Proteomics of Serum Samples for the Exploration of the Pathological Mechanism of Obstetric Antiphospholipid Syndrome.

Obstetric antiphospholipid syndrome (OAPS) is a multisystem disorder characterized by thrombosis or recurrent fetal loss. In this study, we aim to explore the pathological mechanism of OAPS. Herein, we carried out data-independent acquisition (DIA) mass spectrometry quantitative proteomic analysis of serum samples from OAPS patients and healthy controls. A set of 93 differentially expressed proteins was identified, including 75 upregulated and 18 downregulated proteins compared with the levels in controls. Those proteins are enriched in KEGG pathways related to autoimmune diseases, allergic diseases, and pathogen infection. Interestingly, metabolic pathways such as fatty acid degradation and type I diabetes were enriched, indicating that OAPS is metabolic disease related. The significantly increased triglyceride also supported this idea. The differentially expressed proteins insulin-like growth factor-binding protein-1 (IGFBP-1), C-reactive protein (CRP), and ferritin light chain (FTL) were validated by ELISA. Our study presented a deep serum proteomics of OAPS and advanced our understanding of OAPS pathogenesis.

Technology advances in diabetes pregnancy: right technology, right person, right time.

This review outlines some of the extraordinary recent advances in diabetes technology, which are transforming the management of type 1 diabetes before, during and after pregnancy. It highlights recent improvements associated with use of continuous glucose monitoring (CGM) but acknowledges that neither CGM nor insulin pump therapy are adequate for achieving the pregnancy glucose targets. Furthermore, even hybrid closed-loop (HCL) systems that are clinically effective outside of pregnancy may not confer additional benefits throughout pregnancy. To date, there is only one HCL system, the CamAPS FX, with a strong evidence base for use during pregnancy, suggesting that the pregnancy benefits are HCL system specific. This is in stark contrast to HCL system use outside of pregnancy, where benefits are HCL category specific. The CamAPS FX HCL system has a rapidly adaptive algorithm and lower glucose targets with benefits across all maternal glucose categories, meaning that it is applicable for all women with type 1 diabetes, before and during pregnancy. For women of reproductive years living with type 2 diabetes, the relative merits of using non-insulin pharmacotherapies vs diabetes technology (dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors) are unknown. Despite the urgent unmet need and potential benefits, studies of pharmacotherapy and technology use are extremely limited in pregnant women with type 2 diabetes.

Obstetric and Neonatal Invasive Meningococcal Disease Caused by Neisseria meningitidis Serogroup W, Western Australia, Australia.

Three mother-baby pairs with invasive meningococcal disease occurred over 7 months in Western Australia, Australia, at a time when serogroup W sequence type 11 clonal complex was the predominant local strain. One mother and 2 neonates died, highlighting the role of this strain as a cause of obstetric and early neonatal death.

Trophectoderm grade is associated with the risk of placenta previa in frozen-thawed single-blastocyst transfer cycles.

STUDY QUESTION: Do obstetric and perinatal complications vary according to different blastocyst developmental parameters after frozen-thawed single-blastocyst transfer (SBT) cycles? SUMMARY ANSWER: Pregnancies following the transfer of a blastocyst with a grade C trophectoderm (TE) were associated with an increased risk of placenta previa compared to those with a blastocyst of grade A TE. WHAT IS KNOWN ALREADY: Existing studies investigating the effect of blastocyst morphology grades on birth outcomes have mostly focused on fetal growth and have produced conflicting results, while the risk of obstetric complications has rarely been reported. Additionally, growing evidence has suggested that the appearance of TE cells could serve as the most important parameter for predicting implantation and live birth. Given that the TE ultimately develops into the placenta, it is plausible that this independent predictor may also impact placentation. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study at a tertiary-care academic medical center included 6018 singleton deliveries after frozen-thawed SBT cycles between January 2017 and December 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Singleton pregnancies were grouped into two groups according to blastocyst developmental stage (Days 5 and 6), four groups according to embryo expansion (Stages 3, 4, 5, and 6), three groups according to inner cell mass (ICM) quality (A, B, and C), and three groups according to TE quality (A, B, and C). The main outcomes included pregnancy-induced hypertension, preeclampsia, gestational diabetes mellitus, preterm premature rupture of membrane, placenta previa, placental abruption, placenta accreta, postpartum hemorrhage, preterm birth, low birth weight, small for gestational age, and birth defects. Multivariate logistic regressions were performed to evaluate the effect of blastocyst developmental stage, embryo expansion stage, ICM grade, and TE grade on measured outcomes adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: No association was found between blastocyst developmental stage and obstetric or perinatal outcomes both before and after adjusting for potential confounders, and similar results were found with regard to embryo expansion stage and ICM grade. Meanwhile, the incidence of placenta previa derived from a blastocyst with TE of grade C was higher compared with those derived from a blastocyst with TE of grade A (1.7%, 2.4%, and 4.0% for A, B, and C, respectively, P = 0.001 for all comparisons). After adjusting for potential covariates, TE grade C blastocysts had 2.81 times the likelihood of resulting in placenta previa compared to TE grade A blastocysts (adjusted odds ratio 2.81, 95% CI 1.11-7.09). No statistically significant differences were detected between any other measured outcomes and TE grades both before or after adjustment. LIMITATIONS, REASONS FOR CAUTION: The study is limited by its retrospective, single-center design. Additionally, although the sample size was relatively large for the study group, the sample size for certain subgroups was relatively small and lacked adequate power, particularly the ICM grade C group. Therefore, these results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: The study extends our knowledge of the potential downstream effect of TE grade on placental abnormalities. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (2023YFC2705500, 2023YFC2705501, 2023YFC2705505, 2019YFA0802604); National Natural Science Foundation of China (82130046, 82320108009, 82371660, 32300710); Shanghai leading talent program, Innovative research team of high-level local universities in Shanghai (SHSMU-ZLCX20210201, SHSMU-ZLCX20210200, SHSMU-ZLCX20180401), Shanghai Jiaotong University School of Medicine Affiliated Renji Hospital Clinical Research Innovation Cultivation Fund Program (RJPY-DZX-003), Science and Technology Commission of Shanghai Municipality (23Y11901400), Shanghai's Top Priority Research Center Construction Project (2023ZZ02002), and Three-Year Action Plan for Strengthening the Construction of the Public Health System in Shanghai (GWVI-11.1-36). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Bipedalism and the dawn of uterine fibroids.

The high prevalence and burden of uterine fibroids in women raises questions about the origin of these benign growths. Here, we propose that fibroids should be understood in the context of human evolution, specifically the advent of bipedal locomotion in the hominin lineage. Over the ≥7 million years since our arboreal ancestors left their trees, skeletal adaptations ensued, affecting the pelvis, limbs, hands, and feet. By 3.2 million years ago, our ancestors were fully bipedal. A key evolutionary advantage of bipedalism was the freedom to use hands to carry and prepare food and create and use tools which, in turn, led to further evolutionary changes such as brain enlargement (encephalization), including a dramatic increase in the size of the neocortex. Pelvic realignment resulted in narrowing and transformation of the birth canal from a simple cylinder to a convoluted structure with misaligned pelvic inlet, mid-pelvis, and pelvic outlet planes. Neonatal head circumference has increased, greatly complicating parturition in early and modern humans, up to and including our own species. To overcome the so-called obstetric dilemma provoked by bipedal locomotion and encephalization, various compensatory adaptations have occurred affecting human neonatal development. These include adaptations limiting neonatal size, namely altricial birth (delivery of infants at an early neurodevelopmental stage, relative to other primates) and mid-gestation skeletal growth deceleration. Another key adaptation was hyperplasia of the myometrium, specifically the neomyometrium (the outer two-thirds of the myometrium, corresponding to 90% of the uterine musculature), allowing the uterus to more forcefully push the baby through the pelvis during a lengthy parturition. We propose that this hyperplasia of smooth muscle tissue set the stage for highly prevalent uterine fibroids. These fibroids are therefore a consequence of the obstetric dilemma and, ultimately, of the evolution of bipedalism in our hominin ancestors.

Obstetric and neonatal outcomes following taxane use during pregnancy: a systematic review.

BACKGROUND: The use of taxanes following the first trimester of pregnancy is endorsed by current clinical guidelines. However, evidence regarding their safety in terms of obstetric and neonatal outcomes is limited. METHODS: A comprehensive literature search was performed using the MEDLINE, CENTRAL and Web of Sciences databases from their inception up to 12/16/2022. Eligibility criteria included gestational taxane use, presentation of original findings, and individual case data presented. A descriptive statistical analysis was undertaken. RESULTS: A total of 159 patients treated with taxane-containing regimens during pregnancy were identified, resulting in 162 fetuses exposed in utero. The majority of patients had breast cancer (n = 88; 55.3%) or cervical cancer (n = 45; 28.3%). The most commonly employed taxane was paclitaxel (n = 131; 82.4%). A total of 111 (69.8%) patients were also treated with other cytotoxic drugs during pregnancy, including platinum salts (n = 70; 63.0%) and doxorubicin/cyclophosphamide (n = 20; 18.0%). While most patients received taxanes during the second trimester of pregnancy (n = 79; 70.0%), two were exposed to taxanes in the first trimester. Obstetric outcomes were reported in 105 (66.0%) cases, with the most frequent adverse events being preterm contractions or premature rupture of membranes (n = 12; 11.4%), pre-eclampsia/HELLP syndrome (n = 6; 5.7%), and oligohydramnios/anhydramnios (n = 6; 5.7%). All cases with pregnancy outcome available resulted in live births (n = 132). Overall, 72 (54.5%) neonates were delivered preterm, 40 (30.3%) were classified as small for gestational age (SGA), and 2 (1.5%) had an Apgar score of < 7 at 5 min. Perinatal complications included acute respiratory distress syndrome (n = 14; 10.6%), hyperbilirubinemia (n = 5; 3.8%), and hypoglycemia (n = 2; 1.5%). In addition, 7 (5.3%) cases of congenital malformations were reported. At a median follow-up of 16 months, offspring health status was available for 86 (65.2%), of which 13 (15.1%) had a documented complication, including delayed speech development, recurrent otitis media, and acute myeloid leukemia. CONCLUSIONS: Taxanes appear to be safe following the first trimester of pregnancy, with obstetric and fetal outcomes being similar to those observed in the general obstetric population. Future studies should aim to determine the most effective taxane regimen and dosage for use during gestation, with a specific focus on treatment safety.

Difficulties during delivery, brain ventricle enlargement and cognitive impairment in first episode psychosis.

BACKGROUND: Patients with a first episode of psychosis (FEP) display clinical, cognitive, and structural brain abnormalities at illness onset. Ventricular enlargement has been identified in schizophrenia since the initial development of neuroimaging techniques. Obstetric abnormalities have been associated with an increased risk of developing psychosis but also with cognitive impairment and brain structure abnormalities. Difficulties during delivery are associated with a higher risk of birth asphyxia leading to brain structural abnormalities, such as ventriculomegaly, which has been related to cognitive disturbances. METHODS: We examined differences in ventricular size between 142 FEP patients and 123 healthy control participants using magnetic resonance imaging. Obstetric complications were evaluated using the Lewis-Murray scale. We examined the impact of obstetric difficulties during delivery on ventricle size as well as the possible relationship between ventricle size and cognitive impairment in both groups. RESULTS: FEP patients displayed significantly larger third ventricle size compared with healthy controls. Third ventricle enlargement was associated with diagnosis (higher volume in patients), with difficulties during delivery (higher volume in subjects with difficulties), and was highest in patients with difficulties during delivery. Verbal memory was significantly associated with third ventricle to brain ratio. CONCLUSIONS: Our results suggest that difficulties during delivery might be significant contributors to the ventricular enlargement historically described in schizophrenia. Thus, obstetric complications may contribute to the development of psychosis through changes in brain architecture.

Maternal outcomes following postpartum autotransfusion of blood lost during vaginal obstetric hemorrhage.

BACKGROUND: Autotransfusion following vaginal delivery has not been as widely adopted and existing data on this topic are limited to small case series. METHODS: This is a single-center retrospective matched cohort study. Deliveries exposed to autotransfusion during obstetric hemorrhage were matched to unexposed controls with obstetric hemorrhage who did not receive autotransfusion. The primary outcome was allogeneic transfusion of packed red blood cells. Planned secondary analyses included change in hemoglobin following delivery, composite maternal safety outcomes, and unplanned postpartum health care utilization. RESULTS: Thirty-six deliveries exposed to autotransfusion were matched to 144 unexposed controls. There was no significant difference in allogenic transfusion of packed red blood cells in the patients exposed to autotransfusion red with unexposed controls (adjusted OR 1.1; 95% CI 0.5-2.4). Deliveries that received autotransfusion had a less severe pre- to post-delivery decline in hemoglobin compared with unexposed controls across all values of QBL (p = .003). There were no significant differences in maternal morbidity outcomes evaluated in exposed versus unexposed deliveries. CONCLUSION: Autotransfusion in cases of vaginal obstetric hemorrhage did not attenuate rates of allogenic packed red blood cell transfusion but did result in a less severe pre- to postdelivery decline in hemoglobin at discharge. Autotransfusion cases did not have any markers of increased maternal morbidity when compared with a control group. These findings support emerging evidence indicating that autotransfusion of blood lost during vaginal obstetric hemorrhage is a safe and potentially effective tool for use in the management of obstetric hemorrhage.

The influence of hematological profiles on the transfusion management and mortality risk of mothers presenting to the obstetric unit of a South African tertiary medical facility.

BACKGROUND: Laboratory results are frequently abnormal in pregnant mothers. Abnormalities usually relate to pregnancy or associated complications. Hematological abnormalities and age in pregnancy may increase the likelihood for transfusion and mortality. STUDY DESIGN AND METHODS: Hematological profiles and transfusion history of pregnant mothers presenting to a tertiary hospital, were evaluated over 2 years. Age, anemia, leukocytosis and thrombocytopenia were assessed for transfusion likelihood. Iron deficiency and coagulation were assessed in transfused patients. Anemia, leukocytosis, thrombocytopenia, human immunodeficiency virus (HIV) and transfusion were assessed for mortality likelihood. RESULTS: There were 12,889 pregnant mothers included. Mothers <19-years-old had the highest prevalence of anemia (31.5%) and proportion of transfusions (19%). The transfusion likelihood was increased in mothers with anemia (odds ratios [OR] = 6.41; confidence intervals at 95% [95% CI] 5.46-7.71), leukocytosis (OR = 2.35; 95% CI 2.00-2.76) or thrombocytopenia (OR = 2.71; 95% CI 2.21-3.33). Mothers with prolonged prothrombin times received twice as many blood products as their normal counterparts (p = .03) and those with iron deficiency anemia five times more blood products (p < .001). Increased likelihood for mortality was seen in patients with anemia (OR = 4.15, 95% CI 2.03-8.49), leukocytosis (OR = 2.68; 95% CI 1.19-6.04) and those receiving blood transfusion (OR = 3.6, 95% CI 1.75-7.47). DISCUSSION: Adolescence, anemia, leukocytosis and thrombocytopenia expose mothers to a high risk for transfusion and/or mortality. These risk factors should promptly trigger management and referral of patients. Presenting hematological profiles are strong predictors of maternal outcome and transfusion risk.

Epidemiological, anatomoclinical, and therapeutic profile of obstetric fistula in the Democratic Republic of the Congo: About 1267 patients.

OBJECTIVE: Our aim is to describe the epidemiological, anatomoclinical and therapeutic profile of obstetric fistula (OF) in the Democratic Republic of the Congo (DRC). METHODOLOGY: This was a descriptive retrospective study that collected 1416 obstetric fistulas in 1267 patients in seven provinces of the DRC, treated between January 2017 and December 2022. The variables studied were epidemiological, anatomoclinical and therapeutic. RESULTS: The mean age of patients at the time of surgical repair was 33.2 years (range: 15 and 77 years) and 32.8% of patients were aged between 20 and 29 years. The mean age of the fistula at repair was 10 years (range: 3.5 months and 56 years). At the time of fistula, 61.7% of patients had delivered vaginally and 28.7% by caesarean section and 8.2% of patients had a haemostasis hysterectomy. Labour lasted at least 3 days in 47.3% of these patients for the fistula birth. Deliveries took place either at home (27.4%) or in a health facility (72.6%); 83.6% of newborns resulting from these births had died. Taken as a whole, urogenital fistulas are more common than genito-digestive fistulas. Urethro-vaginal (26.2%) and vesico-uterine (24.7%) anatomoclinical entities were predominant among urogenital fistulas. A total of 1416 fistulas were surgically repaired in 1267 patients. These repairs were successful for 1226 (86.6%) fistulas. The main surgical route used was transvaginal (68.8%). CONCLUSION: In the DRC, obstetric fistula is common in young adult women. It often results from vaginal delivery, after prolonged labour. Fistula births often result in the death of newborns. Uro-genital obstetric fistulas are the most frequent with predominance of urethro-vaginal and vesico-uterine anatomoclinical entities. Fistulas remain untreated for a long time. Mostly done transvaginally, surgical repair gives a good result.

Mendelian randomization analysis reveals causal relationship between obstetric-related diseases and COVID-19.

BACKGROUND: Several observational studies demonstrated that pregnant individuals with COVID-19 had a higher risk of preeclampsia and preterm birth. We aimed to determine whether women with COVID-19 diagnosis had adverse pregnancy outcomes. METHODS: A two-sample Mendelian randomization (MR) analysis in this study was used to evaluate the casual relationships between COVID-19 infection and obstetric-related diseases based on genome-wide association studies (GWAS) dataset. Inverse-variance weighted (IVW), MR-Egger and MR-PRESSO were used to infer the connection and estimate the pleiotropy respectively. RESULTS: The significant connection was observed between COVID-19 and placental disorders with betaIVW of 1.57 and odds ratio (OR) of 4.81 (95% confidence interval [CI]: 1.05-22.05, p = 0.04). However, there were no associations between COVID-19 infection and gestational diabetes mellitus (GDM) (OR = 1.12; 95% CI: 0.85-1.45, p = 0.41), other disorders of amniotic fluid and membranes (OR = 0.90; 95% CI: 0.61-1.32, p = 0.59), Intrahepatic Cholestasis of Pregnancy (ICP) (OR = 1.42; 95% CI: 0.85-2.36, p = 0.18), birth weight (OR = 1.02; 95% CI: 0.99-1.05, p = 0.19), gestational hypertension (OR = 1.00; 95% CI: 1.00-1.00, p = 0.85), spontaneous miscarriages (OR = 1.00; 95% CI: 0.96-1.04, p = 0.90) and stillbirth (OR = 1.00; 95% CI: 0.98-1.01, p = 0.62). CONCLUSION: There was no direct causal relationship between COVID-19 infection and maternal and neonatal poor outcomes. Our study could alleviate the anxiety of pregnant women under the COVID-19 pandemic conditions partly.

Endometrial preparation protocols prior to frozen embryo transfer - convenience or safety?

The number of frozen embryo transfer (FET) cycles is increasing rapidly worldwide. Different endometrial preparations for FET result in comparable live birth rates. However, several recent publications have reported higher maternal risks for hypertensive disorders of pregnancy (HDP), pre-eclampsia and postpartum haemorrhage (PPH) in programmed cycles (PC-FET) compared with natural cycles and modified natural cycles with an intact corpus luteum. Nevertheless, PC-FET is frequently used in ovulatory women despite the increased risks for HDP, pre-eclampsia and PPH. Although randomized controlled studies have been suggested, PC-FET raises several methodological problems. Large study populations would be required to investigate the outcomes in question, and the inclusion of ovulatory women, where the intervention may increase the risk of a negative outcome, is ethically troublesome. In the authors' opinion, the existing evidence from large observational studies and systematic reviews is sufficiently strong to recommend an endometrial preparation strategy that aims to maintain or stimulate the corpus luteum to minimize the risk of HDP and pre-eclampsia after FET cycles.

Navigating portal hypertension: Unlocking safe passage to healthy pregnancy in EHPVO.

BACKGROUND AND AIMS: Pregnancy is associated with hyperdynamic circulatory state and increased risk of portal hypertension related complications in patients with extra-hepatic portal vein obstruction (EHPVO). We aim to study the impact of EHPVO on pregnancy-related outcomes with focus on subset of patients with UGIB (upper GI bleed). METHODS: Retrospective analysis of obstetric, maternal and neonatal outcomes of patients with EHPVO registered between January 2006 and December 2022. Forty-five patients were included. Forty-five healthy females with low-risk pregnancies formed the control group. RESULTS: Adverse obstetric and neonatal outcomes were comparable between EHPVO and control group (22% vs. 28.6%; p > .05; low birth weight/ small for gestational age 17.8% vs. 36%, p = .0918 and 14.2% vs. 10%, p = .5698 respectively). Adverse outcomes were similar in patients with and without history of UGIB (26.3% vs. 19.4%, p = .0814; 17.8% vs. 36%, p = .0918; 14.2% vs. 10%, p = .5698). There was no maternal mortality in both the groups. A total of 7% pregnancies in EHPVO patients were complicated by ascites. CONCLUSIONS: EHPVO pregnancies have successful obstetric and neonatal outcomes with adequate management of portal hypertension.

Progestin-primed ovarian stimulation: for whom, when and how?

Progestin-primed ovarian stimulation (PPOS) is being increasingly used for ovarian stimulation in assisted reproductive technology. Different progestins have been used with similar success. The available studies suggest a similar response to ovarian stimulation with gonadotrophin-releasing hormone (GnRH) analogues. Any differences in the duration of stimulation or gonadotrophin consumption are minor and clinically insignificant. PPOS has the advantage of oral administration and lower medication costs than GnRH analogues. As such it is clearly more cost-effective for fertility preservation and planned freeze-all cycles, but when fresh embryo transfer is intended PPOS can be less cost-effective depending on the local direct and indirect costs of the additional initial frozen embryo transfer cycle. Oocytes collected in PPOS cycles have similar developmental potential, including blastocyst euploidy rates. Frozen embryo transfer outcomes of PPOS and GnRH analogue cycles seem to be similar in terms of both ongoing pregnancy/live birth rates and obstetric and perinatal outcomes. While some studies have reported lower cumulative live birth rates with PPOS, they have methodological issues, including arbitrary definitions of the cumulative live birth rate. PPOS has been used in all patient types (except progesterone receptor-positive breast cancer patients) with consistent results and seems a patient friendly and cost-effective choice if a fresh embryo transfer is not intended.

Aspirin pharmacokinetics and pharmacodynamics through gestation.

BACKGROUND: Low dose aspirin is recommended for prevention of preeclampsia, however there is not consensus on the appropriate dose. Pregnancy specific changes have the potential to impact the pharmacology of aspirin in pregnancy, however there are very limited studies on aspirin pharmacokinetics in pregnancy and none linking pharmacokinetics (PK, drug dose and drug level) to pharmacodynamics (PD, drug dose and physiologic response) in pregnancy. As a result, we do not have a good understanding of the pharmacologic response to aspirin in pregnancy, which has important implications for clinical efficacy. We sought to describe the PK and PD of aspirin through pregnancy and to identify individual covariates that impacted aspirin PK/PD. OBJECTIVE: We sought to describe the PK and PD of aspirin through pregnancy (first and third trimester), to identify covariates that significantly impact aspirin PK and to identify the relationship between aspirin PK and PD. STUDY DESIGN: This is a prospective study of patients at high risk for preeclampsia recommended to take 81 mg aspirin daily. This study involved 3 visits as follows: (1) baseline, first trimester (10-16 weeks of gestation) 6-hour PK visit, done before initiation of aspirin; (2) follow-up 1: 2 to 4 weeks after aspirin initiation; and (3) follow-up 2: third trimester 6-hour PK visit (28-32 weeks of gestation). The following were assessed at each visit: weight or body mass index, platelet function analysis-100 (Siemens), urinary thromboxane B2, serum thromboxane B2, and plasma salicylic acid. The PK visits consisted of blood work done at baseline (predose), administration of 81 mg nonenteric coated aspirin, and then plasma blood level of salicylic acid assessed at 30 minutes and then hourly 1 to 6 hours after dose. Pearson correlation and multivariable regression were used to identify associations between parameters and identify relevant covariates. Log-adjusted values were used for regression analysis. P<.05 was considered statistically significant. RESULTS: Nineteen participants were included with first trimester data, and 16 with third trimester data. There was no statistically significant change in mean PK parameters between the first and third trimester, although there was a trend to lower peak concentration in the third than in the first trimester (P=.08). In multivariable regression, baseline obesity and current body mass index as a continuous measures were negatively associated with log-adjusted peak salicylic acid concentration (-0.28 [-0.46 to -0.11], P=.003 and -0.02 [-0.03 to -0.009], P=.001, respectively) and log-adjusted plasma salicylic acid area under the curve 0 to 6 hours postdose (-0.25 [-0.45 to 0.05], P=.02, -0.04 [-0.07 to -0.01], P=.008 respectively). There was a significant decrease in urinary thromboxane 2 to 4 weeks after aspirin initiation compared with baseline, which correlated with a concomitant increase in platelet function analysis-100 closure time. In multivariable regression model, there was a strong association between plasma salicylic acid concentration (area under the curve 0-6 hours postdose) and urinary thromboxane (B=-3.12 [-5.38 to -1.04], P=.006), and with urinary thromboxane suppression and platelet inhibition, platelet function analysis-100 (-0.23 [-0.31 to -0.14], P<.001). With progressive thromboxane suppression, platelet inhibition (platelet function analysis-100 closure time) increased. Individual comorbidities, including weight, hypertension, and pregestational diabetes (Type I or II), also impacted aspirin response. CONCLUSION: We have demonstrated the relationship between individual factors, plasma concentrations of salicylic acid, thromboxane suppression, and platelet inhibition at a single dose (81 mg) of aspirin taken through pregnancy. Our findings suggest that dose modification of aspirin in pregnancy may help to achieve the optimal response. Our results may be used to facilitate computational modeling to identify optimal dosing, taking into consideration individual factors.

Obstetric violence is a misnomer.

The term "obstetric violence" has been used in the legislative language of several countries to protect mothers from abuse during pregnancy. Subsequently, it has been expanded to include a spectrum of obstetric procedures, such as induction of labor, episiotomy, and cesarean delivery, and has surfaced in the peer-reviewed literature. The term "obstetric violence" can be seen as quite strong and emotionally charged, which may lead to misunderstandings or misconceptions. It might be interpreted as implying a deliberate act of violence by healthcare providers when mistreatment can sometimes result from systemic issues, lack of training, or misunderstandings rather than intentional violence. "Obstetric mistreatment" is a more comprehensive term that can encompass a broader range of behaviors and actions. "Violence" generally refers to the intentional use of physical force to cause harm, injury, or damage to another person (eg, physical assault, domestic violence, street fights, or acts of terrorism), whereas "mistreatment" is a more general term and refers to the abuse, harm, or control exerted over another person (such as nonconsensual medical procedures, verbal abuse, disrespect, discrimination and stigmatization, or neglect, to name a few examples). There may be cases where unprofessional personnel may commit mistreatment and violence against pregnant patients, but as obstetrics is dedicated to the health and well-being of pregnant and fetal patients, mistreatment of obstetric patients should never be an intended component of professional obstetric care. It is necessary to move beyond the term "obstetric violence" in discourse and acknowledge and address the structural dimensions of abusive reproductive practices. Similarly, we do not use the term "psychiatric violence" for appropriately used professional procedures in psychiatry, such as electroshock therapy, or use the term "neurosurgical violence" when drilling a burr hole. There is an ongoing need to raise awareness about the potential mistreatment of obstetric patients within the context of abuse against women in general. Using the term "mistreatment in healthcare" instead of the more limited term "obstetric violence" is more appropriate and applies to all specialties when there is unprofessional abuse and mistreatment, such as biased care, neglect, emotional abuse (verbal), or physical abuse, including performing procedures that are unnecessary, unindicated, or without informed patient consent. Healthcare providers must promote unbiased, respectful, and patient-centered professional care; provide an ethical framework for all healthcare personnel; and work toward systemic change to prevent any mistreatment or abuse in our specialty.

Association between stillbirth and severe maternal morbidity.

BACKGROUND: Severe maternal morbidity has been increasing in the past few decades. Few studies have examined the risk of severe maternal morbidity among individuals with stillbirths vs individuals with live-birth deliveries. OBJECTIVE: This study aimed to examine the prevalence and risk of severe maternal morbidity among individuals with stillbirths vs individuals with live-birth deliveries during delivery hospitalization as a primary outcome and during the postpartum period as a secondary outcome. STUDY DESIGN: This was a retrospective cohort study using birth and fetal death certificate data linked to hospital discharge records from California (2008-2018), Michigan (2008-2020), Missouri (2008-2014), Pennsylvania (2008-2014), and South Carolina (2008-2020). Relative risk regression analysis was used to examine the crude and adjusted relative risks of severe maternal morbidity along with 95% confidence intervals among individuals with stillbirths vs individuals with live-birth deliveries, adjusting for birth year, state of residence, maternal sociodemographic characteristics, and the obstetric comorbidity index. RESULTS: Of the 8,694,912 deliveries, 35,012 (0.40%) were stillbirths. Compared with individuals with live-birth deliveries, those with stillbirths were more likely to be non-Hispanic Black (10.8% vs 20.5%); have Medicaid (46.5% vs 52.0%); have pregnancy complications, including preexisting diabetes mellitus (1.1% vs 4.3%), preexisting hypertension (2.3% vs 6.2%), and preeclampsia (4.4% vs 8.4%); have multiple pregnancies (1.6% vs 6.2%); and reside in South Carolina (7.4% vs 11.6%). During delivery hospitalization, the prevalence rates of severe maternal morbidity were 791 cases per 10,000 deliveries for stillbirths and 154 cases per 10,000 deliveries for live-birth deliveries, whereas the prevalence rates for nontransfusion severe maternal morbidity were 502 cases per 10,000 deliveries for stillbirths and 68 cases per 10,000 deliveries for live-birth deliveries. The crude relative risk for severe maternal morbidity was 5.1 (95% confidence interval, 4.9-5.3), whereas the adjusted relative risk was 1.6 (95% confidence interval, 1.5-1.8). For nontransfusion severe maternal morbidity among stillbirths vs live-birth deliveries, the crude relative risk was 7.4 (95% confidence interval, 7.0-7.7), whereas the adjusted relative risk was 2.0 (95% confidence interval, 1.8-2.3). This risk was not only elevated among individuals with stillbirth during the delivery hospitalization but also through 1 year after delivery (severe maternal morbidity adjusted relative risk, 1.3; 95% confidence interval, 1.1-1.4; nontransfusion severe maternal morbidity adjusted relative risk, 1.2; 95% confidence interval, 1.1-1.3). CONCLUSION: Stillbirth was found to be an important contributor to severe maternal morbidity.

Effectiveness of care bundles for prevention and treatment of postpartum hemorrhage: a systematic review.

OBJECTIVE: Care bundles are a promising approach to reducing postpartum hemorrhage-related morbidity and mortality. We assessed the effectiveness and safety of care bundles for postpartum hemorrhage prevention and/or treatment. DATA SOURCES: We searched MEDLINE, Embase, Cochrane CENTRAL, Maternity and Infant Care Database, and Global Index Medicus (inception to June 9, 2023) and ClinicalTrials.gov and the International Clinical Trials Registry Platform (last 5 years) using a phased search strategy, combining terms for postpartum hemorrhage and care bundles. STUDY ELIGIBILITY CRITERIA: Peer-reviewed studies evaluating postpartum hemorrhage-related care bundles were included. Care bundles were defined as interventions comprising ≥3 components implemented collectively, concurrently, or in rapid succession. Randomized and nonrandomized controlled trials, interrupted time series, and before-after studies (controlled or uncontrolled) were eligible. METHODS: Risk of bias was assessed using RoB 2 (randomized trials) and ROBINS-I (nonrandomized studies). For controlled studies, we reported risk ratios for dichotomous outcomes and mean differences for continuous outcomes, with certainty of evidence determined using GRADE. For uncontrolled studies, we used effect direction tables and summarized results narratively. RESULTS: Twenty-two studies were included for analysis. For prevention-only bundles (2 studies), low-certainty evidence suggests possible benefits in reducing blood loss, duration of hospitalization, and intensive care unit stay, and maternal well-being. For treatment-only bundles (9 studies), high-certainty evidence shows that the E-MOTIVE intervention reduced risks of composite severe morbidity (risk ratio, 0.40; 95% confidence interval, 0.32-0.50) and blood transfusion for bleeding, postpartum hemorrhage, severe postpartum hemorrhage, and mean blood loss. One nonrandomized trial and 7 uncontrolled studies suggest that other postpartum hemorrhage treatment bundles might reduce blood loss and severe postpartum hemorrhage, but this is uncertain. For combined prevention/treatment bundles (11 studies), low-certainty evidence shows that the California Maternal Quality Care Collaborative care bundle may reduce severe maternal morbidity (risk ratio, 0.64; 95% confidence interval, 0.57-0.72). Ten uncontrolled studies variably showed possible benefits, no effects, or harms for other bundle types. Nearly all uncontrolled studies did not use suitable statistical methods for single-group pretest-posttest comparisons and should thus be interpreted with caution. CONCLUSION: The E-MOTIVE intervention improves postpartum hemorrhage-related outcomes among women delivering vaginally, and the California Maternal Quality Care Collaborative bundle may reduce severe maternal morbidity. Other bundle designs warrant further effectiveness research before implementation is contemplated.

CT venography for the diagnosis of postpartum venous thromboembolism: a prospective multi-center cohort study.

OBJECTIVES: To assess the role of CT venography (CTV) in the diagnosis of venous thromboembolism (VTE) during the postpartum period. MATERIALS AND METHODS: This multicenter prospective cohort study was conducted between April 2016 and April 2020 in 14 university hospitals. All women referred for CT pulmonary angiography (CTPA) for suspected pulmonary embolism (PE) within the first 6 weeks postpartum were eligible. All CTPAs were performed on multidetector CT machines with the usual parameters and followed by CTV of the abdomen, pelvis, and proximal lower limbs. On-site reports were compared to expert consensus reading, and the added value of CTV was assessed for both. RESULTS: The final study population consisted of 123 women. On-site CTPA reports mentioned PE in seven women (7/123, 5.7%), all confirmed following expert consensus reading, three involving proximal pulmonary arteries and four limited to distal arteries. Positive CTV was reported on-site in nine women, five of whom had negative and two indeterminate CTPAs, bringing the VTE detection rate to 11.4% (14/123) (95%CI: 6.4-18.4, p = 0.03). Expert consensus reading confirmed all positive on-site CTV results, but detected a periuterine vein thrombosis in an additional woman who had a negative CTPA, increasing the VTE detection rate to 12.2% (15/123) (95%CI: 7.0-19.3, p = 0.008). Follow-up at 3 months revealed no adverse events in this woman, who was left untreated. Median Dose-Length-Product was 117 mGy.cm for CTPA and 675 mGy.cm for CTPA + CTV. CONCLUSION: Performing CTV in women suspected of postpartum PE doubles the detection of venous thromboembolism, at the cost of increased radiation exposure. CLINICAL RELEVANCE STATEMENT: CTV can help in the decision-making process concerning curative anticoagulation in women with suspected postpartum PE, particularly those whose CTPA results are indeterminate or whose PE is limited to the subsegmental level. KEY POINTS: Postpartum women are at risk of pulmonary embolism, and CT pulmonary angiography can give equivocal results. CT venography (CTV) positivity increased the venous thromboembolism detection rate from 5.7 to 11.4%. CTV may help clinical decision-making, especially in women with indeterminate CTPA results or subsegmental emboli.

Scaling up Surgical Capacity in Kenya: The Kenya Hospital Assessment Tool (K-HAT).

INTRODUCTION: Although substantial progress has been achieved to bring surgical care to the forefront of global health discussions, a number of low-and middle-income countries are still in the process of developing a National Surgical, Obstetric, and Anesthesia Plan (NSOAP). This paper describes the initial step toward the development of the NSOAP through the creation of the Kenya National Hospital Assessment Tool (K-HAT). METHODS: A study protocol was developed by a multisectoral collaborative group that represented the pillars of surgical capacity development in Kenya. The K-HAT was adapted from two World Health Organization (WHO) tools: the Service Availability and Readiness Assessment tool and the Situational Analysis Tool. The survey tool was deployed on Open Data Kit, an open-source electronic encrypted database. This new locally adapted tool was pilot tested in three hospitals in Kenya and subsequently deployed in Level 4 facilities. RESULTS: Eighty-nine questions representing over 800 data points divided into six WHO Health Systems Strengthening sections comprised the K-HAT which was deployed to over 95% of Level 4 hospitals in Kenya. When compared to the WHO Service Availability and Readiness Assessment tool, the K-HAT collected more detailed information. The pilot test team reported that K-HAT was easy to administer, easily understood by the respondents, and that it took approximately 1 hour to collect data from each facility. CONCLUSIONS: The K-HAT collected comprehensive information that can be used to develop Kenya's NSOAP.