(1) Background: Non-invasive prenatal testing (NIPT) is a screening test for fetal aneuploidy using cell-free fetal DNA. The fetal fragments (FF) of cell-free DNA (cfDNA) are derived from apoptotic trophoblast of the placenta. The level of fetal cfDNA is known to be influenced by gestational age, multiple pregnancies, maternal weight, and height. (2) Methods: This study is a single-center retrospective observational study which examines the relationship between the fetal fraction (FF) of cell-free DNA in non-invasive prenatal testing (NIPT) and adverse pregnancy outcomes in singleton pregnancies. A total of 1393 samples were collected between 10 weeks and 6 days, and 25 weeks and 3 days of gestation. (3) Results: Hypertensive disease of pregnancy (HDP) occurred more frequently in the low FF group than the normal FF group (5.17% vs. 1.91%, p = 0.001). Although the rates of small for gestational age (SGA) and placental abruption did not significantly differ between groups, the composite outcome was significantly higher in the low FF group (7.76% vs. 3.64%, p = 0.002). Furthermore, women who later experienced complications such as HDP or gestational diabetes mellitus (GDM) had significantly lower plasma FF levels compared to those without complications (p < 0.001). After adjustments, the low FF group exhibited a significantly higher likelihood of placental compromise (adjusted odds ratio: 1.946). (4) Conclusions: Low FF in NIPT during the first and early second trimesters is associated with adverse pregnancy outcomes, particularly HDP, suggesting its potential as a predictive marker for such outcomes.

OBJECTIVE: Approximately one-third of women in the U.S. experience an adverse pregnancy outcome (APO), which are recognized as sex-specific cardiovascular disease (CVD) risk factors. We examine if APOs confer additional CVD risk beyond that of traditional CVD risk factors.
METHODS: Women, age 40-79, with a pregnancy history and no pre-existing CVD were identified in the electronic health record of one health system (n = 2306). APOs included any APO, hypertensive disease of pregnancy (HDP), and gestational diabetes (GDM). Hazard ratios of time to CVD event were estimated from survival models using Cox proportional hazard regression. Discrimination, calibration, and net reclassification of re-estimated CVD risk prediction models including APOs were examined.
RESULTS: There was no significant association between any APO, HDP, or GDM and time to CVD outcome in survival models (95% confidence intervals all include 1). Including any APO, HDP, GDM in the CVD risk prediction model did not significantly improve discrimination and there were no clinically relevant changes in net reclassification of cases and non-cases. The strongest predictor of time to CVD event in the survival models was Black race, with hazard ratios ranging from 1.59 to 1.62, statistically significant for all three models.
CONCLUSIONS: Women with APOs did not have an additional risk of CVD, controlling for traditional risk factors in the PCE and this sex-specific factor did not improve risk prediction. Black race was consistently a strong predictor of CVD even with data limitations. Further study of APOs can help determine how to best use this information for CVD prevention in women.

Intrauterine growth restriction (IUGR) complicates up to 10% of human pregnancies and is the second leading cause of perinatal morbidity and mortality after prematurity. The most common etiology of IUGR in developed countries is uteroplacental insufficiency (UPI). For survivors of IUGR pregnancies, long-term studies consistently show a fivefold increased risk for impaired cognition including learning and memory deficits. Among these, only a few human studies have highlighted sex differences with males and females having differing susceptibilities to different impairments. Moreover, it is well established from brain magnetic resonance imaging that IUGR affects both white and gray matter. The hippocampus, composed of the dentate gyrus (DG) and cornu ammonis (CA) subregions, is an important gray matter structure critical to learning and memory, and is particularly vulnerable to the chronic hypoxic-ischemic effects of UPI. Decreased hippocampal volume is a strong predictor for learning and memory deficits. Decreased neuron number and attenuated dendritic and axonal morphologies in both the DG and CA are additionally seen in animal models. What is largely unexplored is the prenatal changes that predispose an IUGR offspring to postnatal learning and memory deficits. This lack of knowledge will continue to hinder the design of future therapy to improve learning and memory. In this review, we will first present the clinical susceptibilities and human epidemiology data regarding the neurological sequelae after IUGR. We will follow with data generated using our laboratory\'s mouse model of IUGR, that mimics the human IUGR phenotype, to dissect at the cellular and molecular alterations in embryonic hippocampal DG neurogenesis. We will lastly present a newer topic of postnatal neuron development, namely the critical period of synaptic plasticity that is crucial in achieving an excitatory/inhibitory balance in the developing brain. To our knowledge, these findings are the first to describe the prenatal changes that lead to an alteration in postnatal hippocampal excitatory/inhibitory imbalance, a mechanism that is now recognized to be a cause of neurocognitive/neuropsychiatric disorders in at-risk individuals. Studies are ongoing in our laboratory to elucidate additional mechanisms that underlie IUGR-induced learning and memory impairment and to design therapy aimed at ameliorating such impairment.

UNASSIGNED: To describe chorioretinal findings in a patient with new-onset systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) after a stillbirth associated with preeclampsia.
UNASSIGNED: Case report.
UNASSIGNED: We report a patient with new-onset SLE and APS after pregnancy, who had a history of preeclampsia and intrauterine death that presented with bilateral visual loss after a seizure. Clinical findings of a unilateral vaso-occlusive retinopathy and choroidopathy associated with intraocular inflammation, serous retinal detachment, and vasculitis are presented, which responded well to immunosuppressive therapy.
UNASSIGNED: New-onset systemic lupus erythematosus (SLE) during or after pregnancy could occur, especially when complicated with preeclampsia, making it difficult to diagnose accurately. Pregnancy-induced hypertension retinopathy and choroidopathy, as well as chorioretinal manifestations of SLE and APS, can share similar ocular manifestations that can overlap and coexist in the same patient, and it is important to recognize them for an adequate management and follow-up.

UNASSIGNED: The gold standard intrapartum treatment for preeclampsia with severe features is magnesium sulfate in order to provide prophylaxis against eclampsia. However, though magnesium sulfate is known to have a relaxant effect on uterine muscle, there have been variable reports in the literature in regard to the association between magnesium and obstetric hemorrhage (OBH).
UNASSIGNED: We aim to compare OBH incidence in patients with hypertensive disease of pregnancy (HDP) with or without exposure to intrapartum magnesium sulfate.
UNASSIGNED: We performed a retrospective cohort study of all deliveries at our institution associated with a diagnosis of hypertensive disease of pregnancy (HDP) (e.g. chronic and gestational hypertension, preeclampsia with or without severe features, eclampsia, or HELLP) from January 1, 2018 to December 31, 2019. The category of HDP diagnosis was determined by a detailed chart review by trained chart abstractors. The primary outcome was total quantitative blood loss (QBL) and the rate of obstetric hemorrhage. Secondary outcomes included a composite of obstetric hemorrhage-related maternal morbidity outcomes (OBH-M), the individual composite components and the incidence of additional hemorrhage-related interventions (e.g. uterotonics and surgical interventions). We also examined the same primary and secondary outcomes in a stratified analysis based on delivery mode (i.e. vaginal deliveries only and cesarean deliveries only).
UNASSIGNED: Of 791 patients with a diagnosis of HDP, 411 patients received magnesium sulfate for eclampsia prophylaxis and 380 patients did not receive magnesium sulfate. For all delivery modes, there was a significantly higher QBL (p < .01), increased rate of OBH (p = .04) and increased OBH-M (p < .01) in deliveries associated with intrapartum exposure to magnesium compared to those without. However, our stratified analysis by delivery mode demonstrated that magnesium-related hemorrhage risk only persisted for vaginal deliveries (QBL p < .01; OBH aOR 1.47, 95% CI: 0.75-2.85; OBH-M aOR 1.47, 95% CI 1.00-7.55) with no significant hemorrhage-related differences among cesareans with or without magnesium exposure (QBL p = .51; OBH aOR 1.45, 95% CI: 0.85-2.47; OBH-M 1.50 95% CI: 0.70-3.23).
UNASSIGNED: Intrapartum exposure to magnesium sulfate use was associated with an increase in QBL and risk of OBH-M in vaginal deliveries, but not associated with any hemorrhage-related outcome differences in cesarean deliveries. More research is needed to explore the effects of hypertensive disease, magnesium exposure, and delivery mode on obstetric hemorrhage risk.

During gestation, the maternal body should increase its activity to fulfil the demands of the developing fetus as pregnancy progresses. Each maternal organ adapts in a unique manner and at a different time during pregnancy. In an organ or system that was already vulnerable before pregnancy, the burden of pregnancy can trigger overt clinical manifestations. After delivery, symptoms usually reside; however, in time, because of the age-related metabolic and pro-atherogenic changes, they reappear. Therefore, it is believed that pregnancy acts as a medical stress test for mothers. Pregnancy complications such as gestational hypertension, preeclampsia and gestational diabetes mellitus foreshadow cardiovascular disease and/or diabetes later in life. Affected women are encouraged to modify their lifestyle after birth by adjusting their diet and exercise habits. Blood pressure and plasmatic glucose level checking are recommended so that early therapeutic intervention can reduce long-term morbidity. Currently, the knowledge of the long-term consequences in women who have had pregnancy-related syndromes is still incomplete. A past obstetric history may, however, be useful in determining the risk of diseases later in life and allow timely intervention.

The opinion on the mechanisms underlying the pathogenesis of preeclampsia still divides scientists and clinicians. This common complication of pregnancy has long been viewed as a disorder linked primarily to placental dysfunction, which is caused by abnormal trophoblast invasion, however, evidence from the previous two decades has triggered and supported a major shift in viewing preeclampsia as a condition that is caused by inherent maternal cardiovascular dysfunction, perhaps entirely independent of the placenta. In fact, abnormalities in the arterial and cardiac functions are evident from the early subclinical stages of preeclampsia and even before conception. Moving away from simply observing the peripheral blood pressure changes, studies on the central hemodynamics reveal two different mechanisms of cardiovascular dysfunction thought to be reflective of the early-onset and late-onset phenotypes of preeclampsia. More recent evidence identified that the underlying cardiovascular dysfunction in these phenotypes can be categorized according to the presence of coexisting fetal growth restriction instead of according to the gestational period at onset, the former being far more common at early gestational ages. The purpose of this review is to summarize the hemodynamic research observations for the two phenotypes of preeclampsia. We delineate the physiological hemodynamic changes that occur in normal pregnancy and those that are observed with the pathologic processes associated with preeclampsia. From this, we propose how the two phenotypes of preeclampsia could be managed to mitigate or redress the hemodynamic dysfunction, and we consider the implications for future research based on the current evidence. Maternal hemodynamic modifications throughout pregnancy can be recorded with simple-to-use, noninvasive devices in obstetrical settings, which require only basic training. This review includes a brief overview of the methodologies and techniques used to study hemodynamics and arterial function, specifically the noninvasive techniques that have been utilized in preeclampsia research.

Preeclampsia and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are both life-threatening disorders when they occur during pregnancy. They are similarly characterized by systemic immune activation and have a deleterious effect on maternal endothelial cells. During the coronavirus disease-2019 (COVID-19) pandemic, there were reports of preeclampsia or a preeclampsia-like syndrome occurring in pregnant women with SARS-CoV-2 infection. We performed a meta-analysis to estimate the risk and prevalence of preeclampsia and SARS-CoV-2 infection in pregnant women. A comprehensive literature search was conducted in PubMed, Web of Science, Scopus, and China National Knowledge Infrastructure to identify all relevant studies published up to February 29, 2020. All studies that reported the prevalence of preeclampsia in pregnant women with SARS-CoV-2 infection were selected. A total of 10 case-control studies and 15 case series met our inclusion criteria. Pooled data revealed no significant difference between infected pregnant women and uninfected pregnant women for the risk of preeclampsia [odds ratio (OR)=1.676, 95% confidence interval (CI) 0.679-4.139, p=0.236]. The stratified analysis revealed significant risk in the infected Asian pregnant women (OR=2.637, 95% CI 1.030-6.747, p=0.043), but not Caucasian. The prevalence of preeclampsia was 8.2% (95% CI 0.057-0.117) in infected pregnant women with COVID-19 in the overall population. Its prevalence was highest in North America (10.7%), followed by Asian (7.9%), Caucasian (6.7%), European (4.9%), and West Asian (2.6%) infected pregnant women. Our pooled data showed that the prevalence of preeclampsia in pregnant women with SARS-CoV-2 infection was 8.2%. However, there was no increased risk of occurrence of preeclampsia among pregnant women with SARS-CoV-2 infection.

Human infants who suffer from intrauterine growth restriction (IUGR), which is a failure to attain their genetically predetermined weight, are at increased risk for postnatal learning and memory deficits. Hippocampal dentate gyrus (DG) granule neurons play an important role in memory formation; however, it is unknown whether IUGR affects embryonic DG neurogenesis, which could provide a potential mechanism underlying abnormal postnatal learning and memory function. Using a mouse model of the most common cause of IUGR, induced by hypertensive disease of pregnancy, we first assessed adult learning and memory function. We quantified the percentages of embryonic hippocampal DG neural stem cells (NSCs) and progenitor cells and developing glutamatergic granule neurons, as well as hippocampal volumes and neuron cell count and morphology 18 and 40 d after delivery. We characterized the differential embryonic hippocampal transcriptomic pathways between appropriately grown and IUGR mouse offspring. We found that IUGR offspring of both sexes had short-term adult learning and memory deficits. Prenatally, we found that IUGR caused accelerated embryonic DG neurogenesis and Sox2+ neural stem cell depletion. IUGR mice were marked by decreased hippocampal volumes and decreased doublecortin+ neuronal progenitors with increased mean dendritic lengths at postnatal day 18. Consistent with its known molecular role in embryonic DG neurogenesis, we also found evidence for decreased Wnt pathway activity during IUGR. In conclusion, we have discovered that postnatal memory deficits are associated with accelerated NSC differentiation and maturation into glutamatergic granule neurons following IUGR, a phenotype that could be explained by decreased embryonic Wnt signaling.

Hypertensive disorders of pregnancy are widespread and have long-standing implications for women\'s health. Historically, the management of \"severe gestational hypertension,\" or the presence of severely elevated blood pressures without any other signs or symptoms of end-organ damage meeting the criteria for preeclampsia, has been unclear. The new American College of Obstetricians and Gynecologists guidelines based on expert opinion recommend that severe gestational hypertension be treated similarly to preeclampsia with severe features, but data regarding outcomes for women with this diagnosis have been limited.
This study aimed to compare the maternal and perinatal sequelae of severe gestational hypertension with that of other types of hypertensive disorders of pregnancy.
This is a retrospective cohort study of women with hypertensive disease of pregnancy who delivered at a single tertiary care center between February and December 2018. Women with chronic hypertension; hemolysis, elevated liver enzymes, and low platelet count syndrome; preexisting kidney, liver, rheumatologic, or hematologic disorders; or multifetal pregnancies were excluded. Women were categorized as having severe gestational hypertension if they had a sustained systolic blood pressure of >160 mm Hg or a diastolic blood pressure of >110 mm Hg without other criteria for preeclampsia. The primary comparison was between women with severe gestational hypertension and women with preeclampsia without severe features. Secondary comparisons included women with severe gestational hypertension vs women with other types of hypertensive disease of pregnancy. The primary outcome for this analysis was small-for-gestational-age birth. We also evaluated other maternal and neonatal morbidities including but not limited to pulmonary embolism, stroke, eclampsia, blood transfusion, mechanical ventilation, intensive care unit admission, death, 5-minute Apgar score of ≤4, umbilical cord pH, neonatal intensive care unit admission of >2 days, respiratory distress syndrome, and neonatal death. Bivariate analyses using chi-square tests and logistic regressions adjusting for race, ethnicity, age, body mass index, parity, and insurance status were performed to compare frequencies of outcomes for each type of hypertensive disease of pregnancy with those of severe gestational hypertension.
Of 2076 women eligible for inclusion, 12.2% (n=254) had severe gestational hypertension and 379 (18.2%) had preeclampsia without severe features. Although there was no difference in the odds of small-for-gestational-age birth between women with severe gestational hypertension and women with preeclampsia without severe features (14.7% vs 9.8%; adjusted odds ratio, 0.72; 95% confidence interval, 0.44-1.21), the latter were significantly less likely to receive a prescription for antihypertensive medication at discharge (OR 0.11, 95% CI 0.06-0.22) or to be readmitted postpartum (OR 0.14, 95% CI 0.04-0.50).
There was no difference in the primary outcome, that is, rate of small-for-gestational-age birth, between women with severe gestational hypertension and women with preeclampsia without severe features. However, women with severe gestational hypertension had greater odds of other maternal and neonatal morbidities than women with preeclampsia without severe features or mild gestational hypertension. These findings support recent recommendations regarding the management of women with severe gestational hypertension.