivity, 73.8% specificity, 96.0% negative predictive value, 3.61 positive likelihood ratio, and 0.07 negative likelihood ratio. For the outcome delivery within 7 days, the test had 93.9% sensitivity, 88.7% specificity, 94.0% negative predictive value, 8.31 positive likelihood ratio, and 0.07 negative likelihood ratio. For the outcomes of spontaneous preterm birth before 34 0/7 and 37 0/7 weeks of gestation, below normal amino-terminal pro-brain natriuretic peptide concentrations had 80.0% sensitivity, 83.0% specificity, 78.0% negative predictive value, 4.70 positive likelihood ratio, and 0.24 negative likelihood ratio and 64.1% sensitivity, 91.7% specificity, 44.0% negative predictive value, 7.70 positive likelihood ratio, and 0.39 negative likelihood ratio, respectively. CONCLUSION: Among patients in spontaneous preterm labor, the detection of lower-than-normal amino-terminal pro-brain natriuretic peptide concentrations (<0.5 multiples of the median) in amniotic fluid has an excellent predictive capacity to identify those patients at low risk of preterm delivery within 48 hours or 7 days.

Intra-amniotic Candida albicans Infection Treated With Liposomal Amphotericin B With a Successful Neonatal Outcome.

Intra-amniotic infection with Candida species is an uncommon but severe condition with high fetal morbimortality and no established clinical guidelines for its management. We report a Candida albicans intra-amniotic infection diagnosed in a 25-week pregnant woman, successfully treated with high-dose liposomal amphotericin B. Pregnancy was prolonged until 30 weeks, and despite persistently positive Candida cultures in amniotic fluid, a healthy newborn was delivered without evidence of systemic infection. Amphotericin concentration was determined at birth, revealing levels over 30 times higher in mother's and cord blood than in the amniotic fluid, probably explaining the clinical protection despite failure in obtaining fungal clearance.

Eficiencia del entrenamiento simulado del parto vaginal en estudiantes de enfermería/obstetricia / The efficiency of simulated vaginal birth training in nursing/midwifery students

Introducción: la competencia "asistencia del parto vaginal" se adquiere, parcialmente, mediante simulación en estudiantes de enfermería/obstetricia. Sin embargo, no se ha reportado cuantos partos simulados son necesarios para que estos estudiantes adquieran la mínima competencia. Métodos: estudio cuasi experimental que incluyó a todos los alumnos del internado hospitalario en salud de la mujer, en el segundo semestre del año 2020, excluyendo aquellos que hubieran tenido exposición a la simulación o atención clínica de partos vagina-les. Se evaluó una intervención de práctica simulada en la atención del parto normal en tres etapas: 1) texto, 2) video y 3) simulación. Los estudiantes efectúan tres atenciones simuladas, un evaluador ciego evaluó su rendimiento con una pauta de cotejo (máximo 37 puntos) y se midió la satisfacción con una pauta de evaluación validada. Resultados: el rendimiento de los alumnos mejora significativamente (p < 0.001) con la repetición de la simulación (28,3; 34,3 y 36,7 puntos en 1°, 2° y 3° intento). El porcentaje de estudiantes que logra el umbral de mínima competencia es de 6%, 67% y 100 %, en cada repetición (p < 0.001) Conclusiones: en este grupo de estudiantes, tres repeti-ciones de la simulación/debriefing son suficientes para superar el umbral de mínima competencia. Esta información es útil para definir los recursos necesarios en simulación en atención del parto vaginal en estudiantes de enfermería/obstetricia.

Introduction: Vaginal delivery assistance competence is acquired partially by simulation in nursing/midwifery students. However, it has yet to be reported how many simulated deliveries are necessary for these students to develop the minimum competence. Methods: Quasi-experimental study, all the hospital internship in women>s health students were included in the second semester of 2020, excluding those exposed to the simulation or clinical care of vaginal births. A simulated practice intervention in vaginal delivery care in three stages: 1) text, 2) video, and 3) simulation, was evaluated. The students performed three simulations, a blind observer evaluated their performance with a comparison guideline (maximum 37 points), and their satisfaction was measured with a validated evaluation guideline. Results: The performance of the students improve significantly (p <0.001) with the repetition of the simulation (28.3, 34.3, and 36.7 points in the first, second and third attempts). The percentage of students who achieve the minimum proficiency threshold is 6%, 67%, and 100% in each repetition (p <0.001). Conclusions: In this group of students, three repetitions of the simulation/debriefing are sufficient to exceed the threshold of minimum competence. This information is helpful in defining the necessary resources in simulation in vaginal delivery care in nursing/midwifery students.

Increased Circulating Levels of PCSK9 and Pro-Atherogenic Lipoprotein Profile in Pregnant Women with Maternal Supraphysiological Hypercholesterolemia.

Maternal physiological hypercholesterolemia (MPH) occurs during pregnancy to assure fetal development. Some pregnant women develop maternal supraphysiological hypercholesterolemia (MSPH) characterized by increased levels of low-density lipoprotein (LDL). We aim to determine if proprotein convertase subtilisin/kexin type 9 (PCSK9) levels (a protein that regulate the availability of LDL receptor in the cells surface), as well as the composition and function of LDL, are modulated in MSPH women. This study included 122 pregnant women. Maternal total cholesterol (TC), LDL, triglycerides and PCSK9 increased from first (T1) to third trimester (T3) in MPH women. At T3, maternal TC, LDL, PCSK9 and placental abundances of PCSK9 were significantly higher in MPSH compared to MPH. Circulating PCSK9 levels were correlated with LDL at T3. In MSPH women, the levels of lipid peroxidation and oxidized LDL were significantly higher compared to MPH. LDL isolated from MSPH women presented significantly higher triglycerides and ApoB but lower levels of ApoAI compared to MPH. The formation of conjugated dienes was earlier in LDL from MSPH and in endothelial cells incubated with these LDLs; the levels of reactive oxygen species were significantly higher compared to LDL from MPH. We conclude that increased maternal PCSK9 would contribute to the maternal elevated levels of pro-atherogenic LDL in MSPH, which could eventually be related to maternal vascular dysfunction.

Maternal and perinatal outcomes of a venous thromboembolism high-risk cohort using a multidisciplinary treatment approach.

OBJECTIVE: To evaluate the maternal and perinatal outcomes in a cohort of pregnant women at high risk of venous thromboembolism (VTE). METHODS: Women at high risk of VTE were evaluated in a multidisciplinary program using a complete diagnostic workup, and specific prophylactic or therapeutic treatment. RESULTS: Women were considered at high risk of VTE in 57% (85/148) because of prior (75) or current (10) thromboembolism, and in 27% (40/148) of the cases due to adverse obstetric history. Thrombophilia was diagnosed in 57% of the cases (85/148), either in patients with previous thromboembolism (48%, 41/85) or without a history of thrombosis (70%, 44/63). The most common thrombophilia was antiphospholipid syndrome in 34% (29/85) of the cases. Under respective prophylactic or therapeutic treatment, there were no VTE during pregnancy (0%, 0/148), whereas four events occurred during the puerperium (3%, 4/148). An adverse obstetric outcome was present in 5% (7/148) of all pregnancies, with four early spontaneous abortions (3%, 4/148) and three late miscarriages (2%, 3/148). CONCLUSION: Pregnant women at high risk of VTE can be effectively managed using a risk-adapted treatment. Our results support prospective enrollment and a multidisciplinary assessment of VTE in high-risk pregnant women.

The Myometrium in Pregnant Women with Obesity.

Obesity is a worldwide public health problem, affecting at least one-third of pregnant women. One of the main problems of obesity during pregnancy is the resulting high rate of cesarean section. The leading cause of this higher frequency of cesarean sections in obese women, compared with that in nonobese women, is an altered myometrial function that leads to lower frequency and potency of contractions. In this article, the disruptions of myometrial myocytes were reviewed in obese women during pregnancy that may explain the dysfunctional labor. The myometrium of obese women exhibited lower expression of connexin43, a lower function of the oxytocin receptor, and higher activity of the potassium channels. Adipokines, such as leptin, visfatin, and apelin, whose concentrations are higher in obese women, decreased myometrial contractility, perhaps by inhibiting the myometrial RhoA/ROCK pathway. The characteristically higher cholesterol levels of obese women alter myometrial myocyte cell membranes, especially the caveolae, inhibiting oxytocin receptor function, and increasing the K+ channel activity. All these changes in the myometrial cells or their environment decrease myometrial contractility, at least partially explaining the higher rate of cesarean of sections in obese women.

[Epidemiological difference could explain the higher infant mortality in Chile compared with Cuba]. / Diferencias epidemiológicas podrían explicar la mayor mortalidad infantil de Chile comparada con Cuba.

INTRODUCTION: Cuba has the lowest infant mortality rate in Latin America, while Chile has an infant mortality rate above the average of Organization for Economic Cooperation and Development (OECD) countries. OBJECTIVE: To compare the epidemiology of infant mortality between Chile and Cuba in order to find characteristics that may explain the differences found. METHOD: Comparative analysis between Chile and Cuba of infant mortality rate, causes of mortality, live birth weight, and maternal age, in 2015. RESULTS: Cuba had a lower infant, neonatal, early and late mortality than Chile, with no differences in post-neonatal mortality. Chile had a higher infant mortality due to, alterations of the nervous system, urinary system, chromosomal alterations, respiratory distress syndrome, and disorders related to the short duration of gestation. Chile had a higher frequency of mothers ≥ 35 years old and live births weighing <2,500 g. The possible effects of health inequities could not be analyzed due to lack of data. CONCLUSIONS: It is possible to attribute the lower infant mortality rate in Cuba to: selective abortion due to congenital malformations and chromosomal anomalies, lower epidemiological risk of the Cuban pregnant population, and lower frequency of live births with low birth weight.

Enseñanza de la atención del parto vaginal utilizando simuladores / Teaching vaginal delivery care using simulators

La simulación en docencia en ciencias de la salud, permite integrar conocimientos y desarrollar habilidades previo a la práctica clínica, logrando competencias complejas. Además, permite a los estudiantes implementar un cuidado personalizado, pensar críticamente y mejorar la confianza en sus capacidades. Objetivo: evaluar la contribución de la simulación de la atención del parto, en la adquisición de una habilidad esencial para alumnos que optan a desempeñarse en el área obstétrica. Materiales y métodos: se realizó una búsqueda bibliográfica basada en datos PubMed que incluyó las palabras claves simulation, labor y education y sus equivalentes en español. Se excluyeron los títulos relacionados con "anestesia en obstetricia" y "hemorragia postparto". Se revisaron investigaciones observacionales, descriptivos, revisiones narrativas y sistemáticas, ensayos controlados, estudios cuasi experimentales y prospectivos. Resultados: Se seleccionaron 50 artículos que contenían al menos una de las palabras clave y estaban relacionados con "obstetricia" o "parto", logrando acceder a 46 de ellos. La simulación de parto es una estrategia educativa exitosa, que permite a los alumnos sentirse más confiados, mejora el trabajo en equipo, incrementa el grado de conocimiento, mejora habilidades y permite cuidar a las usuarias sin riesgos. Conclusiones: la simulación es un método educativo que permite a los estudiantes practicar lo aprendido en clases antes de iniciar la experiencia clínica, disminuyendo el riesgo de la atención de pacientes por alumnos. Se recomienda el uso de la simulación en la docencia de atención del parto vaginal como una herramienta exitosa que contribuye en la adquisición de habilidades clínicas.(AU)

Simulation in health sciences education allows knowledge integration and skills development before clinical practice,achieving complex skills. Also, simulation enhances students personalized care attitude, think critically and gain confidence. Objective: we aim to attest to the contribution of childbirth simulation in the acquisition of essential proficiency for midwifery students. Materials and methods: we conducted a bibliographic search in the PubMed database, using the keywords: simulation, labor, and education, either in English or Spanish. We excluded articles related to obstetric anesthesia and postpartum hemorrhage. We reviewed observational, descriptive, narrative and systematic reviews, controlled trials, quasi-experimental and prospective studies. Results: we select fifty articles, obtaining access to 46 of them. Childbirth simulation educational strategy, improving student's self-confidence, teamwork, knowledge, clinical skills and lowering patient´s risks. Conclusions: simulation is an educational method that allows students to practice what they have learned in class before starting the clinical experience, decreasing the risk of patient care by students The use of simulation in teaching vaginal delivery care is recommended as a successful tool in the acquisition of clinical skills.(AU)

Recomendaciones para el diagnóstico y manejo de la anemia por déficit de hierro en la mujer embarazada / Recommendations for the diagnosis and management of anemia due to iron deficit in pregnant women

La anemia es una condición altamente prevalente a nivel mundial y, el déficit de hierro, la causa más frecuente, sin excepción; la mujer embarazada está particularmente en riesgo dada la mayor demanda de hierro que la gestación significa. La anemia se asocia a mayor morbilidad y mortalidad materno-perinatal. En mujeres embarazadas sin anemia, la prevención, mediante el uso de multivitamínicos que contienen hierro en dosis de 30-60 mg de hierro elemental, ha demostrado ser efectiva y se recomienda durante todo el embarazo. En casos de anemia, el diagnóstico de déficit de hierro se establece cuando la ferritina es menor a 30 mg/L y/o la saturación de transferrina es menor a 20 por ciento. La severidad de la anemia y la situación temporal en el embarazo, son factores modificantes del tratamiento. En mujeres embarazadas, con hemoglobina ≥9.0 g/dL y que tengan <34 semanas de embarazo, la indicación es tratamiento con hierro oral, en dosis de 100 mg al día, en días alternos, hasta normalizar los parámetros antes mencionados. Si la hemoglobina es <9.0 g/dL, o el embarazo es ≥34 semanas, el uso de hierro intravenoso ha demostrado ser más efectivo en corregir la anemia y el déficit de hierro y en disminuir la morbilidad materno-perinatal. En estos casos, sugerimos el uso del hierro carboximaltosa, dado su perfil de seguridad y efectividad favorable. Recomendamos conocer y practicar estas recomendaciones para el diagnóstico y manejo de la anemia por déficit de hierro durante el embarazo.(AU)

Anemia is a highly prevalent condition worldwide, and iron deficiency the most frequent cause, without exception; pregnant women are particularly at risk given the increased iron demand of gestation. Additionally, anemia directly correlates with increased maternal-perinatal morbidity and mortality. For non-anemic pregnant women, prevention using 30-60mg of elemental iron-containing multivitamins, has proven effective, and is recommended throughout all pregnancy. In the case of anemia, the diagnosis of iron deficiency is established when ferritin is under 30 mg/L or when transferrin saturation is under 20 percent. The severity of the anemia and the time course of pregnancy, are treatment determining factors. Pregnant women, with hemoglobin ≥9.0 g/dL, and <34 weeks-pregnant, are best treated with oral iron, at dose of 100 mg of elemental iron, on alternate days, until all altered parameters are corrected. Otherwise, when hemoglobin is <9.0 g/dL, or pregnancy is ≥34 weeks, intravenous iron has demonstrated to be more effective to normalize anemia, iron deficiency and diminish maternal-perinatal morbidity. In those cases, we suggest the use of carboximaltose iron, due to its favorable safety and efficiency profile. We recommend knowing and practicing these recommendations for the diagnosis and management of iron deficiency anemia during pregnancy.(AU)

El ocaso de los libros de texto como fuente de información entre los estudiantes de medicina / The decline of textbooks as a source of information among Medicine students

Introducción: El proceso de enseñanza de la medicina ha cambiado a través de la historia en la medida que sus estudiantes cambian. Los profesores de medicina se adaptan con dificultades a los nuevos estudiantes y muchas veces no son capaces de reconocer los nuevos intereses de sus propios alumnos. En este contexto resulta importante analizar qué métodos de estudio utilizan los actuales alumnos durante los siete años de la carrera de Medicina. Métodos: Estudio basado en metodología mixta: cualitativa (grupales focales)y cuantitativa (encuestas) aplicadas a alumnos de quinto, sexto o séptimo año de la carrera, médicos recién egresados y docentes activos de la Escuela de Medicina de la Pontificia Universidad Católica. Resultados: Los resultados de nuestro estudio muestran que los métodos de estudio que más utilizan los estudiantes de medicina son: apuntes de clases (1-5 años) y los manuales (internado). Los encuestados creen que los manuales son muy importantes, que facilitan el aprendizaje, que deben estar actualizados y que de preferencia deben estar disponibles en formato digital. Los docentes usaron como método preferente de estudio, durante la carrera de medicina, los libros de texto. Conclusión: Los estudiantes de medicina han cambiado, y así han evolucionado sus técnicas de estudio/ aprendizaje. Es indispensable que los métodos docentes se adapten a estas nuevas características; por lo que es indispensable ayudar a los profesores a modernizar sus técnicas docentes adaptándolas a las necesidades de los alumnos.(AU)

Introduction: The process of teaching medicine has changed throughout history as its students change. The medical professors adapt with difficulties to the new students and many times they are not able to recognize the new interests of its own students. In this context, it is important to analyze what methods of study the current students use during the seven years of the medical career. Methods: This study was based on a mixed methodology: qualitative (focus groups) and quantitative (surveys) applied to students in the fifth, sixth or seventh year of the medical studies, recently graduated doctors and active teachers of the Pontificia Universidad Católica de Chile. Results: The results of our study show that the study methods most used by medical students are: class notes (1-5 years) and handbooks (internship). Respondents believe that handbooks are very important, that they facilitate learning, that they should be up to date and that they should preferably be available in digital format. The teachers used as a preferred method of study, during the medical career, textbooks. Conclusion: Medical students have changed, and so have their study / learning techniques evolved. It is essential that teaching methods adapt to these new characteristics; thus, it is essential to help teachers to modernize their teaching techniques by adapting them to the needs of students.(AU)

Cirugía bariátrica antes del embarazo y su impacto en el resultado perinatal; revisión de la literatura / Bariatric surgery before pregnancy and its impact on the perinatal outcome; literature review

La obesidad en mujeres embarazadas se asocia a mal resultado materno y perinatal. El tratamiento de la obesidad, especialmente obesidad mórbida, es complejo, muchas veces requiere del apoyo de técnicas quirúrgicas. La cirugía bariátrica es una solución eficiente para la obesidad al lograr pérdida de peso sostenida en el tiempo, lo que podría ayudar a disminuir las complicaciones asociadas a la obesidad durante el embarazo. En este trabajo presentamos realizar una revisión narrativa de la literatura científica respecto a los efectos de la cirugía bariátrica en los resultados maternos y perinatales. La evidencia actual muestra que la cirugía bariátrica disminuye significativamente complicaciones como: diabetes pregestacional, diabetes gestacional, síndrome hipertensivo del embarazo, preeclampsia y macrosomía fetal, sin producir cambios en la mortalidad perinatal. Sin embargo, la cirugía bariátrica se asocia a mayor frecuencia de recién nacidos pequeños para edad gestacional, parto prematuro y complicaciones quirúrgicas no obstétricas de la cirugía bariátrica. No se ha demostrado un efecto benéfico de la cirugía bariátrica en reducir la tasa de malformaciones congénitas y la frecuencia de operación cesárea. Concluimos que la cirugía bariátrica es recomendable en mujeres en edad reproductiva que desean embarazo, pues reduce las complicaciones asociadas a la obesidad mórbida durante el embarazo, reconociendo que la calidad de la evidencia es baja al sustentarse principalmente en estudios retrospectivos o reportes de casos. (AU)

Obesity in pregnant women is associated with adverse maternal and fetal outcome. Treatment of obesity often need support of surgical procedures. Bariatric surgery is an efficient alternative to lose weight, wich could help reduce complications associated with obesity in pregnant women. In this work we present a review of the scientific literature about the effect of bariatric surgery in fetal and maternal outcomes. We found that there is enought evidence to support that bariatric surgery decreases gestational diabetes, hipertensive disorders, preeclampsia and macrosomia, without changes in perinatal mortality. Nevertheless, bariatric surgery is associated with elevated frecuency of new born small for gestational age, preterm birth and non-obstetric surgical complications of bariatric surgery. There is no evidence to support a decrease in incidence of congenital malformations and frecuency of cesarean delivery. We conclude that bariatric surgery is advisable for women who want to become pregnant, because it reduces the complications associated with obesity in pregnancy. We also recognize that the quality of evidence is poor because it is based on retrospectives studies or case reports. (AU)

Docosahexaenoic acid supplementation early in pregnancy may prevent deep placentation disorders.

Uteroplacental ischemia may cause preterm birth, either due to preterm labor, preterm premature rupture of membranes, or medical indication (in the presence of preeclampsia or fetal growth restriction). Uteroplacental ischemia is the product of defective deep placentation, a failure of invasion, and transformation of the spiral arteries by the trophoblast. The failure of normal placentation generates a series of clinical abnormalities nowadays called "deep placentation disorders"; they include preeclampsia, fetal growth restriction, preterm labor, preterm premature rupture of membranes, in utero fetal death, and placental abruption. Early reports suggested that a LC-PUFAs (long chain polyunsaturated fatty acids) rich diet reduces the incidence of deep placentation disorders. Recent randomized controlled trials are inconsistent to show the benefit of docosahexaenoic acid (DHA) supplementation during pregnancy to prevent deep placentation disorders, but most of them showed that DHA supplementation was associated with lower risk of early preterm birth. We postulate that DHA supplementation, early in pregnancy, may reduce the incidence of deep placentation disorders. If our hypothesis is correct, DHA supplementation, early in pregnancy, will become a safe and effective strategy for primary prevention of highly relevant pregnancy diseases, such as preterm birth, preeclampsia, and fetal growth restriction.

[Women age as a risk factor for maternal, fetal, neonatal and infant mortality]. / La edad de la mujer como factor de riesgo de mortalidad materna, fetal, neonatal e infantil.

BACKGROUND: Adolescent pregnancy and advanced maternal age are associated with increased risk for maternal, perinatal and infant death. However, the maternal age with the lowest reproductive risk has not been established. AIM: To determine the range of maternal age with the lowest reproductive risk. MATERIAL AND METHODS: A population-based study (2005-2010) was performed analyzing raw data from vital statistics yearbooks of the National Institute of Statistics of Chile. The association of maternal, fetal, neonatal and infant mortality with maternal age was analyzed. The latter was stratified in quinquenniums, between ages 10 and 54 years. Maternal, fetal, neonatal and infant mortality rates were calculated for each quinquennium. The lowest rate was selected as a control group for risk analysis, which was estimated according to Odds Ratio with 95% confidence intervals. RESULTS: Women of 20-29, 25-34 and under 30 years, had the lowest rate of fetal, neonatal/infant and maternal death, respectively. Women aged 45-49 years had the higher rate of maternal, fetal, neonatal and infant mortality. The risk of fetal, neonatal and infant mortality doubled from 40-44 years onwards, and maternal mortality from the age of 30-34 years. CONCLUSIONS: Our results suggest that the maternal age range with the lesser general reproductive risk is between 20-29 years. This finding should be considered in future studies of reproductive risk and for an appropriate counseling about conception.

La edad de la mujer como factor de riesgo de mortalidad materna, fetal, neonatal e infantil / Women age as a risk factor for maternal, fetal, neonatal and infant mortality

Background: Adolescent pregnancy and advanced maternal age are associated with increased risk for maternal, perinatal and infant death. However, the maternal age with the lowest reproductive risk has not been established. Aim: To determine the range of maternal age with the lowest reproductive risk. Material and Methods: A population-based study (2005-2010) was performed analyzing raw data from vital statistics yearbooks of the National Institute of Statistics of Chile. The association of maternal, fetal, neonatal and infant mortality with maternal age was analyzed. The latter was stratified in quinquenniums, between ages 10 and 54 years. Maternal, fetal, neonatal and infant mortality rates were calculated for each quinquennium. The lowest rate was selected as a control group for risk analysis, which was estimated according to Odds Ratio with 95% confidence intervals. Results: Women of 20-29, 25-34 and under 30 years, had the lowest rate of fetal, neonatal/infant and maternal death, respectively. Women aged 45-49 years had the higher rate of maternal, fetal, neonatal and infant mortality. The risk of fetal, neonatal and infant mortality doubled from 40-44 years onwards, and maternal mortality from the age of 30-34 years. Conclusions: Our results suggest that the maternal age range with the lesser general reproductive risk is between 20-29 years. This finding should be considered in future studies of reproductive risk and for an appropriate counseling about conception.

The role of brain natriuretic peptide in maintaining myometrial quiescence during pregnancy.

Myometrial quiescence is a physiological stage of the myometrium during pregnancy. It is a period of active relaxation of the myometrial smooth muscle cells; myometrial quiescence is responsible for maintaining pregnancy. The precise mechanisms underlying myometrial quiescence have not been completely elucidated, although many mediators and cellular pathways have been described as playing a role. Fetal membranes (chorion and amnion) produce and release one or more substances that inhibit myometrial contractions, playing a central role in the maintenance of myometrial quiescence. Brain natriuretic peptide (BNP) is more potent than any other natriuretic peptide in inhibiting myometrial contractions in vitro. Brain natriuretic peptide is produced by the chorion and amnion, mainly during myometrial quiescence, and decreasing towards the end of pregnancy. Production of BNP is reduced in fetal membranes obtained from women in preterm labour. It is postulated that BNP, acting in a paracrine fashion, plays a key role in the maintaining myometrial quiescence and, therefore, controlling the duration of pregnancy. Furthermore, it is postulated that a premature decrease of BNP production by the fetal membranes may cause preterm labour and preterm birth.

Uso de hipoglicemiantes orales durante la lactancia / Use of oral hypoglycemic agents during breastfeeding

Antecedentes: Los hipoglicemiantes orales son una alternativa emergente en el tratamiento de la diabetes mellitus gestacional (DMG), pero existe poca información acerca de su uso durante la lactancia. Objetivo: Revisar la evidencia respecto a la seguridad del uso de los hipoglicemiantes orales durante la lactancia. Resultados: Encontramos 3 trabajos que evaluaron el paso de metformina a la leche materna: hubo traspaso de metformina a leche materna en todos los casos. La concentración de metformina excretada a la leche fue en promedio 48 por ciento de la concentración plasmática materna. Las dosis calculadas que recibieron los lactantes en promedio fue 0,38 por ciento de la dosis materna, ajustada por peso. La concentración promedio de metformina en los lactantes fue de 0,025 mg/L. No se reportaron efectos adversos en los lactantes, incluso en el seguimiento a 6 meses de vida. Se encontró sólo un trabajo en relación a glibenclamida y lactancia materna, en el que no se detectó excreción del fármaco a la leche materna. Conclusiones: Los hipoglicemiantes orales parecen ser medicamentos seguros durante la lactancia, sin embargo, la evidencia es escasa. Sugerimos el uso de la glibenclamida por sobre metformina, por su nulo paso a la leche materna.

Background: Oral hypoglycemic agents are an emergent therapy for the treatment of gestational diabetes mellitus (GDM), but there is little information about its use during breastfeeding. Objectives: To review the available evidence regarding the use and safety of oral hypoglycemic agents during breastfeeding. Results: We found 3 studies that described the transfer of metformin to breast milk; there was transfer of metformin to breast milk in all cases. The concentration of metformin in breast milk was 48 percent of the maternal plasma concentration. The calculated dose for the infants was 0.38 percent of the maternal weight adjusted dose. The mean concentration of metformin in the infant's plasma was 0.025 mg/L. No adverse effects were reported in the infants, including 6 months of follow-up. Only one study investigated glyburide and breastfeeding, showing no excretion to breast milk. Conclusion: Oral hypoglycemic agents seem to be safe during breastfeeding; however, the available data is scarce. We suggest the use of glyburide over metformin because of its null excretion to breast milk.

Isoform α of PKC may contribute to the maintenance of pregnancy myometrial quiescence in humans.

We postulate that protein kinase C α (PKCα) may contribute to the maintenance of pregnancy myometrial quiescence in humans. We studied the changes in myometrial PKCα gene products (messenger RNA [mRNA] and protein) in 4 groups of women: preterm not in labor (PT-NL), preterm in labor (PT-L), term not in labor (T-NL), and term in labor (T-L). The degree of PKCα activation was studied by comparing the levels of particulate (active) PKCα with the total PKCα protein levels and by measuring PKCα activity in the cytosolic and particulate fractions. Protein kinase Cα abundance (mRNA and protein) did not increase during myometrial quiescence (PT-NL), whereas the level of PKCα activity significantly increased during quiescence. The activity of PKCα significantly decreased in the T-NL, T-L, and PT-L groups. These findings suggest that PKCα plays a significant role in the maintenance of myometrial quiescence and that PKCα activity must decrease at the end of pregnancy allowing myometrial activation. Additionally, our data demonstrate an association between reduced PKCα activity and preterm labor, which merits further investigation.

Mechanical stretch increases brain natriuretic peptide production and secretion in the human fetal membranes.

Brain natriuretic peptide (BNP) is synthesized by human fetal membranes, both the amnion and chorion. This locally produced BNP inhibits the contraction of the human myometrium, contributing to the maintenance of myometrial quiescence during pregnancy. We tested the hypothesis that BNP production is increased by fetal membrane stretching, which is predicted to occur in the expanding uterus, and inhibited by epidermal growth factor (EGF), whose production in the fetal membranes increases in late pregnancy. Term fetal membranes were obtained during elective cesarean delivery before labor. Sections of membranes were placed in an isolated chamber containing DMEM: F12 medium (37°C) and stretched with a 35 g weight. Medium and tissue samples were collected at 0, 3, 6, 18, and 24 hours for measurement of messenger RNA (mRNA) and BNP levels in the presence/absence of EGF (2 × 10(-9 )mol/L). Inducible nitric oxide synthase (iNOS) and ß-actin were also evaluated to discard a nonspecific effect of mechanical stretch on protein expression. We found that amnion and chorion stretching increased the BNP mRNA (reverse transcription-polymerase chain reaction [RT-PCR]) and protein (radioimmunosorbent assay [RIA]) levels from 18 hours onward. The effect of stretching was inhibited by EGF (2 × 10(-9) mol/L). Stretch did not increase iNOS or ß-actin protein levels. We concluded that chorion and amnion stretching may increase BNP expression in the fetal membranes during pregnancy, while increasing biological activity of EGF may decrease BNP production in the chorion and amnion late in pregnancy. We postulate BNP is an important regulator of myometrial contractility during pregnancy, and its production is modulated by both stretch and progressive increase in EGF levels during pregnancy.