Lung maturity

In an interesting medical application, the formation of a stable black foam film from amniotic fluid can be used as an assessment of fetal lung maturity [206]. 

A 22-year-old female carrying a preterm pregnancy (33 weeks) is in labor. Which of the following drugs can be given to the mother to promote fetal lung maturity ... 

A Cochrane metaanalysis shows the benefit of antenatal corticosteroids for fetal lung maturation to prevent respiratory distress syndrome, intraventricular hemorrhage, and death in infants delivered prematurely. 

To further evaluate the role of CRH in both neuroendocrine and behavioral functions, a mammalian model of CRH deficiency has been generated by targeted mutation in embryonic stem cells (Mugha et al. 1995). CRH-deficient mice reveal a fetal glucocorticoid requirement for lung maturation. Postnatally, they display marked glucocorticoid deficiency and an impaired endocrine response to stress (Jacobson et al. 2000 Mugha et al. 1995). 

Lung maturation in the fetus is regulated by the fetal secretion of cortisol. Treatment of the mother with large doses of glucocorticoid reduces the incidence of respiratory distress syndrome in infants delivered prematurely. When delivery is anticipated before 34 weeks of gestation, intramuscular betamethasone, 12 mg, followed by an additional dose of 12 mg 18-24 hours later, is commonly used. Betamethasone is chosen because maternal protein binding and placental metabolism of this corticosteroid is less than that of cortisol, allowing increased transfer across the placenta to the fetus. 

In children, a leukemoid reaction has been induced by betamethasone treatment (135) this possibility must always be borne in mind, since glucocorticoids can actually be used to treat leukemia or its complications. A case of very high white blood cell count with neutrophilia in a preterm infant whose mother had received two doses of betamethasone prenatally to enhance fetal lung maturation is one of a short list of leukemoid reactions possibly attributable to antenatal glucocorticoid treatment (136). 

In an analysis of 595 preterm infants born at 26-32 weeks gestation during a randomized controlled trial for the prevention of lung disease, glucocorticoids given to women at risk of preterm delivery promoted fetal lung maturation, reduced the incidence of respiratory distress syndrome, and reduced neonatal morbidity and mortality (370). Dexamethasone was given as either two doses of 12 mg 24 hours apart or four doses of 6 mg every 6 hours. Mortality was 9.2% after three or more courses, compared with 4.8% after one or two courses. This association was not explained by other factors (maternal or other common preterm morbidities). 

Prenatal glucocorticoid therapy to enhance fetal lung maturation reduces neonatal morbidity and mortality. However, adverse effects of serial courses of betamethasone on mother and fetus can occur. 

Maternal hyperadrenalism occurred after five courses of betamethasone to enhance fetal lung maturation (374). 

Hyperadrenalism has never otherwise been reported after the sequential use of glucocorticoids for fetal lung maturation. 

Black Film Method for Assessment of Foetal Lung Maturity... 

The creation of sensitive methods for assessment of foetal lung maturity are needed for prophylactics and neonate treatment of RDS. Numerous methods for prediction of lung... 

The results on formation and stability of black foam films, on the first place those on bilayer foam films (NBF) (see Sections 3.4.1.2 and 3.4.4) have promoted the development of methods which enable lung maturity evaluation. The research on stability of amphiphile bilayers and probability for their observation in the grey foam films laid the grounds of the method for assessment of foetal lung maturity created by Exerowa et al. [20,24]. Cordova et al. [25] named it Exerowa Black Film Method. It involves formation of films from amniotic fluid to which 47% ethanol and 7-10 2 mol dm 3 NaCl are added [20,24]. In the presence of alcohol the surface tension of the solution is 29 mN m 1 and the adsorption of proteins from the amniotic fluid at the solution/air interface is suppressed, while that of phospholipids predominates. On introducing alcohol, the CMC increases [26], so that the phospholipids are present also as monomers in the solution. The electrolyte reduces the electrostatic disjoining pressure thus providing formation of black foam lipid films (see Sections 3.4.1.2 and 3.4.4). 

In order to determine the statistical distribution of amniotic fluid samples taken at different gestation weeks, two relations are studied rupture of foam films (VP = 0) and development of RDS, and formation of a bilayer foam film (W = 1) and normal respiratory status of neonates. These correlations allowed to develop a new diagnostic method for estimation of lung maturity [20]. The function of the threshold dilution of various amniotic fluid samples (corresponding to C,) on the gestation age and the clinical results (i.e. yes/no RDS in neonates) is given in Fig. 11.5. The respiratory status of the neonates is studied with the screening system of Masson et al. [26], modified by Hobel et al. [29]. 

The scope of the method for assessment of foetal lung maturity has been extended for evaluation of the risk for development of RDS of new-boms by testing AF with blood and mecomium, obtained from women with normal pregnancy [33]. An experimental study of corticosteroid action on lung surfactant [34] as well as the effect of betamethasone (Celestone) on foetal lung development in rats [35] has been also carried out. 

The experimental curves W(d) and W(C), shown in Fig. 11.6, are very informative with respect to formation of foam bilayers from amniotic fluid because these dependences are very steep. This fact allows precise determination of d, and C,. The clearly pronounced value of Cc (W = 0) practically coincides with the threshold concentration C, for observation of foam bilayer with W = 1, which was defined in the method for assessment of foetal lung maturity. 

The studies discussed expand the use of the method for assessment of foetal lung maturity with the aid of microscopic foam bilayers [20]. It is important to make a clear distinction between this method [20] and the foam test [5]. The disperse system foam is not a mere sum of single foam films. Up to this point in the book, it has been repeatedly shown that the different types of foam films (common thin, common black and bilayer films) play a role in the formation and stability of foams (see Chapter 7). The difference between thin and bilayer foam films [19,48] results from the transition from long- to short-range molecular interactions. The type of the foam film depends considerably also on the capillary pressure of the liquid phase of the foam. That is why the stability of a foam consisting of thin films, and a foam consisting of foam bilayers (NBF) is different and the physical parameters related to this stability are also different. Furthermore, if the structural properties (e.g. drainage, polydispersity) of the disperse system foam are accounted for it becomes clear that the foam and foam film are different physical objects and their stability is described by different physical parameters. 

The above considerations indicate that the phase state of AF foam bilayers is liquid-crystalline and the mean value of the binding energy Q of an amphiphile molecule in the bilayer is 7.6TO 20 J within the temperature range studied. These results are valuable also in relation to the application of foam bilayers for assessment of lung maturity in clinical practice. 

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