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The Cochrane Database of Systematic... Aug 2022Despite the widespread use of antenatal corticosteroids to prevent respiratory distress syndrome (RDS) in preterm infants, there is currently no consensus as to the type... (Review)
Review
BACKGROUND
Despite the widespread use of antenatal corticosteroids to prevent respiratory distress syndrome (RDS) in preterm infants, there is currently no consensus as to the type of corticosteroid to use, dose, frequency, timing of use or the route of administration. OBJECTIVES: To assess the effects on fetal and neonatal morbidity and mortality, on maternal morbidity and mortality, and on the child and adult in later life, of administering different types of corticosteroids (dexamethasone or betamethasone), or different corticosteroid dose regimens, including timing, frequency and mode of administration.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (9 May 2022) and reference lists of retrieved studies.
SELECTION CRITERIA
We included all identified published and unpublished randomised controlled trials or quasi-randomised controlled trials comparing any two corticosteroids (dexamethasone or betamethasone or any other corticosteroid that can cross the placenta), comparing different dose regimens (including frequency and timing of administration) in women at risk of preterm birth. We planned to exclude cross-over trials and cluster-randomised trials. We planned to include studies published as abstracts only along with studies published as full-text manuscripts.
DATA COLLECTION AND ANALYSIS
At least two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. Data were checked for accuracy. We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included 11 trials (2494 women and 2762 infants) in this update, all of which recruited women who were at increased risk of preterm birth or had a medical indication for preterm birth. All trials were conducted in high-income countries. Dexamethasone versus betamethasone Nine trials (2096 women and 2319 infants) compared dexamethasone versus betamethasone. All trials administered both drugs intramuscularly, and the total dose in the course was consistent (22.8 mg or 24 mg), but the regimen varied. We assessed one new study to have no serious risk of bias concerns for most outcomes, but other studies were at moderate (six trials) or high (two trials) risk of bias due to selection, detection and attrition bias. Our GRADE assessments ranged between high- and low-certainty, with downgrades due to risk of bias and imprecision. Maternal outcomes The only maternal primary outcome reported was chorioamnionitis (death and puerperal sepsis were not reported). Although the rate of chorioamnionitis was lower with dexamethasone, we did not find conclusive evidence of a difference between the two drugs (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.48 to 1.06; 1 trial, 1346 women; moderate-certainty evidence). The proportion of women experiencing maternal adverse effects of therapy was lower with dexamethasone; however, there was not conclusive evidence of a difference between interventions (RR 0.63, 95% CI 0.35 to 1.13; 2 trials, 1705 women; moderate-certainty evidence). Infant outcomes We are unsure whether the choice of drug makes a difference to the risk of any known death after randomisation, because the 95% CI was compatible with both appreciable benefit and harm with dexamethasone (RR 1.03, 95% CI 0.66 to 1.63; 5 trials, 2105 infants; moderate-certainty evidence). The choice of drug may make little or no difference to the risk of RDS (RR 1.06, 95% CI 0.91 to 1.22; 5 trials, 2105 infants; high-certainty evidence). While there may be little or no difference in the risk of intraventricular haemorrhage (IVH), there was substantial unexplained statistical heterogeneity in this result (average (a) RR 0.71, 95% CI 0.28 to 1.81; 4 trials, 1902 infants; I² = 62%; low-certainty evidence). We found no evidence of a difference between the two drugs for chronic lung disease (RR 0.92, 95% CI 0.64 to 1.34; 1 trial, 1509 infants; moderate-certainty evidence), and we are unsure of the effects on necrotising enterocolitis, because there were few events in the studies reporting this outcome (RR 5.08, 95% CI 0.25 to 105.15; 2 studies, 441 infants; low-certainty evidence). Longer-term child outcomes Only one trial consistently followed up children longer term, reporting at two years' adjusted age. There is probably little or no difference between dexamethasone and betamethasone in the risk of neurodevelopmental disability at follow-up (RR 1.02, 95% CI 0.85 to 1.22; 2 trials, 1151 infants; moderate-certainty evidence). It is unclear whether the choice of drug makes a difference to the risk of visual impairment (RR 0.33, 95% CI 0.01 to 8.15; 1 trial, 1227 children; low-certainty evidence). There may be little or no difference between the drugs for hearing impairment (RR 1.16, 95% CI 0.63 to 2.16; 1 trial, 1227 children; moderate-certainty evidence), motor developmental delay (RR 0.89, 95% CI 0.66 to 1.20; 1 trial, 1166 children; moderate-certainty evidence) or intellectual impairment (RR 0.97, 95% CI 0.79 to 1.20; 1 trial, 1161 children; moderate-certainty evidence). However, the effect estimate for cerebral palsy is compatible with both an important increase in risk with dexamethasone, and no difference between interventions (RR 2.50, 95% CI 0.97 to 6.39; 1 trial, 1223 children; low-certainty evidence). No trials followed the children beyond early childhood. Comparisons of different preparations and regimens of corticosteroids We found three studies that included a comparison of a different regimen or preparation of either dexamethasone or betamethasone (oral dexamethasone 32 mg versus intramuscular dexamethasone 24 mg; betamethasone acetate plus phosphate versus betamethasone phosphate; 12-hourly betamethasone versus 24-hourly betamethasone). The certainty of the evidence for the main outcomes from all three studies was very low, due to small sample size and risk of bias. Therefore, we were limited in our ability to draw conclusions from any of these studies.
AUTHORS' CONCLUSIONS
Overall, it remains unclear whether there are important differences between dexamethasone and betamethasone, or between one regimen and another. Most trials compared dexamethasone versus betamethasone. While for most infant and early childhood outcomes there may be no difference between these drugs, for several important outcomes for the mother, infant and child the evidence was inconclusive and did not rule out significant benefits or harms. The evidence on different antenatal corticosteroid regimens was sparse, and does not support the use of one particular corticosteroid regimen over another.
Topics: Adrenal Cortex Hormones; Betamethasone; Child; Child, Preschool; Chorioamnionitis; Dexamethasone; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Lung; Pregnancy; Premature Birth; Respiratory Distress Syndrome, Newborn
PubMed: 35943347
DOI: 10.1002/14651858.CD006764.pub4 -
Journal of Critical Care Apr 2024The role of corticosteroids in the treatment of community-acquired pneumonia (CAP) remains uncertain. We conducted an updated meta-analysis to investigate the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The role of corticosteroids in the treatment of community-acquired pneumonia (CAP) remains uncertain. We conducted an updated meta-analysis to investigate the effectiveness and potential effect modifiers of adjunctive corticosteroids in patients with CAP.
METHODS
The protocol of this meta-analysis was registered with PROSPERO (CRD42022354920). We searched MEDLINE, Embase, the Cochrane Library and trial registers from inception till March 2023 to identify randomized controlled trials (RCTs) investigating corticosteroids in adult patients with CAP. Our primary outcome was the risk of all-cause mortality within 30 days after randomization (if not reported at day 30, we extracted the outcome closest to 30 days). Risk ratios (RR) and mean differences (MDs) were pooled under a random-effects model.
RESULTS
Fifteen RCTs (n = 3252 patients) were included in this review. Corticosteroids reduced the risk of all-cause mortality in CAP patients (RR: 0.69, 95% CI: 0.53-0.89; high certainty). This significant result was restricted to hydrocortisone therapy and patients with severe CAP. Additionally, younger patients demonstrated a greater reduction in mortality. Corticosteroids reduced the incidence of shock and the need for mechanical ventilation (MV), and decreased the length of hospital and ICU stay (moderate certainty).
CONCLUSIONS
Corticosteroids reduce the risk of all-cause mortality, especially in younger patients receiving hydrocortisone, and probably decrease the need for MV, the incidence of shock, and the length of hospital and ICU stay in patients with CAP. Our findings indicate that patients with CAP, especially severe CAP, will benefit from adjunctive corticosteroid therapy.
Topics: Adult; Humans; Adrenal Cortex Hormones; Community-Acquired Infections; Hydrocortisone; Pneumonia; Randomized Controlled Trials as Topic
PubMed: 38128217
DOI: 10.1016/j.jcrc.2023.154507 -
The Cochrane Database of Systematic... Dec 2021Infants born at term by elective caesarean section are more likely to develop respiratory morbidity than infants born vaginally. Prophylactic corticosteroids in... (Review)
Review
BACKGROUND
Infants born at term by elective caesarean section are more likely to develop respiratory morbidity than infants born vaginally. Prophylactic corticosteroids in singleton preterm pregnancies accelerate lung maturation and reduce the incidence of respiratory complications. It is unclear whether administration at term gestations, prior to caesarean section, improves the respiratory outcomes for these babies without causing any unnecessary morbidity to the mother or the infant.
OBJECTIVES
The objective of this review was to assess the effect of prophylactic corticosteroid administration before elective caesarean section at term, as compared to usual care (which could be placebo or no treatment), on fetal, neonatal and maternal morbidity. We also assessed the impact of the treatment on the child in later life.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov (20 January 2021) and reference lists of retrieved studies.
SELECTION CRITERIA
We included randomised controlled trials comparing prophylactic antenatal corticosteroid administration (betamethasone or dexamethasone) with placebo or with no treatment, given before elective caesarean section at term (at or after 37 weeks of gestation). Quasi-randomised and cluster-randomised controlled trials were also eligible for inclusion.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two review authors independently assessed trials for inclusion, assessed risk of bias, evaluated trustworthiness (based on predefined criteria developed by Cochrane Pregnancy and Childbirth), extracted data and checked them for accuracy and assessed the certainty of the evidence using the GRADE approach. Our primary outcomes were respiratory distress syndrome (RDS), transient tachypnoea of the neonate (TTN), admission to neonatal special care for respiratory morbidity and need for mechanical ventilation. We planned to perform subgroup analyses for the primary outcomes according to gestational age at randomisation and type of corticosteroid (betamethasone or dexamethasone). We also planned to perform sensitivity analysis, including only studies at low risk of bias.
MAIN RESULTS
We included one trial in which participants were randomised to receive either betamethasone or usual care. The trial included 942 women and 942 neonates recruited from 10 UK hospitals between 1995 and 2002. This review includes only trials that met predefined criteria for trustworthiness. We removed three trials from the analysis that were included in the previous version of this review. The risk of bias was low for random sequence generation, allocation concealment and incomplete outcome data. The risk of bias for selective outcome reporting was unclear because there was no published trial protocol, and therefore it is unclear whether all the planned outcomes were reported in full. Due to a lack of blinding we judged there to be high risk of performance bias and detection bias. We downgraded the certainty of the evidence because of concerns about risk of bias and because of imprecision due to low event rates and wide 95% confidence intervals (CIs), which are consistent with possible benefit and possible harm Compared with usual care, it is uncertain if antenatal corticosteroids reduce the risk of RDS (relative risk (RR) 0.34 95% CI 0.07 to 1.65; 1 study; 942 infants) or TTN (RR 0.52, 95% CI 0.25 to 1.11; 1 study; 938 infants) because the certainty of evidence is low and the 95% CIs are consistent with possible benefit and possible harm. Antenatal corticosteroids probably reduce the risk of admission to neonatal special care for respiratory complications, compared with usual care (RR 0.45, 95% CI 0.22 to 0.90; 1 study; 942 infants; moderate-certainty evidence). The proportion of infants admitted to neonatal special care for respiratory morbidity after treatment with antenatal corticosteroids was 2.3% compared with 5.1% in the usual care group. It is uncertain if antenatal steroids have any effect on the risk of needing mechanical ventilation, compared with usual care (RR 4.07, 95% CI 0.46 to 36.27; 1 study; 942 infants; very low-certainty evidence). The effect of antenatal corticosteroids on the maternal development of postpartum infection/pyrexia in the first 72 hours is unclear due to the very low certainty of the evidence; one study (942 women) reported zero cases. The included studies did not report any data for neonatal hypoglycaemia or maternal mortality/severe mortality.
AUTHORS' CONCLUSIONS
Evidence from one randomised controlled trial suggests that prophylactic corticosteroids before elective caesarean section at term probably reduces admission to the neonatal intensive care unit for respiratory morbidity. It is uncertain if administration of antenatal corticosteroids reduces the rates of respiratory distress syndrome (RDS) or transient tachypnoea of the neonate (TTN). The overall certainty of the evidence for the primary outcomes was found to be low or very low, apart from the outcome of admission to neonatal special care (all levels) for respiratory morbidity, for which the evidence was of moderate certainty. Therefore, there is currently insufficient data to draw any firm conclusions. More evidence is needed to investigate the effect of prophylactic antenatal corticosteroids on the incidence of recognised respiratory morbidity such as RDS. Any future trials should assess the balance between respiratory benefit and potential immediate adverse effects (e.g. hypoglycaemia) and long-term adverse effects (e.g. academic performance) for the infant. There is very limited information on maternal health outcomes to provide any assurances that corticosteroids do not pose any increased risk of harm to the mother. Further research should consider investigating the effectiveness of antenatal steroids at different gestational ages prior to caesarean section. There are nine potentially eligible studies that are currently ongoing and could be included in future updates of this review.
Topics: Adrenal Cortex Hormones; Betamethasone; Cesarean Section; Child; Female; Humans; Infant; Infant, Newborn; Pregnancy; Prenatal Care; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn
PubMed: 34935127
DOI: 10.1002/14651858.CD006614.pub4 -
Fertility and Sterility Apr 2023The necessity of progesterone supplementation for luteal phase support (LPS) in natural cycle frozen embryo transfer (NC-FET) cycles warrants further confirmation. (Meta-Analysis)
Meta-Analysis Review
The effect of progesterone supplementation for luteal phase support in natural cycle frozen embryo transfer: a systematic review and meta-analysis based on randomized controlled trials.
IMPORTANCE
The necessity of progesterone supplementation for luteal phase support (LPS) in natural cycle frozen embryo transfer (NC-FET) cycles warrants further confirmation.
OBJECTIVE
To investigate the effect of progesterone supplementation for LPS on the reproductive outcomes of patients undergoing NC-FET cycles.
DATA SOURCES
The PubMed, Ovid-Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and CBM were electronically searched. The search time frame was from inception up to September 2022.
STUDY SELECTION AND SYNTHESIS
Randomized controlled trials (RCTs) that used progesterone for LPS in NC-FET cycles, including true NC-FET cycles (tNC-FET) and modified NC-FET cycles (mNC-FET), were included. The counted data were analyzed using relative risk (RR) as the effect-size statistic, and each effect size was assigned its 95% confidence interval (CI).
MAIN OUTCOME MEASURES
The primary outcomes were the live birth rate (LBR) and the clinical pregnancy rate (CPR), and the secondary outcome was the miscarriage rate.
RESULTS
Four RCTs were included, which involved 1116 participants. The results of the meta-analysis showed that progesterone supplementation was associated with increased LBR (RR, 1.42; 95% CI, 1.15-1.75; I = 0%, moderate-quality evidence) and CPR (RR, 1.30, 95% CI, 1.07-1.57; I = 0%, moderate-quality evidence) in patients undergoing NC-FET cycles. Subgroup analysis showed that progesterone supplementation was associated with higher LBR and CPR in tNC-FET cycles. However, no association was found between increased LBR and CPR in mNC-FET cycles. In addition, only one RCT reported that oral dydrogesterone had similar CPR and miscarriage rate compared with vaginal progesterone in mNC-FET cycles.
CONCLUSION(S)
Overall, moderate-quality evidence suggested that progesterone supplementation for LPS was associated with increased LBR and CPR in NC-FET cycles. Progesterone supplementation was associated with a higher LBR and CPR in tNC-FET cycles. However, the effectiveness of progesterone supplementation in mNC-FET cycles should be further verified by larger RCTs. Low to very low-quality evidence indicated that oral dydrogesterone and vaginal progesterone have similar reproductive outcomes in mNC-FET cycles, which requires further study, especially in tNC-FET cycles.
REGISTRATION NUMBER
PROSPERO CRD42022355550 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=355550) was registered on September 3, 2022.
Topics: Pregnancy; Female; Humans; Progesterone; Luteal Phase; Abortion, Spontaneous; Dydrogesterone; Pregnancy Rate; Lipopolysaccharides; Randomized Controlled Trials as Topic; Embryo Transfer; Dietary Supplements
PubMed: 36574915
DOI: 10.1016/j.fertnstert.2022.12.035 -
The Journal of Allergy and Clinical... Jun 2020Although nebulized corticosteroids (NebCSs) are a key treatment option for young children with asthma or viral-induced wheezing (VIW), there are no uniform... (Review)
Review
Although nebulized corticosteroids (NebCSs) are a key treatment option for young children with asthma or viral-induced wheezing (VIW), there are no uniform recommendations on their best use. This systematic review aimed to clarify the role of NebCSs in children 5 years or younger for the management of acute asthma exacerbations, asthma maintenance therapy, and the treatment of VIW. Electronic databases were used to identify relevant English language articles with no date restrictions. Studies reporting efficacy data in children 5 years or younger, with a double-blind, placebo- or open-controlled, randomized design, and inclusion of 40 or more participants (no lower patient limit for VIW) were included. Ten articles on asthma exacerbation, 9 on asthma maintenance, and 7 on VIW were identified. Results showed NebCSs to be at least as efficacious as oral corticosteroids in the emergency room for the management of mild to moderate asthma exacerbations. In asthma maintenance, nebulized budesonide, the agent of focus in all trials analyzed, significantly reduced the risk of further asthma exacerbations compared with placebo, cromolyn sodium, and montelukast. Intermittent NebCS treatment of VIW was as effective as continuous daily treatment. In summary, NebCSs are effective and well tolerated in patients 5 years or younger for the management of acute and chronic asthma.
Topics: Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Budesonide; Child; Child, Preschool; Humans; Randomized Controlled Trials as Topic; Respiratory Sounds
PubMed: 32006721
DOI: 10.1016/j.jaip.2020.01.042 -
Advances in Therapy May 2022Many treatment regimens have been evaluated in transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). The objective of this study was to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Many treatment regimens have been evaluated in transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). The objective of this study was to compare the efficacy of relevant therapies for the treatment of TIE patients with NDMM.
METHODS
Progression-free survival (PFS) and overall survival (OS) from large randomised controlled trials (RCTs) evaluating different treatment options for TIE patients with NDMM were compared in a network meta-analysis (NMA). The NMA includes recent primary and long-term OS readouts from SWOG S0777, ENDURANCE, MAIA, and ALCYONE. Relevant trials were identified through a systematic literature review. Relative efficacy measures (i.e., hazard ratios [HRs] for PFS and OS) were extracted and synthesised in random-effects NMAs.
RESULTS
A total of 122 publications describing 45 unique RCTs was identified. Continuous lenalidomide/dexamethasone (Rd) was selected as the referent comparator. Daratumumab-containing treatments (daratumumab/lenalidomide/dexamethasone [D-Rd], daratumumab/bortezomib/melphalan/prednisone [D-VMP]) and bortezomib/lenalidomide/dexamethasone (VRd) had the highest probabilities of being more effective than Rd continuous for PFS (HR: D-Rd, 0.53; D-VMP, 0.57, VRd, 0.77) and OS (HR: D-Rd, 0.68; VRd, 0.77, D-VMP, 0.78). D-Rd had the highest chance of being ranked as the most effective treatment with respect to PFS and OS. Results using a smaller network focusing on only those regimens that are relevant in Europe were consistent with the primary analysis.
CONCLUSIONS
These comparative effectiveness data may help inform treatment selection in TIE patients with NDMM.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Dexamethasone; Humans; Lenalidomide; Multiple Myeloma; Network Meta-Analysis; Treatment Outcome
PubMed: 35246820
DOI: 10.1007/s12325-022-02083-8 -
The Cochrane Database of Systematic... Nov 2021Many infants born preterm develop bronchopulmonary dysplasia (BPD), with lung inflammation playing a role. Corticosteroids have powerful anti-inflammatory effects and... (Review)
Review
BACKGROUND
Many infants born preterm develop bronchopulmonary dysplasia (BPD), with lung inflammation playing a role. Corticosteroids have powerful anti-inflammatory effects and have been used to treat individuals with established BPD. However, it is unclear whether any beneficial effects outweigh the adverse effects of these drugs.
OBJECTIVES
To examine the relative benefits and adverse effects of late (starting at seven or more days after birth) systemic postnatal corticosteroid treatment for preterm infants with evolving or established BPD.
SEARCH METHODS
We ran an updated search on 25 September 2020 of the following databases: CENTRAL via CRS Web and MEDLINE via OVID. We also searched clinical trials databases and reference lists of retrieved articles for randomised controlled trials (RCTs). We did not include quasi-RCTs.
SELECTION CRITERIA
We selected for inclusion in this review RCTs comparing systemic (intravenous or oral) postnatal corticosteroid treatment versus placebo or no treatment started at seven or more days after birth for preterm infants with evolving or established BPD. We did not include trials of inhaled corticosteroids.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. We extracted and analysed data regarding clinical outcomes that included mortality, BPD, and cerebral palsy. We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
Use of the GRADE approach revealed that the certainty of evidence was high for most of the major outcomes considered, except for BPD at 36 weeks for all studies combined and for the dexamethasone subgroup, which were downgraded one level to moderate because of evidence of publication bias, and for the combined outcome of mortality or BPD at 36 weeks for all studies combined and for the dexamethasone subgroup, which were downgraded one level to moderate because of evidence of substantial heterogeneity. We included 23 RCTs (1817 infants); 21 RCTS (1382 infants) involved dexamethasone (one also included hydrocortisone) and two RCTs (435 infants) involved hydrocortisone only. The overall risk of bias of included studies was low; all were RCTs and most trials used rigorous methods. Late systemic corticosteroids overall reduce mortality to the latest reported age (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.66 to 0.99; 21 studies, 1428 infants; high-certainty evidence). Within the subgroups by drug, neither dexamethasone (RR 0.85, 95% CI 0.66 to 1.11; 19 studies, 993 infants; high-certainty evidence) nor hydrocortisone (RR 0.74, 95% CI 0.54 to 1.02; 2 studies, 435 infants; high-certainty evidence) alone clearly reduce mortality to the latest reported age. We found little evidence for statistical heterogeneity between the dexamethasone and hydrocortisone subgroups (P = 0.51 for subgroup interaction). Late systemic corticosteroids overall probably reduce BPD at 36 weeks' postmenstrual age (PMA) (RR 0.89, 95% CI 0.80 to 0.99; 14 studies, 988 infants; moderate-certainty evidence). Dexamethasone probably reduces BPD at 36 weeks' PMA (RR 0.76, 95% CI 0.66 to 0.87; 12 studies, 553 infants; moderate-certainty evidence), but hydrocortisone does not (RR 1.10, 95% CI 0.92 to 1.31; 2 studies, 435 infants; high-certainty evidence) (P < 0.001 for subgroup interaction). Late systemic corticosteroids overall probably reduce the combined outcome of mortality or BPD at 36 weeks' PMA (RR 0.85, 95% CI 0.79 to 0.92; 14 studies, 988 infants; moderate-certainty evidence). Dexamethasone probably reduces the combined outcome of mortality or BPD at 36 weeks' PMA (RR 0.75, 95% CI 0.67 to 0.84; 12 studies, 553 infants; moderate-certainty evidence), but hydrocortisone does not (RR 0.98, 95% CI 0.88 to 1.09; 2 studies, 435 infants; high-certainty evidence) (P < 0.001 for subgroup interaction). Late systemic corticosteroids overall have little to no effect on cerebral palsy (RR 1.17, 95% CI 0.84 to 1.61; 17 studies, 1290 infants; high-certainty evidence). We found little evidence for statistical heterogeneity between the dexamethasone and hydrocortisone subgroups (P = 0.63 for subgroup interaction). Late systemic corticosteroids overall have little to no effect on the combined outcome of mortality or cerebral palsy (RR 0.90, 95% CI 0.76 to 1.06; 17 studies, 1290 infants; high-certainty evidence). We found little evidence for statistical heterogeneity between the dexamethasone and hydrocortisone subgroups (P = 0.42 for subgroup interaction). Studies had few participants who were not intubated at enrolment; hence, it is not possible to make any meaningful comments on the effectiveness of late corticosteroids in preventing BPD in non-intubated infants, including those who might in the present day be supported by non-invasive techniques such as nasal continuous positive airway pressure or high-flow nasal cannula oxygen/air mixture, but who might still be at high risk of later BPD. Results of two ongoing studies are awaited.
AUTHORS' CONCLUSIONS
Late systemic postnatal corticosteroid treatment (started at seven days or more after birth) reduces the risks of mortality and BPD, and the combined outcome of mortality or BPD, without evidence of increased cerebral palsy. However, the methodological quality of studies determining long-term outcomes is limited, and no studies were powered to detect increased rates of important adverse long-term neurodevelopmental outcomes. This review supports the use of late systemic corticosteroids for infants who cannot be weaned from mechanical ventilation. The role of late systemic corticosteroids for infants who are not intubated is unclear and needs further investigation. Longer-term follow-up into late childhood is vital for assessment of important outcomes that cannot be assessed in early childhood, such as effects of late systemic corticosteroid treatment on higher-order neurological functions, including cognitive function, executive function, academic performance, behaviour, mental health, motor function, and lung function. Further RCTs of late systemic corticosteroids should include longer-term survival free of neurodevelopmental disability as the primary outcome.
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Bronchopulmonary Dysplasia; Dexamethasone; Drug Administration Schedule; Glucocorticoids; Humans; Infant; Infant, Newborn; Infant, Premature
PubMed: 34758507
DOI: 10.1002/14651858.CD001145.pub5 -
Archives of Gynecology and Obstetrics Mar 2021Progestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation protocol that has been used over the last decade to enhance reproductive function. The purpose... (Meta-Analysis)
Meta-Analysis
PURPOSE
Progestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation protocol that has been used over the last decade to enhance reproductive function. The purpose of this study is to evaluate whether PPOS is as effective as conventional protocols (without GnRHa downregulation).
METHOD
Search terms included "medroxyprogesterone", "dydrogesterone", "progestin-primed ovarian stimulation", "PPOS", "oocyte retrieval", "in vitro fertilization", "IVF", "ICSI", "ART", and "reproductive". The selection criteria were nonrandomized studies and randomized controlled studies. For data collection and analysis, the Review Manager software, Newcastle-Ottowa Quality Assessment Scale and GRADE approach were used.
RESULTS
The clinical pregnancy rates were not significantly different in either RCTs or NRCTs [RR 0.96, 95% CI (0.69-1.33), I = 71%, P = 0.81]; [RR 0.99, 95% CI (0.83-1.17), I = 38%, P = 0.88]. The live birth rates of RCTs and NRCTs did not differ [RCT: RR 1.08, 95% CI (0.74, 1.57), I = 66%, P = 0.69; NRCT: OR 1.03 95% CI 0.84-1.26), I = 50%, P = 0.79]. The PPOS protocol had a lower rate of OHSS [RR 0.52, 95% CI (0.36-0.75), I = 0%, P = 0.0006]. The secondary results showed that compared to the control protocol, the endometrium was thicker [95% CI (0.00-0.78), I = 0%, P = 0.05], the number of obtained embryos was higher [95% CI (0.04-0.65), I = 17%, P = 0.03] and more hMG was needed [in NRCT: 95% CI (307.44, 572.73), I = 0%, P < 0.00001] with the PPOS protocol.
CONCLUSION
The PPOS protocol produces more obtained embryos and a thicker endometrium than the control protocol, with a lower rate of OHSS and an equal live birth rate. The PPOS protocol could be a safe option as a personalized protocol for infertile patients.
TRIAL REGISTRATION
Registration at PROSPERO: CRD42020176577.
Topics: Dydrogesterone; Female; Fertilization in Vitro; Humans; Oocyte Retrieval; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Progestins; Reproduction
PubMed: 33433705
DOI: 10.1007/s00404-020-05939-y -
Fertility and Sterility Dec 2021To investigate the association between luteal serum progesterone levels and frozen embryo transfer (FET) outcomes. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the association between luteal serum progesterone levels and frozen embryo transfer (FET) outcomes.
DESIGN
Systematic review and meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Women undergoing FET.
INTERVENTION(S)
We conducted electronic searches of MEDLINE, PubMed, CINAHL, EMBASE, the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and grey literature (not widely available) from inception to March 2021 to identify cohort studies in which the serum luteal progesterone level was measured around the time of FET.
MAIN OUTCOME MEASURE(S)
Ongoing pregnancy or live birth rate, clinical pregnancy rate, and miscarriage rate.
RESULT(S)
Among the studies analyzing serum progesterone level thresholds <10 ng/mL, a higher serum progesterone level was associated with increased rates of ongoing pregnancy or live birth (relative risk [RR] 1.47, 95% confidence interval [CI] 1.28 to 1.70), higher chance of clinical pregnancy (RR 1.31, 95% CI 1.16 to 1.49), and lower risk of miscarriage (RR 0.62, 95% CI 0.50 to 0.77) in cycles using exclusively vaginal progesterone and blastocyst embryos. There was uncertainty about whether progesterone thresholds ≥10 ng/mL were associated with FET outcomes in sensitivity analyses including all studies, owing to high interstudy heterogeneity and wide CIs.
CONCLUSION(S)
Our findings indicate that there may be a minimum clinically important luteal serum concentration of progesterone required to ensure an optimal endocrine milieu during embryo implantation and early pregnancy after FET treatment. Future clinical trials are required to assess whether administering higher-dose luteal phase support improves outcomes in women with a low serum progesterone level at the time of FET.
PROSPERO NUMBER
CRD42019157071.
Topics: Cryopreservation; Embryo Transfer; Female; Humans; Live Birth; Luteal Phase; Pregnancy; Pregnancy Rate; Progesterone; Prospective Studies; Reproductive Techniques, Assisted; Retrospective Studies
PubMed: 34384594
DOI: 10.1016/j.fertnstert.2021.07.002 -
Sports Medicine (Auckland, N.Z.) Jun 2022Ageing is accompanied by decreases in physical capacity and physiological regulatory mechanisms including altered hormonal regulation compared with age-matched sedentary...
BACKGROUND
Ageing is accompanied by decreases in physical capacity and physiological regulatory mechanisms including altered hormonal regulation compared with age-matched sedentary people. The potential benefits of exercise in restoring such altered hormone production and secretion compared to age-matched physically inactive individuals who are ageing remains unclear.
OBJECTIVES
The aim of this systematic review was to summarise the findings of exercise training in modulating levels of ostensibly anabolic and catabolic hormones in adults aged > 40 years.
METHODS
We searched the following electronic databases (to July 2021) without a period limit: Cochrane Library, PubMed, Science Direct, Scopus, SPORTDiscus and Web of Science. Additionally, a manual search for published studies in Google Scholar was conducted for analysis of the 'grey literature' (information produced outside of traditional commercial or academic publishing and distribution channels). The initial search used the terms 'ageing' OR 'advanced age' OR 'old people' OR 'older' OR elderly' AND 'anabolic hormones' OR 'catabolic hormones' OR 'steroid hormones' OR 'sex hormones' OR 'testosterone' OR 'cortisol' OR 'insulin' OR 'insulin-like growth factor-1' OR 'IGF-1' OR 'sex hormone-binding globulin' OR 'SHBG' OR 'growth hormone' OR 'hGH' OR 'dehydroepiandrosterone' OR 'DHEA' OR 'dehydroepiandrosterone sulfate (DHEA-S)' AND 'exercise training' OR 'endurance training' OR 'resistance training' OR ' strength training' OR 'weight-lifting' OR 'high-intensity interval training' OR 'high-intensity interval exercise' OR 'high-intensity intermittent training' OR 'high-intensity intermittent exercise' OR 'interval aerobic training' OR 'interval aerobic exercise' OR 'intermittent aerobic training' OR 'intermittent aerobic exercise' OR 'high-intensity training' OR 'high-intensity exercise' OR 'sprint interval training' OR 'sprint interval exercise' OR 'combined exercise training' OR 'anaerobic training'. Only eligible full texts in English or French were considered for analysis.
RESULTS
Our search identified 484 records, which led to 33 studies for inclusion in the analysis. Different exercise training programs were used with nine studies using endurance training programs, ten studies examining the effects of high-intensity interval training, and 14 studies investigating the effects of resistance training. Most training programs lasted ≥ 2 weeks. Studies, regardless of the design, duration or intensity of exercise training, reported increases in testosterone, sex hormone-binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), human growth hormone (hGH) or dehydroepiandrosterone (DHEA) (effect size: 0.19 < d < 3.37, small to very large) in both older males and females. However, there was no consensus on the effects of exercise on changes in cortisol and insulin in older adults.
CONCLUSION
In conclusion, findings from this systematic review suggest that exercise training increases basal levels of testosterone, IGF-1, SHBG, hGH and DHEA in both male and females over 40 years of age. The increases in blood levels of these hormones were independent of the mode, duration and intensity of the training programs. However, the effects of long-term exercise training on cortisol and insulin levels in elderly people are less clear.
Topics: Adult; Aged; Aging; Dehydroepiandrosterone; Exercise; Female; Hormones; Humans; Hydrocortisone; Insulin-Like Growth Factor I; Insulins; Male; Middle Aged; Sex Hormone-Binding Globulin; Testosterone
PubMed: 34936049
DOI: 10.1007/s40279-021-01612-9