Screening for Vaginal and Endocervical Infections in the First Trimester of Pregnancy? A Study That Ignites an Old Debate.

OBJECTIVES: Vaginal and endocervical infections are considered a global health problem, especially after recent evidence of their association with preterm delivery and other adverse obstetric outcomes. Still, there is no consensus on the efficacy of a screening strategy for these infections in the first trimester of pregnancy. This study evaluated their prevalence and whether screening and treatment resulted as effective in reducing pregnancy and perinatal complications. METHODS: A single-center prospective observational study was designed; a sample size of 400 first-trimester pregnant women was established and they were recruited between March 2016-October 2019 at the Puerta de Hierro University Hospital (Spain). They were screened for vaginal and endocervical infections and treated in case of abnormal flora. Pregnancy and delivery outcomes were compared between abnormal and normal flora groups by univariate analysis. RESULTS: 109 patients had an abnormal flora result (27.2%). The most frequently detected infection was Ureaplasma urealyticum (12.3%), followed by Candida spp. (11.8%), bacterial vaginosis (5%), Mycoplasma hominis (1.2%) and Trichomonas vaginalis (0.8%). Patients with abnormal flora had a 5-fold increased risk of preterm premature rupture of membranes (5.3% vs. 1.1% of patients with normal flora, Odds Ratio 5.11, 95% Confidence Interval 1.20-21.71, p = 0.028). No significant differences were observed regarding preterm delivery or neonatal morbidity. CONCLUSIONS: Considering the morbimortality related to prematurity and that the results of our study suggest that the early treatment of abnormal flora could improve perinatal outcomes, the implementation of a screening program during the first trimester should be considered.

SARS-CoV-2 Infection and C-Section: A Prospective Observational Study.

Pregnant women are particularly vulnerable to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In addition to unfavorable perinatal outcomes, there has been an increase in obstetric interventions. With this study, we aimed to clarify the reasons, using Robson's classification model, and risk factors for cesarean section (C-section) in SARS-CoV-2-infected mothers and their perinatal results. This was a prospective observational study that was carried out in 79 hospitals (Spanish Obstetric Emergency Group) with a cohort of 1704 SARS-CoV-2 PCR-positive pregnant women that were registered consecutively between 26 February and 5 November 2020. The data from 1248 pregnant women who delivered vaginally (vaginal + operative vaginal) was compared with those from 456 (26.8%) who underwent a C-section. C-section patients were older with higher rates of comorbidities, in vitro fertilization and multiple pregnancies (p < 0.05) compared with women who delivered vaginally. Moreover, C-section risk was associated with the presence of pneumonia (p < 0.001) and 41.1% of C-sections in patients with pneumonia were preterm (Robson's 10th category). However, delivery care was similar between asymptomatic and mild-moderate symptomatic patients (p = 0.228) and their predisposing factors to C-section were the presence of uterine scarring (due to a previous C-section) and the induction of labor or programmed C-section for unspecified obstetric reasons. On the other hand, higher rates of hemorrhagic events, hypertensive disorders and thrombotic events were observed in the C-section group (p < 0.001 for all three outcomes), as well as for ICU admission. These findings suggest that this type of delivery was associated with the mother's clinical conditions that required a rapid and early termination of pregnancy.

Pregnancy Outcomes and SARS-CoV-2 Infection: The Spanish Obstetric Emergency Group Study.

Pregnant women who are infected with SARS-CoV-2 are at an increased risk of adverse perinatal outcomes. With this study, we aimed to better understand the relationship between maternal infection and perinatal outcomes, especially preterm births, and the underlying medical and interventionist factors. This was a prospective observational study carried out in 78 centers (Spanish Obstetric Emergency Group) with a cohort of 1347 SARS-CoV-2 PCR-positive pregnant women registered consecutively between 26 February and 5 November 2020, and a concurrent sample of PCR-negative mothers. The patients' information was collected from their medical records, and the association of SARS-CoV-2 and perinatal outcomes was evaluated by univariable and multivariate analyses. The data from 1347 SARS-CoV-2-positive pregnancies were compared with those from 1607 SARS-CoV-2-negative pregnancies. Differences were observed between both groups in premature rupture of membranes (15.5% vs. 11.1%, p < 0.001); venous thrombotic events (1.5% vs. 0.2%, p < 0.001); and severe pre-eclampsia incidence (40.6 vs. 15.6%, p = 0.001), which could have been overestimated in the infected cohort due to the shared analytical signs between this hypertensive disorder and COVID-19. In addition, more preterm deliveries were observed in infected patients (11.1% vs. 5.8%, p < 0.001) mainly due to an increase in iatrogenic preterm births. The prematurity in SARS-CoV-2-affected pregnancies results from a predisposition to end the pregnancy because of maternal disease (pneumonia and pre-eclampsia, with or without COVID-19 symptoms).

The association between SARS-CoV-2 infection and preterm delivery: a prospective study with a multivariable analysis.

BACKGROUND: To determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the cause of COVID-19 disease) exposure in pregnancy, compared to non-exposure, is associated with infection-related obstetric morbidity. METHODS: We conducted a multicentre prospective study in pregnancy based on a universal antenatal screening program for SARS-CoV-2 infection. Throughout Spain 45 hospitals tested all women at admission on delivery ward using polymerase-chain-reaction (PCR) for COVID-19 since late March 2020. The cohort of positive mothers and the concurrent sample of negative mothers was followed up until 6-weeks post-partum. Multivariable logistic regression analysis, adjusting for known confounding variables, determined the adjusted odds ratio (aOR) with 95% confidence intervals (95% CI) of the association of SARS-CoV-2 infection and obstetric outcomes. MAIN OUTCOME MEASURES: Preterm delivery (primary), premature rupture of membranes and neonatal intensive care unit admissions. RESULTS: Among 1009 screened pregnancies, 246 were SARS-CoV-2 positive. Compared to negative mothers (763 cases), SARS-CoV-2 infection increased the odds of preterm birth (34 vs 51, 13.8% vs 6.7%, aOR 2.12, 95% CI 1.32-3.36, p = 0.002); iatrogenic preterm delivery was more frequent in infected women (4.9% vs 1.3%, p = 0.001), while the occurrence of spontaneous preterm deliveries was statistically similar (6.1% vs 4.7%). An increased risk of premature rupture of membranes at term (39 vs 75, 15.8% vs 9.8%, aOR 1.70, 95% CI 1.11-2.57, p = 0.013) and neonatal intensive care unit admissions (23 vs 18, 9.3% vs 2.4%, aOR 4.62, 95% CI 2.43-8.94, p <  0.001) was also observed in positive mothers. CONCLUSION: This prospective multicentre study demonstrated that pregnant women infected with SARS-CoV-2 have more infection-related obstetric morbidity. This hypothesis merits evaluation of a causal association in further research.

Impact of Recommended Maternal Vaccination Programs on the Clinical Presentation of SARS-CoV-2 Infection: A Prospective Observational Study.

The COVID-19 pandemic has raised questions about the possible cross immunity resulting from common vaccination programs and SARS-CoV-2 infection. Therefore, the Spanish Obstetric Emergency group performed a multicenter prospective study on the vaccination status of Influenza and Tdap (diphtheria, tetanus and pertussis vaccine boost administered in adulthood) in consecutive cases of SARS-CoV-2 infection in a pregnancy cohort, in order to assess its possible association with the clinical presentation and severity of symptoms of SARS-CoV-2 infection, as well as to determine the factors that may affect vaccination adherence. A total of 1150 SARS-CoV-2 positive pregnant women from 78 Spanish hospitals were analyzed: 183 had not received either vaccine, 23 had been vaccinated for Influenza only, 529 for Tdap only and 415 received both vaccines. No association was observed between the vaccination status and the clinical presentation of SARS-CoV-2 infection and/or the severity of symptoms. However, a lower adherence to the administration of both vaccines was observed in the Latin-American subgroup. Based on the results above, we reinforce the importance of maternal vaccination programs in the actual pandemic. Health education campaigns should be specially targeted to groups less likely to participate in these programs, as well as for a future SARS-CoV-2 vaccination campaign.

Obstetric Outcomes of SARS-CoV-2 Infection in Asymptomatic Pregnant Women.

Around two percent of asymptomatic women in labor test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Spain. Families and care providers face childbirth with uncertainty. We determined if SARS-CoV-2 infection at delivery among asymptomatic mothers had different obstetric outcomes compared to negative patients. This was a multicenter prospective study based on universal antenatal screening for SARS-CoV-2 infection. A total of 42 hospitals tested women admitted for delivery using polymerase chain reaction, from March to May 2020. We included positive mothers and a sample of negative mothers asymptomatic throughout the antenatal period, with 6-week postpartum follow-up. Association between SARS-CoV-2 and obstetric outcomes was evaluated by multivariate logistic regression analyses. In total, 174 asymptomatic SARS-CoV-2 positive pregnancies were compared with 430 asymptomatic negative pregnancies. No differences were observed between both groups in key maternal and neonatal outcomes at delivery and follow-up, with the exception of prelabor rupture of membranes at term (adjusted odds ratio 1.88, 95% confidence interval 1.13-3.11; p = 0.015). Asymptomatic SARS-CoV-2 positive mothers have higher odds of prelabor rupture of membranes at term, without an increase in perinatal complications, compared to negative mothers. Pregnant women testing positive for SARS-CoV-2 at admission for delivery should be reassured by their healthcare workers in the absence of symptoms.

[Spanish registry of Covid-19 screening in asymptomatic pregnants.] / Registro español de cribado de Covid-19 en gestantes asintomáticas.

OBJECTIVE: The Spanish registry of Covid-19 in Spanish pregnant women, made up of 100 centers, is created in response to the need to know the morbidity that Covid-19 generates in pregnant women and their newborns, to know the real incidence of the disease in this population group and to establish and monitor the package of measures to improve their care. The aim of this paper was the creation of a registry of pregnant women with Covid-19 infection in order to establish the interventions and measures necessary to improve the care of these patients during hospital admission. METHODS: To prepare the registry, the main researcher of each center collected weekly / biweekly the number of total pregnant women screened, as well as the total number of positive and negative, sending these data to the responsible researchers so that it could be available in real time of the percentage of infected asymptomatic pregnant population and the evolution by weeks in the centers of each participating province. The data were analyzed using the linear regression test and the Mantel test. RESULTS: As of May 31stsup> 2020, 16,308 screening tests were carried out in these hospitals, in which 338 pregnant women were positive, which translates into 2.07% (95% Confidence Interval: 1.86-2.30) of the asymptomatic pregnant women we attended in our centers were carriers of the virus and could develop the disease in subsequent days. CONCLUSIONS: The Spanish epidemiological registry allows us to know the incidence of infection in pregnant women attended in the Spanish delivery centers, as well as the weekly and / or fortnightly evolution of the same, observing a significant decrease in the proportion of positive pregnant women over the total of screenings throughout this period, with an average of 6.5% in early April 2020 to an average of 0.93% positive in late May 2020.

OBJETIVO: El registro español de Covid-19 en embarazadas españolas, integrado por 100 centros, surge en respuesta a la necesidad de conocer la morbilidad que la Covid-19 genera en las gestantes y sus recién nacidos, de conocer la incidencia real de la enfermedad en este grupo poblacional y de establecer y monitorizar el paquete de medidas para mejorar su atención. El objetivo de este estudio fue la creación de un registro de gestantes con infección por Covid-19 con la finalidad de establecer y monitorizar las intervenciones y medidas necesarias para mejorar la atención de estas pacientes durante el ingreso hospitalario. METODOS: Para la elaboración del registro, el investigador principal de cada centro recogió con carácter semanal/quincenal el número de gestantes totales cribadas, así como el total de positivas y negativas, remitiendo a los investigadores responsables estos datos de manera que se pudiera disponer a tiempo real del porcentaje de población gestante asintomática infectada y de la evolución por semanas en los centros de cada provincia participante. Los datos fueron analizados mediante el Test de regresión lineal y test de Mantel. RESULTADOS: A día 31 de mayo de 2020, se realizaron en estos hospitales 16.308 test de cribado, en los cuales 338 gestantes resultaron positivas, lo que se traduce en que un 2,07% (Intervalo de Confianza del 95%: 1,86-2,30) de las gestantes asintomáticas que atendimos en nuestros centros eran portadoras del virus y podían desarrollar la enfermedad en días posteriores. CONCLUSIONES: El registro epidemiológico español permite conocer la incidencia de infección en gestantes atendidas en los paritorios españoles, así como la evolución semanal y/o quincenal de la misma, observándose un descenso significativo de la proporción de gestantes positivas sobre el total de cribadas a lo largo de este periodo, con una media del 6,5% a principios de abril de 2020 hasta una media del 0,93% de positivas a finales de mayo de 2020.

Immunogenicity, transplacental transfer of pertussis antibodies and safety following pertussis immunization during pregnancy: Evidence from a randomized, placebo-controlled trial.

BACKGROUND: Pertussis immunization during pregnancy is recommended in many countries. Data from large randomized controlled trials are needed to assess the immunogenicity, reactogenicity and safety of this approach. METHODS: This phase IV, observer-blind, randomized, placebo-controlled, multicenter trial assessed immunogenicity, transplacental transfer of maternal pertussis antibodies, reactogenicity and safety of a reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap) during pregnancy. Women received Tdap or placebo at 27-36 weeks' gestation with crossover ≤ 72-hour-postpartum immunization. Immune responses were assessed before the pregnancy dose and 1 month after, and from the umbilical cord at delivery. Superiority (primary objective) was reached if the lower limits of the 95% confidence intervals (CIs) of the pertussis geometric mean concentration (GMC) ratios (Tdap/control) in cord blood were ≥ 1.5. Solicited and unsolicited adverse events (AEs) and pregnancy-/neonate-related AEs of interest were recorded. RESULTS: 687 pregnant women were vaccinated (Tdap: N = 341 control: N = 346). Superiority of the pertussis immune response (maternally transferred pertussis antibodies in cord blood) was demonstrated by the GMC ratios (Tdap/control): 16.1 (95% CI: 13.5-19.2) for anti-filamentous hemagglutinin, 20.7 (15.9-26.9) for anti-pertactin and 8.5 (7.0-10.2) for anti-pertussis toxoid. Rates of pregnancy-/neonate-related AEs of interest, solicited general and unsolicited AEs were similar between groups. None of the serious AEs reported throughout the study were considered related to maternal Tdap vaccination. CONCLUSIONS: Tdap vaccination during pregnancy resulted in high levels of pertussis antibodies in cord blood, was well tolerated and had an acceptable safety profile. This supports the recommendation of Tdap vaccination during pregnancy to prevent early-infant pertussis disease. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02377349.

Registro español de cribado de covid-19 en gestantes asintomáticas / Spanish registry of Covid-19 screening in asymptomatic pregnants

OBJETIVO: El registro español de Covid-19 en embarazadas españolas, integrado por 100 centros, surge en respuesta a la necesidad de conocer la morbilidad que la Covid-19 genera en las gestantes y sus recién nacidos, de conocer la incidencia real de la enfermedad en este grupo poblacional y de establecer y monitorizar el paquete de medidas para mejorar su atención. El objetivo de este estudio fue la creación de un registro de gestantes con infección por Covid-19 con la finalidad de establecer y monitorizar las intervenciones y medidas necesarias para mejorar la atención de estas pacientes durante el ingreso hospitalario. MÉTODOS: Para la elaboración del registro, el investigador principal de cada centro recogió con carácter semanal/quincenal el número de gestantes totales cribadas, así como el total de positivas y negativas, remitiendo a los investigadores responsables estos datos de manera que se pudiera disponer a tiempo real del porcentaje de población gestante asintomática infectada y de la evolución por semanas en los centros de cada provincia participante. Los datos fueron analizados mediante el Test de regresión lineal y test de Mantel. RESULTADOS: A día 31 de mayo de 2020, se realizaron en estos hospitales 16.308 test de cribado, en los cuales 338 gestantes resultaron positivas, lo que se traduce en que un 2,07% (Intervalo de Confianza del 95%: 1,86-2,30) de las gestantes asintomáticas que atendimos en nuestros centros eran portadoras del virus y podían desarrollar la enfermedad en días posteriores. CONCLUSIONES: El registro epidemiológico español permite conocer la incidencia de infección en gestantes atendidas en los paritorios españoles, así como la evolución semanal y/o quincenal de la misma, observándose un descenso significativo de la proporción de gestantes positivas sobre el total de cribadas a lo largo de este periodo, con una media del 6,5% a principios de abril de 2020 hasta una media del 0,93% de positivas a finales de mayo de 2020

OBJECTIVE: The Spanish registry of Covid-19 in Spanish pregnant women, made up of 100 centers, is created in response to the need to know the morbidity that Covid-19 generates in pregnant women and their newborns, to know the real incidence of the disease in this population group and to establish and monitor the package of measures to improve their care. The aim of this paper was the creation of a registry of pregnant women with Covid-19 infection in order to establish the interventions and measures necessary to improve the care of these patients during hospital admission. METHODS: To prepare the registry, the main researcher of each center collected weekly / biweekly the number of total pregnant women screened, as well as the total number of positive and negative, sending these data to the responsible researchers so that it could be available in real time of the percentage of infected asymptomatic pregnant population and the evolution by weeks in the centers of each participating province. The data were analyzed using the linear regression test and the Mantel test. RESULTS: As of May 31stsup> 2020, 16,308 screening tests were carried out in these hospitals, in which 338 pregnant women were positive, which translates into 2.07% (95% Confidence Interval: 1.86-2.30) of the asymptomatic pregnant women we attended in our centers were carriers of the virus and could develop the disease in subsequent days. CONCLUSIONS: The Spanish epidemiological registry allows us to know the incidence of infection in pregnant women attended in the Spanish delivery centers, as well as the weekly and / or fortnightly evolution of the same, observing a significant decrease in the proportion of positive pregnant women over the total of screenings throughout this period, with an average of 6.5% in early April 2020 to an average of 0.93% positive in late May 2020

Gestación heterotópica: dos casos con gestación intrauterina viable a término / Heterotopic pregnancy: two cases with viable intrauterine pregnancy at term

Se presentan dos casos de gestación heterotópica, el primero de ellos espontáneo y el segundo tras técnicas de fecundación in vitro. En ambos la gestación intrauterina evolucionó de forma favorable, con control gestacional normal y llegando a término, con el nacimiento de recién nacidos sanos. La gestación heterotópica se define como la presencia simultánea de gestación en dos lugares de implantación distintos, lo más frecuente una gestación intrauterina acompañada de otra ectópica. Se trata de una situación poco frecuente, con una incidencia de 1/8000 embarazos espontáneos según la bibliografía más reciente.

We report two cases of heterotopic pregnancy, the first one spontaneous and the second one after in vitro fertilization techniques. In both, the intrauterine gestation evolved favorably, normal pregnancy control and coming to terms with the birth of healthy newborns. Heterotopic pregnancy is defined as the simultaneous presence of gestation at two different locations, most often in utero accompanied by another ectopic pregnancy. This is a rare situation, with an incidence of spontaneous pregnancies 1/8000 according to the most recent literature.