Analysis of placental pathology after COVID-19 by timing and severity of infection.

BACKGROUND: COVID-19 during pregnancy can have serious effects on pregnancy outcomes. The placenta acts as an infection barrier to the fetus and may mediate adverse outcomes. Increased frequency of maternal vascular malperfusion has been detected in the placentas of patients with COVID-19 compared with controls, but little is known about how the timing and severity of infection affect placental pathology. OBJECTIVE: This study aimed to examine the effects of SARS-CoV-2 infection on placental pathology, specifically whether the timing and severity of COVID-19 affect pathologic findings and associations with perinatal outcomes. STUDY DESIGN: This was a descriptive retrospective cohort study of pregnant people diagnosed with COVID-19 who delivered between April 2020 and September 2021 at 3 university hospitals. Demographic, placental, delivery, and neonatal outcomes were collected through medical record review. The timing of SARS-CoV-2 infection was noted, and the severity of COVID-19 was categorized on the basis of the National Institutes of Health guidelines. The placentas of all patients with positive nasopharyngeal reverse transcription-polymerase chain reaction COVID-19 testing were sent for gross and microscopic histopathologic examinations at the time of delivery. Nonblinded pathologists categorized histopathologic lesions according to the Amsterdam criteria. Univariate linear regression and chi-square analyses were used to assess how the timing and severity of SARS-CoV-2 infection affected placental pathologic findings. RESULTS: This study included 131 pregnant patients and 138 placentas, with most patients delivered at the University of California, Los Angeles (n=65), followed by the University of California, San Francisco (n=38) and Zuckerberg San Francisco General Hospital (n=28). Most patients were diagnosed with COVID-19 in the third trimester of pregnancy (69%), and most infections were mild (60%). There was no specific placental pathologic feature based on the timing or severity of COVID-19. There was a higher frequency of placental features associated with response to infection in the placentas from infections before 20 weeks of gestation than that from infections after 20 weeks of gestation (P=.001). There was no difference in maternal vascular malperfusion by the timing of infection; however, features of severe maternal vascular malperfusion were only found in the placentas of patients with SARS-CoV-2 infection in the second and third trimesters of pregnancy, not in the placentas of patients with COVID-19 in the first trimester of pregnancy. CONCLUSION: Placentas from patients with COVID-19 showed no specific pathologic feature, regardless of the timing or severity of the disease. There was a higher proportion of placentas from patients with COVID-19-positive tests in earlier gestations with evidence of placental infection-associated features. Future studies should focus on understanding how these placental features in SARS-CoV-2 infections go on to affect pregnancy outcomes.

Delivery trends and obstetric outcomes in patients with Fontan circulation.

BACKGROUND: With improved therapies, an increasing number of patients with Fontan circulation reach reproductive age. Pregnant patients with Fontan circulation are at high risk of obstetrical complications. Most data for pregnancies complicated by Fontan circulation and associated complications stem from single-center studies, with limited national epidemiologic data available. OBJECTIVE: This study aimed to evaluate temporal trends in deliveries to pregnant individuals with Fontan palliation using nationwide data and to estimate associated obstetrical complications among these deliveries. STUDY DESIGN: Delivery hospitalizations were abstracted from the 2000 to 2018 Nationwide Inpatient Sample. Deliveries complicated by Fontan circulation were identified using diagnosis codes, and trends in the rates of these deliveries were assessed using joinpoint regression. Baseline demographics and obstetrical outcomes (including severe maternal morbidity, a composite of serious obstetrical and cardiac complications) were assessed. Univariable log-linear regression models were fit comparing risks of outcomes among deliveries of patients with and without Fontan circulation. RESULTS: A total of 509 pregnancies complicated by Fontan circulation were identified at a rate of 7 per 1 million delivery hospitalizations, with a temporal increase from 2.4 to 30.3 cases per 1 million from 2000 to 2018 (P<.01). Deliveries complicated by Fontan circulation were at higher risk of hypertensive disorders (relative risk, 1.79; 95% confidence interval, 1.42-2.27), preterm delivery (relative risk, 2.37; 95% confidence interval, 1.90-2.96), postpartum hemorrhage (relative risk, 4.28; 95% confidence interval, 3.35-5.45), and severe maternal morbidity (relative risk, 6.09; 95% confidence interval, 4.54-8.17) than deliveries not complicated by Fontan circulation. CONCLUSION: The rates of deliveries of patients with Fontan palliation are increasing on a national level. These deliveries have higher risks of obstetrical complications and severe maternal morbidity. Additional national clinical data are necessary to better understand the complications in pregnancies complicated by Fontan circulation, to improve patient counseling, and to reduce maternal morbidity.

Postpartum Hemorrhage Trends and Outcomes in the United States, 2000-2019.

OBJECTIVE: To analyze temporal trends in and risk factors for postpartum hemorrhage and to analyze the association of risk factors with postpartum hemorrhage-related interventions such as blood transfusion and peripartum hysterectomy. METHODS: This repeated cross-sectional study analyzed delivery hospitalizations from 2000 to 2019 in the National (Nationwide) Inpatient Sample. Trends analyses were conducted using joinpoint regression to estimate the average annual percent change (AAPC) with 95% CIs. Unadjusted and adjusted survey-weighted logistic regression models were performed to evaluate the relationship between postpartum hemorrhage risk factors and likelihood of 1) postpartum hemorrhage, 2) postpartum hemorrhage that requires blood transfusion, and 3) peripartum hysterectomy in the setting of postpartum hemorrhage, with unadjusted odds ratios and adjusted odds ratios with 95% CIs as measures of association. RESULTS: Of an estimated 76.7 million delivery hospitalizations, 2.3 million (3.0%) were complicated by postpartum hemorrhage. From 2000 to 2019, the rate of postpartum hemorrhage increased from 2.7% to 4.3% (AAPC 2.6%, 94% CI 1.7-3.5%). Over the study period, the proportion of deliveries to individuals with at least one postpartum hemorrhage risk factor increased from 18.6% to 26.9% (AAPC 1.9%, 95% CI 1.7-2.0%). Among deliveries complicated by postpartum hemorrhage, blood transfusions increased from 5.4% to 16.7% from 2000 to 2011 and then decreased from 16.7% to 12.6% from 2011 to 2019. Peripartum hysterectomy among hospitalized individuals with postpartum hemorrhage increased from 1.4% to 2.4% from 2000 to 2009, did not change significantly from 2009 to 2016, and then decreased significantly from 2.1% to 0.9% from 2016 to 2019 (AAPC -27.0%, 95% CI -35.2% to -17.6%). Risk factors associated with postpartum hemorrhage and transfusion and hysterectomy in the setting of postpartum hemorrhage included prior cesarean delivery with previa or placenta accreta, placenta previa without prior cesarean delivery, and antepartum hemorrhage or placental abruption. CONCLUSION: Postpartum hemorrhage and related risk factors increased over a 20-year period. Despite the increased postpartum hemorrhage rates, blood transfusions, and hysterectomy rates decreased in recent years.

Traveling to California from out of state to receive abortion services at a hospital-based clinic: A qualitative study of people's experiences.

OBJECTIVE: People seeking abortion care in the Western United States face unique challenges. We conducted a qualitative study among people who traveled to California from out of state to receive abortion services, with the aim of characterizing the interplay of motivators, costs, and facilitators to accessing abortion in this region. METHODS: We recruited English-speaking people residing outside of California who accessed care at an urban abortion clinic in San Francisco between October 2017 and May 2018. Interested participants completed a brief demographic survey and in depth semi-structured telephone interview. We relied on grounded theory methods to perform thematic analysis and stopped recruitment upon reaching thematic saturation. RESULTS: We conducted 18 in-depth interviews. People mostly had to travel to California for abortion due to local clinic gestational age limits, medical necessity, and to reduce cost. Participants also lamented that travel necessitated unwanted disclosure of their abortion, however this disclosure enabled them to get the logistical support needed for travel. People mostly relied on their networks of family and friends to facilitate these logistics. CONCLUSIONS: This study highlights the interplay of motivators, costs, and facilitators people who travel to California from nearby states face when seeking abortion services. IMPLICATIONS: We position the concept of 'unwanted disclosure' as both an emotional cost and an operator that often served to enable people to get the support (logistical, financial, professional) they needed to actualize their abortion in California. These people may benefit from additional financial and social support services in order to actualize their abortion.

COVID-19's impact on contraception experiences: Exacerbation of structural inequities in women's health.

INTRODUCTION: Structural inequities may impact the relationship between COVID-19 and access to contraception. METHODS: In July 2020 and January 2021, we used social media to survey 2 samples of women of reproductive age who had not been surgically sterilized and were not currently pregnant about their experiences seeking contraception. We explore whether experiences differed for people experiencing social and/or economic disadvantage due to COVID-19, using multivariable logistic regression to control for age, education and income. RESULTS: In July 2020, 51.5% of respondents who sought contraception (total N = 3064) reported barriers to care compared to 55.3% in January 2021 (total N = 2276). A larger percent (14% in July 2020 and 22% in Jan 2021) reported not using their preferred method of contraception due to COVID-19. Individuals experiencing income loss (OR = 1.61, 95% CI 1.27-2.04 early in the COVID-19 pandemic and OR = 1.58, 1.21-2.06 mid COVID-19 pandemic) and hunger (OR = 1.73, 1.24-2.40 early and OR = 2.02, 1.55-2.64 mid-COVID-19 pandemic) were more likely to report they would be using a different method if not for COVID-19, compared to respondents without income loss or hunger. CONCLUSIONS: COVID-19 has complicated access to contraception, especially for disadvantaged populations. IMPLICATIONS: Efforts are needed to ensure access to contraception despite the COVID-19 epidemic, especially for disadvantaged populations.

Experiences in Electronic Consultation (eConsult) Service in Gynecology from a Quaternary Academic Medical Center.

To evaluate an academic institution's implementation of a gynecologic electronic consultation (eConsult) service, including the most common queries, turnaround time, need for conversion to in-person visits, and to demonstrate how eConsults can improve access and convenience for patients and providers. This is a descriptive and retrospective electronic chart review. We obtained data from the UCSF eConsult and Smart Referral program manager. The medical system provided institution-wide statistics. Three authors reviewed and categorized gynecologic eConsults for the last fiscal year. The senior author resolved conflicts in coding. The eConsult program manager provided billing information and provider reimbursement. A total of 548 eConsults were submitted to the gynecology service between July 2017 and June 2020 (4.5% of institutional eConsult volume). Ninety-five percent of the eConsults were completed by a senior specialist within our department. Abnormal pap smear management, abnormal uterine bleeding, and contraception questions were the most common queries. Over half (59.3%) of all inquiries were answered on the same day as they were received, with an average of 9% declined. Gynecology was the 10th largest eConsult provider at our institution in 2020. The present investigation describes one large university-based experience with eConsults in gynecology. Results demonstrate that eConsults permit appropriate, efficient triaging of time-sensitive conditions affecting patients especially in the time of the COVID-19 pandemic. eConsult services provide the potential to improve access, interdisciplinary communication, and patient and provider satisfaction.

An 8-week, open-label, dose-finding study of nimodipine for the treatment of progranulin insufficiency from GRN gene mutations.

INTRODUCTION: Frontotemporal lobar degeneration-causing mutations in the progranulin (GRN) gene reduce progranulin protein (PGRN) levels, suggesting that restoring PGRN in mutation carriers may be therapeutic. Nimodipine, a Food and Drug Administration-approved blood-brain barrier-penetrant calcium channel blocker, increased PGRN levels in PGRN-deficient murine models. We sought to assess safety and tolerability of oral nimodipine in human GRN mutation carriers. METHODS: We performed an open-label, 8-week, dose-finding, phase 1 clinical trial in eight GRN mutation carriers to assess the safety and tolerability of nimodipine and assayed fluid and radiologic markers to investigate therapeutic endpoints. RESULTS: There were no serious adverse events; however, PGRN concentrations (cerebrospinal fluid and plasma) did not change significantly following treatment (percent changes of -5.2 ± 10.9% in plasma and -10.2 ± 7.8% in cerebrospinal fluid). Measurable atrophy within the left middle frontal gyrus was observed over an 8-week period. DISCUSSION: While well tolerated, nimodipine treatment did not alter PGRN concentrations or secondary outcomes.

Predicting amyloid status in corticobasal syndrome using modified clinical criteria, magnetic resonance imaging and fluorodeoxyglucose positron emission tomography.

INTRODUCTION: Group comparisons demonstrate greater visuospatial and memory deficits and temporoparietal-predominant degeneration on neuroimaging in patients with corticobasal syndrome (CBS) found to have Alzheimer's disease (AD) pathology versus those with underlying frontotemporal lobar degeneration (FTLD). The value of these features in predicting underlying AD pathology in individual patients is unknown. The goal of this study is to evaluate the utility of modified clinical criteria and visual interpretations of magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) for predicting amyloid deposition (as a surrogate of Alzheimer's disease neuropathology) in patients presenting with CBS. METHODS: In total, 25 patients meeting CBS core criteria underwent amyloid (Pittsburgh compound B; PIB) PET scans. Clinical records, MRI, and FDG scans were reviewed blinded to PIB results. Modified clinical criteria were used to classify CBS patients as temporoparietal variant CBS (tpvCBS) or frontal variant CBS (fvCBS). MRI and FDG-PET were classified based on the predominant atrophy/hypometabolism pattern (frontal or temporoparietal). RESULTS: A total of 9 out of 13 patients classified as tpvCBS were PIB+, compared to 2out of 12 patients classified as fvCBS (P < 0.01, sensitivity 82%, specificity 71% for PIB+ status). Visual MRI reads had 73% sensitivity and 46% specificity for PIB+ status with moderate intra-rater reliability (Cohen's kappa = 0.42). Visual FDG reads had higher sensitivity (91%) for PIB+ status with perfect intra-rater reliability (kappa = 1.00), though specificity was low (50%). PIB results were confirmed in all 8 patients with available histopathology (3 PIB+ with confirmed AD, 5 PIB- with FTLD). CONCLUSIONS: Splitting CBS patients into frontal or temporoparietal clinical variants can help predict the likelihood of underlying AD, but criteria require further refinement. Temporoparietal-predominant neuroimaging patterns are sensitive but not specific for AD.

Diverging patterns of amyloid deposition and hypometabolism in clinical variants of probable Alzheimer's disease.

The factors driving clinical heterogeneity in Alzheimer's disease are not well understood. This study assessed the relationship between amyloid deposition, glucose metabolism and clinical phenotype in Alzheimer's disease, and investigated how these relate to the involvement of functional networks. The study included 17 patients with early-onset Alzheimer's disease (age at onset <65 years), 12 patients with logopenic variant primary progressive aphasia and 13 patients with posterior cortical atrophy [whole Alzheimer's disease group: age = 61.5 years (standard deviation 6.5 years), 55% male]. Thirty healthy control subjects [age = 70.8 (3.3) years, 47% male] were also included. Subjects underwent positron emission tomography with (11)C-labelled Pittsburgh compound B and (18)F-labelled fluorodeoxyglucose. All patients met National Institute on Ageing-Alzheimer's Association criteria for probable Alzheimer's disease and showed evidence of amyloid deposition on (11)C-labelled Pittsburgh compound B positron emission tomography. We hypothesized that hypometabolism patterns would differ across variants, reflecting involvement of specific functional networks, whereas amyloid patterns would be diffuse and similar across variants. We tested these hypotheses using three complimentary approaches: (i) mass-univariate voxel-wise group comparison of (18)F-labelled fluorodeoxyglucose and (11)C-labelled Pittsburgh compound B; (ii) generation of covariance maps across all subjects with Alzheimer's disease from seed regions of interest specifically atrophied in each variant, and comparison of these maps to functional network templates; and (iii) extraction of (11)C-labelled Pittsburgh compound B and (18)F-labelled fluorodeoxyglucose values from functional network templates. Alzheimer's disease clinical groups showed syndrome-specific (18)F-labelled fluorodeoxyglucose patterns, with greater parieto-occipital involvement in posterior cortical atrophy, and asymmetric involvement of left temporoparietal regions in logopenic variant primary progressive aphasia. In contrast, all Alzheimer's disease variants showed diffuse patterns of (11)C-labelled Pittsburgh compound B binding, with posterior cortical atrophy additionally showing elevated uptake in occipital cortex compared with early-onset Alzheimer's disease. The seed region of interest covariance analysis revealed distinct (18)F-labelled fluorodeoxyglucose correlation patterns that greatly overlapped with the right executive-control network for the early-onset Alzheimer's disease region of interest, the left language network for the logopenic variant primary progressive aphasia region of interest, and the higher visual network for the posterior cortical atrophy region of interest. In contrast, (11)C-labelled Pittsburgh compound B covariance maps for each region of interest were diffuse. Finally, (18)F-labelled fluorodeoxyglucose was similarly reduced in all Alzheimer's disease variants in the dorsal and left ventral default mode network, whereas significant differences were found in the right ventral default mode, right executive-control (both lower in early-onset Alzheimer's disease and posterior cortical atrophy than logopenic variant primary progressive aphasia) and higher-order visual network (lower in posterior cortical atrophy than in early-onset Alzheimer's disease and logopenic variant primary progressive aphasia), with a trend towards lower (18)F-labelled fluorodeoxyglucose also found in the left language network in logopenic variant primary progressive aphasia. There were no differences in (11)C-labelled Pittsburgh compound B binding between syndromes in any of the networks. Our data suggest that Alzheimer's disease syndromes are associated with degeneration of specific functional networks, and that fibrillar amyloid-ß deposition explains at most a small amount of the clinico-anatomic heterogeneity in Alzheimer's disease.