My clinical interest in pregnancies complicated with birth defects has led my underlying research interests in genomic abnormalities in the human trophoblast carrying to faulty placentation. The latter began with initial work during K12 and KO8 funding. I took a great interest in the human placenta as it carries potential advantages over other tissues sources: first, this highly metabolically active organ is the potential source of many transcripts. Second, the placenta forms at a very early stage of embryonic development, potentially allowing detection of primary alterations as compared to secondary changes that may mask the underlying causal phenomena. Finally, studying early placentation may provide targets for development of novel molecular approaches, such as up-regulate or down-regulate genes, the protein products of which could potentially serve as molecular surrogates for diagnosis and treatment of pregnancy complication such as miscarriages, pre-eclampsia, pregnancy induced hypertension and intrauterine growth retardation. This work has led to the first Trisomy 21, Trisomy 18, trisomy 13 cell lines established from human placentas making it possible to apply gene editing in the early stages of human trophoblast development.
As my primary clinical responsibility involves treating patients needing medical care and support through their high risk pregnancies, I am interested in factors that may impact outcomes, such as prenatal screening and diagnosis, maternal heart conditions, labor and delivery management, and safety approaches for the second stage of labor. In investigating length of labor and approaches to shorten the second stage, I have found methods of improving perinatal outcomes in diverse maternal populations.
With regards to my interest in fetal medicine, I have worked in collaboration with other specialists such as radiologists and pediatric cardiologists utilizing imagining studies to assess and determine successful perinatal care and fetal survival.
- High Risk Obstetrics
- Obstetrics and Gynecology
- Maternal Cardiac Conditions
Global Health ACOG/ US.Gov Fellow Associate, ACOG (2017 - Present)
Diversity Communication Advisory Board (CAB) member, Stanford University SOM (2016 - Present)
Office of the Dean for Faculty Development and Diversity (OFDD) Liasion, Stanford University SOM (2015 - Present)
Honors & Awards
Peter A. Grannum, M.D Memorial Award". Excellence in Teaching, Yale University (2001-04)
"Lysosomal Diseases and Brain Scholar Award", Children's Gaucher Research Foundation (2008)
Outstanding Faculty Award in Medical Student Teaching, UCSF (2009)
March of Dimes Scholar, "Reproductive Scientist Development Award", NIH/NICHD/ MOD (2011-13)
Outstanding Faculty Award in Medical Student Teaching, UCSF (2012)
Outstanding Faculty Teaching Award, UCSF (2015)
Academy for Leadership and Development Scholar, SMFM (2016)
Stanford Leadership Development Program Scholar, Stanford University/Stanford Heath care System (2018-19)
Boards, Advisory Committees, Professional Organizations
OBGYN, American Board of Obstetrics and Gynecology (2007 - Present)
Medical Geneticist, American Board of Medical genetics and Genomics (2011 - Present)
Maternal-Fetal-Medicine specialist, American Board of Obstetrics and Gynecology (2013 - Present)
Residency: Yale School Of Medicine (2004) CT
Internship: Yale School Of Medicine (2004) CT
Board Certification: American Board of Medical Genetics and Genomics, Clinical Genetics (2011)
Fellowship, University of California, at San Francisco (UCSF), Diagnostic Imagine (2006)
Board Certification: American Board of Obstetrics and Gynecology, Obstetrics and Gynecology (2007)
Board Certification: American Board of Obstetrics and Gynecology, Maternal and Fetal Medicine (2013)
Fellowship: University of California San Francisco (2008) CA
Medical Education: Central University of Venezuela (1997) Venezuela
Community and International Work
Utilization of Obstetrics Simulation to decrease Adverse Perinatal Outcomes
global women's health education
Opportunities for Student Involvement
- Medical Spanish
INDE 274 (Spr)
- Obstetrics and Gynecologic Skills Simulation
OBGYN 222 (Win)
Independent Studies (5)
- Directed Reading in Obstetrics and Gynecology
OBGYN 299 (Win, Spr)
- Early Clinical Experience in Obstetrics and Gynecology
OBGYN 280 (Win, Spr)
- Graduate Research in Reproductive Biology
OBGYN 399 (Win, Spr)
- Medical Scholars Research
OBGYN 370 (Win, Spr, Sum)
- Undergraduate Research in Reproductive Biology
OBGYN 199 (Win, Spr)
- Directed Reading in Obstetrics and Gynecology
- Prior Year Courses
Graduate and Fellowship Programs
Mixed methods evaluation of simulation-based training for postpartum hemorrhage management in Guatemala.
BMC pregnancy and childbirth
2022; 22 (1): 513
BACKGROUND: To assess if simulation-based training (SBT) of B-Lynch suture and uterine balloon tamponade (UBT) for the management of postpartum hemorrhage (PPH) impacted provider attitudes, practice patterns, and patient management in Guatemala, using a mixed-methods approach.METHODS: We conducted an in-country SBT course on the management of PPH in a governmental teaching hospital in Guatemala City, Guatemala. Participants were OB/GYN providers (n=39) who had or had not received SBT before. Surveys and qualitative interviews evaluated provider knowledge and experiences with B-Lynch and UBT to treat PPH.RESULTS: Multiple-choice surveys indicated that providers who received SBT were more comfortable performing and teaching B-Lynch compared to those who did not (p=0.003 and 0.005). Qualitative interviews revealed increased provider comfort with B-Lynch compared to UBT and identified multiple barriers to uterine balloon tamponade implementation.CONCLUSIONS: Simulation-based training had a stronger impact on provider comfort with B-Lynch compared to uterine balloon tamponade. Qualitative interviews provided insight into the challenges that hinder uptake of uterine balloon tamponade, namely resource limitations and decision-making hierarchies. Capturing data through a mixed-methods approach allowed for more comprehensive program evaluation.
View details for DOI 10.1186/s12884-022-04845-2
View details for PubMedID 35751071
Leukocyte telomere dynamics across gestation in uncomplicated pregnancies and associations with stress.
BMC pregnancy and childbirth
2022; 22 (1): 381
Short leukocyte telomere length is a biomarker associated with stress and morbidity in non-pregnant adults. Little is known, however, about maternal telomere dynamics in pregnancy. To address this, we examined changes in maternal leukocyte telomere length (LTL) during uncomplicated pregnancies and explored correlations with perceived stress.In this pilot study, maternal LTL was measured in blood collected from nulliparas who delivered live, term, singleton infants between 2012 and 2018 at a single institution. Participants were excluded if they had diabetes or hypertensive disease. Samples were collected over the course of pregnancy and divided into three time periods: < 200/7 weeks (Timepoint 1); 201/7 to 366/7 weeks (Timepoint 2); and 370/7 to 9-weeks postpartum (Timepoint 3). All participants also completed a survey assessing a multivariate profile of perceived stress at the time of enrollment in the first trimester. LTL was measured using quantitative polymerase chain reaction (PCR). Wilcoxon signed-rank tests were used to compare LTL differences within participants across all timepoint intervals. To determine whether mode of delivery affected LTL, we compared postpartum Timepoint 3 LTLs between participants who had vaginal versus cesarean birth. Secondarily, we evaluated the association of the assessed multivariate stress profile and LTL using machine learning analysis.A total of 115 samples from 46 patients were analyzed. LTL (mean ± SD), expressed as telomere to single copy gene (T/S) ratios, were: 1.15 ± 0.26, 1.13 ± 0.23, and 1.07 ± 0.21 for Timepoints 1, 2, and 3, respectively. There were no significant differences in LTL between Timepoints 1 and 2 (LTL T/S change - 0.03 ± 0.26, p = 0.39); 2 and 3 (- 0.07 ± 0.29, p = 0.38) or Timepoints 1 and 3 (- 0.07 ± 0.21, p = 0.06). Participants who underwent cesareans had significantly shorter postpartum LTLs than those who delivered vaginally (T/S ratio: 0.94 ± 0.12 cesarean versus 1.12 ± 0.21 vaginal, p = 0.01). In secondary analysis, poor sleep quality was the main stress construct associated with shorter Timepoint 1 LTLs (p = 0.02) and shorter mean LTLs (p = 0.03).In this cohort of healthy pregnancies, maternal LTLs did not significantly change across gestation and postpartum LTLs were shorter after cesarean than after vaginal birth. Significant associations between sleep quality and short LTLs warrant further investigation.
View details for DOI 10.1186/s12884-022-04693-0
View details for PubMedID 35501726
Gender-based salary differences in academic medicine: a retrospective review of data from six public medical centers in the Western USA.
2022; 12 (4): e059216
OBJECTIVES: We assessed the effect of gender, rank and research productivity on compensation for faculty at academic medical centres.DESIGN: A web-based retrospective review of salary for professors in 2016.SETTING: Faculty from six state-run, publicly funded academic medical centres in the Western USA.PARTICIPANTS: 799 faculty members, 225 assistant (51%women), 200 associate (40%women) and 374 full professors (32%women) from general surgery (26%women), obstetrics and gynaecology (70%women) and radiology (34%women).METHODS: Archived online faculty profiles were reviewed for gender, rank and compensation (total, baseline and supplemental). Total compensation was defined as baseline compensation plus supplemental income. Baseline compensation was defined as base salary minus reductions due to participation in the voluntary Employee Reduction in Time and phased retirement programmes. Supplemental income was defined as additional salary for clinical care and research (eg, grants). Elsevier's Scopus was used to collect data on h-index, a measure of research productivity. Linear regression models were estimated to determine the relationship between these factors and salary.RESULTS: Total compensation was significantly higher for men across all professorial ranks in both general surgery [Formula: see text] and obstetrics and gynaecology [Formula: see text]. Women faculty members within these departments earned almost US$75000 less than their men colleagues. The disparity in salary originates from gaps in supplemental income, as baseline compensation was not significantly different between men and women. No significant gender difference in total compensation for radiology was found [Formula: see text]. Higher h-index was associated with higher baseline compensation across all departments as well as with supplemental income for general surgery. Higher h-index was related to lower supplemental income for radiology and was not related to supplemental income for obstetrics and gynaecology.CONCLUSIONS: Further investigations should focus on discrepancies in supplemental income, which may preferentially benefit men.
View details for DOI 10.1136/bmjopen-2021-059216
View details for PubMedID 35393330
Leukocyte Telomere Length in the First Trimester of Pregnancy and its Association with Perinatal Outcomes
SPRINGER HEIDELBERG. 2022: 155
View details for Web of Science ID 000762765300282
Cellular Aging and Stress in Pregnant and Non-Pregnant People During the COVID-19 Pandemic
SPRINGER HEIDELBERG. 2022: 191
View details for Web of Science ID 000762765300376
Metabolic profiling of placental tissue and maternal plasma to identify biomarkers of placenta accreta spectrum
MOSBY-ELSEVIER. 2022: S14-S15
View details for Web of Science ID 000737459400018
Cellular aging and pregnancy complications: Examining maternal leukocyte telomere length in two diverse cohorts.
MOSBY-ELSEVIER. 2022: S646
View details for Web of Science ID 000737459401371
Preterm twin gestation: The association between severity of small for gestational age and neonatal outcomes
MOSBY-ELSEVIER. 2022: S391-S392
View details for Web of Science ID 000737459400587
Cellular aging and telomere dynamics in pregnancy.
Current opinion in obstetrics & gynecology
PURPOSE OF REVIEW: Telomere biology is an emerging area of scientific interest. Telomeres are deoxynucleic acid caps at the ends of chromosomes that naturally shorten over one's lifespan; because of this, short telomeres have been studied as a marker of cellular aging. Given the association between short telomeres and genetic and environmental factors, their role in pregnancy has become an intriguing area of research.RECENT FINDINGS: This review describes recent data on telomeres in pregnancy. Specifically, we discuss the association between short maternal leukocyte telomeres and poor nutritional status, between short neonatal telomeres and greater maternal psychosocial stress, and between shorter fetal amniotic membrane telomeres and the spontaneous onset of parturition. We also review recent studies suggesting that events during pregnancy can impact telomeres in the offspring years into the future.SUMMARY: Telomere length varies in maternal, placental, and neonatal cells, but within each of these compartments telomeres may play their own distinct role during pregnancy. Whether telomeres are reflective of the cumulative impact of stressors, or part of an as-yet unknown fetal programming mechanism is an area of interest. With future research, we may work toward a better understanding of gestational biology which could have far reaching intergenerational impacts.
View details for DOI 10.1097/GCO.0000000000000765
View details for PubMedID 34845136
Newborn screen metabolic panels reflect the impact of common disorders of pregnancy.
BACKGROUND: Hypertensive disorders of pregnancy and maternal diabetes profoundly affect fetal and newborn growth, yet disturbances in intermediate metabolism and relevant mediators of fetal growth alterations remain poorly defined. We sought to determine whether there are distinct newborn screen metabolic patterns among newborns affected by maternal hypertensive disorders or diabetes in utero.METHODS: A retrospective observational study investigating distinct newborn screen metabolites in conjunction with data linked to birth and hospitalization records in the state of California between 2005 and 2010.RESULTS: A total of 41,333 maternal-infant dyads were included. Infants of diabetic mothers demonstrated associations with short-chain acylcarnitines and free carnitine. Infants born to mothers with preeclampsia with severe features and chronic hypertension with superimposed preeclampsia had alterations in acetylcarnitine, free carnitine, and ornithine levels. These results were further accentuated by size for gestational age designations.CONCLUSIONS: Infants of diabetic mothers demonstrate metabolic signs of incomplete beta oxidation and altered lipid metabolism. Infants of mothers with hypertensive disorders of pregnancy carry analyte signals that may reflect oxidative stress via altered nitric oxide signaling. The newborn screen analyte composition is influenced by the presence of these maternal conditions and is further associated with the newborn size designation at birth.IMPACT: Substantial differences in newborn screen analyte profiles were present based on the presence or absence of maternal diabetes or hypertensive disorder of pregnancy and this finding was further influenced by the newborn size designation at birth. The metabolic health of the newborn can be examined using the newborn screen and is heavily impacted by the condition of the mother during pregnancy. Utilizing the newborn screen to identify newborns affected by common conditions of pregnancy may help relate an infant's underlying biological disposition with their clinical phenotype allowing for greater risk stratification and intervention.
View details for DOI 10.1038/s41390-021-01753-7
View details for PubMedID 34671094
The impact of the COVID-19 pandemic on postpartum contraception planning
AMERICAN JOURNAL OF OBSTETRICS & GYNECOLOGY MFM
2021; 3 (5)
View details for Web of Science ID 000711236400041
Myocardial Bridge in Pregnancy: Beyond a 'Normal Anatomic Variant'.
SPRINGER HEIDELBERG. 2021: 267A
View details for Web of Science ID 000675441000561
Long Term Patient Follow-Up of Cardiac Disease in Pregnancy: Multidisciplinary Teams Tether At-Risk Patients to the System.
SPRINGER HEIDELBERG. 2021: 268A-269A
View details for Web of Science ID 000675441000564
Novel Approaches to Develop Critical Reference Materials for Noninvasive Prenatal Testing: A Pilot Study.
The journal of applied laboratory medicine
BACKGROUND: Highly characterized reference materials are required to expand noninvasive prenatal testing (NIPT) for low incidence aneuploidies and microdeletions. The goal of this study was to develop reference materials for the development of next generation circulating cell-free DNA (ccfDNA) assays.METHODS: This was a prospective study of pregnancies complicated by positive prenatal genetic screening. ccfDNA was isolated from maternal plasma and amplified. Lymphoblastoid cell lines were prepared from maternal peripheral blood mononuclear cells and fetal cord blood cells. Cells were Epstein-Barr virus immortalized and expanded. Amplified DNA and to a limited extent formulated lymphoblastoid-derived ccfDNA was tested in SNP-based and chromosome counting (CC) based massively parallel sequencing assays.RESULTS: Enrolled cases included fetuses with: T21 (2), T18 (1), T18-XXX (1), XYY (1), microdeletions (1), and euploid (2). Three lymphoblastoid cells lines were prepared. Genomic DNA was extracted from cell lines and fragmented to simulate ccfDNA. ccfDNA isolation yielded about 2000 usable genome equivalents of DNA for each case for amplification. Although the sonicated genomic DNA derived from lymphoblastoid cell lines did not yield results compatible with NIPT assays, when blinded, NIPT platforms correctly identified the amplified ccfDNA isolated from blood in the majority of cases.CONCLUSIONS: This study showed that maternal blood samples from pregnancies complicated by common chromosomal abnormalities can be used to generate materials for the development and evaluation of NIPT assays.
View details for DOI 10.1093/jalm/jfab037
View details for PubMedID 34080621
Outcomes in pregnancies complicated by IUGR before 32 weeks: does the degree of SGA matter?
MOSBY-ELSEVIER. 2021: S519
View details for Web of Science ID 000621547401378
To pull or not to pull: clinical factors associated with failed operative vaginal delivery
MOSBY-ELSEVIER. 2021: S101
View details for Web of Science ID 000621547400148
- The impact of the COVID-19 pandemic on postpartum contraception planning. American journal of obstetrics & gynecology MFM 2021: 100412
Changing the Landscape of Obstetric Resident Education in LMIC Using Simulation-Based Training.
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics
OBJECTIVE: Evaluate simulation-based training (SBT) in low-and-middle-income countries (LMIC) and the long-term retention of knowledge and self-efficacy.METHODS: We conducted a SBT course on the management of post-partum hemorrhage (PPH), shoulder dystocia (SD), and maternal cardiac arrest (MCA) in three governmental teaching hospitals in Guatemala. We evaluated changes in knowledge and self-efficacy using a multiple-choice questionnaire (MCQ) for 46 OB/GYN residents. A paired Student t-test was used to analyze changes at one week and six months after the SBT.RESULTS: There was an increase in scores in clinical knowledge of MCA, P <0. 001, 95% CI [0.81, 1.49], and SD, P<0.001, 95% CI [0.41, 1.02] one week following SBT and a statistically insignificant increase in PPH scores, P= 0.617, 95% CI [-0.96, 0.60]. This increase in scores was maintained after six months, for MCA, P< 0.001, 95% CI [0.69, 1.53], SD, P= 0.02 95% CI [0.07-0.85] and PPH, P=0.04 95% CI [0.01, 1.26]. For MCA and SD levels of self-efficacy were increased one-week following training, P<0.001 95% CI [0.83, 2.30] and P= 0.008 95% CI [0.60, 3.92], respectively, and at six-months P<0.001 95% CI [0.79, 2.42] and P= 0.006 95% CI [0.66, 3.81], respectively. There was a slight increase in PPH self-efficacy scores one-week after SBT, P=0.73, 95% CI [-6.05, 4.41], maintained after six-months P= 0.38 95% CI [-6.85, 2.85].CONCLUSION: SBT was found to be an effective and feasible method to increase short and long-term clinical knowledge and self-efficacy of obstetric emergencies in LMIC.
View details for DOI 10.1002/ijgo.13526
View details for PubMedID 33314149
Measurement of Marginal Placental Cord Insertion by Prenatal Ultrasound Was Found Not to Be Predictive of Adverse Perinatal Outcomes.
Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine
The clinical importance of marginal cord insertion (MCI) is currently controversial. In this study, we examined the association between MCI and adverse perinatal outcomes. We also evaluated the ultrasound-measured distance from the site of placental cord insertion (PCI) to the placental margin (PCI distance) and perinatal outcomes.This was a retrospective cohort study of MCI and control pregnancies presenting to a single institution between September 2014 and August 2016. Marginal cord insertion was diagnosed on routine anatomy ultrasound scans at 20 weeks' gestation. The primary outcome was fetal intolerance to labor. Secondary outcomes of interest included mode of delivery, gestational age at delivery, Apgar scores at 1 and 5 minutes, birth weight, delivery complications, and neonatal intensive care unit admission. The PCI distance was determined by an ultrasound review. Statistical significance was evaluated by a χ2 analysis, descriptive statistics, Wilcoxon tests, and regression models with log-transformed outcomes, the PCI distance, or both as needed.Of 675 abnormal cord insertion cases, we identified 183 that met inclusion criteria. We found no statistically significant association between MCI and fetal intolerance to labor (odds ratio, 1.24 [95% confidence interval, 0.55-2.80]; P = .71) or secondary outcomes. Furthermore, we found no significant correlation between perinatal outcomes and the PCI distance.Our study suggests that MCI pregnancies, regardless of the specific PCI distance, might not be at increased risk of adverse perinatal outcomes. This finding questions the need for heightened antepartum surveillance of this patient population.
View details for DOI 10.1002/jum.15586
View details for PubMedID 33277931
- Use of Remdesivir for Pregnant Patients with Severe Novel 2019 Coronavirus Disease. American journal of obstetrics and gynecology 2020
Changing the Landscape of Obstetric Resident Education in LMIC Using Simulation Based Training
LIPPINCOTT WILLIAMS & WILKINS. 2020: 80S
View details for Web of Science ID 000554572900277
Postpartum Depression Among Women with Cardiac Disease: Considerations During the Delivery Admission
SPRINGER HEIDELBERG. 2020: 246A
View details for Web of Science ID 000525432601113
Perinatal Outcomes in Women With Cardiac Arrhythmia.
SPRINGER HEIDELBERG. 2020: 161A
View details for Web of Science ID 000525432600268
Cellular Aging in Pregnancy: Telomere Dynamics Across Gestation.
SPRINGER HEIDELBERG. 2020: 127A–128A
View details for Web of Science ID 000525432600181
Measurement of Marginal Placental Cord Insertion by Prenatal Ultrasound Was Found Not to Be Predictive of Adverse Perinatal Outcomes
View details for DOI 10.1002/jum.15586
Bicuspid Aortic Valve and Ascending Aortic Aneurysm in a Twin Pregnancy.
JACC. Case reports
2020; 2 (1): 96-100
Bicuspid aortic valve with ascending aortic aneurysm is a common condition encountered in pregnancy. There are limited data on how to manage these patients. To our knowledge, we report the only case of a bicuspid aortic valve and aortic aneurysm with twin gestations. (Level of Difficulty: Intermediate.).
View details for DOI 10.1016/j.jaccas.2019.12.012
View details for PubMedID 34316973
Trisomy 21 is Associated with Caspase-2 Upregulation in Cytotrophoblasts at the Maternal-Fetal Interface
2020; 27 (1): 100–109
Impaired placentation is implicated in poor perinatal outcomes associated with Trisomy 21. Earlier studies revealed abnormal cytotrophoblast differentiation along the invasive pathway as a contributing mechanism. To further elucidate the causes, we evaluated Caspase-2 expression at the protein level (immunolocalization and immunoblot) in samples from Trisomy 21 (n = 9) and euploid (n = 4) age-matched placentas. Apoptosis was investigated via the TUNEL assay. An immunolocalization approach was used to characterize Caspase-3, Fas (CD95), and Fas ligand in the same samples. Caspase-2 was significantly overexpressed in Trisomy 21 placentas, with the highest expression in villous cores and invasive cytotrophoblasts. Immunolocalization showed that Caspase-3 had a similar expression pattern as Caspase-2. Using the TUNEL approach, we observed high variability in the number of apoptotic cells in biopsies from different regions of the same placenta and among different placentas. However, Trisomy 21 placentas had more apoptotic cells, specifically in cell columns and basal plates. Furthermore, Caspase-2 co-immunolocalized with Fas (CD95) and FasL in TUNEL-positive extravillous cytotrophoblasts, but not in villous cores. These results help explain the higher levels of apoptosis among placental cells of Trisomy 21 pregnancies in molecular terms. Specifically, the co-expression of Caspase-2 and Caspase-3 with other regulators of the apoptotic process in TUNEL-positive cells suggests these molecules may cooperate in launching the observed apoptosis. Among trophoblasts, only the invasive subpopulation showed this pattern, which could help explain the higher rates of adverse outcomes in these pregnancies. In future experiments, this relationship will be further examined at a functional level in cultured human trophoblasts.
View details for DOI 10.1007/s43032-019-00002-x
View details for Web of Science ID 000525433300011
View details for PubMedID 32046398
- Contraception uptake among women with cardiovascular disease: The impact of a multidisciplinary team care approach MOSBY-ELSEVIER. 2020: S707–S708
- Impact of gender, rank and research productivity on salary in obstetrics and gynecology MOSBY-ELSEVIER. 2020: S356
Changes in pregnancy-related serum biomarkers early in gestation are associated with later development of preeclampsia.
2020; 15 (3): e0230000
Placental protein expression plays a crucial role during pregnancy. We hypothesized that: (1) circulating levels of pregnancy-associated, placenta-related proteins throughout gestation reflect the temporal progression of the uncomplicated, full-term pregnancy, and can effectively estimate gestational ages (GAs); and (2) preeclampsia (PE) is associated with disruptions in these protein levels early in gestation; and can identify impending PE. We also compared gestational profiles of proteins in the human and mouse, using pregnant heme oxygenase-1 (HO-1) heterozygote (Het) mice, a mouse model reflecting PE-like symptoms.Serum levels of placenta-related proteins-leptin (LEP), chorionic somatomammotropin hormone like 1 (CSHL1), elabela (ELA), activin A, soluble fms-like tyrosine kinase 1 (sFlt-1), and placental growth factor (PlGF)-were quantified by ELISA in blood serially collected throughout human pregnancies (20 normal subjects with 66 samples, and 20 subjects who developed PE with 61 samples). Multivariate analysis was performed to estimate the GA in normal pregnancy. Mean-squared errors of GA estimations were used to identify impending PE. The human protein profiles were then compared with those in the pregnant HO-1 Het mice.An elastic net-based gestational dating model was developed (R2 = 0.76) and validated (R2 = 0.61) using serum levels of the 6 proteins measured at various GAs from women with normal uncomplicated pregnancies. In women who developed PE, the model was not (R2 = -0.17) associated with GA. Deviations from the model estimations were observed in women who developed PE (P = 0.01). The model developed with 5 proteins (ELA excluded) performed similarly from sera from normal human (R2 = 0.68) and WT mouse (R2 = 0.85) pregnancies. Disruptions of this model were observed in both human PE-associated (R2 = 0.27) and mouse HO-1 Het (R2 = 0.30) pregnancies. LEP outperformed sFlt-1 and PlGF in differentiating impending PE at early human and late mouse GAs.Serum placenta-related protein profiles are temporally regulated throughout normal pregnancies and significantly disrupted in women who develop PE. LEP changes earlier than the well-established biomarkers (sFlt-1 and PlGF). There may be evidence of a causative action of HO-1 deficiency in LEP upregulation in a PE-like murine model.
View details for DOI 10.1371/journal.pone.0230000
View details for PubMedID 32126118
Maternal Outcomes in Planned and Unplanned Pregnancies in Women with Cardiac Disease.
SAGE PUBLICATIONS INC. 2019: 323A
View details for Web of Science ID 000459610400771
A Multidisciplinary Approach to Care of Pregnant Patients with History of Open Heart Surgery.
SAGE PUBLICATIONS INC. 2019: 323A–324A
View details for Web of Science ID 000459610400772
- Care of the pregnant cardiac patient e the importance of a multidisciplinary approach MOSBY-ELSEVIER. 2019: S536
- Outcomes of women with primary and secondary pulmonary hypertension during pregnancy MOSBY-ELSEVIER. 2019: S405
- Donor-derived circulating cell-free DNA (ccfDNA) reference materials for concordance studies AMER ASSOC CANCER RESEARCH. 2018
Hospital variations in the use of forceps assisted delivery - results from a state-wide analysis
MOSBY-ELSEVIER. 2018: S344
View details for Web of Science ID 000423616600074
Maternal morbidity after forceps vs vacuum assisted delivery - Outcomes from a large state-wide cohort
MOSBY-ELSEVIER. 2018: S345
View details for Web of Science ID 000423616600075
Fetal intolerance to labor in pregnancies complicated by marginal and eccentric cord insertion
MOSBY-ELSEVIER. 2018: S285
View details for Web of Science ID 000422946900475
Gene expression network analysis in aneuploid human trophoblast progenitor cells (TBPC) reveals modular structures
MOSBY-ELSEVIER. 2018: S163–S164
View details for Web of Science ID 000422946900255
Neonatal outcomes after operative vaginal delivery - are forceps or vacuum safer?
MOSBY-ELSEVIER. 2018: S343–S344
View details for Web of Science ID 000423616600073
Placental transcriptomes in the common aneuploidies reveal critical regions on the trisomic chromosomes and genome-wide effects
2016; 36 (9): 812-822
Chromosomal aberrations are frequently associated with birth defects and pregnancy losses. Trisomy 13, Trisomy 18 and Trisomy 21 are the most common, clinically relevant fetal aneusomies. This study used a transcriptomics approach to identify the molecular signatures at the maternal-fetal interface in each aneuploidy.We profiled placental gene expression (13-22 weeks) in T13 (n = 4), T18 (n = 4) and T21 (n = 8), and in euploid pregnancies (n = 4).We found differentially expressed transcripts (≥2-fold) in T21 (n = 160), T18 (n = 80) and T13 (n = 125). The majority were upregulated and most of the misexpressed genes were not located on the relevant trisomic chromosome, suggesting genome-wide dysregulation. A smaller number of the differentially expressed transcripts were encoded on the trisomic chromosome, suggesting gene dosage. In T21, <10% of the genes were transcribed from the Down syndrome critical region (21q21-22), which contributes to the clinical phenotype. In T13, 15% of the upregulated genes were on the affected chromosome (13q11-14), and in T18, the percentage increased to 24% (18q11-22 region).The trisomic placental (and possibly fetal) phenotypes are driven by the combined effects of genome-wide phenomena and increased gene dosage from the trisomic chromosome. © 2016 John Wiley & Sons, Ltd.
View details for DOI 10.1002/pd.4862
View details for Web of Science ID 000384096800002
View details for PubMedID 27328057
View details for PubMedCentralID PMC5104283
- Human trophoblast progenitor cell (TBPC) lines derived from aneuploid placentas: studying fundamental aspects of trophoblast biology MOSBY-ELSEVIER. 2016: S331
Integrative analysis of 111 reference human epigenomes.
2015; 518 (7539): 317-330
The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.
View details for DOI 10.1038/nature14248
View details for PubMedID 25693563
View details for PubMedCentralID PMC4530010
- Pregnancy complications are increased among women with cardiomyopathy compared to those with other cardiac diseases MOSBY-ELSEVIER. 2015: S68–S69
Congenital Heart Disease and Perinatal Outcomes.
SAGE PUBLICATIONS INC. 2014: 148A
View details for Web of Science ID 000333813001212
Reversal of gene dysregulation in cultured cytotrophoblasts reveals possible causes of preeclampsia
JOURNAL OF CLINICAL INVESTIGATION
2013; 123 (7): 2862–72
During human pregnancy, a subset of placental cytotrophoblasts (CTBs) differentiates into cells that aggressively invade the uterus and its vasculature, anchoring the progeny and rerouting maternal blood to the placenta. In preeclampsia (PE), CTB invasion is limited, reducing placental perfusion and/or creating intermittent flow. This syndrome, affecting 4%-8% of pregnancies, entails maternal vascular alterations (e.g., high blood pressure, proteinuria, and edema) and, in some patients, fetal growth restriction. The only cure is removal of the faulty placenta, i.e., delivery. Previously, we showed that defective CTB differentiation contributes to the placental component of PE, but the causes were unknown. Here, we cultured CTBs isolated from PE and control placentas for 48 hours, enabling differentiation and invasion. In various severe forms of PE, transcriptomics revealed common aberrations in CTB gene expression immediately after isolation, including upregulation of SEMA3B, which resolved in culture. The addition of SEMA3B to normal CTBs inhibited invasion and recreated aspects of the PE phenotype. Additionally, SEMA3B downregulated VEGF signaling through the PI3K/AKT and GSK3 pathways, effects that were observed in PE CTBs. We propose that, in severe PE, the in vivo environment dysregulates CTB gene expression; the autocrine actions of the upregulated molecules (including SEMA3B) impair CTB differentiation, invasion and signaling; and patient-specific factors determine the signs.
View details for DOI 10.1172/JCI66966
View details for Web of Science ID 000321316700016
View details for PubMedID 23934129
View details for PubMedCentralID PMC3999620
Decidua-Placental Interface Show Abnormal Epigenetic Profiles in Common Aneuploidies
SAGE PUBLICATIONS INC. 2013: 254A
View details for Web of Science ID 000329543100649
- Genomic profiles in common aneuploidies: a combination of dose effects and whole genome misregulation MOSBY-ELSEVIER. 2013: S30
Human Placenta Undergoes Global DNA Methylation Modification during Normal Gestation
SAGE PUBLICATIONS INC. 2012: 383A–384A
View details for Web of Science ID 000329543603283
Genomic imprinting in offspring conceived with assisted reproductive technology
31st Annual Scientific Meeting of the Society-of-Maternal-Fetal-Medicine (SMFM)
MOSBY-ELSEVIER. 2011: S284–S285
View details for Web of Science ID 000285927500719
- Stem Cells in Hepatic Regeneration After Injury ADVANCES IN WOUND CARE, VOL 1 2010; 1: 526–31
Effect of estradiol on oocyte development
INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS
2009; 104 (3): 230–32
To determine whether elevated serum estradiol (E(2)) concentrations in oocyte donors affect assisted reproduction outcome.In a retrospective cohort study of 58 consecutive oocyte donation cycles, donors were stratified into 2 groups according to E(2) concentration, group 1 (n=32; E(2)
2000 pg/mL [range, 2062-6957 pg/mL]). Data were analyzed using the t test and chi(2) test.Donors in group 1 produced significantly less oocytes than donors in group 2 (19.3+/-1.7 vs 12.0+/-1.4; P<0.001), and recipients of oocytes from group 1 had significantly fewer numbers of embryos available for transfer (10.4+/-1.1 vs 6.4+/-0.8; P=0.003). However, the mean number (3.3) of embryos transferred and the pregnancy rate were the same in both groups.Elevated estradiol concentration in oocyte donors did not affect pregnancy outcome, suggesting that estradiol levels in donors do not affect oocyte development.
View details for DOI 10.1016/j.ijgo.2008.10.015
View details for Web of Science ID 000264255600015
View details for PubMedID 19056082
View details for PubMedCentralID PMC3107851
- Operative vaginal delivery: Now or later? MOSBY-ELSEVIER. 2007: S97
Fetal cerebellar hemorrhage in parvovirus-associated non-immune hydrops fetalis
JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
2007; 20 (10): 769–72
We report two cases of fetal cerebellar hemorrhage in the setting of parvovirus-associated hydrops fetalis and fetal blood transfusion. In both cases, the cerebellar hemorrhage was diagnosed by fetal magnetic resonance imaging after intrauterine blood transfusion. To our knowledge, this is the first report of fetal cerebellar hemorrhage in the setting of parvovirus-associated hydrops fetalis, and may be the result of cerebrovascular changes both during and after the transfusion.
View details for DOI 10.1080/14767050701580960
View details for Web of Science ID 000250402500011
View details for PubMedID 17763280
Second-trimester ductus venosus measurement and adverse perinatal outcome in fetuses with congenital heart disease
JOURNAL OF ULTRASOUND IN MEDICINE
2006; 25 (8): 979–82
The purpose of this study was to determine whether Doppler velocimetry of the ductus venosus (DV) predicts adverse perinatal outcome in congenital heart disease (CHD).We conducted a retrospective cohort study of all pregnant women undergoing fetal echocardiography for CHD in a single perinatal center during a 2-year period. We compared outcomes for fetuses having a diagnosis of CHD in the second trimester and abnormal DV Doppler velocimetric findings with those having CHD and normal DV Doppler findings. Karyotype, gestational age at delivery, fetal loss rate, and rate of termination were assessed. The referral value for an abnormal DV pulsatility index was above the 95th percentile for gestational age. Statistical analysis included the t test, Fisher exact test, and chi(2) test.The incidence of CHD in our population was 7%. There were 98 patients with CHD; of those, 31 had DV measurement. A total of 9 patients had an abnormal DV. Three of this group (33%) had intrauterine fetal death or perinatal death. In patients with CHD and normal DV measurements, 83% had living children versus 33% in the group with an abnormal DV (P < .05). There was no statistically significant difference in the rate of aneuploidy between the normal DV (15%) and abnormal DV (20%) groups (P = .65). The mean gestational age at delivery was similar between the normal (37.63 weeks) and abnormal (38.33 weeks) DV groups (P = .71). There was no difference in the rate of pregnancy termination.Abnormal second-trimester DV measurements are predictive of adverse perinatal outcome in patients with CHD, independent of karyotype or gestational age at delivery. This information may have a role in the counseling of parents with CHD.
View details for DOI 10.7863/jum.2006.25.8.979
View details for Web of Science ID 000239445000005
View details for PubMedID 16870891
History of miscarriage and increased incidence of fetal aneuploidy in subsequent pregnancy
OBSTETRICS AND GYNECOLOGY
2006; 107 (5): 1098–1102
The purpose of this study was to examine the association between history of spontaneous abortion and aneuploidy in a subsequent pregnancy.This was a retrospective cohort study of women who underwent fetal karyotype analysis with amniocentesis or chorionic villus sampling at a single prenatal diagnosis center. Information on spontaneous abortions, parity, maternal age, ethnicity, type of prenatal diagnosis, and karyotype was assessed. Univariable and multivariable analyses were conducted.A total of 46,939 women were included in our analysis. Women with no prior spontaneous abortions had a 1.39% risk for any aneuploidy. In women with one prior spontaneous abortion, this risk increased to 1.67%; for women with 2 previous spontaneous abortions, the risk increased to 1.84%; and for those women who had had 3 or more prior spontaneous abortions, the risk increased further to 2.18% (P < .007). When controlling for maternal age, parity, ethnicity, and mode of prenatal diagnosis and compared with women with no prior spontaneous abortions, women with one prior spontaneous abortion (adjusted odds ratio [AOR] 1.21, 95% confidence interval [CI] 1.01-1.47) or 3 or more prior spontaneous abortions (AOR 1.51, 95% CI 1.02-2.25) had a statistically significant increase in aneuploidy in a subsequent pregnancy. Women with 2 prior spontaneous abortions had an AOR of 1.26 for aneuploidy, but the 95% CI contained unity.An increased risk of karyotypic abnormality identified at the time of prenatal diagnosis is demonstrated in patients with an increasing number of spontaneous abortions. This study provides information regarding this risk among women presenting for prenatal diagnosis. According to our data, for a woman with an a priori risk of 1 in 300 for Down syndrome, 3 prior spontaneous abortions would increase that risk by 47% to 1 in 204. These results should be confirmed in low-risk populations.
View details for DOI 10.1097/01.AOG.0000215560.86673.22
View details for Web of Science ID 000241296500019
View details for PubMedID 16648416
- Second trimester ductus venosus measurements as a predictor of adverse perinatal outcome in congenital heart disease MOSBY, INC. 2004: S173
Elevated estradiol levels in oocyte donation cycles do not impair ART outcomes for the recipients.
ELSEVIER SCIENCE INC. 2003: S165
View details for Web of Science ID 000185672400441
Chronic antepartum maternal hyperoxygenation in a case of severe fetal Ebstein's anomaly with circular shunt physiology.
Annals of pediatric cardiology
; 10 (3): 284–87
Perinatal mortality remains high among fetuses diagnosed with Ebstein's anomaly of the tricuspid valve. The subgroup of patients with pulmonary valve regurgitation is at particularly high risk. In the setting of pulmonary valve regurgitation, early constriction of the ductus arteriosus may be a novel perinatal management strategy to reduce systemic steal resulting from circular shunt physiology. We report the use of chronic antepartum maternal oxygen therapy for constriction of the fetal ductus arteriosus and modulation of fetal pulmonary vascular resistance in a late presentation of Ebstein's anomaly with severe tricuspid valve regurgitation, reversal of flow in the ductus arteriosus, and continuous pulmonary valve regurgitation.
View details for PubMedID 28928616