Modern possibilities of correction of postcovid disorders in the fetoplacental complex

The objective: to determine the peculiarities of hormonal support, liver enzymatic function and the state of the fetal-placental complex (FPC) in unvaccinated women with fetal growth retardation (FGR) and placental dysfunction (PD) who was ill with the coronavirus disease during the current pregnancy, on the background of the proposed correction scheme of the disorders and evaluation of its effectiveness. Materials and methods. The study included 22 pregnant women with FGR and PD who were being treated and delivered in the Department of Pregnancy and Childbirth Pathology of the State Institution «Institute of Pediatrics, Obstetrics and Gynecology named after Academician O.M. Lukyanova National Academy of Sciences of Ukraine» in 2021–2022 and suffered a coronavirus disease during the current pregnancy. All pregnant women had a general clinical examination and the following parameters were additionally determined: the level of placental lactogen (PL) in blood serum, indicators of liver enzyme activity (alanine aminotransferase – ALT, aspartate aminotransferase – AST, gamma-glutamyl transpeptidase – GHTP), the level of estriol in urine (after the 22d week of pregnancy). The examination was carried out before the start of treatment and preventive measures and 12–14 days after a 10-day course of therapy with simultaneous ultrasound (US) monitoring of the condition of the FPC. In the case of diagnosis of FGR and PD, a course of therapy was carried out, which included daily consecutive intravenous infusions of a balanced crystalloid infusion preparation with lactate and sorbitol in the amount of 200 ml and a solution of levocarnitine and arginine hydrochloride in the amount of 100 ml for 10 days, followed by ultrasound control of the condition of the fetus and FPC. The evaluation of the effectiveness of the treatment was carried out based on a combination of clinical, laboratory and instrumental indicators after 10 days of therapy. Results. All pregnant women had a moderate or mild course of the coronavirus disease at different terms of the current pregnancy. There were 9 (40.9 %) women who were infected with SARS-CoV-2 in the early terms of pregnancy (up to 12 weeks), and they were diagnosed the 2nd and 2nd-3rd degrees of FGR. The majority of pregnant women had gestational complications. Before treatment, 10 (45.5 %) women had oligohydramnios. FGR was diagnosed in 14 (63.6 %) pregnant women, among them: in 3 (13.6 %) persons – fetal growth retardation of the 2nd-3rd degree, in 6 (27.3 %) – of the 2nd degree, in 5 (22.7 %) – 1st degree. The analysis of laboratory indicators demonstrated the increase in the levels of ALT, AST and GHTP, and a decrease in the levels of estriol in urine. After the proposed course of treatment, oligohydramnios was found only in 2 (9.1 %) women. The average amniotic index before treatment was 10.1, after treatment – 15.3. 4 (18.2 %) women were diagnosed FGR after the treatment. As a result of the treatment, the improvement of all determined laboratory parameters and perinatal consequences were determined. Conclusions. The proposed scheme for correcting the identified disorders with the inclusion of balanced crystalloid infusion preparation with lactate and sorbitol and balanced crystalloid infusion preparation with lactate and sorbitol drugs made possible to improve microcirculation, metabolic processes, and to normalize the consequences of postcovid endotheliitis in the vascular system of pregnant women in general and in the FPC, in particular. This was manifested in the improvement of clinical, laboratory and instrumental indicators of conducted studies and had a positive effect on perinatal results. © The Author(s) 2022 This is an open access article under the Creative Commons CC BY license.

FETAL GROWTH RETARDATION AS A COMPLICATION OF POST-COVID ENDOTHELIITIS: CAUSES, CONSEQUENCES, WAYS OF PREVENTION.

The risk of fetal intrauterine growth retardation (IUGR) is increased in women who have experienced acute infections, as well as in pregnant women with gynecological pathology and endocrine diseases. A woman's lack of nutrition also makes a negative contribution to the development of IUGR. The frequency of IUGR in the population is very variable and depends on a number of reasons. In practically healthy pregnant women, IUGR is registered in 3-5% of cases, in case of complicated obstetric and gynecological diagnosis and complicated pregnancy - in 10-25%. Morphofunctional disorders in the chorion/placenta in pregnant women with COVID-19 on the background of post-covid endotheliitis are the main pathogenetic factor in the development of preeclampsia, ectopic pregnancy, antenatal fetal death, and impaired condition of the fetus and newborns. Sufficient saturation of the pregnant woman's body with the nitric oxide donor L-arginine and L-carnitine (main cofactor of fatty acid metabolism in cells) with the improvement of microcirculation and the correction of hypovolemic disorders in the fetoplacental complex can be considered one of the real ways to prevent IUGR in women in the post-covid period. A review of the scientific literature on pathogenesis, diagnosis, impact on the life and health of a newborn with IUGR in women after COVID-19, as well as the possibilities of medical correction of placental dysfunction during pregnancy was performed. This analysis and our own clinical experience allow us to state the fact that after a coronavirus infection during pregnancy, one of the frequent and threatening for the further development of the child is the formation of placental dysfunction and IUGR. One of the ways to prevent these conditions is to saturate the woman's body with the nitric oxide donor L-arginine from the stage of pre-gravid preparation, which will provide the opportunity for adequate angiogenesis and development of the embryo/fetus. In the case of additional risk factors, such as coronavirus disease, complex therapy blood (Rheosorbilact), in combination with a nitric oxide donor and L-carnitine as an endothelium-protective agent (Tivor-L).Copyright © 2022 Authors. All rights reserved.

The sFlt-1/PlGF Ratio in Pregnant Patients Affected by COVID-19.

COVID-19 in pregnant women increases the risk of adverse pregnancy outcomes, including preeclampsia. This meta-analysis aimed to examine the effect of SARS-CoV-2 infection on sFlt-1/PIGF ratio during pregnancy. The study was designed as a systematic review and meta-analysis. PubMed, Web of Science, Embase and Cochrane Library were searched for relevant studies reporting the sFlt-1/PlGF ratio in pregnant women with COVID-19. Results were compared using meta-analysis by the Mantel-Haenszel method. A total of 7 studies were included in the analysis. sFlt-1/PlGF ratios between COVID-19 positive vs. negative women were 45.8 ± 50.3 vs. 37.4 ± 22.5, respectively (SMD = 1.76; 95% CI: 0.43 to 3.09; p = 0.01). sFlt-1/PlGF ratios between asymptomatic vs. symptomatic patients were 49.3 ± 35.7 vs. 37.1 ± 25.6 (SMD = 0.30; 95% CI: -0.35 to 0.95; p = 0.36). sFlt-1/PlGF ratio in non-severe group was 30.7 ± 56.5, compared to 64.7 ± 53.5 for severe patients (SMD = -1.88; 95% CI: -3.77 to 0.01; p = 0.05). sFlt-1/PlGF ratios in COVID-19 patients, with and without hypertensive disease of pregnancy, were 187.0 ± 121.8 vs. 21.6 ± 8.6, respectively (SMD = 2.46; 95% CI: 0.99 to 3.93; p = 0.001). Conclusions: Patients with COVID-19, as compared to patients without COVID-19, were characterized by higher sFlt-1/PlGF ratio. Moreover, severe COVID-19 and SARS-CoV-2 infection in hypertensive pregnant women was related to significantly higher sFlt-1/PlGF ratio.

Imbalanced Angiogenesis in Pregnancies Complicated by SARS-CoV-2 Infection.

COVID-19 and preeclampsia (preE) share the ANG-II mediated endothelial dysfunction, resulting from a significant dysregulation of RAS and an imbalanced proportion of anti-angiogenic and pro-angiogenic soluble plasmatic factors. Of note, an increased incidence of preE has been reported among COVID-19-infected mothers compared to the general pregnant population. The two most promising angiogenic markers are the soluble fms-like tyrosine kinase receptor-1 (sFlt-1), the major antiangiogenic factor, and the placental growth factor (PlGF), a powerful angiogenic factor. Since these markers have proven useful in the prediction, diagnosis, and severity of preE, this study aimed to evaluate their maternal serum levels in pregnancies complicated by SARS-CoV-2 infection and to assess their potential use to guide the management of these women. A retrospective analysis of SARS-CoV-2-positive pregnant women was performed. The serum levels of sFlt-1 and PlGF were collected at the diagnosis of SARS-CoV-2 infection at the hospital, before the beginning of steroid/hydroxychloroquine and/or antithrombotic therapy. The sFlt-1/PlGF ratio was stratified using cut-off values clinically utilized in the diagnosis and prediction of preE (low < 38, intermediate 38-85/110* and high >85/110*, * if before or after the 34th week of gestation). A total of 57 women were included, of whom 20 (35%) had signs and symptoms of COVID-19 at hospital presentation and 37 (65%) were asymptomatic. None were vaccinated. The mean gestational age at diagnosis of SARS-CoV-2 infection was 32 weeks in symptomatic patients and 37 weeks and 5 days in asymptomatic ones (p = 0.089). sFlt-1 serum levels were higher in SARS-CoV-2 positive asymptomatic patients compared to women with COVID-19 related symptoms (4899 ± 4357 pg/mL vs. 3187 ± 2426 pg/mL, p = 0.005). sFlt-1/PlGF at admission was <38 in 18 of the 20 symptomatic women (90%) compared to 22 (59%) of the asymptomatic patients (p = 0.018). Of note, two of the three women admitted to the intensive care unit had a very low ratio (<2). In turn, rates of patients with sFlt-1/PlGF at admission > 85/110 were not significantly different between the two groups: 11% in asymptomatic patients (4/37) vs. none of the symptomatic patients (p = 0.286), and all of them presented a placental dysfunction, like preE (n = 1) and FGR (n = 3). Of note, there were no stillbirths or maternal or neonatal deaths among symptomatic patients; also, no cases of preE, FGR, or small for gestational age neonates were diagnosed. In conclusion, our data suggest that SARS-CoV-2 infection during pregnancy could influence the angiogenic balance. A significant pathological alteration of the sFlt-1/PlGF ratio cannot be identified during the symptomatic phase; however, if left untreated, SARS-CoV-2 infection could potentially trigger placental dysfunction.

Laminar Necrosis and Hypoxic Damage of the Placenta: A Case-Control Study.

The aim of this study is to verify the role of laminar necrosis (LN) in the diagnosis of hypoxic damage of the placenta. This is a retrospective case-control study in which 50 cases with laminar necrosis were compared with 100 gestational age-matched controls without laminar necrosis in a 1:2 ratio. The parameters analyzed were: the presence of other placental lesions, obstetric characteristics and neonatal outcome. For each of the 50 cases, the area affected by the lesion was detected, and the lesions were classified into three groups based on the morphology and time of onset of the lesion in order to understand whether these characteristics of the lesion had a clinical-pathology. The results showed that including the search for LN among placental lesions generally examined is useful to guide the pathologist in the diagnosis of placental dysfunction of hypoxic origin.

A prospective cohort study of confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy evaluating SARS-CoV-2 antibodies in maternal and umbilical cord blood and SARS-CoV-2 in vaginal swabs.

INTRODUCTION: Evidence about the consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is rapidly increasing; however, data on antibody response and risk of transmission during pregnancy and delivery are still limited. The aim of this study was to evaluate if SARS-CoV-2 is detectable in vaginal swabs and whether antibodies against SARS-CoV-2 are present in maternal and umbilical cord blood of pregnant women with confirmed SARS-CoV-2. MATERIAL AND METHODS: A single-unit prospective cohort study in Denmark including pregnant women with SARS-CoV-2 infection confirmed by a pharyngeal swab between August 20, 2020, and March 1, 2021, who gave birth during the same period. All patients admitted to the maternity ward and antepartum clinic were screened for SARS-CoV-2 infection. A maternal blood sample and vaginal swabs were collected at inclusion. If included antepartum, these samples were repeated intrapartum when an umbilical cord blood sample was also collected. Swabs were analyzed for SARS-CoV-2 and blood samples were analyzed for SARS-CoV-2 total antibodies. Placental and neonatal swabs as well as placental histopathological examinations were performed on clinical indications. RESULTS: We included 28 women, of whom four had serious maternal or fetal outcomes including one case of neonatal death. Within the first 8 days after confirmed SARS-CoV-2 infection, SARS-CoV-2 was detectable in two vaginal swabs (2/28) and SARS-CoV-2 antibodies were detected in 1 of 13 women. From 16 days after confirmed infection, antibodies were observed in 19 of 21 of women. Antibodies in cord blood were not detected during the first 16 days after confirmed infection (n = 7). However, from 26 days, antibodies were present in 16 of 17 cord blood samples of seropositive mothers. Placental examination in two cases of severe fetal outcomes preceded by reduced fetal movements revealed SARS-CoV-2 in swabs and severe histopathological abnormalities. CONCLUSIONS: SARS-CoV-2 was detected in only 2 of 28 vaginal swabs within 8 days after confirmed infection in pregnant women. Our data suggest that maternal seroconversion occurs between days 8 and 16, whereas antibodies in cord blood of seropositive mothers were present in the majority from 26 days after confirmed infection. Additional data are needed regarding timing of seroconversion for the mother and appearance of antibodies in cord blood.