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OBJECTIVE: Fetal head and neck masses can result in critical airway obstruction. Our study aimed to evaluate prenatal factors associated with the decision for a definitive airway, including ex-utero intrapartum treatment (EXIT), at birth among at-risk fetuses. METHODS: A single-institution retrospective review evaluated all fetal head and neck masses prenatally diagnosed from 2005 to 2023. The primary outcome was the decision for a definitive airway at birth, including intubation, tracheostomy, or EXIT. RESULTS: Thirty four patients were included, with 23 deliveries occurring at our institution. 8/23 (35%) patients received a definitive airway at birth, six underwent an EXIT procedure, and two required intubation only. Patients who received a definitive airway had higher rates of polyhydramnios (50% vs. 7%, p = 0.03), tracheal narrowing on ultrasound (US) (50% vs. 0%, p = 0.01), tracheal displacement on US (63% vs. 0%, p < 0.01), abnormal fetal breathing on US (50% vs. 0%, p = 0.01), tracheal narrowing or displacement on magnetic resonance imaging (MRI) (75% vs. 7%, p < 0.01), and larger mass maximum diameter (7.9 vs. 4.3 cm, p = 0.02). In our series, 100% of patients with polyhydramnios, tracheal narrowing or displacement on either US or MRI, and abnormal fetal breathing on US received a definitive airway at birth. CONCLUSION: Prenatal findings of tracheal narrowing or displacement, polyhydramnios, and abnormal fetal breathing are strongly associated with the decision for a definitive airway at birth and warrant mobilization of appropriate resources.
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Birthing mechanics are poorly understood, though many injuries during childbirth are mechanical, like fetal and maternal tissue damage. Several biomechanical simulation models of parturition have been proposed to investigate birth, but many do not include the uterus. Additionally, most solid models rely on segmenting anatomical structures from clinical images to generate patient geometry, which can be time-consuming. This work presents two new parametric solid modeling methods for generating patient-specific, at-term uterine three-dimensional geometry. Building from an established method of modeling the sagittal uterine shape, this work improves the uterine coronal shape, especially where the fetal head joins the lower uterine wall. Solid models of the uterus and cervix were built from five at-term patients' magnetic resonance imaging (MRI) sets. Using anatomy measurements from MRI-segmented models, two parametric models were created-one that employs an averaged coronal uterine shape and one with multiple axial measurements of the coronal uterus. Through finite element analysis, the two new parametric methods were compared to the MRI-segmented high-fidelity method and a previously published elliptical low-fidelity method. A clear improvement in the at-term uterine shape was found using the two new parametric methods, and agreement in principal Lagrange strain directions was observed across all modeling methods. These methods provide an effective and efficient way to generate three-dimensional solid models of patient-specific maternal uterine anatomy, advancing possibilities for future research in computational birthing biomechanics.
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Imagenología Tridimensional , Útero , Femenino , Humanos , Útero/diagnóstico por imagen , Imagen por Resonancia Magnética , Cuello del Útero , Simulación por ComputadorRESUMEN
INTRODUCTION: Limited data exist regarding outcomes when pre- and periviable PPROM (PPROM ≤26 weeks of gestation) occurs as a complication of fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS). METHODS: This is a retrospective cohort study of FLS cases performed at a single institution between January 2015 and May 2021. Study inclusion was limited to patients with monochorionic-diamniotic twin pregnancies complicated by TTTS who underwent FLS. Patients were grouped by pPPROM status, and further stratified to those continuing with expectant management, and outcomes were compared between groups. The primary outcome was survival to live birth of at least one twin. RESULTS: During the study period, 171 patients underwent FLS and a total of 96 (56.1%) subjects satisfied inclusion criteria. Among included subjects, 18 (18.8%) experienced pPPROM after FLS and 78 (81.2%) did not. Baseline characteristics were similar between groups. Among patients with pPPROM, 11 (61.1%) pursued expectant management and 7 (38.9%) opted for pregnancy termination. Among expectantly managed subjects, median pPPROM-to-delivery interval was 47.0 days (6.0-66.0 IQR) with a median gestational age at delivery of 29+1 weeks (24 + 4-33 + 6 IQR). Rates of survival to live birth of at least one twin (90.9% vs. 96.2% p = 0.42) were similar between those with pPPROM undergoing expectant management and those without pPPROM. Dual survivorship (45.5% vs. 78.2%, p = 0.03), perinatal survival to live birth (68.2% vs. 87.2%, p = 0.05), and perinatal survival to newborn hospital discharge (59.1% vs. 85.9%, p = <0.01) were all significantly lower among those with pPPROM. Gestational age at delivery was lower among those continuing with pregnancies complicated by pPPROM (29 + 1 vs. 32+5 weeks, p = <0.01). CONCLUSION: Survival of at least one twin to live birth remained high among those pursing expectant management after experiencing post-FLS pPPROM, suggesting that the outlook after this complication is not necessarily poor. However, this complication was associated with lower chances of dual survival and greater prematurity.
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OBJECTIVE: Congenital lymphatic anomalies (LAs) arise due to defects in lymphatic development and often present in utero as pleural effusion, chylothorax, nuchal and soft tissue edema, ascites, or hydrops. Many LAs are caused by single nucleotide variants, which are not detected on routine prenatal testing. METHODS: Demographic data were compared between two subcohorts, those with clinically significant fetal edema (CSFE) and isolated fetal edema. A targeted variant analysis of LA genes was performed using American College of Medical Genetics criteria on whole exome sequencing (WES) data generated for 71 fetal edema cases who remained undiagnosed after standard workup. RESULTS: CSFE cases had poor outcomes, including preterm delivery, demise, and maternal preeclampsia. Pathogenic and likely pathogenic variants were identified in 7% (5/71) of cases, including variants in RASopathy genes, RASA1, SOS1, PTPN11, and a novel PIEZO1 variant. Variants of uncertain significance (VOUS) were identified in 45% (32/71) of cases. In CSFEs, VOUS were found in CELSR1, EPHB4, TIE1, PIEZO1, ITGA9, RASopathy genes, SOS1, SOS2, and RAF1. CONCLUSIONS: WES identified pathogenic and likely pathogenic variants and VOUS in LA genes in 51% of fetal edema cases, supporting WES and expanded hydrops panels in cases of idiopathic fetal hydrops and fluid collections.
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Hidropesía Fetal , Anomalías Linfáticas , Embarazo , Recién Nacido , Femenino , Humanos , Hidropesía Fetal/diagnóstico , Hidropesía Fetal/genética , Feto/anomalías , Anomalías Linfáticas/genética , Canales Iónicos , Proteína Activadora de GTPasa p120RESUMEN
Rationale: Knowledge gaps exist regarding health implications of sleep-disordered breathing (SDB) identified in pregnancy and/or after delivery. Objectives: To determine whether SDB in pregnancy and/or after delivery is associated with hypertension (HTN) and metabolic syndrome (MS). Methods: nuMoM2b-HHS (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be Heart Health Study) (N = 4,508) followed participants initially recruited during their first pregnancy. Participants returned for a visit 2-7 years after pregnancy. This study examined a subgroup who underwent SDB assessments during their first pregnancy (n = 1,964) and a repeat SDB assessment after delivery (n = 1,222). Two SDB definitions were considered: 1) apnea-hypopnea index (AHI) ⩾ 5 and 2) oxygen desaturation index (ODI) ⩾ 5. Associations between SDB and incident HTN and MS were evaluated with adjusted risk ratios (aRRs). Measurements and Main Results: The aRR for MS given an AHI ⩾ 5 during pregnancy was 1.44 (95% confidence interval [CI], 1.08-1.93), but no association with HTN was found. ODI ⩾ 5 in pregnancy was associated with both an increased risk for HTN (aRR, 2.02; 95% CI, 1.30-3.14) and MS (aRR, 1.53; 95% CI, 1.19-1.97). Participants with an AHI ⩾ 5 in pregnancy that persisted after delivery were at higher risk for both HTN (aRR, 3.77; 95% CI, 1.84-7.73) and MS (aRR, 2.46; 95% CI, 1.59-3.76). Similar associations were observed for persistent ODI ⩾ 5 after delivery. Conclusions: An AHI ⩾ 5 in pregnancy was associated with an increased risk of MS. An ODI ⩾ 5 in pregnancy was significantly associated with both HTN and MS. Participants with persistent elevations in AHI and ODI during pregnancy and at 2-7 years after delivery were at the highest risk for HTN and MS. Clinical trial registered with www.clinicaltrials.gov (NCT02231398).
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Enfermedades Cardiovasculares , Síndromes de la Apnea del Sueño , Enfermedades Cardiovasculares/complicaciones , Femenino , Humanos , Oportunidad Relativa , Oxígeno , Polisomnografía , Embarazo , Factores de Riesgo , Síndromes de la Apnea del Sueño/complicacionesRESUMEN
OBJECTIVE: We aimed to investigate the utility of comprehensive screening fetal echocardiography (FE) for patients diagnosed with any type of fetal extracardiac malformation (ECM) at a single multidisciplinary fetal center. METHODS: We retrospectively reviewed all patients presenting to our referral center for FE due to a prenatal diagnosis of ECM (January 2013-December 2018). RESULTS: Among 641 patients with ≥1 ECM referred for FE, 78 (12.2%) had CHD diagnosed at 25.6 ± 0.5 weeks. The frequency of CHD by type of ECM ranged from 35.1% for craniofacial to 9.8% for thoracic. Increasing number of fetal ECMs was strongly associated with CHD: odds ratio 2.01 (95% confidence interval: 1.06-3.69) for two ECMs, 9.57 (2.00-49.05) for three ECMs, and 11.68 (3.84-37.15) for more than three ECMs. Of fetuses with ECM and an abnormal genetic finding, 33.3% had CHD as compared to 10.9% of those without (p < 0.0001). Obstetric anatomy sonogram detected 43.6% of CHD. CONCLUSION: CHD was commonly diagnosed among fetuses with any type of ECM at our center but was not always detected on obstetric sonogram. As the presence of CHD may impact decision-making and perinatal care, patients with a diagnosis of any fetal ECM should be considered for FE.
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Anomalías Congénitas/diagnóstico , Ecocardiografía/métodos , Feto/diagnóstico por imagen , Adulto , Anomalías Congénitas/diagnóstico por imagen , Ecocardiografía/tendencias , Femenino , Edad Gestacional , Humanos , Pruebas Prenatales no Invasivas/instrumentación , Pruebas Prenatales no Invasivas/métodos , Pruebas Prenatales no Invasivas/tendencias , Embarazo , Estudios RetrospectivosRESUMEN
OBJECTIVE: Our institution is in an area of New York City with a large population of immigrants from Zika virus endemic areas. With the recent Zika virus outbreak, we sought to examine our center's experience with screening for Zika virus and outcomes among patients who tested positive for the disease during pregnancy. STUDY DESIGN: We performed a chart review of all pregnant patients who tested positive (positive serum or urine polymerase chain reaction [PCR]) or presumed positive (immunoglobulin M [IgM] enzyme-linked immunosorbent assay [ELISA] positive or IgM ELISA equivocal with positive plaque reduction neutralization test) for Zika virus. All tests were performed by the Department of Health (DOH) and followed Centers for Disease Control and Prevention guidelines in effect at the time of specimen collection. Testing of cord blood, placenta, and/or neonatal blood were/was performed by the DOH for New York County. Prenatal ultrasounds for fetal head size and surveillance for calcifications were performed by maternal-fetal medicine specialists. Infant head ultrasound results were included when available. RESULTS: Between March 2016 and April 2017, 70 pregnant patients were positive or presumed positive for Zika infection during pregnancy. Of those, 16 women had positive urine or serum PCR and the remaining 54 were presumed positive. Among positive cases, five women tested positive via urine PCR only, nine women tested positive via serum PCR only, and two women had both positive urine and serum PCR. Fifteen of 67 infants (22%) born during the study period were born to mothers with positive urine or serum PCR testing. Sixty-five newborns were clinically normal with normal head measurements. Of the intracranial ultrasound performed, one infant had a grade 1 intraventricular hemorrhage, four had incidental choroid plexus cysts, and one had severe ventriculomegaly that was also noted antenatally. There were 2 positive and 15 equivocal infant serum IgM samples and 1 positive placental PCR from these pregnancies. There were four pregnancy terminations and two cases with fetal anomalies in this population that were split evenly between patients who tested positive and those who tested presumed positive for Zika virus during pregnancy. CONCLUSION: We found no differences in pregnancy or neonatal outcomes between women who tested positive and presumed positive for Zika virus during pregnancy. Testing of infants and placenta tissue after delivery was largely inconclusive. Improvement in testing for Zika virus infection is needed to determine which pregnancies are at risk for congenital anomalies. Further research is still needed to determine which children are at risk for poor neurodevelopmental outcomes related to Zika virus and how to best coordinate care among the immigrant population during a new disease epidemic.
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Encefalopatías/diagnóstico por imagen , Emigrantes e Inmigrantes , Complicaciones Infecciosas del Embarazo/diagnóstico , Infección por el Virus Zika/diagnóstico , Virus Zika/aislamiento & purificación , Adulto , Anticuerpos Antivirales/sangre , Encéfalo/diagnóstico por imagen , Continuidad de la Atención al Paciente , República Dominicana/etnología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina M/sangre , Recién Nacido , Masculino , Tamizaje Masivo , Ciudad de Nueva York/epidemiología , Reacción en Cadena de la Polimerasa , Embarazo , Complicaciones Infecciosas del Embarazo/sangre , Complicaciones Infecciosas del Embarazo/epidemiología , Ultrasonografía , Adulto Joven , Virus Zika/genética , Virus Zika/inmunología , Infección por el Virus Zika/sangre , Infección por el Virus Zika/epidemiologíaRESUMEN
OBJECTIVE: This study aimed to (1) determine to what degree prenatal care was able to be transitioned to telehealth at prenatal practices associated with two affiliated hospitals in New York City during the novel coronavirus disease 2019 (COVID-19) pandemic and (2) describe providers' experience with this transition. STUDY DESIGN: Trends in whether prenatal care visits were conducted in-person or via telehealth were analyzed by week for a 5-week period from March 9 to April 12 at Columbia University Irving Medical Center (CUIMC)-affiliated prenatal practices in New York City during the COVID-19 pandemic. Visits were analyzed for maternal-fetal medicine (MFM) and general obstetrical faculty practices, as well as a clinic system serving patients with public insurance. The proportion of visits that were telehealth was analyzed by visit type by week. A survey and semistructured interviews of providers were conducted evaluating resources and obstacles in the uptake of telehealth. RESULTS: During the study period, there were 4,248 visits, of which approximately one-third were performed by telehealth (n = 1,352, 31.8%). By the fifth week, 56.1% of generalist visits, 61.5% of MFM visits, and 41.5% of clinic visits were performed via telehealth. A total of 36 providers completed the survey and 11 were interviewed. Accessing technology and performing visits, documentation, and follow-up using the telehealth electronic medical record were all viewed favorably by providers. In transitioning to telehealth, operational challenges were more significant for health clinics than for MFM and generalist faculty practices with patients receiving public insurance experiencing greater difficulties and barriers to care. Additional resources on the patient and operational level were required to optimize attendance at in-person and video visits for clinic patients. CONCLUSION: Telehealth was rapidly implemented in the setting of the COVID-19 pandemic and was viewed favorably by providers. Limited barriers to care were observed for practices serving patients with commercial insurance. However, to optimize access for patients with Medicaid, additional patient-level and operational supports were required. KEY POINTS: · Telehealth uptake differed based on insurance.. · Medicaid patients may require increased assistance for telehealth.. · Quick adoption of telehealth is feasible..
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Infecciones por Coronavirus/prevención & control , Personal de Salud/organización & administración , Pandemias/estadística & datos numéricos , Seguridad del Paciente/estadística & datos numéricos , Neumonía Viral/prevención & control , Atención Prenatal/métodos , Telemedicina/estadística & datos numéricos , Centros Médicos Académicos , Adulto , Actitud del Personal de Salud , COVID-19 , Infecciones por Coronavirus/epidemiología , Estudios de Evaluación como Asunto , Femenino , Edad Gestacional , Humanos , Control de Infecciones/métodos , Medicaid/estadística & datos numéricos , Ciudad de Nueva York , Pandemias/prevención & control , Neumonía Viral/epidemiología , Embarazo , Investigación Cualitativa , Telemedicina/tendencias , Cuidado de Transición/organización & administración , Estados UnidosRESUMEN
BACKGROUND: Sleep-disordered breathing (SDB) is common in pregnancy, but there are limited data on predictors. OBJECTIVES: The objective of this study was to develop predictive models of sleep-disordered breathing during pregnancy. STUDY DESIGN: Nulliparous women completed validated questionnaires to assess for symptoms related to snoring, fatigue, excessive daytime sleepiness, insomnia, and restless leg syndrome. The questionnaires included questions regarding the timing of sleep and sleep duration, work schedules (eg, shift work, night work), sleep positions, and previously diagnosed sleep disorders. Frequent snoring was defined as self-reported snoring ≥3 days per week. Participants underwent in-home portable sleep studies for sleep-disordered breathing assessment in early (6-15 weeks gestation) and mid pregnancy (22-31 weeks gestation). Sleep-disordered breathing was characterized by an apnea hypopnea index that included all apneas, plus hypopneas with ≥3% oxygen desaturation. For primary analyses, an apnea hypopnea index ≥5 events per hour was used to define sleep-disordered breathing. Odds ratios and 95% confidence intervals were calculated for predictor variables. Predictive ability of the logistic models was estimated with area under the receiver-operating-characteristic curves, along with sensitivities, specificities, and positive and negative predictive values and likelihood ratios. RESULTS: Among 3705 women who were enrolled, data were available for 3264 and 2512 women in early and mid pregnancy, respectively. The corresponding prevalence of sleep-disordered breathing was 3.6% and 8.3%, respectively. At each time point in gestation, frequent snoring, chronic hypertension, greater maternal age, body mass index, neck circumference, and systolic blood pressure were associated most strongly with an increased risk of sleep-disordered breathing. Logistic regression models that included current age, body mass index, and frequent snoring predicted sleep-disordered breathing in early pregnancy, sleep-disordered breathing in mid pregnancy, and new onset sleep-disordered breathing in mid pregnancy with 10-fold cross-validated area under the receiver-operating-characteristic curves of 0.870, 0.838, and 0.809. We provide a supplement with expanded tables, integrated predictiveness, classification curves, and an predicted probability calculator. CONCLUSION: Among nulliparous pregnant women, logistic regression models with just 3 variables (ie, age, body mass index, and frequent snoring) achieved good prediction of prevalent and incident sleep-disordered breathing. These results can help with screening for sleep-disordered breathing in the clinical setting and for future clinical treatment trials.
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Presión Sanguínea/fisiología , Índice de Masa Corporal , Hipertensión/complicaciones , Edad Materna , Complicaciones del Embarazo/etiología , Síndromes de la Apnea del Sueño/etiología , Ronquido/etiología , Adolescente , Adulto , Femenino , Humanos , Hipertensión/fisiopatología , Polisomnografía , Embarazo , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/fisiopatología , Prevalencia , Factores de Riesgo , Síndromes de la Apnea del Sueño/epidemiología , Síndromes de la Apnea del Sueño/fisiopatología , Ronquido/epidemiología , Ronquido/fisiopatología , Adulto JovenRESUMEN
BACKGROUND: Experimental and epidemiologic data suggest that among nonpregnant adults, sleep duration may be an important risk factor for chronic disease. Although pregnant women commonly report poor sleep, few studies objectively evaluated the quality of sleep in pregnancy or explored the relationship between sleep disturbances and maternal and perinatal outcomes. OBJECTIVE: Our objective was to examine the relationship between objectively assessed sleep duration, timing, and continuity (measured via wrist actigraphy) and maternal cardiovascular and metabolic morbidity specific to pregnancy. STUDY DESIGN: This was a prospective cohort study of nulliparous women. Women were recruited between 16 0/7 and 21 6/7 weeks' gestation. They were asked to wear a wrist actigraphy monitor and complete a daily sleep log for a period of 7 consecutive days. The primary sleep exposure variables were the averages of the following over the total valid nights (minimum 5, maximum 7 nights): short sleep duration during the primary sleep period (<7 h/night), late sleep midpoint (midpoint between sleep onset and sleep offset >5 am), and top quartile of minutes of wake time after sleep onset and sleep fragmentation index. The primary outcomes of interest were a composite of hypertensive disorders of pregnancy (mild, severe, or superimposed preeclampsia; eclampsia; or antepartum gestational hypertension) and gestational diabetes mellitus. We used χ2 tests to assess associations between sleep variables and categorical baseline characteristics. Crude odds ratios and 95% confidence intervals were estimated from univariate logistic regression models to characterize the magnitude of the relationship between sleep characteristics and hypertensive disorders of pregnancy and gestational diabetes. For associations significant in univariate analysis, multiple logistic regression was used to explore further the association of sleep characteristics with pregnancy outcomes. RESULTS: In all, 901 eligible women consented to participate; 782 submitted valid actigraphy studies. Short sleep duration and a later sleep midpoint were associated with an increased risk of gestational diabetes (odds ratio, 2.24; 95% confidence interval, 1.11-4.53; and odds ratio, 2.58; 95% confidence interval, 1.24-5.36, respectively) but not of hypertensive disorders. A model with both sleep duration and sleep midpoint as well as their interaction term revealed that while there was no significant interaction between these exposures, the main effects of both short sleep duration and later sleep midpoint with gestational diabetes remained significant (adjusted odds ratio, 2.06; 95% confidence interval, 1.01-4.19; and adjusted odds ratio, 2.37; 95% confidence interval, 1.13-4.97, respectively). Additionally, after adjusting separately for age, body mass index, and race/ethnicity, both short sleep duration and later sleep midpoint remained associated with gestational diabetes. No associations were demonstrated between the sleep quality measures (wake after sleep onset, sleep fragmentation) and hypertensive disorders or gestational diabetes. CONCLUSION: Our results demonstrate a relationship between short sleep duration and later sleep midpoint with gestational diabetes. Our data suggest independent contributions of these 2 sleep characteristics to the risk for gestational diabetes in nulliparous women.
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Diabetes Gestacional/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Actigrafía , Adulto , Índice de Masa Corporal , Estudios de Cohortes , Femenino , Humanos , Hipertensión Inducida en el Embarazo/epidemiología , Admisión y Programación de Personal , Embarazo , Grupos Raciales , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Preterm birth is the leading cause of childhood mortality and can lead to health risks in survivors. The mechanical functions of the uterus, fetal membranes, and cervix have dynamic roles to protect the fetus during gestation. To understand their mechanical function and relation to preterm birth, we built a three-dimensional parameterized finite element model of pregnancy. This model is generated by an automated procedure that is informed by maternal ultrasound measurements. A baseline model at 25 weeks of gestation was characterized, and to visualize the impact of cervical structural parameters on tissue stretch, we evaluated the model sensitivity to (1) anterior uterocervical angle, (2) cervical length, (3) posterior cervical offset, and (4) cervical stiffness. We found that cervical tissue stretching is minimal when the cervical canal is aligned with the longitudinal uterine axis, and a softer cervix is more sensitive to changes in the geometric variables tested.
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Análisis de Elementos Finitos , Fenómenos Mecánicos , Ultrasonografía , Adulto , Fenómenos Biomecánicos , Cuello del Útero/anatomía & histología , Cuello del Útero/diagnóstico por imagen , Femenino , Humanos , Embarazo , Útero/anatomía & histología , Útero/diagnóstico por imagenRESUMEN
Allele-specific DNA methylation (ASM) is well studied in imprinted domains, but this type of epigenetic asymmetry is actually found more commonly at non-imprinted loci, where the ASM is dictated not by parent-of-origin but instead by the local haplotype. We identified loci with strong ASM in human tissues from methylation-sensitive SNP array data. Two index regions (bisulfite PCR amplicons), one between the C3orf27 and RPN1 genes in chromosome band 3q21 and the other near the VTRNA2-1 vault RNA in band 5q31, proved to be new examples of imprinted DMRs (maternal alleles methylated) while a third, between STEAP3 and C2orf76 in chromosome band 2q14, showed non-imprinted haplotype-dependent ASM. Using long-read bisulfite sequencing (bis-seq) in 8 human tissues we found that in all 3 domains the ASM is restricted to single differentially methylated regions (DMRs), each less than 2kb. The ASM in the C3orf27-RPN1 intergenic region was placenta-specific and associated with allele-specific expression of a long non-coding RNA. Strikingly, the discrete DMRs in all 3 regions overlap with binding sites for the insulator protein CTCF, which we found selectively bound to the unmethylated allele of the STEAP3-C2orf76 DMR. Methylation mapping in two additional genes with non-imprinted haplotype-dependent ASM, ELK3 and CYP2A7, showed that the CYP2A7 DMR also overlaps a CTCF site. Thus, two features of imprinted domains, highly localized DMRs and allele-specific insulator occupancy by CTCF, can also be found in chromosomal domains with non-imprinted ASM. Arguing for biological importance, our analysis of published whole genome bis-seq data from hES cells revealed multiple genome-wide association study (GWAS) peaks near CTCF binding sites with ASM.
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Alelos , Proteínas Sanguíneas/genética , Metilación de ADN/genética , Proteínas Fetales/genética , Estudio de Asociación del Genoma Completo , Impresión Genómica , Proteínas Oncogénicas/genética , Hidrocarburo de Aril Hidroxilasas/genética , Factor de Unión a CCCTC , Cromosomas/genética , Familia 2 del Citocromo P450 , Haplotipos , Humanos , Polimorfismo de Nucleótido Simple , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-ets , ARN Largo no Codificante/genética , Proteínas Represoras/genética , Sensibilidad y Especificidad , Factores de Transcripción/genéticaRESUMEN
OBJECTIVE: The objective of the Sleep Disordered Breathing substudy of the Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be (nuMoM2b) is to determine whether sleep disordered breathing during pregnancy is a risk factor for adverse pregnancy outcomes. STUDY DESIGN: NuMoM2b is a prospective cohort study of 10,037 nulliparous women with singleton gestations that was conducted across 8 sites with a central Data Coordinating and Analysis Center. The Sleep Disordered Breathing substudy recruited 3702 women from the cohort to undergo objective, overnight in-home assessments of sleep disordered breathing. A standardized level 3 home sleep test was performed between 6(0)-15(0) weeks' gestation (visit 1) and again between 22(0)-31(0) weeks' gestation (visit 3). Scoring of tests was conducted by a central Sleep Reading Center. Participants and their health care providers were notified if test results met "urgent referral" criteria that were based on threshold levels of apnea hypopnea indices, oxygen saturation levels, or electrocardiogram abnormalities but were not notified of test results otherwise. The primary pregnancy outcomes to be analyzed in relation to maternal sleep disordered breathing are preeclampsia, gestational hypertension, gestational diabetes mellitus, fetal growth restriction, and preterm birth. RESULTS: Objective data were obtained at visit 1 on 3261 women, which was 88.1% of the studies that were attempted and at visit 3 on 2511 women, which was 87.6% of the studies that were attempted. Basic characteristics of the substudy cohort are reported in this methods article. CONCLUSION: The substudy was designed to address important questions regarding the relationship of sleep-disordered breathing on the risk of preeclampsia and other outcomes of relevance to maternal and child health.
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Complicaciones del Embarazo/etiología , Proyectos de Investigación , Síndromes de la Apnea del Sueño/complicaciones , Adolescente , Adulto , Protocolos Clínicos , Método Doble Ciego , Femenino , Humanos , Polisomnografía , Embarazo , Complicaciones del Embarazo/diagnóstico , Resultado del Embarazo , Estudios Prospectivos , Factores de Riesgo , Síndromes de la Apnea del Sueño/diagnóstico , Adulto JovenRESUMEN
The coordinated biomechanical performance, such as uterine stretch and cervical barrier function, within maternal reproductive tissues facilitates healthy human pregnancy and birth. Quantifying normal biomechanical function and detecting potentially detrimental biomechanical dysfunction (e.g., cervical insufficiency, uterine overdistention, premature rupture of membranes) is difficult, largely due to minimal data on the shape and size of maternal anatomy and material properties of tissue across gestation. This study quantitates key structural features of human pregnancy to fill this knowledge gap and facilitate three-dimensional modeling for biomechanical pregnancy simulations to deeply explore pregnancy and childbirth. These measurements include the longitudinal assessment of uterine and cervical dimensions, fetal weight, and cervical stiffness in 47 low-risk pregnancies at four time points during gestation (late first, middle second, late second, and middle third trimesters). The uterine and cervical size were measured via 2-dimensional ultrasound, and cervical stiffness was measured via cervical aspiration. Trends in uterine and cervical measurements were assessed as time-course slopes across pregnancy and between gestational time points, accounting for specific participants. Patient-specific computational solid models of the uterus and cervix, generated from the ultrasonic measurements, were used to estimate deformed uterocervical volume. Results show that for this low-risk cohort, the uterus grows fastest in the inferior-superior direction from the late first to middle second trimester and fastest in the anterior-posterior and left-right direction between the middle and late second trimester. Contemporaneously, the cervix softens and shortens. It softens fastest from the late first to the middle second trimester and shortens fastest between the late second and middle third trimester. Alongside the fetal weight estimated from ultrasonic measurements, this work presents holistic maternal and fetal patient-specific biomechanical measurements across gestation.
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OBJECTIVE: The purpose of the study was to evaluate whether 17-alpha-hydroxyprogesterone caproate (17-OHPC) exposure is associated with the rate of cervical shortening. STUDY DESIGN: Women with a history of spontaneous preterm delivery (PTD) at <37 weeks' gestation who had serial cervical length measurements (2009-2012) were identified. 17-OHPC administration and outcome data were collected. We excluded patients with multiple gestations, indicated PTDs, major fetal anomalies, cerclage, and vaginal progesterone use. The rate of cervical shortening was modeled in relation to 17-OHPC status with the use of methods for longitudinal data analysis. RESULTS: Two hundred thirty-seven patients with 1171 cervical length measurements were included, of whom 184 patients (77.6%) were exposed to 17-OHPC. Gestational age, number of previous PTDs, gestational age at initiation, and interval between cervical length examinations were similar between the 2 groups, although women who were not exposed to 17-OHPC were more likely to have delivered multiples in their previous PTD (24.5% vs 4.4%; P < .01). In the entire cohort, the rate of cervical shortening was identical, regardless of 17-OHPC exposure (0.85 mm per week). Among term deliveries, the rates of cervical shortening per week, on average, were 0.9 and 0.8 mm per week among women with and without 17-OHPC, respectively (P = .76). Among preterm deliveries, the corresponding rates were 0.8 and 1.2 mm, respectively, among women with and without 17-OHPC (P = .67). CONCLUSION: Cervical shortening among women with previous preterm delivery occurs at a similar rate, regardless of exposure to 17-OHPC.
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Cuello del Útero/efectos de los fármacos , Hidroxiprogesteronas/farmacología , Nacimiento Prematuro/prevención & control , Caproato de 17 alfa-Hidroxiprogesterona , Adulto , Medición de Longitud Cervical , Cuello del Útero/fisiología , Femenino , Humanos , EmbarazoRESUMEN
BACKGROUND: Although peripartum hysterectomy for placenta accreta spectrum disorder is known to be associated with complications at the time of delivery, there are limited data on postpartum outcomes and readmission risk in this population. OBJECTIVE: This study aimed to analyze risks for adverse outcomes and postpartum readmissions in the setting of peripartum hysterectomy for placenta accreta spectrum disorder by severity of placenta accreta spectrum disorder subcategory. STUDY DESIGN: Using the 2016-2020 Nationwide Readmissions Database, this retrospective cohort study identified peripartum hysterectomies with a diagnosis of placenta accreta spectrum disorder. The primary exposure was placenta accreta spectrum disorder, subcategorized as placenta accreta vs increta/percreta. The primary outcome was readmission rate and delivery complications. Complications evaluated included the following: (1) nontransfusion severe maternal morbidity (ntSMM), (2) venous thromboembolism, (3) reoperation, (4) intraoperative complications, (5) hemorrhage, (6) sepsis, and (7) surgical site complications. We additionally evaluated delivery hospitalization and readmission mean length of stay, and hospital costs. Unadjusted and adjusted logistic regression models were fit for outcomes adjusting for clinical, demographic, and hospital factors. The association measures were expressed as unadjusted and adjusted odds ratios with 95% confidence intervals. RESULTS: Between 2016 and 2020, 7864 hysterectomies during a delivery hospitalization with a diagnosis of placenta accreta spectrum disorder were identified (66.5% with placenta accreta and 33.5% with placenta increta/percreta diagnoses). The overall 60-day all-cause readmission rate was 7.3%. Most readmissions (57.2%) occurred within 10 days of hospital discharge. Compared with peripartum hysterectomy with a diagnosis of placenta accreta, hysterectomies with placenta increta/percreta diagnoses carried significantly increased risk of 60-day readmission (adjusted odds ratio, 1.31; 95% confidence interval, 1.01-1.71), inpatient mortality (odds ratio, 13.23; 95% confidence interval, 3.35-52.30), nontransfusion severe maternal morbidity (adjusted odds ratio, 1.43; 95% confidence interval, 1.20-1.71), intraoperative complications (adjusted odds ratio, 2.31; 95% confidence interval, 1.93-2.77), and surgical site complications (adjusted odds ratio, 1.55; 95% confidence interval, 1.23-1.95). The median length of stay during delivery hospitalization was longer for placenta increta/percreta (5.8 days; 95% confidence interval, 5.4-6.1) than for placenta accreta (4.2 days; 95% confidence interval, 4.1-4.3; P<.05). In addition, delivery hospitalization costs were higher in cases of placenta increta/percreta (median, $30,686; 95% confidence interval, $28,922-$32,449) than placenta accreta (median, $21,321; 95% confidence interval, $20,480-$22,163). CONCLUSION: Complication and readmission risks after peripartum hysterectomy with placenta accreta spectrum disorder are high. Compared with patients with placenta accreta, patients with placenta increta/percreta had increased risk for delivery and postoperative complications and postpartum readmission, and increased costs and length of stay.
Asunto(s)
Placenta Accreta , Hemorragia Posparto , Embarazo , Femenino , Humanos , Placenta Accreta/diagnóstico , Placenta Accreta/epidemiología , Placenta Accreta/cirugía , Hemorragia Posparto/epidemiología , Hemorragia Posparto/etiología , Estudios Retrospectivos , Periodo Periparto , Histerectomía/efectos adversos , Complicaciones Intraoperatorias/cirugíaRESUMEN
BACKGROUND: Gestational weight gain (GWG) and anthropometric trajectories may affect foetal programming and are potentially modifiable. OBJECTIVES: To assess concomitant patterns of change in weight, circumferences and adiposity across gestation as an integrated prenatal exposure, and determine how they relate to neonatal body composition. METHODS: Data are from a prospective cohort of singleton pregnancies (n = 2182) enrolled in United States perinatal centres, 2009-2013. Overall and by prepregnancy BMI group (overweight/obesity and healthy weight), joint latent trajectory models were fit with prenatal weight, mid-upper arm circumference (MUAC), triceps (TSF) and subscapular (SSF) skinfolds. Differences in neonatal body composition by trajectory class were assessed via weighted least squares. RESULTS: Six trajectory patterns reflecting co-occurring changes in weight and MUAC, SSF and TSF across pregnancy were identified overall and by body mass index (BMI) group. Among people with a healthy weight BMI, some differences were observed for neonatal subcutaneous adipose tissue, and among individuals with overweight/obesity some differences in neonatal lean mass were found. Neonatal adiposity measures were higher among infants born to individuals with prepregnancy overweight/obesity. CONCLUSIONS: Six integrated trajectory patterns of prenatal weight, subcutaneous adipose tissue and circumferences were observed that were minimally associated with neonatal body composition, suggesting a stronger influence of prepregnancy BMI.
Asunto(s)
Sobrepeso , Aumento de Peso , Embarazo , Recién Nacido , Lactante , Femenino , Humanos , Estados Unidos/epidemiología , Estudios Prospectivos , National Institute of Child Health and Human Development (U.S.) , Obesidad , Composición Corporal , Índice de Masa Corporal , Desarrollo FetalRESUMEN
OBJECTIVE: To describe the characteristics of amniotic fluid sludge obtained from patients in term and preterm gestations. METHODS: This cross-sectional study included patients with dense aggregates of particulate matter detected in amniotic fluid, observed with transvaginal sonography. All patients were in labor and had an impending delivery, either preterm or at term. Echogenic material contained within amniotic fluid was retrieved transvaginally by needle amniotomy under direct visualization. The amniotic fluid analysis consisted of a Gram stain, cultures for aerobic/anaerobic bacteria and genital mycoplasmas, and a white blood cell count. RESULTS: Twenty-five patients ranging from 18 to 41 weeks of gestation were included in the study. We observed the following: (1) the appearance of amniotic fluid was consistent with pus-like material, vernix, or meconium by naked eye examination; (2) samples collected before 33 weeks of gestation (n = 13) had a pus-like appearance; however, after this gestational age, most of the samples [83% (10/12)] appeared to be consistent with vernix; (3) amniotic fluid cultures were positive for microorganisms in 13 patients, of which 10 were preterm gestations before 33 weeks; (4) the most frequent microorganisms retrieved by culture were genital mycoplasmas (Ureaplasma urealyticum [46% (6/13)]), followed by Mycoplasma hominis [31% (4/13)] and Candida albicans [15% (2/13)]; and (5) patients with sonographic particulate matter in preterm gestations frequently presented acute histologic chorioamnionitis and funisitis, but these conditions were rare in patients at term. CONCLUSION: The nature of amniotic fluid particulate material varies as a function of gestational age. The material obtained in preterm gestations is frequently related to an inflammatory process, while that obtained at term is often consistent with vernix and appears to represent a maturational process.
Asunto(s)
Corioamnionitis , Complicaciones Infecciosas del Embarazo , Embarazo , Recién Nacido , Femenino , Humanos , Líquido Amniótico/diagnóstico por imagen , Líquido Amniótico/microbiología , Aguas del Alcantarillado , Amniocentesis , Estudios Transversales , Complicaciones Infecciosas del Embarazo/diagnóstico , Corioamnionitis/diagnóstico , Corioamnionitis/microbiología , Material Particulado , SupuraciónRESUMEN
BACKGROUND: The utility of prophylactic endovascular internal iliac balloon placement in the surgical management of placenta accreta spectrum is debated. OBJECTIVE: In this study, we review outcomes of surgical management of placenta accreta spectrum with and without prophylactic endovascular internal iliac balloon catheter use at a single institution. STUDY DESIGN: This is a retrospective cohort study of consecutive viable singleton pregnancies with a confirmed pathologic diagnosis of placenta accreta spectrum undergoing scheduled delivery from October 2018 through November 2020. In the T1 period (October 2018-August 2019), prophylactic endovascular internal iliac balloon catheters were placed in the operating room before the start of surgery. Balloons were inflated after neonatal delivery and deflated after hysterectomy completion. In the T2 period (September 2019-November 2020), endovascular catheters were not used. In both time periods, all surgeries were performed by a dedicated multidisciplinary team using a standardized surgical approach. The outcomes compared included the estimated blood loss, anesthesia duration, operating room time, surgical duration, and a composite of surgical complications. Comparisons were made using the Wilcoxon rank-sum test and the Fisher exact test. RESULTS: A total of 30 patients were included in the study (T1=10; T2=20). The proportion of patients with placenta increta or percreta was 80% in both groups, as defined by surgical pathology. The median estimated blood loss was 875 mL in T1 and 1000 mL in T2 (P=.84). The proportion of patients requiring any packed red blood cell transfusion was 60% in T1 and 40% in T2 (P=.44). The proportion of patients requiring >4 units of packed red blood cells was 20% in T1 and 5% in T2 (P=.25). Surgical complications were observed in 1 patient in each group. Median operative anesthesia duration was 497 minutes in T1 and 296 minutes in T2 (P<.001). Median duration of operating room time was 498 minutes in T1 and 205 minutes in T2 (P<.001). Median surgical duration was 227 minutes in T1 and 182 minutes in T2 (P<.05). The median duration of time for prophylactic balloon catheter placement was 74 minutes (range, 46-109 minutes). The median postoperative length of stay was similar in both groups (6 days in T1 and 5.5 days in T2; P=.36). CONCLUSION: The use of prophylactic endovascular internal iliac balloon catheters was not associated with decreased blood loss, packed red blood cell transfusion, or surgical complications. Catheter use was associated with increased duration of anesthesia, operating room time, and surgical time.