Efectos demográficos, clínicos y biológicos de la postergación de la maternidad / Demographic, clinical, and biological effects of delayed maternity

En el presente artículo se analizan los efectos de la postergación de la maternidad en tres ámbitos: i) demográfico, ii) clínico y iii) biológico. Desde luego, la literatura demográfica existente procede fundamentalmente de países con un buen grado de desarrollo, pero se ha realizado un esfuerzo por reunir la mayor cantidad de datos de países en desarrollo. Así se analiza la situación en Europa, EE.UU. y Latinoamérica para finalizar esta sección con la realidad específica en Chile. Desde el punto de vista clínico, se pone especial interés en los cambios que experimenta la probabilidad de embarazo por ciclo (definida como fecundabilidad) y la fertilidad en general. En los aspectos perinatológicos se enfatiza el incremento de frecuencia de la muerte fetal in útero temprana (aborto espontáneo) y tardía con especial mención de algunas patologías (frecuencia del síndrome de Down y otros). Se establece además la frecuencia significativamente mayor de bajo y muy bajo peso de nacimiento, necesidad de hospitalización del recién nacido (morbilidad perinatal) así como el efecto sobre la mortalidad neonatal.Biológicamente la postergación de la maternidad tiene su correlato en la pérdida de reserva ovárica y la disminución de la calidad ovocitaria que involucra un aumento en la incidencia de fallas de fecundación y embriones con bajo potencial de desarrollo y aneuploidías dependientes fundamentalmente de la edad materna. También se hace mención a algunos aspectos del envejecimiento uterino y sus consecuencias en el desarrollo y función placentaria. El enfoque se centra fundamentalmente en la mujer, pero incluye aspectos de la contribución masculina a esta temática.

This article analyzes the effects of the postponement of maternity in three areas: i) demographic, ii) clinical and perinatological and iii) biological. Of course, the existing demographic literature comes primarily from well-developed countries, but an effort has been made to collect as much data from developing countries. The situation in Europe, the U.S. and Latin America is analyzed to end this section with the specific reality in Chile. From the clinical point of view, special interest is placed on changes in the probability of pregnancy by cycle (defined as fecundability) and fertility in general. In the perinatological aspects, the increased frequency of early fetal death (spontaneous abortion) and stillbirth is emphasized, with special mention of some pathologies (frequency of Down syndrome and others). It is also stressed the significant higher frequency of low and very low birth weight, the need newborn hospitalization (perinatal morbidity), as well as the effects on neonatal mortality. Biologically, the postponement of maternity has its correlation in the loss of ovarian reserve and the decrease in oocyte quality that involves an increased incidence of fertilization failure and embryos with low potential for development and aneuploidies, mainly dependent on maternal age. Some aspects of uterine aging and its consequences on placental development and function are also mentioned. The discussion is mainly focused on women, but includes some aspects of the male contribution to this issue

Niveles socioeconómicos bajo y medio bajo comienzan a postergar la maternidad en Santiago de Chile / Delayed child bearing in a Chilean public hospital

Background: Postponement of motherhood is one of the most striking sociodemographic changes of modernity. Aim: To evaluate the age of primiparous women giving birth at a public hospital in Santiago, Chile. Material and Methods: Retrospective study, assessing the age and nationality of all women whose delivery occurred between 2009 and 2017 in a single hospital. Results: A total of 49,254 deliveries were registered: 43% were in primiparous women (73% Chilean and 27% foreign women). The proportion of foreign women increased from 12% in 2009 to more than 60% of total deliveries in 2017. Four percent of primiparous women were aged over 35 years of age and there was a steady increase in the age increase of primiparous women in the nine years of study. There was a higher proportion of normal-weight newborns among foreign women compared to their Chilean counterparts (86 and 81% respectively). Conclusions: In this sample of women attended at a public hospital, a steady increase in the age at first delivery was noted in a period of nine years. There was also a constant increase in the proportion of foreign women giving birth.

Método de clasificación de mortinatos según condición obstétrica relevante de la muerte fetal, en un hospital público de Chile (Método CORM) / A new fetal death classification system

Background: Stillbirth is the mayor contributor to perinatal mortality. Aim: To report a system for classification of fetal deaths. Material and Methods: Retrospective cohort study of 29,916 births with 258 fetal deaths that occurred in a public hospital. Data were obtained from audit reports of stillbirths. The method for classification “obstetric condition relevant to the death” was applied, based on obstetric and placental pathological findings analyzed exclusively by a single obstetrician and a single pathologist. Results: Ninety two percent of obstetric conditions causing fetal death were identified. The most commonly reported were ascending bacterial infection in 26%, congenital anomalies in 19%, arterial hypertension in 12% and placental pathology in 12%. Fetal growth restriction was identified in 50% of stillbirths. Ninety percent were secondary to a primary obstetric condition and 10% had an unexplained cause. Placental abruption as the final cause of fetal death was identified in 60% of cases with arterial hypertension, 43% of cases with placental pathology and 37% of ascending infections. Fetal deaths occurred during pregnancy in 82% of cases and during labor in 17%. Intrapartum asphyxia occurred in 0.8% of stillbirths and presented in term pregnancies. Conclusions: The “obstetric condition relevant to the death” method for classification of fetal death is effective to identify the originating obstetric cause of stillbirth and reduces the impact of fetal growth restriction and intrapartum asphyxia as the leading causes of death.

Obesidad, factor de riesgo de infección bacteriana ascendente durante el embarazo / Obesity, a risk factor for ascending bacterial infection during pregnancy

Background: Obesity in pregnancy is associated with significantly higher rates of infection. Aim: To compare the infectious morbidity in pregnant women with normal and altered body mass index (BMI). Material and Methods: Cross sectional retrospective study of 6,150 patients who had delivery or second trimester abortion during 2012. The patients were classified according to BMI as underweight, normal weight, overweight and obese. We compared the frequency of pregnancy and perinatal complications related to ascending bacterial infection (ABI). The data was obtained from the hospital’s databases. Results: Obese patients had higher rates of pregnancy and perinatal complications related to ABI compared to patients with normal weight. The odds ratios (OR) and 95% confidence intervals (CI) for second trimester abortion were 3.45 (1.63-7.31) p < 0.01, for preterm delivery 2.42 (1.51-3.87) p < 0.01, for labor and puerperium infections 3.42 (2.06-5.68) p < 0.01 and for early neonatal infectious and perinatal mortality 4.46 (1.75-11.37) p < 0.01. A logistic regression analysis revealed that obesity is an independent risk factor for second trimester abortion related to ABI with an OR of 3.18 (CI 95% 1.46-6.91), premature delivery related to ABI with an OR of 2.51 (CI 95% 1.54-4.09) and for delivery and postpartum infections with an OR of 4.44 (CI 95% 2.62 to 7.51). Conclusions: Obese pregnant women had a 2.5 to 4.5 times increased risk of infectious morbidity compared to normal weight patients. Obesity is an independent risk factor for second trimester abortion and preterm delivery related to ABI and delivery and postpartum infectious.

Differential expression of upstream stimulatory factor (USF) 2 variants in eutopic endometria from women with endometriosis: estradiol regulation

BACKGROUND: Endometriosis, pro-inflammatory and invasive benign disease estrogen dependent, abnormally express in endometria the enzyme P450Arom, positively regulated by steroid factor-1 (SF-1). Our objective was to study the nuclear protein contents of upstream stimulating factor 2 (USF2a and USF2b), a positive regulator of SF-1, throughout the menstrual cycle in eutopic endometria from women with and without (control) endometriosis and the involvement of nuclear estrogen receptors (ER) and G-coupled protein estrogen receptor (GPER)-1. RESULTS: Upstream stimulating factor 2 protein contents were higher in mid (USF2b) and late (USF2a and USF2b) secretory phase in eutopic endometria from endometriosis than control (p < 0.05). In isolated control epithelial cells incubated with E2 and PGE2, to resemble the endometriosis condition, the data showed: (a) significant increase of USF2a and USF2b nuclear protein contents when treated with E2, PPT (specific agonist for ERa) or G1 (specific agonist for GPER1); (b) no increase in USF2 binding to SF-1 E-Box/DNA consensus sequence in E2-treated cells; (c) USF2 variants protein contents were not modified by PGE2; (d) SF-1 nuclear protein content was significantly higher than basal when treated with PGE2, E2 or G1, stimulation unaffected by ICI (nuclear ER antagonist); and (e) increased (p < 0.05) cytosolic protein contents of P450Arom when treated with PGE2, E2, PPT or G1 compared to basal, effect that was additive with E2 + PGE2 together. Nevertheless, in endometriosis cells, the high USF2, SF-1 and P450Arom protein contents in basal condition were unmodified. CONCLUSION: These data strongly suggest that USF2 variants and P450Arom are regulated by E2 through ERa and GPER1, whereas SF-1 through GPER1, visualized by the response of the cells obtained from control endometria, being unaffected the endogenously stimulated cells from endometriosis origin. The lack of E2 stimulation on USF2/SF-1 E-Box/DNA-sequence binding and the absence of PGE2 effect on USF2 variants opposite to the strong induction that they exert on SF1 and P450 proteins suggest different mechanisms and indirect regulations. The sustained USF2 variants protein expression during the secretory phase in eutopic endometria from women with endometriosis may participate in the pathophysiology of this disease strongly associated with infertility and its characteristic endometrial invasion to ectopic sites in the pelvic cavity.

Prevalencia de la endometriosis en mujeres sometidas a esterilización quirúrgica laparoscópica en un hospital de Santiago de Chile / Prevalence of endometriosis in 287 women undergoing surgical sterilization in Santiago Chile

Background: The clinical manifestations of endometriosis are infertility, dysmenorrhea, sexuality disturbances, and chronic pelvic pain. It is the cause of 30 to 50% of infertility cases. In developed countries, the prevalence of endometriosis among women undergoing surgical sterilization is approximately 6%. Aim: To determine the prevalence of endometriosis among women with proven fertility in Santiago de Chile. Material and Methods: Review of surgical protocols of 287 women aged 25 to 49 years, subjected to a surgical sterilization between 2007 and 2011. Results: Endometriosis was found in 14 of the 287 women (4.9%). In spite of being asymptomatic, five of the 14 women with endometriosis were classified as severe, due to the presence of at least one endometrioma. In order of frequency, the most commonly affected anatomical sites were the ovary, the peritoneum, the posterior cul-de-sac and uterosacral ligaments. Conclusions: Our findings are very similar to those found elsewhere and suggest that fertile women could better tolerate endometriosis than their infertile counterparts.

El hábito de fumar se asocia a baja concentración plasmática de hormona antimülleriana en mujeres infértiles / Effects of smoking on plasma antimüllerian hormone concentrations among infertile women

Background: Smoking may hamperfemale fertility, probably modifying ovarian reserve. Antimüllerian hormone (AMH) is an accurate marker for ovarian reserve. Aim: To look for an association between smoking status and plasma AMH concentration. Patients and Methods: A cohort of 141 infertile women in a university setting in Santiago, Chile was studied. Demographic and smoking data, including the number of cigarettes smoked during the last week, were collected. A blood sample was obtained and kept frozen until determination of AMH by ELISA and follicle stimulating hormone (FSH) and estradiol at day three of the menstrual cycle, by radioimmunoanalysis. Results: Thirty two participants smoked (23%). There were no significant differences in age, parity, body mass index, causes of infertility and day three FSH and estradiol between smokers and nonsmokers. According to a regression analysis, there was a significant decrease in AMH concentration with age and active cigarette smoking. A drop in AMH of -0.189 ng/mL with a unitary change in age and a decrease of -2.29 ng/mL when everything else remains constant, except the smoking status, were established (p < 0.001 and r2 = 0.134). However, no dose response was observed when the number of cigarettes smoked during the last week were introduced in the model. Furthermore, no significant association ofplasma AMH with day three plasma FSH and estradiol concentrations was observed. Conclusions: Cigarette smoking is associated with decreased AMHplasma concentrations among infertile women. However there was no dose response relationship. The mechanisms underlying this association are unknown and further investigation is required.

Factores asociados con el parto prematuro entre 22 y 34 semanas en un hospital público de Santiago / Risk factors for preterm deliveries in a public hospital

Background: Preterm births are responsible for 75 to 80% of perinatal mortality. Aim: To determine the factors associated with preterm births, using maternal clinical data, laboratory results and pathological placental findings. Patients and Methods: Retrospective study of 642 preterm single births at 22-34 weeks' gestation. Four hundred and seven cases with pathological placental studies were included. Births were subdivided into preterm births as a consequence of a medical indication and spontaneous births with or without premature rupture of membranes (PROM). Risk factors for preterm births were classified as maternal, fetal, placental, indeterminable and unclassifiable. Results: The proportions of preterm births were spontaneous 69% (with PROM 27% and with intact membranes 42%) and medically indicated births 31%. A risk factor associated with prematurity was identified in 98 and 85% of medically indicated and spontaneous births, respectively. Ascending bacterial infection (ABI) was the most frequently associated factor with spontaneous preterm delivery in 51% of women (142/280, p < 0.01) and with preterm births of less than 30 weeks in 52% of women (82/157, p < 0.01). Vaginal or urinary infection with Group B Streptococcus, was the most common clinical condition associated with ABI related deliveries. Hypertension was present in 94 of 127 medically indicated preterm deliveries (preeclampsia in 62% and chronic hypertension in 12%), and in 29% (preeclampsia 24%) of preterm births of more than 30 weeks. Congenital anomalies were mainly associated with a maternal age over 35 years in 15% (14/92) of women. The frequency of placental diseases was higher in spontaneous preterm deliveries (14%) and in pregnancies of more than 30 weeks in (14%). Conclusions: ABI was the most common factor associated with spontaneous preterm births at 2234 weeks, while preeclampsia is the most common factor associated with medically indicated preterm births.

Postergación de la maternidad en Chile: Una realidad oculta / Association between motherhood postponement and socioeconomic status

Background: Delayed motherhood is a common phenomenon in the developed world, where the age at frst delivery is around 30 years. In Chile the National Institute of Statistics established that this age has remained around 23 years for more than two decades. Motherhood postponement may be modulated by socioeconomic status. Aim: To determine whether the age at frst delivery is higher in a private clinic compared to a public hospital. Patients and Methods: Two cohorts of primiparous women delivering in 1998 and 2008 in the public hospital San Borja Arriarán (HSBA) and a private setting Clínica Las Condes (CLC), were analyzed. Results: The age of all delivering women was significantly lower in HSBA than in CLC in both study periods (26.3 ± 0.8 and 25.7 ± 0.9 compared to 31.6 ± 0.1 and 32.7 ± 0.1 years, respectively). Likewise, the frequency of adolescent pregnancy was significantly higher in HSBA than CLC in both study periods (38.8 and 42.2 percent compared to 1.7 and 1.6 percent respectively). The age at frst delivery was significantly lower in both periods in HSBA (21.8 and 21.3 years compared to 28.6 and 30.6 years, respectively). Excluding primiparous women of less than 20 years, the difference in age was smaller, but remained still significant (24.6 and 24.2 versus 29.9 and 31.0 years, respectively). Conclusions: In Santiago, the postponement of motherhood is more marked among women of high socioeconomic status.

Relación entre enfermedad periodontal, infección bacteriana ascendente y patología placentaria con parto prematuro / Relationship between periodontal diseases and ascending bacterial infection with preterm delivery

Background: There is an association between periodontal diseases and preterm delivery. Aim: To assess the relationship between periodontal diseases, ascending bacterial infection and placental pathology with preterm delivery. Patients and methods: A periodontal examination and collection of amniotic fluid and subgingival plaque samples were performed in women with preterm labor with intact membranes, without an evident clinical cause or preterm premature rupture of membranes, without clinical chorioamnionitis or labor and a gestational age between 24 and 34 weeks. Microbial invasion of the amniotic cavity was defined as the presence of a positive amniotic fluid culture. Cervicovaginal infection was defined as a bacterial vaginosis or positive culture of cervix or vagina with a high neutrophil count. Ascending bacterial infection was diagnosed as the microbial invasion of the amniotic cavity by ascending bacteria or cervicovaginal infection. Corioamnionitis, funisitis or vellositis were diagnosed. Results: Fifty-nine women were included: fortytwowith preterm labor with intact membranes and seventeen with preterm premature rupture of membranes. The prevalence of periodontal diseases was 93.2%. Microbial invasion of the amniotic fluid was detected in 27.1% of patients. Periodontal pathogenic bacteria were isolated in 18.6% of amniotic fluid samples and 71.2% of subgingival plaque samples. The prevalence of ascending bacterial infection was 83.1% and in 72.9% of women it was associated with periodontal disease. Preterm delivery (<37 weeks) occurred in 64.4% of patients and was significantly associated with generalized periodontal disease and with the association of ascending bacterial infection and periodontal diseases. Patients with preterm delivery and generalized periodontal disease had a higher frequency of chorioamnionitis and funisitis...

Los priones, un nuevo desafío evolutivo / Prions: a new evolutionary defiance

El objetivo de esta reseña es actualizar información ya publicada sobre los priones y las patologías que éstos transmiten. La existencia de una nueva variante de la enfermedad de Creutzfeld-Jakob y la confirmación experimental de que es causada por la misma cepa de priones que la encefalopatía espongiforme bovina (BSE), ha incrementado dramáticamente la necesidad de una precisa comprensión de las bases moleculares de la propagación priónica. El agente infeccioso es una proteína cuya conformación se encuentra alterada, que se reproduce a sí misma convirtiendo una proteína normal en una proteína con conformación priónica. La observación de que los priones se replican en los órganos linfoides en estadios muy tempranos de la infección lleva a cuestionar sobre cuáles son los requerimientos de tipo celular a ser infectado en el sistema linforreticular. Las células dendríticas foliculares serían el sitio de elección para la replicación y el reservorio de priores. El diagnóstico de las enfermedades producidas por priones presenta una serie de problemas debido a las peculiaridades de este tipo de patologías. Considerando que los priones se replican en el sistema linforreticular y posteriormente migran al sistema nervioso central, existe un lapso durante el cual podría propagarse este agente infeccioso por medio de la sangre, sus componentes o sus derivados. De esta forma representaría una nueva patología con la potencial capacidad de transmisión transfusional. Esta nueva forma de herencia independiente de los ácidos nucleicos obliga a replantear el axioma de transferencia de la información genética, hasta el momento, y con concordancia con la teoría evolutiva de Darwin, sólo pensando mediante moléculas constituidas por nucleótidos. ¿Será tiempo de cambiar el paradigma?

Microbiología aislada en la rotura prematura de membranas de pretérmino: relación con morbilidad infecciosa materna neonatal e intervalo rotura de membranas-parto / Isolated microbiology in premature rupture of preterm membranes: relation with maternal and neonatal infectious morbility and membranes rupture labor interval

Nuestro objetivo fue conocer la prevalencia de la flora microbiana aislada en la invasión microbiana de la cavidad amniótica e infección cervicovaginal en la rotura de membranas de pretérmino y su influencia sobre la infección materna-neonatal y la duración de la gestación

Rendimiento de la microcirugía en hidrosalpinx: análisis de tablas de vida / Yield of hidrosalpinx microsurgery: analysis of life tables

Se analizan los resultados de la cirugía en hidrosalpinx mediante análisis de tablas de vida de 105 pacientes del Policlínico de Infertilidad del Hospital Clínicp San Borja Arriarán, operadas por vía laparotómica entre 1980-1990, con seguimiento hasta los 48 meses. (Sólo se consideran las pacientes que presentan como único factor de esterilidad un daño tubario dilatado y sometidas a microcirugía por primera vez). Se analizan y comparan los rendimientos según grupo etáreo, tipo y lateralidad del daño tubario, duración de la esterilidad y tipo de cirugía. Se obtuvo una tasa acumulativa de embarazo de 62 por ciento a los 48 meses de seguimiento y la probabilidad de embarazo por ciclo (fecundabilidad) fue de 1,5 por ciento. Estos resultados son comparables a los publicados en otras series nacionales y extranjeras

Hiperprolactinemia: efecto sobre la función reproductiva / Hyperprolactinemia: effect over reproductive function

Se estudiaron 37 mujeres con hiperprolactinemia (HPRL) para establecer los niveles de prolactina (PRL) plasmática en relación con su etiología. Además a través de la medición de Estrógenos totales se determina el efecto de la HPRL sobre la función ovárica. Las mujeres que presentaron microadenomas se asocian a niveles de PRL mayores de 80 ng,ml y para macroadenomas de 200 ng,ml o más. En 22 mujeres con medición de estrógenos totales se encontró una medida de 40 pq,ml y se estableció una relación inversa con los niveles de PRL lo que demostraría el efecto de la HPRL sobre la inhibición de la esteroidogénesis ováric

Evaluación de las terapias de infertilidad en 633 parejas, mediante el uso del método de las tasas acumulativas de embarazo / Evaluation of infertility therapies in 633 couples, throwgh the pregnancy acumulative rates method

Se analizan 633 parejas admitidas en la Unidad de infertilidad del Departamento de Obstetricia y Ginecología del Hospital Jaraquemada, en un período de cuatro años. Los datos obtenidos demuestran una mayor incidencia de infertilidad secundaria, pero las tasas crudas de embrazo no son diferentes entre infertilidad primaria y secundaria. Las tasas de embarazo en distintos grupos etiológicos se calcularon según análisis de Tabla de vida, y se expresaron como tasa acumulativa de embarazo. Esta metodología permite evaluar tratamientos de infertilidad en relación con el comportamiento de la población fértil, casuísticas de distinto tamaño, con tiempos variables de seguimiento y de exposición a embarazo. Las tasas de embarazo obtenidas en las pacientes anovulatorias es similar a la de la población fértil, siendo independiente de su etiología de inducción de ovulación. Las menores tasas de embarazo se observaron en las pacientes con daño tubárico orgánico