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Remdesivir (RDV) is an antiviral medication used most recently for the treatment of COVID-19. Although no adverse effects were observed on perinatal parameters in reproductive and development toxicology studies at doses up to four-fold clinical area under the curve (AUC) exposures, some researchers have reported that therapeutic levels of RDV may impair early embryogenesis, as observed by in vitro studies. In addition, the influence of prenatal RDV exposure on maternal IgG transfer in the placenta is still unknown. Administration of RDV in pregnant humanized mouse model (Tg32), which expresses the human Fc gamma receptor and transporter (FCGRT) gene, was used to further evaluate potential effects on IgG transfer and concurrent perinatal endpoints. Animals were dosed daily from gestational days (GDs) 10- 14 with 25 mg/kg RDV (GS-5734) via intravenous injection (n=3-5 per group). Concurrent vehicle control animals were dosed intravenously with 12% sulfobutyl ether- beta-cyclodextrin in water (pH3.5;NaOH/HCl). All animals were administered 2 mg/kg human IgG via intravenous injection on GD 14. Placentae and fetuses were collected from dams on GD 14, 15, 16, and 18 and evaluated using histopathology and qPCR for inflammation markers. No abnormal morphologies (necrosis/apoptosis) of placentae were observed between the concurrent control and RDVdosed groups. Additionally, no differences in maternal body weights were observed. There were no statistically significant differences in placenta weights. There were no statistically significant changes in pregnancy parameters (implantation sites and dead fetuses/litter) and fetal weights between the RDV-dosed group and concurrent controls at GD 14, 15, 16, and 18. No changes were observed in transcript levels of inflammation markers in the RDV-dosed group when compared to the concurrent control group. There was a slightly lower ratio of fetal IgG level to maternal IgG levels in the RDV-dosed group;however, no statistically significant differences were observed between the RDV-dosed group and concurrent controls on GD 14, 15, 16, and 18. Our results suggest that a daily dose of 25 mg/kg RDV on GDs 10-14 in humanized mice did not cause adverse effects on placenta and fetal development. (Funded by the Perinatal Health Center of Excellence: E0300201.).
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Background: COVID-19 infection during pregnancy is associated with increased rates of adverse perinatal outcomes. The mechanism by which this occurs is not understood. We have previously reported increased rates of placental histopathological lesions in these pregnancies. Aim(s): We hypothesise that, 1. trimester of infection, and 2. vaccination status, affects placental histopathology and neonatal outcomes. Method(s): Pregnant women infected with COVID-19 between January 2020 and May 2022 were retrospectively identified from Monash Health records. Maternal and neonatal data were collected alongside placental histopathological changes as categorised by the Amsterdam Criteria. Result(s): 942/21838 women had COVID-19 infection during pregnancy. Placental histopathology was available in 638 cases. Analysis of infection by trimester revealed that earlier infection was associated with increased preterm birth rate (13.5% vs. 10.3% vs. 4.5%, P = 0.0012), reduced birth weight (3108 vs. 3216 vs. 3345 g, P = 0.0061) and increased fetal loss rate (2.7% vs. 1.8% vs. 0%, P = 0.0023, in T1 vs. T2 vs. T3, respectively) (Table 1). Placental weight increased with trimester of infection (416 vs. 469 vs. 487 g, P = 0.0267). There were no differences in histopathological lesions. 300 patients were unvaccinated (>=1 dose) versus 642 double vaccinated (>=2 doses) against COVID-19 (Table 2). Double vaccination resulted in fewer placental histopathological lesions (59.0% vs. 69.9%, P = 0.0089), particularly maternal vascular malperfusion lesions (20.7% vs. 28.2%, P = 0.0127) but no difference in perinatal outcomes. Conclusion(s): COVID-19 infection earlier in pregnancy is associated with poorer perinatal outcomes. Vaccination reduced the rate of placental lesions but did not change adverse neonatal outcomes.
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Background: The emergence of coronavirus disease 19 (COVID-19) as a novel zoonotic disease has been of international concern, with recent studies highlighting the potential association of COVID-19 with placental vascular dysfunction.1,2 Because the increased incidence of histopathological lesions could imply an aetiologic relationship with SARS-CoV-2 infection, this study aims to audit the spectrum of subacute placental disease occurring in COVID-19 positive mothers. Method(s): Histopathological reports were obtained from Liverpool Hospital from 18 March 2020 to 18 March 2022 and subjected to retrospective histopathological report audit. Three hundred and five placentas from mothers with history of COVID-19 infection during pregnancy were compared with 305 randomly selected controls with no reported COVID-19 infection. Information obtained included maternal age, fetal gestation at delivery, macroscopic measurements and 12 histopathological variables. Missing data was imputed using a random forest algorithm, with downstream multivariate statistical analysis. Validation of findings was performed via non-linear principal component analysis (NLPCA). Result(s): A significant increase in mean placental weight was observed in mothers with a history of COVID-19 (COVID-19 cohort 480g, control cohort 423g, p < 0.0001). Median gestation was significantly increased within the COVID-19 cohort at 38.2 weeks compared to 36.5 weeks in controls (p <0.0001). Surprisingly, there was no increase in histopathological lesions within the COVID-19 cohort. Similar findings were confirmed with NLPCA. These findings highlight the possible resistance of the placental disc to COVID-19 infection and the utility of utilising imputation and NLPCA in the study of potential new pathological entities. References 1. Wong YP, Khong TY, Tan GC. The Effects of COVID-19 on placenta and pregnancy: what do we know so far? Diagnostics 2021;11: 94. 2. Boyraz B, James K, Hornick J, et al. Placental pathology from COVID-19 recovered (nonacute) patients. Human Pathology 2022;125: 18-22.
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Aim: Coronavirus disease 2019 (COVID-19) pandemic is an ongoing emergency with limited data on perinatal outcomes. The aim of the study was to describe key maternal, perinatal, and neonatal outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from low–middle income settings. Materials and methods: We conducted a retrospective observational study in a tertiary level public hospital in India. All pregnant women admitted from May 2020 to July 2020 were included in the study. Maternal demography, medical and obstetric complications, clinical characteristics, and investigations were described. Symptomatic infected women were compared with the asymptomatic group for important outcomes. Key perinatal outcomes such as early pregnancy losses, fetal distress, stillbirths, and placental changes were evaluated. Neonatal characteristics of SARS-CoV-2 positive and negative pregnancies were described and compared. Results: Among the 702 pregnant women enrolled, the incidence of SARS-CoV-2 infection was 16.2%, with the majority being asymptomatic. Infected women had an increased mortality, while symptomatic women had a significant risk of stillbirth. Mean placental weight of infected women was significantly higher. Neonatal infection rate was 9.1%, with 50% manifesting mild respiratory symptoms without any mortality. Conclusion: This study provides a comprehensive description of important antenatal, intrapartum and neonatal complications and outcomes in a low–middle income setting characterized by high disease burden and an overwhelmed health care system. Clinical significance: Incidence of SARS-CoV-2 infection in pregnancy was 16.2%. The symptomatic infected women had increased stillbirth and mortality. Neonatal transmission was seen in 9.1% with good survival.
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Background: Although there are many studies examining the clinical outcomes of women and their infants diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, during pregnancy, the reasons causing the possible adverse outcomes remain unclear1. This study examines placental pathology from women who contracted COVID-19 during pregnancy at this university hospital institution. Design: This study was centered around all 19 placenta specimens from patients infected with COVID-19 at this university hospital. The American College of Obstetricians and Gynecologists (ACOG) allow for the judgement of the Obstetrics physician to be the predominant factor in the decision of sending the placenta specimen for pathology evaluation. Therefore ACOG and CRICO (a risk retention group for medical practitioners) work in conjunction to recommend that placentas be sent for pathology evaluation when clinically indicated. All 19 placenta specimens that were submitted in this study met at least one of these recommendations and therefore 19 age matched controls without COVID-19 infection were reviewed in order to outline any significant clinical trends. The age matched controls were selected within the same time frame as the COVID-19 specimens, which was June 2020 to August 2021. Results: The interval of initial COVID-19 diagnosis and time of placenta evaluation was documented in each case, with the median time interval being 2 days (minimum 1day to maximum 91 days). The gestational age for each patient was calculated, and the average gestational age was a full term pregnancy of 37.2 weeks. 90% of the patients were identified to be of Hispanic ethnicity and heritage, while the other two patients were of Caucasian descent. 63% of the placental weights from the COVID specimens were 25th percentile or lower, whereas only 21% of the age matched controls were 25th percentile or lower. 63% of the cases were recognized to contain histopathological abnormalities, 10.5% in aged matched controls. 4 cases were found to have intra-placental infarction (figure 1), 2 cases were identified to have chorangiosis, 1 case of villous ischemic change, 1 case of decidual laminar necrosis, 1 case of meconium, and 2 cases of acute chorioamnionitis. Conclusions: In this study on average the placenta weight was identified to be lower than age matched controls and placental abnormalities were identified more often in patients infected with COVID 19 (63% vs. 10.5%). (Table Presented).
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Introduction A higher risk for adverse pregnancy outcome has been described in association with SARS-CoV-2 infection, which partially could be explained through alteration of the placental function. However, no significant placental damage in SARS-CoV-2-positive women could be found to date, as no histopathological 'footprint' in association with SARS-CoV-2 is yet available. Birthweight/placental weight ratio (b/p ratio), also defined as gram fetus per gram placenta, is a marker of placental efficiency. A high b/p ratio seems to be associated with adverse obstetrical outcome, revealing an increased nutrient transfer to the fetus, who despite its normal weight, seems to be at risk by 'outgrowing' its placenta. Given the inconsistency of data regarding placental histopathology, we decided for evaluation of the placental weight after SARS-CoV2 infection during pregnancy, by performing a case-control analysis. Methods We included in our study data originating from 153 women who suffered from SARS-CoV-2 infection during pregnancy and delivered since May 2020 at three large obstetrical centres in Switzerland. Placental weight was assessed in a standard manner. Placental weight and b/p ratio were compared to published reference charts (Thompson et al, BJOG 2007). Crude odds ratio (OR) was estimated using simple logistic regression depending on pregnancy trimester at diagnosis of SARS-CoV-2 infection. Results Placental weight was inferior or equal to the 10th centile in 42% (65/153) and inferior or equal to 3rd centile in 19% (29/153) of the cases. The risk of placental low weight was not significantly different between each trimester of infection. Multiparty was the only significant associated factor to the risk of low placental weight. Incidence of fetal growth restriction (FGR) was 11.6% (18/153), whereas presence of preeclampsia was noted in 0.03% of the cases (5/153). Gestational diabetes was present in 19.60% of the cases (30/153). B/p ratio was>50th centile in 80.4% of the cases and>90th centile in 31.37% of the cases. Discussions In our study, the absolute rate of low placentas weight was critically increased, leading to an elevated the b/p ratio, which raises concerns about the stability of the placental/fetal unity in these cases. The upregulated nutrient transfer capacity could be a sign that presumably low-risk fetuses are actually at high risk, and that SARS-CoV-2 could act as a 'promoter' for the destabilisation of the placental-fetal dyad in these pregnancies. Moreover, given the unexplained elevated GDM rate in our population, it remains open if this as well could be partially explained through an 'upregulation' attempt of the placenta, in order to provide more energy to the fetus at risk. This could be particularly relevant for the yet controversial issue of increased stillbirth rate in SARS-CoV-2 infection during pregnancy. In this regard, intensified fetal surveillance could be a reasonable option in these cases.