Respiratory Distress Syndrome In Preterm Neonates Research Articles

Effect of Antenatal Betamethasone on Respiratory Distress Syndrome in Preterm Neonates

Respiratory Distress Syndrome (RDS) is one of the most common complications that cause the death among pre-term neonates (PNs). Use of Antenatal betamethasone is the effective intervention for the prevention of RDS and reducing early neonatal mortality and morbidity. Although there is limited information as to how effective this practice in developing countries. Aim of this study is to evaluate the effectiveness of betamethasone on RDS in PNs. We conducted a prospective, observational multi-centered study at Gynecology and Obstetrics, Neonatal department of two teaching hospitals in South India over a period of 6 months. All babies born alive before 37 weeks of gestation were included in the study. The study population included 70 PNs and they were classified into three based on the consumption of betamethasone (no dose, single dose and double dose). Among them, 28(40%) belonged to no dose, 25(35.7%) in single dose and 17(24.2) in double dose. Neonates whose mothers received two doses of betamethasone had a significantly lower incidence of RDS (P=0.043) than neonates whose mothers received a single dose of betamethasone (P=0.343). We concluded that a single complete course of betamethasone (Two doses of betamethasone 12mg 24 hours apart) is efficacious than one dose of betamethasone in prevention of RDS.

Association between serum vitamin A, D and E status and respiratory distress syndrome in preterm infants - a propensity score matching analysis.

This study aimed to assess whether the serum levels of vitamin A, vitamin D and vitamin E are associated with respiratory distress syndrome (RDS) in preterm infants. This retrospective research included 179 neonates born before 35 weeks of gestation in Jiaxing Maternity and Child Health Care Hospital from January 2020 to December 2020. Depending on whether or not they had RDS, participants were classified into the RDS group (59 neonates) and the control group (120 neonates). The 1:1 propensity score matching (PSM) analysis was performed to balance the baseline confounding factors and then the groups were compared in terms of serum vitamin levels and RDS morbidity. A total of 34 pairs of preterm infants were involved after PSM. There were significant differences in vitamin D level (12.13 (8.44-17.85) ng/mL vs. 16.84 (10.75-25.83) ng/mL), vitamin D deficiency rate (85.3% vs. 55.9%), as well as vitamin A level (134.91 (105.01-156.74) ng/mL vs. 152.46 (120.06-200.00) ng/mL) in the two groups. However, the vitamin A deficiency rate, vitamin E status, as well as vitamin E deficiency rate did not differ significantly between the two groups. Logistic analysis showed that a low level of vitamin D was an independent risk factor for RDS in preterm neonates (OR 0.917, 95%CI 0.851-0.989). Low serum vitamin D levels may contribute to the development of RDS in preterm infants, but no significant effect of serum vitamin A and vitamin E levels was found.

Benefits of a Single Dose of Betamethasone in Imminent Preterm Labour.

Background: A complete course of prenatal corticosteroids reduces the possibility of morbimortality and neonatal respiratory distress syndrome (RDS). Occasionally, it is not possible to initiate or complete the maturation regimen, and the preterm neonate is born in a non-tertiary hospital. This study aimed to assess the effects of a single dose of betamethasone within 3 h before delivery on serious outcomes (mortality and serious sequelae) and RDS in preterm neonates born in tertiary vs. non-tertiary hospitals. Materials and methods: Preterm neonates who were <35 weeks and ≤1500 g, treated during a period of five years in a level IIIC NICU, were included in this retrospective cohort study. Participants were divided into groups as follows: NM, non-matured; PM, partial maturation (one dose of betamethasone up to 3 h antepartum). They were further divided based on their place of birth (NICU-IIIC vs. non-tertiary hospitals). The morbimortality rates and the severity of neonatal RDS were evaluated. Results: A total of 76 preterm neonates were included. A decrease in serious outcomes was found in the PM group in comparison to the NM group (OR = 0.2; 95%CI (0.07–0.9)), as well as reduced need for mechanical ventilation (54% vs. 68%). The mean time between maternal admission and birth was similar in both cohorts. The mean time from the administration of betamethasone to delivery was 1 h in the PM cohort. With regard to births in NICU-IIIC, the PM group performed better in terms of serious outcomes (32% vs. 45%) and the duration of mechanical ventilation (117.75 vs. 132.18 h) compared to the NM group. In neonates born in non-tertiary hospitals with PM in comparison to the NM group, a trend towards a reduced serious outcome (28.5% vs. 62.2%) and a decreased need for mechanical ventilation (OR = 0.09; 95%CI (0.01–0.8)) and maximum FiO2 (p = 0.01) was observed. Conclusions: A single dose of betamethasone up to 3 h antepartum may reduce the rate of serious outcomes and the severity of neonatal RDS, especially in non-tertiary hospitals.

Histological chorioamnionitis and its impact on respiratory outcome in very-low-birth-weight preterm infants

The role of intrauterine infection in the development of neonatal pulmonary disease is unclear and the impact of histological chorioamnionitis (HCAM) on respiratory outcomes in preterm infants remains controversial. The aim of this study was to explore the association between HCAM and neonatal respiratory outcomes in very-low-birth-weight (VLBW) preterm infants and evaluate the stepwise difference in the stage and severity of HCAM among neonatal respiratory outcomes. We retrospectively enrolled 129 VLBW preterm infants with placenta histopathology examinations in this study. HCAM was subdivided into 3 stages (early, intermediate, and advanced) according to the progression of the maternal inflammatory response. The perinatal characteristics, placental histopathology, and neonatal morbidities, including respiratory outcomes (respiratory distress syndrome (RDS), Wilson-Mikity syndrome (WMS) and bronchopulmonary dysplasia (BPD)), were collected for comparison. A total of 52.7% (68/129) of the infants had HCAM, including 23 early (stage 1), 30 intermediate (stage 2), and 15 advanced (stage 3) stage. There was no significant difference in the gestational age, birth body weight or mortality rate between the HCAM and non-HCAM groups. Mothers with HCAM had a significantly lower incidence of pre-eclampsia but a higher rate of premature rupture of membrane. They also had higher WBC counts and C-reactive protein levels before delivery. Neonates with HCAM had a lower incidence of RDS but were at a higher risk for developing WMS and BPD. After multivariate analysis adjustment, HCAM was still negatively associated with RDS (aOR=.069, p<.001) but without correlation with BPD. However, neonates with intermediate to advanced-stage HCAM had a higher risk of developing WMS and increased home oxygen usage rate compared to those with early-stage HCAM. HCAM has a protective effect from RDS in preterm neonates. Additionally, VLBW neonates with intermediate to advanced-stage HCAM are at risk for WMS.

Effectiveness of bubble continuous positive airway pressure as a primary mode of respiratory support in preterm neonates with respiratory distress syndrome at district level tertiary care hospital

Background: Continuous positive airway pressure (CPAP) has become a useful modality in the management of respiratory distress in preterm babies. CPAP when applied to preterm infants with respiratory distress syndrome (RDS) is associated with benefits in terms of reduced respiratory failure and reduced mortality. Objectives: The objectives of the study were to evaluate the efficacy of bubble CPAP in preterm neonates with RDS requiring respiratory support and to study the risk factors associated with its failure. Materials and Methods: A prospective observational study was done on 243 preterm neonates (gestational age [GA] 28 to ?37 weeks) with a diagnosis of RDS admitted from January 2016 to November 2017. All the eligible preterm neonates were started on bubble CPAP with binasal prongs. Surfactant was administered when indicated. Results: A total of 243 preterm neonates were enrolled in this study with a mean GA of 32.40 weeks and birth weight of 1831.49 g. One hundred and fifty-one (62.1%) were male and 92 (37.9%) were female. The mean age of starting of CPAP was 13.44 h of life and antenatal steroid coverage was 3.2% only. Of the 243 neonates, 195 neonates were successfully weaned off CPAP. Among the 48 neonates who failed CPAP, 27 neonates were ventilated, of which 20 (74.1%) survived. The predictors of CPAP failure were GA &lt;32 weeks, birth weight &lt;1.5 kg, and delayed initiation of CPAP. Conclusion: The efficacy of CPAP in neonates with mild-to-moderate RDS in preterm neonates is very well demonstrated despite the low usage of antenatal steroids, surfactant, and delayed initiation of CPAP. Extreme preterm, very low birth weight neonates with severe RDS on chest X-ray are at risk of failure of CPAP.

Genetic Polymorphisms of LPCAT1, CHPT1 and PCYT1B and Risk of Neonatal Respiratory Distress Syndrome among a Chinese Han Population

The study of genetic polymorphisms of surfactant-lipids related genes can help to understand individual variability in the susceptibility to development of pulmonary pathologies. The purpose of this study was to evaluate the association of polymorphisms of surfactant-lipids related genes (LPCAT1, CHPT1 and PCYT1B) with the risk/severity of respiratory distress syndrome (RDS) in preterm neonates among the Chinese Han population in Southern China. Four hundred and forty-six preterm neonates were enrolled in a case-control study. Six polymorphisms of 3 genes were analyzed by PCR amplification of genomic DNA and genotyping was performed using an improved multiplex ligation detection reaction (iMLDR) technique based on LDR. The GG genotype and G allele of LPCAT1-rs9728 were found less frequently in the RDS group than in the controls (11.5% vs. 22.0% and 38.3% vs. 48.2%, respectively) (p < 0.05). This report is the first study to evaluate a direct genetic association between polymorphisms of LPCAT1 and RDS development in Chinese Han preterm infants. Our study raises the possibility that a genetic variation of LPCAT1 could be implicated in the pathophysiology of RDS in preterm neonates. GG genotype and G allele of rs9728 are protective factors for the development of RDS in preterm infants.

Association between interleukin-10 genetic variant (-1082G>A) with detection and severity of respiratory distress syndrome in preterm neonates.

Abnormal cytokine production derived from specific polymorphisms can have effect on development of respiratory distress syndrome (RDS). Therefore, the present study aimed to determine whether polymorphisms of IL10 in preterm newborn are associated with RDS. A total of one hundred and one venous blood samples were collected from preterm neonates, and they were classified as 51 with no RDS and 50 with RDS. Grading of RDS, history of surfactant administration or ventilator was assessed in the diseased group. Genetic variant of IL10-1082G/A (rs1800896) was genotyped by PCR-RFLP. The RDS group showed a higher prevalence of IL10-1082 AA and lower prevalence of IL10-1082 GG (p<.001). We found that the incidence of the allele G in the IL10-1082 polymorphism was lower in the RDS group (24%) than the non-RDS group (51%) (p<.001). Allele model (A vs. G): OR=0.304, 95% CI: 0.166-0.554, p≤.001; Dominant model (AA vs. AG+GG): OR=0 0.470, 95% CI: 0.282-0.783, p=.04. More severe grades of RDS, need for surfactant and mechanical ventilation, were significantly associated with AA genotype when compared to AG+GG genotypes. IL10 (AG+GG) genotypes were considered as an independent predictor for lower risk of RDS within preterm neonates. IL10-1082 A/A genotype associated with increased susceptibility to RDS. Also, A allele has been associated with increase severity of RDS in preterm neonates. Regression analysis revealed that IL10 AG+GG genotypes were considered as independent predictors for lower risk development of RDS within preterm neonates.

Trends in epidemiology and outcomes of respiratory distress syndrome in the United States.

The management practices of Respiratory Distress Syndrome (RDS) in the newborn have changed over time. We examine the trends in the epidemiology, resource utilization, and outcomes (mortality and bronchopulmonary dysplasia [BPD]) of RDS in preterm neonates ≤34 weeks gestational age (GA) in the United States. In this retrospective serial cross-sectional study, we used ICD-9 codes to classify preterm infants GA ≤34 weeks between 2003 and 2014 from the National Inpatient Sample as having RDS or not. Trends in the prevalence of infants defined as RDS by ICD-9 code (ICD9-RDS), length of stay, BPD, and mortality were analyzed using Cochran-Armitage and Jonckheere-Terpstra tests and multivariable logistic regression. Of 1 526 186 preterm live births with GA ≤34 weeks, 554 409 had ICD9-RDS (260 cases per 1000 live births) with the prevalence increasing from 170 to 361 (Ptrend < 0.001) and associated decrease in all-cause mortality (7.6% to 6.1%; Ptrend < 0.001) from 2003 to 2014. Increased utilization of non-invasive mechanical ventilation (NIMV) (69.5% to 74.3%; Ptrend < 0.001) was associated with decreased invasive mechanical ventilation (IMV) use >96 h (60.4 to 56.6%; Ptrend < 0.001). Exclusive NIMV use increased from 16.8% to 29.1% (Ptrend < 0.0001). BPD incidence decreased from 14% to 12.5% (Ptrend < 0.001). LOS increased from 32 days to 38 days (Ptrend < 0.001) and cost increased from $49,521 to $55,394 (Ptrend < 0.001). From 2003 to 2014, the assigned ICD9-RDS diagnosis, and utilization of NIMV increased and mortality among infants assigned the ICD9-RDS diagnosis decreased. With higher survival, hospital cost increased incrementally, indicating the importance of ongoing analysis of appropriate reimbursement for the care provided at tertiary centers for preterm infants.

Association between serum 25 (OH) vitamin D level at birth and respiratory morbidities among preterm neonates

Objectives: To determine the association between 25-hydroxyvitamin D [25(OH)D] levels on first day of life with respiratory distress syndrome (RDS), need and duration of mechanical ventilation, and subsequent development of bronchopulmonary dysplasia (BPD) among preterm neonates.Study design: In this case–control study, serum 25(OH)D was measured on first day of life in 65 preterm neonates <34 weeks: 40 with RDS and 25 without RDS and compared between them. Serum 25(OH)D levels were categorized into normal (above 30 ng/ml), insufficiency (20–30 ng/ml), moderate deficiency (10–20 ng/ml), and severe deficiency (<10 ng/ml). Neonates with different 25(OH)D levels were compared as regard grade of RDS, initial pH, initial CO2, need and duration of mechanical ventilation, development of BPD, and mortality.Results: Only one of 65 studied preterm neonates had normal vitamin D level. Neonates with RDS had significantly lower mean serum 25(OH)D level than controls (10.6 versus 13.9 ng/dl) (p = .028). Neonates with severe 25(OH)D deficiency developed more BPD than those with moderate deficiency (29.4 versus 8.7%) but did not reach significant level (p value = .08). There is no correlation between serum 25(OH)D level and duration of mechanical ventilation. Logistic regression analysis shows that low serum 25(OH)D level is an independent risk factor for RDS.Conclusion: Low 25(OH)D level is far frequent among Egyptian preterm neonates. Vitamin D deficiency is an independent risk factor for development of RDS in preterm neonates.

Surfactant Protein A and B Gene Polymorphisms and Risk of Respiratory Distress Syndrome in Late-Preterm Neonates.

Background and ObjectivesNewborns delivered late-preterm (between 340/7 and 366/7 weeks of gestation) are at increased risk of respiratory distress syndrome (RDS). Polymorphisms within the surfactant protein (SP) A and B gene have been shown to predispose to RDS in preterm neonates. The aim of this study was to investigate whether specific SP-A and/or SP-B genetic variants are also associated with RDS in infants born late-preterm.MethodsThis prospective cross-sectional study included 56 late-preterm infants with and 60 without RDS. Specific SP-A1/SP-A2 haplotypes and SP-B Ile131Thr polymorphic alleles were determined in blood specimens using polymerase-chain-reaction and DNA sequencing.ResultsThe SP-A1 6A4 and the SP-A2 1A5 haplotypes were significantly overrepresented in newborns with RDS compared to controls (OR 2.86, 95%CI 1.20–6.83 and OR 4.68, 95%CI 1.28–17.1, respectively). The distribution of the SP-B Ile131Thr genotypes was similar between the two late-preterm groups. Overall, the SP-A1 6A4 or/and SP-A2 1A5 haplotype was present in 20 newborns with RDS (35.7%), resulting in a 4.2-fold (1.60–11.0) higher probability of RDS in carriers. Multivariable regression analysis revealed that the effect of SP-A1 6A4 and SP-A2 1A5 haplotypes was preserved when adjusting for known risk or protective factors, such as male gender, smaller gestational age, smaller weight, complications of pregnancy, and administration of antenatal corticosteroids.ConclusionsSpecific SP-A genetic variants may influence the susceptibility to RDS in late-preterm infants, independently of the effect of other perinatal factors.

Association of Rho-kinase Gene Polymorphisms with Respiratory Distress Syndrome in Preterm Neonates

Respiratory distress syndrome (RDS) of the newborn is one of the most common causes of morbidity and mortality in preterm infants. Our objective was to determine the association between Rho-kinase (ROCK1 and ROCK2) gene polymorphisms and RDS in preterm neonates. A total of 193 preterm infants with RDS and 186 preterm infants without respiratory problems were included in this study. Polymorphisms were analyzed in genomic DNA using a BioMark 96.96 dynamic array system. We observed that ROCK1 gene rs2271255 (Lys222Glu) and rs35996865 polymorphisms, and ROCK2 gene rs726843, rs2290156, rs10178332, and rs35768389 (Asp601Val) polymorphisms were associated with RDS. However, no associations were found with rs73963110, rs1515219, rs965665, rs2230774 (Thr431Asn), rs6755196, and rs10929732 polymorphisms. Additionally, 12 haplotypes (6 in ROCK1 and 6 in ROCK2) were found to be markedly associated with RDS. This is the first study to examine the involvement of ROCK gene variation in the risk of incident RDS. The results strongly suggest that ROCK gene polymorphisms may modify individual susceptibility to RDS in the Turkish population.

Comparison of Nasal Continuous Positive Airway Pressure Therapy with and without Prophylactic Surfactant in Preterm Neonates

Background: Preterm labor is at risk for respiratory distress syndrome (RDS) and sometimes requires to mechanical ventilation (MV) and surfactant therapy. Continuous positive airway pressure (CPAP) and Nasal Continuous positive airway pressure (NCPAP) are the methods of respiratory support especially for using in RDS of neonates. In other method surfactant is administered to babies via tracheal instillation. The aim of study was comparing nasal continuous positive airway pressure (NCPAP) with and without prophylactic surfactant therapy in preterm neonates’ RDS. Patients and methods: This is a randomized clinical trial study that performed on eighty newborns (28-34 weeks) who were born in Ali-Ebne-Abitaleb Hospital of Zahedan University of Medical Sciences from October 2008 to September 2010. Subjects were randomly classified in two groups whom received nasal CPAP alone or with surfactant (40 patients in each group).The Including criteria for entrance to research were approved suggested RDS, gestational age less than 34 weeks and neonates 72 hours after delivery . The data collected through direct observation and questionnaire contained fourteen items. Groups received either surfactant (Curosurf, Parma, Italy) with NCPAP or NCPAP alone. The data analyzed were conducted through SPSS 17.00 version and followed by Crosstab (Pearson Chi-square). Results: Results revealed that six neonates who received only NCPAP and four patients who received NCAPA plus surfactant required to MACHANICAL VENTILATION (MV) therapy. After a week, 33 neonates who received only NCPAP and 36 patients who received CPAP plus prophylactic surfactant remained alive. There was no significant difference between the groups regarding adverse outcomes (P=0.518). Conclusions: According to the results of this study, NCPAP is affordable as a safe protocol for RDS in preterm neonates. Further research especially with control or placebo groups is required to clarify and validate our findings.

Endothelial NOS gene Glu298Asp polymorphism in preterm neonates with respiratory distress syndrome

Respiratory Distress Syndrome (RDS) due to prematurity is one of the most important causes of morbidity and mortality in Neonatal Intensive Care Units. According to few studies in recent years, endothelial nitric oxide synthase (eNOS) gene polymorphisms are found to be partially responsible for liability to RDS. The purpose of this study was to determine the association between eNOS gene polymorphism and RDS in preterm neonates. The patient group consisted of 152 premature neonates born before 37 weeks of gestation and diagnosed as RDS. The control group consisted of 125 premature neonates born before 37 weeks of gestation, but was not diagnosed as RDS. Genomic DNA from patients and controls was analyzed by polymerase chain reaction. It was found that Glu/Glu, Glu/Asp, and Asp/Asp genotype frequencies of the eNOS gene polymorphism were 35.2%, 59.2%, and 5.6% of the control group, and 32.9%, 65.1%, and 2.0% of the patient group, respectively (P > 0.05). However, significant increases in Glu/Glu genotype and Glu allele frequencies were noted in the RDS groups when the preterm neonates were divided into two groups (24-30 weeks and 31-36 weeks) by gestational age. Additionally, Glu/Asp genotype and Asp allele were markedly less frequent among the RDS groups (P < 0.05). Asp allele frequency in boys and Glu allele frequency in girls were significantly high in RDS group (P < 0.05). These data suggest that there were significant gestational age-related differences between RDS and control groups in terms of Glu298Asp polymorphism. Therefore, RDS seems to develop with alterations in eNOS Glu298Asp genotype frequencies in the Turkish population.

An Open Label, Pilot Study of Aerosurf®Combined with nCPAP to Prevent RDS in Preterm Neonates

Nasal continuous positive airway pressure (nCPAP) is an accepted mode of respiratory support for preterm infants with respiratory insufficiency. To avoid potential sequelae of endotracheal (ET) intubation and mechanical ventilation, prophylactic aerosolization of surfactant delivered via nCPAP has been attempted with limited success. To determine the feasibility and safety of prophylactic aerosolization of a peptide-containing synthetic surfactant, Aerosurf® (lucinactant for inhalation) was delivered by nCPAP to preterm infants at risk for respiratory distress syndrome (RDS). Neonates were enrolled into treatment group 1 (Aerosurf retreatment separated by at least 3 h) or treatment group 2 (Aerosurf retreatment separated by at least 1 h). A vibrating membrane nebulizer Aeroneb Pro® was used to aerosolize 20 mg/mL Aerosurf. All neonates received the initial 3-h treatment, and three retreatments were permitted within 48 h based on clinical response. Seventeen infants were enrolled. Aerosurf was well tolerated, with transient desaturations observed during dosing without bradycardia or hypotension. Variability in output rates of the Aeroneb Pro was observed leading to different average dispensed drug volumes per treatment per patient. All infants survived; 29.4% required subsequent ET surfactant replacement therapy, 23.5% were diagnosed with RDS at 24 h, and 11.8% with bronchopulmonary dysplasia (BPD) at 28 days of life. Mean FiO₂ was 0.4 at baseline, and 0.32 at 4 h posttreatment. Aerosurf can be safely administered via nCPAP in preterm infants at risk for RDS and may provide an alternative to surfactant administration via an ET tube. Further studies are required to evaluate this delivery approach.

Historical Perspectives

Bengt Robertson, a Swedish pediatric pathologist, teamed up with his countryman Goran Enhorning, an obstetrician, in the 1960s and 1970s to conduct seminal basic research on surfactant replacement in animal models of respiratory distress syndrome (RDS). This research formed the foundation for the very successful randomized clinical trials of natural surfactant replacement for RDS in the 1980s and 1990s. Bengt Robertson was born in Stockholm in 1935, just 6 years after another Swede, Kurt van Neergaard, first demonstrated the importance of pulmonary surfactant for normal lung function. (1) Robertson was educated at Sodra Latins Gymnasium in Stockholm and graduated from high school in 1953 before studying medicine at the Karolinska Institutet. He graduated as MD in 1960, and in 1968, he successfully defended his PhD thesis entitled “The intrapulmonary arterial pattern in normal infancy and in transposition of the great arteries” at the Karolinska Institutet in Stockholm. In 1970, he was appointed as a Consultant in Pediatric Pathology at St. Goran's Hospital in Stockholm, and from 1974, he was Director of the Division for Experimental Perinatal Pathology in the Department of Women and Child Health at the Karolinska Institutet. At least two unsuccessful trials of surfactant replacement for RDS in preterm neonates were completed in the 1960s. (2)(3) The surfactant used in these trials was dipalmitoylphosphatidylcholine, and it was administered by aerosolization. Robertson and Enhorning reasoned that natural surfactant administered by direct instillation into the lungs would be …

Weekly Maternal Steroids Can Reduce RDS in Preterm Neonates

A single injection of corticosteroids given to a mother at risk for premature delivery reduces risk for neonatal respiratory distress syndrome (RDS),