Faculty Bibliography

Amniotic fluid contains multipotent cells and could be a source of stem cells for clinical use. Amniotic fluid cells (AFC) are made up of a heterogeneous population of fetal cells that can be retrieved during pregnancy without ethical concernsas 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 AFC 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.

Stem cells are undifferentiated cells with the capacity for differentiation. Amniotic fluid cells (AFC) have only recently emerged as a possible source of stem cells for clinical purposes. There are no ethical or sampling constraints using amniocentesis as a standard clinical procedure for obtaining an abundant supply of AFC. AFC of human origin proliferate rapidly and are multipotent with the potential for expansion in vitro to multiple cell lines. Tissue engineering technologies using AFC are being explored. AFC 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 contains a mixture of cells with capacity to differentiate into all germ layers. These cells are present in large numbers in midtrimester samples obtained for cytogenetic diagnosis, and have been identified by stem cell surface markers and transcription factors. We studied cultured samples from patients who had both direct cultures and matched cultures obtained 2 weeks later from the cytogenetics laboratory as well as patients with cytogenetics material only. Samples were cryogenically frozen, thawed, expanded in culture with excellent viability. There was considerable individual variation unrelated to gestational age or telomere length. Phenotype for embryonic markers was assessed by flow cytometry and by quantitative polymerase chain reaction. The most consistently present stem cell markers in substantial amounts were CD90, SSEA-4, & TRA-1-60. Cells with CD90, SSEA-4 & TRA-1-60 double and triple labeled also could be identified and subcultured, confirming the heterogeneity of the amniotic fluid stem cell population

OBJECTIVES/OBJECTIVE: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.

OBJECTIVES/OBJECTIVE: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. www.ClinicalTrials.gov NCT03232762, Effects of Diet on Pregnancy Outcome and Child Obesity.

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.

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.

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.

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. This report describes the results obtained by a multi-disciplinary pregnancy loss prevention center in the initial 104 patients. 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. 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.