Corticosteroids For Fetal Lung Maturation Research Articles

Association between Maternal Neuraxial Analgesia and Neonatal Outcomes in Very Preterm Infants.

Background Although the use of neuraxial analgesia has been shown to improve uteroplacental blood flow and maternal and fetal hemodynamics related to labor pain, possibly improving immediate outcomes in term neonates, the association between neuraxial analgesia use and outcomes in preterm neonates remains unclear. Objective The aim of this article was to evaluate the association between maternal use of neuraxial analgesia and neonatal outcomes in very preterm infants. Methods This is a retrospective cohort study of women delivering singleton neonates between 23 and 32 weeks' gestation at a large academic center between 2012 and 2016. Outcomes of neonates born to women who used neuraxial analgesia for labor and/or delivery were compared to those whose mothers did not. Multivariable logistic regression was utilized to assess the independent associations of neuraxial analgesia use with neonatal outcomes after controlling for potential confounders, including gestational age, mode of delivery, and existing interventions to improve neonatal outcomes of prematurity. Results Of 478 eligible women who delivered singleton very preterm neonates in this study period, 352 (73.6%) used neuraxial analgesia. Women who used neuraxial analgesia were more likely to have delivered at a later preterm gestational age, to have a higher birthweight, to have preeclampsia and/or hemolysis, elevated liver enzymes, low platelet count (HELLP), to have undergone labor induction, to have delivered by cesarean delivery, and to have received obstetric interventions such as magnesium prophylaxis for fetal neuroprotection, antenatal corticosteroids for fetal lung maturity, and antibiotics prior to delivery; they were less likely to have been diagnosed with a clinical abruption. Neuraxial analgesia was associated with decreased incidence of cord umbilical artery pH less than 7.0 (24.7 vs. 34.9%, p = 0.03), as well as decreased incidence of neonatal intensive care unit length of stay over 60 days (35.5 vs. 48.4%, p = 0.01), although these associations did not persist on multivariable analysis. On multivariable analyses, neuraxial analgesia remained independently associated with decreased odds of necrotizing enterocolitis (adjusted odds ratio [aOR]: 0.28, 95% confidence interval [CI]: 0.12-0.62) and grade III/IV intraventricular hemorrhage (aOR: 0.33, 95% CI: 0.13-0.87). These associations remained significant on sensitivity analyses, which were performed between 10 and 90% of the overall cohort in order to control for outliers, as well as between the subgroup of patients who received obstetric interventions. Conclusions Maternal neuraxial analgesia use may be associated with lower odds of adverse outcomes in very preterm infants, even after controlling for existing interventions for prematurity. Prior work has suggested such effects may be due to improved neonatal acid-base status from changes in placental perfusion and maternal pain management, but further work is required to prospectively investigate such associations.

Repurposing existing drugs as a therapeutic approach for the prevention of preterm birth.

Preterm birth is the leading cause of perinatal morbidity and mortality; however, current therapies offer limited efficacy to delay birth and improve neonatal outcomes. This review explores the potential of repurposing drugs with known safety profiles to quench uterine contractions and inflammation, identifying promising agents for clinical trials. Preterm birth is the leading cause of neonatal morbidity and mortality globally. Despite extensive research into the underlying pathophysiology, rates of preterm birth have not significantly reduced. Currently, preterm labour management is based on optimising neonatal outcomes. Treatment involves administering drugs (tocolytics) to suppress uterine contractions to allow sufficient time for transfer to an appropriate facility and administration of antenatal corticosteroids for fetal lung maturation. Current tocolytics are limited as they are associated with adverse maternal and fetal effects and only delay delivery for a short period. There has been a serious lack of therapeutic development for preterm birth, and new approaches to protect against or delay preterm birth are urgently needed. Repurposing drugs for the prevention of preterm birth presents as a promising approach by reducing the time and costs associated with pharmaceutical drug development. In this review, we explore the evidence for the potential of therapies, specifically proton pump inhibitors, tumour necrosis factor inhibitors, prostaglandin receptor antagonists, aspirin, and statins, to be repurposed as preventatives and/or treatments for preterm birth. Importantly, many of these innovative approaches being explored have good safety profiles in pregnancy. We also review how delivery of these drugs can be enhanced, either through targeted delivery systems or via combination therapy approaches. We aim to present innovative strategies capable of targeting multiple aspects of the complex pathophysiology that underlie preterm birth. There is an urgent unmet need for preterm birth therapeutic development, and these strategies hold great promise for improving neonatal outcomes.

Monochorionic – Monoamniotic Twins’ Placenta

A 33-year-old healthy primigravida with a body mass indexof 21 kg/m², unexplained infertility, pregnancy after IVF, and single embryo transfer, was referred to our department at 12 weeks. We diagnosed monochorionic – monoamniotic twin pregnancy with normal growth, anatomy, and dopplers in both fetuses, anterior normal appearing placenta with eccentric insertion of both umbilical cords, and cervical length of 40 mm. After extensive counseling on the risks and complications of monochorionic – monoamniotic twins, the parents decided to continue with the pregnancy. The course of the pregnancy was uneventful for the mother and fetuses with normal results on all biweekly performed ultrasound examinations. At 30 weeks she received corticosteroids for fetal lung maturation.

Unresolved issues on the antenatal use of corticosteroids for fetal lung maturation

Antenatal corticosteroids (ACS) for fetal lung maturation is celebrating the 50th anniversary. The most recent Cochrane review concluded that there is robust evidence that a single course of ACS reduces the risk of perinatal death and respiratory distress syndrome. Some aspects of ACS remain unresolved, including variations in the steroids regimen, effectiveness in certain groups, long-term effects, optimal timing of ACS administration in elective cases. it is well established that a single course of betamethasone or dexamethasone is beneficial in cases of anticipated preterm birth and delivery eventually occurs between two and seven days from administration. The main focus for future research should be on limiting the unnecessary exposure in low-risk pregnancies and investigating the effect in specific groups, periviable and late preterm fetuses.

Tocolytics for delaying preterm birth: a network meta-analysis (0924).

Tocolytics for delaying preterm birth: a network meta-analysis (0924).

18 Antenatal corticosteroids for fetal lung maturation - Are we doing it right?

Background: Preterm delivery is an important major factor of neonatal morbidity and mortality. Targeted corticosteroid use has been proven to be beneficial in reducing neonatal risk of respiratory distress syndrome, intraventricular haemorrhage and necrotising enterocolitis specifically. The benefits of corticosteroids are greatest at 2 to 7 days after initial dose. Rescue corticosteroids can be considered when the previous administration was 14 days ago. Aim: This study aims to look at the practice of targeted usage of betamethasone injection in the management of preterm deliveries less than 34 and 6 weeks of gestation in Coombe Women and Infants University Hospital.

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

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

VP38.03: Antenatal corticosteroids and perinatal outcomes in late fetal growth restriction: analysis of a prospective cohort

To investigate the role of antenatal corticosteroids (ACS) on perinatal outcomes in pregnancies complicated by late fetal growth restriction (FGR). Secondary analysis of a multicentre prospective observational study (TRUFFLE 2 feasibility study) including singleton pregnancies from 32+0 to 36+6 weeks of gestation with FGR. Women who received ACS (cases), were matched with a control who did not receive ACS, based on gestational age at delivery ± 1 week and birth weight ± 100 g. 90 cases were matched with controls. There were 7 cases of ACS which could not be matched to controls and were excluded from comparisons. Cases and controls were similar regarding gestational age at inclusion, EFW and UCR, gestational age at delivery and birth weight (table 1). No significant differences were observed for composite adverse outcome (31% vs. 38%; p = 0.43) or for any individual complication (table 1). The results of our study show no benefit of antenatal corticosteroids for fetal lung maturation in pregnancies complicated by FGR after 32 weeks in a matched control comparison. A randomised controlled trial is needed to assess the effect of ACS in late preterm FGR. VP38.03: Table 1. Data are given as median (interquartile range) or n (%)

Pregnancy and Covid 19

The COVID19 virus also affects pregnant women. While the vast majority of infected patients have few symptoms, about 10% of them may have a pneumonia that is important to diagnose and treat. Initial data from the literature suggest management similar to that of the general population. There is a greater risk of premature delivery requiring the administration of corticosteroids for fetal lung maturation in the event of imminent delivery.

SARS-CoV-2: do corticosteroids for fetal lung maturation worsen maternal or fetal outcomes?

Immune system changes during pregnancy could make pregnant women more susceptible to SARS-Cov-2 infection. The use of corticosteroids within obstetrics has been shown to reduce the risks of respiratory distress syndrome, intraventricular haemorrhage, necrotizing enterocolitis and neonatal death in the baby associated with premature delivery. During the COVID-19 pandemic, corticosteroids have been trialled as a treatment to dampen the ‘cytokine storm’ and associated inflammatory processes. Corticosteroids have long been known to have immunosuppressive effects that could hinder the body's ability to mount a defence against COVID-19 and thereby delaying viral clearance. In this clinical case studies, antenatal steroids for fetal lung maturation appear to be of benefit and did not result in a deterioration of maternal disease. Our clinical case studies support the current recommendations from the Royal College of Obstetricians and Gynaecologists ie corticosteroids for fetal lung maturation is appropriate in patients who are suspected or have confirmed SARS-CoV-2 infection.

Preterm prelabor rupture of membranes management in Switzerland: a national survey

Objective To gain an overview of the current management of patients with preterm prelabor rupture of membranes (PPROM) in Swiss maternity hospitals. Study design We conducted a survey among all maternity hospitals in Switzerland from January to December 2018, irrespective of their annual birth rate and level of complexity. The survey consisted of an 11-item questionnaire, which was developed to retrieve information relevant to different areas of PPROM management. Results Of 64 questionnaires distributed by email, 36 (56.3%) centers responded to the survey. Up to 12 different antibiotic regimens were reported. Among these, 91.7% included a beta-lactam, with amoxicillin as the preferred agent (55.6%). Combined antibiotic schemes were used in 30.6% of hospitals. All centers considered the use of corticosteroids for fetal lung maturity if PPROM occurred before 34 weeks, although 36.1% would consider their use until 37 weeks’ gestation in the presence of an increased risk of neonatal respiratory distress syndrome. Maternity hospitals who accept deliveries at any gestational age usually used magnesium sulfate as fetal neuroprotection when delivering babies <32 weeks, with the exception of two hospitals where it was either not used or only indicated if maternal preeclampsia was present. Concerning the time to delivery, 58.3% centers tended to wait until 37 weeks’ gestation, while the others considered that it was not necessary to go beyond 34 weeks. Conclusion Our survey shows that the current management of PPROM in Switzerland appears to be mostly in line with international recommendations. However, some heterogeneity exists, thus reflecting a lack of international consensus across guidelines, together with the absence of national Swiss guidelines, and this needs to be addressed to ensure high quality care for all patients and neonates.

Antenatal Corticosteroids and Magnesium Sulfate for Improved Preterm Neonatal Outcomes: A Review of Guidelines.

In cases of anticipated preterm delivery, corticosteroids for fetal lung maturation and magnesium sulfate for fetal neuroprotection may improve neonatal outcomes. The aim of this study was to summarize and compare published guidelines from 4 leading medical societies on the administration of antenatal corticosteroids and magnesium sulfate. A descriptive review of major national guidelines on corticosteroids and magnesium sulfate was conducted: National Institute for Health and Care Excellence on "Preterm labour and birth," World Health Organization on "WHO recommendations on interventions to improve preterm birth outcomes," American College of Obstetricians and Gynecologists on "Antenatal corticosteroid therapy for fetal maturation" and "Magnesium sulfate use in obstetrics," and Society of Obstetricians and Gynecologists of Canada on "Antenatal corticosteroid therapy for improving neonatal outcomes" and "Magnesium sulphate for fetal neuroprotection." A variation in the appropriate timing of administration exists, whereas repeated courses are not routinely recommended for corticosteroids or magnesium sulfate. In addition, the recommendations are the same for singleton and multiple gestations, and no specific recommendation exists according to maternal body mass index. Finally, a variation in guidelines regarding the administration of corticosteroids before cesarean delivery exists. The adoption of an international consensus on corticosteroids and magnesium sulfate may increase their endorsement by health care professionals, leading to more favorable neonatal outcomes after preterm delivery.

Improvement of cardiac function in fetuses with growth restriction following antenatal betamethasone administration: fact or artifact?

Introduction Use of corticosteroids for fetal lung maturation has reduced the perinatal mortality/morbidity from prematurity related complications. There is a paucity of studies evaluating the effect of steroid administration on the fetal circulation and cardiac function in fetal growth restriction (FGR). The aim of the study was to assess changes in fetal Doppler indices and cardiovascular function in pregnancies complicated with FGR after administration of betamethasone. Methods This was a prospective study conducted in a tertiary care research center between July 2017 and May 2018. Pregnant women with FGR between 28 and 36 weeks’ gestation, who were scheduled to receive betamethasone (two doses of 12 mg, 24 h apart) were recruited. Fetal cardiovascular function in fetuses FGR was assessed immediately before first dose and once between 6 and 24 h after the second dose of betamethasone by the same operator. Wilcoxon matched-pairs signed-rank test or paired t-tests were used to compare parameters before and after corticosteroid exposure. Results Fifty cases with FGR were evaluated before and after administration of betamethasone, at mean gestational age of 34.6 ± 2.0 weeks. Fetal heart rate (148.78 ± 9.10 versus 144.73 ± 9.61, p < .001), left heart myocardial performance index ([MPI], 0.66 ± 0.06 versus 0.55 ± 0.09, p ≤ .001) and right heart MPI (0.65 ± 0.04 versus 0.63 ± 0.04, p .016) showed improvement after steroids. Left heart isovolumic relaxation and contraction indices along with ejection time of both sides showed a small but statistically significant improvement (p < .001), but other fetal cardiac functional and Doppler indices remain unchanged after steroids. Conclusions Fetal heart rate, cardiac MPI, left sided isovolumic indices showed an improvement after betamethasone administration. Follow up studies are needed to ascertain whether these effects persist in the long term and to determine whether these are beneficial to a growth restricted fetuses.

Antenatal Corticosteroids for Fetal Lung Maturity - Too Much of a Good Thing?

Between 5-15% of babies are born prematurely worldwide, with preterm birth defined as delivery before 37 completed weeks of pregnancy (term is at 40 weeks of gestation). Women at risk of preterm birth receive antenatal corticosteroids as part of standard care to accelerate fetal lung maturation and thus improve neonatal outcomes in the event of delivery. As a consequence of this treatment, the entire fetal organ system is exposed to the administered corticosteroids. The implications of this exposure, particularly the long-term impacts on offspring health, are poorly understood. This review will consider the origins of antenatal corticosteroid treatment and variations in current clinical practices surrounding the treatment. The limitations in the evidence base supporting the use of antenatal corticosteroids and the evidence of potential harm to offspring are also summarised. Little has been done to optimise the dose and formulation of antenatal corticosteroid treatment since the first clinical trial in 1972. International guidelines for the use of the treatment lack clarity regarding the recommended type of corticosteroid and the gestational window of treatment administration. Furthermore, clinical trials cited in the most recent Cochrane Review have limitations which should be taken into account when considering the use of antenatal corticosteroids in clinical practice. Lastly, there is limited evidence regarding the long-term effects on the different fetal organ systems exposed in utero, particularly when the timing of corticosteroid administration is sub-optimal. Further investigations are urgently needed to determine the most safe and effective treatment regimen for antenatal corticosteroids, particularly regarding the type of corticosteroid and optimal gestational window of administration. A clear consensus on the use of this common treatment could maximise the benefits and minimise potential harms to offspring.

Good clinical practice advice: Antenatal corticosteroids for fetal lung maturation.

Good clinical practice advice: Antenatal corticosteroids for fetal lung maturation.

Tocolysis: A Review of the Literature.

Preterm delivery represents an important cause of infant morbidity and mortality. Various tocolytics have been studied with the objective of stopping preterm labor, increasing gestational age at delivery, and preventing complications related to preterm birth. This review aims to summarize the major classes of tocolytics and review the evidence regarding use of each. A PubMed search of the following terms was performed to gather relevant data: "tocolytic," "preterm labor," "preterm delivery," "PPROM," "magnesium," "indomethacin," "nifedipine," and "betamimetics." The benefits and risks of nonsteroid anti-inflammatory drugs, calcium channel blockers, magnesium, and betamimetics are reviewed. Calcium channel blockers afford superior outcomes in terms of prolonging gestation and decreasing neonatal morbidity and mortality with the fewest adverse effects. Tocolytics, particularly calcium channel blockers, may provide benefit to pregnant women and their infants. Their use should be tailored to the particular clinical circumstances of the patient and used in conjunction with other management strategies (e.g., administration of corticosteroids for fetal lung maturation or magnesium for neuroprotection and transfer to a tertiary medical center). Further research and professional guidelines are needed on optimal use of these agents.

The Value of Late Mid-Trimester Ultrasound Cervical Assessment after Cerclage for the Prediction of Preterm Birth

Background: Spontaneous preterm birth constitutes a significant obstetric dilemma as prematurity is a major risk factor of neonatal death or a lifelong morbidity. Despite extensive efforts to reduce preterm birth, the means to identify and prevent it remains limited. Sonographic surveillance of CL can identify the increased risk of spontaneous preterm birth. Objective: To determine the predictive value of ultrasonographic assessment of the cervix after cerclage insertion for the outcome of preterm birth before 34 weeks of gestation. Patients and Methods: A prospective study included fifty women with singleton pregnancies were followed-up with monthly transvaginal ultrasonographic examinations before and after cerclage insertion. Ultrasonographic parameters of the cervix included the closed endocervical canal length and funneling depth measured from the internal cervical os. Results: The change in cervical length was predictive; as with stable cervical length an association with a later gestational age at delivery was evident. Patients with cerclage who delivered after 34 weeks had a slower rate of cervical shortening compared to those who delivered prior to that date (median = 4mm versus 7mm per 4 weeks). The overall cervical length at 28 weeks was statistically different between patients who delivered before 34 weeks and those who delivered later (24.00±2.92 versus 33.19±5.5 p<0.001). Conclusions: Transvaginal ultrasound for cervical assessment can be a helpful tool in the prediction of preterm birth after cerclage insertion. A late second-trimester cervical transvaginal ultrasound scan can guide the addition of interventions such, progesterone and antenatal corticosteroids for fetal lung maturation.

Differences between evidence-based recommendations and actual clinical practice regarding tocolysis: a prospective multicenter registry study

BackgroundInternational guidelines recommend that tocolytic therapy be restricted to a single 48-h application. However, multiple cycles of tocolytic therapy and maintenance therapy that exceeds 48 h appear to play a role in daily clinical practice. We aimed to evaluate current trends in clinical practice with respect to treatment with tocolytic agents and to identify differences between evidence-based recommendations and daily clinical practice in Austria.MethodsA prospective multicenter registry study was conducted from October 2013 through April 2015 in ten obstetrical departments in Austria. Women ≥18 years of age who received tocolytic therapy following a diagnosis of threatened preterm birth were included, and details were obtained regarding clinical characteristics, tocolytic therapy, and pregnancy outcome.ResultsA total of 309 women were included. We observed a median of 2 cycles of tocolytic therapy per patient (IQR 1–3) with a median duration of 2 days per cycle (IQR 2–5). Repeat tocolysis was administered in 41.7% of women, resulting in up to six tocolysis cycles; moreover, 40.8% of the first tocolysis cycles were maintenance tocolysis (i.e., longer than 48 h). Only 25.6% of women received one single 48-h tocolysis cycle in which they received antenatal corticosteroids for fetal lung maturation in accordance evidence-based recommendations.ConclusionsHere, we report a clear disparity between evidence-based recommendations and daily practice with respect to tocolysis. We believe that the general practice of prescribing tocolytic therapy must be revisited. Furthermore, our findings highlight the need for contemporary studies designed to investigate the effectiveness of performing maintenance and/or repetitive tocolysis treatment.

The Effect of Nifedipine used as Tocolytic Agent on Postpartum Blood Loss among Filipino Pregnant Patients in a Tertiary Hospital: a Prospective Cohort Study

Objective. To determine the risk of postpartum hemorrhage among patients who were treated with nifedipine for tocolysis of preterm labor.&#x0D; Methods. A prospective cohort study was conducted with 66 pregnant women admitted for preterm labor. One group of women was given nifedipine to give time for the administration of corticosteroids for fetal lung maturity and/or control of preterm labor and another group was not given nifedipine as they were admitted in advanced stage of labor (ie, more than or equal to 4 cm cervical dilatation). Independent/paired sample t-test, Mann-Whitney U/Wilcoxon signed rank test, and Fisher’s exact test were used to determine the difference of mean, median, and frequency between and within groups, respectively. STATA 12.0 was used for data analysis.&#x0D; Results. There was more blood loss during delivery, which was statistically significant, among those who received nifedipine compared to those who have not taken the medicine (350 mL versus 250 mL, p = 0.021). Furthermore, the decreases in hemoglobin and hematocrit were also lower among those who did not receive nifedipine compared to those who received nifedipine for tocolysis (8.5 mg/dL versus 16.0 mg/dL, p = 0.014 and 0.03 versus 0.05, p = 0.010), again, statistically significant.&#x0D; Conclusion. Nifedipine used as tocolytic appear to increase blood loss during delivery, which was statistically significant. Greater amount of blood loss may be anticipated among those with nifedipine intake thus helping the obstetrician in preparing for active management of postpartum hemorrhage and preventing maternal morbidity and mortality.

Nicardipin Associated Pulmonary Edema : A Severe Complication of Tocolysis - A Case Report

In preterm labor, tocolytics are used to stop uterine contractions and to allow the administration of corticosteroids for fetal lung maturation, nicardipine is a calcium channel blocker increasingly used for this indication. Several adverse effects have been reported during tocolysis using nicardipine, one of the most serious complications is Acute Pulmonary Edema. We report a case of a parturient who has admitted at 28 weeks of pregnancy for preterm labor and developed a respiratory failure two days following tocolysis with nicardipine. Echocardiography and Computed Tomography Pulmonary Angiography (CTPA) ruled out a pulmonary embolism and a decompensated heart disease. The patient received oxygen therapy and diuresis for Acute Pulmonary Edema with favorable outcomes.The purpose of this paper is to discuss the risk factors for the occurrence of pulmonary edema after tocolysis, the importance of the etiologic investigation to exclude differential diagnoses and therapeutic options for management of this complication.