Care plan for individuals at risk for preeclampsia: shared approach to education, strategies for prevention, surveillance, and follow-up.

Preeclampsia is a multisystemic disorder of pregnancy that affects 250,000 pregnant individuals in the United States and approximately 10 million worldwide per annum. Preeclampsia is associated with substantial immediate morbidity and mortality but also long-term morbidity for both mother and offspring. It is now clearly established that a low dose of aspirin given daily, beginning early in pregnancy modestly reduces the occurrence of preeclampsia. Low-dose aspirin seems safe, but because there is a paucity of information about long-term effects on the infant, it is not recommended for all pregnant individuals. Thus, several expert groups have identified clinical factors that indicate sufficient risk to recommend low-dose aspirin preventive therapy. These risk factors may be complemented by biochemical and/or biophysical tests that either indicate increased probability of preeclampsia in individuals with clinical risk factors, or more importantly, identify increased likelihood in those without other evident risk. In addition, the opportunity exists to provide this population with additional care that may prevent or mitigate the short- and long-term effects of preeclampsia. Patient and provider education, increased surveillance, behavioral modification, and other approaches to improve outcomes in these individuals can improve the chance of a healthy outcome. We assembled a group with diverse, relevant expertise (clinicians, investigators, advocates, and public and private stakeholders) to develop a care plan in which providers and pregnant individuals at risk can work together to reduce the risk of preeclampsia and associated morbidities. The plan is for care of individuals at moderate to high risk for developing preeclampsia, sufficient to receive low-dose aspirin therapy, as identified by clinical and/or laboratory findings. The recommendations are presented using the GRADE methodology with the quality of evidence upon which each is based. In addition, printable appendices with concise summaries of the care plan's recommendations for patients and healthcare providers are provided. We believe that this shared approach to care will facilitate prevention of preeclampsia and its attendant short- and long-term morbidity in patients identified as at risk for development of this disorder.

Assessment of Racial Disparities in Aspirin Prophylaxis for Preeclampsia Prevention.

OBJECTIVE: Low-dose aspirin is recommended for preeclampsia prevention among women with high-risk conditions, including chronic hypertension. Black women have higher rates of hypertensive disorders of pregnancy, and whether this is related to disparities in aspirin prophylaxis is unknown. We investigated the relationship between race and counseling/prescription and uptake of aspirin among a cohort of women with chronic hypertension. STUDY DESIGN: This is a single-institution, retrospective cohort study of women with chronic hypertension who delivered between 2016 and 2018. Medical record review was performed to assess counseling/prescription of aspirin prophylaxis and self-reported uptake. Self-reported uptake was determined by mention in the provider's notes or by inclusion in the medication reconciliation system. Demographic and obstetric outcome data were compared by self-reported race (Black vs. all other races) in univariate analysis. Multivariable logistic regression analysis was performed to evaluate the association between race and aspirin adherence. RESULTS: We included 872 women: 361 (41.4%) Black women and 511 (58.6%) white or other race women. Overall, 567 (65.0%) women were counseled and/or given a prescription for aspirin, and 411 (72.4%) of those women reported uptake. Black women were equally likely to be counseled and/or prescribed aspirin compared with all other races (67.3 vs. 63.4%; p = 0.7). However, Black women were less likely to report uptake of aspirin (63.8 vs. 79.0%; p < 0.001). After adjustment for total prenatal visits and tobacco use, Black race was associated with an adjusted odds ratio of 0.53 (95% confidence interval: 0.36-0.78) for uptake of aspirin. CONCLUSION: In our cohort, recommendation for aspirin prophylaxis was suboptimal in all groups, reaching only 65% of eligible women. Black women were equally likely as women of other races to receive counseling about aspirin, but rates of uptake were lower. Our findings suggest that counseling and prescription of aspirin alone in high-risk Black women are not sufficient for utilization of this intervention. KEY POINTS: · Rates of counseling about aspirin prophylaxis for preeclampsia did not vary by race.. · Black women had lower rates of uptake of aspirin compared with women of other races.. · Counseling about aspirin was inadequate in general, reaching only 65% of eligible women..

Improvements and limitations in developing multivariate models of hemorrhage and transfusion risk for the obstetric population.

BACKGROUND: Maternal hemorrhage protocols involve risk screening. These protocols prepare clinicians for potential hemorrhage and transfusion in individual patients. Patient-specific estimation and stratification of risk may improve maternal outcomes. STUDY DESIGN AND METHODS: Prediction models for hemorrhage and transfusion were trained and tested in a data set of 74 variables from 63 973 deliveries (97.6% of the source population of 65 560 deliveries included in a perinatal database from an academic urban delivery center) with sufficient data at pertinent time points: antepartum, peripartum, and postpartum. Hemorrhage and transfusion were present in 6% and 1.6% of deliveries, respectively. Model performance was evaluated with the receiver operating characteristic (ROC), precision-recall curves, and the Hosmer-Lemeshow calibration statistic. RESULTS: For hemorrhage risk prediction, logistic regression model discrimination showed ROCs of 0.633, 0.643, and 0.661 for the antepartum, peripartum, and postpartum models, respectively. These improve upon the California Maternal Quality Care Collaborative (CMQCC) accuracy of 0.613 for hemorrhage. Predictions of transfusion resulted in ROCs of 0.806, 0.822, and 0.854 for the antepartum, peripartum, and postpartum models, respectively. Previously described and new risk factors were identified. Models were not well calibrated with Hosmer-Lemeshow statistic P values between .001 and .6. CONCLUSIONS: Our models improve on existing risk assessment; however, further enhancement might require the inclusion of more granular, dynamic data. With the goal of increasing translatability, this work was distilled to an online open-source repository, including a form allowing risk factor inputs and outputs of CMQCC risk, alongside our numerical risk estimation and stratification of hemorrhage and transfusion.

Cytogenetic signatures of recurrent pregnancy losses.

OBJECTIVES: To investigate the incidence of chromosomal abnormalities in the products of conception (POC) of patients with spontaneous miscarriages (SM) and with recurrent pregnancy losses (RPL) and to determine biological mechanisms contributing to RPL. METHODS: During a 20-year period, 12 096 POC samples underwent classical chromosome analysis. Cytogenetic findings were compared between the SM and RPL cohorts. RESULTS: Analysis of RPL cohort has identified an increased incidence of inherited and de novo structural chromosome abnormalities, recurrent polyploid conceptions, and complex mosaic alterations. These abnormalities are the signature of genomic instability, posing a high risk of genetic abnormalities to offspring independent of maternal age. Predominance of male conceptions in the RPL cohort points toward an X-linked etiology and gender-specific intolerance for certain genetic abnormalities. CONCLUSIONS: Our study showed several possible genetic etiologies of RPL, including parental structural chromosome rearrangements, predisposition to meiotic nondisjunction, and genomic instability. Loss of karyotypically normal fetuses might be attributed to defects in genes essential for fetal development, as well as aberrations affecting the X chromosome. Molecular studies of parental and POC genomes will help to identify inherited defects in genes involved in meiotic divisions and DNA repair to confirm our hypotheses, and to discover novel fetal-essential genes.

Pancreatic Disorders of Pregnancy.

The pancreas is an organ with both exocrine and endocrine functions that has a vital role in both digestion as well as glucose metabolism. Although pancreatic dysfunction and disorders are rare in pregnancy, they are becoming increasingly more common. Recognition of these disorders and understanding how they can affect pregnancy is imperative to allow for proper management. We provide an overview of the most common pancreatic disorders that are seen in pregnancy.

How do I perform cell salvage in obstetrics?

Maternal mortality in the United States is increasing. The leading cause of death is hemorrhage. Maternal hemorrhage can be profound, with entire blood volumes being lost. In most major blood loss surgery, autotranfusion (also known as cell salvage, cell saving, and intraoperative blood collection and readministration) is a technique that has been used to minimize allogeneic transfusion. Historically, autotransfusion has been considered contraindicated in the face of maternal hemorrhage because of a fear of incorporating amniotic fluid in the salvaged blood. Recent data suggests that this fear is unfounded, with several medical societies now recommending that autotransfusion be used during maternal hemorrhage. In this review, autotransfusion during maternal hemorrhage is discussed, and suggestions are made for how to make it most successful.

Association of Umbilical Cord Milking vs Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants.

Importance: Umbilical cord milking as an alternative to delayed umbilical cord clamping may provide equivalent benefits to preterm infants, but without delaying resuscitation. Objective: To determine whether the rates of death or severe intraventricular hemorrhage differ among preterm infants receiving placental transfusion with umbilical cord milking vs delayed umbilical cord clamping. Design, Setting, and Participants: Noninferiority randomized clinical trial of preterm infants (born at 23-31 weeks' gestation) from 9 university and private medical centers in 4 countries were recruited and enrolled between June 2017 and September 2018. Planned enrollment was 750 per group. However, a safety signal comprising an imbalance in the number of severe intraventricular hemorrhage events by study group was observed at the first interim analysis; enrollment was stopped based on recommendations from the data and safety monitoring board. The planned noninferiority analysis could not be conducted and a post hoc comparison was performed instead. Final date of follow-up was December 2018. Interventions: Participants were randomized to umbilical cord milking (n = 236) or delayed umbilical cord clamping (n = 238). Main Outcomes and Measures: The primary outcome was a composite of death or severe intraventricular hemorrhage to determine noninferiority of umbilical cord milking with a 1% noninferiority margin. Results: Among 540 infants randomized, 474 (88%) were enrolled and completed the trial (mean gestational age of 28 weeks; 46% female). Twelve percent (29/236) of the umbilical cord milking group died or developed severe intraventricular hemorrhage compared with 8% (20/238) of the delayed umbilical cord clamping group (risk difference, 4% [95% CI, -2% to 9%]; P = .16). Although there was no statistically significant difference in death, severe intraventricular hemorrhage was statistically significantly higher in the umbilical cord milking group than in the delayed umbilical cord clamping group (8% [20/236] vs 3% [8/238], respectively; risk difference, 5% [95% CI, 1% to 9%]; P = .02). The test for interaction between gestational age strata and treatment group was significant for severe intraventricular hemorrhage only (P = .003); among infants born at 23 to 27 weeks' gestation, severe intraventricular hemorrhage was statistically significantly higher with umbilical cord milking than with delayed umbilical cord clamping (22% [20/93] vs 6% [5/89], respectively; risk difference, 16% [95% CI, 6% to 26%]; P = .002). Conclusions and Relevance: In this post hoc analysis of a prematurely terminated randomized clinical trial of umbilical cord milking vs delayed umbilical cord clamping among preterm infants born at less than 32 weeks' gestation, there was no statistically significant difference in the rate of a composite outcome of death or severe intraventricular hemorrhage, but there was a statistically significantly higher rate of severe intraventricular hemorrhage in the umbilical cord milking group. The early study termination and resulting post hoc nature of the analyses preclude definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT03019367.

An Overview for the General Psychiatrist Evaluating Patients With Obstetric and Neonatal Complications and Perinatal Loss.

When neonatal and obstetrical complications occur, the identification and management of mood and anxiety disorders become complex with an ever-expanding array of psychiatric needs that include the management of grief- and trauma-related disorders. With high rates of maternal morbidity and mortality in the United States and laws in many states restricting reproductive health access, psychiatrists must be proficient in managing psychiatric sequelae in this context. High-risk groups for peripartum mood and anxiety disorders, posttraumatic stress disorder, and complicated grief include those with neonatal intensive care unit (NICU) stays and those who have experienced infertility and recurrent pregnancy loss. Groups who have been historically marginalized by the medical system (e.g., Black, Indigenous, people of color) and those from LGBTQ+ communities are at similarly high risk, and more interventions are needed to support these groups. Strategies emphasizing trauma-informed care, psychotherapeutic approaches, and using patient-centered language are recommended.

Umbilical Cord Milking Versus Delayed Cord Clamping in Infants 28 to 32 Weeks: A Randomized Trial.

OBJECTIVES: To determine whether rate of severe intraventricular hemorrhage (IVH) or death among preterm infants receiving placental transfusion with UCM is noninferior to delayed cord clamping (DCC). METHODS: Noninferiority randomized controlled trial comparing UCM versus DCC in preterm infants born 28 to 32 weeks recruited between June 2017 through September 2022 from 19 university and private medical centers in 4 countries. The primary outcome was Grade III/IV IVH or death evaluated at a 1% noninferiority margin. RESULTS: Among 1019 infants (UCM n = 511 and DCC n = 508), all completed the trial from birth through initial hospitalization (mean gestational age 31 weeks, 44% female). For the primary outcome, 7 of 511 (1.4%) infants randomized to UCM developed severe IVH or died compared to 7 of 508 (1.4%) infants randomized to DCC (rate difference 0.01%, 95% confidence interval: (-1.4% to 1.4%), P = .99). CONCLUSIONS: In this randomized controlled trial of UCM versus DCC among preterm infants born between 28 and 32 weeks' gestation, there was no difference in the rates of severe IVH or death. UCM may be a safe alternative to DCC in premature infants born at 28 to 32 weeks who require resuscitation.

Multiorganizational consensus to define guiding principles for perioperative pain management in patients with chronic pain, preoperative opioid tolerance, or substance use disorder.

Significant knowledge gaps exist in the perioperative pain management of patients with a history of chronic pain, substance use disorder, and/or opioid tolerance as highlighted in the US Health and Human Services Pain Management Best Practices Inter-Agency Task Force 2019 report. The report emphasized the challenges of caring for these populations and the need for multidisciplinary care and a comprehensive approach. Such care requires stakeholder alignment across multiple specialties and care settings. With the intention of codifying this alignment into a reliable and efficient processes, a consortium of 15 professional healthcare societies was convened in a year-long modified Delphi consensus process and summit. This process produced seven guiding principles for the perioperative care of patients with chronic pain, substance use disorder, and/or preoperative opioid tolerance. These principles provide a framework and direction for future improvement in the optimization and care of 'complex' patients as they undergo surgical procedures.

NSS-Bridge Device for Post-Cesarean Delivery Analgesia: A Randomized Controlled Trial.

Introduction: Percutaneous auricular nerve stimulation has been used for the treatment of symptoms associated with opioid withdrawal, including abdominal pain, nausea, and general discomfort. However, its potential utility for pain management and opioid minimization after surgery has not been investigated. The purpose of this study was to test the feasibility and acceptability of a trial protocol designed to assess the effectiveness of the NSS2-Bridge device as a non-pharmacologic alternative to opioids after cesarean delivery. Methods: In a randomized control design, healthy women receiving cesarean delivery were randomized to receive the active device, placebo device, or no device. Devices were placed on the ear following cesarean delivery and left in place for 5 days. Feasibility and acceptability of the device was assessed by patient reports of device tolerability (rated on a 100mm visual analog scale where 0 is not tolerable at all and 100 is the most tolerable) as well as qualitative reporting. Additional outcomes assessed included proportion of patients not using opioids in hospital, as well as pain at rest, pain with movement, and total opioid consumption in the hospital and for the first 5 days after surgery. Results: There were 60 patients included in the final analysis. Device tolerability was rated highly, with an average daily score of >75 mm on the visual analog scale. The trial retention rate was 89.7% with most exclusions (42.9%) occurring due to unanticipated development of care complexity (e.g., hemorrhage and additional surgical procedures), with only 1 exclusion (14.3%) due to device discomfort. The active device group achieved the highest proportion of opioid-free hospitalizations (40%) compared to placebo (20%) and no device groups (30%). Pain at rest and with movement was similar between treatment groups. Conclusions: This trial protocol designed to test the efficacy of NSS2-Bridge device for post-cesarean pain management is feasible and acceptable. Larger proportions of patients not using opioids in the active device group justifies additional investigation on device effectiveness in pregnant and postpartum people at highest risk for pain.

The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity.

OBJECTIVE: To analyse preterm birth rates worldwide to assess the incidence of this public health problem, map the regional distribution of preterm births and gain insight into existing assessment strategies. METHODS: Data on preterm birth rates worldwide were extracted during a previous systematic review of published and unpublished data on maternal mortality and morbidity reported between 1997 and 2002. Those data were supplemented through a complementary search covering the period 2003-2007. Region-specific multiple regression models were used to estimate the preterm birth rates for countries with no data. FINDINGS: We estimated that in 2005, 12.9 million births, or 9.6% of all births worldwide, were preterm. Approximately 11 million (85%) of these preterm births were concentrated in Africa and Asia, while about 0.5 million occurred in each of Europe and North America (excluding Mexico) and 0.9 million in Latin America and the Caribbean. The highest rates of preterm birth were in Africa and North America (11.9% and 10.6% of all births, respectively), and the lowest were in Europe (6.2%). CONCLUSION: Preterm birth is an important perinatal health problem across the globe. Developing countries, especially those in Africa and southern Asia, incur the highest burden in terms of absolute numbers, although a high rate is also observed in North America. A better understanding of the causes of preterm birth and improved estimates of the incidence of preterm birth at the country level are needed to improve access to effective obstetric and neonatal care.

Interdisciplinary Approach for the Medical Management of Gestational Gigantomastia.

Background Gestational gigantomastia is a rare and debilitating condition that is thought to result from hormone hypersensitivity. Several definitions have been proposed using breast weight and change in body mass index, but the breast growth is best summarized as rapid, diffuse, and excessive. Case We report a case of a 31-year-old woman with a history of infertility and cystic fibrosis that developed pathologic breast growth during hormonal preparation for in vitro fertilization. Her serum laboratories were unremarkable, and she was medically managed until 31 weeks of gestation. After delivery, she experienced rapid decrease in breast size and was followed by plastic surgery with plan to allow spontaneous regression with interval breast reduction Conclusion We highlight a successful interdisciplinary medical management approach, which helped to avoid a morbid, intrapartum breast reduction.

Toll-like receptor 9, maternal cell-free DNA and myometrial cell response to CpG oligodeoxynucleotide stimulation.

PROBLEM: Among mechanisms triggering onset of parturition, it has been recently postulated that Toll-Like Receptor (TLR)9 engagement by cell-free DNA (cfDNA) triggers inflammation, myometrial contractions, and labor in absence of infection. The current study evaluated whether direct (myometrial) or indirect (decidual) TLR9 engagement enhances human myometrial contractility. METHOD OF STUDY: Toll-like receptor 9 expression and cellular localization were surveyed by immunohistochemistry of placenta, fetal membranes, and myometrium in term (gestational age [GA]: >37 weeks) labor (TL, n = 7) or term non-labor (TNL, n = 7) tissues. Non-pregnant myometrium (n = 4) served as reference. TLR9 mRNA expression relative to other TLRs was evaluated through the mining of an RNA-seq dataset and confirmed by RT-PCR. Immortalized human myometrial cells (hTERT-HM) were treated with incremental concentrations of TLR9 agonist ODN2395, TNF-α, or LPS. Secreted cytokines were quantified by multiplex immunoassay, and contractility was assessed by an in-gel cell contraction assay (n = 9). Induction of hTERT-HM contractility was also evaluated indirectly following exposure to conditioned media from primary term decidual cells (n = 4) previously stimulated with ODN2395. RESULTS: Toll-like receptor 9 immunostaining in placenta and amniochorion was strongest in decidual cells, but unrelated to labor. TLR9 staining intensity was significantly decreased in TL compared with TNL myometrium (P = 0.002). Although total cfDNA in maternal circulation increased in TL (P = 0.025 vs TNL), difference in cffDNA was non-significant. Myometrial TLR9 mRNA levels were unaffected by contractile status and far less abundant than other pro-inflammatory TLRs. hTERT-HM contractility was enhanced by LPS (P = 0.002) and TNF-α (P = 0.003), but not by ODN2395 (P = 0.345) or supernatant of TLR9-stimulated decidual cells. CONCLUSION: Myometrial and decidual TLR9 are unlikely to directly regulate human parturition.

A Proactive Approach to Neonates Born at 23 Weeks of Gestation.

OBJECTIVE: To evaluate in-hospital survival, survival without major morbidity, and neurodevelopmental impairment for neonates born at 23 weeks of gestation provided proactive, coordinated, and comprehensive perinatal and neonatal management. METHODS: This was a retrospective cohort study conducted at a single, tertiary care center between 2004 and 2013. Enrollment was limited to mother-neonate dyads at 23 weeks of gestation who were provided a proactive approach defined as documented evidence of antenatal corticosteroid administration, willingness to provide cesarean delivery for fetal distress, and neonatal resuscitation and intensive care. Among survivors, major morbidities (predischarge) and neurodevelopmental assessments at corrected ages of 18-22 months were examined. RESULTS: Among 152 live births identified, 101 neonates received proactive care, of whom 60 (59%) survived to hospital discharge. Preterm premature rupture of membranes (adjusted odds ratio [OR] 0.29, 95% confidence interval [CI] 0.09-0.94), fetal growth restriction (OR 0.16, 95% CI 0.03-0.89), delivery room cardiopulmonary resuscitation (OR 0.07, 95% CI 0.02-0.32), and prolonged intubation sequence (OR 0.15, 95% CI 0.05-0.45) were associated with lower neonatal survival. Among neonatal intensive care unit survivors, 62% had at least one major morbidity. Among 50 survivors with assessment at 18-22 months, six (12%) were unimpaired, 20 (40%) had mild impairment, and 24 (48%) had moderate or severe neurodevelopmental impairment. CONCLUSION: Proactive, interdisciplinary care enabled more than half of the neonates born at 23 weeks of gestation to survive, and approximately half of children evaluated at 18 months exhibited no or mild impairment. This information should be considered when providing prognostic advice to families with threatened preterm birth at 23 weeks of gestation. LEVEL OF EVIDENCE: II.

Augmentation vaginoplasty of colonic neovagina stricture using oral mucosa graft.

BACKGROUND: Vaginal reconstruction is performed for a variety of congenital and acquired anomalies, and several techniques have been described. Conventional neovaginal reconstructions typically involve skin grafts or vascularized intestinal segments. Oral mucosa has been used successfully in urethral reconstruction, and several long-term studies have demonstrated its surgical versatility and durability. CASE REPORT: Here we present the successful use of an oral mucosal graft in the surgical treatment of a strictured, colonic neovagina in a 19-year-old, 46XX female with cloacal exstrophy. CONCLUSION: Though the literature contains reports of oral mucosal grafts in primary gynecologic surgeries, this is the first report describing the use of buccal mucosa for a secondary, neovagina reconstruction. Based on the outcome of our case, we conclude that oral mucosa is a promising graft material suitable for vaginal reconstructions.