Michael House

Tufts Medical Center, Boston, Massachusetts, United States

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Publications (64)192.91 Total impact

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    ABSTRACT: Preterm birth is a strong contributor to perinatal mortality, and preterm infants that survive are at risk for long-term morbidities. During most of pregnancy, appropriate mechanical function of the cervix is required to maintain the developing fetus in utero. Premature cervical softening and subsequent cervical shortening are hypothesized to cause preterm birth. Presently, there is a lack of understanding of the structural and material factors that influence the mechanical function of the cervix during pregnancy. In this study we build finite element models of the pregnant uterus, cervix, and fetal membrane based on magnetic resonance imagining data in order to examine the mechanical function of the cervix under the physiologic loading conditions of pregnancy. We calculate the mechanical loading state of the cervix for two pregnant patients: 22 weeks gestational age with a normal cervical length and 28 weeks with a short cervix. We investigate the influence of (1) anatomical geometry, (2) cervical material properties, and (3) fetal membrane material properties, including its adhesion properties, on the mechanical loading state of the cervix under physiologically relevant intrauterine pressures. Our study demonstrates that membrane-uterus interaction, cervical material modeling, and membrane mechanical properties are factors that must be deliberately and carefully handled in order to construct a high quality mechanical simulation of pregnancy.
    Computer Methods in Biomechanics and Biomedical Engineering 05/2015; DOI:10.1080/10255842.2015.1033163 · 1.79 Impact Factor
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    ABSTRACT: Appropriate mechanical function of the uterine cervix is critical for maintaining a pregnancy to term so that the fetus can develop fully. At the end of pregnancy, however, the cervix must allow delivery, which requires it to markedly soften, shorten and dilate. There are multiple pathways to spontaneous preterm birth, the leading global cause of death in children less than 5 years old, but all culminate in premature cervical change, because that is the last step in the final common pathway to delivery. The mechanisms underlying premature cervical change in pregnancy are poorly understood, and therefore current clinical protocols to assess preterm birth risk are limited to surrogate markers of mechanical function, such as sonographically measured cervical length. This is what motivates us to study the cervix, for which we propose investigating clinical cervical function in parallel with a quantitative engineering evaluation of its structural function. We aspire to develop a common translational language, as well as generate a rigorous integrated clinical-engineering framework for assessing cervical mechanical function at the cellular to organ level. In this review, we embark on that challenge by describing the current landscape of clinical, biochemical, and engineering concepts associated with the mechanical function of the cervix during pregnancy. Our goal is to use this common platform to inspire novel approaches to delineate normal and abnormal cervical function in pregnancy. Copyright © 2015. Published by Elsevier Ltd.
    Journal of Biomechanics 03/2015; 153(9). DOI:10.1016/j.jbiomech.2015.02.065 · 2.50 Impact Factor
  • Helen Feltovich, Michael House
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    ABSTRACT: A multitude of pathophysiologic pathways culminate in the final common denominator of cervical softening, shortening, and dilation that lead to preterm birth. At present, a variety of emerging technology aims to objectively quantify critical cervical parameters such as microstructural organization and softening of the cervix. If the nature and timing of cervical changes can be precisely identified, it should be possible to identify the causative upstream molecular processes and resultant biomechanical events associated with each unique pathway. This would promote molecular studies, ultimately leading to novel approaches to preterm birth prediction, novel treatments, and prevention.
    Clinical Obstetrics and Gynecology 09/2014; 57(3):531-6. DOI:10.1097/GRF.0000000000000049 · 1.53 Impact Factor
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    ABSTRACT: Objective:To evaluate the biocompatibility of silk gel for cervical injection.Study Design:Silk gel was injected into the cervix of pregnant rats on day 13 (n = 11) and harvested at day 17. Histology of silk gel was compared with suture controls. Also, human cervical fibroblasts were cultured on silk gel and tissue culture plastic (TCP) in vitro. Cell viability, proliferation, metabolic activity, gene expression (COL1A1, COL3A1, and COX2), and release of proinflammatory mediators (interleukin [IL] 6 and IL-8) were evaluated.Results:In vivo, a mild foreign body response was seen surrounding the silk gel and suture controls. In vitro, cervical fibroblasts were viable, metabolically active, and proliferating at 72 hours. Release of IL-6 and IL-8 was similar on silk gel and TCP. Collagen and COX2 gene expression was similar or slightly decreased compared with TCP.Conclusions:Silk gel was well tolerated in vivo and in vitro, which supports continuing efforts to develop silk gels as an alternative to cervical cerclage.
    Reproductive sciences (Thousand Oaks, Calif.) 02/2014; 21(10). DOI:10.1177/1933719114522551 · 2.18 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2014; 210(1):S348. DOI:10.1016/j.ajog.2013.10.741 · 3.97 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2014; 210(1):S376. DOI:10.1016/j.ajog.2013.10.799 · 3.97 Impact Factor
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    ABSTRACT: Progesterone supplementation is recommended to prevent preterm birth in women with a short cervix, but the mechanism is unclear. We hypothesize that progesterone acts by altering the composition of cervical extracellular matrix (ECM). We tested this hypothesis using human cervical fibroblasts in both two-dimensional (2D) and three-dimensional (3D) culture. For 2D culture, cells were seeded in six well plates and cultured with media supplemented with estradiol (10(-8) M), progesterone (10(-7) M, 10(-6) M) and vehicle. For 3D culture, cells were cultured on a porous silk protein scaffold system. Progesterone and estrogen receptors were documented by immunohistochemistry and Western blot. In both 2D and 3D culture, decreased collagen synthesis was seen with increased progesterone concentration. 3D cultures could be maintained significantly longer than 2D cultures and the morphology of 3D cultures appeared similar to native cervical tissue. Thus, further studies were performed in 3D culture. To determine the effect of progesterone concentration, 3D scaffolds were cultured with estradiol (10(-8) M) and five progesterone conditions: vehicle, 10(-9) M, 10(-8) M, 10(-7) M and 10(-7) M + 10(-6) M mifepristone. The highest progesterone concentration correlated with the least amount of collagen synthesis. Collagen synthesis progressively increased as progesterone concentration decreased. This effect was partially antagonized by mifepristone, suggesting the mechanism is mediated by the progesterone receptor. This hormonally-responsive 3D culture system supports the hypothesis that progesterone has a direct effect on remodeling cervical ECM during pregnancy. The 3D culture system could be useful for studying the mechanism of progesterone effects on the cervix.
    Biology of Reproduction 11/2013; 90(1). DOI:10.1095/biolreprod.113.112540 · 3.45 Impact Factor
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    ABSTRACT: Globally, an estimated 13 million preterm babies are born each year. These babies are at increased risk of infant mortality and life-long health complications. Interventions to prevent preterm birth (PTB) require an understanding of processes driving parturition. Prostaglandins (PGs) have diverse functions in parturition, including regulation of uterine contractility and tissue remodeling. Our studies on cervical remodeling in mice suggest that although local synthesis of PGs are not increased in term ripening, transcripts encoding PG-endoperoxide synthase 2 (Ptgs2) are induced in lipopolysaccharide (LPS)-mediated premature ripening. This study provides evidence for two distinct pathways of cervical ripening: one dependent on PGs derived from paracrine or endocrine sources and the other independent of PG actions. Cervical PG levels are increased in LPS-treated mice, a model of infection-mediated PTB, consistent with increases in PG synthesizing enzymes and reduction in PG-metabolizing enzymes. Administration of SC-236, a PTGS2 inhibitor, along with LPS attenuated cervical softening, consistent with the essential role of PGs in LPS-induced ripening. In contrast, during term and preterm ripening mediated by the antiprogestin, mifepristone, cervical PG levels, and expression of PG synthetic and catabolic enzymes did not change in a manner that supports a role for PGs. These findings in mice, supported by correlative studies in women, suggest PGs do not regulate all aspects of the parturition process. Additionally, it suggests a need to refocus current strategies toward developing therapies for the prevention of PTB that target early, pathway-specific processes rather than focusing on common late end point mediators of PTB.
    Endocrinology 11/2013; 155(1). DOI:10.1210/en.2013-1304 · 4.64 Impact Factor
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    ABSTRACT: Ascending infection from the colonized vagina to the normally sterile intrauterine cavity is a well-documented cause of preterm birth. The primary physical barrier to microbial ascension is the cervical canal, which is filled with a dense and protective mucus plug. Despite its central role in separating the vaginal from the intrauterine tract, the barrier properties of cervical mucus have not been studied in preterm birth. To study the protective function of the cervical mucus in preterm birth we performed a pilot case-control study to measure the viscoelasticity and permeability properties of mucus obtained from pregnant women at high-risk and low-risk for preterm birth. Using extensional and shear rheology we found that cervical mucus from women at high-risk for preterm birth was more extensible and forms significantly weaker gels compared to cervical mucus from women at low-risk of preterm birth. Moreover, permeability measurements using fluorescent microbeads show that high-risk mucus was more permeable compared with low-risk mucus. Our findings suggest that critical biophysical barrier properties of cervical mucus in women at high-risk for preterm birth are compromised compared to women with healthy pregnancy. We hypothesize that impaired barrier properties of cervical mucus could contribute to increased rates of intrauterine infection seen in women with preterm birth. We furthermore suggest that a robust association of spinnbarkeit and preterm birth could be an effectively exploited biomarker for preterm birth prediction.
    PLoS ONE 08/2013; 8(8):e69528. DOI:10.1371/journal.pone.0069528 · 3.53 Impact Factor
  • 60th Annual Scientific Meeting of the; 03/2013
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    ABSTRACT: Objectives: The purpose of this study was to assess the postnatal outcome and complications that arise in infants with the prenatal diagnosis of gastroschisis. Methods: Prenatal sonograms with the diagnosis of gastroschisis were identified. Maternal age, indication for sonography, gestational age at diagnosis, other sonographic abnormalities, and postnatal outcome were recorded. Results: Ninety-eight fetuses at 14.3 to 36 weeks' gestation had the diagnosis of gastroschisis on sonography. In 14 cases (14%), other fetal anomalies were identified, including hydronephrosis, hydrocephalus, coarctation of the aorta, and a limb anomaly. Bowel dilatation developed in 72 of 84 cases (86%) followed prenatally with sonography, and bowel wall thickening developed in 40 of 73 cases (55%). On postnatal follow-up, 57 of 68 infants (84%) had postnatal complications, many with multisystem complications, including 6 deaths, 40 with bowel-related complications, 30 with infectious complications, and 32 with anomalies involving other systems (genitourinary, cardiac, and central nervous system). The postnatal outcome did not correlate with the presence of bowel dilatation or bowel wall thickening on prenatal sonography. Only 11 infants (16.2%) had a completely uncomplicated postsurgical course. Hospital stays in survivors (n = 92) ranged from 8 to 307 days (mean, 53 days). Conclusions: Although reported survival rates are good for gastroschisis, the postoperative hospital stay is often lengthy, and complications are very common, especially those related to the gastrointestinal tract. Associated anomalies were more common in our study than previously reported.
  • 60th Annual Scientific Meeting of the; 03/2013
  • American Journal of Obstetrics and Gynecology 01/2013; 208(1):S64. DOI:10.1016/j.ajog.2012.10.286 · 3.97 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2013; 208(1):S103. DOI:10.1016/j.ajog.2012.10.388 · 3.97 Impact Factor
  • Michael House, Reid McCabe, Simona Socrate
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    ABSTRACT: Preterm birth affects over 12% of all pregnancies in the United States for an annual healthcare cost of $26 billion. Preterm birth is a multifactorial disorder but cervical abnormalities are a prominent feature in many patients. Women with a short cervix are known to be at increased risk for preterm birth and a short cervix is used to target therapy to prevent preterm birth. Although the clinical significance of a short cervix is well known, the three-dimensional anatomical changes that lead to cervical shortening are poorly understood. Here, we review our previous studies of the three-dimensional anatomy of the cervix and uterus during pregnancy. The rationale for these studies was to improve our understanding of the deformation mechanisms leading to cervical shortening. Both magnetic resonance imaging and three-dimensional (3D) ultrasound were used to obtain anatomical data in healthy, pregnant volunteers. Solid models were constructed from the 3D imaging data. These solid models were used to create numerical models suitable for biomechanical simulation. Three simulations were studied: cervical funneling, uterine growth, and fundal pressure. These simulations showed that cervical changes are a complex function of the tissue properties of the cervical stroma, the loading conditions associated with pregnancy and the 3D anatomical geometry of the cervix and surrounding structures. An improved understanding of these cervical changes could point to new approaches to prevent undesired cervical shortening. This new insight should lead to therapeutic strategies to delay or prevent preterm birth. Clin. Anat., 2012. © 2012 Wiley Periodicals, Inc.
    Clinical Anatomy 01/2013; 26(1). DOI:10.1002/ca.22183 · 1.16 Impact Factor
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    ABSTRACT: Objective:New therapies to prevent preterm birth are needed. Our objective was to study an injectable biomaterial for human cervical tissue as an alternative to cervical cerclage.Study Design:Human cervical tissue specimens were obtained from premenopausal gynecological hysterectomies for benign indications. A 3-part biomaterial was formulated, consisting of silk protein solution blended with a 2-part polyethylene glycol gelation system. The solutions were injected into cervical tissue and the tissue was evaluated for mechanical properties, swelling, cytocompatibility, and histology.Results:The stiffness of cervical tissue more than doubled after injection (P = .02). Swelling properties of injected tissue were no different than native tissue controls. Cervical fibroblasts remained viable for at least 48 hours when cultured on the biomaterial.Conclusions:We report a silk-based, biocompatible, injectable biomaterial that increased the stiffness of cervical tissue compared to uninjected controls. Animal studies are needed to assess this biomaterial in vivo.
    Reproductive sciences (Thousand Oaks, Calif.) 12/2012; 20(8). DOI:10.1177/1933719112468952 · 2.18 Impact Factor
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    ABSTRACT: Objectives- The purpose of this study was to determine whether sonographic formulas for estimating fetal weight are as accurate for fetuses affected with gastroschisis as they are for healthy fetuses. We hypothesized that because the most commonly used Hadlock formulas rely on the abdominal circumference as a biometric variable, estimates of birth weight are less reliable in fetuses with gastroschisis than in healthy fetuses. Methods- We performed a chart review of all fetuses with a prenatal diagnosis of gastroschisis at 3 tertiary care institutions from 1990 to 2008. Charts were reviewed for clinical and sonographic data. The estimated fetal weight at the prenatal sonogram closest to delivery was compared to the birth weight. Published Hadlock formulas using 4 biometric parameters were used to calculate the estimated fetal weight. Data analysis was performed using the Student t test and χ(2) test for continuous and categorical variables, respectively. Results- One hundred eleven patients with gastroschisis were identified. Sixty-six patients had a prenatal sonogram with a calculated estimated fetal weight within 7 days of delivery; 88 patients had a sonogram within 14 days. The mean birth weights ± SD were 2292 ± 559 and 2477 ± 531 g in the 0- to 7- and 8- to 14-day groups, respectively. Sonographic biometric measurements underestimated the birth weight by an average of 5.6%. Intrauterine growth restriction was predicted in 72% of all pregnancies but was only present in 52%. Conclusions- Our study shows a systematic error of birth weight underestimation when using the Hadlock formulas in fetuses affected with gastroschisis.
    Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 11/2012; 31(11):1753-8. · 1.53 Impact Factor
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    ABSTRACT: To estimate the relationship between nuchal translucency thickness and abnormal karyotype, major congenital anomaly, perinatal loss, and composite abnormal outcome in fetuses with first-trimester nuchal cystic hygroma. We performed a retrospective cohort study of first-trimester fetuses with ultrasound-diagnosed nuchal cystic hygroma collected over a 10-year period. There were 944 first-trimester fetuses with nuchal cystic hygroma. A karyotype abnormality occurred in 54.9% (400 of 729) of fetuses. A major congenital anomaly occurred in 28.8% (61 of 212) of fetuses with a normal karyotype. Perinatal loss occurred in 39% (115 of 295) of fetuses not electively terminated. Overall, an abnormal outcome occurred in 86.6% (543 of 627) of fetuses. After adjusting for potential confounders, every 1-mm increase in nuchal translucency thickness increased the odds of an abnormal karyotype by 44% (adjusted odds ratio [OR] 1.44, 95% confidence interval [CI] 1.29-1.60, P<.001), the odds of major congenital anomaly by 26% (adjusted OR 1.26, 95% CI, 1.08-1.47, P=.003), the odds of perinatal loss by 47% (adjusted OR 1.47, 95% CI 1.07-2.02, P=.019), and the odds of a composite abnormal outcome by 77% (adjusted OR 1.77, 95% CI 1.15-2.74, P=.01). First-trimester nuchal cystic hygroma is associated with high rates of karyotype abnormality, major congenital anomaly, perinatal loss, and abnormal outcome. As the thickness of the nuchal translucency increases, the odds of abnormal karyotype, major congenital anomaly, perinatal loss, and abnormal outcome increase.
    Obstetrics and Gynecology 08/2012; 120(3):551-9. DOI:10.1097/AOG.0b013e318264f829 · 4.37 Impact Factor
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    ABSTRACT: To develop a prototype electronic ruler for assessment of fetal heart rate (FHR) variability on an electronic monitor and test its reliability and accuracy. A prototype electronic ruler was designed and developed for assessment of FHR variability on electronic monitors. The electronic ruler consisted of horizontal bands that were sized and colored to embed the four FHR variability categories. The reliability and accuracy of using the electronic ruler to assess FHR variability was studied with expert clinicians. Intrarater and interrater reliability was moderate for both the electronic ruler and paper strips. The amplitude measurement accuracy of expert variability assessment compared with a gold standard was significantly improved (p < 0.001) with the electronic ruler versus paper strips. The accuracy of subjects' FHR variability category responses compared with the gold standard revealed no significant difference (p = 0.50) using either display type. Performance of the electronic ruler was equivalent to paper strips, which may aid assessment of variability on electronic monitors as paper strips become less prevalent.
    American Journal of Perinatology 03/2012; 29(6):409-13. DOI:10.1055/s-0032-1304820 · 1.60 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2012; 206(1):S207. DOI:10.1016/j.ajog.2011.10.468 · 3.97 Impact Factor

Publication Stats

399 Citations
192.91 Total Impact Points

Institutions

  • 2006–2015
    • Tufts Medical Center
      • Department of Obstetrics and Gynecology
      Boston, Massachusetts, United States
  • 2014
    • Meharry Medical College
      • Department of Obstetrics and Gynecology
      Nashville, Tennessee, United States
  • 2001–2013
    • Tufts University
      • • Department of Biomedical Engineering
      • • Department of Obstetrics and Gynecology
      Бостон, Georgia, United States
    • Baylor College of Medicine
      Houston, Texas, United States
  • 2012
    • Society for Maternal-Fetal Medicine
      Boston, Massachusetts, United States
  • 2010
    • The Ohio State University
      Columbus, Ohio, United States
  • 2008
    • University of South Carolina School of Medicine - Greenville
      Гринвилл, South Carolina, United States