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1.
Am J Obstet Gynecol MFM ; 5(11): 101159, 2023 11.
Article in English | MEDLINE | ID: mdl-37709050

ABSTRACT

BACKGROUND: The Society for Maternal-Fetal Medicine uses social media to increase awareness of the Society and its key programs and to foster community and discussion around perinatal health, especially on Twitter. The influence and role of the Society for Maternal-Fetal Medicine Twitter account in public discourse around issues relevant to pregnancy have not been studied. OBJECTIVE: This study aimed to evaluate the trends in engagement with the Society for Maternal-Fetal Medicine on Twitter by analyzing Society for Maternal-Fetal Medicine follower growth and discussion topics on Twitter compared with Facebook and by quantifying public engagement during the Society for Maternal-Fetal Medicine Annual Pregnancy Meeting. STUDY DESIGN: This retrospective study analyzed follower growth data from August 2019 to July 2022 for the Society for Maternal-Fetal Medicine Twitter (@MySMFM) and Society for Maternal-Fetal Medicine Facebook (@SocietyforMaternalFetalMedicine) accounts. We identified the top 10 tweets and Facebook posts during the study period using Twitter Analytics and Facebook data. The popularity of tweets and Facebook posts was determined by "impressions" and "reach," respectively; these metrics reflect the number of times a post was viewed. To evaluate annual trends in Society for Maternal-Fetal Medicine Twitter engagement, we analyzed data associated with the Society for Maternal-Fetal Medicine Annual Pregnancy Meeting, including the number of tweets using the hashtag (#SMFM(Year)) and overall impressions for the Society for Maternal-Fetal Medicine Twitter account for each meeting from 2016 to 2023. RESULTS: The absolute number of new followers for the Society for Maternal-Fetal Medicine Twitter and Facebook accounts was similar, but the relative increase and rate of follower growth was higher for Twitter than for Facebook. The Twitter account consistently gained followers, whereas the Facebook account experienced intermittent periods of stagnancy or follower loss. More than half of the top-ranked posts on Twitter and Facebook mentioned the COVID-19 vaccine; other popular topics included COVID-19 and abortion. During the Society for Maternal-Fetal Medicine Annual Pregnancy Meeting, the number of tweets using the meeting hashtag consistently peaked on meeting day 4, coincident with the opening plenary session (mean 1270±499). An upward trend in annual pregnancy meeting tweets was observed each year until 2021-the first virtual Society for Maternal-Fetal Medicine meeting. CONCLUSION: The trends in Society for Maternal-Fetal Medicine Twitter engagement suggest increasing use and popularity of the platform for timely dissemination of pregnancy-related news, guidelines, and research. The reduction in annual pregnancy meeting tweets and impressions in 2021 and 2022 suggests the potential negative effect of virtual meetings on Society for Maternal-Fetal Medicine member engagement around annual meeting content.


Subject(s)
Social Media , Humans , Retrospective Studies , COVID-19 Vaccines , Perinatology
2.
iScience ; 26(8): 107424, 2023 Aug 18.
Article in English | MEDLINE | ID: mdl-37575192

ABSTRACT

Monochorionic-diamniotic twin pregnancies are susceptible to unique complications arising from a single placenta shared by two fetuses. Twin-twin transfusion syndrome (TTTS) is a constellation of disturbances caused by unequal blood flow within the shared placenta giving rise to a major hemodynamic imbalance between the twins. Here, we applied TTTS as a model to uncover fetal metabolic adaptations to cardiovascular stress. We compared untargeted metabolomic analyses of amniotic fluid samples from severe TTTS cases vs. singleton controls. Amniotic fluid metabolites demonstrated alterations in fatty acid, glucose, and steroid hormone metabolism in TTTS. Among TTTS cases, unsupervised principal component analysis revealed two distinct clusters of disease defined by levels of glucose metabolites, amino acids, urea, and redox status. Our results suggest that the human fetal heart can adapt to hemodynamic stress by modulating its glucose metabolism and identify potential differences in the ability of individual fetuses to respond to cardiovascular stress.

3.
Am J Obstet Gynecol MFM ; 5(10): 101077, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37399892

ABSTRACT

BACKGROUND: Among pregnant people, COVID-19 can lead to adverse outcomes, but the specific pregnancy outcomes that are affected by the disease are unclear. In addition, the effect of the severity of COVID-19 on pregnancy outcomes has not been clearly identified. OBJECTIVE: This study aimed to evaluate the associations between COVID-19 with and without viral pneumonia and cesarean delivery, preterm delivery, preeclampsia, and stillbirth. STUDY DESIGN: We conducted a retrospective cohort study (April 2020-May 2021) of deliveries between 20 and 42 weeks of gestation from US hospitals in the Premier Healthcare Database. The primary outcomes were cesarean delivery, preterm delivery, preeclampsia, and stillbirth. We used a viral pneumonia diagnosis (International Classification of Diseases -Tenth-Clinical Modification codes J12.8 and J12.9) to categorize patients by severity of COVID-19. Pregnancies were categorized into 3 groups: NOCOVID (no COVID-19), COVID (COVID-19 without viral pneumonia), and PNA (COVID-19 with viral pneumonia). Groups were balanced for risk factors by propensity-score matching. RESULTS: A total of 814,649 deliveries from 853 US hospitals were included (NOCOVID: n=799,132; COVID: n=14,744; PNA: n=773). After propensity-score matching, the risks of cesarean delivery and preeclampsia were similar in the COVID group compared with the NOCOVID group (matched risk ratio, 0.97; 95% confidence interval, 0.94-1.00; and matched risk ratio, 1.02; 95% confidence interval, 0.96-1.07; respectively). The risks of preterm delivery and stillbirth were greater in the COVID group than in the NOCOVID group (matched risk ratio, 1.11; 95% confidence interval, 1.05-1.19; and matched risk ratio, 1.30; 95% confidence interval, 1.01-1.66; respectively). The risks of cesarean delivery, preeclampsia, and preterm delivery were higher in the PNA group than in the COVID group (matched risk ratio, 1.76; 95% confidence interval, 1.53-2.03; matched risk ratio, 1.37; 95% confidence interval, 1.08-1.74; and matched risk ratio, 3.33; 95% confidence interval, 2.56-4.33; respectively). The risk of stillbirth was similar in the PNA and COVID group (matched risk ratio, 1.17; 95% confidence interval, 0.40-3.44). CONCLUSION: Within a large national cohort of hospitalized pregnant people, we found that the risk of some adverse delivery outcomes was elevated in people with COVID-19 with and without viral pneumonia, with much higher risks in the group with viral pneumonia.


Subject(s)
COVID-19 , Pneumonia, Viral , Pre-Eclampsia , Premature Birth , Pregnancy , Infant, Newborn , Female , Humans , Stillbirth , COVID-19/complications , Retrospective Studies , Pre-Eclampsia/diagnosis , Pneumonia, Viral/diagnosis
5.
Transl Pediatr ; 12(5): 1028-1040, 2023 May 30.
Article in English | MEDLINE | ID: mdl-37305724

ABSTRACT

Advances in prenatal/neonatal genetic screening practices and next generation sequencing (NGS) technologies have made the detection of molecular causes of pediatric diseases increasingly more affordable, accessible, and rapid in return of results. In the past, families searching for answers often required diagnostic journeys leading to delays in targeted care and missed diagnoses. Non-invasive prenatal NGS is now used routinely in pregnancy, significantly altering the obstetric approach to early screening and evaluation of fetal anomalies. Similarly, exome sequencing (ES) and genome sequencing (GS) were once only available for research but are now used in patient care, impacting neonatal care and the field of neonatology as a whole. In this review we will summarize the growing body of literature on the role of ES/GS in prenatal/neonatal care, specifically in neonatal intensive care units (NICU), and the molecular diagnostic yield. Furthermore, we will discuss the impact of advances in genetic testing in prenatal/neonatal care and discuss challenges faced by clinicians and families. Clinical application of NGS has come with many challenges in counseling families on interpretation of diagnostic results and incidental findings, as well as re-interpretation of prior genetic test results. How genetic results may influence medical decision-making is highly nuanced and needs further study. The ethics of parental consent and disclosure of genetic conditions with limited therapeutic options continue to be debated in the medical genetics community. While these questions remain unanswered, the benefits of a standardized approach to genetic testing in the NICU will be highlighted by two case vignettes.

6.
Am J Perinatol ; 40(5): 557-566, 2023 04.
Article in English | MEDLINE | ID: mdl-34058765

ABSTRACT

OBJECTIVE: This study aimed to evaluate whether racial and ethnic disparities in adverse perinatal outcomes exist at term. STUDY DESIGN: We performed a secondary analysis of a multicenter observational study of 115,502 pregnant patients and their neonates (2008-2011). Singleton, nonanomalous pregnancies delivered from 37 to 41 weeks were included. Race and ethnicity were abstracted from the medical record and categorized as non-Hispanic White (White; referent), non-Hispanic Black (Black), non-Hispanic Asian (Asian), or Hispanic. The primary outcome was an adverse perinatal composite defined as perinatal death, Apgar score < 4 at 5 minutes, ventilator support, hypoxic-ischemic encephalopathy, subgaleal hemorrhage, skeletal fracture, infant stay greater than maternal stay (by ≥ 3 days), brachial plexus palsy, or facial nerve palsy. RESULTS: Of the 72,117 patients included, 48% were White, 20% Black, 5% Asian, and 26% Hispanic. The unadjusted risk of the primary outcome was highest for neonates of Black patients (3.1%, unadjusted relative risk [uRR] = 1.16, 95% confidence interval [CI]: 1.04-1.30), lowest for neonates of Hispanic patients (2.1%, uRR = 0.80, 95% CI: 0.71-0.89), and no different for neonates of Asian (2.6%), compared with those of White patients (2.7%). In the adjusted model including age, body mass index (BMI), smoking, obstetric history, and high-risk pregnancy, differences in risk for the primary outcome were no longer observed for neonates of Black (adjusted relative risk [aRR] = 1.06, 95% CI: 0.94-1.19) and Hispanic (aRR = 0.92, 95% CI: 0.81-1.04) patients. Adding insurance to the model lowered the risk for both groups (aRR = 0.85, 95% CI: 0.75-0.96 for Black; aRR = 0.68, 95% CI: 0.59-0.78 for Hispanic). CONCLUSION: Although neonates of Black patients have the highest frequency of adverse perinatal outcomes at term, after adjustment for sociodemographic factors, this higher risk is no longer observed, suggesting the importance of developing strategies that address social determinants of health to lessen extant health disparities. KEY POINTS: · Term neonates of Black patients have the highest crude frequency of adverse perinatal outcomes.. · After adjustment for confounders, higher risk for neonates of Black patients is no longer observed.. · Disparities in outcomes are strongly related to insurance status..


Subject(s)
Ethnicity , Health Status Disparities , Perinatal Death , Female , Humans , Infant, Newborn , Pregnancy , Hispanic or Latino , Pregnancy, High-Risk , Retrospective Studies , White People , Black People , Asian People
7.
Obstet Gynecol ; 139(5): 846-854, 2022 05 01.
Article in English | MEDLINE | ID: mdl-35576343

ABSTRACT

OBJECTIVE: To evaluate whether pregnancy is an independent risk factor for in-hospital mortality among patients of reproductive age hospitalized with coronavirus disease 2019 (COVID-19) viral pneumonia. METHODS: We conducted a retrospective cohort study (April 2020-May 2021) of 23,574 female inpatients aged 15-45 years with an International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code for COVID-19 discharged from 749 U.S. hospitals in the Premier Healthcare Database. We used a viral pneumonia diagnosis to select for patients with symptomatic COVID-19. The associations between pregnancy and in-hospital mortality, intensive care unit (ICU) admission, and mechanical ventilation were analyzed using propensity score-matched conditional logistic regression. Models were matched for age, marital status, race and ethnicity, Elixhauser comorbidity score, payer, hospital number of beds, season of discharge, hospital region, obesity, hypertension, diabetes mellitus, chronic pulmonary disease, deficiency anemias, depression, hypothyroidism, and liver disease. RESULTS: In-hospital mortality occurred in 1.1% of pregnant patients and 3.5% of nonpregnant patients hospitalized with COVID-19 and viral pneumonia (propensity score-matched odds ratio [OR] 0.39, 95% CI 0.25-0.63). The frequency of ICU admission for pregnant and nonpregnant patients was 22.0% and 17.7%, respectively (OR 1.34, 95% CI 1.15-1.55). Mechanical ventilation was used in 8.7% of both pregnant and nonpregnant patients (OR 1.05, 95% CI 0.86-1.29). Among patients who were admitted to an ICU, mortality was lower for pregnant compared with nonpregnant patients (OR 0.33, 95% CI 0.20-0.57), though mechanical ventilation rates were similar (35.7% vs 38.3%, OR 0.90, 95% CI 0.70-1.16). Among patients with mechanical ventilation, pregnant patients had a reduced risk of in-hospital mortality compared with nonpregnant patients (0.26, 95% CI 0.15-0.46). CONCLUSION: Despite a higher frequency of ICU admission, in-hospital mortality was lower among pregnant patients compared with nonpregnant patients with COVID-19 viral pneumonia, and these findings persisted after propensity score matching.


Subject(s)
COVID-19 , Pneumonia, Viral , Female , Hospital Mortality , Hospitalization , Hospitals , Humans , Intensive Care Units , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Pregnancy , Respiration, Artificial , Retrospective Studies , Risk Factors
8.
Am J Obstet Gynecol ; 226(1): 1-11, 2022 01.
Article in English | MEDLINE | ID: mdl-34998476

ABSTRACT

Obstetricians know the statistics-1 out of every 10 babies is born premature; preeclampsia affects 1 in 25 pregnant people; the United States has the highest rate of maternal mortality in the developed world. Yet, physicians and scientists still do not fully understand the biology of normal pregnancy, let alone what causes these complications. Obstetrics and gynecology-trained physician-scientists are uniquely positioned to fill critical knowledge gaps by addressing clinically-relevant problems through fundamental research and interpreting insights from basic and translational studies in the clinical context. Within our specialty, however, physician-scientists are relatively uncommon. Inadequate guidance, lack of support and community, and structural barriers deter fellows and early stage faculty from pursuing the physician-scientist track. One approach to help cultivate the next generation of physician-scientists in obstetrics and gynecology is to demystify the process and address the common barriers that contribute to the attrition of early stage investigators. Here, we review major challenges and propose potential pathways forward in the areas of mentorship, obtaining protected research time and resources, and ensuring diversity, equity, and inclusion, from our perspective as early stage investigators in maternal-fetal medicine. We discuss the roles of early stage investigators and leaders at the institutional and national level in the collective effort to retain and grow our physician-scientist workforce. We aim to provide a framework for early stage investigators initiating their research careers and a starting point for discussion with academic stakeholders. We cannot afford to lose the valuable contributions of talented individuals due to modifiable factors or forfeit our voices as advocates for the issues that impact pregnant populations.


Subject(s)
Gynecology , Medical Laboratory Personnel , Mentors , Obstetrics , Physicians , Biomedical Research , Female , Humans , Pregnancy , United States
10.
Open Forum Infect Dis ; 8(5): ofab180, 2021 May.
Article in English | MEDLINE | ID: mdl-34056031

ABSTRACT

As the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines passed UK and US regulatory milestones in late 2020 and early 2021, multiple professional societies offered recommendations to assist pregnant and breastfeeding people as they choose whether to undergo vaccination. Despite such guidance, the lack of data describing vaccine safety, immunogenicity, and efficacy in pregnant and breastfeeding people has made this decision challenging for many. However, even considering the paucity of data, the known risks of coronavirus disease 2019 during pregnancy likely outweigh the not yet fully elucidated risks of SARS-CoV-2 vaccines, which have reassuring safety and efficacy profiles among nonpregnant people.

11.
EClinicalMedicine ; 33: 100760, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33681746
12.
Am J Obstet Gynecol ; 224(5): 484-495, 2021 05.
Article in English | MEDLINE | ID: mdl-33529575

ABSTRACT

The coronavirus disease 2019 has caused over 2 million deaths worldwide, with over 412,000 deaths reported in Unites States. To date, at least 57,786 pregnant women in the United States have been infected, and 71 pregnant women have died. Although pregnant women are at higher risk of severe coronavirus disease 2019-related illness, clinical trials for the available vaccines excluded pregnant and lactating women. The safety and efficacy of the vaccines for pregnant women, the fetus, and the newborn remain unknown. A review of maternal and neonatal coronavirus disease 2019 morbidity and mortality data along with perinatal vaccine safety considerations are presented to assist providers with shared decision-making regarding vaccine administration for this group, including the healthcare worker who is pregnant, lactating, or considering pregnancy. The coronavirus disease 2019 vaccine should be offered to pregnant women after discussing the lack of safety data, with preferential administration for those at highest risk of severe infection, until safety and efficacy of these novel vaccines are validated.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Pregnancy Complications, Infectious/prevention & control , SARS-CoV-2/immunology , Vaccination , COVID-19 Vaccines/adverse effects , Female , Humans , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy
13.
JCI Insight ; 6(2)2021 01 25.
Article in English | MEDLINE | ID: mdl-33301424

ABSTRACT

The pathogenesis of preeclampsia and other hypertensive disorders of pregnancy remains poorly defined despite the substantial burden of maternal and neonatal morbidity associated with these conditions. In particular, the role of genetic variants as determinants of disease susceptibility is understudied. Storkhead-box protein 1 (STOX1) was first identified as a preeclampsia risk gene through family-based genetic linkage studies in which loss-of-function variants were proposed to underlie increased preeclampsia susceptibility. We generated a genetic Stox1 loss-of-function mouse model (Stox1 KO) to evaluate whether STOX1 regulates blood pressure in pregnancy. Pregnant Stox1-KO mice developed gestational hypertension evidenced by a significant increase in blood pressure compared with WT by E17.5. While severe renal, placental, or fetal growth abnormalities were not observed, the Stox1-KO phenotype was associated with placental vascular and extracellular matrix abnormalities. Mechanistically, we found that gestational hypertension in Stox1-KO mice resulted from activation of the uteroplacental renin-angiotensin system. This mechanism was supported by showing that treatment of pregnant Stox1-KO mice with an angiotensin II receptor blocker rescued the phenotype. Our study demonstrates the utility of genetic mouse models for uncovering links between genetic variants and effector pathways implicated in the pathogenesis of hypertensive disorders of pregnancy.


Subject(s)
Carrier Proteins/physiology , Hypertension, Pregnancy-Induced/etiology , Placenta/abnormalities , Renin-Angiotensin System/physiology , Angiotensin II Type 1 Receptor Blockers/pharmacology , Animals , Blood Pressure/genetics , Blood Pressure/physiology , Carrier Proteins/genetics , Disease Models, Animal , Extracellular Matrix/pathology , Female , Humans , Hypertension, Pregnancy-Induced/pathology , Hypertension, Pregnancy-Induced/physiopathology , Mice , Mice, Knockout , Placenta/blood supply , Placenta/pathology , Pregnancy , RNA, Messenger/genetics , RNA, Messenger/metabolism , Renin-Angiotensin System/genetics
16.
Obstet Gynecol ; 135(4): 925-934, 2020 04.
Article in English | MEDLINE | ID: mdl-32168221

ABSTRACT

OBJECTIVE: To assess whether racial and ethnic disparities in adverse infant and maternal outcomes exist among low-risk term pregnancies. METHODS: This population-based retrospective cohort study used U.S. vital statistics data from 2014 to 2017. Women with low-risk, nonanomalous singleton pregnancies who labored and delivered at 37-41 weeks of gestation were included and categorized by maternal race and ethnicity: non-Hispanic white (white), non-Hispanic black (black), Hispanic, and non-Hispanic Asian (Asian). Multivariable Poisson regression models were used to estimate the associations of composite neonatal adverse outcome (Apgar score less than 5 at 5 minutes, assisted ventilation for more than 6 hours, neonatal seizure, or neonatal death), infant mortality, and composite maternal adverse outcome (blood transfusion, admission to the intensive care unit, uterine rupture, or unplanned hysterectomy) with maternal race and ethnicity. RESULTS: Of 9,205,873 women included, 55.5% were white, 13.7% were black, 24.3% were Hispanic, and 6.5% were Asian. Risk for the composite neonatal adverse outcome was higher among neonates of black women (unadjusted relative risk [uRR] 1.16, 95% CI 1.13-1.18; adjusted relative risk [aRR] 1.07, 95% CI 1.05-1.10), and lower for neonates of Hispanic and Asian women compared with neonates of white women. A similar pattern of disparity was observed for infant mortality; the risk for infants of black women was significantly increased (uRR 1.89, 95% CI 1.81-1.98; aRR 1.33, 95% CI 1.26-1.39). For the composite maternal adverse outcome, the risk was highest for Asian mothers (uRR 1.09, 95% CI 1.03-1.14; aRR 1.12, 95% CI 1.06-1.18), lowest for Hispanic mothers, and similar for black mothers when compared with white mothers after adjustment for confounders. CONCLUSION: Among low-risk term pregnancies, the risk for adverse outcomes varied by maternal race and ethnicity. Infants of black women were at the highest risk for neonatal morbidity and infant mortality, and Asian mothers were most likely to experience maternal adverse outcomes.


Subject(s)
Infant Mortality/trends , Maternal Mortality/trends , Adult , Apgar Score , Cohort Studies , Ethnicity , Female , Humans , Infant , Pregnancy , Pregnancy Outcome , Retrospective Studies , United States/epidemiology , Young Adult
17.
Obstet Gynecol ; 135(3): 665-673, 2020 03.
Article in English | MEDLINE | ID: mdl-32028495

ABSTRACT

OBJECTIVE: To evaluate whether abnormal plasma placental growth factor (PlGF) level is associated with adverse neonatal and maternal outcomes. METHODS: This was a secondary analysis of the Preeclampsia Triage by Rapid Assay Trial (PETRA), a prospective, multicenter, observational study that enrolled women with suspected preeclampsia. Our analysis included women age 18-45 years with a singleton pregnancy between 20 and 41 weeks of gestation. Plasma collected at enrollment was used for PlGF measurement. Abnormal PlGF was defined as low (100 pg/mL or less) or very low (less than 12 pg/mL). The primary outcomes were composite adverse neonatal and maternal outcomes. We used multivariable Poisson regression models to examine the association between PlGF and outcomes. RESULTS: Of 1,112 women who met the inclusion criteria, plasma PlGF was low in 742 (67%) and very low in 353 (32%). In the cohort, the overall rates of the composite adverse neonatal and maternal outcomes were 6.4% and 4.8%, respectively. Compared with normal PlGF (more than 100 pg/mL), low PlGF was significantly associated with an increased risk of the composite neonatal outcome (9.2% vs 0.8%; adjusted relative risk [aRR] 17.2, 95% CI 5.2-56.3), and the composite maternal outcome (6.2% vs 1.9%; aRR 3.6, 95% CI 1.7-8.0). Very low PlGF was also significantly associated with both neonatal and maternal outcomes. The sensitivity and specificity of low PlGF were 95.8% and 35.3%, respectively, for the composite neonatal outcome, and 86.8% and 34.3% for the composite maternal outcome. Although the positive predictive values were low (9.2% and 6.2%, respectively), the negative predictive value of low PlGF for neonatal and maternal outcomes was 99.2% and 98.1%, respectively. CONCLUSION: Among women being evaluated for preeclampsia, those with abnormal PlGF are significantly more likely to experience adverse neonatal and maternal outcomes. These outcomes occur infrequently when the PlGF is normal. These findings suggest that PlGF may be useful for risk stratification of women with suspected preeclampsia. FUNDING SOURCE: No funding was received for this study. The original PETRA study was supported by funding from Alere.


Subject(s)
Placenta Growth Factor/blood , Pre-Eclampsia/blood , Pregnancy Outcome/epidemiology , Female , Humans , Infant, Newborn , North America/epidemiology , Pregnancy , Prospective Studies
18.
J Clin Invest ; 128(11): 5008-5017, 2018 11 01.
Article in English | MEDLINE | ID: mdl-30179860

ABSTRACT

Preeclampsia remains a clinical challenge due to its poorly understood pathogenesis. A prevailing notion is that increased placental production of soluble fms-like tyrosine kinase-1 (sFlt-1) causes the maternal syndrome by inhibiting proangiogenic placental growth factor (PlGF) and VEGF. However, the significance of PlGF suppression in preeclampsia is uncertain. To test whether preeclampsia results from the imbalance of angiogenic factors reflected by an abnormal sFlt-1/PlGF ratio, we studied PlGF KO (Pgf-/-) mice and noted that the mice did not develop signs or sequelae of preeclampsia despite a marked elevation in circulating sFLT-1. Notably, PlGF KO mice had morphologically distinct placentas, showing an accumulation of junctional zone glycogen. We next considered the role of placental PlGF in an established model of preeclampsia (pregnant catechol-O-methyltransferase-deficient [COMT-deficient] mice) by generating mice with deletions in both the Pgf and Comt genes. Deletion of placental PlGF in the context of COMT loss resulted in a reduction in maternal blood pressure and increased placental glycogen, indicating that loss of PlGF might be protective against the development of preeclampsia. These results identify a role for PlGF in placental development and support a complex model for the pathogenesis of preeclampsia beyond an angiogenic factor imbalance.


Subject(s)
Blood Pressure , Models, Biological , Placenta Growth Factor/deficiency , Placenta/metabolism , Pre-Eclampsia/metabolism , Animals , Disease Models, Animal , Female , Glycogen/genetics , Glycogen/metabolism , Mice , Mice, Knockout , Placenta/pathology , Pre-Eclampsia/genetics , Pre-Eclampsia/pathology , Pregnancy , Vascular Endothelial Growth Factor Receptor-1/genetics , Vascular Endothelial Growth Factor Receptor-1/metabolism
19.
Prenat Diagn ; 38(2): 140-147, 2018 01.
Article in English | MEDLINE | ID: mdl-29297200

ABSTRACT

OBJECTIVE: The objective of this study was to determine the association of copy number variants (CNV) with perinatal outcomes among fetuses with sonographic abnormalities. METHODS: This was a retrospective cohort study of anomalous fetuses evaluated at a single fetal center, who underwent chromosomal microarray (CMA) testing. Pathogenic CNV or variants of uncertain significance were classified as abnormal. The primary outcome of perinatal death was compared among fetuses with normal vs abnormal CMA. Secondary outcomes included preterm birth, small for gestational age birth weight, and death prior to discharge. The odds ratio (OR) of perinatal death was determined, adjusting for potential confounders. RESULTS: Of 280 fetuses, 60 (21.4%) had abnormal CMA results-21 (35.0%) were classified as pathogenic, 39 (65.0%) were variants of uncertain significance. Among 212 (75.7%) continuing pregnancies, abnormal CMA was not associated with increased odds of perinatal death (adjusted OR 0.81, 95% CI 0.34-1.93), after adjustment for the presence of hydrops and specific anomalies. The overall frequency of perinatal death was 21.2%. No differences in secondary outcomes were observed. CONCLUSIONS: Abnormal CMA was not associated with increased odds of perinatal death in this cohort. Fetal CNV are common among fetal center patients; such fetuses are at high risk of perinatal death irrespective of CMA results.


Subject(s)
Chromosomes/genetics , Congenital Abnormalities/genetics , Microarray Analysis/methods , Prenatal Diagnosis/methods , Adult , Chromosome Aberrations/embryology , Cohort Studies , Congenital Abnormalities/diagnostic imaging , Congenital Abnormalities/embryology , Female , Humans , Infant, Newborn , Karyotyping , Male , Perinatal Death , Pregnancy , Pregnancy Outcome , Prognosis , Retrospective Studies , Ultrasonography, Prenatal
20.
Cell Rep ; 12(5): 760-73, 2015 Aug 04.
Article in English | MEDLINE | ID: mdl-26212322

ABSTRACT

The evolutionarily conserved miR-302 family of microRNAs is expressed during early mammalian embryonic development. Here, we report that deletion of miR-302a-d in mice results in a fully penetrant late embryonic lethal phenotype. Knockout embryos have an anterior neural tube closure defect associated with a thickened neuroepithelium. The neuroepithelium shows increased progenitor proliferation, decreased cell death, and precocious neuronal differentiation. mRNA profiling at multiple time points during neurulation uncovers a complex pattern of changing targets over time. Overexpression of one of these targets, Fgf15, in the neuroepithelium of the chick embryo induces precocious neuronal differentiation. Compound mutants between mir-302 and the related mir-290 locus have a synthetic lethal phenotype prior to neurulation. Our results show that mir-302 helps regulate neurulation by suppressing neural progenitor expansion and precocious differentiation. Furthermore, these results uncover redundant roles for mir-290 and mir-302 early in development.


Subject(s)
Cell Differentiation/physiology , Embryo, Mammalian/embryology , MicroRNAs/biosynthesis , Neural Stem Cells/metabolism , Neural Tube/embryology , Animals , Chick Embryo , Embryo, Mammalian/cytology , Mice , MicroRNAs/genetics , Neural Stem Cells/cytology , Neural Tube/cytology
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