Antenatal Corticosteroid Treatment Research Articles

Characterisation of ciclesonide metabolism in human placentae across gestation

IntroductionCurrent clinical management of pregnancies at risk of preterm delivery includes maternal antenatal corticosteroid (ACS) treatment. ACS activate the glucocorticoid receptor (GR) in all fetal tissues, maturing the lungs at the cost of impaired brain development, creating a need for novel treatments. The prodrug ciclesonide (CIC) activates the GR only when converted to des-CIC by specific enzymes, including acetylcholinesterase (ACHE) and carboxylesterase 1 and 2 (CES1, CES2). Importantly, the human placenta expresses ACHE and CES, and could potentially produce des-CIC, resulting in systemic fetal exposure and GR activation in all fetal tissues. We therefore investigated CES gene expression and conversion of CIC to des-CIC in human placentae collected during the second trimester (Tri2), and at preterm and term birth. MethodsDifferential expression analysis was performed in Tri2 (n = 27), preterm (n = 34), and term (n = 40) placentae using the DESeq2 R-package. Conversion of CIC to des-CIC was measured in a subset of placenta samples (Tri2 n = 7, preterm n = 26, term n = 20) using functional assays. ResultsACHE mRNA expression was higher in Tri2 male than preterm and term male placentae only, whereas CES1 mRNA expression was higher in Tri2 than preterm or term placentae of both sexes. Conversion of CIC to des-CIC did not differ between gestational ages. DiscussionConversion of CIC to des-CIC by the human placenta may preclude its use as a novel GR-agonist in threatened preterm birth. In vivo studies are required to confirm the extent to which placental activation occurs after maternal treatment.

The Impact of Antenatal Corticosteroids on the Metabolome of Preterm Newborns: An Untargeted Approach.

We analyzed and compared variations in the urinary metabolome, as well as postnatal clinical outcomes among preterm infants, based on the timing of antenatal corticosteroid (ACS) administration in response to preterm labor onset in their mothers. This was a prospective observational study held in the Neonatal Intensive Care Unit, Department of Woman's and Child's Health, Padova University Hospital (Italy). A urine sample was obtained from each patient within 24 h of birth; Mass Spectrometry-based untargeted metabolomics analysis was then conducted. We searched for any significant disparities in the metabolomic profile of preterm newborns subjected to antenatal corticosteroid (ACS) treatment at varying timings; their correlation with clinical outcomes were also evaluated. The group receiving ACS within the optimal time window (1-7 days before delivery) exhibited elevated levels of cysteine, N-acetylglutamine, propionyl carnitine and 5-hydroxyindolacetic acid, coupled with a decrease in pipecolic acid. Clinically, this group demonstrated a reduced need for invasive ventilation (p = 0.04). In conclusion, metabolomics analysis identified several metabolites that discriminated preterm infants whose mothers received ACS within the recommended time window. Elevated levels of cysteine and 5-Hydroxyindoleacetic acid, metabolites characterized by antioxidant and anti-inflammatory properties, were observed in these infants. This metabolic profile correlated with improved respiratory outcomes, as evidenced by a reduced necessity for invasive ventilation at birth.

The use of late preterm antenatal corticosteroids in women with gestational diabetes : a puzzle worth solving

BackgroundTo investigate the association between late preterm antenatal corticosteroid treatment and outcome in late preterm neonates born to mothers with gestational diabetes mellitus,MethodsAll patients with gestational diabetes mellitus who had a late preterm delivery at Etlik Lady Zübeyde Hospital between 2017 and 2021 were included. Women who met the inclusion criteria and were not given antenatal corticosteroid treatment during current pregnancy before 34 0/7 weeks of gestation were divided into two groups according to whether or not they received late preterm antenatal corticosteroid treatment. The two groups were compared in terms of adverse neonatal complications. The main outcomes were composite respiratory outcome and composite neonatal outcome. Logistic regression analysis was used to determine additional potential predictors of neonatal outcome.ResultsThis retrospective cohort study included a total of 400 participants with gestational diabetes mellitus who had a late preterm delivery within the study period. Of these women, 196 (49%) received late preterm antenatal corticosteroid treatment. Main outcomes showed no difference. Decreasing gestational age at birth was identified as an independent risk factor predicting both composite respiratory outcome and composite neonatal outcome in multivariate logistic regression analysis.ConclusionsAntenatal corticosteroid treatment at or after 34 0/7 weeks of gestation in women with gestational diabetes mellitus who had a late preterm delivery was not associated with improvement in adverse neonatal outcomes. Decreasing gestational age at birth was the only independent risk factor predicting composite neonatal and composite respiratory outcomes.

Antenatal corticosteroid treatment and infectious diseases in children: a nationwide observational study.

Antenatal Corticosteroid Treatment (ACT) improves the outcome of preterm infants, but may influence immune system development and risk of immune-related diseases. We investigated whether ACT is associated with infectious diseases in children born at term (≥37 gestational weeks), and very-to-moderate (<34 gestational weeks), and late (34-36 completed gestational weeks) preterm. All singleton live births in Finland between 01/01/2006 and 31/12/2021, were followed-up until 31/12/2021. Exposure was maternal ACT. Primary outcomes were numbers of inpatient treatment days, episodes, and specialized care outpatient visits with any infectious disease diagnoses between ages 0 and 4 years. We considered mother- and child-related covariates, and conducted term-born co-sibling comparisons. Data comprised 855,234 children. Of the 20,858 (2.4%) treatment-exposed children, 5981 (28.2%) were very-to-moderate preterm-born, 5809 (27.9%) late preterm-born, and 9069 (43.5%) term-born. Of the 271,767 term-born co-sibling pairs, 5010 (1.8%) were treatment-exposure-discordant, and 266,522 (98.1%) nonexposure-concordant. Among the term- and late preterm-born, treatment-exposed children had more inpatient treatment days than nonexposed children (term: 0.87 vs. 0.56 day/y, adjusted mean difference [aMD] 0.19, 95% CI 0.17-0.28; late preterm: 1.35 vs. 1.00 days/y, aMD 0.31,0.13-0.31), more inpatient treatment episodes (term: 0.43 vs. 0.33 episodes/y, aMD 0.06, 0.06-0.11; late preterm: 0.55 vs. 0.48 episodes/y, aMD 0.12, 0.06-0.18), and specialized care treatment visits (term: 1.46 vs. 0.95 visits/y, aMD 0.38; 0.34-0.43; late preterm: 1.63 vs. 1.28 visits/y, aMD 0.22, 0.12-0.32). Treatment-exposed and nonexposed very-to-moderate preterm-born children were similar in these outcomes, though they had less inpatient treatment days and episodes at 3-4 years. Differences remained in term-born co-sibling comparisons. These findings reinforce previous suggestions for careful consideration of risks and benefits of ACT. Academy of Finland, HiLIFE Fellows-Programme.

Antenatal Corticosteroid Treatment During the Late-Preterm Period and Neonatal Outcomes for Twin Pregnancies

Antenatal corticosteroid treatment of individuals with singletons at risk for delivery during the late-preterm period has been academically recommended. However, the evidence on the use of antenatal corticosteroid treatment for twins at risk for delivery during the late-preterm period is still lacking. To evaluate whether antenatal corticosteroid treatment during the late-preterm period in twin pregnancies was associated with a lower risk of newborn morbidity. This retrospective cohort study of twin pregnancies delivered from February 1, 2013, to September 30, 2020, in a university-affiliated hospital in China included 1974 individuals with twin pregnancies who were at risk for late preterm birth (34 weeks and 0 days to 36 weeks and 6 days of gestation). Data were analyzed from June 30 to July 13, 2023. Antenatal corticosteroid treatment during the late-preterm period. The primary outcome measure was composite neonatal respiratory morbidity, defined as at least 1 of the following postnatal occurrences in at least 1 neonate of the twins: respiratory distress syndrome, mechanical ventilation, surfactant administration, transferred with respiratory complications, or neonatal death. Propensity score overlap weighting was used to analyze the association between antenatal corticosteroid treatment and the risk of neonatal outcomes. The study population consisted of 1974 individuals with twin pregnancies, including 303 (15.3%; mean [SD] maternal age, 30.8 [4.2] years) who received antenatal corticosteroid treatment and 1671 (84.7%; mean [SD] maternal age, 31.2 [4.0] years) who did not receive antenatal corticosteroid treatment. The propensity score overlap weighting showed no significant differences between the antenatal corticosteroid treatment group and the no-antenatal corticosteroid treatment group in the risk of neonatal primary outcome (29 of 303 [9.6%] vs 41 of 1671 [2.5%]; weighted odds ratio, 1.27 [95% CI, 0.60-2.76]). None of the subgroup interaction tests were significant for the neonatal primary outcome in terms of gestational age at delivery, year of delivery, chorionicity, at least 1 infant small for gestational age, intertwin growth discordance, and infant sex, and neither was the sensitivity analysis of using propensity score matching and a different administration-to-birth interval and treating twin infants as individuals. This cohort study found insufficient evidence that antenatal corticosteroid treatment during the late-preterm period in twin pregnancies could be associated with a lower risk of newborn morbidity. This new finding can provide a reference for clinical practice.

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.

Neonatal Mortality Rate among Twin and Singleton Births with the Gestational Age of 34-37 Weeks: A Population-Based Study

Introduction: Twin pregnancy, compared to a singleton pregnancy, is associated with a higher risk of preterm birth and other neonatal complications. This study aimed to compare neonatal mortality rates and risk factors among births with the gestational age of 34 weeks - 37 weeks in twin and singleton pregnancies. Methods: The study design was cross-sectional and population-based. We extracted the data from the birth information registry in Iran. Mothers' and neonates' information was removed from the registry systems between 2018 and 2020. We used Statistical R software to compare neonatal mortality rate, demographic variables, and risk factors between two groups of twin and singleton neonates. Results: Out of 579,873 live births with a gestational age of 34 weeks - 37 weeks, 729 (1.4/1000) singleton and 54(0.77/1000) twins (one out of two) neonates died in the delivery room in the first hour of life. Of the neonates who left the delivery room alive, 3129 (4.9 per 1000) neonates had died (5.7/1000 singleton and 3.04/1000 twin). The neonatal mortality rate in hospitalized singleton neonates (1.85%) was higher than twin group (1.06%). After adjustment of other variables, the mortality rate in twin pregnancy was significantly lower than in singletons (p value &lt; 1/1000), with an odds ratio of 0.47 (CI: 0.39 - 0.55). Antenatal corticosteroid treatment in the twin group was significantly higher than in singletons. Conclusion: Twin neonatal mortality rate was lower than singletons in the neonates with gestational age 34 weeks - 37 weeks. Clinicians could consider these results for delivery timing in uncomplicated twin pregnancies. Antenatal corticosteroid therapy can be considered to reduce the mortality rate of late preterm neonates in resource-limited countries.

A Reduction in Antenatal Steroid Dose Was Associated with Reduced Cardiac Dysfunction in a Sheep Model of Pregnancy

Despite widespread use, dosing regimens for antenatal corticosteroid (ACS) therapy are poorly unoptimized. ACS therapy exerts a programming effect on fetal development, which may be associated with an increased risk of cardiovascular disease. Having demonstrated that low-dose steroid therapy is an efficacious means of maturing the preterm lung, we hypothesized that a low-dose steroid exposure would exert fewer adverse functional and transcriptional changes on the fetal heart. We tested this hypothesis using low-dose steroid therapy (10 mg delivered to the ewe over 36 h via constant infusion) and compared cardiac effects with those of a higher dose treatment (30 mg delivered to the ewe over 24 h by intramuscular injection; simulating currently employed clinical ACS regimens). Fetal cardiac function was assessed by ultrasound on the day of ACS treatment initiation. Transcriptomic analyses were performed on fetal myocardial tissue. Relative to saline control, fetuses in the higher-dose clinical treatment group had significantly lower ratios between early diastolic ventricular filling and ventricular filling during atrial systole, and showed the differential expression of myocardial hypertrophy-associated transcripts including βMHC, GADD45γ, and PPARγ. The long-term implications of these changes remain unstudied. Irrespective, optimizing ACS dosing regimens to maximize respiratory benefit while minimizing adverse effects on key organ systems, such as the heart, offers a means of improving the acute and long-term outcomes associated with this important obstetric therapy.

Optimizing the timing of antenatal corticosteroid administration prior to anticipated preterm birth: A retrospective cohort study.

To examine suboptimal antenatal corticosteroid (ACS) administration based on indications and maternal-obstetrical factors. Women who prematurely delivered (24 + 0 to 36 + 6 gestational weeks) a viable neonate following ACS treatment between 2012 and 2019 were identified by a retrospective database review. The cohort was divided into patients in whom ACS administration was optimally timed (≥24 h to ≤7 days) or suboptimally timed (>7 days). The groups were compared for ACS indications and maternal, obstetrical, and neonatal parameters. The cohort included 399 women. ACS timing was optimal in 233 patients (58%) and was associated with nulliparity (109 [46.8%] vs. 54 [32.5%], P = 0.004) and preterm premature rupture of membranes (89 [38.2%] vs. 45 [27.1%], P = 0.021). Suboptimal timing was associated with chronic hypertension (22 [9.4%] vs. 36 [21.7%], P < 0.001) and asymptomatic cervical shortening (23 [9.9%] vs. 26 [15.7%], P = 0.020). Optimal ACS timing was associated with higher neonatal intensive care unit admission (135 [58%] vs. 71 [42.8%], P = 0.003). On multivariate analysis, the adjusted odds ratio (aOR) of neonatal intensive care unit admission was 0.69 (95% confidence interval [CI], 0.58-0.83, P < 0.001) and 0.99 (95% CI, 0.99-1, P = 0.003) when adjusted for gestational age and birth weight, respectively. When adjusting for maternal age, the aOR for suboptimal ACS administraion due to chronic hypertension was 2.65 (95% CI, 1.49-4.72; P < 0.001). Optimal timing of ACS varies based on different maternal characteristics and clinical indications. In the presence of certain parameters physicians tend to administer ACS suboptimally, diminishing its beneficial effect.

Do improvements in clinical practice guidelines alter pregnancy outcomes in asthmatic women? A single-center retrospective cohort study

Objective Asthma occurs in ∼17% of Australian pregnancies and is associated with adverse perinatal outcomes, which worsen with poor asthma control. Consequently, the South Australian ‘Asthma in Pregnancy’ perinatal guidelines were revised in 2012 to address management according to severity. This study investigated if these revised guidelines reduced the impact of maternal asthma on risks of adverse perinatal outcomes before (Epoch 1, 2006–2011) and after the revision (Epoch 2, 2013–2018). Methods Routinely collected perinatal and neonatal datasets from the Women’s and Children’s Hospital (Adelaide, Australia) were linked. Maternal asthma (prevalence:7.5%) was defined as asthma medication use or symptoms described to midwives. In imputation (n = 59131) and complete case datasets (n = 49594), analyses were conducted by inverse proportional weighting and multivariate logistic regression, accounting for confounders. Results Overall, maternal asthma was associated with increased risks of any antenatal corticosteroid treatment for threatened preterm birth (aOR 1.319, 95% CI 1.078–1.614), any Cesarean section (aOR 1.196, 95% CI 1.059–1.351), Cesarean section without labor (aOR 1.241, 95% CI 1.067–1.444), intrauterine growth restriction (IUGR, aOR 1.285, 95% CI 1.026–1.61), and small for gestational age (aOR 1.324, 95% CI 1.136–1.542). After guideline revision, asthma-associated risks of any Cesarean section (p < 0.001), any antenatal corticosteroids (p = 0.041), and small for gestational age (p = 0.050), but not IUGR and Cesarean section without labor, were reduced. Conclusions Clinical practice guidelines based on the latest evidence do not guarantee clinical efficacy. Since adverse perinatal outcomes did not all improve, this work highlights the need to evaluate the ongoing impact of guidelines on clinical outcomes.

A randomized clinical trial of antibiotic treatment duration in preterm premature rupture of membranes: 7 days versus until delivery.

Antibiotic treatment in preterm premature rupture of membranes (PPROM) can prolong the interval from membrane rupture to delivery and improve neonatal outcomes; however the duration of antibiotic treatment for PPROM has rarely been compared in prospective studies. To investigate the optimal duration of antibiotic treatment for PPROM, we performed a randomized controlled trial comparing neonatal morbidity and infantile neurological outcomes between two groups of PPROM patients who received antibiotic treatment for 7 days or until delivery. This prospective randomized study included patients who were diagnosed with PPROM between 22+0 weeks and 33+6 weeks of gestation. The enrolled patients were randomly assigned to receive intravenous cefazolin (1 g dose every 12 hours) and oral clarithromycin (500 mg dose every 12 hours) for 7 days or until delivery. The study protocol was registered at clinicaltrials.gov (NCT01503606). The primary outcome was neonatal composite morbidity, and the secondary outcome was neurological outcomes at 12 months of corrected age. We enrolled 150 patients and allocated 74 and 76 of them to the 7-day and until-delivery groups, respectively. Analysis was done by per protocol. After excluding cases lost to follow-up or with protocol violations, 63 (7-day regimen) and 61 (until-delivery regimen) PPROM patients and their babies were compared. There was no significant difference in pregnancy outcomes, including gestational age at delivery and interval from rupture of membranes (ROM) to delivery, between the two groups. Among the neonatal outcomes, bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity, necrotizing enterocolitis, and proven neonatal sepsis did not differ between the groups. However, the rate of respiratory distress syndrome (RDS) (32.8% vs. 50.8%, P=.039) and composite neonatal morbidities (34.4% vs. 53.9%, P=.026) were lower in the until-delivery group compared to the 7-day group. This difference remained statistically significant after a multivariable analysis adjusting for maternal age, twin pregnancy, use of antenatal corticosteroids, the ROM to delivery interval, and gestational age at delivery. Infantile neurological outcomes were evaluated in 70% of the enrolled patients and did not differ between the groups. Overall, until-delivery regimen of cefazolin and clarithromycin in PPROM showed lower incidence of composite neonatal morbidities, and of RDS compared to the 7-day regimen and both regimens showed otherwise similar other individual neonatal morbidities and infantile neurological outcomes.

Rescue doses of antenatal corticosteroids, children's neurodevelopment, and salivary cortisol after a threatened preterm labor: a 30-month follow-up study

Antenatal corticosteroids (ACS) reduce neonatal complications when are administered to women at risk of preterm birth. Moreover, ACS rescue doses are recommended in women who remain at risk after the initial course. However, there is controversy about the most appropriate frequency and exact timing for administering additional ACS doses since there are potential long-term negative effects on infants´ neurodevelopment and physiological stress functioning. The aims of this study were: i) to assess the long-term neurodevelopmental effects of receiving ACS rescue doses vs. receiving only the initial course; ii) to measure cortisol levels of infants that received ACS rescue doses; iii) to examine a potential dose-response effect of the number of ACS rescue doses on children´s neurodevelopment and salivary cortisol. The study followed 110 mother-infant pairs who underwent a spontaneous episode of threatened preterm labor (TPL) until the children were 30 months old, regardless of their gestational age at birth. Among the participants, 61 received only the initial course of corticosteroids (no rescue dose [NRD] group), and 49 participants required at least one rescue dose of corticosteroids (rescue doses [RD] group). The follow-up was carried out at three different times: [T1] at TPL diagnosis, [T2] at the children´s age of 6 months, and [T3] at the children's age of 30 months, corrected age for prematurity. Neurodevelopment was assessed using the Ages & Stages Questionnaires-Third Edition. Saliva samples were collected for cortisol level determination. First, the RD group showed lower problem-solving skills at age 30-months compared to the NRD group. Second, the RD group demonstrated higher salivary cortisol levels at 30-months. Third, a dose-response effect was found, indicating that the higher number of rescue doses the RD group received, the lower the problem-solving skills and the higher the salivary cortisol levels they showed at 30 months of age. Our findings reinforce the hypothesis that additional doses provided after the initial course of ACS may have long-term effects on offspring's neurodevelopment and glucocorticoid metabolism. In this regard, the results raise concerns about the negative effects of repeated doses in addition to a full course of ACS. Further studies are necessary to confirm this hypothesis and help physicians to reassess the standard ACS treatment regimens.

On optimal timing of antenatal corticosteroids: time to reformulate the question.

Administration of antenatal corticosteroids (ACS) for accelerating foetal lung maturation in threatened preterm birth is one of the cornerstones of prevention of neonatal mortality and morbidity. To identify the optimal timing of ACS administration, most studies have compared subgroups based on treatment-to-delivery intervals. Such subgroup analysis of the first placebo-controlled randomised controlled trial indicated that a one to seven day interval between ACS administration and birth resulted in the lowest rates of neonatal respiratory distress syndrome. This efficacy window was largely confirmed by a series of subgroup analyses of subsequent trials and observational studies and strongly influenced obstetric management. However, these subgroup analyses suffer from a methodological flaw that often seems to be overlooked and potentially has important consequences for drawing valid conclusions. In this commentary, we point out that studies comparing treatment outcomes between subgroups that are retrospectively identified at birth (i.e. after randomisation) may not only be plagued by post-randomisation confounding bias but, more importantly, may not adequately inform decision making before birth, when the projected duration of the interval is still unknown. We suggest two more formal interpretations of these subgroup analyses, using a counterfactual framework for causal inference, and demonstrate that each of these interpretations can be linked to a different hypothetical trial. However, given the infeasibility of these trials, we argue that none of these rescue interpretations are helpful for clinical decision making. As a result, guidelines based on these subgroup analyses may have led to suboptimal clinical practice. As an alternative to these flawed subgroup analyses, we suggest a more principled approach that clearly formulates the question about optimal timing of ACS treatment in terms of the protocol of a future randomised study. Even if this 'target trial' would never be conducted, its protocol may still provide important guidance to avoid repeating common design flaws when conducting observational 'real world' studies using statistical methods for causal inference.

Antenatal Corticosteroid Exposure is Associated with Childhood Mental Disorders in Late Preterm and Term Infants.

To study the association between antenatal corticosteroids treatment and childhood mental disorders in infants born at different gestational ages, and to investigate the effect of different administration timing. This population-based cohort study used data from the Taiwan National Health Insurance Research Database. All singleton live births born between 2004 and 2010 were enrolled and followed up for at least 6years. The primary outcome was any childhood mental disorder. Secondary outcomes included 7 specific subgroups of mental disorders. A total of 1 163 443 singleton infants were included in the analysis, and 16 847 (1.45%) infants were exposed to antenatal corticosteroid treatment. Children exposed to antenatal corticosteroids were found to have a higher risk of developing childhood mental disorders in the entire cohort (hazard ratio [HR], 1.13; 95% CI, 1.08-1.18), the term group (HR, 1.11; 95% CI, 1.05-1.16), and the late-preterm group (HR, 1.15; 95% CI, 1.06-1.25). The administration of corticosteroids in the early stage of pregnancy (<28weeks of gestation) significantly increased the risk of childhood mental disorders (HR, 1.22; 95% CI, 1.14-1.31). Exposure to antenatal corticosteroid treatment increases the cumulative risk of childhood mental disorders and attention deficit hyperactivity disorders, both in term and late preterm infants. The administration of corticosteroids in the early stage of pregnancy tends to increase the risk of mental disorders.

Neonatal Respiratory Morbidity after Late Preterm, Singleton, Cesarean Delivery before Labor by Mothers Who Did Not Receive Antenatal Corticosteroids.

Some evidence suggests that administration of antenatal corticosteroids (ACS) reduces neonatal respiratory complications among women at risk for late preterm birth. However, because of concerns regarding long-term outcomes of children, ACS is not recommended in Japan for pregnant women at risk in late preterm. We assessed the risk of neonatal respiratory morbidity after late preterm, singleton, cesarean delivery before labor by mothers who did not receive ACS. We retrospectively reviewed and analyzed data on singleton cesarean deliveries of late preterm infants. The prevalence of neonatal respiratory morbidity requiring ventilatory support, such as continuous positive airway pressure or mechanical ventilation, was analyzed in relation to gestational age in late preterm. Respiratory distress syndrome (RDS) in neonates was also evaluated. We analyzed data from 100 late preterm, singleton, cesarean deliveries: 22 neonates were delivered at 34 weeks, 34 at 35 weeks, and 44 at 36 weeks. Respiratory morbidity significantly decreased in relation to gestational age (p < 0.001). Similarly, there was a significant difference in RDS, which was most frequent at 34 weeks (18.2%, p = 0.017). There were no cases of RDS at 36 weeks. Late preterm, singleton, cesarean delivery before labor in mothers who did not receive ACS was associated with a need for ventilation, especially for infants born at 34 and 35 weeks. ACS treatment might therefore be beneficial before elective cesarean section for mothers with a risk of preterm delivery before 35 weeks and 6 days.

Antenatal prediction models for outcomes of extremely and very preterm infants based on machine learning.

Predicting individual risks for adverse outcomes in preterm infants is necessary for perinatal management and antenatal counseling for their parents. To evaluate whether a machine learning approach can improve the prediction of severe infant outcomes beyond the performance of conventional logistic models, and to identify maternal and fetal factors that largely contribute to these outcomes. A population-based retrospective study was performed using clinical data of 31,157 infants born at < 32weeks of gestation and weighing ≤ 1500g, registered in the Neonatal Research Network of Japan between 2006 and 2015. We developed a conventional logistic model and 6 types of machine learning models based on 12 maternal and fetal factors. Discriminative ability was evaluated using the area under the receiver operating characteristic curves (AUROCs), and the importance of each factor in terms of its contribution to outcomes was evaluated using the SHAP (SHapley Additive exPlanations) value. The AUROCs of the most discriminative machine learning models were better than those of the conventional models for all outcomes. The AUROCs for in-hospital death and short-term adverse outcomes in the gradient boosting decision tree were significantly higher than those in the conventional model (p = 0.015 and p = 0.002, respectively). The SHAP value analyses showed that gestational age, birth weight, and antenatal corticosteroid treatment were the three most important factors associated with severe infant outcomes. Machine learning models improve the prediction of severe infant outcomes. Moreover, the machine learning approach provides insight into the potential risk factors for severe infant outcomes.

Obesity - a still underestimated risk factor during antenatal corticosteroids therapy.

Pregnant obese patients are at a greater risk of developing gestational diabetes (GDM). We present a case of an obese patient who developed GDM G2 and periventricular leukomalacia in the neonate after antenatal corticosteroids (ACS) treatment. We suggest that routine blood glucose monitoring should be considered during a course of prenatal steroid therapy in all patients in a higher risk group for glucose intolerance. In cases of hyperglycemia, intensive insulin therapy should be advised. More research and new recommendations are needed on antenatal glucocorticoids (GCS), obesity, and GDM.

Antenatal corticosteroids and outcomes of small for gestational age infants born at 24-31 gestational weeks: a population-based propensity score matching analysis.

To evaluate the effect of antenatal corticosteroid (ACS) treatment on neonatal outcomes in small for gestational age (SGA) infants born at 24-31 gestational weeks compared with non-SGA infants. A population-based retrospective study was conducted that analyzed clinical data from the Neonatal Research Network of Japan database, which enrolls neonates born at < 32 gestational weeks and weighing 1500g or less (n = 22,414). Propensity score matching (with the ratio of ACS to no-ACS groups of 1:1) was performed in SGA (n = 7028) and non-SGA (n = 15,386) infants, respectively. Univariate logistic and interaction analyses were performed to compare the short-term neonatal outcomes of infants with and without ACS treatment in utero. In the SGA and non-SGA infants, ACS treatment significantly reduced in-hospital mortality (odds ratio 0.67 95% confidence interval [0.50-0.88] and 0.62 [0.50-0.78], respectively), respiratory distress syndrome (0.77 [0.69-0.87] and 0.63 [0.58-0.68], respectively), and composite adverse outcomes (0.73 [0.58-0.91] and 0.57 [0.50-0.65], respectively). ACS treatment also significantly reduced intraventricular hemorrhage (grade III/IV), periventricular leukomalacia, and sepsis in the non-SGA infants, but not in the SGA infants. However, interaction analyses revealed no significant differences between the SGA and non-SGA infants in the efficacy of ACS treatment on short-term outcomes except for respiratory distress syndrome. ACS treatment was associated with beneficial effects on mortality, respiratory distress syndrome, and adverse composite outcomes in extremely and very preterm SGA infants, with similar efficacy on all neonatal outcomes except for respiratory distress syndrome observed in the non-SGA infants.

Point: Antenatal corticosteroid treatment in the late preterm period-Are the benefits worth the potential risks?

Point: Antenatal corticosteroid treatment in the late preterm period-Are the benefits worth the potential risks?

DNA methylation signatures in human neonatal blood following maternal antenatal corticosteroid treatment

DNA methylation signatures in human neonatal blood following maternal antenatal corticosteroid treatment