Antenatal Betamethasone Administration Research Articles

Regional Variation in Antenatal Late Preterm Steroid Use Following the ALPS Trial

The publication of the Antenatal Late Preterm Steroids (ALPS) trial in February 2016 demonstrated that antenatal administration of betamethasone in the late preterm period (between 34 to 36 weeks of gestation) for individuals with a high risk of delivery decreased neonatal respiratory morbidity. National estimates have suggested the trial did change obstetric practice, but little is known if the evidence was adopted uniformly or equitably. To assess regional variation in the use of late preterm steroids after the publication of the Antenatal Late Preterm Steroids (ALPS) Trial and to understand factors associated with a region's pace of adoption. This cross-sectional study used US natality data from February 2015 to October 2017 from hospital referral regions (HRRs) within the US. Inclusion criteria included live-born, nonanomalous, singleton, late preterm (34 to 36 completed weeks of gestation) neonates born to individuals without pregestational diabetes. This study was conducted from November 15, 2022, to January 13, 2023. HRRs were categorized as either a slower adopter or faster adopter of antenatal late preterm steroids based on the observed vs expected pace of antenatal steroid adoption in a 1-year period after the trial's dissemination. Patient and regional factors hypothesized a priori to be associated with the uptake of late preterm steroids were compared between faster and slower adopters. Comparisons were made using Student t test or Wilcoxon rank-sum test, as appropriate. A multivariable logistic regression was constructed to identify factors associated with faster adopter status in the postperiod. There were 666 097 late preterm births in 282 HRRs. The mean (SD) maternal age in HRRs was 27.9 (1.2) years. The median (IQR) percentage of births by race categories in HRRs for patients identifying as American Indian or Alaskan Native was 0.5% (0.2%-1.3%); Asian or Pacific Islander, 3.0% (1.7%-5.3%); Black, 12.9% (5.1%-29.1%); and White, 78.6% (66.6%-87.0%). The median percentage of births in HRRs to patients of Hispanic ethnicity was 11.2% (6.3%-27.4%). In this study, 136 HRRs (48.2%) were classified as faster adopters and 146 (51.8%) were classified as slower adopters. Faster adopters increased their steroid use by 12.1 percentage points (from 5.9% to 18.0%) compared with a 5.5 percentage point increase (from 3.7% to 9.2%) among slower adopters (P < .001). Most examined patient and regional factors were not associated with a region's pace of adoption, with the exception of the regional prevalence of prior preterm birth (adjusted odds ratio [aOR], 2.04 [95% CI, 1.48-2.82]) and the percentage of deliveries at 34 to 35 weeks of gestation (aOR, 0.68 [95% CI, 0.47-0.99]) compared with 36 weeks. In this cross-sectional study, there was widespread geographic variation in the adoption of antenatal steroid administration for late preterm births that largely remained unexplained by population factors. These findings should prompt further investigations to barriers to timely or equitable access to new evidence-based practices and guide future dissemination strategies with the goal of more uniform adoption.

Factors associated with maternal hyperglycaemia and neonatal hypoglycaemia after antenatal betamethasone administration in women with diabetes in pregnancy.

Bespoke glycaemic control strategies following antenatal corticosteroids for women with diabetes in pregnancy (DIP) may mitigate hyperglycaemia. This study aims to identify predictive factors for the glycaemic response to betamethasone in a large cohort of women with DIP. Evaluation of a prospective cohort study of 347 consecutive DIP pregnancies receiving two doses of 11.4 mg betamethasone 24 h apart between 2017 and 2021 and treated with the Pregnancy-IVI intravenous insulin protocol. Regression modelling identified factors associated with maternal glycaemic time-in-range (TIR) and maternal insulin requirements following betamethasone. Factors associated with neonatal hypoglycaemia (glucose <2.6 mmol/L) in infants born within 48 h of betamethasone administration (n = 144) were investigated. The mean maternal age was 31.9 ± 5.8 years, with gestational age at betamethasone of 33.5 ± 3.4 weeks. Gestational diabetes was present in 81% (12% type 1; 7% type 2). Pre-admission subcutaneous insulin was prescribed for 63%. On-infusion maternal glucose TIR (4.0-7.8 mmol/L) was 83% [IQR 77%-90%] and mean on-IVI glucose was 6.6 ± 0.5 mmol/L. Maternal hypoglycaemia (<3.8 mmol/L) was uncommon (0.47 h/100 on-IVI woman hours). Maternal glucose TIR was negatively associated with indicators of insulin resistance (type 2 diabetes, polycystic ovary syndrome), late-pregnancy complications (pre-eclampsia, chorioamnionitis) and the 1-h OGTT result. Intravenous insulin requirements were associated with type of diabetes, pre-eclampsia and intrauterine infection, the 1-h OGTT result and the timing of betamethasone administration. Neonatal hypoglycaemia was associated with pre-existing diabetes but not with measures of glycaemic control. An intravenous infusion protocol effectively controls maternal glucose after betamethasone. A risk-factor-based approach may allow individualisation of therapy.

Late preterm antenatal corticosteroids in singleton and twin gestations: a retrospective cohort study

BackgroundIn 2016, the American College of Obstetricians and Gynecologists recommended antenatal corticosteroids in the late preterm period for women at risk for preterm delivery. Limited real-world evidence exists on neonatal outcomes, particularly for twin gestations, following the guideline change. The study objective is to determine the association of antenatal corticosteroids in late preterm singleton and twin pregnancies with respiratory complications and hypoglycemia in a real-world clinical setting.MethodsThis is a retrospective cohort study comprising late preterm deliveries (4,341 mother–child pairs) within the Mount Sinai Health System, 2012–2018. The exposure of interest is antenatal corticosteroid administration of betamethasone during pregnancy between 34 0/7 and 36 6/7 weeks. Our primary outcomes are neonatal respiratory complications and hypoglycemia. Multivariable logistic regression was used to estimate the association between antenatal corticosteroid exposure and these two outcomes. We stratified the study population by singleton gestations and twins to minimize the potential confounding from different obstetric management between the two groups.ResultsAmong a total of 4,341 mother–child pairs (3,309 singleton and 1,032 twin mother–child pairs), 745 mothers received betamethasone, of which 40.94% (305/745) received the full course. Relative to no treatment, a full course of betamethasone was associated with reduced odds of respiratory complications (OR = 0.53, 95% CI:[0.31–0.85], p < 0.01) and increased odds of hypoglycemia (OR = 1.86, 95%CI:[1.34–2.56], p < 0.01) in singletons; however, the association with respiratory complications was not significant in twins (OR = 0.42, 95% CI:[0.11–1.23], p = 0.16), but was associated with increased odds of hypoglycemia (OR = 2.18, 95% CI:[1.12–4.10], p = 0.02).A partial course of betamethasone (relative to no treatment) was not significantly associated with any of the outcomes, other than respiratory complications in twins (OR = 0.34, 95% CI:[0.12–0.82], p = 0.02).ConclusionsExposure to antenatal corticosteroids in singletons and twins is associated with increased odds of hypoglycemia. Among singletons, exposure to the full dosage (i.e. two doses) was associated with decreased odds of respiratory complications but this was only the case for partial dose among twins. Twin gestations were not studied by the Antenatal Late Preterm Steroids trial. Therefore, our study findings will contribute to the paucity of evidence on the benefit of antenatal corticosteroids in this group. Health systems should systematically monitor guideline implementations to improve patient outcomes.

Effect of Maternal Body Mass Index on the Efficacy of Antenatal Betamethasone Administration in Neonatal Outcomes

Effect of Maternal Body Mass Index on the Efficacy of Antenatal Betamethasone Administration in Neonatal Outcomes

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.

Observations on Glucose Excursions With the Use of a Simple Protocol for Insulin, Following Antenatal Betamethasone Administration.

AimsPregnant women with diabetes often require preterm delivery. Antenatal betamethasone reduces perinatal morbidity and mortality, but induces hyperglycemia. The primary objective was to observe glucose excursions and determine the preliminary safety of a protocol for subcutaneous insulin following betamethasone administration in an antenatal ward.Material and MethodsThis retrospective study included all women with diabetes who received betamethasone due to anticipated preterm delivery. Glucose excursions were evaluated in the fasting state and 2-h postprandial. Blood glucose values ≥14mmol/L or ≤3.5mmol/L were regarded as unacceptable hyper- and hypoglycemia respectively. Events over the first 96 h were documented.ResultsThis study spanned 52 months and included fifty-nine women. Eleven episodes of defined hypoglycemia occurred in six women, all receiving insulin therapy, but none after a corrective dose of insulin. No serious hypoglycemic incident was reported. Seventeen women experienced hyperglycemic incidents almost entirely (47/56) within 48 h of betamethasone administration, most often postprandially (34/56) and in 85% of episodes, preceded by pre-prandial values >9 mmol/L (29/34). 14 (82.4%) of these women were receiving background insulin therapy. No case with gestational diabetes encountered defined hyperglycemia.ConclusionsThis small study demonstrated preliminary safety of the protocol. Enhanced surveillance is necessary for 72 h after initiation of betamethasone.

Antenatal corticosteroids for women at risk of preterm delivery: the “Emperor’s New Clothes” tale in medical practice

Objective To introduce the effect of a single course of betamethasone for pregnant women at risk of preterm delivery (PTD). Materials and methods In this study, a single course of 12 mg Bethamethasone was administered twice in 24 h (between 24–34 gestational weeks) for antenatal corticosteroid prophylaxis. Four hundred ninety-three neonates fulfilled the inclusion criteria and they were categorized (259 singletons, 192 twins and 42 triplets who met the inclusion criteria) into two groups according to the utilization of antenatal corticosteroid as control (n = 202) and study (n = 291) groups. We used respiratory distress syndrome (RDS), congenital pneumonia, intraventricular hemorrhage (IVH), neonatal sepsis, and bronchopulmonary dysplasia (BPD) as primary outcomes for the evaluation of neonatal morbidity. Results Study and control groups were similar in terms of clinical characteristics. RDS, congenital pneumonia, neonatal sepsis, and BPD rates were significantly higher in the study group (betamethasone) (p = .05, p = .007, 0.003, and 0.004, respectively) between 24–34 gestational weeks (when the neonates of multiple pregnancies were excluded from the analysis, we have demonstrated that congenital pneumonia (p = .033) and neonatal sepsis (p = .030) were still significantly higher in the betamethasone group). The neonates of 24–28 gestational weeks were compared separately and we demonstrated that RDS (p = .012), congenital pneumonia (p = .022), IVH (p = .044), neonatal sepsis (p = .023), and BPD (0.001) were also more frequent in the study group. When the 28–32 gestational week data were compared, IVH (p = .020) and neonatal sepsis (p = .017) were more frequent in the single course betamethasone users. However, we could not demonstrate a significant difference between the control and study groups between 32–34 gestational weeks in terms of the primary neonatal outcomes used in this study. Conclusion Single course antenatal betamethasone administration may be ineffective on the respiratory complications of preterm and very preterm infants while it may be unfavorable for extremely preterm infants. What is new about the paper, what could add to the current knowledge Pregnant women at risk for preterm labor must be under intensive antenatal care programs, and if possible, necessary precautions must be undertaken to prevent fetal hypoxia together with etiology specific treatments. This approach might contribute to better perinatal outcomes than just administering antenatal corticosteroid therapy.

Antenatal betamethasone administration before elective caesarean section in term pregnant women

Objective: The aim of this study is to show that respiratory problems such as respiratory distressed syndrome and transient tachypnea of newborn can be reduced by antenatal betamethasone administration. Method: The study was conducted on 50 mothers and their babies aged between 21 and 38 years in the Obstetrics and Gynecology Clinic of Haydarpasa Numune Training and Research Hospital between January 2007 and March 2008. Betamethasone was administered to 25 patients who were planned for cesarean section at term due to elective reasons (Group I). The Group II consisted of 25 patients planned for elective caesarean section at term and no betamethasone was administered. Groups were compared according to maternal age, maternal smoking, maternal chronic disease history, gestation day, cesarean section type of anesthesia, birth weight and sex of the baby. Postnatal infants were evaluated according to Apgar scores of 1 and 5 minutes, ventilation with mask, intubation, resuscitation or intensive care needs. RDS and TNT were recorded. Results: I n the non-corticosteroid-treated group (group 2), two babies developed TNT of the newborn. However, no statistically significant difference was found between the groups (p> 0.05). Respiratory distress syndrome did not develop in any of our patients. The abortion rate in Group I (20%) was significantly higher than the abortion rate in Group II (0%) (p 0.05). Conclusions: T he use of antenatal corticosteroid in elective caesarean sections over 37 weeks may cause a decrease in the development of respiratory problems such as RDS and YGT.

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.

Effects of Antenatal Betamethasone on Fetal Doppler Indices andShort Term Fetal Heart Rate Variation in Early Growth RestrictedFetuses.

To investigate the effects of the antenatal administration of betamethasone on fetal Doppler and short term fetal heart rate variation (CTG-STV) in early growth restricted (FGR) fetuses. Post hoc analysis of data derived from the TRUFFLE study, a prospective, multicenter, randomized management trial of severe early onset FGR. Repeat Doppler and CTG-STV measurements between the last recording within 48 hours before the first dose of betamethasone (baseline value) and for 10 days after were evaluated. Multilevel analysis was performed to analyze the longitudinal course of the umbilico-cerebral ratio (UC ratio), the ductus venosus pulsatility index (DVPIV) and CTG-STV. We included 115 fetuses. A significant increase from baseline in CTG-STV was found on day + 1 (p = 0.019) but no difference thereafter. The DVPIV was not significantly different from baseline in any of the 10 days following the first dose of betamethasone (p = 0.167). Multilevel analysis revealed that, over 10 days, the time elapsed from antenatal administration of betamethasone was significantly associated with a decrease in CTG-STV (p = 0.045) and an increase in the DVPIV (p = 0.001) and UC ratio (p < 0.001). Although steroid administration in early FGR has a minimal effect on increasing CTG-STV one day afterwards, the effects on Doppler parameters were extremely slight with regression coefficients of small magnitude suggesting no clinical significance, and were most likely related to the deterioration with time in FGR. Hence, arterial and venous Doppler assessment of fetal health remains informative following antenatal steroid administration to accelerate fetal lung maturation.

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.

The Effect of Antenatal Betamethasone on White Matter Inflammation and Injury in Fetal Sheep and Ventilated Preterm Lambs

Antenatal administration of betamethasone (BM) is a common antecedent of preterm birth, but there is limited information about its impact on the acute evolution of preterm neonatal brain injury. We aimed to compare the effects of maternal BM in combination with mechanical ventilation on the white matter (WM) of late preterm sheep. At 0.85 of gestation, pregnant ewes were randomly assigned to receive intra-muscular (i.m.) saline (n = 9) or i.m. BM (n = 13). Lambs were delivered and unventilated controls (UVC_Sal, n = 4; UVC_BM, n = 6) were humanely killed without intervention; ventilated lambs (Vent_Sal, n = 5; Vent_BM, n = 7) were injuriously ventilated for 15 min, followed by conventional ventilation for 75 min. Cardiovascular and cerebral haemodynamics and oxygenation were measured continuously. The cerebral WM underwent assessment of inflammation and injury, and oxidative stress was measured in the cerebrospinal fluid (CSF). In the periventricular and subcortical WM tracts, the proportion of amoeboid (activated) microglia, the density of astrocytes, and the number of blood vessels with protein extravasation were higher in UVC_BM than in UVC_Sal (p < 0.05 for all). During ventilation, tidal volume, mean arterial pressure, carotid blood flow, and oxygen delivery were higher in ­Vent_BM lambs (p < 0.05 vs. Vent_Sal). In the subcortical WM, microglial infiltration was increased in the Vent_Sal group compared to UVC_Sal. The proportion of activated microglia and protein extravasation was higher in the Vent_BM group compared to Vent_Sal within the periventricular and subcortical WM tracts (p < 0.05). CSF oxidative stress was increased in the Vent_BM group compared to UVC_Sal, UVC_BM, and Vent_Sal groups (p < 0.05). Antenatal BM was associated with inflammation and vascular permeability in the WM of late preterm fetal sheep. During the immediate neonatal period, the increased carotid perfusion and oxygen delivery in BM-treated lambs was associated with increased oxidative stress, microglial activation and microvascular injury.

Evaluation of Cortisol Level in Premature Neonates: Are There any Correlations between Prevalence of Patent Ductus Arteriosus and Prenatal Administration of Betamethasone?

Background: The results of previous studies suggested that there is an increased risk of patent ductus arteriosus (PDA) in the neonates with lower serum cortisol levels. This study aimed to assess the association between serum cortisol values and PDA and investigate if there is an association between PDA and the antenatal administration of betamethasone. Methods: The present study was carried out on the neonates with gestational age between 28 to 35 weeks. The prenatal administration of betamethasone to the mothers was extracted from the records. A pediatric cardiologist performed an echocardiographic assessment on the second day of life (DOL) and fifth DOL and the infants were evaluated for the presence of PDA. The blood samples were obtained on the second and fifth DOL and serum cortisol levels were measured. We evaluated the association between serum cortisol levels and PDA. Also, the correlation between PDA and the antenatal administration of betamethasone was assessed. Results: The mean scores of serum cortisol levels on the second DOL in the neonates with and without PDA were 4.99±2.69 (μg/dl) and 7.23±2.87 (μg/dl), respectively that were significantly lower in the first group, compared to those of the second group. However, the mean levels of serum cortisol in the neonates with and without the prenatal administration of betamethasone were not significant (P=0.522). Conclusion: We have concluded that lower serum cortisol level was associated with the increase in the risk of PDA and the prenatal administration of glucocorticoids may not reduce the occurrence of PDA.

Evaluation of the effect of antenatal betamethasone on neonatal respiratory morbidities in late preterm deliveries (34–37 weeks)

Background: Since late preterm neonates (34–36 weeks) are more at risk of respiratory morbidities, the present study was conducted to evaluate the effect of antenatal betamethasone on neonatal respiratory morbidities in women with late preterm delivery.Methods: This randomized clinical trial was performed on 240 women with single pregnancy that was at high risk of late preterm delivery (34–37 weeks). The patients were randomly assigned to either betamethasone (intramuscular injection of 12 mg of betamethasone in two doses with an interval of 24 hours) or the control group. The two groups were compared with each other in terms of respiratory morbidities, NICU admission and its cause and duration, hospitalization in the neonatal ward for more than 6 hours, and the duration of hospitalization.Results: Of all, 79 neonates (33%) had one or more respiratory morbidities. The observed morbidities in the betamethasone group were significantly less prevalent than those in the control group (19 neonates (16%) and 60 neonates (50%), respectively, p < .001). The most frequently observed respiratory morbidity was needed for oxygen for more than an hour (34 infants, 14%). The need for oxygen for more than an hour, the need for continuous positive airway pressure (CPAP), respiratory distress syndrome (RDS), and the need for surfactant were significantly less observed in betamethasone group than in the control group. A total of 43 neonates (18%) were admitted to NICU and then hospitalized in the neonatal ward; the number of admitted neonates were significantly lower in the betamethasone group than in the control group (11 neonates (9%) and 32 neonates (27%), respectively, p < .001). Moreover, 15 neonates (6%) were admitted to the neonatal ward and there were no significant differences between the betamethasone and control groups (10 neonates (8%) and 5 neonates (4%), respectively, p = .182). Totally, 58 neonates (24%) were hospitalized; the number of hospitalized neonates was significantly lower in the betamethasone group than in the control group (21 neonates (18%) and 37 neonates (31%), respectively, p = .016).Conclusion: The results of this study showed that the antenatal administration of betamethasone in late preterm delivery (34–37 weeks) can improve respiratory morbidities and decrease the frequency of NICU admission.

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 antenatal betamethasone administration on rat cerebellar expression of type 1a metabotropic glutamate receptors (mGluR1a) and anxiety-like behavior in the elevated plus maze

Preclinical studies indicate that endogenous or exogenous glucocorticoids acting during the pre- or postnatal periods produce a significant Purkinje cell dendritic atrophy, especially during late postnatal ages. The present authors hypothesized that the underlying substrate that may contribute in part to this morphological change is the under-expression of the metabotropic glutamate 1a receptor (mGluR1a) because its expression is correlated with Purkinje cell dendritic outgrowth. Therefore, in the current study, they analyzed the impact of antenatal betamethasone on the immunoreactive expression of the mGluR1a and on anxiety-like behavior in the elevated plus maze (EPM). Pregnant rats were randomly divided into two experimental groups: control (CONT) and betamethasone-treated (BET). At gestational day 20 (G20), BET rats were subcutaneously injected with a solution of 170 &#x03BC;g.kg-1 of betamethasone, and CONT animals received a similar volume of saline. At postnatal days 22 (P22) and P52, BET and CONT offspring were evaluated behaviorally in the EPM, and their cerebella were immunohistochemically processed. Contrary to the uthors’ expected results, animals that were prenatally treated with a single course of betamethasone did not exhibit under-expression of mGluR1a or behavioral changes consistent with anxiety-like behaviors.

Effect of antenatal betamethasone administration on Doppler velocimetry of fetal and uteroplacental vessels: a prospective study.

To examine the effect of antenatal betamethasone administration on Doppler parameters of fetal and uteroplacental circulation. Seventy-six singleton pregnancies that received betamethasone therapy were prospectively evaluated. Doppler measurements of pulsatility indices (PI) in fetal umbilical artery (UA), middle cerebral artery (MCA), ductus venosus and maternal uterine arteries were performed before (0 h) and 24, 48, 72 and 96 h after the first dose of betamethasone. Women with positive end-diastolic flow (EDF) in UA and those with absent or reversed EDF in UA were evaluated separately. Fifty-two women with EDF in UA and 24 women with absent or reversed flow in UA were examined. Administration of maternal betamethasone was followed by a significant decrease in the PI of the MCA at 24 h (P<0.05). Additionally, return of absent to positive, reversed to absent or from reversed to positive diastolic flow in UA was detected within 24 h in 19 (79.2%) fetuses with absent or reversed UA-EDF. All alterations were transient and maintained up to 72 h. Antenatal administration of betamethasone is associated with significant but transient changes in the fetal blood flow. Hence, intensive surveillance of fetuses with Doppler ultrasonography is warranted following betamethasone therapy.

Effect of Maternal Steroid on Developing Diaphragm Integrity

Antenatal steroids reduce the severity of initial respiratory distress of premature newborn babies but may have an adverse impact on other body organs. The study aimed to examine the effect of maternal steroids on postnatal respiratory muscle function during development and elucidate the mechanisms underlying the potential myopathy in newborn rats. Pregnant rats were treated with intramuscular injections of 0.5 mg/kg betamethasone 7 d and 3 d before birth. Newborn diaphragms were dissected for assessment of contractile function at 2 d, 7 d or 21 d postnatal age (PNA), compared with age-matched controls. The expression of myosin heavy chain (MHC) isoforms and atrophy-related genes and activity of intracellular molecular signalling were measured using quantitative PCR and/or Western blot. With advancing PNA, neonatal MHC gene expression decreased progressively while MHC IIb and IIx isoforms increased. Protein metabolic signalling showed high baseline activity at 2 d PNA, and significantly declined at 7 d and 21 d. Antenatal administration of betamethasone significantly decreased diaphragm force production, fatigue resistance, total fast fibre content and anabolic signalling activity (Akt and 4E-BP1) in 21 d diaphragm. These responses were not observed in 2 d or 7 d postnatal diaphragm. Results demonstrate that maternal betamethasone treatment causes postnatal diaphragmatic dysfunction at 21 d PNA, which is attributed to MHC II protein loss and impairment of the anabolic signalling pathway. Developmental modifications in MHC fibre composition and protein signalling account for the age-specific diaphragm dysfunction.

Umbilical Artery Aneurysm

Umbilical artery aneurysm is a rare and often lethal condition frequently associated with fetal anomalies, fetal demise, and neonatal complications. We report a case of umbilical artery aneurysm discovered at 21 weeks 2 days of gestation in a fetus of normal karyotype. Maternal hospitalization occurred at 28 weeks for antenatal testing, betamethasone administration, and monitoring for expansion of the aneurysm. Delivery of a live neonate by repeat cesarean delivery was performed at 32 weeks 2 days. Pathology confirmed a 3-vessel cord with an umbilical artery aneurysm. Neonatal course was complicated by respiratory distress of the newborn, hyperbilirubinemia, anemia, difficulty feeding, and cardiac defects. The newborn was discharged from the neonatal intensive care unit on day of life 19. Umbilical artery aneurysm is highly associated with fetal complications including trisomy 18, single umbilical artery, cardiac anomalies, and intrauterine fetal demise. A normal karyotype, antenatal monitoring, and early delivery have been suggested to impact the likeliness of survival. Antenatal management strategies include consideration of nonstress testing 3 times daily, serial ultrasound assessments, testing to identify intrauterine growth restriction, and delivery by planned cesarean delivery between 32 and 34 weeks. We recommend that patients be counseled on the high risks associated with umbilical artery aneurysm and be included in discussions regarding antenatal management and delivery planning.

The association of antenatal corticosteroids with neonatal hypoglycemia and hyperbilirubinemia

Objective: While antenatal corticosteroids reduce the risk of neonatal morbidity and mortality, perhaps the maternal hyperglycemia they produce has other neonatal effects. Thus, we sought to examine the association between antenatal betamethasone exposure and neonatal hypoglycemia and hyperbilirubinemia.Methods: We designed a retrospective cohort study of all preterm deliveries from 32 to 37 weeks of gestation at a single university hospital from 1990 to 2007. Data were collected on antenatal betamethasone administration and the neonatal outcomes. Univariable, multivariable and stratified analyses were conducted.Results: Of 6675 preterm deliveries, significantly higher rates of neonatal hypoglycemia (5.7% versus 4.2%, p < 0.05) and hyperbilirubinemia (45.9% versus 24.1%, p < 0.05) were observed in neonates exposed to antenatal betamethasone. Controlling for potential confounders including gestational age, these findings persisted with betamethasone-exposed neonates 1.6 times more likely to have hypoglycemia (aOR 1.60, 95% CI 1.24–2.07) and 3.2 times more likely to have hyperbilirubinemia (aOR 3.23, 95% CI 2.92–3.58).Conclusions: Antenatal betamethasone was associated with neonatal hypoglycemia and hyperbilirubinemia. Further work to determine whether this association is related to maternal hyperglycemia should be conducted, given this could be addressed with strict maternal glycemic control during betamethasone administration.