Evidence of Placental Villous Inflammation and Apoptosis in Third-Trimester Symptomatic SARS-CoV-2 Maternal Infection.

PURPOSE: In view of conflicting reports on the ability of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to infect placental tissue, this study aimed to further evaluate the impact of inflammation and placental damage from symptomatic third-trimester maternal COVID-19 infection. MATERIALS AND METHODS: This case-control study included 32 placenta samples each from symptomatic COVID-19 pregnancy and normal non-COVID-19 pregnancy. The villous placental area's inflammatory expression [angiotensin converting enzyme-2 (ACE-2), transmembrane protease serine-2 (TMPRSS2), interferon-γ (IFN-γ), interleukin-6 (IL-6), and SARS-CoV-2 spike protein] and apoptotic rate were examined using immunohistochemistry and Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) assay. Comparison and correlation analysis were used based on COVID-19 infection, placental SARS-CoV-2 spike protein evidence, and maternal severity status. RESULTS: Higher expressions of TMPRSS2, IFN-γ, and trophoblast apoptotic rate were observed in the COVID-19 group (p<0.001), whereas ACE-2 and IL-6 expressions were not significantly different from the control group (p>0.05). Additionally, SARS-CoV-2 spike protein was detected in 8 (25%) placental samples of COVID-19 pregnancy. COVID-19 subgroup analysis revealed increased IFN-γ, trophoblast, and stromal apoptosis (p<0.01). Moreover, the results of the current study revealed no correlation between maternal COVID-19 severity and placental inflammation as well as the apoptotic process. CONCLUSION: The presence of SARS-CoV-2 spike protein as well as altered inflammatory and apoptotic processes may indicate the presence of placental disturbance in third-trimester maternal COVID-19 infection. The lack of correlation between placental disruption and maternal severity status suggests the need for more research to understand the infection process and any potential long-term impacts on all offsprings born to COVID-19-infected pregnant women.

Uterine conservative-resective surgery for selected placenta accreta spectrum cases: Surgical-vascular control methods.

INTRODUCTION: The incidence of placenta accreta spectrum (PAS) has increased, but the optimal management and the optimal way to achieve vascular control are still controversial. This study aims to compare maternal outcomes between different methods of vascular control in surgical PAS management. MATERIAL AND METHODS: A retrospective cohort study on consecutive cases diagnosed with PAS between 2013 and 2020 in single tertiary hospital. The final diagnosis of PAS was made following preoperative ultrasound and confirmation during surgery. Management of PAS using cesarean hysterectomy with internal iliac artery ligation (IIAL) was compared with two types of vascular control in uterine conservative-resective surgery (IIAL vs identification-ligation of the upper vesical, upper vaginal, and uterine arteries). RESULTS: Over an 8-year period, 234 pregnant women were diagnosed with PAS meeting the inclusion criteria. Uterine conservative-resective surgery (200 cases) was associated with lower mean blood loss compared with cesarean hysterectomy with IIAL (34 cases) in all PAS cases (1379 ± 769 mL vs 3168 ± 1916 mL; p < 0.001). In sub-analysis of the two uterine conservative-resective surgery subgroups, the group with identification-ligation of the upper vesical, upper vaginal, and uterine arteries had a significantly lower blood loss compared with uterine conservative-resective surgery with IIAL (1307 ± 743 mL vs 1701 ± 813 mL; p = 0.005). Women in the hysterectomy with IIAL group had more massive transfusion (35.3% vs 2.5%; p < 0.001; odds ratio [OR] 21.3, 95% confidence interval [CI] 6.9-66), major blood loss (>1500 mL) (70.6% vs 34%, p < 0.001; OR 4.7; 95% CI 2.1-10.3), catastrophic blood loss (>2500 mL) (64.7% vs 12.5%;p < 0.001; OR 12.8, 95% CI 5.7-29.1), other complications (32% vs 12.4%; p = 0.007; OR 3.4, 95% CI 1.5-7.7), and intensive care unit admission (32.4% vs 1.5%; p < 0.001; OR 31.4, 95% CI 8.2-120.7) compared with the uterine conservative-resective surgery groups. The identification-ligation of the upper vesical, upper vaginal and uterine arteries had a significant lower risk for major blood loss (30.5% vs 50%; p = 0.041; OR 0.44, 95% CI = 0.2-0.9) compared with IIAL for vascular control of uterine conservative-resective surgery. CONCLUSIONS: Cesarean hysterectomy is not the default treatment for PAS, PAS with invasion above the vesical trigone are suitable for uterine conservative-resective surgery with upper vesical, upper vaginal and uterine artery vascular control.

mRNA Covid-19 vaccines in pregnancy: A systematic review.

OBJECTIVE: Pregnancy is a known risk factor for severe Coronavirus disease 2019. It is important to develop safe vaccines that elicit strong maternal and fetal antibody responses. METHODS: Registries (ClinicalTrials.gov, the WHO Clinical Trial Registry, and the European Union Clinical Trial Registry) and databases (MEDLINE, ScienceDirect, Cochrane Library, Proquest, Springer, medRxiv, and bioRxiv) were systematically searched in June 20-22, 2021, for research articles pertaining to Covid-19 and pregnancy. Manual searches of bioRxiv and medRxiv were also conducted. Inclusion criteria were studies that focused on Covid-19 vaccination among pregnant women, while review articles and non-human studies were excluded. Infection rate, maternal antibody response, transplacental antibody transfer, and adverse events were described. RESULTS: There were 13 observational studies with a total of 48,039 pregnant women who received mRNA vaccines. Of those, three studies investigated infection rate, six studies investigated maternal antibody response, seven studies investigated antibody transfer, three studies reported local adverse events, and five studies reported systemic adverse events. The available data suggested that the mRNA-based vaccines (Pfizer-BioNTech and Moderna) can prevent future SARS-CoV-2 infection. These vaccines did not show clear harm in pregnancy. The most commonly encountered adverse reactions were pain at the injection site, fatigue, and headache, but these were transient. Antibody responses were rapid after the first vaccine dose. After the booster, antibody responses were stronger and associated with better transplacental antibody transfer. Longer intervals between first vaccination dose and delivery were also associated with higher antibody fetal IgG and a better antibody transfer ratio. CONCLUSIONS: The SARS-CoV-2 mRNA vaccines are encouraged for pregnancy. These vaccines can be a safe option for pregnant women and their fetuses. Two vaccine doses are recommended for more robust maternal and fetal antibody responses. Longer latency is associated with higher fetal antibody responses. Further research about its long-term effect on pregnancy is needed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42021261684).

Remdesivir for pregnancy: A systematic review of antiviral therapy for COVID-19.

OBJECTIVE: The use of remdesivir for pregnant patients with coronavirus disease 2019 (COVID-19) showed conflicting results in prior studies. We aimed to systematically review its efficacy and safety for this population from the existing literature. METHODS: On July 26, 2021, registries (ClinicalTrials.gov) and databases (MEDLINE, ScienceDirect, Cochrane Library, JSTOR, DOAJ, and medRxiv) were systematically searched for research articles investigating remdesivir use in pregnant people with COVID-19. Clinical outcome, hospitalization duration, laboratory outcome, mortality, and adverse events were investigated. RESULTS: We obtained 13 observation studies with 113 pregnant people. In these studies, remdesivir improved the clinical condition of pregnant patients with COVID-19, especially those who had a better clinical status at baseline and received earlier remdesivir treatment. Most fetuses were delivered via cesarean section, primarily because of emergency causes. No vertical transmissions were noted. The most reported adverse event was transaminitis, in which 10-day remdesivir treatment yielded more incidence than the 5-day treatment. CONCLUSIONS: In pregnancy, the use of Remdesivir in combination with other COVID-19 treatments is inconclusive but its use should be followed with careful monitoring of adverse reactions and transaminase enzyme levels. Further studies are required to confirm its finding.

Clinical manifestations and pregnancy outcomes of COVID-19 in indonesian referral hospital in central pandemic area.

OBJECTIVE: s Data on the clinical manifestations and pregnancy outcomes of pregnant women with COVID-19 are limited, particularly in developing countries. The aim of this study was to analyze the clinical manifestations and pregnancy outcomes in COVID-19 maternal cases in a large referral hospital in Indonesia. METHODS: This study used a prospective cohort design and included all pregnant women with suspected COVID-19. Subjects were divided into COVID-19 and non-COVID-19 groups based on the results of real-time polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2. Clinical characteristics, laboratory results, and pregnancy outcomes were compared between the two groups. RESULTS: Of the 141 suspected maternal cases, 62 cases were COVID-19-confirmed (43.9%), while 79 suspected cases were negative (56.1%). The clinical manifestations and laboratory findings between the two groups were not significantly different (P>0.05). However, the maternal mortality directly caused by COVID-19 was significantly higher than that in the non-COVID-19 group (8.3% vs. 1.3%; P=0.044; odd ratio, 6.91; 95% confidence interval, 0.79-60.81). CONCLUSION: The clinical manifestations and laboratory results of suspected pregnant women with positive and negative RT-PCR COVID-19 results were similar. However, within the Indonesian setting, COVID-19 significantly increases the risk of maternal death through both direct and indirect factors.

Management of placenta accreta spectrum disorders in COVID 19 patients.

INTRODUCTION: The COVID-19 pandemic has made it difficult to respond to demands in maternal health around the world. Placenta accreta spectrum (PAS) is one of the most severe obstetric conditions and usually requires the use of multiple health resources We describe the clinical results of the management of PAS patients during the COVID-19 pandemic and analyze how the pandemic may affect the functioning of a PAS team. METHODOLOGY: This was a descriptive, retrospective study including all patients treated for PAS in two low- to middle-income country reference hospitals between January 2020 and March 2021. The clinical results of patients with SARS-CoV-2 infection during PAS surgery (Group 1) were compared with those of PAS patients without SARS-CoV-2 infection (Group 2). RESULTS: One hundred forty-five patients undergoing surgery for PAS were included. Group 1 patients (11 cases) showed a longer operative time (250 min, IQR 200-300) and a higher frequency of intra- or postoperative complications (54.5%) than group 2 patients (180 min [IQR 125-240], and 17.9%). CONCLUSION: Placenta accreta spectrum patients undergoing surgery during acute SARS-CoV-2 infection have a higher frequency of postoperative complications. PAS teams must prepare to modify their management protocols to minimize risks for patients and healthcare personnel.

INA-CBGs claim versus total hospital cost: A vaginal delivery investigation at Airlangga University Academic Hospital, Indonesia.

Background: Inadequate funding for vaginal delivery can be one of the barriers to reducing the maternal mortality rate. It could be therefore critical to compare the vaginal delivery cost between total hospital cost and INA-CBGs cost in national health insurance. Methods: This was a retrospective cross-sectional study conducted from October to December 2019 in Universitas Airlangga Academic Hospital. It collected data on primary diagnosis, length of stay, total hospital cost, INA-CBGs cost, and counted disparity. The data analyzed statistically using t-test independent sample (or Mann-Whitney test). Results: A total of 149 vaginal delivery claims were found, with the majority having a level II severity (79.87%) and moderate preeclampsia as a primary diagnosis (20.1%). There was a significant disparity in higher total hospital costs compared with government INA-CBGs costs (Rp. 9,238,022.09±1,265,801.88 vs 1,881,521.48±12,830.15; p<0.001). There was also an increase of LOS (p<0.001), total hospital cost (p<0.001), and cost disparity (p<0.01) in a higher severity level of vaginal delivery. Conclusion: Vaginal delivery costs in INA-CBGs scheme are underneath the actuarial value. There was also an increase in total hospital costs and a more significant disparity in the higher severity levels of vaginal delivery.

New three-dimensional/four-dimensional volume rendering imaging software for detecting the abnormally invasive placenta.

OBJECTIVE: This study aimed to determine the role of three-dimensional (3D)/four-dimensional (4D) volume rendering ultrasound (VRU) in the diagnosis of abnormally invasive placenta (AIP). MATERIALS AND METHODS: Twelve consecutive patients strongly suspected of having AIP on the basis of conventional ultrasound (US) and clinical history performed between September 2016 and December 2016 in the main tertiary referral hospital in Surabaya, East Java were included in this prospective observational study. A Samsung WS 80A Elite US scanner with a 3D/4D "crystal vue" and "realistic vue" volume rendering mode was used to establish the diagnosis of AIP and evaluate the site, and depth of placental invasion. The VRU images were compared with the intraoperative findings. RESULTS: Using this novel US technique, all cases of suspected AIP were subsequently confirmed during surgery. Importantly, the new US technique provided a correct diagnosis of the degree of invasion in 11 out of these 12 suspected AIP cases: 5/5 for placenta percreta, 3/3 for placenta increta, and 2/3 for placenta accreta; one patient was misdiagnosed in terms of the degree of placenta accreta, and one patient had normal implantation). CONCLUSION: This new software of 3D/4D VRU represents a promising technique for the preoperative diagnosis and staging of AIP.

Serum heme oxygenase 1 (HO-1), soluble FMS like tyrosine kinase (sFlt-1) level, and neonatal outcome in early onset, late onset preeclampsia, and normal pregnancy.

OBJECTIVE: To compare the level of serum heme oxygenase 1 (HO-1), soluble FMS like tyrosine kinase (sFlt-1), and neonatal outcome in early onset preeclampsia (EO-PE), late onset preeclampsia (LO-PE), and normal pregnancy (NP). METHODS: In this prospective observational case control study, HO-1 and sFlt-1 levels were measured in blood samples within 24 h of hospital admission. Preeclampsia cases were divided into two groups based on gestational age at delivery: EO-PE (<34 weeks) and LO-PE (≥34 weeks). A total of 45 patients were involved in this study. RESULT: Maternal serum level of sFlt-1 was higher in EO-PE than LO-PE and NP groups (mean ± SD; 14.50 ± 17.12 ng/ml vs 5.20 ± 6.69 ng/ml vs 2.72 ± 1.2 ng/ml [p = 0.020]. Maternal serum level of HO-1 was not different between EO-PE, LO-PE, and NP groups (p = 0.681). Birthweights were significantly lower in the EO-PE group compared with the LO-PE and NP groups (1580 ± 536 g vs 2635 ± 578 g vs 3010 ± 371 g [p = 0.000]). The rate of small for gestational age infant (26.7% vs 6.7% vs 0%; p = 0.046) and perinatal death (20% vs 0 vs 0; p = 0.037) was also significantly higher in EO-PE compared to LO-PE and NP. The maternal sFlt-1 level was negatively correlated with birthweight (p = 0.006; CC = -0.445). CONCLUSION: This study did not find a correlation between maternal HO-1 levels and sFlt-1 levels. Maternal serum sFLt-1 levels in preeclampsia were higher in EO-PE and were associated with a worse perinatal outcome.

Pulmonary edema in preeclampsia: an Indonesian case-control study.

OBJECTIVE: To analyze risk factors, obstetric outcome and the need for mechanical ventilation in preeclampsia complicated by pulmonary edema. MATERIALS AND METHODS: Case-control study using medical record on preeclampsia complicated by pulmonary edema patients in East Java tertiary referral hospital over 2 years. A simple scoring system was developed to predict the need for mechanical ventilation, using logistic regression. RESULTS: 1106 cases of preeclampsia were admitted, with 62 cases (5.6%) had pulmonary edema. Postpartum (p < .001) and cesarean delivery (p = .001) proportions were higher in the preeclampsia with pulmonary edema group. Of the 62 cases with pulmonary edema, 81% required intensive care admission and 60% needed mechanical ventilation support. Mechanical ventilation used was associated with eclampsia (p = .04), hypertensive crisis (p = .02), lower serum albumin (p = .05) and higher creatinine (p = .01). A simple scoring model developed could predict a 46%-99% probability of need for mechanical ventilation (AUC (ROC): 0.856, 95%CI 0.763-0.95). CONCLUSIONS: Pulmonary edema is a common complication of preeclampsia in Indonesian referral hospitals. This severe complication increased maternal and perinatal morbidity and mortality. The developed scoring model in this study can be used as a triage tool to predict the probability of mechanical ventilation use due to this complication.