Multicentre randomised trial of screening with sFlt1/PlGF and planned delivery to prevent pre-eclampsia at term: protocol of the PE37 study.

INTRODUCTION: Pre-eclampsia affects ~5%-7% of pregnancies. Although improved obstetric care has significantly diminished its associated maternal mortality, it remains a leading cause of maternal morbidity and mortality in the world. Term pre-eclampsia accounts for 70% of all cases and a large proportion of maternal-fetal morbidity related to this condition. Unlike in preterm pre-eclampsia, the prediction and prevention of term pre-eclampsia remain unsolved. Previously proposed approaches are based on combined third-trimester screening and/or prophylactic drugs, but these policies are unlikely to be widely implementable in many world settings. Recent evidence shows that the soluble fms-like tyrosine kinase-1 (s-Flt-1) to placental growth factor (PlGF) ratio measured at 35-37 weeks' gestation predicts term pre-eclampsia with an 80% detection rate. Likewise, recent studies demonstrate that induction of labour beyond 37 weeks is safe and well accepted by women. We hypothesise that a single-step universal screening for term pre-eclampsia based on sFlt1/PlGF ratio at 35-37 weeks followed by planned delivery beyond 37 weeks reduces the prevalence of term pre-eclampsia without increasing the caesarean section rates or worsening the neonatal outcomes. METHODS AND ANALYSIS: We propose an open-label randomised clinical trial to evaluate the impact of a screening of term pre-eclampsia with the sFlt-1/PlGF ratio followed by planned delivery in asymptomatic nulliparous women at 35-37 weeks. Women will be assigned 1:1 to revealed (sFlt-1/PlGF known to clinicians) versus concealed (unknown) arms. A cut-off of >90th centile is used to define the high risk of subsequent pre-eclampsia and offer planned delivery from 37 weeks. The efficacy variables will be analysed and compared between groups primarily following an intention-to-treat approach, by ORs and their 95% CI. This value will be computed using a Generalised Linear Mixed Model for binary response (study group as fixed effect and the centre as intercept random effect). ETHICS AND DISSEMINATION: The study is conducted under the principles of Good Clinical Practice. This study was accepted by the Clinical Research Ethics Committee of Hospital Clinic Barcelona on 20 November 2020. Subsequent approval by individual ethical committees and competent authorities was granted. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT04766866.

Efficacy and safety of hydroxychloroquine for treatment of mild SARS-CoV-2 infection and prevention of COVID-19 severity in pregnant and postpartum women: A randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Pregnant women have an increased risk of severe COVID-19. Evaluation of drugs with a safety reproductive toxicity profile is a priority. At the beginning of the pandemic, hydroxychloroquine (HCQ) was recommended for COVID-19 treatment. MATERIAL AND METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted in eight teaching hospitals in Spain to evaluate the safety and efficacy of HCQ in reducing viral shedding and preventing COVID-19 progression. Pregnant and postpartum women with a positive SARS-CoV-2 PCR (with or without mild COVID-19 signs/symptoms) and a normal electrocardiogram were randomized to receive either HCQ orally (400 mg/day for 3 days and 200 mg/day for 11 days) or placebo. PCR and electrocardiogram were repeated at day 21 after treatment start. Enrollment was stopped before reaching the target sample due to low recruitment rate. Trial registration EudraCT #: 2020-001587-29, on April 2, 2020. CLINICAL TRIALS: gov # NCT04410562, registered on June 1, 2020. RESULTS: A total of 116 women (75 pregnant and 41 post-partum) were enrolled from May 2020 to June 2021. The proportion of women with a positive SARS-CoV-2 PCR at day 21 was lower in the HCQ group (21.8%, 12/55) than in the placebo group (31.6%, 18/57), although the difference was not statistically significant (P = 0.499). No differences were observed in COVID-19 progression, adverse events, median change in QTc, hospital admissions, preeclampsia or poor pregnancy and perinatal outcomes between groups. CONCLUSIONS: HCQ was found to be safe in pregnant and postpartum women with asymptomatic or mild SARS-CoV-2 infection. Although the prevalence of infection was decreased in the HCQ group, the statistical power was insufficient to confirm the potential beneficial effect of HCQ for COVID-19 treatment.

Implementación de un programa de corta estancia hospitalaria maternoinfantil / Early post-partum discharge program in a maternity unit

Objetivo: El objetivo del estudio fue analizar el perfil sociodemográfico y obstétrico, así como la incidencia de consultas y reingresos, de las mujeres acogidas a un programa de corta estancia puerperal en el hospital del estudio. Metodología: Se realizó un estudio descriptivo de las variables relativas al perfil sociodemográfico, el embarazo, el parto y el puerperio de las mujeres con parto vaginal y alta precoz antes de 48 horas en el Hospital del Mar (Barcelona), desde junio de 2017 a junio de 2019. Resultados: 188 mujeres (un 8,2% del total de partos vaginales) se acogieron a la corta estancia hospitalaria durante el periodo de estudio. El 53,7% (n= 101) eran de nacionalidad española, y el resto eran de 32 nacionalidades distintas más. El 74,5% (n= 140) habían tenido uno o más partos previos, y el 84,6% (159) eran gestantes sin riesgo. El 95,7% de las mujeres (n= 180) tuvieron partos eutócicos. Un 7% (n= 13) de mujeres tuvieron que consultar en el hospital durante la primera semana después del alta por diferentes motivos. Tuvieron que consultar e ingresar un 2,1% (n= 4) de los neonatos con alta precoz, todos ellos por ictericia. No hubo ningún reingreso materno. Conclusiones: El perfil de mujeres que se acogen al programa de alta precoz en el centro del estudio son gestantes de bajo riesgo y presentan menos complicaciones en el parto que el resto de la población. No hubo más complicaciones o readmisiones hospitalarias en las mujeres con alta precoz respecto al global de los partos del centro del estudio. La implementación de un programa de corta estancia puerperal en nuestra institución es un procedimiento seguro, pero aceptado por un perfil de mujeres específico. (AU)

Objective: The objective of the study is to analyze the different mothers and newborns profiles who attend this program, and to analyze the different readmission rates comparing to the overall population that come for the usual childbirth in the hospital. Methodology: A descriptive study was performed, analyzing socio-demographic, obstetrical and partum and post-partum outcomes in women who attended to an early post-partum discharge before 48h after a vaginal delivery in Hospital del Mar (Barcelona), from June 2017 to June 2019. Results: 188 women (8.2% of total of vaginal deliveries) had the early post-partum discharge, 53.7% (n= 101) were Spanish women, 74.5% (n= 140) of women had already children, and 84.6% (n= 159) had no obstetrical risk factors. 95.7% (n= 180) women had eutocic deliveries, 7% (n= 13) of mother had to readmission to the hospital after the early discharge during the first week. There was only a 2.1% (n= 4) of newborns with early discharge that need to readmission; all of them because of neonatal hyperbilirubinemia. Conclusions: Most of women who attend to an early post-partum discharge are low risk pregnancies and deliveries. There are no higher mother readmission rates respect to the overall population. The implementation of an early post-partum discharge in the maternity unit in the institution is a safe process, but still accepted by a specific maternal profile of women. (AU)

Incidencia y factores asociados al metabolismo alterado de la glucosa un año después del parto en una población multiétnica de mujeres con diabetes mellitus gestacional en España / Gestational diabetes mellitus in a multiethnic population in Spain: Incidence and factors associated to impaired glucose tolerance one year after delivery

Antecedentes y objetivo: Las mujeres con antecedentes de diabetes mellitus gestacional (DMG) tienen mayor riesgo de diabetes. Si bien la etnia puede modificar este riesgo, no disponemos de estudios específicos en nuestro entorno. El objetivo del presente estudio fue determinar la incidencia de diabetes mellitus tipo 2 y prediabetes en el primer año posparto en mujeres con DMG y en un entorno multiétnico e identificar los factores asociados. Pacientes y métodos: Análisis retrospectivo de una cohorte observacional prospectiva de mujeres con DMG que acudieron al control posparto anual en el Hospital del Mar, entre enero de 2004 y marzo de 2016. Resultados: Trescientas cinco mujeres asistieron a las revisiones posparto. De estas, un 47,2% fueron caucásicas, un 22% del centro-sur de Asia, un 12% fueron de origen hispano y un 10% procedían de Marruecos y del este de Asia. La incidencia de diabetes mellitus tipo 2 y de prediabetes fue del 5,2 y el 36,6%, respectivamente. Los factores asociados al metabolismo alterado de la glucosa fueron la etnia no caucásica (OR=3,15, IC 95% [1,85-5,39]), los antecedentes previos de DMG (OR=2,26, IC 95% [1,11-4,59]) y el índice de masa corporal previo al embarazo (OR=1,09, IC 95% [1,04-1,15]). Conclusiones: En una población española de origen multiétnico, la incidencia de alteraciones del metabolismo hidrocarbonado en el primer año posparto de mujeres con antecedentes de DMG fue del 41,8%, siendo el riesgo 3 veces superior en las mujeres no caucásicas que en las caucásicas

Background and aim: Women with history of gestational diabetes mellitus (GDM) are at increased risk for diabetes. Ethnicity may modify such risk, but no studies have been conducted in our environment. The aim of this study was to assess the incidence of type 2 diabetes mellitus and prediabetes one year after delivery in women with GDM and in a multiethnic background and to identify the associated factors. Patients and methods: A retrospective analysis of a prospective, observational cohort of women with GDM who attended annual postpartum follow-up visits at Hospital del Mar from January 2004 to March 2016. Results: Three hundred and five women attended postpartum follow-up visits. Of these, 47.2% were Caucasian, 22% from South-Central Asia, 12% from Latin America, and 10% from Morocco and East Asia. Incidence rates of type 2 diabetes mellitus and prediabetes in these patients were 5.2 and 36.6%, respectively. In a multivariate analysis, non-Caucasian origin (OR=3.15, 95% CI [1.85-5.39]), recurrent gestational diabetes (OR=2.26, 95% CI [1.11-4.59]), and pre-pregnancy body mass index (OR=1.09, 95% CI [1.04-1.15]) were independent predictors of impaired glucose tolerance. Conclusions: In a multiethnic Spanish population of women with GDM, incidence of impaired glucose tolerance in the first year after delivery was 41.8%, with a three-fold increased risk for women of non-Caucasian ethnicity

Gestational diabetes mellitus in a multiethnic population in Spain: Incidence and factors associated to impaired glucose tolerance one year after delivery. / Incidencia y factores asociados al metabolismo alterado de la glucosa un año después del parto en una población multiétnica de mujeres con diabetes mellitus gestacional en España.

BACKGROUND AND AIM: Women with history of gestational diabetes mellitus (GDM) are at increased risk for diabetes. Ethnicity may modify such risk, but no studies have been conducted in our environment. The aim of this study was to assess the incidence of type 2 diabetes mellitus and prediabetes one year after delivery in women with GDM and in a multiethnic background and to identify the associated factors. PATIENTS AND METHODS: A retrospective analysis of a prospective, observational cohort of women with GDM who attended annual postpartum follow-up visits at Hospital del Mar from January 2004 to March 2016. RESULTS: Three hundred and five women attended postpartum follow-up visits. Of these, 47.2% were Caucasian, 22% from South-Central Asia, 12% from Latin America, and 10% from Morocco and East Asia. Incidence rates of type 2 diabetes mellitus and prediabetes in these patients were 5.2 and 36.6%, respectively. In a multivariate analysis, non-Caucasian origin (OR=3.15, 95% CI [1.85-5.39]), recurrent gestational diabetes (OR=2.26, 95% CI [1.11-4.59]), and pre-pregnancy body mass index (OR=1.09, 95% CI [1.04-1.15]) were independent predictors of impaired glucose tolerance. CONCLUSIONS: In a multiethnic Spanish population of women with GDM, incidence of impaired glucose tolerance in the first year after delivery was 41.8%, with a three-fold increased risk for women of non-Caucasian ethnicity.

Previous Gestational Diabetes Increases Atherogenic Dyslipidemia in Subsequent Pregnancy and Postpartum.

In a cohort of women with previous gestational diabetes mellitus (GDM), we aimed to ascertain whether women with abnormal glucose tolerance 1-year postdelivery had a more atherogenic lipid profile during and after pregnancy than those with normal glucose tolerance. A prospective cohort study with longitudinal design between January 2004 and March 2016 was conducted. Three hundred and six (56.8%) of 537 women diagnosed with GDM during the studied period attended a control visit during the first year after delivery. Of these, 112 (36.6%) had prediabetes and 16 (5.2%) had type 2 diabetes mellitus. No significant differences during pregnancy were found in total, low-density lipoprotein, high-density lipoprotein (HDL) cholesterol, and triacylglycerol (TAG) concentrations among the three groups. Only HDL cholesterol and TAG levels differed significantly among groups at 2 and 12 months after delivery. Logistic regression analysis revealed pregnancy HDL and glucose metabolism status to be associated with the HDL cholesterol concentration 1-year postdelivery. Furthermore, the only independent factor associated with TAG levels 1 year after delivery was the gestational TAG concentration. In summary, an overweight multiethnic group of women with prior GDM presented a high incidence of postpartum dysglycemia (41.8%). HDL-cholesterol and TAG levels, both components of the metabolic syndrome, differed significantly among the three study groups in the glucose-metabolism status at 2 and 12 months after delivery. Women with previous GDM must be followed up in the postpartum period for early detection and management of lipid and glucose disorders.

Gestational diabetes in a multiethnic population of Spain: clinical characteristics and perinatal outcomes.

AIMS: To compare clinical characteristics and perinatal outcomes between immigrant and Spanish women with gestational diabetes mellitus (GDM) in a multiethnic population of Barcelona and to identify factors independently associated with the development of large-for-gestational-age (LGA) infants. METHODS: Prospective study of women with GDM from five ethnic groups (Caucasian, South-Central Asian, Latin American, East Asian and Moroccan) at a single institution in Barcelona between 2004 and 2011. Maternal, gestational and newborn characteristics were recorded. RESULTS: The cohort included 456 patients. In univariate analyses, Moroccan women had more frequently a pre-gestational body mass index (BMI)>25 kg/m(2) (76.4%, P=0.012), while East Asian women had lower BMI (23.41 ± 2.79 kg/m(2), P<0.001), less need for insulin therapy (14.3%, P=0.013) and the highest rate of spontaneous labor (69.8%, P=0.014) and eutocic delivery (63.8%, P=0.032). Also, Latin American women had a higher rate of Cesarean section (52.9%, P<0.001) and LGA infants (28.6%, P=0.004), and their newborns had lower umbilical cord pH (7.23 ± 0.06, P=0.005) and Apgar scores (9 [4-10], P<0.01) and a higher incidence of neonatal hypoglycemia (51.4%, P=0.045). Logistic regression analysis identified pre-gestational BMI (OR: 1.18; 95% CI: 1.09-1.27), pregnancy weight gain (OR: 1.19; 95% CI: 1.1-1.28) and insulin use during gestation (OR: 2.29; 95% CI: 1.09-4.82) as predictors of LGA infants. CONCLUSIONS: Significant ethnic differences were found in clinical characteristics and perinatal outcomes of women with GDM. Latin American women had a higher frequency of adverse perinatal outcomes. Pregestational BMI, pregnancy weight gain and insulin use during pregnancy were independent predictors of LGA.

Descriptive analysis of childbirth healthcare costs in an area with high levels of immigration in Spain.

BACKGROUND: The aim of this study was to estimate the cost of childbirth in a teaching hospital in Barcelona, Spain, including the costs of prenatal care, delivery and postnatal care (3 months). Costs were assessed by taking into account maternal origin and delivery type. METHODS: We performed a cross-sectional study of all deliveries in a teaching hospital to mothers living in its catchment area between October 2006 and September 2007. A process cost analysis based on a full cost accounting system was performed. The main information sources were the primary care program for sexual and reproductive health, and hospital care and costs records. Partial and total costs were compared according to maternal origin and delivery type. A regression model was fit to explain the total cost of the childbirth process as a function of maternal age and origin, prenatal care, delivery type, maternal and neonatal severity, and multiple delivery. RESULTS: The average cost of childbirth was 4,328€, with an average of 18.28 contacts between the mother or the newborn and the healthcare facilities. The delivery itself accounted for more than 75% of the overall cost: maternal admission accounted for 57% and neonatal admission for 20%. Prenatal care represented 18% of the overall cost and 75% of overall acts. The average overall cost was 5,815€ for cesarean sections, 4,064€ for vaginal instrumented deliveries and 3,682€ for vaginal non-instrumented deliveries (p < 0.001). The regression model explained 45.5% of the cost variability. The incremental cost of a delivery through cesarean section was 955€ (an increase of 31.9%) compared with an increase of 193€ (6.4%) for an instrumented vaginal delivery. The incremental cost of admitting the newborn to hospital ranged from 420€ (14.0%) to 1,951€ (65.2%) depending on the newborn's severity. Age, origin and prenatal care were not statistically significant or economically relevant. CONCLUSIONS: Neither immigration nor prenatal care were associated with a substantial difference in costs. The most important predictors of cost were delivery type and neonatal severity. Given the impact of cesarean sections on the overall cost of childbirth, attempts should be made to take into account its higher cost in the decision of performing a cesarean section.

Peripartum metabolic control in gestational diabetes.

OBJECTIVE: We sought to evaluate intrapartum metabolic control in gestational diabetes mellitus (GDM) patients and maternal factors influencing intrapartum glycemic control and neonatal hypoglycemia risk. STUDY DESIGN: A prospective observational study included 129 women with GDM admitted for delivery. Data collected included maternal intrapartum capillary blood glucose (CBG) and ketonemia, use of insulin, and neonatal hypoglycemia. RESULTS: In all, 86% of maternal intrapartum CBG values fell within target range (3.3-7.2 mmol/L) without need for insulin use. There were no cases of maternal hypoglycemia or severe ketosis. Intrapartum CBG >7.2 mmol/L was associated with third-trimester glycated hemoglobin (P = .02) and lack of endocrinologic follow-up (P = .04). Risk of neonatal hypoglycemia was related with pregnancy insulin use compared with dietary control (60.5% vs 29.5%; P = .02). CONCLUSION: Peripartum metabolic control in GDM patients was achieved without insulin in most cases. Intrapartum glycemic control was related with third-trimester glycated hemoglobin and with no endocrinologic follow-up. Neonatal hypoglycemia was associated with insulin use during pregnancy.