COVID 19 y embarazo en Chile: Informe preliminar del estudio multicéntrico GESTACOVID / COVID-19 and pregnancy in Chile: preliminary report of the GESTACOVID multicenter study

INTRODUCCIÓN: En Chile, los efectos maternos y perinatales de la pandemia por SARS-CoV-2 son aún desconocidos. GESTACOVID es un estudio multicéntrico que incluye embarazadas y puérperas hasta el día 42 con COVID-19. El objetivo de este estudio es presentar un informe preliminar, describiendo el impacto de la enfermedad en las embarazadas, factores de riesgo asociados y resultados perinatales. MÉTODOS: Estudio de cohorte descriptivo que incluye 661 pacientes enroladas entre el 7 de marzo y el 6 de julio de 2020, en 23 centros hospitalarios del país. Se analizaron variables demográficas, comorbilidades, características clínicas y del diagnóstico de COVID-19 y resultado materno y perinatal. RESULTADOS: Las pacientes hospitalizadas por COVID-19 tuvieron mayor prevalencia de hipertensión arterial crónica [10% vs 3%; OR=3,1 (1,5-6,79); p=0,003] y de diabetes tipo 1 y 2 [7% vs 2%; OR=3,2 (1,3-7,7); p=0,009] que las pacientes manejadas ambulatoriamente. Un IMC >40 kg/mt2 se asoció con un riesgo dos veces mayor de requerir manejo hospitalizado [OR=2,4 (1,2 - 4,6); p=0,009]. Aproximadamente la mitad de las pacientes (54%) tuvo un parto por cesárea, y un 8% de las interrupciones del embarazo fueron por COVID-19. Hasta la fecha de esta publicación, 38% de las pacientes continuaban embarazadas. Hubo 21 PCR positivas en 316 neonatos (6,6%), la mayoría (17/21) en pacientes diagnosticadas por cribado universal. CONCLUSIONES: Las embarazadas con COVID-19 y comorbilidades como diabetes, hipertensión crónica y obesidad mórbida deben ser manejadas atentamente y deberán ser objeto de mayor investigación. La tasa de transmisión vertical requiere una mayor evaluación para diferenciar el mecanismo y tipo de infección involucrada.

INTRODUCTION: In Chile, effects of the SARS-CoV-2 infection in pregnant women are unknown. GESTACOVID is a multicenter collaborative study including pregnant women and those in the postpartum period (until 42 days) who have had COVID-19. The purpose of this study is to report our preliminary results describing the clinical impact of COVID-19 in pregnant women, the associated risk factors and perinatal results. METHODS: Descriptive cohort study including 661 patients between April 7th and July 6th, 2020, in 23 hospitals. Demographical, comorbidities, clinical and diagnostic characteristics of COVID-19 disease and maternal and perinatal outcomes were analyzed. RESULTS: Pregnant women with COVID-19 admitted to the hospital were more likely to have chronic hypertension [10% vs 3%; OR=3.1 (1.5-6.79); p=0,003] and diabetes type 1 and 2 [7% vs 2%; OR=3.2 (1.3-7.7); p=0.009] than those with outpatient management. A body mass index of >40 kg/mt2 was associated with two-fold higher risk of hospitalization [OR=2.4 (1.2-4.6); p=0.009]. Almost half of patients (54%) were delivered by cesarean section, and 8% of the medically indicated deliveries were due to COVID-19. So far, 38% of the patients are still pregnant. Among 316 newborns, there were 21 positive PCR tests (6.6%), mostly from asymptomatic mothers undergoing universal screening. CONCLUSIONS: Pregnant women with COVID-19 and comorbidities such as diabetes, chronic hypertension and morbid obesity need a close follow up and should be a matter for further research. Vertical transmission of COVID-19 should be thoroughly studied to define the mechanisms and type of infection involved.

Mortalidad perinatal en el parto prematuro entre 22 y 34 semanas en un hospital público de Santiago, Chile / Perinatal mortality in premature birth between 22 and 34 weeks of gestation

Objetivo: Conocer la mortalidad perinatal del parto prematuro y los factores de riesgo asociados, usando los datos perinatales clínicos, los resultados de laboratorio y los hallazgos patológicos del feto, neonato y placenta. Métodos: Estudio retrospectivo, cohorte de 407 nacimientos prematuros, únicos, entre 22.0 y 34.0 semanas de gestación. Se estudiaron las muertes fetales y neonatales hasta los 7 días de vida. Fallecieron 122 niños (64 muertes fetales y 58 neonatales), 78 tuvieron autopsia. Resultados: La mortalidad perinatal fue de 30 por ciento (122/407). El 71 por ciento (87/122) de las muertes ocurrieron antes de las 30 semanas y el 81 por ciento (99/122) en nacidos con peso menor de 1500 gramos. Las principales causas de muerte perinatal según el factor asociado con el parto prematuro fueron: infección bacteriana ascendente (IBA) 41 por ciento (50/122), anomalía congénita 20 por ciento (24/122) e hipertensión arterial 12 por ciento (15/122). Los factores de riesgo de muerte perinatal, identificados mediante análisis de regresión logística, fueron: edad gestacional al parto (p<0,001), anomalía congênita (p<0,001), IBA (p=0,02) e hipertensión arterial (p=0,03). Las principales causas de muerte perinatal fueron: hipoxia (aguda o crónica) 28 por ciento, infección congénita 23 por ciento (preferentemente neumonía 18 por ciento), desprendimiento prematuro de placenta con hipoxia y shock hipovolémico 18 por ciento, anomalía congénita 18 por ciento y síndrome hipertensivo con hipoxia aguda o crónica 7 por ciento. Conclusiones: Entre las 22 y 34 semanas de gestación, el parto prematuro por IBA fue la causa más frecuente de muerte perinatal, la edad gestacional al parto fue el principal factor de riesgo de mortalidad y la hipoxia fue la causa más frecuente de muerte.

Aim: To determine perinatal mortality of premature birth and the risk factors associated using perinatal clinical data, laboratory results and histopathological fetal, neonatal and placental findings. Methods: Retrospective cohort study of 407 preterm single births at 22.0-34.0 weeks gestation. Fetal and neonatal deaths until 7 days of life were studied. One hundred and twenty two children died (64 fetal deaths and 58 neonatal deaths), 78 had autopsy. Results: Perinatal mortality was 30 percent (122/407). Of total deaths, 71 percent (87/122) occurred before 30 weeks gestation and 81 percent (99/122) occurred in very low birth weight infants (<1500 g). The main causes of perinatal mortality according to associated factors for premature birth were: ascending bacterial infection (ABI) 41 percent (50/122), congenital anomalies 20 percent (24/122) and hypertension 12 percent (15/122). Risk factors for perinatal mortality, identified by logistic regression analisis were: births at gestational age p<0.001, congenital anomalies p<0.001, ABI p=0.02 and hypertension p=0.03. The major causes of perinatal death were: hypoxia produced by diverse conditions (acute or chronic) 28 percent, congenital infections 23 percent (mostly congenital pneumonia 18 percent), abruptio placentae with hypoxia and hypovolemic shock 18 percent, congenital anomalies 18 percent and hypertensive syndrome with acute or chronic hypoxia 7 percent. Conclusions: In gestations between 22.0-34.0 weeks, premature birth caused by ABI was the most important cause of perinatal death, gestational age at birth was identified as the major risk factor for mortality and hypoxia the main cause of death.

Vasomotion in human umbilical and placental veins: role of gap junctions and intracellular calcium reservoirs in their synchronous propagation.

Vasomotion was characterized using human placentae vessel rings; force displacement transducers recorded isometric contractions. Umbilical vein rings display rhythmic contractions occurring with a frequency of 1.47+/-0.01 min(-1) and 274+/-2.2 mg (n=211) of amplitude, which corresponds to 11.1+/-0.4% of the maximal KCl contracture. Vasomotion waves were recorded for up to 8 h; their amplitude and duration was larger in umbilical veins than arteries or chorionic vessels (p<0.001), vasomotion frequency was indistinguishable among these vessels. Segments of the umbilical vein closer to the fetus showed larger amplitudes and longer-lasting waves. Gap junction blockers, including peptide Gap 27, 18alpha-glycyrrhetinic acid, hexanol, heptanol or octanol, reduced the amplitude but not the frequency of vasomotion; all these drugs, in addition, decreased tissue basal tension. The role of intracellular calcium stores was evidenced using calcium-free buffer, which reduced oscillation amplitude and tissue basal tension. Cyclopiazonic acid increased wave amplitude and tissue basal tension, reducing oscillatory frequency. We propose that biological oscillators localized in the smooth muscle layer of the umbilical cord, trigger vasomotion waves, which are synchronized and propagated via gap junctions; internal calcium reservoirs are essential for their maintenance. These myogenic oscillations may be relevant for maternal-fetus blood flow and contribute to fetal nutrition and development.