American journal of obstetrics and gynecology最新文献

Cell-free DNA to determine the fetal RHD genotype from the maternal circulation was first described in 1993. High throughput assays using polymerase chain reaction technology were introduced in Europe and gained widespread acceptance in the management of the Rhesus alloimmunized pregnancy. The specificity and sensitivity of these assays approached 99%. As confidence was gained with these results, Scandinavian countries began to employ cell-free DNA for fetal RHD typing as an integral component of their introduction of antenatal Rhesus immune globulin in non-alloimmunized pregnancies. Since 40% of RhD-negative pregnant women will carry an RhD-negative fetus, doses of Rhesus immune globulin were conserved. Recently 2 U.S. companies have introduced cell-free DNA assays for RHD as part of their noninvasive prenatal testing assays. Both utilize next generation sequencing and have developed methodologies to detect the aberrant RHD pseudogene and the hybrid RHD-CE-D^s genotype. In addition, excellent correlation studies with either neonatal genotyping or serology have been reported. The manufacturer of RhoGAM has recently announced a national shortage. Given the current availability of reliable cell-free DNA assays for determining the RHD status of the fetus, the time has come to implement this strategy to triage the antenatal use of Rhesus immune globulin in the U.S.

Background: The Multi-Omics for Mothers and Infants consortium aims to improve birth outcomes. Preterm birth is a major obstetrical complication globally and causes significant infant and childhood morbidity and mortality.

Objective: We analyzed placental samples (basal plate, placenta or chorionic villi, and the chorionic plate) collected by the 5 Multi-Omics for Mothers and Infants sites, namely The Alliance for Maternal and Newborn Health Improvement Bangladesh, The Alliance for Maternal and Newborn Health Improvement Pakistan, The Alliance for Maternal and Newborn Health Improvement Tanzania, The Global Alliance to Prevent Prematurity and Stillbirth Bangladesh, and The Global Alliance to Prevent Prematurity and Stillbirth Zambia. The goal was to analyze the morphology and gene expression of samples collected from preterm and uncomplicated term births.

Study design: The teams provided biopsies from 166 singleton preterm (<37 weeks' gestation) and 175 term (≥37 weeks' gestation) deliveries. The samples were fixed in formalin and paraffin embedded. Tissue sections from these samples were stained with hematoxylin and eosin and subjected to morphologic analyses. Other placental biopsies (n=35 preterm, 21 term) were flash frozen, which enabled RNA purification for bulk transcriptomics.

Results: The morphologic analyses revealed a surprisingly high rate of inflammation that involved the basal plate, placenta or chorionic villi, and the chorionic plate. The rate of inflammation in chorionic villus samples, likely attributable to chronic villitis, ranged from 25% (Pakistan site) to 60% (Zambia site) of cases. Leukocyte infiltration in this location vs in the basal plate or chorionic plate correlated with preterm birth. Our transcriptomic analyses identified 267 genes that were differentially expressed between placentas from preterm vs those from term births (123 upregulated, 144 downregulated). Mapping the differentially expressed genes onto single-cell RNA sequencing data from human placentas suggested that all the component cell types, either singly or in subsets, contributed to the observed dysregulation. Consistent with the histopathologic findings, gene ontology analyses highlighted the presence of leukocyte infiltration or activation and inflammatory responses in both the fetal and maternal compartments.

Conclusion: The relationship between placental inflammation and preterm birth is appreciated in developed countries. In this study, we showed that this link also exists in developing geographies. In addition, among the participating sites, we found geographic- and population-based differences in placental inflammation and preterm birth, suggesting the importance of local factors.

Background: Postpartum hemorrhage is difficult to predict, is associated with significant maternal morbidity, and is the leading cause of maternal mortality worldwide. The identification of maternal biomarkers that can predict increased postpartum hemorrhage risk would enhance clinical care and may uncover mechanisms that lead to postpartum hemorrhage.

Objective: This retrospective case-control study employed agnostic proteomic profiling of maternal plasma samples to identify differentially abundant proteins in controls and postpartum hemorrhage cases.

Study design: Maternal plasma samples were procured from a cohort of >60,000 participants in a single institution's perinatal repository. Postpartum hemorrhage was defined as a decrease in hematocrit of ≥10% or receipt of transfusion within 24 hours after delivery. Postpartum hemorrhage cases (n=30) were matched by maternal age and delivery mode (vaginal or cesarean) with controls (n=56). Mass spectrometry was used to identify differentially abundant proteins using integrated peptide peak areas. Statistically significant differences between groups were defined as P<.05 after controlling for multiple comparisons.

Results: By study design, cases and controls did not differ in race, ethnicity, gestational age at delivery, blood type, or predelivery platelet count. Cases had slightly but significantly lower predelivery and postdelivery hematocrit and hemoglobin. Mass spectrometry detected 1140 proteins, including 77 proteins for which relative abundance differed significantly between cases and controls (fold change >1.15, P<.05). Of these differentially abundant plasma proteins, most had likely liver or placental origins. Gene ontology term analysis mapped to protein clusters involved in responses to wound healing, stress response, and host immune defense. Significantly differentially abundant proteins with the highest fold change (prostaglandin D2 synthase, periostin, and several serine protease inhibitors) did not correlate with predelivery hematocrit or hemoglobin but identified postpartum hemorrhage cases with logistic regression modeling revealing good-to-excellent area under the operator receiver characteristic curves (0.802-0.874). Incorporating predelivery hemoglobin with these candidate proteins further improved the identification of postpartum hemorrhage cases.

Conclusion: Agnostic analysis of maternal plasma samples identified differentially abundant proteins in controls and postpartum hemorrhage cases. Several of these proteins are known to participate in biologically plausible pathways for postpartum hemorrhage risk and have potential value for predicting postpartum hemorrhage. These findings identify candidate protein biomarkers for future validation and mechanistic studies.

Background: Preterm preeclampsia, a product of vascular dysfunction, is associated with prolonged hospital admission and proteinuria, significant risk factors for thromboembolism in pregnancy. The risk of thromboembolism in preterm preeclampsia warrants further investigation.

Objective: To determine the relationship between preterm preeclampsia and thromboembolic risk. We hypothesize that preterm preeclampsia is an independent risk factor for thromboembolism in pregnancy.

Study design: This is a retrospective cohort study using the National Inpatient Sample database via Healthcare Cost and Utilization Project-Agency for Healthcare Cost and Utilization Project from 2017-2019. All subjects with an International Classification of Diseases, Tenth Revision code for pregnancy or peripartum encounter were included. Subjects were excluded if the gestational age at delivery was <20 weeks or if they had a history of thromboembolism, inherited thrombophilia, or antiphospholipid syndrome. Patients with preterm (delivered <37 weeks) preeclampsia and term (delivered ≥37 weeks) preeclampsia were compared with those without preeclampsia. The primary outcome was a composite of any thromboembolic event, including pulmonary embolism, deep vein thrombosis, cerebral thrombosis or transient ischemic attack, or other thromboses. The secondary outcomes were rates of each type of thromboembolic event. The groups were compared via variance analysis, chi-square, and logistic regression analyses. The logistic regression included those variables that differed between groups with P<.05.

Results: Of individuals in the database, >2.2 million met the inclusion criteria. A total of 56,446 (2.7%) had preterm preeclampsia, and 86,152 (6.7%) had term preeclampsia. Those with preterm preeclampsia were more likely to be older, identify as non-Hispanic black, have obesity, have chronic hypertension among other chronic diseases, and be in the lowest quartile of income (P<.001). Among patients with preterm preeclampsia, 0.32% experienced thromboembolism, whereas those with term preeclampsia and without preeclampsia experienced thromboembolism at 0.10% and 0.09%, respectively. After controlling for confounders that differed between groups with P<.05, preterm preeclampsia remained independently associated with any thromboembolic event (adjusted odds ratio, 2.21 [95% confidence interval, 1.84-2.65]), and each type of thromboembolism. Term preeclampsia was not associated with an increased risk of thromboembolism (adjusted odds ratio, 1.18 [95% confidence interval, 0.94-1.48]).

Conclusion: Preterm preeclampsia is independently associated with an increased risk of thromboembolic events.