Courses Of Antenatal Corticosteroids Research Articles

Effective and simple interventions to improve outcomes for preterm infants worldwide: The FIGO PremPrep-5 initiative.

Preterm birth remains the leading cause of mortality among under-5's and is a major contributor to the reduction in quality-of-life adjusted years and reduction in human capital. Globally, there are many interventions and care bundles that aim to reduce the impact of preterm birth once preterm labor has ensued and into the neonatal period; not all of these are applicable in all settings. Here, we introduce the FIGO PremPrep-5 initiative, which aims to disseminate key information on the most simple and effective interventions with the aim of increasing implementation globally. Before delivery, we recommend a course of antenatal corticosteroids, and intrapartum magnesium sulfate. At delivery, we recommend delayed cord clamping. Postnatally, we recommend early feeding with breast milk and immediate kangaroo care. While there are many other interventions that may improve outcomes at the time of labor and after preterm birth, these are clinically effective and relatively inexpensive options that can be practiced in most settings and supplemented with more advanced care. We include examples of a training video and infographics that will be used for dissemination.

The Impact of Infant Sex on Multiple Courses versus a Single Course of Antenatal Corticosteroids: A Secondary Analysis of a Randomized Controlled Trial

Objective Animal literature has suggested that the impact of antenatal corticosteroids (ACS) may vary by infant sex. Our objective was to assess the impact of infant sex on the use of multiple courses versus a single course of ACS and perinatal outcomes. Study Design We conducted a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth trial, which randomly allocated pregnant people to multiple courses versus a single course of ACS. Our primary outcome was a composite of perinatal mortality or clinically significant neonatal morbidity (including neonatal death, stillbirth, severe respiratory distress syndrome, intraventricular hemorrhage [grade III or IV], cystic periventricular leukomalacia, and necrotizing enterocolitis [stage II or III]). Secondary outcomes included individual components of the primary outcome as well as anthropometric measures. Baseline characteristics were compared between participants who received multiple courses versus a single course of ACS. An interaction between exposure to ACS and infant sex was assessed for significance and multivariable regression analyses were conducted with adjustment for predefined covariates, when feasible. Results Data on 2,300 infants were analyzed. The interaction term between treatment status (multiple courses vs. a single course of ACS) and infant sex was not significant for the primary outcome (p = 0.86), nor for any of the secondary outcomes (p > 0.05). Conclusion Infant sex did not modify the association between exposure to ACS and perinatal outcomes including perinatal mortality or neonatal morbidity or anthropometric outcomes. However, animal literature indicates that sex-specific differences after exposure to ACS may emerge over time and thus investigating long-term sex-specific outcomes warrants further attention. Key Points

Association between antenatal corticosteroid treatment and severe adverse events in pregnant women

BackgroundAntenatal corticosteroids are considered the standard of care for pregnant women at risk for preterm birth, but studies examining their potential risks are scarce. We aimed to estimate the associations of antenatal corticosteroids with three severe adverse events: sepsis, heart failure, and gastrointestinal bleeding, in pregnant women.MethodsOf 2,157,321 pregnant women, 52,119 at 24 weeks 0/7 days to 36 weeks 6/7 days of gestation were included in this self-controlled case series study during the study period of 2009–2018. We estimated incidence rates of three severe adverse events: sepsis, heart failure, and gastrointestinal bleeding. Conditional Poisson regression was used to calculate incidence rate ratios (IRRs) for comparing incidence rates of the adverse events in each post-treatment period compared to those during the baseline period among pregnant women exposed to a single course of antenatal corticosteroid treatment.ResultsAmong 52,119 eligible participants who received antenatal corticosteroid treatment, the estimated incidence rates per 1000 person-years were 0.76 (95% confidence interval (CI): 0.69–0.83) for sepsis, 0.31 (95% CI: 0.27–0.36) for heart failure, and 11.57 (95% CI: 11.27–11.87) for gastrointestinal bleeding. The IRRs at 5 ~ 60 days after administration of antenatal corticosteroids were 5.91 (95% CI: 3.10–11.30) for sepsis and 4.45 (95% CI: 2.63–7.55) for heart failure, and 1.26 (95% CI: 1.02–1.55) for gastrointestinal bleeding; and the IRRs for days 61 ~ 180 were 2.00 (95% CI: 1.01–3.96) for sepsis, 3.65 (95% CI: 2.14–6.22) for heart failure, and 1.81 (95% CI: 1.56–2.10) for gastrointestinal bleeding.ConclusionsThis nationwide population-based study suggests that a single course of antenatal corticosteroids is significantly associated with a 1.3- to 5.9-fold increased risk of sepsis, heart failure, and gastrointestinal bleeding in pregnant women. Maternal health considerations, including recommendations for adverse event monitoring, should be included in future guidelines for antenatal corticosteroid treatment.

Study of Perinatal Outcome in Premature Babies with Complete and Incomplete Course of Antenatal Corticosteroids

The rate of preterm birth sweeps from 5-18% across 184 countries. India has a lofty number of preterm births as well as neonatal deaths due to prematurity. Preterm birth is a risk factor in at least 50% of all neonatal deaths and is the second most common cause of death (after pneumonia) among children under the age of five. In the Indian context, many pregnant women are registered late or are referred to a peripheral center when a preterm delivery is suspected. Many receive an incomplete course (only one dose) of corticosteroids. Therefore, in this proximity of the truncation researcher’s attempt to analyze the efficacy of a single dose, to see whether it is as good as two doses in averting impediment, especially RDS in preterm babies. This study aims to determine the differences in survival and short-term morbidity in neonates receiving an incomplete course (one dose) of steroids in comparison to those receiving a complete course (two doses) and to know the relation between co-morbidity with respect to those receiving a complete course of drug (two doses). The study depicts that RDS more common in premature babies who did not receive ANCS that who did. It also shows that requirement of surfactant and no. of doses of surfactant less in babies who received ANCS than babies who did not.

Association between antenatal corticosteroids and risk of serious infection in children: nationwide cohort study

ObjectiveTo investigate the associations between exposure to antenatal corticosteroids and serious infection in children during the first three, six, and 12 months of life.DesignNationwide cohort study.SettingNational Health Insurance Research Database,...

One vs 2 courses of antenatal corticosteroids in pregnancies at risk of preterm birth: a secondary analysis of the MACS trial

Birth is unpredictable and many patients who receive antenatal corticosteroids for preterm birth remain pregnant. Some professional societies recommend rescue antenatal corticosteroids for those who remain pregnant ≥14 days following the initial course. This study aimed to explore a single vs a second course of antenatal corticosteroids in terms of severe neonatal morbidity and mortality. This is a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth (MACS) trial. The MACS study was a randomized clinical trial conducted in 80 centers in 20 different countries from 2001 to 2006. Participants who received only 1 course of intervention (ie, either a second course of antenatal corticosteroids or placebo) were included in this study. The primary outcome was a composite of stillbirth, neonatal mortality in the first 28 days of life or before discharge, severe respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage stage III and IV, periventricular leukomalacia, and necrotizing enterocolitis. Two subgroup analyses were planned to address the effect of a second course of antenatal corticosteroids on infants born before 32 weeks or within 7 days from the intervention. Moreover, a sensitivity analysis was performed to assess the effect of intervention on singleton pregnancies. Baseline characteristics were compared between the groups using chi-square and Student t tests. Multivariable regression analysis was performed to adjust for confounding variables. There were 385 and 365 participants included in the antenatal corticosteroid and placebo groups, respectively. The composite primary outcome occurred in 24% and 20% of participants in the antenatal corticosteroid and placebo groups, respectively (adjusted odds ratio, 1.09; 95% confidence interval, 0.76-1.57). Moreover, severe respiratory distress syndrome rate was similar between the 2 groups (adjusted odds ratio, 0.98; 95% confidence interval, 0.65-1.48). Newborns exposed to antenatal corticosteroids were more likely to be small for gestational age (14.9% vs 10.6%; adjusted odds ratio, 1.63; 95% confidence interval, 1.07-2.47). These findings remained true among singleton pregnancies for the primary composite outcome and birthweight <10th percentile (adjusted odds ratio, 1.29 [0.82-2.01]; and adjusted odds ratio, 1.74 [1.06-2.87]; respectively). Subgroup analyses of infants born before 32 weeks or within 7 days from the intervention did not show any benefits in terms of the composite primary outcome with antenatal corticosteroids vs placebo (50.5% vs 41.8% [adjusted odds ratio, 1.16; 95% confidence interval, 0.78-1.72]; and 42.3% vs 37.1% [adjusted odds ratio, 1.02; 95% confidence interval, 0.67-1.57]; respectively). Neonatal mortality and severe morbidities, including severe respiratory distress syndrome, were not improved by a second course of antenatal corticosteroids. Policy makers need to be thoughtful when recommending a second course of antenatal corticosteroids and consider whether not only short-term but also long-term benefits can be gained from such administration.

The role of infant sex as a potential effect modifier between multiple courses versus a single course of antenatal corticosteroids and perinatal outcomes: A secondary analysis of the MACS randomized controlled trial

To assess the role of infant sex as a potential effect modifier on the use of multiple courses versus a single course of antenatal corticosteroids (ACS) and perinatal outcomes through a secondary analysis of a randomized controlled trial.

Booster course of antenatal corticosteroids after preterm prelabor rupture of membranes: a double-blind randomized trial

Preterm prelabor rupture of membranes is a leading cause of preterm birth and is responsible for 18% to 20% of perinatal deaths in the United States. An initial course of antenatal corticosteroids has been shown to reduce morbidity and mortality in patients with preterm prelabor rupture of membranes. For patients who remain undelivered for 7 days or more after the initial course of antenatal corticosteroids, it is uncertain whether a booster course of antenatal corticosteroids reduces neonatal morbidity or increases the infection risk. The American College of Obstetricians and Gynecologists has concluded that the current evidence is insufficient to make a recommendation. This study aimed to evaluate if a single booster course of antenatal corticosteroids improves neonatal outcomes after preterm prelabor rupture of membranes. We conducted a multicenter, placebo-controlled randomized clinical trial. The inclusion criteria were preterm prelabor rupture of membranes, gestational age of 24.0 to 32.9 weeks, singleton, initial antenatal corticosteroid course administered at least 7 days before randomization, and planned expectant management. Consenting patients were randomized in gestational age blocks to either receive booster antenatal corticosteroids (12 mg betamethasone every 24 hours for 2 days) or a saline placebo. The primary outcome was composite neonatal morbidity or death. A sample size of 194 patients was calculated to yield 80% power at P<.05 to detect a reduction in primary outcome from 60% in placebo group to 40% in antenatal corticosteroids group. From April 2016 through August 2022, 194 patients consented and were randomized (47% of 411 eligible patients). Intent-to-treat analysis was performed on 192 patients (2 placebo patients left hospital, outcomes unknown). The groups had similar baseline characteristics. The primary outcome occurred in 64% of patients who received booster antenatal corticosteroids vs in 66% of patients who received the placebo (odds ratio, 0.82; 95% confidence interval, 0.43-1.57; gestational age-stratified Cochran-Mantel-Haenszel test). Individual components of the primary outcome and secondary neonatal and maternal outcomes were not significantly different between the antenatal corticosteroids and placebo groups. Specifically, chorioamnionitis (22% vs 20%), postpartum endometritis (1% vs 2%), wound infections (2% vs 0%), and proven neonatal sepsis (5% vs 3%) were not different between the groups. A booster course of antenatal corticosteroids at least 7 days after the first antenatal corticosteroids course in patients with preterm prelabor rupture of membranes did not improve neonatal morbidity or any other outcome in this adequately-powered, double-blind randomized clinical trial. Booster antenatal corticosteroids did not increase maternal or neonatal infection.

Booster course of antenatal corticosteroids after preterm prelabor rupture of membranes, double-blind randomized trial

Booster course of antenatal corticosteroids after preterm prelabor rupture of membranes, double-blind randomized trial

One vs. two courses of antenatal corticosteroids: A secondary analysis of the MACS trial

One vs. two courses of antenatal corticosteroids: A secondary analysis of the MACS trial

Glucocorticoids in preterm human milk.

BackgroundGlucocorticoids (GCs), cortisol and cortisone, are essential regulators of many physiological responses, including immunity, stress and mammary gland function. GCs are present in human milk (HM), but whether maternal and infant factors are associated with HM GC concentration following preterm birth is unclear.Materials and methodsHM samples were collected on postnatal day 5 and 10 and at 4 months’ corrected age (4m CA) in a cohort of moderate- and late-preterm infants. GCs in HM were measured by liquid chromatography-tandem mass spectrometry. Relationships between GCs in HM and both maternal and infant characteristics were investigated using Spearman’s correlations and linear mixed models.Results170 mothers of 191 infants provided 354 HM samples. Cortisol concentrations in HM increased from postnatal day 5–4m CA (mean difference [MD] 0.6 ± 0.1 ng/ml, p < 0.001). Cortisone concentration did not change across lactation but was higher than cortisol throughout. Compared to no antenatal corticosteroid (ANS), a complete course of ANS was associated with lower GC concentrations in HM through to 4m CA (cortisol: MD –0.3 ± 0.1 ng/ml, p < 0.01; cortisone MD –1.8 ± 0.4 ng/ml, p < 0.001). At 4m CA, higher maternal perceived stress was negatively associated with GC concentrations in HM (cortisol adjusted beta-coefficient [aβ] –0.01 ± 0.01 ng/ml, p = 0.05; and cortisone aβ –0.1 ± 0.03 ng/ml, p = 0.01), whereas higher postpartum depression and maternal obesity were associated with lower cortisone concentrations (aβ –0.1 ± 0.04 ng/ml p < 0.05; MD [healthy versus obese] –0.1 ± 0.04 ng/ml p < 0.05, respectively). There was a weak positive correlation between GC concentrations in HM and gestational age at birth (r = 0.1, p < 0.05). Infant birth head circumference z-score was negatively associated with cortisol concentrations (aβ –0.01 ± 0.04 ng/ml, p < 0.05). At hospital discharge, fat-free mass showed a weak positive correlation with cortisol concentrations (r = 0.2, p = 0.03), while fat mass showed a weak negative correlation with cortisone concentrations (r = –0.25, p < 0.001).ConclusionThe mammary gland appears to protect the infant from cortisol through inactivation into cortisone. Maternal and infant characteristics were associated with concentration of GCs in HM, including ANS, stress and depression scores, obesity, gestational age and infant size. The effects of HM glucocorticoids on long-term health outcomes requires further research.

Neonatal outcomes by delivery indication after administration of antenatal late preterm corticosteroids

Antenatal corticosteroids, specifically betamethasone, administered to patients at risk for late preterm delivery have been associated with reduced rates of neonatal respiratory complications. However, whether these risks vary by delivery indication among betamethasone-exposed, late-preterm infants is not known. This study aimed to evaluate if spontaneous preterm labor or preterm prelabor rupture of membranes, compared with indicated late preterm delivery, is associated with better neonatal respiratory outcomes after accounting for betamethasone administration in the late preterm period. This was a secondary analysis of the Antenatal Late Preterm Steroids trial, a multicenter, placebo-controlled trial in which patients with singleton pregnancies at risk for delivery at 34 0/7 to 36 5/7 weeks of gestation were randomized to a single course of antenatal corticosteroids (betamethasone) or placebo. Patients were eligible if they had spontaneous preterm labor, preterm prelabor rupture of membranes, or if they were undergoing indicated late preterm delivery. The primary outcome was a composite of need for respiratory support, stillbirth, or neonatal death within 72 hours after delivery. Secondary outcomes included individual neonatal morbidities. Bivariate analyses were performed, and multivariable logistic regression models were used to control for potential confounders. Using the indicated preterm delivery group as the reference group, adjusted odds ratios and 95% confidence intervals were calculated for the outcomes by delivery indication. Subgroup analyses separately examined the treatment and placebo groups to determine the odds of the primary outcome by delivery indication. Of 2827 participants at high risk for late preterm delivery, 1427 (50.5%) received betamethasone. There were 790 (27.9%) infants born after preterm labor, 620 (21.9%) born after preterm prelabor rupture of membranes, and 1417 (50.1%) born after indicated preterm delivery. Compared with indicated preterm delivery, the odds of the primary outcome were lower among those born after preterm labor (7.3% vs 16.4%; adjusted odds ratio, 0.57; 95% confidence interval, 0.40-0.82) and among those born after preterm prelabor rupture of membranes (12.4% vs 16.4%; adjusted odds ratio, 0.49; 95% confidence interval, 0.35-0.69). Preterm labor had lower odds of all neonatal complications except feeding problems, and preterm prelabor rupture of membranes had lower odds of all neonatal complications except newborn intensive care unit admission for ≥3 days when compared with indicated preterm delivery. For the placebo group, the odds of the primary outcome were lower for the preterm labor group (8.2% vs 18.5%; adjusted odds ratio, 0.55; 95% confidence interval, 0.34-0.91) and the preterm prelabor rupture of membranes group (13.2% vs 18.5%; adjusted odds ratio, 0.46; 95% confidence interval, 0.29-0.73) than for the indicated preterm delivery group. For those exposed to betamethasone, the odds of the primary outcome remained lower for the preterm labor group (6.5% vs 14.3%; adjusted odds ratio, 0.58; 95% confidence interval, 0.34-0.99) and the preterm prelabor rupture of membranes group (11.7% vs 14.3%, adjusted odds ratio, 0.56; 95% confidence interval, 0.34-0.91) than for the indicated preterm delivery group. Compared with indicated preterm delivery, preterm labor and preterm prelabor rupture of membranes were associated with reduced odds of neonatal respiratory complications irrespective of betamethasone exposure in the late preterm period.

Partial vs. complete course of antenatal corticosteroid prophylaxis: An Italian single center retrospective study.

IntroductionThis study aimed to compare the outcomes of preterm infants given 12 vs. 24mg of betamethasone prophylaxis to understand whether a partial course of antenatal corticosteroids (CCS) could prevent or mitigate the major preterm birth complications.MethodsThis is a retrospective single-center cohort study including neonates born between 24 and 34 weeks of gestation from 2001 to 2019 at the University Hospital of Udine. The study population was divided into two groups: one group received 12mg, and another received a 24mg dose of betamethasone before the delivery. A separate analysis was performed for single and multiple pregnancies. The two groups were evaluated for various neonatal outcomes.ResultsThe study population included a total of 1,258 pregnancies and 1,543 neonates delivered between 24 and 34 weeks of gestation, of which 1,022 (803 single and 219 multiple pregnancies) were exposed to the complete CCS prophylaxis, whereas 236 (192 single and 44 multiple pregnancies) received the incomplete CCS prophylaxis. In single pregnancies, as for maternal characteristics, the most significant differences observed between the two groups are the following: a higher prevalence of spontaneous vaginal deliveries in the incomplete CCS prophylaxis (36.46 vs. 23.91%) and, by contrast, a higher prevalence of cesarean deliveries in the complete CCS prophylaxis group (75.72 vs. 63.02%). As for neonatal outcomes, the low Apgar score in the first and fifth min was significantly more prevalent in the incomplete CCS prophylaxis group compared with the complete CCS prophylaxis group. The group of incomplete CCS prophylaxis reported a higher occurrence of the following outcomes: IVH grade 3-4 (7.81 vs. 3.74%, p < 0.05), PVL (7.29 vs. 1.99% p < 0.05), ROP (23.96 vs. 18.06% p = 0.062), and RDS (84.38 vs. 78.83% p = 0.085). After adjusting for covariates, the complete CCS prophylaxis group in single pregnancies was significantly protective for IVH grade 3-4, PVL, and low Apgar's scores. Similar results were found in multiple pregnancies except for RDS.DiscussionThis retrospective single-center cohort study found that, compared with preterm infants treated with 24mg betamethasone in utero, those given half course of betamethasone had a significantly higher prevalence of IVH grade 3-4, PVL, RDS, and lower Apgar scores at 1 and 5 min. In conclusion, the evidence from this single-center retrospective study supports the preference for the complete CCS prophylaxis in women at risk of preterm birth because of its beneficial effect on the main adverse outcomes.

Effect of Single Course Versus Repeated Single Course of Antenatal Corticosteroid (Dexamethasone) in Preterm Premature Rupture of Membranes on Neonatal Respiratory Outcome "Randomized Control Trials"

Effect of Single Course Versus Repeated Single Course of Antenatal Corticosteroid (Dexamethasone) in Preterm Premature Rupture of Membranes on Neonatal Respiratory Outcome "Randomized Control Trials"

The Effect of Incompletely Administered Antenatal Corticosteroids on Neonatal Pulmonary Outcomes in Late Preterm Infants

Purpose: Recent obstetric guidelines recommend the administration of antenatal corticosteroids in pregnant women at risk of delivering infants at a gestational age between 34 and 36 weeks. We examined the effect of incompletely administered antenatal corticosteroids on the neonatal pulmonary outcomes in late preterm infants.Methods: Late preterm infants (34&lt;sup&gt;+0&lt;/sup&gt; to 36&lt;sup&gt;+6&lt;/sup&gt; weeks gestational age) born at the Seoul National University Bundang Hospital from January 2019 to June 2020 were retrospectively enrolled. We excluded multiple births except twins, those with major congenital anomalies, deaths, or transfers to other hospitals. An incomplete course of antenatal corticosteroids was defined as one in which the first or the second dose of betamethasone was administered within 24 hours before delivery. The rates of neonatal pulmonary morbidities were compared between late preterm infants given incomplete courses antenatal corticosteroids and their peers who not given antenatal corticosteroids; these morbidities included respiratory distress syndrome and transient tachypnea of the newborn, assisted ventilation including invasive mechanical ventilation, nasal continuous positive airway pressure and high-flow nasal cannula, and admission to neonatal intensive care unit.Results: Logistic regression models were constructed while adjusting for factors which were significant in bivariate models. After adjusting for baseline maternal and neonatal characteristics, we found no significant differences in the rates of neonatal pulmonary morbidities, assisted ventilation, or admission to the neonatal intensive care unit between late preterm infants who received incomplete antenatal corticosteroid therapy and their peers who were not given any antenatal corticosteroids.Conclusion: Incompletely administered antenatal corticosteroids did not significantly alter the neonatal pulmonary outcomes in late preterm infants.

Evaluation of Long-term Outcomes Associated With Preterm Exposure to Antenatal Corticosteroids

Animal studies have found that antenatal corticosteroids affect many organs across multiple stages of life. However, the long-term outcomes in human children are not well understood. To conduct a systematic review and meta-analysis of long-term outcomes associated with preterm exposure to antenatal corticosteroids compared with no exposure in all children as well as children with preterm and full-term birth. Academic databases were searched for articles published from January 1, 2000, to October 29, 2021, including Ovid MEDLINE, Ovid Embase, PsycInfo, CINAHL (Cumulative Index of Nursing and Allied Health Literature), Web of Science, ClinicalTrials.gov, and Google Scholar. References of articles were also searched for relevant studies. Randomized clinical trials (RCTs), quasi-RCTs, and cohort studies that assessed long-term neurodevelopmental, psychological, or other outcomes at 1 year or older in those who had preterm exposure to antenatal corticosteroids were included. No language restrictions were set. Two reviewers independently extracted data using a piloted data extraction form. Data on study population, pregnancy characteristics, exposure to antenatal corticosteroids, and outcomes were collected. Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines were followed, and random-effects models were used for the meta-analysis. The primary outcome was an author-defined composite of any adverse neurodevelopmental and/or psychological disorder. The secondary outcomes included specific measures of psychological disorders; neurodevelopmental delay; and anthropometric, metabolic, and cardiorespiratory outcomes. A total of 30 studies met the inclusion criteria, and involved more than 1.25 million children who were at least 1 year of age when the outcomes were assessed. Exposure to a single course of antenatal corticosteroids for children with extremely preterm birth was associated with a significant reduction in risk of neurodevelopmental impairment (adjusted odds ratio, 0.69 [95% CI, 0.57-0.84]; I2 = 0%; low certainty). For children with late-preterm birth, exposure to antenatal corticosteroids was associated with a higher risk of investigation for neurocognitive disorders (n = 25 668 children; adjusted hazard ratio [aHR], 1.12 [95% CI, 1.05-1.20]; low certainty). For children with full-term birth, exposure to antenatal corticosteroids was associated with a higher risk of mental or behavioral disorders (n = 641 487 children; aHR, 1.47 [95% CI, 1.36-1.60]; low certainty) as well as proven or suspected neurocognitive disorders (n = 529 205 children; aHR, 1.16 [95% CI, 1.10-1.21]; low certainty). Results of this study showed that exposure to a single course of antenatal corticosteroids was associated with a significantly lower risk of neurodevelopmental impairment in children with extremely preterm birth but a significantly higher risk of adverse neurocognitive and/or psychological outcomes in children with late-preterm and full-term birth, who made up approximately half of those with exposure to antenatal corticosteroids. The findings suggest a need for caution in administering antenatal corticosteroids.

Effect of Antenatal Dexamethasone in Late Preterm Period on Neonatal Hypoglycemia: A Prospective Cohort Study from a Developing Country.

This study compared the risk of hypoglycemia within 72 h of life in infants with and without exposure to antenatal dexamethasone in the late preterm period (34-366/7 week's gestational age). This prospective cohort study was conducted in a tertiary care neonatal unit of Eastern India from May 2021 to November 2021. Babies in the exposed group received at least one dose of antenatal dexamethasone in the late preterm period between 7 days before delivery and birth. 'Complete course' of antenatal steroid was defined as four doses of injection dexamethasone at 12 h intervals and <4 doses were considered as 'Partial course'. Primary outcome was incidence of hypoglycemia within 72 h of life, defined as whole blood glucose <45 mg/dl. Total 298 infants (98 in control, 134 in partial and 66 in complete group) were assessed for final outcome. No significant difference in outcomes were seen in the exposed group compared to unexposed group. However, incidence of hypoglycemia within 72 h (complete vs. partial p= 0.008, complete vs. control p=0.005) and 12 h of life (complete vs. partial p=0.013, complete vs. control p=0.013) was significantly less in complete steroid group. Logistic regression analysis revealed complete course of antenatal corticosteroid significantly decreased the risk of hypoglycemia [adjusted odds ratio, 95% confidence interval (CI) 0.15 (0.03-0.69), p=0.015]. Number needed to be exposed for one additional benefit was 7 (95% CI, 6.35-22.14). Complete course of dexamethasone administered to mothers at risk of late preterm delivery reduces risk of neonatal hypoglycemia within 72 h of life.

Antenatal Corticosteroids Decrease the Risk of Composite Neonatal Respiratory Morbidity in Planned Early Term Cesarean Deliveries.

While administration of antenatal corticosteroids prior to term elective cesarean deliveries has been shown in international randomized controlled trials to decrease the rates of respiratory distress syndrome and transient tachypnea of the newborn, this is not a standard practice in the United States. We aim to determine if the administration of antenatal corticosteroids for fetal lung maturation within 1 week of scheduled early term cesarean delivery resulted in decreased composite respiratory morbidity. Historical cohort study including women who underwent scheduled early term cesarean delivery of a singleton, non-anomalous neonate at Mount Sinai Hospital between May 2015 and August 2019, comparing those who completed a course of antenatal corticosteroids within 1 week of delivery to those who did not. The primary outcome was composite respiratory morbidity defined as respiratory distress syndrome, transient tachypnea of the newborn, and neonatal intensive care unit admission for respiratory morbidity. Maternal and neonatal characteristics were compared between groups using t-tests or Wilcoxon-Rank Sum tests for continuous measures and Chi-square or Fisher's exact tests for categorical measures, as appropriate. The outcomes were assessed using logistic regression. History of preterm birth was significantly higher in those who received antenatal corticosteroids compared with those who did not (24.0 vs. 10.9%, p = 0.01). Neonates who were not exposed to antenatal corticosteroids were more likely to experience the composite respiratory morbidity compared with those who were exposed (RR 4.1, 95% CI 1.2-13.7; p = 0.02). Between 37 and 38 weeks, neonates who did not receive steroids were at increased risk of composite respiratory morbidity (RR 11.7, 95% CI 1.5-89.0, p < 0.01), however, there was no difference for those born between 38 and 39 weeks. Betamethasone course administered prior to planned early term cesarean delivery was associated with a statistically significant reduction in the neonatal composite respiratory morbidity compared with routine management. · Steroids administered prior to scheduled cesarean lead to decreased neonatal respiratory morbidity.. · Steroid administration was not associated with increased adverse neonatal outcomes.. · Steroid administration was most beneficial between 37 and 38 weeks..

Antenatal corticosteroids for prevention of neonatal respiratory distress syndrome multiple vs simple doses

Objective: To analyze the major outcomes comparing single versus multiple courses of antenatal corticosteroids (ACS) therapy in women at high risk of premature delivery. Methods: This systematic review analyzed 20 articles that were selected from “Biblioteca Virtual em Saúde" of Pan American Health Organization. The terms “multiple courses” and “antenatal corticosteroids” were used to search in databases: MEDLINE, LILAC, CUMED and IBECS. Another 4 relevant articles outside this search and fit our inclusion criteria were added. Results: There is no consensus in literature about whether multiple doses of ACS are beneficial or harmful for the infant and women. The majority of the reviewed articles positioned against multiple corticosteroid therapy, due to possible neurological effects to the newborn and the no outstanding results compared to single dose. Although some studies demonstrated that multiple ACS might have benefits greater than harms. Independently of those opinions, there is one major difficulty to establish the benefits of multiple ACS: insufficient long-term evaluation of these infants. For this reason, there are several neutral articles. Conclusion: The different criteria of each study (e.g. gestational age, dosage of ACS, sample size), made it difficult to analyze the articles in a standard format. There might be advantages in corticoid therapy in lower gestational age. However, there is a lack of long-term studies with exposed infants, besides insufficient studies about the best methods to administer the ACS (dosage, number of doses, rescue dose, gestational age). More long-dated follow-up and studies about methodologies are necessary to conclude this hypothesis.

Glucocorticoids regulate mitochondrial fatty acid oxidation in fetal cardiomyocytes

The late gestational rise in glucocorticoids contributes to the structural and functional maturation of the perinatal heart. Here, we hypothesized that glucocorticoid action contributes to the metabolic switch in perinatal cardiomyocytes from carbohydrate to fatty acid oxidation. In primary mouse fetal cardiomyocytes, dexamethasone treatment induced expression of genes involved in fatty acid oxidation and increased mitochondrial oxidation of palmitate, dependent upon a glucocorticoid receptor (GR). Dexamethasone did not, however, induce mitophagy or alter the morphology of the mitochondrial network. In vivo, in neonatal mice, dexamethasone treatment induced cardiac expression of fatty acid oxidation genes. However, dexamethasone treatment of pregnant C57Bl/6 mice at embryonic day (E)13.5 or E16.5 failed to induce fatty acid oxidation genes in fetal hearts assessed 24h later. Instead, at E17.5, fatty acid oxidation genes were downregulated by dexamethasone, as was GR itself. PGC-1α, required for glucocorticoid-induced maturation of primary mouse fetal cardiomyocytes in vitro, was also downregulated in fetal hearts at E17.5, 24h after dexamethasone administration. Similarly, following a course of antenatal corticosteroids in a translational sheep model of preterm birth, both GR and PGC-1α were downregulated in heart. These data suggest that endogenous glucocorticoids support the perinatal switch to fatty acid oxidation in cardiomyocytes through changes in gene expression rather than gross changes in mitochondrial volume or mitochondrial turnover. Moreover, our data suggest that treatment with exogenous glucocorticoids may interfere with normal fetal heart maturation, possibly by downregulating GR. This has implications for clinical use of antenatal corticosteroids when preterm birth is considered a possibility. KEY POINTS: Glucocorticoids are steroid hormones that play a vital role in late pregnancy in maturing fetal organs, including the heart. In fetal cardiomyocytes in culture, glucocorticoids promote mitochondrial fatty acid oxidation, suggesting they facilitate the perinatal switch from carbohydrates to fatty acids as the predominant energy substrate. Administration of a synthetic glucocorticoid in late pregnancy in mice downregulates the glucocorticoid receptor and interferes with the normal increase in genes involved in fatty acid metabolism in the heart. In a sheep model of preterm birth, antenatal corticosteroids (synthetic glucocorticoid) downregulates the glucocorticoid receptor and the gene encoding PGC-1α, a master regulator of energy metabolism. These experiments suggest that administration of antenatal corticosteroids in anticipation of preterm delivery may interfere with fetal heart maturation by downregulating the ability to respond to glucocorticoids.