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).

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.

Objective To evaluate the perinatal and maternal outcomes of pregnancies in SARS-CoV-2 infected women, comparing spontaneous and In Vitro Fertilization (IVF) pregnancies (with either own or donor oocytes). Design Multicentre, prospective, observational study. Setting 78 centres participating in the Spanish COVID19 Registry. Patients 1,347 SARS-CoV-2 positive pregnant women registered consecutively between February 26 th and November 5 th , 2020. Interventions Patient´s information was collected from their medical records, and multivariable regression analyses were performed, controlling for maternal age and the clinical presentation of infection. Main outcome measures Obstetrics and neonatal outcomes, pregnancy comorbidities, intensive care unit admission, mechanical ventilation need and medical conditions. Results The IVF group was composed of 74 (5.5%) women whereas the spontaneous group included 1,275 (94.5%) women. Operative delivery rate was high in all patients, especially in the IVF group, where C-section became the most frequent method of delivery (55.4%, compared to 26.1% of spontaneous). The reason for C-section was induction failure in 56.1% of IVF patients. IVF women had more gestational hypertensive disorders [16.2% vs 4.5% among spontaneous, adjusted Odds Ratio (aOR) 5.31, 95% Confidence Interval (CI) 2.45-10.93) irrespective of oocyte origin. The higher rate of ICU admittance observed in the IVF group (8.1% vs 2.4% spontaneous) was attributed to pre-eclampsia (aOR 11.82, 95% CI 5.25-25.87), not to the type of conception, Conclusions High rate of operative delivery has been observed in SARS-CoV-2 infected women, especially in IVF pregnancies; method of conception does not affect foetal or maternal outcomes, except for pre-eclampsia.

Background Fetal smallness affects 10% of pregnancies. Small fetuses are at a higher risk of adverse outcomes. Their management using estimated fetal weight and feto-maternal Doppler has a high sensitivity for adverse outcomes; however, more than 60% of fetuses are electively delivered at 37 to 38 weeks. On the other hand, classification using angiogenic factors seems to have a lower false-positive rate. Here, we present a protocol for the Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) trial, which compares the use of angiogenic factors and Doppler to manage small fetuses at term. Objective The primary objective is to demonstrate that classification based on angiogenic factors is not inferior to estimated fetal weight and Doppler at detecting fetuses at risk of adverse perinatal outcomes. Methods This is a multicenter, open-label, randomized controlled trial conducted in 20 hospitals across Spain. A total of 1030 singleton pregnancies with an estimated fetal weight ≤10th percentile at 36+0 to 37+6 weeks+days will be recruited and randomly allocated to either the control or the intervention group. In the control group, standard Doppler-based management will be used. In the intervention group, cases with a soluble fms-like tyrosine kinase to placental growth factor ratio ≥38 will be classified as having fetal growth restriction; otherwise, they will be classified as being small for gestational age. In both arms, the fetal growth restriction group will be delivered at ≥37 weeks and the small for gestational age group at ≥40 weeks. We will assess differences between the groups by calculating the relative risk, the absolute difference between incidences, and their 95% CIs. Results Recruitment for this study started on September 28, 2020. The study results are expected to be published in peer-reviewed journals and disseminated at international conferences in early 2023. Conclusions The angiogenic factor–based protocol may reduce the number of pregnancies classified as having fetal growth restriction without worsening perinatal outcomes. Moreover, reducing the number of unnecessary labor inductions would reduce costs and the risks derived from possible iatrogenic complications. Additionally, fewer inductions would lower the rate of early-term neonates, thus improving neonatal outcomes and potentially reducing long-term infant morbidities. Trial Registration ClinicalTrials.gov NCT04502823; https://clinicaltrials.gov/ct2/show/NCT04502823 International Registered Report Identifier (IRRID) DERR1-10.2196/37452

BACKGROUND Fetal smallness affects 10% of pregnancies. These fetuses are at a higher risk of adverse outcomes. Their management using estimated fetal weight (EFW) and feto-maternal Doppler has a high sensitivity for adverse outcomes; however, more than 60% of fetuses are electively delivered at 37-38 weeks. On the other hand, the classification using angiogenic factors (AF) seems to have a lower false positive rate. Here we present a protocol for the GRAFD trial, which compares the management of small fetuses at term using AF or Doppler. OBJECTIVE The primary objective is to demonstrate that classification based on AF is not inferior to EFW and Doppler to detect fetuses at risk of adverse perinatal outcomes. METHODS This is a multicentre, open-label, randomized controlled trial conducted in 20 hospitals across Spain. A total of 1,030 singleton pregnancies with an EFW ≤10th percentile at 36+0 to 37+6 weeks will be recruited and randomly allocated to either the control or the intervention group. In the control group, standard Doppler-based management will be used. In the intervention group, cases with a soluble fms-like tyrosine kinase to placental growth factor ratio (sFlt-1/PlGF) ≥38 will be classified as fetal growth restriction (FGR), otherwise as small for gestational age (SGA). In both arms, FGR will be delivered at ≥37 weeks and SGA at ≥40 weeks. We will assess the differences between groups calculating the relative risks (RR) and their 95% confidence intervals. RESULTS The study is in the recruitment and data collection phase. The study results are expected to be published in peer-reviewed journals and disseminated at international conferences by the end of 2022 or in early 2023. CONCLUSIONS The AF-based protocol may reduce the number of pregnancies with classified as FGR without worsening perinatal outcomes. Moreover, reducing the number of unnecessary labor inductions would reduce costs and the risks derived from possible iatrogenic complications. Additionally, fewer inductions would lower the rate of early-term neonates, thus improving neonatal outcomes and potentially reducing long-term infant morbidities. CLINICALTRIAL NCT04502823