Clinical course of novel COVID-19 infection in pregnant women

Objectives: Evaluation of clinical course of COVID-19 during pregnancy and maternal and perinatal outcomes of this pregnancy. Methods: 66 women with polymerase chain reaction (PCR)–confirmed SARS-CoV-2 and their 42 neonates were included in the prospective observational study. Demographic, epidemiological, clinical, laboratory and instrumental data of pregnancy, delivery, postpartum period, including pharmacotherapy and neonatal outcomes were analyzed. Results: 15 (22.7%) women were asymptomatic, 25 (38%) had mild disease, while moderate and severe forms were detected in 20 (30.2%) and 6 (9.1%) cases, respectively. Additional oxygenation was required in 6 (9%) cases: 4 (6%) received CPAP therapy and 2 (3%)–mechanical ventilation. Main clinical symptoms were cough (51.5%), anosmia (34.9%), and hyperthermia (33.3%). Laboratory changes included increased levels of lactate dehydrogenase (LDH), creatinine, d-dimer, and C-reactive protein (CRP), anemia, and leukopenia. All pregnant women received low molecular weight heparin and interferon alfa-2b according to the National clinical recommendations. Antimicrobial drugs included Amoxicillin/Clavulanic acid (46%) and macrolides (28%) or carbapenems in severe cases of disease. Spontaneous abortion was reported in 6.1% of cases. Eight preterm (19%) and 34 term deliveries (81%) occurred. The mean weight of neonates was (3283 ± 477) g, 1- and 5-min Apgar score was (7.8 ± 0.6) and (8.7 ± 0.5), respectively. No cases of neonatal COVID-19 infection were reported. Conclusions: Mostly, the manifestations of COVID-19 were mild. However, 9% of cases were severe, and could contribute to preterm delivery or maternal morbidity. Main predictors of severe COVID-19 course in pregnant women were a decrease in the levels of erythrocytes and lymphocytes and increase in the levels of alanine aminotransferase and CRP. Elimination of the virus in pregnant women required more time due to altered immunity. No evidence of vertical transmission during pregnancy and delivery was found. However, the possibility of this cannot be excluded

Oncological management and obstetric and neonatal outcomes for women diagnosed with cancer during pregnancy: a 20-year international cohort study of 1170 patients

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Association of Chemotherapy Timing in Pregnancy With Congenital Malformation

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Clusterin and Its Potential Regulatory microRNAs as a Part of Secretome for the Diagnosis of Abnormally Invasive Placenta: Accreta, Increta, and Percreta Cases

Magnetic resonance imaging (MRI) and ultrasound methods used for the diagnosis of an abnormally invasive placenta (AIP) have a wide range of sensitivity (Se, 33–93%) and specificity (Sp, 71–100%) levels, which results in a high risk of unfavorable maternal and perinatal outcomes. The relevance of optimizing the diagnosis of AIP is beyond doubt. Given the epigenetic nature of trophoblast invasion, we aimed to quantitate microRNAs and proteins of their target genes that are potentially associated with AIP in blood plasma samples from 64 pregnant women at gestation weeks 30–34 by reverse transcription coupled with polymerase chain reaction (RT-PCR) and Western blotting, respectively. Statistically significant increases in the expression levels of hsa-miR-17-5p, hsa-miR-21-5p, hsa-miR-25-3p, hsa-miR-92a-3p, and hsa-miR-320a-3p were revealed in the groups of women with AIP (accreta, increta, percreta) relative to the group of women with scars on the uterus or to the group with placenta previa. Opposite changes in the expression level of “gene–target protein/miRNA” pairs were found for the α-subunit of the clusterin secretory form and any of the hsa-miR-21-5p, hsa-miR-25-3p, hsa-miR-92a-3p, hsa-miR-320a-3p, and hsa-miR-17-5p in all cases of AIP. The developed logistic regression models to diagnose AIP cases of various severity gave Se values of 88.8–100% and Sp values of 91.6–100% using a combination of hsa-miR-21-5p, hsa-miR-92a-3p, hsa-miR-320a-3p, or clusterin levels

Vertical Transmission of SARS-CoV-2 in Second Trimester Associated with Severe Neonatal Pathology

The effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in women on the gestation course and the health of the fetus, particularly in the first and second trimesters, remain very poorly explored. This report describes a case in which the normal development of pregnancy was complicated immediately after the patient had experienced Coronavirus disease 2019 (COVID-19) at the 21st week of gestation. Specific conditions included critical blood flow in the fetal umbilical artery, fetal growth restriction (1st percentile), right ventricular hypertrophy, hydropericardium, echo-characteristics of hypoxic-ischemic brain injury (leukomalacia in periventricular area) and intraventricular hemorrhage at the 25th week of gestation. Premature male neonate delivered at the 26th week of gestation died after 1 day 18 h due to asystole. The results of independent polymerase chain reaction (PCR), mass spectrometry and immunohistochemistry analyses of placenta tissue, umbilical cord blood and child blood jointly indicated vertical transmission of SARS–CoV-2 from mother to the fetus, which we conclude to be the major cause for the development of maternal vascular malperfusion in the studied case

Maternal and neonatal outcomes in 80 patients diagnosed with non-Hodgkin lymphoma during pregnancy: results from the International Network of Cancer, Infertility and Pregnancy

This cohort study of the International Network on Cancer, Infertility and Pregnancy (INCIP) reports the maternal and neonatal outcomes of 80 pregnant patients diagnosed with non-Hodgkin lymphoma (NHL) between 1986 and 2019, focussing on 57 (71%) patients with diffuse large B-cell lymphoma (DLBCL). Of all 80 patients, 54 (68%) pregnant patients received chemotherapy; mostly (89%) CHOP-like (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens. Four early pregnancies were terminated. Among 76 ongoing pregnancies, there was one stillbirth (1·3%). Overall, there was a high incidence of small for gestational age neonates (39%), preterm delivery (52%), obstetric (41%) and neonatal complications (12·5%), and this could not exclusively be explained by the receipt of antenatal chemotherapy. Half of preterm deliveries (46%) were planned in order to tailor oncological treatment. The 3-year progression-free and overall survival for patients with DLBCL treated with rituximab-CHOP was 83·4% and 95·7% for limited stage (n = 29) and 60·6% and 73·3% for advanced stage (n = 15). Of 36 pregnant patients who received rituximab, five (13%) cases with neonatal complications and three (8%) with maternal infections were reported. In conclusion, standard treatment for DLBCL can be offered to pregnant patients in obstetric centres that cater for high-risk patients.status: publishe

Maternal and neonatal outcomes in 80 patients diagnosed with non-Hodgkin lymphoma during pregnancy: results from the International Network of Cancer, Infertility and Pregnancy

This cohort study of the International Network on Cancer, Infertility and Pregnancy (INCIP) reports the maternal and neonatal outcomes of 80 pregnant patients diagnosed with non-Hodgkin lymphoma (NHL) between 1986 and 2019, focussing on 57 (71%) patients with diffuse large B-cell lymphoma (DLBCL). Of all 80 patients, 54 (68%) pregnant patients received chemotherapy; mostly (89%) CHOP-like (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens. Four early pregnancies were terminated. Among 76 ongoing pregnancies, there was one stillbirth (1·3%). Overall, there was a high incidence of small for gestational age neonates (39%), preterm delivery (52%), obstetric (41%) and neonatal complications (12·5%), and this could not exclusively be explained by the receipt of antenatal chemotherapy. Half of preterm deliveries (46%) were planned in order to tailor oncological treatment. The 3-year progression-free and overall survival for patients with DLBCL treated with rituximab-CHOP was 83·4% and 95·7% for limited stage (n = 29) and 60·6% and 73·3% for advanced stage (n = 15). Of 36 pregnant patients who received rituximab, five (13%) cases with neonatal complications and three (8%) with maternal infections were reported. In conclusion, standard treatment for DLBCL can be offered to pregnant patients in obstetric centres that cater for high-risk patients

Intermediate-dose versus low-dose low-molecular-weight heparin in pregnant and post-partum women with a history of venous thromboembolism (Highlow study):an open-label, multicentre, randomised, controlled trial

BACKGROUND: Pregnancy-related venous thromboembolism is a leading cause of maternal morbidity and mortality, and thromboprophylaxis is indicated in pregnant and post-partum women with a history of venous thromboembolism. The optimal dose of low-molecular-weight heparin to prevent recurrent venous thromboembolism in pregnancy and the post-partum period is uncertain. METHODS: In this open-label, randomised, controlled trial (Highlow), pregnant women with a history of venous thromboembolism were recruited from 70 hospitals in nine countries (the Netherlands, France, Ireland, Belgium, Norway, Denmark, Canada, the USA, and Russia). Women were eligible if they were aged 18 years or older with a history of objectively confirmed venous thromboembolism, and with a gestational age of 14 weeks or less. Eligible women were randomly assigned (1:1), before 14 weeks of gestational age, using a web-based system and permuted block randomisation (block size of six), stratified by centre, to either weight-adjusted intermediate-dose or fixed low-dose low-molecular-weight heparin subcutaneously once daily until 6 weeks post partum. The primary efficacy outcome was objectively confirmed venous thromboembolism (ie, deep-vein thrombosis, pulmonary embolism, or unusual site venous thrombosis), as determined by an independent central adjudication committee, in the intention-to-treat (ITT) population (ie, all women randomly assigned to treatment). The primary safety outcome was major bleeding which included antepartum, early post-partum (within 24 h after delivery), and late post-partum major bleeding (24 h or longer after delivery until 6 weeks post partum), assessed in all women who received at least one dose of assigned treatment and had a known end of treatment date. This study is registered with ClinicalTrials.gov, NCT01828697, and is now complete. FINDINGS: Between April 24, 2013, and Oct 31, 2020, 1339 pregnant women were screened for eligibility, of whom 1110 were randomly assigned to weight-adjusted intermediate-dose (n=555) or fixed low-dose (n=555) low-molecular-weight heparin (ITT population). Venous thromboembolism occurred in 11 (2%) of 555 women in the weight-adjusted intermediate-dose group and in 16 (3%) of 555 in the fixed low-dose group (relative risk [RR] 0·69 [95% CI 0·32-1·47]; p=0·33). Venous thromboembolism occurred antepartum in five (1%) women in the intermediate-dose group and in five (1%) women in the low-dose group, and post partum in six (1%) women and 11 (2%) women. On-treatment major bleeding in the safety population (N=1045) occurred in 23 (4%) of 520 women in the intermediate-dose group and in 20 (4%) of 525 in the low-dose group (RR 1·16 [95% CI 0·65-2·09]). INTERPRETATION: In women with a history of venous thromboembolism, weight-adjusted intermediate-dose low-molecular-weight heparin during the combined antepartum and post-partum periods was not associated with a lower risk of recurrence than fixed low-dose low-molecular-weight heparin. These results indicate that low-dose low-molecular-weight heparin for thromboprophylaxis during pregnancy is the appropriate dose for the prevention of pregnancy-related recurrent venous thromboembolism. FUNDING: French Ministry of Health, Health Research Board Ireland, GSK/Aspen, and Pfizer

Differential Diagnosis of Preeclampsia Based on Urine Peptidome Features Revealed by High Resolution Mass Spectrometry

Preeclampsia (PE) is a severe pregnancy complication, which may be considered as a systemic response in the second half of pregnancy to physiological failures in the first trimester, and can lead to very serious consequences for the health of the mother and fetus. Since PE is often associated with proteinuria, urine proteomic assays may represent a powerful tool for timely diagnostics and appropriate management. High resolution mass spectrometry was applied for peptidome analysis of 127 urine samples of pregnant women with various hypertensive complications: normotensive controls (n = 17), chronic hypertension (n = 16), gestational hypertension (n = 15), mild PE (n = 25), severe PE (n = 25), and 29 patients with complicated diagnoses. Analysis revealed 3869 peptides, which mostly belong to 116 groups with overlapping sequences. A panel of 22 marker peptide groups reliably differentiating PE was created by multivariate statistics, and included 15 collagen groups (from COL1A1, COL3A1, COL2A1, COL4A4, COL5A1, and COL8A1), and single loci from alpha-1-antitrypsin, fibrinogen, membrane-associated progesterone receptor component 1, insulin, EMI domain-containing protein 1, lysine-specific demethylase 6B, and alpha-2-HS-glycoprotein each. ROC analysis of the created model resulted in 88% sensitivity, 96.8% specificity, and receiver operating characteristic curve (AUC) = 0.947. Obtained results confirm the high diagnostic potential of urinary peptidome profiling for pregnancy hypertensive disorders diagnostics