Full Course Of Antenatal Corticosteroids Research Articles

Rescue doses of antenatal corticosteroids, children's neurodevelopment, and salivary cortisol after a threatened preterm labor: a 30-month follow-up study

Antenatal corticosteroids (ACS) reduce neonatal complications when are administered to women at risk of preterm birth. Moreover, ACS rescue doses are recommended in women who remain at risk after the initial course. However, there is controversy about the most appropriate frequency and exact timing for administering additional ACS doses since there are potential long-term negative effects on infants´ neurodevelopment and physiological stress functioning. The aims of this study were: i) to assess the long-term neurodevelopmental effects of receiving ACS rescue doses vs. receiving only the initial course; ii) to measure cortisol levels of infants that received ACS rescue doses; iii) to examine a potential dose-response effect of the number of ACS rescue doses on children´s neurodevelopment and salivary cortisol. The study followed 110 mother-infant pairs who underwent a spontaneous episode of threatened preterm labor (TPL) until the children were 30 months old, regardless of their gestational age at birth. Among the participants, 61 received only the initial course of corticosteroids (no rescue dose [NRD] group), and 49 participants required at least one rescue dose of corticosteroids (rescue doses [RD] group). The follow-up was carried out at three different times: [T1] at TPL diagnosis, [T2] at the children´s age of 6 months, and [T3] at the children's age of 30 months, corrected age for prematurity. Neurodevelopment was assessed using the Ages & Stages Questionnaires-Third Edition. Saliva samples were collected for cortisol level determination. First, the RD group showed lower problem-solving skills at age 30-months compared to the NRD group. Second, the RD group demonstrated higher salivary cortisol levels at 30-months. Third, a dose-response effect was found, indicating that the higher number of rescue doses the RD group received, the lower the problem-solving skills and the higher the salivary cortisol levels they showed at 30 months of age. Our findings reinforce the hypothesis that additional doses provided after the initial course of ACS may have long-term effects on offspring's neurodevelopment and glucocorticoid metabolism. In this regard, the results raise concerns about the negative effects of repeated doses in addition to a full course of ACS. Further studies are necessary to confirm this hypothesis and help physicians to reassess the standard ACS treatment regimens.

A History of Preterm Delivery Is Associated with Aberrant Postpartal MicroRNA Expression Profiles in Mothers with an Absence of Other Pregnancy-Related Complications.

This prospective cross-sectional case-control study investigated the postpartal gene expression of microRNAs associated with diabetes/cardiovascular/cerebrovascular diseases in the peripheral white blood cells of women with anamnesis of preterm prelabor rupture of membranes (n = 58), spontaneous preterm birth (n = 55), and term delivery (n = 89) by a quantitative reverse transcription polymerase chain reaction. After pregnancies complicated by preterm prelabor rupture of membranes or spontaneous preterm birth, mothers showed diverse expression profiles for 25 out of 29 tested microRNAs (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-499a-5p, and miR-574-3p). The earliest gestational ages at delivery and the lowest birth weights of newborns were associated with the highest postpartal levels of the previously mentioned microRNAs in maternal peripheral white blood cells. Administration of tocolytic drugs in order to prolong pregnancy, used in order to administer and complete a full course of antenatal corticosteroids, was associated with alterations in postpartal microRNA expression profiles to a lesser extent than in women with imminent delivery, where there was insufficient time for administration of tocolytics and antenatal corticosteroids. Overall, mothers who did not receive tocolytic therapy (miR-24-3p and miR-146a-5p) and mothers who did not receive corticosteroid therapy (miR-1-3p, miR-100-5p, and miR-143-3p) had increased or showed a trend toward increased postpartal microRNA expression when compared with mothers given tocolytic and corticosteroid therapy. In addition, mothers with serum C-reactive protein levels above 20 mg/L, who experienced preterm labour, showed a trend toward increased postpartal expression profiles of miR-143-3p and miR-199a-5p when compared with mothers with normal serum C-reactive protein levels. On the other hand, the occurrence of maternal leukocytosis, the presence of intra-amniotic inflammation (higher levels of interleukin 6 in the amniotic fluid), and the administration of antibiotics at the time of preterm delivery had no impact on postpartal microRNA expression profiles in mothers with a history of preterm delivery. Likewise, the condition of the newborns at the moment of birth, determined by Apgar scores at 5 and 10 min and the pH of cord arterial blood, had no influence on the postpartal expression profiles of mothers with a history of preterm delivery. These findings may contribute to explaining the increased cardiovascular risk in mothers with anamnesis of preterm delivery, and the greater increase of maternal cardiovascular risk with the decrease of gestational age at delivery. Women with preterm delivery in their anamnesis represent a high-risk group with special needs on a long-term basis, with a need to apply preventive and therapeutic interventions as early as possible.

The effect of antenatal corticosteroids on small-for-gestational age preterm neonates

Objective Treatment of preterm small-for-gestational age (SGA) neonates with antenatal corticosteroids (ACS) is not entirely straightforward. We sought to examine the effect of a full course of ACS on outcomes of SGA and non-SGA preterm singletons. Patients and methods We compared maternal characteristics and outcomes of preterm births at <28 and 28 + 0–33 + 0 weeks’ gestation that received a complete course of ACS within a week before birth. We further divided our cohort into those with or without a SGA neonate. Results We included 290 infants: 73 (25.2%) and 217 (74.8%) born at <28 and 28 + 0–33 + 0 weeks’ gestation, respectively. Analysis of maternal characteristics showed a strong association of maternal body mass index (p = .01), along with smoking during pregnancy (OR 0.4, 95% CI 0.2, 0.9), with being SGA. Spontaneous onset of delivery more commonly occurred in non-SGA preterm neonates, whereas iatrogenic induction of labor prevailed with SGA neonates (p < .01). There was no significant difference between SGA and non-SGA infants in all the tested neonatal variables except for necrotizing enterocolitis, which prevailed in the SGA group. Conclusion A full course of ACS appears to have the same effect in SGA and non-SGA preterm singletons in our studied cohort on all neonatal outcomes but for necrotizing enterocolitis, where its role in SGA preterm neonates seems to be detrimental rather than beneficial to the fetus.

Disparities in the use of antenatal corticosteroids among women with hypertension in North Carolina.

To evaluate antenatal corticosteroids (ANS) use in pregnant women with hypertension. Retrospective analysis of ANS use in the Perinatal Quality Collaborative of North Carolina between 2015 and 2017. Twenty-five centers participated, with 9% (1580/17,692) of mothers delivering at <34 weeks; of these, 81% (1286/1580) received a full course of ANS, which was not different between phases (p = 0.32), or between Level III/IV neonatal intensive care units (NICUs; 82%), and I/II NICUs (76%) (p = 0.05). In Level III/IV NICUs, White mothers were more likely to receive ANS (87%) than African Americans (77%) or other race/ethnicity (80%) (including Hispanics) (p = 0.001). ANS use did not differ among mothers with different payers (p = 0.94). The rates of full ANS courses did not significantly increase from 2015-2017 and disparities persisted. Targeted efforts to improve ANS exposures among hypertensive African American and Hispanic mothers, as well as in community hospital settings are needed.

Impact of routine transvaginal ultrasound monitoring of cervical length in twins on administration of antenatal corticosteroids

To evaluate whether routine measurement of cervical length (CL) by transvaginal ultrasound (TVU) in twin pregnancies can enable identification of women who will give birth before 34 weeks and require antenatal corticosteroids (ACSs), and whether it can limit their administration to women who will give birth later. Retrospective comparative study in two tertiary referral centers in France. Women with twin gestations followed in two tertiary university hospital maternity units and who delivered from January 1, 2007 to December 31, 2009 were included. In one center, TVU was targeted to women with cases of suspected preterm labor, while the other center used it monthly for all twin pregnancies. The main outcome measure was the administration of a full course of ACS to twins delivered before 34 weeks. Two hundred and seventy women were eligible in the "targeted use" group, and 296 women in the "routine use" group. The rate of administration of at least one full course of ACS for twins born before 34 weeks did not differ between the two groups (85.0% in the targeted use group and 90.0% in the routine use group, P=0.40), but the rate of such administration for those born after 34 weeks was lower in the targeted use group (25.7% vs. 81.2%, P<0.01). On adjusting for confounders using logistic regression modeling, no significant difference in ACS administration before 34 weeks was found between the two groups [adjusted odds ratio (aOR), 0.71, 95% confidence interval (CI), 0.39-1.30]. Routine monitoring performed every month of CL with TVU does not affect the rate of administration of ACS to twins born before 34 weeks, but is associated with a higher rate of such administration for those born later in the specific center of the study.

Legal Briefs: Aggressive Gavage Feeding and Gastric Perforation

Twins at 341/7 weeks’ gestation were born to a 33-year-old healthy mother with a pregnancy remarkable for in vitro fertilization, diamniotic, dichorionic twins, and preterm labor. After a full course of antenatal corticosteroids, the twins were born by cesarean delivery. Twin A was a 2,410-g male infant with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively. His examination findings were normal, and his complete blood count was unremarkable. On day 1 an order was written to begin feeding the infant with either breast milk or premature formula (20 calories per ounce). The feedings were to be initiated by gavage or nipple feeding at 5 mL every 3 hours for two times and subsequently to increase by 3 mL every 3 hours to a maximum feed of 20 mL/kg every 3 hours; a concomitant order to decrease the intravenous fluid rate was written as the oral feeds increased. On day 1 the infant fed well, taking each feed by nipple within 20 minutes. By the end of day 1, he was nippling 17 mL. The mean heart rate (HR) was 131 beats per minute. The abdominal girth, measured 4 times, was 28 cm. Instead of losing weight at this point, he gained 60 g. On day 2 the infant was initially nippling his feeds well, but when the amount reached 30 mL, he began feeding poorly; he needed stimulation to suck, was sleepy, needed chin support, and required an increasing time to nipple feed. At this point the nurse decided to gavage feed the infant to keep up with the feeding schedule of an increase of 3 mL every feed. The nurse inserted a nasogastric tube. She did not document the depth of insertion. The nurse maintained at her deposition that she inserted the …

Legal Briefs: Extremely Preterm Infant, Pronounced Dead, Comes to Life, But Outcome Is Compromised

A 233/7 weeks’, 592-g female infant was born to a 19-year-old-mother with a benign prenatal course until the development of preterm labor. When contractions began, the mother was hospitalized and received tocolysis and a full course of antenatal corticosteroids. After 3 days of hospitalization, the membranes spontaneously ruptured, labor progressed, and her footling breech fetus was delivered by emergency cesarean section. The neonatologist discussed medical intervention, comfort care, and data on mortality and morbidity in infants of similar gestation with the parents before delivery. The parents wanted resuscitation and full medical intervention after birth if the estimated gestational age and birth weight before birth were validated after delivery and if no unforeseen findings that would alter the outcome appeared. The fetal heart rate (HR) pattern was unremarkable, with the fetal HR being 145 beats per minute immediately before birth. At delivery, the infant had a similar HR, palpable pulses, and respiratory effort. At 30 seconds after birth, a 2.5-mm endotracheal tube (ETT) was inserted through which positive pressure ventilation was started because the respiratory effort was weak. The HR decreased to 58 beats per minute at 1 minute at which point chest compressions were initiated. Two rounds of endotracheal epinephrine via ETT were given because of a HR that continued to decrease. At 11 …

Mental health of extremely low birth weight survivors in their 30s.

To determine the risk for psychiatric disorders among extremely low birth weight (ELBW) survivors in their early to mid-30s and to determine whether those born small for gestational age or those exposed to a full course of antenatal corticosteroids (ACS) were at particularly high risk. A prospective, longitudinal, population-based cohort of 84 ELBW survivors and 90 normal birth weight (NBW) control participants born in Ontario, Canada from 1977 to 1982 were assessed by interviewers naive to birth weight status using the Mini-International Neuropsychiatric Interview. ELBW survivors had lower odds of an alcohol or substance use disorder but higher odds of current non-substance-related psychiatric problems (odds ratio [OR] = 2.47; 95% confidence interval [CI], 1.19-5.14). Those born ELBW and SGA exhibited the same patterns with larger effects. ACS-exposed ELBW survivors had even higher odds of any current non-substance-related psychiatric disorder (OR = 4.41; 95% CI, 1.65-11.82), particularly generalized anxiety disorder (OR = 3.42; 95% CI, 1.06-11.06), the generalized type of social phobia (OR = 5.80; 95% CI, 1.20-27.99), and the inattentive subtype of attention-deficit/hyperactivity disorder (OR = 11.45; 95% CI, 2.06-63.50). In their early to mid-30s, ELBW survivors were less likely to have alcohol or substance use disorders but may be at greater risk for other psychiatric problems. Those exposed to ACS were at especially high risk and manifested no reduction in alcohol or substance use disorders. ELBW survivors exposed to ACS may be a special group at risk for psychopathology in adulthood.

Antenatal corticosteroid administration: understanding its use as an obstetric quality metric

In 1994, the National Institutes of Health recommended a full course of antenatal corticosteroids (ACS) to women who were at risk of delivery at 24-32 weeks of gestation. In 2010, the Joint Commission on Accreditation of Healthcare Organization incorporated ACS administration rates as a perinatal core quality measure. The objective of this study is (1) to assess ACS administration rates among eligible patients at a tertiary care center and (2) to identify modifiable factors to optimize administration rates. A retrospective chart review of preterm deliveries at <37 weeks of gestation from July 2009 to July 2011 was performed. Hospital level data, delivery information, obstetric history, and neonatal outcomes were abstracted. Categoric variables were compared with the use of the χ(2) test. Continuous variables were compared with the use of a 2-sample t-test, Wilcoxon rank-sum, or Kruskal Wallis tests. Nine hundred four women had preterm delivery; 38% of them delivered from 24-34 weeks of gestation. Of the eligible patients, 81.3% received at least 1 dose of ACS, and 69.6% received both doses before delivery. The median time from evaluation to ACS administration was 2.6 hours (interquartile range, 1.6-4.8 hours). Thirty-three percent of the patients who did not receive ACS had had a previous triage visit within 2 weeks of delivery (66.6% of them were evaluated for symptoms of preterm labor) vs 2.8% for those women who received ACS. Of the eligible patients, 81.3% received at least 1 dose of ACS. Tangible opportunities that were identified for systems-based improvement in ACS administration rates included decreasing the time interval from patient evaluation to ACS administration and standardizing outpatient follow-up evaluation for patients who were discharged with symptoms of preterm labor.

Antenatal Corticosteroids for Late-Preterm Infants: A Decision-Analytic and Economic Analysis

Objectives. Antenatal corticosteroids (ACS) are not routinely administered to patients at risk for delivery between 34 and 36 6/7 weeks. Our objective was to determine whether ACS are cost-effective for late-preterm infants at risk for imminent preterm delivery. We hypothesized that the preferred strategy <36 weeks would include ACS while the preferred strategy ≥36 weeks would not. Methods. We performed decision-analytic and cost-effectiveness analyses to determine whether ACS was cost-effective at 34, 35, and 36 weeks. We conducted a literature review to determine probability, utility, and cost estimates absent of patient-level data. Base-case cost-effectiveness analysis, univariable sensitivity analysis, and Monte Carlo simulation were performed. A threshold of $100,000/QALY was considered cost-effective. Results. The incremental cost-effectiveness ratio favored the administration of a full course of ACS at 34, 35, and 36 weeks ($62,888.25/QALY, $64,425.67/QALY, and $64,793.71/QALY, resp.). A partial course of ACS was not cost-effective. While ACS was the consistently dominant strategy for acute respiratory outcomes, all models were sensitive to changes in variables associated with chronic respiratory disease. Conclusions. Our findings suggest that the administration of ACS to patients at risk of imminent delivery 34-36 weeks could significantly reduce the cost and acute morbidity associated with late-preterm birth.

Morbimortalidad de recién nacidos con menos de 1500 gramos asistidos en hospitales públicos de la Ciudad de Buenos Aires

The Neonatal Network of Public Hospitals in the city of Buenos Aires closely monitors the progress of newborn infants with a birth weight less than 1500 g (very low birth weight, VLBW) because it largely contributes to neonatal morbidity and mortality. To analyze the morbidity and mortality of VLBW infants and determine their riskadjusted mortality using the score of the South American Neonatal Network (Red Neonatal de los países del Conosur de América, NEOCOSUR). Live infants born in the network hospitals with a birth weight of 500-1499 g between 2008 and 2010 were included in the study. Data was recorded prospectively using a standardized methodology. Mortality, morbidity and risk-adjusted mortality rates according to the NEOCOSUR score were estimated. Results. There were 92,698 infants born during the study period. Of them, 1.26% weighed less than 1500 g at birth. Only 40.4% of these received a full course of antenatal corticosteroids. A total of 62.7% of these developed respiratory distress syndrome, 5.4% enterocolitis, 10.1% intracranial hemorrhage, and 13.4% severe retinopathy. Early sepsis was observed in 5.6%, and late sepsis in 9.6%. Bronchopulmonary dysplasia was present in 10.7% of the cases. Neonatal mortality was 29.2%, and the adjusted mortality with no major malformations was 25.4%. Survival of infants with a birth weight of =750 g and a gestational age of =26 weeks was 50%. The observed/expected mortality ratio was 1.04, with a large variability. The percentage of VLBW infants who received antenatal corticosteroids was low. The incidence of sepsis and the rate of infants with severe retinopathy of prematurity are high. The risk-adjusted mortality is higher than expected.

Population based trends in mortality, morbidity and treatment for very preterm- and very low birth weight infants over 12 years.

BackgroundOver the last two decades, improvements in medical care have been associated with a significant increase and better outcome of very preterm (VP, < 32 completed gestational weeks) and very low birth weight (VLBW, < 1500 g) infants. Only a few publications analyse changes of their short-term outcome in a geographically defined area over more than 10 years. We therefore aimed to investigate the net change of VP- and VLBW infants leaving the hospital without major complications.MethodsOur population-based observational cohort study used the Minimal Neonatal Data Set, a database maintained by the Swiss Society of Neonatology including information of all VP- and VLBW infants. Perinatal characteristics, mortality and morbidity rates and the survival free of major complications were analysed and their temporal trends evaluated.ResultsIn 1996, 2000, 2004, and 2008, a total number of 3090 infants were enrolled in the Network Database. At the same time the rate of VP- and VLBW neonates increased significantly from 0.87% in 1996 to 1.10% in 2008 (p < 0.001). The overall mortality remained stable by 13%, but the survival free of major complications increased from 66.9% to 71.7% (p < 0.01). The percentage of infants getting a full course of antenatal corticosteroids increased from 67.7% in 1996 to 91.4% in 2008 (p < 0.001). Surfactant was given more frequently (24.8% in 1996 compared to 40.1% in 2008, p < 0.001) and the frequency of mechanical ventilation remained stable by about 43%. However, the use of CPAP therapy increased considerably from 43% to 73.2% (p < 0.001). Some of the typical neonatal pathologies like bronchopulmonary dysplasia, necrotising enterocolitis and intraventricular haemorrhage decreased significantly (p ≤ 0.02) whereas others like patent ductus arteriosus and respiratory distress syndrome increased (p < 0.001).ConclusionsOver the 12-year observation period, the number of VP- and VLBW infants increased significantly. An unchanged overall mortality rate and an increase of survivors free of major complication resulted in a considerable net gain in infants with potentially good outcome.

Antenatal corticosteroids and cranial ultrasonographic abnormalities

Objective: This study was undertaken to determine whether very-low-birth-weight infants whose mothers received a course of antenatal corticosteroids were at decreased risk for 3 cranial ultrasonographic entities that predict neurodevelopmental dysfunction. Study Design: This retrospective cohort study evaluated 1604 infants weighing 500 to 1500 g who underwent ≥1 of 3 cranial ultrasonographic scans required by design at specified postnatal intervals and whose own and mother’s hospital charts were reviewed. Infants were classified according to mother’s course of antenatal corticosteroids (none, partial, or complete). Results: In the total sample the risks of intraventricular hemorrhage and of an echolucent image in the cerebral white matter were only modestly (and not statistically significantly) reduced after a full course of antenatal corticosteroids, whereas antenatal corticosteroids appeared to significantly reduce the risk of ventriculomegaly after even a partial course. Antenatal corticosteroids appeared to halve the risk of ventriculomegaly and echolucent image among the gestationally youngest infants and those with intraventricular hemorrhage, hypothyroxinemia, or vasculitis of the umbilical cord or chorionic plate of the placenta. Conclusion: These observations are consistent with the hypothesis that antenatal corticosteroids protect very-low-birth-weight infants, especially those who are most vulnerable, against the risk of cranial ultrasonographic abnormalities. (Am J Obstet Gynecol 1999;181:1007-17.)

Antenatal Corticosteroids Appear to Reduce the Risk of Postnatal Germinal Matrix Hemorrhage in Intubated Low Birth Weight Newborns

To determine to what extent the reduced risk in preterm newborns of intracranial hemorrhage attributed to antenatal corticosteroids (ANCS) reflects reductions in the incidence of respiratory distress and its correlates. In a sample of 239 very low birth weight newborns recruited for a clinical trial of phenobarbital prophylaxis of subependymal/intraventricular hemorrhage, we explored the relationship between ANCS, the occurrence of germinal matrix hemorrhage (GMH) that first became evident after the 12th postnatal hour, and putative intervening variables such as acidosis, elevated peak inspiratory pressure, pneumothorax-pulmonary interstitial emphysema, and elevated continuous positive airway pressure. In multivariate models adjusting for confounders, newborns exposed to ANCS were at approximately one third the risk of GMH experienced by newborns not exposed to a full course of ANCS. The additions of measures and correlates of respiratory distress severity to these models did not change the GMH risk associated with ANCS. The GMH-protective effect of ANCS does not appear to be a consequence of enhanced pulmonary maturation.