Placental Infection Associated with SARS-CoV-2 Wildtype Variant and Variants of Concern.

The original SARS-CoV-2 lineages have been replaced by successive variants of concern (VOCs) over time. The aim of this study was to perform an assessment of the placental infection by SARS-CoV-2 according to the predominant variant at the moment of COVID-19 diagnosis. This was a prospective study of SARS-CoV-2-positive pregnant women between March 2020 and March 2022. The population was divided into pregnancies affected by COVID-19 disease during 2020 (Pre-VOC group) and pregnancies affected after December 2020 by SARS-CoV-2 variants of concern (VOC group). The presence of virus was assessed by RT-PCR, and the viral variant was determined by whole genome sequencing. A total of 104 placentas were examined, among which 54 cases belonged to the Pre-VOC group and 50 cases belonged to the VOC group. Sixteen positive placental RT-PCR tests for SARS-CoV-2 were reported. The NGS analysis confirmed the SARS-CoV-2 lineage in placenta tissue. All samples corresponded to the Pre-VOC group, whereas no placental presence of SARS-CoV-2 was detected in the VOC group (16, 29.6% vs. 0, 0.0% p = 0.000). Preterm birth (9, 16.7% vs. 2, 4%; p = 0.036) and hypertensive disorders of pregnancy (14, 25.9% vs. 3, 6%; p = 0.003) were more frequent in the Pre-VOC group than in the VOC group. Finally, the VOC group was composed of 23 unvaccinated and 27 vaccinated pregnant women; no differences were observed in the sub-analysis focused on vaccination status. In summary, SARS-CoV-2-positive placentas were observed only in pregnancies infected by SARS-CoV-2 wildtype. Thus, placental SARS-CoV-2 presence could be influenced by SARS-CoV-2 variants, infection timing, or vaccination status. According to our data, the current risk of SARS-CoV-2 placental infection after maternal COVID disease during pregnancy should be updated.

First-Trimester Sequential Screening for Preeclampsia Using Angiogenic Factors: Study Protocol for a Prospective, Multicenter, Real Clinical Setting Study.

Introduction: The incidence of preeclampsia (PE) is about 2-8%, making it one of the leading causes of perinatal morbidity and maternal mortality in the world. Early prophylactic low dose administration (150 mg) of acetylsalicylic acid is associated with a significant reduction in the incidence of early-onset PE, intrauterine growth restriction (IUGR), and neonatal mean stay in the intensive care unit (ICU). Universal implementation of a first-trimester screening system including angiogenic and antiangiogenic markers [the Placental Growth Factor (PlGF) and/or soluble fms-like Tyrosine Kinase-1 (sFlt-1)] has shown a prediction rate of 90% for early-onset PE but entails a high financial cost. The aim of this study is to determine the predictive and preventive capacity of a universal PE first-trimester two-step sequential screening model, determining the PlGF only in patients previously classified as intermediate risk by means of a multivariate model based on resources already used in the standard pregnancy control, in a real clinical setting. We hypothesize that this screening model will achieve similar diagnostic performance as the universal determination of PlGF but at a lower economic cost. Methods and Analysis: This is a prospective, multicentric, cohort study in a real-world clinical setting. Every singleton pregnancy will be recruited at the routine first pregnancy visit. In a first step, the first-trimester risk of PE will be calculated using a multivariate Gaussian distribution model, based on medical history, mean blood pressure, Pregnancy-Associated Plasma Protein A (PAPP-A), and Uterine Artery Doppler Pulsatility Index (UTPI). Patients will be classified into three risk groups for PE: (1) risk ≥ 1/50, high-risk with no further testing (blinded PlGF); (2) risk between 1/51 and 1/500, medium-risk requiring further testing; and (3) risk ≤ 1/501, low-risk with no further testing. In a second step, the PlGF will only be determined in those patients classified as intermediate risk after this first step, and then reclassified into high- or low-risk groups. Prophylactic administration of aspirin (150 mg/day) will be prescribed only in high risk patients. As a secondary objective, sFlt-1 values will be blindly determined in patients with high and intermediate risk to assess its potential performance in the screening for PE. Ethics and Dissemination: The study will be conducted in accordance with the principles of Good Clinical Practice. This study is approved by the Aragon Research Ethics Committee (CEICA) on 3 July 2020 (15/2020). Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04767438.

Frequent Placental SARS-CoV-2 in Patients with COVID-19-Associated Hypertensive Disorders of Pregnancy.

INTRODUCTION: Studies described an increased frequency of hypertensive disorders of pregnancy (HDP) after a COVID-19 episode. There is limited evidence about SARS-CoV-2 viral load in placenta. This study aimed to investigate the relationship between SARS-CoV-2 viral load in the placenta and clinical development of HDP after COVID-19 throughout different periods of gestation. METHODS: This is a case-control study in women with and without gestational hypertensive disorders after SARS-CoV-2 infection diagnosed by RT-PCR during pregnancy. Patients were matched by gestational age at the moment of COVID-19 diagnosis. We performed an analysis of SARS-CoV-2 RNA levels in placenta. RESULTS: A total of 28 women were enrolled. Sixteen patients were diagnosed with COVID-19 during the third trimester and the remaining 12 patients in the other trimesters. Ten placentas (35.7%) were positive for SARS-CoV-2, 9 of them (9/14, 64.3%) belonged to the HDP group versus 1 (1/14, 7.2%) in the control group (p = 0.009). Those cases with the highest loads of viral RNA developed severe preeclampsia (PE). CONCLUSION: Among women diagnosed with COVID-19 during pregnancy, the presence of SARS-CoV-2 in the placenta was more frequent among women suffering from PE or gestational hypertension. Furthermore, the most severe cases of HDP were associated with high placental viral load, not necessarily associated with a positive nasopharyngeal RT-PCR at delivery. Our data suggest that SARS-CoV-2 infection during pregnancy could trigger gestational hypertensive disorders through persistent placental infection and resulting placental damage.

The influence of fetal sex on the antenatal diagnosis of small for gestational age.

OBJECTIVE: We evaluated the influence of fetal sex on the antenatal diagnosis and detection of small for gestational age (SGA). METHODS: The cohort consisted of unselected singleton pregnancies, undergoing routine biometry and cerebroplacental ratio (CPR) assessment at 36 weeks. Locally fitted equations for centiles and Z scores were used. "Ultrasound SGA" was defined as estimated fetal weight (EFW) < 10th centile, "SGA at birth" as birthweight (BW) < 10th centile adjusted for sex. RESULTS: Among 4112 pregnancies, there were 235 female "ultrasound SGA" fetuses and 177 male; (odds ratios (OR) 1.502 (1.223 - 1.845)); the detection rate of SGA at birth was 50.6% and 40.9%, respectively (OR 1.479 (0.980 - 2.228)). In "ultrasound SGA" girls the abdominal circumference growth velocity (ACGV) between 20 and 36 weeks was less frequently in the lowest decile (OR 0.490 (0.320 - 0.750)), with no differences in CPR. CONCLUSIONS: Females are more commonly diagnosed as SGA; those diagnosed may be at less risk than males.

A reference range of fetal abdominal circumference growth velocity between 20 and 36 weeks' gestation.

OBJECTIVE: To create a single equation and reference range for abdominal circumference growth velocity (ACGV) between 20 and 36 weeks in singleton pregnancies. METHOD: Observational study of pregnant women having routine scans for abdominal circumference (AC) at 20 and 36 weeks' gestation. Exclusion criteria were multiple pregnancy, abnormal karyotype, major fetal abnormalities, and absent data on first-trimester dating. Scan image quality and AC measurement reliability were assessed according to INTERGROWTH-21st criteria. Regression models for the AC mean and standard deviation were fitted separately at 20 and 36 weeks, and z scores were calculated. Abdominal circumference growth velocity was defined as the z score difference between 20 and 36 weeks divided by the interval in days and multiplied by 100. RESULTS: The study population included 3334 fetuses. The equation for ACGV is (((AC36  - 53.090 - 1.081*GA36 )/(0.057638*GA36  + 0.622741)) - ((AC20  + 68.349 - 1.571*GA20 )/(0.06265*GA20  - 2.55361)))*100/(GA36  - GA20 ), where AC is expressed in millimeters and GA is gestational age in days. The 3rd, 5th, 10th, 50th, 90th, 95th, and 97th centiles are -1.8997, -1.6785, -1.3091, -0.0069, 1.3255, 1.7279, 1.9973, respectively. CONCLUSION: We have defined ACGV between 20 and 36 weeks, and we have established its reference range. Further studies are needed to evaluate the clinical significance of growth patterns in the tail ends of this distribution.