Sonia S Hassan

Eunice Kennedy Shriver National Institute of Child Health and Human Development, Роквилл, Maryland, United States

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Publications (388)1007.26 Total impact

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    ABSTRACT: To prospectively evaluate the performance of Fetal Intelligent Navigation Echocardiography (FINE) applied to spatiotemporal image correlation (STIC) volume datasets of the normal fetal heart. In all patients with normal fetal hearts (19-30 gestational weeks), an attempt was made to acquire STIC volume datasets of the apical four-chamber view if the following criteria were met: 1) fetal spine located between the 5- and 7-o'clock positions; 2) minimal or absent shadowing (including a clearly visible transverse aortic arch); 3) absent fetal breathing, hiccups, or movement; and 4) adequate image quality. Each STIC volume successfully acquired was evaluated by STICLoop™ to determine its appropriateness before applying the FINE method. Visualization rates for fetal echocardiography views using diagnostic planes and/or Virtual Intelligent Sonographer Assistance (VIS-Assistance®) were calculated. One or more STIC volumes (n = 365 total) were successfully obtained in 72.5% (150/207) of women undergoing ultrasound examination. Of the 365 volumes evaluated by STICLoop™, 96.2% (n = 351) were determined to be appropriate. From these, only one STIC volume per patient (n = 150) was analyzed using the FINE method, and nine fetal echocardiography views were generated using: 1) diagnostic planes in 76-100% of cases; 2) VIS-Assistance® in 98-100% of cases; and 3) a combination of diagnostic planes and/or VIS-Assistance® in 98-100% of cases. In women with normal fetal hearts (19-30 gestational weeks) undergoing prospective sonographic examination, STIC volumes can be successfully obtained in 72.5%. In such cases, the FINE method can be applied to generate nine standard fetal echocardiography views using a combination of diagnostic planes and/or VIS-Assistance® in 98-100% of cases. This suggests that FINE could be implemented in fetal cardiac screening programs. This article is protected by copyright. All rights reserved.
    Ultrasound in Obstetrics and Gynecology 08/2015; DOI:10.1002/uog.15676 · 3.14 Impact Factor
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    ABSTRACT: To determine (1) whether maternal plasma concentrations of angiogenic and anti-angiogenic factors can predict which mothers diagnosed with "suspected small for gestational age fetuses (sSGA)" will develop pre-eclampsia (PE) or require an indicated early preterm delivery (≤ 34 weeks of gestation); and (2) whether risk assessment performance is improved using these proteins in addition to clinical factors and Doppler parameters. This prospective cohort study included women with singleton pregnancies diagnosed with sSGA (estimated fetal weight <10th percentile) between 24 and 34 weeks of gestation (n = 314). Plasma concentrations of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), soluble endoglin (sEng) and placental growth factor (PlGF) were determined in maternal blood obtained at the time of diagnosis. Doppler velocimetry of the umbilical (Umb) and uterine (UT) arteries was performed. The outcomes were (1) subsequent development of PE; and (2) indicated preterm delivery at ≤34 weeks of gestation (excluding deliveries as a result of spontaneous preterm labor, preterm pre-labor rupture of membranes or chorioamnionitis). (1) The prevalence of PE and indicated preterm delivery was 9.2% (n = 29/314) and 7.3% (n = 23/314), respectively; (2) the area under the receiver operating characteristic curve (AUC) for the identification of patients who developed PE and/or required indicated preterm delivery was greater than 80% for the UT artery pulsatility index (PI) z-score and each biochemical marker (including their ratios) except sVEGFR-1 MoM; (3) using cutoffs at a false positive rate of 15%, women with abnormal plasma concentrations of angiogenic/anti-angiogenic factors were 7-13 times more likely to develop PE, and 12-22 times more likely to require preterm delivery than those with normal plasma MoM concentrations of these factors; (4) sEng, PlGF, PIGF/sEng and PIGF/sVEGFR-1 ratios MoM, each contributed significant information about the risk of PE beyond that provided by clinical factors and/or Doppler parameters: women who had low MoM values for these biomarkers were at 5-9 times greater risk of developing PE than women who had normal values, adjusting for clinical factors and Doppler parameters (adjusted odds ratio for PlGF: 9.1, PlGF/sEng: 5.6); (5) the concentrations of sVEGFR-1 and PlGF/sVEGFR-1 ratio MoM, each contributed significant information about the risk of indicated preterm delivery beyond that provided by clinical factors and/or Doppler parameters: women who had abnormal values were at 8-9 times greater risk for indicated preterm delivery, adjusting for clinical factors and Doppler parameters; and (6) for a two-stage risk assessment (Umb artery Doppler followed by Ut artery Doppler plus biochemical markers), among women who had normal Umb artery Doppler velocimetry (n = 279), 21 (7.5%) developed PE and 11 (52%) of these women were identified by an abnormal UT artery Doppler mean PI z-score (>2SD): a combination of PlGF/sEng ratio MoM concentration and abnormal UT artery Doppler velocimetry increased the sensitivity of abnormal UT artery Doppler velocimetry to 76% (16/21) at a fixed false-positive rate of 10% (p = 0.06). Angiogenic and anti-angiogenic factors measured in maternal blood between 24 and 34 weeks of gestation can identify the majority of mothers diagnosed with "suspected SGA" who subsequently developed PE or those who later required preterm delivery ≤34 weeks of gestation. Moreover, incorporation of these biochemical markers significantly improves risk assessment performance for these outcomes beyond that of clinical factors and uterine and umbilical artery Doppler velocimetry.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 08/2015; DOI:10.3109/14767058.2015.1048431 · 1.21 Impact Factor
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    ABSTRACT: To evaluate the intermediate intracardiac diastolic velocities in fetuses with growth restriction. Doppler waveforms of the two atrioventricular valves were obtained. Peak velocities of the E (early) and A (atrial) components, and the lowest intermediate velocity (IDV) between them, were measured in 400 normally grown and in 100 growth-restricted fetuses. The prevalence of abnormal IDV, E/IDV, and A/IDV ratios in fetuses presenting with perinatal death or acidemia at birth (pH ≤7.1) was estimated. IDV was significantly lower and E/IDV ratios significantly higher in the two ventricles of growth-restricted fetuses with reduced diastolic velocities in the umbilical artery (p < 0.05). In 13 fetuses presenting with perinatal death or acidemia at birth, 11 (85%) had either an E/IDV or A/IDV ratio >95th percentile, whereas 5 (38%) showed absent or reversed atrial velocities in the ductus venosus (DV-ARAV; p < 0.04). Fetuses without DV-ARAV but with elevated E/IDV ratios in either ventricle were nearly 7-fold more likely to have perinatal demise or acidemia at birth (OR 6.9, 95% CI 1.4-34) than those with E/IDV ratios <95th percentile. The E/IDV and A/IDV ratios in the two cardiac ventricles might provide information about the risk of perinatal demise or acidemia in growth-restricted fetuses. © 2015 S. Karger AG, Basel.
    Fetal Diagnosis and Therapy 08/2015; DOI:10.1159/000431321 · 2.30 Impact Factor
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    ABSTRACT: Progestogen [vaginal progesterone or 17-alpha-hydroxyprogesterone caproate (17OHP-C)] administration to patients at risk for preterm delivery is widely used for the prevention of preterm birth (PTB). The mechanisms by which these agents prevent PTB are poorly understood. Progestogens have immunomodulatory functions; therefore, we investigated the local effects of vaginal progesterone and 17OHP-C on adaptive and innate immune cells implicated in the process of parturition. Pregnant C57BL/6J mice received vaginal progesterone (1mg/200μL, n=10) or Replens (control, 200μL, n=10) from 13 to 17 days post coitum (dpc), or were subcutaneously injected with 17OHP-C (2mg/100μL, n=10) or castor oil (control, 100μL, n=10) on 13, 15, and 17 dpc. Decidual and myometrial leukocytes were isolated prior to term delivery (18.5 dpc) for immunophenotyping by flow cytometry. Cervical tissues were collected to determine MMP-9 activity by in situ zymography and visualization of collagen content by Masson's trichrome staining. Plasma concentrations of progesterone, estradiol, and cytokines (IFNγ, IL1β, IL2, IL4, IL5, IL6, IL10, IL12p70, KC/GRO, and TNFα) were quantified by ELISAs. Pregnant mice pretreated with vaginal progesterone or Replens were injected with 10μg of an endotoxin on 16.5 dpc (n=10 each) and monitored via infrared camera until delivery to determine the effect of vaginal progesterone on the rate of PTB. 1) vaginal progesterone, but not 17OHP-C, increased the proportion of decidual CD4+ Tregs; 2) vaginal progesterone, but not 17OHP-C, decreased the proportion of decidual CD8+CD25+Foxp3+ T cells and macrophages; 3) vaginal progesterone did not cause an M1→M2 macrophage polarization, but reduced the proportion of myometrial IFNγ+ neutrophils and cervical active MMP-9+ neutrophils and monocytes; 5) 17OHP-C did not reduce the proportion of myometrial IFNy+ neutrophils; however, it increased the abundance of cervical active MMP-9+ neutrophils and monocytes; 6) vaginal progesterone immune effects were associated with reduced systemic concentrations of IL1β, but not with alterations in progesterone or estradiol concentrations; and 7) vaginal progesterone pretreatment protected against endotoxin-induced PTB (effect size 50%, p=0.008). Vaginal progesterone, but not 17OHP-C, has local anti-inflammatory effects at the maternal-fetal interface and the cervix, and protects against endotoxin-induced PTB. Copyright © 2015 Elsevier Inc. All rights reserved.
    American journal of obstetrics and gynecology 08/2015; DOI:10.1016/j.ajog.2015.08.010 · 3.97 Impact Factor
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    ABSTRACT: Intra-amniotic infection/inflammation is the only mechanism of disease with persuasive evidence of causality for spontaneous preterm labor/delivery. Previous studies about the behavior of cytokines in preterm labor have been largely based on the analysis of the behavior of each protein independently. Emerging evidence indicates that the study of biological networks can provide insight into the pathobiology of disease, and improve biomarker discovery. The goal of this study is to characterize the inflammatory-related proteins network in the amniotic fluid in patients with preterm labor. A retrospective cohort study was conducted, and included women with singleton pregnancies who presented with spontaneous preterm labor and intact membranes (n=135). These patients were classified according to the results of amniotic fluid culture, broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS), and amniotic fluid concentration of interleukin (IL)-6 into the following groups: 1) those without intra-amniotic inflammation (n=85); 2) those with microbial-associated intra-amniotic inflammation (n=15); and 3) those with intra-amniotic inflammation without detectable bacteria (n=35). Amniotic fluid concentrations of 33 inflammatory-related proteins were determined using a multiplex bead array assay. 1) Patients with preterm labor and intact membranes who had microbial-associated intra-amniotic inflammation had a higher amniotic fluid inflammatory-related protein concentration correlation than those without intra-amniotic inflammation (113 perturbed correlations). IL-1β, IL-6, MIP-1α, and IL-1α were the most connected nodes (highest degree) in this differential correlation network (degree of 20, 16, 12, and 12, respectively); 2) patients with sterile intra-amniotic inflammation had correlation patterns of inflammatory-related proteins that were both increased and decreased when compared to those without intra-amniotic inflammation (50 perturbed correlations). IL-1α, MIP-1α, and IL-1β were the most connected nodes in this differential correlation network (degrees of 12, 10, and 7, respectively); and 3) there were more coordinated inflammatory-related protein concentrations in the amniotic fluid of women with microbial-associated intra-amniotic inflammation than in those with sterile intra-amniotic inflammation (60 perturbed correlations), with IL-4 and IL-33 having the largest number of perturbed correlations (degree of 15 and 13, respectively). We report for the first time an analysis of the inflammatory-related protein network in spontaneous preterm labor. Patients with preterm labor who had microbial-associated intra-amniotic inflammation had more coordinated amniotic fluid inflammatory-related proteins than either those with sterile intra-amniotic inflammation or those without intra-amniotic inflammation. The correlations were also stronger in patients with sterile intra-amniotic inflammation than in those without intra-amniotic inflammation. The findings herein could be of value in the development of biomarkers of preterm labor. Copyright © 2015 Elsevier Inc. All rights reserved.
    American journal of obstetrics and gynecology 07/2015; DOI:10.1016/j.ajog.2015.07.037 · 3.97 Impact Factor
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    Journal of Visualized Experiments 05/2015; DOI:10.3791/52863 · 1.33 Impact Factor
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    ABSTRACT: Recent studies indicate that clinical chorioamnionitis is a heterogeneous condition and only approximately one-half of the patients have bacteria in the amniotic cavity, which is often associated with intra-amniotic inflammation. The objective of this study is to characterize the nature of the inflammatory response within the amniotic cavity in patients with clinical chorioamnionitis at term according to the presence or absence of 1) bacteria in the amniotic cavity and 2) intra-amniotic inflammation. A retrospective cross-sectional case-control study was conducted to examine cytokine and chemokine concentrations in the amniotic fluid (AF). Cases consisted of women with clinical chorioamnionitis at term (n=45). Controls were women with uncomplicated pregnancies at term who did not have intra-amniotic inflammation and were in labor (n=24). Women with clinical chorioamnionitis were classified according to the results of AF cultures, broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry, and AF concentration of interleukin-6 (IL-6) into those: 1) without intra-amniotic inflammation, 2) with microbial-associated intra-amniotic inflammation, and 3) with intra-amniotic inflammation without detectable bacteria. The AF concentrations of 29 cytokines/chemokines were determined using sensitive and specific V-PLEX immunoassays. 1) The AF concentrations of pro- and anti-inflammatory cytokines/chemokines such as interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin-4 (IL-4), macrophage inflammatory protein-1 beta (MIP-1β), and interleukin-8 (IL-8) (except Eotaxin-3) were significantly higher in women with clinical chorioamnionitis at term than in controls (term labor without intra-amniotic inflammation); 2) patients with microbial-associated intra-amniotic inflammation, and those with intra-amniotic inflammation without detectable bacteria, had a dramatic differential expression of cytokines and chemokines in AF compared to patients with spontaneous labor without intra-amniotic inflammation. However, no difference could be detected in the pattern of the intra-amniotic inflammatory response between patients with intra-amniotic inflammation with and without detectable bacteria; and 3) in patients with clinical chorioamnionitis at term but without intra-amniotic inflammation, the behavior of cytokines and chemokines in the AF was similar to those in spontaneous labor at term. Patients with clinical chorioamnionitis who had microbial-associated intra-amniotic inflammation or intra-amniotic inflammation without detectable bacteria had a dramatic upregulation of the intra-amniotic inflammatory response assessed by amniotic fluid concentrations of cytokines. A subset of patients with term clinical chorioamnionitis does not have intra-amniotic infection/inflammation, as demonstrated by elevated AF concentrations of inflammation-related proteins, when compared to women in term labor with uncomplicated pregnancies, suggesting over-diagnosis. These observations constitute the first characterization of the cytokine/chemokine network in the amniotic cavity of patients with clinical chorioamnionitis at term.
    Journal of Perinatal Medicine 05/2015; DOI:10.1515/jpm-2015-0045 · 1.43 Impact Factor
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    ABSTRACT: The diagnosis of clinical chorioamnionitis is based on a combination of signs [fever, maternal or fetal tachycardia, foul-smelling amniotic fluid (AF), uterine tenderness and maternal leukocytosis]. Bacterial infections within the amniotic cavity are considered the most frequent cause of clinical chorioamnionitis and an indication for antibiotic administration to reduce maternal and neonatal morbidity. Recent studies show that only 54% of patients with the diagnosis of clinical chorioamnionitis at term have bacteria in the AF and evidence of intra-amniotic inflammation. The objective of this study was to examine the performance of the clinical criteria for the diagnosis of chorioamnionitis to identify patients with microbial-associated intra-amniotic inflammation (also termed intra-amniotic infection). This retrospective cross-sectional study included 45 patients with the diagnosis of clinical chorioamnionitis at term, whose AF underwent analysis for: 1) the presence of microorganisms using both cultivation and molecular biologic techniques [polymerase chain reaction (PCR) with broad primers], and 2) interleukin (IL)-6 concentrations by enzyme-linked immunosorbent assay. The diagnostic performance (sensitivity, specificity, accuracy, and likelihood ratios) of each clinical sign and their combination to identify clinical chorioamnionitis were determined using microbial-associated intra-amniotic inflammation [presence of microorganisms in the AF using cultivation or molecular techniques and elevated AF IL-6 concentrations (≥2.6 ng/mL)] as the gold standard. The accuracy of each clinical sign for the identification of microbial-associated intra-amniotic inflammation (intra-amniotic infection) ranged between 46.7% and 57.8%. The combination of fever with three or more clinical criteria did not substantially improve diagnostic accuracy. In the presence of a fever during labor at term, signs used to diagnose clinical chorioamnionitis do not accurately identify the patient with proven intra-amniotic infection (i.e., those with microorganisms detected by culture or molecular microbiologic techniques and an associated intra-amniotic inflammatory response).
    Journal of Perinatal Medicine 04/2015; DOI:10.1515/jpm-2015-0044 · 1.43 Impact Factor
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    ABSTRACT: Massive perivillous fibrin deposition of the placenta (MPFD) or maternal floor infarction (MFI) is a serious condition associated with recurrent complications including fetal death and severe fetal growth restriction. There is no method to evaluate the risk of adverse outcome in subsequent pregnancies, or effective prevention. Recent observations suggest that MFI is characterized by an imbalance in angiogenic/anti-angiogenic factors in early pregnancy; therefore, determination of these biomarkers may identify the patient at risk for recurrence. We report the case of a pregnant woman with a history of four consecutive pregnancy losses, the last of which was affected by MFI. Abnormalities of the anti-angiogenic factor, sVEGFR-1, and soluble endoglin (sEng) were detected early in the index pregnancy, and treatment with pravastatin corrected the abnormalities. Treatment resulted in a live birth infant at 34 weeks of gestation who had normal biometric parameters and developmental milestones at the age of 2. This is the first reported successful use of pravastatin to reverse an angiogenic/anti-angiogenic imbalance and prevent fetal death.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 04/2015; DOI:10.3109/14767058.2015.1022864 · 1.21 Impact Factor
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    ABSTRACT: Massive perivillous fibrin deposition of the placenta (MPFD) or maternal floor infarction (MFI) is a serious condition associated with recurrent complications including fetal death and severe fetal growth restriction. There is no method to evaluate the risk of adverse outcome in subsequent pregnancies, or effective prevention. Recent observations suggest that MFI is characterized by an imbalance in angiogenic/anti-angiogenic factors in early pregnancy; therefore, determination of these biomarkers may identify the patient at risk for recurrence. We report the case of a pregnant woman with a history of four consecutive pregnancy losses, the last of which was affected by MFI. Abnormalities of the anti-angiogenic factor, sVEGFR-1, and soluble endoglin (sEng) were detected early in the index pregnancy, and treatment with pravastatin corrected the abnormalities. Treatment resulted in a live birth infant at 34 weeks of gestation who had normal biometric parameters and developmental milestones at the age of 2. This is the first reported successful use of pravastatin to reverse an angiogenic/anti-angiogenic imbalance and prevent fetal death.
  • PLoS ONE 04/2015; 10(4):e0119547. DOI:10.1371/journal.pone.0119547 · 3.23 Impact Factor
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    ABSTRACT: Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality worldwide. A transition from an anti-inflammatory state to a pro-inflammatory state in the mother and at the maternal-fetal interface has been implicated in the pathophysiology of microbial-induced preterm labor. However, it is unclear which immune cells mediate this transition. We hypothesized that an imbalance between innate and adaptive immune cells at the maternal-fetal interface will occur prior to microbial-induced preterm labor. Using an established murine model of endotoxin-induced PTB, our results demonstrate that prior to delivery there is a reduction of CD4+ regulatory T cells (Tregs) in the uterine tissues. This reduction is neither linked to a diminished number of Tregs in the spleen, nor to an impaired production of IL10, CCL17, or CCL22 by the uterine tissues. Endotoxin administration to pregnant mice does not alter effector CD4+ T cells at the maternal-fetal interface. However, it causes an imbalance between Tregs (CD4+ and CD8+), effector CD8+ T cells, and Th17 cells in the spleen. In addition, endotoxin administration to pregnant mice leads to an excessive production of CCL2, CCL3, CCL17, and CCL22 by the uterine tissues as well as abundant neutrophils. This imbalance in the uterine microenvironment is accompanied by scarce APC-like cells such as macrophages and MHC II+ neutrophils. Collectively, these results demonstrate that endotoxin administration to pregnant mice causes an imbalance between innate and adaptive immune cells at the maternal-fetal interface.Cellular & Molecular Immunology advance online publication, 6 April 2015; doi:10.1038/cmi.2015.22.
    Cellular & molecular immunology 04/2015; DOI:10.1038/cmi.2015.22 · 4.19 Impact Factor
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    ABSTRACT: Neurocognitive impairment among children born preterm may arise from complex interactions between genes and the intra-uterine environment. (1) To characterize the transcriptomic profiles of chorioamniotic membranes in preterm neonates with and without neurocognitive impairment via microarrays and (2) to determine if neonates with neurocognitive impairment can be identified at birth. A retrospective case-control study was conducted to examine the chorioamniotic transcriptome of gestational-age matched very preterm neonates with and without neurocognitive impairment at 18-24 months' corrected-age defined by a Bayley-III Cognitive Composite Score <80 (n = 14 each). Pathway analysis with down-weighting of overlapping genes (PADOG) was performed to identify KEGG pathways relevant to the phenotype. Select differentially expressed genes were profiled using qRT-PCR and a multi-gene disease prediction model was developed using linear discriminant analysis. The model's predictive performance was tested on a new set of cases and controls (n = 19 each). 1) 117 genes were differentially expressed among neonates with and without subsequent neurocognitive impairment (p<0.05 and fold change >1.5); 2) Gene ontology analysis indicated enrichment of 19 biological processes and 3 molecular functions; 3)PADOG identified 4 significantly perturbed KEGG pathways: oxidative phosphorylation, Parkinson's disease, Alzheimer's disease and Huntington's disease (q-value <0.1); 4) 48 of 90 selected differentially expressed genes were confirmed by qRT-PCR, including genes implicated in energy metabolism, neuronal signaling, vascular permeability and response to injury (e.g., up-regulation of SEPP1, APOE, DAB2, CD163, CXCL12, VWF; down-regulation of HAND1, OSR1)(p<0.05); and 5) a multi-gene model predicted 18-24 month neurocognitive impairment (using the ratios of OSR1/VWF and HAND1/VWF at birth) in a larger, independent set (sensitivity = 74%, at specificity = 83%). Gene expression patterns in the chorioamniotic membranes link neurocognitive impairment in preterm infants to neurodegenerative disease pathways and might be used to predict neurocognitive impairment. Further prospective studies are needed.
    PLoS ONE 03/2015; 10(3):e0118573. DOI:10.1371/journal.pone.0118573 · 3.23 Impact Factor
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    ABSTRACT: To evaluate the association between cervical strain assessed with quasi-static elastography and spontaneous preterm delivery. Quasi-static elastography was used to estimate cervical strain in 545 pregnant women with singleton pregnancies from 11 weeks to 28 weeks of gestation. Cervical strain was evaluated in one sagittal plane and in the cross-sectional planes of the internal cervical os and external cervical os. The distribution of strain values was categorized into quartiles for each studied region and their association with spontaneous preterm delivery at ≤34 weeks and at <37 weeks of gestation was evaluated using logistic regression. The prevalence of spontaneous preterm delivery at <37 weeks of gestation was 8.2% (n=45), and that at ≤34 weeks of gestation was 3.8% (n=21). Strain in the internal cervical os was the only elastography value associated with spontaneous preterm delivery. Women with strain values in the 3rd and 4th quartiles had a significantly higher risk of spontaneous preterm delivery at ≤34 weeks and at <37 weeks of gestation when compared to women with strain values in the lowest quartile. When adjusting for a short cervix (<25 mm) and gestational age at examination, women with strain values in the 3rd quartile maintained a significant association with spontaneous preterm delivery at ≤34 weeks (OR 9.0; 95% CI, 1.1-74.0; P=0.02), whereas women with strain values in the highest quartile were marginally more likely than women with lowest quartile strain values to deliver spontaneously at ≤37 weeks of gestation (OR 95% CI: 2.8; [0.9-9.0]; P=0.08). Increased strain in the internal cervical os is associated with higher risk of spontaneous preterm delivery both at ≤34 and <37 weeks of gestation.
    Journal of Perinatal Medicine 03/2015; DOI:10.1515/jpm-2014-0382 · 1.43 Impact Factor
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    ABSTRACT: Preterm prelabor rupture of membranes (preterm PROM) accounts for 30-40% of spontaneous preterm deliveries and thus is a major contributor to perinatal morbidity and mortality. An amniotic fluid (AF) interleukin-6 (IL-6) concentration is a key cytokine for the identification of intra-amniotic inflammation, and patients at risk of impending preterm delivery, and adverse pregnancy complications. The conventional method to determine IL-6 concentrations in AF is an enzyme-linked immunosorbent assay (ELISA). However, this technique is not available in clinical settings and the results may take several days. A lateral flow-based immunoassay, or point of care (POC) test, has been developed to address this issue. The objective of this study was to compare the performance of AF IL-6 determined by the POC test to that determined by ELISA for the identification of intra-amniotic inflammation in patients with preterm PROM. This retrospective cohort study includes 56 women with singleton pregnancies who presented with preterm PROM. Amniocentesis was performed at the time of diagnosis and AF was analyzed using cultivation techniques for aerobic and anaerobic bacteria as well as genital mycoplasmas. AF Gram stain and AF white blood cell counts were determined. AF IL-6 concentrations were measured using both lateral flow-based immunoassay and ELISA. The primary outcome was intra-amniotic inflammation defined as AF ELISA IL-6 > 2,600 pg/ml. A previously determined cut-off of 745 pg/ml was used to define a positive POC test. 1) The POC test for AF IL-6 concentrations had 97% sensitivity and 96% specificity for the identification of intra-amniotic inflammation, as defined using ELISA among patients with preterm PROM; and 2) the diagnostic performance of the POC test for IL-6 was strongly correlated to that of an ELISA test for the identification of intra-amniotic inflammation and was equivalent for the identification of acute inflammatory placental lesions and MIAC. A point of care AF IL-6 test can identify intra-amniotic inflammation in patients with preterm PROM. Results can be available within 20 minutes - this makes it possible to implement interventions designed to treat intra-amniotic inflammation and improve pregnancy outcomes.
    Journal of Maternal-Fetal and Neonatal Medicine 03/2015; DOI:10.3109/14767058.2015.1006621 · 1.21 Impact Factor
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    ABSTRACT: Preterm birth is associated with 5 to 18% of pregnancies and is the leading cause of neonatal morbidity and mortality. Amniotic fluid (AF) interleukin-6 (IL-6) is a key cytokine for the identification of intra-amniotic inflammation, and patients with an elevated amniotic fluid IL-6 are at risk for impending preterm delivery. However, results of the conventional method of measurement (enzyme-linked immunosorbent assay; ELISA) are usually not available in time to inform care. The objective of this study was to determine whether a point of care (POC) test or lateral-flow based immunoassay for measurement of amniotic fluid (AF) IL-6 concentrations can identify patients with intra-amniotic inflammation and/or infection, and those destined to deliver spontaneously before term among women with preterm labor and intact membranes. One hundred thirty six women with singleton pregnancies who presented with symptoms of preterm labor and underwent amniocentesis were included in this study. Amniocentesis was performed at the time of diagnosis of preterm labor. AF Gram stain and AF white blood cell counts were determined. Microbial invasion of the amniotic cavity (MIAC) was defined according to the results of AF culture (aerobic and anaerobic as well as genital mycoplasmas). AF IL-6 concentrations were determined by both lateral flow-based immunoassay and ELISA. The primary outcome was intra-amniotic inflammation, defined as AF ELISA IL-6 > 2,600 pg/ml . 1) AF IL-6 concentrations determined by a POC test have high sensitivity (93%), specificity (91%), and a positive likelihood ratio of 10 for the identification of intra-amniotic inflammation by using a threshold of 745 pg/ml; 2) the POC test and ELISA for IL-6 perform similarly in the identification of MIAC, acute inflammatory lesions of placenta, and patients at risk of impending spontaneous preterm delivery. A point of care AF IL-6 test can identify intra-amniotic inflammation in women who present with preterm labor and intact membranes and those who will subsequently deliver spontaneously before 34 weeks of gestation. Results can be available within 20 minutes-this has important clinical implications and opens avenues for early diagnosis as well as treatment of intra-amniotic inflammation/infection.
    Journal of Maternal-Fetal and Neonatal Medicine 03/2015; DOI:10.3109/14767058.2015.1006620 · 1.21 Impact Factor
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    ABSTRACT: The traditional approach to understand health and disease has relied on the analyses of individual genes or proteins. Yet, biological functions are the expression of integrated and interdependent networks. We examined the behavior of protein networks in peripheral blood of normal pregnant women and those with preeclampsia (PE). A cross-sectional study was conducted to include: (1) normal pregnancy (n=50); (2) early PE (delivered <34 weeks; n=44); and (3) late PE (n=43). Multiplex assay systems were used to measure proteins. Log transformed and normalized protein concentrations in normal pregnancies were modeled using locally weighted linear quantile regression. Protein abundance was represented as MOM. Differentially expressed proteins were retained to conduct a network analysis. (1) Eighty-six and 24 proteins were differentially expressed in early and late PE, respectively (fold >1.5 and adjusted p 4); (2) network analysis demonstrated a more coordinated protein activity in early PE with four distinct modules (Figure). These modules represented proteins involved in cell adhesion molecules, cytokine-cytokine receptor interaction; and coagulation cascade; and (3) the cyan module which was enriched in proteins involved in cell adhesion molecules pathway was present in early, but not in normal or late PE. We report for the first time increased connectivity in protein-protein correlation networks in PE. We propose that characterizing the protein network structure and behavior provides insight into complex diseases. Figure Legend Protein correlation network in early preeclampsia. Four protein modules were identified (green, blue, gold, magenta). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.) P. Chaemsaithong: None. R. Romero: None. A.L. Tarca: None. Z. Xu: None. M. Shaman: None. K. Lannaman: None. A.I. Ahmed: None. S.S. Hassan: None. L. Yeo: None. T. Chaiworapongsa: None. Copyright © 2014.
    01/2015; 5(1):42-3. DOI:10.1016/j.preghy.2014.10.084
  • American Journal of Obstetrics and Gynecology 01/2015; 212(1):S251. DOI:10.1016/j.ajog.2014.10.543 · 3.97 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2015; 212(1):S298. DOI:10.1016/j.ajog.2014.10.805 · 3.97 Impact Factor
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    ABSTRACT: Objective: To investigate dynamic changes in myometrial thickness during the third stage of labor. Methods: Myometrial thickness was measured using ultrasound at one-minute time intervals during the third stage of labor in the mid-region of the upper and lower uterine segments in 151 patients including: women with a long third stage of labor (n = 30), postpartum hemorrhage (n = 4), preterm delivery (n = 7) and clinical chorioamnionitis (n = 4). Differences between myometrial thickness of the uterine segments and as a function of time were evaluated. Results: There was a significant linear increase in the mean myometrial thickness of the upper uterine segments, as well as a significant linear decrease in the mean myometrial thickness of the lower uterine segments until the expulsion of the placenta (p < 0.001). The ratio of the measurements of the upper to the lower uterine segments increased significantly as a function of time (p < 0.0001). In women with postpartum hemorrhage, preterm delivery, and clinical chorioamnionitis, an uncoordinated pattern among the uterine segments was observed. Conclusion: A well-coordinated activity between the upper and lower uterine segments is demonstrated in normal placental delivery. In some clinical conditions this pattern is not observed, increasing the time for placental delivery and the risk of postpartum hemorrhage. © 2015 S. Karger AG, Basel.
    Gynecologic and Obstetric Investigation 01/2015; DOI:10.1159/000370001 · 1.25 Impact Factor

Publication Stats

7k Citations
1,007.26 Total Impact Points

Institutions

  • 2007–2015
    • Eunice Kennedy Shriver National Institute of Child Health and Human Development
      • Division of Intramural Research (DIR)
      Роквилл, Maryland, United States
    • University of Texas Medical Branch at Galveston
      • Department of Obstetrics and Gynecology
      Galveston, Texas, United States
  • 2000–2015
    • Wayne State University
      • Department of Obstetrics and Gynecology
      Detroit, Michigan, United States
  • 2012
    • University of Ulsan
      Urusan, Ulsan, South Korea
  • 2007–2011
    • National Institute of Child Health and Human Development
      베서스다, Maryland, United States
  • 2006
    • Vanderbilt University
      Нашвилл, Michigan, United States
    • University of Iowa
      • Department of Obstetrics and Gynecology
      Iowa City, Iowa, United States
    • Universitair Medisch Centrum Groningen
      Groningen, Groningen, Netherlands
    • University College Dublin
      Dublin, Leinster, Ireland
  • 2000–2006
    • Detroit Medical Center
      Detroit, Michigan, United States
  • 2003
    • Thomas Jefferson University
      • Department of Obstetrics & Gynecology
      Filadelfia, Pennsylvania, United States