THE HUMAN FETAL LUNG XENOGRAFT: VALIDATION AS MODEL OF MICROVASCULAR REMODELING IN THE POSTGLANDULAR LUNG

PubMed Central

De Paepe, Monique E.; Chu, Sharon; Hall, Susan; Heger, Nicholas; Thanos, Chris; Mao, Quanfu

2012-01-01

Background Coordinated remodeling of epithelium and vasculature is essential for normal postglandular lung development. The value of the human-to-rodent lung xenograft as model of fetal microvascular development remains poorly defined. Aim The aim of this study was to determine the fate of the endogenous (human-derived) microvasculature in fetal lung xenografts. Methods Lung tissues were obtained from spontaneous pregnancy losses (14–22 weeks’ gestation) and implanted in the renal subcapsular or dorsal subcutaneous space of SCID-beige mice (T, B and NK-cell-deficient) and/or nude rats (T-cell-deficient). Informed parental consent was obtained. Lung morphogenesis, microvascular angiogenesis and epithelial differentiation were assessed at two and four weeks post-transplantation by light microscopy, immunohistochemical and gene expression studies. Archival age-matched postmortem lungs served as control. Results The vascular morphology, density and proliferation of renal subcapsular grafts in SCID-beige mice were similar to age-matched control lungs, with preservation of the physiologic association between epithelium and vasculature. The microvasculature of subcutaneous grafts in SCID-beige mice was underdeveloped and dysmorphic, associated with significantly lower VEGF, endoglin, and angiopoietin-2 mRNA expression than renal grafts. Grafts at both sites displayed mild airspace dysplasia. Renal subcapsular grafts in nude rats showed frequent infiltration by host lymphocytes and obliterating bronchiolitis-like changes, associated with markedly decreased endogenous angiogenesis. Conclusion This study demonstrates the critical importance of host and site selection to ensure optimal xenograft development. When transplanted to severely immune suppressed, NK-cell-deficient hosts and engrafted in the renal subcapsular site, the human-to-rodent fetal lung xenograft provides a valid model of postglandular microvascular lung remodeling. PMID:22811288

Intrinsic catch-up growth of hypoplastic fetal lungs is mediated by interleukin-6.

PubMed

Nogueira-Silva, Cristina; Moura, Rute S; Esteves, Nuno; Gonzaga, Sílvia; Correia-Pinto, Jorge

2008-07-01

Fetal lung hypoplasia is a common finding in several fetal conditions such as congenital diaphragmatic hernia (CDH). Interestingly, previous studies have demonstrated that hypoplastic lungs have the ability to recover to normal size, when relieved from mechanical factors. However, the underlying mechanisms remain largely unknown. Recently, interleukin-6 (IL-6) has been involved in catch-up growth phenomenon in children. Thus, we hypothesized that IL-6 could mediate fetal growth recover from hypoplastic lungs. Control and nitrofen-induced hypoplastic lung explants were cultured either in normal conditions or with IL-6 neutralizing antibodies. The total number of peripheral airway buds, epithelial perimeter, and total explant area were analyzed and daily branching rates were calculated. Additionally, IL-6 mRNA and protein expression was assessed both in qualitative (by in situ hybridization and immunohistochemistry) and in quantitative (by real-time PCR and Western blot) approaches, in control and hypoplastic lungs (nitrofen and CDH groups). Nitrofen-induced hypoplastic lungs showed in vitro, out of systemic environment, the ability to recover from hypoplasia and presented daily branching rates significantly higher than controls. Blocking IL-6 activity significantly diminished the intrinsic capacity of hypoplastic fetal lungs to recover from hypoplasia and attenuated their daily branching rates. Although more exacerbated in CDH, both nitrofen-exposed lungs presented significant IL-6 mRNA and protein over-expression throughout all studied gestational ages. The present study suggests, for the first time, that fetal lung is able to recover from growth retardation through a way that resembles the catch-up growth phenomenon, and it seems to be, at least partially, orchestrated by intrinsic mechanisms implicating IL-6.

The effect of in vitro tracheal occlusion on branching morphogenesis in fetal lung explants from the rat nitrofen model of congenital diaphragmatic hernia.

PubMed

Grushka, Jeremy R; Al-Abbad, Saleh; Baird, Robert; Puligandla, Pramod; Kaplan, Feige; Laberge, Jean-Martin

2010-05-01

Fetal tracheal occlusion (TO) has been investigated as a treatment option for lung hypoplasia secondary to congenital diaphragmatic hernia. Tracheal occlusion has been shown to accelerate lung growth, but its effect on bronchial branching is unknown. In this study, we characterize the effects of in vitro TO on bronchial branch development in fetal lung explants derived from the nitrofen rat model of congenital diaphragmatic hernia. Rat dams were gavaged nitrofen on gestational day 9.5, and fetal lungs were harvested for explant culture on gestational day 14 (term, 22 days). Four experimental groups were investigated, with TO performed ex vivo using cautery: control, control + TO, nitrofen, and nitrofen + TO. Explants were incubated for 72 hours. Representative photographs were taken at 0, 24, 48, and 72 hours from the time of culture, and the number of distal branches was counted for each explant. The Student t test was used to compare distal branch measurements. A minimum of 12 fetal lung explants were cultured for each group. By 24 hours, all explants undergoing TO had more branch iterations than explants that did not. Moreover, TO in nitrofen-exposed explants increased bronchial branching to control levels by 24 hours in culture. Our results suggest that TO at day 14 increases branching in normal and nitrofen-exposed lung explants. In addition, TO increases airway branching in nitrofen-exposed explants to control levels suggesting that early TO reverses the lung hypoplasia seen in this model. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Contribution of Fetal, but Not Adult, Pulmonary Mesothelium to Mesenchymal Lineages in Lung Homeostasis and Fibrosis.

PubMed

von Gise, Alexander; Stevens, Sean M; Honor, Leah B; Oh, Jin Hee; Gao, Chi; Zhou, Bin; Pu, William T

2016-02-01

The lung is enveloped by a layer of specialized epithelium, the pulmonary mesothelium. In other organs, mesothelial cells undergo epithelial-mesenchymal transition and contribute to organ stromal cells. The contribution of pulmonary mesothelial cells (PMCs) to the developing lung has been evaluated with differing conclusions. PMCs have also been indirectly implicated in lung fibrosis in the progressive, fatal lung disease idiopathic pulmonary fibrosis. We used fetal or postnatal genetic pulse labeling of PMCs to assess their fate in murine development, normal lung homeostasis, and models of pulmonary fibrosis. We found that most fetal PMC-derived mesenchymal cells (PMCDCs) expressed markers of pericytes and fibroblasts, only a small minority expressed smooth muscle markers, and none expressed endothelial cell markers. Postnatal PMCs did not contribute to lung mesenchyme during normal lung homeostasis or in models of lung fibrosis. However, fetal PMCDCs were abundant and actively proliferating within fibrotic regions in lung fibrosis models, suggesting that they actively participate in the fibrotic process. These data clarify the role of fetal and postnatal PMCDCs in lung development and disease.

Prenatal stress challenge impairs fetal lung development and asthma severity sex-specifically in mice.

PubMed

Zazara, Dimitra E; Perani, Clara V; Solano, María E; Arck, Petra C

2018-02-01

Allergic asthma is an increasing health problem worldwide. Interestingly, prenatal challenges such as stress have been associated with an increased risk for asthma during childhood. The underlying pathogenesis of how prenatal stress increases the risk for asthma still remains unclear. Potential targets could be that the fetal immune ontogeny or fetal lung development are compromised by prenatal challenges. Here, we aimed to identify whether prenatal stress challenge affects fetal lung development in mice. C57BL/6 pregnant mice were challenged with sound stress and fetal lung development was assessed histologically. Whilst prenatal stress challenge did not profoundly affect lung development in male fetuses, it resulted in less extensive terminal sacs, surrounded by thicker mesenchymal tissue in female fetuses. Thus, prenatal stress disrupted fetal lung development sex-specifically. Interestingly, upon prenatal stress challenge, the airway hyperresponsiveness and eosinophilic inflammation- two hallmarks of asthma - were significantly increased in adult female offspring, whilst regulatory CD4+ T cells were reduced. These findings strongly underpin the sex-specific association between s challenged fetal development and a sex-specific altered severity of asthma in adult offspring. Our model now allows to identify maternal markers through which the risk for asthma and possible other diseases is vertically transferred before birth in response to challenges. Such identification then opens avenues for primary disease prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

Small-volume amnioinfusion: a potential stimulus of intrapartum fetal heart rate accelerations.

PubMed

Wax, Joseph R; Flaherty, Nina; Pinette, Michael G; Blackstone, Jacquelyn; Cartin, Angelina

2004-02-01

We describe a recurrent nonreassuring fetal heart rate pattern in which small-volume amnioinfusions apparently evoked fetal heart rate accelerations suggested fetal well-being, allowing that progressive labor that culminated in the vaginal delivery of a healthy infant.

Tricuspid valve dysplasia with severe tricuspid regurgitation: fetal pulmonary artery size predicts lung viability in the presence of small lung volumes.

PubMed

Nathan, A T; Marino, B S; Dominguez, T; Tabbutt, S; Nicolson, S; Donaghue, D D; Spray, T L; Rychik, J

2010-01-01

Congenital tricuspid valve disease (Ebstein's anomaly, tricuspid valve dysplasia) with severe tricuspid regurgitation and cardiomegaly is associated with poor prognosis. Fetal echocardiography can accurately measure right atrial enlargement, which is associated with a poor prognosis in the fetus with tricuspid valve disease. Fetal lung volumetric assessments have been used in an attempt to predict viability of fetuses using ultrasonogram and prenatal MRI. We describe a fetus with tricuspid dysplasia, severe tricuspid regurgitation, right atrial enlargement and markedly reduced lung volumes. The early gestational onset of cardiomegaly with bilateral lung compression raised the possibility of severe lung hypoplasia with decreased broncho-alveolar development. Use of fetal echocardiography with measurement of pulmonary artery size combined with prenatal MRI scanning of lung volumes resulted in an improved understanding of this anomaly and directed the management strategy towards a successful Fontan circulation. 2010 S. Karger AG, Basel.

Peroxisome proliferator-activated receptor ligands regulate lipid content, metabolism, and composition in fetal lungs of diabetic rats.

PubMed

Kurtz, M; Capobianco, E; Careaga, V; Martinez, N; Mazzucco, M B; Maier, M; Jawerbaum, A

2014-03-01

Maternal diabetes impairs fetal lung development. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors relevant in lipid homeostasis and lung development. This study aims to evaluate the effect of in vivo activation of PPARs on lipid homeostasis in fetal lungs of diabetic rats. To this end, we studied lipid concentrations, expression of lipid metabolizing enzymes and fatty acid composition in fetal lungs of control and diabetic rats i) after injections of the fetuses with Leukotriene B4 (LTB4, PPARα ligand) or 15deoxyΔ(12,14)prostaglandin J2 (15dPGJ2, PPARγ ligand) and ii) fed during pregnancy with 6% olive oil- or 6% safflower oil-supplemented diets, enriched with PPAR ligands were studied. Maternal diabetes increased triglyceride concentrations and decreased expression of lipid-oxidizing enzymes in fetal lungs of diabetic rats, an expression further decreased by LTB4 and partially restored by 15dPGJ2 in lungs of male fetuses in the diabetic group. In lungs of female fetuses in the diabetic group, maternal diets enriched with olive oil increased triglyceride concentrations and fatty acid synthase expression, while those enriched with safflower oil increased triglyceride concentrations and fatty acid transporter expression. Both olive oil- and safflower oil-supplemented diets decreased cholesterol and cholesteryl ester concentrations and increased the expression of the reverse cholesterol transporter ATP-binding cassette A1 in fetal lungs of female fetuses of diabetic rats. In fetal lungs of control and diabetic rats, the proportion of polyunsaturated fatty acids increased with the maternal diets enriched with olive and safflower oils. Our results revealed important changes in lipid metabolism in fetal lungs of diabetic rats, and in the ability of PPAR ligands to modulate the composition of lipid species relevant in the lung during the perinatal period.

Autoradiographic localization of specific (/sup 3/H)dexamethasone binding in fetal lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beer, D.G.; Butley, M.S.; Cunha, G.R.

1984-10-01

The cellular and subcellular localization of specific (/sup 3/H)dexamethasone binding was examined in fetal mouse lung at various stages of development and in human fetal lung at 8 weeks of gestation using a rapid in vitro steroid incubation technique followed by thaw-mount autoradiography. Competition studies with unlabeled steroids demonstrate the specificity of (/sup 3/H)dexamethasone labeling, and indicate that fetal lung mesenchyme is a primary glucocorticoid target during lung development. Autoradiographs of (/sup 3/H)dexamethasone binding in lung tissue at early stages of development demonstrate that the mesenchyme directly adjacent to the more proximal portions of the bronchiolar network is heavily labeled.more » In contrast, the epithelium which will later differentiate into bronchi and bronchioles, is relatively unlabeled. Distal portions of the growing epithelium, destined to become alveolar ducts and alveoli, do show nuclear localization of (/sup 3/H)dexamethasone. In addition, by utilizing a technique which allows the simultaneous examination of extracellular matrix components and (/sup 3/H)dexamethasone binding, a relationship is observed between extensive mesenchymal (/sup 3/H)dexamethasone binding and extensive extracellular matrix accumulation. Since glucocorticoids stimulate the synthesis of many extracellular matrix components, these results suggest a role for these hormones in affecting mesenchymal-epithelial interactions during lung morphogenesis.« less

Fetal and post-natal lung defects reveal a novel and required role for Fgf8 in lung development

PubMed Central

Yu, Shibin; Poe, Bryan; Schwarz, Margaret; Elliot, Sarah; Albertine, Kurt H.; Fenton, Stephen; Garg, Vidu; Moon, Anne M.

2016-01-01

The fibroblast growth factor, FGF8, has been shown to be essential for vertebrate cardiovascular, craniofacial, brain and limb development. Here we report that Fgf8 function is required for normal progression through the late fetal stages of lung development that culminate in alveolar formation. Budding, lobation and branching morphogenesis are unaffected in early stage Fgf8 hypomorphic and conditional mutant lungs. Excess proliferation during fetal development disrupts distal airspace formation, mesenchymal and vascular remodeling, and Type I epithelial cell differentiation resulting in postnatal respiratory failure and death. Our findings reveal a previously unknown, critical role for Fgf8 function in fetal lung development and suggest that this factor may also contribute to postnatal alveologenesis. Given the high number of premature infants with alveolar dysgenesis and lung dysplasia, and the accumulating evidence that short-term benefits of available therapies may be outweighed by long term detrimental effects on postnatal alveologenesis, the therapeutic implications of identifying a factor or pathway that can be targeted to stimulate normal alveolar development are profound. PMID:20727874

Amniotic fluid derived mesenchymal stromal cells augment fetal lung growth in a nitrofen explant model.

PubMed

Di Bernardo, Julie; Maiden, Michael M; Hershenson, Marc B; Kunisaki, Shaun M

2014-06-01

Recent experimental work suggests the therapeutic role of mesenchymal stromal cells (MSCs) during lung morphogenesis. The purpose of this study was to investigate the potential paracrine effects of amniotic fluid-derived MSCs (AF-MSCs) on fetal lung growth in a nitrofen explant model. Pregnant Sprague-Dawley dams were gavage fed nitrofen on gestational day 9.5 (E9.5). E14.5 lung explants were subsequently harvested and cultured ex vivo for three days on filter membranes in conditioned media from rat AF-MSCs isolated from control (AF-Ctr) or nitrofen-exposed (AF-Nitro) dams. The lungs were analyzed morphometrically and by quantitative gene expression. Although there were no significant differences in total lung surface area among hypoplastic lungs, there were significant increases in terminal budding among E14.5+3 nitrofen explants exposed to AF-Ctr compared to explants exposed to medium alone (58.8±8.4 vs. 39.0±10.0 terminal buds, respectively; p<0.05). In contrast, lungs cultured in AF-Nitro medium failed to augment terminal budding. Nitrofen explants exposed to AF-Ctr showed significant upregulation of surfactant protein C to levels observed in normal fetal lungs. AF-MSCs can augment branching morphogenesis and lung epithelial maturation in a fetal explant model of pulmonary hypoplasia. Cell therapy using donor-derived AF-MSCs may represent a novel strategy for the treatment of fetal congenital diaphragmatic hernia. Copyright © 2014 Elsevier Inc. All rights reserved.

Origin of bombesin-like peptides in human fetal lung.

PubMed

Yoshizaki, K; de Bock, V; Solomon, S

1984-02-27

Four different forms of bombesin-like immunoreactive peaks were detected in extracts of human fetal lung by the use of reversed-phase high performance liquid chromatography (HPLC). Peaks I, II, III and IV, (increasing retention time), were eluted using a 14-38% of acetonitrile gradient containing 0.1% trifluoroacetic acid (TFA). Peak II was the major material found in the extract of human fetal lung obtained at 16-20 weeks gestation. None of the four compounds contained in the eluted peaks had the same retention time as amphibian bombesin or porcine gastrin releasing peptide (GRP). On reversed-phase HPLC using two different solvent systems TFA or heptafluorobutyric acid (HFBA) as a hydrophobic counter ion, and in gel filtration chromatography, the chromatographic behavior of the main peak (peak II) was the same as that of the carboxyl terminal fragments of GRP, GRP18-27 or GRP19-27. This suggested that the peptide(s) in peak II resembled in composition the carboxy terminal 9 or 10 amino acids of porcine GRP. Following tryptic digestion the material in peak IV was converted to the more polar compound present in peak II. Two other peptide peaks were eluted close to peak II and these were presumed to be a modification of this main peak. One of the possible biosynthetic steps in the formation of bombesin-like peptides in human fetal lung could be a tryptic conversion of a less polar peptide to a more polar form (peak IV to II).

Choriodecidual Group B Streptococcal Inoculation Induces Fetal Lung Injury without Intra-Amniotic Infection and Preterm Labor in Macaca nemestrina

PubMed Central

Adams Waldorf, Kristina M.; Gravett, Michael G.; McAdams, Ryan M.; Paolella, Louis J.; Gough, G. Michael; Carl, David J.; Bansal, Aasthaa; Liggitt, H. Denny; Kapur, Raj P.; Reitz, Frederick B.; Rubens, Craig E.

2011-01-01

Background Early events leading to intrauterine infection and fetal lung injury remain poorly defined, but may hold the key to preventing neonatal and adult chronic lung disease. Our objective was to establish a nonhuman primate model of an early stage of chorioamnionitis in order to determine the time course and mechanisms of fetal lung injury in utero. Methodology/Principal Findings Ten chronically catheterized pregnant monkeys (Macaca nemestrina) at 118–125 days gestation (term = 172 days) received one of two treatments: 1) choriodecidual and intra-amniotic saline (n = 5), or 2) choriodecidual inoculation of Group B Streptococcus (GBS) 1×106 colony forming units (n = 5). Cesarean section was performed regardless of labor 4 days after GBS or 7 days after saline infusion to collect fetal and placental tissues. Only two GBS animals developed early labor with no cervical change in the remaining animals. Despite uterine quiescence in most cases, blinded review found histopathological evidence of fetal lung injury in four GBS animals characterized by intra-alveolar neutrophils and interstitial thickening, which was absent in controls. Significant elevations of cytokines in amniotic fluid (TNF-α, IL-8, IL-1β, IL-6) and fetal plasma (IL-8) were detected in GBS animals and correlated with lung injury (p<0.05). Lung injury was not directly caused by GBS, because GBS was undetectable in amniotic fluid (∼10 samples tested/animal), maternal and fetal blood by culture and polymerase chain reaction. In only two cases was GBS cultured from the inoculation site in low numbers. Chorioamnionitis occurred in two GBS animals with lung injury, but two others with lung injury had normal placental histology. Conclusions/Significance A transient choriodecidual infection can induce cytokine production, which is associated with fetal lung injury without overt infection of amniotic fluid, chorioamnionitis or preterm labor. Fetal lung injury may, thus, occur silently

LGL1 modulates proliferation, apoptosis, and migration of human fetal lung fibroblasts.

PubMed

Zhang, Hui; Sweezey, Neil B; Kaplan, Feige

2015-02-15

Rapid growth and formation of new gas exchange units (alveogenesis) are hallmarks of the perinatal lung. Bronchopulmonary dysplasia (BPD), common in very premature infants, is characterized by premature arrest of alveogenesis. Mesenchymal cells (fibroblasts) regulate both lung branching and alveogenesis through mesenchymal-epithelial interactions. Temporal or spatial deficiency of late-gestation lung 1/cysteine-rich secretory protein LD2 (LGL1/CRISPLD2), expressed in and secreted by lung fibroblasts, can impair both lung branching and alveogenesis (LGL1 denotes late gestation lung 1 protein; LGL1 denotes the human gene; Lgl1 denotes the mouse/rat gene). Absence of Lgl1 is embryonic lethal. Lgl1 levels are dramatically reduced in oxygen toxicity rat models of BPD, and heterozygous Lgl1(+/-) mice exhibit features resembling human BPD. To explore the role of LGL1 in mesenchymal-epithelial interactions in developing lung, we developed a doxycycline (DOX)-inducible RNA-mediated LGL1 knockdown cellular model in human fetal lung fibroblasts (MRC5(LGL1KD)). We assessed the impact of LGL1 on cell proliferation, cell migration, apoptosis, and wound healing. DOX-induced MRC5(LGL1KD) suppressed cell growth and increased apoptosis of annexin V(+) staining cells and caspase 3/7 activity. LGL1-conditioned medium increased migration of fetal rat primary lung epithelial cells and human airway epithelial cells. Impaired healing by MRC5(LGL1KD) cells of a wound model was attenuated by addition of LGL1-conditioned medium. Suppression of LGL1 was associated with dysregulation of extracellular matrix genes (downregulated MMP1, ColXVα1, and ELASTIN) and proapoptosis genes (upregulated BAD, BAK, CASP2, and TNFRSF1B) and inhibition of 44/42MAPK phosphorylation. Our findings define a role for LGL1 in fibroblast expansion and migration, epithelial cell migration, and mesenchymal-epithelial signaling, key processes in fetal lung development. Copyright © 2015 the American Physiological

CD10/neutral endopeptidase 24.11 in developing human fetal lung. Patterns of expression and modulation of peptide-mediated proliferation.

PubMed

Sunday, M E; Hua, J; Torday, J S; Reyes, B; Shipp, M A

1992-12-01

The cell membrane-associated enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) functions in multiple organ systems to downregulate responses to peptide hormones. Recently, CD10/NEP was found to hydrolyze bombesin-like peptides (BLP), which are mitogens for normal bronchial epithelial cells and small cell lung carcinomas. Growth of BLP-responsive small cell lung carcinomas was potentiated by CD10/NEP inhibition, implicating CD10/NEP in regulation of BLP-mediated tumor growth. BLP are also likely to participate in normal lung development because high BLP levels are found in fetal lung, and bombesin induces proliferation and maturation of human fetal lung in organ cultures and murine fetal lung in utero. To explore potential roles for CD10/NEP in regulating peptide-mediated human fetal lung development, we have characterized temporal and cellular patterns of CD10/NEP expression and effects of CD10/NEP inhibition in organ cultures. Peak CD10/NEP transcript levels are identified at 11-13 wk gestation by Northern blots and localized to epithelial cells and mesenchyme of developing airways by in situ hybridization. CD10/NEP immunostaining is most intense in undifferentiated airway epithelium. In human fetal lung organ cultures, inhibition of CD10/NEP with either phosphoramidon or SCH32615 increases thymidine incorporation by 166-182% (P < 0.025). The specific BLP receptor antagonist, [Leu13-psi(CH2NH)Leu14]bombesin abolishes these effects on fetal lung growth, suggesting that CD10/NEP modulates BLP-mediated proliferation. CD10/NEP expression in the growing front of airway epithelium and the effects of CD10/NEP inhibitors in lung explants implicate the enzyme in the regulation of peptide-mediated fetal lung growth.

Bombesin-like peptides and receptors in normal fetal baboon lung: roles in lung growth and maturation.

PubMed

Emanuel, R L; Torday, J S; Mu, Q; Asokananthan, N; Sikorski, K A; Sunday, M E

1999-11-01

Previously, we have shown that bombesin-like peptide (BLP) promotes fetal lung development in rodents and humans but mediates postnatal lung injury in hyperoxic baboons. The present study analyzed the normal ontogeny of BLP and BLP receptors as well as the effects of BLP on cultured normal fetal baboon lungs. Transcripts encoding gastrin-releasing peptide (GRP), a pulmonary BLP, were detectable on gestational day 60 (ED60), peaked on approximately ED90, and then declined before term (ED180). Numbers of BLP-immunopositive neuroendocrine cells peaked from ED80 to ED125 and declined by ED160, preceding GRP-receptor mRNAs detected from ED125 until birth. BLP (0.1-10 nM) stimulated type II cell differentiation in organ cultures as assessed by [(3)H]choline incorporation into surfactant phospholipids, electron microscopy, and increased surfactant protein (SP) A- and/or SP-C-immunopositive cells and SP-A mRNA. BLP also induced neuroendocrine differentiation on ED60. Cell proliferation was induced by GRP, peaking on ED90. Similarly, blocking BLP degradation stimulated lung growth and maturation, which was completely reversed by a BLP-specific antagonist. The dissociation between GRP and GRP-receptor gene expression during ontogeny suggests that novel BLP receptors and/or peptides might be implicated in these responses.

Effect of Fetal Mouse Lung Tissue Co-Culture on In Vitro Maturation of Mouse Immature Oocytes.

PubMed

Belbasi, Masomeh; Jorsaraei, Seyed Gholam Ali; Gholamitabar Tabari, Maryam; Khanbabaei, Ramzan

2017-10-01

The aim of this study was to evaluate the fetal mouse lung tissue co-culture on in vitro maturation (IVM) of mouse immature oocytes. In this experimental study, germinal vesicle (GV) oocytes from ovaries of a group of 25 female mice, 6-8 weeks of age, were dissected after being stimulated by 7.5 IU pregnant mare serum gonadotropin (PMSG) through an intraperitoneal (IP) injection. The fetal lung tissues were then prepared and cultured individually. A total number of 300 oocytes were cultured in the following three groups for 24 hours: control group (n=100) containing only base medium, group I (n=100) containing base medium co-cultured with 11.5- to 12.5-day old fetal mouse lung tissues, and group II (n=100) containing base medium co-cultured with 12.5- to 13.5-day old fetal mouse lung tissues. The proportion of GV and metaphase І (MI) oocytes matured into MІІ oocytes were compared among the three groups using analysis of variance (ANOVA). Correlation test were also used to evaluate the successful rate of IVM oocytes. The proportions of GV oocytes reaching MІІ stage were 46, 65, and 56%, in control, I and II groups, respectively (P<0.05). The percentage of the oocytes remaining at the GV stage were higher in control group as compared with two treatment groups (P<0.05). This study indicated that fetal mouse lung tissue co-culture method increased the percentage of GV oocytes reaching MII stage. Copyright© by Royan Institute. All rights reserved.

Canine fetal heart rate: do accelerations or decelerations predict the parturition day in bitches?

PubMed

Gil, E M U; Garcia, D A A; Giannico, A T; Froes, T R

2014-10-15

Ultrasonography is a safe and efficient technique for monitoring fetal development and viability. One of the most important and widely used parameters to verify fetal viability is the fetal heart rate (HR). In human medicine, the fetal HR normally oscillates during labor in transient accelerations and decelerations associated with uterine contractions. The present study investigated whether these variations also occur in canine fetuses and its relationship to parturition. A cohort study was conducted in 15 pregnant bitches undergoing two-dimensional high-resolution ultrasonographic examination during the 8th and 9th week of gestation. Fetal HR was assessed in M-mode for 5 minutes in each fetus in all bitches. In addition, the bitches were monitored for clinical signs of imminent parturition. Associations between the HR, antepartum time, and delivery characteristics were evaluated with a Poisson regression model. Fetal HR acceleration and deceleration occurred in canine fetuses and predicted the optimal time of parturition. These findings can help veterinarians and sonographers better understand this phenomenon in canine fetuses. Copyright © 2014 Elsevier Inc. All rights reserved.

The role of integrin α8β1 in fetal lung morphogenesis and injury

PubMed Central

Benjamin, John T.; Gaston, David C.; Halloran, Brian A.; Schnapp, Lynn M.; Zent, Roy; Prince, Lawrence S.

2009-01-01

Prenatal inflammation prevents normal lung morphogenesis and leads to bronchopulmonary dysplasia (BPD), a common complication of preterm birth. We previously demonstrated in a bacterial endotoxin mouse model of BPD that disrupting fibronectin localization in the fetal lung mesenchyme causes arrested saccular airway branching. In this study we show that expression of the fibronectin receptor, integrin α8β1, is decreased in the lung mesenchyme in the same inflammation model suggesting it is required for normal lung development. We verified a role for integrin α8β1 in lung development using integrin α8-null mice, which develop fusion of the medial and caudal lobes as well as abnormalities in airway division. We further show in vivo and vitro that α8-null fetal lung mesenchymal cells fail to form stable adhesions and have increased migration. Thus we propose that integrin α8β1 plays a critical role in lung morphogenesis by regulating mesenchymal cell adhesion and migration. Furthermore, our data suggests that disruption of the interactions between extracellular matrix and integrin α8β1 may contribute to the pathogenesis of BPD. PMID:19769957

Effects of intratracheal budesonide during early postnatal life on lung maturity of premature fetal rabbits.

PubMed

Li, Ling; Yang, Chen; Feng, Xiuliang; Du, Yongping; Zhang, Zhihong; Zhang, Yueping

2018-01-01

This study aimed to study the effects of intratracheal instillation of budesonide on lung maturity of premature fetal rabbits. The developmental pattern of pulmonary alveoli in rabbits is similar to that in humans. Fetal rabbits were taken out from female rabbits on the 28th day of pregnancy (full term = 31 days) by cesarean section (c-section). The fetal rabbits were divided into four groups: control (normal saline, NS), budesonide (budesonide, BUD), calf pulmonary surfactant for injection (pulmonary surfactant, PS), and calf pulmonary surfactant + budesonide for injection (pulmonary surfactant + budesonide, PS + BUD). All premature rabbits were kept warm after c-section. After 15-min autonomous respiration, a tracheal cannula was implemented for instilling NS, BUD, PS, and PS + BUD. The morphology of lung tissues of premature fetal rabbits was analyzed using optical and electron microscopes. Surfactant protein B (SP-B) mRNA and protein levels in lung tissues were determined using polymerase chain reaction and Western blotting, respectively. Intratracheal instillation of BUD could increase the alveolar area of the fetal rabbits (P < 0.01), decrease the alveolar wall thickness (P < 0.01), and increase the mean density of lamellar bodies (P < 0.05) and SP-B protein levels in type II epithelial cells of pulmonary alveoli (P < 0.05). Intratracheal instillation of BUD during early postnatal life is effective in promoting alveolarization and increasing SP-B expression, the pro-pulmonary maturity of BUD combined with PS is superior to that of BUD or PS alone. However, the long-term effect of BUD on lung development needs further exploration. © 2017 Wiley Periodicals, Inc.

Maternal Azithromycin Therapy for Ureaplasma Intra-Amniotic Infection Delays Preterm Delivery and Reduces Fetal Lung Injury in a Primate Model

PubMed Central

Grigsby, Peta L.; Novy, Miles J.; Sadowsky, Drew W.; Morgan, Terry K.; Long, Mary; Acosta, Ed; Duffy, Lynn B; Waites, Ken B.

2012-01-01

Objective We assessed the efficacy of a maternal multi–dose azithromycin (AZI) regimen, with and without anti–inflammatory agents to delay preterm birth and to mitigate fetal lung injury associated with Ureaplasma parvum intra–amniotic infection (IAI). Study Design Long–term catheterized rhesus monkeys (n=16) received intra–amniotic inoculation of U. parvum (107 CFU/ml, serovar 1). After contraction onset, rhesus monkeys received either no treatment (n=6); AZI (12.5mg/kg, q12h, IV for 10 days; n=5); or AZI plus dexamethasone (DEX) and indomethacin (INDO; n=5). Outcomes included amniotic fluid pro–inflammatory mediators, U. parvum cultures & PCR, AZI pharmacokinetics and the extent of fetal lung inflammation. Results Maternal AZI therapy eradicated U. parvum IAI from the amniotic fluid within 4 days. Placenta and fetal tissues were 90% culture negative at delivery. AZI therapy significantly delayed preterm delivery and prevented advanced fetal lung injury, although residual acute chorioamnionitis persisted. Conclusions Specific maternal antibiotic therapy can eradicate U. parvum from the amniotic fluid and key fetal organs, with subsequent prolongation of pregnancy which provides a therapeutic window of opportunity to effectively reduce the severity of fetal lung injury. PMID:23111115

Ghrelin expression in human and rat fetal lungs and the effect of ghrelin administration in nitrofen-induced congenital diaphragmatic hernia.

PubMed

Santos, Marta; Bastos, Pedro; Gonzaga, Silvia; Roriz, José-Mário; Baptista, Maria J; Nogueira-Silva, Cristina; Melo-Rocha, Gustavo; Henriques-Coelho, Tiago; Roncon-Albuquerque, Roberto; Leite-Moreira, Adelino F; De Krijger, Ronald R; Tibboel, Dick; Rottier, Robbert; Correia-Pinto, Jorge

2006-04-01

Ghrelin is a strong physiologic growth hormone secretagogue that exhibits endocrine and non-endocrine actions. In this study, ghrelin expression in humans and rats was evaluated throughout development of normal and hypoplastic lungs associated with congenital diaphragmatic hernia (CDH). Additionally, the effect of antenatal treatment with ghrelin in the nitrofen-induced CDH rat model was tested. In normal lungs, ghrelin was expressed in the primitive epithelium at early stages of development and decreased in levels of expression with gestational age. In hypoplastic lungs ghrelin was overexpressed in both human and rat CDH fetuses when compared with controls. Exogenous administration of ghrelin to nitrofen-treated dams led to an attenuation of pulmonary hypoplasia of CDH pups. Furthermore, the growth hormone, secretagogue receptor (GHSR1a), could not be amplified from human or rat fetal lungs by RT-PCR. In conclusion, of all the lungs studied so far, the fetal lung is one of the first to express ghrelin during development and might be considered a new source of circulating fetal ghrelin. Overexpression of ghrelin in hypoplastic lungs and the effect of exogenous administration of ghrelin to nitrofen-treated dams strongly suggest a role for ghrelin in mechanisms involved in attenuation of fetal lung hypoplasia, most likely through a GHSR1a-independent pathway.

Fetal Onset of Aberrant Gene Expression Relevant to Pulmonary Carcinogenesis in Lung Adenocarcinoma Development Induced by In Utero Arsenic Exposure

PubMed Central

Shen, Jun; Liu, Jie; Xie, Yaxiong; Diwan, Bhalchandra A.; Waalkes, Michael P.

2009-01-01

Arsenic is a human pulmonary carcinogen. Our work indicates that in utero arsenic exposure in mice can induce or initiate lung cancer in female offspring. To define early molecular changes, pregnant C3H mice were given 85 ppm arsenic in drinking water from days 8 to 18 of gestation and expression of selected genes in the fetal lung or in lung tumors developing in adults was examined. Transplacental arsenic exposure increased estrogen receptor-α (ER-α) transcript and protein levels in the female fetal lung. An overexpression of various estrogen-regulated genes also occurred, including trefoil factor-3, anterior gradient-2, and the steroid metabolism genes 17-β-hydroxysteroid dehydrogenase type 5 and aromatase. The insulin growth factor system, which can be influenced by ER and has been implicated in the pulmonary oncogenic process, was activated in fetal lung after gestational arsenic exposure. in utero arsenic exposure also induced overexpression of α-fetoprotein, epidermal growth factor receptor, L-myc, and metallothionein-1 in fetal lung, all of which are associated with lung cancer. Lung adenoma and adenocarcinoma from adult female mice exposed to arsenic in utero showed widespread, intense nuclear ER-α expression. In contrast, normal adult lung and diethylnitrosamine-induced lung adenocarcinoma showed little evidence of ER-α expression. Thus, transplacental arsenic exposure at a carcinogenic dose produced aberrant estrogen-linked pulmonary gene expression. ER-α activation was specifically associated with arsenic-induced lung adenocarcinoma and adenoma but not with nitrosamine-induced lung tumors. These data provide evidence that arsenic-induced aberrant ER signaling could disrupt early life stage genetic programing in the lung leading eventually to lung tumor formation much later in adulthood. PMID:17077188

Fetal onset of aberrant gene expression relevant to pulmonary carcinogenesis in lung adenocarcinoma development induced by in utero arsenic exposure.

PubMed

Shen, Jun; Liu, Jie; Xie, Yaxiong; Diwan, Bhalchandra A; Waalkes, Michael P

2007-02-01

Arsenic is a human pulmonary carcinogen. Our work indicates that in utero arsenic exposure in mice can induce or initiate lung cancer in female offspring. To define early molecular changes, pregnant C3H mice were given 85 ppm arsenic in drinking water from days 8 to 18 of gestation and expression of selected genes in the fetal lung or in lung tumors developing in adults was examined. Transplacental arsenic exposure increased estrogen receptor-alpha (ER-alpha) transcript and protein levels in the female fetal lung. An overexpression of various estrogen-regulated genes also occurred, including trefoil factor-3, anterior gradient-2, and the steroid metabolism genes 17-beta-hydroxysteroid dehydrogenase type 5 and aromatase. The insulin growth factor system, which can be influenced by ER and has been implicated in the pulmonary oncogenic process, was activated in fetal lung after gestational arsenic exposure. In utero arsenic exposure also induced overexpression of alpha-fetoprotein, epidermal growth factor receptor, L-myc, and metallothionein-1 in fetal lung, all of which are associated with lung cancer. Lung adenoma and adenocarcinoma from adult female mice exposed to arsenic in utero showed widespread, intense nuclear ER-alpha expression. In contrast, normal adult lung and diethylnitrosamine-induced lung adenocarcinoma showed little evidence of ER-alpha expression. Thus, transplacental arsenic exposure at a carcinogenic dose produced aberrant estrogen-linked pulmonary gene expression. ER-alpha activation was specifically associated with arsenic-induced lung adenocarcinoma and adenoma but not with nitrosamine-induced lung tumors. These data provide evidence that arsenic-induced aberrant ER signaling could disrupt early life stage genetic programing in the lung leading eventually to lung tumor formation much later in adulthood.

Overexpression of transforming growth factor-β1 in fetal monkey lung results in prenatal pulmonary fibrosis

PubMed Central

Tarantal, A.F.; Chen, H.; Shi, T.T.; Lu, C-H.; Fang, A.B.; Buckley, S.; Kolb, M.; Gauldie, J.; Warburton, D.; Shi, W.

2011-01-01

Altered transforming growth factor (TGF)-β expression levels have been linked to a variety of human respiratory diseases, including bronchopulmonary dysplasia and pulmonary fibrosis. However, a causative role for aberrant TGF-β in neonatal lung diseases has not been defined in primates. Exogenous and transient TGF-β1 overexpression in fetal monkey lung was achieved by transabdominal ultrasound-guided fetal intrapulmonary injection of adenoviral vector expressing TGF-β1 at the second or third trimester of pregnancy. The lungs were then harvested near term, and fixed for histology and immunohistochemistry. Lung hypoplasia was observed where TGF-β1 was overexpressed during the second trimester. The most clearly marked phenotype consisted of severe pulmonary and pleural fibrosis, which was independent of the gestational time point when TGF-β1 was overexpressed. Increased cell proliferation, particularly in α-smooth muscle actin-positive myofibroblasts, was detected within the fibrotic foci. But epithelium to mesenchyme transdifferentiation was not detected. Massive collagen fibres were deposited on the inner and outer sides of the pleural membrane, with an intact elastin layer in the middle. This induced fibrotic pathology persisted even after adenoviral-mediated TGF-β1 overexpression was no longer evident. Therefore, overexpression of TGF-β1 within developing fetal monkey lung results in severe and progressive fibrosis in lung parenchyma and pleural membrane, in addition to pulmonary hypoplasia. PMID:20351039

Surfactant protein secreted by the maturing mouse fetal lung acts as a hormone that signals the initiation of parturition

PubMed Central

Condon, Jennifer C.; Jeyasuria, Pancharatnam; Faust, Julie M.; Mendelson, Carole R.

2004-01-01

Parturition is timed to begin only after the developing embryo is sufficiently mature to survive outside the womb. It has been postulated that the signal for the initiation of parturition arises from the fetus although the nature and source of this signal remain obscure. Herein, we provide evidence that this signal originates from the maturing fetal lung. In the mouse, secretion of the major lung surfactant protein, surfactant protein A (SP-A), was first detected in amniotic fluid (AF) at 17 days postcoitum, rising progressively to term (19 days postcoitum). Expression of IL-1β in AF macrophages and activation of NF-κB in the maternal uterus increased with the gestational increase in SP-A. SP-A stimulated IL-1β and NF-κB expression in cultured AF macrophages. Studies using Rosa 26 Lac-Z (B6;129S-Gt(rosa)26Sor) (Lac-Z) mice revealed that fetal AF macrophages migrate to the uterus with the gestational increase in AF SP-A. Intraamniotic (i.a.) injection of SP-A caused preterm delivery of fetuses within 6-24 h. By contrast, injection of an SP-A antibody or NF-κB inhibitor into AF delayed labor by >24 h. We propose that augmented production of SP-A by the fetal lung near term causes activation and migration of fetal AF macrophages to the maternal uterus, where increased production of IL-1β activates NF-κB, leading to labor. We have revealed a response pathway that ties augmented surfactant production by the maturing fetal lung to the initiation of labor. We suggest that SP-A secreted by the fetal lung serves as a hormone of parturition. PMID:15044702

CD10/neutral endopeptidase 24.11 regulates fetal lung growth and maturation in utero by potentiating endogenous bombesin-like peptides.

PubMed

King, K A; Hua, J; Torday, J S; Drazen, J M; Graham, S A; Shipp, M A; Sunday, M E

1993-05-01

Bombesin-like peptides (BLPs) are mitogens for bronchial epithelial cells and small cell lung carcinomas, and increase fetal lung growth and maturation in utero and in organ cultures. BLPs are hydrolyzed by the enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) which is expressed in bronchial epithelium and functions to inhibit BLP-mediated growth of small cell lung carcinomas. To determine whether CD10/NEP regulates peptide-mediated lung development, we administered a specific CD10/NEP inhibitor, SCH32615, to fetal mice in utero from gestational days e15-17. Fetal lung tissues were evaluated on e18 for: (a) growth using [3H]thymidine incorporation into nuclear DNA; and (b) maturation using: [3H]-choline incorporation into surfactant phospholipids, electron microscopy for type II pneumocytes, and Northern blot analyses for surfactant apoproteins A, B, and C. Inhibition of CD10/NEP stimulated [3H]thymidine incorporation into DNA (70% above baseline, P < 0.005), [3H]choline incorporation into surfactant phospholipids (38% above baseline, P < 0.005), increased numbers of type II pneumocytes (36% above baseline, P = 0.07), and fivefold higher surfactant protein A transcripts (P < 0.05). CD10/NEP-mediated effects were completely blocked by the specific bombesin receptor antagonist, [D-Phe12, Leu14]bombesin. These observations suggest that CD10/NEP regulates fetal lung growth and maturation mediated by endogenous BLPs.

Growth Patterns of Fetal Lung Volumes in Healthy Fetuses and Fetuses With Isolated Left-Sided Congenital Diaphragmatic Hernia.

PubMed

Ruano, Rodrigo; Britto, Ingrid Schwach Werneck; Sananes, Nicolas; Lee, Wesley; Sangi-Haghpeykar, Haleh; Deter, Russell L

2016-06-01

To evaluate fetal lung growth using 3-dimensional sonography in healthy fetuses and those with congenital diaphragmatic hernia (CDH). Right and total lung volumes were serially evaluated by 3-dimensional sonography in 66 healthy fetuses and 52 fetuses with left-sided CDH between 20 and 37 weeks' menstrual age. Functions fitted to these parameters were compared for 2 groups: (1) healthy versus those with CDH; and (2) fetuses with CHD who survived versus those who died. Fetal right and total lung volumes as well as fetal observed-to-expected right and total lung volume ratios were significantly lower in fetuses with CDH than healthy fetuses (P< .001) and in those fetuses with CDH who died (P< .001). The observed-to-expected right and total lung volume ratios did not vary with menstrual age in healthy fetuses or in those with CDH (independent of outcome). Lung volume rates were lower in fetuses with left-sided CDH compared to healthy fetuses, as well as in fetuses with CDH who died compared to those who survived. The observed-to-expected right and total lung volume ratios were relatively constant throughout menstrual age in fetuses with left-sided CDH, suggesting that the origin of their lung growth abnormalities occurred before 20 weeks and did not progress. The observed-to-expected ratios may be useful in predicting the outcome in fetuses with CDH independent of menstrual age. © 2016 by the American Institute of Ultrasound in Medicine.

Fetal lung apparent diffusion coefficient measurement using diffusion-weighted MRI at 3 Tesla: Correlation with gestational age.

PubMed

Afacan, Onur; Gholipour, Ali; Mulkern, Robert V; Barnewolt, Carol E; Estroff, Judy A; Connolly, Susan A; Parad, Richard B; Bairdain, Sigrid; Warfield, Simon K

2016-12-01

To evaluate the feasibility of using diffusion-weighted magnetic resonance imaging (DW-MRI) to assess the fetal lung apparent diffusion coefficient (ADC) at 3 Tesla (T). Seventy-one pregnant women (32 second trimester, 39 third trimester) were scanned with a twice-refocused Echo-planar diffusion-weighted imaging sequence with 6 different b-values in 3 orthogonal diffusion orientations at 3T. After each scan, a region-of-interest (ROI) mask was drawn to select a region in the fetal lung and an automated robust maximum likelihood estimation algorithm was used to compute the ADC parameter. The amount of motion in each scan was visually rated. When scans with unacceptable levels of motion were eliminated, the lung ADC values showed a strong association with gestational age (P < 0.01), increasing dramatically between 16 and 27 weeks and then achieving a plateau around 27 weeks. We show that to get reliable estimates of ADC values of fetal lungs, a multiple b-value acquisition, where motion is either corrected or considered, can be performed. J. Magn. Reson. Imaging 2016;44:1650-1655. © 2016 International Society for Magnetic Resonance in Medicine.

Prenatally diagnosed fetal lung lesions with associated conotruncal heart defects: is there a genetic association?

PubMed

Hüsler, Margaret R; Wilson, R Douglas; Rychik, Jack; Bebbington, Michael W; Johnson, Mark P; Mann, Stephanie E; Hedrick, Holly L; Adzick, Scott

2007-12-01

Congenital lung malformation can easily be diagnosed by prenatal ultrasound. Associated extrapulmonary malformations such as heart defects and chromosomal aberrations are rare. The objective of this study was to describe the natural history, outcome and other associated malformations in fetuses with lung lesions and an associated heart defect. Retrospective analysis of 4 cases of prenatally diagnosed fetal CCAMs and hybrid lesions with an associated heart defect and review of 8 cases in the literature. At a single referral center 1.9% of the fetuses with Congenital cystic adenomatoid malformation (CCAM) were diagnosed with an associated heart defect. Seven of the total 12 cases (58%) reviewed had a conotruncal heart abnormality. Chromosomal abnormalities were found in 5 (42%) of the cases. This retrospective review shows that karyotyping in fetal lung lesions with an associated heart defect or isolated large lung lesions is indicated. It also suggests that there is a subpopulation of fetuses with CCAMs who have conotruncal heart defects. This finding may suggest a common genetic background. Copyright (c) 2007 John Wiley & Sons, Ltd.

Left ventricular obstruction with restrictive inter-atrial communication leads to retardation in fetal lung maturation.

PubMed

Goltz, Diane; Lunkenheimer, Jean-Marc; Abedini, Mojtaba; Herberg, Ulrike; Berg, Christoph; Gembruch, Ulrich; Fischer, Hans-Peter

2015-05-01

Intact atrial septum or highly restrictive inter-atrial communication (I/HRAS) combined with either severe aortic stenosis (SAS) or hypoplastic left heart syndrome (HLHS), respectively, is associated with adverse outcome. This study focusses on changes in alveolo-septal lung parenchyma due to increased left atrial pressure. In a retrospective cross-sectional autoptic study, we investigated fetal/neonatal lung specimens of 18 patients with SAS/HLHS with I/HRAS, 11 patients with SAS/HLHS and unrestrictive inter-atrial communications and 18 controls. Pulmonary maturation was investigated by means of morphometric and immunohistochemical analyses. In a comparison of all three groups, alveolo-capillary membrane maturation was significantly disturbed in I/HRAS fetuses from week 23 of pregnancy on. I/HRAS lungs showed angiomatoid hyper-capillarisation and significantly wider inter-airspace mesenchyme. Differences in width ranged between 34.58 µm (95% CI: 11.41-57.75 µm) and 46.74 µm (95% CI: 13.97-79.50 µm) in the second and third trimesters. In I/HRAS infants with HLHS, inter-airspace mesenchymal diameters steadily normalised with age; however, significant fibroelastosis of alveolar septae developed. Fetal lung maturation with respect to alveolo-capillary membrane formation is severely disordered in patients with SAS/HLHS with I/HRAS. Our findings indicate that, from a morphological point of view, timing of fetal invention in fetuses with I/HRAS should be fixed within the second trimester of pregnancy. © 2015 John Wiley & Sons, Ltd.

CD10/neutral endopeptidase 24.11 regulates fetal lung growth and maturation in utero by potentiating endogenous bombesin-like peptides.

PubMed Central

King, K A; Hua, J; Torday, J S; Drazen, J M; Graham, S A; Shipp, M A; Sunday, M E

1993-01-01

Bombesin-like peptides (BLPs) are mitogens for bronchial epithelial cells and small cell lung carcinomas, and increase fetal lung growth and maturation in utero and in organ cultures. BLPs are hydrolyzed by the enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) which is expressed in bronchial epithelium and functions to inhibit BLP-mediated growth of small cell lung carcinomas. To determine whether CD10/NEP regulates peptide-mediated lung development, we administered a specific CD10/NEP inhibitor, SCH32615, to fetal mice in utero from gestational days e15-17. Fetal lung tissues were evaluated on e18 for: (a) growth using [3H]thymidine incorporation into nuclear DNA; and (b) maturation using: [3H]-choline incorporation into surfactant phospholipids, electron microscopy for type II pneumocytes, and Northern blot analyses for surfactant apoproteins A, B, and C. Inhibition of CD10/NEP stimulated [3H]thymidine incorporation into DNA (70% above baseline, P < 0.005), [3H]choline incorporation into surfactant phospholipids (38% above baseline, P < 0.005), increased numbers of type II pneumocytes (36% above baseline, P = 0.07), and fivefold higher surfactant protein A transcripts (P < 0.05). CD10/NEP-mediated effects were completely blocked by the specific bombesin receptor antagonist, [D-Phe12, Leu14]bombesin. These observations suggest that CD10/NEP regulates fetal lung growth and maturation mediated by endogenous BLPs. Images PMID:8486767

Endotoxin-induced nitric oxide production rescues airway growth and maturation in atrophic fetal rat lung explants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rae, C.; Cherry, J.I.; Land, F.M.

Inflammation induces premature maturation of the fetal lung but the signals causing this effect remain unclear. We determined if nitric oxide (NO) synthesis, evoked by Escherichia coli lipopolysaccharide (LPS, 2 {mu}g ml{sup -1}), participated in this process. Fetal rat lung airway surface complexity rose 2.5-fold over 96 h in response to LPS and was associated with increased iNOS protein expression and activity. iNOS inhibition by N6-(1-iminoethyl)-L-lysine-2HCl (L-NIL) abolished this and induced airway atrophy similar to untreated explants. Surfactant protein-C (SP-C) expression was also induced by LPS and abolished by L-NIL. As TGF{beta} suppresses iNOS activity, we determined if feedback regulationmore » modulated NO-dependent maturation. LPS induced TGF{beta}1 release and SMAD4 nuclear translocation 96 h after treatment. Treatment of explants with a blocking antibody against TGF{beta}1 sustained NO production and airway morphogenesis whereas recombinant TGF{beta}1 antagonized these effects. Feedback regulation of NO synthesis by TGF{beta} may, thus, modulate airway branching and maturation of the fetal lung.« less

The innate immune response in fetal lung mesenchymal cells targets VEGFR2 expression and activity.

PubMed

Medal, Rachel M; Im, Amanda M; Yamamoto, Yasutoshi; Lakhdari, Omar; Blackwell, Timothy S; Hoffman, Hal M; Sahoo, Debashis; Prince, Lawrence S

2017-06-01

In preterm infants, soluble inflammatory mediators target lung mesenchymal cells, disrupting airway and alveolar morphogenesis. However, how mesenchymal cells respond directly to microbial stimuli remains poorly characterized. Our objective was to measure the genome-wide innate immune response in fetal lung mesenchymal cells exposed to the bacterial endotoxin lipopolysaccharide (LPS). With the use of Affymetrix MoGene 1.0st arrays, we showed that LPS induced expression of unique innate immune transcripts heavily weighted toward CC and CXC family chemokines. The transcriptional response was different between cells from E11, E15, and E18 mouse lungs. In all cells tested, LPS inhibited expression of a small core group of genes including the VEGF receptor Vegfr2 Although best characterized in vascular endothelial populations, we demonstrated here that fetal mouse lung mesenchymal cells express Vegfr2 and respond to VEGF-A stimulation. In mesenchymal cells, VEGF-A increased cell migration, activated the ERK/AKT pathway, and promoted FOXO3A nuclear exclusion. With the use of an experimental coculture model of epithelial-mesenchymal interactions, we also showed that VEGFR2 inhibition prevented formation of three-dimensional structures. Both LPS and tyrosine kinase inhibition reduced three-dimensional structure formation. Our data suggest a novel mechanism for inflammation-mediated defects in lung development involving reduced VEGF signaling in lung mesenchyme. Copyright © 2017 the American Physiological Society.

Fetal laser ablation of feeding artery of cystic lung lesions with systemic arterial blood supply.

PubMed

Cruz-Martinez, R; Martínez-Rodríguez, M; Bermúdez-Rojas, M; Magaña-Abarca, C; Narvaez-Dominguez, V; Rojas-Macedo, A; Bautista-García, N; Alcocer-Alcocer, M

2017-06-01

To assess the effectiveness of laser surgery in fetuses with a cystic lung lesion with systemic arterial blood supply (hybrid lung lesion) at risk of perinatal death. A cohort of five consecutive fetuses with a large hybrid lung lesion associated with hydrops and/or pleural effusion with severe lung compression was selected for percutaneous ultrasound-guided fetal laser ablation of the feeding artery (FLAFA) before 32 weeks' gestation in a single tertiary national referral center in Queretaro, Mexico. The primary outcomes were survival and need for postnatal surgery. FLAFA was performed successfully in all cases at a median gestational age of 24.9 (range, 24.4-31.7) weeks. After fetal intervention, dimensions in both lungs increased and fluid effusions resolved in all cases. All cases were delivered liveborn at term at a median gestational age of 39.6 (range, 38.0-39.7) weeks, without respiratory morbidity or need for oxygen support, resulting in perinatal survival of 100%. During follow-up, three (60%) cases showed progressive regression of the entire lung mass and did not require postnatal surgery, whereas in two (40%) cases a progressive decrease in size of the mass was observed but a cystic portion of the lung mass persisted and postnatal lobectomy was required. In fetuses with large hybrid lung lesions at risk of perinatal death, FLAFA is feasible and could improve survival and decrease the need for postnatal surgery. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

The natural history of fetal cells in postpartum murine maternal lung and bone marrow: a two-stage phenomenon.

PubMed

Pritchard, Stephanie; Peter, Inga; Johnson, Kirby L; Bianchi, Diana W

2012-01-01

During pregnancy, fetal cells cross into the maternal organs where they reside postpartum. Evidence from multiple laboratories suggests that these microchimeric fetal cells contribute to maternal tissue repair after injury. In mouse models, most injury experiments are performed during pregnancy; however, in a clinical setting most injuries or diseases occur postpartum. Therefore, experiments using animal models should be designed to address questions in the time period following delivery. In order to provide a baseline for such experiments, we analyzed the natural history of fetal cells in the postpartum maternal organs. Female C57BL/6J mice were mated to males homozygous for the enhanced green fluorescent protein gene. Fetal cells in the maternal lungs and bone marrow were identified by their green fluorescence using in a high-speed flow cytometer and their counts were compared between the lung and bone marrow. Spearman correlation analysis was used to identify relationships between the duration of time postpartum and the cell counts and ratio of live and dead cells. Our results show that fetal cells persist in these organs until at least three months postpartum in healthy female mice. We show a two-stage decline, with an initial two and a half-week rapid clearance followed by a trend of gradual decrease. Additionally, an increase in the ratio of live to dead cells within the lung over time suggests that these cells may replicate in vivo. The results presented here will inform the design of future experiments and may have implications for women's health.

Leptin Promotes Fetal Lung Maturity and Upregulates SP-A Expression in Pulmonary Alveoli Type-II Epithelial Cells Involving TTF-1 Activation

PubMed Central

Huang, Hui; Wang, Zhen-Hua; Cheng, Rui; Cai, Wei-Bin

2013-01-01

The placental hormone leptin has important functions in fetal and neonatal growth, and prevents depressed respiration in leptin-deficient mice. The effect of leptin on respiratory distress suffered by low birth weight and premature infants has been studied. However, it is unclear how leptin enhances lung maturity in the fetus and ameliorates neonatal respiratory distress. In the present study, we found that antenatal treatment with leptin for 2 d significantly enhanced the relative alveolus area and improved the maturity of fetal lungs in a rat model of fetal growth restriction (FGR). Mean birth weight and lung wet weight were higher in the leptin-treated group than in the PBS-treated group, indicating promotion of fetal growth. Leptin upregulated the intracellular expression and extracellular secretion of surfactant protein (SP) A in type-II alveolar epithelial cells (AECs) in vivo and in vitro. Dual positive effects of leptin were found on protein expression and transcriptional activity of thyroid transcription factor-1 (TTF-1), a nuclear transcription essential for branching morphogenesis of the lung and expression of SP-A in type-II AECs. Knockdown of TTF-1 by RNA interference indicated that TTF-1 may play a vital role in leptin-induced SP-A expression. These results suggest that leptin may have great therapeutic potential for the treatment of FGR, and leptin-mediated SP-A induction and lung maturity of the fetus are TTF-1 dependent. PMID:23894445

Effects of exogenous fatty acids and inhibition of de novo fatty acid synthesis on disaturated phosphatidylcholine production by fetal lung cells and adult type II cells.

PubMed

Maniscalco, W M; Finkelstein, J N; Parkhurst, A B

1989-05-01

De novo fatty acid synthesis may be an important source of saturated fatty acids for fetal lung disaturated phosphatidylcholine (DSPC) production. To investigate the roles of de novo fatty acid synthesis and exogenous fatty acids, we incubated dispersed fetal lung cells and freshly isolated adult type II cells with exogenous palmitate and oleate and measured DSPC synthesis. Unlike adult type II cells, fetal lung cells did not increase DSPC synthesis when exogenous palmitate was available; adult type II cells increased DSPC synthesis by 70% in the presence of palmitate. Exogenous oleate decreased DSPC synthesis by 48% in fetal cells but not in adult type II cells. Incubation of fetal lung cells with TOFA [2-furancarboxylate, 5-(tetradecyloxy)-sodium], a metabolic inhibitor of fatty acid synthesis, decreased fatty acid synthesis by 65%. There was a simultaneous 56% inhibition of DSPC production, but no effect on protein, DNA, or glyceride-glycerol production, measured by precursor incorporation. The inhibition of DSPC synthesis associated with TOFA was partially prevented by exogenous palmitate but not oleate. Fetal cells prepared from explants that had been cultured in dexamethasone also had TOFA-associated inhibition of DSPC synthesis that was similar to non-dexamethasone-exposed cells. These studies suggest that under baseline conditions of low fatty acid availability, such as in the fetus, de novo fatty acid synthesis in fetal cells, but not in adult type II cells, provides sufficient saturated fatty acids to support maximal DSPC production. Inhibition of de novo fatty acid synthesis resulting in decreased DSPC production in fetal lung cells in conditions of low fatty acid availability suggests that fatty acid synthesis may be central to maintain DSPC synthesis in the fetus.

Embryonic essential myosin light chain regulates fetal lung development in rats.

PubMed

Santos, Marta; Moura, Rute S; Gonzaga, Sílvia; Nogueira-Silva, Cristina; Ohlmeier, Steffen; Correia-Pinto, Jorge

2007-09-01

Congenital diaphragmatic hernia (CDH) is currently the most life-threatening congenital anomaly the major finding of which is lung hypoplasia. Lung hypoplasia pathophysiology involves early developmental molecular insult in branching morphogenesis and a late mechanical insult by abdominal herniation in maturation and differentiation processes. Since early determinants of lung hypoplasia might appear as promising targets for prenatal therapy, proteomics analysis of normal and nitrofen-induced hypoplastic lungs was performed at 17.5 days after conception. The major differentially expressed protein was identified by mass spectrometry as myosin light chain 1a (MLC1a). Embryonic essential MLC1a and regulatory myosin light chain 2 (MLC2) were characterized throughout normal and abnormal lung development by immunohistochemistry and Western blot. Disruption of MLC1a expression was assessed in normal lung explant cultures by antisense oligodeoxynucleotides. Since early stages of normal lung development, MLC1a was expressed in vascular smooth muscle (VSM) cells of pulmonary artery, and MLC2 was present in parabronchial smooth muscle and VSM cells of pulmonary vessels. In addition, early smooth muscle differentiation delay was observed by immunohistochemistry of alpha-smooth muscle actin and transforming growth factor-beta1. Disruption of MLC1a expression during normal pulmonary development led to significant growth and branching impairment, suggesting a role in branching morphogenesis. Both MLC1a and MLC2 were absent from hypoplastic fetal lungs during pseudoglandular stage of lung development, whereas their expression partially recovered by prenatal treatment with vitamin A. Thus, a deficiency in contractile proteins MLC1a and MLC2 might have a role among the early molecular determinants of lung hypoplasia in the rat model of nitrofen-induced CDH.

Accelerated deflation promotes homogeneous airspace liquid distribution in the edematous lung

PubMed Central

Wu, You; Nguyen, Tam L.

2017-01-01

Edematous lungs contain regions with heterogeneous alveolar flooding. Liquid is trapped in flooded alveoli by a pressure barrier—higher liquid pressure at the border than in the center of flooded alveoli—that is proportional to surface tension, T. Stress is concentrated between aerated and flooded alveoli, to a degree proportional to T. Mechanical ventilation, by cyclically increasing T, injuriously exacerbates stress concentrations. Overcoming the pressure barrier to redistribute liquid more homogeneously between alveoli should reduce stress concentration prevalence and ventilation injury. In isolated rat lungs, we test whether accelerated deflation can overcome the pressure barrier and catapult liquid out of flooded alveoli. We generate a local edema model with normal T by microinfusing liquid into surface alveoli. We generate a global edema model with high T by establishing hydrostatic edema, which does not alter T, and then gently ventilating the edematous lungs, which increases T at 15 cmH2O transpulmonary pressure by 52%. Thus ventilation of globally edematous lungs increases T, which should increase stress concentrations and, with positive feedback, cause escalating ventilation injury. In the local model, when the pressure barrier is moderate, accelerated deflation causes liquid to escape from flooded alveoli and redistribute more equitably. Flooding heterogeneity tends to decrease. In the global model, accelerated deflation causes liquid escape, but—because of elevated T—the liquid jumps to nearby, aerated alveoli. Flooding heterogeneity is unaltered. In pulmonary edema with normal T, early ventilation with accelerated deflation might reduce the positive feedback mechanism through which ventilation injury increases over time. NEW & NOTEWORTHY We introduce, in the isolated rat lung, a new model of pulmonary edema with elevated surface tension. We first generate hydrostatic edema and then ventilate gently to increase surface tension. We investigate

Menopause Is Associated with Accelerated Lung Function Decline.

PubMed

Triebner, Kai; Matulonga, Bobette; Johannessen, Ane; Suske, Sandra; Benediktsdóttir, Bryndís; Demoly, Pascal; Dharmage, Shyamali C; Franklin, Karl A; Garcia-Aymerich, Judith; Gullón Blanco, José Antonio; Heinrich, Joachim; Holm, Mathias; Jarvis, Debbie; Jõgi, Rain; Lindberg, Eva; Moratalla Rovira, Jesús Martínez; Muniozguren Agirre, Nerea; Pin, Isabelle; Probst-Hensch, Nicole; Puggini, Luca; Raherison, Chantal; Sánchez-Ramos, José Luis; Schlünssen, Vivi; Sunyer, Jordi; Svanes, Cecilie; Hustad, Steinar; Leynaert, Bénédicte; Gómez Real, Francisco

2017-04-15

Menopause is associated with changes in sex hormones, which affect immunity, inflammation, and osteoporosis and may impair lung function. Lung function decline has not previously been investigated in relation to menopause. To study whether lung function decline, assessed by FVC and FEV 1 , is accelerated in women who undergo menopause. The population-based longitudinal European Community Respiratory Health Survey provided serum samples, spirometry, and questionnaire data about respiratory and reproductive health from three study waves (n = 1,438). We measured follicle-stimulating hormone and luteinizing hormone and added information on menstrual patterns to determine menopausal status using latent class analysis. Associations with lung function decline were investigated using linear mixed effects models, adjusting for age, height, weight, pack-years, current smoking, age at completed full-time education, spirometer, and including study center as random effect. Menopausal status was associated with accelerated lung function decline. The adjusted mean FVC decline was increased by -10.2 ml/yr (95% confidence interval [CI], -13.1 to -7.2) in transitional women and -12.5 ml/yr (95% CI, -16.2 to -8.9) in post-menopausal women, compared with women menstruating regularly. The adjusted mean FEV 1 decline increased by -3.8 ml/yr (95% CI, -6.3 to -2.9) in transitional women and -5.2 ml/yr (95% CI, -8.3 to -2.0) in post-menopausal women. Lung function declined more rapidly among transitional and post-menopausal women, in particular for FVC, beyond the expected age change. Clinicians should be aware that respiratory health often deteriorates during reproductive aging.

Predicting fetal lung maturity by visual assessment of amniotic fluid turbidity: comparison with fluorescence polarization assay.

PubMed

Adair, C D; Sanchez-Ramos, L; McDyer, D L; Gaudier, F L; Del Valle, G O; Delke, I

1995-10-01

We prospectively studied 159 patients having clinically indicated amniocentesis. Amniotic fluid (3 to 5 mL) was placed in a nonheparinized glass tube. This sample was then classified as turbid (indicating maturity) or clear (indicating immaturity) on the basis of a single examiner's ability to read newspaper print through the glass tube. These results were then compared with fluorescence polarization values for the same sample. A value of 70 mg/g was considered positive evidence of fetal lung maturity. By study criteria, 62 samples (39%) indicated immaturity and 97 (61%) indicated maturity. Turbidity correctly identified 89 samples that produced fluorescence polarization values of at least 70 mg/g. Turbidity as a predictor of fetal lung maturity when compared with fluorescence polarization assay has a 91% positive and 87% negative predictive value. Visual inspection of amniotic fluid may be of value in areas where sophisticated methods are unavailable.

Prematurity and fetal lung response after tracheal occlusion in fetuses with severe congenital diaphragmatic hernia.

PubMed

Sananes, Nicolas; Rodo, Carlota; Peiro, Jose Luis; Britto, Ingrid Schwach Werneck; Sangi-Haghpeykar, Haleh; Favre, Romain; Joal, Arnaud; Gaudineau, Adrien; Silva, Marcos Marques da; Tannuri, Uenis; Zugaib, Marcelo; Carreras, Elena; Ruano, Rodrigo

2016-09-01

To evaluate the independent association of fetal pulmonary response and prematurity to postnatal outcomes after fetal tracheal occlusion for congenital diaphragmatic hernia. Fetal pulmonary response, prematurity (<37 weeks at delivery) and extreme prematurity (<32 weeks at delivery) were evaluated and compared between survivors and non-survivors at 6 months of life. Multivariable analysis was conducted with generalized linear mixed models for variables significantly associated with survival in univariate analysis. Eighty-four infants were included, of whom 40 survived (47.6%) and 44 died (52.4%). Univariate analysis demonstrated that survival was associated with greater lung response (p=0.006), and the absence of extreme preterm delivery (p=0.044). In multivariable analysis, greater pulmonary response after FETO was an independent predictor of survival (aOR 1.87, 95% CI 1.08-3.33, p=0.023), whereas the presence of extreme prematurity was not statistically associated with mortality after controlling for fetal pulmonary response (aOR 0.52, 95% CI 0.12-2.30, p=0.367). Fetal pulmonary response after FETO is the most important factor associated with survival, independently from the gestational age at delivery.

Accelerated deflation promotes homogeneous airspace liquid distribution in the edematous lung.

PubMed

Wu, You; Nguyen, Tam L; Perlman, Carrie E

2017-04-01

Edematous lungs contain regions with heterogeneous alveolar flooding. Liquid is trapped in flooded alveoli by a pressure barrier-higher liquid pressure at the border than in the center of flooded alveoli-that is proportional to surface tension, T Stress is concentrated between aerated and flooded alveoli, to a degree proportional to T Mechanical ventilation, by cyclically increasing T , injuriously exacerbates stress concentrations. Overcoming the pressure barrier to redistribute liquid more homogeneously between alveoli should reduce stress concentration prevalence and ventilation injury. In isolated rat lungs, we test whether accelerated deflation can overcome the pressure barrier and catapult liquid out of flooded alveoli. We generate a local edema model with normal T by microinfusing liquid into surface alveoli. We generate a global edema model with high T by establishing hydrostatic edema, which does not alter T , and then gently ventilating the edematous lungs, which increases T at 15 cmH 2 O transpulmonary pressure by 52%. Thus ventilation of globally edematous lungs increases T , which should increase stress concentrations and, with positive feedback, cause escalating ventilation injury. In the local model, when the pressure barrier is moderate, accelerated deflation causes liquid to escape from flooded alveoli and redistribute more equitably. Flooding heterogeneity tends to decrease. In the global model, accelerated deflation causes liquid escape, but-because of elevated T -the liquid jumps to nearby, aerated alveoli. Flooding heterogeneity is unaltered. In pulmonary edema with normal T , early ventilation with accelerated deflation might reduce the positive feedback mechanism through which ventilation injury increases over time. NEW & NOTEWORTHY We introduce, in the isolated rat lung, a new model of pulmonary edema with elevated surface tension. We first generate hydrostatic edema and then ventilate gently to increase surface tension. We investigate the

Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases: An NHLBI Resource for the Gene Therapy Community

PubMed Central

Skarlatos, Sonia I.

2012-01-01

Abstract The goals of the National Heart, Lung, and Blood Institute (NHLBI) Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases are to conduct gene transfer studies in monkeys to evaluate safety and efficiency; and to provide NHLBI-supported investigators with expertise, resources, and services to actively pursue gene transfer approaches in monkeys in their research programs. NHLBI-supported projects span investigators throughout the United States and have addressed novel approaches to gene delivery; “proof-of-principle”; assessed whether findings in small-animal models could be demonstrated in a primate species; or were conducted to enable new grant or IND submissions. The Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases successfully aids the gene therapy community in addressing regulatory barriers, and serves as an effective vehicle for advancing the field. PMID:22974119

Maternal smoke exposure decreases mesenchymal proliferation and modulates Rho-GTPase-dependent actin cytoskeletal signaling in fetal lungs.

PubMed

Unachukwu, Uchenna; Trischler, Jordis; Goldklang, Monica; Xiao, Rui; D'Armiento, Jeanine

2017-06-01

The present study tested the hypothesis that maternal smoke exposure results in fetal lung growth retardation due to dysregulation in various signaling pathways, including the Wnt (wingless-related integration site)/β-catenin pathway. Pregnant female C57BL/6J mice were exposed to cigarette smoke (100-150 mg/m 3 ) or room air, and offspring were humanely killed on 12.5, 14.5, 16.5, and 18.5 d post coitum (dpc). We assessed lung stereology with Cavalieri estimation; apoptosis with proliferating cell nuclear antigen, TUNEL, and caspase assays; and gene expression with quantitative PCR (qPCR) and RNA sequencing on lung epithelium and mesenchyme retrieved by laser capture microdissection. Results demonstrated a significant decrease in body weight and lung volume of smoke-exposed embryos. At 16.5 dpc, the reduction in lung volume was due to loss of lung mesenchymal tissue correlating with a decrease in cell proliferation ( n = 10; air: 61.65% vs. smoke: 44.21%, P < 0.05). RNA sequence analysis demonstrated an alteration in the Wnt pathway, and qPCR confirmed an increased expression of secreted frizzled-related protein 1 (sFRP-1) [ n = 12; relative quantification (RQ) 1 vs. 2.33, P < 0.05] and down-regulation of Cyclin D1 ( n = 7; RQ 1 vs. 0.61, P < 0.05) in mesenchymal tissue. Furthermore, genome expression studies revealed a smoke-induced up-regulation of Rho-GTPase-dependent actin cytoskeletal signaling that can lead to loss of tissue integrity.-Unachukwu, U., Trischler, J., Goldklang, M., Xiao, R., D'Armiento, J. Maternal smoke exposure decreases mesenchymal proliferation and modulates Rho-GTPase-dependent actin cytoskeletal signaling in fetal lungs. © FASEB.

Does corticosteroid therapy impact fetal pulmonary artery blood flow in women at risk for preterm birth?

PubMed

Lindsley, William; Hale, Richard; Spear, Ashley; Adusumalli, Jasvant; Singh, Jasbir; DeStefano, Kimberly; Haeri, Sina

2015-09-01

Maternal corticosteroid administration in pregnancy is known to enhance fetal lung maturity in at risk fetuses. The aim of this study was to test the hypothesis that corticosteroid therapy alters fetal pulmonary blood flow in pregnancies at risk for preterm birth (PTB). We prospectively evaluated main fetal pulmonary artery (MPA) blood flow in pregnant women at risk for PTB and treated with corticosteroids (betamethasone), compared to an uncomplicated cohort without steroid therapy. The Doppler indices of interest included Peak Systolic Velocity (PSV), Resistive Index (RI), Pulsatility Index (PI), Systolic/Diastolic ratio (S/D ratio), Acceleration Time (AT), and Acceleration Time/Ejection Time Ratio (AT/ET ratio), with the latter serving as the primary outcomes due to its stability irrespective of gestational age. When compared with controls, fetuses treated with corticosteroids demonstrated significantly decreased pulmonary artery acceleration time (median: 28.89 (22.22-51.11) vs. 33.33 (22.20-57.00), p=0.006), while all other indices remained similar. We found no difference in pulmonary blood flow between fetuses who developed respiratory distress syndrome (RDS) and those that did not (31.56 +/- 6.842 vs. 32.36 +/- 7.265, p= 0.76). Our data demonstrate altered fetal pulmonary blood flow with corticosteroid therapy, possibly due to increased arterial elastance brought on by medication effect, which leads to the decreased acceleration time or possible gestational age affect. Contrary to a recent report, we did not observe any Doppler differences in fetuses with RDS, which underscores the need for further examination of this proposed association.

Automated Fetal Heart Rate Analysis in Labor: Decelerations and Overshoots

NASA Astrophysics Data System (ADS)

Georgieva, A. E.; Payne, S. J.; Moulden, M.; Redman, C. W. G.

2010-10-01

Electronic fetal heart rate (FHR) recording is a standard way of monitoring fetal health in labor. Decelerations and accelerations usually indicate fetal distress and normality respectively. But one type of acceleration may differ, namely an overshoot that may atypically reflect fetal stress. Here we describe a new method for detecting decelerations, accelerations and overshoots as part of a novel system for computerized FHR analysis (OxSyS). There was poor agreement between clinicians when identifying these FHR features visually, which precluded setting a gold standard of interpretation. We therefore introduced `modified' Sensitivity (SE°) and `modified' Positive Predictive Value (PPV°) as appropriate performance measures with which the algorithm was optimized. The relation between overshoots and fetal compromise in labor was studied in 15 cases and 15 controls. Overshoots showed promise as an indicator of fetal compromise. Unlike ordinary accelerations, overshoots cannot be considered to be reassuring features of fetal health.

Automated Image Analysis of Lung Branching Morphogenesis from Microscopic Images of Fetal Rat Explants

PubMed Central

Rodrigues, Pedro L.; Rodrigues, Nuno F.; Duque, Duarte; Granja, Sara; Correia-Pinto, Jorge; Vilaça, João L.

2014-01-01

Background. Regulating mechanisms of branching morphogenesis of fetal lung rat explants have been an essential tool for molecular research. This work presents a new methodology to accurately quantify the epithelial, outer contour, and peripheral airway buds of lung explants during cellular development from microscopic images. Methods. The outer contour was defined using an adaptive and multiscale threshold algorithm whose level was automatically calculated based on an entropy maximization criterion. The inner lung epithelium was defined by a clustering procedure that groups small image regions according to the minimum description length principle and local statistical properties. Finally, the number of peripheral buds was counted as the skeleton branched ends from a skeletonized image of the lung inner epithelia. Results. The time for lung branching morphometric analysis was reduced in 98% in contrast to the manual method. Best results were obtained in the first two days of cellular development, with lesser standard deviations. Nonsignificant differences were found between the automatic and manual results in all culture days. Conclusions. The proposed method introduces a series of advantages related to its intuitive use and accuracy, making the technique suitable to images with different lighting characteristics and allowing a reliable comparison between different researchers. PMID:25250057

Structural Development, Cellular Differentiation and Proliferation of the Respiratory Epithelium in the Bovine Fetal Lung.

PubMed

Drozdowska, J; Cousens, C; Finlayson, J; Collie, D; Dagleish, M P

2016-01-01

Fetal bovine lung samples of 11 different gestational ages were assigned to a classical developmental stage based on histological morphology. Immunohistochemistry was used to characterize the morphology of forming airways, proliferation rate of airway epithelium and the presence of epithelial cell types (i.e. ciliated cells, club cells, neuroepithelial cells (NECs) and type II pneumocytes). Typical structural organization of pseudoglandular (84-98 days gestational age [DGA]), canalicular (154-168 DGA) and alveolar (224-266 DGA) stages was recognized. In addition, transitional pseudoglandular-canalicular (112-126 DGA) and canalicular-saccular (182 DGA) morphologies were present. The embryonic stage was not observed. A significantly (P <0.05) higher proliferation rate of pulmonary epithelium, on average 5.5% and 4.4% in bronchi and bronchioles, respectively, was present in the transitional pseudoglandular-canalicular phase (112-126 DGA) compared with all other phases, while from 8 weeks before term (224-266 DGA) proliferation had almost ceased. The first epithelial cells identified by specific marker proteins in the earliest samples available for study (84 DGA) were ciliated cells and NECs. Club cells were present initially at 112 DGA and type II pneumocytes at 224 DGA. At the latest time points (224-226 DGA) these latter cell types were still present at a much lower percentage compared with adult cattle. This study characterized bovine fetal lung development by histological morphology and cellular composition of the respiratory epithelium and suggests that the apparent structural anatomical maturity of the bovine lung at term is not matched by functional maturity of the respiratory epithelium. Copyright © 2015 Elsevier Ltd. All rights reserved.

Placental hormones, nutrition, and fetal development.

PubMed

Mulay, S; Browne, C A; Varma, D R; Solomon, S

1980-02-01

Fetal growth retardation due to maternal malnutrition is widespread especially in the Third World. Little is known about the mechanisms that regulate the growth of the fetus and placenta during protein malnutrition. It is known that the placental size and levels of circulating placental hormones such as human chorionic gonadotrophins (hCG), human placental lactogen (hPL), and estrogens are affected by the nutritional status of the mother. There is suggestive evidence that during malnutrition, hPL may increase lipolysis and exert a glucose sparing effect in the mother, thereby promoting glucose availability to the fetus. We have studied the influence of dietary protein deficiency on the binding of dexamethasone to the specific cytosol receptors in adult and fetal tissues. A low protein diet in adult male rats is associated with a decrease in dexamethasone binding to liver cytosol receptors. On the other hand, protein deprivation in pregnant female rats leads to an increase in dexamethasone binding to liver cytosol receptors of both the mother and fetus. However, the influences of maternal protein deprivation on dexamethasone receptors in the fetal liver and lungs are not similar. At 21 days gestation the binding of dexamethasone to fetal lung receptors of protein-deficient mothers is lower than that in the controls. These differences at a critical time in the fetal lung development indicate that a fall in receptors for dexamethasone may lead to impaired phospholipid synthesis in fetuses of protein-deficient mothers and point to the importance of nutritional factors in the biochemistry of fetal development.

The pulmonary neuroendocrine system and drainage of the fetal lung: effects of serotonin.

PubMed

Chua, B A; Perks, A M

1999-03-01

The neuroendocrine system of the lungs is maximally developed and activated at birth, but has no clear function. Here, one of its products, serotonin, was tested for an ability to stop lung fluid production or activate reabsorption. Lungs from fetal guinea pigs (61 +/- 2 days of gestation) were supported in vitro for 3 h; lung liquid production was monitored by a dye dilution method. Initial studies on 36 young fetuses (61 +/- 1 days of gestation) showed that untreated controls produced fluid at 1.17 +/- 0.23 ml.kg-1.h-1, with no significant change over 3 h (ANOVA; regression analysis); those given 10(-8) M serotonin during the middle hour showed no significant changes, but those given 5 x 10(-8), 10(-7), 10(-6), or 10(-5) M serotonin reduced production significantly (P < 0.01 to P < 0.0005). Responses were linear up to 10(-7) M (threshold, 10(-9) M) and then become maximal at 50% reduction. However, responses increased with age. Comparison of 40 fetuses divided into groups of 60-61 or 65-67 days of gestation showed a large and significant increase in responses in the older fetuses (P < 0.01), where half the preparations reabsorbed fluid. Serotonin receptors were involved, since 10(-6) M cyproheptadine abolished responses (based on 24 preparations). Amiloride-sensitive Na+ channels were involved, since 10(-6) M amiloride abolished responses (based on 24 preparations). These results, in combination with earlier results from somatostatin and dopamine, together with histochemical and clinical observations, strongly suggest that the neuroendocrine system of the lungs may find a function in clearing fluid from the lungs at time of birth. Copyright 1999 Academic Press.

hPSC-derived lung and intestinal organoids as models of human fetal tissue

PubMed Central

Aurora, Megan; Spence, Jason R.

2016-01-01

In vitro human pluripotent stem cell (hPSC) derived tissues are excellent models to study certain aspects of normal human development. Current research in the field of hPSC derived tissues reveals these models to be inherently fetal-like on both a morphological and gene expression level. In this review we briefly discuss current methods for differentiating lung and intestinal tissue from hPSCs into individual 3-dimensional units called organoids. We discuss how these methods mirror what is known about in vivo signaling pathways of the developing embryo. Additionally, we will review how the inherent immaturity of these models lends them to be particularly valuable in the study of immature human tissues in the clinical setting of premature birth. Human lung organoids (HLOs) and human intestinal organoids (HIOs) not only model normal development, but can also be utilized to study several important diseases of prematurity such as respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), and necrotizing enterocolitis (NEC). PMID:27287882

Decay-Accelerating Factor Mitigates Controlled Hemorrhage-Instigated Intestinal and Lung Tissue Damage and Hyperkalemia in Swine

DTIC Science & Technology

2011-07-01

Decay-Accelerating Factor Mitigates Controlled Hemorrhage- Instigated Intestinal and Lung Tissue Damage and Hyperkalemia in Swine Jurandir J. Dalle...DAF treatment improved hemorrhage- induced hyperkalemia . The protective effects of DAF appear to be related to its ability to reduce tissue complement...Decay-accelerating factor mitigates controlled hemorrhage-instigated intestinal and lung tissue damage and hyperkalemia in swine 5a. CONTRACT NUMBER

Fetal motion estimation from noninvasive cardiac signal recordings.

PubMed

Biglari, Hadis; Sameni, Reza

2016-11-01

Fetal motility is a widely accepted indicator of the well-being of a fetus. In previous research, it has be shown that fetal motion (FM) is coherent with fetal heart rate accelerations and an indicator for active/rest cycles of the fetus. The most common approach for FM and fetal heart rate (FHR) assessment is by Doppler ultrasound (DUS). While DUS is the most common approach for studying the mechanical activities of the heart, noninvasive fetal electrocardiogram (ECG) and magnetocardiogram (MCG) recording and processing techniques have been considered as a possible competitor (or complement) for the DUS. In this study, a fully automatic and robust framework is proposed for the extraction, ranking and alignment of fetal QRS-complexes from noninvasive fetal ECG/MCG. Using notions from subspace tracking, two measures, namely the actogram and rotatogram, are defined for fetal motion tracking. The method is applied to four fetal ECG/MCG databases, including twin MCG recordings. By defining a novel measure of causality, it is shown that there is significant coherency and causal relationship between the actogram/rotatogram and FHR accelerations/decelerations. Using this measure, it is shown that in many cases, the actogram and rotatogram precede the FHR variations, which supports the idea of motion-induced FHR accelerations/decelerations for these cases and raises attention for the non-motion-induced FHR variations, which can be associated to the fetal central nervous system developments. The results of this study can lead to novel perspectives of the fetal sympathetic and parasympathetic brain systems and future requirements of fetal cardiac monitoring.

Fetal cardiac cine imaging using highly accelerated dynamic MRI with retrospective motion correction and outlier rejection

PubMed Central

Lloyd, David F.A.; Price, Anthony N.; Kuklisova Murgasova, Maria; Aljabar, Paul; Malik, Shaihan J.; Lohezic, Maelene; Rutherford, Mary A.; Pushparajah, Kuberan; Razavi, Reza; Hajnal, Joseph V.

2017-01-01

Purpose Development of a MRI acquisition and reconstruction strategy to depict fetal cardiac anatomy in the presence of maternal and fetal motion. Methods The proposed strategy involves i) acquisition and reconstruction of highly accelerated dynamic MRI, followed by image‐based ii) cardiac synchronization, iii) motion correction, iv) outlier rejection, and finally v) cardiac cine reconstruction. Postprocessing entirely was automated, aside from a user‐defined region of interest delineating the fetal heart. The method was evaluated in 30 mid‐ to late gestational age singleton pregnancies scanned without maternal breath‐hold. Results The combination of complementary acquisition/reconstruction and correction/rejection steps in the pipeline served to improve the quality of the reconstructed 2D cine images, resulting in increased visibility of small, dynamic anatomical features. Artifact‐free cine images successfully were produced in 36 of 39 acquired data sets; prolonged general fetal movements precluded processing of the remaining three data sets. Conclusions The proposed method shows promise as a motion‐tolerant framework to enable further detail in MRI studies of the fetal heart and great vessels. Processing data in image‐space allowed for spatial and temporal operations to be applied to the fetal heart in isolation, separate from extraneous changes elsewhere in the field of view. Magn Reson Med 79:327–338, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID:28370252

Upregulation of fibroblast growth factor receptor 2 and 3 in the late stages of fetal lung development in the nitrofen rat model.

PubMed

Friedmacher, Florian; Doi, Takashi; Gosemann, Jan-Hendrik; Fujiwara, Naho; Kutasy, Balazs; Puri, Prem

2012-02-01

Nitrofen model of congenital diaphragmatic hernia (CDH) has been widely used to investigate the pathogenesis of pulmonary hypoplasia (PH). Fibroblast growth factor (FGF) signaling pathway plays a fundamental role in fetal lung development. FGF7 and FGF10, which are critical for lung morphogenesis, have been reported to be downregulated in nitrofen-induced PH. FGF signaling is mediated by a family of four single transmembrane receptors, FGFR1-4. FGFR2 and FGFR3 have been shown to be expressed predominantly in the late stages of developing lungs. In addition, the upregulation of FGFR2 gene expression has been associated with severe defects in lung development and resulted in arrested alveologenesis similar to PH seen in the nitrofen model. Furthermore, FGFR3(-/-)FGFR4(-/-) double mutants showed thinner mesenchyme and larger air spaces. We designed this study to test the hypothesis that FGFR gene expression is upregulated in the late stages of lung development in the nitrofen CDH model. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Cesarean section was performed and fetuses were harvested on D18 and D21. Fetal lungs were divided into three groups: control, nitrofen without CDH [CDH(-)], and nitrofen with CDH [CDH(+)] (n = 24 at each time-point). Pulmonary gene expression levels of FGFR1-4 were analyzed by real-time RT-PCR. Immunohistochemistry was also performed to evaluate protein expression/distribution at each time-point. The relative messenger RNA expression levels of pulmonary FGFR2 and FGFR3 on D21 were significantly increased in CDH(-) (6.38 ± 1.93 and 7.84 ± 2.86, respectively) and CDH(+) (7.09 ± 2.50 and 7.25 ± 3.43, respectively) compared to controls (P < 0.05 and P < 0.01, respectively), whereas no significant alteration was observed on D18. There were no differences in FGFR1 and FGFR4 expression at both time-points. Increased immunoreactivity of FGFR2 and FGFR3, mainly in the distal epithelium and mesenchyme

Prenatal MRI fetal lung volumes and percent liver herniation predict pulmonary morbidity in congenital diaphragmatic hernia (CDH).

PubMed

Zamora, Irving J; Olutoye, Oluyinka O; Cass, Darrell L; Fallon, Sara C; Lazar, David A; Cassady, Christopher I; Mehollin-Ray, Amy R; Welty, Stephen E; Ruano, Rodrigo; Belfort, Michael A; Lee, Timothy C

2014-05-01

The purpose of this study was to determine whether prenatal imaging parameters are predictive of postnatal CDH-associated pulmonary morbidity. The records of all neonates with CDH treated from 2004 to 2012 were reviewed. Patients requiring supplemental oxygen at 30 days of life (DOL) were classified as having chronic lung disease (CLD). Fetal MRI-measured observed/expected total fetal lung volume (O/E-TFLV) and percent liver herniation (%LH) were recorded. Receiver operating characteristic (ROC) curves and multivariate regression were applied to assess the prognostic value of O/E-TFLV and %LH for development of CLD. Of 172 neonates with CDH, 108 had fetal MRIs, and survival was 76%. 82% (89/108) were alive at DOL 30, 46 (52%) of whom had CLD. Neonates with CLD had lower mean O/E-TFLV (30 vs.42%; p=0.001) and higher %LH (21.3±2.8 vs.7.1±1.8%; p<0.001) compared to neonates without CLD. Using ROC analysis, the best cutoffs in predicting CLD were an O/E-TFLV<35% (AUC=0.74; p<0.001) and %LH>20% (AUC=0.78; p<0.001). On logistic regression, O/E-TFLV<35% and a %LH>20% were highly associated with indicators of long-term pulmonary sequelae. On multivariate analysis, %LH was the strongest predictor of CLD in patients with CDH (OR: 10.96, 95%CI: 2.5-48.9, p=0.002). Prenatal measurement of O/E-TFLV and %LH is predictive of CDH pulmonary morbidity and can aid in establishing parental expectations of postnatal outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Derivation of lung mesenchymal lineages from the fetal mesothelium requires hedgehog signaling for mesothelial cell entry

PubMed Central

Dixit, Radhika; Ai, Xingbin; Fine, Alan

2013-01-01

Recent studies have shown that mesothelial progenitors contribute to mesenchymal lineages of developing organs. To what extent the overlying mesothelium contributes to lung development remains unknown. To rigorously address this question, we employed Wt1CreERT2/+ mice for high-fidelity lineage tracing after confirming that Cre recombinase was mesothelial specific and faithfully recapitulated endogenous Wilms’ tumor 1 (Wt1) gene expression. We visualized WT1+ mesothelial cell entry into the lung by live imaging and identified their progenies in subpopulations of bronchial smooth muscle cells, vascular smooth muscle cells and desmin+ fibroblasts by lineage tagging. Derivation of these lineages was only observed with Cre recombinase activation during early lung development. Using loss-of-function assays in organ cultures, and targeted mesothelial-restricted hedgehog loss-of-function mice, we demonstrated that mesothelial cell movement into the lung requires the direct action of hedgehog signaling. By contrast, hedgehog signaling was not required for fetal mesothelial heart entry. These findings further support a paradigm wherein the mesothelium is a source of progenitors for mesenchymal lineages during organogenesis and indicate that signals controlling mesothelial cell entry are organ specific. PMID:24130328

Derivation of lung mesenchymal lineages from the fetal mesothelium requires hedgehog signaling for mesothelial cell entry.

PubMed

Dixit, Radhika; Ai, Xingbin; Fine, Alan

2013-11-01

Recent studies have shown that mesothelial progenitors contribute to mesenchymal lineages of developing organs. To what extent the overlying mesothelium contributes to lung development remains unknown. To rigorously address this question, we employed Wt1(CreERT2/+) mice for high-fidelity lineage tracing after confirming that Cre recombinase was mesothelial specific and faithfully recapitulated endogenous Wilms' tumor 1 (Wt1) gene expression. We visualized WT1(+) mesothelial cell entry into the lung by live imaging and identified their progenies in subpopulations of bronchial smooth muscle cells, vascular smooth muscle cells and desmin(+) fibroblasts by lineage tagging. Derivation of these lineages was only observed with Cre recombinase activation during early lung development. Using loss-of-function assays in organ cultures, and targeted mesothelial-restricted hedgehog loss-of-function mice, we demonstrated that mesothelial cell movement into the lung requires the direct action of hedgehog signaling. By contrast, hedgehog signaling was not required for fetal mesothelial heart entry. These findings further support a paradigm wherein the mesothelium is a source of progenitors for mesenchymal lineages during organogenesis and indicate that signals controlling mesothelial cell entry are organ specific.

[MRI-Based Ratio of Fetal Lung to Body Volume as New Prognostic Marker for Chronic Lung Disease in Patients with Congenital Diaphragmatic Hernia].

PubMed

Winkler, Melissa M; Weis, Meike; Henzler, Claudia; Weiß, Christel; Kehl, Sven; Schoenberg, Stefan O; Neff, Wolfgang; Schaible, Thomas

2017-03-01

Background Our aim was to evaluate the prognostic value of magnetic resonance imaging (MRI)-based ratio of fetal lung volume (FLV) to fetal body volume (FBV) as a marker for development of chronic lung disease (CLD) in fetuses with congenital diaphragmatic hernia (CDH). Patients and Methods FLV and FBV were measured and the individual FLV/FBV ratio was calculated in 132 fetuses. Diagnosis of CLD was established following prespecified criteria and graded into mild/moderate/severe if present. Logistic regression analysis was used to calculate the probability of postnatal development of CLD in dependence of the FLV/FBV ratio. Receiver operating characteristic curves were analysed by calculating the area under the curve to evaluate the prognostic accuracy of this marker. Results 61 of 132 fetuses developed CLD (46.21%). The FLV/FBV ratio was significantly lower in fetuses with CLD (p=0.0008; AUC 0.743). Development of CLD was significantly associated with thoracic herniation of liver parenchyma (p<0.0001), requirement of extracorporal membrane oxygenation (ECMO) (p<0.0001) and gestational age at delivery (p=0.0052). Conclusion The MRI-based ratio of FLV to FBV is a highly valuable prenatal parameter for development of CLD. The ratio is helpful for early therapeutic decisions by estimating the probability to develop CLD. Perinatally, gestational age at delivery and ECMO requirement are useful additional parameters to further improve prediction of CLD. © Georg Thieme Verlag KG Stuttgart · New York.

Massive hemoptysis and complete unilateral lung collapse in pregnancy due to pulmonary tuberculosis with good maternal and fetal outcome: a case report.

PubMed

Masukume, Gwinyai; Sengurayi, Elton; Moyo, Phinot; Feliu, Julio; Gandanhamo, Danboy; Ndebele, Wedu; Ngwenya, Solwayo; Gwini, Rudo

2013-08-22

We report an extremely rare case of massive hemoptysis and complete left-sided lung collapse in pregnancy due to pulmonary tuberculosis in a health care worker with good maternal and fetal outcome. A 33-year-old human immuno deficiency virus seronegative African health care worker in her fourth pregnancy with two previous second trimester miscarriages and an apparently healthy daughter from her third pregnancy presented coughing up copious amounts of blood at 18 weeks and two days of gestation. She had a cervical suture in situ for presumed cervical weakness. Computed tomography of her chest showed complete collapse of the left lung; subsequent bronchoscopy was apparently normal. Her serum β-human chorionic gonadotropin, tests for autoimmune disease and echocardiography were all normal. Her lung re-inflated spontaneously. Sputum for acid alcohol fast bacilli was positive; our patient was commenced on anti-tuberculosis medication and pyridoxine. At 41 weeks and three days of pregnancy our patient went into spontaneous labor and delivered a live born female baby weighing 2.6 kg with APGAR scores of nine and 10 at one and five minutes respectively. She and her baby are apparently doing well about 10 months after delivery. It is possible to have massive hemoptysis and complete unilateral lung collapse with spontaneous resolution in pregnancy due to pulmonary tuberculosis with good maternal and fetal outcome.

Human fetal lung morphometry at autopsy with new modeling to quantitate structural maturity.

PubMed

Lipsett, Jill

2017-06-01

To demonstrate a simplified morphometric procedure, including a new model for acinar structural maturity, applicable to autopsy fetal lung and present reference values for these parameters. Cases with autopsy consent for research were studied. To simplify analysis only critical morphometric parameters were measured to allow calculation of gas-exchange surface area. A total of 58 fetuses, 16-40 weeks were included. Subjects were rejected with any condition predisposing to pulmonary hypo/hyperplasia, significant maceration, or if lung weight/bodyweight or microscopy identified pulmonary hypoplasia or lung growth disorders. Lungs were inflation fixed, weights and volumes determined, sampled, then returned to the body. Volume densities (V V ) of parenchyma/non-parenchyma and air-space/gas-exchange tissue, gas-exchange surface density (S V ), and total surface area (SA) were determined. The number, mean radius, and septal thickness of modeled airspace-spheres were calculated. Equations were generated for each parameter function of gestation and bodyweight. From 16 to 40-week weights and volumes increased as power functions from ∼4 g/mL to ∼90 g/mL. Parenchyma/non-parenchyma changed little-75:25 (16 weeks) to 71:29 (term). Parenchyma was 10% airspace:90% tissue early and 50:50 by term. Gas-exchange S V increased from 175 to 450 cm 2 /cm 3 and total SA increased from 0.059 to 4.793 m 2 . There were 3.31 × 10 6 airspace-spheres, 12 µ radius, septal thickness 30 µ at 16 weeks, increasing to 56.92 × 10 6 , 26 µ radius, septal thickness 13 µ by term. Morphometry can feasibly be performed at autopsy, providing more informative quantitative data on lung structural development than current methods utilized. This reference data set compares well with published data. © 2017 Wiley Periodicals, Inc.

The role of glutamine and other alternate substrates as energy sources in the fetal rat lung type II cell.

PubMed

Fox, R E; Hopkins, I B; Cabacungan, E T; Tildon, J T

1996-07-01

Glucose has been thought to be the primary substrate for energy metabolism in the developing lung; however, alternate substrates are used for energy metabolism in other organs. To examine the role of alternate substrates in the lung, we measured rates of oxidation of glutamine, glucose, lactate, and 3-hydroxybutyrate in type II pneumocytes isolated from d 19 fetal rat lungs by measuring the production of 14CO2 from labeled substrates. Glutamine had a rate of 24.36 +/- 4.51 nmol 14CO2 produced/ h/mg of protein (mean +/- SEM), whereas lactate had a significantly higher rate, 40.29 +/- 4.42. 3-Hydroxybutyrate had a rate of 14.91 +/- 1.93. The rate of glucose oxidation was 2.13 +/- 0.36, significantly lower than that of glutamine. To examine the interactions of substrates normally found in the intracellular milieu, we measured the effect of unlabeled substrates as competitors on labeled substrate. This identifies multiple metabolic compartments of energy metabolism. Glucose, but not lactate, inhibited the oxidation of glutamine, suggesting a compartmentation of tricarboxylic acid cycle activity, rather than simple dilution by glucose. Glucose and lactate had reciprocal inhibition. Our data suggest at least two separate compartments in the type II cells for substrate oxidation, one for glutamine metabolism and a second for glucose metabolism. In summary, we have documented that glutamine and other alternate substrates are oxidized preferentially over glucose for energy metabolism in the d 19 fetal rat lung type II pneumocyte. In addition, we have delineated some of the compartmentation that occurs within the developing type II cell, which may determine how these substrates are used.

Fetal Brain Behavior and Cognitive Development.

ERIC Educational Resources Information Center

Joseph, R.

2000-01-01

Presents information on prenatal brain development, detailing the functions controlled by the medulla, pons, and midbrain, and the implications for cognitive development. Concludes that fetal cognitive motor activity, including auditory discrimination, orienting, the wake-sleep cycle, fetal heart rate accelerations, and defensive reactions,…

Maternal obesity accelerates fetal pancreatic beta-cell but not alpha-cell development in sheep: prenatal consequences.

PubMed

Ford, Stephen P; Zhang, Liren; Zhu, Meijun; Miller, Myrna M; Smith, Derek T; Hess, Bret W; Moss, Gary E; Nathanielsz, Peter W; Nijland, Mark J

2009-09-01

Maternal obesity affects offspring weight, body composition, and organ function, increasing diabetes and metabolic syndrome risk. We determined effects of maternal obesity and a high-energy diet on fetal pancreatic development. Sixty days prior to breeding, ewes were assigned to control [100% of National Research Council (NRC) recommendations] or obesogenic (OB; 150% NRC) diets. At 75 days gestation, OB ewes exhibited elevated insulin-to-glucose ratios at rest and during a glucose tolerance test, demonstrating insulin resistance compared with control ewes. In fetal studies, ewes ate their respective diets from 60 days before to 75 days after conception when animals were euthanized under general anesthesia. OB and control ewes increased in body weight by approximately 43% and approximately 6%, respectively, from diet initiation until necropsy. Although all organs were heavier in fetuses from OB ewes, only pancreatic weight increased as a percentage of fetal weight. Blood glucose, insulin, and cortisol were elevated in OB ewes and fetuses on day 75. Insulin-positive cells per unit pancreatic area were 50% greater in fetuses from OB ewes as a result of increased beta-cell mitoses rather than decreased programmed cell death. Lambs of OB ewes were born earlier but weighed the same as control lambs; however, their crown-to-rump length was reduced, and their fat mass was increased. We conclude that increased systemic insulin in fetuses from OB ewes results from increased glucose exposure and/or cortisol-induced accelerated fetal beta-cell maturation and may contribute to premature beta-cell function loss and predisposition to obesity and metabolic disease in offspring.

Maternal obesity accelerates fetal pancreatic β-cell but not α-cell development in sheep: prenatal consequences

PubMed Central

Ford, Stephen P.; Zhang, Liren; Zhu, Meijun; Miller, Myrna M.; Smith, Derek T.; Hess, Bret W.; Moss, Gary E.; Nathanielsz, Peter W.; Nijland, Mark J.

2009-01-01

Maternal obesity affects offspring weight, body composition, and organ function, increasing diabetes and metabolic syndrome risk. We determined effects of maternal obesity and a high-energy diet on fetal pancreatic development. Sixty days prior to breeding, ewes were assigned to control [100% of National Research Council (NRC) recommendations] or obesogenic (OB; 150% NRC) diets. At 75 days gestation, OB ewes exhibited elevated insulin-to-glucose ratios at rest and during a glucose tolerance test, demonstrating insulin resistance compared with control ewes. In fetal studies, ewes ate their respective diets from 60 days before to 75 days after conception when animals were euthanized under general anesthesia. OB and control ewes increased in body weight by ∼43% and ∼6%, respectively, from diet initiation until necropsy. Although all organs were heavier in fetuses from OB ewes, only pancreatic weight increased as a percentage of fetal weight. Blood glucose, insulin, and cortisol were elevated in OB ewes and fetuses on day 75. Insulin-positive cells per unit pancreatic area were 50% greater in fetuses from OB ewes as a result of increased β-cell mitoses rather than decreased programmed cell death. Lambs of OB ewes were born earlier but weighed the same as control lambs; however, their crown-to-rump length was reduced, and their fat mass was increased. We conclude that increased systemic insulin in fetuses from OB ewes results from increased glucose exposure and/or cortisol-induced accelerated fetal β-cell maturation and may contribute to premature β-cell function loss and predisposition to obesity and metabolic disease in offspring. PMID:19605766

The influence of betamethasone on fetal heart rate variability, obtained by non-invasive fetal electrocardiogram recordings.

PubMed

Verdurmen, Kim M J; Warmerdam, Guy J J; Lempersz, Carlijn; Hulsenboom, Alexandra D J; Renckens, Joris; Dieleman, Jeanne P; Vullings, Rik; van Laar, Judith O E H; Oei, S Guid

2018-04-01

Betamethasone is widely used to enhance fetal lung maturation in case of threatened preterm labour. Fetal heart rate variability is one of the most important parameters to assess in fetal monitoring, since it is a reliable indicator for fetal distress. To describe the effect of betamethasone on fetal heart rate variability, by applying spectral analysis on non-invasive fetal electrocardiogram recordings. Prospective cohort study. Patients that require betamethasone, with a gestational age from 24 weeks onwards. Fetal heart rate variability parameters on day 1, 2, and 3 after betamethasone administration are compared to a reference measurement. Following 68 inclusions, 12 patients remained with complete series of measurements and sufficient data quality. During day 1, an increase in absolute fetal heart rate variability values was seen. During day 2, a decrease in these values was seen. All trends indicate to return to pre-medication values on day 3. Normalised high- and low-frequency power show little changes during the study period. The changes in fetal heart rate variability following betamethasone administration show the same pattern when calculated by spectral analysis of the fetal electrocardiogram, as when calculated by cardiotocography. Since normalised spectral values show little changes, the influence of autonomic modulation seems minor. Copyright © 2018 Elsevier B.V. All rights reserved.

A simplified form of cardiotocography for antenatal fetal assessment.

PubMed

Mahomed, K; Gupta, B K; Matikiti, L; Murape, T S

1992-12-01

Antenatal cardiotocography has become the primary method of evaluation of fetal wellbeing, and the relationship between the presence of fetal heart rate accelerations in response to fetal movement and subsequent good fetal outcome has been demonstrated. However, in areas where electronic monitors are few or not available it would be useful if such accelerations could be demonstrated using the Pinard stethoscope. A prospective study involving 200 women with a singleton pregnancy of more than 34 weeks gestation was performed at Harare Maternity Hospital, Harare, Zimbabwe, when a 6 min electronic trace using an external transducer was compared with simultaneously performed 6 min manual record using the Pinard stethoscope. The findings showed that the manual record has a sensitivity of 75% and although traces with excessive base line variability would show an acceleration on the manual record, in no case with a flat trace was an acceleration noted on the manual record. This acceptable degree of sensitivity would allow for a significant decrease in the number of women being referred for electronic tracing and would be a more appropriate use of limited resources in terms of manpower and equipment.

Enhanced ventricular pump function and decreased reservoir backflow sustain rise in pulmonary blood flow after reduction of lung liquid volume in fetal lambs.

PubMed

Smolich, Joseph J

2014-02-15

Although a reduction in lung liquid volume increases fetal pulmonary blood flow, the changes in central flow patterns that sustain this increased pulmonary perfusion are unknown. To address this issue, eight anesthetized late-gestation fetal sheep were instrumented with pulmonary trunk (PT), ductus arteriosus (DA), and left pulmonary artery (PA) micromanometer catheters and transit-time flow probes, with blood flow profile and wave intensity analyses performed at baseline and after withdrawal of lung liquid via an endotracheal tube. Reducing lung liquid volume by 19 ± 6 ml/kg (mean ± SD) augmented right ventricular power by 34% (P < 0.001), with distribution of an accompanying increase in mean PT blood flow (245 ± 63 ml/min, P < 0.001) to the lungs (169 ± 91 ml/min, P = 0.001) and across the DA (77 ± 92 ml/min, P = 0.04). However, although PT and DA flow increments were confined to systole and were related to an increased magnitude of flow-increasing, forward-running compression waves, the rise in PA flow spanned both systole (108 ± 66 ml/min) and diastole (61 ± 32 ml/min). Flow profile analysis showed that the step-up in PA diastolic flow was associated with diminished PA diastolic backflow and accompanied by a lesser degree of diastolic right-to-left DA shunting. These data suggest that an increased pulmonary blood flow after reduction of lung liquid volume is associated with substantial changes in PT-DA-PA interactions and underpinned by two main factors: 1) enhanced right ventricular pump function that increases PA systolic inflow and 2) decreased PA diastolic backflow that arises from a fundamental change in PA reservoir function, thereby resulting in greater passage of systolic inflow through the lungs.

Fetal immune response to chorioamnionitis

PubMed Central

Kallapur, Suhas G.; Presicce, Pietro; Rueda, Cesar M.; Jobe, Alan H.; Chougnet, Claire A.

2014-01-01

Chorioamnionitis is a frequent cause of preterm birth and is associated with an increased risk for injury responses in the lung, GI tract, brain and other fetal organs. Chorioamnionitis is a polymicrobial non-traditional infectious disease because the organisms causing chorioamnionitis are generally of low virulence and colonize the amniotic fluid often for extended periods, and the host (mother and the fetus) does not have typical infection related symptoms such as fever. In this review, we discuss the effects of chorioamnionitis in experimental animal models that mimic the human disease. Our focus is on the immune changes in multiple fetal organs and the pathogenesis of chorioamnionitis induced injury in different fetal compartments. Since chorioamnionitis disproportionately affects preterm infants, we discuss the relevant developmental context for the immune system. We also provide a clinical context for the fetal responses. PMID:24390922

Fatty acids of pulmonary surfactant phosphatidylcholine from fetal rabbit lung tissue in culture. Biosynthesis of n-10 monoenoic fatty acids.

PubMed

Longmuir, K J; Resele-Tiden, C; Rossi, M E

1988-08-01

We have previously reported that fetal rabbit lung tissue in organ culture produces a lamellar body material (pulmonary surfactant) with a lower percentage of disaturated phosphatidylcholine than is typically found in rabbit lung in vivo (Longmuir, K.J., C. Resele-Tiden, and L. Sykes. 1985. Biochim. Biophys. Acta. 833: 135-143). This investigation was conducted to identify all fatty acids present in the lamellar body phosphatidylcholine, and to determine whether the low level of disaturated phosphatidylcholine is due to excessive unsaturated fatty acid at position sn-1, sn-2, or both. Fetal rabbit lung tissue, 23 days gestation, was maintained in culture for 7 days in defined (serum-free) medium. Phospholipids were labeled in culture with [1-14C]acetate or [U-14C]glycerol (to follow de novo fatty acid biosynthesis), or with [1-14C]palmitic acid (to follow incorporation of exogenously supplied fatty acid). Radiolabeled fatty acid methyl esters obtained from lamellar body phosphatidylcholine were first separated by reverse-phase thin-layer chromatography (TLC) into two fractions of 1) 14:0 + 16:1 and 2) 16:0 + 18:1. Complete separation of the individual saturated and monoenoic fatty acids was achieved by silver nitrate TLC of the two fractions. Monoenoic fatty acid double bond position was determined by permanganate-periodate oxidation followed by HPLC of the carboxylic acid phenacyl esters. Lamellar body phosphatidylcholine contained four monoenoic fatty acids: 1) palmitoleic acid, 16:1 cis-9; 2) oleic acid, 18:1 cis-9; 3) cis-vaccenic acid, 18:1 cis-11; and 4) 6-hexadecenoic acid, 16:1 cis-6. In addition, 8-octadecenoic acid, 18:1 cis-8, was found in the fatty acids of the tissue homogenate. The abnormally low disaturated phosphatidylcholine content in lamellar body material was the result of abnormally high levels of monoenoic fatty acid (principally 16:1 cis-9) found at position sn-2. Position sn-1 contained normal levels of saturated fatty acid. The biosynthesis

Fetal lung volume in congenital diaphragmatic hernia: association of prenatal MR imaging findings with postnatal chronic lung disease.

PubMed

Debus, Angelika; Hagelstein, Claudia; Kilian, A Kristina; Weiss, Christel; Schönberg, Stefan O; Schaible, Thomas; Neff, K Wolfgang; Büsing, Karen A

2013-03-01

To assess whether chronic lung disease (CLD) in surviving infants with congenital diaphragmatic hernia (CDH) is associated with lung hypoplasia on the basis of the results of antenatal observed-to-expected fetal lung volume (FLV) ratio measurement at magnetic resonance (MR) imaging. The study received approval from the institutional review board, with waiver of informed consent for this retrospective review from patients who had previously given informed consent for prospective studies. The ratio of observed to expected FLV at MR imaging was calculated in 172 fetuses with CDH. At postpartum day 28, the need for supplemental oxygen implicated the diagnosis of CLD. At day 56, patients with CLD were assigned to one of three groups-those with mild, moderate, or severe CLD-according to their demand for oxygen. Logistic regression analysis was used to assess the prognostic value of the individual observed-to-expected FLV ratio for association with postnatal development of CLD. Children with CLD were found to have significantly smaller observed-to-expected FLV ratios at MR imaging than infants without CLD (P < .001). Grading of CLD revealed significant differences in observed-to-expected FLV ratio between patients with mild CLD and those with moderate (P = .012) or severe (P = .007) CLD. For an observed-to-expected FLV ratio of 5%, 99% of patients with CDH developed CLD, compared with less than 5% of fetuses with an observed-to-expected FLV ratio of 50%. Perinatally, development and grade of CLD were further influenced by the need for extracorporeal membrane oxygenation (ECMO) (P < .001) and gestational age at delivery (P = .009). Manifestation of CLD in surviving infants with CDH is associated with the prenatally determined observed-to-expected FLV ratio. Early neonatal therapeutic decisions can additionally be based on this ratio. Perinatally, ECMO requirement and gestational age at delivery are useful in further improving the estimated probability of CLD.

Acute Lung Injury: Making the Injured Lung Perform Better and Rebuilding Healthy Lungs

DTIC Science & Technology

2014-04-01

A. Derivation Lung Mesenchymal Lineages from the Fetal Mesothelium Requires Hedgehog Signaling for Mesothelial Cell Entry. Development 140:4398-4405...mesothelial cell entry into the developing lung are largely unknown. The importance of the hedgehog (Hh) signaling pathway in mesenchymal...et al., 1997; Weaver et al., 2003; Polizio et al., 2011; Yoo et al., 2011). Mammals express three Hh ligands: Indian hedgehog (IHH), desert hedgehog

'TOTAL' (Tracheal Occlusion To Accelerate Lung Growth) Trial

ClinicalTrials.gov

2018-01-25

Hernia; Hernia, Diaphragmatic; Hernia, DIaphragmatic, Congenital; Pathological Conditions, Anatomical; Congenital Abnormalities; Congenital Diaphragmatic Hernia; Fetal Anomaly; Fetal Surgery; Pulmonary Hypoplasia

Implantable ultra-low pulmonary pressure monitoring system for fetal surgery.

PubMed

Etemadi, Mozziyar; Heller, J Alex; Schecter, Samuel C; Shue, Eveline H; Miniati, Doug; Roy, Shuvo

2012-11-01

Congenital pulmonary hypoplasia is a devastating condition affecting fetal and newborn pulmonary physiology, resulting in great morbidity and mortality. The fetal lung develops in a fluid-filled environment. In this work, we describe a novel, implantable pressure sensing and recording device which we use to study the pressures present in the fetal pulmonary tree throughout gestation. The system achieves 0.18 cm H2O resolution and can record for twenty one days continuously at 256 Hz. Sample tracings of in vivo fetal lamb recordings are shown.

Misidentification of maternal heart rate as fetal on cardiotocography during the second stage of labor: the role of the fetal electrocardiograph.

PubMed

Nurani, Raisha; Chandraharan, Edwin; Lowe, Virginia; Ugwumadu, Austin; Arulkumaran, Sabaratnam

2012-12-01

To identify the incidence of fetal heart rate (FHR) accelerations in the second stage of labor and the role of fetal electrocardiograph (ECG) in avoiding misidentification of maternal heart rate (MHR) as FHR. Retrospective observational study. University hospital labor ward, London, UK. Cardiotocograph (CTG) tracings of 100 fetuses monitored using external transducers and internal scalp electrodes. CTG traces that fulfilled inclusion criteria were selected from an electronic FHR monitoring database. Rate of accelerations during external and internal monitoring as well as decelerations for a period of 60 minutes prior to delivery were determined. The role of fetal ECG in differentiating between MHR and FHR trace was explored. Decelerations occurred in 89% of CTG traces during the second stage of labor. Accelerations indicating possible recording of FHR or MHR were found in 28.1 and 10.9% of cases recorded by an external ultrasound transducer as well as internal scalp electrode, respectively. Accelerations coinciding with uterine contractions occurred only in 11.7 and 4% of external and internal recording of FHR, respectively. Absence of 'p-wave' of the ECG waveform was associated with MHR trace. Decelerations were the commonest CTG feature during the second stage of labor. The incidence of accelerations coinciding with uterine contractions was less than half in fetuses monitored using a fetal scalp electrode. Analysing the ECG waveform for the absence of 'p-wave' helps in differentiating MHR from FHR. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

Insulin Treatment Cannot Promote Lipogenesis in Rat Fetal Lung in Gestational Diabetes Mellitus Because of Failure to Redress the Imbalance Among SREBP-1, SCAP, and INSIG-1.

PubMed

Li, Jinyan; Qian, Guanhua; Zhong, Xiaocui; Yu, Tinghe

2018-03-01

Gestational diabetes mellitus (GDM) has a higher incidence of neonatal respiratory distress syndrome, and lipogenesis is required for the synthesis of pulmonary surfactants. The aim of this study was to determine the effect of insulin treatment in GDM on the production of lipids in the lungs of fetal rats. GDM was induced by streptozotocin, and insulin was used to manage diabetes. Type II alveolar epithelial cells (AEC II), bronchoalveolar lavage fluid (BALF), and lung tissues of the neonatal rats were sampled for analyses. Insulin treatment could not decrease plasma glucose to normal level at a later gestational stage. Lipids/phospholipids in AEC II, BALF, and lung tissues decreased in GDM, and insulin treatment could not increase the levels; quantitative PCR and western blotting demonstrated a lower level of sterol regulator element-binding protein 1 (SREBP-1), SREBP cleavage-activating protein (SCAP), and insulin-induced gene 1 (INSIG-1) in GDM, but insulin treatment upregulated only SREBP-1. Nuclear translocation of the SREBP-1 protein in AEC II was impaired in GDM, which could not be ameliorated by insulin treatment. These findings indicated that insulin treatment in GDM cannot promote lipogenesis in the fetal lung because of failure to redress the imbalance among SREBP-1, SCAP, and INSIG-1.

Assessing effects of BL67 points stimulation on fetal heart rate parameters and fetal movements during nonstress test.

PubMed

Pirhadi, Masume; Valiani, Mahboube

2017-01-01

One of the main goals of antenatal testing is to identify fetuses at the risk of neurologic injury or death so that these adverse outcomes can be prevented. We want to assess the effects of BL67 points' stimulation on fetal heart rate parameters and fetal movements during nonstress test (NST). We did a quasi-experimental design in Shahid Beheshti Hospital in Isfahan in 2011. This study aims to assessment of the effects of BL67 points' stimulation on fetal heart rate parameters and fetal movements. We did a randomized controlled clinical trial in Shahid Beheshti Hospital in Isfahan in 2011. This study is a quasi-experimental design that was conducted in one group and the two steps (before-after study). Participants were pregnant women (primigravida) who were 35-18 years that refer to Shahid Beheshti Hospital in Isfahan in 2011 to receive routine prenatal care. The 32 pregnant women were selected for acupressure during the second NST. The statistical processing was performed by descriptive, paired t -test through SPSS version 20. There was no significant difference in mean number of accelerations in fetal heart rate and mean number of fetal movement before and after intervention; however, there was a significant difference in mean time to the second acceleration before and after the intervention ( P = 0.04). No difference between parameters of the fetal heart rate before and after stimulation and lack of uterine response by this method is a significant advantage and is probably why stimulating this point could not create a risk to the fetuses.

Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts.

PubMed

Mahemuti, Laziyan; Chen, Qixuan; Coughlan, Melanie C; Qiao, Cunye; Chepelev, Nikolai L; Florian, Maria; Dong, Dillon; Woodworth, Robert G; Yan, Jin; Cao, Xu-Liang; Scoggan, Kylie A; Jin, Xiaolei; Willmore, William G

2018-04-01

Experimental and/or epidemiological studies suggest that prenatal exposure to bisphenol A (BPA) may delay fetal lung development and maturation and increase the susceptibility to childhood respiratory disease. However, the underlying mechanisms remain to be elucidated. In our previous study with cultured human fetal lung fibroblasts (HFLF), we demonstrated that 24-h exposure to 1 and 100 µM BPA increased GPR30 protein in the nuclear fraction. Exposure to 100 μM BPA had no effects on cell viability, but increased cytoplasmic expression of ERβ and release of GDF-15, as well as decreased release of IL-6, ET-1, and IP-10 through suppression of NFκB phosphorylation. By performing global gene expression and pathway analysis in this study, we identified molecular pathways, gene networks, and key molecules that were affected by 100, but not 0.01 and 1 µM BPA in HFLF. Using multiple genomic and proteomic tools, we confirmed these changes at both gene and protein levels. Our data suggest that 100 μM BPA increased CYP1B1 and HSD17B14 gene and protein expression and release of endogenous estradiol, which was associated with increased ROS production and DNA double-strand breaks, upregulation of genes and/or proteins in steroid synthesis and metabolism, and activation of Nrf2-regulated stress response pathways. In addition, BPA activated ATM-p53 signaling pathway, resulting in increased cell cycle arrest at G1 phase, senescence and autophagy, and decreased cell proliferation in HFLF. The results suggest that prenatal exposure to BPA at certain concentrations may affect fetal lung development and maturation, and thereby affecting susceptibility to childhood respiratory diseases.

Isolation, in vitro culture and identification of a new type of mesenchymal stem cell derived from fetal bovine lung tissues.

PubMed

Hu, Pengfei; Pu, Yabin; Li, Xiayun; Zhu, Zhiqiang; Zhao, Yuhua; Guan, Weijun; Ma, Yuehui

2015-09-01

Lung‑derived mesenchymal stem cells (LMSCs) are considered to be important in lung tissue repair and regenerative processes. However, the biological characteristics and differentiation potential of LMSCs remain to be elucidated. In the present study, fetal lung‑derived mesenchymal stem cells (FLMSCs) were isolated from fetal bovine lung tissues by collagenase digestion. The in vitro culture conditions were optimized and stabilized and the self‑renewal ability and differentiation potential were evaluated. The results demonstrated that the FLMSCs were morphologically consistent with fibroblasts, were able to be cultured and passaged for at least 33 passages and the cell morphology and proliferative ability were stable during the first 10 passages. In addition, FLMSCs were found to express CD29, CD44, CD73 and CD166, however, they did not express hematopoietic cell specific markers, including CD34, CD45 and BOLA‑DRα. The growth kinetics of FLMSCs consisted of a lag phase, a logarithmic phase and a plateau phase, and as the passages increased, the proliferative ability of cells gradually decreased. The majority of FLMSCs were in G0/G1 phase. Following osteogenic induction, FLMSCs were positive for the expression of osteopontin and collagen type I α2. Following neurogenic differentiation, the cells were morphologically consistent with neuronal cells and positive for microtubule‑associated protein 2 and nestin expression. It was concluded that the isolated FLMSCs exhibited typical characteristics of mesenchymal stem cells and that the culture conditions were suitable for their proliferation and the maintenance of stemness. The present study illustrated the potential application of lung tissue as an adult stem cell source for regenerative therapies.

Intra-amniotic Ureaplasma parvum-Induced Maternal and Fetal Inflammation and Immune Responses in Rhesus Macaques.

PubMed

Senthamaraikannan, Paranthaman; Presicce, Pietro; Rueda, Cesar M; Maneenil, Gunlawadee; Schmidt, Augusto F; Miller, Lisa A; Waites, Ken B; Jobe, Alan H; Kallapur, Suhas G; Chougnet, Claire A

2016-11-15

 Although Ureaplasma species are the most common organisms associated with prematurity, their effects on the maternal and fetal immune system remain poorly characterized.  Rhesus macaque dams at approximately 80% gestation were injected intra-amniotically with 10 7 colony-forming units of Ureaplasma parvum or saline (control). Fetuses were delivered surgically 3 or 7 days later. We performed comprehensive assessments of inflammation and immune effects in multiple fetal and maternal tissues.  Although U. parvum grew well in amniotic fluid, there was minimal chorioamnionitis. U. parvum colonized the fetal lung, but fetal systemic microbial invasion was limited. Fetal lung inflammation was mild, with elevations in CXCL8, tumor necrosis factor (TNF) α, and CCL2 levels in alveolar washes at day 7. Inflammation was not detected in the fetal brain. Significantly, U. parvum decreased regulatory T cells (Tregs) and activated interferon γ production in these Tregs in the fetus. It was detected in uterine tissue by day 7 and induced mild inflammation and increased expression of connexin 43, a gap junction protein involved with labor.  U. parvum colonized the amniotic fluid and caused uterine inflammation, but without overt chorioamnionitis. It caused mild fetal lung inflammation but had a more profound effect on the fetal immune system, decreasing Tregs and polarizing them toward a T-helper 1 phenotype. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Non-invasive pulsed cavitational ultrasound for fetal tissue ablation: feasibility study in a fetal sheep model.

PubMed

Kim, Y; Gelehrter, S K; Fifer, C G; Lu, J C; Owens, G E; Berman, D R; Williams, J; Wilkinson, J E; Ives, K A; Xu, Z

2011-04-01

Currently available fetal intervention techniques rely on invasive procedures that carry inherent risks. A non-invasive technique for fetal intervention could potentially reduce the risk of fetal and obstetric complications. Pulsed cavitational ultrasound therapy (histotripsy) is an ablation technique that mechanically fractionates tissue at the focal region using extracorporeal ultrasound. In this study, we investigated the feasibility of using histotripsy as a non-invasive approach to fetal intervention in a sheep model. The experiments involved 11 gravid sheep at 102-129 days of gestation. Fetal kidney, liver, lung and heart were exposed to ultrasound pulses (< 10 µs) delivered by an external 1-MHz focused ultrasound transducer at a 0.2-1-kHz pulse-repetition rate and 10-16 MPa peak negative pressure. Procedures were monitored and guided by real-time ultrasound imaging. Treated organs were examined by gross and histological inspection for location and degree of tissue injury. Hyperechoic, cavitating bubble clouds were successfully generated in 19/31 (61%) treatment attempts in 27 fetal organs beneath up to 8 cm of overlying tissue and fetal bones. Histological assessment confirmed lesion locations and sizes corresponding to regions where cavitation was monitored, with no lesions found when cavitation was absent. Inability to generate cavitation was primarily associated with increased depth to target and obstructing structures such as fetal limbs. Extracorporeal histotripsy therapy successfully created targeted lesions in fetal sheep organs without significant damage to overlying structures. With further improvements, histotripsy may evolve into a viable technique for non-invasive fetal intervention procedures. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

Chronic fetal exposure to Ureaplasma parvum suppresses innate immune responses in sheep

PubMed Central

Kallapur, Suhas G.; Kramer, Boris W.; Knox, Christine L.; Berry, Clare A.; Collins, Jennifer J.P; Kemp, Matthew W.; Nitsos, Ilias; Polglase, Graeme R.; Robinson, James; Hillman, Noah H.; Newnham, John P.; Chougnet, Claire; Jobe, Alan H.

2011-01-01

The chorioamnionitis associated with preterm delivery is often polymicrobial with ureaplasma being the most common isolate. To evaluate interactions between the different pro-inflammatory mediators, we hypothesized that ureaplasma exposure would increase fetal responsiveness to LPS. Fetal sheep were given intra-amniotic injections of media (control) or Ureaplasma parvum serovar 3 either 7d or 70d before preterm delivery. Another group received an intraamniotic injection of E.coli lipo-polysaccharide (LPS) 2d prior to delivery. To test for interactions, intraamniotic U. parvum exposed animals were challenged with intraamniotic LPS and delivered 2d later. All animals were delivered at 124±1d gestation (Term=150d). Compared to the 2d LPS exposure group, the U. parvum 70d+LPS group had: 1) decreased lung pro and anti-inflammatory cytokine expression 2) fewer CD3+ T-lymphocytes, CCL2+, myeloperoxidase+, and PU.1+ cells in the lung. Interestingly, exposure to U. parvum for 7d did not change responses to a subsequent intraamniotic LPS challenge, and exposure to intraamniotic U. parvum alone induced mild lung inflammation. Exposure to U. parvum increased pulmonary TGFβ1 expression but did not change mRNA expression of either the receptor TLR4 or some of the downstream mediators in the lung. Monocytes from fetal blood and lung isolated from U. parvum 70d+LPS but not U. parvum 7d+LPS animals had decreased in vitro responsiveness to LPS. These results are consistent with the novel finding of down-regulation of LPS responses by chronic but not acute fetal exposures to U. parvum. The findings increase our understanding of how chorioamnionitis exposed preterm infants may respond to lung injury and postnatal nosocomial infections. PMID:21784974

HOX Genes in Human Lung

PubMed Central

Golpon, Heiko A.; Geraci, Mark W.; Moore, Mark D.; Miller, Heidi L.; Miller, Gary J.; Tuder, Rubin M.; Voelkel, Norbert F.

2001-01-01

HOX genes belong to the large family of homeodomain genes that function as transcription factors. Animal studies indicate that they play an essential role in lung development. We investigated the expression pattern of HOX genes in human lung tissue by using microarray and degenerate reverse transcriptase-polymerase chain reaction survey techniques. HOX genes predominantly from the 3′ end of clusters A and B were expressed in normal human adult lung and among them HOXA5 was the most abundant, followed by HOXB2 and HOXB6. In fetal (12 weeks old) and diseased lung specimens (emphysema, primary pulmonary hypertension) additional HOX genes from clusters C and D were expressed. Using in situ hybridization, transcripts for HOXA5 were predominantly found in alveolar septal and epithelial cells, both in normal and diseased lungs. A 2.5-fold increase in HOXA5 mRNA expression was demonstrated by quantitative reverse transcriptase-polymerase chain reaction in primary pulmonary hypertension lung specimens when compared to normal lung tissue. In conclusion, we demonstrate that HOX genes are selectively expressed in the human lung. Differences in the pattern of HOX gene expression exist among fetal, adult, and diseased lung specimens. The altered pattern of HOX gene expression may contribute to the development of pulmonary diseases. PMID:11238043

Fetal heart rate patterns at 20 to 24 weeks gestation as recorded by fetal electrocardiography

PubMed Central

Hofmeyr, F; Groenewald, CA; Nel, DG; Myers, MM; Fifer, WP; Signore, C; Hankins, GDV; Odendaal, HJ

2014-01-01

Introduction With advancing technology it has become possible to accurately record and assess fetal heart rate (FHR) patterns from gestations as early as 20 weeks. The aim of our study was to describe early patterns of FHR, as recorded by transabdominal fetal electrocardiogram according to the Dawes-Redman criteria. Accordingly, short-term variability, basal heart rate, accelerations and decelerations were quantified at 20-24 weeks gestation among women with uncomplicated pregnancies. Methods This study was conducted in a subset of participants enrolled in a large prospective pregnancy cohort study. Our final data set consisted of 281 recordings of women with good perinatal outcomes that had undergone fetal electrocardiographic assessment as part of the Safe Passage Study. Results The success rate of the recordings was 95.4%. The mean frequency of small and large accelerations was 0.5 and 0.1 per 10 minutes respectively and that of small and large decelerations 0.3 and 0.008 per 10 minutes respectively. The mean and basal heart rates were both equal to 148.0 bpm at a median gestation of 161 days. The mean short term variation was 6.2 (SD 1.4) milliseconds and mean minute range 35.1 (SD 7.1) milliseconds. Conclusion The 20 to 24 week fetus demonstrates FHR patterns with more accelerations and decelerations, as well as higher baseline variability than was anticipated. Information from this study provides an important foundation for further, more detailed, studies of early FHR patterns. PMID:23991757

Fetal-to-maternal signaling to initiate parturition

PubMed Central

Reinl, Erin L.; England, Sarah K.

2015-01-01

Multiple processes are capable of activating the onset of parturition; however, the specific contributions of the mother and the fetus to this process are not fully understood. In this issue of the JCI, Gao and colleagues present evidence that steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2) regulate surfactant protein-A (SP-A) and platelet-activating factor (PAF) expression, which increases in the developing fetal lung. WT dams crossed with males deficient for both SRC-1 and SRC-2 had suppressed myometrial inflammation, increased serum progesterone, and delayed parturition, which could be reconciled by injection of either SP-A or PAF into the amnion. Together, the results of this study demonstrate that the fetal lungs produce signals to initiate labor in the mouse. This work underscores the importance of the fetus as a contributor to the onset of murine, and potentially human, parturition. PMID:26098207

Comparison of the Effects of Two Auditory Methods by Mother and Fetus on the Results of Non-Stress Test (Baseline Fetal Heart Rate and Number of Accelerations) in Pregnant Women: A Randomized Controlled Trial

PubMed Central

Khoshkholgh, Roghaie; Keshavarz, Tahereh; Moshfeghy, Zeinab; Akbarzadeh, Marzieh; Asadi, Nasrin; Zare, Najaf

2016-01-01

Objective: To compare the effects of two auditory methods by mother and fetus on the results of NST in 2011-2012. Materials and methods: In this single-blind clinical trial, 213 pregnant women with gestational age of 37-41 weeks who had no pregnancy complications were randomly divided into 3 groups (auditory intervention for mother, auditory intervention for fetus, and control) each containing 71 subjects. In the intervention groups, music was played through the second 10 minutes of NST. The three groups were compared regarding baseline fetal heart rate and number of accelerations in the first and second 10 minutes of NST. The data were analyzed using one-way ANOVA, Kruskal-Wallis, and paired T-test. Results: The results showed no significant difference among the three groups regarding baseline fetal heart rate in the first (p = 0.945) and second (p = 0.763) 10 minutes. However, a significant difference was found among the three groups concerning the number of accelerations in the second 10 minutes. Also, a significant difference was observed in the number of accelerations in the auditory intervention for mother (p = 0.013) and auditory intervention for fetus groups (p < 0.001). The difference between the number of accelerations in the first and second 10 minutes was also statistically significant (p = 0.002). Conclusion: Music intervention was effective in the number of accelerations which is the indicator of fetal health. Yet, further studies are required to be conducted on the issue. PMID:27385971

Comparison of the Effects of Two Auditory Methods by Mother and Fetus on the Results of Non-Stress Test (Baseline Fetal Heart Rate and Number of Accelerations) in Pregnant Women: A Randomized Controlled Trial.

PubMed

Khoshkholgh, Roghaie; Keshavarz, Tahereh; Moshfeghy, Zeinab; Akbarzadeh, Marzieh; Asadi, Nasrin; Zare, Najaf

2016-03-01

To compare the effects of two auditory methods by mother and fetus on the results of NST in 2011-2012. In this single-blind clinical trial, 213 pregnant women with gestational age of 37-41 weeks who had no pregnancy complications were randomly divided into 3 groups (auditory intervention for mother, auditory intervention for fetus, and control) each containing 71 subjects. In the intervention groups, music was played through the second 10 minutes of NST. The three groups were compared regarding baseline fetal heart rate and number of accelerations in the first and second 10 minutes of NST. The data were analyzed using one-way ANOVA, Kruskal-Wallis, and paired T-test. The results showed no significant difference among the three groups regarding baseline fetal heart rate in the first (p = 0.945) and second (p = 0.763) 10 minutes. However, a significant difference was found among the three groups concerning the number of accelerations in the second 10 minutes. Also, a significant difference was observed in the number of accelerations in the auditory intervention for mother (p = 0.013) and auditory intervention for fetus groups (p < 0.001). The difference between the number of accelerations in the first and second 10 minutes was also statistically significant (p = 0.002). Music intervention was effective in the number of accelerations which is the indicator of fetal health. Yet, further studies are required to be conducted on the issue.

Precision-cut vibratome slices allow functional live cell imaging of the pulmonary neuroepithelial body microenvironment in fetal mice.

PubMed

Schnorbusch, Kathy; Lembrechts, Robrecht; Brouns, Inge; Pintelon, Isabel; Timmermans, Jean-Pierre; Adriaensen, Dirk

2012-01-01

We recently developed an ex vivo lung slice model that allows for confocal live cell imaging (LCI) of neuroepithelial bodies (NEBs) in postnatal mouse lungs (postnatal days 1-21 and adult). NEBs are morphologically well-characterized, extensively innervated groups of neuroendocrine cells in the airway epithelium, which are shielded from the airway lumen by 'Clara-like' cells. The prominent presence of differentiated NEBs from early embryonic development onwards, strongly suggests that NEBs may exert important functions during late fetal and neonatal life. The main goal of the present study was to adapt the current postnatal LCI lung slice model to enable functional studies of fetal mouse lungs (gestational days 17-20).In vibratome lung slices of prenatal mice, NEBs could be unequivocally identified with the fluorescent stryryl pyridinium dye 4-Di-2-ASP. Changes in the intracellular free calcium concentration and in mitochondrial membrane potential could be monitored using appropriate functional fluorescent indicators (e.g. Fluo-4).It is clear that the described fetal mouse lung slice model is suited for LCI studies of Clara cells, ciliated cells, and the NEB microenvironment, and offers excellent possibilities to further unravel the significance of NEBs during the prenatal and perinatal period.

Peroxisome Proliferator-Activated Receptors Alpha, Beta, and Gamma mRNA and Protein Expression in Human Fetal Tissues

PubMed Central

Abbott, Barbara D.; Wood, Carmen R.; Watkins, Andrew M.; Das, Kaberi P.; Lau, Christopher S.

2010-01-01

Peroxisome proliferator-activated receptors (PPARs) regulate lipid and glucose homeostasis, are targets of pharmaceuticals, and are also activated by environmental contaminants. Almost nothing is known about expression of PPARs during human fetal development. This study examines expression of PPARα, β, and γ mRNA and protein in human fetal tissues. With increasing fetal age, mRNA expression of PPARα and β increased in liver, but PPARβ decreased in heart and intestine, and PPARγ decreased in adrenal. Adult and fetal mean expression of PPARα, β, and γ mRNA did not differ in intestine, but expression was lower in fetal stomach and heart. PPARα and β mRNA in kidney and spleen, and PPARγ mRNA in lung and adrenal were lower in fetal versus adult. PPARγ in liver and PPARβ mRNA in thymus were higher in fetal versus adult. PPARα protein increased with fetal age in intestine and decreased in lung, kidney, and adrenal. PPARβ protein in adrenal and PPARγ in kidney decreased with fetal age. This study provides new information on expression of PPAR subtypes during human development and will be important in evaluating the potential for the developing human to respond to PPAR environmental or pharmaceutical agonists. PMID:20706641

Group B Streptococcus β-hemolysin/Cytolysin Breaches Maternal-Fetal Barriers to Cause Preterm Birth and Intrauterine Fetal Demise in Vivo

PubMed Central

Randis, Tara M.; Gelber, Shari E.; Hooven, Thomas A.; Abellar, Rosanna G.; Akabas, Leor H.; Lewis, Emma L.; Walker, Lindsay B.; Byland, Leah M.; Nizet, Victor; Ratner, Adam J.

2014-01-01

Background. Maternal vaginal colonization with Streptococcus agalactiae (Group B Streptococcus [GBS]) is a precursor to chorioamnionitis, fetal infection, and neonatal sepsis, but the understanding of specific factors in the pathogenesis of ascending infection remains limited. Methods. We used a new murine model to evaluate the contribution of the pore-forming GBS β-hemolysin/cytolysin (βH/C) to vaginal colonization, ascension, and fetal infection. Results. Competition assays demonstrated a marked advantage to βH/C-expressing GBS during colonization. Intrauterine fetal demise and/or preterm birth were observed in 54% of pregnant mice colonized with wild-type (WT) GBS and 0% of those colonized with the toxin-deficient cylE knockout strain, despite efficient colonization and ascension by both strains. Robust placental inflammation, disruption of maternal-fetal barriers, and fetal infection were more frequent in animals colonized with WT bacteria. Histopathologic examination revealed bacterial tropism for fetal lung and liver. Conclusions. Preterm birth and fetal demise are likely the direct result of toxin-induced damage and inflammation rather than differences in efficiency of ascension into the upper genital tract. These data demonstrate a distinct contribution of βH/C to GBS chorioamnionitis and subsequent fetal infection in vivo and showcase a model for this most proximal step in GBS pathogenesis. PMID:24474814

Cigarette Smoke Exposure during Pregnancy Alters Fetomaternal Cell Trafficking Leading to Retention of Microchimeric Cells in the Maternal Lung

PubMed Central

Vogelgesang, Anja; Scapin, Cristina; Barone, Caroline; Tam, Elaine

2014-01-01

Cigarette smoke exposure causes chronic oxidative lung damage. During pregnancy, fetal microchimeric cells traffic to the mother. Their numbers are increased at the site of acute injury. We hypothesized that milder chronic diffuse smoke injury would attract fetal cells to maternal lungs. We used a green-fluorescent-protein (GFP) mouse model to study the effects of cigarette smoke exposure on fetomaternal cell trafficking. Wild-type female mice were exposed to cigarette smoke for about 4 weeks and bred with homozygote GFP males. Cigarette smoke exposure continued until lungs were harvested and analyzed. Exposure to cigarette smoke led to macrophage accumulation in the maternal lung and significantly lower fetal weights. Cigarette smoke exposure influenced fetomaternal cell trafficking. It was associated with retention of GFP-positive fetal cells in the maternal lung and a significant reduction of fetal cells in maternal livers at gestational day 18, when fetomaternal cell trafficking peaks in the mouse model. Cells quickly clear postpartum, leaving only a few, difficult to detect, persisting microchimeric cells behind. In our study, we confirmed the postpartum clearance of cells in the maternal lungs, with no significant difference in both groups. We conclude that in the mouse model, cigarette smoke exposure during pregnancy leads to a retention of fetal microchimeric cells in the maternal lung, the site of injury. Further studies will be needed to elucidate the effect of cigarette smoke exposure on the phenotypic characteristics and function of these fetal microchimeric cells, and confirm its course in cigarette smoke exposure in humans. PMID:24832066

Induction of apoptosis by accelerated heavy-ion beams in cultured fetal rat testes and its modification

NASA Astrophysics Data System (ADS)

Wang, Bing; Tanaka, Kaoru; Shang, Yi; Fujita, Kazuko; Ninomiya, Yasuharu; Moreno, Stephanie G.; Coffigny, Herve; Hayata, Isamu; Murakami, Masahiro; Eguchi-Kasai, Kiyomi; Nenoi, Mitsuru

The increasing human activities in space missions make the study on effects from high-LET ionizing radiation an important issue to be addressed. We reported previously that prenatal irradiations with heavy-ion beams on gestation day 15 generally induced markedly detrimental effects on prenatal gonads, postnatal testicular development and male breeding activity in rats. To explore the mechanisms involved in radiation-induced gonocyte apoptosis in fetal gonads, which played a critical role in the fate of postnatal testis development, accelerated heavy-ion irradiations and organotypic culture of Wistar fetal rat testes were applied to investigations focused on cellular and molecular events after irradiations with or without chemical addition. Results showed that, in addition to the clustered distribution, both the time course and the percentage of apoptosis in gonocytes on gestation day 15 equivalent in vitro appeared similar to that in utero after exposure to either carbon-ion beams with a LET value of about 13 keV/µm or neon-ion beams with a LET value of about 30 keV/µm. Irradiations induced increased p53 expression in a dose dependent manner and decreased expressions of p21 and Bcl- 2 by Western Blot examination. Administration of pan-caspase inhibitor prior to irradiations effectively inhibited apoptosis occurrence and reduced the extent of clustered apoptosis, while such effects were not observed with the presence of p53 inhibitor, gap junction inhibitor, or nitric oxide specific scavenger. These findings indicated that irradiations of cultured fetal rat testes manifested pathologically similar apoptosis induction in gonocytes to that in utero. P53 expression was possibly responsible for the response to radiation damage rather than induction of apoptosis. The syncytial organization of gonocytes played a key role in formation of the clustered apoptosis, an event that both gap junction inhibitor and nitric oxide specific scavenger were incapable of preventing.

STATs in Lung Development: Distinct Early and Late Expression, Growth Modulation and Signaling Dysregulation in Congenital Diaphragmatic Hernia.

PubMed

Piairo, Paulina; Moura, Rute S; Baptista, Maria João; Correia-Pinto, Jorge; Nogueira-Silva, Cristina

2018-01-01

Congenital diaphragmatic hernia (CDH) is a life-threatening developmental anomaly, intrinsically combining severe pulmonary hypoplasia and hypertension. During development, signal transducers and activators of transcription (STAT) are utilized to elicit cell growth, differentiation, and survival. We used the nitrofen-induced CDH rat model. At selected gestational time points, lungs were divided into two experimental groups, i.e., control or CDH. We performed immunohistochemistry and western blotting analysis to investigate the developmental expression profile of the complete family of STATs (STAT1-6), plus specific STATs activation (p-STAT3, p-STAT6) and regulation by SOCS (SOCS3) in normal lungs against those of diseased lungs. The normal fetal lung explants were treated with piceatannol (STAT3 inhibitor) in vitro followed by morphometrical analysis. Molecular profiling of STATs during the lung development revealed distinct early and late expression signatures. Experimental CDH altered the STATs expression, activation, and regulation in the fetal lungs. In particular, STAT3 and STAT6 were persistently over-expressed and early over-activated. Piceatannol treatment dose-dependently stimulated the fetal lung growth. These findings suggest that STATs play an important role during normal fetal lung development and CDH pathogenesis. Moreover, functionally targeting STAT signaling modulates fetal lung growth, which highlights that STAT3 and STAT6 signaling might be promising therapeutic targets in reducing or preventing pulmonary hypoplasia in CDH. © 2018 The Author(s). Published by S. Karger AG, Basel.

Influence of carbon monoxide poisoning on the fetal heart monitor tracing: a report of 3 cases.

PubMed

Towers, Craig V; Corcoran, Vincent A

2009-03-01

The diagnosis of carbon monoxide poisoning in the third trimester of pregnancy requires an index of suspicion, and the appearance of the fetal heart monitor tracing may help in this regard. Three cases of third-trimester acute carbon monoxide poisoning occurred. In each pregnancy, the fetal heart monitor tracing on admission was correlated with the maternal carboxyhemoglobin level, and how the pattern changed following the institution of therapy was analyzed. In all 3 cases, the initial fetal heart rate pattern demonstrated decreased variability with an elevated baseline and an absence of accelerations and decelerations. Within 45-90 minutes of treatment onset, the baseline fetal heart rate dropped by 20-40 beats per minute, the variability became moderate, and accelerations occurred. Absent accelerations with minimal variability, if caused by uteroplacental insufficiency, are usually preceded by recurrent decelerations. Absent accelerations with minimal variability in the absence of recurrent decelerations may suggest another cause, of which carbon monoxide intoxication can be added to the differential, especially since this disorder often has nonspecific clinical symptoms.

Computerized intrapartum electronic fetal monitoring: analysis of the decision to deliver for fetal distress.

PubMed

Georgieva, Antoniya; Payne, Stephen J; Moulden, Mary; Redman, Christopher W G

2011-01-01

We applied computerized methods to assess the Electronic Fetal Monitoring (EFM) in labor. We analyzed retrospectively the last hour of EFM for 1,370 babies, delivered by emergency Cesarean sections before the onset of pushing (data collected at the John Radcliffe Hospital, Oxford, UK). There were two cohorts according to the reason for intervention: (a) fetal distress, n(1) = 524 and (b) failure to progress and/or malpresentation, n(2) = 846. The cohorts were compared in terms of classical EFM features (baseline, decelerations, variability and accelerations), computed by a dedicated Oxford system for automated analysis--OxSys. In addition, OxSys was employed to simulate current clinical guidelines for the classification of fetal monitoring, i.e. providing in real time a three-tier grading system of the EFM (normal, indeterminate, or abnormal). The computerized features and the simulated guidelines corresponded well to the clinical management and to the actual labor outcome (measured by umbilical arterial pH).

Twist1 Suppresses Senescence Programs and Thereby Accelerates and Maintains Mutant Kras-Induced Lung Tumorigenesis

PubMed Central

Thiyagarajan, Saravanan; Das, Sandhya T.; Zabuawala, Tahera; Chen, Joy; Cho, Yoon-Jae; Luong, Richard; Tamayo, Pablo; Salih, Tarek; Aziz, Khaled; Adam, Stacey J.; Vicent, Silvestre; Nielsen, Carsten H.; Withofs, Nadia; Sweet-Cordero, Alejandro; Gambhir, Sanjiv S.; Rudin, Charles M.; Felsher, Dean W.

2012-01-01

KRAS mutant lung cancers are generally refractory to chemotherapy as well targeted agents. To date, the identification of drugs to therapeutically inhibit K-RAS have been unsuccessful, suggesting that other approaches are required. We demonstrate in both a novel transgenic mutant Kras lung cancer mouse model and in human lung tumors that the inhibition of Twist1 restores a senescence program inducing the loss of a neoplastic phenotype. The Twist1 gene encodes for a transcription factor that is essential during embryogenesis. Twist1 has been suggested to play an important role during tumor progression. However, there is no in vivo evidence that Twist1 plays a role in autochthonous tumorigenesis. Through two novel transgenic mouse models, we show that Twist1 cooperates with KrasG12D to markedly accelerate lung tumorigenesis by abrogating cellular senescence programs and promoting the progression from benign adenomas to adenocarcinomas. Moreover, the suppression of Twist1 to physiological levels is sufficient to cause Kras mutant lung tumors to undergo senescence and lose their neoplastic features. Finally, we analyzed more than 500 human tumors to demonstrate that TWIST1 is frequently overexpressed in primary human lung tumors. The suppression of TWIST1 in human lung cancer cells also induced cellular senescence. Hence, TWIST1 is a critical regulator of cellular senescence programs, and the suppression of TWIST1 in human tumors may be an effective example of pro-senescence therapy. PMID:22654667

Intrauterine Candida albicans infection elicits severe inflammation in fetal sheep

PubMed Central

Payne, Matthew S.; Kemp, Matthew W.; Kallapur, Suhas G.; Kannan, Paranthaman Senthamarai; Saito, Masatoshi; Miura, Yuichiro; Newnham, John P.; Stock, Sarah; Ireland, Demelza J.; Kramer, Boris W.; Jobe, Alan H.

2014-01-01

Background Preventing preterm birth and subsequent adverse neonatal sequelae is among the greatest clinical challenges of our time. Recent studies suggest a role for Candida spp. in preterm birth and fetal injury, as a result of their colonization of either the vagina and/or the amniotic cavity. We hypothesised that intraamniotic C. albicans would cause a vigorous, acute fetal inflammatory response. Methods Sheep carrying singleton pregnancies received single intraamniotic (IA) injections of either saline (control) or 107 CFU C. albicans 1 or 2 d prior to surgical delivery and euthanasia at 124 ± 2 d gestation. Results Colonization of the amniotic cavity by C. albicans resulted in a modest inflammatory response at 1 d and florid inflammation at 2 d, characterised by fetal thrombocytopenia, lymphopenia and significant increases of inflammatory cytokines/chemokines in the fetal membranes skin, lung and the amniotic fluid. Conclusion Acute colonization of the amniotic cavity by C. albicans causes severe intrauterine inflammation and fetal injury. C. albicans is a potent fetal pathogen which can contribute to adverse pregnancy outcomes. PMID:24632681

Biomimetics of fetal alveolar flow phenomena using microfluidics.

PubMed

Tenenbaum-Katan, Janna; Fishler, Rami; Rothen-Rutishauser, Barbara; Sznitman, Josué

2015-01-01

At the onset of life in utero, the respiratory system begins as a liquid-filled tubular organ and undergoes significant morphological changes during fetal development towards establishing a respiratory organ optimized for gas exchange. As airspace morphology evolves, respiratory alveolar flows have been hypothesized to exhibit evolving flow patterns. In the present study, we have investigated flow topologies during increasing phases of embryonic life within an anatomically inspired microfluidic device, reproducing real-scale features of fetal airways representative of three distinct phases of in utero gestation. Micro-particle image velocimetry measurements, supported by computational fluid dynamics simulations, reveal distinct respiratory alveolar flow patterns throughout different stages of fetal life. While attached, streamlined flows characterize the shallow structures of premature alveoli indicative of the onset of saccular stage, separated recirculating vortex flows become the signature of developed and extruded alveoli characteristic of the advanced stages of fetal development. To further mimic physiological aspects of the cellular environment of developing airways, our biomimetic devices integrate an alveolar epithelium using the A549 cell line, recreating a confluent monolayer that produces pulmonary surfactant. Overall, our in vitro biomimetic fetal airways model delivers a robust and reliable platform combining key features of alveolar morphology, flow patterns, and physiological aspects of fetal lungs developing in utero.

Accelerated fetal growth in early pregnancy and risk of severe large-for-gestational-age and macrosomic infant: a cohort study in a low-risk population.

PubMed

Simic, Marija; Wikström, Anna-Karin; Stephansson, Olof

2017-10-01

Our objective was to examine the association between fetal growth in early pregnancy and risk of severe large-for-gestational-age (LGA) and macrosomia at birth in a low-risk population. Cohort study that included 68 771 women with non-anomalous singleton pregnancies, without history of diabetes or hypertension, based on an electronic database on pregnancies and deliveries in Stockholm-Gotland Region, Sweden, 2008-2014. We performed multivariable logistic regression to estimate the association between accelerated fetal growth occurring in the first through early second trimester as measured by ultrasound and LGA and macrosomia at birth. Restricted analyses were performed in the groups without gestational diabetes and with normal body mass index (18.5-24.9 kg/m 2 ). When adjusting for confounders, the odds of having a severely LGA or macrosomic infant were elevated in mothers with fetuses that were at least 7 days larger than expected as compared with mothers without age discrepancy at the second-trimester scan (adjusted odds ratio 1.80; 95% CI 1.23-2.64 and adjusted odds ratio 2.15; 95% CI 1.55-2.98, respectively). Additionally, mothers without gestational diabetes and mothers with normal weight had an elevated risk of having a severely LGA or macrosomic infant when the age discrepancy by second-trimester ultrasound was at least 7 days. In a low-risk population, ultrasound-estimated accelerated fetal growth in early pregnancy was associated with an increased risk of having a severely LGA or macrosomic infant. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Remodelling of the bovine placenta: Comprehensive morphological and histomorphological characterization at the late embryonic and early accelerated fetal growth stages.

PubMed

Estrella, Consuelo Amor S; Kind, Karen L; Derks, Anna; Xiang, Ruidong; Faulkner, Nicole; Mohrdick, Melina; Fitzsimmons, Carolyn; Kruk, Zbigniew; Grutzner, Frank; Roberts, Claire T; Hiendleder, Stefan

2017-07-01

Placental function impacts growth and development with lifelong consequences for performance and health. We provide novel insights into placental development in bovine, an important agricultural species and biomedical model. Concepti with defined genetics and sex were recovered from nulliparous dams managed under standardized conditions to study placental gross morphological and histomorphological parameters at the late embryo (Day48) and early accelerated fetal growth (Day153) stages. Placentome number increased 3-fold between Day48 and Day153. Placental barrier thickness was thinner, and volume of placental components, and surface areas and densities were higher at Day153 than Day48. We confirmed two placentome types, flat and convex. At Day48, there were more convex than flat placentomes, and convex placentomes had a lower proportion of maternal connective tissue (P < 0.01). However, this was reversed at Day153, where convex placentomes were lower in number and had greater volume of placental components (P < 0.01- P < 0.001) and greater surface area (P < 0.001) than flat placentomes. Importantly, embryo (r = 0.50) and fetal (r = 0.30) weight correlated with total number of convex but not flat placentomes. Extensive remodelling of the placenta increases capacity for nutrient exchange to support rapidly increasing embryo-fetal weight from Day48 to Day153. The cellular composition of convex placentomes, and exclusive relationships between convex placentome number and embryo-fetal weight, provide strong evidence for these placentomes as drivers of prenatal growth. The difference in proportion of maternal connective tissue between placentome types at Day48 suggests that this tissue plays a role in determining placentome shape, further highlighting the importance of early placental development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects and molecular mechanisms of intrauterine infection/inflammation on lung development.

PubMed

Pan, Jiarong; Zhan, Canyang; Yuan, Tianming; Wang, Weiyan; Shen, Ying; Sun, Yi; Wu, Tai; Gu, Weizhong; Chen, Lihua; Yu, Huimin

2018-05-10

Intrauterine infection/inflammation plays an important role in the development of lung injury and bronchopulmonary dysplasia (BPD) in preterm infants, While a multifactorial genesis is likely, mechanisms involved in BPD after intrauterine infection/inflammation are largely unknown. Recent studies have suggested microRNAs (miRNAs) are likely to play a role. Therefore, this study aimed to study the effects and mechanisms of intrauterine infection/inflammation on lung development, and to identify miRNAs related to lung injury and BPD. An animal model of intrauterine infection/inflammation was established with pregnant SD rats endocervically inoculated with E.coli. The fetal and neonatal rats were observed at embryonic day (E) 17, 19, 21 and postnatal day (P) 1, 3, 7, 14, respectively. Body weight, lung weight, the expression levels of NLRP3, TNF-α, IL-lβ, IL-6, VEGF, Collagen I, SP-A, SP-B and SP-C in the lung tissues of fetal and neonatal rats were measured. Expression profiles of 1218 kinds of miRNAs in the lungs of neonatal rats were detected by miRNA microarray technique. Target genes of the identified miRNAs were predicted through online software. Intrauterine infection/inflammation compromised not only weight development but also lung development of the fetal and neonatal rats. The results showed significantly increased expression of NLRP3, TNF-α, IL-1β, IL-6, Collagen I, and significantly decreased expression of VEGF, SP-A, SP-B and SP-C in the fetal and neonatal rat lung tissues in intrauterine infection group compared to the control group at different observation time point (P < 0.05). Forty-three miRNAs with significant differential expression were identified. Possible target genes regulated by the identified miRNAs are very rich. Intrauterine infection/inflammation results in lung histological changes which are very similar to those observed in BPD. Possible mechanisms may include NLRP3 inflammasome activation followed by inflammatory cytokines

[Fetal urology].

PubMed

Jakobovits, Akos; Jakobovits, Antal

2009-06-14

Although it becomes vitally important only after birth, renal function already plays significant role in maintaining fetal metabolic equilibrium. The kidneys significantly contribute to production of amniotic fluid. Adequate amount of amniotic fluid is needed to stimulate the intrauterine fetal respiratory activity. Intrauterine breathing is essential for lung development. As a result, oligohydramnion is conducive to pulmonary hypoplasia. The latter may lead to neonatal demise soon after birth. In extrauterine life kidneys eliminate nitrogen containing metabolic byproducts. Inadequate renal function results therefore lethal uremia. Integrity of ureters and the urethra is essential for the maintenance of renal function. Retention of urine causes degeneration of the functional units of the kidneys and ensuing deterioration of renal function. Intrauterine kidney puncture or shunt procedure may delay this process in some cases. On the other hand, once renal function has been damaged, no therapy can restart it. Certain anomalies of renal excretory pathways may also be associated with other congenital abnormalities, making the therapeutic efforts pointless. Presence of these associated intrauterine defects makes early pregnancy termination a management alternative, as well as it affects favorably perinatal mortality rates.

Prenatal administration of neuropeptide bombesin promotes lung development in a rat model of nitrofen-induced congenital diaphragmatic hernia.

PubMed

Sakai, Kohei; Kimura, Osamu; Furukawa, Taizo; Fumino, Shigehisa; Higuchi, Koji; Wakao, Junko; Kimura, Koseki; Aoi, Shigeyoshi; Masumoto, Kouji; Tajiri, Tatsuro

2014-12-01

Fetal medical treatment to improve lung hypoplasia in congenital diaphragmatic hernia (CDH) has yet to be established. The neuropeptide bombesin (BBS) might play an important role in lung development. The present study aims to determine whether prenatally administered BBS could be useful to promote fetal lung development in a rat model of nitrofen-induced CDH. Pregnant rats were administered with nitrofen (100mg) on gestation day 9.5 (E9.5). BBS (50mg/kg/day) was then daily infused intraperitoneally from E14, and fetal lungs were harvested on E21. The expression of PCNA was assessed by both immunohistochemical staining and RT-PCR to determine the amount of cell proliferation. Lung maturity was assessed as the expression of TTF-1, a marker of alveolar epithelial cell type II. The lung-body-weight ratio was significantly increased in CDH/BBS(+) compared with CDH/BBS(-) (p<0.05). The number of cells stained positive for PCNA and TTF-1 was significantly decreased in CDH/BBS(+) compared with CDH/BBS(-) (p<0.01). The TTF-1 mRNA expression levels were significantly decreased in CDH/BBS(+) compared with CDH/BBS(-) (p<0.05). Prenatally administered BBS promotes lung development in a rat model of nitrofen-induced CDH. Neuropeptide BBS could help to rescue lung hypoplasia in fetal CDH. Copyright © 2014 Elsevier Inc. All rights reserved.

Intrauterine growth restriction decreases nuclear factor-kappa B signaling in fetal pulmonary artery endothelial cells of fetal sheep.

PubMed

Dodson, R Blair; Powers, Kyle N; Gien, Jason; Rozance, Paul J; Seedorf, Gregory J; Astling, David; Jones, Kenneth Lloyd; Crombleholme, Timothy M; Abman, Steven H; Alvira, Cristina M

2018-05-03

Intrauterine growth restriction (IUGR) in premature newborns increases the risk for bronchopulmonary dysplasia (BPD), a chronic lung disease characterized by disrupted pulmonary angiogenesis and alveolarization. We previously showed that experimental IUGR impairs angiogenesis, however, mechanisms that impair pulmonary artery endothelial cell (PAEC) function are uncertain. The nuclear factor-kappa-B (NFκB) pathway promotes vascular growth in the developing mouse lung, and we hypothesized that IUGR disrupts NFκB-regulated pro-angiogenic targets in fetal PAEC. PAECs were isolated from lungs of control fetal sheep and sheep with experimental IUGR from an established model of chronic placental insufficiency. Microarray analysis identified suppression of NFκB signaling and significant alterations in extracellular matrix (ECM) pathways in IUGR PAEC, including decreases in collagen 4α1 and laminin α4, components of the basement membrane and putative NFκB targets. In comparison with controls: (i) immunostaining of active NFκB complexes; (ii) NFκB-DNA binding; (iii) baseline expression of NFκB subunits, p65 and p50; and (iv) LPS-mediated inducible activation of NFκB signaling were decreased in IUGR PAEC. Although pharmacologic NFκB inhibition did not affect angiogenic function in IUGR PAEC, angiogenic function of control PAEC was reduced to a similar degree as that observed in IUGR PAEC. These data identify reductions in endothelial NFκB signaling as central to the disrupted angiogenesis observed in IUGR, likely by impairing both intrinsic PAEC angiogenic function and NFκB-mediated regulation of ECM components necessary for vascular development. These data further suggest that strategies that preserve endothelial NFκB activation may be useful in lung diseases marked by disrupted angiogenesis such as IUGR.

Effect of electromagnetic field emitted by cellular phones on fetal heart rate patterns.

PubMed

Celik, Onder; Hascalik, Seyma

2004-01-15

The study was planned to determine the effects of electromagnetic fields produced by cellular phones on baseline fetal heart rate, acceleration and deceleration. Forty pregnant women undergoing non-stress test were admitted to the study. Non-stress test was obtained while the subjects were holding the CP on stand by mode and on dialing mode, each for 5 min. Similar recordings were taken while there were no phones around for 10 min. Electromagnetic fields produced by cellular phones do not cause any demonstrable affect in fetal heart rate, acceleration and deceleration.

Fetal circulatory responses to oxygen lack.

PubMed

Jensen, A; Berger, R

1991-10-01

The knowledge on fetal and neonatal circulatory physiology accumulated by basic scientists and clinicians over the years has contributed considerably to the recent decline of perinatal morbidity and mortality. This review will summarize the peculiarities of the fetal circulation, the distribution of organ blood flow during normoxemia, and that during oxygen lack caused by various experimental perturbations. Furthermore, the relation between oxygen delivery and tissue metabolism during oxygen lack as well as evidence to support a new concept will be presented along with the principal cardiovascular mechanisms involved. Finally, blood flow and oxygen delivery to the principal fetal organs will be examined and discussed in relation to organ function. The fetal circulatory response to hypoxemia and asphyxia is a centralization of blood flow in favour of the brain, heart, and adrenals and at the expense of almost all peripheral organs, particularly of the lungs, carcass, skin and scalp. This response is qualitatively similar but quantitatively different under various experimental conditions. However, at the nadir of severe acute asphyxia the circulatory centralization cannot be maintained. Then there is circulatory decentralization, and the fetus will experience severe brain damage if not expire unless immediate resuscitation occurs. Future work in this field will have to concentrate on the important questions, what factors determine this collapse of circulatory compensating mechanisms in the fetus, how does it relate to neuronal damage, and how can the fetal brain be pharmacologically protected against the adverse effects of asphyxia.

The Effects of Hemodynamic Alterations on Lung Volumes in Fetuses with Tetralogy of Fallot: An MRI Study.

PubMed

Berger-Kulemann, Vanessa; Berger, Rudolf; Mlczoch, Elisabeth; Sternal, Daniel; Mailath-Pokorny, Mariella; Hachemian, Nilouparak; Prayer, Daniela; Weber, Michael; Salzer-Muhar, Ulrike

2015-08-01

This study assessed whether the presence of tetralogy of Fallot (TOF) affects fetal lung development and whether these fetuses are at risk of pulmonary hypoplasia (PH). Furthermore, we investigated whether the degree of the concomitant pulmonary valve (PV) stenosis or a stenosis in the branch pulmonary arteries correlates with the fetal lung volume. Lung volumetry was performed in 16 fetuses with TOF who underwent MRI between gestational weeks 21 and 35 and in 22 controls. Fetal biometric data and the diameters of the PVs were evaluated by ultrasound. PV and branch pulmonary artery diameters were standardized (z-scores), and fetal lung volume/fetal body weight (FLV/FBW) ratios (ml/g) were calculated. The mean FLV/FBW ratio (0.031 ± 0.009 ml/g) in the TOF group was statistically significantly lower than in the control group (0.041 ± 0.009 ml/g; P = 0.003). None of the fetuses with TOF met the criterion for PH. FLV did not correlate with the degree of PV stenosis, but rather with the presence of a significant stenosis in at least one branch pulmonary artery. The presence of TOF moderately affects fetal lung growth, which is apparently not dependent on the degree of the PV stenosis. However, only an additional stenosis in at least one branch pulmonary artery was associated with a small FLV, but not with PH. Thus, reduced pulmonary blood flow may be offset by additional factors, such as the ability to establish a sufficient collateral system and to alter structural vascular size and, thus, pulmonary vascular resistance.

IGFBP-4 gene overexpression in the nitrofen-induced hypoplastic lung.

PubMed

Ruttenstock, E M; Doi, T; Dingemann, J; Puri, P

2011-01-01

The precise mechanism of pulmonary hypoplasia (HP) associated with congenital diaphragmatic hernia (CDH) remains unclear. Insulin-like growth factors (IGFs) play an essential role in fetal lung development through IGF receptors (IGFRs) by regulating cellular proliferation, differentiation and survival. It has been reported that the expression of genes involved in IGF-IGFR signaling is altered in the nitrofen-induced hypoplastic lung during the later stages of lung development. IGF-binding proteins (IGFBPs) control bioavailability, activity and disruption of IGFs through the high affinity IGFBP/IGF complexes. IGFBP-4 is a key inhibitor of IGF-IGFR signaling-mediated cell proliferation. It has been revealed that cell proliferation in fetal lung fibroblasts is inhibited by increased IGFBP-4 production. We hypothesized that IGFBP-4 gene expression is increased during the later stages of lung development in the nitrofen-induced CDH lung. Pregnant Sprague-Dawley rats were exposed to either olive oil or nitrofen on day 9 (D9) of gestation. Fetuses were harvested by cesarean section on D18 and D21. Fetal lungs were divided into 3 groups: control, nitrofen without CDH [CDH(-)] and nitrofen with CDH [CDH(+)] (n=24 at each time point). Relative mRNA levels of IGFBP-4 were determined using real-time RT-PCR. Immunohistochemistry was performed to evaluate the protein expression of IGFBP-4. The relative expression levels of IGFBP-4 mRNA were significantly increased in CDH(-) and CDH(+) groups on D18 and D21 compared to controls. Immunohistochemistry showed increased IGFBP-4 expression in mesenchymal compartments on D18 and D21 in hypoplastic lungs compared to controls. Overexpression of pulmonary IGFBP-4 during the later stages of lung development may contribute to pulmonary hypoplasia in the nitrofen-induced CDH model by inhibiting IGF-mediated cell proliferation. © Georg Thieme Verlag KG Stuttgart · New York.

“Pulmonary Effects of Maternal Smoking on the Fetus and Child: Effects on Lung Development, Respiratory Morbidities, and Life Long Lung Health”

PubMed Central

McEvoy, Cindy T.; Spindel, Eliot R.

2016-01-01

Summary Maternal smoking during pregnancy is the largest preventable cause of abnormal in-utero lung development. Despite well known risks, rates of smoking during pregnancy have only slightly decreased over the last ten years, with rates varying from 5-40% worldwide resulting in tens of millions of fetal exposures. Despite multiple approaches to smoking cessation about 50% of smokers will continue to smoke during pregnancy. Maternal genotype plays an important role in the likelihood of continued smoking during pregnancy and the degree to which maternal smoking will affect the fetus. The primary effects of maternal smoking on offspring lung function and health are decreases in forced expiratory flows, decreased passive respiratory compliance, increased hospitalization for respiratory infections, and an increased prevalence of childhood wheeze and asthma. Nicotine appears to be the responsible component of tobacco smoke that affects lung development, and some of the effects of maternal smoking on lung development can be prevented by supplemental vitamin C. Because nicotine is the key agent for affecting lung development, e-cigarette usage during pregnancy is likely to be as dangerous to fetal lung development as is maternal smoking. PMID:27639458

A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids.

PubMed

Dye, Briana R; Dedhia, Priya H; Miller, Alyssa J; Nagy, Melinda S; White, Eric S; Shea, Lonnie D; Spence, Jason R

2016-09-28

Human pluripotent stem cell (hPSC) derived tissues often remain developmentally immature in vitro, and become more adult-like in their structure, cellular diversity and function following transplantation into immunocompromised mice. Previously we have demonstrated that hPSC-derived human lung organoids (HLOs) resembled human fetal lung tissue in vitro (Dye et al., 2015). Here we show that HLOs required a bioartificial microporous poly(lactide-co-glycolide) (PLG) scaffold niche for successful engraftment, long-term survival, and maturation of lung epithelium in vivo. Analysis of scaffold-grown transplanted tissue showed airway-like tissue with enhanced epithelial structure and organization compared to HLOs grown in vitro. By further comparing in vitro and in vivo grown HLOs with fetal and adult human lung tissue, we found that in vivo transplanted HLOs had improved cellular differentiation of secretory lineages that is reflective of differences between fetal and adult tissue, resulting in airway-like structures that were remarkably similar to the native adult human lung.

Fetal Cardiac Responding: Maturational and Behavioral Correlates.

ERIC Educational Resources Information Center

Emory, Eugene K.; Noonan, John R.

1984-01-01

Classified fetuses as accelerators or decelerators based on intrapartum fetal heart rate (FHR). Explored the relationship of the classification with gestational age and neonatal behavior in clinically healthy neonates to provide an empirical basis for using FHR in the study of infant behavior. Subjects were 48 "healthy term" or…

[Effect of Music Intervention on Maternal Anxiety and Fetal Heart Rate Pattern During Non-Stress Test].

PubMed

Oh, Myung Ok; Kim, Young Jeoum; Baek, Cho Hee; Kim, Ju Hee; Park, No Mi; Yu, Mi Jeong; Song, Han Sol

2016-06-01

The purpose of this cross-over experimental study was to examine effects of music intervention on maternal anxiety, fetal heart rate pattern and testing time during non-stress tests (NST) for antenatal fetal assessment. Sixty pregnant women within 28 to 40 gestational weeks were randomly assigned to either the experimental group (n=30) or control group (n=30). Music intervention was provided to pregnant women in the experimental group during NST. Degree of maternal anxiety and fetal heart rate pattern were our primary outcomes. State-trait anxiety inventory, blood pressure, pulse rate, and changes in peripheral skin temperature were assessed to determine the degree of maternal anxiety. Baseline fetal heart rate, frequency of acceleration in fetal heart rate, fetal movement test and testing time for reactive NST were assessed to measure the fetal heart rate pattern. The experimental group showed significantly lower scores in state anxiety than the control group. There were no significant differences in systolic blood pressure and pulse rate between the two groups. Baseline fetal heart rate was significantly lower in the experimental group than in the control group. Frequency of acceleration in fetal heart rate was significantly increased in the experimental group compared to the control group. There were no significant differences in fetal movement and testing time for reactive NST between the two groups. Present results suggest that music intervention could be an effective nursing intervention for alel viating anxiety during non-stress test.

Expression of Iroquois genes is up-regulated during early lung development in the nitrofen-induced pulmonary hypoplasia.

PubMed

Doi, Takashi; Lukošiūtė, Aušra; Ruttenstock, Elke; Dingemann, Jens; Puri, Prem

2011-01-01

Iroquois homeobox (Irx) genes have been implicated in the early lung morphogenesis of vertebrates. Irx1-3 and Irx5 gene expression is seen in fetal lung in rodents up to day (D) 18.5 of gestation. Fetal lung in Irx knockdown mice shows loss of mesenchyme and dilated airspaces, whereas nitrofen-induced hypoplastic lung displays thickened mesenchyme and diminished airspaces. We hypothesized that the Irx genes are up-regulated during early lung morphogenesis in the nitrofen-induced hypoplastic lung. Pregnant rats were exposed either to olive oil or nitrofen on D9. Fetal lungs harvested on D15 were divided into control and nitrofen groups; and the lungs harvested on D18 were divided into control, nitrofen without congenital diaphragmatic hernia (CDH[-]), and nitrofen with CDH (CDH[+]). Irx gene expression levels were analyzed by reverse transcriptase polymerase chain reaction. Immunohistochemistry was performed to evaluate protein expression of Irx family. Pulmonary Irx1-3 and Irx5 messenger RNA expression levels were significantly up-regulated in nitrofen group compared with controls at D15. On D15, Irx immunoreactivity was increased in nitrofen-induced hypoplastic lung compared with controls. Overexpression of Irx genes in the early lung development may cause pulmonary hypoplasia in the nitrofen CDH model by inducing lung dysmorphogenesis with thickened mesenchyme and diminished airspaces. Copyright © 2011 Elsevier Inc. All rights reserved.

Insulin receptor is downregulated in the nitrofen-induced hypoplastic lung.

PubMed

Ruttenstock, Elke; Doi, Takashi; Dingemann, Jens; Puri, Prem

2010-05-01

The pathogenesis of pulmonary hypoplasia in congenital diaphragmatic hernia (CDH) is still poorly understood. During fetal lung development, the insulin receptor (IR) plays an important role by mediating the cellular uptake of glucose, which is a major substrate for the biosynthesis of surfactant phospholipids. In fetal rat lung, IR gene expression has been revealed on type II pneumocytes. Recent studies have demonstrated that downregulation of pulmonary IR in late gestation causes pulmonary hypoplasia by inhibition of surfactant synthesis. We hypothesized that pulmonary gene expression of IR is downregulated during the late stages of lung development in the nitrofen-induced CDH model. Timed pregnant Sprague-Dawley rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Cesarean deliveries were performed on D15, D18, and D21. Fetal lungs were divided into 3 groups: control, nitrofen without CDH (CDH[-]), and nitrofen with CDH (CDH[+]) (n = 8 at each time-point, respectively). Relative messenger RNA (mRNA) levels of IR were determined by using real time reverse transcription polymerase chain reaction. Immunohistochemistry was performed to evaluate protein expression of IR. Relative expression levels of IR mRNA on D21 were significantly decreased in CDH(-) and CDH(+) group (3.99 +/- 1.50 and 5.14 +/- 0.99, respectively) compared to control (7.45 +/- 3.95; P < .05). Immunohistochemistry showed decreased IR expression in the proximal alveolar epithelium on D21 in hypoplastic lungs compared to control lungs. Downregulation of IR gene and protein expression in hypoplastic lung during late stages of lung development may interfere with normal surfactant synthesis, causing pulmonary hypoplasia in the nitrofen-induced CDH model. Copyright (c) 2010 Elsevier Inc. All rights reserved.

STUDIES IN FETAL BEHAVIOR: REVISITED, RENEWED, AND REIMAGINED.

PubMed

DiPietro, Janet A; Costigan, Kathleen A; Voegtline, Kristin M

2015-09-01

Among the earliest volumes of this monograph series was a report by Lester Sontag and colleagues, of the esteemed Fels Institute, on the heart rate of the human fetus as an expression of the developing nervous system. Here, some 75 years later, we commemorate this work and provide historical and contemporary context on knowledge regarding fetal development, as well as results from our own research. These are based on synchronized monitoring of maternal and fetal parameters assessed between 24 and 36 weeks gestation on 740 maternal-fetal pairs compiled from eight separate longitudinal studies, which commenced in the early 1990s. Data include maternal heart rate, respiratory sinus arrhythmia, and electrodrmal activity and fetal heartrate, motor activity, and their integration. Hierarchical linear modeling of developmental trajectories reveals that the fetus develops in predictable ways consistent with advancing parasympathetic regulation. Findings also include:within-fetus stability (i.e., preservation of rank ordering over time) for heart rate, motor, and coupling measures; a transitional period of decelerating development near 30 weeks gestation; sex differences in fetal heart rate measures but not in most fetal motor activity measures; modest correspondence in fetal neurodevelopment among siblings as compared to unrelated fetuses; and deviations from normative fetal development in fetuses affected by intrauterine growth restriction and other conditions. Maternal parameters also change during this period of gestation and there is evidence that fetal sex and individual variation in fetal neurobehavior influence maternal physio-logical processes and the local intrauterine context. Results are discussed within the framework of neuromaturation, the emergence of individual differences, and the bidirectional nature of the maternal-fetal relationship.We pose a number of open questions for future research. Although the human fetus remains just out of reach, new

Studies in Fetal Behavior: Revisited, Renewed, and Reimagined

PubMed Central

DiPietro, Janet A.; Costigan, Kathleen A.; Voegtline, Kristin M.

2016-01-01

Among the earliest volumes of this Monograph series was a report by Lester Sontag and colleagues, of the esteemed Fels Institute, on the heart rate of the human fetus as an expression of the developing nervous system. Here, some 75 years later, we commemorate this work and provide historical and contemporary context on knowledge regarding fetal development, as well as results from our own research. These are based on synchronized monitoring of maternal and fetal parameters assessed between 24 and 36 weeks gestation on 740 maternal-fetal pairs compiled from eight separate longitudinal studies, which commenced in the early 1990s. Data include maternal heart rate, respiratory sinus arrhythmia, and electrodermal activity and fetal heart rate, motor activity, and their integration. Hierarchical linear modeling of developmental trajectories reveals that the fetus develops in predictable ways consistent with advancing parasympathetic regulation. Findings also include: within-fetus stability (i.e., preservation of rank ordering over time) for heart rate, motor, and coupling measures; a transitional period of decelerating development near 30 weeks gestation; sex differences in fetal heart rate measures but not in most fetal motor activity measures; modest correspondence in fetal neurodevelopment among siblings as compared to unrelated fetuses; and deviations from normative fetal development in fetuses affected by intrauterine growth restriction and other conditions. Maternal parameters also change during this period of gestation and there is evidence that fetal sex and individual variation in fetal neurobehavior influence maternal physiological processes and the local intrauterine context. Results are discussed within the framework of neuromaturation, the emergence of individual differences, and the bidirectional nature of the maternal-fetal relationship. We pose a number of open questions for future research. Although the human fetus remains just out of reach, new

Intrauterine Intervention for the Treatment of Fetal Growth Restriction.

PubMed

Spiroski, A-M; Oliver, M H; Harding, J E; Bloomfield, F H

2016-01-01

Fetal growth restriction (FGR) is associated with an increased incidence of fetal and neonatal death, and of neonatal morbidity. Babies born following FGR also are at risk of a range of postnatal complications, which may contribute to an increased incidence of disease later in life. There currently are no effective clinical interventions which improve perinatal survival, intrauterine growth and later outcomes of the FGR baby. Postnatal interventions aimed at promoting or accelerating growth in FGR babies to improve outcome, particularly neurodevelopmental outcomes, may further increase the risk of metabolic dysregulation and, therefore, the risk of developing chronic disease in adulthood. An intrauterine intervention to improve nutrition and growth in the FGR fetus may have the potential to decrease mortality and improve long-term outcomes by delaying preterm delivery and mitigating the need for and risks of accelerated postnatal growth.

Chorioamnionitis and chronic lung disease of prematurity: a path analysis of causality.

PubMed

Dessardo, Nada Sindičić; Mustać, Elvira; Dessardo, Sandro; Banac, Srđan; Peter, Branimir; Finderle, Aleksandar; Marić, Marinko; Haller, Herman

2012-02-01

Current evidence suggests that additional pathogenetic factors could play a role in the development of chronic lung disease of prematurity, other than mechanical ventilation and free radical injury. The introduction of the concept of "fetal inflammatory response syndrome" offers a new perspective on the pathogenesis of chronic lung disease of prematurity. New statistical approaches could be useful tools in evaluating causal relationships in the development of chronic morbidity in preterm infants. The aim of this study was to test a new statistical framework incorporating path analysis to evaluate causality between exposure to chorioamnionitis and fetal inflammatory response syndrome and the development of chronic lung disease of prematurity. We designed a prospective cohort study that included consecutively born premature infants less than 32 weeks of gestation whose placentas were collected for histological analysis. Histological chorioamnionitis, clinical data, and neonatal outcomes were related to chronic lung disease. Along with standard statistical methods, a path analysis was performed to test the relationship between histological chorioamnionitis, gestational age, mechanical ventilation, and development of chronic lung disease of prematurity. Among the newborns enrolled in the study, 69/189 (36%) had histological chorioamnionitis. Of those with histological chorioamnionitis, 28/69 (37%) were classified as having fetal inflammatory response syndrome, according to the presence of severe chorioamnionitis and funisitis. Histological chorioamnionitis was associated with a lower birth weight, shorter gestation, higher frequency of patent ductus arteriosus, greater use of surfactant, and higher frequency of chronic lung disease of prematurity. Severe chorioamnionitis and funisitis were significantly associated with lower birth weight, lower gestational age, lower Apgar score at 5 minutes, more frequent use of mechanical ventilatory support and surfactant, as well

Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF

PubMed Central

De Kleer, Ismé; Henri, Sandrine; Post, Sijranke; Vanhoutte, Leen; De Prijck, Sofie; Deswarte, Kim; Malissen, Bernard; Hammad, Hamida; Lambrecht, Bart N.

2013-01-01

Tissue-resident macrophages can develop from circulating adult monocytes or from primitive yolk sac–derived macrophages. The precise ontogeny of alveolar macrophages (AMFs) is unknown. By performing BrdU labeling and parabiosis experiments in adult mice, we found that circulating monocytes contributed minimally to the steady-state AMF pool. Mature AMFs were undetectable before birth and only fully colonized the alveolar space by 3 d after birth. Before birth, F4/80hiCD11blo primitive macrophages and Ly6ChiCD11bhi fetal monocytes sequentially colonized the developing lung around E12.5 and E16.5, respectively. The first signs of AMF differentiation appeared around the saccular stage of lung development (E18.5). Adoptive transfer identified fetal monocytes, and not primitive macrophages, as the main precursors of AMFs. Fetal monocytes transferred to the lung of neonatal mice acquired an AMF phenotype via defined developmental stages over the course of one week, and persisted for at least three months. Early AMF commitment from fetal monocytes was absent in GM-CSF–deficient mice, whereas short-term perinatal intrapulmonary GM-CSF therapy rescued AMF development for weeks, although the resulting AMFs displayed an immature phenotype. This demonstrates that tissue-resident macrophages can also develop from fetal monocytes that adopt a stable phenotype shortly after birth in response to instructive cytokines, and then self-maintain throughout life. PMID:24043763

A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids

PubMed Central

Dye, Briana R; Dedhia, Priya H; Miller, Alyssa J; Nagy, Melinda S; White, Eric S; Shea, Lonnie D; Spence, Jason R

2016-01-01

Human pluripotent stem cell (hPSC) derived tissues often remain developmentally immature in vitro, and become more adult-like in their structure, cellular diversity and function following transplantation into immunocompromised mice. Previously we have demonstrated that hPSC-derived human lung organoids (HLOs) resembled human fetal lung tissue in vitro (Dye et al., 2015). Here we show that HLOs required a bioartificial microporous poly(lactide-co-glycolide) (PLG) scaffold niche for successful engraftment, long-term survival, and maturation of lung epithelium in vivo. Analysis of scaffold-grown transplanted tissue showed airway-like tissue with enhanced epithelial structure and organization compared to HLOs grown in vitro. By further comparing in vitro and in vivo grown HLOs with fetal and adult human lung tissue, we found that in vivo transplanted HLOs had improved cellular differentiation of secretory lineages that is reflective of differences between fetal and adult tissue, resulting in airway-like structures that were remarkably similar to the native adult human lung. DOI: http://dx.doi.org/10.7554/eLife.19732.001 PMID:27677847

Human Fetal Membranes at Term: Dead Tissue or Signalers of Parturition?

PubMed Central

MENON, Ramkumar

2017-01-01

Various endocrine, immune, and mechanical factors produced by feto-maternal compartments at term increase intrauterine inflammatory loads to induce labor. The role of fetal (placental) membranes (amniochorion) as providers of parturition signals has not been well investigated. Fetal membranes line the intrauterine cavity and grow with and protect the fetus. Fetal membranes exist as an entity between the mother and fetus and perform unique functions during pregnancy. Membranes undergo a telomere-dependent p38 MAPK-induced senescence and demonstrate a decline in functional and mechanical abilities at term, showing signs of aging. Fetal membrane senescence is also allied with completion of fetal maturation at term as the fetus readies for delivery, which may also indicate the end of independent life and longevity of fetal membranes as their functional role concludes. Fetal membrane senescence is accelerated at term because of oxidative stress and increased stretching. Senescent fetal membranes cells produce senescence-associated secretory phenotype (SASP-inflammation) and also release proinflammatory damage-associated molecular patterns (DAMPs), namely HMGB1 and cell-free fetal telomere fragments. In a feedback loop, SASP and DAMPs increase senescence and enhance the inflammatory load to promote labor. Membranes increase the inflammatory load to disrupt homeostatic balance to transition quiescent uterine tissues toward a labor phenotype. Therefore, along with other well-described labor-promoting signals, senescent fetal membranes may also contribute to human term parturition. PMID:27452431

Fetal Cardiac Responding: A Correlate of Birth Weight and Neonatal Behavior.

ERIC Educational Resources Information Center

Emory, Eugene K.; Noonan, John R.

1984-01-01

Explores whether an empirical classification of healthy fetuses as fetal heart rate accelerators or decelerators would predict birth weight and neonatal behavior scored with the Brazelton Neonatal Behavior Assessment Scale. (Author/RH)

Steroid receptor coactivators 1 and 2 mediate fetal-to-maternal signaling that initiates parturition

PubMed Central

Gao, Lu; Rabbitt, Elizabeth H.; Condon, Jennifer C.; Renthal, Nora E.; Johnston, John M.; Mitsche, Matthew A.; Chambon, Pierre; Xu, Jianming; O’Malley, Bert W.; Mendelson, Carole R.

2015-01-01

The precise mechanisms that lead to parturition are incompletely defined. Surfactant protein-A (SP-A), which is secreted by fetal lungs into amniotic fluid (AF) near term, likely provides a signal for parturition; however, SP-A–deficient mice have only a relatively modest delay (~12 hours) in parturition, suggesting additional factors. Here, we evaluated the contribution of steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2), which upregulate SP-A transcription, to the parturition process. As mice lacking both SRC-1 and SRC-2 die at birth due to respiratory distress, we crossed double-heterozygous males and females. Parturition was severely delayed (~38 hours) in heterozygous dams harboring SRC-1/-2–deficient embryos. These mothers exhibited decreased myometrial NF-κB activation, PGF2α, and expression of contraction-associated genes; impaired luteolysis; and elevated circulating progesterone. These manifestations also occurred in WT females bearing SRC-1/-2 double-deficient embryos, indicating that a fetal-specific defect delayed labor. SP-A, as well as the enzyme lysophosphatidylcholine acyltransferase-1 (LPCAT1), required for synthesis of surfactant dipalmitoylphosphatidylcholine, and the proinflammatory glycerophospholipid platelet-activating factor (PAF) were markedly reduced in SRC-1/-2–deficient fetal lungs near term. Injection of PAF or SP-A into AF at 17.5 days post coitum enhanced uterine NF-κB activation and contractile gene expression, promoted luteolysis, and rescued delayed parturition in SRC-1/-2–deficient embryo-bearing dams. These findings reveal that fetal lungs produce signals to initiate labor when mature and that SRC-1/-2–dependent production of SP-A and PAF is crucial for this process. PMID:26098214

Steroid receptor coactivators 1 and 2 mediate fetal-to-maternal signaling that initiates parturition.

PubMed

Gao, Lu; Rabbitt, Elizabeth H; Condon, Jennifer C; Renthal, Nora E; Johnston, John M; Mitsche, Matthew A; Chambon, Pierre; Xu, Jianming; O'Malley, Bert W; Mendelson, Carole R

2015-07-01

The precise mechanisms that lead to parturition are incompletely defined. Surfactant protein-A (SP-A), which is secreted by fetal lungs into amniotic fluid (AF) near term, likely provides a signal for parturition; however, SP-A-deficient mice have only a relatively modest delay (~12 hours) in parturition, suggesting additional factors. Here, we evaluated the contribution of steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2), which upregulate SP-A transcription, to the parturition process. As mice lacking both SRC-1 and SRC-2 die at birth due to respiratory distress, we crossed double-heterozygous males and females. Parturition was severely delayed (~38 hours) in heterozygous dams harboring SRC-1/-2-deficient embryos. These mothers exhibited decreased myometrial NF-κB activation, PGF2α, and expression of contraction-associated genes; impaired luteolysis; and elevated circulating progesterone. These manifestations also occurred in WT females bearing SRC-1/-2 double-deficient embryos, indicating that a fetal-specific defect delayed labor. SP-A, as well as the enzyme lysophosphatidylcholine acyltransferase-1 (LPCAT1), required for synthesis of surfactant dipalmitoylphosphatidylcholine, and the proinflammatory glycerophospholipid platelet-activating factor (PAF) were markedly reduced in SRC-1/-2-deficient fetal lungs near term. Injection of PAF or SP-A into AF at 17.5 days post coitum enhanced uterine NF-κB activation and contractile gene expression, promoted luteolysis, and rescued delayed parturition in SRC-1/-2-deficient embryo-bearing dams. These findings reveal that fetal lungs produce signals to initiate labor when mature and that SRC-1/-2-dependent production of SP-A and PAF is crucial for this process.

The effects of different concentrations of cocoa in the chocolate intaken by the mother on fetal heart rate.

PubMed

Buscicchio, Giorgia; Lorenzi, Sara; Tranquilli, Andrea Luigi

2013-10-01

To analyze the effects of different concentrations (30% and 80%) of cocoa on fetal heart rate (FHR). One hundred pregnant women with uncomplicated gestation, matched for age and parity, underwent computerized FHR recording before and after the consumption of 30 g of 30% and 80% cocoa chocolate. After 1 week, those who had received 30% were shifted to 80% and vice versa to have a crossover. Computerized cardiotocography parameters (contractions, fetal movements, baseline FHR, accelerations greater than 15 bpm for 15 s, number of decelerations, minutes of high variability, short term variability in ms) were recorded and expressed as mean and SD. The differences were tested for statistical significance using the paired t test, with the significance at p < 0.05. The percent change after chocolate intake for accelerations and short-term FHR variation was calculated. The number of fetal movements, accelerations, the duration of episodes of high variation and the short-term FHR variation were significantly higher (p < 0.0001) after 80% cocoa intake. After 30% cocoa chocolate intake, only the number of accelerations was significantly increased. The percent change of the number of accelerations and the short-term FHR variation were significantly higher after 80% cocoa chocolate maternal intake. Maternal intake of dark chocolate has a stimulating action on fetal reactivity. The effect is more marked with high concentrations (80%) of cocoa. This finding is likely due to the pharmacological action of theobromine, a methilxanthine present in cocoa.

Inhaled carbon monoxide does not cause pulmonary vasodilation in the late-gestation fetal lamb.

PubMed

Grover, T R; Rairigh, R L; Zenge, J P; Abman, S H; Kinsella, J P

2000-04-01

As observed with nitric oxide (NO), carbon monoxide (CO) binds and may activate soluble guanylate cyclase and increase cGMP levels in smooth muscle cells in vitro. Because inhaled NO (I(NO)) causes potent and sustained pulmonary vasodilation, we hypothesized that inhaled CO (I(CO)) may have similar effects on the perinatal lung. To determine whether I(CO) can lower pulmonary vascular resistance (PVR) during the perinatal period, we studied the effects of I(CO) on late-gestation fetal lambs. Catheters were placed in the main pulmonary artery, left pulmonary artery (LPA), aorta, and left atrium to measure pressure. An ultrasonic flow transducer was placed on the LPA to measure blood flow to the left lung. After baseline measurements, fetal lambs were mechanically ventilated with a hypoxic gas mixture (inspired O(2) fraction < 0.10) to maintain a constant fetal arterial PO(2). After 60 min (baseline), the lambs were treated with I(CO) [5-2,500 parts/million (ppm)]. Comparisons were made with I(NO) (5 and 20 ppm) and combined I(NO) (5 ppm) and I(CO) (100 and 2,500 ppm). We found that I(CO) did not alter left lung blood flow or PVR at any of the study doses. In contrast, low-dose I(NO) decreased PVR by 47% (P < 0.005). The combination of I(NO) and I(CO) did not enhance the vasodilator response to I(NO). To determine whether endogenous CO contributes to vascular tone in the fetal lung, zinc protoporphyrin IX, an inhibitor of heme oxygenase, was infused into the LPA in three lambs. Zinc protoporphyrin IX had no effect on baseline PVR, aortic pressure, or the pressure gradient across the ductus arteriosus. We conclude that I(CO) does not cause vasodilation in the near-term ovine transitional circulation, and endogenous CO does not contribute significantly to baseline pulmonary vascular tone or ductus arteriosus tone in the late-gestation ovine fetus.

Prognostic usefulness of derived T2-weighted fetal magnetic resonance imaging measurements in congenital diaphragmatic hernia.

PubMed

Sebastià, C; Gomez, O; Salvador, R; Buñesch, L; Garcia, R; Nicolau, C

2015-01-01

To determine the usefulness of various parameters based on T2-weighted fetal magnetic resonance (MR) imaging measurements of the uninvolved lung for the neonatal prognosis of congenital diaphragmatic hernia (CDH). We used ultrasonography and MR imaging to study 28 fetuses with CDH. We retrospectively analyzed a) on fetal ultrasonography, the observed-to-expected lung to head ratio (O/E LHR) and the position of the liver, and b) on fetal MR imaging, the lung-liver signal ratio (LLSR) and the lungcerebrospinal fluid ratio (L/CSF SR). To determine the prognostic value of these parameters, we compared them with the following postnatal parameters: survival, pulmonary hypertension, need for oxygen supplementation, and need for extracorporeal membrane oxygenation. We found significant differences between O/E LHR and the need for postnatal extracorporeal membrane oxygenation (P=.033) and postnatal survival (P=.01). We also found significant differences in LLSR between fetuses that survived more than 45 days and those that died within 45 days (1.91 vs. 2.56; P=.039). In fetuses with CDH, the LLSR correlates with postnatal survival and can potentially be used as a prognostic parameter in CDH. Copyright © 2013 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

GMP-grade human fetal liver-derived mesenchymal stem cells for clinical transplantation.

PubMed

Larijani, Bagher; Aghayan, Hamid-Reza; Goodarzi, Parisa; Arjmand, Babak

2015-01-01

Stem cell therapy seems a promising avenue in regenerative medicine. Within various stem cells, mesenchymal stem cells have progressively used for cellular therapy. Because of the age-related decreasing in the frequency and differentiating capacity of adult MSCs, fetal tissues such as fetal liver, lung, pancreas, spleen, etc. have been introduced as an alternative source of MSCs for cellular therapy. On the other hand, using stem cells as advanced therapy medicinal products, must be performed in compliance with cGMP as a quality assurance system to ensure the safety, quality, and identity of cell products during translation from the basic stem cell sciences into clinical cell transplantation. In this chapter the authors have demonstrated the manufacturing of GMP-grade human fetal liver-derived mesenchymal stem cells.

Maternal Therapy with Ad.VEGF-A165 Increases Fetal Weight at Term in a Guinea-Pig Model of Fetal Growth Restriction.

PubMed

Swanson, Anna M; Rossi, Carlo A; Ofir, Keren; Mehta, Vedanta; Boyd, Michael; Barker, Hannah; Ledwozyw, Agata; Vaughan, Owen; Martin, John; Zachary, Ian; Sebire, Neil; Peebles, Donald M; David, Anna L

2016-12-01

In a model of growth-restricted sheep pregnancy, it was previously demonstrated that transient uterine artery VEGF overexpression can improve fetal growth. This approach was tested in guinea-pig pregnancies, where placental physiology is more similar to humans. Fetal growth restriction (FGR) was attained through peri-conceptual nutrient restriction in virgin guinea pigs. Ad.VEGF-A 165 or Ad.LacZ (1 × 10 10 vp) was applied at mid-gestation via laparotomy, delivered externally to the uterine circulation with thermosensitive gel. At short-term (3-8 days post surgery) or at term gestation, pups were weighed, and tissues were sampled for vector spread analysis, VEGF expression, and its downstream effects. Fetal weight at term was increased (88.01 ± 13.36 g; n = 26) in Ad.VEGF-A 165 -treated animals compared with Ad.LacZ-treated animals (85.52 ± 13.00 g; n = 19; p = 0.028). The brain, liver, and lung weight and crown rump length were significantly larger in short-term analyses, as well as VEGF expression in transduced tissues. At term, molecular analyses confirmed the presence of VEGF transgene in target tissues but not in fetal samples. Tissue histology analysis and blood biochemistry/hematological examination were comparable with controls. Uterine artery relaxation in Ad.VEGF-A 165 -treated dams was higher compared with Ad.LacZ-treated dams. Maternal uterine artery Ad.VEGF-A 165 increases fetal growth velocity and term fetal weight in growth-restricted guinea-pig pregnancy.

Fetal and infant growth patterns associated with total and abdominal fat distribution in school-age children.

PubMed

Gishti, Olta; Gaillard, Romy; Manniesing, Rashindra; Abrahamse-Berkeveld, Marieke; van der Beek, Eline M; Heppe, Denise H M; Steegers, Eric A P; Hofman, Albert; Duijts, Liesbeth; Durmuş, Büşra; Jaddoe, Vincent W V

2014-07-01

Higher infant growth rates are associated with an increased risk of obesity in later life. We examined the associations of longitudinally measured fetal and infant growth patterns with total and abdominal fat distribution in childhood. We performed a population-based prospective cohort study among 6464 children. We measured growth characteristics in the second and third trimesters of pregnancy, at birth, and at 6, 12, and 24 months. Body mass index, fat mass index (body fat mass/height(2)), lean mass index (body lean mass/height(2)), android/gynoid fat ratio measured by dual-energy x-ray absorptiometry, and sc and preperitoneal abdominal fat measured by ultrasound at the median age of 6.0 years (90% range, 5.7-7.4). We observed that weight gain in the second and third trimesters of fetal life and in early, mid, and late infancy were independently and positively associated with childhood body mass index (P < .05). Only infant weight gain was associated with higher fat mass index, android/gynoid fat ratio, and abdominal fat in childhood (P < .05). Children with both fetal and infant growth acceleration had the highest childhood body mass index, fat mass index, and sc abdominal fat, whereas children with fetal growth deceleration and infant growth acceleration had the highest value for android/gynoid fat ratio and the lowest value for lean mass index (P < .05). Growth in both fetal life and infancy affects childhood body mass index, whereas only infant growth directly affects measured total body and abdominal fat. Fetal growth deceleration followed by infant growth acceleration may lead to an adverse body fat distribution in childhood.

[Intrauterine fetal therapy of NIHF with massive pleural effusion - a case study].

PubMed

Sobczuk, Kamila; Wojtera, Justyna; Celewicz, Zbigniew; Szaflik, Krzysztof

2013-05-01

Hydrops fetalis (fetal hydrops) is a serious fetal condition defined as abnormal accumulation of fluid in two or more extravascular compartments, including ascites, pleural effusion, pericardial effusion, and skin edema. Edema is classified as immune or non-immune. Today more than 90% of fetal edema has non-immune cause. This paper presents a case of a pregnant woman who was admitted to the Obstetrics and Gynecology Department because of fetal hydrops with massive pleural effusion and polyhydramnios at 34 weeks gestation. The intrauterine therapy consisted of two treatments. During the first surgery amnioreduction, evacuation of fluid from the pleural cavity of the fetus, and shunts to both pleural cavities were performed. During the second surgery amnioreduction, cordocentesis with albumin administration and pleural shunt were performed. Intrauterine therapy led to a reduction of swelling of the fetus from 7mm up to 1-2 mm and the total evacuation of fluid from the pleural cavity and the fetal lung expansion. We also present the condition of the neonate after birth and after 12 months of life.

Human fetal membranes at term: Dead tissue or signalers of parturition?

PubMed

Menon, Ramkumar

2016-08-01

Various endocrine, immune, and mechanical factors produced by feto-maternal compartments at term increase intrauterine inflammatory loads to induce labor. The role of fetal (placental) membranes (amniochorion) as providers of parturition signals has not been well investigated. Fetal membranes line the intrauterine cavity and grow with and protect the fetus. Fetal membranes exist as an entity between the mother and fetus and perform unique functions during pregnancy. Membranes undergo a telomere-dependent p38 MAPK-induced senescence and demonstrate a decline in functional and mechanical abilities at term, showing signs of aging. Fetal membrane senescence is also allied with completion of fetal maturation at term as the fetus readies for delivery, which may also indicate the end of independent life and longevity of fetal membranes as their functional role concludes. Fetal membrane senescence is accelerated at term because of oxidative stress and increased stretching. Senescent fetal membranes cells produce senescence-associated secretory phenotype (SASP-inflammation) and also release proinflammatory damage-associated molecular patterns (DAMPs), namely HMGB1 and cell-free fetal telomere fragments. In a feedback loop, SASP and DAMPs increase senescence and enhance the inflammatory load to promote labor. Membranes increase the inflammatory load to disrupt homeostatic balance to transition quiescent uterine tissues toward a labor phenotype. Therefore, along with other well-described labor-promoting signals, senescent fetal membranes may also contribute to human term parturition. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of adrenaline and of spontaneous labour on the secretion and absorption of lung liquid in the fetal lamb.

PubMed Central

Brown, M J; Olver, R E; Ramsden, C A; Strang, L B; Walters, D V

1983-01-01

In the chronically catheterized fetal lamb, intravenous infusion of adrenaline at 0.5 microgram/min produced slowing of the secretion of lung liquid or its absorption, an effect which increased exponentially with advancing gestation. Between 120 and 130 days, the characteristic response was slowing of secretion, whereas after 130 days it was absorption. Stimulus-response curves, relating secretion or absorption rate to plasma adrenaline concentration, were obtained by infusing adrenaline into the fetus intravenously at rates between 0.1 and 1.0 microgram/min (0.55-5.5 nmol/min). These curves allowed estimation of the minimum concentration of adrenaline required to inhibit secretion [( Ai]) and this was found to decrease from 0.43 ng/ml. (2.35 nM) at 132-4 days' gestation to 0.029 ng/ml. (0.16 nM) at gestations above 140 days. During spontaneous labour there was a slowing of lung liquid secretion in the early stages followed by absorption during the last 50-150 min. The mean concentration of adrenaline in plasma increased from 0.087 ng/ml. (0.48 nM) in early labour to 6.86 ng/ml. (37.5 nM) in the last 50 min and to 7.17 ng/ml. (39.2 nM) in the early post-natal period. Mean noradrenaline levels at the same times were 1.71 ng/ml. (10.1 nM), 12.14 ng/ml. (71.8 nM) and 9.10 ng/ml. (53.9 nM). The relationship between the plasma adrenaline concentration and the rate of absorption during labour was similar to that found when adrenaline was infused at various rates into the non-labouring fetus of comparable gestational age. The upper airway of the fetus was shown to be capable of acting as a one-way valve allowing outflow but not inflow of liquid. Thus withdrawal of liquid at 5-20 ml./hr from the fetal trachea below the larynx caused closure of the upper airway and this result was obtained both when the recurrent laryngeal nerves were intact and when they were divided. PMID:6655575

First and second trimester screening for fetal structural anomalies.

PubMed

Edwards, Lindsay; Hui, Lisa

2018-04-01

Fetal structural anomalies are found in up to 3% of all pregnancies and ultrasound-based screening has been an integral part of routine prenatal care for decades. The prenatal detection of fetal anomalies allows for optimal perinatal management, providing expectant parents with opportunities for additional imaging, genetic testing, and the provision of information regarding prognosis and management options. Approximately one-half of all major structural anomalies can now be detected in the first trimester, including acrania/anencephaly, abdominal wall defects, holoprosencephaly and cystic hygromata. Due to the ongoing development of some organ systems however, some anomalies will not be evident until later in the pregnancy. To this extent, the second trimester anatomy is recommended by professional societies as the standard investigation for the detection of fetal structural anomalies. The reported detection rates of structural anomalies vary according to the organ system being examined, and are also dependent upon factors such as the equipment settings and sonographer experience. Technological advances over the past two decades continue to support the role of ultrasound as the primary imaging modality in pregnancy, and the safety of ultrasound for the developing fetus is well established. With increasing capabilities and experience, detailed examination of the central nervous system and cardiovascular system is possible, with dedicated examinations such as the fetal neurosonogram and the fetal echocardiogram now widely performed in tertiary centers. Magnetic resonance imaging (MRI) is well recognized for its role in the assessment of fetal brain anomalies; other potential indications for fetal MRI include lung volume measurement (in cases of congenital diaphragmatic hernia), and pre-surgical planning prior to fetal spina bifida repair. When a major structural abnormality is detected prenatally, genetic testing with chromosomal microarray is recommended over

Radiotherapy for glioma during pregnancy: fetal dose estimates, risk assessment and clinical management.

PubMed

Haba, Y; Twyman, N; Thomas, S J; Overton, C; Dendy, P; Burnet, N G

2004-05-01

Cancer in pregnancy is relatively uncommon, but constitutes a major problem. We report the measurement of scatter dose to the fetus and the estimated fetal risk from that exposure in an illustrative case of a patient, 20 weeks pregnant, with a grade 3 anaplastic astrocytoma. A clinical decision was made to withhold radiotherapy, if possible, until after delivery. Sequential magnetic resonance imaging (MRI) showed no progression during the pregnancy. In the event, she was managed conservatively until the successful completion of her pregnancy. In case radiotherapy was required, an estimation of the fetal risk was made. Phantom measurements were undertaken to assess the likely fetal dose. Film badges were used to estimate the scattered radiation energy. Measurements were made on a Varian 600C at 6 MV and Asea Brown Boveri (ABB) accelerator at 8 and 16 MV. Doses were measured at 30, 45 and 60 cm from the isocentre; the fetus was assumed to lie at about 60 cm and not closer than 45 cm from the isocentre. Estimated doses to the position of the fetus were lowest with the 6 MV Varian accelerator. Using this machine without additional abdominal shielding, the estimated dose on the surface at 45 cm from the tumour volume was 2.2 cGy for a tumour dose of 54 Gy; using the ABB accelerator, the dose varied between 49-59 cGy. The energy of scattered radiation was in the range 208-688 keV, so that additional shielding would be practical to further reduce the fetal dose. The risk of cancer up to the age of 15 years attributable to radiation is 1 in 1700 per cGy, of which half will be fatal (i.e. 1 in 3300 per cGy). A dose of 2.2 cGy adds a risk of fatal cancer by the age 15 years of only 1 in 1500. Because the addition of shielding might halve the fetal dose, this risk should be reduced to 1 in 3000. For comparison, the overall UK risk of cancer up to the age 15 years is 1 in 650. In conclusion, careful choice of linear accelerator for the treatment of a pregnant woman and the use

Preconditioning allows engraftment of mouse and human embryonic lung cells, enabling lung repair in mice.

PubMed

Rosen, Chava; Shezen, Elias; Aronovich, Anna; Klionsky, Yael Zlotnikov; Yaakov, Yasmin; Assayag, Miri; Biton, Inbal Eti; Tal, Orna; Shakhar, Guy; Ben-Hur, Herzel; Shneider, David; Vaknin, Zvi; Sadan, Oscar; Evron, Shmuel; Freud, Enrique; Shoseyov, David; Wilschanski, Michael; Berkman, Neville; Fibbe, Willem E; Hagin, David; Hillel-Karniel, Carmit; Krentsis, Irit Milman; Bachar-Lustig, Esther; Reisner, Yair

2015-08-01

Repair of injured lungs represents a longstanding therapeutic challenge. We show that human and mouse embryonic lung tissue from the canalicular stage of development (20-22 weeks of gestation for humans, and embryonic day 15-16 (E15-E16) for mouse) are enriched with progenitors residing in distinct niches. On the basis of the marked analogy to progenitor niches in bone marrow (BM), we attempted strategies similar to BM transplantation, employing sublethal radiation to vacate lung progenitor niches and to reduce stem cell competition. Intravenous infusion of a single cell suspension of canalicular lung tissue from GFP-marked mice or human fetal donors into naphthalene-injured and irradiated syngeneic or SCID mice, respectively, induced marked long-term lung chimerism. Donor type structures or 'patches' contained epithelial, mesenchymal and endothelial cells. Transplantation of differentially labeled E16 mouse lung cells indicated that these patches were probably of clonal origin from the donor. Recipients of the single cell suspension transplant exhibited marked improvement in lung compliance and tissue damping reflecting the energy dissipation in the lung tissues. Our study provides proof of concept for lung reconstitution by canalicular-stage human lung cells after preconditioning of the pulmonary niche.

HOX genes in human lung: altered expression in primary pulmonary hypertension and emphysema.

PubMed

Golpon, H A; Geraci, M W; Moore, M D; Miller, H L; Miller, G J; Tuder, R M; Voelkel, N F

2001-03-01

HOX genes belong to the large family of homeodomain genes that function as transcription factors. Animal studies indicate that they play an essential role in lung development. We investigated the expression pattern of HOX genes in human lung tissue by using microarray and degenerate reverse transcriptase-polymerase chain reaction survey techniques. HOX genes predominantly from the 3' end of clusters A and B were expressed in normal human adult lung and among them HOXA5 was the most abundant, followed by HOXB2 and HOXB6. In fetal (12 weeks old) and diseased lung specimens (emphysema, primary pulmonary hypertension) additional HOX genes from clusters C and D were expressed. Using in situ hybridization, transcripts for HOXA5 were predominantly found in alveolar septal and epithelial cells, both in normal and diseased lungs. A 2.5-fold increase in HOXA5 mRNA expression was demonstrated by quantitative reverse transcriptase-polymerase chain reaction in primary pulmonary hypertension lung specimens when compared to normal lung tissue. In conclusion, we demonstrate that HOX genes are selectively expressed in the human lung. Differences in the pattern of HOX gene expression exist among fetal, adult, and diseased lung specimens. The altered pattern of HOX gene expression may contribute to the development of pulmonary diseases.

A Comparative Study on Fetal Heart Rates Estimated from Fetal Phonography and Cardiotocography

PubMed Central

Ibrahim, Emad A.; Al Awar, Shamsa; Balayah, Zuhur H.; Hadjileontiadis, Leontios J.; Khandoker, Ahsan H.

2017-01-01

The aim of this study is to investigate that fetal heart rates (fHR) extracted from fetal phonocardiography (fPCG) could convey similar information of fHR from cardiotocography (CTG). Four-channel fPCG sensors made of low cost (<$1) ceramic piezo vibration sensor within 3D-printed casings were used to collect abdominal phonogram signals from 20 pregnant mothers (>34 weeks of gestation). A novel multi-lag covariance matrix-based eigenvalue decomposition technique was used to separate maternal breathing, fetal heart sounds (fHS) and maternal heart sounds (mHS) from abdominal phonogram signals. Prior to the fHR estimation, the fPCG signals were denoised using a multi-resolution wavelet-based filter. The proposed source separation technique was first tested in separating sources from synthetically mixed signals and then on raw abdominal phonogram signals. fHR signals extracted from fPCG signals were validated using simultaneous recorded CTG-based fHR recordings.The experimental results have shown that the fHR derived from the acquired fPCG can be used to detect periods of acceleration and deceleration, which are critical indication of the fetus' well-being. Moreover, a comparative analysis demonstrated that fHRs from CTG and fPCG signals were in good agreement (Bland Altman plot has mean = −0.21 BPM and ±2 SD = ±3) with statistical significance (p < 0.001 and Spearman correlation coefficient ρ = 0.95). The study findings show that fHR estimated from fPCG could be a reliable substitute for fHR from the CTG, opening up the possibility of a low cost monitoring tool for fetal well-being. PMID:29089896

Prenatal retinoic acid treatment upregulates late gestation lung protein 1 in the nitrofen-induced hypoplastic lung in late gestation.

PubMed

Ruttenstock, Elke Maria; Doi, Takashi; Dingemann, Jens; Puri, Prem

2011-02-01

Pulmonary hypoplasia (PH), the leading cause of mortality in congenital diaphragmatic hernia (CDH), is associated with arrested alveolarization. Late gestation lung protein 1 (LGL1) plays a crucial role in the regulation of alveolarization. Inhibition of LGL1 impairs alveolar maturation in fetal rat lungs. LGL1 heterozygotus knockout mice display delayed lung maturation. It is well known that prenatal administration of retinoic acid (RA) stimulates alveologenesis in nitrofen-induced PH. In vitro studies have reported that RA is a key modulator of LGL1 during alveologenesis. We hypothesized, that pulmonary gene expression of LGL1 is downregulated in the late stage of lung development, and that prenatal administration of RA upregulates pulmonary LGL1 expression in the nitrofen CDH model. Pregnant rats were exposed to nitrofen on day 9 (D9) of gestation. RA was given intraperitoneally on D18, D19 and D20. Fetal lungs were dissected on D21 and divided into control, control + RA, CDH and CDH + RA group. Expression levels of LGL1 were determined using RT-PCR and immunohistochemistry. On D21, LGL1 relative mRNA expression levels were significantly downregulated in CDH group compared to controls. After RA treatment, gene expression levels of LGL1 were significantly upregulated in CDH + RA and control + RA compared to CDH group. Immunohistochemical studies confirmed these results. Downregulation of pulmonary LGL1 gene expression in the late stage of lung development may interfere with normal alveologenesis. Upregulation of LGL1 pulmonary gene expression after RA treatment may promote lung growth by stimulating alveologenesis in the nitrofen CDH model.

Proliferation, apoptosis and expression of matrix metalloproteinase-9 in human fetal lung.

PubMed

Kraljevic, Daniela; Vukojevic, Katarina; Karan, Dragana; Rajic, Borko; Todorovic, Jelena; Miskovic, Josip; Tomic, Vajdana; Kordic, Mario; Soljic, Violeta

2015-01-01

Expression pattern of the Ki-67, caspase-3 and matrix metalloproteinases-9 (MMP-9) factors were immunohistochemically analyzed in 48 human fetal lungs from 12 to 40 weeks of gestation. The number of Ki-67 positive cells in the epithelium of canaliculare (88cells/mm(2)) and sacculare stage (93cells/mm(2)) were significantly higher than in the epithelium of pseudoglandular stage (12cells/mm(2)) (p=0.0008 vs. p=0.003). The number of Ki-67 positive cells in the mesenchyme of canaliculare stage (132cells/mm(2)) was significantly higher than in the mesenchyme of pseudoglandular stage (37cells/mm(2)) (p=0.001). The proliferation of mesenchymal cells was higher than the epithelial cells in all developmental stages, especially in the canaliculare stage (p=0.007). Similarly, the number of caspase-3 positive cells in the epithelium of canalicular stage (13cells/mm(2)) was significantly higher than in the epithelium of pseudoglandular stage (6cells/mm(2)) (p=0.002) with peaks in the conductive epithelium of canalicular stage. The number of caspase-3 positive cells in the mesenchyme of canaliculare stage (3cells/mm(2)) was significantly higher than in the mesenchyme of saccular stage (0cells/mm(2)) (p=0.05). There were no caspase-3 positive cells in the mesenchyme of pseudoglandular stage. However, unlike the Ki-67 expression, mesenchymal cells in comparison to epithelial cells express substantially less caspase-3 in all developmental stages. Up to the saccular stage, the expression of MMP-9 in mesenchymal cells showed a linear increase with most pronounced expression in that stage. The number of MMP-9 positive cells in the mesenchyme of canaliculare (20cells/mm(2)) and sacculare (39cells/mm(2)) stage were significantly higher than in the mesenchyme of pseudoglandular stage (12cells/mm(2)) (p=0.04 vs. p=0.004). The first epithelial cells that express MMP-9 were present only at the alveolar stage. Increased proliferation and apoptosis of the mesenchymal cells of canalicular

Lung density change after SABR: A comparative study between tri-Co-60 magnetic resonance-guided system and linear accelerator

PubMed Central

Kim, Eunji; Wu, Hong-Gyun; Park, Jong Min; Kim, Jung-in; Kim, Hak Jae

2018-01-01

Radiation-induced lung damage is an important treatment-related toxicity after lung stereotactic ablative radiotherapy (SABR). After implementing a tri-60Co magnetic-resonance image guided system, ViewRayTM, we compared the associated early radiological lung density changes to those associated with a linear accelerator (LINAC). Eight patients treated with the tri-60Co system were matched 1:1 with patients treated with LINAC. Prescription doses were 52 Gy or 60 Gy in four fractions, and lung dose-volumetric parameters were calculated from each planning system. The first two follow-up computed tomography (CT) were co-registered with the planning CT through deformable registration software, and lung density was measured by isodose levels. Tumor size was matched between the two groups, but the planning target volume of LINAC was larger than that of the tri-60Co system (p = 0.036). With regard to clinically relevant dose-volumetric parameters in the lungs, the ipsilateral lung mean dose, V10Gy and V20Gy were significantly poorer in tri-60Co plans compared to LINAC plans (p = 0.012, 0.036, and 0.017, respectively). Increased lung density was not observed in the first follow-up scan compared to the planning scan. A significant change of lung density was shown in the second follow-up scan and there was no meaningful difference between the tri-60Co system and LINAC for all dose regions. In addition, no patient developed clinical radiation pneumonitis until the second follow-up scan. Therefore, there was no significant difference in the early radiological lung damage between the tri-60Co system and LINAC for lung SABR despite of the inferior plan quality of the tri-60Co system compared to that of LINAC. Further studies with a longer follow-up period are needed to confirm our findings. PMID:29608606

Early and late effects of prenatal corticosteroid treatment on the microRNA profiles of lung tissue in rats

PubMed Central

YU, HONG-REN; LI, SUNG-CHOU; TSENG, WAN-NING; TAIN, YOU-LIN; CHEN, CHIH-CHENG; SHEEN, JIUNN-MING; TIAO, MAO-MENG; KUO, HO-CHANG; HUANG, CHAO-CHENG; HSIEH, KAI-SHENG; HUANG, LI-TUNG

2016-01-01

Glucocorticoids have been administered to mothers at risk of premature delivery to induce maturation of preterm fetal lungs and prevent the development of respiratory distress syndrome. Micro (mi)RNAs serve various crucial functions in cell proliferation, differentiation and organ development; however, few studies have demonstrated an association between miRNAs and lung development. The aim of the present study was to investigate alterations in the miRNA profiles of rat lung tissue following prenatal glucocorticoid therapy for fetal lung development. The differences in miRNA expression profiles were compared between postnatal days 7 (D7) and 120 (D120) rat lung tissues, followed by validation using reverse transcription-quantitative polymerase chain reaction. The miRNA profiles of rat lung tissues following prenatal dexamethasone (DEX) therapy were also investigated. miRNAs with 2-fold changes were selected for further analysis. At D120, 6 upregulated and 6 downregulated miRNAs were detected, compared with D7. Among these differentially expressed miRNAs, miR-101-3p and miR-99b-5p were associated with the lowest and highest expressions of miRNA at D7, respectively. A limited impact on the miRNA profiles of rat lung tissues was observed following prenatal DEX treatment, which may help to further clarify the mechanisms underlying normal lung development. However, the results of the present study cannot entirely elucidate the effects of prenatal DEX treatment on the lung development of premature infants, and further studies investigating the impact of prenatal corticosteroids on fetal lung miRNA profiles are required. PMID:26997989

Increased fetal epicardial fat thickness: A novel ultrasound marker for altered fetal metabolism in diabetic pregnancies.

PubMed

Akkurt, Mehmet O; Turan, Ozhan M; Crimmins, Sarah; Harman, Christopher R; Turan, Sifa

2018-05-08

To evaluate whether fetal epicardial fat thickness (EFT) differs in diabetic and nondiabetic pregnant women. Retrospective case-control study of pregnancies between 24 and 36 weeks complicated by preexisting (PDM) or gestational (GDM) diabetes mellitus, matched one to one with controls for body mass index and gestational age (GA). Epicardial fat was identified as the hypoechogenic area between myocardium and visceral pericardium over the right ventricle and its thickness was measured by a single observer blinded to clinical condition and outcomes. A linear regression analysis was performed to assess the relationship between GA and EFT, and regression lines were compared between diabetics and controls. 53 PDM and 53 GDM pregnant women were matched with controls. With the exception of maternal age, the demographics were similar among groups. EFT increased significantly with advancing gestation in both diabetics and controls (P < 0.0001) and was significantly greater in diabetics than in controls (P < 0.0001). The best fit lines were different between diabetics (EFT = 0.05 × GA + 0.07 mm; R 2  = 0.70) and controls (EFT = 0.07 × GA + 0.04 mm; R 2  = 0.93) (P < 0.0001). Fetal EFT was greater in diabetics than in nondiabetics, and even greater in pregestational diabetics. EFT maybe an additional and/or earlier marker to identify early changes in fetal metabolism before accelerated fetal growth and polyhydramnios is apparent. © 2018 Wiley Periodicals, Inc.

Prediction of fetal lung maturity using the lecithin/sphingomyelin (L/S) ratio analysis with a simplified sample preparation, using a commercial microtip-column combined with mass spectrometric analysis.

PubMed

Kwak, Ho-Seok; Chung, Hee-Jung; Choi, Young Sik; Min, Won-Ki; Jung, So Young

2015-07-01

Fetal lung maturity is estimated using the lecithin/sphingomyelin ratio (L/S ratio) in amniotic fluid and it is commonly measured with thin-layer chromatography (TLC). The TLC method is time consuming and technically difficult; however, it is widely used because there is no alternative. We evaluated a novel method for measuring the L/S ratio, which involves a tip-column with a cation-exchange resin and mass spectrometry. Phospholipids in the amniotic fluid were extracted using methanol and chloroform. Choline-containing phospholipids such as lecithin and sphingomyelin were purified by passing them through the tip-column. LC-MS/MS and MALDI-TOF were used to directly analyze the purified samples. The L/S ratio by mass spectrometry was calculated from the sum peak intensity of the six lecithin, and that of sphingomyelin 34:1. In 20 samples, the L/S ratio determined with TLC was significantly correlated with that obtained by LC-MS/MS and MALDI-TOF. There was a 100% concordance between the L/S ratio by TLC and that by LC-MS/MS (kappa value=1.0). The concordance between the L/S ratio by TLC and that by MALDI-TOF was also 100% (kappa value=1.0). Our method provides a faster, simpler, and more reliable assessment of fetal lung maturity. The L/S ratio measured by LC-MS/MS and MALDI-TOF offers a compelling alternative method to traditional TLC. Copyright © 2015 Elsevier B.V. All rights reserved.

Numerical modeling of the fetal blood flow in the placental circulatory system

NASA Astrophysics Data System (ADS)

Shannon, Alexander; Gallucci, Sergio; Mirbod, Parisa

2015-11-01

The placenta is a unique organ of exchange between the growing fetus and the mother. It incorporates almost all functions of the adult body, acting as the fetal lung, digestive and immune systems, to mention a few. The exchange of oxygen and nutrients takes place at the surface of the villous tree. Using an idealized geometry of the fetal villous trees in the mouse placenta, in this study we performed 3D computational analysis of the unsteady fetal blood flow, gas, and nutrient transport over the chorionic plate. The fetal blood was treated as an incompressible Newtonian fluid, and the oxygen and nutrient were treated as a passive scalar dissolved in blood plasma. The flow was laminar, and a commercial CFD code (COMSOL Multiphysics) has been used for the simulation. COMSOL has been selected because it is multi-physics FEM software that allows for the seamless coupling of different physics represented by partial differential equations. The results clearly illustrate that the specific branching pattern and the in-plane curvature of the fetal villous trees affect the delivery of blood, gas and nutrient transport to the whole placenta.

Fetal Research

NASA Astrophysics Data System (ADS)

Hansen, John T.; Sladek, John R.

1989-11-01

This article reviews some of the significant contributions of fetal research and fetal tissue research over the past 20 years. The benefits of fetal research include the development of vaccines, advances in prenatal diagnosis, detection of malformations, assessment of safe and effective medications, and the development of in utero surgical therapies. Fetal tissue research benefits vaccine development, assessment of risk factors and toxicity levels in drug production, development of cell lines, and provides a source of fetal cells for ongoing transplantation trials. Together, fetal research and fetal tissue research offer tremendous potential for the treatment of the fetus, neonate, and adult.

Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Shows that Fetal Heart Rate Correlates with Maternal Glycemia.

PubMed

Cypryk, Katarzyna; Bartyzel, Lukasz; Zurawska-Klis, Monika; Mlynarski, Wojciech; Szadkowska, Agnieszka; Wilczynski, Jan; Nowakowska, Dorota; Wozniak, Lucyna A; Fendler, Wojciech

2015-09-01

Much evidence has shown that pregnancies in women with preexisting diabetes are affected by an increased risk of maternal and fetal adverse outcomes, probably linked to poor glycemic control. Despite great progress in medical care, the rate of stillbirths remains much higher in diabetes patients than in the general population. Recent technological advances in the field of glucose monitoring and noninvasive fetal heart rate monitoring made it possible to observe the fetal-maternal dependencies in a continuous manner. Fourteen type 1 diabetes patients were involved into the study and fitted with a blinded continuous glucose monitoring (CGM) recorder. Fetal electrocardiogram data were recorded using the Monica AN24™ device (Monica Healthcare Ltd., Nottingham, United Kingdom), the recordings of which were matched with CGM data. Statistical analysis was performed using a generalized mixed-effect logistic regression to account for individual factors. The mean number of paired data points per patient was 254±106, representing an observation period of 21.2±8.8 h. Mean glycemia equaled 5.64±0.68 mmol/L, and mean fetal heart rate was 135±6 beats/min. Higher glycemia correlated with fetal heart rate (R=0.32; P<0.0001) and was associated with higher odds of the fetus developing small accelerations (odds ratio=1.05; 95% confidence interval, 1.00-1.10; P=0.04). Elevated maternal glycemia of mothers with diabetes is associated with accelerations of fetal heart rate.

New formulas for calculating the lung-to-head ratio in healthy fetuses between 20 and 40 weeks' gestation.

PubMed

Kehl, Sven; Eckert, Sven; Berlit, Sebastian; Tuschy, Benjamin; Sütterlin, Marc; Siemer, Jörn

2013-11-01

The purpose of this study was to develop new formulas for the expected fetal lung area-to-head circumference ratio in normal singleton pregnancies between 20 and 40 weeks' gestation. The lung-to-head ratio and complete fetal biometric parameters of 126 fetuses between 20 and 40 weeks' gestation were prospectively measured. The lung-to-head ratio was measured by 3 different methods (longest diameter, anteroposterior diameter, and tracing). Formulas for predicting right and left lung-to-head ratios with regard to gestational age and biometric parameters were derived by stepwise regression analysis. New formulas for calculating right and left lung-to-head ratios by each measurement method were derived. The formulas included gestational age only and no biometric parameters. The new formulas for estimating the expected lung-to-head ratio by the 3 different methods in normal singleton pregnancies up to 40 weeks' gestation may help improve the prognostic power of observed-to-expected lung-to-head ratio assessment in fetuses with congenital diaphragmatic hernias.

PPAR-γ in innate and adaptive lung immunity.

PubMed

Nobs, Samuel Philip; Kopf, Manfred

2018-05-16

The transcription factor PPAR-γ (peroxisome proliferator-activated receptor-γ) is a key regulator of lung immunity exhibiting multiple cell type specific roles in controlling development and function of the lung immune system. It is strictly required for the generation of alveolar macrophages by controlling differentiation of fetal lung monocyte precursors. Furthermore, it plays an important role in lung allergic inflammation by licensing lung dendritic cell t helper 2 (Th2) priming capacity as well as acting as a master transcription factor for pathogenic Th2 cells. Due to this plethora of functions and its involvement in multiple pulmonary diseases including asthma and pulmonary alveolar proteinosis, understanding the role of PPAR-γ in lung immunity is an important subject of ongoing research. ©2018 Society for Leukocyte Biology.

Fetal Heart Rate Monitoring During Surgical Correction of Spontaneous Pneumothorax During Pregnancy: Lessons in In Utero Resuscitation.

PubMed

Wilson, Bailey; Burt, Bryan; Baker, Byron; Clark, Steven L; Belfort, Michael; Gandhi, Manisha

2016-01-01

Spontaneous pneumothorax during pregnancy has potentially serious implications for the mother and fetus. When surgical correction is required, complex maternal physiologic alterations may significantly affect fetal well-being. A woman underwent thoracoscopic lung resection and pleurodesis at 29 weeks of gestation. At various points during the procedure, maternal hemodynamic and respiratory consequences of anesthetic and surgical management resulted in severe fetal heart rate (FHR) decelerations and bradycardia. In each instance, physiologic manipulations based on an understanding of the likely cause of fetal hypoxia allowed correction of the FHR abnormalities without delivery. Nonsurgical perinatal intervention based on FHR monitoring and analysis of the likely pathophysiologic abnormalities underlying fetal decelerations may allow the gravid woman to undergo complex procedures and continue the pregnancy.

Interdependence of arterial PO2 and O2 consumption in the fetal sheep.

PubMed

Asakura, H; Ball, K T; Power, G G

1990-04-01

These experiments were undertaken to measure the effects of changing arterial oxygen tension (PaO2) on oxygen use by the fetal body (VO2). Six fetal sheep at 130-140 days gestation were prepared with an endotracheal tube, carotid artery catheter, body-core thermistor, cooling coil and loosely-applied umbilical cord snare. The next day the cord was occluded and the fetal lungs were ventilated with gas mixtures containing different concentrations of oxygen. While fetal core temperature was kept constant, fetal arterial PO2 was cycled between high and low values (span = 7 to 359 mmHg, n = 103) and O2 consumption was measured by the rate of O2 uptake from a closed-rebreathing circuit. VO2 changed directly with changes in PO2 from 10 to 40 mmHg but became insensitive to changes in PO2 above about 50 mmHg. The results were well described over the entire range by the equation: VO2 (ml/min per kg fetal wt) = -9.62 + 6.99 ln PO2(mmHg)-0.66 ln2 PO2. Thus the oxygen consumption of the near-term fetal sheep varies with changes in arterial PO2 in the physiologic range. This finding is distinctly different than the adult at rest but resembles adult tissues such as exercising muscle at VO2max. This finding is consistent with differences in fetal metabolic controls, limited cardiac reserve, and limited tissue diffusion rates in actively metabolizing tissues.

Automated Software Analysis of Fetal Movement Recorded during a Pregnant Woman's Sleep at Home.

PubMed

Nishihara, Kyoko; Ohki, Noboru; Kamata, Hideo; Ryo, Eiji; Horiuchi, Shigeko

2015-01-01

Fetal movement is an important biological index of fetal well-being. Since 2008, we have been developing an original capacitive acceleration sensor and device that a pregnant woman can easily use to record fetal movement by herself at home during sleep. In this study, we report a newly developed automated software system for analyzing recorded fetal movement. This study will introduce the system and compare its results to those of a manual analysis of the same fetal movement signals (Experiment I). We will also demonstrate an appropriate way to use the system (Experiment II). In Experiment I, fetal movement data reported previously for six pregnant women at 28-38 gestational weeks were used. We evaluated the agreement of the manual and automated analyses for the same 10-sec epochs using prevalence-adjusted bias-adjusted kappa (PABAK) including quantitative indicators for prevalence and bias. The mean PABAK value was 0.83, which can be considered almost perfect. In Experiment II, twelve pregnant women at 24-36 gestational weeks recorded fetal movement at night once every four weeks. Overall, mean fetal movement counts per hour during maternal sleep significantly decreased along with gestational weeks, though individual differences in fetal development were noted. This newly developed automated analysis system can provide important data throughout late pregnancy.

Bioenergetics of lung tumors: alteration of mitochondrial biogenesis and respiratory capacity.

PubMed

Bellance, N; Benard, G; Furt, F; Begueret, H; Smolková, K; Passerieux, E; Delage, J P; Baste, J M; Moreau, P; Rossignol, R

2009-12-01

Little is known on the metabolic profile of lung tumors and the reminiscence of embryonic features. Herein, we determined the bioenergetic profiles of human fibroblasts taken from lung epidermoid carcinoma (HLF-a) and fetal lung (MRC5). We also analysed human lung tumors and their surrounding healthy tissue from four patients with adenocarcinoma. On these different models, we measured functional parameters (cell growth rates in oxidative and glycolytic media, respiration, ATP synthesis and PDH activity) as well as compositional features (expression level of various energy proteins and upstream transcription factors). The results demonstrate that both the lung fetal and cancer cell lines produced their ATP predominantly by glycolysis, while oxidative phosphorylation was only capable of poor ATP delivery. This was explained by a decreased mitochondrial biogenesis caused by a lowered expression of PGC1alpha (as shown by RT-PCR and Western blot) and mtTFA. Consequently, the relative expression of glycolytic versus OXPHOS markers was high in these cells. Moreover, the re-activation of mitochondrial biogenesis with resveratrol induced cell death specifically in cancer cells. A consistent reduction of mitochondrial biogenesis and the subsequent alteration of respiratory capacity was also observed in lung tumors, associated with a lower expression level of bcl2. Our data give a better characterization of lung cancer cells' metabolic alterations which are essential for growth and survival. They designate mitochondrial biogenesis as a possible target for anti-cancer therapy.

Fetal Heart Sounds Detection Using Wavelet Transform and Fractal Dimension

PubMed Central

Koutsiana, Elisavet; Hadjileontiadis, Leontios J.; Chouvarda, Ioanna; Khandoker, Ahsan H.

2017-01-01

Phonocardiography is a non-invasive technique for the detection of fetal heart sounds (fHSs). In this study, analysis of fetal phonocardiograph (fPCG) signals, in order to achieve fetal heartbeat segmentation, is proposed. The proposed approach (namely WT–FD) is a wavelet transform (WT)-based method that combines fractal dimension (FD) analysis in the WT domain for the extraction of fHSs from the underlying noise. Its adoption in this field stems from its successful use in the fields of lung and bowel sounds de-noising analysis. The efficiency of the WT–FD method in fHS extraction has been evaluated with 19 simulated fHS signals, created for the present study, with additive noise up to (3 dB), along with the simulated fPCGs database available at PhysioBank. Results have shown promising performance in the identification of the correct location and morphology of the fHSs, reaching an overall accuracy of 89% justifying the efficacy of the method. The WT–FD approach effectively extracts the fHS signals from the noisy background, paving the way for testing it in real fHSs and clearly contributing to better evaluation of the fetal heart functionality. PMID:28944222

Respiratory syncytial virus infection accelerates lung fibrosis through the unfolded protein response in a bleomycin-induced pulmonary fibrosis animal model.

PubMed

Wang, Lina; Cheng, Wei; Zhang, Zhimin

2017-07-01

Emerging evidence has demonstrated that endoplasmic reticulum stress (ER) is involved in the pathogenesis of idiopathic pulmonary fibrosis, however, the underlying mechanism remains unclear. Viral infection often triggers a hyperinflammatory response by an expansion of the ER. The present study was designed to observe the role of respiratory syncytial virus infection (RSV)‑induced ER stress on lung fibrosis. In order to determine the role of ER stress on the onset and progression of pulmonary fibrosis, mice received an intratracheal combined injection of RSV and bleomycin on day 0. At day 7, 14 and 21 following combined injection, RSV in the lung tissues was assayed by immunohistochemistry, cellular classification was assayed by direct microscopic observation after Wright staining and the secretion of cytokines in the broncho‑alveolar lavage fluid (BALF) was assayed by ELISA. The expression of collagen type I was assayed by immunofluorescence and western blot analysis. The expression of ER stress related proteins was analyzed by western blot. In addition, the correlations of ER‑stress related proteins with collagen type‑1 were examined. RSV administration resulted in increased inflammation, as demonstrated by increased levels of leukocytes and pro‑inflammatory cytokines in the BALF, and increased collagen type‑1 deposition in the lung tissues of bleomycin-induced pulmonary fibrosis animal model at 7, 14 and 21 days. RSV promoted the expression of phosphorylated protein kinase R‑like endoplasmic reticulum kinase (p‑PERK), 78 kDa glucose‑regulated protein (GRP78) and activating transcription factor 6α (ATF6α), which accelerated the severity and process of fibrosis in bleomycin‑induced animal models. The present study provides evidence that RSV infection accelerated the unfolded protein response and bleomycin‑induced lung fibrosis, which may improve our understanding of the pathogenesis of pulmonary fibrosis.

Automated Software Analysis of Fetal Movement Recorded during a Pregnant Woman’s Sleep at Home

PubMed Central

Nishihara, Kyoko; Ohki, Noboru; Kamata, Hideo; Ryo, Eiji; Horiuchi, Shigeko

2015-01-01

Fetal movement is an important biological index of fetal well-being. Since 2008, we have been developing an original capacitive acceleration sensor and device that a pregnant woman can easily use to record fetal movement by herself at home during sleep. In this study, we report a newly developed automated software system for analyzing recorded fetal movement. This study will introduce the system and compare its results to those of a manual analysis of the same fetal movement signals (Experiment I). We will also demonstrate an appropriate way to use the system (Experiment II). In Experiment I, fetal movement data reported previously for six pregnant women at 28-38 gestational weeks were used. We evaluated the agreement of the manual and automated analyses for the same 10-sec epochs using prevalence-adjusted bias-adjusted kappa (PABAK) including quantitative indicators for prevalence and bias. The mean PABAK value was 0.83, which can be considered almost perfect. In Experiment II, twelve pregnant women at 24-36 gestational weeks recorded fetal movement at night once every four weeks. Overall, mean fetal movement counts per hour during maternal sleep significantly decreased along with gestational weeks, though individual differences in fetal development were noted. This newly developed automated analysis system can provide important data throughout late pregnancy. PMID:26083422

The effect of fetal sex on customized fetal growth charts.

PubMed

Rizzo, Giuseppe; Prefumo, Federico; Ferrazzi, Enrico; Zanardini, Cristina; Di Martino, Daniela; Boito, Simona; Aiello, Elisa; Ghi, Tullio

2016-12-01

To evaluate the effect of fetal sex on singleton pregnancy growth charts customized for parental characteristics, race, and parity Methods: In a multicentric cross-sectional study, 8070 ultrasonographic examinations from low-risk singleton pregnancies between 16 and 40 weeks of gestation were considered. The fetal measurements obtained were biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). Quantile regression was used to examine the impact of fetal sex across the biometric percentiles of the fetal measurements considered together with parents' height, weight, parity, and race. Fetal gender resulted to be a significant covariate for BDP, HC, and AC with higher values for male fetuses (p ≤ 0.0009). Minimal differences were found among sexes for FL. Parity, maternal race, paternal height and maternal height, and weight resulted significantly related to the fetal biometric parameters considered independently from fetal gender. In this study, we constructed customized biometric growth charts for fetal sex, parental, and obstetrical characteristics using quantile regression. The use of gender-specific charts offers the advantage to define individualized normal ranges of fetal biometric parameters at each specific centile. This approach may improve the antenatal identification of abnormal fetal growth.

Engine and radiator: fetal and placental interactions for heat dissipation.

PubMed

Schröder, H J; Power, G G

1997-03-01

The 'engine' of fetal metabolism generates heat (3-4 W kg-1 in fetal sheep) which has to be dissipated to the maternal organism. Fetal heat may move through the amniotic/allantoic fluids to the uterine wall (conductive pathway; total conductance, 1.1 W degrees C-1 kg-1) and with the umbilical arterial blood flow (convective pathway) to the placenta. Because resistance to heat flow is larger than zero fetal temperature exceeds maternal temperature by about 0.5 degree C (0.3-1 degree C). Probably 85% of fetal heat is lost to the maternal organism through the placenta, which thus serves as the main 'radiator'. Placental heat conductivity appears to be extremely high and this may lead to impaired heat exchange (guinea-pig placenta). A computer simulation demonstrates that fetal temperature is essentially clamped to maternal temperature, and that fetal thermoregulatory efforts to gain thermal independence would be futile. Indeed, when the late gestational fetus in utero is challenged by cold stress, direct and indirect indicators of (non-shivering) thermogenesis (oxygen consumption, increase of plasma glycerol and free fatty acid levels) change only moderately. In prematurely delivered lambs, however, cold stress provokes summit metabolism and maximum heat production. Only when birth is imitated in utero (by cord clamping, external artificial lung ventilation and cooling) do thermogenic efforts approach levels typical of extra-uterine life. This suggests the presence of inhibitors of thermogenesis of placental origin, e.g. prostaglandins and adenosine. When the synthesis of prostaglandins is blocked by pretreatment with indomethacin, sheep fetuses react to intra-uterine cooling with vigorous thermogenic responses, which can be subdued by infusion of prostaglandin E2 (PGE2). Since the sheep placenta is known to produce sufficient amounts of PGE2, it seems that the placenta controls fetal thermogenic responses to some extent. This transforms the fetus into an ectothermic

Interplay effect on a 6-MV flattening-filter-free linear accelerator with high dose rate and fast multi-leaf collimator motion treating breast and lung phantoms.

PubMed

Netherton, Tucker; Li, Yuting; Nitsch, Paige; Shaitelman, Simona; Balter, Peter; Gao, Song; Klopp, Ann; Muruganandham, Manickam; Court, Laurence

2018-06-01

Using a new linear accelerator with high dose rate (800 MU/min), fast MLC motions (5.0 cm/s), fast gantry rotation (15 s/rotation), and 1 cm wide MLCs, we aimed to quantify the effects of complexity, arc number, and fractionation on interplay for breast and lung treatments under target motion. To study lung interplay, eight VMAT plans (1-6 arcs) and four-nine-field sliding-window IMRT plans varying in complexity were created. For the breast plans, four-four-field sliding-window IMRT plans were created. Using the Halcyon 1.0 linear accelerator, each plan was delivered five times each under sinusoidal breathing motion to a phantom with 20 implanted MOSFET detectors; MOSFET dose (cGy), delivery time, and MU/cGy values were recorded. Maximum and mean dose deviations were calculated from MOSFET data. The number of MOSFETs with at least 19 of 20 detectors agreeing with their expected dose within 5% per fraction was calculated across 10 6 iterations to model dose deviation as function of fraction number for all plan variants. To put interplay plans into clinical context, additional IMRT and VMAT plans were created and delivered for the sites of head and neck, prostate, whole brain, breast, pelvis, and lung. Average modulation and interplay effect were compared to those from conventional linear accelerators, as reported from previous studies. The mean beam modulation for plans created for the Halcyon 1.0 linear accelerator was 2.9 MU/cGy (two- to four-field IMRT breast plans), 6.2 MU/cGy (at least five-field IMRT), and 3.6 MU/cGy (four-arc VMAT). To achieve treatment plan objectives, Halcyon 1.0 VMAT plans require more arcs and modulation than VMAT on conventional linear accelerators. Maximum and mean dose deviations increased with increasing plan complexity under tumor motion for breast and lung treatments. Concerning VMAT plans under motion, maximum, and mean dose deviations were higher for one arc than for two arcs regardless of plan complexity. For plan variants

Gallic acid induces apoptosis in EGFR-mutant non-small cell lung cancers by accelerating EGFR turnover.

PubMed

Nam, Boas; Rho, Jin Kyung; Shin, Dong-Myung; Son, Jaekyoung

2016-10-01

Gallic acid is a common botanic phenolic compound, which is present in plants and foods worldwide. Gallic acid is implicated in various biological processes such as cell growth and apoptosis. Indeed, gallic acid has been shown to induce apoptosis in many cancer types. However, the molecular mechanisms of gallic acid-induced apoptosis in cancer, particularly lung cancer, are still unclear. Here, we report that gallic acid induces apoptosis in EGFR-mutant non-small cell lung cancer (NSCLC) cells, but not in EGFR-WT NSCLC cells. Treatment with gallic acid resulted in a significant reduction in proliferation and induction of apoptosis, only in EGFR-mutant NSCLC cells. Interestingly, treatment with gallic acid led to a robust decrease in EGFR levels, which is critical for NSCLC survival. Treatment with gallic acid had no significant effect on transcription, but induced EGFR turnover. Indeed, treatment with a proteasome inhibitor dramatically reversed gallic acid-induced EGFR downregulation. Moreover, treatment with gallic acid induced EGFR turnover leading to apoptosis in EGFR-TKI (tyrosine kinase inhibitor)-resistant cell lines, which are dependent on EGFR signaling for survival. Thus, these studies suggest that gallic acid can induce apoptosis in EGFR-dependent lung cancers that are dependent on EGFR for growth and survival via acceleration of EGFR turnover. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fetal endocrinology

PubMed Central

Kota, Sunil Kumar; Gayatri, Kotni; Jammula, Sruti; Meher, Lalit Kumar; Kota, Siva Krishna; Krishna, S. V. S.; Modi, Kirtikumar D.

2013-01-01

Successful outcome of pregnancy depends upon genetic, cellular, and hormonal interactions, which lead to implantation, placentation, embryonic, and fetal development, parturition and fetal adaptation to extrauterine life. The fetal endocrine system commences development early in gestation and plays a modulating role on the various physiological organ systems and prepares the fetus for life after birth. Our current article provides an overview of the current knowledge of several aspects of this vast field of fetal endocrinology and the role of endocrine system on transition to extrauterine life. We also provide an insight into fetal endocrine adaptations pertinent to various clinically important situations like placental insufficiency and maternal malnutrition. PMID:23961471

Downregulation of Midkine gene expression and its response to retinoic acid treatment in the nitrofen-induced hypoplastic lung.

PubMed

Doi, Takashi; Shintaku, Mika; Dingemann, Jens; Ruttenstock, Elke; Puri, Prem

2011-02-01

Nitrofen-induced congenital diaphragmatic hernia (CDH) model has been widely used to investigate the pathogenesis of pulmonary hypoplasia (PH) in CDH. Recent studies have suggested that retinoids may be involved in the molecular mechanisms of PH in CDH. Prenatal treatment with retinoic acid (RA) has been reported to improve the growth of hypoplastic lung in the nitrofen CDH model. Midkine (MK), a RA-responsive growth factor, plays key roles in various organogenesis including lung development. In fetal lung, MK mRNA expression has its peak at E13.5-E16.5 and is markedly decreased during mid-to-late gestation, indicating its important role in early lung morphogenesis. We designed this study to investigate the hypothesis that the pulmonary MK gene expression is downregulated in the early lung morphogenesis in the nitrofen-induced PH, and to evaluate the effect of prenatal RA treatment on pulmonary MK gene expression in the nitrofen-induced CDH model. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetal lungs were harvested on D15, D18, and D21 and divided into control, nitrofen with or without CDH [CDH(+) or CDH(-)]. In addition, RA was given on days D18, D19, and D20 and fetal lungs were harvested on D21, and then divided into control + RA and nitrofen + RA. The pulmonary gene expression levels of MK were evaluated by real-time RT-PCR and statistically analyzed. Immunohistochemistry was also performed to examine protein expression/distribution of MK in fetal lung. The relative mRNA expression levels of MK were significantly downregulated in nitrofen group compared to controls at D15 ((§)p < 0.01), whereas there were no significant differences at D18 and D21. MK gene expression levels were significantly upregulated in nitrofen + RA (0.71 ± 0.17) compared to the control (0.35 ± 0.16), CDH(-) (0.24 ± 0.15), CDH(+) (0.39 ± 0.19) and control + RA (0.47 ± 0.13) (*p < 0.05). Immunoreactivity of MK was also markedly decreased in

[Evaluation of the diagnostic usefulness for ultrasonographic and echocardiographic lethal markers in fetal pulmonary hypoplasia. Analysis of 11 cases].

PubMed

Kieszek, S; Kaczmarek, P; Czichos, E; Respondek, M

1996-07-01

Results of ultrasonographic and echocardiographic studies of 11 fetuses were analysed retrospectively in relation to their pulmonary hypoplasia. Congenital malformations, quality of hydramnios and echocardiographical measurements of fetal chest were estimated. The best symptoms of pulmonary hypoplasia were: oligo/ahydramnios, absence of fetal breathing movements and malformations in fetal chest cavity (diaphragmatic hernia, cardiomegaly, hydrothorax). Systemic malformations were present in each case. The measurements such as CC, CA, HA, (CA-HA) x 100/CA were not accurate enough and we did not find any statistical differences between the control and the studied group. Finding several factors predisposing to lung hypoplasia means that its lethal form may be present in fetus.

Recent advances in the prenatal interrogation of the human fetal genome.

PubMed

Hui, Lisa; Bianchi, Diana W

2013-02-01

The amount of genetic and genomic information obtainable from the human fetus during pregnancy is accelerating at an unprecedented rate. Two themes have dominated recent technological advances in prenatal diagnosis: interrogation of the fetal genome in increasingly high resolution and the development of non-invasive methods of fetal testing using cell-free DNA in maternal plasma. These two areas of advancement have now converged with several recent reports of non-invasive assessment of the entire fetal genome from maternal blood. However, technological progress is outpacing the ability of the healthcare providers and patients to incorporate these new tests into existing clinical care, and further complicates many of the economic and ethical dilemmas in prenatal diagnosis. This review summarizes recent work in this field and discusses the integration of these new technologies into the clinic and society. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effects of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Fetal Pulmonary Circulation: An Experimental Study in Fetal Lambs

PubMed Central

Sharma, Dyuti; Aubry, Estelle; Ouk, Thavarak; Houeijeh, Ali; Houfflin-Debarge, Véronique; Besson, Rémi; Deruelle, Philippe; Storme, Laurent

2017-01-01

Background: Persistent pulmonary hypertension of the newborn (PPHN) causes significant morbidity and mortality in neonates. n-3 Poly-unsaturated fatty acids have vasodilatory properties in the perinatal lung. We studied the circulatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fetal sheep and in fetal pulmonary arterial rings. Methods: At 128 days of gestation, catheters were placed surgically in fetal systemic and pulmonary circulation, and a Doppler probe around the left pulmonary artery (LPA). Pulmonary arterial pressure and LPA flow were measured while infusing EPA or DHA for 120 min to the fetus, to compute pulmonary vascular resistance (PVR). The dose effects of EPA or DHA were studied in vascular rings pre-constricted with serotonin. Rings treated with EPA were separated into three groups: E+ (intact endothelium), E− (endothelium stripped) and LNA E+ (pretreatment of E+ rings with l-nitro-arginine). Results: EPA, but not DHA, induced a significant and prolonged 25% drop in PVR (n = 8, p < 0.001). Incubation of vascular rings with EPA (100 µM) caused a maximum relaxation of 60% in the E+ (n = 6), whereas vessel tone did not change in the E− (n = 6, p < 0.001). The vascular effects of EPA were significantly decreased in LNA E+ (n = 6). Incubation with DHA resulted in only a mild relaxation at the highest concentration of DHA (300 µM) compared to E+. Conclusions: EPA induces a sustained pulmonary vasodilatation in fetal lambs. This effect is endothelium- and dose-dependent and involves nitric oxide (NO) production. We speculate that EPA supplementation may improve pulmonary circulation in clinical conditions with PPHN. PMID:28714905

Effects of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Fetal Pulmonary Circulation: An Experimental Study in Fetal Lambs.

PubMed

Sharma, Dyuti; Aubry, Estelle; Ouk, Thavarak; Houeijeh, Ali; Houfflin-Debarge, Véronique; Besson, Rémi; Deruelle, Philippe; Storme, Laurent

2017-07-16

Background: Persistent pulmonary hypertension of the newborn (PPHN) causes significant morbidity and mortality in neonates. n -3 Poly-unsaturated fatty acids have vasodilatory properties in the perinatal lung. We studied the circulatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fetal sheep and in fetal pulmonary arterial rings. Methods: At 128 days of gestation, catheters were placed surgically in fetal systemic and pulmonary circulation, and a Doppler probe around the left pulmonary artery (LPA). Pulmonary arterial pressure and LPA flow were measured while infusing EPA or DHA for 120 min to the fetus, to compute pulmonary vascular resistance (PVR). The dose effects of EPA or DHA were studied in vascular rings pre-constricted with serotonin. Rings treated with EPA were separated into three groups: E+ (intact endothelium), E- (endothelium stripped) and LNA E+ (pretreatment of E+ rings with l-nitro-arginine). Results: EPA, but not DHA, induced a significant and prolonged 25% drop in PVR ( n = 8, p < 0.001). Incubation of vascular rings with EPA (100 µM) caused a maximum relaxation of 60% in the E+ ( n = 6), whereas vessel tone did not change in the E- ( n = 6, p < 0.001). The vascular effects of EPA were significantly decreased in LNA E+ ( n = 6). Incubation with DHA resulted in only a mild relaxation at the highest concentration of DHA (300 µM) compared to E+. Conclusions: EPA induces a sustained pulmonary vasodilatation in fetal lambs. This effect is endothelium- and dose-dependent and involves nitric oxide (NO) production. We speculate that EPA supplementation may improve pulmonary circulation in clinical conditions with PPHN.

Increasing fetal ovine number per gestation alters fetal plasma clinical chemistry values.

PubMed

Zywicki, Micaela; Blohowiak, Sharon E; Magness, Ronald R; Segar, Jeffrey L; Kling, Pamela J

2016-08-01

Intrauterine growth restriction (IUGR) is interconnected with developmental programming of lifelong pathophysiology. IUGR is seen in human multifetal pregnancies, with stepwise rises in fetal numbers interfering with placental nutrient delivery. It remains unknown whether fetal blood analyses would reflect fetal nutrition, liver, and excretory function in the last trimester of human or ovine IUGR In an ovine model, we hypothesized that fetal plasma biochemical values would reflect progressive placental, fetal liver, and fetal kidney dysfunction as the number of fetuses per gestation rose. To determine fetal plasma biochemical values in singleton, twin, triplet, and quadruplet/quintuplet ovine gestation, we investigated morphometric measures and comprehensive metabolic panels with nutritional measures, liver enzymes, and placental and fetal kidney excretory measures at gestational day (GD) 130 (90% gestation). As anticipated, placental dysfunction was supported by a stepwise fall in fetal weight, fetal plasma glucose, and triglyceride levels as fetal number per ewe rose. Fetal glucose and triglycerides were directly related to fetal weight. Plasma creatinine, reflecting fetal renal excretory function, and plasma cholesterol, reflecting placental excretory function, were inversely correlated with fetal weight. Progressive biochemical disturbances and growth restriction accompanied the rise in fetal number. Understanding the compensatory and adaptive responses of growth-restricted fetuses at the biochemical level may help explain how metabolic pathways in growth restriction can be predetermined at birth. This physiological understanding is important for clinical care and generating interventional strategies to prevent altered developmental programming in multifetal gestation. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Correlation of fetal oxygen saturation to fetal heart rate patterns. Evaluation of fetal pulse oximetry with two different oxisensors.

PubMed

Luttkus, A K; Friedmann, W; Homm-Luttkus, C; Dudenhausen, J W

1998-03-01

The purpose of this study was the correlation of fetal oxygen saturation values to various fetal heart rate patterns, as well as to oxygen saturation values obtained by fetal blood analysis. These objectives need to be evaluated from the perspective that two generations of fetal oxisensors have been used. Two different oxisensor systems (FS10: 660+890 nm and FS14: 735+890 nm) and a blinded pulse oximeter (type N400, Nellcor Puritan Bennett) were utilized to monitor 112 fetuses. All data, including oxygen saturation, fetal heart rate patterns, signal and contact quality were stored on a personal computer and evaluated after delivery. The following median fetal oxygen saturation values were obtained: during reassuring fetal heart rate sequences 54% with the oxisensor FS10 and 48% with the newer FS14 oxisensor, during intervals of variable decelerations 43% with the FS10 oxisensor and 40% with the FS14 oxisensor. These differences between values obtained during normal and abnormal fetal heart rate patterns are significant. Due to non-reassuring fetal heart rate patterns 81 fetal blood analyses were performed. The values of pulse oximetry were 9% higher (6% for the FS14) than those of spectrophotometry. Correlation of both methods was r=0.66 (0.74 for the FS14). In combination with fetal heart rate monitoring, fetal pulse oximetry promises a better differentiation between low and high risk heart rate patterns. Oxygen saturation values from intermittent fetal blood sampling reassure the clinician concerning the accuracy of this new method of intrapartum fetal surveillance and underline the increased quality of the new generation of oxisensor using light of a wavelength of 735 and 890 nm.

Fetal thrombocytopenia in pregnancies with fetal human parvovirus-B19 infection.

PubMed

Melamed, Nir; Whittle, Wendy; Kelly, Edmond N; Windrim, Rory; Seaward, P Gareth R; Keunen, Johannes; Keating, Sarah; Ryan, Greg

2015-06-01

Fetal infection with human parvovirus B19 (hParvo-B19) has been associated mainly with fetal anemia, although data regarding other fetal hematologic effects are limited. Our aim was to assess the rate and consequences of severe fetal thrombocytopenia after fetal hParvo-B19 infection. We conducted a retrospective study of pregnancies that were complicated by fetal hParvo-B19 infection that underwent fetal blood sampling (FBS). The characteristics and outcomes of fetuses with severe thrombocytopenia (<50 × 10(9)/L) were compared with those of fetuses with a platelet concentration of ≥50 × 10(9)/L (control fetuses). Fetuses in whom 3 FBSs were performed (n = 4) were analyzed to assess the natural history of platelet levels after fetal hParvo-B19 infection. A total of 37 pregnancies that were affected by fetal hParvo-B19 infection were identified. Of the 29 cases that underwent FBS and had information regarding fetal platelets, 11 cases (38%) were complicated by severe fetal thrombocytopenia. Severely thrombocytopenic fetuses were characterized by a lower hemoglobin concentration (2.6 ± 0.9 g/dL vs 5.5 ± 3.6 g/dL; P = .01), lower reticulocyte count (9.1% ± 2.8% vs 17.3% ± 10.6%; P = .02), and lower gestational age at the time of diagnosis (21.4 ± 3.1 wk vs 23.6 ± 2.2 wk; P = .03). Both the fetal death rate within 48 hours of FBS (27.3% vs 0%; P = .02) and the risk of prematurity (100.0% vs 13.3%; P < .001) were higher in fetuses with severe thrombocytopenia. Fetal thrombocytopenia was more common during the second trimester but, in some cases, persisted into the third trimester. Intrauterine transfusion (IUT) of red blood cells resulted in a further mean decrease of 40.1% ± 31.0% in fetal platelet concentration. Severe fetal thrombocytopenia is relatively common after fetal hParvo-B19 infection, can be further worsened by IUT, and may be associated with an increased risk of procedure-related fetal loss after either FBS or IUT. Copyright © 2015. Published by

Transabdominal amnioinfusion for improving fetal outcomes after oligohydramnios secondary to preterm prelabour rupture of membranes before 26 weeks.

PubMed

Van Teeffelen, Stijn; Pajkrt, Eva; Willekes, Christine; Van Kuijk, Sander M J; Mol, Ben Willem J

2013-08-03

Preterm prelabour rupture of membranes (PPROM) before 26 weeks can delay lung development and can cause pulmonary hypoplasia, as a result of oligohydramnios. Restoring the amniotic fluid volume by transabdominal amnioinfusion might prevent abnormal lung development and might have a protective effect for neurological complications, fetal deformities and neonatal sepsis. To assess the effectiveness of transabdominal amnioinfusion in improving perinatal outcome in women with oligohydramnios secondary to rupture of fetal membranes before 26 weeks. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013). All randomised controlled trials comparing transabdominal amnioinfusion with no transabdominal amnioinfusion. Cluster- or quasi-randomised trials were not eligible for inclusion. In cases where only an abstract was available, we attempted to find the full articles. Two review authors assessed trials for inclusion. No eligible trials were identified. There are no included studies. There is currently no evidence to evaluate the use of transabdominal amnioinfusion in women with oligohydramnios secondary to rupture of fetal membranes before 26 weeks for improving perinatal outcome. Further research examining the effects of this intervention is needed. Two randomised controlled trials are ongoing but final data have not yet been published.

Stachybotrys chartarum alters surfactant-related phospholipid synthesis and CTP:cholinephosphate cytidylyltransferase activity in isolated fetal rat type II cells.

PubMed

Hastings, C; Rand, T; Bergen, H T; Thliveris, J A; Shaw, A R; Lombaert, G A; Mantsch, H H; Giles, B L; Dakshinamurti, S; Scott, J E

2005-03-01

Stachybotry chartarum, a fungal contaminant of water-damaged buildings commonly grows on damp cellulose-containing materials. It produces a complex array of mycotoxins. Their mechanisms of action on the pulmonary system are not entirely clear. Previous studies suggest spore products may depress formation of disaturated phosphatidylcholine (DSPC), the major surface-active component of pulmonary surfactant (PS). If S. chartarum can indeed affect formation of this phospholipid, then mold exposure may be a significant issue for pulmonary function in both mature lung and developing fetal lung. To address this possibility, fetal rat type II cells, the principal source of DSPC, were used to assess effects of S. chartarum extract on formation of DSPC. Isolated fetal rat lung type II cells prelabeled with 3H-choline and incubated with spore extract showed decreased incorporation of 3H-choline into DSPC. The activity of CTP:cholinephosphate cytidylyltransferase (CPCT), the rate-limiting enzyme in phosphatidylcholine synthesis was reduced by approximately 50% by a 1:10 dilution of spore extract. Two different S. chartarum extracts (isolates from S. chartarum (Cleveland) and S. chartarum (Hawaiian)) were used to compare activity of CPCT in the presence of phosphatidylglycerol (PG), a known activator. PG produced an approximate two-fold increase in CPCT activity. The spore isolate from Hawaii did not alter enzyme activity. S. chartarum (Cleveland) eliminated the PG-induced activation of CPCT. These results support previous observations that mold products alter PS metabolism and may pose a risk in developing lung, inhibiting surfactant synthesis. Different isolates of the same species of fungus are not equivalent in terms of potential exposure risks.

Effects of chronic carbon monoxide exposure on fetal growth and development in mice

PubMed Central

2011-01-01

Background Carbon monoxide (CO) is produced endogenously, and can also be acquired from many exogenous sources: ie. cigarette smoking, automobile exhaust. Although toxic at high levels, low level production or exposure lends to normal physiologic functions: smooth muscle cell relaxation, control of vascular tone, platelet aggregation, anti- inflammatory and anti-apoptotic events. In pregnancy, it is unclear at what level maternal CO exposure becomes toxic to the fetus. In this study, we hypothesized that CO would be embryotoxic, and we sought to determine at what level of chronic CO exposure in pregnancy embryo/fetotoxic effects are observed. Methods Pregnant CD1 mice were exposed to continuous levels of CO (0 to 400 ppm) from conception to gestation day 17. The effect on fetal/placental growth and development, and fetal/maternal CO concentrations were determined. Results Maternal and fetal CO blood concentrations ranged from 1.12- 15.6 percent carboxyhemoglobin (%COHb) and 1.0- 28.6%COHb, respectively. No significant difference was observed in placental histological morphology or in placental mass with any CO exposure. At 400 ppm CO vs. control, decreased litter size and fetal mass (p < 0.05), increased fetal early/late gestational deaths (p < 0.05), and increased CO content in the placenta and the maternal spleen, heart, liver, kidney and lung (p < 0.05) were observed. Conclusions Exposure to levels at or below 300 ppm CO throughout pregnancy has little demonstrable effect on fetal growth and development in the mouse. PMID:22168775

STRAIN-SPECIFIC SENSITIVITY TO INDUCTION OF MURINE LUNG TUMORS FOLLOWING IN UTERO EXPOSURE TO 3-METHYLCHOLANTHRENE

EPA Science Inventory

We previously demonstrated that different strains of fetal mice were more sensitive to lung tumor induction by 3-methylcholanthrene (MC) than were adults. Offspring from either a D2 x B6D2F1 backcross or from parental Balb/c mice exhibited a similar high incidence of lung tumors ...

Intrapartum fetal heart rate monitoring: evaluation of a standardized system of interpretation for prediction of metabolic acidosis at delivery and neonatal neurological morbidity.

PubMed

Soncini, Emanuele; Paganelli, Simone; Vezzani, Cristina; Gargano, Giancarlo; Giovanni Battista, La Sala

2014-09-01

To assess the ability of the intrapartum fetal heart rate interpretation system developed in 2008 by the National Institute of Child Health and Human Development (NICHD) to predict fetal metabolic acidosis at delivery and neonatal neurological morbidity. We analyzed the intrapartum fetal heart rate tracings of 314 singleton fetuses at ≥ 37 weeks using the NICHD three-tier system of interpretation: Category I (normal), Category II (indeterminate) and Category III (abnormal). Category II was further divided into Category IIA, with moderate fetal heart rate variability or accelerations, and Category IIB, with minimal/absent fetal heart rate variability and no accelerations. The presence and duration of the different patterns were compared with several clinical neonatal outcomes and with umbilical artery acid-base balance at birth. The mean values of pH and base excess decreased proportionally as tracings worsened (p < 0.001). The duration of at least 30 min for Category III tracings was highly predictive of a pH <7.00 and a base excess ≤-12 mmol/L. The same was true for the duration of Category IIB tracings that lasted for at least 50 min. Our study demonstrates that the interpretation of fetal heart rate tracings based on a strictly standardized system is closely associated with umbilical artery acid-base status at delivery.

Predictive value of late decelerations for fetal acidemia in unselective low-risk pregnancies.

PubMed

Sameshima, Hiroshi; Ikenoue, Tsuyomu

2005-01-01

We evaluated the clinical significance of late decelerations (LD) of intrapartum fetal heart rate (FHR) monitoring to detect low pH (< 7.1) in low-risk pregnancies. We selected two secondary and two tertiary-level institutions where 10,030 women delivered. Among them, 5522 were low-risk pregnancies. The last 2 hours of FHR patterns before delivery were interpreted according to the guidelines of the National Institute of Child Health and Human Development. The correlation between the incidence of LD (occasional, < 50%; recurrent, > or = 50%) and severity (reduced baseline FHR accelerations and variability) of LD, and low pH (< 7.1) were evaluated. Statistical analyses included a contingency table with chi2 and the Fisher test, and one-way analysis of variance with the Bonferroni/Dunn test. In the 5522 low-risk pregnancies, 301 showed occasional LD and 99 showed recurrent LD. Blood gases and pH values deteriorated as the incidence of LD increased and as baseline accelerations or variability was decreased. Positive predictive value for low pH (< 7.1) was exponentially elevated from 0% at no deceleration, 1% in occasional LD, and > 50% in recurrent LD with no baseline FHR accelerations and reduced variability. In low-risk pregnancies, information on LD combined with acceleration and baseline variability enables us to predict the potential incidence of fetal acidemia.

The Effects of Meperidine Analgesia during Labor on Fetal Heart Rate

PubMed Central

Sekhavat, Leila; Behdad, Shecoofah

2009-01-01

To estimate the effects of intramuscular meperidine analgesia on fetal heart rate (FHR) patterns compared with placebo. In a prospective randomized study, 150 healthy women with singleton term pregnancy requesting analgesia during active labor were planned to receive either intramuscular meperidin 50 mg (meperidin group) or normal saline (control group) when they requested analgesia. Fetal heart rate patterns occurring within 40 minutes of initiation of labor analgesia were retrospectively read by maternal fetal medicine specialist who was blind to type of labor analgesia. Meperidine, compared with placebo, was associated with statistically significantly less beat to beat variability (absent or less than 5 beats per minute) (28% versus 5% of fetuses, P<0.05), lower proportion of accelerations (37.3% versus 17.3% P<0.05) and of the FHR. Also FHR deceleration was significantly more than control group (25.5% versus 4%, P<0.05). Meperidine has deleterious effects on FHR. PMID:23675116

Pulmonary and systemic inflammatory responses to intra-amniotic IL-1α in fetal sheep

PubMed Central

Kramer, Boris W.; Nitsos, Ilias; Pillow, J. Jane; Collins, Jennifer J. P.; Polglase, Graeme R.; Newnham, John P.; Jobe, Alan H.

2011-01-01

Clinical and epidemiological studies implicate IL-1 as an important mediator of perinatal inflammation. We tested the hypothesis that intra-amniotic IL-1α would induce pulmonary and systemic fetal inflammatory responses. Sheep with singleton fetuses were given an intra-amniotic injection of recombinant sheep IL-1α (100 μg) and were delivered 1, 3, or 7 days later, at 124 ± 1 days gestation (n=5–8/group). A separate group of sheep were given two intra-amniotic IL-1α injections (100 μg dose each): 7 days and again 1 day prior to delivery. IL-1α induced a robust increase in monocytes, neutrophils, lymphocytes, and IL-8 protein in bronchoalveolar lavage fluid. H2O2 secretion was increased in inflammatory cells isolated from lungs of IL-1α-exposed lambs upon LPS challenge in vitro compared with control monocytes. T lymphocytes were recruited to the lung. IL-1β, cyclooxygenase-1, and cyclooxygenase-2 mRNA expression increased in the lung 1 day after intra-amniotic IL-1α exposure. Lung volumes increased 7 days after intra-amniotic IL-1α exposure, with minimal anatomic changes in air space morphology. The weight of the posterior mediastinal lymph node draining the lung and the gastrointestinal tract doubled, inducible nitric oxide synthase (NOSII)-positive cells increased, and Foxp3-positive T-regulatory lymphocytes decreased in the lymph node after IL-1α exposure. In the blood, neutrophil counts and plasma haptoglobin increased after IL-1α exposure. Compared with a single exposure, exposure to intra-amniotic IL-1α 7 days and again 1 day before delivery had a variable effect (increases in some inflammatory markers, but not pulmonary cytokines). IL-1α is a potent mediator of the fetal inflammatory response syndrome. PMID:21665964

On the flow through the normal fetal aortic arc at late gestation

NASA Astrophysics Data System (ADS)

Pekkan, Kerem; Nourparvar, Paymon; Yerneni, Srinivasu; Dasi, Lakshmi; de Zelicourt, Diane; Fogel, Mark; Yoganathan, Ajit

2006-11-01

During the fetal stage, the aortic arc is a complex junction of great vessels (right and left ventricular outflow tracks (RVOT, LVOT), pulmonary arteries (PA), ductus, head-neck vessels, decending aorta (Dao)) delicately distributing the oxygenated blood flow to the lungs and the body -preferential to the brain. Experimental and computational studies are performed in idealized models of the fetal aorta to understand and visualize the unsteady hemodynamics. Unsteady in vitro flow, generated by two peristaltic pumps (RVOT and LVOT) is visualized with two colored dyes and a red laser in a rigid glass model with physiological diameters. Helical flow patterns at the PA's and ductal shunting to the Dao are visualized. Computational fluid dynamics of the same geometry is modeled using the commercial code Fidap with porous boundary conditions representing systemic and pulmonary resistances (˜400000 tetrahedral elements). Combined (RVOT+LVOT) average flow rates ranging from 1.9 to 2.1-L/min for 34 to 38-weeks gestation were simulated with the Reynolds and Womersly numbers (Dao) of 500 and 8. Computational results are compared qualitatively with the flow visualizations at this target flow condition. Understanding fetal hemodynamics is critical for congenital heart defects, tissue engineering, fetal cardiac MRI and surgeries.

Fetal bladder catheterization in severe obstructive uropathy before the 24th week of pregnancy.

PubMed

Szaflik, K; Kozarzewski, M; Adamczewski, D

1998-01-01

for normal development of the fetal lungs.

Evidence for decreased lipofibroblast expression in hypoplastic rat lungs with congenital diaphragmatic hernia.

PubMed

Friedmacher, Florian; Fujiwara, Naho; Hofmann, Alejandro Daniel; Takahashi, Hiromizu; Gosemann, Jan-Hendrik; Puri, Prem

2014-10-01

Pulmonary hypoplasia (PH) is a serious condition in newborns with congenital diaphragmatic hernia (CDH). Lipid-containing interstitial fibroblasts (LIFs) play an essential role in fetal lung maturation by stimulating alveolarization and lipid homeostasis. In rodents, LIFs are first evident during the canalicular phase of lung development with a significant increase over the last 4 days of gestation. Adipocyte differentiation-related protein (ADRP), a functional lipogenic molecular marker characterizing LIFs, is highly expressed in fetal lungs during this critical time period. We hypothesized that LIF expression in hypoplastic rat lungs is decreased in the nitrofen-induced CDH model, which is accompanied by reduced alveolar ADRP expression and lipid content. On embryonic day 9.5 (E9.5), time-mated rats received either nitrofen or vehicle. Fetuses were sacrificed on selected time points E18.5 and E21.5, and dissected lungs were divided into controls and CDH-associated PH. Pulmonary gene expression levels of ADRP were determined by quantitative real-time polymerase chain reaction. ADRP immunohistochemistry and oil red O staining were used to assess pulmonary protein expression and lipid content. Immunofluorescence double staining for alpha smooth muscle actin, which is known to be absent in LIFs, and lipid droplets was performed to evaluate the pulmonary expression of this specific subset of fibroblasts. Relative mRNA expression of ADRP was significantly reduced in lungs of CDH-associated PH on E18.5 and E21.5 compared to controls. ADRP immunoreactivity and lipid staining were markedly diminished in alveolar mesenchymal cells of CDH-associated PH on E18.5 and E21.5 compared to controls. Confocal laser scanning microscopy demonstrated markedly decreased LIF expression in alveolar interstitium of CDH-associated PH on E18.5 and E21.5 compared to controls. Decreased pulmonary LIF expression during late gestation suggests impaired LIF functioning in the nitrofen

Passive fetal heart rate monitoring apparatus and method with enhanced fetal heart beat discrimination

NASA Technical Reports Server (NTRS)

Zahorian, Stephen A. (Inventor); Livingston, David L. (Inventor); Pretlow, III, Robert A. (Inventor)

1996-01-01

An apparatus for acquiring signals emitted by a fetus, identifying fetal heart beats and determining a fetal heart rate. Multiple sensor signals are outputted by a passive fetal heart rate monitoring sensor. Multiple parallel nonlinear filters filter these multiple sensor signals to identify fetal heart beats in the signal data. A processor determines a fetal heart rate based on these identified fetal heart beats. The processor includes the use of a figure of merit weighting of heart rate estimates based on the identified heart beats from each filter for each signal. The fetal heart rate thus determined is outputted to a display, storage, or communications channel. A method for enhanced fetal heart beat discrimination includes acquiring signals from a fetus, identifying fetal heart beats from the signals by multiple parallel nonlinear filtering, and determining a fetal heart rate based on the identified fetal heart beats. A figure of merit operation in this method provides for weighting a plurality of fetal heart rate estimates based on the identified fetal heart beats and selecting the highest ranking fetal heart rate estimate.

Passive fetal heart rate monitoring apparatus and method with enhanced fetal heart beat discrimination

NASA Technical Reports Server (NTRS)

Zahorian, Stephen A. (Inventor); Livingston, David L. (Inventor); Pretlow, Robert A., III (Inventor)

1994-01-01

An apparatus for acquiring signals emitted by a fetus, identifying fetal heart beats and determining a fetal heart rate is presented. Multiple sensor signals are outputted by a passive fetal heart rate monitoring sensor. Multiple parallel nonlinear filters filter these multiple sensor signals to identify fetal heart beats in the signal data. A processor determines a fetal heart rate based on these identified fetal heart beats. The processor includes the use of a figure of merit weighting of heart rate estimates based on the identified heart beats from each filter for each signal. The fetal heart rate thus determined is outputted to a display, storage, or communications channel. A method for enhanced fetal heart beat discrimination includes acquiring signals from a fetus, identifying fetal heart beats from the signals by multiple parallel nonlinear filtering, and determining a fetal heart rate based on the identified fetal heart beats. A figure of merit operation in this method provides for weighting a plurality of fetal heart rate estimates based on the identified fetal heart beats and selecting the highest ranking fetal heart rate estimate.

Fetal Surgery

PubMed Central

Laberge, Jean-Martin

1986-01-01

Fetal surgery has come of age. For decades experimental fetal surgery proved essential in studying normal fetal physiology and development, and pathophysiology of congenital defects. Clinical fetal surgery started in the 1960s with intrauterine transfusions. In the 1970s, the advent of ultrasonography revolutionized fetal diagnosis and created a therapeutic vacuum. Fetal treatment, medical and surgical, is slowly trying to fill the gap. Most defects detected are best treated after birth, some requiring a modification in the time, mode and place of delivery for optimal obstetrical and neonatal care. Surgical intervention in utero should be considered for malformations that cause progressive damage to the fetus, leading to death or severe morbidity; that can be corrected or palliated in utero with a reasonable expectation of normal postnatal development; that cannot wait to be corrected after birth, even considering pre-term delivery; that are not accompanied by chromosomal or other major anomalies. At present, congenital hydronephrosis is the most common indication for fetal surgery, followed by obstructive hydrocephalus. Congenital diaphragmatic hernia also fulfills the criteria, but its correction poses more problems, and no clinical attempts have been reported so far. In the future many other malformations or diseases may become best treated in utero. The ethical and moral issues are complex and need to be discussed as clinical and experimental progress is made. PMID:21267309

Propofol Pharmacokinetics and Estimation of Fetal Propofol Exposure during Mid-Gestational Fetal Surgery: A Maternal-Fetal Sheep Model

PubMed Central

Niu, Jing; Venkatasubramanian, Raja; Vinks, Alexander A.; Sadhasivam, Senthilkumar

2016-01-01

Background Measuring fetal drug concentrations is extremely difficult in humans. We conducted a study in pregnant sheep to simultaneously describe maternal and fetal concentrations of propofol, a common intravenous anesthetic agent used in humans. Compared to inhalational anesthesia, propofol supplemented anesthesia lowered the dose of desflurane required to provide adequate uterine relaxation during open fetal surgery. This resulted in better intraoperative fetal cardiac outcome. This study describes maternal and fetal propofol pharmacokinetics (PK) using a chronically instrumented maternal-fetal sheep model. Methods Fetal and maternal blood samples were simultaneously collected from eight mid-gestational pregnant ewes during general anesthesia with propofol, remifentanil and desflurane. Nonlinear mixed-effects modeling was performed by using NONMEM software. Total body weight, gestational age and hemodynamic parameters were tested in the covariate analysis. The final model was validated by bootstrapping and visual predictive check. Results A total of 160 propofol samples were collected. A 2-compartment maternal PK model with a third fetal compartment appropriately described the data. Mean population parameter estimates for maternal propofol clearance and central volume of distribution were 4.17 L/min and 37.7 L, respectively, in a typical ewe with a median heart rate of 135 beats/min. Increase in maternal heart rate significantly correlated with increase in propofol clearance. The estimated population maternal-fetal inter-compartment clearance was 0.0138 L/min and the volume of distribution of propofol in the fetus was 0.144 L. Fetal propofol clearance was found to be almost negligible compared to maternal clearance and could not be robustly estimated. Conclusions For the first time, a maternal-fetal PK model of propofol in pregnant ewes was successfully developed. This study narrows the gap in our knowledge in maternal-fetal PK model in human. Our study confirms

The quality of fetal arm movements as indicators of fetal stress.

PubMed

Reissland, Nadja; Francis, Brian

2010-12-01

Although a number of studies have found that maternal stress affects the fetus, it is unclear whether jerky fetal movements observed on ultrasound scans are indicative of fetal stress, or whether they are part of normal development. The present study was designed to examine the relationship between jerky fetal arm movements in relation to fetal age and stress. Video recordings were made of routine ultrasound scans of 57 fetuses (age range 8 to 33 weeks) classified into three age groups: 1st trimester (8-12 weeks, N=9), 2nd trimester (13-24 weeks, N=38), and 3rd trimester (26-33 weeks, N=10). Following previous research on stress behaviour in neonates, a fetal index of stress was derived from frequency of hiccup, back arch and rhythmical mouthing. Results indicated that while stress level was unrelated to fetal age, jerkiness of arm movements was significantly associated with the fetal stress index but not age. Our findings suggest that jerky arm movements in fetuses are suggestive of fetal stress. Copyright © 2010 Elsevier Ltd. All rights reserved.

Regulation of mouse lung development by the extracellular calcium-sensing receptor, CaR

PubMed Central

Finney, Brenda A; del Moral, Pierre M; Wilkinson, William J; Cayzac, Sebastien; Cole, Martin; Warburton, David; Kemp, Paul J; Riccardi, Daniela

2008-01-01

Postnatal lung function is critically dependent upon optimal embryonic lung development. As the free ionized plasma calcium concentration ([Ca2+]o) of the fetus is higher than that of the adult, the process of lung development occurs in a hypercalcaemic environment. In the adult, [Ca2+]o is monitored by the G-protein coupled, extracellular calcium-sensing receptor (CaR), but neither its ontogeny nor its potential role in lung development are known. Here, we demonstrate that CaR is expressed in the mouse lung epithelium, and that its expression is developmentally regulated, with a peak of expression at embryonic day 12.5 (E12.5) and a subsequent decrease by E18, after which the receptor is absent. Experiments carried out using the lung explant culture model in vitro show that lung branching morphogenesis is sensitive to [Ca2+]o, being maximal at physiological adult [Ca2+]o (i.e. 1.0–1.3 mm) and lowest at the higher, fetal (i.e. 1.7 mm) [Ca2+]o. Administration of the specific CaR positive allosteric modulator, the calcimimetic R-568, mimics the suppressive effects of high [Ca2+]o on branching morphogenesis while both phospholipase C and PI3 kinase inhibition reverse these effects. CaR activation suppresses cell proliferation while it enhances intracellular calcium signalling, lung distension and fluid secretion. Conditions which are restrictive either to branching or to secretion can be rescued by manipulating [Ca2+]o in the culture medium. In conclusion, fetal Cao2+, acting through a developmentally regulated CaR, is an important extrinsic factor that modulates the intrinsic lung developmental programme. Our observations support a novel role for the CaR in preventing hyperplastic lung disease in utero. PMID:18955379

Hemodynamic, pulmonary vascular, and myocardial abnormalities secondary to pharmacologic constriction of the fetal ductus arteriosus. A possible mechanism for persistent pulmonary hypertension and transient tricuspid insufficiency in the newborn infant.

PubMed

Levin, D L; Mills, L J; Weinberg, A G

1979-08-01

The prostaglandin synthetase inhibitor indomethacin was given orally or intravenously to pregnant ewes. This resulted in a significant rise in the fetal pulmonary-to-systemic arterial mean blood pressure difference across the ductus arteriosus, presumably secondary to constriction of the ductus arteriosus. In five experiments the pressure difference could be promptly but temporarily reversed by the administration of prostaglandin E1 (PGE1) into the fetal inferior vena cava. Fetal lungs from study and control animals were fixed by perfusion at measured pulmonary arterial mean blood pressure, and fifth-generation resistance vessels were studied. The medial width/external diameter ratio was significantly increased in the study vs the control lungs due to increased smooth muscle and decreased external diameter. In addition, study fetuses had acute degenerative myocardial changes in the tricuspid valve papillary muscles, the right ventricular free wall and the interventricular septum. Similar changes were not seen in control fetuses. Indomethacin administration during pregnancy causes constriction of the fetal ductus arteriosus, fetal pulmonary arterial hypertension, and right ventricular damage. If severe, this may cause rapid fetal death. If less severe, in the newborn infant, this mechanism may be one cause of persistent pulmonary hypertension due to vasoconstriction and increased pulmonary arterial smooth muscle and/or tricuspid insufficiency due to papillary muscle infarction.

Contribution of fetal brain MRI in management of severe fetal anemia.

PubMed

Ghesquière, L; Houfflin-Debarge, V; Verpillat, P; Fourquet, T; Joriot, S; Coulon, C; Vaast, P; Garabedian, C

2018-06-06

Intrauterine transfusion (IUT) has changed fetal anemia prognosis. However, long-term neurodevelopmental outcome is altered in 5% of children. Our objective was to study the contribution of fetal MRI to diagnosis brain lesions in case of fetal anemia. Retrospective monocentric descriptive study from 2005 to 2016, including all patients followed for fetal anemia requiring IUT. The indications for MRI were: hydrops fetalis and / or hemoglobin <5 g / dL and / or more than 3 IUTs and / or acute severe anemia and / or ultrasound abnormality. Fetal and neonatal outcome and pediatric neurological monitoring were studied. 89 patients were followed for fetal anemia with IUT and 28 (29.1%) had fetal MRI, 12 of which were abnormal. Two out of twelve had abnormal ultrasound. Seven out of twelve had poor neurological prognosis: 2 medical terminations of pregnancy were performed; 2 children had severe developmental delay and 3 children had schooling difficulties. Five out of twelve children had favorable neurological prognosis. MRI of the fetal brain makes it possible to better detect brain lesions than ultrasound does in the management of severe fetal anemia and seems particularly appropriate in cases of acute anemia. Copyright © 2018 Elsevier B.V. All rights reserved.

Fetal acoustic stimulation test for early intrapartum fetal monitoring.

PubMed

Goonewardene, M; Hanwellage, K

2011-03-01

The fetal acoustic stimulation test (FAST) is a simple cost effective screening test for antenatal fetal monitoring. The aim of the study was to evaluate the FAST as a screening test for early intrapartum fetal well being. An initial non stress test (NST) followed by a FAST using corometric model 146 was carried out in 486 participants in early labour with uncomplicated singleton pregnancies and > 32 weeks gestation. A repeat NST was recorded in the participants who had an initial non reactive NST. The results of the NST and FAST were compared with fetal outcome. Maternal perception of fetal movements after FAST, results of NST before and after FAST, and the babies' 5 minute APGAR scores were measured. Of the 486 participants 413 (85%) noticed fetal movements after FAST. Initial NST was non reactive in 203 (42%) but 149 (31%) became reactive after FAST. Compared to the NST, FAST had a better sensitivity (97% vs 62%, p < 0.001), specificity (100% vs 87%, p = 0.017), positive predictive value (100% vs 98%, p = 0.024), negative predictive value (79% vs 17%, p < 0.001) and accuracy (99%vs 64%, p < 0.001) in predicting 5 minute APGAR < 7 in the baby. FAST is a reliable screening test for assessing fetal well being in early labour. It complements the NST and is better than the NST alone.

[Subretinal transplantation of human fetal lung fibroblasts expressed ciliary neurotrophic factor gene prevent photoreceptor degeneration in RCS rats].

PubMed

Huang, Qian; Xu, Ping; Xia, Xin; Hu, Hong-hui; Wang, Feng; Li, Hui-ming

2006-02-01

To investigate the efficacy of subretinal transplantation of CNTF gene transfected fibroblasts for preventing photoreceptor degeneration in RCS. The human fetal lung fibroblasts with high level expression of CNTF were established by liposome mediated gene transfer and MTX selection. A 5 microl of cell suspension, containing 1 x 10(5) cells, was injected through pars plana of ciliary body into the subretinal space of the right eye at postnatal 4-5 weeks, the left eye was left without injection or injected with PBS as controls. The both eyes were enucleated for histopathological examinations at 2, 4, 6, 8, 10, 12 and 15 weeks following transplantation. The level of CNTF protein (91,046.15 pg/ml) expressed in the transfected cells was determined by sandwich enzyme-linked immunosorbent assay (ELISA). The four of seven eyes examined by light microscopy and the ten of 14 eyes examined by electro microscopy showed rescue effect. The prolonged photoreceptor survival, reduction of apoptotic cells and debris were observed in transplanted eyes in comparison with untreated or sham-injected eyes. This study provides the first indication that transplanted human fibroblasts with high level expression of CNTF are able to rescue photoreceptor degeneration in RCS dystrophic rat retina.

Fetal behavioral teratology.

PubMed

Visser, Gerard H A; Mulder, Eduard J H; Tessa Ververs, F F

2010-10-01

Ultrasound studies of fetal motor behavior provide direct – in vivo – insight in the functioning of the motor component of the fetal central nervous system. In this article, studies are reviewed showing changes in the first timetable of appearance of fetal movements, changes in quality and/or quantity of movements and disturbances in the development of fetal behavioral states in case of endogenous malfunctions, maternal diseases and exogenous behavioral teratogens.

Fetal Fibroblasts and Keratinocytes with Immunosuppressive Properties for Allogeneic Cell-Based Wound Therapy

PubMed Central

Zuliani, Thomas; Saiagh, Soraya; Knol, Anne-Chantal; Esbelin, Julie; Dréno, Brigitte

2013-01-01

Fetal skin heals rapidly without scar formation early in gestation, conferring to fetal skin cells a high and unique potential for tissue regeneration and scar management. In this study, we investigated the possibility of using fetal fibroblasts and keratinocytes to stimulate wound repair and regeneration for further allogeneic cell-based therapy development. From a single fetal skin sample, two clinical batches of keratinocytes and fibroblasts were manufactured and characterized. Tolerogenic properties of the fetal cells were investigated by allogeneic PBMC proliferation tests. In addition, the potential advantage of fibroblasts/keratinocytes co-application for wound healing stimulation has been examined in co-culture experiments with in vitro scratch assays and a multiplex cytokines array system. Based on keratin 14 and prolyl-4-hydroxylase expression analyses, purity of both clinical batches was found to be above 98% and neither melanocytes nor Langerhans cells could be detected. Both cell types demonstrated strong immunosuppressive properties as shown by the dramatic decrease in allogeneic PBMC proliferation when co-cultured with fibroblasts and/or keratinocytes. We further showed that the indoleamine 2,3 dioxygenase (IDO) activity is required for the immunoregulatory activity of fetal skin cells. Co-cultures experiments have also revealed that fibroblasts-keratinocytes interactions strongly enhanced fetal cells secretion of HGF, GM-CSF, IL-8 and to a lesser extent VEGF-A. Accordingly, in the in vitro scratch assays the fetal fibroblasts and keratinocytes co-culture accelerated the scratch closure compared to fibroblast or keratinocyte mono-cultures. In conclusion, our data suggest that the combination of fetal keratinocytes and fibroblasts could be of particular interest for the development of a new allogeneic skin substitute with immunomodulatory activity, acting as a reservoir for wound healing growth factors. PMID:23894651

The effects of own fetal growth on reported hypertension in parous women aged 33.

PubMed

Hennessy, E; Alberman, E

1997-06-01

Data from the study of the British 1958 birth cohort, National Child Development Study (NCDS), has allowed wider investigation of the relationship between retarded fetal growth and risk of adult hypertension. A history of self-reported hypertension was related to fetal growth in 3308 parous cohort members. Fetal growth, the measure used, is the difference in actual birthweight from that expected for the gestational age and subsequent adult height. The relationships were investigated both linearly and non-linearly adjusting for potential confounders. After adjustment for confounding factors, including adult weight for height, retarded fetal growth was associated with reported hypertension particularly when not confined to pregnancy. The latter was also associated with accelerated fetal growth, moderate or severe hypertension in the mother when pregnant with the cohort member, being relatively taller than your mother, and lack of educational qualifications. Hypertension confined to pregnancy was more likely among women who were themselves firstborn or older at childbirth. Neither maternal smoking during cohort's gestation nor cohort member's gestational age had a significant effect. The results are consistent with previous reports that fetal growth effects are less marked if gestation is short. The relationships between fetal growth and subsequent hypertension are extremely complex and variable, and need to be studied allowing for deviations from growth potential. Adult weight for height remains the strongest predictor of hypertension. The results suggest that losing weight is likely to have the same proportional benefit in women with and without a history of retarded fetal growth.

Ethics of fetal tissue transplantation.

PubMed Central

Sanders, L M; Giudice, L; Raffin, T A

1993-01-01

Now that the Clinton Administration has overturned the ban on federal funding for fetal tissue transplantation, old ethical issues renew their relevance and new ethical issues arise. Is fetal tissue transplantation necessary and beneficial? Are fetal rights violated by the use of fetal tissue in research? Is there a moral danger that the potential of fetal tissue donation will encourage elective abortions? Should pregnant women be allowed to designate specific fetal transplant recipients? What criteria should be used to select fetal tissue transplants? Whose consent should be required for the use of fetal tissue for transplantation? We review the current state of clinical research with fetal tissue transplantation, the legal history of fetal tissue research, the major arguments against the use of fetal tissue for transplantation, and the new postmoratorium ethical dilemmas. We include recommendations for guidelines to govern the medical treatment of fetal tissue in transplantation. Images PMID:8236984

Accelerated acidosis in response to variable fetal heart rate decelerations in chronically hypoxic ovine fetuses.

PubMed

Amaya, Kevin E; Matushewski, Brad; Durosier, L Daniel; Frasch, Martin G; Richardson, Bryan S; Ross, Michael G

2016-02-01

Due to limitations of technology, clinicians are typically unable to determine if human fetuses are normoxic or moderately, chronically hypoxic. Risk factors for chronic hypoxia include fetal growth restriction, which is associated with an increased incidence of oligohydramnios and thus a risk for umbilical cord occlusion (UCO) and variable fetal heart rate (FHR) decelerations. At delivery, fetal growth restriction infants (<3rd percentile) have nearly twice the incidence of low Apgar scores and umbilical pH <7.0. Despite the risks of oligohydramnios and intermittent UCO, there is little understanding of the acid/base responses rates of chronically hypoxic fetuses to variable FHR decelerations as might occur during human labor. We sought to compare the increase in base deficit (BD) among chronically hypoxic as compared to normoxic ovine fetuses in response to simulated mild, moderate, and severe variable FHR decelerations. Near-term ovine fetuses were chronically prepared with brachial artery catheters and an inflatable umbilical cuff occluder. Following a recovery period, normoxic (n = 9) and spontaneously hypoxic (n = 5) fetuses were identified (arterial O2 saturation ≤55%). Both animal groups underwent graded, 1-minute occlusions every 2.5 minutes with 1 hour of mild (∼30 beats/min [bpm] decrease from baseline), 1 hour of moderate (∼60 bpm decrease from baseline), and up to 2 hours of severe (∼90 bpm decrease from baseline) variable FHR decelerations until fetal arterial pH reached 7.00, when occlusions were stopped. Repetitive UCO resulted in development of acidosis (pH <7.0) in both groups. Hypoxic and normoxic fetuses demonstrated similar BD increases in response to both mild (0.39, interquartile range [IQR] 0.28-0.45 vs 0.26, IQR 0.01-0.30 mEq/L/10 min, P = .25) and severe (1.97, IQR 1.50-2.43 vs 1.51, IQR 0.97-2.45 mEq/L/10 min, P = .63) variable decelerations. However, moderate variable decelerations increased BD in hypoxic fetuses at 2.5 times the

An Autopsy Case of a Pregnant Woman With Severe Placental and Fetal Damage From Domestic Violence.

PubMed

Kanawaku, Yoshimasa; Takahashi, Shirushi; Kanetake, Jun; Funayama, Masato

2015-09-01

We present an autopsy case of a pregnant woman who was a victim of domestic violence. The deceased showed injuries mainly to her head and abdomen. Postmortem examination revealed 1400 mL of abdominal hemorrhage, ablation of the perimetrium, placental avulsion, and intracranial hematoma. The cause of death was diagnosed as hemorrhagic shock. The uterus contained a fetus of 7 months' gestational age. Fetal autopsy revealed laceration of the lungs, laceration and avulsion of the liver, and 15 mL of hemoperitoneum. Both placental and fetal injuries suggested repeated severe attacks to the abdomen, such as those expected to result from kicking or hitting.

Fetal and maternal outcomes in pregnancies complicated with fetal macrosomia.

PubMed

Alsammani, Mohamed Alkahatim; Ahmed, Salah Roshdy

2012-06-01

Fetal macrosomia remains a considerable challenge in current obstetrics due to the fetal and maternal complications associated with this condition. This study was designed to determine the prevalence of fetal macrosomia and associated fetal and maternal morbidity and mortality in the Al Qassim Region of Saudi Arabia. This register-based study was conducted from January 1, 2011 through December 30, 2011 at the Maternity and Child Hospital, Qassim, Saudi Arabia. Macrosomia was defined as birth weight of 4 kg or greater. Malformed babies and those born dead were excluded. The total number of babies delivered was 9241; of these, 418 were macrosomic. Thus, the prevalence of fetal macrosomia was 4.5%. The most common maternal complications were postpartum hemorrhage (5 cases, 1.2%), perineal tear (7 cases, 1.7%), cervical lacerations (3 cases, 0.7%), and shoulder dystocia (40 cases, 9.6%) that resulted in 4 cases of Erb's palsy (0.96%), and 6 cases of bone fractures (1.4%). The rate of cesarean section among women delivering macrosomic babies was 47.6% (199), while 52.4% (219) delivered vaginally. Despite extensive efforts to reduce fetal and maternal complications associated with macrosomia, considerable fetal and maternal morbidity remain associated with this condition.

The Pulmonary Surfactant: Impact of Tobacco Smoke and Related Compounds on Surfactant and Lung Development

PubMed Central

Scott, J Elliott

2004-01-01

Cigarette smoking, one of the most pervasive habits in society, presents many well established health risks. While lung cancer is probably the most common and well documented disease associated with tobacco exposure, it is becoming clear from recent research that many other diseases are causally related to smoking. Whether from direct smoking or inhaling environmental tobacco smoke (ETS), termed secondhand smoke, the cells of the respiratory tissues and the lining pulmonary surfactant are the first body tissues to be directly exposed to the many thousands of toxic chemicals in tobacco. Considering the vast surface area of the lung and the extreme attenuation of the blood-air barrier, it is not surprising that this organ is the primary route for exposure, not just to smoke but to most environmental contaminants. Recent research has shown that the pulmonary surfactant, a complex mixture of phospholipids and proteins, is the first site of defense against particulates or gas components of smoke. However, it is not clear what effect smoke has on the surfactant. Most studies have demonstrated that smoking reduces bronchoalveolar lavage phospholipid levels. Some components of smoke also appear to have a direct detergent-like effect on the surfactant while others appear to alter cycling or secretion. Ultimately these effects are reflected in changes in the dynamics of the surfactant system and, clinically in changes in lung mechanics. Similarly, exposure of the developing fetal lung through maternal smoking results in postnatal alterations in lung mechanics and higher incidents of wheezing and coughing. Direct exposure of developing lung to nicotine induces changes suggestive of fetal stress. Furthermore, identification of nicotinic receptors in fetal lung airways and corresponding increases in airway connective tissue support a possible involvement of nicotine in postnatal asthma development. Finally, at the level of the alveoli of the lung, colocalization of nicotinic

The Pulmonary Surfactant: Impact of Tobacco Smoke and Related Compounds on Surfactant and Lung Development

PubMed Central

Scott, J Elliott

2004-01-01

Cigarette smoking, one of the most pervasive habits in society, presents many well established health risks. While lung cancer is probably the most common and well documented disease associated with tobacco exposure, it is becoming clear from recent research that many other diseases are causally related to smoking. Whether from direct smoking or inhaling environmental tobacco smoke (ETS), termed secondhand smoke, the cells of the respiratory tissues and the lining pulmonary surfactant are the first body tissues to be directly exposed to the many thousands of toxic chemicals in tobacco. Considering the vast surface area of the lung and the extreme attenuation of the blood-air barrier, it is not surprising that this organ is the primary route for exposure, not just to smoke but to most environmental contaminants. Recent research has shown that the pulmonary surfactant, a complex mixture of phospholipids and proteins, is the first site of defense against particulates or gas components of smoke. However, it is not clear what effect smoke has on the surfactant. Most studies have demonstrated that smoking reduces bronchoalveolar lavage phospholipid levels. Some components of smoke also appear to have a direct detergent-like effect on the surfactant while others appear to alter cycling or secretion. Ultimately these effects are reflected in changes in the dynamics of the surfactant system and, clinically in changes in lung mechanics. Similarly, exposure of the developing fetal lung through maternal smoking results in postnatal alterations in lung mechanics and higher incidents of wheezing and coughing. Direct exposure of developing lung to nicotine induces changes suggestive of fetal stress. Furthermore, identification of nicotinic receptors in fetal lung airways and corresponding increases in airway connective tissue support a possible involvement of nicotine in postnatal asthma development. Finally, at the level of the alveoli of the lung, colocalization of nicotinic

RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer

PubMed Central

Rao, Shuan; Sigl, Verena; Wimmer, Reiner Alois; Novatchkova, Maria; Jais, Alexander; Wagner, Gabriel; Handschuh, Stephan; Uribesalgo, Iris; Hagelkruys, Astrid; Kozieradzki, Ivona; Tortola, Luigi; Nitsch, Roberto; Cronin, Shane J.; Orthofer, Michael; Branstetter, Daniel; Canon, Jude; Rossi, John; D'Arcangelo, Manolo; Botling, Johan; Micke, Patrick; Fleur, Linnea La; Edlund, Karolina; Bergqvist, Michael; Ekman, Simon; Lendl, Thomas; Popper, Helmut; Takayanagi, Hiroshi; Kenner, Lukas; Hirsch, Fred R.; Dougall, William

2017-01-01

Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women; however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts. Clonal genetic inactivation of KRasG12D in mouse lung epithelial cells markedly impairs the progression of KRasG12D-driven lung cancer, resulting in a significant survival advantage. Mechanistically, RANK rewires energy homeostasis in human and murine lung cancer cells and promotes expansion of lung cancer stem-like cells, which is blocked by inhibiting mitochondrial respiration. Our data also indicate survival differences in KRasG12D-driven lung cancer between male and female mice, and we show that female sex hormones can promote lung cancer progression via the RANK pathway. These data uncover a direct role for RANK in lung cancer and may explain why female sex hormones accelerate lung cancer development. Inhibition of RANK using the approved drug denosumab may be a therapeutic drug candidate for primary lung cancer. PMID:29118048

3D image display of fetal ultrasonic images by thin shell

NASA Astrophysics Data System (ADS)

Wang, Shyh-Roei; Sun, Yung-Nien; Chang, Fong-Ming; Jiang, Ching-Fen

1999-05-01

Due to the properties of convenience and non-invasion, ultrasound has become an essential tool for diagnosis of fetal abnormality during women pregnancy in obstetrics. However, the 'noisy and blurry' nature of ultrasound data makes the rendering of the data a challenge in comparison with MRI and CT images. In spite of the speckle noise, the unwanted objects usually occlude the target to be observed. In this paper, we proposed a new system that can effectively depress the speckle noise, extract the target object, and clearly render the 3D fetal image in almost real-time from 3D ultrasound image data. The system is based on a deformable model that detects contours of the object according to the local image feature of ultrasound. Besides, in order to accelerate rendering speed, a thin shell is defined to separate the observed organ from unrelated structures depending on those detected contours. In this way, we can support quick 3D display of ultrasound, and the efficient visualization of 3D fetal ultrasound thus becomes possible.

Fetal electrocardiogram (ECG) for fetal monitoring during labour.

PubMed

Neilson, James P

2015-12-21

Hypoxaemia during labour can alter the shape of the fetal electrocardiogram (ECG) waveform, notably the relation of the PR to RR intervals, and elevation or depression of the ST segment. Technical systems have therefore been developed to monitor the fetal ECG during labour as an adjunct to continuous electronic fetal heart rate monitoring with the aim of improving fetal outcome and minimising unnecessary obstetric interference. To compare the effects of analysis of fetal ECG waveforms during labour with alternative methods of fetal monitoring. The Cochrane Pregnancy and Childbirth Group's Trials Register (latest search 23 September 2015) and reference lists of retrieved studies. Randomised trials comparing fetal ECG waveform analysis with alternative methods of fetal monitoring during labour. One review author independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. One review author assessed the quality of the evidence using the GRADE approach. Seven trials (27,403 women) were included: six trials of ST waveform analysis (26,446 women) and one trial of PR interval analysis (957 women). The trials were generally at low risk of bias for most domains and the quality of evidence for ST waveform analysis trials was graded moderate to high. In comparison to continuous electronic fetal heart rate monitoring alone, the use of adjunctive ST waveform analysis made no obvious difference to primary outcomes: births by caesarean section (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.96 to 1.08; six trials, 26,446 women; high quality evidence); the number of babies with severe metabolic acidosis at birth (cord arterial pH less than 7.05 and base deficit greater than 12 mmol/L) (average RR 0.72, 95% CI 0.43 to 1.20; six trials, 25,682 babies; moderate quality evidence); or babies with neonatal encephalopathy (RR 0.61, 95% CI 0.30 to 1.22; six trials, 26,410 babies; high quality evidence). There were, however, on average

Protein deficiency and intestinal nematode infection in pregnant mice differentially impact fetal growth through specific stress hormones, growth factors, and cytokines.

PubMed

Starr, Lisa M; Scott, Marilyn E; Koski, Kristine G

2015-01-01

Protein deficiency (PD) and intestinal nematode infections commonly co-occur during pregnancy and impair fetal growth, but the complex network of signals has not been explored. Our objective was to assess those stress hormones, growth factors, and cytokines affected by maternal PD and nematode infection and associated with fetal growth. Using a 2 × 2 factorial design, CD-1 mice, fed protein-sufficient (PS; 24%) or protein-deficient (PD; 6%) isoenergetic diets, were either uninfected or infected every 5 d with Heligmosomoides bakeri, beginning on gestational day (GD) 5. Biomarker concentrations were measured on GD 18 in maternal serum (m), fetal serum (f), and amniotic fluid (af) by using Luminex. Maternal PD lowered fetal body mass (PS/uninfected 1.25 ± 0.02 g, PS/infected 1.19 ± 0.02 g vs. PD/uninfected 1.11 ± 0.02 g, PD/infected 0.97 ± 0.02 g; P = 0.02), fetal lung (P = 0.005), and liver (P = 0.003) but not brain mass, whereas maternal infection lowered fetal length (PS/uninfected 2.28 ± 0.02 cm, PD/uninfected 2.27 ± 0.03 cm vs. PS/infected 2.21 ± 0.03 cm, PD/infected 2.11 ± 0.02 cm; P = 0.05) and kidney mass (P = 0.04). PD elevated stress hormones (m-adrenocortiotropic hormone, f-corticosterone, af-corticosterone) and reduced insulin-like growth factor 1 in all compartments (P ≤ 0.01), but these were unassociated with fetal mass or length. Fetal mass was positively associated with f-leptin (R(2) = 0.71, P = 0.0001) and negatively with fetal cytokines [tumor necrosis factor-α: R(2) = 0.62, P = 0.001; interleukin-4 (IL-4): R(2) = 0.63, P = 0.0004]. In contrast, maternal infection lowered f-prolactin (P = 0.02) that was positively associated with fetal length (R(2) = 0.43; P = 0.03); no other biomarker was affected by infection. Regression analyses showed associations between organ growth, cytokines, and growth factors: 1) thymus, spleen, heart, and brain with m-IL-10; 2) brain and kidney with f-vascular endothelial growth factor, af

Fetal endocrine and metabolic adaptations to hypoxia: the role of the hypothalamic-pituitary-adrenal axis

PubMed Central

Newby, Elizabeth A.; Myers, Dean A.

2015-01-01

In utero, hypoxia is a significant yet common stress that perturbs homeostasis and can occur due to preeclampsia, preterm labor, maternal smoking, heart or lung disease, obesity, and high altitude. The fetus has the extraordinary capacity to respond to stress during development. This is mediated in part by the hypothalamic-pituitary-adrenal (HPA) axis and more recently explored changes in perirenal adipose tissue (PAT) in response to hypoxia. Obvious ethical considerations limit studies of the human fetus, and fetal studies in the rodent model are limited due to size considerations and major differences in developmental landmarks. The sheep is a common model that has been used extensively to study the effects of both acute and chronic hypoxia on fetal development. In response to high-altitude-induced, moderate long-term hypoxia (LTH), both the HPA axis and PAT adapt to preserve normal fetal growth and development while allowing for responses to acute stress. Although these adaptations appear beneficial during fetal development, they may become deleterious postnatally and into adulthood. The goal of this review is to examine the role of the HPA axis in the convergence of endocrine and metabolic adaptive responses to hypoxia in the fetus. PMID:26173460

[Incidence of fetal macrosomia: maternal and fetal morbidity].

PubMed

Rodríguez-Rojas, R R; Cantú-Esquivel, M G; Benavides-de la Garza, L; Benavides-de Anda, L

1996-06-01

The macrosomia is an obstetric eventuality associated to high maternal-fetal morbidity-mortality. This assay was planned in order to know the incidence of macrosomia in our institution, the relation between vaginal and abdominal deliveries and the fetal-maternal morbidity we reviewed 3590 records and we found 5.6% incidence of macrosomia in the global obstetric population. There was 58% of vaginal deliveries, 68% of the newborn were male. The main complications were in the C. sections, 2 laceration of the hysterectomy, and 2 peroperative atonias. In the vaginal deliveries, the lacerations of III and IV grade were 9 of each grade. The main fetal complications were 5 slight to severe asphyxia and 4 shoulder dystocias. This assay concludes that the macrosomia in our service is similar to the already published ones, a 42% were C. section and the maternal-fetal morbidity was low.

The use of non-invasive fetal electrocardiography in diagnosing second-degree fetal atrioventricular block.

PubMed

Lakhno, Igor; Behar, Joachim A; Oster, Julien; Shulgin, Vyacheslav; Ostras, Oleksii; Andreotti, Fernando

2017-01-01

Complete atrioventricular block in fetuses is known to be mostly associated with autoimmune disease and can be irreversible if no steroids treatment is provided. Conventional methods used in clinical practice for diagnosing fetal arrhythmia are limited since they do not reflect the primary electrophysiological conduction processes that take place in the myocardium. The non-invasive fetal electrocardiogram has the potential to better support fetal arrhythmias diagnosis through the continuous analysis of the beat to beat variation of the fetal heart rate and morphological analysis of the PQRST complex. We present two retrospective case reports on which atrioventricular block diagnosis could have been supported by the non-invasive fetal electrocardiogram. The two cases comprised a 22-year-old pregnant woman with the gestational age of 31 weeks and a 25-year-old pregnant woman with the gestational age of 41 weeks. Both women were admitted to the Department of Maternal and Fetal Medicine at the Kyiv and Kharkiv municipal perinatal clinics. Patients were observed using standard fetal monitoring methods as well as the non-invasive fetal electrocardiogram. The non-invasive fetal electrocardiographic recordings were analyzed retrospectively, where it is possible to identify the presence of the atrioventricular block. This study demonstrates, for the first time, the feasibility of the non-invasive fetal electrocardiogram as a supplementary method to diagnose of the fetal atrioventricular block. Combined with current fetal monitoring techniques, non-invasive fetal electrocardiography could support clinical decisions.

Quantification of fetal heart rate regularity using symbolic dynamics

NASA Astrophysics Data System (ADS)

van Leeuwen, P.; Cysarz, D.; Lange, S.; Geue, D.; Groenemeyer, D.

2007-03-01

Fetal heart rate complexity was examined on the basis of RR interval time series obtained in the second and third trimester of pregnancy. In each fetal RR interval time series, short term beat-to-beat heart rate changes were coded in 8bit binary sequences. Redundancies of the 28 different binary patterns were reduced by two different procedures. The complexity of these sequences was quantified using the approximate entropy (ApEn), resulting in discrete ApEn values which were used for classifying the sequences into 17 pattern sets. Also, the sequences were grouped into 20 pattern classes with respect to identity after rotation or inversion of the binary value. There was a specific, nonuniform distribution of the sequences in the pattern sets and this differed from the distribution found in surrogate data. In the course of gestation, the number of sequences increased in seven pattern sets, decreased in four and remained unchanged in six. Sequences that occurred less often over time, both regular and irregular, were characterized by patterns reflecting frequent beat-to-beat reversals in heart rate. They were also predominant in the surrogate data, suggesting that these patterns are associated with stochastic heart beat trains. Sequences that occurred more frequently over time were relatively rare in the surrogate data. Some of these sequences had a high degree of regularity and corresponded to prolonged heart rate accelerations or decelerations which may be associated with directed fetal activity or movement or baroreflex activity. Application of the pattern classes revealed that those sequences with a high degree of irregularity correspond to heart rate patterns resulting from complex physiological activity such as fetal breathing movements. The results suggest that the development of the autonomic nervous system and the emergence of fetal behavioral states lead to increases in not only irregular but also regular heart rate patterns. Using symbolic dynamics to

Tumor necrosis factor-α accelerates the resolution of established pulmonary fibrosis in mice by targeting profibrotic lung macrophages.

PubMed

Redente, Elizabeth F; Keith, Rebecca C; Janssen, William; Henson, Peter M; Ortiz, Luis A; Downey, Gregory P; Bratton, Donna L; Riches, David W H

2014-04-01

Idiopathic pulmonary fibrosis (IPF) is a relentless, fibrotic parenchymal lung disease in which alternatively programmed macrophages produce profibrotic molecules that promote myofibroblast survival and collagen synthesis. Effective therapies to treat patients with IPF are lacking, and conventional therapy may be harmful. We tested the hypothesis that therapeutic lung delivery of the proinflammatory cytokine tumor necrosis factor (TNF)-α into wild-type fibrotic mice would reduce the profibrotic milieu and accelerate the resolution of established pulmonary fibrosis. Fibrosis was assessed in bleomycin-instilled wild-type and TNF-α(-/-) mice by measuring hydroxyproline levels, static compliance, and Masson's trichrome staining. Macrophage infiltration and programming status was assessed by flow cytometry of enzymatically digested lung and in situ immunostaining. Pulmonary delivery of TNF-α to wild-type mice with established pulmonary fibrosis was found to reduce their fibrotic burden, to improve lung function and architecture, and to reduce the number and programming status of profibrotic alternatively programmed macrophages. In contrast, fibrosis and alternative macrophage programming were prolonged in bleomycin-instilled TNF-α(-/-) mice. To address the role of the reduced numbers of alternatively programmed macrophages in the TNF-α-induced resolution of established pulmonary fibrosis, we conditionally depleted macrophages in MAFIA (MAcrophage Fas-Induced Apoptosis) mice. Conditional macrophage depletion phenocopied the resolution of established pulmonary fibrosis observed after therapeutic TNF-α delivery. Taken together, our results show for the first time that TNF-α is involved in the resolution of established pulmonary fibrosis via a mechanism involving reduced numbers and programming status of profibrotic macrophages. We speculate that pulmonary delivery of TNF-α or augmenting its signaling pathway represent a novel therapeutic strategy to resolve

Placental Inflammation and Fetal Injury in a Rare Zika Case Associated With Guillain-Barré Syndrome and Abortion.

PubMed

Rabelo, Kíssila; Souza, Luiz J; Salomão, Natália G; Oliveira, Edson R A; Sentinelli, Lynna de Paula; Lacerda, Marcelle S; Saraquino, Pedro B; Rosman, Fernando C; Basílio-de-Oliveira, Rodrigo; Carvalho, Jorge J; Paes, Marciano V

2018-01-01

Zika virus (ZIKV) is an emerging virus involved in recent outbreaks in Brazil. The association between the virus and Guillain-Barré syndrome (GBS) or congenital disorders has raised a worldwide concern. In this work, we investigated a rare Zika case, which was associated with GBS and spontaneous retained abortion. Using specific anti-ZIKV staining, the virus was identified in placenta (mainly in Hofbauer cells) and in several fetal tissues, such as brain, lungs, kidneys, skin and liver. Histological analyses of the placenta and fetal organs revealed different types of tissue abnormalities, which included inflammation, hemorrhage, edema and necrosis in placenta, as well as tissue disorganization in the fetus. Increased cellularity (Hofbauer cells and TCD8 + lymphocytes), expression of local pro-inflammatory cytokines such as IFN-γ and TNF-α, and other markers, such as RANTES/CCL5 and VEGFR2, supported placental inflammation and dysfunction. The commitment of the maternal-fetal link in association with fetal damage gave rise to a discussion regarding the influence of the maternal immunity toward the fetal development. Findings presented in this work may help understanding the ZIKV immunopathogenesis under the rare contexts of spontaneous abortions in association with GBS.

Uterine artery blood flow, fetal hypoxia and fetal growth

PubMed Central

Browne, Vaughn A.; Julian, Colleen G.; Toledo-Jaldin, Lillian; Cioffi-Ragan, Darleen; Vargas, Enrique; Moore, Lorna G.

2015-01-01

Evolutionary trade-offs required for bipedalism and brain expansion influence the pregnancy rise in uterine artery (UtA) blood flow and, in turn, reproductive success. We consider the importance of UtA blood flow by reviewing its determinants and presenting data from 191 normotensive (normal, n = 125) or hypertensive (preeclampsia (PE) or gestational hypertension (GH), n = 29) Andean residents of very high (4100–4300 m) or low altitude (400 m, n = 37). Prior studies show that UtA blood flow is reduced in pregnancies with intrauterine growth restriction (IUGR) but whether the IUGR is due to resultant fetal hypoxia is unclear. We found higher UtA blood flow and Doppler indices of fetal hypoxia in normotensive women at high versus low altitude but similar fetal growth. UtA blood flow was markedly lower in early-onset PE versus normal high-altitude women, and their fetuses more hypoxic as indicated by lower fetal heart rate, Doppler indices and greater IUGR. We concluded that, despite greater fetal hypoxia, fetal growth was well defended by higher UtA blood flows in normal Andeans at high altitude but when compounded by lower UtA blood flow in early-onset PE, exaggerated fetal hypoxia caused the fetus to respond by decreasing cardiac output and redistributing blood flow to help maintain brain development at the expense of growth elsewhere. We speculate that UtA blood flow is not only an important supply line but also a trigger for stimulating the metabolic and other processes regulating feto-placental metabolism and growth. Studies using the natural laboratory of high altitude are valuable for identifying the physiological and genetic mechanisms involved in human reproductive success. PMID:25602072

Mechanical stretch-induced serotonin release from pulmonary neuroendocrine cells: implications for lung development.

PubMed

Pan, Jie; Copland, Ian; Post, Martin; Yeger, Herman; Cutz, Ernest

2006-01-01

Pulmonary neuroendocrine cells (PNEC) produce amine (serotonin, 5-HT) and peptides (e.g., bombesin, calcitonin) with growth factor-like properties and are thought to play an important role in lung development. Because physical forces are essential for lung growth and development, we investigated the effects of mechanical strain on 5-HT release in PNEC freshly isolated from rabbit fetal lung and in the PNEC-related tumor H727 cell line. Cultures exposed to sinusoidal cyclic stretch showed a significant 5-HT release inhibitable with gadolinium chloride (10 nM), a blocker of mechanosensitive channels. In contrast to hypoxia (Po2 approximately 20 mmHg), stretch-induced 5-HT release was not affected by Ca2+-free medium or nifedipine (50 microM), excluding the exocytic pathway. In H727 cells, stretch failed to release calcitonin, a peptide stored within dense core vesicles (DCV), whereas hypoxia caused massive calcitonin release. 5-HT released by mechanical stretch is derived predominantly from the cytoplasmic pool, because it is rapid ( approximately 5 min) and is releasable from early (20 days of gestation) fetal PNEC containing few DCV. Both mechanical stretch and hypoxia upregulated expression of tryptophan hydroxylase, the rate-limiting enzyme of 5-HT synthesis. We conclude that mechanical strain is an important physiological stimulus for the release of 5-HT from PNEC via mechanosensitive channels with potential effects on lung development and resorption of lung fluid at the time of birth.

Development of a piezopolymer pressure sensor for a portable fetal heart rate monitor

NASA Technical Reports Server (NTRS)

Zuckerwar, A. J.; Pretlow, R. A.; Stoughton, J. W.; Baker, D. A.

1993-01-01

A piezopolymer pressure sensor has been developed for service in a portable fetal heart rate monitor, which will permit an expectant mother to perform the fetal nonstress test, a standard predelivery test, in her home. Several sensors are mounted in an array on a belt worn by the mother. The sensor design conforms to the distinctive features of the fetal heart tone, namely, the acoustic signature, frequency spectrum, signal amplitude, and localization. The components of a sensor serve to fulfill five functions: signal detection, acceleration cancellation, acoustical isolation, electrical shielding, and electrical isolation of the mother. A theoretical analysis of the sensor response yields a numerical value for the sensor sensitivity, which is compared to experiment in an in vitro sensor calibration. Finally, an in vivo test on patients within the last six weeks of term reveals that nonstress test recordings from the acoustic monitor compare well with those obtained from conventional ultrasound.

Evidence supporting contemporary post-operative radiation therapy (PORT) using linear accelerators in N2 lung cancer.

PubMed

Patel, Suchit H; Ma, Yan; Wernicke, A Gabriella; Nori, Dattatreyudu; Chao, K S C; Parashar, Bhupesh

2014-05-01

Post-operative radiotherapy (PORT) treatment for lung cancer declined since a meta-analysis failed to show benefit in patients with N2 disease. Because several included studies employed outmoded radiation planning and delivery techniques, we sought to determine whether PORT with modern technology benefits patients with N2 disease. We conducted searches of the published literature. For inclusion, studies must have included patients with stage III-N2 lung cancer treated with PORT using only linear accelerators, used a control group that did not receive PORT, and reported outcome data for overall survival (OS). Prospective and retrospective analyses were included. Exclusion criteria were the use of cobalt devices or orthovoltage radiation. Data were evaluated with random-effects models. Three prospective and eight retrospective studies were included. The PORT and no-PORT groups included 1368 and 1360 patients, respectively. The PORT group had significantly improved OS over the no-PORT group (hazard ratio [HR] = 0.77, 95% confidence interval [CI] 0.62-0.96, P = 0.020). Locoregional recurrence-free survival (LRFS) in 10 studies for which data was available was also improved in the PORT group (HR = 0.51, CI 0.41-0.65, P < 0.001). PORT was associated with significantly lower risk of death and locoregional recurrence in patients with N2 lung cancer. Our study was limited by lack of access to individual patient data, which would have enabled more detailed analyses. Regardless, data thus far suggest PORT may be associated with a survival benefit. Given a lack of large-scale prospective data, clinical trials evaluating PORT with modern technology are warranted. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Acceleration of lung disease in children with cystic fibrosis after Pseudomonas aeruginosa acquisition.

PubMed

Kosorok, M R; Zeng, L; West, S E; Rock, M J; Splaingard, M L; Laxova, A; Green, C G; Collins, J; Farrell, P M

2001-10-01

As part of the ongoing Wisconsin Cystic Fibrosis (CF) Neonatal Screening Project, we had the unique opportunity to study the longitudinal relationship between Pseudomonas aeruginosa (Pa) acquisition and infection and developing lung disease in children with CF. The primary objective was to determine whether acquisition of Pa was associated with a measurable change in the progression of lung disease. Two outcome measures were used to study 56 patients who were diagnosed through newborn screening: 1) Wisconsin additive chest radiograph score (WCXR), based on the average of scores from a pulmonologist and a radiologist, and 2) the highest forced expired volume in 1 sec (FEV(1))/forced vital capacity (FVC) ratio. We used two measures of Pa acquisition: 1) time of first positive protocol-determined oropharyngeal (with cough) culture, and 2) the magnitude of antibody titer detected by ELISA assays, using as antigen a crude cell lysate, purified exotoxin A, or an elastase toxoid prepared from three Pa strains. Other predictor variables included age, pancreatic status, height-for age, and weight-for-age-percentiles. The best regression model for predicting changes in the WCXR included time to first positive culture and antibody titer for Pa elastase. Prior to Pa acquisition, WCXR worsened by 0.45 points/year (P > 0.25); after Pa acquisition, the rate of worsening increased significantly (P < 0.001) to 1.40 points/year. Each antibody titer level (log base 2) increased the score by 0.48 points (P < 0.001). The best regression model for predicting change in the FEV(1)/FVC included only time to first positive culture. Prior to Pa acquisition, the FEV(1)/FVC ratio declined by 1.29%/year; after Pa infection, the rate of decrease significantly accelerated to 1.81%/year (P = 0.001). Our data show that Pa acquisition is associated with declining pulmonary status in children with CF, and that this effect is probably gradual rather than precipitous. Because these patients were

Cumulative exposure to dust causes accelerated decline in lung function in tunnel workers

PubMed Central

Ulvestad, B; Bakke, B; Eduard, W; Kongerud, J; Lund, M

2001-01-01

most important risk factor for respiratory symptoms. The finding of accelerated decline in lung function in tunnel workers suggests that better control of exposures is needed.


Keywords: heavy construction; respirable dust; lung function PMID:11555688

Antenatal fetal heart rate and "maternal intuition" as predictors of fetal sex.

PubMed

Genuis, S; Genuis, S K; Chang, W C

1996-06-01

To determine if the antenatal fetal heart rate is a reliable predictor of fetal sex, if there is any correlation between "maternal intuition" and fetal gender, and if maternal intuition favors one sex over the other. Two hundred twelve consecutive maternity patients with singleton gestations underwent a total of 2,261 antepartum visits. Fetal heart rate assessment was carried out between 14 and 41 weeks of gestation. At 32 weeks, participants were asked if they had a strong intuitive feeling regarding the fetal gender. Following birth, data on the infant were recorded, and the information was analyzed. There was no significant difference in the baseline fetal heart rate between male and female fetuses at any recorded gestational age. One hundred ten patients (51.9%) in the sample indicated a strong belief about the sex of their fetuses, with the majority (63.6%) predicting a male. The accuracy of maternal intuition, however, was not significantly different from that of random guessing. In the current era of declining family size, an increased focus on absolute reproductive choice and proliferating reproductive technological services, prenatal sex determination and sex selection will continue to provoke increasing attention. Fetal heart rate determination and maternal intuition, however, are not valid predictors of fetal gender.

Survival Benefit of Lung Transplantation in the Modern Era of Lung Allocation.

PubMed

Vock, David M; Durheim, Michael T; Tsuang, Wayne M; Finlen Copeland, C Ashley; Tsiatis, Anastasios A; Davidian, Marie; Neely, Megan L; Lederer, David J; Palmer, Scott M

2017-02-01

Lung transplantation is an accepted and increasingly employed treatment for advanced lung diseases, but the anticipated survival benefit of lung transplantation is poorly understood. To determine whether and for which patients lung transplantation confers a survival benefit in the modern era of U.S. lung allocation. Data on 13,040 adults listed for lung transplantation between May 2005 and September 2011 were obtained from the United Network for Organ Sharing. A structural nested accelerated failure time model was used to model the survival benefit of lung transplantation over time. The effects of patient, donor, and transplant center characteristics on the relative survival benefit of transplantation were examined. Overall, 73.8% of transplant recipients were predicted to achieve a 2-year survival benefit with lung transplantation. The survival benefit of transplantation varied by native disease group (P = 0.062), with 2-year expected benefit in 39.2 and 98.9% of transplants occurring in those with obstructive lung disease and cystic fibrosis, respectively, and by lung allocation score at the time of transplantation (P < 0.001), with net 2-year benefit in only 6.8% of transplants occurring for lung allocation score less than 32.5 and in 99.9% of transplants for lung allocation score exceeding 40. A majority of adults undergoing transplantation experience a survival benefit, with the greatest potential benefit in those with higher lung allocation scores or restrictive native lung disease or cystic fibrosis. These results provide novel information to assess the expected benefit of lung transplantation at an individual level and to enhance lung allocation policy.

Internal fetal monitoring (image)

MedlinePlus

Internal fetal monitoring involves placing a electrode directly on the fetal scalp through the cervix. This test is performed to evaluate fetal heart rate and variability between beats, especially ...

RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer.

PubMed

Rao, Shuan; Sigl, Verena; Wimmer, Reiner Alois; Novatchkova, Maria; Jais, Alexander; Wagner, Gabriel; Handschuh, Stephan; Uribesalgo, Iris; Hagelkruys, Astrid; Kozieradzki, Ivona; Tortola, Luigi; Nitsch, Roberto; Cronin, Shane J; Orthofer, Michael; Branstetter, Daniel; Canon, Jude; Rossi, John; D'Arcangelo, Manolo; Botling, Johan; Micke, Patrick; Fleur, Linnea La; Edlund, Karolina; Bergqvist, Michael; Ekman, Simon; Lendl, Thomas; Popper, Helmut; Takayanagi, Hiroshi; Kenner, Lukas; Hirsch, Fred R; Dougall, William; Penninger, Josef M

2017-10-15

Lung cancer is the leading cause of cancer deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung cancer in women; however, the underlying mechanisms remain unclear. Here we report that the receptor activator of nuclear factor-kB (RANK), the key regulator of osteoclastogenesis, is frequently expressed in primary lung tumors, an active RANK pathway correlates with decreased survival, and pharmacologic RANK inhibition reduces tumor growth in patient-derived lung cancer xenografts. Clonal genetic inactivation of KRas G12D in mouse lung epithelial cells markedly impairs the progression of KRas G12D -driven lung cancer, resulting in a significant survival advantage. Mechanistically, RANK rewires energy homeostasis in human and murine lung cancer cells and promotes expansion of lung cancer stem-like cells, which is blocked by inhibiting mitochondrial respiration. Our data also indicate survival differences in KRas G12D -driven lung cancer between male and female mice, and we show that female sex hormones can promote lung cancer progression via the RANK pathway. These data uncover a direct role for RANK in lung cancer and may explain why female sex hormones accelerate lung cancer development. Inhibition of RANK using the approved drug denosumab may be a therapeutic drug candidate for primary lung cancer. © 2017 Rao et al.; Published by Cold Spring Harbor Laboratory Press.

Regulation of intramembranous absorption and amniotic fluid volume by constituents in fetal sheep urine

PubMed Central

Jonker, Sonnet S.; Louey, Samantha; Cheung, Cecilia Y.; Brace, Robert A.

2013-01-01

Our objective was to test the hypothesis that fetal urine contains a substance(s) that regulates amniotic fluid volume by altering the rate of intramembranous absorption of amniotic fluid. In late gestation ovine fetuses, amniotic fluid volumes, urine, and lung liquid production rates, swallowed volumes and intramembranous volume and solute absorption rates were measured over 2-day periods under control conditions and when urine was removed and continuously replaced at an equal rate with exogenous fluid. Intramembranous volume absorption rate decreased by 40% when urine was replaced with lactated Ringer solution or lactated Ringer solution diluted 50% with water. Amniotic fluid volume doubled under both conditions. Analysis of the intramembranous sodium and chloride fluxes suggests that the active but not passive component of intramembranous volume absorption was altered by urine replacement, whereas both active and passive components of solute fluxes were altered. We conclude that fetal urine contains an unidentified substance(s) that stimulates active intramembranous transport of amniotic fluid across the amnion into the underlying fetal vasculature and thereby functions as a regulator of amniotic fluid volume. PMID:23824958

Self-gated fetal cardiac MRI with tiny golden angle iGRASP: A feasibility study.

PubMed

Haris, Kostas; Hedström, Erik; Bidhult, Sebastian; Testud, Frederik; Maglaveras, Nicos; Heiberg, Einar; Hansson, Stefan R; Arheden, Håkan; Aletras, Anthony H

2017-07-01

To develop and assess a technique for self-gated fetal cardiac cine magnetic resonance imaging (MRI) using tiny golden angle radial sampling combined with iGRASP (iterative Golden-angle RAdial Sparse Parallel) for accelerated acquisition based on parallel imaging and compressed sensing. Fetal cardiac data were acquired from five volunteers in gestational week 29-37 at 1.5T using tiny golden angles for eddy currents reduction. The acquired multicoil radial projections were input to a principal component analysis-based compression stage. The cardiac self-gating (CSG) signal for cardiac gating was extracted from the acquired radial projections and the iGRASP reconstruction procedure was applied. In all acquisitions, a total of 4000 radial spokes were acquired within a breath-hold of less than 15 seconds using a balanced steady-state free precession pulse sequence. The images were qualitatively compared by two independent observers (on a scale of 1-4) to a single midventricular cine image from metric optimized gating (MOG) and real-time acquisitions. For iGRASP and MOG images, good overall image quality (2.8 ± 0.4 and 2.6 ± 1.3, respectively, for observer 1; 3.6 ± 0.5 and 3.4 ± 0.9, respectively, for observer 2) and cardiac diagnostic quality (3.8 ± 0.4 and 3.4 ± 0.9, respectively, for observer 1; 3.6 ± 0.5 and 3.6 ± 0.9, respectively, for observer 2) were obtained, with visualized myocardial thickening over the cardiac cycle and well-defined myocardial borders to ventricular lumen and liver/lung tissue. For iGRASP, MOG, and real time, left ventricular lumen diameter (14.1 ± 2.2 mm, 14.2 ± 1.9 mm, 14.7 ± 1.1 mm, respectively) and wall thickness (2.7 ± 0.3 mm, 2.6 ± 0.3 mm, 3.0 ± 0.4, respectively) showed agreement and no statistically significant difference was found (all P > 0.05). Images with iGRASP tended to have higher overall image quality scores compared with MOG and particularly

Down-regulation of lung Kruppel-like factor in the nitrofen-induced hypoplastic lung.

PubMed

Lukošiūtė, A; Doi, T; Dingemann, J; Ruttenstock, E M; Puri, P

2011-01-01

Pulmonary hypoplasia is a primary cause of high morbidity and mortality in neonates with Congenital Diaphragmatic Hernia (CDH). However, the precise pathogenesis of PH associated with CDH is still not clearly understood. It has been recently reported that lung Kruppel-like factor (LKLF), a member of the Kruppel-like factor family of transcription factors, is predominantly expressed in lungs and plays an important role in lung morphogenesis and functional maturation. It has been reported that homozygous deletion of LKLF gene in mice results in reduced lung morphogenesis. It is further reported that chimeric mice derived from LKLF (-/-) embryonic stem cells exhibit delayed lung development especially in the later gestational stages. We therefore designed this study to test the hypothesis that the LKLF gene is down-regulated during later stages of lung development in nitrofen-induced hypoplastic lungs. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetal lungs were harvested on D15, D18, and D21 and divided into 3 groups:control, nitrofen without CDH(CDH(-)) and nitrofen with CDH(CDH(+)) (n=24 for each group). Real-time RT-PCR analysis was performed to investigate pulmonary gene expression levels of LKLF. Differences between the 3 groups at each time point were tested statistically and significance was accepted at p<0.05. Immunohistochemistry was also performed to evaluate LKLF protein expression and distribution. The relative mRNA expression levels of LKLF on D18 and D21 were significantly decreased (p<0.01) in CDH(-) and CDH(+) groups compared to controls. The gene expression levels of LKLF on D15 did not differ significantly between the nitrofen group and controls. Immunohistochemical study showed strong LKLF immunoreactivity on D18 and D21 in nitrofen-induced hypoplastic lung compared to controls, whereas no difference was seen on D15. Our results provide evidence for the first time that LKLF is down-regulated in the later

Existence, functional impairment, and lung repair potential of endothelial colony-forming cells in oxygen-induced arrested alveolar growth.

PubMed

Alphonse, Rajesh S; Vadivel, Arul; Fung, Moses; Shelley, William Chris; Critser, Paul John; Ionescu, Lavinia; O'Reilly, Megan; Ohls, Robin K; McConaghy, Suzanne; Eaton, Farah; Zhong, Shumei; Yoder, Merv; Thébaud, Bernard

2014-05-27

Bronchopulmonary dysplasia and emphysema are life-threatening diseases resulting from impaired alveolar development or alveolar destruction. Both conditions lack effective therapies. Angiogenic growth factors promote alveolar growth and contribute to alveolar maintenance. Endothelial colony-forming cells (ECFCs) represent a subset of circulating and resident endothelial cells capable of self-renewal and de novo vessel formation. We hypothesized that resident ECFCs exist in the developing lung, that they are impaired during arrested alveolar growth in experimental bronchopulmonary dysplasia, and that exogenous ECFCs restore disrupted alveolar growth. Human fetal and neonatal rat lungs contain ECFCs with robust proliferative potential, secondary colony formation on replating, and de novo blood vessel formation in vivo when transplanted into immunodeficient mice. In contrast, human fetal lung ECFCs exposed to hyperoxia in vitro and neonatal rat ECFCs isolated from hyperoxic alveolar growth-arrested rat lungs mimicking bronchopulmonary dysplasia proliferated less, showed decreased clonogenic capacity, and formed fewer capillary-like networks. Intrajugular administration of human cord blood-derived ECFCs after established arrested alveolar growth restored lung function, alveolar and lung vascular growth, and attenuated pulmonary hypertension. Lung ECFC colony- and capillary-like network-forming capabilities were also restored. Low ECFC engraftment and the protective effect of cell-free ECFC-derived conditioned media suggest a paracrine effect. Long-term (10 months) assessment of ECFC therapy showed no adverse effects with persistent improvement in lung structure, exercise capacity, and pulmonary hypertension. Impaired ECFC function may contribute to arrested alveolar growth. Cord blood-derived ECFC therapy may offer new therapeutic options for lung diseases characterized by alveolar damage. © 2014 American Heart Association, Inc.

Pulmonary FGF-18 gene expression is downregulated during the canalicular-saccular stages in nitrofen-induced hypoplastic lungs.

PubMed

Takahashi, Hiromizu; Friedmacher, Florian; Fujiwara, Naho; Hofmann, Alejandro; Kutasy, Balazs; Gosemann, Jan-Hendrik; Puri, Prem

2013-11-01

Pulmonary hypoplasia (PH) associated with congenital diaphragmatic hernia (CDH) represents one of the major challenges in neonatal intensive care. However, the molecular pathogenesis of PH is still poorly understood. In developing fetal lungs, fibroblast growth factor 18 (FGF-18) plays a crucial role in distal airway maturation. FGF-18 knockouts show smaller lung sizes with reduced alveolar spaces and thicker interstitial mesenchymal compartments, highlighting its important function for fetal lung growth and differentiation. We hypothesized that pulmonary FGF-18 gene expression is downregulated during late gestation in nitrofen-induced hypoplastic lungs. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetuses were harvested on D18 and D21, and lungs were divided into three groups: controls, hypoplastic lungs without CDH [CDH(-)], and hypoplastic lungs with CDH [CDH(+)] (n = 24 at each time-point). Pulmonary FGF-18 gene expression levels were analyzed by qRT-PCR. Immunohistochemistry was performed to investigate FGF-18 protein expression/distribution. Relative mRNA levels of pulmonary FGF-18 gene expression were significantly decreased in CDH(-) and CDH(+) on D18 and D21 compared to controls (p < 0.05 and p < 0.01, respectively). Immunoreactivity of FGF-18 was markedly diminished in mesenchymal cells surrounding the airway epithelium on D18 and D21 compared to controls. Downregulation of FGF-18 gene expression in nitrofen-induced hypoplastic lungs suggests that decreased FGF-18 expression during the canalicular-saccular stages may interfere with saccular-alveolar differentiation and distal airway maturation resulting in PH.

Adverse fetal outcome in road accidents: Injury mechanism study and injury criteria development in a pregnant woman finite element model.

PubMed

Auriault, F; Thollon, L; Pérès, J; Behr, M

2016-12-01

This study documents the development of adverse fetal outcome predictors dedicated to the analysis of road accidents involving pregnant women. To do so, a pre-existing whole body finite element model representative of a 50th percentile 26 weeks pregnant woman was used. A total of 8 accident scenarios were simulated with the model positioned on a sled. Each of these scenarios was associated to a risk of adverse fetal outcome based on results from real car crash investigations involving pregnant women from the literature. The use of airbags and accidents involving unbelted occupants were not considered in this study. Several adverse fetal outcome potential predictors were then evaluated with regard to their correlation to this risk of fetal injuries. Three predictors appeared strongly correlated to the risk of adverse fetal outcome: (1) the intra uterine pressure at the placenta fetal side area (r=0.92), (2) the fetal head acceleration (HIC) (r=0.99) and (3) area of utero-placental interface over a strain threshold (r=0.90). Finally, sensitivity analysis against slight variations of the simulation parameters was performed and assess robustness of these criteria. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tumor Necrosis Factor-α Accelerates the Resolution of Established Pulmonary Fibrosis in Mice by Targeting Profibrotic Lung Macrophages

PubMed Central

Redente, Elizabeth F.; Keith, Rebecca C.; Janssen, William; Henson, Peter M.; Ortiz, Luis A.; Downey, Gregory P.; Bratton, Donna L.

2014-01-01

Idiopathic pulmonary fibrosis (IPF) is a relentless, fibrotic parenchymal lung disease in which alternatively programmed macrophages produce profibrotic molecules that promote myofibroblast survival and collagen synthesis. Effective therapies to treat patients with IPF are lacking, and conventional therapy may be harmful. We tested the hypothesis that therapeutic lung delivery of the proinflammatory cytokine tumor necrosis factor (TNF)-α into wild-type fibrotic mice would reduce the profibrotic milieu and accelerate the resolution of established pulmonary fibrosis. Fibrosis was assessed in bleomycin-instilled wild-type and TNF-α−/− mice by measuring hydroxyproline levels, static compliance, and Masson’s trichrome staining. Macrophage infiltration and programming status was assessed by flow cytometry of enzymatically digested lung and in situ immunostaining. Pulmonary delivery of TNF-α to wild-type mice with established pulmonary fibrosis was found to reduce their fibrotic burden, to improve lung function and architecture, and to reduce the number and programming status of profibrotic alternatively programmed macrophages. In contrast, fibrosis and alternative macrophage programming were prolonged in bleomycin-instilled TNF-α−/− mice. To address the role of the reduced numbers of alternatively programmed macrophages in the TNF-α–induced resolution of established pulmonary fibrosis, we conditionally depleted macrophages in MAFIA (MAcrophage Fas-Induced Apoptosis) mice. Conditional macrophage depletion phenocopied the resolution of established pulmonary fibrosis observed after therapeutic TNF-α delivery. Taken together, our results show for the first time that TNF-α is involved in the resolution of established pulmonary fibrosis via a mechanism involving reduced numbers and programming status of profibrotic macrophages. We speculate that pulmonary delivery of TNF-α or augmenting its signaling pathway represent a novel therapeutic strategy to resolve

Fibroblast Activation Protein (FAP) Accelerates Collagen Degradation and Clearance from Lungs in Mice*

PubMed Central

Fan, Ming-Hui; Zhu, Qiang; Li, Hui-Hua; Ra, Hyun-Jeong; Majumdar, Sonali; Gulick, Dexter L.; Jerome, Jacob A.; Madsen, Daniel H.; Christofidou-Solomidou, Melpo; Speicher, David W.; Bachovchin, William W.; Feghali-Bostwick, Carol; Puré, Ellen

2016-01-01

Idiopathic pulmonary fibrosis is a disease characterized by progressive, unrelenting lung scarring, with death from respiratory failure within 2–4 years unless lung transplantation is performed. New effective therapies are clearly needed. Fibroblast activation protein (FAP) is a cell surface-associated serine protease up-regulated in the lungs of patients with idiopathic pulmonary fibrosis as well as in wound healing and cancer. We postulate that FAP is not only a marker of disease but influences the development of pulmonary fibrosis after lung injury. In two different models of pulmonary fibrosis, intratracheal bleomycin instillation and thoracic irradiation, we find increased mortality and increased lung fibrosis in FAP-deficient mice compared with wild-type mice. Lung extracellular matrix analysis reveals accumulation of intermediate-sized collagen fragments in FAP-deficient mouse lungs, consistent with in vitro studies showing that FAP mediates ordered proteolytic processing of matrix metalloproteinase (MMP)-derived collagen cleavage products. FAP-mediated collagen processing leads to increased collagen internalization without altering expression of the endocytic collagen receptor, Endo180. Pharmacologic FAP inhibition decreases collagen internalization as expected. Conversely, restoration of FAP expression in the lungs of FAP-deficient mice decreases lung hydroxyproline content after intratracheal bleomycin to levels comparable with that of wild-type controls. Our findings indicate that FAP participates directly, in concert with MMPs, in collagen catabolism and clearance and is an important factor in resolving scar after injury and restoring lung homeostasis. Our study identifies FAP as a novel endogenous regulator of fibrosis and is the first to show FAP's protective effects in the lung. PMID:26663085

Fetal Abuse.

ERIC Educational Resources Information Center

Kent, Lindsey; And Others

1997-01-01

Five cases of fetal abuse by mothers suffering from depression are discussed. Four of the women had unplanned pregnancies and had considered termination of the pregnancy. Other factors associated with fetal abuse include pregnancy denial, pregnancy ambivalence, previous postpartum depression, and difficulties in relationships. Vigilance for…

Survival Benefit of Lung Transplantation in the Modern Era of Lung Allocation

PubMed Central

Tsuang, Wayne M.; Copeland, C. Ashley Finlen; Tsiatis, Anastasios A.; Davidian, Marie; Neely, Megan L.; Lederer, David J.; Palmer, Scott M.

2017-01-01

Rationale: Lung transplantation is an accepted and increasingly employed treatment for advanced lung diseases, but the anticipated survival benefit of lung transplantation is poorly understood. Objectives: To determine whether and for which patients lung transplantation confers a survival benefit in the modern era of U.S. lung allocation. Methods: Data on 13,040 adults listed for lung transplantation between May 2005 and September 2011 were obtained from the United Network for Organ Sharing. A structural nested accelerated failure time model was used to model the survival benefit of lung transplantation over time. The effects of patient, donor, and transplant center characteristics on the relative survival benefit of transplantation were examined. Measurements and Main Results: Overall, 73.8% of transplant recipients were predicted to achieve a 2-year survival benefit with lung transplantation. The survival benefit of transplantation varied by native disease group (P = 0.062), with 2-year expected benefit in 39.2 and 98.9% of transplants occurring in those with obstructive lung disease and cystic fibrosis, respectively, and by lung allocation score at the time of transplantation (P < 0.001), with net 2-year benefit in only 6.8% of transplants occurring for lung allocation score less than 32.5 and in 99.9% of transplants for lung allocation score exceeding 40. Conclusions: A majority of adults undergoing transplantation experience a survival benefit, with the greatest potential benefit in those with higher lung allocation scores or restrictive native lung disease or cystic fibrosis. These results provide novel information to assess the expected benefit of lung transplantation at an individual level and to enhance lung allocation policy. PMID:27779905

Intrapartum fetal scalp lactate sampling for fetal assessment in the presence of a non-reassuring fetal heart rate trace.

PubMed

East, Christine E; Leader, Leo R; Sheehan, Penelope; Henshall, Naomi E; Colditz, Paul B; Lau, Rosalind

2015-05-01

Fetal scalp blood sampling for lactate estimation may be considered following identification of an abnormal or non-reassuring fetal heart rate pattern. The smaller volume of blood required for this test, compared with the more traditional pH estimation, may improve sampling rates. The appropriate use of this practice mandates systematic review of its safety and clinical effectiveness prior to widespread introduction. To evaluate the effectiveness and risks of fetal scalp lactate sampling in the assessment of fetal well-being during labour, compared with no testing or alternative testing. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2015). All published and unpublished randomised and quasi-randomised trials that compared fetal scalp lactate testing with no testing or alternative testing to evaluate fetal status in the presence of a non-reassuring cardiotocograph during labour. We used the standard methodological procedures of the Cochrane Pregnancy and Childbirth Group. Two review authors independently assessed the studies. The search identified two completed randomised controlled trials (RCTs) and two ongoing trials. The two published RCTs considered outcomes for 3348 mother-baby pairs allocated to either lactate or pH estimation of fetal blood samples when clinically indicated in labour. Overall, the published RCTs were of low or unclear risk of bias. There was a high risk of performance bias, because it would not have been feasible to blind clinicians or participants.No statistically significant between-group differences were found for neonatal encephalopathy (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.32 to 3.09, one study, 2992 infants) or death. No studies reported neonatal seizures. We had planned to report death with other morbidities, for example, neonatal encephalopathy; however, the data were not available in a format suitable for this, therefore death due to congenital abnormality was considered alone

Fetal short time variation during labor: a non-invasive alternative to fetal scalp pH measurements?

PubMed

Schiermeier, Sven; Reinhard, Joscha; Hatzmann, Hendrike; Zimmermann, Ralf C; Westhof, Gregor

2009-01-01

To determine whether short time variation (STV) of fetal heart beat correlates with scalp pH measurements during labor. From 1279 deliveries, 197 women had at least one fetal scalp pH measurement. Using the CTG-Player, STVs were calculated from the electronically saved cardiotocography (CTG) traces and related to the fetal scalp pH measurements. There was no correlation between STV and fetal scalp pH measurements (r=-0.0592). Fetal STV is an important parameter with high sensitivity for antenatal fetal acidosis. This study shows that STV calculations do not correlate with fetal scalp pH measurements during labor, hence are not helpful in identifying fetal acidosis.

Fibroblast Activation Protein (FAP) Accelerates Collagen Degradation and Clearance from Lungs in Mice.

PubMed

Fan, Ming-Hui; Zhu, Qiang; Li, Hui-Hua; Ra, Hyun-Jeong; Majumdar, Sonali; Gulick, Dexter L; Jerome, Jacob A; Madsen, Daniel H; Christofidou-Solomidou, Melpo; Speicher, David W; Bachovchin, William W; Feghali-Bostwick, Carol; Puré, Ellen

2016-04-08

Idiopathic pulmonary fibrosis is a disease characterized by progressive, unrelenting lung scarring, with death from respiratory failure within 2-4 years unless lung transplantation is performed. New effective therapies are clearly needed. Fibroblast activation protein (FAP) is a cell surface-associated serine protease up-regulated in the lungs of patients with idiopathic pulmonary fibrosis as well as in wound healing and cancer. We postulate that FAP is not only a marker of disease but influences the development of pulmonary fibrosis after lung injury. In two different models of pulmonary fibrosis, intratracheal bleomycin instillation and thoracic irradiation, we find increased mortality and increased lung fibrosis in FAP-deficient mice compared with wild-type mice. Lung extracellular matrix analysis reveals accumulation of intermediate-sized collagen fragments in FAP-deficient mouse lungs, consistent within vitrostudies showing that FAP mediates ordered proteolytic processing of matrix metalloproteinase (MMP)-derived collagen cleavage products. FAP-mediated collagen processing leads to increased collagen internalization without altering expression of the endocytic collagen receptor, Endo180. Pharmacologic FAP inhibition decreases collagen internalization as expected. Conversely, restoration of FAP expression in the lungs of FAP-deficient mice decreases lung hydroxyproline content after intratracheal bleomycin to levels comparable with that of wild-type controls. Our findings indicate that FAP participates directly, in concert with MMPs, in collagen catabolism and clearance and is an important factor in resolving scar after injury and restoring lung homeostasis. Our study identifies FAP as a novel endogenous regulator of fibrosis and is the first to show FAP's protective effects in the lung. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Alterations of peroxisome proliferator-activated receptor γ and monocyte chemoattractant protein 1 gene expression in the nitrofen-induced hypoplastic lung.

PubMed

Gosemann, Jan-Hendrik; Doi, Takashi; Kutasy, Balazs; Friedmacher, Florian; Dingemann, Jens; Puri, Prem

2012-05-01

Peroxisome proliferator-activated receptor γ (PPARγ) plays a key role in normal lung development. Peroxisome proliferator-activated receptor γ messenger RNA (mRNA) is detectable at 18 days of gestation in fetal rat lungs, and levels peak just before birth. Peroxisome proliferator-activated receptor γ agonists are reported to stimulate lung development, whereas inhibition of PPARγ disrupts postnatal lung maturation. Monocyte chemoattractant protein 1 (MCP-1), which is inhibited by PPARγ, is reported to disrupt late lung morphogenesis. This study was designed to investigate the hypothesis that PPARγ expression is downregulated and that MCP-1 expression is upregulated during the late stages of lung development in nitrofen-induced hypoplastic lungs. Pregnant rats were treated with nitrofen or vehicle on D9. RNA was extracted from fetal lungs (D18 and D21), and relative mRNA expression levels of PPARγ and MCP-1 were determined by reverse transcriptase-polymerase chain reaction. Immunohistochemistry was performed to evaluate protein expression/distribution of PPARγ and MCP-1. Relative mRNA expression levels of PPARγ were significantly downregulated in the nitrofen group compared with controls on D21, whereas MCP-1 levels were upregulated. Immunohistochemical study showed markedly decreased PPARγ and increased MCP-1 immunoreactivity in the nitrofen-induced hypoplastic lungs compared with controls on gestational day 21. Altered pulmonary gene expression of PPARγ and MCP-1 during late gestation may impair lung development and maturation, contributing to pulmonary hypoplasia in the nitrofen-induced congenital diaphragmatic hernia model. Copyright © 2012 Elsevier Inc. All rights reserved.

Fetal bile salt metabolism

PubMed Central

Smallwood, R. A.; Lester, R.; Piasecki, G. J.; Klein, P. D.; Greco, R.; Jackson, B. T.

1972-01-01

Bile salt metabolism was studied in fetal dogs 1 wk before term. The size and distribution of the fetal bile salt pool were measured, and individual bile salts were identified. The hepatic excretion of endogenous bile salts was studied in bile fistula fetuses, and the capacity of this excretory mechanism was investigated by the i.v. infusion of a load of sodium taurocholate-14C up to 20 times the endogenous pool size. The total fetal bile salt pool was 30.9±2.7 μmoles, of which two-thirds was in the fetal gallbladder. Expressed on a body weight basis, this was equal to approximately one-half the estimated pool size in the adult dog (119.2±11.3 vs. 247.5±33.1 μmoles/kg body wt). Measurable quantities of bile salt were found in small bowel (6.0±1.8 μmoles), large bowel (1.1±0.3 μmoles), liver (1.2±0.5 μmoles), and plasma (0.1±0.03 μmoles). Plasma bile salt levels were significantly greater in fetal than in maternal plasma (1.01±0.24 μg/ml vs. 0.36±0.06 μg/ml; P < 0.05). Fetal hepatic bile salt excretion showed a fall over the period of study from 2.04±0.34 to 0.30±0.07 μmoles/hr. The maximal endogenous bile salt concentration in fetal hepatic bile was 18.7±1.5 μmoles/ml. The concentration in fetal gallbladder bile was 73.9±8.6 μmoles/ml; and, in those studies in which hepatic and gallbladder bile could be compared directly, the gallbladder appeared to concentrate bile four- to fivefold. Taurocholate, taurochenodeoxycholate, and taurodeoxycholate were present in fetal bile, but no free bile salts were identified. The presence of deoxycholate was confirmed by thin-layer chromatography and gas liquid chromatography, and the absence of microorganisms in fetal gut suggests that it was probably transferred from the maternal circulation. After infusion of a taurocholate load, fetal hepatic bile salt excretion increased 30-fold, so that 85-95% of the dose was excreted by the fetal liver during the period of observation. Placental transfer accounted

Prospective evaluation of the fetal heart using Fetal Intelligent Navigation Echocardiography (FINE).

PubMed

Garcia, M; Yeo, L; Romero, R; Haggerty, D; Giardina, I; Hassan, S S; Chaiworapongsa, T; Hernandez-Andrade, E

2016-04-01

To evaluate prospectively the performance of Fetal Intelligent Navigation Echocardiography (FINE) applied to spatiotemporal image correlation (STIC) volume datasets of the normal fetal heart. In all women between 19 and 30 weeks' gestation with a normal fetal heart, 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 5- and 7-o'clock positions; (2) minimal or absent shadowing (including a clearly visible transverse aortic arch); (3) absence of 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 of fetal echocardiography views using diagnostic planes and/or Virtual Intelligent Sonographer Assistance (VIS-Assistance®) were calculated. One or more STIC volumes (365 in total) were obtained successfully in 72.5% (150/207) of women undergoing ultrasound examination. Of the 365 volumes evaluated by STICLoop, 351 (96.2%) were considered to be appropriate. From the 351 STIC volumes, only one STIC volume per patient (n = 150) was analyzed using the FINE method, and consequently nine fetal echocardiography views were generated in 76-100% of cases using diagnostic planes only, in 98-100% of cases using VIS-Assistance only, and in 98-100% of cases when using a combination of diagnostic planes and/or VIS-Assistance. In women between 19 and 30 weeks' gestation with a normal fetal heart undergoing prospective sonographic examination, STIC volumes can be obtained successfully in 72.5% of cases. The FINE method can be applied to generate nine standard fetal echocardiography views in 98-100% of these cases using a combination of diagnostic planes and/or VIS-Assistance. This suggests that FINE could be implemented in fetal cardiac screening programs. Published 2015. This article is a U.S. Government work and is in

Cysticercus tenuicollis vesicle in fetal structures: report of a case.

PubMed

Payan-Carreira, R; Silva, F; Rodrigues, M; dos Anjos Pires, M

2008-12-01

Cysticercus tenuicollis is the larval stage of the canine tapeworm Taenia hydatigena, the presence of which has been reported in wild and domestic ruminants all over the world. It is a common parasite of small ruminants in the north of Portugal. C. tenuicollis is generally seen attached to the omenta, the mesenteries or also found in the liver. In the ewe, tissue lesions have been associated with degenerative cysts or with oncosphere migrations. Unusual locations of the cysticerci of T. hydatigena have been described. The most frequent unusual locations are in the lungs, the kidneys and the brain. Less common locations have been reported to occur in the ovaries, uterine tubes, uterus, cervix and vagina. In the case described here, and for the first time, an aberrant location of a C. tenuicollis vesicle was found inside the chorion-allantoic membrane of a goat's foetus, in a gemelar gestation of approximately 70 days. Finding a C. tenuicollis vesicle inside fetal membranes forewarns of the possibility of larval migrations into the fetal structures during pregnancy, which is particularly concerning in human populations that are infested.

Fetal cell carcinogenesis of the thyroid: a modified theory based on recent evidence.

PubMed

Takano, Toru

2014-01-01

Thyroid cancer cells were believed to be generated by multi-step carcinogenesis, in which cancer cells are derived from thyrocytes, via multiple incidences of damage to their genome, especially in oncogenes or anti-oncogenes that accelerate proliferation or foster malignant phenotypes, such as the ability to invade the surrounding tissue or metastasize to distant organs, until a new hypothesis, fetal cell carcinogenesis, was presented. In fetal cell carcinogenesis, thyroid tumor cells are assumed to be derived from three types of fetal thyroid cell which only exist in fetuses or young children, namely, thyroid stem cells (TSCs), thyroblasts and prothyrocytes, by proliferation without differentiation. Genomic alternations, such as RET/PTC and PAX8-PPARγ1 rearrangements and a mutation in the BRAF gene, play an oncogenic role by preventing thyroid fetal cells from differentiating. Fetal cell carcinogenesis effectively explains recent molecular and clinical evidence regarding thyroid cancer, including thyroid cancer initiating cells (TCICs), and it underscores the importance of identifying a stem cells and clarifying the molecular mechanism of organ development in cancer research. It introduces three important concepts, the reverse approach, stem cell crisis and mature and immature cancers. Further, it implies that analysis of a small population of cells in a cancer tissue will be a key technique in establishing future laboratory tests. In the contrary, mass analysis such as gene expression profiling, whole genomic scan, and proteomics analysis may have definite limitations since they can only provide information based on many cells.

Value of amniocentesis versus fetal tissue for cytogenetic analysis in cases of fetal demise.

PubMed

Bryant Borders, Ann E; Greenberg, Jessica; Plaga, Stacey; Shepard-Hinton, Megan; Yates, Carin; Elias, Sherman; Shulman, Lee P

2009-01-01

Use of fetal tissue for cytogenetic analysis in cases of second- and third-trimester fetal demise frequently results in unacceptably high failure rates. We reviewed our ongoing use of amniocentesis prior to uterine evacuation to determine if this provided a better source of cells for cytogenetic analysis. We compared cytogenetic results using fetal tissues obtained following uterine evacuation to our ongoing use of amniotic fluid cell obtained by transabdominal amniocentesis prior to uterine evacuation from 2003 to 2008. In 49 of the 63 cases evaluated by fetal tissue biopsies performed after uterine evacuation, a karyotypic analysis was obtained (77.8%). Among the 38 cases evaluated by amniocentesis, an amniotic fluid sample and fetal cytogenetic results were obtained in all 38 (100%) cases. Our findings indicate that amniocentesis is a more reliable source of cytogenetic information than fetal tissue in cases of second- and third-trimester fetal demise.

Human Fetal Brain Connectome: Structural Network Development from Middle Fetal Stage to Birth

PubMed Central

Song, Limei; Mishra, Virendra; Ouyang, Minhui; Peng, Qinmu; Slinger, Michelle; Liu, Shuwei; Huang, Hao

2017-01-01

Complicated molecular and cellular processes take place in a spatiotemporally heterogeneous and precisely regulated pattern in the human fetal brain, yielding not only dramatic morphological and microstructural changes, but also macroscale connectomic transitions. As the underlying substrate of the fetal brain structural network, both dynamic neuronal migration pathways and rapid developing fetal white matter (WM) fibers could fundamentally reshape early fetal brain connectome. Quantifying structural connectome development can not only shed light on the brain reconfiguration in this critical yet rarely studied developmental period, but also reveal alterations of the connectome under neuropathological conditions. However, transition of the structural connectome from the mid-fetal stage to birth is not yet known. The contribution of different types of neural fibers to the structural network in the mid-fetal brain is not known, either. In this study, diffusion tensor magnetic resonance imaging (DT-MRI or DTI) of 10 fetal brain specimens at the age of 20 postmenstrual weeks (PMW), 12 in vivo brains at 35 PMW, and 12 in vivo brains at term (40 PMW) were acquired. The structural connectome of each brain was established with evenly parcellated cortical regions as network nodes and traced fiber pathways based on DTI tractography as network edges. Two groups of fibers were categorized based on the fiber terminal locations in the cerebral wall in the 20 PMW fetal brains. We found that fetal brain networks become stronger and more efficient during 20–40 PMW. Furthermore, network strength and global efficiency increase more rapidly during 20–35 PMW than during 35–40 PMW. Visualization of the whole brain fiber distribution by the lengths suggested that the network reconfiguration in this developmental period could be associated with a significant increase of major long association WM fibers. In addition, non-WM neural fibers could be a major contributor to the structural

Screening for fetal growth restriction using fetal biometry combined with maternal biomarkers.

PubMed

Gaccioli, Francesca; Aye, Irving L M H; Sovio, Ulla; Charnock-Jones, D Stephen; Smith, Gordon C S

2018-02-01

Fetal growth restriction is a major determinant of perinatal morbidity and mortality. Screening for fetal growth restriction is a key element of prenatal care but it is recognized to be problematic. Screening using clinical risk assessment and targeting ultrasound to high-risk women is the standard of care in the United States and United Kingdom, but the approach is known to have low sensitivity. Systematic reviews of randomized controlled trials do not demonstrate any benefit from universal ultrasound screening for fetal growth restriction in the third trimester, but the evidence base is not strong. Implementation of universal ultrasound screening in low-risk women in France failed to reduce the risk of complications among small-for-gestational-age infants but did appear to cause iatrogenic harm to false positives. One strategy to making progress is to improve screening by developing more sensitive and specific tests with the key goal of differentiating between healthy small fetuses and those that are small through fetal growth restriction. As abnormal placentation is thought to be the major cause of fetal growth restriction, one approach is to combine fetal biometry with an indicator of placental dysfunction. In the past, these indicators were generally ultrasonic measurements, such as Doppler flow velocimetry of the uteroplacental circulation. However, another promising approach is to combine ultrasonic suspicion of small-for-gestational-age infant with a blood test indicating placental dysfunction. Thus far, much of the research on maternal serum biomarkers for fetal growth restriction has involved the secondary analysis of tests performed for other indications, such as fetal aneuploidies. An exemplar of this is pregnancy-associated plasma protein A. This blood test is performed primarily to assess the risk of Down syndrome, but women with low first-trimester levels are now serially scanned in later pregnancy due to associations with placental causes of

Unexpected fetal death during pregnancy--a problem of unrecognized fetal disorders during antenatal care?

PubMed

Künzel, Wolfgang; Misselwitz, Björn

2003-09-22

To investigate the causes of ante partum fetal death (APFD) and to evaluate the diagnostic methods for prevention. A population-based retrospective study was conducted in 293091 deliveries from 1996 to 2000 in the State of Hesse, Germany. The investigations focus on mortality of infants during pregnancy, separated between singletons of 37-42 weeks (n=361) and 23-36 weeks (n=550), and multiple births (n=76). In 44 cases, the gestational age was unknown and in 19 cases lower than 23 weeks or greater than 43 weeks. In total 1006 cases remained and were subject for evaluation. Perinatal mortality (PM) was 0.56%. APFD occurred in 1050 cases (0.3%), i.e. 63.5% of PM. Risk factors from the medical history during pregnancy could be identified in 515 cases (51.2%). Significant risk factors were social burden (odds ratio (OR) 58.3), diabetes mellitus (OR 5.4) and gestational diabetes (OR 2.1), psychological burden (OR 4.8), proteinuria (OR 2.8), maternal age (OR 1.7) and maternal smoking, depending on the number of cigarettes. The risk factors show a difference in significance, if related to the gestational age and multiple pregnancies. The contribution of malformations to APFD was 7.8%. There was however a number of unexpected fetal deaths with unidentified risk factors: n=415 (41.3%). In this group, fetal growth restriction was observed in 38.1%. Compared to control, APFD was three to five times higher in fetal growth retardation below the 10th percentile. Fetal death was closely related to fetal surveillance, i.e. the number of antenatal visits, ultrasound measurements, and fetal heart rate monitoring. Fetal ante partum fetal death can be reduced at least by 50%, if the available methods for fetal surveillance are employed aiming to detect indications of fetal oxygen deprivation at an early stage.

Impact of fetal death reporting requirements on early neonatal and fetal mortality rates and racial disparities.

PubMed

Tyler, Crystal P; Grady, Sue C; Grigorescu, Violanda; Luke, Barbara; Todem, David; Paneth, Nigel

2012-01-01

Racial disparities in infant and neonatal mortality vary substantially across the U.S. with some states experiencing wider disparities than others. Many factors are thought to contribute to these disparities, but state differences in fetal death reporting have received little attention. We examined whether such reporting requirements may explain national variation in neonatal and fetal mortality rates and racial disparities. We used data on non-Hispanic white and non-Hispanic black infants from the U.S. 2000-2002 linked birth/infant death and fetal death records to determine the degree to which state fetal death reporting requirements explain national variation in neonatal and fetal mortality rates and racial disparities. States were grouped depending upon whether they based the lower limit for fetal death reporting on birthweight alone, gestational age alone, both birthweight and gestational age, or required reporting of all fetal deaths. Traditional methods and the fetuses-at-risk approach were used to calculate mortality rates, 95% confidence intervals, and relative and absolute racial disparity measures in these four groups. States with birthweight-alone fetal death thresholds substantially underreported fetal deaths at lower gestations and slightly overreported neonatal deaths at older gestations. This finding was reflected by these states having the highest neonatal mortality rates and disparities, but the lowest fetal mortality rates and disparities. Using birthweight alone as a reporting threshold may promote some shift of fetal deaths to newborn deaths, contributing to racial disparities in neonatal mortality. The adoption of a uniform national threshold for reporting fetal deaths could reduce systematic differences in live birth and fetal death reporting.

[Autopsies for fetal anomalies].

PubMed

Kidron, Debora; Eidel, Jouly; Aviram, Rami

2013-06-01

Fetal autopsies are effective in identifying the cause and/or mechanisms leading to death in cases of intrauterine fetal death. Autopsies for fetal anomalies are different. To summarize our experience with 569 autopsies of fetal anomalies which were performed during an 18-year period. A retrospective analysis of 569 autopsies of fetal anomalies was conducted, out of a total of 1067 fetal autopsies. The pregnancy weeks were 14 - 41. Among 569 cases, 88% were termination of pregnancies, 10% intrauterine death and 2% perinatal deaths. The diagnosis of a syndrome or disease process was made when a constellation of gross and/or histologic findings was met. Specific diagnoses were offered in cases of cystic diseases of kidneys, types of dwarfism, tumors and fetal hydrops. Teratogenic (acquired) processes, such as congenital infections, thrombosis and cerebral hemorrhages, were differentiated from malformations. In cases of multiple congenital anomalies, documentation of the entire spectrum of malformations facilitated the genetic counseling. First and foremost, the autopsy is performed in the interest of the parents, with their written consent and in accordance with limitations and requests which they pose. Autopsy results provide feedback to the prenatal imaging. They assist in focusing the genetic counseling. Autopsy reports provide tools of control for the health authorities. Autopsies for fetal anomalies are time consuming. They require skill and experience. They are helpfuL when the prenatal diagnosis raises differential diagnosis. They are Less helpful when the diagnosis is clear, i.e. chromosomal trisomy.

Diagnosis and treatment of fetal cardiac disease: a scientific statement from the American Heart Association.

PubMed

Donofrio, Mary T; Moon-Grady, Anita J; Hornberger, Lisa K; Copel, Joshua A; Sklansky, Mark S; Abuhamad, Alfred; Cuneo, Bettina F; Huhta, James C; Jonas, Richard A; Krishnan, Anita; Lacey, Stephanie; Lee, Wesley; Michelfelder, Erik C; Rempel, Gwen R; Silverman, Norman H; Spray, Thomas L; Strasburger, Janette F; Tworetzky, Wayne; Rychik, Jack

2014-05-27

The goal of this statement is to review available literature and to put forth a scientific statement on the current practice of fetal cardiac medicine, including the diagnosis and management of fetal cardiovascular disease. A writing group appointed by the American Heart Association reviewed the available literature pertaining to topics relevant to fetal cardiac medicine, including the diagnosis of congenital heart disease and arrhythmias, assessment of cardiac function and the cardiovascular system, and available treatment options. The American College of Cardiology/American Heart Association classification of recommendations and level of evidence for practice guidelines were applied to the current practice of fetal cardiac medicine. Recommendations relating to the specifics of fetal diagnosis, including the timing of referral for study, indications for referral, and experience suggested for performance and interpretation of studies, are presented. The components of a fetal echocardiogram are described in detail, including descriptions of the assessment of cardiac anatomy, cardiac function, and rhythm. Complementary modalities for fetal cardiac assessment are reviewed, including the use of advanced ultrasound techniques, fetal magnetic resonance imaging, and fetal magnetocardiography and electrocardiography for rhythm assessment. Models for parental counseling and a discussion of parental stress and depression assessments are reviewed. Available fetal therapies, including medical management for arrhythmias or heart failure and closed or open intervention for diseases affecting the cardiovascular system such as twin-twin transfusion syndrome, lung masses, and vascular tumors, are highlighted. Catheter-based intervention strategies to prevent the progression of disease in utero are also discussed. Recommendations for delivery planning strategies for fetuses with congenital heart disease including models based on classification of disease severity and delivery room

A novel surgical approach for intratracheal administration of bioactive agents in a fetal mouse model.

PubMed

Carlon, Marianne S; Toelen, Jaan; da Cunha, Marina Mori; Vidović, Dragana; Van der Perren, Anke; Mayer, Steffi; Sbragia, Lourenço; Nuyts, Johan; Himmelreich, Uwe; Debyser, Zeger; Deprest, Jan

2012-10-31

Prenatal pulmonary delivery of cells, genes or pharmacologic agents could provide the basis for new therapeutic strategies for a variety of genetic and acquired diseases. Apart from congenital or inherited abnormalities with the requirement for long-term expression of the delivered gene, several non-inherited perinatal conditions, where short-term gene expression or pharmacological intervention is sufficient to achieve therapeutic effects, are considered as potential future indications for this kind of approach. Candidate diseases for the application of short-term prenatal therapy could be the transient neonatal deficiency of surfactant protein B causing neonatal respiratory distress syndrome(1,2) or hyperoxic injuries of the neonatal lung(3). Candidate diseases for permanent therapeutic correction are Cystic Fibrosis (CF)(4), genetic variants of surfactant deficiencies(5) and α1-antitrypsin deficiency(6). Generally, an important advantage of prenatal gene therapy is the ability to start therapeutic intervention early in development, at or even prior to clinical manifestations in the patient, thus preventing irreparable damage to the individual. In addition, fetal organs have an increased cell proliferation rate as compared to adult organs, which could allow a more efficient gene or stem cell transfer into the fetus. Furthermore, in utero gene delivery is performed when the individual's immune system is not completely mature. Therefore, transplantation of heterologous cells or supplementation of a non-functional or absent protein with a correct version should not cause immune sensitization to the cell, vector or transgene product, which has recently been proven to be the case with both cellular and genetic therapies(7). In the present study, we investigated the potential to directly target the fetal trachea in a mouse model. This procedure is in use in larger animal models such as rabbits and sheep(8), and even in a clinical setting(9), but has to date not been

ZnO, TiO(2), SiO(2,) and Al(2)O(3) nanoparticles-induced toxic effects on human fetal lung fibroblasts.

PubMed

Zhang, Xiao Qiang; Yin, Li Hong; Tang, Meng; Pu, Yue Pu

2011-12-01

This study aims to investigate and compare the toxic effects of four types of metal oxide (ZnO, TiO(2), SiO(2,) and Al(2)O(3)) nanoparticles with similar primary size (∼20 nm) on human fetal lung fibroblasts (HFL1) in vitro. The HFL1 cells were exposed to the nanoparticles, and toxic effects were analyzed by using MTT assay, cellular morphology observation and Hoechst 33 258 staining. The results show that the four types of metal oxide nanoparticles lead to cellular mitochondrial dysfunction, morphological modifications and apoptosis at the concentration range of 0.25-1.50 mg/mL and the toxic effects are obviously displayed in dose-dependent manner. ZnO is the most toxic nanomaterials followed by TiO(2), SiO(2), and Al(2)O(3) nanoparticles in a descending order. The results highlight the differential cytotoxicity associated with exposure to ZnO, TiO(2), SiO(2), and Al(2)O(3) nanoparticles, and suggest an extreme attention to safety utilization of these nanomaterials. Copyright © 2011 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.

Is Abdominal Fetal Electrocardiography an Alternative to Doppler Ultrasound for FHR Variability Evaluation?

PubMed Central

Jezewski, Janusz; Wrobel, Janusz; Matonia, Adam; Horoba, Krzysztof; Martinek, Radek; Kupka, Tomasz; Jezewski, Michal

2017-01-01

Great expectations are connected with application of indirect fetal electrocardiography (FECG), especially for home telemonitoring of pregnancy. Evaluation of fetal heart rate (FHR) variability, when determined from FECG, uses the same criteria as for FHR signal acquired classically—through ultrasound Doppler method (US). Therefore, the equivalence of those two methods has to be confirmed, both in terms of recognizing classical FHR patterns: baseline, accelerations/decelerations (A/D), long-term variability (LTV), as well as evaluating the FHR variability with beat-to-beat accuracy—short-term variability (STV). The research material consisted of recordings collected from 60 patients in physiological and complicated pregnancy. The FHR signals of at least 30 min duration were acquired dually, using two systems for fetal and maternal monitoring, based on US and FECG methods. Recordings were retrospectively divided into normal (41) and abnormal (19) fetal outcome. The complex process of data synchronization and validation was performed. Obtained low level of the signal loss (4.5% for US and 1.8% for FECG method) enabled to perform both direct comparison of FHR signals, as well as indirect one—by using clinically relevant parameters. Direct comparison showed that there is no measurement bias between the acquisition methods, whereas the mean absolute difference, important for both visual and computer-aided signal analysis, was equal to 1.2 bpm. Such low differences do not affect the visual assessment of the FHR signal. However, in the indirect comparison the inconsistencies of several percent were noted. This mainly affects the acceleration (7.8%) and particularly deceleration (54%) patterns. In the signals acquired using the electrocardiography the obtained STV and LTV indices have shown significant overestimation by 10 and 50% respectively. It also turned out, that ability of clinical parameters to distinguish between normal and abnormal groups do not depend on

Predicting intrapartum fetal compromise using the fetal cerebro-umbilical ratio.

PubMed

Sabdia, S; Greer, R M; Prior, T; Kumar, S

2015-05-01

The aim of this study was to explore the association between the cerebro-umbilical ratio measured at 35-37 weeks and intrapartum fetal compromise. This retrospective cross sectional study was conducted at the Mater Mothers' Hospital in Brisbane, Australia. Maternal demographics and fetal Doppler indices at 35-37 weeks gestation for 1381 women were correlated with intrapartum and neonatal outcomes. Babies born by caesarean section or instrumental delivery for fetal compromise had the lowest median cerebro-umbilical ratio 1.60 (IQR 1.22-2.08) compared to all other delivery groups (vaginal delivery, emergency delivery for failure to progress, emergency caesarean section for other reasons or elective caesarean section). The percentage of infants with a cerebro-umbilical ratio <10th centile that required emergency delivery (caesarean section or instrumental delivery) for fetal compromise was 22%, whereas only 7.3% of infants with a cerebro-umbilical ratio between the 10th-90th centile and 9.6% of infants with a cerebro-umbilical ratio > 90th centile required delivery for the same indication (p < 0.001). A lower cerebro-umbilical ratio was associated with an increased risk of emergency delivery for fetal compromise, OR 2.03 (95% CI 1.41-2.92), p < 0.0001. This study suggests that a low fetal cerebro-umbilical ratio measured at 35-37 weeks is associated with a greater risk of intrapartum compromise. This is a relatively simple technique which could be used to risk stratify women in diverse healthcare settings. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Morphologic study of the intestine in an experimental model of amnioinfusion in fetal rabbits with gastroschisis].

PubMed

Muñoz, M E; Albert, A; Juliá, V; Sancho, M A; Grande, C; Martínez, A; Morales, L

2002-10-01

An experimental model of serial amnioinfusion has been developed in fetal rabbits with gastroschisis, using an intraamniotic catheter connected to a subcutaneous port. Fetuses of 4 groups were compared 7 days after surgery: group A: gastroschisis and daily amnioinfusion through an implanted catheter; group C: gastroschisis and blind amniotic catheter; group G: gastroschisis without catheter; group O: nonoperated fetuses. Survival rate, fetal body weight, lung weight, intestinal weight and length were determined. Computer aided morphometric analysis was performed, in which intestinal diameter, thickness and villi length were measured. Amniotic fluid samples were recovered along the experimental period. Intestinal length was significantly shorter and had a significantly thicker wall than nonoperated fetuses; we found no other morphometric differences between gastroschisis treated with amnioinfusion (group A) and the other gastroschisis groups (C and G). Amnioinfusion did not affect fetal survival rate; the amniotic catheter alone did not cause pulmonary hypoplasia due to significant amniotic leak. The physiological decrease in amniotic volume towards the end of gestation has not been modified by this regime of amnioinfusion.

21 CFR 884.2900 - Fetal stethoscope.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Fetal stethoscope. (a) Identification. A fetal stethoscope is a device used for listening to fetal heart sounds. It is designed to transmit the fetal heart sounds not only through sound channels by air...

21 CFR 884.2900 - Fetal stethoscope.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Fetal stethoscope. (a) Identification. A fetal stethoscope is a device used for listening to fetal heart sounds. It is designed to transmit the fetal heart sounds not only through sound channels by air...

21 CFR 884.2900 - Fetal stethoscope.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Fetal stethoscope. (a) Identification. A fetal stethoscope is a device used for listening to fetal heart sounds. It is designed to transmit the fetal heart sounds not only through sound channels by air...

21 CFR 884.2900 - Fetal stethoscope.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Fetal stethoscope. (a) Identification. A fetal stethoscope is a device used for listening to fetal heart sounds. It is designed to transmit the fetal heart sounds not only through sound channels by air...

21 CFR 884.2900 - Fetal stethoscope.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Fetal stethoscope. (a) Identification. A fetal stethoscope is a device used for listening to fetal heart sounds. It is designed to transmit the fetal heart sounds not only through sound channels by air...

Impact of placental insufficiency on fetal skeletal muscle growth

PubMed Central

Hay, William W.

2016-01-01

Intrauterine growth restriction (IUGR) caused by placental insufficiency is one of the most common and complex problems in perinatology, with no known cure. In pregnancies affected by placental insufficiency, a poorly functioning placenta restricts nutrient supply to the fetus and prevents normal fetal growth. Among other significant deficits in organ development, the IUGR fetus characteristically has less lean body and skeletal muscle mass than their appropriately-grown counterparts. Reduced skeletal muscle growth is not fully compensated after birth, as individuals who were born small for gestational age (SGA) from IUGR have persistent reductions in muscle mass and strength into adulthood. The consequences of restricted muscle growth and accelerated postnatal “catch-up” growth in the form of adiposity may contribute to the increased later life risk for visceral adiposity, peripheral insulin resistance, diabetes, and cardiovascular disease in individuals who were formerly IUGR. This review will discuss how an insufficient placenta results in impaired fetal skeletal muscle growth and how lifelong reductions in muscle mass might contribute to increased metabolic disease risk in this vulnerable population. PMID:26994511

Fetal Alcohol Syndrome and Fetal Alcohol Effects in Child Development.

ERIC Educational Resources Information Center

Pancratz, Diane R.

This literature review defines Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE) and considers their causes, diagnoses, prevalence, and educational ramifications. Effects of alcohol during each of the trimesters of pregnancy are summarized. Specific diagnostic characteristics of FAS are listed: (1) growth deficiency, (2) a…

BPI-fold (BPIF) containing/plunc protein expression in human fetal major and minor salivary glands.

PubMed

Alves, Daniel Berretta Moreira; Bingle, Lynne; Bingle, Colin David; Lourenço, Silvia Vanessa; Silva, Andréia Aparecida; Pereira, Débora Lima; Vargas, Pablo Agustin

2017-01-16

The aim of this study was to determine expression, not previously described, of PLUNC (palate, lung, and nasal epithelium clone) (BPI-fold containing) proteins in major and minor salivary glands from very early fetal tissue to the end of the second trimester and thus gain further insight into the function of these proteins. Early fetal heads, and major and minor salivary glands were collected retrospectively and glands were classified according to morphodifferentiation stage. Expression of BPI-fold containing proteins was localized through immunohistochemistry. BPIFA2, the major BPI-fold containing protein in adult salivary glands, was detected only in the laryngeal pharynx; the lack of staining in salivary glands suggested salivary expression is either very late in development or is only in adult tissues. Early expression of BPIFA1 was seen in the trachea and nasal cavity with salivary gland expression only seen in late morphodifferentiation stages. BPIFB1 was seen in early neural tissue and at later stages in submandibular and sublingual glands. BPIFA1 is significantly expressed in early fetal oral tissue but BPIFB1 has extremely limited expression and the major salivary BPIF protein (BPIFA2) is not produced in fetal development. Further studies, with more sensitive techniques, will confirm the expression pattern and enable a better understanding of embryonic BPIF protein function.

Special Tests for Monitoring Fetal Health

MedlinePlus

... a nonstress test? The nonstress test measures the fetal heart rate in response to fetal movement over time. The ... A belt with a sensor that measures the fetal heart rate is placed around your abdomen. The fetal heart ...

Anesthesia for fetal surgery.

PubMed

Hoagland, Monica A; Chatterjee, Debnath

2017-04-01

Fetal therapy is an exciting and growing field of medicine. Advances in prenatal imaging and continued innovations in surgical and anesthetic techniques have resulted in a wide range of fetal interventions including minimally invasive, open mid-gestation, and ex-utero intrapartum treatment procedures. The potential for maternal morbidity is significant and must be carefully weighed against claimed benefits to the fetus. Appropriate patient selection is critical, and a multidisciplinary team-based approach is strongly recommended. The anesthetic management should focus on maintaining uteroplacental circulation, achieving profound uterine relaxation, optimizing surgical conditions, monitoring fetal hemodynamics, and minimizing maternal and fetal risk. © 2017 John Wiley & Sons Ltd.

Calcineurin/Nfat signaling is required for perinatal lung maturation and function.

PubMed

Davé, Vrushank; Childs, Tawanna; Xu, Yan; Ikegami, Machiko; Besnard, Valérie; Maeda, Yutaka; Wert, Susan E; Neilson, Joel R; Crabtree, Gerald R; Whitsett, Jeffrey A

2006-10-01

Pulmonary surfactant proteins and lipids are required for lung function after birth. Lung immaturity and resultant surfactant deficiency cause respiratory distress syndrome, a common disorder contributing to morbidity and mortality in preterm infants. Surfactant synthesis increases prior to birth in association with formation of the alveoli that mediate efficient gas exchange. To identify mechanisms controlling perinatal lung maturation, the Calcineurin b1 (Cnb1) gene was deleted in the respiratory epithelium of the fetal mouse. Deletion of Cnb1 caused respiratory failure after birth and inhibited the structural maturation of the peripheral lung. Synthesis of surfactant and a lamellar body-associated protein, ABC transporter A3 (ABCA3), was decreased prior to birth. Nuclear factor of activated T cells (Nfat) calcineurin-dependent 3 (Nfatc3), a transcription factor modulated by calcineurin, was identified as a direct activator of Sftpa, Sftpb, Sftpc, Abca3, Foxa1, and Foxa2 genes. The calcineurin/Nfat pathway controls the morphologic maturation of lungs prior to birth and regulates expression of genes involved in surfactant homeostasis that are critical for adaptation to air breathing.

Fetal blood drawing.

PubMed

Hobbins, J C; Mahoney, M J

1975-07-19

A small sample of fetal blood suitable for studies of haemoglobin synthesis was obtained from a placental vessel under endoscopic visualisation in 23 of 26 patients in whom the procedure was attempted prior to second-trimester abortion. Fetal blood loss, calculated in 23 cases, was between 0-2 ml. and 2-5 ml., and fetal blood-volume depletion varied from 0-5% to 15%. No short-term ill-effects were demonstrated in mother or fetus in any of 16 patients in whom the injection of aborti-facient was postponed for between 16 and 24 hours after the procedure.

Examiner's finger-mounted fetal tissue oximetry.

PubMed

Kanayama, Naohiro; Niwayama, Masatsugu

2014-06-01

The best way to assess fetal condition is to observe the oxygen status of the fetus (as well as to assess the condition of infants, children, and adults). Previously, several fetal oximeters have been developed; however, no instrument has been utilized in clinical practice because of the low-capturing rate of the fetal oxygen saturation. To overcome the problem, we developed a doctor's finger-mounted fetal tissue oximeter, whose sensor volume is one hundredth of the conventional one. Additionally, we prepared transparent gloves. The calculation algorithm of the hemoglobin concentration was derived from the light propagation analysis based on the transport theory. We measured neonatal and fetal oxygen saturation (StO₂) with the new tissue oximeter. Neonatal StO₂ was measured at any position of the head regardless of amount of hair. Neonatal StO₂ was found to be around 77%. Fetal StO₂ was detected in every position of the fetal head during labor regardless of the presence of labor pain. Fetal StO₂ without labor pain was around 70% in the first stage of labor and around 60% in the second stage of labor. We concluded that our new concept of fetal tissue oximetry would be useful for detecting fetal StO₂ in any condition of the fetus.

Examiner's finger-mounted fetal tissue oximetry

NASA Astrophysics Data System (ADS)

Kanayama, Naohiro; Niwayama, Masatsugu

2014-06-01

The best way to assess fetal condition is to observe the oxygen status of the fetus (as well as to assess the condition of infants, children, and adults). Previously, several fetal oximeters have been developed; however, no instrument has been utilized in clinical practice because of the low-capturing rate of the fetal oxygen saturation. To overcome the problem, we developed a doctor's finger-mounted fetal tissue oximeter, whose sensor volume is one hundredth of the conventional one. Additionally, we prepared transparent gloves. The calculation algorithm of the hemoglobin concentration was derived from the light propagation analysis based on the transport theory. We measured neonatal and fetal oxygen saturation (StO2) with the new tissue oximeter. Neonatal StO was measured at any position of the head regardless of amount of hair. Neonatal StO was found to be around 77%. Fetal StO was detected in every position of the fetal head during labor regardless of the presence of labor pain. Fetal StO without labor pain was around 70% in the first stage of labor and around 60% in the second stage of labor. We concluded that our new concept of fetal tissue oximetry would be useful for detecting fetal StO in any condition of the fetus.

Fetal pain perception and pain management.

PubMed

Van de Velde, Marc; Jani, Jacques; De Buck, Frederik; Deprest, J

2006-08-01

This paper gives an overview of current science related to the concept of fetal pain. We have answered three important questions: (1) does fetal pain exist? (2) does management of fetal pain benefit the unborn child? and (3) which techniques are available to provide good fetal analgesia?

Fetal and neonatal thyrotoxicosis

PubMed Central

Batra, Chandar Mohan

2013-01-01

Fetal thyrotoxicosis is a rare disease occurring in 1 out of 70 pregnancies with Grave's disease or in 1 out of 4000-50,000 deliveries. The mortality is 12-20%, usually from heart failure, but other complications are tracheal compression, infections and thrombocytopenia. It results from transfer of thyroid stimulating immunoglobulins from mother to fetus through the placenta. This transplacental transfer begins around 20th week of pregnancy and reaches its maximum by 30th week. These autoantibodies bind to the fetal thyroid stimulating hormone (TSH) receptors and increase the secretion of the thyroid hormones. The mother has an active autoimmune thyroid disease or has been treated for it in the past. She may be absolutely euthyroid due to past treatment by drugs, surgery or radioiodine ablation, but still have active TSH receptor stimulating autoantibodies, which can cause fetal thyrotoxicosis. The other features of this disease are fetal tachycardia, fetal goiter and history of spontaneous abortions and findings of goiter, ascites, craniosyntosis, fetal growth retardation, maceration and hydrops at fetal autopsy. If untreated, this disease can result in intrauterine death. The treatment for this disease consists of giving carbimazole to the mother, which is transferred through the placenta to the fetus. The dose of carbimazole is titrated with the fetal heart rate. If the mother becomes hypothyroid due to carbimazole, thyroxine is added taking advantage of the fact that very little of thyroxine is transferred across the placenta. Neonatal thyrotoxicosis patients are very sick and require emergency treatment. The goal of the treatment is to normalize thyroid functions as quickly as possible, to avoid iatrogenic hypothyroidism while providing management and supportive therapy for the infant's specific signs and symptoms. PMID:24251220

[Physiological significance of IGF-I and its binding proteins on fetal growth and maturation].

PubMed

Iwashita, M

1994-08-01

Insulin-like growth factor-I (IGF-I) is one of growth factors that circulates bound to specific, high affinity binding proteins (IGFBPs). Physiological significance of IGF-I and IGFBPs on fetal growth is investigated in this study. In mother, circulating levels of IGF-I are increased during pregnancy in which placental hormones take the place of pituitary GH to regulate IGF-I during pregnancy and correlates with fetal birth weight. IGFBPs except IGFBP-1 in the maternal circulation are markedly reduced compared to those of non pregnant women due to increased activity of protease(s) while IGFBP-1 gradually increased throughout pregnancy and negatively correlates with fetal weight. IGF-I stimulated 3H-AIB uptake and release by cultured trophoblast cells in a dose dependent manner. Furthermore, fetal growth and the transfer of 3H-AIB to fetus is inhibited when IGF-I is neutralized by polyclonal antibody. These results indicate that maternal IGF-I stimulates fetal growth by activating placental transport of nutrients to fetus. In contrast, IGFBP-1 inhibits both 125I-IGF-I binding to placental membrane and 3H-glycine uptake of trophoblast cells by IGF-I in a dose dependent manner. Moreover, fetal growth and the transfer of 3H-AIB to fetus are accelerated when IGFBP-1 is neutralized by polyclonal antibody, suggesting that maternal IGFBP-1 inhibits fetal growth by inhibiting IGF-I action on the placenta. IGF-I and four IGFBPs including IGFBP-1, -2, -3, and -4 are localized in cytotrophoblast of term placenta. Similarly IGFBP-1, -2, and -4 are detected in medium conditioned by term decidua cells by Western ligand blot in which release of IGFBP-1 and -4 are diminished by IGF-I and all three IGFBPs are increased by progesterone. Thus, there is a complicated autocrine/paracrine regulation between decidua and placenta and IGF-I action on fetal growth is presumed to be modified by this local regulation. Fetal levels of IGF-I and IGFBP-1 are positively and negatively correlate

Is Chronic Obstructive Pulmonary Disease an Accelerated Aging Disease?

PubMed

MacNee, William

2016-12-01

Aging is one of the most important risk factors for most chronic diseases. The worldwide increase in life expectancy has been accompanied by an increase in the prevalence of age-related diseases that result in significant morbidity and mortality and place an enormous burden on healthcare and resources. Aging is a progressive degeneration of the tissues that has a negative impact on the structure and function of vital organs. The lung ages, resulting in decreased function and reduced capacity to respond to environmental stresses and injury. Many of the changes that occur in the lungs with normal aging, such as decline in lung function, increased gas trapping, loss of lung elastic recoil, and enlargement of the distal air spaces, also are present in chronic obstructive pulmonary disease (COPD). The prevalence of COPD is two to three times higher in people over the age of 60 years than in younger age groups. Indeed, COPD has been considered a condition of accelerated lung aging. Several mechanisms associated with aging are present in the lungs of patients with COPD. Cell senescence is present in emphysematous lungs and is associated with shortened telomeres and decreased antiaging molecules, suggesting accelerated aging in the lungs of patients with COPD. Increasing age leads to elevated basal levels of inflammation and oxidative stress (inflammaging) and to increased immunosenescence associated with changes in both the innate and adaptive immune responses. These changes are similar to those that occur in COPD and may enhance the activity of the disease as well as increase susceptibility to exacerbations in patients with COPD. Understanding the mechanism of age-related changes in COPD may identify novel therapies for this condition.

Prenatal Depression Restricts Fetal Growth

PubMed Central

Diego, Miguel A.; Field, Tiffany; Hernandez-Reif, Maria; Schanberg, Saul; Kuhn, Cynthia; Gonzalez-Quintero, Victor Hugo

2009-01-01

Objective To identify whether prenatal depression is a risk factor for fetal growth restriction. Methods Midgestation (18-20 weeks GA) estimated fetal weight and urine cortisol and birth weight and gestational age at birth data were collected on a sample of 40 depressed and 40 non-depressed women. Estimated fetal weight and birthweight data were then used to compute fetal growth rates. Results Depressed women had a 13% greater incidence of premature delivery (Odds Ratio (OR) = 2.61) and 15% greater incidence of low birthweight (OR = 4.75) than non-depressed women. Depressed women also had elevated prenatal cortisol levels (p = .006) and fetuses who were smaller (p = .001) and who showed slower fetal growth rates (p = .011) and lower birthweights (p = .008). Mediation analyses further revealed that prenatal maternal cortisol levels were a potential mediator for the relationship between maternal symptoms of depression and both gestational age at birth and the rate of fetal growth. After controlling for maternal demographic variables, prenatal maternal cortisol levels were associated with 30% of the variance in gestational age at birth and 14% of the variance in the rate of fetal growth. Conclusion Prenatal depression was associated with adverse perinatal outcomes, including premature delivery and slower fetal growth rates. Prenatal maternal cortisol levels appear to play a role in mediating these outcomes. PMID:18723301

Inhaled Vitamin D: A Novel Strategy to Enhance Neonatal Lung Maturation.

PubMed

Taylor, Sneha K; Sakurai, Reiko; Sakurai, Tokusho; Rehan, Virender K

2016-12-01

The physiologic vitamin D (VD), 1α,25(OH) 2 D 3 (1,25D) is a local paracrine/autocrine effecter of fetal lung maturation. By stimulating alveolar type II cell and lipofibroblast proliferation and differentiation, parenterally administered 1,25D has been shown to enhance neonatal lung maturation; but due to the potential systemic side effects of the parenteral route, the translational value of these findings might be limited. To minimize the possibility of systemic toxicity, we examined the effects of VD on neonatal lung maturation, when delivered directly to lungs via nebulization. One-day-old rat pups were administered three different doses of 1,25D and its physiologic precursor 25(OH)D (25D), or the diluent, via nebulization daily for 14 days. Pups were sacrificed for lung, kidneys, and blood collection to determine markers of lung maturation, and serum 25D and calcium levels. Compared to controls, nebulized 25D and 1,25D enhanced lung maturation as evidenced by the increased expression of markers of alveolar epithelial (SP-B, leptin receptor), mesenchymal (PPARγ, C/EBPα), and endothelial (VEGF, FLK-1) differentiation, surfactant phospholipid synthesis, and lung morphology without any significant increases in serum 25D and calcium levels. Inhaled VD is a potentially safe and effective novel strategy to enhance neonatal lung maturation.

Poster — Thur Eve — 31: Dosimetric Effect of Respiratory Motion on RapidArc Lung SBRT Treatment Delivered by TrueBeam Linear Accelerator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Runqing; Zhan, Lixin; Osei, Ernest

2014-08-15

Volumetric modulated arc therapy (VMAT) allows fast delivery of stereotactic radiotherapy. However, the discrepancies between the calculated and delivered dose distributions due to respiratory motion and dynamic multileaf collimators (MLCs) interplay are not avoidable. The purpose of this study is to investigate RapidArc lung SBRT treatment delivered by the flattening filter-free (FFF) beam and flattened beam with Varian TrueBeam machine. CIRS Dynamic Thorax Phantom with in-house made lung tumor insertion was CT scanned both in free breathing and 4DCT. 4DCT was used to determine the internal target volume. The free breathing CT scan was used for treatment planning. A 5more » mm margin was given to ITV to generate a planning target volume. Varian Eclipse treatment planning was used to generate RapidArc plans based on the 6 MV flattened beam and 6MV FFF beam. The prescription dose was 48 Gy in 4 fractions. At least 95% of PTV was covered by the prescribed dose. The RapidArc plans with 6 MV flattened beam and 6MV FFF beam were delivered with Varian TrueBeam machine. The dosimetric measurements were performed with Gafchromic XR-RV3 film, which was placed in the lung tumor insertion. The interplay between the dynamic MLC-based delivery of VMAT and the respiratory motion of the tumor degraded target coverage and created undesired hot or cold dose spots inside the lung tumor. Lung SBRT RapidArc treatments delivered by the FFF beam of TrueBeam linear accelerator is superior to the flattened beam. Further investigation will be performed by Monte Carlo simulation.« less

Prediction of postnatal outcomes in fetuses with isolated congenital diaphragmatic hernias using different lung-to-head ratio measurements.

PubMed

Kehl, Sven; Siemer, Jörn; Brunnemer, Suna; Weiss, Christel; Eckert, Sven; Schaible, Thomas; Sütterlin, Marc

2014-05-01

The purpose of this study was to compare different methods for measuring the fetal lung area-to-head circumference ratio and to investigate their prediction of postpartum survival and the need for neonatal extracorporeal membrane oxygenation (ECMO) therapy in fetuses with isolated congenital diaphragmatic hernias. This prospective study included 118 fetuses of at least 20 weeks' gestation with isolated left-sided congenital diaphragmatic hernias. The lung-to-head ratio was measured with 3 different methods (longest diameter, anteroposterior diameter, and tracing). To eliminate the influence of gestational age, the observed-to-expected lung-to-head ratio was calculated. Receiver operating characteristic (ROC) curves were calculated for the statistical prediction of survival and need for ECMO therapy by the observed-to-expected lung-to-head ratio measured with the different methods. For survival and ECMO necessity 118 and 102 cases (16 neonates were not eligible for ECMO) were assessed, respectively. For prediction of postpartum survival and ECMO necessity, the areas under the ROC curves and 95% confidence intervals showed very similar results for the 3 methods for prediction of survival (tracing, 0.8445 [0.7553-0.9336]; longest diameter, 0.8248 [0.7360-0.9136]; and anteroposterior diameter, 0.8002 [0.7075-0.8928]) and for ECMO necessity (tracing, 0.7344 [0.6297-0.8391]; longest diameter, 0.7128 [0.6027-0.8228]; and anteroposterior diameter, 0.7212 [0.6142-0.8281]). Comparisons between the areas under the ROC curves showed that the tracing method was superior to the anteroposterior diameter method in predicting postpartum survival (P = .0300). Lung-to-head ratio and observed-to-expected lung-to-head ratio measurements were shown to accurately predict postnatal survival and the need for ECMO therapy in fetuses with left-sided congenital diaphragmatic hernias. Tracing the limits of the lungs seems to be the favorable method for calculating the fetal lung area.

Maternal perception of fetal movements in late pregnancy is affected by type and duration of fetal movement.

PubMed

Brown, Rebecca; Higgins, Lucy E; Johnstone, Edward D; Wijekoon, Jayawan H; Heazell, Alexander E P

2016-01-01

A reduction in fetal movements has been proposed to identify pregnancies at risk of stillbirth. The utility of this approach is limited by variability in maternal perception of fetal movements. We aimed to determine the proportion of fetal movements observed by ultrasound that were maternally perceived and identify factors that affected maternal perception. During 30-min recordings, women (n = 21) depressed a trigger upon perception of a fetal movement, while an ultrasound operator recorded observed movements according to the fetal parts involved. Women perceived between 2.4% and 81.0% (median 44.8%) of movements observed on scan. Synchronous movement of the fetal trunk and limbs was more likely to be recognized than either part in isolation (60.5% versus 37.5% and 30%, respectively). The ultrasound operator judged the fetus to be moving for a significantly greater proportion of the time than mothers (median 1.5% of total recording time versus 0.7%). There was no significant relationship between the ability to perceive fetal activity and placental site, parity, amniotic fluid index or maternal body mass index. Variations in maternal perception of fetal movements may affect detection of a clinically significant reduction in fetal movements for some women.

CD10/NEP in non-small cell lung carcinomas. Relationship to cellular proliferation.

PubMed Central

Ganju, R K; Sunday, M; Tsarwhas, D G; Card, A; Shipp, M A

1994-01-01

The cell surface metalloproteinase CD10/neutral endopeptidase 24.11 (NEP) hydrolyzes a variety of peptide substrates and reduces cellular responses to specific peptide hormones. Because CD10/NEP modulates peptide-mediated proliferation of small cell carcinomas of the lung (SCLC) and normal fetal bronchial epithelium, we evaluated the enzyme's expression in non-small cell lung carcinomas (NSCLC). Bronchoalveolar and large cell carcinoma cell lines had low levels of CD10/NEP expression whereas squamous, adenosquamous, and adenocarcinoma cell lines had higher and more variable levels of the cell surface enzyme. Regional variations in CD10/NEP immunostaining in primary NSCLC specimens prompted us to correlate CD10/NEP expression with cell growth. In primary carcinomas of the lung, clonal NSCLC cell lines and SV40-transformed fetal airway epithelium, subsets of cells expressed primarily CD10/NEP or the proliferating cell nuclear antigen (PCNA). Cultured airway epithelial cells had the lowest levels of CD10/NEP expression when the highest percentage of cells were actively dividing; in addition, these cells grew more rapidly when cell surface CD10/NEP was inhibited. NSCLC cell lines had receptors for a variety of mitogenic peptides known to be CD10/NEP substrates, underscoring the functional significance of growth-related variability in CD10/NEP expression. Images PMID:7962523

Fetal Neurobehavioral Development.

ERIC Educational Resources Information Center

DiPietro, Janet A.; And Others

1996-01-01

Investigated the ontogeny of fetal autonomic, motoric, state, and interactive functioning in 31 healthy fetuses from 20 weeks through term. Found that male fetuses were more active than female fetuses, and that greater maternal stress appraisal was associated with reduced fetal heart rate variability. Found that an apparent period of…

Rapid clearance of surfactant-associated palmitic acid from the lungs of developing and adult animals.

PubMed

Tabor, B; Ikegami, M; Yamada, T; Jobe, A

1990-03-01

Palmitic acid is a minor component of natural surfactant and has been used to modify lipid extracts of natural surfactants to optimize their in vitro surface properties. The metabolic fate of palmitic acid in surfactant is unknown. The clearance of surfactant-associated radiolabeled palmitic acid after intratracheal administration was investigated with trace doses of surfactant in the adult rabbit and with trace and treatment doses in the 28-d fetal rabbit and the 132-d fetal sheep. Palmitic acid was cleared rapidly from the airways, with less than 2% of the radiolabel recovered as free palmitic acid in the alveolar wash by 1 h in all models. Recovery as free palmitic acid in the total lung at 2 h was 2% in the adult rabbit and 3% both doses in the preterm rabbit. In the preterm sheep, the recovery as free palmitic acid in the total lung was approximately 2% of the trace dose and 1% of the treatment dose by 5 h. Between 5 and 15% of the instilled palmitic acid was used as substrate for phospholipid synthesis by the lung in the different models. About 30% of the palmitate derived label was recovered in lipid extracts of liver 30 min after tracheal instillation of labeled surfactant in adult rabbits, whereas only 5-10% of the palmitate derived label was found in liver lipids in the preterm animals. In contrast to palmitic acid, radiolabeled triglyceride was cleared much more slowly from the airspaces and lungs of preterm sheep. Inasmuch as large amounts of palmitic acid are cleared rapidly from airspaces and lung tissue, it will not have a prolonged effect on the surface properties of surfactant but it may serve as a precursor for lung lipid metabolism.

Nitrofen increases total retinol levels in placenta during lung morphogenesis in the nitrofen model of congenital diaphragmatic hernia.

PubMed

Kutasy, Balazs; Pes, Lara; Friedmacher, Florian; Paradisi, Francesca; Puri, Prem

2014-10-01

It has been shown that pulmonary retinol level is decreased during lung morphogenesis in the nitrofen-induced PH in congenital diaphragmatic hernia (CDH). Placenta has a major role in the retinol homeostasis in fetal life. Since there is no fetal retinol synthesis, maternal retinol has to cross the placenta. Placenta is the main fetal retinol store where retinol is stored in retinyl-ester formation. Trophoblasts have to produce its own retinol-binding protein (RBP) for retinol transport from placenta to fetus. Recently, we demonstrated that trophoblastic RBP expression is decreased in the nitrofen model of CDH. The aim of this study was to investigate the retinol transfer from mother to the placenta in nitrofen model of CDH. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetal placenta harvested on D21 and divided into two groups: control (n = 11) and nitrofen with CDH (n = 11). Retinoid levels in placenta were measured using HPLC. Immunohistochemistry was performed to evaluate trophoblastic expression of main RSP genes. Total retinol levels in the placenta were significantly increased in CDH placenta compared to control placenta. The retinyl-ester levels were significantly increased in CDH placenta compared to control placenta. Markedly, decreased immunoreactivity of retinoid signaling pathway was observed in trophoblast cells in CDH compared to control placenta. Increased placental retinol levels show that retinol is transferred from mother to placenta and stored in the placenta in nitrofen model of CDH during lung morphogenesis. Nitrofen may disturb the mobilization of retinol from placenta to fetal circulation causing PH in CDH.

Fetal hydrops and other variables associated with the fetal hematocrit decrease after the first intrauterine transfusion for red cell alloimmunization.

PubMed

Lobato, Gustavo; Soncini, Cristina Silveira

2008-01-01

To evaluate the influence of fetal hydrops and other variables on fetal hematocrit (Hct) decrease after the first intrauterine transfusion (IUT) in alloimmunized pregnancies. From 1996 to 2006, the data of all alloimmunized pregnancies submitted to IUT were assessed. Exclusion criteria included: fetuses submitted to intraperitoneal transfusion; pregnancies complicated by other fetal abnormalities; pregnancies submitted to only one IUT, and cases in which posttransfusion or pretransfusion blood samples were not obtained. Linear regression models were implemented to assess the relationship between the rate of Hct fall after the first IUT and the following variables: fetal hydrops; antibody titer; gestational age at the first IUT; number of days between the first and second IUT; pretransfusion and posttransfusion fetal Hct values. Fifty fetuses fulfilled the study criteria. The fetal Hct decrease after the first IUT was 1.21 (range 0.18-2.3) %/day. The variables independently associated with the fetal Hct drop after the first IUT were the fetal hydrops (p = 0.000), the pretransfusion fetal Hct (p = 0.001) and the posttransfusion fetal Hct (p = 0.016). Fetal hydrops, pretransfusion fetal Hct and posttransfusion fetal Hct seem to influence the fetal Hct decrease between the first and second IUT. These findings may be helpful for estimating the rate of fetal Hct drop and programming the following IUT. Copyright 2008 S. Karger AG, Basel.

Radiation-induced lung damage promotes breast cancer lung-metastasis through CXCR4 signaling

PubMed Central

Feys, Lynn; Descamps, Benedicte; Vanhove, Christian; Vral, Anne; Veldeman, Liv; Vermeulen, Stefan; De Wagter, Carlos; Bracke, Marc; De Wever, Olivier

2015-01-01

Radiotherapy is a mainstay in the postoperative treatment of breast cancer as it reduces the risks of local recurrence and mortality after both conservative surgery and mastectomy. Despite recent efforts to decrease irradiation volumes through accelerated partial irradiation techniques, late cardiac and pulmonary toxicity still occurs after breast irradiation. The importance of this pulmonary injury towards lung metastasis is unclear. Preirradiation of lung epithelial cells induces DNA damage, p53 activation and a secretome enriched in the chemokines SDF-1/CXCL12 and MIF. Irradiated lung epithelial cells stimulate adhesion, spreading, growth, and (transendothelial) migration of human MDA-MB-231 and murine 4T1 breast cancer cells. These metastasis-associated cellular activities were largely mimicked by recombinant CXCL12 and MIF. Moreover, an allosteric inhibitor of the CXCR4 receptor prevented the metastasis-associated cellular activities stimulated by the secretome of irradiated lung epithelial cells. Furthermore, partial (10%) irradiation of the right lung significantly stimulated breast cancer lung-specific metastasis in the syngeneic, orthotopic 4T1 breast cancer model. Our results warrant further investigation of the potential pro-metastatic effects of radiation and indicate the need to develop efficient drugs that will be successful in combination with radiotherapy to prevent therapy-induced spread of cancer cells. PMID:26396176

Radiation-induced lung damage promotes breast cancer lung-metastasis through CXCR4 signaling.

PubMed

Feys, Lynn; Descamps, Benedicte; Vanhove, Christian; Vral, Anne; Veldeman, Liv; Vermeulen, Stefan; De Wagter, Carlos; Bracke, Marc; De Wever, Olivier

2015-09-29

Radiotherapy is a mainstay in the postoperative treatment of breast cancer as it reduces the risks of local recurrence and mortality after both conservative surgery and mastectomy. Despite recent efforts to decrease irradiation volumes through accelerated partial irradiation techniques, late cardiac and pulmonary toxicity still occurs after breast irradiation. The importance of this pulmonary injury towards lung metastasis is unclear. Preirradiation of lung epithelial cells induces DNA damage, p53 activation and a secretome enriched in the chemokines SDF-1/CXCL12 and MIF. Irradiated lung epithelial cells stimulate adhesion, spreading, growth, and (transendothelial) migration of human MDA-MB-231 and murine 4T1 breast cancer cells. These metastasis-associated cellular activities were largely mimicked by recombinant CXCL12 and MIF. Moreover, an allosteric inhibitor of the CXCR4 receptor prevented the metastasis-associated cellular activities stimulated by the secretome of irradiated lung epithelial cells. Furthermore, partial (10%) irradiation of the right lung significantly stimulated breast cancer lung-specific metastasis in the syngeneic, orthotopic 4T1 breast cancer model.Our results warrant further investigation of the potential pro-metastatic effects of radiation and indicate the need to develop efficient drugs that will be successful in combination with radiotherapy to prevent therapy-induced spread of cancer cells.

Diagnosis and Treatment of Fetal Arrhythmia

PubMed Central

Wacker-Gussmann, Annette; Strasburger, Janette F.; Cuneo, Bettina F.; Wakai, Ronald T.

2014-01-01

Detection and careful stratification of fetal heart rate (FHR) is extremely important in all pregnancies. The most lethal cardiac rhythm disturbances occur during apparently normal pregnancies where FHR and rhythmare regular and within normal or low-normal ranges. These hidden depolarization and repolarization abnormalities, associated with genetic ion channelopathies cannot be detected by echocardiography, and may be responsible for up to 10% of unexplained fetal demise, prompting a need for newer and better fetal diagnostic techniques. Other manifest fetal arrhythmias such as premature beats, tachycardia, and bradycardia are commonly recognized. Heart rhythm diagnosis in obstetrical practice is usually made by M-mode and pulsed Doppler fetal echocardiography, but not all fetal cardiac time intervals are captured by echocardiographic methods. This article reviews different types of fetal arrhythmias, their presentation and treatment strategies, and gives an overview of the present and future diagnostic techniques. PMID:24858320

Interobserver agreement in CTG interpretation using the 2015 FIGO guidelines for intrapartum fetal monitoring.

PubMed

Rei, Mariana; Tavares, Sara; Pinto, Pedro; Machado, Ana P; Monteiro, Sofia; Costa, Antónia; Costa-Santos, Cristina; Bernardes, João; Ayres-De-Campos, Diogo

2016-10-01

Visual analysis of cardiotocographic (CTG) tracings has been shown to be prone to poor intra- and interobserver agreement when several interpretation guidelines are used, and this may have an important impact on the technology's performance. The aim of this study was to evaluate agreement in CTG interpretation using the new 2015 FIGO guidelines on intrapartum fetal monitoring. A pre-existing database of intrapartum CTG tracings was used to sequentially select 151 cases acquired with a fetal electrode, with duration exceeding 60minutes, and signal loss less than 15%. These tracings were presented to six clinicians, three with more than 5 years' experience in the labor ward, and three with 5 or less years' experience. Observers were asked to evaluate tracings independently, to assess basic CTG features: baseline, variability, accelerations, decelerations, sinusoidal pattern, tachysystole, and to classify each tracing as normal, suspicious or pathologic, according to the 2015 FIGO guidelines on intrapartum fetal monitoring. Agreement between observers was evaluated using the proportions of agreement (Pa), with 95% confidence intervals (95%CI). A good interobserver agreement was found in the evaluation of most CTG features, but not bradycardia, reduced variability, saltatory pattern, absence of accelerations and absence of decelerations. For baseline classification Pa was 0.85 [0.82-0.90], for variability 0.82 [0.78-0.85], for accelerations 0.72 [0.68-0.75], for tachysystole 0.77 [0.74-0.81], for decelerations 0.92 [0.90-0.95], for variable decelerations 0.62 [0.58-0.65], for late decelerations 0.63 [0.59-0.66], for repetitive decelerations 0.73 [0.69-0.78], and for prolonged decelerations 0.81 [0.77-0.85]. For overall CTG classification, Pa were 0.60 [0.56-0.64], for classification as normal 0.67 [0.61-0.72], for suspicious 0.54 [0.48-0.60] and for pathologic 0.59 [0.51-0.66]. No differences in agreement according to the level of expertise were observed, except in the

Racial/ethnic standards for fetal growth: the NICHD Fetal Growth Studies.

PubMed

Buck Louis, Germaine M; Grewal, Jagteshwar; Albert, Paul S; Sciscione, Anthony; Wing, Deborah A; Grobman, William A; Newman, Roger B; Wapner, Ronald; D'Alton, Mary E; Skupski, Daniel; Nageotte, Michael P; Ranzini, Angela C; Owen, John; Chien, Edward K; Craigo, Sabrina; Hediger, Mary L; Kim, Sungduk; Zhang, Cuilin; Grantz, Katherine L

2015-10-01

Fetal growth is associated with long-term health yet no appropriate standards exist for the early identification of undergrown or overgrown fetuses. We sought to develop contemporary fetal growth standards for 4 self-identified US racial/ethnic groups. We recruited for prospective follow-up 2334 healthy women with low-risk, singleton pregnancies from 12 community and perinatal centers from July 2009 through January 2013. The cohort comprised: 614 (26%) non-Hispanic whites, 611 (26%) non-Hispanic blacks, 649 (28%) Hispanics, and 460 (20%) Asians. Women were screened at 8w0d to 13w6d for maternal health status associated with presumably normal fetal growth (aged 18-40 years; body mass index 19.0-29.9 kg/m(2); healthy lifestyles and living conditions; low-risk medical and obstetrical history); 92% of recruited women completed the protocol. Women were randomized among 4 ultrasonography schedules for longitudinal fetal measurement using the Voluson E8 (GE Healthcare, Milwaukee, WI). In-person interviews and anthropometric assessments were conducted at each visit; medical records were abstracted. The fetuses of 1737 (74%) women continued to be low risk (uncomplicated pregnancy, absent anomalies) at birth, and their measurements were included in the standards. Racial/ethnic-specific fetal growth curves were estimated using linear mixed models with cubic splines. Estimated fetal weight (EFW) and biometric parameter percentiles (5th, 50th, 95th) were determined for each gestational week and comparisons made by race/ethnicity, with and without adjustment for maternal and sociodemographic factors. EFW differed significantly by race/ethnicity >20 weeks. Specifically at 39 weeks, the 5th, 50th, and 95th percentiles were 2790, 3505, and 4402 g for white; 2633, 3336, and 4226 g for Hispanic; 2621, 3270, and 4078 g for Asian; and 2622, 3260, and 4053 g for black women (adjusted global P < .001). For individual parameters, racial/ethnic differences by order of detection were

Fetal shielding combined with state of the art CT dose reduction strategies during maternal chest CT.

PubMed

Chatterson, Leslie C; Leswick, David A; Fladeland, Derek A; Hunt, Megan M; Webster, Stephen; Lim, Hyun

2014-07-01

Custom bismuth-antimony shields were previously shown to reduce fetal dose by 53% on an 8DR (detector row) CT scanner without dynamic adaptive section collimation (DASC), automatic tube current modulation (ATCM) or adaptive statistical iterative reconstruction (ASiR). The purpose of this study is to compare the effective maternal and average fetal organ dose reduction both with and without bismuth-antimony shields on a 64DR CT scanner using DASC, ATCM and ASiR during maternal CTPA. A phantom with gravid prosthesis and a bismuth-antimony shield were used. Thermoluminescent dosimeters (TLDs) measured fetal radiation dose. The average fetal organ dose and effective maternal dose were determined using 100 kVp, scanning from the lung apices to the diaphragm utilizing DASC, ATCM and ASiR on a 64DR CT scanner with and without shielding in the first and third trimester. Isolated assessment of DASC was done via comparing a new 8DR scan without DASC to a similar scan on the 64DR with DASC. Average third trimester unshielded fetal dose was reduced from 0.22 mGy ± 0.02 on the 8DR to 0.13 mGy ± 0.03 with the conservative 64DR protocol that included 30% ASiR, DASC and ATCM (42% reduction, P<0.01). Use of a shield further reduced average third trimester fetal dose to 0.04 mGy ± 0.01 (69% reduction, P<0.01). The average fetal organ dose reduction attributable to DASC alone was modest (6% reduction from 0.17 mGy ± 0.02 to 0.16 mGy ± 0.02, P=0.014). First trimester fetal organ dose on the 8DR protocol was 0.07 mGy ± 0.03. This was reduced to 0.05 mGy ± 0.03 on the 64DR protocol without shielding (30% reduction, P=0.009). Shields further reduced this dose to below accurately detectable levels. Effective maternal dose was reduced from 4.0 mSv on the 8DR to 2.5 mSv on the 64DR scanner using the conservative protocol (38% dose reduction). ASiR, ATCM and DASC combined significantly reduce effective maternal and fetal organ dose during CTPA. Shields continue to be an effective

Prediction of neonatal respiratory morbidity by quantitative ultrasound lung texture analysis: a multicenter study.

PubMed

Palacio, Montse; Bonet-Carne, Elisenda; Cobo, Teresa; Perez-Moreno, Alvaro; Sabrià, Joan; Richter, Jute; Kacerovsky, Marian; Jacobsson, Bo; García-Posada, Raúl A; Bugatto, Fernando; Santisteve, Ramon; Vives, Àngels; Parra-Cordero, Mauro; Hernandez-Andrade, Edgar; Bartha, José Luis; Carretero-Lucena, Pilar; Tan, Kai Lit; Cruz-Martínez, Rogelio; Burke, Minke; Vavilala, Suseela; Iruretagoyena, Igor; Delgado, Juan Luis; Schenone, Mauro; Vilanova, Josep; Botet, Francesc; Yeo, George S H; Hyett, Jon; Deprest, Jan; Romero, Roberto; Gratacos, Eduard

2017-08-01

Prediction of neonatal respiratory morbidity may be useful to plan delivery in complicated pregnancies. The limited predictive performance of the current diagnostic tests together with the risks of an invasive procedure restricts the use of fetal lung maturity assessment. The objective of the study was to evaluate the performance of quantitative ultrasound texture analysis of the fetal lung (quantusFLM) to predict neonatal respiratory morbidity in preterm and early-term (<39.0 weeks) deliveries. This was a prospective multicenter study conducted in 20 centers worldwide. Fetal lung ultrasound images were obtained at 25.0-38.6 weeks of gestation within 48 hours of delivery, stored in Digital Imaging and Communication in Medicine format, and analyzed with quantusFLM. Physicians were blinded to the analysis. At delivery, perinatal outcomes and the occurrence of neonatal respiratory morbidity, defined as either respiratory distress syndrome or transient tachypnea of the newborn, were registered. The performance of the ultrasound texture analysis test to predict neonatal respiratory morbidity was evaluated. A total of 883 images were collected, but 17.3% were discarded because of poor image quality or exclusion criteria, leaving 730 observations for the final analysis. The prevalence of neonatal respiratory morbidity was 13.8% (101 of 730). The quantusFLM predicted neonatal respiratory morbidity with a sensitivity, specificity, positive and negative predictive values of 74.3% (75 of 101), 88.6% (557 of 629), 51.0% (75 of 147), and 95.5% (557 of 583), respectively. Accuracy was 86.5% (632 of 730) and positive and negative likelihood ratios were 6.5 and 0.3, respectively. The quantusFLM predicted neonatal respiratory morbidity with an accuracy similar to that previously reported for other tests with the advantage of being a noninvasive technique. Copyright © 2017. Published by Elsevier Inc.

21 CFR 884.1560 - Fetal blood sampler.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fetal blood sampler. 884.1560 Section 884.1560... § 884.1560 Fetal blood sampler. (a) Identification. A fetal blood sampler is a device used to obtain fetal blood transcervically through an endoscope by puncturing the fetal skin with a short blade and...

21 CFR 884.1560 - Fetal blood sampler.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Fetal blood sampler. 884.1560 Section 884.1560... § 884.1560 Fetal blood sampler. (a) Identification. A fetal blood sampler is a device used to obtain fetal blood transcervically through an endoscope by puncturing the fetal skin with a short blade and...

21 CFR 884.1560 - Fetal blood sampler.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Fetal blood sampler. 884.1560 Section 884.1560... § 884.1560 Fetal blood sampler. (a) Identification. A fetal blood sampler is a device used to obtain fetal blood transcervically through an endoscope by puncturing the fetal skin with a short blade and...

21 CFR 884.1560 - Fetal blood sampler.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Fetal blood sampler. 884.1560 Section 884.1560... § 884.1560 Fetal blood sampler. (a) Identification. A fetal blood sampler is a device used to obtain fetal blood transcervically through an endoscope by puncturing the fetal skin with a short blade and...

21 CFR 884.1560 - Fetal blood sampler.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Fetal blood sampler. 884.1560 Section 884.1560... § 884.1560 Fetal blood sampler. (a) Identification. A fetal blood sampler is a device used to obtain fetal blood transcervically through an endoscope by puncturing the fetal skin with a short blade and...

Fetal Cardiac Impairment in Nitrofen-Induced Congenital Diaphragmatic Hernia: Postmortem Microcomputed Tomography Imaging Study.

PubMed

Pelizzo, Gloria; Calcaterra, Valeria; Lombardi, Claudio; Bussani, Rossana; Zambelli, Vanessa; De Silvestri, Annalisa; Custrin, Ana; Belgrano, Manuel; Zennaro, Floriana

2017-08-01

We assessed the post-mortem micro-CT utility to evaluate fetal cardiac impairment in nitrofen-induced congenital diaphragmatic hernia (CDH). At 9.5d postconception (dpc), pregnant rats were exposed to nitrofen. At +18 and +21dpc, fetuses were harvested by cesarean section. Postmortem micro-CT and autopsy were performed. Fetuses were assigned to three experimental groups: Control group (C), Nitrofen group (N, exposition to nitrofen without CDH), CDH group. Cardio-pulmonary indices were evaluated. An accurate morphological evaluation of the lung and heart was obtained. Early cardiac impairment was present in the N and CDH groups. At term pregnancy, an increased maximum diameter and decreased minimum diameter of the ventricles and increased interventricular septal thickness were noted in CDH. Histology showed a myocardial "disarray" and an high density of mitotic myocytes in CDH at midgestation. The potential utility of post-mortem fetal micro-CT examination in CDH was introduced. The results highlighted the presence of cardiac adaptation in affected fetuses.

Lung surfactant.

PubMed Central

Rooney, S A

1984-01-01

Aspects of pulmonary surfactant are reviewed from a biochemical perspective. The major emphasis is on the lipid components of surfactant. Topics reviewed include surfactant composition, cellular and subcellular sites as well as pathways of biosynthesis of phosphatidylcholine, disaturated phosphatidylcholine and phosphatidylglycerol. The surfactant system in the developing fetus and neonate is considered in terms of phospholipid content and composition, rates of precursor incorporation, activities of individual enzymes of phospholipid synthesis and glycogen content and metabolism. The influence of the following hormones and other factors on lung maturation and surfactant production is discussed: glucocorticoids, thyroid hormone, estrogen, prolactin, cyclic AMP, beta-adrenergic and cholinergic agonists, prostaglandins and growth factors. The influence of maternal diabetes, fetal sex, stress and labor are also considered. Nonphysiologic and toxic agents which influence surfactant in the fetus, newborn and adult are reviewed. PMID:6145585

Fetal Tissues Tested for Microbial Sterility by Culture- and PCR-Based Methods Can be Safely Used in Clinics.

PubMed

Vitrenko, Yakov; Kostenko, Iryna; Kulebyakina, Kateryna; Duda, Alla; Klunnyk, Mariya; Sorochynska, Khrystyna

2017-02-16

Cell preparations to be used in clinical practice must be free of infectious agents. Safety concerns are especially elevated upon the use of human fetal tissues, which are otherwise highly advantageous in cell therapy. We demonstrate that treating fetal samples with antibiotic, extensive washing, and homogenization prior to cryoconservation efficiently removes microbes in general. Screening a large collection by an automatic culture system showed that 89.2% fetal tissue samples were sterile, while contamination was detected in 10.8% samples. Liver and chorion were contaminated more than the brain, kidney, lung, and soft tissues. Broad-range PCR from the bacterial 16s rRNA gene was adopted as a confirmatory assay; however, the concordance between the culture-based and PCR assays was weak. Taxonomic identification was done for contaminated samples by bacteriological methods and sequencing 16s rRNA PCR products. The two approaches revealed different spectra of taxonomic groups sharing only Lactobacillus, the most frequently found genus. In addition, other representatives of vaginal microbiota were detected by culture-based identification, while PCR product sequencing has also revealed a subset of nosocomial microorganisms. Importantly, species known to cause sepsis were identified by both techniques, arguing for their indispensability and mutual complementarity. We suggest that most contaminations are taken up during collection of fetal material rather than originating from an in utero infection. In conclusion, a rigorous microbiological control by culture and PCR is a prerequisite for safe clinical use of fetal tissue suspensions.

Adaptation of an articulated fetal skeleton model to three-dimensional fetal image data

NASA Astrophysics Data System (ADS)

Klinder, Tobias; Wendland, Hannes; Wachter-Stehle, Irina; Roundhill, David; Lorenz, Cristian

2015-03-01

The automatic interpretation of three-dimensional fetal images poses specific challenges compared to other three-dimensional diagnostic data, especially since the orientation of the fetus in the uterus and the position of the extremities is highly variable. In this paper, we present a comprehensive articulated model of the fetal skeleton and the adaptation of the articulation for pose estimation in three-dimensional fetal images. The model is composed out of rigid bodies where the articulations are represented as rigid body transformations. Given a set of target landmarks, the model constellation can be estimated by optimization of the pose parameters. Experiments are carried out on 3D fetal MRI data yielding an average error per case of 12.03+/-3.36 mm between target and estimated landmark positions.

Volumetric MRI of the lungs during forced expiration.

PubMed

Berman, Benjamin P; Pandey, Abhishek; Li, Zhitao; Jeffries, Lindsie; Trouard, Theodore P; Oliva, Isabel; Cortopassi, Felipe; Martin, Diego R; Altbach, Maria I; Bilgin, Ali

2016-06-01

Lung function is typically characterized by spirometer measurements, which do not offer spatially specific information. Imaging during exhalation provides spatial information but is challenging due to large movement over a short time. The purpose of this work is to provide a solution to lung imaging during forced expiration using accelerated magnetic resonance imaging. The method uses radial golden angle stack-of-stars gradient echo acquisition and compressed sensing reconstruction. A technique for dynamic three-dimensional imaging of the lungs from highly undersampled data is developed and tested on six subjects. This method takes advantage of image sparsity, both spatially and temporally, including the use of reference frames called bookends. Sparsity, with respect to total variation, and residual from the bookends, enables reconstruction from an extremely limited amount of data. Dynamic three-dimensional images can be captured at sub-150 ms temporal resolution, using only three (or less) acquired radial lines per slice per timepoint. The images have a spatial resolution of 4.6×4.6×10 mm. Lung volume calculations based on image segmentation are compared to those from simultaneously acquired spirometer measurements. Dynamic lung imaging during forced expiration is made possible by compressed sensing accelerated dynamic three-dimensional radial magnetic resonance imaging. Magn Reson Med 75:2295-2302, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Fetal Alcohol Syndrome and Fetal Alcohol Effects-- Support for Teachers and Families.

ERIC Educational Resources Information Center

Duckworth, Susanna V.; Norton, Terry L.

2000-01-01

Reviews genesis of fetal alcohol syndrome and fetal alcohol effects in children. Identifies physical characteristics and behavioral indicators found and provides three checklists of observable signs for both disorders. Recommends seven steps for educators to follow in seeking assistance with these conditions. (DLH)

Long non-coding RNA RUNXOR accelerates MDSC-mediated immunosuppression in lung cancer.

PubMed

Tian, Xinyu; Ma, Jie; Wang, Ting; Tian, Jie; Zheng, Yu; Peng, Rongrong; Wang, Yungang; Zhang, Yue; Mao, Lingxiang; Xu, Huaxi; Wang, Shengjun

2018-06-18

RUNX1 overlapping RNA (RUNXOR) is a long non-coding RNA that has been indicated as a key regulator in the development of myeloid cells by targeting runt-related transcription factor 1 (RUNX1). Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells consisting of immature granulocytes and monocytes with immunosuppression. However, the impact of lncRNA RUNXOR on the development of MDSCs remains unknown. Both the expressions of RUNXOR and RUNX1 in the peripheral blood were measured by qRT-PCR. Human MDSCs used in this study were isolated from tumor tissue of patients with lung cancer by FCM or induced from PBMCs of healthy donors with IL-1β + GM-CSF. Specific siRNA was used to knockdown the expression of RUNXOR in MDSCs. In this study, we found that the lncRNA RUNXOR was upregulated in the peripheral blood of lung cancer patients. In addition, as a target gene of RUNXOR, the expression of RUNX1 was downregulated in lung cancer patients. Finally, the expression of RUNXOR was higher in MDSCs isolated from the tumor tissues of lung cancer patients compared with cells from adjacent tissue. In addition, RUNXOR knockdown decreased Arg1 expression in MDSCs. Based on our findings, it is illustrated that RUNXOR is significantly associated with the immunosuppression induced by MDSCs in lung cancer patients and may be a target of anti-tumor therapy.

[Fetal bone and joint disorders].

PubMed

Jakobovits, Akos

2008-12-21

The article discusses the physiology and pathology of fetal bone and joint development and functions. The bones provide static support for the body. The skull and the bones of spinal column encase the central and part of the peripheral nervous system. The ribs and the sternum shield the heart and the lungs, while the bones of the pelvis protect the intraabdominal organs. Pathological changes of these bony structures may impair the functions of the respective systems or internal organs. Movements of the bones are brought about by muscles. The deriving motions are facilitated by joints. Bony anomalies of the extremities limit their effective functions. Apart from skeletal and joint abnormalities, akinesia may also be caused by neurological, muscular and skin diseases that secondarily affect the functions of bones and joints. Such pathological changes may lead to various degrees of physical disability and even to death. Some of the mentioned anomalies are recognizable in utero by ultrasound. The diagnosis may serve as medical indication for abortion in those instances when the identified abnormality is incompatible with independent life.

Developmental expression of the receptor for advanced glycation end-products (RAGE) and its response to hyperoxia in the neonatal rat lung

PubMed Central

Lizotte, Pierre-Paul; Hanford, Lana E; Enghild, Jan J; Nozik-Grayck, Eva; Giles, Brenda-Louise; Oury, Tim D

2007-01-01

Background The receptor for advanced glycation end products (mRAGE) is associated with pathology in most tissues, while its soluble form (sRAGE) acts as a decoy receptor. The adult lung is unique in that it expresses high amounts of RAGE under normal conditions while other tissues express low amounts normally and up-regulate RAGE during pathologic processes. We sought to determine the regulation of the soluble and membrane isoforms of RAGE in the developing lung, and its expression under hyperoxic conditions in the neonatal lung. Results Fetal (E19), term, 4 day, 8 day and adult rat lung protein and mRNA were analyzed, as well as lungs from neonatal (0–24 hrs) 2 day and 8 day hyperoxic (95% O2) exposed animals. mRAGE transcripts in the adult rat lung were 23% greater than in neonatal (0–24 hrs) lungs. On the protein level, rat adult mRAGE expression was 2.2-fold higher relative to neonatal mRAGE expression, and adult sRAGE protein expression was 2-fold higher compared to neonatal sRAGE. Fetal, term, 4 day and 8 day old rats had a steady increase in both membrane and sRAGE protein expression evaluated by Western Blot and immunohistochemistry. Newborn rats exposed to chronic hyperoxia showed significantly decreased total RAGE expression compared to room air controls. Conclusion Taken together, these data show that rat pulmonary RAGE expression increases with age beginning from birth, and interestingly, this increase is counteracted under hyperoxic conditions. These results support the emerging concept that RAGE plays a novel and homeostatic role in lung physiology. PMID:17343756

Fetal MRI: head and neck.

PubMed

Mirsky, David M; Shekdar, Karuna V; Bilaniuk, Larissa T

2012-08-01

Abnormalities of the fetal head and neck may be seen in isolation or in association with central nervous system abnormalities, chromosomal abnormalities, and syndromes. Magnetic resonance imaging (MRI) plays an important role in detecting associated abnormalities of the brain as well as in evaluating for airway obstruction that may impact prenatal management and delivery planning. This article provides an overview of the common indications for MRI of the fetal head and neck, including abnormalities of the fetal skull and face, masses of the face and neck, and fetal goiter. Copyright © 2012 Elsevier Inc. All rights reserved.

Models of Lung Transplant Research: a consensus statement from the National Heart, Lung, and Blood Institute workshop.

PubMed

Lama, Vibha N; Belperio, John A; Christie, Jason D; El-Chemaly, Souheil; Fishbein, Michael C; Gelman, Andrew E; Hancock, Wayne W; Keshavjee, Shaf; Kreisel, Daniel; Laubach, Victor E; Looney, Mark R; McDyer, John F; Mohanakumar, Thalachallour; Shilling, Rebecca A; Panoskaltsis-Mortari, Angela; Wilkes, David S; Eu, Jerry P; Nicolls, Mark R

2017-05-04

Lung transplantation, a cure for a number of end-stage lung diseases, continues to have the worst long-term outcomes when compared with other solid organ transplants. Preclinical modeling of the most common and serious lung transplantation complications are essential to better understand and mitigate the pathophysiological processes that lead to these complications. Various animal and in vitro models of lung transplant complications now exist and each of these models has unique strengths. However, significant issues, such as the required technical expertise as well as the robustness and clinical usefulness of these models, remain to be overcome or clarified. The National Heart, Lung, and Blood Institute (NHLBI) convened a workshop in March 2016 to review the state of preclinical science addressing the three most important complications of lung transplantation: primary graft dysfunction (PGD), acute rejection (AR), and chronic lung allograft dysfunction (CLAD). In addition, the participants of the workshop were tasked to make consensus recommendations on the best use of these complimentary models to close our knowledge gaps in PGD, AR, and CLAD. Their reviews and recommendations are summarized in this report. Furthermore, the participants outlined opportunities to collaborate and directions to accelerate research using these preclinical models.

Digital atlas of fetal brain MRI.

PubMed

Chapman, Teresa; Matesan, Manuela; Weinberger, Ed; Bulas, Dorothy I

2010-02-01

Fetal MRI can be performed in the second and third trimesters. During this time, the fetal brain undergoes profound structural changes. Interpretation of appropriate development might require comparison with normal age-based models. Consultation of a hard-copy atlas is limited by the inability to compare multiple ages simultaneously. To provide images of normal fetal brains from weeks 18 through 37 in a digital format that can be reviewed interactively. This will facilitate recognition of abnormal brain development. T2-W images for the atlas were obtained from fetal MR studies of normal brains scanned for other indications from 2005 to 2007. Images were oriented in standard axial, coronal and sagittal projections, with laterality established by situs. Gestational age was determined by last menstrual period, earliest US measurements and sonogram performed on the same day as the MR. The software program used for viewing the atlas, written in C#, permits linked scrolling and resizing the images. Simultaneous comparison of varying gestational ages is permissible. Fetal brain images across gestational ages 18 to 37 weeks are provided as an interactive digital atlas and are available for free download from http://radiology.seattlechildrens.org/teaching/fetal_brain . Improved interpretation of fetal brain abnormalities can be facilitated by the use of digital atlas cataloging of the normal changes throughout fetal development. Here we provide a description of the atlas and a discussion of normal fetal brain development.

Fetal Heart Rate Monitoring during Labor

MedlinePlus

... of monitoring? • How is auscultation performed? • How is electronic fetal monitoring performed? • How is external monitoring performed? • ... method of periodically listening to the fetal heartbeat. Electronic fetal monitoring is a procedure in which instruments ...

Recent advances in fetal near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

D'Antona, Donato; Aldrich, Clive J.; O'Brien, Patrick; Lawrence, Sally; Delpy, David T.; Wyatt, John S.

1997-01-01

Fetal brain injury resulting from hypoxia and ischemia during labor remains an important cause of death and long- term disability. However, little is known about fetal brain oxygenation and hemodynamics. There are currently no satisfactory clinical techniques for fetal monitoring and there remains a need for a new method to assess brain oxygenation. Fetal near infrared spectroscopy (NIRS) is a new technique that allows noninvasive observation of changes in the cerebral concentrations of oxyhemoglobin and deoxyhemoglobin to be made during labor. A specially designed optical probe is inserted through the dilated cervix and placed against the fetal head. It is then possible to compare changes in NIRS data with other observations of fetal conditions, such as fetal heart rate and acid-base status.

Lipoprotein Profile Modifications during Gestation: A Current Approach to Cardiovascular risk surrogate markers and Maternal-fetal Unit Complications.

PubMed

Santos, Ana Paula Caires Dos; Couto, Ricardo David

2018-05-16

Several changes occur in lipid metabolism during gestation due to hormonal and metabolic changes, which are essential to satisfy the nutritional demands of the maternal-fetal unit development. The gestation shows two distinct periods that begin with fat accumulation, mainly in maternal adipose tissue, and the late phase, characterized by accelerated catabolism, with the increase of fatty acids in the circulation that causes hyperlipidemia, especially the one characterized as hypertriglyceridemia. Maternal hyperlipidemia may be associated with the development of maternal-fetal complications (preterm birth, preeclampsia, vascular complications) and the development of long-term cardiovascular disease. The cardiovascular risk may not only be related to lipoproteins cholesterol content, but also to the number and functionality of circulating lipoprotein particles. This review reports the major changes that occur in lipoprotein metabolism during pregnancy and that are associated with the development of dyslipidemias, lipoprotein atherogenic phenotype, and maternal-fetal unit complications. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

Fetal Growth and Childhood Acute Lymphoblastic Leukemia: Findings from the Childhood Leukemia International Consortium (CLIC)

PubMed Central

Milne, Elizabeth; Greenop, Kathryn R.; Metayer, Catherine; Schüz, Joachim; Petridou, Eleni; Pombo-de-Oliveira, Maria S.; Infante-Rivard, Claire; Roman, Eve; Dockerty, John D.; Spector, Logan G.; Koifman, Sérgio; Orsi, Laurent; Rudant, Jérémie; Dessypris, Nick; Simpson, Jill; Lightfoot, Tracy; Kaatsch, Peter; Baka, Margarita; Faro, Alessandra; Armstrong, Bruce K.; Clavel, Jacqueline; Buffler, Patricia A.

2013-01-01

Positive associations have been reported between measures of accelerated fetal growth and risk of childhood acute lymphoblastic leukemia (ALL). We investigated this association by pooling individual-level data from 12 case-control studies participating in the Childhood Leukemia International Consortium. Two measures of fetal growth – weight-for-gestational-age and proportion of optimal birth weight (POBW) – were analysed. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression, and combined in fixed effects meta-analyses. Pooled analyses of all data were also undertaken using multivariable logistic regression. Subgroup analyses were undertaken when possible. Data on weight for gestational age were available for 7,348 cases and 12,489 controls from all 12 studies and POBW data were available for 1,680 cases and 3,139 controls from three studies. The summary ORs from the meta-analyses were 1.24 (95% CI 1.13, 1.36) for children who were large for gestational age relative to appropriate for gestational age, and 1.16 (95% CI: 1.09, 1.24) for a one standard deviation increase in POBW. The pooled analyses produced similar results. The summary and pooled ORs for small-for-gestational-age children were 0.83 (95% CI: 0.75, 0.92) and 0.86 (95% CI 0.77, 0.95) respectively. Results were consistent across subgroups defined by sex, ethnicity and immunophenotype, and when the analysis was restricted to children who did not have high birth weight. The evidence that accelerated fetal growth is associated with a modest increased risk of childhood ALL is strong and consistent with known biological mechanisms involving insulin like growth factors. PMID:23754574

Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development.

PubMed

Dunford, Louise J; Sinclair, Kevin D; Kwong, Wing Y; Sturrock, Craig; Clifford, Bethan L; Giles, Tom C; Gardner, David S

2014-11-01

This paper identifies a common nutritional pathway relating maternal through to fetal protein-energy malnutrition (PEM) and compromised fetal kidney development. Thirty-one twin-bearing sheep were fed either a control (n=15) or low-protein diet (n=16, 17 vs. 8.7 g crude protein/MJ metabolizable energy) from d 0 to 65 gestation (term, ∼ 145 d). Effects on the maternal and fetal nutritional environment were characterized by sampling blood and amniotic fluid. Kidney development was characterized by histology, immunohistochemistry, vascular corrosion casts, and molecular biology. PEM had little measureable effect on maternal and fetal macronutrient balance (glucose, total protein, total amino acids, and lactate were unaffected) or on fetal growth. PEM decreased maternal and fetal urea concentration, which blunted fetal ornithine availability and affected fetal hepatic polyamine production. For the first time in a large animal model, we associated these nutritional effects with reduced micro- but not macrovascular development in the fetal kidney. Maternal PEM specifically impacts the fetal ornithine cycle, affecting cellular polyamine metabolism and microvascular development of the fetal kidney, effects that likely underpin programming of kidney development and function by a maternal low protein diet. © FASEB.

Fetal body weight and the development of the control of the cardiovascular system in fetal sheep.

PubMed

Frasch, M G; Müller, T; Wicher, C; Weiss, C; Löhle, M; Schwab, K; Schubert, H; Nathanielsz, P W; Witte, O W; Schwab, M

2007-03-15

Reduced birth weight predisposes to cardiovascular diseases in later life. We examined in fetal sheep at 0.76 (n = 18) and 0.87 (n = 17) gestation whether spontaneously occurring variations in fetal weight affect maturation of autonomic control of cardiovascular function. Fetal weights at both gestational ages were grouped statistically in low (LW) and normal weights (NW) (P < 0.01). LW fetuses were within the normal weight span showing minor growth dysproportionality at 0.76 gestation favouring heart and brain, with a primary growth of carcass between 0.76 and 0.87 gestation (P < 0.05). While twins largely contributed to LW fetuses, weight differences between singletons and twins were absent at 0.76 and modest at 0.87 gestation, underscoring the fact that twins belong to normality in fetal sheep not constituting a major malnutritive condition. Mean fetal blood pressure (FBP) of all fetuses was negatively correlated to fetal weight at 0.76 but not 0.87 gestation (P < 0.05). At this age, FBP and baroreceptor reflex sensitivity were increased in LW fetuses (P < 0.05), suggesting increased sympathetic activity and immaturity of circulatory control. Development of vagal modulation of fetal heart rate depended on fetal weight (P < 0.01). These functional associations were largely independent of twin pregnancies. We conclude, low fetal weight within the normal weight span is accompanied by a different trajectory of development of sympathetic blood pressure and vagal heart rate control. This may contribute to the development of elevated blood pressure in later life. Examination of the underlying mechanisms and consequences may contribute to the understanding of programming of cardiovascular diseases.

Incorporation of Prior Knowledge of Signal Behavior Into the Reconstruction to Accelerate the Acquisition of Diffusion MRI Data.

PubMed

Abascal, Juan F P J; Desco, Manuel; Parra-Robles, Juan

2018-02-01

Diffusion MRI data are generally acquired using hyperpolarized gases during patient breath-hold, which yields a compromise between achievable image resolution, lung coverage, and number of -values. In this paper, we propose a novel method that accelerates the acquisition of diffusion MRI data by undersampling in both the spatial and -value dimensions and incorporating knowledge about signal decay into the reconstruction (SIDER). SIDER is compared with total variation (TV) reconstruction by assessing its effect on both the recovery of ventilation images and the estimated mean alveolar dimensions (MADs). Both methods are assessed by retrospectively undersampling diffusion data sets ( =8) of healthy volunteers and patients with Chronic Obstructive Pulmonary Disease (COPD) for acceleration factors between x2 and x10. TV led to large errors and artifacts for acceleration factors equal to or larger than x5. SIDER improved TV, with a lower solution error and MAD histograms closer to those obtained from fully sampled data for acceleration factors up to x10. SIDER preserved image quality at all acceleration factors, although images were slightly smoothed and some details were lost at x10. In conclusion, we developed and validated a novel compressed sensing method for lung MRI imaging and achieved high acceleration factors, which can be used to increase the amount of data acquired during breath-hold. This methodology is expected to improve the accuracy of estimated lung microstructure dimensions and provide more options in the study of lung diseases with MRI.

Fetal sigmoid colon mesentery - In relevance in fetal ultrasound application. A pilot study.

PubMed

Wozniak, Slawomir; Florjanski, Jerzy; Kordecki, Henryk; Podhorska-Okolow, Marzena; Domagala, Zygmunt

2018-03-01

Ultrasound examinations during pregnancy are routine procedures used to detect fetal congenital malformations. Ultrasound monitoring of sigmoid colon mesenterial development could be useful for early detection of subjects at risk of sigmoid colon volvulus. The aim of our paper was to assess the sigmoid colon length, and sigmoid colon mesentery width and height in the late fetal period, and, using the results, to estimate the surface area of the mesocolon (in mm 2 ) in living fetuses. Moreover, we attempted to repeat some of these measurements in living fetuses using ultrasound imaging. The study was carried out on 209 formalin fixed human fetuses (100 female and 109 male) aged from 4th to 7th gestational months (102-203 days), with a crown-rump length of 132-342mm. The length of the sigmoid colon, as well as the height and width of its mesentery were measured. The surface area of the mesocolon was estimated. Correction for formalin induced shrinkage was applied. Pilot ultrasound examinations of live fetuses were performed. Mean values of sigmoid colon length, mesenteric width and height (formalin fixed fetuses) for respective gestational ages were: month 4: 21.46±6.7mm, 6.80±2.1mm, 5.5±1.49mm; month 5: 27.32±1.2mm, 7.62±2.01mm, 7.33±2.17mm; month 6: 47.56±9.57mm, 11.68±3.8mm, 10.3±3.05mm; month 7: 56.92±17.48mm. 15.32±8 mm, 12.81±3.16mm. The surface area ranges of the sigmoid colon mesentery found for respective gestational months (intrauterine fetuses) were as follows: month 4: 33.24-51.95mm 2 ; month 5: 49.63-77.6mm 2 ; month 6: 106.89-167.15mm 2 and month 7: 145.69-272.53mm 2 . The surface area of the sigmoid colon mesentery can be used as a simple parameter applied in fetal ultrasonographic evaluation. The development of the sigmoid colon accelerates in the 6th gestational month, and decelerates in the 7th gestational month. The sigmoid colon mesentery width was larger than its height between the 4th and 7th gestational months. Copyright © 2017

Influence of maternal hyperthyroidism in the rat on the expression of neuronal and astrocytic cytoskeletal proteins in fetal brain.

PubMed

Evans, I M; Pickard, M R; Sinha, A K; Leonard, A J; Sampson, D C; Ekins, R P

2002-12-01

Maternal hypothyroidism during pregnancy impairs brain function in human and rat offspring, but little is known regarding the influence of maternal hyperthyroidism on neurodevelopment. We have previously shown that the expression of neuronal and glial differentiation markers in fetal brain is compromised in hypothyroid rat dam pregnancies and have now therefore extended this investigation to hyperthyroid rat dams. Study groups comprised partially thyroidectomised dams, implanted with osmotic pumps infusing either vehicle (TX dams) or a supraphysiological dose of thyroxine (T4) (HYPER dams), and euthyroid dams infused with vehicle (N dams). Cytoskeletal protein abundance was determined in fetal brain at 21 days of gestation by immunoblot analysis. Relative to N dams, circulating total T4 levels were reduced to around one-third in TX dams but were doubled in HYPER dams. Fetal brain weight was increased in HYPER dams, whereas litter size and fetal body weight were reduced in TX dams. Glial fibrillary acidic protein expression was similar in HYPER and TX dams, being reduced in both cases relative to N dams. alpha-Internexin (INX) abundance was reduced in HYPER dams and increased in TX dams, whereas neurofilament 68 (NF68) exhibited increased abundance in HYPER dams. Furthermore, INX was inversely related to - and NF68 directly related to - maternal serum total T4 levels, independently of fetal brain weight. In conclusion, maternal hyperthyroidism compromises the expression of neuronal cytoskeletal proteins in late fetal brain, suggestive of a pattern of accelerated neuronal differentiation.

Professionals' views of fetal-monitoring support the development of devices to provide objective longer-term assessment of fetal wellbeing.

PubMed

Brown, Rebecca; Johnstone, Edward D; Heazell, Alexander E P

2016-01-01

Continuous longer-term fetal monitoring has been proposed to address limitations of current technologies in the detection of fetal compromise. We aimed to assess professionals' views regarding current fetal-monitoring techniques and proposed longer-term continuous fetal monitoring. A questionnaire was designed and validated to assess obstetricians' and midwives' use of current fetal-monitoring techniques and their views towards continuous monitoring. 125 of 173 received responses (72% obstetricians, 28% midwives) were analysed. Professionals had the strongest views about supporting evidence for the most commonly employed fetal-monitoring techniques (maternal awareness of fetal movements, ultrasound assessment of fetal growth and umbilical artery Doppler). 45.1% of professionals agreed that a continuous monitoring device would be beneficial (versus 28.7% who disagreed); this perceived benefit was not influenced by professionals' views regarding current techniques or professional background. Professionals have limited experience of continuous fetal monitoring, but most respondents believed that it would increase maternal anxiety (64.3%) and would have concerns with its use in clinical practice (81.7%). Continuous fetal monitoring would be acceptable to the majority of professionals. However, development of these technologies must be accompanied by extended examination of professionals' and women's views to determine barriers to its introduction.

Microfluidic chest cavities reveal that transmural pressure controls the rate of lung development.

PubMed

Nelson, Celeste M; Gleghorn, Jason P; Pang, Mei-Fong; Jaslove, Jacob M; Goodwin, Katharine; Varner, Victor D; Miller, Erin; Radisky, Derek C; Stone, Howard A

2017-12-01

Mechanical forces are increasingly recognized to regulate morphogenesis, but how this is accomplished in the context of the multiple tissue types present within a developing organ remains unclear. Here, we use bioengineered 'microfluidic chest cavities' to precisely control the mechanical environment of the fetal lung. We show that transmural pressure controls airway branching morphogenesis, the frequency of airway smooth muscle contraction, and the rate of developmental maturation of the lungs, as assessed by transcriptional analyses. Time-lapse imaging reveals that branching events are synchronized across distant locations within the lung, and are preceded by long-duration waves of airway smooth muscle contraction. Higher transmural pressure decreases the interval between systemic smooth muscle contractions and increases the rate of morphogenesis of the airway epithelium. These data reveal that the mechanical properties of the microenvironment instruct crosstalk between different tissues to control the development of the embryonic lung. © 2017. Published by The Company of Biologists Ltd.

Fetal response to maternal hunger and satiation - novel finding from a qualitative descriptive study of maternal perception of fetal movements.

PubMed

Bradford, Billie; Maude, Robyn

2014-08-26

Maternal perception of decreased fetal movements is a specific indicator of fetal compromise, notably in the context of poor fetal growth. There is currently no agreed numerical definition of decreased fetal movements, with the subjective perception of a decrease on the part of the mother being the most significant definition clinically. Both qualitative and quantitative aspects of fetal activity may be important in identifying the compromised fetus.Yet, how pregnant women perceive and describe fetal activity is under-investigated by qualitative means. The aim of this study was to explore normal fetal activity, through first-hand descriptive accounts by pregnant women. Using qualitative descriptive methodology, interviews were conducted with 19 low-risk women experiencing their first pregnancy, at two timepoints in their third trimester. Interview transcripts were later analysed using qualitative content analysis and patterns of fetal activity identified were then considered along-side the characteristics of the women and their birth outcomes. This paper focuses on a novel finding; the description by pregnant women of fetal behaviour indicative of hunger and satiation. Full findings will be presented in later papers. Most participants (74% 14 of 19) indicated mealtimes were a time of increased fetal activity. Eight participants provided detailed descriptions of increased activity around meals, with seven (37% 7 of 19) of these specifying increased fetal activity prior to meals or in the context of their own hunger. These movements were interpreted as a fetal demand for food often prompting the mother to eat. Interestingly, the women who described increased fetal activity in the context of hunger subsequently gave birth to smaller infants (mean difference 364 gm) than those who did not describe a fetal response to hunger. Food seeking behaviour may have a pre-birth origin. Maternal-fetal interaction around mealtimes could constitute an endocrine mediated

Ethical challenges in fetal surgery.

PubMed

Smajdor, Anna

2011-02-01

Fetal surgery has been practised for some decades now. However, it remains a highly complex area, both medically and ethically. This paper shows how the routine use of ultrasound has been a catalyst for fetal surgery, in creating new needs and new incentives for intervention. Some of the needs met by fetal surgery are those of parents and clinicians who experience stress while waiting for the birth of a fetus with known anomalies. The paper suggests that the role of technology and visualisation techniques in creating and meeting such new needs is ethically problematic. It then addresses the idea that fetal surgery should be restricted to interventions that are life-saving for the fetus, arguing that this restriction is unduly paternalistic. Fetal surgery poses challenges for an autonomy-based system of ethics. However, it is risky to circumvent these challenges by restricting the choices open to pregnant women, even when these choices appear excessively altruistic.

Fetal heart rate monitoring.

PubMed

Nageotte, Michael P

2015-06-01

Electronic fetal heart rate monitoring is a widely utilized means of assessment of fetal status during labor. Whereas little evidence exists regarding efficacy, this modality continues to be used extensively in every modern labor and delivery unit in developed countries. It is of importance that all providers of health care to the woman in labor and her newborn have a clear understanding of the basic pathophysiology of fetal heart rate monitoring and an appreciation for labor course and concerns as they arise in order to optimize outcomes and patient safety. Copyright © 2015 Elsevier Ltd. All rights reserved.

Thrombophilic disorders and fetal loss: a meta-analysis.

PubMed

Rey, Evelyne; Kahn, Susan R; David, Michèle; Shrier, Ian

2003-03-15

Our aim was to assess the strength of the controversial association between thrombophilia and fetal loss, and to examine whether it varies according to the timing or definition of fetal loss. We searched Medline and Current Contents for articles published between 1975 and 2002 and their references with terms denoting recurrent fetal and non-recurrent fetal loss combined with various thrombophilic disorders. We included in our meta-analysis case-control, cohort, and cross-sectional studies published in English, the methodological quality of which was rated as moderate or strong. Pooled odds ratios (OR) with 95% CI were generated by random effects models with Cochrane Review Manager software. We included 31 studies. Factor V Leiden was associated with early (OR 2.01, 95% CI 1.13-3.58) and late (7.83, 2.83-21.67) recurrent fetal loss, and late non-recurrent fetal loss (3.26, 1.82-5.83). Exclusion of women with other pathologies that could explain fetal loss strengthened the association between Factor V Leiden and recurrent fetal loss. Activated protein C resistance was associated with early recurrent fetal loss (3.48, 1.58-7.69), and prothrombin G20210A mutation with early recurrent (2.56, 1.04-.29) and late non-recurrent (2.30, 1.09-4.87) fetal loss. Protein S deficiency was associated with recurrent fetal loss (14.72, 0.99-218.01) and late non-recurrent fetal loss (7.39, 1.28-42.63). Methylenetetrahydrofolate mutation, protein C, and antithrombin deficiencies were not significantly associated with fetal loss. The magnitude of the association between thrombophilia and fetal loss varies, according to type of fetal loss and type of thrombophilia.

HI-CHART: a phase I/II study on the feasibility of high-dose continuous hyperfractionated accelerated radiotherapy in patients with inoperable non-small-cell lung cancer.

PubMed

De Ruysscher, Dirk; Wanders, Rinus; van Haren, Erik; Hochstenbag, Monique; Geraedts, Wiel; Pitz, Cordula; Simons, Jean; Boersma, Liesbeth; Verschueren, Tom; Minken, Andre; Bentzen, Søren M; Lambin, Philippe

2008-05-01

To determine the feasibility of high-dose continuous hyperfractionated accelerated radiotherapy in patients with inoperable non-small-cell lung cancer (NSCLC). In a prospective, Phase I/II study, according to the risk for radiation pneumonitis, three risk groups were defined: V(20) <25%, V(20) 25-37%, and V(20) >37%. The dose was administered in three steps from 61.2 Gy/34 fractions/23 days to 64.8 Gy/36 fractions/24 days to 68.40 Gy/38 fractions/25 days (1.8 Gy b.i.d. with 8-h interval), using a three-dimensional conformal technique. Only the mediastinal lymph node areas that were positive on the pretreatment (18)F-deoxy-D-glucose positron emission tomography scan were included in the target volume. The primary endpoint was toxicity. A total of 48 Stage I-IIIB patients were included. In all risk groups, 68.40 Gy/38 fractions/25 days could be administered. Maximal toxicity according to the risk groups was as follows: V(20) <25% (n = 35): 1 Grade 4 (G4) lung and 1 G3 reversible esophageal toxicity; V(20) 35-37% (n = 12): 1 G5 lung and 1 G3 reversible esophageal toxicity. For the whole group, local tumor recurrence occurred in 25% (95% confidence interval 14%-40%) of the patients, with 1 of 48 (2.1%; upper one-sided 95% confidence limit 9.5%) having an isolated nodal recurrence. The median actuarial overall survival was 20 months, with a 2-year survival rate of 36%. High-dose continuous hyperfractionated accelerated radiotherapy up to a dose of 68.40 Gy/38 fractions/25 days (a biologic equivalent of approximately 80 Gy when delivered in conventional fractionation) in patients with inoperable NSCLC and a V(20) up to 37% is feasible.

Maternal hemodynamics, fetal biometry and Dopplers in pregnancies followed up for suspected fetal growth restriction.

PubMed

Roberts, Llinos A; Ling, Hua Zen; Poon, Liona; Nicolaides, Kypros H; Kametas, Nikos A

2018-04-01

To assess whether in a cohort of patients with small for gestational age (SGA) foetuses with estimated fetal weight ≤10 th percentile, maternal hemodynamics, fetal biometry and Dopplers at presentation, can predict the subsequent development of abnormal fetal Dopplers or delivery with birthweight <3 rd percentile. The study population comprised of 86 singleton pregnancies with SGA fetuses presenting at a median gestational age of 32 (range 26-35) weeks. We measured maternal cardiac function with a non-invasive transthoracic bioreactance monitor (NICOM, Cheetah), mean arterial pressure, fetal biometry, umbilical artery (UA), middle cerebral artery (MCA) and uterine artery (UT) pulsatility index (PI) and the deepest vertical pool (DVP) of amniotic fluid. Z-scores of these variables were calculated based on reported reference ranges and the values were compared between those with evidence of abnormal fetal Dopplers at presentation (group 1), those that developed abnormal Dopplers in subsequent visits (group 2) and those who did not develop abnormal Dopplers throughout pregnancy (group 3). Abnormal fetal Dopplers were defined as UAPI >95 th percentile, or MCA PI <5 th percentile. Differences in measured variables at presentation were also compared between pregnancies delivering a baby with birthweight <3 rd and ≥3 rd percentile. Multivariate logistic regression analysis was used to determine significant predictors of birthweight <3 rd percentile and evolution from normal fetal Dopplers to abnormal fetal Dopplers in groups 2 and 3. In the study population 14 (16%) cases were in group 1, 19 (22%) in group 2 and 53 (62%) in group 3. The birthweight was <3 rd percentile in 39 (45%) cases and ≥3 rd percentile in 47 (55%). In the study groups, compared to normal populations, there was decreased cardiac output and stroke volume and increased peripheral vascular resistance and mean arterial pressure (MAP) and the deviations from normal were most marked in group 1

Passive Fetal Heart Monitoring System

NASA Technical Reports Server (NTRS)

Zuckerwar, Allan J. (Inventor); Mowrey, Dennis L. (Inventor)

2003-01-01

A fetal heart monitoring system and method for detecting and processing acoustic fetal heart signals transmitted by different signal transmission modes. One signal transmission mode, the direct contact mode, occurs in a first frequency band when the fetus is in direct contact with the maternal abdominal wall. Another signal transmission mode, the fluid propagation mode, occurs in a second frequency band when the fetus is in a recessed position with no direct contact with the maternal abdominal wall. The second frequency band is relatively higher than the first frequency band. The fetal heart monitoring system and method detect and process acoustic fetal heart signals that are in the first frequency band and in the second frequency band.

High-dose accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine and carboplatin chemotherapy in locally advanced non-small-cell lung cancer: a feasibility study.

PubMed

Liu, Yue-E; Lin, Qiang; Meng, Fan-Jie; Chen, Xue-Ji; Ren, Xiao-Cang; Cao, Bin; Wang, Na; Zong, Jie; Peng, Yu; Ku, Ya-Jun; Chen, Yan

2013-08-11

Increasing the radiotherapy dose can result in improved local control for non-small-cell lung cancer (NSCLC) and can thereby improve survival. Accelerated hypofractionated radiotherapy can expose tumors to a high dose of radiation in a short period of time, but the optimal treatment regimen remains unclear. The purpose of this study was to evaluate the feasibility of utilizing high-dose accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine (NVB) and carboplatin (CBP) chemotherapy for the treatment of local advanced NSCLC. Untreated patients with unresectable stage IIIA/IIIB NSCLC or patients with a recurrence of NSCLC received accelerated hypofractionated three-dimensional conformal radiotherapy. The total dose was greater than or equal to 60 Gy. The accelerated hypofractionated radiotherapy was conducted once daily at 3 Gy/fraction with 5 fractions per week, and the radiotherapy was completed in 5 weeks. In addition to radiotherapy, the patients also received at least 1 cycle of a concurrent two-drug chemotherapy regimen of NVB and CBP. A total of 26 patients (19 previously untreated cases and 7 cases of recurrent disease) received 60Gy-75Gy radiotherapy with concurrent chemotherapy. All of the patients underwent evaluations for toxicity and preliminary therapeutic efficacy. There were no treatment-related deaths within the entire patient group. The major acute adverse reactions were radiation esophagitis (88.5%) and radiation pneumonitis (42.3%). The percentages of grade III acute radiation esophagitis and grade III radiation pneumonitis were 15.4% and 7.7%, respectively. Hematological toxicities were common and did not significantly affect the implementation of chemoradiotherapy after supportive treatment. Two patients received high dose of 75 Gy had grade III late esophageal toxicity, and none had grade IV and above. Grade III and above late lung toxicity did not occur. High-dose accelerated

High-dose accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine and carboplatin chemotherapy in locally advanced non-small-cell lung cancer: a feasibility study

PubMed Central

2013-01-01

Background Increasing the radiotherapy dose can result in improved local control for non-small-cell lung cancer (NSCLC) and can thereby improve survival. Accelerated hypofractionated radiotherapy can expose tumors to a high dose of radiation in a short period of time, but the optimal treatment regimen remains unclear. The purpose of this study was to evaluate the feasibility of utilizing high-dose accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine (NVB) and carboplatin (CBP) chemotherapy for the treatment of local advanced NSCLC. Methods Untreated patients with unresectable stage IIIA/IIIB NSCLC or patients with a recurrence of NSCLC received accelerated hypofractionated three-dimensional conformal radiotherapy. The total dose was greater than or equal to 60 Gy. The accelerated hypofractionated radiotherapy was conducted once daily at 3 Gy/fraction with 5 fractions per week, and the radiotherapy was completed in 5 weeks. In addition to radiotherapy, the patients also received at least 1 cycle of a concurrent two-drug chemotherapy regimen of NVB and CBP. Results A total of 26 patients (19 previously untreated cases and 7 cases of recurrent disease) received 60Gy-75Gy radiotherapy with concurrent chemotherapy. All of the patients underwent evaluations for toxicity and preliminary therapeutic efficacy. There were no treatment-related deaths within the entire patient group. The major acute adverse reactions were radiation esophagitis (88.5%) and radiation pneumonitis (42.3%). The percentages of grade III acute radiation esophagitis and grade III radiation pneumonitis were 15.4% and 7.7%, respectively. Hematological toxicities were common and did not significantly affect the implementation of chemoradiotherapy after supportive treatment. Two patients received high dose of 75 Gy had grade III late esophageal toxicity, and none had grade IV and above. Grade III and above late lung toxicity did not occur

Fetal motor activity and maternal cortisol

PubMed Central

DiPietro, Janet A.; Kivlighan, Katie T.; Costigan, Kathleen A.; Laudenslager, Mark L.

2009-01-01

The contemporaneous association between maternal salivary cortisol and fetal motor activity was examined at 32 and 36 weeks gestation. Higher maternal cortisol was positively associated with the amplitude of fetal motor activity at 32 weeks, r(48) = .39, p < .01, and 36 weeks, r(77)=.27, p < .05, and the amount of time fetuses spent moving at 32 weeks during the 50 minute observation period, r(48) = 33, p < .05. Observation of periods of unusually intense fetal motor activity were more common in fetuses of women with higher cortisol, Mann-Whitney U = 58.5. There were no sex differences in fetal motor activity, but the associations between maternal cortisol and fetal motor amplitude and overall movement were significantly stronger for male than female fetuses. PMID:19630038

Fetal Treatment 2017: the Evolution of Fetal Therapy Centers

PubMed Central

MOON-GRADY, Anita J.; BASCHAT, Ahmet; CASS, Darrell; CHOOLANI, Mahesh; COPEL, Joshua; CROMBLEHOLME, Timothy M.; DEPREST, Jan; EMERY, Stephen P.; EVANS, Mark I.; LUKS, Francois; NORTON, Mary E.; RYAN, Greg; TSAO, Kuojen; WELCH, Ross; HARRISON, Michael

2017-01-01

More than 3 decades ago, a small group of physicians and other practitioners active in what they called “fetal treatment” authored an opinion piece outlining the current status and future challenges anticipated in the field. Many advances in maternal, neonatal, and perinatal care and diagnostic and therapeutic modalities have been made in the intervening years, yet a thoughtful re-assessment of the basic tenets put forth in 1982 has not been published. The present effort will aim to provide a framework for contemporary redefinition of the field of fetal treatment, with brief discussion of the necessary minimum expertise and systems-base for provision of different types of interventions on both a mother and fetus. Our goal will be to present an opinion that encourages the advancement of thoughtful practice, ensuring that current and future patients have realistic access to centers with a range of fetal therapies with appropriate expertise, experience, subspecialty and institutional support while remaining focused on excellence in care, collaborative scientific discovery, and maternal autonomy and safety. PMID:28531885

The "Fetal Reserve Index": Re-Engineering the Interpretation and Responses to Fetal Heart Rate Patterns.

PubMed

Eden, Robert D; Evans, Mark I; Evans, Shara M; Schifrin, Barry S

2018-01-01

Electronic fetal monitoring (EFM) correlates poorly with neonatal outcome. We present a new metric: the "Fetal Reserve Index" (FRI), formally incorporating EFM with maternal, obstetrical, fetal risk factors, and excessive uterine activity for assessment of risk for cerebral palsy (CP). We performed a retrospective, case-control series of 50 term CP cases with apparent intrapartum neurological injury and 200 controls. All were deemed neurologically normal on admission. We compared the FRI against ACOG Category (I-III) system and long-term outcome parameters against ACOG monograph (NEACP) requirements for labor-induced fetal neurological injury. Abnormal FRI's identified 100% of CP cases and did so hours before injury. ACOG Category III identified only 44% and much later. Retrospective ACOG monograph criteria were found in at most 30% of intrapartum-acquired CP patients; only 27% had umbilical or neonatal pH <7.0. In this initial, retrospective trial, an abnormal FRI identified all cases of labor-related neurological injury more reliably and earlier than Category III, which may allow fetal therapy by intrauterine resuscitation. The combination of traditional EFM with maternal, obstetrical, and fetal risk factors creating the FRI performed much better as a screening test than EFM alone. Our quantified screening system needs further evaluation in prospective trials. © 2017 S. Karger AG, Basel.

Lung cancer in the pregnant woman: to treat or not to treat, that is the question.

PubMed

Azim, Hatem A; Peccatori, Fedro A; Pavlidis, Nicholas

2010-03-01

Lung cancer in pregnancy is a rare situation; however, it is increasingly reported in the past two decades. The association might be more encountered in the coming years due to the rising trends of cigarette smoking among young women and tendency to delay pregnancy to later in life. We performed a literature search without any date or language restriction and identified 44 cases diagnosed and/or treated for lung cancer during the course of pregnancy. Patients had poor post-partum outcome with less than one-forth alive at 1 year following delivery. There was a high incidence of metastases to the products of conception reaching 26%. Eight patients were treated with systemic therapies during the course of gestation with normal fetal outcome and no evidence of fetal or placental metastases. Counseling of these patients is very important. Apart from the clinical conflict they pose, some ethical aspects should be taken in consideration. The poor maternal prognosis should be discussed and the patient's autonomy should be respected to decide whether she wants to keep the pregnancy or not.

Effects of tracheal occlusion with retinoic acid administration on normal lung development.

PubMed

Delabaere, Amélie; Marceau, Geoffroy; Coste, Karen; Blanchon, Loïc; Déchelotte, Pierre-Jean; Blanc, Pierre; Sapin, Vincent; Gallot, Denis

2017-05-01

Tracheal occlusion (TO) is an investigational therapy for severe congenital diaphragmatic hernia that decreases pulmonary hypoplasia, but sustained TO also induces deficient surfactant synthesis. Intramuscular maternal administration of retinoic acid (RA) in a surgical rabbit model of congenital diaphragmatic hernia showed a beneficial effect on lung maturation. We evaluated the potential of RA delivery into the trachea and studied the combined effects of TO and RA on normal lung development. Experiments were performed on normal rabbit fetuses. Liposomes and capric triglyceride (Miglyol ® ), alone and with RA, were administered in the trachea just before TO (d26). Lung morphology and surfactant production were studied at term (d30). Tracheal occlusion increased lung weight and enhanced alveolar development but increased apoptotic activity and decreased surfactant expression. Tracheal injection of RA improved surfactant production to levels of normal controls. We established the potential of liposome and Miglyol as RA vehicle for delivering this bioactive molecule in the fetal airways. Tracheal RA injection seems to oppose the effects of TO in fetuses with normal lungs. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

Nitric oxide alterations following acute ductal constriction in the fetal lamb: a role for superoxide

PubMed Central

Hsu, Jong-Hau; Oishi, Peter; Wiseman, Dean A.; Hou, Yali; Chikovani, Omar; Datar, Sanjeev; Sajti, Eniko; Johengen, Michael J.; Harmon, Cynthia; Black, Stephen M.

2010-01-01

Acute partial compression of the fetal ductus arteriosus (DA) results in an initial abrupt increase in pulmonary blood flow (PBF), which is followed by a significant reduction in PBF to baseline values over the ensuing 2–4 h. We have previously demonstrated that this potent vasoconstricting response is due, in part, to an endothelin-1 (ET-1)-mediated decrease in nitric oxide synthase (NOS) activity. In addition, in vitro data demonstrate that ET-1 increases superoxide levels in pulmonary arterial smooth muscle cells and that oxidative stress alters NOS activity. Therefore, the objectives of this study were to determine the potential role of superoxide in the alterations of hemodynamics and NOS activity following acute ductal constriction in the late-gestation fetal lamb. Eighteen anesthetized near-term fetal lambs were instrumented, and a lung biopsy was performed. After a 48-h recovery, acute constriction of the DA was performed by inflating a vascular occluder. Polyethylene glycol-superoxide dismutase (PEG-SOD; 1,000–1,500 units/kg, n = 7) or PEG-alone (vehicle control group, n = 5) was injected into the pulmonary artery before ductal constriction. Six animals had a sham operation. In PEG-alone-treated lambs, acute ductal constriction rapidly decreased pulmonary vascular resistance (PVR) by 88%. However, by 4 h, PVR returned to preconstriction baseline. This vasoconstriction was associated with an increase in lung superoxide levels (82%), a decrease in total NOS activity (50%), and an increase in P-eNOS-Thr495 (52%) (P < 0.05). PEG-SOD prevented the increase of superoxide after ductal constriction, attenuated the vasoconstriction, preserved NOS activity, and increased P-eNOS Ser1177 (307%, P < 0.05). Sham procedure induced no changes. These data suggest that an acute decrease in NOS activity that is mediated, in part, by increased superoxide levels, and alterations in the phosphorylation status of the endothelial NOS isoform, underlie the pulmonary vascular

Dose-per-fraction escalation of accelerated hypofractionated three-dimensional conformal radiotherapy in locally advanced non-small cell lung cancer.

PubMed

Kepka, Lucyna; Tyc-Szczepaniak, Dobromira; Bujko, Krzysztof

2009-07-01

To determine the efficacy of accelerated hypofractionated three-dimensional conformal radiotherapy (3D-CRT) with dose-per-fraction escalation for treatment of stage III non-small cell lung cancer (NSCLC). Between 2001 and 2007, 173 patients with stage III NSCLC were treated using accelerated 3D-CRT and the simultaneous boost technique. Initially, the total dose of 56.7 Gy (including 39.9 Gy to the elective area) was delivered over 4 weeks in fractions of 2.7 Gy (1.9 Gy to the elective area). The dose-per-fraction escalation study commenced after the outcomes of 70 patients had been evaluated. The dose per fraction was increased from 2.7 through 2.8 Gy (level 1 escalation) to 2.9 Gy (level 2 escalation); the total dose increased, respectively, from 56.7 Gy through 58.8 Gy to 60.9 Gy. The dose to the elective area and the overall treatment time remained unchanged. Fit patients received two to three courses of chemotherapy before radiotherapy. The 2- and 3-year overall survival rates were 32 and 19%, respectively (median survival = 17 months). Of the patients, 7% had grade III acute esophageal toxicity and 6% had grade III or greater late pulmonary toxicity. Two of the nine patients who received the level 2 escalation (60.9 Gy) died of pulmonary toxicity. The study was terminated at a dose of 58.8 Gy and this schema was adopted as the institutional policy for treatment of stage III NSCLC. Although dose escalation with accelerated hypofractionated 3D-CRT was limited, the results and toxicity profiles obtained using this technique are promising.

Models of Lung Transplant Research: a consensus statement from the National Heart, Lung, and Blood Institute workshop

PubMed Central

Lama, Vibha N.; Belperio, John A.; Christie, Jason D.; El-Chemaly, Souheil; Fishbein, Michael C.; Gelman, Andrew E.; Hancock, Wayne W.; Keshavjee, Shaf; Kreisel, Daniel; Looney, Mark R.; McDyer, John F.; Shilling, Rebecca A.; Panoskaltsis-Mortari, Angela; Wilkes, David S.; Eu, Jerry P.; Nicolls, Mark R.

2017-01-01

Lung transplantation, a cure for a number of end-stage lung diseases, continues to have the worst long-term outcomes when compared with other solid organ transplants. Preclinical modeling of the most common and serious lung transplantation complications are essential to better understand and mitigate the pathophysiological processes that lead to these complications. Various animal and in vitro models of lung transplant complications now exist and each of these models has unique strengths. However, significant issues, such as the required technical expertise as well as the robustness and clinical usefulness of these models, remain to be overcome or clarified. The National Heart, Lung, and Blood Institute (NHLBI) convened a workshop in March 2016 to review the state of preclinical science addressing the three most important complications of lung transplantation: primary graft dysfunction (PGD), acute rejection (AR), and chronic lung allograft dysfunction (CLAD). In addition, the participants of the workshop were tasked to make consensus recommendations on the best use of these complimentary models to close our knowledge gaps in PGD, AR, and CLAD. Their reviews and recommendations are summarized in this report. Furthermore, the participants outlined opportunities to collaborate and directions to accelerate research using these preclinical models. PMID:28469087

Electronic fetal monitoring: family medicine obstetrics.

PubMed

Rodney, John R M; Huntley, Benjamin J F; Rodney, Wm Macmillan

2012-03-01

Electronic fetal monitoring assesses fetal health during the prenatal and intrapartum process. Intermittent auscultation does not detect key elements of fetal risk, such as beat-to-beat variability. Family medicine obstetric fellowships have contributed new knowledge to this process by articulating a method of analysis that builds on evidence-based recommendations from the American College of Obstetrics and Gynecology as well as the National Institute of Child Health and Development. This article summarizes the development, interpretation, and management of electronic fetal heart rate patterns and tracings. Copyright © 2012 Elsevier Inc. All rights reserved.

Findings and differential diagnosis of fetal intracranial haemorrhage and fetal ischaemic brain injury: what is the role of fetal MRI?

PubMed Central

Kennedy, Anne

2017-01-01

Ventriculomegaly (VM) is a non-specific finding on fetal imaging. Identification of the specific aetiology is important, as it affects prognosis and may even change the course of current or future pregnancies. In this review, we will focus on the application of fetal MRI to demonstrate intracranial haemorrhage and ischaemic brain injury as opposed to other causes of VM. MRI is able to identify the specific aetiology of VM with much more sensitivity and specificity than ultrasound and should be considered whenever VM is identified on obstetric ultrasound. Advances in both fetal and neonatal MRI have the potential to shed further light on mechanisms of brain injury and the impact of chronic hypoxia; such information may guide future interventions. PMID:27734711

Relationship between glutamate, GOT and GPT levels in maternal and fetal blood: a potential mechanism for fetal neuroprotection.

PubMed

Zlotnik, Alexander; Tsesis, Svetlana; Gruenbaum, Benjamin Fredrick; Ohayon, Sharon; Gruenbaum, Shaun Evan; Boyko, Matthew; Sheiner, Eyal; Brotfain, Evgeny; Shapira, Yoram; Teichberg, Vivian Itzhak

2012-09-01

Excess glutamate in the brain is thought to be implicated in the pathophysiology of fetal anoxic brain injury, yet little is known about the mechanisms by which glutamate is regulated in the fetal brain. This study examines whether there are differences between maternal and fetal glutamate concentrations, and whether a correlation between them exists. 10 ml of venous blood was extracted from 87 full-term (>37 weeks gestation) pregnant women in active labor. Immediately after delivery of the neonate, 10 ml of blood from the umbilical artery and vein was extracted. Samples were analyzed for levels of glutamate, glutamate-oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT). Fetal blood glutamate concentrations in both the umbilical artery and vein were found to be significantly higher than maternal blood (p<0.001). Similarly, fetal serum GOT levels in the umbilical artery and vein were found to be significantly higher than maternal GOT levels (p<0.001). The difference in GPT levels between maternal and fetal serum was not statistically significant. There was no difference in fetal glutamate, GOT or GPT between the umbilical artery and vein. There was an association observed between glutamate levels in maternal blood and glutamate levels in both venous (R=0.32, p<0.01) and arterial (R=0.33, p<0.05) fetal blood. This study demonstrated that higher baseline concentrations of blood glutamate are present in fetal blood compared with maternal blood, and this was associated with elevated GOT, but not GPT levels. An association was observed between maternal and fetal blood glutamate levels. Copyright © 2012 Elsevier Ltd. All rights reserved.

New insights into saccular development and vascular formation in lung allografts under the renal capsule

PubMed Central

Vu, Thiennu H.; Alemayehu, Yemisrach; Werb, Zena

2009-01-01

The study of distal lung morphogenesis and vascular development would be greatly facilitated by an in vitro or ex vivo experimental model. In this study we show that the growth of mouse embryonic day 12.5 lung rudiments implanted underneath the kidney capsules of syngeneic or immunodeficient hosts follows closely lung development in utero. The epithelium develops extensively with both proximal and distal differentiation to the saccular stage. The vasculature also develops extensively. Large blood vessels accompany large airways and capillaries develop within the saccular walls. Interestingly, vessels in the lung grafts develop from endothelial progenitor cells endogenous to the explants and host vessels do not vascularize the grafts independently. This suggests that embryonic lungs possess mechanisms to prevent the inappropriate ingrowth of surrounding vessels. However, vessels in the lung grafts do connect to host vessels, showing that embryonic lungs have the ability to stimulate host angiogenesis and recruit host vessel connections. These data support the hypothesis that the lung vasculature develops by both vasculogenic and angiogenic processes: a vascular network develops in situ in lung mesenchyme, which is then connected to angiogenic processes from central vessels. The lung renal capsule allograft is thus an excellent model to study the development of the pulmonary vasculature and of late fetal lung development that requires a functional blood supply. PMID:12591600

Vitamin D treatment improves survival and infant lung structure after intra-amniotic endotoxin exposure in rats: potential role for the prevention of bronchopulmonary dysplasia

PubMed Central

Seedorf, Gregory; Gien, Jason; Abman, Steven H.

2013-01-01

Vitamin D (vit D) has anti-inflammatory properties and modulates lung growth, but whether vit D can prevent lung injury after exposure to antenatal inflammation is unknown. We hypothesized that early and sustained vit D treatment could improve survival and preserve lung growth in an experimental model of bronchopulmonary dysplasia induced by antenatal exposure to endotoxin (ETX). Fetal rats (E20) were exposed to ETX (10 μg), ETX + Vit D (1 ng/ml), or saline (control) via intra-amniotic (IA) injections and delivered 2 days later. Newborn pups exposed to IA ETX received daily intraperitoneal injections of vit D (1 ng/g) or saline for 14 days. Vit D treatment improved oxygen saturations (78 vs. 87%; P < 0.001) and postnatal survival (84% vs. 57%; P < 0.001) after exposure to IA ETX compared with IA ETX alone. Postnatal vit D treatment improved alveolar and vascular growth at 14 days by 45% and 25%, respectively (P < 0.05). Vit D increased fetal sheep pulmonary artery endothelial cell (PAEC) growth and tube formation by 64% and 44%, respectively (P < 0.001), and prevented ETX-induced reductions of PAEC growth and tube formation. Vit D directly increased fetal alveolar type II cell (ATIIC) growth by 26% (P < 0.001) and enhanced ATIIC growth in the presence of ETX-induced growth suppression by 73% (P < 0.001). We conclude that antenatal vit D therapy improved oxygenation and survival in newborn rat pups and enhanced late lung structure after exposure to IA ETX in vivo, which may partly be due to direct effects on vascular and alveolar growth. PMID:24414254

Pregnancy interruption after second trimester diagnosis of fetal structural anomalies: the New Jersey Fetal Abnormalities Registry.

PubMed

Rauch, Eden R; Smulian, John C; DePrince, Kristin; Ananth, Cande V; Marcella, Stephen W

2005-10-01

The purpose of this study was to identify factors that predict a decision to interrupt a pregnancy in which there are fetal anomalies in the second trimester. The New Jersey Fetal Abnormalities Registry prospectively recruits and collects information on pregnancies (> or = 15 weeks of gestation) from New Jersey residents in whom a fetal structural anomaly has been suspected by maternal-fetal medicine specialists. Enrolled pregnancies that have major fetal structural abnormalities identified from 15 to 23 weeks of gestation were included. Outcomes were classified as either elective interruption or a natural pregnancy course, which might include a spontaneous fetal death or live birth. Predictors of elective interruption of pregnancy were examined with univariable and multivariable logistic regression analyses. Of the 97 cases, 33% of the women (n = 32) interrupted the pregnancy. Significant variables in the regression model that were associated with a decision to interrupt a pregnancy were earlier identification of fetal anomalies (19.0 +/- 2 weeks of gestation vs 20.5 +/- 2 weeks of gestation; P = .003), the presence of multiple anomalies (78% [25/32] vs 52% [33/63]; P = .01], and a presumption of lethality (56% [18/32] vs 14% [9/65]; P = .0001). These variables corresponded to an odds ratio for pregnancy interruption of 4.2 (95% CI, 1.0, 17.0) for multiple anomalies, 0.8 (95% CI, 0.7, 1.0) for each week of advancing gestational age, and 36.1 (95% CI, 2.9, 450.7) for presumed lethal abnormalities. Early diagnosis, the identification of multiple abnormalities, and an assessment of likely lethality of fetal anomalies are important factors for the optimization of parental autonomy in deciding pregnancy management.

[Evaluation of fetal lung maturity using a modified lecithin-sphingomyelin determination and Clements' foam test].

PubMed

Neumann, G; Gartzke, J; Faber, G

1978-01-01

The modified thin layer chromatographic method for the determination of the phospholipids lecithin and sphingomyelin from amniotic fluid is useful in estimating fetal pulmonary maturity. The foam test of Clements is a simple rapid method for screening of suspicious cases of pregnancies at risk and of great value as bed side test even performing by the doctor. In comparing Clements-Test with thin layer chromatographic for L/S-Ratio determination we found a good correlation of 81,8% of all cases.

SU-E-T-436: Accelerated Gated IMRT: A Feasibility Study for Lung Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilles, M; Boussion, N; Visvikis, D

Purpose: To evaluate the feasibility of delivering a gated Intensity Modulated Radiotherapy (IMRT) treatment using multiple respiratory phases in order to account for all anatomic changes during free breathing and accelerate the gated treatment without increasing the dose per fraction. Methods: For 7 patients with lung cancer, IMRT treatment plans were generated on a full inspiration (FI) Computed Tomography (CT) and a Mid Intensity Position (MIP) CT. Moreover, in order to achieve an accelerated gated IMRT, multiple respiratory phase plans were calculated: 2-phase plans including the FI and the full expiration phases, and 3-phase plans by adding the mid-inspiration phase.more » In order to assess the tolerance limits, plans' doses were registered and summed to the FI-based plan. Mean dose received by Organs at Risk (OARs) and target volumes were used to compare obtained plans. Results: The mean dose differences between the FI plans and the multi-phase plans never exceeded 0.4 Gy (Fig. 1). Concerning the clinical target volume these differences were even smaller: less than 0.1 Gy for both the 2-phase and 3-phase plans. Regarding the MIP treatment plan, higher doses in different healthy structures were observed, with a relative mean increase of 0.4 to 1.5 Gy. Finally, compared to the prescribed dose, the FI as well as the multi-phase plans were associated with a mean difference of 0.4 Gy, whereas in the case of MIP a higher mean difference of 0.6 Gy was observed. Conclusion: The doses obtained while planning a multi-phase gated IMRT treatment were within the tolerance limits. Compared to MIP, a better healthy tissue sparing was observed in the case of treatment planning based on one or multiple phases. Future work will consist in testing the multi-phase treatment delivery while accounting for the multileaf collimator speed constraints.« less

Relative IGF-1 and IGF-2 gene expression in maternal and fetal tissues from diabetic swine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolverton, C.K.; Leaman, D.W.; White, M.E.

1990-02-26

Fourteen pregnant, crossbred gilts were utilized in this study. Seven gilts were injected with alloxan (50 mg/kg) at day 75 of gestation to induce diabetes. Gilts underwent caesarean section on day 105 of gestation. Samples were collected from maternal skeletal muscle, adipose tissue, uterus and endometrium; and from fetal skeletal muscle, adipose tissue, placenta, liver, lung, kidney, heart, brain and spleen. Tissues were frozen in liquid nitrogen for later analysis of IGF-1 and IGF-2 gene expression. Samples were pooled and total RNA was isolated using the guanidine isothiocynate method. Total mRNA was analyzed by dot blot hybridization. Blots were probedmore » with {sup 32}P-cDNA for porcine IGF-1 and rat IGF-2. IGF-1 gene expression in maternal tissues was unaffected by diabetes. Maternal diabetes increased IGF-2 mRNA in maternal adipose tissue but exhibited no effect in muscle or uterus. Expression of IGF-2 by maternal endometrium was decreased by diabetes. Maternal diabetes induced an increase in IGF-1 gene expression in muscle and placenta while causing an increase in IGF-2 expression in fetal liver and placenta. IGF-2 mRNA was lower in lung from fetuses of diabetic mothers than in controls. These results suggest that maternal diabetes alters IGF-1 and IGF-2 gene expression in specific tissues and differential regulation of these genes appears to exist in the mother and developing fetus.« less

Oxygen Supplementation to Stabilize Preterm Infants in the Fetal to Neonatal Transition: No Satisfactory Answer.

PubMed

Torres-Cuevas, Isabel; Cernada, Maria; Nuñez, Antonio; Escobar, Javier; Kuligowski, Julia; Chafer-Pericas, Consuelo; Vento, Maximo

2016-01-01

Fetal life elapses in a relatively low oxygen environment. Immediately after birth with the initiation of breathing, the lung expands and oxygen availability to tissue rises by twofold, generating a physiologic oxidative stress. However, both lung anatomy and function and the antioxidant defense system do not mature until late in gestation, and therefore, very preterm infants often need respiratory support and oxygen supplementation in the delivery room to achieve postnatal stabilization. Notably, interventions in the first minutes of life can have long-lasting consequences. Recent trials have aimed to assess what initial inspiratory fraction of oxygen and what oxygen targets during this transitional period are best for extremely preterm infants based on the available nomogram. However, oxygen saturation nomogram informs only of term and late preterm infants but not on extremely preterm infants. Therefore, the solution to this conundrum may still have to wait before a satisfactory answer is available.

Management of Mediastinal Relapse after Treatment with Stereotactic Body Radiotherapy or Accelerated Hypofractionated Radiotherapy for Stage I/II Non–Small-Cell Lung Cancer

PubMed Central

Kilburn, Jeremy M.; Lester, Scott C.; Lucas, John T.; Soike, Michael H.; Blackstock, A. William; Kearns, William T.; Hinson, William H.; Miller, Antonius A.; Petty, William J.; Munley, Michael T.; Urbanic, James J.

2014-01-01

Purpose/Objective(s) Regional failures occur in up to 15% of patients treated with stereotactic body radiotherapy (SBRT) for stage I/II lung cancer. This report focuses on the management of the unique scenario of isolated regional failures. Methods Patients treated initially with SBRT or accelerated hypo-fractionated radiotherapy were screened for curative intent treatment of isolated mediastinal failures (IMFs). Local control, regional control, progression-free survival, and distant control were estimated from the date of salvage treatment using the Kaplan–Meier method. Results Among 160 patients treated from 2002 to 2012, 12 suffered IMF and were amenable to salvage treatment. The median interval between treatments was 16 months (2–57 mo). Median salvage dose was 66 Gy (60–70 Gy). With a median follow-up of 10 months, the median overall survival was 15 months (95% confidence interval, 5.8–37 mo). When estimated from original treatment, the median overall survival was 38 months (95% confidence interval, 17–71 mo). No subsequent regional failures occurred. Distant failure was the predominant mode of relapse following salvage for IMF with a 2-year distant control rate of 38%. At the time of this analysis, three patients have died without recurrence while four are alive and no evidence of disease. High-grade toxicity was uncommon. Conclusions To our knowledge, this is first analysis of salvage mediastinal radiation after SBRT or accelerated hypofractionated radiotherapy in lung cancer. Outcomes appear similar to stage III disease at presentation. Distant failures were common, suggesting a role for concurrent or sequential chemotherapy. A standard full course of external beam radiotherapy is advisable in this unique clinical scenario. PMID:24736084

Fetal microchimeric cells in autoimmune thyroid diseases

PubMed Central

Lepez, Trees; Vandewoestyne, Mado; Deforce, Dieter

2013-01-01

Autoimmune thyroid diseases (AITD) show a female predominance, with an increased incidence in the years following parturition. Fetal microchimerism has been suggested to play a role in the pathogenesis of AITD. However, only the presence of fetal microchimeric cells in blood and in the thyroid gland of these patients has been proven, but not an actual active role in AITD. Is fetal microchimerism harmful for the thyroid gland by initiating a Graft versus Host reaction (GvHR) or being the target of a Host versus Graft reaction (HvGR)? Is fetal microchimerism beneficial for the thyroid gland by being a part of tissue repair or are fetal cells just innocent bystanders in the process of autoimmunity? This review explores every hypothesis concerning the role of fetal microchimerism in AITD. PMID:23723083

Prediction of fetal compromise in labor.

PubMed

Prior, Tomas; Mullins, Edward; Bennett, Phillip; Kumar, Sailesh

2014-06-01

The majority of intrapartum fetal hypoxia occurs in uncomplicated pregnancies. Current intrapartum monitoring techniques have not resulted in a reduction in the incidence of cerebral palsy in term neonates. We report the development of a composite risk score to allow risk stratification of normal pregnancies before labor. Six hundred one women were recruited to this prospective observational study. All women underwent an ultrasound examination before active labor, during which fetal biometry and fetal Doppler flow resistance indices were measured. A composite risk score, amalgamating data from the umbilical artery, middle cerebral artery, and umbilical vein, was then developed and correlated with intrapartum outcomes. In cases with the highest composite risk scores, the incidence of fetal compromise (the primary outcome) was 80.0% compared with just 15.3% in cases with the lowest risk scores (relative risk 5.2, 95% confidence interval 2.7-10.1). These cases were also at increased risk of cesarean delivery (53.3% compared with 3.4%, P<.001) and of developing a fetal heart rate pattern considered pathologic by National Institute for Health and Clinical Excellence criteria (P=.003). No significant variation in Apgar scores or umbilical artery pH was observed. Intrapartum fetal compromise remains a significant global health issue. The composite risk score reported here can identify fetuses at both high risk and low risk of a subsequent diagnosis of intrapartum fetal compromise. This may enable more judicious use of current intrapartum fetal monitoring techniques, which are hampered by low specificity. II.

Fetal electrocardiograph

NASA Astrophysics Data System (ADS)

Rios, Heriberto; Andrade, Armando; Puente, Ernestina; Lizana, Pablo R.; Mendoza, Diego

2002-11-01

The high intra-uterine death rate is due to failure in appropriately diagnosing some problems in the cardiobreathing system of the fetus during pregnancy. The electrocardiograph is one apparatus which might detect problems at an early stage. With electrodes located near the womb and uterus, in a way similar to the normal technique, the detection of so-called biopotential differences, caused by concentrations of ions, can be achieved. The fetal electrocardiograph is based on an ultrasound technique aimed at detecting intrauterine problems in pregnant women, because it is a noninvasive technique due to the very low level of ultrasound power used. With this system, the following tests can be done: Heart movements from the ninth week onwards; Rapid and safe diagnosis of intrauterine fetal death; Location and size of the placenta. The construction of the fetal electrocardiograph requires instrument level components directly mounted on the printed circuit board, in order to avoid stray capacitance in the cabling which prevents the detection of the E.C.G. activity. The low cost of the system makes it affordable to low budget institutions; in contrast, available commercial systems are priced in U.S. Dollars. (To be presented in Spanish.)

Minimal alteration in the ratio of circulatory fetal DNA to fetal corticotropin-releasing hormone mRNA level in preeclampsia.

PubMed

Zhong, Xiao Yan; Holzgreve, Wolfgang; Gebhardt, Stefan; Hillermann, Renate; Tofa, Kashefa Carelse; Gupta, Anurag Kumar; Huppertz, Berthold; Hahn, Sinuhe

2006-01-01

We have recently observed that fetal DNA and fetal corticotropin-releasing hormone (CRH) mRNA are associated with in vitro generated syncytiotrophoblast-derived microparticles, and that the ratio of fetal DNA to mRNA (CRH) varied according to whether the particles were derived by predominantly apoptotic, apo-necrotic or necrotic pathways. Hence, we examined whether these ratios varied in maternal plasma samples taken from normotensive and preeclamptic pregnancies in vivo. Maternal plasma samples were collected from 18 cases with preeclampsia and 29 normotensive term controls. Circulatory fetal CRH mRNA and DNA levels were quantified by real-time PCR and RT-PCR. Circulatory fetal mRNA and fetal DNA levels were significantly elevated in the preeclampsia study group when compared to normotensive controls. Alterations in the fetal mRNA to DNA ratio between the study and control groups were minimal, even when stratified into early (<34 weeks of gestation) and late (>34 weeks of gestation) onset preeclampsia. Our data suggest that although circulatory fetal DNA and mRNA levels are significantly elevated in preeclampsia, the ratios in maternal plasma are not dramatically altered. Copyright 2006 S. Karger AG, Basel.

Curcumin protects the developing lung against long-term hyperoxic injury

PubMed Central

Sakurai, R.; Villarreal, P.; Husain, S.; Liu, Jie; Sakurai, T.; Tou, E.; Torday, J. S.

2013-01-01

Curcumin, a potent anti-inflammatory and antioxidant agent, modulates peroxisome proliferator-activated receptor-γ signaling, a key molecule in the etiology of bronchopulmonary dysplasia (BPD). We have previously shown curcumin's acute protection against neonatal hyperoxia-induced lung injury. However, its longer-term protection against BPD is not known. Hypothesizing that concurrent treatment with curcumin protects the developing lung against hyperoxia-induced lung injury long-term, we determined if curcumin protects against hyperoxic neonatal rat lung injury for the first 5 days of life, as determined at postnatal day (PND) 21. One-day-old rat pups were exposed to either 21 or 95% O2 for 5 days with or without curcumin treatment (5 mg/kg) administered intraperitoneally one time daily, following which the pups grew up to PND21 in room air. At PND21 lung development was determined, including gross and cellular structural and functional effects, and molecular mediators of inflammatory injury. To gain mechanistic insights, embryonic day 19 fetal rat lung fibroblasts were examined for markers of apoptosis and MAP kinase activation following in vitro exposure to hyperoxia for 24 h in the presence or absence of curcumin (5 μM). Curcumin effectively blocked hyperoxia-induced lung injury based on systematic analysis of markers for lung injury (apoptosis, Bcl-2/Bax, collagen III, fibronectin, vimentin, calponin, and elastin-related genes) and lung morphology (radial alveolar count and alveolar septal thickness). Mechanistically, curcumin prevented the hyperoxia-induced increases in cleaved caspase-3 and the phosphorylation of Erk1/2. Molecular effects of curcumin, both structural and cytoprotective, suggest that its actions against hyperoxia-induced lung injury are mediated via Erk1/2 activation and that it is a potential intervention against BPD. PMID:23812632

Phase 1 Dose Escalation Study of Accelerated Radiation Therapy With Concurrent Chemotherapy for Locally Advanced Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelsey, Chris R., E-mail: christopher.kelsey@duke.edu; Das, Shiva; Gu, Lin

2015-12-01

Purpose: To determine the maximum tolerated dose of radiation therapy (RT) given in an accelerated fashion with concurrent chemotherapy using intensity modulated RT. Methods and Materials: Patients with locally advanced lung cancer (non-small cell and small cell) with good performance status and minimal weight loss received concurrent cisplatin and etoposide with RT. Intensity modulated RT with daily image guidance was used to facilitate esophageal avoidance and delivered using 6 fractions per week (twice daily on Fridays with a 6-hour interval). The dose was escalated from 58 Gy to a planned maximum dose of 74 Gy in 4 Gy increments in a standardmore » 3 + 3 trial design. Dose-limiting toxicity (DLT) was defined as acute grade 3-5 nonhematologic toxicity attributed to RT. Results: A total of 24 patients were enrolled, filling all dose cohorts, all completing RT and chemotherapy as prescribed. Dose-limiting toxicity occurred in 1 patient at 58 Gy (grade 3 esophagitis) and 1 patient at 70 Gy (grade 3 esophageal fistula). Both patients with DLTs had large tumors (12 cm and 10 cm, respectively) adjacent to the esophagus. Three additional patients were enrolled at both dose cohorts without further DLT. In the final 74-Gy cohort, no DLTs were observed (0 of 6). Conclusions: Dose escalation and acceleration to 74 Gy with intensity modulated RT and concurrent chemotherapy was tolerable, with a low rate of grade ≥3 acute esophageal reactions.« less

Fetal scalp pH testing

MedlinePlus

... such as HIV/AIDS or hepatitis C. Normal Results Normal fetal blood sample results are: Normal pH: ... meaning of your specific test results. What Abnormal Results Mean A fetal scalp blood pH level of ...

Fetal human airway smooth muscle cell production of leukocyte chemoattractants is differentially regulated by fluticasone.

PubMed

Pearson, Helen; Britt, Rodney D; Pabelick, Christine M; Prakash, Y S; Amrani, Yassine; Pandya, Hitesh C

2015-12-01

Adult human airway smooth muscle (ASM) produce cytokines involved in recruitment and survival of leukocytes within airway walls. Cytokine generation by adult ASM is glucocorticoid-sensitive. Whether developing lung ASM produces cytokines in a glucocorticoid-sensitive fashion is unknown. Cultured fetal human ASM cells stimulated with TNF-α (0-20 ng/ml) were incubated with TNF-α receptor-blocking antibodies, fluticasone (1 and 100 nm), or vehicle. Supernatants and cells were assayed for the production of CCL5, CXCL10, and CXCL8 mRNA and protein and glucocorticoid receptor phosphorylation. CCL5, CXCL10, and CXCL8 mRNA and protein production by fetal ASM cell was significantly and dose-dependently following TNF-α treatment. Cytokine mRNA and protein production were effectively blocked by TNF-α R1 and R2 receptor neutralizing antibodies but variably inhibited by fluticasone. TNF-α-induced TNF-R1 and R2 receptor mRNA expression was only partially attenuated by fluticasone. Glucocorticoid receptor phosphorylation at serine (Ser) 211 but not at Ser 226 was enhanced by fluticasone. Production of CCL5, CXCL10, and CXCL8 by fetal ASM appears to involve pathways that are both qualitatively and mechanistically distinct to those described for adult ASM. The findings imply developing ASM has potential to recruit leukocyte into airways and, therefore, of relevance to childhood airway diseases.

Incidence of fetal bradycardia and effect of placental injury on fetal heart rate during second-trimester genetic amniocentesis.

PubMed

Hanprasertpong, T; Petpichetchian, C; Ponglopisit, S; Suksai, M; Kor-Anantakul, O; Geater, A; Pruksanusak, N; Hanprasertpong, J

2016-05-01

A prospective study was conducted for comparing the incidence of fetal bradycardia and level of fetal heart rate change following a second-trimester genetic amniocentesis with and without placental injury. A total of 257 and 495 participants in injured and non-injured groups were analysed. The incidence of fetal bradycardia following amniocentesis was not statistically different between the two groups (1.17%, [95% CI 0.24, 3.37] and 0.20%, [95% CI 0.005, 1.12]) in injured and non-injured placenta groups, respectively; p = 0.118). The mean change in baseline fetal heart rate before and after amniocentesis was also not significantly different between the two groups (p = 0.844). No fetal death or pregnancy loss occurred within 4 weeks after the procedure. All 4 bradycardia participants were normal and healthy and had an appropriate weight for their gestational age. We conclude that placental injury during a second-trimester genetic amniocentesis due to advanced maternal age poses only a low risk of fetal bradycardia, and there is no evidence of differences between subjects with injured and non-injured placenta in the changes in fetal heart rate.

Smad1 and WIF1 genes are downregulated during saccular stage of lung development in the nitrofen rat model.

PubMed

Fujiwara, Naho; Doi, Takashi; Gosemann, Jan-Hendrik; Kutasy, Balazs; Friedmacher, Florian; Puri, Prem

2012-02-01

The exact pathogenesis of pulmonary hypoplasia in the nitrofen-induced congenital diaphragmatic hernia (CDH) still remains unclear. Smad1, one of the bone morphogenesis protein (BMP) receptor downstream signaling proteins, plays a key role in organogenesis including lung development and maturation. Smad1 knockout mice display reduced sacculation, an important feature of pulmonary hypoplasia. Wnt inhibitor factor 1 (Wif1) is a target gene of Smad1 in the developing lung epithelial cells (LECs). Smad1 directly regulates Wif1 gene expression and blockade of Smad1 function in fetal LECs is reported to downregulate Wif1 gene expression. We designed this study to test the hypothesis that pulmonary Smad1 and Wif1 gene expression is downregulated during saccular stage of lung development in the nitrofen CDH model. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetuses were harvested on D18, and D21. Fetal lungs were dissected and divided into 2 groups: control and nitrofen (n = 9 at each time point, respectively). Pulmonary gene expression of Smad1 and Wif1 were analyzed by real-time RT-PCR. Immunohistochemistry was performed to evaluate protein expression/distribution of Smad1 and Wif1. The relative mRNA expression levels of Smad1 and Wif1 were significantly downregulated in the nitrofen group compared to controls on D18 and D21 (*p < 0.01, **p < 0.05). Immunoreactivity of Smad1 and Wif1 was also markedly decreased in nitrofen lungs compared to controls on D18 and D21. We provide evidence, for the first time, that the pulmonary gene expression of Smad1 and Wif1 is downregulated on D18 and D21 (saccular stage of lung development) in the nitrofen-induced hypoplastic lung. These findings suggest that the downregulation of Smad1/Wif1 gene expression may contribute to pulmonary hypoplasia in the nitrofen CDH model by retardation of lung development during saccular stage.

Fetal heart rate variation after corticosteroids for fetal maturation.

PubMed

Knaven, Olga; Ganzevoort, Wessel; de Boer, Marjon; Wolf, Hans

2017-09-01

Several studies report a decrease of fetal heart rate (FHR) short-term variation (STV) after corticosteroids for improvement of fetal maturity and advice not to deliver a fetus for low STV within 2-3days after corticosteroids. However, literature is not unanimous in this respect. This study intends to asses STV longitudinally after corticosteroid administration. A retrospective cohort study in a tertiary perinatal centre from 2009 to 2015 included all women who had been treated with corticosteroids at gestational age of 26-34 weeks, had a computerized cardiotocography (cCTG) before and after medication and did not deliver within 48h. FHR and STV were stratified over 12-h periods and compared before and after corticosteroids. Women with imminent preterm labour (including PPROM) and women with placental problems (fetal growth restriction (FGR) or preeclampsia) (PE) were analysed separately. The effect of co-medication and gestational age was assessed. The study included 406 women, 211 with imminent preterm labour, 195 with FGR-PE. After corticosteroids STV increased 1-2ms (median 1.4; IQR 0.1-3.1) during the first 36h after start of corticosteroids. Thereafter a small decrease of less than 1ms (median -0,6; IQR -1.6 to 0.3) compared to before CC was seen. The most conspicuous effect of corticosteroids is a short term increase of STV and decrease of FHR. A slight decrease after 48-71h is possible, but abnormally low values should be considered as a sign of fetal distress. The clinical guidance, given by some, not to intervene because of a low STV after corticosteroids appears invalid. Copyright © 2017 Elsevier B.V. All rights reserved.

Fetal deaths in Brazil: a systematic review

PubMed Central

Barbeiro, Fernanda Morena dos Santos; Fonseca, Sandra Costa; Tauffer, Mariana Girão; Ferreira, Mariana de Souza Santos; da Silva, Fagner Paulo; Ventura, Patrícia Mendonça; Quadros, Jesirée Iglesias

2015-01-01

OBJECTIVE To review the frequency of and factors associated with fetal death in the Brazilian scientific literature. METHODS A systematic review of Brazilian studies on fetal deaths published between 2003 and 2013 was conducted. In total, 27 studies were analyzed; of these, 4 studies addressed the quality of data, 12 were descriptive studies, and 11 studies evaluated the factors associated with fetal death. The databases searched were PubMed and Lilacs, and data extraction and synthesis were independently performed by two or more examiners. RESULTS The level of completeness of fetal death certificates was deficient, both in the completion of variables, particularly sociodemographic variables, and in defining the underlying causes of death. Fetal deaths have decreased in Brazil; however, inequalities persist. Analysis of the causes of death indicated maternal morbidities that could be prevented and treated. The main factors associated with fetal deaths were absent or inadequate prenatal care, low education level, maternal morbidity, and adverse reproductive history. CONCLUSIONS Prenatal care should prioritize women that are most vulnerable (considering their social environment or their reproductive history and morbidities) with the aim of decreasing the fetal mortality rate in Brazil. Adequate completion of death certificates and investment in the committees that investigate fetal and infant deaths are necessary. PMID:25902565

Fetal myosin immunoreactivity in human dystrophic muscle.

PubMed

Schiaffino, S; Gorza, L; Dones, I; Cornelio, F; Sartore, S

1986-01-01

We report immunofluorescence observations on normal and dystrophic human muscle using an antibody (anti-bF) raised against bovine fetal myosin and specific for fetal myosin heavy chains. In rat skeletal muscle, anti-bF was previously found to react selectively with myosin isoforms expressed during fetal and early postnatal development and in regenerating muscles. Anti-bF stained most fibers in human fetal and neonatal muscle, whereas only nuclear chain fibers of muscle spindles were labeled in normal adult muscle. In muscle biopsies from patients with Duchenne's muscular dystrophy, numerous extrafusal fibers were stained: some were small regenerating fibers, others were larger fibers presumably resulting from previous regenerative events. Fetal myosin immunoreactivity in Duchenne's dystrophy appears to reflect the reexpression of fetal-specific myosin isoforms and provides a new valuable tool for identifying regenerating fibers and following their destiny in dystrophic muscle.

Preschool Teacher Attitude and Knowledge Regarding Fetal Alcohol Syndrome and Fetal Alcohol Effects.

ERIC Educational Resources Information Center

Mack, Faite R-P.

The Centers for Disease Control estimate that each year more than 8,000 Fetal Alcohol Syndrome (FAS) babies are born, and that many more babies go undiagnosed with Fetal Alcohol Effects (FAE), a less severe condition. FAS and FAE have been identified as major contributors to poor memory, shorter attention spans, lower IQs, diminished achievement…

[Fetal magnetic resonance imaging evaluation of congenital diaphragmatic hernia].

PubMed

Sebastià, C; Garcia, R; Gomez, O; Paño, B; Nicolau, C

2014-01-01

A diaphragmatic hernia is defined as the protrusion of abdominal viscera into the thoracic cavity through a normal or pathological orifice. The herniated viscera compress the lungs, resulting in pulmonary hypoplasia and secondary pulmonary hypertension, which are the leading causes of neonatal death in patients with congenital diaphragmatic hernia. Congenital diaphragmatic hernia is diagnosed by sonography in routine prenatal screening. Although magnetic resonance imaging is fundamentally used to determine whether the liver is located within the abdomen or has herniated into the thorax, it also can provide useful information about other herniated structures and the degree of pulmonary hypoplasia. The aim of this article is to review the fetal magnetic resonance findings for congenital diaphragmatic hernia and the signs that enable us to establish the neonatal prognosis when evaluating pulmonary hypoplasia. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

21 CFR 884.2620 - Fetal electroencephalographic monitor.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Fetal electroencephalographic monitor. 884.2620... (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Monitoring Devices § 884.2620 Fetal electroencephalographic monitor. (a) Identification. A fetal...

21 CFR 884.2620 - Fetal electroencephalographic monitor.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Fetal electroencephalographic monitor. 884.2620... (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Monitoring Devices § 884.2620 Fetal electroencephalographic monitor. (a) Identification. A fetal...

21 CFR 884.2620 - Fetal electroencephalographic monitor.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Fetal electroencephalographic monitor. 884.2620... (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Monitoring Devices § 884.2620 Fetal electroencephalographic monitor. (a) Identification. A fetal...

A feasibility study to calculate unshielded fetal doses to pregnant patients in 6-MV photon treatments using Monte Carlo methods and anatomically realistic phantoms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bednarz, Bryan; Xu, X. George

2008-07-15

A Monte Carlo-based procedure to assess fetal doses from 6-MV external photon beam radiation treatments has been developed to improve upon existing techniques that are based on AAPM Task Group Report 36 published in 1995 [M. Stovall et al., Med. Phys. 22, 63-82 (1995)]. Anatomically realistic models of the pregnant patient representing 3-, 6-, and 9-month gestational stages were implemented into the MCNPX code together with a detailed accelerator model that is capable of simulating scattered and leakage radiation from the accelerator head. Absorbed doses to the fetus were calculated for six different treatment plans for sites above the fetusmore » and one treatment plan for fibrosarcoma in the knee. For treatment plans above the fetus, the fetal doses tended to increase with increasing stage of gestation. This was due to the decrease in distance between the fetal body and field edge with increasing stage of gestation. For the treatment field below the fetus, the absorbed doses tended to decrease with increasing gestational stage of the pregnant patient, due to the increasing size of the fetus and relative constant distance between the field edge and fetal body for each stage. The absorbed doses to the fetus for all treatment plans ranged from a maximum of 30.9 cGy to the 9-month fetus to 1.53 cGy to the 3-month fetus. The study demonstrates the feasibility to accurately determine the absorbed organ doses in the mother and fetus as part of the treatment planning and eventually in risk management.« less

Expression of T-box transcription factors 2, 4 and 5 is decreased in the branching airway mesenchyme of nitrofen-induced hypoplastic lungs.

PubMed

Takahashi, Toshiaki; Friedmacher, Florian; Zimmer, Julia; Puri, Prem

2017-02-01

Pulmonary hypoplasia (PH), characterized by smaller lung size and reduced airway branching, remains a major therapeutic challenge in newborns with congenital diaphragmatic hernia (CDH). T-box transcription factors (Tbx) have been identified as key components of the gene network that regulates fetal lung development. Tbx2, Tbx4 and Tbx5 are expressed throughout the mesenchyme of the developing lung, regulating the process of lung branching morphogenesis. Furthermore, lungs of Tbx2-, Tbx4- and Tbx5-deficient mice are hypoplastic and exhibit decreased lung branching, similar to PH in human CDH. We hypothesized that the expression of Tbx2, Tbx4 and Tbx5 is decreased in the branching airway mesenchyme of hypoplastic rat lungs with nitrofen-induced CDH. Time-mated rats received either nitrofen or vehicle on gestational day 9 (D9). Fetuses were killed on D15, D18 and D21, and dissected lungs were divided into control and nitrofen-exposed specimens. Pulmonary gene expression of Tbx2, Tbx4 and Tbx5 was investigated by quantitative real-time polymerase chain reaction. Immunofluorescence double staining for Tbx2, Tbx4 and Tbx5 was combined with the mesenchymal marker Fgf10 to assess protein expression and localization in branching airway tissue. Relative mRNA levels of Tbx2, Tbx4 and Tbx5 were significantly reduced in lungs of nitrofen-exposed fetuses on D15, D18 and D21 compared to controls. Confocal laser scanning microscopy showed markedly diminished immunofluorescence of Tbx2, Tbx4 and Tbx5 in mesenchymal cells surrounding branching airways of nitrofen-exposed fetuses on D15, D18 and D21 compared to controls. Decreased expression of Tbx2, Tbx4 and Tbx5 in the pulmonary mesenchyme during fetal lung development may lead to a decrease or arrest of airway branching, thus contributing to PH in the nitrofen-induced CDH model.

Structural development of human brain white matter from mid-fetal to perinatal stage

NASA Astrophysics Data System (ADS)

Ouyang, Austin; Yu, Qiaowen; Mishra, Virendra; Chalak, Lina; Jeon, Tina; Sivarajan, Muraleedharan; Jackson, Greg; Rollins, Nancy; Liu, Shuwei; Huang, Hao

2015-03-01

The structures of developing human brain white matter (WM) tracts can be effectively quantified by DTI-derived metrics, including fractional anisotropy (FA), mean, axial and radial diffusivity (MD, AD and RD). However, dynamics of WM microstructure during very early developmental period from mid-fetal to perinatal stage is unknown. It is difficult to accurately measure microstructural properties of these WM tracts due to severe contamination from cerebrospinal fluid (CSF). In this study, high resolution DTI of fetal brains at mid-fetal stage (20 weeks of gestation or 20wg), 19 brains in the middle of 3rd trimester (35wg) and 17 brains around term (40wg) were acquired. We established first population-averaged DTI templates at these three time points and extracted WM skeleton. 16 major WM tracts in limbic, projection, commissural and association tract groups were traced with DTI tractography in native space. The WM skeleton in the template space was inversely transformed back to the native space for measuring core WM microstructures of each individual tract. Continuous microstructural enhancement and volumetric increase of WM tracts were found from 20wg to 40wg. The microstructural enhancement from FA measurement is decelerated in late 3rd trimester compared to mid-fetal to middle 3rd trimester, while volumetric increase of prefrontal WM tracts is accelerated. The microstructural enhancement from 35wg to 40wg is heterogeneous among different tract groups with microstructures of association tracts undergoing most dramatic change. Besides decreases of RD indicating active myelination, the decrease of AD for most WM tracts during late 3rd trimester suggests axonal packing process.

Impact of childhood anthropometry trends on adult lung function.

PubMed

Suresh, Sadasivam; O'Callaghan, Michael; Sly, Peter D; Mamun, Abdullah A

2015-04-01

Poor fetal growth rate is associated with lower respiratory function; however, there is limited understanding of the impact of growth trends and BMI during childhood on adult respiratory function. The current study data are from the Mater-University of Queensland Study of Pregnancy birth cohort. Prospective data were available from 1,740 young adults who performed standard spirometry at 21 years of age and whose birth weight and weight, height, and BMI at 5, 14, and 21 years of age were available. Catch-up growth was defined as an increase of 0.67 Z score in weight between measurements. The impact of catch-up growth on adult lung function and the relationship between childhood BMI trends and adult lung function were assessed using regression analyses. Lung function was higher at 21 years in those demonstrating catch-up growth from birth to 5 years (FVC, men: 5.33 L vs 5.54 L; women: 3.78 L vs 4.03 L; and FEV1, men: 4.52 L/s vs 4.64 L/s; women: 3.31 L/s vs 3.45 L/s). Subjects in the lowest quintile of birth (intrauterine growth retardation) also showed improved lung function if they had catch-up growth in the first 5 years of life. There was a positive correlation between increasing BMI and lung function at 5 years of age. However, in the later measurements when BMI increased into the obese category, a drop in lung function was observed. These data show evidence for a positive contribution of catch-up growth in early life to adult lung function. However, if weight gain or onset of obesity occurs after 5 years of age, an adverse impact on adult lung function is noted.

Serologic response to hepatitis B vaccination among lung transplantation candidates.

PubMed

Galar, Alicia; Engelson, Brian A; Kubiak, David W; Licona, Jose H; Boukedes, Steve; Goldberg, Hilary J; Baden, Lindsey R; Marty, Francisco M; Issa, Nicolas C

2014-09-27

Optimal hepatitis B (HBV) vaccination strategies for lung transplantation (LT) candidates are not well established. LT candidates with negative anti-HBs and anti-HBc antibody titers at baseline who received standard-dose HBV vaccination (Recombivax-HB 10 mcg/mL or Engerix-B 20 mcg/mL) administered at months 0, 1, and 6 or an accelerated vaccination schedule on days 0, 7 to 14, and 21 to 28 between June 1988 and October 2012 were studied. Patients who were more likely to undergo LT within 6 months of evaluation received the accelerated vaccination schedule starting in August 2009. Ninety-six HBV-seronegative patients who completed the vaccination series and had postvaccination anti-HBs titers available were identified. Median age was 60 years; 55.2% were female, and 92.7% were white. Underlying lung diseases included COPD (44.8%), idiopathic pulmonary fibrosis (22.9%), interstitial lung disease (15.6%), and cystic fibrosis (8.3%). The overall anti-HBs response rate was 54.2%. There was no significant difference in vaccine responses between accelerated and standard vaccination schedules (54.2% vs. 54.1%; P=1.0). Patients who received steroids or other immunosuppressants before transplantation had lower response rates compared with those who did not (38.9% vs. 63.3%; P=0.03). Better vaccination strategies to improve response rate are needed in this population. The accelerated HBV vaccination schedule elicited similar anti-HBs responses as the standard schedule and could be advantageous in this population, given current organ allocation practices, and it could allow repeat vaccination series for initial nonresponders before transplantation.

Fetal auditory evoked responses to onset of amplitude modulated sounds. A fetal magnetoencephalography (fMEG) study.

PubMed

Draganova, R; Schollbach, A; Schleger, F; Braendle, J; Brucker, S; Abele, H; Kagan, K O; Wallwiener, D; Fritsche, A; Eswaran, H; Preissl, H

2018-06-01

The human fetal auditory system is functional around the 25th week of gestational age when the thalamocortical connections are established. Fetal magnetoencephalography (fMEG) provides evidence for fetal auditory brain responses to pure tones and syllables. Fifty-five pregnant women between 31 and 40 weeks of gestation were included in the study. Fetal MEG was recorded during the presentation of an amplitude modulated tone (AM) with a carrier frequency of 500 Hz to the maternal abdomen modulated by low modulation rates (MRs) - 2/s and 4/s, middle MR - 8/s and high MRs - 27/s, 42/s, 78/s and 91/s. The aim was to determine whether the fetal brain responds differently to envelope slopes and intensity change at the onset of the AM sounds. A significant decrease of the response latencies of transient event-related responses (ERR) to high and middle MRs in comparison to the low MRs was observed. The highest fetal response rate was achieved by modulation rates of 2/s, 4/s and 27/s (70%, 57%, and 86%, respectively). Additionally, a maturation effect of the ERR (response latency vs. gestational age) was observed only for 4/s MR. The significant difference between the response latencies to low, middle, and high MRs suggests that still before birth the fetal brain processes the sound slopes at the onset in different integration time-windows, depending on the time for the intensity increase or stimulus power density at the onset, which is a prerequisite for language acquisition. Copyright © 2018 Elsevier B.V. All rights reserved.

Prevention of fetal demise and growth restriction in a mouse model of fetal alcohol syndrome.

PubMed

Spong, C Y; Abebe, D T; Gozes, I; Brenneman, D E; Hill, J M

2001-05-01

Two peptides [NAPVSIPQ (NAP) and SALLRSIPA (ADNF-9)], that are associated with novel glial proteins regulated by vasoactive intestinal peptide, are shown now to provide protective intervention in a model of fetal alcohol syndrome. Fetal demise and growth restrictions were produced after intraperitoneal injection of ethanol to pregnant mice during midgestation (E8). Death and growth abnormalities elicited by alcohol treatment during development are believed to be associated, in part, with severe oxidative damage. NAP and ADNF-9 have been shown to exhibit antioxidative and antiapoptotic actions in vitro. Pretreatment with an equimolar combination of the peptides prevented the alcohol-induced fetal death and growth abnormalities. Pretreatment with NAP alone resulted in a significant decrease in alcohol-associated fetal death; whereas ADNF-9 alone had no detectable effect on fetal survival after alcohol exposure, indicating a pharmacological distinction between the peptides. Biochemical assessment of the fetuses indicated that the combination peptide treatment prevented the alcohol-induced decreases in reduced glutathione. Peptide efficacy was evident with either 30-min pretreatment or with 1-h post-alcohol administration. Bioavailability studies with [(3)H]NAPVSIPQ indicated that 39% of the total radioactivity comigrated with intact peptide in the fetus 60 min after administration. These studies demonstrate that fetal death and growth restriction associated with prenatal alcohol exposure were prevented by combinatorial peptide treatment and suggest that this therapeutic strategy be explored in other models/diseases associated with oxidative stress.

New operational technology of intrauterine ventilation the fetus lungs by breathing gas

NASA Astrophysics Data System (ADS)

Urakov, A. L.; Nikityuk, D. B.; Urakova, N. A.; Kasankin, A. A.; Chernova, L. V.; Dementiev, V. B.

2015-11-01

New operational technology for elimination intrauterine hypoxia and asphyxia of the fetus using endoscopic artificial ventilation lungs by respiratory gas was developed. For intrauterine ventilation of fetal lung it is proposed to enter into the uterus a special breathing mask and wear it on the head of the fetus using the original endoscopic technology. The breathing mask, developed by us is connected with external breathing apparatus with a hose. The device is called "intrauterine aqualung". Intrauterine aqualung includes a ventilator and breathing circuit with a special fold-out breathing mask that is put on inside the uterus on the head of fetus like a mesh hat. Controlled by ultrasound the technology of the introduction of the mask inside of the uterus through the natural opening in the cervix and technology of putting on the respiratory mask on the head of the fetus with its head previa were developed. The technology intrauterine ventilation of the fetus lungs by respiratory gas was developed.

Maternal Obesity Accelerates Fetal Pancreatic Beta Cell but not Alpha Cell Development in the Sheep: Prenatal and Postnatal Consequences

USDA-ARS?s Scientific Manuscript database

Maternal obesity affects offspring weight, body composition and organ function, increasing diabetes and metabolic syndrome risk. We determined effects of maternal obesity and a high energy diet on fetal pancreatic development. Sixty days prior to breeding. ewes were assigned to control (C, 100% of N...

Linear and nonlinear features of fetal heart rate on the assessment of fetal development in the course of pregnancy and the impact of fetal gender.

PubMed

Spyridou, K; Chouvarda, I; Hadjileontiadis, L; Maglaveras, N

2018-01-30

This work aims to investigate the impact of gestational age and fetal gender on fetal heart rate (FHR) tracings. Different linear and nonlinear parameters indicating correlation or complexity were used to study the influence of fetal age and gender on FHR tracings. The signals were recorded from 99 normal pregnant women in a singleton pregnancy at gestational ages from 28 to 40 weeks, before the onset of labor. There were 56 female fetuses and 43 male. Analysis of FHR shows that the means as well as measures of irregularity of FHR, such as approximate entropy and algorithmic complexity, decrease as gestation progresses. There were also indications that mutual information and multiscale entropy were lower in male fetuses in early pregnancy. Fetal age and gender seem to influence FHR tracings. Taking this into consideration would improve the interpretation of FHR monitoring.

Gene Regulatory Networks governing lung specification

PubMed Central

Rankin, Scott A.; Zorn, Aaron M.

2014-01-01

The epithelial lining of the respiratory system originates from a small group of progenitor cells in the ventral foregut endoderm of the early embryo. Research in the last decade has revealed a number of paracrine signaling pathways that are critical for the development of these respiratory progenitors. In the post genomic era the challenge now is to figure out at the genome wide level how these different signaling pathways and their downstream transcription factors interact in a complex “gene regulatory network” (GRN) to orchestrate early lung development. In this prospective we review our growing understanding of the GRN governing lung specification. We discuss key gaps in our knowledge and describe emerging opportunities that will soon provide an unprecedented understanding of lung development and accelerate our ability to apply this knowledge to regenerative medicine. PMID:24644080

Phase I Study of Accelerated Conformal Radiotherapy for Stage I Non–Small-Cell Lung Cancer in Patients With Pulmonary Dysfunction: CALGB 39904

PubMed Central

Bogart, Jeffrey A.; Hodgson, Lydia; Seagren, Stephen L.; Blackstock, A. William; Wang, Xiaofei; Lenox, Robert; Turrisi, Andrew T.; Reilly, John; Gajra, Ajeet; Vokes, Everett E.; Green, Mark R.

2010-01-01

Purpose The optimal treatment for medically inoperable stage I non–small-cell lung cancer (NSCLC) has not been defined. Patients and Methods Cancer and Leukemia Group B trial 39904 prospectively assessed accelerated, once-daily, three-dimensional radiotherapy for early-stage NSCLC. The primary objectives were to define the maximally accelerated course of conformal radiotherapy and to describe the short-term and long-term toxicity of therapy. Entry was limited to patients with clinical stage T1N0 or T2N0 NSCLC (< 4 cm) and pulmonary dysfunction. The nominal total radiotherapy dose remained at 70 Gy, while the number of daily fractions in each successive cohort was reduced. Results Thirty-nine eligible patients were accrued (eight patients each on cohorts 1 to 4 and seven patients on cohort 5) between January 2001 and July 2005. One grade 3 nonhematologic toxicity was observed in both cohort 3 (dyspnea) and cohort 4 (pain). The major response rate was 77%. After a median follow-up time of 53 months, the actuarial median survival time of all eligible patients was 38.5 months. Local relapse was observed in three patients. Conclusion Accelerated conformal radiotherapy was well tolerated in a high-risk population with clinical stage I NSCLC. Outcomes are comparable to prospective reports of alternative therapies, including stereotactic body radiation therapy and limited resection, with less apparent severe toxicity. Further investigation of this approach is warranted. PMID:19933904

The impact of fetal growth restriction on latency in the setting of expectant management of preeclampsia.

PubMed

McKinney, David; Boyd, Heather; Langager, Amanda; Oswald, Michael; Pfister, Abbey; Warshak, Carri R

2016-03-01

Fetal growth restriction is a common complication of preeclampsia. Expectant management for qualifying patients has been found to have acceptable maternal safety while improving neonatal outcomes. Whether fetal growth restriction influences the duration of latency during expectant management of preeclampsia is unknown. The objective of the study was to determine whether fetal growth restriction is associated with a reduced interval to delivery in women with preeclampsia being expectantly managed prior to 34 weeks. We performed a retrospective cohort of singleton, live-born, nonanomalous deliveries at the University of Cincinnati Medical Center between 2008 and 2013. Patients were included in our analysis if they were diagnosed with preeclampsia prior to 34 completed weeks and if the initial management plan was to pursue expectant management beyond administration of steroids for fetal lung maturity. Two study groups were determined based on the presence or absence of fetal growth restriction. Patients were delivered when they developed persistent neurological symptoms, severe hypertension refractory to medical therapy, renal insufficiency, nonreassuring fetal status, pulmonary edema, or hemolysis elevated liver low platelet syndrome or when they reached 37 weeks if they remained stable without any other indication for delivery. Our primary outcome was the interval from diagnosis of preeclampsia to delivery, measured in days. Secondary outcomes included indications for delivery, rates of induction and cesarean delivery, development of severe morbidities of preeclampsia, and select neonatal outcomes. We performed a multivariate logistic regression analysis comparing those with fetal growth restriction with those with normally grown fetuses to determine whether there is an association between fetal growth restriction and a shortened interval to delivery, neonatal intensive care unit admission, prolonged neonatal stay, and neonatal mortality. A total of 851 patients met

Disturbance of parathyroid hormone-related protein signaling in the nitrofen-induced hypoplastic lung.

PubMed

Doi, Takashi; Lukosiūte, Ausra; Ruttenstock, Elke; Dingemann, Jens; Puri, Prem

2010-01-01

Despite remarkable progress in resuscitation and intensive care, the morbidity and mortality rates in congenital diaphragmatic hernia (CDH) remain high due to severe pulmonary hypoplasia. The pathogenesis of pulmonary hypoplasia associated with CDH is still not clearly understood. Pulmonary parathyroid hormone-related protein (PTHrP) is expressed in the type II epithelial cells and stimulates surfactant production by a paracrine feedback loop regulated by PTHrP receptor (PTHrP-R), which is expressed in the mesenchyme, during terminal airway differentiation. It has been reported that PTHrP knockout and PTHrP-R null mice both exhibit pulmonary hypoplasia, disrupting alveolar maturation before birth. We designed this study to test the hypothesis that gene expression of PTHrP and PTHrP-R is downregulated in the late stages of lung morphogenesis in the nitrofen-induced hypoplastic lung. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetal lungs were harvested on D15, 18, and 21 and divided into three groups: control, nitrofen without CDH [CDH(-)], and nitrofen with CDH [CDH(+)] (n = 8 at each time point for each group, respectively). Total mRNA was extracted from fetal lungs and mRNA expression of PTHrP and PTHrP-R was analyzed by real-time RT-PCR and the significant differences between the groups were accepted at P < 0.05 by statistical analysis. Immunohistochemical studies were also performed to evaluate PTHrP and PTHrP-R protein expression at each time point. Pulmonary mRNA expression of PTHrP-R was significantly decreased in both nitrofen groups [CDH(-) and CDH(+)] compared to controls at D18 and 21. The mRNA level of PTHrP was significantly decreased at D21 in both nitrofen groups compared to controls. Immunoreactivity of PTHrP and PTHrP-R at D18 and 21 was diminished in the distal epithelium and in the mesenchyme, respectively, in the nitrofen-induced hypoplastic lung compared to control lungs. There were no significant

MicroRNA-26a modulates transforming growth factor beta-1-induced proliferation in human fetal lung fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Xiaoou; Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan; Liu, Lian

2014-11-28

Highlights: • Endogenous miR-26a inhibits TGF-beta 1 induced proliferation of lung fibroblasts. • miR-26a induces G1 arrest through directly targeting 3′-UTR of CCND2. • TGF indispensable receptor, TGF-beta R I, is regulated by miR-26a. • miR-26a acts through inhibiting TGF-beta 2 feedback loop to reduce TGF-beta 1. • Collagen type I and connective tissue growth factor are suppressed by miR-26a. - Abstract: MicroRNA-26a is a newly discovered microRNA that has a strong anti-tumorigenic capacity and is capable of suppressing cell proliferation and activating tumor-specific apoptosis. However, whether miR-26a can inhibit the over-growth of lung fibroblasts remains unclear. The relationship betweenmore » miR-26a and lung fibrosis was explored in the current study. We first investigated the effect of miR-26a on the proliferative activity of human lung fibroblasts with or without TGF-beta1 treatment. We found that the inhibition of endogenous miR-26a promoted proliferation and restoration of mature miR-26a inhibited the proliferation of human lung fibroblasts. We also examined that miR-26a can block the G1/S phase transition via directly targeting 3′-UTR of CCND2, degrading mRNA and decreasing protein expression of Cyclin D2. Furthermore, we showed that miR-26a mediated a TGF-beta 2-TGF-beta 1 feedback loop and inhibited TGF-beta R I activation. In addition, the overexpression of miR-26a also significantly suppressed the TGF-beta 1-interacting-CTGF–collagen fibrotic pathway. In summary, our studies indicated an essential role of miR-26a in the anti-fibrotic mechanism in TGF-beta1-induced proliferation in human lung fibroblasts, by directly targeting Cyclin D2, regulating TGF-beta R I as well as TGF-beta 2, and suggested the therapeutic potential of miR-26a in ameliorating lung fibrosis.« less

21 CFR 884.2620 - Fetal electroencephalographic monitor.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fetal electroencephalographic monitor. 884.2620... Devices § 884.2620 Fetal electroencephalographic monitor. (a) Identification. A fetal electroencephalographic monitor is a device used to detect, measure, and record in graphic form (by means of one or more...

Safe fetal platelet genotyping: new developments.

PubMed

Le Toriellec, Emilie; Chenet, Christophe; Kaplan, Cecile

2013-08-01

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is due to maternal alloimmunization against fetal platelet (PLT) antigens. Antenatal management strategies have been developed to avoid complications such as intracranial hemorrhage. The aim of this study was to set up two reliable, noninvasive fetal genotyping assays to determine the fetal risk in pregnancies in which the father is heterozygous for the offending antigen. This study focused on human PLT antigen (HPA)-1, the most frequently implicated antigen in FNAIT in Caucasians. Two assays based on cell-free fetal DNA extracted from maternal blood samples and on real-time polymerase chain reaction (QPCR) were developed: an allele-specific QPCR specifically targeting the polymorphic sequence in HPA-1 and the study of the variation in the high-resolution melting curve of amplicons containing the polymorphic region. All results from the 49 samples obtained from 29 pregnant women were consistent with expectations. Six women were compatible with their fetuses (three HPA-1aa women and three HPA-1bb women), 41 HPA-1bb women were incompatible with their fetuses, as were two HPA-1aa women. Two fetal PLT genotyping assays on maternal blood samples proved to be reliable as of 15 weeks of gestation, thereby avoiding invasive techniques such as amniocentesis. © 2012 American Association of Blood Banks.

Noninvasive fetal RhCE genotyping from maternal blood.

PubMed

Geifman-Holtzman, O; Grotegut, C A; Gaughan, J P; Holtzman, E J; Floro, C; Hernandez, E

2009-01-01

The successful prevention of RhD disease has brought attention to other red blood cells' antigens causing alloimmunisation including RhC/c and RhE/e. Prenatal diagnosis of fetal Rh genotype from maternal blood is in clinical use in Europe but not in the USA. To estimate the collective reported diagnostic accuracy of fetal RhCE genotyping from peripheral maternal blood and compare the results of genotyping when fetal cells and free fetal DNA (FfDNA) are used. English-written literature describing fetal RhCE determination from maternal blood using fetal cells or FfDNA was performed using medical subject headings and text words. The sources included Pubmed (1966-2007), Ovid (1966-2007), CINAHL, The Cochrane Library, ACP Journal Club and OCLC. Key words were prenatal diagnosis, fetal RhCE, fetal DNA in maternal blood and alloimmunisation. A study was considered eligible if it described fetal RhCE type determination using maternal peripheral blood reported in the English literature. Abstracts were excluded. From each study, we determined the number of samples tested, fetal RhCE genotype, the source of the fetal DNA, gestational age, presence of alloimmunisation and confirmation of fetal RhCE type. Exclusions and inclusions were noted. We calculated composite estimates of accuracy using a weighted random effects model. We assessed the papers against an international quality, STARD checklist which is standards for reporting studies of diagnostic accuracy. We identified 20 protocols in six English-written publications reporting fetal RhC/c (seven protocols) and/or E/e (13 protocols) genotyping using DNA obtained from maternal blood for a total of 369 samples. For RhC/c, 176 samples were tested and for RhE/e, 193 samples were tested. Accuracy was determined for each study and for all studies. The combined accuracy of fetal genotype was 96.3% for RhC/c and 98.2% for RhE/e. Only a few samples of the sorted cells were found to be a source for accurate diagnosis, but plasma was

WHO multicentre study for the development of growth standards from fetal life to childhood: the fetal component.

PubMed

Merialdi, Mario; Widmer, Mariana; Gülmezoglu, Ahmet Metin; Abdel-Aleem, Hany; Bega, George; Benachi, Alexandra; Carroli, Guillermo; Cecatti, Jose Guilherme; Diemert, Anke; Gonzalez, Rogelio; Hecher, Kurt; Jensen, Lisa N; Johnsen, Synnøve L; Kiserud, Torvid; Kriplani, Alka; Lumbiganon, Pisake; Tabor, Ann; Talegawkar, Sameera A; Tshefu, Antoinette; Wojdyla, Daniel; Platt, Lawrence