Confirmation of preeclampsia-like syndrome induced by severe COVID-19: an observational study.

BACKGROUND: Since the outbreak of the COVID-19 pandemic, some studies have reported an increased preeclampsia incidence in pregnant women with SARS-CoV-2 infection. Several explanations for this association have been proposed, including a preeclampsia-like syndrome induced by severe COVID-19. This syndrome was described in a small case series and has not been confirmed in larger studies, and its effect on perinatal outcomes has not been studied. OBJECTIVE: This study aimed to confirm the preeclampsia-like syndrome because of COVID-19 and to investigate its implications on pregnancy outcomes and prognosis. STUDY DESIGN: This was a prospective, observational study conducted in a tertiary referral hospital. The inclusion criteria were pregnant women admitted to the intensive care unit for severe pneumonia because of COVID-19. They were classified into 3 groups based on clinical and laboratory findings: preeclampsia, preeclampsia-like syndrome, and women without preeclampsia features. The 3 cohorts were analyzed and compared at 3 different times: before, during, and after severe pneumonia. The main outcomes were incidence of adverse perinatal outcomes and signs and symptoms of PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, and increased angiogenic factors (soluble fms-like tyrosine kinase 1-to-placental growth factor ratio). RESULTS: A total of 106 women were admitted to the intensive care unit because of severe pneumonia, and 68 women were included in the study. Of those, 53 (50.0%) did not meet the diagnostic criteria for preeclampsia and remained pregnant after pneumonia (non-preeclampsia); 7 (6.6%) met the diagnostic criteria for preeclampsia, had abnormal (>38) soluble fms-like tyrosine kinase 1-to-placental growth factor ratio (preeclampsia), and delivered during severe pneumonia, and 8 (7.5%) met the diagnostic criteria for preeclampsia, had normal (≤38) soluble fms-like tyrosine kinase 1-to-placental growth factor ratio (preeclampsia like), and did not deliver during pneumonia. Despite not having delivered, most preeclampsia-related features improved after severe pneumonia in women with preeclampsia-like syndrome. Women with preeclampsia had significantly poorer outcomes than women with preeclampsia-like syndrome or without preeclampsia. CONCLUSION: More than 50% of women with severe COVID-19 and diagnostic criteria for preeclampsia may not be preeclampsia but a preeclampsia-like syndrome, which may affect up to 7.5% of women with severe COVID-19. Preeclampsia-like syndrome might have similar perinatal outcomes to those of normotensive women with severe pneumonia because of COVID-19. For these reasons, preeclampsia-like syndrome should be excluded by using soluble fms-like tyrosine kinase 1-to-placental growth factor ratio in future research and before making clinical decisions.

Social Support and Mental Health in the Postpartum Period in Times of SARS-CoV-2 Pandemic: Spanish Multicentre Cohort Study.

BACKGROUND: To explore the depression and anxiety symptoms in the postpartum period during the SARS-CoV-2 pandemic and to identify potential risk factors. METHODS: A multicentre observational cohort study including 536 women was performed at three hospitals in Spain. The Edinburgh Postnatal Depression Scale (EPDS), the State-Trait Anxiety Inventory (STAI) Scale, the Medical Outcomes Study Social Support Survey (MOS-SSS), and the Postpartum Bonding Questionnaire (PBQ) were assessed after birth. Depression (EPDS) and anxiety (STAI) symptoms were measured, and the cut-off scores were set at 10 and 13 for EPDS, and at 40 for STAI. RESULTS: Regarding EPDS, 32.3% (95% CI, 28% to 36.5%) of women had a score ≥ 10, and 17.3% (95% CI, 13.9% to 20.7%) had a score ≥ 13. Women with an STAI score ≥ 40 accounted for 46.8% (95% CI, 42.3% to 51.2%). A lower level of social support (MOS-SSS), a fetal malformation diagnosis and a history of depression (p = 0.000, p = 0.019 and p = 0.043) were independent risk factors for postpartum depression. A lower level of social support and a history of mental health disorders (p = 0.000, p = 0.003) were independent risk factors for postpartum anxiety. CONCLUSION: During the SARS-CoV-2 pandemic, an increase in symptoms of anxiety and depression were observed during the postpartum period.

Shared risk factors for COVID-19 and preeclampsia in the first trimester: An observational study.

INTRODUCTION: The association between preeclampsia and coronavirus disease 2019 (COVID-19) is under study. Previous publications have hypothesized the existence of shared risk factors for both conditions or a deficient trophoblastic invasion as possible explanations for this association. The primary aim of this study was to examine baseline risk factors measured in the first-trimester combined screening for preeclampsia in pregnant women with COVID-19 compared with the general population. A secondary aim of this study was to compare risk factors among patients with mild and severe COVID-19. MATERIAL AND METHODS: This was an observational retrospective study conducted at Vall d'Hebron Hospital Campus (Catalonia, Spain). Study patients were 231 pregnant women undergoing the first-trimester screening for preeclampsia and positive for severe acute respiratory syndrome coronavirus 2 between February 2020 and September 2021. The reference cohort were 13 033 women of the general population from six centers across Catalonia from May 2019 to June 2021. Based on the need for hospitalization, patients were classified in two groups: mild and severe COVID-19. First-trimester screening for preeclampsia included maternal history, mean arterial blood pressure, mean uterine artery pulsatility index (UtAPI), placental growth factor (PlGF), and pregnancy-associated plasma protein-A (PAPP-A). RESULTS: The proportion of cases at high risk for preeclampsia was significantly higher among the COVID-19 group compared with the general population (19.0% and 13.2%, respectively; p = 0.012). When analyzing risk factors for preeclampsia individually, women with COVID-19 had higher median body mass index (25.2 vs 24.5, p = 0.041), higher UtAPI multiple of the median (MoM) (1.08 vs 1.00, p < 0.001), higher incidence of chronic hypertension (2.8% vs 0.9%, p = 0.015), and there were fewer smokers (5.7% vs 11.6%, p = 0.007). The MoMs of PlGF and PAPP-A did not differ significantly between both groups (0.96 vs 0.97, p = 0.760 and 1.00 vs 1.01, p = 0.432; respectively). CONCLUSIONS: In patients with COVID-19, there was a higher proportion of women at high risk for preeclampsia at the first-trimester screening than in the general population, mainly because of maternal risk factors, rather than placental signs of a deficient trophoblastic invasion.

Congenital infection of SARS-CoV-2 in live-born neonates: a population-based descriptive study.

OBJECTIVE: To evaluate the evidence of mother-to-child transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This is a descriptive, multicentre, observational study in nine tertiary care hospitals throughout Spain. The study population was women with coronavirus disease 2019 during pregnancy. Mother-to-child transmission was defined as positive real-time RT-PCR of SARS-CoV-2 in amniotic fluid, cord blood, placenta or neonatal nasopharyngeal swabs taken immediately after birth. RESULTS: We included 43 women with singleton pregnancies and one with a twin pregnancy, as a result we obtained 45 samples of placenta, amniotic fluid and umbilical cord blood. The median gestational age at diagnosis was 34.7 weeks (range 14-41.3 weeks). The median interval between positive RT-PCR and delivery was 21.5 days (range 0-141 days). Fourteen women (31.8%, 95% CI 18.6%-47.6%) were positive at the time of delivery. There was one singleton pregnancy with SARS-CoV-2 RT-PCR positive in the placenta, amniotic fluid and umbilical cord blood (2.2%, 95% CI 0.1%-11.8%). Nasopharyngeal aspiration was performed on 38 neonates at birth, all of which were negative (0%, 95% CI 0%-9.3%). In 11 neonates the nasopharyngeal aspiration was repeated at 24-48 hours, and one returned positive (9.1%, 95% CI 0.2%-41.3%). CONCLUSIONS: The presence of SARS-CoV-2 in placenta, amniotic fluid and cord blood shows that mother-to-child transmission is possible but uncommon.

Diffuse trophoblast damage is the hallmark of SARS-CoV-2-associated fetal demise.

Placental pathology in SARS-CoV-2-infected pregnancies seems rather unspecific. However, the identification of the placental lesions due to SARS-CoV-2 infection would be a significant advance in order to improve the management of these pregnancies and to identify the mechanisms involved in a possible vertical transmission. The pathological findings in placentas delivered from 198 SARS-CoV-2-positive pregnant women were investigated for the presence of lesions associated with placental SARS-CoV-2 infection. SARS-CoV-2 infection was investigated in placental tissues through immunohistochemistry, and positive cases were further confirmed by in situ hybridization. SARS-CoV-2 infection was also investigated by RT-PCR in 33 cases, including all the immunohistochemically positive cases. Nine cases were SARS-CoV-2-positive by immunohistochemistry, in situ hybridization, and RT-PCR. These placentas showed lesions characterized by villous trophoblast necrosis with intervillous space collapse and variable amounts of mixed intervillous inflammatory infiltrate and perivillous fibrinoid deposition. Such lesions ranged from focal to massively widespread in five cases, resulting in intrauterine fetal death. Two of the stillborn fetuses showed some evidence of SARS-CoV-2 positivity. The remaining 189 placentas did not show similar lesions. The strong association between trophoblastic damage and placenta SARS-CoV-2 infection suggests that this lesion is a specific marker of SARS-CoV-2 infection in placenta. Diffuse trophoblastic damage, massively affecting chorionic villous tissue, can result in fetal death associated with COVID-19 disease.

Safety of tocilizumab in COVID-19 pregnant women and their newborn: A retrospective study.

WHAT IS KNOWN AND OBJECTIVE: Tocilizumab is an IL-6 receptor inhibitor agent which has been proposed as a candidate to stop the inflammatory phase of infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, safety data of tocilizumab in pregnant women and their newborn are scarce. We aimed to describe maternal and neonatal safety outcomes associated with tocilizumab treatment in pregnant women with severe COVID-19. METHODS: This is a retrospective study of severe COVID-19 pregnant women, treated with tocilizumab in two Spanish hospitals between 1 March and 31 April 2020. Demographics, medical history, clinical and radiologic findings, treatment information and laboratory data of mothers and their newborns were collected from electronic medical records. RESULTS AND DISCUSSION: A total of 12 pregnant women were identified to have received tocilizumab during pregnancy in the two hospitals. Median gestational age at admission was 27.7 weeks (interquartile range, 18.0-36.4). Most of them received lopinavir/ritonavir, azithromycin and hydroxychloroquine, two patients received corticosteroids and one received interferon beta 1B. All 12 pregnancies resulted in live births. Somatometric values were normal for all newborns, and evolution at 14 and 28 days was favourable for all of them. Hepatotoxicity was observed in 2 patients, which improved or resolved at discharge. Cytomegalovirus reactivation was detected in another patient who had also received corticosteroids for 15 days, causing a congenital infection in her newborn. Both hepatotoxicity and viral reactivation adverse events were classified as possibly related to tocilizumab administration according to Naranjo's causality algorithm. WHAT IS NEW AND CONCLUSIONS: It does not appear that tocilizumab has detrimental effects for the mother and newborn. Close monitoring of infections should be considered, especially if other immunosuppressive agents are used.

Fetal Transient Skin Edema in Two Pregnant Women With Coronavirus Disease 2019 (COVID-19).

BACKGROUND: The risk of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. Positive reverse-transcription polymerase chain reaction (RT-PCR) test results for SARS-CoV-2 infection in neonates and placental tissue have been reported, and immunoglobulin M antibodies have been detected in neonates born to mothers with infection. CASES: The first case is a woman at 22 3/7 weeks of gestation with coronavirus disease 2019 (COVID-19) who was admitted to the intensive care unit. In the second case, the patient remained at home with mild symptoms, starting at 20 weeks of gestation. In both cases, fetal skin edema was observed on ultrasound examination while maternal SARS-COV-2 RT-PCR test results were positive and resolved when maternal SARS-COV-2 RT-PCR test results became negative. The RT-PCR test result for SARS-CoV-2 in amniotic fluid was negative in both cases. The two pregnancies are ongoing and uneventful. CONCLUSION: Transient fetal skin edema noted in these two patients with COVID-19 in the second trimester may represent results of fetal infection or altered fetal physiology due to maternal disease or may be unrelated to the maternal illness.

Psychological impact and social support in pregnant women during lockdown due to SARS-CoV2 pandemic: A cohort study.

INTRODUCTION: Anxiety and depression during pregnancy can lead to adverse maternal and neonatal outcomes. The SARS CoV-2 pandemic, and the complete lockdown required during the first wave in most countries are stressors for pregnant women and can lead to anxiety and depression during pregnancy. The aim of this study was to explore depression and anxiety symptoms, and social support in pregnant women during the SARS CoV-2 lockdown, as well as to explore demographic risk factors. MATERIAL AND METHODS: A prospective cohort study was performed at Hospital Universitari Vall d'Hebron, Barcelona, including pregnant women attending the antenatal clinic during the SARS-CoV2 lockdown period. Three questionnaires were administered to study depression (EPDS), anxiety (STAI) and Social Support (MOS-SSS). STAI state (STAIs) described the actual state of anxiety and the STAI trait (STAIt) described the trait of anxiety. A cut-off of 10 for EPDS and 40 for STAI was considered to be clinically relevant. The main outcome measures were depression and anxiety symptoms. RESULTS: A total of 217 women were invited to participate, and 204 accepted (94%). From these, 164 filled in the EPDS, 109 STAI and 159 MOS-SSS questionnaires: 37.8% (95% confidence interval [CI] 30.5%-45.7%) (62/164) of women showed an EPDS result ≥10, 59.6% (95% CI 49.8%-68.8%) (65/109) a STAI state (STAIs) ≥40, and 58.7% (95% CI 48.9%-67.9%) (64/109) a STAI trait (STAIt) ≥40. Regression analysis showed that mental health disorder, Latin American origin and lack of social support were independent risk factors for anxiety symptoms in the STAIs (P = .032, P = .040 and P = .029, respectively). Regarding depressive symptoms, maternal body mass index, mental health disorders and social support were independent factors (P = .013, P = .015 and P = .000, respectively). CONCLUSIONS: A lockdown scenario during the first wave of the SARS-CoV 2 pandemic increased the symptoms of anxiety and depression among pregnant women, particularly affecting those with less social support.

Gestation and COVID-19: clinical and microbiological observational study (Gesta-COVID19).

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) is a novel disease which has been having a worldwide affect since December 2019. Evidence regarding the effects of SARS-CoV-2 during pregnancy is conflicting. The presence of SARS-CoV-2 has been demonstrated in biological samples during pregnancy (placenta, umbilical cord or amniotic fluid); however, maternal and fetal effects of the virus are not well known. METHODS: Descriptive, multicentre, longitudinal, observational study in eight tertiary care hospitals throughout Spain, that are referral centres for pregnant women with COVID-19. All pregnant women with positive SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction during their pregnancy or 14 days preconception and newborns born to mothers infected with SARS-CoV-2 will be included. They will continue to be followed up until 4 weeks after delivery. The aim of the study is to investigate both the effect of COVID-19 on the pregnancy, and the effect of the pregnancy status with the evolution of the SARS-CoV-2 disease. Other samples (faeces, urine, serum, amniotic fluid, cord and peripheral blood, placenta and breastmilk) will be collected in order to analyse whether or not there is a risk of vertical transmission and to describe the behaviour of the virus in other fluids. Neonates will be followed until 6 months after delivery to establish the rate of neonatal transmission. We aim to include 150 pregnant women and their babies. Ethics approval will be obtained from all the participating centres. DISCUSSION: There is little information known about COVID-19 and its unknown effects on pregnancy. This study will collect a large number of samples in pregnant women which will allow us to demonstrate the behaviour of the virus in pregnancy and postpartum in a representative cohort of the Spanish population.

Complications and outcomes of SARS-CoV-2 in pregnancy: where and what is the evidence?

OBJECTIVES: To add to the growing evidence on SARS-CoV-2 infection during pregnancy, so as to better inform clinical decision making and optimize patient outcomes. METHODS: A systematic search of relevant databases was perfomed on 25 March 2020 and a repeat search, on 10 April 2020. Reports of pregnant patients with SARS-CoV-2 infection at any time during their pregnancy were reviewed and summarized . RESULTS: We summarized the outcomes of a total of 155 pregnant women and 118 neonates. The evidence suggests a similar rate of severe COVID-19 cases in pregnant women and the general population. The frequency of cesarean deliveries is high, against guidelines recommendations. CONCLUSION: Limited data on COVID-19 during preganacy, associated with a wide variation in the methodology make accurate data interpretation difficult.

SARS-CoV-2 in Pregnancy: A Comprehensive Summary of Current Guidelines.

Since the declaration of the global pandemic of COVID-19 by the World Health Organization on 11 March 2020, we have continued to see a steady rise in the number of patients infected by SARS-CoV-2. However, there is still very limited data on the course and outcomes of this serious infection in a vulnerable population of pregnant patients and their fetuses. International perinatal societies and institutions including SMFM, ACOG, RCOG, ISUOG, CDC, CNGOF, ISS/SIEOG, and CatSalut have released guidelines for the care of these patients. We aim to summarize these current guidelines in a comprehensive review for patients, healthcare workers, and healthcare institutions. We included 15 papers from 10 societies through a literature search of direct review of society's websites and their journal publications up till 20 April 2020. Recommendations specific to antepartum, intrapartum, and postpartum were abstracted from the publications and summarized into Tables. The summary of guidelines for the management of COVID-19 in pregnancy across different perinatal societies is fairly consistent, with some variation in the strength of recommendations. It is important to recognize that these guidelines are frequently updated, as we continue to learn more about the course and impact of COVID-19 in pregnancy.