Amniotic fluid embolism: a reappraisal.

OBJECTIVES: Using cases from our own experience and from the published literature on amniotic fluid embolism (AFE), we seek to improve on existing criteria for diagnosis and discern associated risk factors. Additionally, we propose a novel theory of pathophysiology. METHODS: This retrospective case review includes eight cases of AFE from two hospital systems and 21 from the published literature. All cases were evaluated using the modified criteria for research reporting of AFE by Clark et al. in Am J Obstet Gynecol, 2016;215:408-12 as well as our proposed criteria for diagnosis. Additional clinical and demographic characteristics potentially correlated with a risk of AFE were included and analyzed using descriptive analysis. RESULTS: The incidence of AFE was 2.9 per 100,000 births, with five maternal deaths in 29 cases (17.2 %) in our series. None of the cases met Clark's criteria while all met our criteria. 62.1 % of patients were over the age of 32 years and two out of 29 women (6.9 %) conceived through in-vitro fertilization. 6.5 % of cases were complicated by fetal death. Placenta previa occurred in 13.8 %. 86.2 % of women had cesarean sections of which 52.0 % had no acute maternal indication. CONCLUSIONS: Our criteria identify more patients with AFE than others with a low likelihood of false positives. Clinical and demographic associations in our review are consistent with those previously reported. A possible relationship between cesarean birth and risk of AFE was identified using our criteria. Additionally, we propose a new hypothesis of pathophysiology.

Clinical potential of human amniotic fluid stem cells.

OBJECTIVES: To determine whether amniotic fluid derived stem cells maintain their stem cell characteristics (a) after processing by a licensed cell therapy center and (b) after the cells undergo simulated clinical application. METHODS: Amniotic fluid was collected by laparotomy - a small uterine incision was made at proposed site for delivery and a sterile catheter inserted to collect fluid into a sterile bag. After flow stopped the catheter was withdrawn, the cesarean completed and the collected fluid delivered to the cell therapy center for processing and cryostorage. A clinical setting was simulated where amniotic fluid cells received from cell therapy center were thawed at room temperature for a maximum of 3 h and passed through a clinical cell delivery device to monitor cell viability. The cells were examined for viability, stability, growth, differentiation, and markers of stemness. RESULTS: Amniotic fluid stem cells processed from a clinical cell therapy center behave similarly to amniotic fluid stem cells processed in a research laboratory with respects to viability, stability, growth, differentiation and maintain markers of stemness. There were differences due to heterogeneity of samples which were not methodological. Growth in cell culture and differentiation were satisfactory. Simulation of treating the cells in a clinical environment show a general stability in viability of amniotic fluid cells at room temperature for 3 h minimum and when passed through a clinically approved delivery device. CONCLUSIONS: The data indicate human amniotic fluid processed in a clinical facility could be used therapeutically if proven to be safe.

A randomized controlled trial of the effects of whole grains versus refined grains diets on the microbiome in pregnancy.

Dietary whole grain consumption has been postulated to have metabolic benefits. The purpose of this study was to compare a pregnancy diet containing 75% of total carbohydrates as refined grains with a diet of 75% of total carbohydrates as whole grains for pregnancy outcomes and effects on the microbiome. Gestational weight gain, glucose tolerance and newborn outcomes were measured on 248 enrolled compliant women from whom a subset of 103 women consented to give 108 vaginal and 109 anal swabs. The data presented here are limited to the patients from whom the vaginal and anal swabs were obtained in order to study the microbiome. A microbiome-16SrRNA survey-was characterized in these samples. Samples and measurements were obtained at the first obstetrical visit, before beginning a prescribed diet (T1-baseline) and after 17-32 weeks on the prescribed diet (T3). Food frequency questionnaires and total plasma alkylresorcinols were used as a measure of whole grain consumption. There were no dietary differences in maternal weight gain, birth weight, or glucose tolerance test. Mothers consuming the whole grains diet showed a trend of gestational decrease in vaginal bacterial alpha diversity, with increasing Lactobacillus-dominance. No significant difference was observed for the anal microbiome. The results suggest that diet modulations of the vaginal microbiome during gestation may have important implications for maternal and neonatal health and in the intergenerational transfer of maternal microbiome. Trial registration: ClinicalTrials.gov Identifier: NCT03232762.

Pregnancy outcomes with differences in grain consumption: a randomized controlled trial.

OBJECTIVES: Contemporary obstetrics has begun to appreciate the importance of diet in pregnancy, but guidelines are not based on robust data. The hypothesis that a whole grains diet improves pregnancy outcomes is tested in this study. We compared maternal and neonatal outcomes for a pregnancy diet containing 75% of total carbohydrates as refined grains with outcomes for a diet with 75% of total carbohydrates as whole grains. METHODS: This was a randomized interventional study in a clinic population over the last 4-7 months of normal pregnancy with extensive compliance measures. Besides obstetrical and neonatal outcomes, anthropometric measurements were done. In addition to food frequency questionnaires (FFQs), total plasma alkyl resorcinols, a unique quantitative measure of whole grains, were used as a measure of whole grain consumption. RESULTS: The data show effective compliance and no difference in outcomes between the diets with regard to maternal weight gain, birth weights, subcutaneous fat and glucose tolerance. CONCLUSIONS: Ensuring compliance to a proper pregnancy diet resulted in satisfactory weight gain and normal outcomes even when the proportion of whole grains consumed is only 25% of total carbohydrates.

Multi-modal Framework for Fetal Heart Rate Estimation: Fusion of Low-SNR ECG and Inertial Sensors.

This study presents a novel multi-modal framework for fetal heart rate extraction, which incorporates wearable seismo-cardiography (SCG), gyro-cardiography (GCG), and electrocardiography (ECG) readings from ten pregnant women. Firstly, a signal refinement method based on empirical mode decomposition (EMD) is proposed to extract the desired signal components associated with fetal heart rate (FHR). Afterwards, two techniques are developed to fuse the information from different modalities. The first method, named early fusion, is intended to combine the refined signals of different modalities through intra-modality fusion, intermodality fusion, and FHR estimation. The other fusion approach, i.e., late fusion, includes FHR estimation and intermodality FHR fusion. FHR values are estimated and compared with readings from a simultaneously-recorded cardiotocography (CTG) sensor. It is demonstrated that the best performance belongs to the late-fusion approach with 87.00% of positive percent agreement (PPA), 6.30% of absolute percent error (APE), and 10.55 beats-per-minute (BPM) of root-meansquare-error (RMSE).Clinical Relevance- The proposed framework allows for the continuous monitoring of the health status of the fetus in expectant women. The approach is accurate and cost-effective due to the use of advanced signal processing techniques and lowcost wearable sensors, respectively.

Cesarean section one hundred years 1920-2020: the Good, the Bad and the Ugly.

In present-day obstetrics, cesarean delivery occurs in one in three women in the United States, and in up to four of five women in some regions of the world. The history of cesarean section extends well over four centuries. Up until the end of the nineteenth century, the operation was avoided because of its high mortality rate. In 1926, the Munro Kerr low transverse uterine incision was introduced and became the standard method for the next 50 years. Since the 1970's, newer surgical techniques gradually became the most commonly used method today because of intraoperative and postpartum benefits. Concurrently, despite attempts to encourage vaginal birth after previous cesareans, the cesarean delivery rate increased steadily from 5 to 30-32% over the last 10 years, with a parallel increase in costs as well as short- and long-term maternal, neonatal and childhood complications. Attempts to reduce the rate of cesarean deliveries have been largely unsuccessful because of the perceived safety of the operation, short-term postpartum benefits, the legal climate and maternal request in the absence of indications. In the United States, as the cesarean delivery rate has increased, maternal mortality and morbidity have also risen steadily over the last three decades, disproportionately impacting black women as compared to other races. Extensive data on the prenatal diagnosis and management of cesarean-related abnormal placentation have improved outcomes of affected women. Fewer data are available however for the improvement of outcomes of cesarean-related gynecological conditions. In this review, the authors address the challenges and opportunities to research, educate and change health effects associated with cesarean delivery for all women.

A multidisciplinary approach to pregnancy loss: the pregnancy loss prevention center.

Background Pregnancy loss is probably the most common problem faced by women worldwide. There are differences in the rates of early and late pregnancy loss based on geography among the developing compared with the developed nations of the world. Most physicians worldwide have different criteria for treating pregnancy loss. Although pregnancy loss is not a disease, it might be best approached with a medical evaluation in order to define the cause and offer specific treatment. Methods This report describes the results obtained by a multi-disciplinary pregnancy loss prevention center in the initial 104 patients. Results The most common diagnoses were Asherman syndrome (intrauterine adhesions), cervical insufficiency and uterine fibroids, accounting for 47% of the patients. When the diagnosis was not obtained, which occurred in 19% of the patients, in vitro fertilization (IVF) was the treatment provided. Specifically diagnosed and treated patients achieved a 91% success rate. The 19 patients without a specific diagnosis who were treated with IVF had a 60% success rate. Thus patients for whom it was possible to specifically diagnose and treat had better results (P<0.01 t-test). There was an overall success rate of 87% including patients lost to follow-up with this multidisciplinary medical approach. Conclusion A pregnancy loss prevention center using the described multidisciplinary model can accomplish success rates of 85-90%. Preventing recurrent pregnancy loss we suggest can best be achieved by a dedicated center with a multidisciplinary medical approach.

Effects of Pharmacological Agents on Human Amniotic Fluid-Derived Stem Cells in Culture.

Amniotic fluid contains multipotent cells and could be a source of stem cells for clinical use. Amniotic fluid cells (AFCs) are made up of a heterogeneous population of fetal cells that can be retrieved during pregnancy without ethical concerns as it is a standard clinical procedure. Studies of proliferation, multipotent marker expression, differentiation, and gene expression were performed after culturing with dexamethasone, valproic acid, and magnesium sulfate. There were correlations between known drug effects on the human fetus and changes seen in human AFCs in culture, as well as previously undescribed observations in neural and chondrogenic inducibility. Gene expression profiles confirmed these observations. AFC culture may provide a novel method to evaluate pharmacological agents before clinical use in pregnancy.

Human amniotic fluid: a source of stem cells for possible therapeutic use.

Stem cells are undifferentiated cells with the capacity for differentiation. Amniotic fluid cells have emerged only recently as a possible source of stem cells for clinical purposes. There are no ethical or sampling constraints for the use of amniocentesis as a standard clinical procedure for obtaining an abundant supply of amniotic fluid cells. Amniotic fluid cells of human origin proliferate rapidly and are multipotent with the potential for expansion in vitro to multiple cell lines. Tissue engineering technologies that use amniotic fluid cells are being explored. Amniotic fluid cells may be of clinical benefit for fetal therapies, degenerative disease, and regenerative medicine applications. We present a comprehensive review of the evolution of human amniotic fluid cells as a possible modality for therapeutic use.

Amniotic fluid as a source of multipotent cells for clinical use.

Amniotic fluid cells (AFC) from 2nd trimester amniocentesis have been found to be a source of multipotent stem cells which might overcome the limitations of expansion, histocompatibility, tumorigenesis, and ethical issues associated with using human embryonic cells, umbilical cord, cord blood, bone marrow, and induced pluripotent cells. Previous work by our group and others demonstrated multipotency and the ability to grow well in culture. However, all these studies were done in media containing fetal calf serum. We sought to observe the properties of AFC grown in serum-free media as that would be required for clinical transplantation in humans. Fresh samples were obtained from three patients, and each sample divided into a culture whose cells were not exposed to fetal calf serum, and the other half into a standard culture medium containing fetal calf serum. Doubling time and stem cell marker expression by flow cytometry were assessed. Differentiation to neural, osteoid, and chondrogenic lineages was induced using appropriate media and confirmed by fluorescent microscopy, histology, and immunohistochemistry. There were no statistically significant differences between cells grown serum-free and in standard media in any of these parameters. The data supports the possibility of clinical use of AFC in stem cell transplantation.

Identification and isolation of putative stem cells from the murine placenta.

OBJECTIVE: The placenta of mid-gestation mice is a known rich source of hematopoietic stem cells. We hypothesized that it is also a source of other multipotent stem cells. METHODS: We isolated fetal cells from the murine placenta across the second half of gestation and characterized their expression of surface antigens known to be associated with mesenchymal stem cells (MSCs) on a subset of hematopoietic lineage-negative cells. Using real-time reverse-transcriptase quantitative polymerase chain reaction, we also evaluated the expression of intracellular transcription factors (TFs) known to be associated with renal development and/or multipotent stem cells. RESULTS: Cell phenotypes with surface marker and TF expression consistent with multipotent stem cells of a mesenchymal lineage as well as renal cell progenitors were found in the placenta. The expression of MSC and renal progenitor surface markers varied throughout gestation, but was highest on E12-15 where such cells represented a small but significant percentage of the population. Of the studied TFs, 10 of 11 renal TFs were found at moderate to high levels, and all stem cell TFs were found. CONCLUSION: The mid-gestation murine placenta may serve as a source of multipotent stem cells and also contains cells which may be renal cell progenitors.

Co-ordinate expression of Th1/Th2 phenotypes in maternal and fetal blood: evidence for a transplacental nexus.

If maternal atopy and environmental exposure affect prenatal Th cell development, the maternal and fetal immune systems should display common Th1/Th2 phenotypes. To test this hypothesis, we studied maternal and neonatal blood samples from mothers with total serum IgE <300 IU/mL. Basal levels of IFN-γ, IL-4, and eotaxin in paired maternal and fetal sera were tightly correlated. Polyclonal T cell activation in vitro by Staphylococcal exotoxin B induced co-ordinate IFN-γ production from paired maternal and fetal mononuclear cells, accompanied by co-ordinate increases in activated CD4+CD69+ cells that display the CCR4+Th2 and CXCR3+ Th1 phenotypes. Maternal and fetal CD4+CXCR3+ T cells were subsequently identified as the major producers of IFN-γ. The data established that a transplacental nexus exists during normal pregnancy and that fetal Th cell responses may be biased by the maternal immune system.

Terbutaline: effects on the fetal heart at term.

The aims of this study were to evaluate the cardiac effects of subcutaneous terbutaline on the mother and fetus. Terbutaline was given in 250 or 500 µg doses to term gravidas not in labor. The mean arterial pressure (MAP), pulse, and uterine activity were measured. The fetal heart rate (FHR), accelerations, and decelerations were recorded. There were significant increases in maternal heart rate, FHR, and FHR accelerations, and a decrease in uterine basal activity after 500 µg, but not significantly after 250 µg of terbutaline. MAP was not significantly increased with either dose, although a small mean increase was observed. Terbutaline has a direct effect on the fetal heart apart from the effect of uterine relaxation.

Parallel maternal and fetal immune activation by bacterial toxins in vitro.

This study evaluated in vitro immune responses to Escherichia coli lipopolysaccharide in maternal and fetal blood. Samples were concurrently obtained from maternal venipuncture and umbilical cord blood samples and cultured with the E. coli endotoxin, and cytokines were assayed. There were statistically significant correlations between maternal and fetal samples. This demonstrates maternal and fetal immune communication and mutual programming during pregnancy. Subclinical infection, which predisposes to premature labor, could be detectable from a maternal blood sample even if derived only from the fetal compartment. A maternal blood panel test might serve as a diagnostic screen for subclinical infection in patients at risk for preterm labor.

Practice patterns in the management of isolated oligohydramnios: a survey of perinatologists.

OBJECTIVE: Optimal management of isolated oligohydramnios (IO) remains debatable. We surveyed Society for Maternal-Fetal Medicine (SMFM) members regarding their opinions and practice patterns. STUDY DESIGN: Questionnaires were mailed to perinatologists across the US. IO was defined as sonographic low fluid (per the practitioner's definition) in the absence of intrauterine growth restriction, fetal anomaly or significant maternal comorbidity. RESULTS: The overall response rate was 35% (n = 632). Ninety-two percent of respondents consider IO to be a risk factor for various adverse outcomes. With a favourable cervix, 34% and 82% would consider inducing labour without documented lung maturity prior to 37 and 39 weeks, respectively. When asked whether induction of labour in cases of IO reduces perinatal morbidity, 45% were unsure and 21.4% thought it would not. Only 33% believe induction could decrease adverse outcomes. Newer members of SMFM (<10 years) and those of private practice were more likely to believe that induction is efficacious in decreasing morbidity. CONCLUSION: There is significant divergence regarding the management of IO. Despite being unsure of its benefit, most practitioners lean towards intervention. The available literature is insufficient to make firm recommendations supporting intervention for IO.