Antenatal Corticosteroid Administration Research Articles

77 Antenatal MgS04 in very preterm babies is not related to improved 36 month neurodevelopmental outcomes once accounting for neonatal interventions

Abstract Background Magnesium Sulphate (MgSO4) has become a standard practice for fetal neuroprotection prior to delivery of very-preterm babies due to an association with MgSO4 and reduction of cerebral palsy at 2 years of age in randomized clinical trials. Objectives In a prospective cohort of very preterm babies, we aimed to define the association between antenatal MgSO4 administration and neurodevelopmental outcome. Design/Methods We included a prospective cohort of 265 infants born ≤ 32 weeks’ gestation recruited at three tertiary neonatal intensive care units (NICU). Infants underwent two brain MRIs, one in the initial weeks after birth and one at term-equivalent age. Neurodevelopmental follow-up assessments were completed using the Bayley-3 at 3 years. Univariate analysis was undertaken to determine whether MgSO4 was associated with outcome. Multiple maternal and neonatal factors were analyzed according to their relationship with outcome. Gestational age was accounted for in all models. Maternal factors associated with MgSO4 administration were hypertension, multiple births and antenatal corticosteroid administration. Neonatal factors were sex, neonatal resuscitation, major surgery, and moderate-severe white matter injury (volume >40mm3). Multivariable linear regression models of maternal and neonatal risk factors were used to account for potential confounders based on those factors that were significantly (p<0.05) associated in univariate analysis. Results On univariate analysis, MgSO4 administration was inversely associated with 36-month motor scores (p<0.05). On the multivariable analysis, no maternal confounders had an impact on the relationship between MgSO4 and outcome (Table 2). MgS04 was no longer statistically related to any Bayley outcomes after adjusting for confounders at 36 months (Table 2). Neonatal surgery was related to poorer 36-month motor and cognitive outcomes. Conclusion Antenatal MgSO4 exposure was not associated with improved measures on the Bayley scales at 3 years after adjusting for potential confounders. However, neonatal interventions remained significant risk factors for poorer neurodevelopmental outcome.

Evaluation of a Standardized Obstetrics Insulin Drip Protocol and Order Set

Objective The prevalence of pregnancies affected by diabetes is increasing, with the Centers for Disease Control and Prevention reporting that 1–2% of pregnant women have type 1 or type 2 diabetes and up to 10% of pregnancies are affected by gestational diabetes as of 2018. Maternal glycemic management is directly related to fetal and neonatal outcomes, and aberrant maternal hyperglycemia has known negative outcomes. Although most of glycemic management centers on outpatient treatment, evidence exists to support the use of intravenous insulin drips during inpatient admissions. This study aimed to evaluate an intravenous insulin protocol specific to the obstetric (OB) population. Research Design and Methods This was a single-center retrospective pre-/post- cohort study of OB patients with diabetes admitted to an academic medical center. Groups were differentiated based on admission date and protocol implementation with a 6-month washout period. Included patients received an intravenous insulin drip around either antenatal corticosteroid administration or during labor and delivery. Those who were within 7 days of receiving a diabetic ketoacidosis diagnosis or who were admitted to an intensive care unit were excluded. Results Fifty-nine patients received 69 distinct insulin drip orders. Twelve drips were included in the group admitted before initiation of the insulin drop protocol (pre-group) and 57 in the group admitted after the protocol went into effect (post-group). Time spent within the goal glucose range while on an insulin drip in the pre-group was 1.63% compared with 39.30% in the post-group (P <0.001). Glucose levels <70 mg/dL was 0.00% in the pre-group compared with 3.23% in the post-group (P = 0.045). There were no differences in severe hypoglycemia (glucose <50 mg/dL), hyperglycemia (glucose >110 mg/dL), or neonatal outcomes. Conclusion Implementation of a nursing-driven, obstetrics-specific intravenous insulin drip protocol significantly improved maternal glycemic management within a goal glucose range of 70–110 mg/dL during antenatal corticosteroid administration and labor and delivery.

The influence of antenatal betamethasone timing on neonatal outcome in late preterm infants: a single-center cohort study.

Many pregnancies continue after antenatal corticosteroid exposure. Since long-term effects on late preterm neonatal outcome remain controversial, it remains unknown whether pregnant women who are at risk for preterm birth during the late preterm period and had prior antenatal corticosteroid exposure would benefit from an additional course of antenatal corticosteroids. We evaluated the need for future trials on this topic by comparing short term effects from antenatal betamethasone to long-term effects. We also examined the value of a risk-adapted approach. We observed neonatal outcomes in late preterm infants (34/0-36/0 weeks of gestation) who were exposed to antenatal betamethasone either up to 10 days prior birth (n = 8) or earlier in pregnancy (n = 89). We examined a real world population from the University Hospital Magdeburg (Germany) between 01 January 2012 and 31 December 2018, and a simulated high-risk population that was derived from the original data. The indicators for relevant adverse outcomes did not differ in the unselected population. In the simulated high-risk population, recent antenatal corticosteroid administration significantly reduced the incidence of relevant cardiorespiratory morbidities (OR = 0.00, p = 0.008), and reduced the number needed to treat from 3.7 to 1.5. The superiority of recent antenatal corticosteroid administration in the late preterm period over earlier exposure strongly depended on the prevalence of respiratory disease. Before considering clinical trials on additional antenatal corticosteroid courses in the late preterm period, antenatal assessment tools to predict respiratory morbidity need to be developed.

Letter to the Editor: Administration of Antenatal Corticosteroids: Optimal Timing.

Letter to the Editor: Administration of Antenatal Corticosteroids: Optimal Timing.

Reply to: Letter to the Editor: Administration of Antenatal Corticosteroids: Optimal Timing.

Reply to: Letter to the Editor: Administration of Antenatal Corticosteroids: Optimal Timing.

Should the sex of the fetus be considered when administering antenatal corticosteroids to preterm fetuses?

We aimed to determine whether the effect of antenatal corticosteroids (ANS) differs in male and female fetuses without anomalies born before 32 weeks in terms of mortality and short-term morbidity. This single-center retrospective study included infants born before 32 weeks' gestation and admitted to the neonatal intensive care unit between January 1, 2018, and December 31, 2020. The study included 210 infants with a median gestational age of 28.6 weeks (24-31.6), a birth weight of 1065 g (445-2165), and an ANS use rate of 80%. Compared to female fetuses exposed to ANS, male fetuses exposed to ANS had a lower mortality rate (23% and 11%, respectively, p = 0.038), but there were no differences in intraventricular hemorrhage, retinopathy of prematurity, necrotizing enterocolitis, respiratory distress syndrome, and APGAR scores of 1st and 5th but an increased rate of bronchopulmonary dysplasia (moderate/severe) (p = 0.008). In addition, the mortality rate was similar in exposed and unexposed female fetuses (p = 0.850). Enzyme activities and steroid levels in the placenta might be different in male and female fetuses, which could explain the results of ANS administration. In our study, we have shown that ANS has no effect on mortality in female fetuses younger than 32 weeks. Future studies may focus on adjusting the administration of ANS based on fetal sex, altering the dose or taking fetal sex into account when performing ANS.

The effect of antenatal corticosteroid administration on umbilical artery Doppler velocimetry in pregnancies complicated with fetal growth restriction

Objective: To examine the effect of antenatal corticosteroid administration on umbilical artery (UA) Doppler measurements in pregnancies complicated with fetal growth restriction (FGR). Methods: This cross-sectional study was conducted with 149 pregnant women scheduled for antenatal corticosteroid therapy because of the possibility of preterm birth. UA Doppler measurements (PI, S/D ratio, RI) before antenatal corticosteroid administration and 24 and 48 hours after the last dose of corticosteroid administration were evaluated and compared with each other in pregnant groups complicated with FGR and uncomplicated with FGR. Results: No statistically significant change was observed in UA Doppler parameters 24 and 48 hours after antenatal corticosteroid treatment in each group with and without FGR. While there was no significant difference between the precorticosteroid UA Doppler parameters (PI, S/D ratio, RI) of the two groups with and without FGR, the values of these parameters 24 hours after the last dose of treatment were statistically higher in the group complicated with FGR than in the uncomplicated group. However, no statistical difference was observed in UA Doppler parameters between the two groups 48 hours after the last dose of treatment. Conclusion: Antenatal corticosteroid does not permanently affect UA Doppler parameters in the case of FGR. Close monitoring of the fetus for 72 hours after the first dose of antenatal corticosteroid may be helpful in pregnant women complicated by FGR.

The Role of Corticosteroids in Prevention of Neonatal Respiratory Morbidity in Term Elective Cesarean Section A Prospective Observation Study

Abstract Background Caesarean sections continue to increase day by day in both developed and developing countries, which is associated with increased respiratory distress syndrome (RDS), the key reason for early neonatal morbidity and mortality. Objective To assess the effect of routine prophylactic corticosteroids before elective caesarean section after 37 weeks of gestational age, on neonatal respiratory morbidity. Methods A prospective observational study was conducted on all pregnant women undergoing elective caesarean sections between 37-42 weeks at Ain Shams University Maternity Hospital. Over an 8- month period (from November 2020 to June 2021), 1105 cases were divided into the exposed group (A), (N = 877) who received prophylactic dexamethasone, and 228 cases in the non-exposed group (B) who did not receive dexamethasone. Outcome measures were the incidence of transient tachypnea of the newborn, and NICU admissions due to respiratory morbidity. Data were analyzed using SPSS 22. Results Overall, there was no statistically significant difference in the incidence of TTN or RDS. No cases of TTN were found in exposed subgroup, versus 1 (0.4%) in non-exposed group (p = 0.745). The respiratory distress (RDS) in the exposed subgroup was 4 cases (16.7%) versus 18 (7.9%) in non- exposed group (p = 0.148). While the admission to the neonatal intensive care unit (NICU) due to respiratory morbidity after an elective caesarean section was 4 cases (16.7%) in the exposed subgroup versus 19 cases (8.3%) in the non-exposed group (p = 0.178). Conclusion Routine administration of prophylactic antenatal corticosteroids before elective caesarean sections at term does not reduce the risk of admission to the NICU compared to non- administration.

Factors affecting neonatal respiratory distress syndrome at Wangaya General Hospital

Introduction: The neonatal period is a crucial window at the start of life. According to the American Academy of Pediatrics, 10% of all newborns require early respiratory support. Neonates with respiratory distress syndrome have a fourfold increased risk of death. Multiple maternal and neonatal risk factors affect the incidence of respiratory distress syndrome. This study aims to identify the relationship between method of delivery, maternal illness, premature rupture of membrane, amniotic fluid, low birth weight, gestational age, asphyxia, gender, multiple gestation, and perinatal infections towards the incidence of respiratory distress syndrome in Wangaya General Hospital. Methods: This is a retrospective case-control study. Secondary data was collected from the medical record. The sample size was 56 neonates aged 0-28 days with respiratory distress and without. Univariate analysis using Chi-square and Fisher’s Exact test and multivariate analysis using logistic regression. Results: Of the 114 neonates with respiratory distress, asphyxia (p < 0.001) and low birth weight (p = 0.014) were correlated with respiratory distress when analyzed using bivariate and multivariate analysis. Maternal factors analyzed in the study did not affect the incidence of respiratory distress. Conclusion: Neonatal factors of birth asphyxia and low birth weight increased the risk of development of respiratory distress syndrome, while maternal factors did not increase such risks. Limitations of the study include secondary data and a lack of analysis of other detrimental factors, such as the administration of antenatal corticosteroids.

Association of different doses of antenatal corticosteroids exposure with early major outcomes and early weight loss percentage in extremely preterm infants or extremely low birthweight infants: a multicentre cohort study

ObjectivesTo determine the dose-dependent associations between antenatal corticosteroids (ANS) exposure and the rates of major morbidities, and the early weight loss percentage (EWLP) in hospital among extremely preterm infants (EPI)...

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

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

Management advances for congenital diaphragmatic hernia: integrating prenatal and postnatal perspectives.

In congenital diaphragmatic hernia (CDH), abdominal organs are displaced into the chest, compress the lungs, and cause mediastinal shift. This contributes to development of pulmonary hypoplasia and hypertension, which is the primary determinant of morbidity and mortality for affected newborns. The severity is determined using prenatal imaging as early as the first trimester and is related to the laterality of the defect, extent of lung compression, and degree of liver herniation. Comprehensive evaluation of fetal CDH includes imaging-based severity assessment, severity assessment, and evaluation for structural or genetic abnormalities to differentiate isolated from complex cases. Prenatal management involves multispecialty counseling, consideration for fetal therapy with fetoscopic endoluminal tracheal occlusion (FETO) for severe cases, monitoring and intervention for associated polyhydramnios or signs of preterm labor if indicated, administration of antenatal corticosteroids in the appropriate setting, and planned delivery to optimize the fetal condition at birth. Integrated programs that provide a smooth transition from prenatal to postnatal care produce better outcomes. Neonatal care involves gentle ventilation to avoid hyperinflation and must account for transitional physiology to avoid exacerbating cardiac dysfunction and decompensation. Infants who have undergone and responded to FETO have greater pulmonary capacity than expected, but cardiac dysfunction seems unaffected. In about 25-30% of CDH neonates extracorporeal life support is utilized, and this provides a survival benefit for patients with the highest predicted mortality, including those who underwent FETO. Surgical repair after initial medical management for the first 24-48 hours of life is preferred since later repair is associated with delayed oral feeding, increased need for tube feeds, and increased post-repair ventilation requirement and supplemental oxygen at discharge. With overall survival rates >70%, contemporary care involves management of chronic morbidities in the context of a multidisciplinary clinic setting.

Trends in antenatal corticosteroid administration: did our timing improve?

We aimed to analyze trends in the rate of effective antenatal corticosteroid prophylaxis (ACS) administrations across a spectrum of typical diagnoses associated with preterm birth. In this retrospective study we utilized delivery data after ACS from 2014 to 2020 at Charité Berlin, Germany. We evaluated the rate of effective ACS administrations defined as≤10days between last dose of ACS and delivery as well as the rate of post-ACS births on/after 37+0weeks. We explored conditions associated with high rates of ineffective ACS administrations (>10days before delivery). We analyzed the trend of ACS-effectiveness during the study period in the overall cohort and in placental dysfunction and cervical insufficiency diagnoses. The overall rate of effective ACS administrations was 42 % (709/1,672). The overall percentage of deliveries after/at 37+0weeks following ACS administration was 19 % (343). Placenta previa, twin pregnancy and isthmocervical insufficiency were associated with ineffective ACS (19-34 % effective i.e.≤10days before delivery). The overall ratio of effective ACS applications rose over time (p=0.002). Over the course of this study ACS effectiveness increased in placental dysfunction and isthmocervical insufficiency diagnoses (p=0.028; p=0.001). Compared to a previous publication we founda decrease of post-ACS deliveries after/at 37+0weeks (19 vs. 27 %). Ineffective ACS administrations are still frequent in patients with placenta previa, twin pregnancy and isthmocervical insufficiency. It remains to be investigated in future trials if the introduction of new diagnostic tools such as soluble Fms-like tyrosinkinase-1/placental growth factor (sFlt-1/PlGF) testing and placental alpha-microglobulin-1 (PAMG-1) testing directly led to an increased ACS effectiveness.

Neurodevelopmental Outcomes After Late Preterm Antenatal Corticosteroids

The Antenatal Late Preterm Steroids (ALPS) trial changed clinical practice in the United States by finding that antenatal betamethasone at 34 to 36 weeks decreased short-term neonatal respiratory morbidity. However, the trial also found increased risk of neonatal hypoglycemia after betamethasone. This follow-up study focused on long-term neurodevelopmental outcomes after late preterm steroids. To evaluate whether administration of late preterm (34-36 completed weeks) corticosteroids affected childhood neurodevelopmental outcomes. Prospective follow-up study of children aged 6 years or older whose birthing parent had enrolled in the multicenter randomized clinical trial, conducted at 13 centers that participated in the Maternal-Fetal Medicine Units (MFMU) Network cycle from 2011-2016. Follow-up was from 2017-2022. Twelve milligrams of intramuscular betamethasone administered twice 24 hours apart. The primary outcome of this follow-up study was a General Conceptual Ability score less than 85 (-1 SD) on the Differential Ability Scales, 2nd Edition (DAS-II). Secondary outcomes included the Gross Motor Function Classification System level and Social Responsiveness Scale and Child Behavior Checklist scores. Multivariable analyses adjusted for prespecified variables known to be associated with the primary outcome. Sensitivity analyses used inverse probability weighting and also modeled the outcome for those lost to follow-up. Of 2831 children, 1026 enrolled and 949 (479 betamethasone, 470 placebo) completed the DAS-II at a median age of 7 years (IQR, 6.6-7.6 years). Maternal, neonatal, and childhood characteristics were similar between groups except that neonatal hypoglycemia was more common in the betamethasone group. There were no differences in the primary outcome, a general conceptual ability score less than 85, which occurred in 82 (17.1%) of the betamethasone vs 87 (18.5%) of the placebo group (adjusted relative risk, 0.94; 95% CI, 0.73-1.22). No differences in secondary outcomes were observed. Sensitivity analyses using inverse probability weighting or assigning outcomes to children lost to follow-up also found no differences between groups. In this follow-up study of a randomized clinical trial, administration of antenatal corticosteroids to persons at risk of late preterm delivery, originally shown to improve short-term neonatal respiratory outcomes but with an increased rate of hypoglycemia, was not associated with adverse childhood neurodevelopmental outcomes at age 6 years or older.

Shorter Intervals of Antenatal Corticosteroid Administration Can Influence Short- and Long-Term Outcomes in Premature Infants

Shorter Intervals of Antenatal Corticosteroid Administration Can Influence Short- and Long-Term Outcomes in Premature Infants

Analysis of Factors Contributing to Antenatal Corticosteroid Administration in Threatened Preterm Labor [ID: 1375840]: Correction.

Analysis of Factors Contributing to Antenatal Corticosteroid Administration in Threatened Preterm Labor [ID: 1375840]: Correction.

Antenatal corticosteroid administration is associated with lower risk of severe ROP in preterm twin infants

IntroductionRobust evidence revealed the impact of antenatal corticosteroid (ACS) administration on lower mortality and short-term neonatal outcomes in singleton preterm infants. We aimed to investigate the impact of ACS therapy on morbidity and mortality in preterm twin infants. MethodsWe conducted this retrospective single-center study from to the records of twin babies of 24–30 weeks of gestation admitted to the neonatal intensive care unit. The study population was grouped based on the exposure to ACS 1–7 days before birth as received or not. Groups were compared regarding in-hospital mortality and neonatal outcomes. ResultsData from 160 twin infants were analyzed. Of those, 102 (64 %) were administered ACS. The median (IQR) gestational age and birth weight of the whole cohort were 28 (27–29) weeks and 1060 (900–1240) g, respectively. ACS administration was associated with a significant decline in respiratory distress syndrome (RDS), requirement ≥2 doses of surfactant, severe intraventricular hemorrhage (IVH), early-onset sepsis (EOS), and retinopathy of prematurity (ROP) requiring treatment (p < 0.05). Logistic regression analysis revealed that gestational age (OR 0.29 95 % CI 0.14–0.62; p = 0.001), ACS administration (OR 0.14 95 % CI 0.03–0.85; p = 0.032), and time to achieve full enteral feeding (OR 1.16 95 % CI 1.03–1.31; p = 0.019) were independently associated with the risk of severe ROP. ConclusionThe reduction in the risk of severe ROP besides RDS, severe IVH, and EOS among preterm twins who received ACS was remarkable in our study similar to the trials conducted in preterm singletons. However, large-scale prospective observational studies are required to reveal the efficacy of ACS in preterm twins.

Antenatal corticosteroids and newborn respiratory outcomes in twins: A regression discontinuity study.

To estimate the effect of antenatal corticosteroids on newborn respiratory morbidity in twins. Regression discontinuity applied to population-based birth registry data. British Columbia, Canada, 2008-2018. Twin pregnancies admitted for birth between 31+0 and 36+6 weeks of gestation. During our study period, Canadian clinical practice guidelines recommended antenatal corticosteroid administration for imminent preterm birth up to 33+6 weeks. We used a logistic model to compare the predicted risks of our outcomes among pregnancies admitted for birth immediately before this clinical cut-point (higher probability of exposure to antenatal corticosteroids) versus immediately after it (lower probability). Our primary outcome was a composite of newborn respiratory distress or in-hospital death. Our secondary outcome was a composite of newborn respiratory intervention or in-hospital death. Among 2524 pregnancies (5035 liveborn twins), 47% of admissions before 34+0 weeks of gestation were exposed to antenatal corticosteroids but only 4.2% of admissions after this cut-point were exposed. The risk of newborn respiratory distress or in-hospital mortality increased abruptly at 34+0 weeks, corresponding to a protective effect of treatment (risk ratio [RR] 0.69, 95% CI 0.53-0.90; risk difference [RD]-12 cases per 100 births, 95% CI -20 to -4.1). There was no clear evidence for or against an effect on newborn respiratory intervention or in-hospital death (RR 0.89, 95% CI 0.70-1.13; RD -4.2 per 100, 95% CI -13 to +4.2). Our findings provide evidence for the effectiveness of antenatal corticosteroids in preventing adverse newborn respiratory outcomes in twins.

Gestational age at birth in pregnancies with antenatal corticosteroid administration in relation to risk factors: a retrospective cohort study.

The aim was to investigate gestational age at birth of women after induction of fetal lung maturation (antenatal corticosteroids = ACS) because of imminent preterm birth (PTB), and to quantify incidence of late PTB (gestational age < 260 days) and extreme immaturity (gestational age < 196 days) in relation to several diagnoses (PPROM, placental bleeding, premature labor, preeclampsia, oligohydramnios, amniotic infection syndrome (AIS), cervical insufficiency) and risk factors (age > 35, history of preterm delivery, multifetal gestation, gestational diabetes, hypertension, nicotine abuse). The study was designed as a retrospective cohort trial, in which the data of all births taking place in 2016 in the German federal state Rhineland-Palatinate were evaluated. Frequency analyses, subgroup analysis (Chi-square tests and Friedman's tests), as well as multinomial logistic regressions and linear regressions were used to determine odds ratios (OR). In total, N = 1,544 patients were included who had been hospitalized due to an imminent PTB and had received ACS, of whom 52% had a late PTB and 8% a PTB with extreme immaturity. Regarding the gestational age at birth, there were only minor differences between the individual risk factors and diagnoses, only AIS patients showed a significantly lower gestational age (mean: 207 days). A significantly increased risk of PTB with extreme immaturity was found in patients with AIS (OR = 5.57) or placental bleeding (OR = 2.10). There is a need for further research in order to be able to apply therapeutic measures more accurately in relation to risk factors and diagnoses.

Administration of Antenatal Corticosteroids: Optimal Timing.

The effectiveness of antenatal corticosteroids (ACS) in significantly reducing respiratory distress syndrome (RDS) depends crucially on the timing. It is successful if delivery takes place between 24 hours and seven days following administration; after this period, the side effects seem to predominate. In addition, an increased rate of mental impairment and behavioral disorders are observed in children born full-term after ACS administration. The optimal timing of ACS administration depends crucially on the given indication; to date, it has been achieved in only 25-40% of cases. ACS administration is always indicated in PPROM, in severe early pre-eclampsia, in fetal IUGR with zero or reverse flow in the umbilical artery, in placenta previa with bleeding, and in patients experiencing premature labor with a cervical length <15mm. The risk of women with asymptomatic cervical insufficiency giving birth within seven days is very low. In this case, ACS should not be administered even if the patient's cervical length is less than 15mm, provided that the cervix is closed and there are no other risk factors for a premature birth. The development of further diagnostic methods with improved power to predict premature birth is urgently needed in order to optimize the timing of ACS administration in this patient population. Caution when administering ACS is also indicated in women experiencing premature labor who have a cervical length ≥15mm. Further studies using amniocentesis are needed in order to identify the patient population with microbial invasion of the amniotic cavity/intra-amniotic infection (MIAC/IAI), and to define threshold values at which delivery is indicated. ACS administration is not performed as an emergency measure, usually not even before transfer to a perinatal center. Therefore, whenever possible, the indication for ACS administration should be determined by a clinician who is highly experienced in perinatology.