Preventing posttraumatic stress disorder following childbirth: a systematic review and meta-analysis.

OBJECTIVE: Women can develop posttraumatic stress disorder in response to experienced or perceived traumatic, often medically complicated, childbirth; the prevalence of these events remains high in the United States. Currently, no recommended treatment exists in routine care to prevent or mitigate maternal childbirth-related posttraumatic stress disorder. We conducted a systematic review and meta-analysis of clinical trials that evaluated any therapy to prevent or treat childbirth-related posttraumatic stress disorder. DATA SOURCES: PsycInfo, PsycArticles, PubMed (MEDLINE), ClinicalTrials.gov, CINAHL, ProQuest, Sociological Abstracts, Google Scholar, Embase, Web of Science, ScienceDirect, Scopus, and the Cochrane Central Register of Controlled Trials were searched for eligible trials published through September 2023. STUDY ELIGIBILITY CRITERIA: Trials were included if they were interventional, if they evaluated any therapy for childbirth-related posttraumatic stress disorder for the indication of symptoms or before posttraumatic stress disorder onset, and if they were written in English. METHODS: Independent coders extracted the sample characteristics and intervention information of the eligible studies and evaluated the trials using the Downs and Black's quality checklist and Cochrane's method for risk of bias evaluation. RESULTS: A total of 41 studies (32 randomized controlled trials, 9 nonrandomized trials) were reviewed. They evaluated brief psychological therapies including debriefing, trauma-focused therapies (including cognitive behavioral therapy and expressive writing), memory consolidation and reconsolidation blockage, mother-infant-focused therapies, and educational interventions. The trials targeted secondary preventions aimed at buffering childbirth-related posttraumatic stress disorder usually after traumatic childbirth (n=24), tertiary preventions among women with probable childbirth-related posttraumatic stress disorder (n=14), and primary prevention during pregnancy (n=3). A meta-analysis of the combined randomized secondary preventions showed moderate effects in reducing childbirth-related posttraumatic stress disorder symptoms when compared with usual treatment (standardized mean difference, -0.67; 95% confidence interval, -0.92 to -0.42). Single-session therapy within 96 hours of birth was helpful (standardized mean difference, -0.55). Brief, structured, trauma-focused therapies and semi-structured, midwife-led, dialogue-based psychological counseling showed the largest effects (standardized mean difference, -0.95 and -0.91, respectively). Other treatment approaches (eg, the Tetris game, mindfulness, mother-infant-focused treatment) warrant more research. Tertiary preventions produced smaller effects than secondary prevention but are potentially clinically meaningful (standardized mean difference, -0.37; -0.60 to -0.14). Antepartum educational approaches may help, but insufficient empirical evidence exists. CONCLUSION: Brief trauma-focused and non-trauma-focused psychological therapies delivered early in the period following traumatic childbirth offer a critical and feasible opportunity to buffer the symptoms of childbirth-related posttraumatic stress disorder. Future research that integrates diagnostic and biologic measures can inform treatment use and the mechanisms at work.

SARS-CoV-2 Infection in Unvaccinated High-Risk Pregnant Women in the Bronx, NY, USA Is Associated with Decreased Apgar Scores and Placental Villous Infarcts.

Babies born to severe acute respiratory syndrome corona virus-2 (SARS-CoV-2)-infected mothers are at greater risk for perinatal morbidity and more likely to receive a neurodevelopmental diagnosis in the first year of life. However, the effect of maternal infection on placental function and neonatal outcomes varies depending upon the patient population. We set out to test our hypothesis that maternal SARS-CoV-2 infection in our underserved, socioeconomically disadvantaged, mostly unvaccinated, predominantly African American and Latina population in the Bronx, NY would have effects evident at birth. Under IRB approval, 56 SARS-CoV-2-positive patients infected during the "first wave" of the pandemic with alpha and beta strains of the virus, 48 patients infected during the "second wave" of the pandemic with delta and omicron strains and 61 negative third-trimester high-risk patients were randomly selected from Montefiore Medical Center (MMC), Bronx, NY. In addition, two positive cases from Yale New Haven Hospital, CT were included as controls. All 104 placentas delivered by SARS-CoV-2-positive mothers were uninfected by the virus, based on immunohistochemistry, in situ hybridization, and qPCR analysis. However, placental villous infarcts were significantly increased in first-wave cases compared to second-wave cases or negative controls. Significantly lower Apgar scores at 1 min and 5 min were observed in neonates born to infected mothers with severe symptoms. These findings suggest that even without entering the placenta, SARS-CoV-2 can affect various systemic pathways, culminating in altered placental development and function, which may adversely affect the fetus, especially in a high-risk patient population such as ours. These results underline the importance of vaccination among pregnant women, particularly in low-resource areas.

Incidence and characteristics of stillbirths before and during the Coronavirus 2019 pandemic.

OBJECTIVE: The aim of this study was to determine the incidence and characteristics of stillbirths during the initial wave of the Coronavirus 2019 (COVID-19) pandemic and whether or not this differed from the incidence and characteristics of stillbirths that occurred in the pre-pandemic period. STUDY DESIGN: This was a single-center retrospective cohort study of pregnant individuals who delivered stillbirths during two different time periods: March-September in 2017, 2018, and 2019 (pre-COVID-19 pandemic period) and March-September 2020 (COVID-19 pandemic period). RESULTS: No difference in the rate of stillbirths was found between the two time periods. The women who experienced a stillbirth during the pre-pandemic period attended on average more prenatal visits than women who experienced a stillbirth during the pandemic period (p < .05). During the pandemic period, a higher proportion of stillbirths were suspected to be due to poorly controlled hypertension (p = .04). CONCLUSIONS: The incidence of stillbirth during the pandemic period was similar to that during the pre-pandemic period; however, there were more stillbirths that occurred due to poorly controlled hypertension, a potentially preventable cause of stillbirth, during the pandemic period when compared to those of the pre-pandemic period. While the impact of the disease process of COVID-19 on stillbirth remains uncertain, the change in the provision of prenatal care during the pandemic period may have had unintended consequences with respect to the prevention and management of hypertension and the risk of potentially preventable stillbirths.

Prediction of Maternal Hemorrhage Using Machine Learning: Retrospective Cohort Study.

BACKGROUND: Postpartum hemorrhage remains one of the largest causes of maternal morbidity and mortality in the United States. OBJECTIVE: The aim of this paper is to use machine learning techniques to identify patients at risk for postpartum hemorrhage at obstetric delivery. METHODS: Women aged 18 to 55 years delivering at a major academic center from July 2013 to October 2018 were included for analysis (N=30,867). A total of 497 variables were collected from the electronic medical record including the following: demographic information; obstetric, medical, surgical, and family history; vital signs; laboratory results; labor medication exposures; and delivery outcomes. Postpartum hemorrhage was defined as a blood loss of ≥1000 mL at the time of delivery, regardless of delivery method, with 2179 (7.1%) positive cases observed. Supervised learning with regression-, tree-, and kernel-based machine learning methods was used to create classification models based upon training (21,606/30,867, 70%) and validation (4630/30,867, 15%) cohorts. Models were tuned using feature selection algorithms and domain knowledge. An independent test cohort (4631/30,867, 15%) determined final performance by assessing for accuracy, area under the receiver operating curve (AUROC), and sensitivity for proper classification of postpartum hemorrhage. Separate models were created using all collected data versus models limited to data available prior to the second stage of labor or at the time of decision to proceed with cesarean delivery. Additional models examined patients by mode of delivery. RESULTS: Gradient boosted decision trees achieved the best discrimination in the overall model. The model including all data mildly outperformed the second stage model (AUROC 0.979, 95% CI 0.971-0.986 vs AUROC 0.955, 95% CI 0.939-0.970). Optimal model accuracy was 98.1% with a sensitivity of 0.763 for positive prediction of postpartum hemorrhage. The second stage model achieved an accuracy of 98.0% with a sensitivity of 0.737. Other selected algorithms returned models that performed with decreased discrimination. Models stratified by mode of delivery achieved good to excellent discrimination but lacked the sensitivity necessary for clinical applicability. CONCLUSIONS: Machine learning methods can be used to identify women at risk for postpartum hemorrhage who may benefit from individualized preventative measures. Models limited to data available prior to delivery perform nearly as well as those with more complete data sets, supporting their potential utility in the clinical setting. Further work is necessary to create successful models based upon mode of delivery and to validate the findings of this study. An unbiased approach to hemorrhage risk prediction may be superior to human risk assessment and represents an area for future research.

Epigenetic and Transcriptomic Programming of HSC Quiescence Signaling in Large for Gestational Age Neonates.

Excessive fetal growth is associated with DNA methylation alterations in human hematopoietic stem and progenitor cells (HSPC), but their functional impact remains elusive. We implemented an integrative analysis combining single-cell epigenomics, single-cell transcriptomics, and in vitro analyses to functionally link DNA methylation changes to putative alterations of HSPC functions. We showed in hematopoietic stem cells (HSC) from large for gestational age neonates that both DNA hypermethylation and chromatin rearrangements target a specific network of transcription factors known to sustain stem cell quiescence. In parallel, we found a decreased expression of key genes regulating HSC differentiation including EGR1, KLF2, SOCS3, and JUNB. Our functional analyses showed that this epigenetic programming was associated with a decreased ability for HSCs to remain quiescent. Taken together, our multimodal approach using single-cell (epi)genomics showed that human fetal overgrowth affects hematopoietic stem cells' quiescence signaling via epigenetic programming.

Novel Evidence-Based Labor Induction Algorithm Associated with Increased Vaginal Delivery within 24 Hours.

OBJECTIVE: This study aimed to assess whether concordance with our proposed labor induction algorithm is associated with an increased rate of vaginal delivery within 24 hours. STUDY DESIGN: We conducted a retrospective review of 287 induction of labors (IOLs) at a single urban, tertiary, academic medical center which took place before we created an evidence-based IOL algorithm. We then compared the IOL course to the algorithm to assess for concordance and outcomes. Patients age 18 years or over with a singleton, cephalic pregnancy of 366/7 to 420/7 weeks' gestation were included. Patients were excluded with a Bishop's score >6, contraindication to misoprostol or cervical Foley catheter, major fetal anomalies, or intrauterine fetal death. Patients with 100% concordance were compared with <100% concordant patients, and patients with ≥80% concordance were compared with <80% concordant patients. Adjusted hazard ratios (AHRs) were calculated for rate of vaginal delivery within 24 hours, our primary outcome. Competing risk's analysis was conducted for concordant versus nonconcordant groups, using vaginal delivery as the outcome of interest, with cesarean delivery (CD) as a competing event. RESULTS: Patients with 100% concordance were more likely to have a vaginal delivery within 24 hours, n = 66 of 77 or 85.7% versus n = 120 of 210 or 57.1% (p < 0.0001), with an AHR of 2.72 (1.98, 3.75, p < 0.0001) after adjusting for delivery indication and scheduled status. Patients with 100% concordance also had shorter time from first intervention to delivery (11.9 vs. 19.4 hours). Patients with ≥80% concordance had a lower rate of CD (11/96, 11.5%) compared with those with <80% concordance (43/191 = 22.5%; p = 0.0238). There were no differences in neonatal outcomes assessed. CONCLUSION: Our IOL algorithm may offer an opportunity to standardize care, improve the rate of vaginal delivery within 24 hours, shorten time to delivery, and reduce the CD rate for patients undergoing IOL. KEY POINTS: · Studies on IOL have focused on individual steps. A labor induction algorithm allows for standardization.. · Algorithm concordance is associated with decreased time to delivery.. · Algorithm concordance is associated with decreased CD rate..

Fetal Screening for Chromosomal Abnormalities.

With more and more reproductive-aged women opting to pursue genetic screening during pregnancy, health care professionals must understand the variety of testing options available as well as the advantages and limitations of each testing option. Presently, no single screening test is universally believed to be superior because the combination of the specific test and the population being tested determines the range of potential identifiable conditions as well as the positive predictive values. As a result, pre- and posttest counseling are not always straightforward and may require discussions with multiple specialists including genetic counselors, obstetricians, and pediatricians/neonatologists. The purpose of this review is to summarize the screening options currently available to pregnant women to determine their risk of having a child affected by a chromosomal disorder. Screening for chromosomal abnormalities using ultrasonography, maternal serum analytes, cell-free DNA, and preimplantation genetic testing will be discussed here. Advances in the field, including the possible future use of cell-based noninvasive prenatal screening (NIPS) as a more accurate method for genetic screening and the incorporation of screening for copy number variants (microdeletions and duplications) into traditional cell-free NIPS will also be reviewed.

Prenatal Hyperglycemia Exposure and Cellular Stress, a Sugar-Coated View of Early Programming of Metabolic Diseases.

Worldwide, the number of people with diabetes has quadrupled since 1980 reaching 422 million in 2014 (World Health Organization). This distressing rise in diabetes also affects pregnant women and thus, in regard to early programming of adult diseases, creates a vicious cycle of metabolic dysfunction passed from one generation to another. Metabolic diseases are complex and caused by the interplay between genetic and environmental factors. High-glucose exposure during in utero development, as observed with gestational diabetes mellitus (GDM), is an established risk factor for metabolic diseases. Despite intense efforts to better understand this phenomenon of early memory little is known about the molecular mechanisms associating early exposure to long-term diseases risk. However, evidence promotes glucose associated oxidative stress as one of the molecular mechanisms able to influence susceptibility to metabolic diseases. Thus, we decided here to further explore the relationship between early glucose exposure and cellular stress in the context of early development, and focus on the concept of glycemic memory, its consequences, and sexual dimorphic and epigenetic aspects.

From the trenches: inpatient management of coronavirus disease 2019 in pregnancy.

The novel coronavirus disease 2019 caused by the severe acute respiratory syndrome coronavirus 2 has become a pandemic. It has quickly swept across the globe, leaving many clinicians to care for infected patients with limited information about the disease and best practices for care. Our goal is to share our experiences of caring for pregnant and postpartum women with novel coronavirus disease 2019 in New York, which is the coronavirus disease 2019 epicenter in the United States, and review current guidelines. We offer a guide, focusing on inpatient management, including testing policies, admission criteria, medical management, care for the decompensating patient, and practical tips for inpatient antepartum service management.

Physician Burnout among Members of the Society for Maternal-Fetal Medicine.

OBJECTIVE: This study aimed to determine the rate of physician burnout among maternal-fetal medicine subspecialists and identify associated factors. STUDY DESIGN: Noninternational members of the Society for Maternal-Fetal Medicine (SMFM) were surveyed regarding burnout using a validated tool specifically designed for health professionals (Maslach Burnout Inventory-Human Services Survey). Burnout was defined as exceeding established cutoffs for emotional exhaustion or depersonalization. Demographic information and potential contributors associated with the presence of burnout were also examined. RESULTS: The survey was sent to 1,220 members and 44.1% of members completed the entire survey. The physician burnout rate was 56.5%. Factors associated with burnout included female gender, being 5 to 20 years in practice, self-perceived burnout, being somewhat or very dissatisfied with career or supervisor and charting for more than 4 hours per day. Factors associated with less burnout were being male, having some protected time for education and regular exercise. Women scored higher on emotional exhaustion and depersonalization and lower personal accomplishment compared with men. CONCLUSION: Physician burnout among the SMFM members is higher than has been reported in other specialties. While some of these factors are modifiable, further study into why women have higher rates of burnout needs to be performed.

Prophylactic percutaneous left ventricular assist device in pregnancy.

Pregnancy-associated cardiomyopathy can present earlier in gestation than traditionally defined peripartum cardiomyopathy. Management and optimal delivery timing for these patients are not well defined. We present the case of a 30-year-old primigravid at 26 weeks who presented with new onset ventricular tachycardia, biventricular cardiac failure, and severe mitral regurgitation. She was medically stabilized for two weeks prior to delivery with modest improvement in her condition. Due to concern for life-threatening cardiac failure and pulmonary edema at the time of delivery, a percutaneous left ventricular assist device was inserted immediately prior to cesarean delivery. She remained on mechanical circulatory support for 36 h. We discuss considerations regarding use of a percutaneous left ventricular assist device as a novel therapy to support the hemodynamic changes following delivery in parturients with decompensated heart failure.

Correction: Genetic variants influence on the placenta regulatory landscape.

[This corrects the article DOI: 10.1371/journal.pgen.1007785.].

Ovarian Stimulation Increases the Risk of Fetal Cardiac Defects of Pups Exposed to Severe Maternal Hyperglycemia.

OBJECTIVES: To study the incidence of congenital heart defects (CHD) in offspring born to hyperglycemic mothers with and without ovarian stimulation. DESIGN: Reproductive biology. SETTING: Mouse model. PATIENTS: N/A. INTERVENTION: Hyperglycemia was induced in CD-1 wild type female mice using a single intraperitoneal dose of 150 mg/kg of streptozotocin. Stimulated dams (SD); (n=3) were injected with pregnant mare serum and human chorionic gonadotropin 48 hours apart. Non-stimulated dams (NSD); (n=4) were not injected. Both groups were mated with normal male CD-1 mice for timed pregnancies. Fetal hearts were extracted on embryonic day 16.5 and histological analyses was performed. Student's t-tests were employed to compare the incidence of cardiac defects in the SD and NSD groups. P ≤ 0.05 was significant. MAIN UUTCOME MEASURE: The incidence of CHD in progeny of diabetic dams with and without ovarian hyperstimulation. RESULTS & CONCLUSIONS: The average litter size was higher in SD compared to NSD. The average blood glucose for the SD and NSD was similar. Overall, the incidence of cardiac malformations did not differ between the two groups. However, in severe maternal hyperglycemia (>400 mg/dL), there was a higher incidence of fetal cardiac malformations in the pups born to SD vs NSD.

Genetic variants influence on the placenta regulatory landscape.

From genomic association studies, quantitative trait loci analysis, and epigenomic mapping, it is evident that significant efforts are necessary to define genetic-epigenetic interactions and understand their role in disease susceptibility and progression. For this reason, an analysis of the effects of genetic variation on gene expression and DNA methylation in human placentas at high resolution and whole-genome coverage will have multiple mechanistic and practical implications. By producing and analyzing DNA sequence variation (n = 303), DNA methylation (n = 303) and mRNA expression data (n = 80) from placentas from healthy women, we investigate the regulatory landscape of the human placenta and offer analytical approaches to integrate different types of genomic data and address some potential limitations of current platforms. We distinguish two profiles of interaction between expression and DNA methylation, revealing linear or bimodal effects, reflecting differences in genomic context, transcription factor recruitment, and possibly cell subpopulations. These findings help to clarify the interactions of genetic, epigenetic, and transcriptional regulatory mechanisms in normal human placentas. They also provide strong evidence for genotype-driven modifications of transcription and DNA methylation in normal placentas. In addition to these mechanistic implications, the data and analytical methods presented here will improve the interpretability of genome-wide and epigenome-wide association studies for human traits and diseases that involve placental functions.

Sexism in obstetrics and gynecology: not just a "women's issue".

Women in medicine have made strides towards equality and yet the gender gap continues to exist. Despite being the specialty dedicated to the promotion of women's health, obstetrics and gynecology is also marred by gender disparity. Obstetrician-gynecologists who are women continue to face barriers to advancement to leadership positions and earn $36,000 per year less than men in obstetrics and gynecology according to a recent study. Similarly, men in obstetrics and gynecology may be negatively affected by unconscious bias and socially prescribed roles for men and women, resulting in patient preferences for providers who are women. Both men and women have a vested interest in promoting greater gender parity in obstetrics and gynecology, and participation of men is critical for realization of this goal. For the obstetrician-gynecologist, sexism is not just a "women's issue".

Intrauterine Hyperglycemia Is Associated with an Impaired Postnatal Response to Oxidative Damage.

Hyperglycemia and other adverse exposures early in life that reprogram stem cells may lead to long-lasting phenotypic influences over the lifetime of an individual. Hyperglycemia and oxidative stress cause DNA damage when they exceed the protective capabilities of the cell, in turn affecting cellular function. DNA damage in response to hyperglycemia and oxidative stress was studied in human umbilical cord mesenchymal stem cells (hUC-MSCs) from large-for-gestational-age (LGA) infants of mothers with gestational diabetes mellitus (LGA-GDM) and control subjects. We tested the response of these cells to hyperglycemia and oxidative stress, measuring reactive oxygen species (ROS) levels and antioxidant enzyme activities. We find that hUC-MSCs from LGA-GDM infants have increased DNA damage when exposed to oxidative stress. With the addition of hyperglycemic conditions, these cells have an increase in ROS and a decrease in antioxidant glutathione peroxidase (GPx) activity, indicating a mechanism for the increased ROS and DNA damage. This study demonstrates that a memory of in utero hyperglycemia, mediated through downregulation of GPx activity, leads to an increased susceptibility to oxidative stress. The alteration of GPx function in self-renewing stem cells, can mediate the effect of intrauterine hyperglycemia to be propagated into adulthood and contribute to disease susceptibility.

Nonreassuring Status: Improving Obstetrician-Gynecologist Wellness.

Physician wellness directly affects patient and physician health and has broader implications for our health systems. A summary of what is known about physician wellness in medicine, and obstetrics and gynecology in particular, identifies several areas for future focus. To change our culture and the structure of our academic health centers in a way that promotes resilience, we suggest greater attention to preparedness for practice and attention to work-life integration as well as mentoring and professional development.

Benefits and costs of ecological restoration: Rapid assessment of changing ecosystem service values at a U.K. wetland.

Restoration of degraded land is recognized by the international community as an important way of enhancing both biodiversity and ecosystem services, but more information is needed about its costs and benefits. In Cambridgeshire, U.K., a long-term initiative to convert drained, intensively farmed arable land to a wetland habitat mosaic is driven by a desire both to prevent biodiversity loss from the nationally important Wicken Fen National Nature Reserve (Wicken Fen NNR) and to increase the provision of ecosystem services. We evaluated the changes in ecosystem service delivery resulting from this land conversion, using a new Toolkit for Ecosystem Service Site-based Assessment (TESSA) to estimate biophysical and monetary values of ecosystem services provided by the restored wetland mosaic compared with the former arable land. Overall results suggest that restoration is associated with a net gain to society as a whole of $199 ha(-1)y(-1), for a one-off investment in restoration of $2320 ha(-1). Restoration has led to an estimated loss of arable production of $2040 ha(-1)y(-1), but estimated gains of $671 ha(-1)y(-1) in nature-based recreation, $120 ha(-1)y(-1) from grazing, $48 ha(-1)y(-1) from flood protection, and a reduction in greenhouse gas (GHG) emissions worth an estimated $72 ha(-1)y(-1). Management costs have also declined by an estimated $1325 ha(-1)y(-1). Despite uncertainties associated with all measured values and the conservative assumptions used, we conclude that there was a substantial gain to society as a whole from this land-use conversion. The beneficiaries also changed from local arable farmers under arable production to graziers, countryside users from towns and villages, and the global community, under restoration. We emphasize that the values reported here are not necessarily transferable to other sites.

Ecophysiology of riparian cottonwoods: stream flow dependency, water relations and restoration.

Cottonwoods (Populus spp.) are adapted to riparian or floodplain zones throughout the Northern Hemisphere; they are also used as parents for fast-growing hybrid poplars. We review recent ecophysiological studies of the native cottonwoods Populus angustifolia James, P. balsamifera L., P. deltoides Marsh., P. fremontii S. Watson and P. trichocarpa T. & G. in North America, and P. nigra L. in Europe. Variation exists within and across species and hybrids; however, all riparian cottonwoods are dependent on shallow alluvial groundwater that is linked to stream water, particularly in semi-arid regions. This conclusion is based on studies of their natural occurrence, decline following river damming and dewatering (water removal), water relations, isotopic composition of xylem water, and by the establishment of cottonwoods along formerly barren natural channels after flow augmentation in response to the conveyance of irrigation water. When alluvial groundwater is depleted as a result of river dewatering or groundwater pumping, riparian cottonwoods exhibit drought-stress responses including stomatal closure and reduced transpiration and photosynthesis, altered 13C composition, reduced predawn and midday water potentials, and xylem cavitation. These physiological responses are accompanied by morphological responses including reduced shoot growth, altered root growth, branch sacrifice and crown die-back. In severe cases, mortality occurs. For example, severe dewatering of channels of the braided Big Lost River in Idaho led to mortality of the narrowleaf cottonwood, P. angustifolia, and adjacent sandbar willows, Salix exigua Nutt., within 5 years, whereas riparian woodlands thrived along flowing channels nearby. The conservation and restoration of cottonwoods will rely on the provision of river flow regimes that satisfy these ecophysiological requirements for survival, growth and reproduction.