Maternal Hemodynamics from Preconception to Delivery: Research and Potential Diagnostic and Therapeutic Implications: Position Statement by Italian Association of Pre-Eclampsia and Italian Society of Perinatal Medicine.

OBJECTIVE: The Italian Association of Preeclampsia (AIPE) and the Italian Society of Perinatal Medicine (SIMP) developed clinical questions on maternal hemodynamics state of the art. STUDY DESIGN: AIPE and SIMP experts were divided in small groups and were invited to propose an overview of the existing literature on specific topics related to the clinical questions proposed, developing, wherever possible, clinical and/or research recommendations based on available evidence, expert opinion, and clinical importance. Draft recommendations with a clinical rationale were submitted to 8th AIPE and SIMP Consensus Expert Panel for consideration and approval, with at least 75% agreement required for individual recommendations to be included in the final version. RESULTS: More and more evidence in literature underlines the relationship between maternal and fetal hemodynamics, as well as the relationship between maternal cardiovascular profile and fetal-maternal adverse outcomes such as fetal growth restriction and hypertensive disorders of pregnancy. Experts agreed on proposing a classification of pregnancy hypertension, complications, and cardiovascular states based on three different hemodynamic profiles depending on total peripheral vascular resistance values: hypodynamic (>1,300 dynes·s·cm-5), normo-dynamic, and hyperdynamic (<800 dynes·s·cm-5) circulation. This differentiation implies different therapeutical strategies, based drugs' characteristics, and maternal cardiovascular profile. Finally, the cardiovascular characteristics of the women may be useful for a rational approach to an appropriate follow-up, due to the increased cardiovascular risk later in life. CONCLUSION: Although the evidence might not be conclusive, given the lack of large randomized trials, maternal hemodynamics might have great importance in helping clinicians in understanding the pathophysiology and chose a rational treatment of patients with or at risk for pregnancy complications. KEY POINTS: · Altered maternal hemodynamics is associated to fetal growth restriction.. · Altered maternal hemodynamics is associated to complicated hypertensive disorders of pregnancy.. · Maternal hemodynamics might help choosing a rational treatment during hypertensive disorders..

The cumulative incidence of neonatal metabolic acidemia after terminal bradycardia in the 2nd stage of labor: a survival-based model.

PURPOSE: The aim of the study was to estimate by a survival analysis model the hazard function (HF) for neonatal metabolic acidemia (MA) throughout the 2nd stage of labor (2STG) at the time of occurrence of a terminal bradycardia ≥ 10 min requiring expedited delivery, and the cumulative incidence function (CIF) for MA according with the duration of bradycardia stratified in 10-12 min and > 12 min. METHODS: Singleton pregnancies experiencing terminal fetal bradycardia requiring expedited delivery in the 2STG at 38 + 0-41 + 3 weeks and delivering in the year 2019, were identified. The presence of MA (pH < 7 and/or BE ≤ - 12 mmol/L) was determined based on the acid-base status in the umbilical artery cord blood. Survival analysis was used to assess the hazard function (HF) and the cumulative incidence function (CIF) for MA occurring after terminal fetal bradycardia, at the 2STG. RESULTS: Out of a non-consecutive population of 12,331 pregnancies, there were 52 cases that fit the inclusion criteria. Twenty-four (46.2%) of those develop MA. Abnormal quantitative pH values and the HF for MA correlated with the duration of 2STG at the time of bradycardia onset, but not with bradycardia duration. After 60 min of duration of 2STG, the HF (or instantaneous rate of failure) increased dramatically (from 1.2 to 20 about at 120 min). At paired duration of 2STG, a higher CIF was observed for the terminal bradycardia > 12 min. CONCLUSION: Forty-six percent of term fetuses with terminal bradycardia had MA at birth. Despite the low sensitivity and a non-significant association with quantitative pH values, the duration of terminal bradycardia in the 2STG is associated with a higher CIF for MA.

Umbilical vein blood flow: State-of-the-art.

Placental blood supply to the fetus can be measured by evaluating the umbilical vein blood flow. Despite its potential application in healthcare, the umbilical vein blood flow volume is still used only in research setting. One of the reasons is a concern regarding its reproducibility, partly due to technology issues. Nowadays, technology improvements make this evaluation accurate and reproducible. The aim of this review is to refresh basic elements of the physiology of umbilical vein blood flow and its analysis. Its evaluation in normal and abnormal fetal growth is also discussed.

Sociodemographic characteristics of pregnant women tested positive for COVID-19 admitted to a referral center in Northern Italy during lockdown period.

INTRODUCTION: We investigated association between sociodemographic characteristics and COVID-19 disease among pregnant women admitted to our unit, the largest high-risk maternity unit in the Milan metropolitan area. METHODS: Between March 1, 2020 and April 30, 2020, 896 pregnant women were admitted to our Institution and tested for COVID-19. We collected information regarding their sociodemographic characteristics. Additional information on geographical area of residence, number of family members, number of family members tested positive for COVID-19, and clinical data was collected for women tested positive for COVID-19. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of developing COVID-19 according to sociodemographic characteristics were estimated by unconditional logistic regression models. RESULTS: Among the 896 women enrolled, 50 resulted positive for COVID-19. Pregnant women aged ≥35 years had a significantly lower risk of developing the infection (crude OR = 0.29; 95% CI:0.16-0.55). Conversely, foreign women (crude OR = 3.32; 95% CI:1.89-5.81), unemployed women (crude OR = 3.09; 95% CI: 1.77-5.40), and women with an unemployed partner (crude OR = 3.16; 95% CI: 1.48-6.79) showed a significantly higher risk of infection. Ethnicity was positively associated with the risk of developing COVID-19 (mutually adjusted OR = 2.15; 95% CI:1.12-4.11) in the multivariate analysis. Foreign women with COVID-19 were more likely to have a lower education level (p < 0.01), to be unemployed (p < 0.01), and to live in larger families (p < 0.01) compared to Italian pregnant women. CONCLUSIONS: The socioeconomic conditions described are characteristic of immigration patterns in our metropolitan area. These factors may increase the risk of viral transmission, reducing the effectiveness of lockdown and social distancing.

Higher rate of early-onset preeclampsia in pregnancies following oocyte donation according to increasing maternal age.

OBJECTIVE: To assess the influence of maternal age on the incidence of early-onset preeclampsia requiring delivery before 34 weeks of gestation in pregnancies obtained after oocyte donation. METHODS: We carried out a prospective cohort analysis of 431 single and twin pregnancies, admitted to 3 Tertiary Referral Hospital in Northern Italy between 2008 and 2017. The rate of early-onset PE was calculated and stratified according to maternal age (from 30 to 49 years). A reference population of 11,197 single pregnancies collected prospectively at the first trimester of pregnancy in the same geographic area of Italy and in same hospitals was used to calculate the expected incidence of early-onset PE. RESULTS: In women who delivered after 24 weeks of gestation, the rate of early-onset PE was much higher in oocyte-donation pregnancies, reaching 6.7% (29/431), than the expected rate of 0.5% of the cohort of reference. The mean early PE rate was 4.1% (10/242) in singletons and 10.1% (19/189) in twin pregnancies. According to maternal age, the rate of early PE was 1.16% and 3.12% at 30 years, and 4.98% and 13.14% at 49 years in single and twin pregnancies obtained after oocyte donation, respectively. CONCLUSION: Pregnancies obtained after oocyte donation delivering after 24 weeks had a higher risk of early-onset PE requiring delivery before 34 weeks of gestation, than the general population. The risk is directly correlated with the increase of maternal age and is also higher in twin pregnancies.

Comparison of two "a priori" risk assessment algorithms for preeclampsia in Italy: a prospective multicenter study.

PURPOSE: To compare the performance of the algorithms proposed by the Fetal Medicine Foundation in 2012 and BCNatal in 2013 in an Italian population. METHODS: A multicentric prospective study was carried out which included pregnancies at 11-13 weeks' gestation from Jan 2014 through May 2017. Two previously published algorithms were used for the calculation of the "a priori" risk of preeclampsia (based on risk factors from medical history) in each individual. RESULTS: In a study population of 11,632 cases, 67 (0.6%) developed early preeclampsia and 211 (1.8%) developed late preeclampsia. The detection rates (95% CI) for early and late preeclampsia were 58.2% (45.5-70.2) vs. 41.8% (29.6-54.5) (p value < 0.05) and 44.1% (37.3-51.1) vs. 38% (31.3-44.8) (p value < 0.05) for the Fetal Medicine Foundation and BCNatal, respectively (at a 10% false positive rate). The associated risk was 1:226 and 1:198 (p value ns) for early PE, and 1:17 and 1:24 (p value ns) for late PE for the Fetal Medicine Foundation and BCNatal, respectively. CONCLUSIONS: The Fetal Medicine Foundation screening for preeclampsia at 11-13 weeks' gestation scored the highest detection rate for both early and late PE. At a fixed 10% false positive rate, the estimated "a priori" risks of both the Fetal Medicine Foundation and the BCNatal algorithms in an Italian population were quite similar, and both were reliable and consistent.

Evaluation of Chimerism Dynamics after Allogeneic Hematopoietic Stem Cell Transplantation in Children with Nonmalignant Diseases.

It is recognized that chimerism following hematopoietic stem cell transplantation (HSCT) is a dynamic process. The aims of this study were to describe the evolution of chimerism in children with nonmalignant diseases who underwent allogeneic HSCT, and to analyze the risk factors influencing chimerism status. A total of 101 HSCTs were performed in 85 patients with nonmalignant diseases. The donor was unrelated in 62.4% of HSCTs. Reduced-intensity conditioning (RIC) regimen was administered in 48.5% of patients. Acute graft-versus-host disease (aGVHD) occurred in 51.7% and chronic GVHD (cGVHD) in 39.7% of patients. Analysis of chimerism was performed through amplification of 9 specific short tandem repeats by polymerase chain reaction at engraftment and 1, 6, and 12 months after HSCT. Upon first evaluation, complete chimerism (CC) was detected in 34.7% and mixed chimerism (MC) in 55.4%, whereas graft failure occurred in 9.9% of patients. Severe aGVHD was associated with CC (P = .031). The last chimerism evaluation showed CC in 72.1%, stable MC in 12.8%, and progressive MC in 3.5%. CC was associated with a higher incidence of aGVHD (P = .016) and cGVHD (P = .022), whereas the RIC regimen was associated with graft failure (P = .026). One- and 3-year overall survival (OS) was 87.4% and 80.5%, respectively, with a lower OS at 3 years in patients with CC compared with those with MC (P = .008). aGVHD and cGVHD represent factors favoring CC, thus close, careful follow-up of chimerism is recommended in patients affected by nonmalignant disease.

Maternal hemodynamics: a method to classify hypertensive disorders of pregnancy.

BACKGROUND: The classification of hypertensive disorders of pregnancy is based on the time at the onset of hypertension, proteinuria, and other associated complications. Maternal hemodynamic interrogation in hypertensive disorders of pregnancy considers not only the peripheral blood pressure but also the entire cardiovascular system, and it might help to classify the different clinical phenotypes of this syndrome. OBJECTIVE: This study aimed to examine cardiovascular parameters in a cohort of patients affected by hypertensive disorders of pregnancy according to the clinical phenotypes that prioritize fetoplacental characteristics and not the time at onset of hypertensive disorders of pregnancy. STUDY DESIGN: At the fetal-maternal medicine unit of Ziekenhuis Oost-Limburg (Genk, Belgium), maternal cardiovascular parameters were obtained through impedance cardiography using a noninvasive continuous cardiac output monitor with the patients placed in a standing position. The patients were classified as pregnant women with hypertensive disorders of pregnancy who delivered appropriate- and small-for-gestational-age fetuses. Normotensive pregnant women with an appropriate-for-gestational-age fetus at delivery were enrolled as the control group. The possible impact of obesity (body mass index ≥30 kg/m2) on maternal hemodynamics was reassessed in the same groups. RESULTS: Maternal age, parity, body mass index, and blood pressure were not significantly different between the hypertensive disorders of pregnancy/appropriate-for-gestational-age and hypertensive disorders of pregnancy/small-for-gestational-age groups. The mean uterine artery pulsatility index was significantly higher in the hypertensive disorders of pregnancy/small-for-gestational-age group. The cardiac output and cardiac index were significantly lower in the hypertensive disorders of pregnancy/small-for-gestational-age group (cardiac output 6.5 L/min, cardiac index 3.6) than in the hypertensive disorders of pregnancy/appropriate-for-gestational-age group (cardiac output 7.6 L/min, cardiac index 3.9) but not between the hypertensive disorders of pregnancy/appropriate-for-gestational-age and control groups (cardiac output 7.6 L/min, cardiac index 4.0). Total vascular resistance was significantly higher in the hypertensive disorders of pregnancy/small-for-gestational-age group than in the hypertensive disorders of pregnancy/appropriate-for-gestational-age group and the control group. All women with hypertensive disorders of pregnancy showed signs of central arterial dysfunction. The cardiovascular parameters were not influenced by gestational age at the onset of hypertensive disorders of pregnancy, and no difference was observed between the women with appropriate-for-gestational-age fetuses affected by preeclampsia or by gestational hypertension with appropriate-for-gestational-age fetuses. Women in the obese/hypertensive disorders of pregnancy/appropriate-for-gestational-age and obese/hypertensive disorders of pregnancy/small-for-gestational-age groups showed a significant increase in cardiac output, as well as significant changes in other parameters, compared with the nonobese/hypertensive disorders of pregnancy/appropriate-for-gestational-age and nonobese/hypertensive disorders of pregnancy/small-for-gestational-age groups. CONCLUSION: Significantly low cardiac output and high total vascular resistance characterized the women with hypertensive disorders of pregnancy associated with small for gestational age due to placental insufficiency, independent of the gestational age at the onset of hypertension. The cardiovascular parameters were not significantly different in the women with appropriate-for-gestational-age or small-for-gestational-age fetuses affected by preeclampsia or gestational hypertension. These findings support the view that maternal hemodynamics may be a candidate diagnostic tool to identify hypertensive disorders in pregnancies associated with small-for-gestational-age fetuses. This additional tool matches other reported evidence provided by uterine Doppler velocimetry, low vascular growth factors in the first trimester, and placental pathology. Obesity is associated with a significantly higher cardiac output and outweighs other determinants of hemodynamics in pregnancy; therefore, in future studies on hypertensive disorders, obesity should be studied as an additional disease and not simply as a demographic characteristic.

Egyptian Grave Goods of Kha and Merit Studied by Neutron and Gamma Techniques.

Artifacts from the Egyptian grave goods of Kha and Merit preserved at the Museo Egizio in Turin were studied through a combination of non-destructive and non-invasive neutron and gamma techniques (namely neutron imaging, neutron diffraction and prompt gamma activation analysis). The results provide unprecedented morphological reconstructions of the inner parts of the two alabaster and metallic vases and their isotopic and phase composition, thereby extending our knowledge of the hitherto unknown content of the vases and their functions.

Allogeneic hematopoietic stem cell transplantation in congenital disorders: A single-center experience.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the treatment of choice for a variety of congenital disorders. We report the experience of children affected by congenital diseases other than bone marrow failure syndromes who received allo-HSCT over a period of 25 years at G. Gaslini Paediatric Research Institute. HSCTs were performed in 57 children with congenital diseases (25 with congenital immunodeficiencies, 10 with severe combined immunodeficiencies, and 22 with metabolic diseases). Overall survival rate at 3 years in the whole group of patients was 76.9%, with a trend in favor of better outcome in children with metabolic diseases and in those who received cord blood cells (85.9%) vs bone marrow cells (72.4%).

The "Preeclampsia and Hypertension Target Treatment" study: a multicenter prospective study to evaluate the effectiveness of the antihypertensive therapy based on maternal hemodynamic findings.

BACKGROUND: Despite major advances in the pharmacologic treatment of hypertension in the nonpregnant population, treatments for hypertension in pregnancy have remained largely unchanged over the years. There is recent evidence that a more adequate control of maternal blood pressure is achieved when the first given antihypertensive drug is able to correct the underlying hemodynamic disorder of the mother besides normalizing the blood pressure values. OBJECTIVE: This study aimed to compare the blood pressure control in women receiving an appropriate or inappropriate antihypertensive therapy following the baseline hemodynamic findings. STUDY DESIGN: This was a prospective multicenter study that included a population of women with de novo diagnosis of hypertensive disorders of pregnancy. A noninvasive assessment of the following maternal parameters was performed on hospital admission via Ultrasound Cardiac Output Monitor before any antihypertensive therapy was given: cardiac output, heart rate, systemic vascular resistance, and stroke volume. The clinician who prescribed the antihypertensive therapy was blinded to the hemodynamic evaluation and used as first-line treatment a vasodilator (nifedipine or alpha methyldopa) or a beta-blocker (labetalol) based on his preferences or on the local protocols. The first-line pharmacologic treatment was retrospectively considered hemodynamically appropriate in either of the following circumstances: (1) women with a hypodynamic profile (defined as low cardiac output [≤5 L/min] and/or high systemic vascular resistance [≥1300 dynes/second/cm2]) who were administered oral nifedipine or alpha methyldopa and (2) women with a hyperdynamic profile (defined as normal or high cardiac output [>5 L/min] and/or low systemic vascular resistances [<1300 dynes/second/cm2]) who were administered oral labetalol. The primary outcome of the study was to compare the occurrence of severe hypertension between women treated with a hemodynamically appropriate therapy and women treated with an inappropriate therapy. RESULTS: A total of 152 women with hypertensive disorders of pregnancy were included in the final analysis. Most women displayed a hypodynamic profile (114 [75.0%]) and received a hemodynamically appropriate treatment (116 [76.3%]). The occurrence of severe hypertension before delivery was significantly lower in the group receiving an appropriate therapy than in the group receiving an inappropriately treated (6.0% vs 19.4%, respectively; P=.02). Moreover, the number of women who achieved target values of blood pressure within 48 to 72 hours from the treatment start was higher in the group who received an appropriate treatment than in the group who received an inappropriate treatment (70.7% vs 50.0%, respectively; P=.02). CONCLUSION: In pregnant individuals with de novo hypertensive disorders of pregnancy, a lower occurrence of severe hypertension was observed when the first-line antihypertensive agent was tailored to the correct maternal hemodynamic profile.

Low-background gamma spectrometry and neutron diffraction in the study of stony meteorites.

Non-destructive characterisation of meteorites is here performed on a stony meteorite. The identification of the sample is performed by low-background γ-ray spectrometry in order to determine the presence of certain cosmogenic radionuclides, whereas a mineralogical phase quantitative analysis is carried out by Time-of-Flight Neutron Diffraction (ToF-ND) on the sample as-it-is. The protocol is then validated by applying micro-Raman Spectroscopy (µRS) and Energy Dispersive X-ray Spectroscopy (EDS). This paper is focused on γ-ray spectrometry, proving the meteoric origin of the sample, and it also presents some preliminary results of ToF-ND.

An uncommon presentation of Wernicke-Korsakoff's syndrome in pregnancy: Case report.

Wernicke's encephalopathy is an acute neuropsychiatric syndrome resulting from severe thiamine (vitamin B1) deficiency. Symptoms occur with an acute onset and may vary according to the brain area involved. Altered consciousness is the most common clinical feature, together with ocular abnormalities and ataxia. We report the case of a pregnant women affected by pre-gestational hyperthyroidism that caused an uncommon presentation of Wernicke's encephalopathy. Symptoms differed from the classic triad and diagnosis was made possible by a thorough analysis of anamnestic factors and brain MRI. Alongside thiamine supplementation, a multidisciplinary approach which included physiokinesis and a phoniatric support was fundamental for the patient's recovery.

Maternal hemodynamic profile during pregnancy and in the post-partum in hypertensive disorders of pregnancy and fetal growth restriction.

BACKGROUND: Maternal cardiovascular changes, occurring since the beginning of pregnancy, are necessary for normal placentation and regular evolution of pregnancy. OBJECTIVE: This study aimed to compare the hemodynamic profiles and cardiac remodeling of women with hypertensive disorders of pregnancy and either appropriate for gestational age fetuses or growth-restricted fetuses, women with normotensive pregnancies complicated by fetal growth restriction, and women with uncomplicated pregnancies, during pregnancy and the postpartum period. STUDY DESIGN: A prospective longitudinal case-control design was used for this study. Over the study period, 220 eligible women with singleton pregnancies were selected for the analysis and divided into 4 groups: (1) hypertensive disorders of pregnancy with appropriate for gestational age fetuses; (2) hypertensive disorders of pregnancy with fetal growth restriction; (3) normotensive fetal growth restriction; and (4) controls. Ultrasound fetal biometry and fetoplacental Doppler velocimetry were performed at recruitment. Maternal hemodynamic assessment using transthoracic echocardiography was performed at the time of recruitment by a dedicated cardiologist blinded to maternal clinical data. The same assessments were performed in 104 patients at 32 weeks (interquartile range, 24-40) after delivery by the same cardiologist. RESULTS: During pregnancy, women in the hypertensive-disorders-of-pregnancy-fetal-growth-restriction group showed significantly lower cardiac output and increased compared with those in the control group. These values were associated with concentric remodeling of the left ventricle owing to relatively increased wall thickness, which was not accompanied by an increase in left ventricular mass. Isolated fetal growth restriction presented similar but less important hemodynamic changes; however, there was no change in relative wall thickness. At postpartum follow-up, the hemodynamic parameters of women in the hypertensive-disorders-of-pregnancy-fetal-growth-restriction and isolated-fetal-growth-restriction groups reverted to values similar to those of the control group. Only 8.3% of women in these groups experienced hypertension even in the postpartum period, and asymptomatic stage-B cardiac failure was observed for 17% at echocardiography. In the group of women with hypertensive disorders of pregnancy and appropriate for gestational age fetuses, cardiac output increased as in normal pregnancies, but total vascular resistance was significantly higher; hypertension then occurred, along with ventricular concentric hypertrophy and diastolic dysfunction. At postpartum follow-up, women in the hypertensive-disorders-of-pregnancy-appropriate-for-gestational-age-fetus group showed significantly higher mean arterial pressure, total vascular resistance, and left ventricular mass compared with those in the control group. Persistent hypertension and asymptomatic stage-B cardiac failure were observed in 39.1% and 13% of women in the former group, respectively. CONCLUSION: Pregnancies with hypertensive disorders of pregnancy and fetal growth restriction and normotensive pregnancies with fetal growth restriction were associated with the hemodynamic profile of lower heart rate and cardiac output, most likely because of abnormal adaptation to pregnancy, as confirmed by abnormal changes from pregnancy to the postpartum period. The heart rates and cardiac output of women in the hypertensive-disorders-of-pregnancy-appropriate-for-gestational-age-fetus group showed changes opposite to those observed in the hypertensive-disorders-of-pregnancy-fetal-growth-restriction and fetal-growth-restriction groups. Obesity and other metabolic risk factors, significantly prevalent in women in the hypertensive-disorders-of-pregnancy-appropriate-for-gestational-age-fetus group, predispose to hypertension and cardiovascular diseases during pregnancy and the postpartum period, potentially offering a window for personalized prevention. Such preventive strategies could differ in women with hypertensive disorders of pregnancy and fetal growth restriction characterized by poor early placental development.

Hematopoietic stem cell transplantation for inborn errors of immunity: 30-year single-center experience.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents an effective treatment for a variety of inborn errors of immunity (IEI). We report the experience of children affected by IEI who received allo-HSCT over a period of 32 years at IRCCS Istituto Giannina Gaslini, Genoa, Italy. HSCTs were performed in 67 children with IEI. Kaplan-Meier estimates of overall survival (OS) rate at 5 years in the whole group of patients was 83.4% after a median follow-up of 4 years. Median age at transplant was 2.5 years. Eight allo-HSCTs were complicated by either primary or secondary graft failure (GF), the overall incidence of this complication being 10.9%. Incidence of grade 3-4 acute GvHD (aGvHD) was 18.7%, significantly lower in the haploidentical transplant cohort (p = 0.005). Year of transplant (≤2006 vs. >2006) was the main factor influencing the outcome. In fact, a significant improvement in 5-year OS was demonstrated (92.5% >2006 vs. 65% ≤2006, p = 0.049). Frequency of severe aGvHD was significantly reduced in recent years (≤2006 61.5%, vs. >2006 20%, p = 0.027). A significant progress has been the introduction of the TCR αß/CD19-depleted haploidentical platform, which was associated with the absence of severe aGvHD. However, it was associated with 23.5% incidence of GF. All but one patient experiencing GF in the this specific cohort were successfully retransplanted. In summary, allo-HSCT is confirmed to be an effective treatment for children with IEI, even in the absence of an HLA-matched donor.

Umbilical Vein Blood Flow in Uncomplicated Pregnancies: Systematic Review of Available Reference Charts and Comparison with a New Cohort.

The objectives of the study were (1) to perform a systematic review of the available umbilical vein blood flow volume (UV-Q) reference ranges in uncomplicated pregnancies; and (2) to compare the findings of the systematic review with UV-Q values obtained from a local cohort. Available literature in the English language on this topic was identified following the PRISMA guidelines. Selected original articles were further grouped based on the UV sampling sites and the formulae used to compute UV-Q. The 50th percentiles, the means, or the best-fitting curves were derived from the formulae or the reported tables presented by authors. A prospective observational study of uncomplicated singleton pregnancies from 20+0 to 40+6 weeks of gestation was conducted to compare UV-Q with the results of this systematic review. Fifteen sets of data (fourteen sets belonging to manuscripts identified by the research strategy and one obtained from our cohort) were compared. Overall, there was a substantial heterogeneity among the reported UV-Q central values, although when using the same sampling methodology and formulae, the values overlap. Our data suggest that when adhering to the same methodology, the UV-Q assessment is accurate and reproducible, thus encouraging further investigation on the possible clinical applications of this measurement in clinical practice.

Glycation-Driven Inflammation: COVID-19 Severity in Pregnant Women and Perinatal Outcomes.

The link between being pregnant and overweight or obese and the infectivity and virulence of the SARS CoV-2 virus is likely to be caused by SARS-CoV-2 spike protein glycosylation, which may work as a glycan shield. Methylglyoxal (MGO), an important advanced glycation end-product (AGE), and glycated albumin (GA) are the results of poor subclinical glucose metabolism and are indices of oxidative stress. Forty-one consecutive cases of SARS-CoV-2-positive pregnant patients comprising 25% pre-pregnancy overweight women and 25% obese women were recruited. The aim of our study was to compare the blood levels of MGO and GA in pregnant women with asymptomatic and symptomatic SARS-CoV-2 infection with pregnant women without SARS-CoV-2 infection with low risk and uneventful pregnancies and to evaluate the relative perinatal outcomes. The MGO and GA values of the SARS-CoV-2 cases were statistically significantly higher than those of the negative control subjects. In addition, the SARS-CoV-2-positive pregnant patients who suffered of moderate to severe COVID-19 syndrome had higher values of GA than those infected and presenting with mild symptoms or those with asymptomatic infection. Premature delivery and infants of a small size for their gestational age were overrepresented in this cohort, even in mild-asymptomatic patients for whom delivery was not indicated by the COVID-19 syndrome. Moreover, ethnic minorities were overrepresented among the severe cases. The AGE-RAGE oxidative stress axis on the placenta and multiple organs caused by MGO and GA levels, associated with the biological mechanisms of the glycation of the SARS-CoV-2 spike protein, could help to explain the infectivity and virulence of this virus in pregnant patients affected by being overweight or obese or having gestational diabetes, and the increased risk of premature delivery and/or low newborn weight.

The sFlt-1/PlGF Ratio in Patients Affected by Gestational Diabetes and SARS-CoV-2 Infection.

Low values of the ratio of plasmatic soluble blocking factor FMS-like tyrosine Kinase 1 and placental growth factor (sFlt-1/PlGF) are required for an adequate placental angiogenesis and function. It has been shown that patients affected by gestational diabetes (GD) and patients with pneumonia from SARS-CoV-2 are characterized by an increased sFlt-1/PlGF ratio. The aim of the present study was to evaluate the sFlt-1-PlGF ratio in pregnancies complicated by COVID-19 and GD. We compared the plasmatic sFlt-1/PlGF ratio among the following groups of pregnant women: COVID-19, GD patients; COVID-19, non-GD patients; non-COVID-19, GD patients; and non-COVID-19, non-GD controls. We enrolled 62 women in the present study, who were divided as follows: 14 COVID-19, GD patients; 12 COVID-19, non-GD patients; 11 non-COVID-19, GD patients; and 25 non-COVID-19, non-GD controls. The COVID-19, GD patients presented a higher pre-pregnancy BMI, a higher prevalence of hypertensive disorders of pregnancy as a co-morbidity, and an increased need for medication for their diabetes. Neonatal data were similar between the groups. The controls showed a significantly lower sFlt-1/PlGF ratio compared to pregnancies complicated by GD and SARS-CoV-2 infection. The sFlt-1/PlGF ratio was higher in patients affected by both GD and SARS-CoV-2 infection; these subjects were characterized by a greater incidence of obesity and hypertensive disorders of pregnancy.

sFlt-1/PlGF ratio in hypertensive disorders of pregnancy in patients affected by COVID-19.

OBJECTIVES: To analyze soluble Fms-like tyrosine Kinase 1 (sFlt-1) and Placental Growth Factor (PlGF) ratio concentrations in COVID-19 pregnant patients with and without Hypertensive Disorders of Pregnancy (HDP), compared with non COVID-19 pregnant patients with HDP and a control group. STUDY DESIGN: We recruited and obtained a complete follow-up of 19 COVID-19 pregnant patients with HDP and of 24 COVID-19 normotensive pregnant patients. Demographic, clinical and sFlt-1/PlGF ratio findings were compared with a group of 185 non COVID-19 pregnant patients with HDP and 41 non COVID normotensive patients. Findings were based on univariate analysis and on a multivariate adjusted model, and a case by case analysis of COVID-19 pregnant patients with an abnormal sFlt-1/PlGF ratio > 38 at recruitment. MAIN OUTCOME MEASURES: sFlt-1/PlGF ratio. RESULTS: We confirmed a significant higher prevalence of HDP in women affected by COVID-19 compared to control population. sFlt-1/PlGF ratio was found high in HDP patients, with and without of Sars-Cov2 infection. COVID-19 patients with worse evolution of the disease showed greater rates of obesity and other comorbidities. sFlt/PlGF ratio proved not to be helpful in the differential diagnosis of the severity of this infection. CONCLUSIONS: COVID-19 pregnant patients showed a higher prevalence of HDP compared to non COVID-19 controls, as well as higher comorbidity rates. In spite of the possible common endothelial target and damage, between Sars-Cov-2 infection and HDP, the sFlt1/PlGF ratio did not correlate with the severity of this syndrome.