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Steroid Pathway Genes and Neonatal Respiratory Distress After Betamethasone Use in Anticipated Preterm Birth.

ABSTRACT: To test several key glucocorticoid genes that are enhanced in lung development for associations with respiratory distress syndrome (RDS) after antenatal corticosteroid use.A prospective cohort of women received betamethasone to accelerate fetal lung maturity for threatened preterm delivery. DNA was obtained from mothers and newborns. Neonatal RDS was the primary outcome. Genotyping for single-nucleotide polymorphisms (SNPs) in 68 glucocorticoid genes found to be differentially expressed during lung development was performed. Multivariable analysis tested for associations of SNPs in the candidate genes with RDS.Genotypic results for 867 SNPs in 96 mothers and 73 babies were included. Thirty-nine (53.4%) babies developed RDS. Maternal SNPs in the centromeric protein E (CENPE), GLRX, CD9, and AURKA genes provided evidence of association with RDS (P < .01). In newborns, SNPs in COL4A3, BHLHE40, and SRGN provided evidence of association with RDS (P < .01).Single-nucleotide polymorphisms in several glucocorticoid responsive genes suggest association with neonatal RDS after antenatal corticosteroid use.

SUBMITTER: Haas DM

PROVIDER: S-EPMC5933159 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Steroid Pathway Genes and Neonatal Respiratory Distress After Betamethasone Use in Anticipated Preterm Birth.

Haas David M DM Lai Dongbing D Sharma Sunita S Then Jenny J Kho Alvin A Flockhart David A DA Tantisira Kelan K Foroud Tatiana T

Reproductive sciences (Thousand Oaks, Calif.) 20151027 5

<h4>Objective</h4>To test several key glucocorticoid genes that are enhanced in lung development for associations with respiratory distress syndrome (RDS) after antenatal corticosteroid use.<h4>Methods</h4>A prospective cohort of women received betamethasone to accelerate fetal lung maturity for threatened preterm delivery. DNA was obtained from mothers and newborns. Neonatal RDS was the primary outcome. Genotyping for single-nucleotide polymorphisms (SNPs) in 68 glucocorticoid genes found to be ...[more]

PMID: 26507871

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Project description:BackgroundAlthough antenatal betamethasone is recommended worldwide for women at risk of preterm delivery, concerns persist regarding the long-term effects associated with this treatment. Indeed, adverse events, mainly dose-related, have been reported. The current recommended dose of antenatal betamethasone directly derives from sheep experiments performed in the late 60's and has not been challenged in 45 years. Therefore, randomized trials evaluating novel dose regimens are urgently needed.MethodsA randomised, double blind, placebo-controlled, non-inferiority trial will be performed in 37 French level 3 maternity units. Women with a singleton pregnancy at risk of preterm delivery before 32 weeks of gestation having already received a first 11.4 mg injection of betamethasone will be randomised to receive either a second injection of 11.4 mg betamethasone (full dose arm) or placebo (half dose arm) administered intramuscularly 24 h after the first injection. The primary binary outcome will be the occurrence of severe respiratory distress syndrome (RDS), defined as the need for exogenous intra-tracheal surfactant in the first 48 h of life. Considering that 20% of the pregnant women receiving the full dose regimen would have a neonate with severe RDS, 1571 patients in each treatment group are required to show that the half dose regimen is not inferior to the full dose, that is the difference in severe RDS rate do not exceed 4% (corresponding to a Relative Risk of 20%), with a 1-sided 2.5% type-1 error and a 80% power. Interim analyses will be done after every 300 neonates who reach the primary outcome on the basis of intention-to-treat, using a group-sequential non-inferiority design.DiscussionIf the 50% reduced antenatal betamethasone dose is shown to be non-inferior to the full dose to prevent severe RDS associated with preterm birth, then it should be used consistently in women at risk of preterm delivery and would be of great importance to their children.Trial registrationClinicalTrials.gov identifier: NCT 02897076 (registration date 09/13/2016).

Project description:Neonatal respiratory distress syndrome, as a consequence of preterm birth, is a major cause of early mortality and morbidity. The withdrawal of progesterone, either actual or functional, is thought to be an antecedent to the onset of labour. There remains limited information on clinically relevant health outcomes as to whether vaginal progesterone may be of benefit for pregnant women with a history of a previous preterm birth, who are at high risk of a recurrence. Our primary aim was to assess whether the use of vaginal progesterone pessaries in women with a history of previous spontaneous preterm birth reduced the risk and severity of respiratory distress syndrome in their infants, with secondary aims of examining the effects on other neonatal morbidities and maternal health and assessing the adverse effects of treatment.Women with a live singleton or twin pregnancy between 18 to <24 weeks' gestation and a history of prior preterm birth at less than 37 weeks' gestation in the preceding pregnancy, where labour occurred spontaneously or in association with cervical incompetence or following preterm prelabour rupture of the membranes, were eligible. Women were recruited from 39 Australian, New Zealand, and Canadian maternity hospitals and assigned by randomisation to vaginal progesterone pessaries (equivalent to 100 mg vaginal progesterone) (n = 398) or placebo (n = 389). Participants and investigators were masked to the treatment allocation. The primary outcome was respiratory distress syndrome and severity. Secondary outcomes were other respiratory morbidities; other adverse neonatal outcomes; adverse outcomes for the woman, especially related to preterm birth; and side effects of progesterone treatment. Data were analysed for all the 787 women (100%) randomised and their 799 infants.Most women used their allocated study treatment (740 women, 94.0%), with median use similar for both study groups (51.0 days, interquartile range [IQR] 28.0-69.0, in the progesterone group versus 52.0 days, IQR 27.0-76.0, in the placebo group). The incidence of respiratory distress syndrome was similar in both study groups-10.5% (42/402) in the progesterone group and 10.6% (41/388) in the placebo group (adjusted relative risk [RR] 0.98, 95% confidence interval [CI] 0.64-1.49, p = 0.912)-as was the severity of any neonatal respiratory disease (adjusted treatment effect 1.02, 95% CI 0.69-1.53, p = 0.905). No differences were seen between study groups for other respiratory morbidities and adverse infant outcomes, including serious infant composite outcome (155/406 [38.2%] in the progesterone group and 152/393 [38.7%] in the placebo group, adjusted RR 0.98, 95% CI 0.82-1.17, p = 0.798). The proportion of infants born before 37 weeks' gestation was similar in both study groups (148/406 [36.5%] in the progesterone group and 146/393 [37.2%] in the placebo group, adjusted RR 0.97, 95% CI 0.81-1.17, p = 0.765). A similar proportion of women in both study groups had maternal morbidities, especially those related to preterm birth, or experienced side effects of treatment. In 9.9% (39/394) of the women in the progesterone group and 7.3% (28/382) of the women in the placebo group, treatment was stopped because of side effects (adjusted RR 1.35, 95% CI 0.85-2.15, p = 0.204). The main limitation of the study was that almost 9% of the women did not start the medication or forgot to use it 3 or more times a week.Our results do not support the use of vaginal progesterone pessaries in women with a history of a previous spontaneous preterm birth to reduce the risk of neonatal respiratory distress syndrome or other neonatal and maternal morbidities related to preterm birth. Individual participant data meta-analysis of the relevant trials may identify specific women for whom vaginal progesterone might be of benefit.Current Clinical Trials ISRCTN20269066.

Project description:BackgroundNeonatal acute respiratory distress syndrome (ARDS) is a critical clinical disease with high disability and mortality rates. Early identification and treatment of neonatal ARDS is critical. This study aimed to build a perinatal prediction nomogram for early prediction of neonatal ARDS.MethodsA prediction model was built including 243 late-preterm and full-term infants from Daping Hospital in Chongqing, China, hospitalised between Jan 1, 2018 and Dec 31, 2019. 80 patients from the Children's Hospital in Chongqing, China, hospitalised between Jan 1, 2018 and June 30, 2018 were considered for external validation. Multivariate logistic regression was performed to identify independent predictors and establish a nomogram to predict the occurrence of neonatal ARDS. Both discrimination and calibration were assessed by bootstrapping with 1000 resamples.FindingsMultivariate logistic regression demonstrated that mother's education level (odds ratio [OR] 0·478, 95% confidence interval [CI] 0·324-0·704), premature rupture of membrane (OR 0·296, 95% CI 0·133-0·655), infectious disease within 7 days before delivery (OR 0·275, 95% CI 0·083-0·909), hospital level (OR 2·479, 95% CI 1·260-4·877), and Apgar 5-min score (OR 0·717, 95% CI 0·563-0·913) were independent predictors for neonatal ARDS in late-preterm and full-term infants, who experienced dyspnoea within 24 h after birth and required mechanical ventilation. The area under the curve and concordance index of the nomogram constructed from the above five factors were 0·760 and 0·757, respectively. The Hosmer-Lemeshow test showed that the model was a good fit (P = 0.320). The calibration curve of the nomogram was close to the ideal diagonal line. Furthermore, the decision curve analysis demonstrated significantly better net benefit in the model. The external validation proved the reliability of the prediction nomogram.InterpretationA nomogram based on perinatal factors was developed to predict the occurrence of neonatal ARDS in late-preterm and full-term infants who experienced dyspnoea within 24 h after birth and required mechanical ventilation. It provided clinicians with an accurate and effective tool for the early prediction and timely management of neonatal ARDS.FundingNo funding was associated with this study.

Project description:BackgroundRespiratory distress syndrome (RDS) is one of the leading causes of early neonatal morbidity and mortality in late preterm infants (LPIs) worldwide. This matched cohort study aimed to assess how the antenatal dexamethasone use affect the respiratory distress (RD) proportion in preterm newborns between 34 0/7 weeks and 36 6/7 weeks of gestation.MethodsThis was a prospective cohort study on 78 women with singleton pregnancy who were in threatened preterm birth and had not received prior dexamethasone, who were admitted between 34 0/7 weeks and 36 6/7 weeks at Hue University of Medicine and Pharmacy Hospital from June 2018 to May 2020. The matched control group without dexamethasone use included 78 pregnant women diagnosed with threatened late preterm births who were at similar gestational ages and estimated fetal weights as the treatment group. The treatment group received 6 mg intramuscular dexamethasone every 12 h for a total of 4 doses or until delivery. Primary outcome was the rate of neonatal RD. Secondary neonatal outcomes included the need for respiratory support, neonatal intensive care unit (NICU) admission, hypoglycemia, necrotizing enterocolitis, intraventricular hemorrhage, and neonatal death. Statistical analyses were performed by using SPSS software, version 26.0.ResultsThe proportion of RD in LPI was significantly lower in the treatment group than in the matched control group (10.3% vs. 23.1%, respectively), adjusted Odds Ratio [aOR] 0.29; 95% confidence interval [CI] 0.10 - 0.83 and p = 0.021. Neonatal hypoglycemia was more common in the dexamethasone group than in the matched group (25.6% vs. 12.8%, respectively; aOR, 2.59; 95% CI, 1.06 - 6.33; p = 0.037). There were no significant between-groups differences in the incidence of respiratory support, NICU admission or length of hospital stay.ConclusionsAdministration of antenatal dexamethasone to women at risk for late preterm birth could help to lower the proportion of respiratory distress in late preterm infants.

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Steroid Pathway Genes and Neonatal Respiratory Distress After Betamethasone Use in Anticipated Preterm Birth.

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Steroid Pathway Genes and Neonatal Respiratory Distress After Betamethasone Use in Anticipated Preterm Birth.

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