The window of improved neonatal respiratory compliance after rescue antenatal steroids.
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ABSTRACT:
SUBMITTER: Jordan BK
PROVIDER: S-EPMC6070394 | biostudies-literature | 2018 Jul
REPOSITORIES: biostudies-literature
Publications
The window of improved neonatal respiratory compliance after rescue antenatal steroids.
Jordan Brian K BK Schilling Diane D McEvoy Cindy T CT
Journal of perinatology : official journal of the California Perinatal Association 20180524 7
<h4>Objective</h4>To evaluate whether premature infants delivered ≤7 days after rescue antenatal steroid treatment (ideal treatment) have increased passive respiratory compliance compared to those delivered >7 days after treatment (remote treatment).<h4>Methods</h4>Secondary analysis of a randomized trial of rescue antenatal steroids on respiratory compliance. Infants in the treatment group were stratified by the interval between rescue antenatal steroids and delivery. We then compared the respi ...[more]
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Project description:ObjectiveTo compare respiratory compliance and functional residual capacity in infants randomized to a rescue course of antenatal steroids vs placebo.Study designRandomized, double-blinded trial. Pregnant women > or =14 days after initial antenatal steroids were randomized to rescue antenatal steroids or placebo. The primary outcomes were measurements of respiratory compliance and functional residual capacity. This study is registered with clinicaltrials.gov (NCT00669383).ResultsForty-four mothers (56 infants) received rescue antenatal steroids and 41 mothers (57 infants) received placebo. There was no significant difference in birthweight, or head circumference. Infants in the rescue group had an increased respiratory compliance (1.21 vs 1.01 mL/cm H(2)O/kg; adjusted 95% confidence interval, 0.01-0.49; P = .0433) compared with placebo. 13% in the rescue vs 29% in the placebo group required > or =30% oxygen (P < .05). Patients delivered at < or =34 weeks had greater pulmonary benefits.ConclusionInfants randomized to rescue antenatal steroids have a significantly increased respiratory compliance compared with placebo.
| S-EPMC2878893 | biostudies-literature
Project description:Our objective was to obtain follow-up pulmonary function testing and assessment of clinical respiratory outcomes, at 1-2 years, in preterm infants whose mothers were randomized to a single rescue course of antenatal steroids (AS) versus placebo.Follow-up of a randomized, double-blinded trial. In the original trial pregnant women ?14 days after initial course of AS were randomized to rescue AS or placebo. Pulmonary function testing and a standardized respiratory questionnaire were obtained at 1-2 years of corrected age. Respiratory compliance (Crs) was measured with the single-breath occlusion and functional residual capacity (FRC) with the nitrogen washout method. Analysis was by intention-to-treat.A total of 96 (87%) of available survivors were administered a respiratory questionnaire. Seventy-seven percent of available patients had pulmonary function testing performed. There was no significant difference between groups in incidence of wheezing, asthma, respiratory syncytial virus infection, respiratory readmissions, use of bronchodilators or other medications, or in measurements of pulmonary function. There was also no significant difference in corrected age at study, race, gender, or length at the time of pulmonary function testing. Infants in the rescue group had a comparable mean FRC (249.4?mL vs 246.2?mL; adjusted 95%CI for difference -15.45, 38.20; P?=?0.37) versus placebo. There were no differences in tidal volume or Crs.A rescue course of AS significantly increases Crs within 72?h of age and decreases oxygen need in newborn infants, without an adverse impact on pulmonary function or clinical respiratory outcomes at 1-2 years of age [NCT00669383].
| S-EPMC5561489 | biostudies-literature
Project description:ImportanceThe Antenatal Late Preterm Steroids (ALPS) trial demonstrated a 20% reduction in the risk of respiratory complications in neonates at risk for a late-preterm birth who were exposed to antenatal corticosteroids compared with those who were not.ObjectiveTo assess whether new evidence of steroid administration for neonatal respiratory benefit in the late-preterm period is associated with changes in obstetric practice and the use of assisted ventilation for the neonate after delivery.Design, setting, and participantsThis cross-sectional study of US births from February 1, 2015, to October 31, 2017, as ascertained from US natality data, included live-born, singleton neonates born between 34 and 36 completed weeks of gestation to people without pregestational diabetes. An interrupted time series analysis using Poisson regression models was conducted. Data were analyzed from July 11, 2022, to November 9, 2022.ExposuresPublic dissemination of the ALPS trial results, which occurred during a 9-month period from February 1, 2016 (first published online), to October 31, 2016 (time of the last major professional society's guideline update in the months after the trial's publication).Main outcomes and measuresSteroid use, any assisted ventilation use, and assisted ventilation use for more than 6 hours immediately after the dissemination period.ResultsA total of 707 862 births were included, divided among the 12-month predissemination period (n = 250 643), dissemination period (n = 195 736), and 12-month postdissemination period (n = 261 493). Most births were at 36 weeks of gestation (53.9% in the predissemination and postdissemination period; P = .10). Small but significant differences were found between the predissemination and postdissemination period cohorts: there were more individuals 35 years or older (19.5% vs 17.9%), fewer White individuals (67.8% vs 69.8%), and more publicly insured individuals (50.5% vs 50.1%) in the postdissemination period compared with the predissemination period, respectively (P < .001 for all). Compared with what rates were expected based on the predissemination trends, the adjusted rate of steroid use increased from 5.0% to 11.7% (adjusted incidence rate ratio [IRR], 2.34; 95% CI, 2.13-2.57), and assisted ventilation use decreased from 8.9% to 8.2% (adjusted IRR, 0.91; 95% CI, 0.85-0.98) after the dissemination period. No change was observed in assisted ventilation use for more than 6 hours (adjusted IRR, 0.98; 95% CI, 0.87-1.10).Conclusions and relevanceThese findings suggest that there was an immediate change in practice of administering antenatal steroids and a reduction in neonatal morbidity among late-preterm births associated with the dissemination of the ALPS trial, suggesting that this evidence may be translating into a reduction in immediate respiratory morbidity outside the context of a clinical trial.
| S-EPMC9118048 | biostudies-literature
Project description:ObjectiveTo compare the pulmonary function, measured at birth and at hospital discharge, of infants whose mothers had been randomized to a single rescue course of antenatal steroids versus those whose mothers had been randomized to placebo.Study designThis study involved follow-up at hospital discharge of subjects of a randomized, double-blinded trial. In the original trial, pregnant women at ≥14 days after their initial course of antenatal steroids and <34 weeks' gestation were randomized to rescue antenatal steroids (44 mothers, 56 infants) or placebo (41 mothers, 57 infants). Passive respiratory compliance (Crs), passive respiratory resistance, and functional residual capacity were measured in all infants at birth and again at discharge to evaluate changes in pulmonary mechanics over time. Statistical analyses were based on intention to treat.ResultsWe previously reported that compared with infants in the placebo group, infants in the rescue antenatal steroids group had a higher mean Crs value measured within 72 hours of birth (1.21 vs 1.01 mL/cm H2O/kg; P < .05). Here we show that the Crs benefit in the antenatal steroids group was sustained until discharge. Infants in the placebo group demonstrated improvement in Crs such that by discharge, there was no difference in mean Crs between the rescue antenatal steroids and placebo groups (1.18 vs 1.22 mL/cm H2O/kg).ConclusionsRescue antenatal steroids significantly increased Crs measured within 72 hours of birth, and this increase was sustained until hospital discharge. Preterm infants in the placebo group demonstrated a decreased initial Crs compared with the rescue antenatal steroids group, but achieved a comparable Crs by the time of discharge.Trial registrationClinicalTrials.gov: NCT00669383.
| S-EPMC5274607 | biostudies-literature
Project description:Many premature infants are born without exposure to antenatal steroids (ANS) or with incomplete courses. This study evaluates the dose-dependent effect of ANS on rates of neonatal morbidities and early childhood neurodevelopmental outcomes of extremely premature infants.To compare rates of neonatal morbidities and 18- to 22-month neurodevelopmental outcomes of extremely premature infants exposed to no ANS or partial or complete courses of ANS.In this observational cohort study, participants were extremely premature infants (birth weight range, 401-1000 g; gestational age, 22-27 weeks) who were born at participating centers of the National Institute of Child Health and Human Development Neonatal Research Network between January 2006 and December 2011. Data were analyzed between October 2013 and May 2016.Rates of death or neurodevelopmental impairment at 18 to 22 months' corrected age. Neurodevelopmental impairment was defined as the presence of any of the following: moderate to severe cerebral palsy, a cognitive score less than 85 on the Bayley Scales of Infant and Toddler Development III, blindness, or deafness.There were 848 infants in the no ANS group, 1581 in the partial ANS group, and 3692 in the complete ANS group; the mean (SD) birth weights were 725 (169), 760 (173), and 753 (170) g, respectively, and the mean (SD) gestational ages were 24.5 (1.4), 24.9 (2), and 25.1 (1.1) weeks. Of 6121 eligible infants, 4284 (70.0%) survived to 18- to 22-month follow-up, and data were available for 3892 of 4284 infants (90.8%). Among the no, partial, and complete ANS groups, there were significant differences in the rates of mortality (43.1%, 29.6%, and 25.2%, respectively), severe intracranial hemorrhage among survivors (23.3%, 19.1%, and 11.7%), death or necrotizing enterocolitis (48.1%, 37.1%, and 32.5%), and death or bronchopulmonary dysplasia (74.9%, 68.9%, and 65.5%). Additionally, death or neurodevelopmental impairment occurred in 68.1%, 54.4%, and 48.1% of patients in the no, partial, and complete ANS groups, respectively. Logistic regression analysis revealed that complete (odds ratio, 0.63; 95% CI, 0.53-0.76) and partial (odds ratio, 0.77; 95% CI, 0.63-0.95) ANS courses were associated with lower rates of death or neurodevelopmental impairment compared with the no ANS group. The reduction in the rate of death or neurodevelopmental impairment associated with exposure to a complete ANS course may be mediated through a reduction in rates of severe intracranial hemorrhage and/or cystic periventricular leukomalacia in the neonatal period.Antenatal steroid exposure was associated with a dose-dependent protective effect against death or neurodevelopmental impairment in extremely preterm infants. The effect was partly mediated by ANS-associated reductions in rates of severe intracranial hemorrhage and/or cystic periventricular leukomalacia. These results support prompt administration of ANS, with the goal of a complete course prior to delivery.
| S-EPMC5294968 | biostudies-literature
Project description:ObjectiveWe previously demonstrated that maternal and fetal genotypes are associated independently with neonatal respiratory distress syndrome. The objective of the current study was to determine the impact of maternal and fetal single-nucleotide polymorphisms (SNPs) in key betamethasone pathways on respiratory outcomes that serve as markers for severity of disease.Study designDNA was obtained from women who were given betamethasone and from their infants. Samples were genotyped for 73 exploratory drug metabolism and glucocorticoid pathway SNPs. Clinical variables and neonatal outcomes were obtained. Logistic regression analysis that controlled for relevant clinical variables to determine SNP impact on bronchopulmonary dysplasia (BPD), the need for respiratory support, and surfactant therapy use was performed.ResultsData from 109 women who delivered 117 infants were analyzed: 14.5% of the infants experienced BPD; 70.8% of the infants needed some respiratory support after birth, and 27.5% of the infants needed surfactant therapy. In a multivariable regression analysis, gestational age at delivery was associated with most neonatal respiratory outcomes (P ≤ .01), and chorioamnionitis was associated with BPD (P < .03). The following genotypes were associated with respiratory severity outcomes: BPD-fetal Importin 13 gene (IPO13; rs4448553; odds ratio [OR], 0.01; 95% confidence interval [CI], 0.00-0.92); surfactant use-maternal IPO13 (rs2428953 and 2486014; OR, 13.8; 95% CI, 1.80-105.5; and OR, 35.5; 95% CI, 1.71-736.6, respectively).ConclusionSeveral discrete maternal and fetal SNPs in the IPO13 family may be associated with neonatal respiratory outcomes after maternal antenatal corticosteroid treatment for anticipated preterm birth.
| S-EPMC3583196 | biostudies-literature
Project description:ObjectiveTo test whether steroids reduce respiratory distress in babies born by elective caesarean section at term.DesignMulticentre pragmatic randomised trial.Setting10 maternity units.Participants998 consenting women randomised at decision to deliver by elective caesarean section; 503 randomised to treatment group.InterventionsThe treatment group received two intramuscular doses of 12 mg betamethasone in the 48 hours before delivery. The control group received treatment as usual.Outcome measuresThe primary outcome was admission to special care baby unit with respiratory distress. Secondary outcomes were severity of respiratory distress and level of care in response.ResultsSex, birth weight, and gestation were not different between the two groups. Of the 35 babies admitted to special baby units with respiratory distress, 24 were in the control group and 11 in the intervention group (P = 0.02). The incidence of admission with respiratory distress was 0.051 in the control group and 0.024 in the treatment group (relative risk 0.46, 95% confidence interval 0.23 to 0.93). The incidence of transient tachypnoea of the newborn was 0.040 in the control group and 0.021 in the treatment group (0.54, 0.26 to 1.12). The incidence of respiratory distress syndrome was 0.011 in the control group and 0.002 in the treatment group (0.21, 0.03 to 1.32).ConclusionsAntenatal betamethasone and delaying delivery until 39 weeks both reduce admissions to special care baby units with respiratory distress after elective caesarean section at term.
| S-EPMC1226243 | biostudies-literature
Project description:BackgroundLate preterm steroid administration can induce transient maternal and thus fetal hyperglycemia, which can increase production of fetal insulin and C-peptide. Infants delivered in this setting are subsequently at increased risk for hypoglycemia. Although maternal glycemic control before delivery is a key component of care for parturients with diabetes, this intervention has not been studied in the setting of late preterm steroid administration.ObjectiveThis study aimed to determine the effect of maternal screening for and treatment of hyperglycemia after late preterm steroid administration on fetal C-peptide levels and other metabolic markers.Study designThis was a multicenter, randomized trial (NCT03076775) of nondiabetic parturients with a singleton gestation receiving betamethasone at 34 0/7 weeks to 36 5/7 weeks for anticipated preterm birth. Participants randomized to maternal glycemic control received fasting and 1-hour postprandial or serial intrapartum capillary blood glucose screening with insulin treatment as indicated. Those randomized to expectant management did not receive any glucose screening or treatment. The primary outcome was fetal C-peptide level measured from umbilical cord blood at delivery. Secondary outcomes included other fetal metabolic markers and neonatal hypoglycemia (glucose level <40 mg/dL). Baseline characteristics and outcomes were compared between the groups. We estimated that we would need a sample size of 144 to provide >90% power to show a 1 ng/mL decrease in C-peptide concentration (±1.5 ng/mL) at ⍺=0.05 using a 2-sample t test and 1 interim analysis. After the interim analysis, the trial was stopped for futility.ResultsOf 491 screened parturients, 163 (33%) were deemed eligible and 86 (53%) were randomized to 1 of the treatment groups (June 2017 to February 2021). One person was lost to follow-up because of delivery at another hospital. Baseline characteristics were similar between groups. The median interval from betamethasone administration to delivery was 24 hours (interquartile range, 13-96 hours) and did not differ between groups (P=.82). Most (82%) randomized to maternal glycemic control had hyperglycemia: 80% had at least 1 fasting glucose level >95 mg/dL, 75% had at least one 1-hour postprandial glucose level >140 mg/dL, and 80% had at least 1 intrapartum glucose level >110 mg/dL. In addition, 15% had at least 1 glucose level >180 mg/dL. None had maternal hypoglycemia after insulin treatment. Compared with expectant management, maternal glycemic control did not affect the median fetal C-peptide level (1.02; interquartile range, 0.52-1.85 vs 1.09; interquartile range, 0.61-1.65; P=.97) or other metabolic markers. Maternal glycemic control also did not affect neonatal hypoglycemia (49% vs 51%; P=.83) or other secondary neonatal or maternal outcomes. There was no evidence of effect modification by gestational age or body mass index at randomization, indication for betamethasone, duration from betamethasone to delivery, maternal race or ethnicity, or neonatal sex. In addition, the results were unchanged in a sensitivity analysis using a per-protocol approach.ConclusionMaternal hyperglycemia was observed in most nondiabetic parturients after receiving late preterm betamethasone. However, there was no improvement in fetal metabolic status, neonatal hypoglycemia, or other neonatal or maternal outcomes with maternal glycemic control. Therefore, maternal glucose surveillance and treatment does not seem to be beneficial in nondiabetic parturients receiving late preterm steroids.
| S-EPMC9195161 | biostudies-literature
Project description:BackgroundThe external validity of randomised trials can be compromised when trial participants differ from real-world populations. In the Antenatal Late Preterm Steroids (ALPS) trial of antenatal corticosteroids at late preterm ages, participants had systematically younger gestational ages than those outside the trial setting. As risk of respiratory morbidity (the primary trial outcome) is higher at younger gestations, absolute benefits of corticosteroids calculated in the trial population may overestimate real-world treatment benefits.ObjectivesTo estimate the real-world absolute risk reduction and number-needed-to-treat (NNT) for antenatal corticosteroids at late preterm ages, accounting for gestational age differences between the ALPS and real-world populations.MethodsIndividual participant data from the ALPS trial (which recruited 2831 women with imminent preterm birth at 34+0 to 36+5 weeks') was appended to population-based data for 15,741 women admitted for delivery between 34+0 and 36+5 weeks' from British Columbia, Canada, 2000-2013. We used logistic regression to calculate inverse odds of sampling weights for each trial participant and re-estimated treatment effects of corticosteroids on neonatal respiratory morbidity in ALPS participants, weighted to reflect the gestational age distribution of the population-based (real-world) sample.ResultsThe real-world absolute risk reduction was estimated to be -2.2 (95% CI -4.6, 0.0) cases of respiratory morbidity per 100, compared with -2.8 (95% CI -5.3, -0.3) in original trial data. Corresponding NNTs were 46 in the real-world setting vs 35 in the trial. Our focus on absolute measures also highlighted that the benefits of antenatal corticosteroids may be meaningfully greater at 34 weeks vs. 36 weeks (e.g., risk reductions of -3.7 vs. -1.2 per 100 respectively).ConclusionsThe absolute risk reductions and NNTs associated with antenatal corticosteroid administration at late preterm ages estimated in our study may be more appropriate for patient counselling as they better reflect the anticipated benefits of treatment when used in a real-world situation.
| S-EPMC9250943 | biostudies-literature
Project description:LARGE is a glycosyltransferase involved in glycosylation of α-dystroglycan (α-DG). Absence of this protein in the LARGEmyd mouse results in α-DG hypoglycosylation, and is associated with central nervous system abnormalities and progressive muscular dystrophy. Up-regulation of LARGE has previously been proposed as a therapy for the secondary dystroglycanopathies: overexpression in cells compensates for defects in multiple dystroglycanopathy genes. Counterintuitively, LARGE overexpression in an FKRP-deficient mouse exacerbates pathology, suggesting that modulation of α-DG glycosylation requires further investigation. Here we demonstrate that transgenic expression of human LARGE (LARGE-LV5) in the LARGEmyd mouse restores α-DG glycosylation (with marked hyperglycosylation in muscle) and that this corrects both the muscle pathology and brain architecture. By quantitative analyses of LARGE transcripts we also here show that levels of transgenic and endogenous LARGE in the brains of transgenic animals are comparable, but that the transgene is markedly overexpressed in heart and particularly skeletal muscle (20-100 fold over endogenous). Our data suggest LARGE overexpression may only be deleterious under a forced regenerative context, such as that resulting from a reduction in FKRP: in the absence of such a defect we show that systemic expression of LARGE can indeed act therapeutically, and that even dramatic LARGE overexpression is well-tolerated in heart and skeletal muscle. Moreover, correction of LARGEmyd brain pathology with only moderate, near-physiological LARGE expression suggests a generous therapeutic window.
| S-EPMC4965172 | biostudies-literature