Maternal Betamethasone Administration Research Articles

Integrative analysis of bulk and single-cell RNA sequencing reveals the gene expression profile and the critical signaling pathways of type II CPAM

BackgroudType II congenital pulmonary airway malformation (CPAM) is a rare pulmonary microcystic developmental malformation. Surgical excision is the primary treatment for CPAM, although maternal steroids and betamethasone have proven effective in reducing microcystic CPAM. Disturbed intercellular communication may contribute to the development of CPAM. This study aims to investigate the expression profile and analyze intercellular communication networks to identify genes potentially associated with type II CPAM pathogenesis and therapeutic targets.MethodsRNA sequencing (RNA-seq) was performed on samples extracted from both the cystic area and the adjacent normal tissue post-surgery in CPAM patients. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify genes specifically expressed in type II CPAM. Single-cell RNA-seq (scRNA-seq) was integrated to unveil the heterogeneity in cell populations and analyze the communication and interaction within epithelial cell sub-populations.ResultsA total of 2,618 differentially expressed genes were identified, primarily enriched in cilium-related biological process and inflammatory response process. Key genes such as EDN1, GPR17, FPR2, and CHRM1, involved in the G protein-coupled receptor (GPCR) signaling pathway and playing roles in cell differentiation, apoptosis, calcium homeostasis, and the immune response, were highlighted based on the protein-protein interaction network. Type II CPAM-associated modules, including ciliary function-related genes, were identified using iWGCNA. By integrating scRNA-seq data, AGR3 (related to calcium homeostasis) and SLC11A1 (immune related) were identified as the only two differently expressed genes in epithelial cells of CPAM. Cell communication analysis revealed that alveolar type 1 (AT1) and alveolar type 2 (AT2) cells were the predominant communication cells for outgoing and incoming signals in epithelial cells. The ligands and receptors between epithelial cell subtypes included COLLAGEN genes enriched in PI3K-AKT singaling and involved in epithelial to mesenchymal transition.ConclusionsIn summary, by integrating bulk RNA-seq data of type II CPAM with scRNA-seq data, the gene expression profile and critical signaling pathways such as GPCR signaling and PI3K-AKT signaling pathways were revealed. Abnormally expressed genes in these pathways may disrupt epithelial-mesenchymal transition and contribute to the development of CPAM. Given the effectiveness of prenatal treatments of microcystic CPAM using maternal steroids and maternal betamethasone administration, targeting the genes and signaling pathways involved in the development of CPAM presents a promising therapeutic strategy.

Perinatal outcomes of prenatal diagnosis of congenital pulmonary airway malformation: an experience.

This study aimed to assess the perinatal outcomes of pregnancies with a prenatal diagnosis of congenital cystic adenomatoid malformation. We conducted a retrospective cohort study based on information contained in the medical records of pregnant women whose fetuses had been prenatally diagnosed with congenital cystic adenomatoid malformation by ultrasonography. Sample analysis was based on 21 singleton pregnancies with confirmed isolated fetal congenital cystic adenomatoid malformations. The mean maternal±standard deviation age was 28±7.7 years. Types I, II, and III congenital cystic adenomatoid malformation were detected in 19% (4/21), 52.4% (11/21), and 28.6% (6/21), respectively. All fetuses presented with unilateral congenital cystic adenomatoid malformation (21/21) without associated anomalies, and 52.3% (11/21) were in the right lung. In total, 33.3% (7/21) of fetuses presented a "congenital cystic adenomatoid malformation volume ratio" >1.6 and were managed with maternal betamethasone administration. The mean gestational age at the time of steroid administration was 28.5±0.9 weeks, with a reduction in the lesion dimensions of 9.5% (2/21) (Types I and III of congenital cystic adenomatoid malformation). The mean gestational age at delivery was 38.7±2.4 weeks, and a cesarean section was performed in 76.2% (16/21) cases. Postsurgical resection was necessary for 23.8% (5/21) of the patients, and 4.7% (1/21) of them died because of respiratory complications after surgery. Pulmonary hypoplasia occurred in 9.5% (2/21) of the patients, and 4.7% (1/21) of them died because of respiratory insufficiency. The survival rate was 90.5% (19/21), and 57.2% (12/21) remained asymptomatic. Despite the isolated prenatal diagnosis of congenital cystic adenomatoid malformation, which showed good survival, congenital cystic adenomatoid malformation is associated with significant perinatal morbidity. Maternal betamethasone administration did not significantly reduce fetal lung lesion dimensions.

Betamethasone use and risk factors for pulmonary edema during the perinatal period: a single-center retrospective cohort study in Japan

BackgroundA few studies have reported that maternal administration of antenatal corticosteroids increased the risk of pulmonary edema (PE). However, despite the increasing usage rate of betamethasone as antenatal corticosteroid, maternal administration of betamethasone as a risk factor for PE has not been well studied. This study aimed to evaluate how maternal backgrounds and complications, tocolytic agents, and betamethasone affect the incidence of PE during the perinatal period and determine the risk factor for PE.MethodsThis was a single-center retrospective cohort study in Kurashiki, Japan. The study subjects were patients who had been admitted to our hospital for perinatal management including pregnancy, delivery and puerperium between 2017 and 2020. The primary outcome measure was defined as the incidence of PE during hospitalization. First, in all study subjects, Cox proportional hazards model was used to determine the risk factor for PE during the perinatal period. Next, using propensity score matching, we divided the patients into the betamethasone and betamethasone-free groups and examined the association between betamethasone use and the incidence of PE with Cox proportional hazards model.ResultsDuring the study period, 4919 cases were hospitalized, and there were 16 PE cases (0.3%). In all analyzed subjects, the occurrence of PE was significantly associated with preeclampsia (hazard ratio 16.8, 95% confidence intervals (CI) 5.39–52.7, P < 0.001) and the combined use of the tocolytic agents such as ritodrine hydrochloride and magnesium sulfate, and betamethasone (hazard ratio 11.3, 95% CI 2.66–48.1, P = 0.001). In contrast, after propensity score matching, no statistically significant difference was found between the betamethasone and betamethasone-free groups in the incidence of PE (hazard ratio 3.19, 95% CI 0.67–15.3, P = 0.145).ConclusionsA combined use of tocolytic agents and antenatal corticosteroids such as betamethasone may be an independent risk factor for PE during the perinatal period. On the other hand, betamethasone use alone may not be associated with the incidence of PE. When tocolytic agents and betamethasone are administrated to pregnant women, it is important to pay attention to the appearance of maternal respiratory symptoms.

The effects of betamethasone on the amplitude integrated EEG of infants born at 34- or 35-weeks gestation.

Assess if maternal betamethasone administration at 34-35 weeks accelerated neonatal amplitude integrated EEG (aEEG) maturation. Nested, observational cohort in 7 centers participating in the Antenatal Late Preterm Steroid randomized trial. Up to 2 aEEGs were obtained in neonates born from 340-356 weeks gestation before 72 h (aEEG 1) and at 5-7 days (aEEG 2) if hospitalized. Personnel and aEEG central readers were masked to the intervention. The primary outcome was maturation reflected by cycle frequency; secondary outcomes were border voltage, span, and discontinuity. 58 neonates were enrolled (betamethasone, 28, placebo, 30). On aEEG 1, cycle frequency did not differ, but betamethasone exposed infants had a greater lower border voltage and a broader span. On aEEG 2, both groups displayed increases in lower border voltage. Betamethasone associated changes in lower border voltage support accelerated electrical activity. Further investigation is needed to understand the broader span.

The impact of betamethasone on fetal pulmonary, umbilical and middle cerebral artery Doppler velocimetry and its relationship with neonatal respiratory distress syndrome

BackgroundPrenatal corticosteroid administration is known to be an effective strategy in improving fetal pulmonary maturity. This study aimed to evaluate the impact of maternal betamethasone administration on fetal pulmonary and other arteries Doppler velocity and the correlation between RDS development and Doppler indices results.MethodsFifty one singleton pregnancies between 26 and 34 gestational weeks with a diagnosis of preterm labor were included in the exposed group and received betamethasone. Fifty one uncomplicated pregnancies were included in the non-exposed group. Fetal pulmonary, umbilical and middle cerebral arteries Doppler parameters were evaluated before and 24 to 48 h after steroid administration in the exposed group and two times at same intervals in the non-exposed group. Maternal records were matched to neonatal charts if delivery happened, and demographic and outcome data were abstracted.ResultsWhen compared with the nonexposed group, fetuses treated with corticosteroids demonstrated significantly decreased umbilical artery Pulsatility index (PI) and significantly increased the middle cerebral artery PI, pulmonary artery Acceleration time (AT) and pulmonary artery AT/ET (Ejection time), while all other indices remained similar. We found significantly decreased pulmonary artery AT in the fetuses with respiratory distress syndrome (RDS) compared to those that did not.ConclusionsThe results of our study showed that maternal antenatal betamethasone administration caused significant changes in the fetus blood velocity waveforms and also affected the blood flow in the pulmonary artery which led to an increase in the pulmonary artery AT and AT/ET. Among those fetuses with RDS, we found a significant decrease in the pulmonary artery AT, but we did not observe any pulmonary artery AT/ET differences.

Routine betamethasone therapy of non-hydropic fetuses with CPAM - the way to improve perinatal outcome?

Authors discuss novel approach to the management of fetal congenital pulmonary cystic malformation (CPAM) and possible benefit of routine administration of betamethasone, which is currently recommended only for severe cases. The article presents authors' own experience with antenatally diagnosed CPAM and describes 4 cases of prenatally diagnosed CPAM without hydrops treated by two doses of betamethasone at 21-31 weeks of gestation with the aim of improving the perinatal prognosis by effect on not only mortality but also postnatal morbidity. Article also summarizes current knowledge on all aspects of the prenatal CPAM focusing on its treatment options. Data were obtained from the literature search based on the PubMed and Scopus database with additional search of particular articles from reference list of the selected publications.All 4 patients from the case reports showed regression of the pulmonary mass after maternal administration of betamethasone with 100 % survival rate. Even though it is not possible to say if the CPAM regression was due to the betamethasone treatment, we did not observe any complication in relation to the treatment and all cases survived until discharge. During the literature search, we did not find any data on betamethasone administration in non-hydropic fetuses with CPAM in relation to the overall perinatal and postnatal morbidity, neither data comparing the outcome between the treated versus observed only fetuses.Routine betamethasone treatment should be discussed in antenatally diagnosed CPAM cases without fetal hydrops in order to reduce the perinatal morbidity associated with CPAM (Tab. 1, Ref. 47). Keywords: betamethasone, CPAM (congenital pulmonary adenomatoid malformation), fetal therapy.

Antenatal betamethasone and the risk of neonatal hypoglycemia: it's all about timing.

Our objective was to evaluate whether there is a relationship between the "time during the day" of maternal betamethasone administration between 24 and 34weeks' gestation and the risk for neonatal hypoglycemia. A retrospective study included cases between 2008 and 2018. Eligible cases were pregnant women with singleton pregnancies who received a single course of betamethasone between 24 and 34weeks' gestation. Each woman was allocated into one of four pre-defined groups based on the time when intramuscular betamethasone was administered. Group 1 (23:00-04:59) represents the lowest daily natural corticosteroids' activity, group 2 (05:00-10:59) represents the peak daily natural corticosteroids' activity, whereas group 3 (11:00-16:59) and group 4 (17:00-22:59) present an intermediate natural state of steady corticosteroids' secretion and activity. The primary outcome of the study was the incidence of neonatal hypoglycemia (glucose level of less than 40mg/dL). We have identified 868 women who received a single complete course of betamethasone, of which 353 women (40.7%) had a steroid treatment latency to delivery up to 14days. The incidence of neonatal hypoglycemia was significantly higher in group 2 (39.5%, 30/76, p = 0.0063), compared to group 1, who had the lowest incidence of neonatal hypoglycemia (16.9%, 12/71), and to group 3 and group 4. The "time during the day" when betamethasone administered is important when considering the risk for neonatal hypoglycemia. The risk was significantly higher when betamethasone was administered during the peak time and significantly lower when administered at the nadir time of maternal endogenous corticosteroid activity.

Morphometric and functional pulmonary changes of premature neonatal puppies after antenatal corticoid therapy

Among prematurity complications, the most important disorder is structural immaturity and inadequate production of pulmonary surfactant. Betamethasone is the drug of choice to artificially improve pulmonary capacity, thus we aimed to verify the effect of prenatal maternal treatment on lung development of premature puppies. Pregnant bitches were allocated in Term Group (n = 7), Preterm-Treated Group (interrupted pregnancies with maternal administration of betamethasone; n = 7), Preterm-Control Group (untreated interrupted pregnancies; n = 7), Extremely-Preterm Group (interrupted pregnancies at 55d; n = 6). Puppies were subjected to chest radiographic at birth, morphometric description of pulmonary structures and immunohistochemical analysis of surfactant protein B, proliferating cell nuclear antigen and cytokeratin were performed. In Preterm-Treated Group it was possible to more clearly identify cardiac silhouette and lung parenchyma by X-Ray. Saccular formation was higher in Preterm Groups, while Term Group had higher subsaccular development. Lung septation was higher in Treated and Term Groups. Term Group had higher number of cells marked for SP-B, whereas higher proliferation was observed in Extreme-Preterm and Preterm-Control Groups. Preterm Treated and Term Groups had higher tissue differentiation. In conclusion, antenatal maternal corticotherapy in dogs acted by increasing lung morphology and development of areas of gas exchange, regulate metabolism of pulmonary fluids rather than stimulate surfactant production.

Effect of maternal betamethasone administration on feto-placental vascular resistance in the mouse†.

Antenatal corticosteroids are often administered to women at risk of preterm birth to accelerate fetal lung development; however, there is evidence that this treatment may adversely affect placental function in some fetuses. Our group has recently demonstrated that wave reflections in the umbilical artery (UA), measured using high-frequency ultrasound, are sensitive to placental vascular abnormalities. In the present study, we used this approach to investigate the effect of maternal administration of betamethasone, a clinically relevant corticosteroid, on the feto-placental vasculature of the mouse. Fetuses were assessed at embryonic day (E)15.5 and E17.5 in C57BL6/J mice. At both gestational ages, the UA diameter, UA blood flow, and the wave reflection coefficient were significantly elevated in the betamethasone-treated mice compared to vehicle-treated controls. These observations support the interpretation that placental vascular resistance dropped with betamethasone treatment to an extent that could not be explained by vasodilation of the UA alone. Consistent with clinical studies, the effect of betamethasone on UA end-diastolic velocity was heterogeneous. Our results suggest that UA wave reflections are more sensitive to acute changes in placental vascular resistance compared with the UA pulsatility index, and this technique may have clinical application to identify a favorable placental vascular response to fetal therapies such as antenatal corticosteroids, where the fetal heart rate is likely to vary.

Alterations of the Short-Term Variation of the Fetal Heart Rate after Antenatal Maternal Betamethasone Administration: Validation with Two Different Computational Algorithms.

Antenatal betamethasone administration in the context of foetal lung maturity enhancement has a transient impact on the short-term variation (STV) of the foetal heart rate. There are currently various algorithms for computing the STV, each one resulting in different STV values. We studied the results of betamethasone administration on the STV using 2 different algorithms in order to investigate whether the effects of steroids on the STV depend on the algorithm used or not. In the context of a larger, single-centre, prospective, observational study, we gathered CTG traces under and without the influence of steroids in order to study their effect on the STV using 2 different computational algorithms (STV240 and STV16). A total of 285 CTGs were registered and subsequently analysed with both algorithms. When compared to the STV240 and STV16 without or at least 72 h after the first intramuscular corticosteroid administration, a transient increase of both the STV240 and STV16 was documented in the first 24 h, followed by a transient decrease of both the STV240 and STV16 between 24 h and 72 h after the first intramuscular corticosteroid injection. Our results confirmed that betamethasone administration has a transient but significant effect on the STV independently of the algorithm used. These observations stress once again the fact that a decreased STV within the first 72 h after maternal bethametasone administration should not be an indication for early delivery.

A Complication of Percutaneous Sclerotherapy for Congenital Pulmonary Airway Malformation: Intravascular Injection and Cardiac Necrosis

ABSTRACTIntroduction: A congenital pulmonary airway malformation (CPAM) type III may become large enough to cause hydrops fetalis. In such circumstances, the fetus can be treated with open fetal resection, maternal betamethasone administration, or percutaneous sclerotherapy. Case report: A 24 week gestation fetus with a CPAM type III was treated by percutaneous sclerotherapy using ethanolamine oleate (EO). The EO inadvertently entered the left atrium and ventricle with subsequent fetal bradycardia and demise. Autopsy revealed myocardial necrosis. Conclusion: Percutaneous sclerotherapy has been previously described in the literature for the treatment of microcystic CPAMs with secondary hydrops. This is the first reported case of an adverse event after fetal sclerotherapy.

Reduced short-term variation following antenatal administration of betamethasone: Is reduced fetal size a predisposing factor?

ObjectiveTo assess the association between fetal size and the incidence of reduced short-term variability (STV) following bethametasone administration for fetal lung maturity. Study designThis was a retrospective, multicenter, cohort study conducted in two Tertiary University Units. Only uncomplicated singleton pregnancies admitted for threatened preterm labor between 26 and 34 weeks and submitted to betamethasone for fetal lung maturity were included. Delivery occurring within 72h from betamethasone administration represented criteria for exclusion. Computerized cardiotocography was carried out on a daily basis. Cases were identified by persistently reduced STV, defined as <5th percentile for gestational age and lasting for at least 72h after the first dose of betamethasone. The primary outcome was estimated fetal weight (EFW) at ultrasound in fetuses with normal and in those with persistently reduced STV. Pregnancy outcomes were also evaluated. ResultsPersistently reduced STV occurred in 33/405 of the included patients (8.1%). Compared to women with normal STV, those with persistently reduced STV had significantly lower EFW (1472±435 vs 1812±532g, p 0.04), lower birthweight (2353±635 vs 2857±796g, p<0.01) and earlier gestational age at delivery (35.1±4.2 vs 37.3±2.4weeks, p<0.01), whereas all the other variables including gestational age on admission were comparable. ConclusionsReduced STV following maternal betamethasone administration among appropriately grown fetuses seems to correlate with lower fetal size. Furthermore, fetuses with such abnormal response to steroids seem to carry a higher risk of perinatal complications, including lower birthweight and earlier gestational age at delivery.

Effect of Betamethasone on Fetal Pulmonary and Umbilical Artery Doppler Velocimetry and Relationship With Respiratory Distress Syndrome Development.

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. 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. 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). There were no significant differences in PA Doppler indices for fetuses with or without RDS after steroid administration.

The Effect of Betamethasone on Middle Cerebral Artery Doppler Flow in Fetuses With Elevated Peak Systolic Velocities [27Q

INTRODUCTION: Administration of betamethasone (BMZ) has been shown to decrease the morbidity and mortality associated with preterm birth, and is given to patients with a variety of complications such as preterm labor, PPROM, fetal growth restriction, and alloimmunization, among others. As middle cerebral artery (MCA) Dopplers are used to monitor fetal hemodynamics in patients with many of these conditions, we sought to determine if administration of betamethasone is associated with changes in MCA Doppler parameters in fetuses with an abnormally elevated MCA peak systolic velocity (PSV). METHODS: A retrospective longitudinal study was conducted including women with a fetal MCA PSV greater than 1.3 MoM that had an MCA Doppler assessment within one week before and one week after betamethasone administration. Pre- and post-BMZ MCA PSV were compared using a repeated measures t-test. RESULTS: 20 fetuses met inclusion criteria with diagnoses of alloimmunization (13), parvovirus infection (3), fetal growth restriction (2), and twin-twin transfusion (2). The pre-BMZ PSV of 1.60±0.16 MoM was significantly lower than the post-BMZ PSV of 1.41±0.16 MoM (p &lt; 0.0001). 13 of the 20 fetuses had a second post-BMZ MCA Doppler performed with a PSV of 1.5±0.24 MoM which was not significantly different from the initial post-BMZ MCA PSV (p=0.231). CONCLUSION: Our data suggest that maternal betamethasone administration lowers the MCA PSV in fetuses with an initially elevated MCA PSV. This should be taken into account when using MCA Dopplers to monitor fetal hemodynamics in patients receiving BMZ.

Influence of prenatal maternal corticosteroid therapy on clinical and metabolic features and pulmonary function of preterm newborn puppies

Although the effects of antenatal corticosteroid therapy in clinical improvement and pulmonary maturation in preterm have been described, little is known on premature newborn puppies. This study aimed to evaluate the effect of maternal administration of a single dose of prenatal betamethasone on lung function of preterm newborn puppies in the first hours of life, especially from the clinical point of view and acid-base balance. A prospective study was conducted involving 21 puppies allocated into three experimental groups: Term Group (63 days post-ovulation), Preterm-Treated Group (57 days post-ovulation and maternal administration of a single dose of 0.5 mg/kg of betamethasone) and Preterm-Control Group (57 days post-ovulation). Puppies were analyzed clinically through the Apgar score, heart rate, respiratory rate and neurological tests (muscular tone and irritability reflex) and for oximetry and blood acid-base balance in distinct experimental moments. Premature puppies had marked degree of prematurity, reversed by maternal administration of betamethasone. Prenatal corticosteroid therapy promoted better pulmonary and metabolic condition, with more efficient compensatory response to acid-base imbalance and better pulmonary gas exchange capacity. Therefore, prenatal treatment with betamethasone can be adopted as clinical lung maturation protocol for pregnancies at risk in order to prevent low vitality and increase neonatal survival.

Longitudinal progression of fetal short-term variation and average acceleration and deceleration capacity after antenatal maternal betamethasone application

ObjectiveTo analyze the effect of maternal betamethasone given for fetal lung maturation on fetal short-term variation (STV) and average acceleration and deceleration capacity (AAC/ADC). Both of these factors are calculated by phase-rectified signal averaging (PRSA) and represent new parameters to assess the fetal autonomic nervous system. Study designA longitudinal prospective study including 26 pregnant women at risk for preterm delivery was performed. Two injections of 12mg betamethasone were administered intramuscularly at a 24h interval for lung maturation. Cardiotocography recordings were performed at defined time intervals: day 0 (before the first injection) and days 1, 2, 4 after the first corticosteroid administration. AAC/ADC and STV were calculated. ResultsAn increase of all parameters (STV, AAC and ADC) was documented between day 0 and day 1. Between day 1 and day 2, all three indices were significantly reduced (p<0.05). STV declined by 19.8%, AAC by 10.1% and ADC by 14.8%. A normalization of these values was seen after 96h. ConclusionSimilar to STV, AAC/ADC shows significant changes after maternal betamethasone administration. The corticosteroid-induced transient decrease of the levels needs to be taken into account in the assessment of the fetal status to avoid misinterpretation of these parameters.

The fetal sheep lung does not respond to cortisol infusion during the late canalicular phase of development

The prepartum surge in plasma cortisol concentrations in humans and sheep promotes fetal lung and surfactant system maturation in the support of air breathing after birth. This physiological process has been used to enhance lung maturation in the preterm fetus using maternal administration of betamethasone in the clinical setting in fetuses as young as 24 weeks gestation (term = 40 weeks). Here, we have investigated the impact of fetal intravenous cortisol infusion during the canalicular phase of lung development (from 109- to 116-days gestation, term = 150 ± 3 days) on the expression of genes regulating glucocorticoid (GC) activity, lung liquid reabsorption, and surfactant maturation in the very preterm sheep fetus and compared this to their expression near term. Cortisol infusion had no impact on mRNA expression of the corticosteroid receptors (GC receptor and mineralocorticoid receptor) or HSD11B-2, however, there was increased expression of HSD11B-1 in the fetal lung. Despite this, cortisol infusion had no effect on the expression of genes involved in lung sodium (epithelial sodium channel -α, -β, or -γ subunits and sodium–potassium ATPase-β1 subunit) or water (aquaporin 1, 3, and 5) reabsorption when compared to the level of expression during exposure to the normal prepartum cortisol surge. Furthermore, in comparison to late gestation, cortisol infusion does not increase mRNA expression of surfactant proteins (SFTP-A, -B, and -C) or the number of SFTP-B-positive cells present in the alveolar epithelium, the cells that produce pulmonary surfactant. These data suggest that there may be an age before which the lung is unable to respond biochemically to an increase in fetal plasma cortisol concentrations.

406 The Combined Effects of Antenatal Inflammation and Betamethasone on Lung Morphometry in a Rat

AimTo investigate the effects of antenatal maternal glucocorticoids on fetal lung inflammation by determining lung morphology and inflammatory cell influx in bronchoalveolar lavage fluid.MethodsRat pups were divided into four experimental...

Fetal hemodynamic changes following maternal betamethasone administration in monochorionic twin pregnancies featuring one twin with selective growth restriction and abnormal umbilical artery Doppler

To evaluate fetal hemodynamic changes following maternal betamethasone administration in monochorionic twin pregnancies featuring one twin with selective intrauterine growth restriction (sIUGR) and absence of end-diastolic velocity in umbilical artery (UA) Doppler. sIUGR was defined as fetal weight below the 10th percentile in one twin and inter-twin birth weight discordance >25%. The results of Doppler examinations including UA, middle cerebral artery (MCA) and ductus venosus directly prior to (D0), at 24 h (D1) and 48 h (D2) after administration of the first dose of betamethasone were recorded. Cerebral-placenta ratio was defined as MCA pulsatility index (PI) divided by UA-PI. In four (20%) of the 20 cases, the UA Doppler of the growth-restricted twin returned to positive end-diastolic velocity after betamethasone administration. The UA-PI and MCA-PI of the sIUGR twin changed significantly after betamethasone administration: UA-PI was decreased at D1, the MCA-PI was reduced at both D1 and D2, and the cerebral-placenta ratio was not altered after betamethasone administration in the sIUGR twin. The hemodynamic changes after betamethasone administration were different between the two monochorionic twin fetuses where one presented with sIUGR and absence of UA end-diastolic velocity. The etiology of a low rate of return of end-diastolic velocity in the sIUGR twin needs further evaluation.

Preterm rabbit lung tissue mechanics: Maturational changes and effect of antenatal steroids

Describe lung tissue and central airway mechanics using forced oscillation in preterm rabbits at different gestational ages and after maternal administration of betamethasone (BM). One hundred twelve fetuses from 54 does were studied. Ventilation was done using a Flexivent (Scireq, Montreal, Canada). Resistance (Rrs), compliance/bodyweight (Crs/bw), Newtonian resistance (Rn), tissue damping (G(L)), and elastance (H(L)) were assessed. Maturational changes were studied in normal controls at days 27-31. The effect of BM (0.05 mg/kg on days 25 and 26) or placebo was studied in preterm fetuses at days 27, 28, and 29. In unmanipulated control fetuses, Rrs decreased and Crs/bw increased with advancing gestation. Rn remained stable while G(L) and H(L) decreased. After day 29 no differences in pulmonary mechanics were observed. At 28 days Rrs and Crs/bw in BM and placebo fetuses were better compared to controls. At 29 days, Crs/bw and Rrs were higher, respectively, lower in control fetuses than BM or placebo exposed pups. Maturational changes in preterm rabbits occur mainly up to day 29 of gestation and are largely due to changes in tissue mechanics. Maternal BM injection improves lung mechanics at 28 days but placebo has equal effects.