Prevention Of RDS Research Articles

Current strategies for the prevention of RDS in premature infants and possibilities of using them in the RT

Aim. To analyze modern strategies for the prevention of respiratory distress syndrome and the possibility of their use in RT.Material and methods. The analysis was carried out based on directives of the Government of the Republic of Tajikistan, regulations, and normative documents for obstetric institutions approved by the Ministry of Health and Social Protection of the Population of the Republic of Tajikistan, and the data from annual reports of structural units.Results. The paper outlines an approach to monitoring a pregnant woman based on the 5th updated European Consensus Guidelines for the Management of Newborns with Respiratory Distress Syndrome. It presents positive and negative arguments for the effect of steroid drugs on the fetus and recommendations for their use at the stage of management of pregnant women with a high risk of preterm birth, depending on the gestation period. It also includes a brief comparative analysis with national clinical protocols for the management of preterm labor and tocolytic therapy.Conclusion. Early identification of pregnant women at high risk of termination and providing them with effective care following modern strategies, reduce the adverse perinatal outcomes.

Corticosteroids in Pregnancy for Preventing RDS: Overview of Systematic Reviews.

The objective of this study was to analyze the available evidence of systematic reviews that evaluated the efficacy of antenatal corticosteroids in order to contribute to a reduction in magnitude and transcendence of respiratory distress syndrome of the newborn (RDS). Thus, an overview was conducted including all systematic reviews of randomized controlled trials (RCTs) that evaluated women who received corticosteroid treatment during pregnancy to prevent RDS. Therefore, a search strategy was developed using the terms "respiratory distress syndrome, newborn," "corticosteroids," "perinatal death," "neonatal death," "neonate," and "pregnancy." The electronic databases searched were MEDLINE, EMBASE, Cochrane Library, LILACS, and Google Scholar, for studies published until June 2020. We identified 354 references, 38 of which were relevant after the initial screening. Ten systematic reviews met the inclusion criteria. For RDS, 1522 cases occurred in the control group composed of 8716 participants, while in the intervention group was 1088 in 8740 participants (RR = 0.67, 95% CI 0.60-0.75). For neonatal death, 343 cases occurred in 5248 participants of the control group, while in the intervention group, there were 227 cases in 5246 participants (RR = 0.66, 95% CI 0.56-0.78). For perinatal death, there were 344 cases in 3345 participants in the control group, while in the intervention group, the number of cases was 264 in 3384 participants (RR = 0.72, 95% CI 0.58-0.89). Thus, the use of corticosteroids during pregnancy in women at risk of preterm birth is effective for the prevention of RDS in neonates and reducing the number of neonatal and perinatal deaths in preterm. PROSPERO protocol no: CRD42017074604.

Does surfactant nebulization prevent early intubation in preterm infants? A protocol for a systematic review and meta-analysis

BackgroundRespiratory distress syndrome (RDS) is the most common cause of respiratory failure in preterm infants. Treatment consists of respiratory support and exogenous surfactant administration. Commonly, surfactant is administered intratracheally. However, this requires airway instrumentation and subsequent fluid instillation which may be harmful. Surfactant nebulization (SN) may offer a safe and effective alternative for surfactant administration, but the clinical efficacy is not yet established. Thus, this systematic review and meta-analysis of randomized controlled trials will summarize the available evidence to determine the effectiveness and safety of SN for the prevention of intubation and subsequent mechanical ventilation at 72 h after birth.MethodsA systematic literature search in Medline, Embase, and The Cochrane Library will be performed, and all randomized controlled trials (RCTs) and quasi-RCTs from published articles, presentations, and trial registries will be included in this meta-analysis. Titles and abstracts of all records identified in the search will be screened by two reviewers independently.Data on preterm infants (≤ 37 weeks) receiving nebulized surfactant in the first 72 h after birth for the treatment or prevention of RDS will be evaluated. Primary outcome is the intubation rate by 72 h after birth, and secondary outcomes include peridosing safety effects as well as major neonatal morbidities.Risk of bias will be assessed using the revised Cochrane ROB tool, and subgroup analyses will be performed to evaluate potential confounding factors. Publication bias will be assessed by examining a funnel plot. The meta-analysis will be performed using a fixed-effects model.DiscussionThis review will provide an evidence-based tool for information about surfactant nebulization, illustrating the current knowledge and hopefully revealing potential novel avenues for researchers and clinicians alike.Systematic review registrationThis review is registered with the publicly available resource PROSPERO (CRD42020175625).

The possibilities of prolongation of pregnancy in women with leaking of amniotic fluid in the second and in the beginning of third trimester

Abstract: With the development of premature rupture of membranes in terms 28–30.5 weeks, prolongation of pregnancy more than 48 hours, held-Niemi prevention of RDS contributes to significant decrease in perinatal mental and postnatal lethality, and lengthening the latent period of more than 168 hours, significantly reduce child morbidity. Keywords: Prolongation of pregnancy, amniotic fluid. The main tasks of Obstetrics are creating optimal condi-tions for the woman function of maternity, maintaining her health and providing the birth of healthy offspring. On the background of low birth rate the perinatal mortality remains rather high and exceeds the 12%, although it has a tendency to decrease over the last 10 years [1; 2].The premature labor has special significance in the structure of perinatal morbidity and mortality are against the backdrop of premature rupture of membranes, which is one of the most frequent reasons for initiating of patrimonial activity in 34.9–56 % of all preterm births [3].Studying of features of pregnancy in case of premature rupture of membranes and determination of optimal duration of of anhydrous interval, methods of preventing of infectious complications, the timing and method of the delivery at vari -ous gestational periods will reduce the number unfavorable outcomes in this serious pathology [4, 5].Taking into account the national particularities, the liv-ing conditions of our women (chronic anemia, endemicity, resulting in frequent thyroid disease, isthmic cervical insuffi-ciency, congenital malformations of the uterus, stress, etc.) the primary goal of our study to highlight the major prognostic factors and the development of preventive measures for pro-longation of incomplete pregnancy complicated by premature rupture of membranes in the second and in the beginning of third of trimesters [3].Searching more information about the mechanisms of premature rupture of membranes allows developing drugs of pathogenetic action, which should help doctors around the world to cope with the problem of reducing the incidence of premature births [6].Now the challenges of prolonging pregnancy for preterm rupture of membranes and determination of the optimal duration of anhydrous interval poorly studied and were not worked out prognostic criteria of prolonging pregnancy.

Could a combined administration of dexamethasone and 3,5-dimethyl-3′-isopropyl- l-thyronine (DIMIT) be a more effective alternative to dexamethasone alone in the prevention of RDS?

Objective: To test whether the combined application of dexamethasone (DEXA) and 3,5-dimethyl-3′-isopropyl- l-thyronine (DIMIT) induces the synthesis of surfactant protein A (SP-A) mRNA at a higher rate than both substances given alone? Study design: Organoid culture of fetal rat lungs (Wistar rats; day 19 of gestation) was prepared. After 48 h of incubation we added DEXA (10 −5, 10 −7, 10 −8 and 10 −9 mol/l), DIMIT (10 −5, 10 −7 and 10 −9 mol/l) and the combination of DEXA in 10 −8 mol/l with various concentrations of DIMIT. After another 48 h of incubation, northern blot and hybridization with a 32 P -labeled SP-A cDNA probe was performed. One-way-variance-analysis with a Scheffé-test, Levene-test and one-sample- t-test were used for statistical analysis. Results: DEXA alone above 10 −8 mol/l resulted in a significant increase, DIMIT resulted in a decrease of SP-A mRNA induction. Combined application of DIMIT and DEXA resulted in a significant increase compared to the controls. Compared to DEXA alone in 10 −8 mol/l, we found an increased induction, but the data were not significant. Conclusions: The combined application of DEXA and DIMIT shows a higher induction of SP-A mRNA than both drugs given alone.

471 A randomized controlled trial of betamethasone in the prevention of RDS at 24?28 weeks

471 A randomized controlled trial of betamethasone in the prevention of RDS at 24?28 weeks

1504 Intra amniotic thyroxine (IA T4) In the prevention of RDS

We have previously reported on the decrease of the microviscosity after IA T4 treatment suggesting enhancement of lung maturity. In the present study we report on the outcome of non-selected 856 pregnancies in 4 groups of patients. (1) No treatment; (2) intra-amnotic T4 500 ug (1 to 3 injections, a week apart); (3) betamethasone (B) (1 to 4 courses); and (4) combined IA T4 + B. There was no significant difference in the age and weight at birth in the 4 groups. There was no significant difference in the incidence of RDS or the mortality from RDS between the 4 groups; there was a significant difference (p < 0.05) in the overall mortality (*after congenital letal malformation were excluded). These data suggest that: (1) T4 and/or betamethasone therapy may decrease RDS and non-RDS related mortality and (2) the intra-amnotic route of T4 represents a safe, effective method of hormone administration. This approach deserves further investigation as a tool to help us understand and treat fetal abnormalities during the intrauterine period.

Combined hormonal treatment and lung maturation.

Despite the proven efficacy of glucocorticoids for the prevention of RDS, this treatment is not effective in every case. One possible approach to improving the outcome is combined treatment with thyroid hormone and corticosteroid. Thyroid hormones accelerate morphological development and surfactant production in animals after treatment in vivo. With lung tissue in culture, T3 enhances phospholipid synthesis, apparently acting at different biochemical sites from those stimulated by corticosteroids. The effects of T3 are mediated through nuclear receptors, indicating that physiologic concentrations of T3 are stimulatory in the fetal lung. Furthermore, the developmental pattern for endogenous T3, as well as effects of thyroidectomy in fetal lambs, support the concept that endogenous thyroid hormones contribute to the timing of normal lung maturation in vivo. Combined treatment with thyroid hormones and glucocorticoids produces additive or supra-additive effects on phosphatidylcholine synthesis in the fetal lungs of rats, rabbits, and humans. The enhanced and faster response with both hormones v glucocorticoid alone suggests that clinical benefit might occur after shorter treatment intervals than currently observed with corticosteroid therapy. As there is little placental transfer of T3 and T4 in humans, maternal treatment with these hormones is not likely to be a useful approach for fetal therapy. Potentially, such therapy could be achieved by intraamniotic injection of T3 or T4, maternal treatment with synthetic thyroid hormones that pass the placenta, or by maternal treatment with TRH. This latter approach has been shown to elevate T3 levels in the cord blood of infants at term, mimicking the normal surge immediately after birth. If additional animal studies confirm the benefit of combined therapy on pulmonary function, clinical trials with glucocorticoid plus thyroid hormone may be appropriate in the near future.

1693 LABOR STIMULATES SURFACTANT SECRETION IN NEWBORN RABBIT LUNG SLICES

We previously reported that labor increased the amount of surfactant phospholipid in newborn rabbit lung lavage but it was unclear if the effect was on synthesis or secretion. We have now examined the effect of labor on secretion in a slice model. Newborn rabbits are injected i.p. with 3H-choline and killed 4 h later. Slices from the blood-free lungs are incubated in buffer for 2.5 h. Initially the lipids secreted are similar to those of lung tissue but after 3 changes of buffer the lipids secreted are very similar to those of lung lavage. We measure the rate of secretion of 3H-phosphatidylcholine (PC) during this period. At 31 days gestation the rate of secretion increased from 198±18 cpm/h/mg tissue protein in 16 litters delivered before labor to 281±21 in 31 litters delivered after oxytocin-induced labor (P<0.02). Spontaneous labor was also stimulatory while oxytocin without labor was not. We attempted to mimic and abolish the effect of labor on PC secretion by incubating the slices with various agents. 10−5M prostaglandin E2 and 10−4M terbutaline stimulated secretion in slices from animals delivered prior to labor by 20% and 33%, respectively. Pilocarpine had no effect. 2×10−4M indomethacin and 10−4M propranolol inhibited secretion in slices from animals delivered after labor by 49% and 42%, respectively. Atropine had no effect. These data show that labor stimulates surfactant secretion and thus may be an important factor in the prevention of RDS. The effect of labor may be mediated, at least in part, by prostaglandins and catecholamines both of which increase during labor and birth. (Supported by HD-11018).

1715 EFFECT OF INSULIN (I) AND ISOXSUPRINE (X) ON LUNG SURFACTANT PRODUCTION IN THE FETAL RHESUS MONKEY

We examined the effect of chronic hyperinsulinemia on lung lavage phospholipid (PL) content and composition. I (19 U/d for 20 d) was administered to fetal rhesus monkeys with an Alzet minipump implanted in the hind leg (Diabetes 28: 1058, 1979). Shamand non-operated animals were used as controls (C). X (5-10 mg/d for 20 d) was administered to additional mothers. Fetuses were delivered by cesarean section at 134-147 d (term is 165 d). I levels were 49±14 and 4470±780 μU/ml and glucose levels were 43±6 and 21±6 mg/dl in the C and I-treated groups respectively. Results are shown in the table. Hyperinsulinemia did not inhibit surfactant production. This suggests that the increased incidence of RDS in infants of diabetic mothers may not be due to hyperinsulinemia but rather possibly to the concomitant hyperglycemia. X increased surfactant production. X may be useful in the prevention of RDS in humans. Supported by HD-11018 and HD-11343.

MATERNAL ADMINISTRATION OF GLUCOCORTICOIDS

No definite comment can be made, at this time, with respect to the safety of glucocorticoid therapy in the human fetus and newborn. Obstetricians and pediatricians need to be aware of the potential risks. Whether the fetal changes that have been reported thus far are permanent and whether they will have any postnatal functional significance are questions of major importance. Probably the greatest risk associated with antenatal steroid therapy is the potential abuse of this treatment. Longer treatment periods or higher doses of steroids will increase the risk for potentially adverse side effects. The recently stated opinion of Taeusch et al seems appropriate: "We conclude that steroids are effective in reducing risk of RDS, but safer and more efficacious approaches for the prevention of RDS should be sought" (91). Further studies are needed to determine the mechanisms of action of glucocorticoids and their risk/benefit ratios in regard to fetal and neonatal well being.

963 THYMUS SIZE AND ITS RELATIONSHIP TO RESPIRATORY DISTRESS SYNDROME

In an attempt to correlate the thymolytic effect of glucocorticoids with their role in the induction of surfactant synthesis and the prevention of RDS, the size of the thymus on the initial chest radiographs of newborns who required intensive care was reviewed. Utilizing a ratio of the cardiothymic silhouette at the carina to the thoracic width (C-T/T) we found an increase in C-T/T with increasing gestational age. Newborn infants with RDS had a significantly elevated mean C-T/T (0.40 vs 0.36; p. <0.001) an increased percentage of ‘enlarged’ (C-T/T ≥ 0.45) thymuses (28% vs 8% in non-RDS babies), and a decreased percentage of ‘small’ (C-T/T ≥ 0.30) thymuses (11% vs. 26%). Moreover, in a series of 8 multiple gestations that were discordant for RDS, the larger thymus was seen in those with RDS in 6 of 8, while in only one did the converse hold true. Surprisingly, babies whose mothers had received prepartum dexamethasone to prevent RDS showed no difference in thymic size when compared to a control population. These data are consistent with the theory that endogenous gluco-corticoids play a physiologic role in the prevention of RDS. The initial size of the thymus may also be of predictive value in differentiating between the diverse causes of respiratory distress in newborn infants.

Transient neonatal diabetes: Delayed maturation of the pancreatic beta cell

1. McCann, M. L., and Likly, B. F.: The role of epinephrine prophylactic therapy in infants of diabetic mothers, Atlantic City, N. J., 1967, Society for Pediatric Research. 2. Porte, D., Jr., Graber, A. L., Kuzuya, T., and Williams, R. H. : The effect of epinephrine on immunoreactive insulin leveIs in man, J. Clin. Invest. 45: 228, 1966. 3. Chen, C. H., Adam, P. A. J., Laskowski, D. E., McCann, M. L., and Schwartz, R.: The plasma free fatty acid composition and blood glucose of normal and diabetic pregnant women and of their newborns, Pediatrics 36: 843, 1965. 4. Light, I. J., Sutherland, J. M., Loggie, J. M., and Gaffney, T. E.: Impaired epinephrine release in hypoglycemic infants of diabetic mothers, N. Engl. J. Med. 277: 394, 1967. 5. Stern, L., Ramos, A., and Leduc, J.: Urinary catecholamine excretion in infants of diabetic mothers, Pediatrics 42: 598, 1968. 6. McCann, M. L.: Prevention of RDS and decreased mortality in infants of insulin dependent diabetic mothers (IDM) treated with epinephrine, Atlantic City, N. J., 1971, Society for Pediatric Research. 7. Cornblath, M., and Schwartz, R.: Disorders of carbohydrate metabolism in infancy, Philadelphia, 1966, W. B. Saunders Company, p. 57. 8. Huggett, A. St. G., and Nixon, D. A.: The use of glucose oxidase, peroxidase and odianisldine in determination of blood and urinary glucose, Lancet 2: 368, 1957. 9. Hohorst, H. J.: L-(+)-lactate determination with lactic dehydrogenase and DPN, in Bergmeyer, H. V., editor: Methods of enzymatic analysis, New York, 1963, Academic Press, Inc., p. 266. 10. Stevens, J. F.: Biochemical changes in the blood of the newborn, J. Med. Lab. Technol. 22: 47, 1965.