Neonatal pulmonary hypoplasia with premature rupture of fetal membranes and oligohydramnios

Thibeault, Donald W.; Beatty, Eugene C.; Hall, Robert T.; Bowen, Sandra K.; O'Neill, Diane

doi:10.1016/s0022-3476(85)80148-7

Cited by 135 publications

(58 citation statements)

References 16 publications

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“…However, recent clinical evidence suggests that another threat should be considered when rupture of the membranes leads to oligohydramnios, i.e. fetal lung hypoplasia (22,23). Clinically we are particularly interested in what happens to lung growth with oligohydramnios during the canalicular to early terminal sac stages of lung development.…”

Section: Discussionmentioning

confidence: 99%

“…Nimrod et al (22) observed that both gestational age at rupture and length of the latent period (until delivery) were associated with lung hypoplasia, particularly below 26 wk of gestation. Of note, Thibeault et al (23) observed that lung hypoplasia was "relatively common" in infants born prematurely with ruptured membranes for more than 5 days.…”

Section: Discussionmentioning

confidence: 99%

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Oligohydramnios-Induced Lung Hypoplasia: The Influence of Timing and Duration in Gestation

et al. 1986

Pediatr Res

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MATERIALS AND METHODSplasia is also found as an isolated anomaly (3,4) or in association with minor deformities compatible with survival, i.e. oligohydramnios deformation sequence following prolonged rupture of the fetal membranes (5).Over 20 years ago, both Blanc et al. (6) and Bain et al. (7) demonstrated, using perinatal autopsy data, that prolonged oligohydramnios, irrespective of its cause, was associated with fetal lung hypoplasia. More recently, experimental evidence derived from work in various mammalian species confirmed this association (8-11). Two important questions remain unanswered: I) what is the mechanism by which lack of amniotic fluid interferes with fetal lung growth? 2) What are the influences of both gestational age at the onset of oligohydramnios, and its duration, on the degree of lung hypoplasia? This report focuses on the latter question using the guinea pig model of oligohydramnios. A preliminary account of these experiments has been published previously (12).Fetal lung growth proceeds in three consecutive stages, i.e. the pseudoglandular, canalicular, and terminal sac stages. Although this sequence is invariable, its timing in gestation varies among species. We induced oligohydramnios between days 40 and 55 of gestation in the guinea pig, a period roughly corresponding to 18 to 29 wk of gestation in the human. The five time-frames studied are illustrated in Figure I, along with the stages of fetal lung development involved. More specifically, the experiments were as follows: experiment A: drainage between days 40 and 45 (5 days); experiment B: drainage between 45 and 50 (5 days); experiment C: drainage between days 50 and 55 (5 days); experiment D: drainage between days 40 and 50 (10 days); experiment E: drainage between days 45 and 55 (10 days).All fetuses were sacrificed at the end of the 5-or 10-days study period to assess fetal and lung growth. In order to overcome the effects of variation between litters, we used untouched littermate fetuses as controls. Whenever possible, untouched littermate fetuses located at the same level in the opposite uterine horn were chosen as paired controls in order to control for the naturally occurring intralitter variation in fetal size.Pregnant guinea pigs (Cavia porcellus, Camm-Hartley strain) were obtained 30 days after mating from the Camm Research Laboratory, Wayne, NJ. Pregnant animals were caged individually and provided with guinea pig chow no. 5025 (Ralston Purina Co.) and tap water ad libitum. Following an overnight fast, the animals were anesthetized with intramuscular injections of ketamine hydrochloride (40 mg/kg) (Ketaset, Bristol Lab.) and acepromazine maleate (3 mg/kg) (Tech America Group, Inc.). After local anesthesia with lidocaine, a midline laparotomy was performed. Both uterine horns were exteriorized and the position of each fetus was recorded. Half the litter was randomly assigned to the experimental group and the other half served as 951 ABSTRACf. We drained amniotic fluid for periods of 5 and 10 days at various times in g...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Oligohydramnios-Induced Lung Hypoplasia: The Influence of Timing and Duration in Gestation

et al. 1986

Pediatr Res

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“…The impaired growth and structural development of the lung associated with LH has been reported in previous morphometric studies in human infants and experimental animal models. For example, radial alveolar counts are reduced in preterm infants with LH after premature rupture of membranes (10). Similarly, studies in animal models of LH have found reduced size and number of alveoli and alveolar ducts and thickened alveolar walls (12)(13)(14).…”

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confidence: 99%

Effect of Lung Hypoplasia on Birth-Related Changes in the Pulmonary Circulation in Sheep

et al. 2005

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Lung hypoplasia (LH) is a serious cause of neonatal compromise, but little is known of its functional effects on the pulmonary circulation. Our aim was to characterize birth-related changes in the pulmonary circulation of newborn lambs with LH and to compare them with alterations in respiratory function. LH was induced in six ovine fetuses by the creation of a tracheoamniotic shunt as well as amniotic fluid drainage starting at 105.6 Ϯ 1.5 (mean Ϯ SEM) days of gestation (term~147 d). At 139.9 Ϯ 0.3 d, fetuses were exteriorized under anesthesia to implant vascular catheters and an ultrasonic flow probe around the left pulmonary artery. The lambs then were delivered and ventilated for 2 h, during which systemic and pulmonary artery pressures, left pulmonary blood flow, and measures of respiratory function were recorded. At autopsy, lungs were weighed and volume was measured at 20 cm H 2 O. In LH lambs, lung weight was 25% lower and respiratory system compliance was 30% lower than in controls. Mean pulmonary blood flow in LH lambs was 42% lower and pulmonary vascular resistance was 138% higher than in controls. Morphometry showed that volume density of pulmonary arteries in LH was 30% lower than in controls. We conclude that, in this LH model, changes in ventilatory indices were proportional to the change in lung size, whereas changes in the pulmonary circulation were greater than the change in lung size and were associated with reduced density of pulmonary arteries. Abbreviations AaDO 2 , alveolar-arterial difference of oxygen tension BW, body weight CDH, congenital diaphragmatic hernia Crs, total respiratory system compliance EEP, end-expiratory pressure FIO 2 , fraction of inspired oxygen LH, lung hypoplasia LV, lung volume LW, lung weight MAP, mean airway pressure PaCO 2 , partial pressure of carbon dioxide in the arterial blood PaO 2 , partial pressure of oxygen in the arterial blood PAP, pulmonary artery pressure PBF, pulmonary blood flow PIP, peak inspiratory pressure PVR, pulmonary vascular resistance SAP, systemic artery pressure V a , volume density of arteries in the lung (tissue and airspace) V at , volume density of arteries in lung tissue alone VEI, ventilatory efficiency index V t , tidal volume Fetal lung hypoplasia (LH) results from impaired lung tissue growth during fetal development and can result in severe respiratory insufficiency in the neonate. LH is present in approximately one in 1000 human live births (1,2), and, despite recent advances in the treatment of newborn infants with respiratory insufficiency, it remains one of the major causes of neonatal mortality and morbidity (3-5). The incidence of LH in neonatal autopsies is reportedly increasing because death rates as a result of other neonatal diseases are decreasing (6).LH is associated with many predisposing conditions (7), including chronic oligohydramnios, as a result of fetal anuria or amniotic fluid leakage (8 -10), intrathoracic masses, as in congenital diaphragmatic hernia (CDH), and decreased fetal breathing movements (5,11). The...

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“…The process of septation involves budding from the primary septum (saccular wall), formation of a double-capillary network, elongation of septa, coalescence of vessels to form a single capillary layer, and thinning of the septal walls (1,2). Exposure of neonatal rats to hyperoxia during alveolarization interferes with the process of septation; alveolar number and internal surface area are decreased and the parenchymal airspace is enlarged (3)(4)(5). These parameters persist up to d 40 (6).…”

mentioning

confidence: 99%

Hyperoxia Decreases Matrix Metalloproteinase-9 and Increases Tissue Inhibitor of Matrix Metalloproteinase-1 Protein in the Newborn Rat Lung: Association with Arrested Alveolarization

2004

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ABTRACT Matrix metalloproteinases (MMP) are likely effectors of normal lung development, especially branching morphogenesis, angiogenesis, and extracellular matrix degradation. Because hyperoxia exposure (Ͼ95% O 2 ) from d 4 to 14 in newborn rat pups leads to arrest of alveolarization and mimics newborn chronic lung disease, we tested whether hyperoxia altered MMP-2 and -9 mRNA, protein, and enzymatic activity, and the mRNA and protein expression of the endogenous tissue inhibitor of MMP, TIMP-1. No changes due to hyperoxia exposure were observed in MMP-2 mRNA or pro-enzyme (72 kD) protein levels between d 6 and 14, although the overall protein mass and zymographic activity of the active (68 kD) enzyme were diminished (p Ͻ 0.05, ANOVA). However, hyperoxia significantly decreased levels of MMP-9 mRNA and pro-MMP-9 protein and diminished overall MMP-9 pro-enzyme activity.TIMP-1 mRNA was not elevated by hyperoxia until d 14, but protein levels were significantly (p Ͻ 0.001) elevated by hyperoxia from d 9 to 14. To estimate the potential of MMP inhibition to arrest alveolarization, administration of doxycycline (20 mg/ kg, twice daily by gavage), a pan-MMP proteolysis inhibitor, arrested lung alveolarization. We conclude that hyperoxia decreases MMP-9 mRNA, protein, and activity and elevates TIMP-1 protein, and these changes have the potential to contribute to the arrest of normal lung development. Lung alveoli are formed when immature saccules subdivide into functional gas-exchange units through formation of secondary septa (1, 2). The process of septation involves budding from the primary septum (saccular wall), formation of a double-capillary network, elongation of septa, coalescence of vessels to form a single capillary layer, and thinning of the septal walls (1, 2). Exposure of neonatal rats to hyperoxia during alveolarization interferes with the process of septation; alveolar number and internal surface area are decreased and the parenchymal airspace is enlarged (3-5). These parameters persist up to d 40 (6). Hyperoxia during the neonatal period also alters lung connective tissue, alters elastic fiber structure and concentration (7), and causes an inflammatory reaction characterized by interalveolar edema and proteinosis (3,5,8). Chronic inflammation of the neonatal lung leads to fibrosis and thickening of the septa (3, 5).MMP are a group of proteases that exist as pro-enzymes and are cleaved by other MMP to active forms that have several specialized functions, including extracellular matrix turnover. Some of their functions regulate processes associated with development, such as branching morphogenesis and angiogenesis as well as inflammatory processes and wound healing (9). MMP-2 and MMP-9, also called gelatinases-A and -B, respectively, cleave gelatin, type IV and V collagen, and elastin. Types IV, V, and VII collagens are associated with basement membranes (10). MMP-2 and MMP-9 exhibit increased gelatinolytic activities as the lung develops (11), and during the postnatal lung growth stage both MMP-2 and MM...

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Neonatal pulmonary hypoplasia with premature rupture of fetal membranes and oligohydramnios

Cited by 135 publications

References 16 publications

Oligohydramnios-Induced Lung Hypoplasia: The Influence of Timing and Duration in Gestation

Oligohydramnios-Induced Lung Hypoplasia: The Influence of Timing and Duration in Gestation

Effect of Lung Hypoplasia on Birth-Related Changes in the Pulmonary Circulation in Sheep

Hyperoxia Decreases Matrix Metalloproteinase-9 and Increases Tissue Inhibitor of Matrix Metalloproteinase-1 Protein in the Newborn Rat Lung: Association with Arrested Alveolarization

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