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

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]

Purpose: To compare 3 consecutive days of hyperglycemic response following antenatal dexamethasone regimens of 12-mg or 6-mg doses 12 hourly in diet-controlled gestational diabetes.Methods: A randomized controlled trial was carried out in a university hospital in Malaysia. Women with lifestyle-controlled gestational diabetes scheduled to receive clinically indicated antenatal corticosteroids (dexamethasone) were randomized to 12-mg 12 hourly for one day (2 × 12-mg) or 6-mg 12-hourly for two days (4 × 6-mg). 6-point (pre and 2-h postprandial) daily self-monitoring of capillary blood sugar profile for up to 3 consecutive days was started after the first dexamethasone injection. Hyperglycemia is defined as blood glucose pre-meal ≥ 5.3 or 2 h postprandial ≥ 6.7 mmol/L. The primary outcome was a number of hyperglycemic episodes in Day-1 (first 6 BSP points). A sample size of 30 per group (N = 60) was planned.Results: Median [interquartile range] hyperglycemic episodes 4 [2.5-5] vs. 4 [3-5] p = 0.3 in the first day, 3 [2-4] vs. 1 [0-3] p = 0.01 on the second day, 0 [0-1] vs. 0 [0-1] p = 0.6 on the third day and over the entire 3 trial days 7 [6-9] vs. 6 [4-8] p = 0.17 for 6-mg vs. 12-mg arms, respectively. 2/30 (7%) in each arm received an anti-glycemic agent during the 3-day trial period (capillary glucose exceeded 11 mmol/L). Mean birth weight (2.89 vs. 2.49 kg p < 0.01) and gestational age at delivery (37.7 vs. 36.6 weeks p = 0.03) were higher and median delivery blood loss (300 vs. 400 ml p = 0.02) was lower in the 12-mg arm; all other secondary outcomes were not significantly different.Conclusion: In gestational diabetes, 2 × 12-mg could be preferred over 4 × 6-mg dexamethasone as hyperglycemic episodes were fewer on Day-2, fewer injections were needed and the regimen was completed sooner.Clinical Trial Registration: http://www.isrctn.com/ISRCTN16613220 . [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]

Objective: To evaluate the association between antenatal corticosteroid treatment and neonatal outcome when delivery occurs at term.Study Design: A retrospective cohort study of all women with singleton gestations who delivered at term (37 + 0 to 41 + 6 weeks) in a tertiary medical center (2012-2015). Women with diabetes, suspected fetal growth restriction, antepartum fetal death, and fetal structural or chromosomal anomalies were excluded. The cohort was divided according to prior preterm (24 + 0 to 33 + 6 weeks) antenatal corticosteroids treatment due to threatened preterm labor (study group), vs. no such treatment (control group). Primary outcome was birthweight at delivery. Secondary outcomes were composites neonatal adverse outcomes. Logistic regression analysis was utilized to adjust results for potential confounders.Results: Of 25,872 women who were included in the study, 722 (3%) were treated with antenatal corticosteroids. Women in the treatment group had higher rates of nulliparity compared to controls (43% vs. 38%, p = 0.002). Birth weight was significantly lower in the corticosteroid treatment group (3077 g vs. 3264 g, p = 0.001), with higher rates of small for gestational age (11% vs. 6%, p = 0.001). Multivariate analysis adjusting for parity and gestational age demonstrated that corticosteroid treatment was associated with lower birth weight (B = - 93 g, 95% CI - 123 to - 66, p = 0.001). Treatment was not found to be associated with adverse neonatal outcomes composites.Conclusion: Antenatal corticosteroid treatment is associated with lower birth weight and higher rates of small for gestational age neonates among women who eventually deliver at term. However, it is not associated with short-term adverse neonatal outcomes. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between antenatal corticosteroid treatment and neonatal complications in diabetic mothers delivering after 34 weeks of gestation.Methods: A retrospective cohort study of women with singleton pregnancies diagnosed with gestational diabetes who delivered after 34 weeks of gestation in a university-affiliated medical center (2012-2016). Mothers treated with corticosteroids prior to 34 + 0 weeks of gestation were divided according to gestational age at delivery: late-preterm (34 + 0 to 36 + 6) and term (37 + 0 to 41 + 6). Each group was compared to women delivering at the same gestational age who were not treated with corticosteroids. Primary outcome was defined as a neonatal adverse composite outcome. Birth weight was amongst secondary outcomes measured. Logistic regression analysis was utilized to adjust results to potential confounders.Results: During the study period, 161 diabetic mothers delivered at late-preterm. Amongst them, 47 (30%) were treated with corticosteroids. 2101 diabetic mothers delivered at term, amongst them 82 (4%) were treated with corticosteroids. Primary outcome did not differ between groups. Multivariate analysis demonstrated that corticosteroid treatment was not associated with neonatal adverse composite outcome when delivery occurred at the late preterm, nor at term (adjusted odds ratio (aOR) = 0.708, 95% CI 0.2-2.3, p = 0.572, and aOR = 1.6, 95% CI 0.2-12.7, p = 0.635, respectively). Birth weight was significantly lower in women treated with corticosteroids (2486 vs. 2675 g, p = 0.02 at late-preterm, and 3160 vs. 3319 g, p < 0.001 at term).Conclusion: Corticosteroid treatment for diabetic mothers was not associated with neonatal adverse outcomes, but was found associated with a lower birth weight, when delivery occurs after 34 weeks of gestation. [ABSTRACT FROM AUTHOR]

Objective: Antenatal corticosteroids before preterm births are considered to be most effective 48 h after and up to 1 week after the first dose. We aim to evaluate: (1) our practice of administration of antenatal corticosteroids in Singapore; (2) admission characteristics of women for discriminatory factors of spontaneous preterm delivery within 1 week.Methods: This is a retrospective study in a tertiary obstetrics unit in Singapore. 3044 women who delivered live births (at term or preterm) from 1st November 2014 to 31st January 2015, who were at risk of spontaneous or induced preterm delivery, were included. Data related to the time of and indications for antenatal corticosteroids administration, characteristics assessed at the time of presentation, and time of delivery were collected and analysed.Results: 85.9% of women who delivered at gestational age ≤ 34+6 received at least one dose. 22.1% had delivered within the window of efficacy. Gestational age > 32 weeks at presentation, uterine activity on tocography and cervical dilation with effacement were associated with preterm delivery within 1 week of presentation.Conclusion: Overall, our antenatal corticosteroids administration rate is comparable to that attained by centres in other developed countries. It is difficult but important to discriminate women who will benefit from this timely intervention. [ABSTRACT FROM AUTHOR]

Objective: To determine whether antenatal corticosteroids administration prior to an elective cesarean section (ECS) at 34-37 weeks gestation is associated with improved neonatal outcome.Materials and Methods: A case control study of women with singleton pregnancies who underwent ECS between 34 and 37 weeks of gestation including two groups: (1) study group in which patients were treated with betamethasone prior to ECS (n = 58) and (2) control group matched for gestational age at delivery in which patients did not receive betamethasone (n = 107). Neonatal measures including respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), oxygen requirement, admission to the special care unit, hypoglycemia, hyperbilirubinemia and length of hospitalization were determined in both groups. Composite respiratory morbidity was defined as the presence of either RDS, TTN, mechanical ventilation or oxygen requirement.Results: There was no significant difference in the rate of composite respiratory morbidity nor its components between patients with and without betamethasone treatment (25.9 vs. 25.2%, respectively, p = 0.9).Conclusion: Antenatal treatment with corticosteroids prior to ECS at 34-37 weeks of gestation did not result in significant reduction in neonatal respiratory morbidity in our cohort of patients. [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]

Purpose: To evaluate the effect of antenatal corticosteroids (AC) therapy on short- and long-term outcomes among very low birth weight preterm infants after histologic chorioamnionitis (HCA).Methods: We performed a retrospective analysis of 5240 single very low birth weight (VLBW) infants born at 22 + 0 and 33 + 6 weeks of gestation between 2003 and 2007, who registered to the Neonatal Research Network Japan. The effects of AC therapy on mortality, neurodevelopmental outcomes at 3 years of age and neonatal morbidities were analyzed in the groups with or without HCA using logistic regression analysis.Results: In the study subjects, 840 were with HCA, 2734 were without HCA, and 1666 were excluded without data for HCA. AC therapy was significantly associated with decreasing mortality before 3 years of age; [0.52 (0.32-0.86)], [odds ratio (95 % confidence intervals]. There were no differences between the two groups regarding neurodevelopmental outcomes, including cerebral palsy [0.90 (0.41-1.99)], development quotient <70 [0.93 (0.48-1.81)], visual impairment [0.46 (0.04-5.18)], and severe hearing impairment [4.00 (0.30-53.4)] in the group with HCA as well as without HCA. Regarding neonatal morbidities, AC therapy was associated with a lower incidence of respiratory distress syndrome [0.67 (0.50-0.91)], sepsis [0.62 (0.41-0.94)], late-onset adrenal insufficiency [0.62 (0.39-0.98)] and an increased incidence of chronic lung disease [1.62 (1.18-2.24)] in the group with HCA. In the group without HCA, AC therapy was associated with decreasing respiratory distress syndrome [0.60 (0.43-0.84)] and increasing chronic lung disease [1.34 (1.11-1.62)].Conclusion: AC therapy is significantly associated with reduced mortality before 3 years of age in VLBW infants with HCA, but not with neurodevelopmental outcomes, which was same as the results found in infants without HCA. AC therapy is recommended for women with suspected chorioamnionitis, as well as those without chorioamnionitis. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effectiveness of antenatal corticosteroids (AC) therapy on outcomes of very low birthweight infants with histologic chorioamnionitis. Methods: We performed a retrospective analysis of 10,935 single infants born at a gestational age between 22 + 0 and 33 + 6 weeks and birth weight <1,500 g. Clinical data were obtained from the Neonatal Research Network that included the tertiary neonatal intensive care units throughout Japan between 2003 and 2008. Results: Data of 7,896 infants were available for the period 2003-2008 and were included in the analysis. According to logistic regression analysis, AC were significantly associated with reduced mortality [odds ratio (OR) = 0.50; p < 0.001], lower incidence of respiratory distress syndrome (OR = 0.72; p < 0.001), neonatal seizure (OR = 0.65; p = 0.003) and intraventricular hemorrhage (OR = 0.68; p = 0.001) in cases after histologic chorioamnionitis compared with the cases had no AC therapy ( n = 3,271 vs. 4,625). Antenatal corticosteroids were significantly associated with reduced mortality [odds ratio (OR) = 0.60; p < 0.001] among the cases without histologic chorioamnionitis. Conclusion: In the retrospective population-based study in Japan, AC exposure was significantly associated with a lower rate of death and neurological morbidity in cases with histologic chorioamnionitis. These outcome data in Japan will be important for further improvement of antenatal practice and care. [ABSTRACT FROM AUTHOR]

Purpose: Our purpose was to conduct a systematic review of the literature to determine whether synthetic pharmaceutical glucocorticoids (betamethasone and dexamethasone) are safe as well as effective in reducing neonatal respiratory morbidity at term of pregnancy prior to elective caesarean section. The overall incidence of respiratory disorders is estimated at 2.8 %, and the main risk factors are gestational age and mode of delivery. Newborns delivered by elective caesarean section (CS after 37 weeks) are more susceptible to serious respiratory complications than babies born by vaginal delivery. Neonatal respiratory morbidity at term of pregnancy is low but not negligible. Further, it is increasing due to a drastic decline in trial of labour in those pregnant women who underwent a caesarean section in the past. Because prophylaxis is inexpensive, easy to administer, and safe, other studies should be conducted to confirm its effectiveness. Methods: We conducted a systematic review of literature since 1965 on the discovery of action mechanisms, pharmaceutical development, proper dosage, and potential side effects of corticosteroids on the mother and offspring to extrapolate their efficacy as no clinical trial has directly demonstrated it. Results: We extrapolated no negative effects on mother and foetus behaviour. Conclusions: Human studies suggest that corticosteroid administration may become a proper clinical indication prior to caesarean section in the reduction of neonatal respiratory problems. [ABSTRACT FROM AUTHOR]