Use Of Antenatal Corticosteroids Research Articles

Trends in outcomes of very preterm infants in Romania: A tale of three cities.

Although survival of preterm infants has improved, prematurity remains the second most frequent cause of death before 5years of age in Romania. Data on the changing mortality of Romanian preterm infants born before 29weeks of gestation have not been available. Outcomes of infants of gestational age 25-28weeks born in 2007-2010 (n=247) were compared with those born in 2011-2014 (n=235). Data were analyzed from three tertiary neonatal intensive care centers. Mortality rates and major morbidities were compared between these two epochs. Infants in the later epoch were more likely to have been born by cesarean section and had higher 1 and 5min Apgar scores. Mortality rate decreased significantly with increasing gestational age at birth. Between the two epochs, the in-hospital mortality rate decreased from 65.6% to 29.4% (P<0.001); death in the first 48h decreased from 30.0% to 8.5% (P<0.001); and prevalence of severe intraventricular hemorrhage decreased from 52.2% to 11.9% (P<0.001). There were significant increases in the rates of necrotizing enterocolitis and bronchopulmonary dysplasia among survivors but no change in the rate of retinopathy of prematurity. The rate of antenatal corticosteroid use did not change and was only 47% in the more recent epoch (2011-2014). Overall mortality is decreasing, and infants admitted in the later epoch had substantially different rates of mortality and several serious morbidities. The low rate of antenatal corticosteroid use provides an opportunity for further reductions in mortality and morbidity among very preterm infants born in Romania.

A review of antenatal corticosteroid use in premature neonates in a middle-income country.

Antenatal corticosteroid (ANS) use in premature neonates has become a standard of practice. However, there is low ANS coverage in low- to middle-income countries (LMICs). Recent studies have questioned the efficacy of ANSs in such countries. To review the use of ANSs in preterm neonates at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), South Africa. This was a retrospective observational study of all neonates with a birth weight of 500 - 1 800 g born at CMJAH between 1 January 2013 and 30 June 2016. Neonatal and maternal characteristics of neonates exposed to ANSs were compared with those of neonates who were not exposed. The ANS coverage of the final sample was 930/2 109 (44.1%). The mean (standard deviation (SD)) birth weight was 1 292.4 (323.2)g and the mean gestational age 30.2 (2.9) weeks. Attending antenatal care and maternal hypertension were associated with increased use of ANSs, whereas vaginal delivery was associated with decreased use. In neonates weighing &lt;1 500 g, the use of ANSs was associated with decreased mortality, decreased intraventricular haemorrhage and decreased patent ductus arteriosus. There was no association between ANSs and respiratory distress syndrome, necrotising enterocolitis, sepsis or need for respiratory support in all premature neonates, and no association with improved outcomes in those weighing ≥1 500 g. The benefits of ANSs in terms of neonatal morbidity in this study were not as marked as those published in high-income countries. A randomised controlled trial may be indicated in LMICs.

Early Mortality and Morbidity in Infants with Birth Weight of 500 Grams or Less in Japan

To assess the short-term prognosis of Japanese infants with a birth weight (BW) of ≤500 g. Demographic and clinical data were reviewed for 1473 live born infants with a BW ≤500 g at gestational age ≥22 weeks who were treated in the 204 affiliated hospitals of the Neonatal Research Network of Japan between 2003 and 2012. Survival to hospital discharge occurred in 811 of 1473 infants (55%; 95% CI 53%-58%). The survival rates of BW ≤300 g, 301-400 g, and 401-500 g were 18% (95% CI 10%-31%), 41% (95% CI 36%-47%), and 60% (95% CI 57%-63%), respectively. In a multivariable Cox proportional hazards analysis, antenatal corticosteroid use (adjusted hazard ratio: 0.68; 95% CI 0.58-0.81; P < .01), cesarean delivery (0.69; 95% CI 0.56-0.85; P < .01), advanced gestational age per week (0.94; 95% CI 0.89-0.99; P = .02), BW per 100-g increase (0.55; 95% CI 0.49-0.64; P < .01), Apgar score ≥4 at 5 minutes (0.51; 95% CI 0.43-0.61; P < .01), and no major congenital abnormalities (0.38; 95% CI 0.29-0.51; P < .01) were associated with survival to discharge. Despite the improved survival rate over the 10-year study period (from 40% in 2003 [95% CI 30%-51%] to 68% in 2012 [95% CI 61%-75%]), at least 1 severe morbidity was present in 81%-89% of the survivors. Improvements in perinatal-neonatal medicine have improved the survival, but not the rate of major morbidities, of infants with a BW ≤500 g in Japan.

Extended-interval Dosing of Gentamicin in Premature Neonates Born at 7 Days of age

PurposeExtended-interval dosing (EID) regimens of gentamicin have been validated for treating confirmed or suspected early- and late-onset sepsis in preterm infants in the first week of life. Despite the marked changes in volume of distribution and renal clearance in preterm infants after the first few days of life, few studies have validated EID regimens of gentamicin in this population. The objective of the study was to evaluate an EID regimen of gentamicin in infants born at <32 weeks’ gestational age and aged >7 days. MethodsThis observational study of an EID regimen was conducted in 39 infants. Dosing interval was based on the serum drug concentration at 22 hours after the administration of the first dose of 5 mg/kg. Gentamicin peak (5–12 µg/mL) and trough (<2 µg/mL) levels were compared to those in a historical control group of 39 infants who received traditional-interval dosing (TID) of 2.5 mg/kg of gentamicin with dosing intervals of 8, 12, or 24 hours. FindingsThere were no differences in birthweight, gestational age at birth, postmenstrual age, weight at the start of gentamicin administration, postnatal age, small for gestational age status, antenatal corticosteroid use, or postnatal indomethacin exposure between the 2 groups. In the EID group, dosing intervals were 24 hours in 30 infants, 36 hours in 6 infants, and 48 hours in 3 infants. Compared with the TID group (n = 39), the EID group had a significantly higher peak level (median, 9.0 vs 4.7 µg/mL) and a significantly lower trough level (median, 0.7 vs 1.1 µg/mL) (both, P < 0.001). On regression analysis, the postmenstrual age was correlated significantly with trough levels in the EID group. There was no adverse effect on renal function in either group. On follow-up, 1 infant in the EID group and 2 infants in the TID group had evidence of sensorineural hearing loss. ImplicationsIn infants born at <32 weeks’ gestation and >7 days of age, an EID gentamicin regimen, with a dosing interval based on a single concentration measurement at 22 hours after the administration of the first dose, achieved therapeutic peak and trough levels and performed significantly better than did a TID regimen in reaching target peak and trough levels. Larger-scale trials are needed for assessing the clinical efficacy (treatment failure/success) of these regimens.

Use of antenatal corticosteroids in special circumstances: a comprehensive review.

The aim of this study was to determine, in pregnancies complicated by preterm premature rupture of membranes (PPROM), hypertension, intrauterine growth restriction, multi-fetal gestations and pregnancies 23-26weeks and ≥34weeks' gestation, whether antenatal corticosteroids benefit the fetus. Literature review using PubMed, Web of Science, Clinical trials.gov, Cochrane Database of Systematic Reviews (1990-2015). Search terms linked special circumstances with corticosteroids. Randomized clinical trials, retrospective and prospective cohort studies, and case control studies were reviewed. In all, 468 abstracts were identified and 84 added from selected article bibliographies; of these, 503 abstracts were excluded, leaving 49 articles as the basis of review. The literature supports corticosteroids for PPROM up to 32-34weeks without chorioamnionitis. Antenatal corticosteroids are beneficial for preterm infants of women with HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome/severe preeclampsia. Postpartum corticosteroid treatment of HELLP patients results in more rapid correction of liver enzymes, platelet counts, and urinary output, which can reduce maternal morbidity. Corticosteroids in twin pregnancies decrease respiratory distress syndrome but the effect is less than in singleton pregnancies. Corticosteroid effects on intrauterine growth restriction pregnancies are conflicting and steroid use should be individualized. Corticosteroid use for 23-26weeks reduces neonatal mortality but not morbidity. In pregnancies of 34weeks to 366/7 weeks, corticosteroids reduce respiratory distress syndrome, but follow-up studies are unavailable. No long-term adverse child developmental effects have been observed with one or two courses of corticosteroids, but three or more steroid courses lowers birthweight and organ weight, and there may be an increase in neurodevelopmental abnormalities. Longer follow up of corticosteroid-treated fetuses is required.

Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth.

Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth.

Population-based study on antenatal corticosteroid treatment in preterm small for gestational age and non-small for gestational age twin infants

Objectives: To assess the associations between antenatal corticosteroid use (ACU), mortality and severe morbidities in preterm, twin neonates and compare these between small for gestational age (SGA) and non-SGA twins.Materials and methods: Population-based study using data collected by the Israel National Very Low Birth Weight infant database from 1995 to 2012, comprising twin infants of 24–31 weeks' gestation, without major malformations. Univariate and multivariable logistic regression analyses were performed.Results: Among the 6195 study twin infants, 784 were SGA. Among SGA neonates, ACU were associated with decreased mortality (23.9% vs. 39.2%, p < 0.0001) and composite adverse outcome including mortality or severe neonatal morbidity (43.8% vs. 56.8%, p = 0.0015), similar to the effect in non-SGA neonates (mortality 13.0% vs. 24.5%, p < 0.0001; composite outcome 34.2% vs. 44.8%, p < 0.0001). In the multivariable logistic regression analyses, ACU were associated with an almost 50% reduced mortality risk among SGA twin neonates (OR = 0.52, 95% CI 0.31–0.88) similar to the effect in non-SGA twin neonates (OR = 0.56, 95% CI 0.45–0.70), Pinteraction = 0.69. Composite adverse outcome risk was also reduced in SGA (OR = 0.78, 95% CI 0.50–1.23) and non-SGA groups (OR = 0.78, 95% CI 0.65–0.95), Pinteraction = 0.95.Conclusions: ACU should be considered in all mothers with twin gestation, at risk for preterm delivery at 24–31 weeks, in order to improve perinatal outcome.

Extreme Prematurity Outcomes: Have We Really Reached the Limit?

Health care professionals and laypeople alike are convinced that outcomes of very preterm infants have been steadily improving over the years. Yet in an interesting article published in this issue of Pediatrics , Stensvold et al1 challenge this belief. In short, the authors conducted an area-based study in Norway in 2013–2014, collecting data on outcomes of all pregnancies ending either in stillbirth or in a live birth from 22 to 26 weeks of gestation. Compared with an analogous study carried out in 1999–2000, they found an increase in the absolute number of such pregnancies, with an increase of intrauterine deaths before admission to the hospital and no improvement thereafter. These results are both surprising and thought-provoking. This lack of improvement is surprising in view of the great improvements in obstetric and neonatal care in the past decade, including the widespread use of antenatal corticosteroids even at low gestational weeks, improvements in delivery room management and thermoregulation, and improved ventilatory and nutritional strategies. Many studies, both area-based and not,2–9 have shown an improvement in mortality and morbidity over … Address correspondence to Luigi Gagliardi, MD, Woman and Child Health Department, Pediatrics and Neonatology Division, Ospedale Versilia, Via Aurelia 335, 55043 Lido di Camaiore (LU), Italy. E-mail: l.gagliardi{at}neonatalnet.org

Factores perinatales asociados a la mortalidad neonatal en recién nacidos de muy bajo peso: estudio multicéntrico

Objectives. To assess risk factors associated withneonatal mortality in very low birth weight (VLBW) infants (< 1500 g) and the impact of the administration of antenatal corticosteroids. Retrospective analysis of a VLBW infant cohort from 26 tertiary care and teaching sites member of the South American Neonatal Network (NEOCOSUR), which includes Argentina, Brazil, Chile, Paraguay, Peru, and Uruguay, conducted between 2000 and 2011 on 11 455 records. Maternal and neonatal characteristics and morbidity were compared between deceased VLBW infants and those who survived to discharge. Outcome measures associated with neonatal mortality were established by logistic regression. The effect of antenatal corticosteroids on neonatal morbidity and mortality was estimated using the matching method. The neonatal mortality rate was 22.3%, and variability among sites was elevated. Factors that were independently associated with a lower mortality of VLBW infants included the administration of antenatal corticosteroids (OR: 0.49, 95% CI: 0.43-0.54), a better birth weight Z-score (OR: 0.63, 0.61-0.65), arterial hypertension (OR: 0.67, 0.58-0.77), and C-section (OR: 0.75, 0.65-0.85). The matching method allowed reducing the risk of death by 38% in association with antenatal corticosteroids. Major perinatal factors were identified in association with neonatal mortality in VLBW infants, and the impact of antenatal corticosteroid use in the NEOCOSUR Network was demonstrated.

Antenatal corticosteroids are currently used excessively and more stringent controls on their use should be established: AGAINST: Current use of antenatal corticosteroids effectively reduces neonatal morbidity and mortality.

Antenatal corticosteroids are currently used excessively and more stringent controls on their use should be established: AGAINST: Current use of antenatal corticosteroids effectively reduces neonatal morbidity and mortality.

Antenatal corticosteroids are currently used excessively and more stringent controls on their use should be established: FOR: The use of antenatal corticosteroids should be restricted if we are to avoid causing harm.

Antenatal corticosteroids are currently used excessively and more stringent controls on their use should be established: FOR: The use of antenatal corticosteroids should be restricted if we are to avoid causing harm.

Providing antenatal corticosteroids for preterm birth: a quality improvement initiative in Cambodia and the Philippines.

ObjectiveTo determine whether a simple quality improvement initiative consisting of a technical update and regular audit and feedback sessions will result in increased use of antenatal corticosteroids among pregnant women at risk of imminent preterm birth delivering at health facilities in the Philippines and Cambodia.DesignNon-randomized, observational study using a pre-/post-intervention design conducted between October 2013 and June 2014.SettingA total of 12 high volume facilities providing Emergency Obstetric and Newborn Care services in Cambodia (6) and Philippines (6).InterventionA technical update on preterm birth and use of antenatal corticosteroids, followed by monthly audit and feedback sessions.Main Outcome MeasureThe proportion of women at risk of imminent preterm birth who received at least one dose of dexamethasone.ResultsCoverage of at least one dose of dexamethasone increased from 35% at baseline to 86% at endline in Cambodia (P < 0.0001) and from 34% at baseline to 56% at endline in the Philippines (P < 0.0001), among women who had births at 24–36 weeks. In both settings baseline coverage and magnitude of improvement varied notably by facility. Availability of dexamethasone, knowledge of use and cost were not major barriers to coverage.ConclusionsA simple quality improvement strategy was feasible and effective in increasing use of dexamethasone in the management of preterm birth in 12 hospitals in Cambodia and Philippines.

Maternal and Placental Factors Associated with Congenital Hearing Loss in Very Preterm Neonates

Sensorineural hearing loss (SNHL) is a multifactorial disease that more frequently affects preterm newborns. Although a number of maternal conditions have been reported to be associated with preterm birth, little information is available concerning maternal risk factors for the development of SNHL. We aimed to identify maternal and placental risk factors associated with a "refer" result on the newborn hearing screening (NHS) test and subsequently confirmed SNHL in very preterm neonates. This retrospective cohort study included 267 singleton neonates who were born alive after≤32weeks. Histopathologic examination of the placenta was performed, and clinical data were retrieved from a computerized perinatal database. Cases with two abnormal findings, "refer" on the NHS test, and presence of SNHL on the confirmation test were retrospectively reviewed based on electronic medical records. Forty-two neonates (15.7%) showed a "refer" result, and, on the confirmation test, permanent SNHL was identified in 1.87% (5/267) of all neonates. Multivariate regression analysis revealed that the presence of funisitis was independently associated with a "refer" on the NHS test, whereas use of antenatal corticosteroids was statistically significantly associated with a reduced incidence of "refer" on the screening test. Neither histologic chorioamnionitis nor prematurity (as defined by low gestational age and birth weight) was associated with a "refer" on the NHS test. By contrast, multivariate analysis with occurrence of SNHL as a dependent variable identified no significant associations with the parameters studied, probably owing to the small total number of neonates with permanent SNHL. Presence of funisitis was significantly and independently associated with increased risk of abnormal NHS results, while administration of antenatal corticosteroids was related to a normal NHS result. These findings support the hypothesis that a systemic fetal inflammatory response, manifested as funisitis, might play a role in the pathogenesis of SNHL in preterm neonates.

Evaluation of Score for Neonatal Acute Physiology and Perinatal Extension II and Clinical Risk Index for Babies with additional parameters.

The aim of this study was to determine mortality risk by calculating Score for Neonatal Acute Physiology and Perinatal Extension II (SNAP-PE-II) and Clinical Risk Index for Babies (CRIB) score, and evaluate prediction of the effects of antenatal corticosteroid and surfactant treatment on mortality. This multicenter study was conducted simultaneously in five different centers in four different provinces in Southern Turkey between July 2012 and July 2013. A total of 1668 inborn subjects hospitalized in the neonatal intensive care unit within the first 12 h of delivery, and meeting the selection criteria, were included in the study, and CRIB and SNAP-PE-II were used to determine mortality. The SNAP-PE-II scoring system was applied to all patients, and the CRIB scoring system was used for 310 newborns with gestational age <32 weeks and weighing <1500 g. Of the 1668 patients, 188 died (mortality rate, 11.3%). Cut-off was found to vary with center, which changed specificity and sensitivity of the mortality scores. SNAP-PE-II significantly predicted mortality (P < 0.05) compared with CRIB. SNAP-PE-II also successfully predicted mortality in the group receiving antenatal corticosteroid compared with the group not receiving antenatal corticosteroid. SNAP-PE-II was a significant predictor of mortality in newborns with birthweight <1500 g compared with CRIB, and assessment of antenatal corticosteroid use in conjunction with SNAP-PE-II increased the accuracy of the prediction of mortality.

Use of antenatal corticosteroids at health facilities and communities in low-and-middle income countries.

BackgroundAntenatal corticosteroids (ACS) for women at high risk of preterm birth is an effective intervention to reduce neonatal mortality among preterm babies delivered in hospital settings, but has not been widely used in low-middle resource settings. We sought to assess the rates of ACS use at all levels of health care in low and middle income countries (LMIC).MethodsWe assessed rates of ACS in 7 sites in 6 LMIC participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Global Network for Women and Children’s Health Research Antenatal Corticosteroids Trial (ACT), a cluster-randomized trial to assess the feasibility, effectiveness, and safety of a multifaceted intervention designed to increase the use of ACS. We conducted this analysis using data from the control clusters, which did not receive any components of the intervention and intended to follow usual care. We included women who delivered an infant with a birth weight <5th percentile, a proxy for preterm birth, and were enrolled in the Maternal Newborn Health (MNH) Registry between October 2011 and March 2014 in all clusters. A survey of the site investigators regarding existing policies on ACS in health facilities and for health workers in the community was part of pre-trial activities.ResultsOverall, of 51,523 women delivered in control clusters across all sites, the percentage of <5th percentile babies ranged from 3.5 % in Kenya to 10.7 % in Pakistan. There was variation among the sites in the use of ACS at all hospitals and among those hospitals having cesarean section and neonatal care capabilities (bag and mask and oxygen or mechanical ventilation). Rates of ACS use for <5th percentile babies in all hospitals ranged from 3.8 % in the Kenya sites to 44.5 % in the Argentina site, and in hospitals with cesarean section and neonatal care capabilities from 0 % in Zambia to 43.5 % in Argentina. ACS were rarely used in clinic or home deliveries at any site. Guidelines for ACS use at all levels of the health system were available for most of the sites.ConclusionOur study reports an overall low utilization of ACS among mothers of <5th percentile infants in hospital and clinic deliveries in LMIC.Trial Registrationclinicaltrials.gov (NCT01084096)

The Antenatal Corticosteroids Trial (ACT)'s explanations for neonatal mortality - a secondary analysis.

BackgroundThe Antenatal Corticosteroid Trial assessed the feasibility, effectiveness, and safety of a multifaceted intervention to increase the use of antenatal corticosteroids (ACS) in mothers at risk of preterm birth at all levels of care in low and middle-income countries. The intervention effectively increased the use of ACS but was associated with an overall increase in neonatal deaths. We aimed to explore plausible pathways through which this intervention increased neonatal mortality.MethodsWe conducted a series of secondary analyses to assess whether ACS or other components of the multifaceted intervention that might have affected the quality of care contributed to the increased mortality observed: 1) we compared the proportion of neonatal deaths receiving ACS between the intervention and control groups; 2) we compared the antenatal and delivery care process in all births between groups; 3) we compared the rates of possible severe bacterial infection between groups; and 4) we compared the frequency of factors related to ACS administration or maternal high risk conditions at administration between the babies who died and those who survived 28 days among all births in the intervention group identified as high risk for preterm birth and received ACS.ResultsThe ACS exposure among the infants who died up to 28 days was 29 % in the intervention group compared to 6 % in controls. No substantial differences were observed in antenatal and delivery care process between groups. The risk of pSBI plus neonatal death was significantly increased in intervention clusters compared to controls (2.4 % vs. 2.0 %, adjusted RR 1.17, 95 % CI 1.04–1.30, p = 0.008], primarily for infants with birth weight at or above the 25th percentile. Regarding factors related to ACS administration, term infants who died were more likely to have mothers who received ACS within 7 days of delivery compared to those who survived 28 days (26.5 % vs 17.9 %, p = 0.014), and their mothers were more likely to have been identified as high risk for hypertension and less likely for signs of preterm labor.ConclusionsThese results suggest that ACS more than other components of the intervention may have contributed to the overall increased neonatal mortality. ACS may have also been involved in the observed increased risk of neonatal infection and death. Further trials are urgently needed to clarify the effectiveness and safety of ACS on neonatal health in low resource settings.

The Antenatal Corticosteroids Trial (ACT): a secondary analysis to explore site differences in a multi-country trial.

BackgroundThe Antenatal Corticosteroid Trial (ACT) assessed the feasibility, effectiveness, and safety of a multifaceted intervention to increase the use of antenatal corticosteroids (ACS) in mothers at risk of preterm birth at all levels of care in low and middle-income countries. The intervention effectively increased the use of ACS but had no overall impact on neonatal mortality in the targeted <5th percentile birth weight infants. Being in the intervention clusters was also associated with an overall increase in neonatal deaths. We sought to explore plausible pathways through which this intervention increased neonatal mortality.MethodsWe conducted secondary analyses to assess site differences in outcome and potential explanations for the differences in outcomes if found. By site, and in the intervention and control clusters, we evaluated characteristics of the mothers and care systems, the proportion of the <5th percentile infants and the overall population that received ACS, the rates of possible severe bacterial infection (pSBI), determined from clinical signs, and neonatal mortality rates.ResultsThere were substantial differences between the sites in both participant and health system characteristics, with Guatemala and Argentina generally having the highest levels of care. In some sites there were substantial differences in the health system characteristics between the intervention and control clusters. The increase in ACS in the intervention clusters was similar among the sites. While overall, there was no difference in neonatal mortality among <5th percentile births between the intervention and control clusters, Guatemala and Pakistan both had significant reductions in neonatal mortality in the <5th percentile infants in the intervention clusters. The improvement in neonatal mortality in the Guatemalan site in the <5th percentile infants was associated with a higher level of care at the site and an improvement in care in the intervention clusters. There was a significant increase overall in neonatal mortality in the intervention clusters compared to the control. Across sites, this increase in neonatal mortality was statistically significant and most apparent in the African sites. This increase in neonatal mortality was accompanied by a significant increase in pSBI in the African sites.ConclusionsThe improvement in neonatal mortality in the Guatemalan site in the <5th percentile infants was associated with a higher level of care and an improvement in care in the intervention clusters. The increase in neonatal mortality in the intervention clusters across all sites was largely driven by the poorer outcomes in the African sites, which also had an increase in pSBI in the intervention clusters. We emphasize that these results come from secondary analyses. Additional prospective studies are needed to assess the effectiveness and safety of ACS on neonatal health in low resource settings.Trial registrationTrial registration: clinicaltrials.gov (NCT01084096)

Reducing neonatal mortality associated with preterm birth: gaps in knowledge of the impact of antenatal corticosteroids on preterm birth outcomes in low-middle income countries.

The Global Network’s Antenatal Corticosteroids Trial (ACT), was a multi-country, cluster-randomized trial to improve appropriate use of antenatal corticosteroids (ACS) in low-resource settings in low-middle income countries (LMIC). ACT substantially increased ACS use in the intervention clusters, but the intervention failed to show benefit in the targeted < 5th percentile birth weight infants and was associated with increased neonatal mortality and stillbirth in the overall population. In this issue are six papers which are secondary analyses related to ACT that explore potential reasons for the increase in adverse outcomes overall, as well as site differences in outcomes. The African sites appeared to have increased neonatal mortality in the intervention clusters while the Guatemalan site had a significant reduction in neonatal mortality, perhaps related to a combination of ACS and improving obstetric care in the intervention clusters. Maternal and neonatal infections were increased in the intervention clusters across all sites and increased infections are a possible partial explanation for the increase in neonatal mortality and stillbirth in the intervention clusters, especially in the African sites. The analyses presented here provide guidance for future ACS trials in LMIC. These include having accurate gestational age dating of study subjects and having care givers who can diagnose conditions leading to preterm birth and predict which women likely will deliver in the next 7 days. All study subjects should be followed through delivery and the neonatal period, regardless of when they deliver. Clearly defined measures of maternal and neonatal infection should be utilized. Trials in low income country facilities including clinics and those without newborn intensive care seem to be of the highest priority.

Steroid Pathway Genes and Neonatal Respiratory Distress After Betamethasone Use in Anticipated Preterm Birth.

To test several key glucocorticoid genes that are enhanced in lung development for associations with respiratory distress syndrome (RDS) after antenatal corticosteroid use. A prospective cohort of women received betamethasone to accelerate fetal lung maturity for threatened preterm delivery. DNA was obtained from mothers and newborns. Neonatal RDS was the primary outcome. Genotyping for single-nucleotide polymorphisms (SNPs) in 68 glucocorticoid genes found to be differentially expressed during lung development was performed. Multivariable analysis tested for associations of SNPs in the candidate genes with RDS. Genotypic results for 867 SNPs in 96 mothers and 73 babies were included. Thirty-nine (53.4%) babies developed RDS. Maternal SNPs in the centromeric protein E (CENPE), GLRX, CD9, and AURKA genes provided evidence of association with RDS (P < .01). In newborns, SNPs in COL4A3, BHLHE40, and SRGN provided evidence of association with RDS (P < .01). Single-nucleotide polymorphisms in several glucocorticoid responsive genes suggest association with neonatal RDS after antenatal corticosteroid use.

Implementation of the use of antenatal corticosteroids in the late preterm birth period in women at risk for preterm delivery

Implementation of the use of antenatal corticosteroids in the late preterm birth period in women at risk for preterm delivery