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Preterm birth (PTB; delivery prior to 37 weeks' gestation) is the leading cause of early childhood death in Singapore today. Approximately 9% of Singaporean babies are born preterm; the PTB rate is likely to increase given the increased use of assisted reproduction technologies, changes in the incidence of gestational diabetes/high body mass index and the ageing maternal population. Antenatal administration of dexamethasone phosphate is a key component of the obstetric management of Singaporean women who are at risk of imminent preterm labour. Dexamethasone improves preterm outcomes by crossing the placenta to functionally mature the fetal lung. The dexamethasone regimen used in Singapore today affords a very high maternofetal drug exposure over a brief period of time. Drawing on clinical and experimental data, we reviewed the pharmacokinetic profile and pharmacodynamic effects of dexamethasone treatment regimen in Singapore, with a view to creating a development pipeline for optimising this critically important antenatal therapy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of dexamethasone administration on cardiotocographic parameters. Material & Methods: A prospective cohort study was carried out in the department of Obstetrics and Gynaecology in collaboration with Department of physiology, Jawaharlal Nehru Medical College & Hospital. Total 100 pregnant women between gestational age of 28 weeks to 38 weeks were enrolled in the study. They underwent cardiotocography on day 0 i.e. before administration of injection dexamethasone, on day 2 (after 48 hours of first dose) and on day 4-7. Patients received injection dexamethasone 6 mg i.m. 4 doses at an interval of 12 hours for various indications like preterm labor (PTL), preterm prelabor rupture of membrane (PPROM), placenta previa and previous CS. Outcome measures were changes in Baseline FHR(Fetal Heart Rate), Baseline variability, Acceleration and DFMC before and after dexamethasone administration. Results: All parameters including Baseline FHR, Accelerations, baseline variability and daily fetal movement counts were significantly reduced on day 2 of injection dexamethasone administration and returned to baseline values after 4 to 7 days of receiving dexamethasone. Conclusions: Dexamethasone administration resulted in transient reduction in baseline FHR, acceleration, variability and DFMC that mimic fetal compromise, hence clinicians should be aware of this phenomena to avoid iatrogenic preterm delivery of the fetus. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: To investigate the association between late preterm antenatal corticosteroid treatment and outcome in late preterm neonates born to mothers with gestational diabetes mellitus, Methods: All 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. Results: This 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. Conclusions: Antenatal 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. [ABSTRACT FROM AUTHOR]

Background: Hypertensive disorders of pregnancy (HDP) is the most common cause of indicated preterm delivery, but the impact of prenatal steroid exposure on the outcomes of preterm infants born to HDP mothers, who may be at risk for intrauterine hypoxia-ischemia, remains uncertain. The study objective is to evaluate the mortality and morbidities in HDP for very preterm infants (VPIs) exposed to different course of ANS. Methods: This is a prospective cohort study comprising infants with < 32 weeks gestation born to women with HDP only from 1 Jan. 2019 to 31 Dec. 2021 within 40 participating neonatal intensive care units (NICUs) in Sino-northern network. ANS courses included completed, partial, repeated, and no ANS. Univariate and multivariable analyses were performed on administration of ANS and short-term outcomes before discharge. Results: Among 1917 VPIs born to women with HDP only, 987(51.4%) received a complete course of ANS within 48 h to 7 days before birth, 560(29.2%) received partial ANS within 24 h before delivery, 100(5.2%) received repeat ANS and 270 (14.1%) did not receive any ANS. Compared to infants who received complete ANS, infants unexposed to ANS was associated with higher odds of death (AOR 1.85; 95%CI 1.10, 3.14), Severe Neurological Injury (SNI) or death (AOR 1.68; 95%CI 1.29,3.80) and NEC or death (AOR 1.78; 95%CI 1.55, 2.89), the repeated ANS group exhibits a significant negative correlation with the duration of oxygen therapy days (correlation coefficient − 18.3; 95%CI-39.2, -2.1). However, there were no significant differences observed between the full course and partial course groups in terms of outcomes. We can draw similar conclusions in the non-SGA group, while the differences are not significant in the SGA group. From KM curve, it showed that the repeated group had the highest survival rate, but the statistical analysis did not indicate a significant difference. Conclusions: Even partial courses of ANS administered within 24 h before delivery proved to be protective against death and other morbidities. The differences mentioned above are more pronounced in the non-SGA group. Repeat courses demonstrate a trend toward protection, but this still needs to be confirmed by larger samples. [ABSTRACT FROM AUTHOR]

Background: Cesarean delivery (CD) is associated with increased maternal and neonatal morbidity compared to vaginal delivery, particularly in cases classified as emergency procedures or when there are multiple CDs. This retrospective cohort study aims to examine the incidence of maternal and neonatal complications in women with multiple CDs.Methods: This study used data from a national perinatal database obtained from a single tertiary maternity care hospital. Women who delivered a singleton live birth after 24 weeks of gestation by CD were stratified into five groups based on the number of CDs, with the last group having five or more CDs. The women were divided into those with five or more CDs (Group 5) versus those with fewer than five (Groups 1 to 4). The maternal outcomes included intra-operative surgical complications, blood loss, and intensive care unit (ICU) admission. The neonatal outcomes included preterm birth, neonatal ICU (NICU) admission, respiratory distress syndrome (RDS), and perinatal death.Results: Of the 6,316 women in the study, 2,608 (41.3%) had a primary CD. 30.3%, 17.5%, and 7.3% of the cohort had their second, third, and fourth CDs, respectively. Women undergoing the 5th CD and above formed the remaining 3.5% (227). Women in Group 5 had the highest risk of suffering a surgical complication (3.1%, p = 0.015) and postpartum hemorrhage (7.5%, p = 0.010). 24% of babies in Group 5 were born preterm (p < 0.001). They also had a 3.5 times higher risk of having a surgical complication (RR = 3.5, 95% CI 1.6-7.6, p = 0.002), a 1.8 times higher risk of developing postpartum hemorrhage (RR = 1.8, 95% CI 1.1-2.9, p = 0.014), a 1.7 times higher risk of delivering between 32-37 weeks of gestation (RR = 1.7, 95% CI 1.3-2.2, p < 0.001), a higher risk of the baby getting admitted to NICU (RR = 1.3, 95% CI 1.0-1.6, p = 0.038), and developing RDS (RR = 1.5, 95% CI 1.2-2.0, p = 0.002) compared to Groups 1-4. The risks of neonatal outcomes such as NICU admission (RR 2.9, 95% CI 2.1-4.0) and RDS (RR 3.5, 95% CI 2.3-5.5) were much higher in elective CDs performed at term compared to preterm births (p < 0.001 for both).Conclusion: Maternal morbidity significantly increases with the increasing number of CD. The increased risk of RDS and NICU admissions in the neonate with multiple CDs reflects lower gestational age and birthweight in these groups—consideration of preoperative steroids for lung maturation in these women to reduce neonatal morbidity warrants further discussion. [ABSTRACT FROM AUTHOR]

The administration of antenatal corticosteroids (ACS) to accelerate fetal lung maturation is considered one of the most valuable antenatal therapies in preterm labour. Although early indications that administering antenatal corticosteroids has a positive impact on fetal lung maturation and despite the widespread recommendations to use this treatment in women at risk of preterm birth, there is still some uncertainty regarding its effectiveness, particularly in lower-resource settings and in high-risk groups such as women with hypertension or multiple pregnancies. The optimal timing of administration has not improved in over 50 years. This assessment aimed to evaluate the effects of administering a course of corticosteroids to women before anticipated preterm birth (before 37 weeks of pregnancy) on fetal and neonatal morbidity and mortality, maternal mortality and morbidity, and the child's health later in life. It is advised that clinicians only administer a single course of ACS in high-risk cases of preterm birth likely to occur within the next seven days, and the gestational age is between 22+0 and 33+6 weeks. The diagnosis of preterm labour should be made based on available resources and expertise and supported by comprehensive protocols in the relevant setting. [ABSTRACT FROM AUTHOR]

Introduction: Vasa previa, a condition where unprotected fetal blood vessels lie in proximity to the internal cervical opening, is a potentially lethal obstetric complication. The precarious situation of these vessels increases the risk of fetal hemorrhage with spontaneous or artificial rupture of membranes, frequently causing fetal/neonatal demise or severe morbidity. As a result, in many centers, inpatient management forms the mainstay when vasa previa is diagnosed antenatally. This study aimed to determine whether a subpopulation of pregnancies diagnosed antenatally with vasa previa could be safely managed as outpatients. Material and methods: We reviewed all cases of vasa previa in singleton pregnancies, with no fetal anomalies, diagnosed at Mount Sinai Hospital, Toronto, from January 2008 to December 2017. Cases were categorized into three arms for analysis: outpatients (OP), asymptomatic hospitalized (ASH) and symptomatic hospitalized (SH). The SH arm included patients admitted with any antepartum bleeding or suspicious fetal non‐stress test. Those that presented with symptomatic uterine activity/threatened preterm labor and delivered within 7 days of diagnosis were excluded from the study. Records were analyzed for details on hospitalization, antenatal corticosteroid administration, cervical length measurements, and fetal/neonatal mortality and morbidity. Results: Of the 84 antenatally‐diagnosed cases of vasa previa, 47 fulfilled eligibility criteria. A total of 15 cases were managed as OP, 22 as ASH and 10 as SH. Unplanned cesareans were highest in the SH arm (40% vs. 0% ASH vs. 13.3% OP). Those in the SH arm delivered earliest (median 33.8 weeks, interquartile range (IQR) 33.2–34.3 weeks). Of the asymptomatic patients, those in the ASH arm delivered earlier than those in the OP arm (35.3 [34.6–36.2] weeks vs. 36.7 [35.6–37.2] weeks, p = 0.037). There were no cases of fetal/neonatal death, anemia or severe neonatal morbidity and no significant differences between groups based on cervical length or antenatal corticosteroid administration. Conclusions: Our study suggests that asymptomatic women with an antenatal diagnosis of vasa previa, singleton pregnancies, and at low risk for preterm birth may safely managed as outpatients, as long as they are able to access hospital promptly in the event of antepartum bleeding or early labor. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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Background: The use of antenatal corticosteroids beyond 34 weeks of gestation to prevent certain neonatal complications remains a debate. This study sought to determine the effect of the use of antenatal corticosteroids in late preterm delivery on neonatal morbidity. Methodology: It was a randomized double-blind placebo and active-controlled multi-arm trial. There were two study groups and one control group. It was conducted at the Department of Obstetrics and Gynaecology and the Department of Paediatrics of Ahmadu Bello University Teaching Hospital Zaria, Nigeria. Pregnant women at 34 weeks to 36 weeks 6 days of gestation scheduled for elective delivery or who had emergency delivery were recruited for the study. The first study group had 2 doses of 12mg intramuscular dexamethasone and the second study group had 2 doses of 12mg betamethasone. The control group had 2 doses of a placebo. The primary outcome was the incidence of respiratory distress syndrome evidenced by tachypnoea with grunting, recession, or nasal flaring with diffuse reticulogranular infiltrate on X-ray or respiratory distress requiring the need for respiratory support by 72 hours of age. Secondary outcome measures included the need for neonatal resuscitation at birth, admission into the Special Care Baby Unit/Neonatal Intensive Care Unit, transient tachypnoea of the newborn, and apnoea. Results: A total of 138 mothers and 146 preterm neonates were included. A pairwise analysis was done to test for differences between the groups. There was no difference in the incidence of respiratory distress syndrome between the groups. However, the need for neonatal resuscitation was significantly higher (RR: 7.0; CI: 2.49-19.4; p = <0.001) in the placebo group when compared to the betamethasone group and also significantly higher (RR:4.0; CI: 1.86-26.03; p= 0.01) in the placebo group when compared to the dexamethasone group. Conclusion: Antenatal corticosteroids may decrease the need for neonatal resuscitation at birth in late preterm neonates. Funding: The research was funded by the Tertiary Education Trust Fund (TETFUND) of Nigeria. Trial registration: ClinicalTrial.gov, NCT03446937. [ABSTRACT FROM AUTHOR]

Background: Antenatal corticosteroids (ACS) are recommended in threatened preterm labour to improve short‐term neonatal outcome. Preclinical animal studies suggest detrimental effects of ACS exposure on offspring cardiac development; their effects in humans are unknown. Objectives: To systematically review the human clinical literature to determine the effects of ACS on offspring cardiovascular function. Search strategy: A systematic review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) guidelines in MEDLINE, EMBASE and Cochrane databases. Selection criteria: Offspring who had been exposed to ACS during fetal life, in comparison with those not receiving steroids, those receiving a placebo or population data, were included. Studies not performed in humans or that did not assess cardiovascular function were excluded. Data collection and analysis: Two authors independently screened the studies, extracted the data and assessed the quality of the studies. Results were combined descriptively and analysed using a standardised Excel form. Main results: Twenty‐six studies including 1921 patients were included, most of which were cohort studies of mixed quality. The type of ACS exposure, gestational age at exposure, dose and number of administrations varied widely. Offspring cardiovascular outcomes were assessed from 1 day to 36 years postnatally. The most commonly assessed parameter was arterial blood pressure (18 studies), followed by echocardiography (eight studies), heart rate (five studies), electrocardiogram (ECG, three studies) and cardiac magnetic resonance imaging (MRI, one study). There were no clinically significant effects of ACS exposure on offspring blood pressure. However, there were insufficient studies assessing cardiac structure and function using echocardiography or cardiac MRI to be able to determine an effect. Conclusions: The administration of ACS is not associated with long‐term effects on blood pressure in exposed human offspring. The effects on cardiac structure and other measures of cardiac function were unclear because of the small number, heterogeneity and mixed quality of the studies. Given the preclinical and human evidence of potential harm following ACS exposure, there is a need for further research to assess central cardiac function in human offspring exposed to ACS. Linked article: This article is commented on by Peter W. Nathanielsz, pp. 334‐335 in this issue. To view this mini commentary visit https://doi.org/10.1111/1471-0528.17346 [ABSTRACT FROM AUTHOR]

Respiratory distress syndrome (RDS) care pathways evolve slowly as new evidence emerges. We report the sixth version of "European Guidelines for the Management of RDS" by a panel of experienced European neonatologists and an expert perinatal obstetrician based on available literature up to end of 2022. Optimising outcome for babies with RDS includes prediction of risk of preterm delivery, appropriate maternal transfer to a perinatal centre, and appropriate and timely use of antenatal steroids. Evidence-based lung-protective management includes initiation of non-invasive respiratory support from birth, judicious use of oxygen, early surfactant administration, caffeine therapy, and avoidance of intubation and mechanical ventilation where possible. Methods of ongoing non-invasive respiratory support have been further refined and may help reduce chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease, although minimising time spent on mechanical ventilation by targeted use of postnatal corticosteroids remains essential. The general care of infants with RDS is also reviewed, including emphasis on appropriate cardiovascular support and judicious use of antibiotics as being important determinants of best outcome. We would like to dedicate this guideline to the memory of Professor Henry Halliday who died on November 12, 2022.These updated guidelines contain evidence from recent Cochrane reviews and medical literature since 2019. Strength of evidence supporting recommendations has been evaluated using the GRADE system. There are changes to some of the previous recommendations as well as some changes to the strength of evidence supporting recommendations that have not changed. This guideline has been endorsed by the European Society for Paediatric Research (ESPR) and the Union of European Neonatal and Perinatal Societies (UENPS). [ABSTRACT FROM AUTHOR]

Background: The external validity of randomised trials can be compromised when trial participants differ from real‐world populations. In the Antenatal Late Preterm Steroids (ALPS) trial of antenatal corticosteroids at late preterm ages, participants had systematically younger gestational ages than those outside the trial setting. As risk of respiratory morbidity (the primary trial outcome) is higher at younger gestations, absolute benefits of corticosteroids calculated in the trial population may overestimate real‐world treatment benefits. Objectives: To estimate the real‐world absolute risk reduction and number‐needed‐to‐treat (NNT) for antenatal corticosteroids at late preterm ages, accounting for gestational age differences between the ALPS and real‐world populations. Methods: Individual participant data from the ALPS trial (which recruited 2831 women with imminent preterm birth at 34+0 to 36+5 weeks') was appended to population‐based data for 15,741 women admitted for delivery between 34+0 and 36+5 weeks' from British Columbia, Canada, 2000–2013. We used logistic regression to calculate inverse odds of sampling weights for each trial participant and re‐estimated treatment effects of corticosteroids on neonatal respiratory morbidity in ALPS participants, weighted to reflect the gestational age distribution of the population‐based (real‐world) sample. Results: The real‐world absolute risk reduction was estimated to be −2.2 (95% CI −4.6, 0.0) cases of respiratory morbidity per 100, compared with −2.8 (95% CI −5.3, −0.3) in original trial data. Corresponding NNTs were 46 in the real‐world setting vs 35 in the trial. Our focus on absolute measures also highlighted that the benefits of antenatal corticosteroids may be meaningfully greater at 34 weeks vs. 36 weeks (e.g., risk reductions of −3.7 vs. −1.2 per 100 respectively). Conclusions: The absolute risk reductions and NNTs associated with antenatal corticosteroid administration at late preterm ages estimated in our study may be more appropriate for patient counselling as they better reflect the anticipated benefits of treatment when used in a real‐world situation. [ABSTRACT FROM AUTHOR]

The WHO ACTION-I trial, the largest placebo-controlled trial on antenatal corticosteroids (ACS) efficacy and safety to date, reaffirmed the benefits of ACS on mortality reduction among early preterm newborns in low-income settings. We discuss here lessons learned from ACTION-I trial that are relevant to a strategy for ACS implementation to optimize impact. Key elements included (i) gestational age dating by ultrasound (ii) application of appropriate selection criteria by trained obstetric physicians to identify women with a likelihood of preterm birth for ACS administration; and (iii) provision of a minimum package of care for preterm newborns in facilities. This strategy accurately identified a large proportion of women who eventually gave birth preterm, and resulted in a 16% reduction in neonatal mortality from ACS use. Policy-makers, programme managers and clinicians are encouraged to consider this implementation strategy to effectively scale and harness the benefits of ACS in saving preterm newborn lives. [ABSTRACT FROM AUTHOR]

Background Infants who are born at 34°/7 to 366/7 weeks of gestation (late preterm) are at greater risk for respiratory and other neonatal morbidities. The objective of this study was to examine the effects of the administration of antenatal corticosteroids (ACS) to women at risk for late preterm delivery on the incidence of neonatal outcomes. Method This was a prospective cohort study of singleton gestations at risk of imminent delivery between 34°/7 and 366/7 weeks. Neonatal outcomes were compared between mothers who received ACS and those who did not. The primary outcome was the rate of composite respiratory morbidity defined as the need for treatment within 72 h of life (continuous positive airway pressure or high flow nasal cannula for least 2 h or supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least four continuous hours or mechanical ventilation). Results During the 3-year study period, 595 subjects were included in this study, comprising 234 subjects that received ACS and 361 that did not. Administration of ACS significantly reduced the rates of composite respiratory morbidity (aOR 0.63 95% CI 0.40–0.99), the use of CPAP or HFNC for at least 2 h (aOR 0.57 95% CI 0.35–0.94), and transient tachypnea of the newborn (aOR 0.48 95% CI 0.28–0.82). Neonatal hypoglycemia was more significantly increased in the ACS group compared with controls (aOR 1.64 95% CI 1.04–2.59). We found no significant between-group differences in the rate of respiratory distress syndrome, surfactant use, need for resuscitation, jaundice requiring phototherapy, admission to neonatal intensive care or special care nursery, and duration of hospitalization. Conclusion Administration of ACS during the late preterm period decreased neonatal respiratory complications, however, increased the rate of hypoglycemia. [ABSTRACT FROM AUTHOR]

Introduction: Performing elective caesarean section prior to 39 completed weeks, it can lead to breathing problems in neonates as compare to those, who are born through caesarean section without antenatal Corticosteroid. WHO recommends the administration of intramuscular corticosteroids either dexamethasone or betamethason (total 24mg in divided doses) in the antenatal period, when there is a risk of preterm birth. The advantages and disadvantages of a similar regimen given after 37 weeks of pregnancy prior to elective caesarean section (LSCS) to prevent respiratory morbidity in a newborn is yet a topic of discussion. In Pakistan still, many clinicians are doing caesarean section at 37 or 38 weeks without antenatal Corticosteroids. The rationale is to emphasize the use of steroids before caesarean at 39 weeks. Objective: To compare neonatal respiratory distress in neonates delivered between 37--38+6 weeks of gestation by elective caesarean section with and without antenatal Corticosteroid. Study design: Randomized controlled trial. Setting: Department of Gynae & Obstetrics, unit 2, Shalamar Hospital, Lahore. Duration: Six months from 12th September 2018 to 12th March 2019. Materials and Methods: The study included women who were, planned for elective LSCS at 37-38+6 weeks, divided into two groups. The sample size was 140 (70 in each group), recruited by non-probability consécutive sampling. Inclusion criteria were singleton pregnancy, at 37 to 38+6 weeks for elective LSCS due to indications like primi breech, previous caesarian scar/scars, and maternal wish. All eligible participants were allocated to one of the following groups. Group (A) received an injection of dexamethasone 48 to 72 hours before elective LSCS. Group (B), did not receive an injection of dexamethasone. The outcome to be measured in this study were the Apgar score at 1& 5 minutes, the incidence of transient tachpnea of the neonate (TTN) and respiratory distress syndrome (RDS) in newborns, and the need for mechanical ventilation among neonates from two different groups. The data was collected and analyzed by SPSS version 20. Descriptive statistic were applied to calculate the mean and SD for age, gestation age & BMI. Student T-test was used to compare the continuous outcome measures. Neonatal respiratory morbidity was compared in two groups by using the chi-square test at the level of significance of 0.05. Results: Mean age in Group-A was 28.12± 5.6 and in Group-B was 28.97± 6.3 years. There was no statistically significant difference in these groups in terms of Body mass index, gestational age at the time of delivery, age of mother, birth weight, Apgar score at 1 and 5 min, and indications for cesarean section. Neonatal respiratory morbidity was higher in Group-B as compared to Group-A (30% vs.12.9%) p-value-0.013. Conclusion: Antenatal dexamethasone administration significantly reduces the respiratory morbidity among neonates delivered at 37 to 38+6 by elective cesarean section. But further studies are required to assess the beneficial role of dexamethasone in the reduction of neonatal respiratory morbidity with a large sample size. [ABSTRACT FROM AUTHOR]

Aim: No study has evaluated the betamethasone pharmacokinetics in twin pregnancies according to chorionicity. This study aimed to describe and compare the betamethasone pharmacokinetic parameters in singleton and dichorionic (DC) and monochorionic twin pregnancies in the third trimester of pregnancy. Methods: Twenty‐six pregnant women received 2 intramuscular doses of 6 mg of betamethasone sodium phosphate plus 6 mg betamethasone acetate due to preterm labour. Serial blood samples were collected for 24 hours after the first intramuscular dose of betamethasone esters. Betamethasone plasma concentrations were quantified using a validated liquid chromatography–tandem mass spectrometry analytical method, and the pharmacokinetic parameters were obtained employing a noncompartmental model. Preliminary data on the betamethasone placental transfer are also presented. Results: The geometric mean (95% confidence interval) of AUC0‐∞ 645.1 (504.3–825.2) vs. 409.8 (311.2–539.6) ng.h/mL and CL/F 17.70 (13.84–22.65) vs. 27.87 (21.17–36.69) were significantly different, respectively, in singleton pregnancies when compared to DC twins. Conclusion: Data from this study suggest that the presence of 2 foetoplacental units may increase the betamethasone metabolism by hepatic CYP3A4 and/or placental 11β‐HSD2 enzymes. Pharmacokinetic–pharmacodynamic clinical studies are needed to investigate whether these betamethasone pharmacokinetic changes have clinical repercussions for the newborns and require dose adjustment in DC twin pregnancies. [ABSTRACT FROM AUTHOR]

Respiratory distress syndrome is one of the most frequently researched and always of immediate interest topics, representing one of the main causes of morbidity and mortality in the neonatal population. Therefore, the antenatal ad ministration of corticosteroids in preterm births (between the 24th week and the 34th week of gestational age) is one of the most important antenatal therapies available, with a positive influence on the longterm neonatal prognosis. The effects on both the interstitium and other organs re duce the risk of respiratory distress syndrome, necrotizing enterocolitis and intracranial hemorrhage. Scientific data about corticosteroid use in women at risk for preterm birth under 34 weeks of gestation and the benefits on the new born adaptation to the extrauterine life, especially when it comes to caesarean delivery, are abundant. Of course, the benefit of corticoprophylaxis versus the possible longterm results on neurodevelopment, especially in school age, in this category of newborns should be considered. Among earlyterms and fullterm newborns, delivered by caesarean section, the pathophysiology of respiratory distress is closely related to the absorption of alveolar fluid and to the con centration of catecholamines in the fetal blood, and if there is no labor, these latter ones are affected. In this article, we present the observations obtained in a study conducted on 81 newborns from pregnancies with ages between 36 0/7 and 37 0/7 weeks, who received dexamethasone less than seven days before birth, conducted within the Obstetrics Gynecology and Neonatology Clinic of the “Elias” University Emergency Hospital, Bucharest. We compared the results with data published in the field research, having as purpose to elucidate the controversies of antenatal corticosteroid therapy for various populations and, possibly, to establish individualized therapies. [ABSTRACT FROM AUTHOR]

Abstract Background Antenatal corticosteroids (ACS) are increasingly used to improve prematurity-related neonatal outcome. A recognized and common adverse effect from administration of antenatal corticosteroid is maternal hyperglycemia. Even normal pregnancy is characterized by relative insulin resistance and glucose intolerance. Treatment of maternal hyperglycemia after ACS might be indicated due to the higher risk of neonatal acidosis which may coincide with premature birth. Metformin is increasingly used to manage diabetes mellitus during pregnancy as it is effective and more patient friendly. There is no data on prophylactic metformin to maintain euglycemia following antenatal corticosteroids administration. Methods A double blind randomized trial. 103 women scheduled to receive two doses of 12-mg intramuscular dexamethasone 12-hour apart were separately randomized to take prophylactic metformin or placebo after stratification according to their gestational diabetes (GDM) status. First oral dose of allocated study drug was taken at enrolment and continued 500 mg twice daily for 72 hours if not delivered. Six-point blood sugar profiles were obtained each day (pre- and two-hour post breakfast, lunch and dinner) for up to three consecutive days. A hyperglycemic episode is defined as capillary glucose fasting/pre-meal ≥ 5.3 mmol/L or two-hour post prandial/meal ≥ 6.7 mmol/L. Primary outcome was hyperglycemic episodes on Day-1 (first six blood sugar profile points) following antenatal corticosteroids. Results Number of hyperglycemic episodes on the first day were not significantly different (mean ± standard deviation) 3.9 ± 1.4 (metformin) vs. 4.1 ± 1.6 (placebo) p = 0.64. Hyperglycemic episodes markedly reduced on second day in both arms to 0.9 ± 1.0 (metformin) vs. 1.2 ± 1.0 (placebo) p = 0.15 and further reduced to 0.6 ± 1.0 (metformin) vs. 0.7 ± 1.0 (placebo) p = 0.67 on third day. Hypoglycemic episodes during the 3-day study period were few and all other secondary outcomes were not significantly different. Conclusions In euglycemic and diet controllable gestational diabetes mellitus women, antenatal corticosteroids cause sustained maternal hyperglycemia only on Day-1. The magnitude of Day-1 hyperglycemia is generally low. Prophylactic metformin does not reduce antenatal corticosteroids’ hyperglycemic effect. Trial registration The trial is registered in the ISRCTN registry on May 4 2017 with trial identifier https://doi.org/10.1186/ISRCTN10156101 .

Background/Aim: Although antenatal corticosteroid (ANCS) is beneficial for preventing respiratory distress in preterm infants, the effect of ANCS on late preterm infants (LPI) is still unknown. This study aimed at investigating the effect of ANCS on respiratory morbidity of LPI. Materials and Methods: In matched cohort study, LPI of mothers who received ANCS (ANCS group) at 24-34 weeks of GA were matched with LPI of no ANCS (non-ANCS group) by gestational age and birth weight. Results: During 2 years, the ANCS group was 10.6% (191/1,810) in LPI and only 177 neonates met the criteria for inclusion and were ANCS group. The mean gestational age was 34.6 ± 0.7 weeks in both groups. Birth weights were 2270 ± 405 g and 2265 ± 401 g in ANCS and non-ANCS groups, respectively. Of the 177 infants whose mothers received ANCS, overall respiratory morbidities were 31.6% comparing to 30.5% in non-steroid group. Although decrease trend toward of RDS (4% vs. 8.5%, P = 0.07) and surfactant administration (3.4% vs. 6.2%, P = 0.21) was observed in steroid group, administration of steroid < 24 h before gestation significantly increase RDS compared with non-treatment (33.3% vs. 8.5%, P = 0.04). Conclusions: ANCS did not decrease risk of respiratory morbidity. Nevertheless, treatment with ANCS for a short period (<24 h) may increase RDS in LPI. [ABSTRACT FROM AUTHOR]

To assess the frequency of antenatal corticosteroid (ACS) administration in cases with shortened cervical length by addition of placental alpha-microglobulin-1 (PAMG-1) testing to sonographic examination. Single centre retrospective cohort study. Rate of ACS administration was compared between cases with cervical length between 15 and 25 mm and cases with positive PAMG-1 testing and cervical length between 15 and 25 mm. We evaluated the following outcome parameters: Rate of ACS administration, gestational age at delivery, time to delivery, delivery within seven days, delivery <34 and <37 weeks' gestation, rate of admission to neonatal intensive care unit (NICU). In total, 130 cases were included. "PAMG-1 group" consisted of 68 women, 62 cases built the "historical control group". ACS administration was performed less frequently in the "PAMG-1 cohort" (18 (26%) vs. 46 (74%); p<0.001). The rate of delivery within seven days did not differ (2 (3%) vs. 4 (6.5%); p=0.4239). The rates of delivery <34 weeks' gestation (7 (10%) vs. 9 (15%); p=0.4643) and <37 weeks' gestation (19 (28%) vs. 26 (42%); p=0.0939) did not differ. Time to delivery interval was longer in the PAMG-1 group (61.5 vs. 43 days, p=0.0117). NICU admission occurred more often in the "historical control group" (22 (38%) vs. 28 (60%); p=0.0272). Addition of biomarker testing can help to avoid unnecessary ACS administrations in women with shortened cervical length. [ABSTRACT FROM AUTHOR]

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 24 h 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, 24 h 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. [ABSTRACT FROM AUTHOR]

The administration of antenatal corticosteroids has been widely adopted as the standard of care in the management of pregnancies at risk for preterm delivery before 37 weeks of gestation, with the primary goal of reducing neonatal morbidity. However, the long-term risks associated with antenatal corticosteroid use remain uncertain. The purpose of this Consult is to review the current literature on the benefits and risks of antenatal corticosteroid use in the late preterm period and to provide recommendations based on the available evidence. The recommendations by the Society for Maternal-Fetal Medicine are as follows: (1) we recommend offering a single course of antenatal corticosteroids (2 doses of 12 mg of intramuscular betamethasone 24 hours apart) to patients who meet the inclusion criteria of the Antenatal Late Preterm Steroids trial, ie, those with a singleton pregnancy between 34 0/7 and 36 6/7 weeks of gestation who are at high risk of preterm birth within the next 7 days and before 37 weeks of gestation (GRADE 1A); (2) we suggest consideration for the use of antenatal corticosteroids in select populations not included in the original Antenatal Late Preterm Steroids trial, such as patients with multiple gestations reduced to a singleton gestation on or after 14 0/7 weeks of gestation, patients with fetal anomalies, or those who are expected to deliver in <12 hours (GRADE 2C); (3) we recommend against the use of antenatal corticosteroids for fetal lung maturity in pregnant patients with a low likelihood of delivery before 37 weeks of gestation (GRADE 1B); (4) we recommend against the use of late preterm corticosteroids in pregnant patients with pregestational diabetes mellitus, given the risk of worsening neonatal hypoglycemia (GRADE 1C); (5) we recommend that patients at risk for late preterm delivery be thoroughly counseled regarding the potential risks and benefits of antenatal corticosteroid administration and be advised that the long-term risks remain uncertain (GRADE 1C). [ABSTRACT FROM AUTHOR]

Purpose: Treatment with antenatal corticosteroids (ACS) to women at risk for preterm birth (PTB) is associated with a reduction in adverse neonatal outcomes. Obstetricians occasionally shorten the interval between the doses of steroids if delivery is predicted to occur before ACS are fully administered. In this study, we aimed to investigate predicting factors to identify patients that will deliver prematurely, less than 48 h from presentation. Methods: The computerized medical files of all PTBs (< 34 weeks) were reviewed. Maternal demographics, pregnancy and delivery characteristics were compared between PTB that occurred < 48 h vs. > 48 h from triage presentation. Results: In total, 494 PTB cases were included: 302 women in the study group (PTB < 48 h) and 192 women in the control group (PTB > 48 h). No significant differences were found in demographic characteristics between the groups. At presentation, the study group had higher rates of uterine contractions (p < 0.001) and cervical length < 25 mm (p < 0.001) as well as a higher rate of non-reassuring fetal (NRFHR) monitor (p < 0.001). In contrast, the control group presented with higher rates of preeclampsia (p = 0.003) and preterm premature rupture of membranes (p = 0.038). In multivariable analysis, all of the above factors remained significant after controlling for background confounders. Conclusions: Various factors at presentation can predict delivery < 48 h. These factors can be used to predict patients to whom the ACS interval should be shortened. Future prospective studies should investigate the effect of this shortening on neonatal outcomes. [ABSTRACT FROM AUTHOR]

Although delivery timing is physician dictated in indicated preterm births, suboptimal antenatal corticosteroids (ACS) administration occurs in most cases. We aimed to characterize the patterns of use of ACS in indicated preterm births and identify missed opportunities of optimal ACS administration. We reviewed the records of women who received ACS and were delivered due to maternal or fetal indications at 24–34 weeks of gestation during 2015–2017 at a university hospital. Optimal ACS timing was defined as delivery ≥24 h ≤7 d from the previous ACS course. Overall, 188 pregnancies were included. The median gestational age at delivery was 32 weeks. Considering only the initial ACS course, the rate of optimal timing was 32.4%. Of 105 (55.8%) women eligible (delivery >7 d since the initial ACS course), only a third (n = 38) received a rescue ACS course. Among women who did not receive rescue ACS course despite their eligibility (n = 67), the decision-to-delivery was ≥3 h in 36 (53.7%), and ≥24 h in 20 (29.9%), representing 19.1 and 10.6% of the entire cohort, respectively. The urgency of the decision to deliver (i.e. in the upcoming 24 h and later) and allowing a trial of labor, were both positively associated with decision-to-delivery interval ≥3 h and ≥24 h. The rate of delivery within any optimal window (either initial or rescue course) was 40.4%, with gestational hypertensive disorders (OR [95% CI]: 2.40 (1.23, 4.72), p =.01) and decision to deliver made at first hospitalization (OR [95% CI]: 2.27 (1.04, 4.76), p =.04) as independent positive predictors of optimal ACS timing. The rate of composite adverse neonatal outcome was significantly lower in those with optimal ACS administration as compared to those with suboptimal timing (32.9 versus 50.9%, OR [95% CI]: 0.47 (0.26, 0.87), p =.02). Suboptimal ACS administration occurred in most indicated preterm births. Underutilization of rescue ACS course and a substantial rate of missed opportunities for optimal ACS administration were identified as potentially modifiable contributors to improve ACS timing. [ABSTRACT FROM AUTHOR]

Background: Betamethasone (BMZ) is used to accelerate fetal lung maturation in women with threatened preterm birth, but its efficacy is variable and limited by the lack of patient individualization in its dosing and administration. To determine sources of variability and potential opportunities for individualization of therapy, the objective of this study was to evaluate maternal factors associated with development of neonatal respiratory distress syndrome (RDS) in a cohort of women who received betamethasone.Methods: This study prospectively enrolled women, gestational ages 23-34 weeks, who received betamethasone for threatened preterm birth. Maternal demographics, prenatal history, and neonatal outcomes were abstracted from hospital records. RDS was the primary outcome. Associations between RDS diagnosis and maternal demographics, prenatal history, and betamethasone dosing were evaluated in a case-control analysis and multivariable regression adjusted for gestational age at delivery. Secondary analyses limited the cohort to women who delivered within 1 or 2 weeks of betamethasone dosing.Results: Of 209 deliveries, 90 (43 %) resulted in neonatal RDS. Within the overall cohort and controlling for gestational age at birth, RDS was only associated with cesarean births compared to vaginal births (adjusted OR 1.17 [1.06-1.29]). Route of delivery was also the only significant factor related to RDS in the 83 neonates delivered within 7 days of BMZ dosing. However, among 101 deliveries within 14 days of betamethasone dosing and controlling for gestational age at birth, women who experienced preterm premature rupture of membranes (PPROM) had lower RDS rates than those without PPROM (57.9 % vs. 80.2 %, adjusted OR 0.81 [0.67-0.99]). Maternal age, BMI, race, and ethnicity were not associated with RDS in the regression models.Conclusions: Of maternal characteristics analyzed, only delivery by cesarean was associated with neonatal RDS after antenatal betamethasone use. [ABSTRACT FROM AUTHOR]

Randomized controlled trials (RCTs) are a cornerstone for the assessment of the effectiveness of interventions. Appropriate randomization, design, sample size, statistical analyses, and conduct that reduces the risk of bias, enhance the chance they will deliver true research findings. The credibility of RCTs is difficult to assess without objective evidence of compliance with Good Clinical Practice standards. Remarkably, no mechanisms are in place both in the initial peer review process and during meta-analysis to assess these, and little guidance on how to assess data where research integrity cannot be confirmed (e.g. where data originated from a setting without established infrastructure or an era preceding current standards). We describe the case of the use of antenatal steroids. When these drugs are used in early preterm birth, their benefits outweigh the harms. However, later in pregnancy, and specifically at term, this balance is less clear. We describe that the four randomised clinical trials that inform clinical practice through the Cochrane meta-analysis, for various reasons, lack clear governance which makes it difficult to verify provenance and reliability of the data. We conclude that transparency and assessment of data credibility need to be inbuilt both at the time of publication and at the time of meta-analysis. This will drive up standards and encourage appropriate interpretation of results and the context from which they were derived. [ABSTRACT FROM AUTHOR]

Objective: To identify risk factors associated with neonatal intermediate or intensive care unit (NICU) stay ≥3 days among women with threatened late preterm birth (PTB).Study Design: Secondary analysis of women with nonanomalous, singleton gestations enrolled in multicenter trial of betamethasone versus placebo for late PTB. Maternal and obstetric characteristics at time of presentation with threatened PTB were compared between those with and without NICU stay ≥3 days. Multivariable logistic regression identified risk factors for NICU stay ≥3 days.Result: Of 2795 eligible mother-neonate dyads, 962 (34%) had NICU stay ≥3 days. Gestational age and fetal growth restriction as the reason for threatened PTB had the strongest association with NICU stay ≥3 days in the final model (AUC 0.76).Conclusion: Maternal and obstetric characteristics at the time of admission for threatened late PTB should be considered when counseling patients about the probability of NICU stay ≥3 days. [ABSTRACT FROM AUTHOR]

Background: Antenatal corticosteroids (ACS) are increasingly used to improve prematurity-related neonatal outcome. A recognized and common adverse effect from administration of antenatal corticosteroid is maternal hyperglycemia. Even normal pregnancy is characterized by relative insulin resistance and glucose intolerance. Treatment of maternal hyperglycemia after ACS might be indicated due to the higher risk of neonatal acidosis which may coincide with premature birth. Metformin is increasingly used to manage diabetes mellitus during pregnancy as it is effective and more patient friendly. There is no data on prophylactic metformin to maintain euglycemia following antenatal corticosteroids administration.Methods: A double blind randomized trial. 103 women scheduled to receive two doses of 12-mg intramuscular dexamethasone 12-hour apart were separately randomized to take prophylactic metformin or placebo after stratification according to their gestational diabetes (GDM) status. First oral dose of allocated study drug was taken at enrolment and continued 500 mg twice daily for 72 hours if not delivered. Six-point blood sugar profiles were obtained each day (pre- and two-hour post breakfast, lunch and dinner) for up to three consecutive days. A hyperglycemic episode is defined as capillary glucose fasting/pre-meal ≥ 5.3 mmol/L or two-hour post prandial/meal ≥ 6.7 mmol/L. Primary outcome was hyperglycemic episodes on Day-1 (first six blood sugar profile points) following antenatal corticosteroids.Results: Number of hyperglycemic episodes on the first day were not significantly different (mean ± standard deviation) 3.9 ± 1.4 (metformin) vs. 4.1 ± 1.6 (placebo) p = 0.64. Hyperglycemic episodes markedly reduced on second day in both arms to 0.9 ± 1.0 (metformin) vs. 1.2 ± 1.0 (placebo) p = 0.15 and further reduced to 0.6 ± 1.0 (metformin) vs. 0.7 ± 1.0 (placebo) p = 0.67 on third day. Hypoglycemic episodes during the 3-day study period were few and all other secondary outcomes were not significantly different.Conclusions: In euglycemic and diet controllable gestational diabetes mellitus women, antenatal corticosteroids cause sustained maternal hyperglycemia only on Day-1. The magnitude of Day-1 hyperglycemia is generally low. Prophylactic metformin does not reduce antenatal corticosteroids' hyperglycemic effect.Trial Registration: The trial is registered in the ISRCTN registry on May 4 2017 with trial identifier https://doi.org/10.1186/ISRCTN10156101 . [ABSTRACT FROM AUTHOR]

Purpose: To evaluate whether antenatal corticosteroids (ACS) administration during the late-preterm (LPT) period in twin pregnancies is associated with decreased rate of neonatal morbidity. Methods: A retrospective cohort study including a total of 290 women with twin pregnancies resulting in live births of 580 neonates who delivered during LPT period between 2016 and 2018 at a tertiary medical center. Patients were allocated into two groups according to ACS exposure. Obstetric and neonatal outcomes were compared between the groups. Primary outcome was neonatal composite respiratory morbidity, defined as the occurrence of at least one of the followings: RDS, TTN, O2 requirement, CPAP use or mechanical ventilation. Results: Patients exposed to ACS were older and more commonly complicated by gestational diabetes compared to the non-exposed group. Moreover, women exposed to ACS delivered earlier (35.6 vs. 36.3 weeks, P < 0.001) and more frequently by cesarean section (76.4% vs. 54.1%, P = 0.002) compared to the non-exposed group. The rate of composite respiratory morbidity did not differ between the groups. Nevertheless, neonates exposed to ACS had higher rates of neonatal intensive care unit (NICU) admission and hypoglycemia compared to neonates without prior ACS exposure (27.8% vs. 11.7%, P = 0.001; 49.3% vs. 27.1%, P < 0.001, respectively). Multivariable logistic regression revealed that gestational age at delivery was the sole independent risk factor for NICU admission, whereas late-preterm ACS exposure was the only risk factor for hypoglycemia. Conclusion: LPT–ACS administration in twin pregnancies complicated by LPT birth in our study did not reduce neonatal respiratory morbidity but was associated with higher rates of hypoglycaemia. [ABSTRACT FROM AUTHOR]

Introduction: Our main objective was to evaluate whether antenatal corticosteroids increase the risk of small head circumference in children born at term. Secondary objectives were to evaluate whether they increase the risk of small birthweight and birth length among those children.Material and Methods: A historical cohort included 275 270 live term born children between 2000 and 2013 in 175 French maternity units. The rate of head circumference below the 5th percentile among children born at term and exposed to antenatal corticosteroids was compared with that of two unexposed groups: those children born at term whose mothers had an episode of threatened preterm labor without corticosteroids and those whose mothers had neither threatened preterm labor nor corticosteroids. The association between this treatment and head circumference was evaluated by calculating adjusted risk ratios (aRRs) and their 95% confidence intervals (CIs). The main outcome measure was a head circumference below the 5th percentile at birth, adjusted for sex, and gestational age according to the Pediatric, Obstetrics, and Gynecology Electronic Records Users Association (AUDIPOG) curves. Secondary outcomes were birthweight and birth length below the 5th percentile.Results: The rate of head circumference below the 5th percentile was 5.8% (n = 3388) among children exposed to antenatal corticosteroids and 4.3% (n = 7077) and 4.6% (n = 198 462), respectively, for the two unexposed groups. After adjustment, the risk of having a head circumference below the 5th percentile did not differ between the exposed group and the two control groups (aRR 1.28, 95% confidence interval [CI] 0.97-1.69] and aRR 0.91, 95% CI 0.74-1.13). We did not find an association between antenatal corticosteroids and the rate of birthweight below the 5th percentile. Children exposed to antenatal corticosteroids had a higher risk of a birth length below the 5th percentile when compared with those not exposed to threatened preterm labor or corticosteroids.Conclusions: We found no association between antenatal corticosteroids and increased risk of head circumference below the 5th percentile in children born at term. [ABSTRACT FROM AUTHOR]

Objective: To evaluate variation in management of diabetic women with threatened preterm birth (PTB).Study design: Thirty-two-question electronic maternal-fetal medicine (MFM) provider survey advertised on the Society for MFM website, newsletter, and Facebook page with questions about antenatal steroid use in diabetic women and glycemic management strategy after steroid administration. Descriptive statistics were used to summarize respondent characteristics, practice patterns, and satisfaction with current practice. Multivariable logistic regression was performed to determine if there were any factors independently associated with provider-reported satisfaction.Result: We obtained 159 completed surveys: 69% from board-certified MFM providers and 31% from MFM fellows. Almost half (48%) of respondents reported caring for diabetic women with threatened PTB at least weekly. Overall, 74% were concerned about the risk of maternal hyperglycemia after steroids, but 86% believed the neonatal benefit outweighed maternal risk. More than half (64%) agreed or strongly agreed that steroids for diabetic pregnant women were "evidence-based," and as such, the majority answered that they administer steroids always or most of the time, ranging from 92% for women with uncontrolled type 1 diabetes to 100% for women with diet-controlled gestational diabetes. The frequency of hospitalization and management approach to obtain glycemic control varied by diabetes type and degree of antepartum glycemic control. Two-thirds of MFM providers reported being satisfied with their current practice in caring for these women. Use of a standard protocol for glycemic management was also associated with increased odds of satisfaction (aOR 4.5, 95% CI 1.3-16.1) whereas use of a continuous insulin infusion for all women with insulin-dependent diabetes was associated with decreased odds of satisfaction (aOR 0.3, 95% CI 0.1-0.8). There was no significant association observed between number of years in practice or frequency of care for diabetic women with threatened PTB and provider satisfaction. Overall, 49% of respondents desired a protocol to guide glycemic management, and 74% believed more research is needed to optimize care of diabetic women receiving steroids for threatened PTB.Conclusion: While there are no prospective studies examining the neonatal benefit of antenatal steroids in diabetic women, MFM respondents believe steroid use in this context is evidence-based and report they are administering steroids almost universally in this population. Variation exists in the glycemic management strategy used after steroid administration. While use of a standard protocol for glycemic control was associated with practice satisfaction, routine use of a continuous insulin infusion for all women with insulin-dependent diabetes was associated with lower odds of satisfaction. More research is needed to optimize care of diabetic women receiving steroids for threatened PTB as maternal and neonatal outcomes related to these practices remain unknown. [ABSTRACT FROM AUTHOR]

Antenatal corticosteroids have been used for the prevention of respiratory complications, intraventricular hemorrhage, necrotizing enterocolitis, and other adverse neonatal outcomes for over 50 years, with limited evidence about their optimal doses. Higher steroid doses or frequencies of antenatal corticosteroids in preterm newborns pose adverse effects such as prolonged adrenal suppression, negative effects on fetal programming and metabolism, and increased risks of neurodevelopmental and neuropsychological impairments. Conversely, lower doses of antenatal corticosteroids may be an effective alternative to induce fetal lung maturation with less risk to the fetus. Late preterm births represent the largest population of all preterm neonates, with a respiratory distress syndrome risk of 8.83%. Therefore, determining the optimal antenatal corticosteroid dosage is of particular importance for this population. This study aimed to compare the efficacy of 5-mg and 6-mg dexamethasone in preventing neonatal respiratory distress syndrome in women with preterm births at 320 to 366 weeks of gestation. This was an open-label, randomized, controlled, noninferiority trial. Singleton pregnant women (n=370) at 320 to 366 weeks of gestation with spontaneous preterm labor or preterm premature rupture of membranes were enrolled. They were randomly assigned (1:1) to a 5-mg or 6-mg dexamethasone group. Dexamethasone was administered intramuscularly every 12 hours for 4 doses or until delivery. The primary outcome was the reduction in neonatal respiratory distress syndrome cases, whereas the secondary outcomes were any adverse maternal or neonatal events. Between December 2020 and April 2022, 370 eligible women, anticipating deliveries within the gestational range of 32 0/7 to 36 6/7 weeks, willingly participated in the study. They were evenly split, with 185 women assigned to the 5-mg group and 185 to the 6-mg group. The study revealed that the demographic profiles of the participants in the 2 groups were remarkably similar, with no statistically significant disparities (P >.05). It is noteworthy that most of these women gave birth after 34 weeks of gestation. Despite a substantial proportion not completing the full course of steroid treatment, the 5-mg dose exhibited noninferiority compared with the 6-mg dose of dexamethasone, as indicated by a modest proportional difference of 0.5% (95% confidence interval, −2.8 to 43.9). Neonatal respiratory distress syndrome occurred in a relatively low percentage of newborns in both groups, affecting 2.2% in the 5-mg group and 1.6% in the 6-mg group. Notably, the risk difference of 0.6% fell comfortably within the predefined noninferiority threshold of 10%. Our study suggests that a 5-mg dexamethasone dose is noninferior to a standard 6-mg dose in preventing neonatal respiratory distress syndrome in preterm births. [Display omitted] [ABSTRACT FROM AUTHOR]

The efficacy of antenatal corticosteroids for neonatal preterm complications wanes beyond 7 days after treatment. The neurodevelopmental effects of longer treatment-to-birth intervals have not been adequately evaluated. This study aimed to assess the impact of antenatal corticosteroid timing on survival without moderate or severe neurologic disabilities at 5½ years. This was a secondary analysis of the EPIPAGE-2 study, a national population-based cohort (France) that recruited neonates in 2011 and followed them up at 5½ years (results first reported in 2021). Participants were children born alive between 24+0 and 34+6 weeks, with a complete corticosteroid course, delivery >48 hours after the first injection, and neither limitation of care decided before birth nor severe congenital malformation. The study included 2613 children, 2427 of whom were alive at 5½ years; 71.9% (1739/2427) had a neurologic assessment at this age; 1537 had a clinical examination (complete for 1532), and 202 were assessed with a postal questionnaire. Exposure was defined as the interval between the first injection of the last antenatal corticosteroid course and delivery in days, studied in 2 categories (days 3–7 and after day 7), in 4 categories (days 3–7, 8–14, 15–21, and after day 21), and continuously in days. The main outcome was survival at 5½ years without moderate/severe neurologic disabilities, defined as moderate/severe cerebral palsy, or unilateral or bilateral blindness or deafness, or Full-Scale Intelligence Quotient 2 standard deviations below the mean. A multivariate analysis with a generalized estimated equation logistic regression model assessed the statistical association between the main outcomes and the interval from the first corticosteroid injection of the last course to birth. Multivariate analyses were adjusted for potential confounders, defined with a directed acyclic graph: gestational age in days, number of corticosteroid courses, multiple pregnancy, and cause of prematurity in 5 categories. Because neurologic follow-up was complete in only 63.2% of cases (1532/2427), the analyses used imputed data. Among 2613 children, 186 died between birth and 5½ years. Overall survival was 96.6% (95% confidence interval, 95.9–97.0), and survival without moderate or severe neurologic disabilities was 86.0% (95% confidence interval, 84.7–87.0). Survival without moderate or severe neurologic disabilities was lower after day 7 (85.0%) than during the interval from day 3 to day 7 (87.0%) (adjusted odds ratio, 0.70; 95% confidence interval, 0.54–0.89). The association of a >7-day interval between antenatal corticosteroid administration and birth with a lower rate of survival without moderate or severe neurologic disabilities among children aged 5½ years emphasizes the importance of better targeting women at risk of preterm delivery to optimize the timing and thus benefits of treatment. [ABSTRACT FROM AUTHOR]

Background: Administrating a single course of antenatal corticosteroids to women at risk of preterm birth between 24 and 34 weeks of gestation has been shown to decrease neonatal morbidity and mortality. There is evidence that the optimal timing for the administration of antenatal corticosteroids is within 1-7 days before birth as the effect of antenatal corticosteroids has been shown to decline 7 days after administration. Therefore, given that antenatal corticosteroids are the single most effective intervention in cases of preterm birth, efforts should be made to optimize the timing of administration of antenatal corticosteroids. Objective: To test the hypothesis that the timing of antenatal corticosteroids in women with vaginal bleeding due to placenta previa or low-lying placenta can be optimized by identifying women at low risk of imminent delivery. Study design: This was a retrospective cohort study of all women admitted to a tertiary referral center at 24-34 weeks' gestation with vaginal bleeding due to placenta previa or low-lying placenta between 2003 and 2014. Multivariable logistic regression analysis was used to identify factors that are independently associated with delivery within 14 days from admission. Results: A total of 202 women who met the inclusion criteria were admitted with vaginal bleeding in the presence of placenta previa or low-lying placenta during the study period, of whom 31 (15.3%) and 44 (21.8%) gave birth within 7 and 14 days from admission, respectively. The following factors were independently associated with delivery within 14 days from admission: complete placenta previa (odds (OR) 3.57, 95%CI 1.57-9.03), severe bleeding at presentation (OR 17.14, 95%CI 2.92-100.70), uterine contractions at presentation (OR 6.02, 95%CI 1.91-19.00), and cervical length <25 mm at presentation (OR 6.33, 95%CI 1.37-29.11). A predictive test based on the presence of ≥1 of these risk factors was associated with a sensitivity of 90.9% and a negative predictive value of 94.6% for delivery within 14 days of presentation. Conclusions: In women presenting with vaginal bleeding due to placenta previa or low-lying placenta, it seems possible to identify a subgroup of women in whom the likelihood of delivery within 14 days is low. This information may allow for selective (rather than routine) administration of antenatal corticosteroids in this scenario, and may thereby contribute to the optimization of the timing of administration of antenatal corticosteroids. [ABSTRACT FROM AUTHOR]

Background: Administrating a single course of antenatal corticosteroids to women at risk of preterm birth between 24 and 34 weeks of gestation has been shown to decrease neonatal morbidity and mortality. There is evidence that the optimal timing for the administration of antenatal corticosteroids is within 1-7 days before birth as the effect of antenatal corticosteroids has been shown to decline 7 days after administration. Therefore, given that antenatal corticosteroids are the single most effective intervention in cases of preterm birth, efforts should be made to optimize the timing of administration of antenatal corticosteroids. Objective: To test the hypothesis that the timing of antenatal corticosteroids in women with vaginal bleeding due to placenta previa or low-lying placenta can be optimized by identifying women at low risk of imminent delivery. Study design: This was a retrospective cohort study of all women admitted to a tertiary referral center at 24-34 weeks' gestation with vaginal bleeding due to placenta previa or low-lying placenta between 2003 and 2014. Multivariable logistic regression analysis was used to identify factors that are independently associated with delivery within 14 days from admission. Results: A total of 202 women who met the inclusion criteria were admitted with vaginal bleeding in the presence of placenta previa or low-lying placenta during the study period, of whom 31 (15.3%) and 44 (21.8%) gave birth within 7 and 14 days from admission, respectively. The following factors were independently associated with delivery within 14 days from admission: complete placenta previa (odds (OR) 3.57, 95%CI 1.57-9.03), severe bleeding at presentation (OR 17.14, 95%CI 2.92-100.70), uterine contractions at presentation (OR 6.02, 95%CI 1.91-19.00), and cervical length <25 mm at presentation (OR 6.33, 95%CI 1.37-29.11). A predictive test based on the presence of ≥1 of these risk factors was associated with a sensitivity of 90.9% and a negative predictive value of 94.6% for delivery within 14 days of presentation. Conclusions: In women presenting with vaginal bleeding due to placenta previa or low-lying placenta, it seems possible to identify a subgroup of women in whom the likelihood of delivery within 14 days is low. This information may allow for selective (rather than routine) administration of antenatal corticosteroids in this scenario, and may thereby contribute to the optimization of the timing of administration of antenatal corticosteroids. [ABSTRACT FROM AUTHOR]

Objective: To measure the extent to which the evidence underpinning prenatal corticosteroids for preterm fetal lung maturity is at risk of bias due to selective outcome reporting.Study Design: Five biomedical databases (Medline, ClinicalTrials.gov, Embase, OVID and HMIC) were searched for trials published between February 2016 and September 2017. Randomised trials of prenatal steroids for women at risk of preterm birth were identified. For each, we recorded the registration status and timing, and whether the registered primary outcome had been reported. For unregistered trials, we estimated the potential for selective outcome reporting indirectly by tabulating all reported outcomes and by comparing the first outcome reported in the methods to the first in the results section.Results: Twenty seven trials were identified. Only three (11%) trials had been registered. All three reported their pre-specified primary outcome. Among the unregistered trials, thirteen (54%) had different first reported outcomes in the methods and results sections, and among all trials many different outcomes were reported suggesting considerable potential for selective reporting. However, the single outcome of respiratory distress syndrome, albeit defined in different ways, was reported in all but two trials. This is reassuring evidence that the beneficial effect of steroids on this outcome has not been exaggerated by selective outcome reporting.Conclusion: We conclude that the evidence that steroids reduce respiratory distress syndrome is secure. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this review is to describe the historical and scientific basis of antenatal corticosteroids (ACS) therapy, to improve the management of preterm birth and decreasing rates of respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis and perinatal mortality in premature infants.Study Design: We searched MEDLINE/PubMed electronic database, the Cochrane Library, using medical subheading search words such as "ACS", "corticosteroids", "betamethasone" or "dexamethasone", matching with "preterm birth".Results: This practice was initiated by Liggins and Howie in 1972 and is supported by the initial comprehensive meta-analysis of Crowley, Chambers and Keirse, in 1990, the NIH Consensus Development Conference in 1994, the second Consensus Conference to evaluate repeated courses of corticosteroids in 2000 and the practice recommendations of obstetric societies worldwide. ACS therapy before anticipated preterm birth is one of the most important antenatal therapies and an important evidence-based practice for reducing mortality, and decreasing rates of complications in premature infants.Conclusions: Today, there is no controversy that women with preterm birth <34 weeks should be ACS treated. Actually, rescue courses are recommended; while multiple, serial, repeated or weekly courses, are not recommended. In any clinical conditions, as preterm premature rupture of membranes, multiple pregnancies, severe preeclampsia/HELLP syndrome and fetal growth restriction; ACS is recommended. [ABSTRACT FROM AUTHOR]

Introduction: Previous reports have shown that suboptimal antenatal corticosteroids administration occurs in most cases. However, as multifetal gestations were either excluded or constituted a small proportion of the participants in these studies, little is known about the patterns of use of antenatal corticosteroids in twin pregnancies.Material and Methods: We reviewed the records of women who received antenatal corticosteroids and delivered between 240/7 and 346/7 weeks of gestation during 2015-2017 at 2 university hospitals. Optimal antenatal corticosteroids timing was defined as delivery ≥24 hours ≤7 days from the previous antenatal corticosteroids course.Results: Of 424 pregnancies, 307 (72.4%) were singleton and 117 were (27.6%) twin. For twin compared with singleton pregnancies, gestational age at initial antenatal corticosteroids administration was lower (P = 0.02), the proportion of deliveries within the optimal window of the initial antenatal corticosteroids course was lower (19.7% vs 33.2%, P = 0.001), and the proportion of women eligible for a rescue antenatal corticosteroids course was higher (58.1% vs 32.9%, P < 0.0001). However, despite similar rates of rescue antenatal corticosteroids administration (P = 0.64), the overall rate of delivery within any optimal window (either initial or rescue course) was lower in twin than singleton pregnancies (26.5% vs 42.3%, P = 0.004), and the antenatal corticosteroids-to-delivery interval was longer (median 6.9 vs 4.2 days, P = 0.0009). In multivariate analysis, optimal antenatal corticosteroids administration was negatively associated with twin pregnancy (P = 0.04) and preterm labor (P = 0.05), and positively associated with the presence of gestational hypertensive disorders (P = 0.03).Conclusions: Twin pregnancy is an independent risk factor for suboptimal antenatal corticosteroids administration. Directed efforts should be made to improve the utilization of antenatal corticosteroids in this vulnerable group of women. [ABSTRACT FROM AUTHOR]

Purpose: We sought to determine if administration of antenatal corticosteroids in early preterm births (<34 weeks) is associated with an increased risk of developing neonatal hypoglycemia (<40 mg/dL) within the first 48 h of neonatal life.Materials and Methods: Retrospective cohort of all indicated singleton preterm births (23-34 weeks) in a single tertiary center from 2011 to 2014. The primary outcome was neonatal hypoglycemia (<40 mg/dL) within the first 48 h of life. The outcome was compared by antenatal corticosteroids received at any point during the gestation, within 2-7 d of delivery, and whether the patient received a partial, full, or repeat course of antenatal corticosteroids. Logistic regression was used to adjust for confounders.Results: Six hundred thirty-five patients underwent an indicated preterm birth during the study period. Six hundred and four (95%) received antenatal corticosteroids prior to delivery and 31 (5%) did not. The incidence of neonatal hypoglycemia within 48 h of life was not significantly different between those who received any antenatal corticosteroids and those who did not (23.0 versus 16.1%, adjusted odds ratio [OR] 1.3, 95%CI 0.5-3.6). Infants who received a full antenatal corticosteroid course within 2-7 d of delivery had similar incidences of hypoglycemia compared with those who received antenatal corticosteroids more than 7 d before delivery (20.4 versus 25.4%, adjusted OR 1.5, 95% confidence interval(CI) 0.8-2.9). Neonatal hypoglycemia was not increased by the number of antenatal corticosteroid doses (partial, full, or repeat course) administered. There was not a correlation between timing of antenatal corticosteroid administration before delivery, up to 250 h, and the lowest neonatal blood sugar in the first 48 h of life.Conclusion: Our findings suggest antenatal corticosteroid administration in indicated early preterm infants (<34 weeks) may not increase the risk of developing neonatal hypoglycemia within the first 48 h of life. Further studies should validate our findings. [ABSTRACT FROM AUTHOR]

Purpose: We sought to determine if administration of antenatal corticosteroids in early preterm births (<34 weeks) is associated with an increased risk of developing neonatal hypoglycemia (<40 mg/dL) within the first 48 h of neonatal life.Materials and Methods: Retrospective cohort of all indicated singleton preterm births (23-34 weeks) in a single tertiary center from 2011 to 2014. The primary outcome was neonatal hypoglycemia (<40 mg/dL) within the first 48 h of life. The outcome was compared by antenatal corticosteroids received at any point during the gestation, within 2-7 d of delivery, and whether the patient received a partial, full, or repeat course of antenatal corticosteroids. Logistic regression was used to adjust for confounders.Results: Six hundred thirty-five patients underwent an indicated preterm birth during the study period. Six hundred and four (95%) received antenatal corticosteroids prior to delivery and 31 (5%) did not. The incidence of neonatal hypoglycemia within 48 h of life was not significantly different between those who received any antenatal corticosteroids and those who did not (23.0 versus 16.1%, adjusted odds ratio [OR] 1.3, 95%CI 0.5-3.6). Infants who received a full antenatal corticosteroid course within 2-7 d of delivery had similar incidences of hypoglycemia compared with those who received antenatal corticosteroids more than 7 d before delivery (20.4 versus 25.4%, adjusted OR 1.5, 95% confidence interval(CI) 0.8-2.9). Neonatal hypoglycemia was not increased by the number of antenatal corticosteroid doses (partial, full, or repeat course) administered. There was not a correlation between timing of antenatal corticosteroid administration before delivery, up to 250 h, and the lowest neonatal blood sugar in the first 48 h of life.Conclusion: Our findings suggest antenatal corticosteroid administration in indicated early preterm infants (<34 weeks) may not increase the risk of developing neonatal hypoglycemia within the first 48 h of life. Further studies should validate our findings. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Identify which obstetrical diagnoses are associated with suboptimal antenatal betamethasone administration. METHODS: We present a retrospective, cohort study of patients who received betamethasone due to a risk for preterm delivery, between 7/2013 and 9/2016 at our institution. Details of betamethasone administration were recorded including the diagnosis leading to betamethasone. Optimal administration was defined as two doses of betamethasone given 24 hours apart, with delivery occurring at greater than 24 hours but less than seven days after completion of the second dose of betamethasone. Suboptimal administration included any betamethasone dosing that did not meet the optimal criteria. RESULTS: 428 patients were identified for the study with 20.1% of patients receiving optimal betamethasone. Patients presenting with hypertensive disorders of pregnancy (36.1%) and preterm premature rupture of membranes (PPROM) (22.1%) were more likely to receive optimal betamethasone, while patients presenting with preterm labor (PTL) (41.8%) and placental abruption (24.6%) were more likely to receive suboptimal betamethasone (p-value < 0.0001). Among PTL patients, those presenting with contractions and cervical dilation/short cervix (19.15%) were more likely to receive optimal betamethasone (p-value 0.0349). Optimal betamethasone decreased the incidence of respiratory distress syndrome (RDS) among 32.1 to 34 week neonates. CONCLUSION: Hypertensive disorders of pregnancy and PPROM are associated with optimal betamethasone, whereas PTL and placental abruption are associated with suboptimal betamethasone. [ABSTRACT FROM AUTHOR]

Antenatal corticosteroids are standard of care for pregnancies at risk of preterm delivery between 24-34 weeks' gestational age. Recent trials demonstrate modest benefits from antenatal corticosteroids for late preterm and elective cesarean deliveries, and antenatal corticosteroids for periviable deliveries should be considered with family discussion. However, many women with threatened preterm deliveries receive antenatal corticosteroids but do not deliver until >34 weeks or at term. The net effect is that a substantial fraction of the delivery population will be exposed to antenatal corticosteroids. There are gaps in accurate assessments of benefits of antenatal corticosteroids because the randomized controlled trials were performed prior to about 1990 in pregnancies generally >28 weeks. The care practices for the mother and infant survival were different than today. The randomized controlled trial data also do not strongly support the optimal interval from antenatal corticosteroid treatment to delivery of 1-7 days. Epidemiology-based studies using large cohorts with >85% of at-risk pregnancies treated with antenatal corticosteroids probably overestimate the benefits of antenatal corticosteroids. Although most of the prematurity-associated mortality is in low-resource environments, the efficacy and safety of antenatal corticosteroids in those environments remain to be evaluated. The short-term benefits of antenatal corticosteroids for high-risk pregnancies in high-resource environments certainly justify antenatal corticosteroids as few risks have been identified over many years. However, cardiovascular and metabolic abnormalities have been identified in large animal models and cohorts of children exposed to antenatal corticosteroids that are consistent with fetal programming for adult diseases. These late effects of antenatal corticosteroids suggest caution for the expanded use of antenatal corticosteroids beyond at-risk pregnancies at 24-34 weeks. A way forward is to develop noninvasive fetal assessments to identify pregnancies across a wider gestational age that could benefit from antenatal corticosteroids. [ABSTRACT FROM AUTHOR]

Introduction: An antenatal corticosteroid (ACS) delivery interval of 24 h to seven days is commonly referred to as optimal timing. We aimed to investigate whether the ACS delivery interval was associated with the obstetric indication for treatment and with neonatal complications.Material and Methods: The study was a retrospective chart review of clinical data from preterm neonates delivered at the Skåne University Hospital, Lund University, Sweden, from 1 January 2013 to 31 December 2016. The ACS delivery intervals were compared between groups of women with various clinical scenarios and related to neonatal outcomes.Results: The study included 498 preterm neonates from 431 women. One to seven days before delivery, 41% of the women received ACS. Women with preterm prelabor rupture of membranes or vaginal bleeding had a median ACS delivery interval of 7.5 and eight days, respectively, compared with women with maternal/fetal indications or preterm labor (three and two days, respectively) (p < 0.001). Neonates with an ACS delivery interval of more than seven days were at a higher risk of respiratory distress syndrome [odds ratio (OR) 2.00, 95% confidence interval (CI) 1.05-3.79] and moderate or severe bronchopulmonary dysplasia (OR 2.78, 95% CI 1.45-5.33) than were neonates with an ACS delivery interval of one to seven days.Conclusion: Optimal timing of ACS treatment varied significantly based on the clinical indication. Women with preterm prelabor rupture of membranes or vaginal bleeding were more likely to have an ACS delivery interval of more than seven days. A prolonged ACS delivery interval was associated with an increased risk of neonatal respiratory morbidity and a prolonged stay in the neonatal care unit, but not with neonatal mortality. [ABSTRACT FROM AUTHOR]

Objective A short cervix is an important risk factor for spontaneous preterm birth. There is substantial evidence that antenatal exposure to corticosteroids significantly benefits infants that are born when delivery occurs between 24 and 34 weeks' gestation and after 48 hours but within 7 days of their administration. Our study was to evaluate whether asymptomatic women who are given a course of antenatal corticosteroids (ACS) at the time a short cervix is identified deliver within the window of proven steroid benefit. Study Design This was a retrospective chart review of patients who had a cervical length of < 2.5 cmbetween 23 and 34 weeks and who did not have cervical dilation or significant symptoms of preterm labor. Results Of 367 asymptomatic patients with a short cervix, only two (0.5%) delivered within 7 days of the time a short cervix was identified.With a policy of giving ACS at the time an ultrasound shows a short cervix, 184 patients would have to be treated for each one who realizes a steroid benefit by delivering within 7 days. Conclusion We conclude that unless future studies show that neonates benefit from ACS givenmore than 7 days before delivery, giving ACS to asymptomatic women solely because the cervix is short is not advised. [ABSTRACT FROM AUTHOR]

Objective: Antenatal corticosteroid (ACS) has long been regarded as the standard of care for women at risk of preterm labour. There are, however, varying practices and regimes in ACS administration. It is unclear if "a window of efficacy" truly exists and if the benefits of ACS would diminish after 7 days from the first dose. The objective of this study is to determine if the time interval between antenatal corticosteroids and delivery influences the neonatal outcomes in preterm deliveries from 23+5 to 36+6 weeks' gestation.Methods: This is a retrospective analysis of 302 women and 352 infants who delivered from 23+5 to 36+6 weeks' gestation in KK Women's and Children's Hospital from 1st November 2014 to 31st January 2015. The timings of the first two doses of corticosteroids and the delivery were retrieved. Neonatal outcomes were compared between those delivering within 7 days and those delivering beyond 7 days of first dose of ACS.Results: 61.2% of preterm infants received at least one dose of antenatal corticosteroids, of which 23.6% received it within the window of efficacy. Overall incidence of respiratory distress asyndrome in our study is 17.6%. Significantly, neonates with ACS exposure beyond 7 days were seven times more likely to have RDS as compared to those exposed to ACS within the window of efficacy (RR 0.535, 95% CI 0.166-1.72), after adjusting for potential confounders.Conclusion: The results of this study support the current practice among obstetricians to aim to administer ACS within 7 days of delivery. [ABSTRACT FROM AUTHOR]

Objectives Respiratory distress syndrome (RDS) is a major cause of neonatal morbidity and mortality. It is primarily a disease of premature neonates. The aim of this study was to evaluate the impact of maternal betamethasone administration on the fetal pulmonary arteries (PAs) and umbilical arteries (UAs) and the correlation between RDS development and PA Doppler results. Methods Forty singleton pregnancies between 24 and 34 gestational weeks with a diagnosis of preterm birth were included prospectively. They received corticosteroids to enhance fetal lung maturity. Fetal PA and UA Doppler parameters were evaluated before and 48 to 72 hours after steroid administration. Maternal records were matched to neonatal charts, and demographic and outcome data were abstracted. Results There were no differences between groups for maternal age, body mass index, mode of delivery, and mean GA at steroid administration. Apgar scores at 1 and 5 minutes were significantly lower for neonates who developed RDS ( P < .05). There were no statistically significant differences in PA Doppler results between fetuses who developed RDS and those who did not, and there were no significant differences in PA Doppler results before and after steroid administration for both groups. The UA pulsatility and resistive indices were significantly lower after steroid administration for the neonates who developed RDS ( P < .05). Conclusions There were no significant differences in PA Doppler indices for fetuses with or without RDS after steroid administration. [ABSTRACT FROM AUTHOR]

Background: The effects of antenatal corticosteroids (ANS) in multiple pregnancies are disputed. In this article, we examined whether estimated effects differ in singletons and multiples and in small for gestational age (SGA) preterm infants.Methods: We studied 17 073 singletons (81% treated with ANS) and 8274 multiples (86% treated) born at 24-33 weeks from the Italian Neonatal Network (2005-2013). We used Poisson regression models with robust variance to estimate adjusted risk ratios (RR) of in-hospital death, severe intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL), and the composite outcome of severe IVH and death.Results: Mortality was lower among ANS-treated vs. ANS-untreated infants, both in singletons (RR 0.63, 95% confidence interval (CI) 0.58, 0.68) and in multiples (RR 0.85, 95% CI 0.73, 0.98). IVH and the composite outcome of IVH and death, but not PVL, also occurred less frequently among ANS-treated infants. For these outcomes, the effect of ANS was stronger in singletons than in multiples (+35%, +32%, and +22% for death, IVH, and the composite outcome, respectively). Also among SGA infants, singletons, and multiples, ANS-treated infants had lower risk of death, IVH and of composite outcome than untreated ones.Conclusions: In this large cohort of preterm infants, both multiples and singletons treated with ANS had a lower risk of mortality, of severe IVH, and of composite outcome of IVH and death, both in the overall sample and in SGA infants. Although ANS effect was weaker in multiples, our results support current recommendations to administer ANS prophylaxis in multiple pregnancies at risk of preterm delivery. [ABSTRACT FROM AUTHOR]

Background: The efficacy of antenatal corticosteroid treatment for women with threatened preterm birth depends on timely administration within 7 days before delivery. We modelled the probability of delivery within 7 days of admission to hospital among women presenting with threatened preterm birth, using routinely collected clinical characteristics.Methods: Data from the Canadian Perinatal Network (CPN) were used, 2005-11, including women admitted to hospital with preterm labour, preterm pre-labour rupture of membranes, short cervix without contractions, or dilated cervix or prolapsed membranes without contractions at preterm gestation. Women with fetal anomaly, intrauterine fetal demise, twin-to-twin transfusion syndrome, and quadruplets were excluded. Logistic regression was undertaken to create a predictive model that was assessed for its calibration capacity, stratification ability, and classification accuracy (ROC curve).Results: We included 3012 women admitted at 24-28 weeks gestation, or readmitted at up to 34 weeks gestation, to 16 tertiary-care CPN hospitals. Of these, 1473 (48.9%) delivered within 7 days of admission. Significant predictors of early delivery included maternal age, parity, gestational age at admission, smoking, preterm labour, prolapsed membranes, preterm pre-labour rupture of membranes, and antepartum haemorrhage. The area under the ROC curve was 0.724 (95% CI 0.706-0.742).Conclusion: We propose a useful tool to improve prediction of delivery within 7 days after admission among women with threatened preterm birth. This information is important for optimal corticosteroid treatment. [ABSTRACT FROM AUTHOR]