Biweekly Versus Monthly Hyperimmune Globulin Therapy for Primary Cytomegalovirus Infection in Pregnancy.

Primary cytomegalovirus (CMV) infection during pregnancy is associated with an increased risk of congenital CMV (cCMV). Hyperimmune globulin (HIG) therapy has been proposed as a potential prophylaxis to reduce maternal-fetal transmission. Data on whether the administration of HIG every 2 weeks offers benefits over HIG administration every 4 weeks are lacking. This was a retrospective analysis including pregnant women with primary CMV infection diagnosed in the first or early second trimester between 2010 and 2022 treated with HIG every 4 weeks (300 IE HIG per kg) or every 2 weeks (200 IE HIG per kg), respectively. In total, 36 women (4 weeks: n = 26; 2 weeks: n = 10) and 39 newborns (4 weeks: n = 29; 2 weeks: n = 10) were included. The median gestational age at the first HIG administration was 13.1 weeks. There was no significant difference in the cCMV rates between the women who received HIG every 4 versus every 2 weeks (n = 8/24 [33.3%] vs. 3/10 [30.0%]; p = 0.850). An abnormal fetal ultrasound was present in three fetuses and fetal magnetic resonance imaging (MRI) anomalies in four fetuses were related to cCMV infection, with no significant difference in the frequency between the two groups. A larger study will be needed to determine whether HIG administration every 2 instead of every 4 weeks improves the maternal-fetal transmission rates.

Effects of Intrauterine Growth Restriction (IUGR) on Growth and Body Composition Compared to Constitutionally Small Infants.

(1) Intrauterine growth restriction (IUGR) is associated with multiple morbidities including growth restriction and impaired neurodevelopment. Small for gestational age (SGA) is defined as a birth weight <10th percentile, regardless of the etiology. The term is commonly used as a proxy for IUGR, but it may represent a healthy constitutionally small infant. Differentiating between IUGR and constitutionally small infants is essential for the nutritional management. (2) Infants born at <37 weeks of gestation between 2017 and 2022, who underwent body composition measurement (FFM: fat-free mass; FM: fat mass) at term-equivalent age, were included in this study. Infants with IUGR and constitutionally small infants (SGA) were compared to infants appropriate for gestational age (AGA). (3) A total of 300 infants (AGA: n = 249; IUGR: n = 40; SGA: n = 11) were analyzed. FFM (p < 0.001) and weight growth velocity (p = 0.022) were significantly lower in IUGR compared to AGA infants, but equal in SGA and AGA infants. FM was not significantly different between all groups. (4) The FFM Z-score was significantly lower in IUGR compared to AGA infants (p = 0.017). Being born constitutionally small compared to AGA had no impact on growth and body composition. These data showed that early aggressive nutritional management is essential in IUGR infants to avoid impaired growth and loss of FFM.

Catestatin-A Potential New Therapeutic Target for Women with Preeclampsia? An Analysis of Maternal Serum Catestatin Levels in Preeclamptic Pregnancies.

BACKGROUND: Catestatin has been identified as an important factor in blood pressure control in non-pregnant adults. A possible impact on the development of hypertensive disorders of pregnancy has been indicated. Data on catestatin levels in pregnancy are scarce. The aim of this study was to investigate a potential association of maternal serum catestatin levels to the pathogenesis of preeclampsia. METHODS: We evaluated serum catestatin levels of 50 preeclamptic singleton pregnancies and 50 healthy gestational-age-matched pregnancies included in the obstetric biobank registry of the Medical University of Vienna. Receiver operating characteristic curves and logistic regression models were performed to investigate an association between catestatin levels and development of preeclampsia. RESULTS: Catestatin levels were significantly decreased in women with preeclampsia compared to healthy controls (median CST: 3.03 ng/mL, IQR [1.24-7.21 ng/mL] vs. 4.82 ng/mL, IQR [1.82-10.02 ng/mL]; p = 0.010), indicating an association between decreased catestatin values and the development of preeclampsia. There was no significant difference in catestatin values between early-onset preeclampsia and late-onset preeclampsia. Modelling the occurrence of preeclampsia via logistic regression was improved when adding catestatin as a predictive factor. CONCLUSIONS: Decreased serum catestatin levels are associated with the presence of preeclampsia. Further investigations into the diagnostic value and possible therapeutic role of catestatin in preeclampsia are warranted.

Maternal haemodynamics in Hypertensive Disorders of Pregnancy under antihypertensive therapy (HyperDiP): study protocol for a prospective observational case-control study.

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) are associated with a high incidence of maternal and perinatal morbidity and mortality. HDP, in particular pre-eclampsia, have been determined as risk factors for future cardiovascular disease. Recently, the common hypothesis of pre-eclampsia being a placental disorder was challenged as numerous studies show evidence for short-term and long-term cardiovascular changes in pregnancies affected by HDP, suggesting a cardiovascular origin of the disease. Despite new insights into the pathophysiology of HDP, concepts of therapy remain unchanged and evidence for improved maternal and neonatal outcome by using antihypertensive agents is lacking. METHODS AND ANALYSIS: A prospective observational case-control study, including 100 women with HDP and 100 healthy controls, which will assess maternal haemodynamics using the USCOM 1A Monitor and Arteriograph along with cardiovascular markers (soluble fms-like kinase 1/placental-like growth factor, N-terminal pro-B type natriuretic peptide) in women with HDP under antihypertensive therapy, including a follow-up at 3 months and 1 year post partum, will be conducted over a 50-month period in Vienna. A prospective, longitudinal study of cardiovascular surrogate markers conducted in Oslo will serve as a comparative cohort for the Vienna cohort of haemodynamic parameters in pregnancy including a longer follow-up period of up to 3 years post partum. Each site will provide a dataset of a patient group and a control group and will be assessed for the outcome categories USCOM 1A measurements, Arteriograph measurements and Angiogenic marker measurements. To estimate the effect of antihypertensive therapy on outcome parameters, ORs with 95% CIs will be computed. Longitudinal changes of outcome parameters will be compared between normotensive and hypertensive pregnancies using mixed-effects models. ETHICS AND DISSEMINATION: Ethical approval has been granted to all participating centres. Results will be published in international peer-reviewed journals and will be presented at national and international conferences.

Longitudinal Assessment of Serum 25-Hydroxyvitamin D Levels during Pregnancy and Postpartum-Are the Current Recommendations for Supplementation Sufficient?

(1) Background: Pregnant women are at risk of vitamin D deficiency. Data on pregnancy outcomes in women with vitamin D deficiency during pregnancy are controversial, and prospective longitudinal data on vitamin D deficiency with consistent definitions in pregnant women are scarce. (2) Methods: The aim of this prospective longitudinal cohort study was to investigate 25-hydroxyvitamin D levels over the course of pregnancy and postpartum in singleton and twin pregnancies with regard to dietary and supplemental vitamin D intake and environmental factors influencing vitamin D levels, evaluated by a standardized food frequency questionnaire. (3) Results: We included 198 healthy singleton and 51 twin pregnancies for analysis. A total of 967 study visits were performed over a 3-year period. Overall, 59.5% of pregnant women were classified as vitamin D deficient in the first trimester, 54.8% in the second trimester, 58.5% in the third trimester, 66.9% at birth, and 60% 12 weeks postpartum, even though 66.4% of the study population reported daily pregnancy vitamin intake containing vitamin D. Dietary vitamin D intake did not affect vitamin D levels significantly. (4) Conclusions: The majority of pregnant women evaluated in this study were vitamin D deficient, despite administration of pregnancy vitamins containing vitamin D. Individualized vitamin D assessment during pregnancy should be considered to ensure adequate supplementation and prevention of hypovitaminosis D.

Awareness of obstetricians for long-term risks in women with a history of preeclampsia or HELLP syndrome.

PURPOSE: Hypertensive disorders of pregnancy are still a leading cause of maternal and neonatal morbidity and mortality worldwide. Women with a history of preeclampsia have an increased risk for future cardiovascular and cerebrovascular disease, renal disease as well as diabetes mellitus. There is little knowledge on postpartum risk management. The aim of this study was to assess follow-up care for patients after pre-eclampsia or HELLP syndrome. METHODS: This questionnaire-based cross-sectional study aimed to evaluate the current recommendations of obstetricians in Austria regarding follow-up care, long-term risk counselling and risk of recurrence in future pregnancies after preeclampsia or HELLP syndrome. Data were collected using a survey, based on recommendations given by three substantial guidelines on hypertensive disorders of pregnancy, which was distributed via e-mail to 69 public obstetric departments in Austria. Each obstetric department was required to answer one questionnaire per local protocol. RESULTS: Our results revealed that of the 48 participating hospitals most obstetricians are aware of the importance of follow-up care for women after a pregnancy complicated by preeclampsia. Our data show that most physicians counselled patients about the future cardiovascular health risks associated with preeclampsia or HELLP syndrome (79.2%). Most obstetricians recommended lifestyle modification (77.1%) and continued blood pressure measurements (97.9%). All centers stated to counsel about the risk of recurrence (100%). However, counselling regarding follow-up care to exclude kidney damage (37.5%) and underlying diseases like thrombophilia (39.6%) were less prioritized. CONCLUSIONS: We were able to show that counselling concerning the risk of long-term cardiovascular disease and risk of recurrence after a pregnancy complicated by preeclampsia or HELLP syndrome has been established in obstetric departments in public hospitals. Regarding the evaluation of underlying chronic diseases such as thrombophilia or renal disease, as well as counselling on the future risk of renal disease is still improvable according to our data. Further evaluation of follow-up care after hypertensive disorders of pregnancy in the outpatient and private sector and implementation of structured guidelines for follow-up, as well as screening for cardiovascular disease are necessary to ensure adequate risk management and to provide opportunities for prevention.

An internally validated prediction model for critical COVID-19 infection and intensive care unit admission in symptomatic pregnant women.

BACKGROUND: Pregnant women are at an increased risk of mortality and morbidity owing to COVID-19. Many studies have reported on the association of COVID-19 with pregnancy-specific adverse outcomes, but prediction models utilizing large cohorts of pregnant women are still lacking for estimating the risk of maternal morbidity and other adverse events. OBJECTIVE: The main aim of this study was to develop a prediction model to quantify the risk of progression to critical COVID-19 and intensive care unit admission in pregnant women with symptomatic infection. STUDY DESIGN: This was a multicenter retrospective cohort study including 8 hospitals from 4 countries (the United Kingdom, Austria, Greece, and Turkey). The data extraction was from February 2020 until May 2021. Included were consecutive pregnant and early postpartum women (within 10 days of birth); reverse transcriptase polymerase chain reaction confirmed SARS-CoV-2 infection. The primary outcome was progression to critical illness requiring intensive care. The secondary outcomes included maternal death, preeclampsia, and stillbirth. The association between the primary outcome and 12 candidate predictors having a known association with severe COVID-19 in pregnancy was analyzed with log-binomial mixed-effects regression and reported as adjusted risk ratios. All the potential predictors were evaluated in 1 model and only the baseline factors in another. The predictive accuracy was assessed by the area under the receiver operating characteristic curves. RESULTS: Of the 793 pregnant women who were positive for SARS-CoV-2 and were symptomatic, 44 (5.5%) were admitted to intensive care, of whom 10 died (1.3%). The 'mini-COvid Maternal Intensive Therapy' model included the following demographic and clinical variables available at disease onset: maternal age (adjusted risk ratio, 1.45; 95% confidence interval, 1.07-1.95; P=.015); body mass index (adjusted risk ratio, 1.34; 95% confidence interval, 1.06-1.66; P=.010); and diagnosis in the third trimester of pregnancy (adjusted risk ratio, 3.64; 95% confidence interval, 1.78-8.46; P=.001). The optimism-adjusted area under the receiver operating characteristic curve was 0.73. The 'full-COvid Maternal Intensive Therapy' model included body mass index (adjusted risk ratio, 1.39; 95% confidence interval, 1.07-1.95; P=.015), lower respiratory symptoms (adjusted risk ratio, 5.11; 95% confidence interval, 1.81-21.4; P=.007), neutrophil to lymphocyte ratio (adjusted risk ratio, 1.62; 95% confidence interval, 1.36-1.89; P<.001); and serum C-reactive protein (adjusted risk ratio, 1.30; 95% confidence interval, 1.15-1.44; P<.001), with an optimism-adjusted area under the receiver operating characteristic curve of 0.85. Neither model showed signs of a poor fit. Categorization as high-risk by either model was associated with a shorter diagnosis to intensive care unit admission interval (log-rank test P<.001, both), higher maternal death (5.2% vs 0.2%; P<.001), and preeclampsia (5.7% vs 1.0%; P<.001). A spreadsheet calculator is available for risk estimation. CONCLUSION: At presentation with symptomatic COVID-19, pregnant and recently postpartum women can be stratified into high- and low-risk for progression to critical disease, even where resources are limited. This can support the nature and place of care. These models also highlight the independent risk for severe disease associated with obesity and should further emphasize that even in the absence of other comorbidities, vaccination is particularly important for these women. Finally, the model also provides useful information for policy makers when prioritizing national vaccination programs to quickly protect those at the highest risk of critical and fatal COVID-19.

Multiprofessional perinatal care in a pregnant patient with acute respiratory distress syndrome due to COVID-19.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has caused ongoing challenges in health services worldwide. Despite the growing body of literature on COVID-19, reports on perinatal care in COVID-19 cases are limited. CASE PRESENTATION: We describe a case of severe acute respiratory distress syndrome (ARDS) in a 36-year-old G5/P2 pregnant woman with morbid obesity, confirmed severe acute respiratory syndrome coronavirus 2 infection, and fulminant respiratory failure. At 28+ 1 gestational weeks, the patient delivered an uninfected newborn. Using ImmunoCAP ISAC® technology, we found no immunoglobulin (Ig) M antibodies, suggesting that no mother-to-child viral transmission occurred during pregnancy or delivery. The maternal respiratory state improved rapidly after delivery; both maternal and neonatal outcomes were encouraging given the early gestational age and fulminant course of respiratory failure in our patient. CONCLUSIONS: The management of ARDS in pregnant women with COVID-19 is complex and requires an individualized, multidisciplinary approach, while considering maternal and fetal outcomes.

Prognostic Value of Angiogenic Markers in Pregnant Women With Chronic Hypertension.

Background Women with chronic hypertension face a 5- to 6-fold increased risk of developing preeclampsia compared with normotensive women. Angiogenic markers, especially soluble fms-like kinase 1 (sFlt-1) and placental growth factor (PlGF), were identified as clinically useful markers predicting the development of preeclampsia, but data on the prediction of superimposed preeclampsia are scarce. Therefore, we aimed to evaluate the predictive value of the sFlt-1/PlGF ratio for delivery because of superimposed preeclampsia in women with chronic hypertension. Methods and Results This retrospective study included 142 women with chronic hypertension and suspected superimposed preeclampsia. Twenty-seven women (19.0%) delivered because of maternal indications only, 17 women (12.0%) because of fetal indications primarily, and 98 women (69.0%) for other reasons. Women who both delivered because of maternal indications and for fetal indications had a significantly higher sFlt-1/PlGF ratio (median 99.9 and 120.2 versus 7.3, respectively, P<0.001 for both) and lower PlGF levels (median 73.6 and 53.3 versus 320.0 pg/mL, respectively, P<0.001 for both) compared with women who delivered for other reasons. SFlt-1/PlGF ratio and PlGF were strong predictors for delivery because of superimposed preeclampsia, whether for maternal or fetal indications (P<0.05). Half of women with angiogenic imbalance (sFlt-1/PlGF ratio ≥85 or PlGF levels <100 pg/mL) delivered because of maternal or fetal indications within 1.6 weeks (95% CI, 1.0-2.4 weeks). Conclusions Angiogenic marker imbalance in women with suspected superimposed preeclampsia can predict delivery because of maternal and fetal indications related to superimposed preeclampsia and is associated with a significantly shorter time to delivery interval.

Angiogenic markers and their longitudinal change for predicting adverse outcomes in pregnant women with chronic hypertension.

BACKGROUND: Women with chronic hypertension are at increased risk for adverse maternal and perinatal outcomes. Maternal serum angiogenic markers, such as soluble fms-like tyrosine kinase 1 and placental growth factor, can be used to triage women with suspected preeclampsia. However, data about these markers in pregnant women with chronic hypertension are scarce. OBJECTIVE: We aimed to evaluate the predictive accuracy of maternal serum levels of soluble fms-like tyrosine kinase 1, placental growth factor, and their ratio for predicting adverse maternal and perinatal outcomes in women with chronic hypertension. STUDY DESIGN: This was a retrospective analysis of prospectively collected data from January 2013 to October 2019 at the University of Vienna Hospital, Vienna, Austria. The inclusion criteria were pregnant women with chronic hypertension and suspected preeclampsia. The primary outcome of this study was the prognostic performance of angiogenic markers for the prediction of adverse maternal and perinatal outcomes in pregnant women with chronic hypertension. The accuracy of angiogenic markers for predicting adverse composite outcomes was assessed with a binomial logistic regression. The accuracy of each marker was assessed using receiver operating characteristics curves and area under the curve values. Area under the curve values were compared using De Long's test. RESULTS: Of the 145 included women with chronic hypertension and suspected superimposed preeclampsia, 26 (17.9%) women developed complications (ie, composite adverse maternal or fetal outcomes) within 1 week of assessment (average gestational age at assessment, 29.9 weeks) and 35 (24.1%) developed complications at any time (average gestational age at assessment, 30.1 weeks). In women who developed complications at any time, the median maternal serum soluble fms-like tyrosine kinase-1 to placental growth factor ratio was 149.4 (interquartile range, 64.6-457.4) compared with 8.0 (interquartile range, 3.37-41.2) for women who did not develop complications (P<.001). The area under the curve values for the maternal serum soluble fms-like tyrosine kinase-1 to placental growth factor ratio Z-score (0.95; 95% confidence interval, 0.90-0.99) and placental growth factor level Z-score (0.94; 95% confidence interval, 0.88-0.99) for predicting complications within 1 week of assessment were very high. The area under the curve values for new-onset edema (0.61; 95% confidence interval, 0.52-0.70), proteinuria (0.62; 95% confidence interval, 0.52-0.71), high mean arterial pressure (0.52; 95% confidence interval, 0.50-0.54), and other symptoms of preeclampsia (0.57; 95% confidence interval, 0.49-0.65) were all significantly lower than for the angiogenic markers (P<.001 for all). Women who had an angiogenic imbalance and/or proteinuria had the highest rate of complications (28/57, 49.1%). The rate of complications in women with an angiogenic imbalance and/or proteinuria was significantly higher than in women with either proteinuria, other symptoms, or intrauterine growth restriction in the absence of an angiogenic imbalance (49.1% vs 16.7%; P=.039). The highest positive and negative predictive values for predicting adverse outcomes were demonstrated by an angiogenic imbalance and/or proteinuria criteria with a positive predictive value of 49.1% (95% confidence interval, 50.4%-57.9%) and a negative predictive value of 92% (95% confidence interval, 85.5%-95.8%). Longitudinal changes in measurements of the gestational age-corrected ratio of soluble fms-like tyrosine kinase-1 to placental growth factor up to the last measurement had a significantly higher area under the curve value than the last measurement alone (area under the curve, 0.95; 95% confidence interval, 0.92-0.99 vs 0.87; 95% confidence interval, 0.79-0.95; P=.024) CONCLUSION: Maternal serum angiogenic markers are superior to clinical assessment in predicting adverse maternal and perinatal outcomes in pregnant women with chronic hypertension. Repeated measurements of the ratio of soluble fms-like tyrosine kinase-1 to placental growth factor seems beneficial given the better predictive accuracy compared with a single measurement alone. The use of angiogenic makers should be implemented in clinical management guidelines for pregnant women with chronic hypertension.

The Prognostic Value of Angiogenic Markers in Twin Pregnancies to Predict Delivery Due to Maternal Complications of Preeclampsia.

The sFlt-1 (soluble fms-like tyrosine kinase-1), PlGF (placental growth factor), and their ratio are useful for predicting delivery because of preeclampsia in singleton pregnancies. Evidence on the utility of sFlt-1/PlGF ratio in twin pregnancies is lacking. We aimed to evaluate the predictive value of sFlt-1/PlGF ratio for delivery because of preeclampsia in twins. A retrospective data analysis of 164 twin pregnancies with suspected preeclampsia was performed. The sFlt-1/PlGF ratio, which was known to clinicians, was significantly higher in women who delivered within 1 and 2 weeks compared with those who did not (median: 98.9 and 84.2 versus 23.5 pg/mL, respectively; P<0.001). The area under the curve values sFlt-1/PlGF ratio levels were 0.88 (95% CI, 0.83-0.84) and 0.88 (95% CI, 0.83-0.93) for predicting delivery because of preeclampsia within 1 and 2 weeks of blood sampling, respectively. The predictive accuracy of sFlt-1/PlGF was independent of gestational age at sampling and chorionicity (P>0.100 for interaction). The area under the curve values of sFlt-1/PlGF were significantly higher than for PlGF alone (mean 0.88 and 0.88 versus 0.81 and 0.80) for predicting delivery because of preeclampsia within 1 and 2 weeks of blood sampling (P=0.055 and 0.001, respectively). sFlt-1/PlGF ratio lower than 38 was able to rule-out delivery within 1 and 2 weeks with a negative predictive value of 98.8% and 96.4% for delivery because of preeclampsia within 1 and 2 weeks, respectively. A cutoff of 38 is applicable for ruling out delivery because of preeclampsia in twin pregnancies.

The influence of brain iron and myelin on magnetic susceptibility and effective transverse relaxation - A biochemical and histological validation study.

Quantitative susceptibility mapping (QSM) and effective transverse relaxation rate (R2*) mapping are both highly sensitive to variations in brain iron content. Clinical Magnetic Resonance Imaging (MRI) studies report changes of susceptibilities and relaxation rates in various neurological diseases which are often equated with changes in regional brain iron content. However, these mentioned metrics lack specificity for iron, since they are also influenced by the presence of myelin. In this study, we assessed the extent to which QSM and R2* reflect iron concentration as well as histological iron and myelin intensities. Six unfixed human post-mortem brains were imaged in situ with a 7 T MRI scanner. After formalin fixation, the brains were sliced axially and punched. 671 tissue punches were subjected to ferrozine iron quantification. Subsequently, brain slices were embedded in paraffin, and histological double-hemispheric axial brain slices were stained for Luxol fast blue (myelin) and diaminobenzidine (DAB)-enhanced Turnbull blue (iron). 3331 regions of interest (ROIs) were drawn on the histological stainings to assess myelin and iron intensities, which were compared with MRI data in corresponding ROIs. QSM more closely reflected quantitative ferrozine iron values (r = 0.755 vs. 0.738), whereas R2* correlated better with iron staining intensities (r = 0.619 vs. 0.445). Myelin intensities correlated negatively with QSM (r = -0.352), indicating a diamagnetic effect of myelin on susceptibility. Myelin intensities were higher in the thalamus than in the basal ganglia. A significant relationship was nonetheless observed between quantitative iron values and QSM, confirming the applicability of the latter in this brain region for iron quantification.