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Fetal lung maturation

Reshama Navathe, Vincenzo Berghella
PURPOSE OF REVIEW: Tocolytic agents have been used for over 60 years in the fight against preterm labor, which ultimately can lead to preterm birth. Currently, clinicians can choose from a variety of drug classes to achieve the primary goal of delaying delivery by 48 h, thereby allowing time for administration of corticosteroids for fetal lung maturity, and if appropriate, starting magnesium sulfate for fetal neuroprotection. However, there are currently no known therapies to maintain the tocolytic effect beyond those initial 48 h...
October 18, 2016: Current Opinion in Obstetrics & Gynecology
Elizabeth M Todd, Julie Y Zhou, Taylor P Szasz, Lauren E Deady, June A D'Angelo, Matthew D Cheung, Alfred H J Kim, Sharon Celeste Morley
Alveolar macrophages are lung-resident sentinel cells that develop perinatally and protect against pulmonary infection. Molecular mechanisms controlling alveolar macrophage generation have not been fully defined. Here we show that the actin-bundling protein L-plastin (LPL) is required for the perinatal development of alveolar macrophages. Mice expressing a conditional allele of LPL (CD11c.Cre(pos)-LPL(fl/fl)) exhibited significant reductions in alveolar macrophages and failed to effectively clear pulmonary pneumococcal infection, showing that immunodeficiency results from reduced alveolar macrophage numbers...
October 6, 2016: Blood
Laziyan Mahemuti, Qixuan Chen, Melanie C Coughlan, Min Zhang, Maria Florian, Ryan J Mailloux, Xu-Liang Cao, Kylie A Scoggan, William G Willmore, Xiaolei Jin
Bisphenol A (BPA) has been shown to exert biological effects through estrogen receptor (ER)-dependent and ER-independent mechanisms. Recent studies suggest that prenatal exposure to BPA may increase the risk of childhood asthma. To investigate the underlying mechanisms in the actions of BPA, human fetal lung fibroblasts (hFLFs) were exposed to varying doses of BPA in culture for 24hr. Effects of BPA on localization and uptake of BPA, cell viability, release of immune and developmental modulators, cellular localization and expression of ERα, ERβ and G-protein coupled estrogen receptor 30 (GPR30), and effects of ERs antagonists on BPA-induced changes in endothelin-1 (ET-1) release were examined...
October 2016: Journal of Environmental Sciences (China)
Erin V McGillick, Sandra Orgeig, Dino A Giussani, Janna L Morrison
Exposure to altered intrauterine conditions during pregnancy influences both fetal growth and organ development. Chronic fetal hypoxaemia is a common pregnancy complication associated with intrauterine growth restriction (IUGR) that may influence the risk of infants experiencing respiratory complications at birth. There are a variety of signalling pathways that contribute to normal fetal lung development at the molecular level. The specific molecular effects of chronic hypoxaemia associated with IUGR on lung development are likely to be dependent on the specific aetiology (maternal, placental and/or fetal factors) that can alter hormone concentrations, oxygen and nutrient transport to the fetus...
August 21, 2016: Paediatric Respiratory Reviews
Briana R Dye, Priya H Dedhia, Alyssa J Miller, Melinda S Nagy, Eric S White, Lonnie D Shea, Jason R Spence
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...
September 28, 2016: ELife
M B Azad, B L Moyce, L Guillemette, C D Pascoe, B Wicklow, J M McGavock, A J Halayko, V W Dolinsky
Diabetes is an increasingly common complication of pregnancy. In parallel with this trend, a rise in chronic lung disease in children has been observed in recent decades. While several adverse health outcomes associated with exposure to diabetes in utero have been documented in epidemiological and experimental studies, few have examined the impact of diabetes in pregnancy on offspring lung health and respiratory disease. We provide a comprehensive overview of current literature on this topic, finding suggestive evidence that exposure to diabetes in utero may have adverse effects on lung development...
August 19, 2016: Paediatric Respiratory Reviews
Anouk Bokslag, Mirjam van Weissenbruch, Ben Willem Mol, Christianne J M de Groot
Preeclampsia is a common pregnancy specific disease, that presents with hypertension and a variety of organ failures, including malfunction of kidneys, liver and lungs. At present, the only definitive treatment of preeclampsia is end the pregnancy and deliver the neonate and placenta. For women with mild preeclampsia in the preterm phase of pregnancy, expectant management is generally indicated to improve fetal maturity, often requiring maternal medical treatment. Last decades, more evidence is available that the underlying mechanism of preeclampsia, endothelial disease, is not limited to pregnancy but increases cardiovascular risk in later life...
September 19, 2016: Early Human Development
Anita Soni, Seeru Garg, Khushboo Patel, Zarna Patel
BACKGROUND: Oligohydramnios is a known obstetric complication which is associated with operative interferences and perinatal morbidity and mortality. l-arginine is a precursor of nitric oxide and may play a role in local vasodilatation. Administration of l-arginine has been suggested to improve amniotic fluid index (AFI) in oligohydramnios. AIMS AND OBJECTIVES: To study the effect of l-arginine in optimizing fetal outcome in cases of oligohydramnios. MATERIALS AND METHODS: A retrospective study was conducted at Dr L H Hiranandani hospital consisting of 100 antenatal patients diagnosed with oligohydramnios [AFI < 8 cm] remote from term...
October 2016: Journal of Obstetrics and Gynaecology of India
Andrew M South, Patricia A Nixon, Mark C Chappell, Debra I Diz, Gregory B Russell, Beverly M Snively, Hossam A Shaltout, James C Rose, T Michael O'Shea, Lisa K Washburn
BACKGROUND: Antenatal corticosteroid (ANCS) treatment hastens fetal lung maturity and improves survival of premature infants, but the long-term effects of ANCS are not well-described. Animal models suggest that ANCS increases the risk of cardiovascular disease through programmed changes in the renin-angiotensin (Ang)-aldosterone system (RAAS). We hypothesized that ANCS exposure alters the RAAS in adolescents born prematurely. METHODS: A cohort of 173 adolescents born prematurely was evaluated, of whom 92 were exposed to ANCS...
October 5, 2016: Pediatric Research
Carole R Mendelson, Alina P Montalbano, Lu Gao
Preterm birth remains the major cause of neonatal morbidity and mortality throughout the world. This is due, in part, to our incomplete understanding of the mechanisms that underlie the maintenance of pregnancy and the initiation of parturition at term. In this article, we review our current knowledge of the complex, interrelated and concerted mechanisms whereby progesterone maintains myometrial quiescence throughout most of pregnancy, as well as those that mediate the upregulation of the inflammatory response and decline in progesterone receptor function leading to parturition...
September 11, 2016: Journal of Steroid Biochemistry and Molecular Biology
Sneha K Taylor, Reiko Sakurai, Tokusho Sakurai, Virender K Rehan
INTRODUCTION: The physiologic vitamin D (VD), 1α,25(OH)2D3 (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...
September 10, 2016: Lung
Nicole Marquardt, Martin A Ivarsson, Erik Sundström, Elisabet Åkesson, Elisa Martini, Liv Eidsmo, Jenny Mjösberg, Danielle Friberg, Marius Kublickas, Sverker Ek, Gunilla Tegerstedt, Åke Seiger, Magnus Westgren, Jakob Michaëlsson
Amniotic fluid (AF) surrounds the growing fetus, and cells derived from AF are commonly used for diagnosis of genetic diseases. Intra-amniotic infections are strongly linked to preterm birth, which is the leading cause of perinatal mortality worldwide. Surprisingly little is known, however, about mature hematopoietic cells in AF, which could potentially be involved in immune responses during pregnancy. In this study, we show that the dominating population of viable CD45(+) cells in AF is represented by a subset of fetal CD103(+) group 3 innate lymphoid cells (ILCs) producing high levels of IL-17 and TNF...
September 2, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
P Anegroaie, M G Frasch, S Rupprecht, I Antonow-Schlorke, T Müller, H Schubert, O W Witte, M Schwab
AIM: Antenatal glucocorticoids are used to accelerate foetal lung maturation in babies threatened with premature labour. We examined the influence of glucocorticoids on functional and structural maturation of the central somatosensory pathway in foetal sheep. Somatosensory-evoked potentials (SEP) reflect processing of somatosensory stimuli. SEP latencies are determined by afferent stimuli transmission while SEP amplitudes reveal cerebral processing. METHODS: After chronic instrumentation of foetal sheep, mothers received saline (n = 9) or three courses of betamethasone (human equivalent dose of 2 × 110 μg kg(-1) betamethasone i...
September 1, 2016: Acta Physiologica
Yu-Chieh Chen, Ying-Hua Huang, Jiunn-Ming Sheen, You-Lin Tain, Hong-Ren Yu, Chih-Cheng Chen, Miao-Meng Tiao, Ho-Chang Kuo, Li-Tung Huang
BACKGROUND: There is increasing epidemiological evidence indicating that many chronic diseases originate during early life, even before birth, through what are termed fetal programming effects. Prenatal glucocorticoid is frequently used clinically to accelerate the maturation of the lung, but its long-term effects remain unclear. METHODS: We gave pregnant Sprague-Dawley rats either intraperitoneal dexamethasone (0.1 mg/kg body weight) or vehicle at Gestational Days 14-20 and assessed the effects to pancreas at Postnatal Days 7 and 120...
June 18, 2016: Pediatrics and Neonatology
Ayten Hijazi, Haiyan Guan, Kaiping Yang
We previously demonstrated that prenatal exposure to Bisphenol A (BPA) disrupts fetal lung maturation likely through the glucocorticoid signalling pathway, but the precise molecular mechanisms remain obscure. Given that BPA diminished the expression of epithelial sodium channel-γ (ENaCγ), a well-known glucocorticoid receptor (GR) target gene, in fetal lungs, we used this GR target gene to delineate the molecular pathway through which BPA exerts its effects on lung cells. The A549 lung epithelial cell line was used as an in vitro model system...
August 13, 2016: Archives of Toxicology
Michelle L Baack, Benjamin J Forred, Tricia D Larsen, Danielle N Jensen, Angela L Wachal, Muhammad Ali Khan, Peter F Vitiello
RATIONALE: Infants born to diabetic or obese mothers are at risk of respiratory distress and persistent pulmonary hypertension of the newborn (PPHN), conceivably through fuel-mediated pathogenic mechanisms. Prior research and preventative measures focus on controlling maternal hyperglycemia, but growing evidence suggests a role for additional circulating fuels including lipids. Little is known about the individual or additive effects of a maternal high-fat diet on fetal lung development...
2016: PloS One
Gloria Pelizzo, Maria Chiara Mimmi, Jose Luis Peiro, Mario Marotta, Francesco Amoroso, Mario Fusillo, Veronica Carlini, Valeria Calcaterra
OBJECTIVE: To compare endotracheal fluid (EF) and amniotic fluid (AF) phospholipidic profile changes following tracheal occlusion (TO) in the congenital diaphragmatic hernia (CDH) fetal lamb model, in order to support the efficacy of TO on lung maturity. METHODS: A diaphragmatic defect was induced at 70 days' gestation, TO was carried out at day 102 and cesarean section at 136 days' gestation. EF and AF samples, collected at delivery, were evaluated using mass spectrometry (the analysis focused on palmitoyloleoyl-phosphatidylcholine [POPC, PC(18:1/16:0)], dipalmitoyl-phosphatidylcholine [DPPC, PC(16:0/16:0)] and sphingomyelins [SMs])...
August 11, 2016: Journal of Perinatal Medicine
Carolyn I Freeman, Natasha L Hezelgrave, Andrew H Shennan
Antenatal corticosteroids for fetal lung maturation have become mainstay treatment in women thought to be at high-risk of premature birth. To ensure treatment efficacy before delivery, the current practice is to administer steroids early to a woman considered at risk; however, neonatal benefit is lost after the seven-day treatment-to-delivery window. Over half of women who deliver before 34 weeks' gestation do not receive antenatal corticosteroids within this timeframe, but many still deliver prematurely; however, clinicians are reluctant to administer repeated courses of steroids due to concerns, among others, of impaired fetal growth...
December 2015: Obstetric Medicine
Kjell Haram, Jan Helge Mortensen, Everett F Magann, John C Morrison
Antenatal corticosteroid therapy improves both fetal lung mechanism and gas exchange due to accelerated morphologic development of type one and two pneumocytes. This therapy also enhances the production of surfactant binding proteins and fetal lung antioxidant enzymes. In women with threatening preterm delivery, a single course is advocated between 24 and 34 weeks' gestation with either betamethasone (two doses of 12 mg 24 hours apart) or dexamethasone (4-doses of 6 mg at 12-h intervals). Such treatment reduces the rate of respiratory distress syndrome, comorbidity and mortality in neonates in the first 48 hours of life...
August 3, 2016: Journal of Maternal-fetal & Neonatal Medicine
A Freis, M Elsässer, C Sohn, H Fluhr
Twin pregnancy consisting of one fetus and one complete mole (CMCF, complete hydatidiform mole and a coexistent fetus) is an obstetric rarity with an incidence of 1/22 000 to 1/100 000 pregnancies. Associated risks include prematurity, intrauterine death, vaginal bleeding, preeclampsia, hyperthyroidism, theca lutein cysts, uterine rupture and the development of malignant neoplasia in the form of a trophoblastic tumour (GTD, persistent gestational trophoblastic disease), which is thought to be the most common complication...
July 2016: Geburtshilfe und Frauenheilkunde
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