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From part of the guide:. Bro, can i ask? Atlantica Indonesia now hv caps If someone is Lvthey should get a higher quality box, but that is all dependent on if the developers of AO Indonesia actually made that change.

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Antenatal steroids delivery

Hypoglycemia was more common in the infants exposed to betamethasone The rates of hypoglycemia found in the trial are similar to what is reported in the general population of late preterm infants Although not studied in this trial, long-term adverse outcomes of prolonged and persistent neonatal hypoglycemia have been described 26 The American Academy of Pediatrics recommends the monitoring of neonatal blood sugars for late preterm infants because late preterm birth is a known risk factor for hypoglycemia.

There are important considerations specific to the administration of late preterm corticosteroids that should be noted and are derived from the methodology used by the trial. Late preterm administration of antenatal corticosteroids is not indicated in women diagnosed with clinical chorioamnionitis intrauterine infection Furthermore, tocolysis should not be used in an attempt to delay delivery in order to administer antenatal corticosteroids in the late preterm period, nor should an indicated late preterm delivery such as for preeclampsia with severe features be postponed for corticosteroid administration Groups not studied by the Antenatal Late Preterm Steroids trial include women with multiple gestations, women with pregestational diabetes, women who previously had received a course of corticosteroids, and women who gave birth by cesarean at term.

Whether or not late preterm corticosteroids provide benefit in these populations is unknown. Because of concerns for maternal and fetal harm, and the balance of risk and benefits, planned multiple courses are not recommended. In a randomized trial of single versus serial courses of antenatal corticosteroids, a reduction in birth weight and an increase in the number of infants who were small for gestational age were found, especially after four courses of corticosteroids Although not consistent, six studies found decreased birth weight and head circumference with repeat courses 29 30 31 32 33 34 35 and three studies did not 36 37 Follow-up of children at 2 years of age who were exposed to repeat courses of antenatal corticosteroids showed no significant difference in physical or neurocognitive measures in two studies 39 40 , and the same outcome was found in younger children in a third study Although not statistically significant, the relative risk of cerebral palsy in infants exposed to serial courses of antenatal corticosteroids RR, 5.

Maternal effects include increased risk of infection and suppression of the hypothalamic—pituitary—adrenal axis 31 Regularly scheduled repeat courses or serial courses more than two are not currently recommended Although the initial data 43 suggested the benefit of corticosteroids may decrease after 7 days, the duration of corticosteroid benefit remains controversial No increase in newborn complications or intrauterine growth restriction was identified, although the power to evaluate these individual outcomes was low.

There was no difference in bronchopulmonary dysplasia, and long-term outcome developmental data are not available for these patients. The Crowther Cochrane meta-analysis 10 trials, 4, women and 5, infants included trials with a repeat course of corticosteroids as early as 7 days from initial course. The results of the meta-analysis showed reduction in RDS and there was noted an associated small reduction in size at birth, but no significant adverse outcomes. Rescue course corticosteroids could be provided as early as 7 days from the prior dose, if indicated by the clinical scenario, given the Cochrane meta-analysis results 11 Whether to administer a rescue course of corticosteroids with PROM is controversial, and there is insufficient evidence to make a recommendation for or against 6 The concern that corticosteroids may have the potential to adversely affect neurodevelopmental outcomes is largely based on animal data and from studies of multiple course corticosteroids The MFMU study of repeat course corticosteroids suggested that four or more courses may be associated with the development of cerebral palsy This single signal does not lead us to caution against corticosteroid use, particularly as it refers to term exposure, but continued surveillance of long-term outcomes should be supported.

The year neurodevelopmental follow-up of this cohort were exposed to corticosteroids from Cognitive functioning as measured by the Weschler scales, working memory and attention, and other neurocognitive assessments were not different between exposure groups. The MFMU Antenatal Late Preterm Steroids study has not yet obtained long-term outcome data but doing so would add significantly to limited available literature.

A final additional consideration regarding corticosteroid risks is that in the context of maternal critical care, antenatal corticosteroids are not contraindicated, even in the setting of sepsis 1 Perinatal Quality Collaboratives, such as the Ohio Perinatal Quality Collaborative, California Perinatal Quality Care Collaborative, and the March of Dimes Big 5 State Perinatal Collaborative have worked to improve use of antenatal corticosteroids through a focus on the identification of missed opportunities and use of quality improvement strategies to optimize appropriate and timely antenatal corticosteroid administration.

Implementation of preterm labor assessment toolkits, standardized order sets for women at risk of early delivery, timely availability of medication in settings where pregnant women are cared for, maternal transfer protocols that indicate corticosteroids should be given before transport, and appropriate documentation of first course and rescue course antenatal corticosteroids in inpatient and outpatient health records, have been among the proposed strategies to improve appropriate and timely antenatal corticosteroid use.

One study reported qualitative focus group data describing conditions that enable delivery of antenatal corticosteroids with high reliability at hospitals that participated in the Ohio Perinatal Quality Collaborative antenatal corticosteroid project Six major themes supporting reliable implementation of antenatal corticosteroids were described, including 1 presence of a high reliability culture, 2 processes that emphasize high reliability, 3 timely and efficient administration process, 4 involvement of multiple disciplines, 5 evidence of benefit supports antenatal corticosteroid use, and 6 benefit is recognized at all levels of the care team.

Participating obstetrician—gynecologists or other health care providers and staff described that these key processes and supports were needed to ensure appropriate and timely delivery of antenatal corticosteroids with high reliability A collaborative of 54 hospitals from across the Big 5 States has been convened to pilot the new resources to standardize the identification of eligible patients and to improve the appropriate timing of corticosteroid therapy.

The Ohio Perinatal Quality Collaborative reported that antenatal corticosteroid rates increase and are maintained at high levels when hospitals are aware that antenatal corticosteroid use is monitored, and missed opportunities are identified and reviewed. The collaborative worked with Ohio vital records to add antenatal corticosteroid administration to the Ohio birth certificate registry. Monitoring hospital rates provided incentive for hospitals to improve appropriate administration and documentation.

This work by state and regional collaboratives demonstrates that quality improvement strategies to optimize appropriate and timely antenatal corticosteroid administration are effective and should be encouraged. Therefore, the administration of antenatal corticosteroids should be monitored and missed opportunities reviewed.

Overuse of antenatal corticosteroids was recently addressed at the Society for Maternal—Fetal Medicine conference in In view of this, it is critical to have ongoing development of strategies that encourage timely corticosteroid administration to women at risk of preterm delivery within 7 days and avoid overuse of corticosteroids for low risk women.

Collecting measures that track antenatal corticosteroids use for infants born before 34 weeks of gestation and timing of corticosteroids in relation to delivery will support quality improvement efforts to optimize appropriate and timely antenatal corticosteroid administration. The American College of Obstetricians and Gynecologists has identified additional resources on topics related to this document that may be helpful for ob-gyns, other health care providers, and patients.

You may view these resources at www. These resources are for information only and are not meant to be comprehensive. The resources may change without notice. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, posted on the Internet, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior written permission from the publisher.

Antenatal corticosteroid therapy for fetal maturation. Committee Opinion No. American College of Obstetricians and Gynecologists. Obstet Gynecol ;e—9. This information is designed as an educational resource to aid clinicians in providing obstetric and gynecologic care, and use of this information is voluntary.

This information should not be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. It is not intended to substitute for the independent professional judgment of the treating clinician. Variations in practice may be warranted when, in the reasonable judgment of the treating clinician, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology.

The American College of Obstetricians and Gynecologists reviews its publications regularly; however, its publications may not reflect the most recent evidence. Any updates to this document can be found on www.

ACOG does not guarantee, warrant, or endorse the products or services of any firm, organization, or person. Neither ACOG nor its officers, directors, members, employees, or agents will be liable for any loss, damage, or claim with respect to any liabilities, including direct, special, indirect, or consequential damages, incurred in connection with this publication or reliance on the information presented.

Bulk pricing was not found for item. Please try reloading page. For additional quantities, please contact sales acog. The literature search retrieved potentially relevant citations Fig 1. Total of citations removed as duplicate. After carefully reviewing the abstracts and titles citations were excluded. Total 29 citations were read in details and 22 were excluded for reasons mentioned in the flow chart.

Five studies provided data for the primary outcome of need for any respiratory support [ 10 , 20 — 22 , 25 ] whereas only 4 reported on hypoglycemia [ 10 , 20 , 21 , 25 ]. The characteristics of the included studies are shown in Table 1. Results of the sensitivity analysis including only studies with low ROB Gyamifi- Bannerman and Porto et al showed no difference in any respiratory support between ANC vs. This was not possible due to lack of stratified data based on gestational age, mode of delivery and maternal diabetes.

The results of this comparative analysis showed that majority of the outcomes including both primary outcomes were similar with both models. S2 Table. For the primary outcome of need for any respiratory support, the evidence was graded as moderate whereas it was deemed high for hypoglycaemia. For secondary outcomes the evidence was deemed as very low to moderate.

Our systematic review showed that exposure to ANC was beneficial in reducing the need for respiratory support but with the increased risk of hypoglycemia in neonates born at late preterm gestation. Exposure to ANC also reduced the need for resuscitation at birth. None of the included trials reported long term follow up data. Respiratory morbidities in LPNs relate to developmental immaturity of the lungs.

The mechanisms for benefits of ANC include enhanced alveolar differentiation with the induction of type 2 pneumocytes and activation of endothelial nitric oxide synthase [ 27 , 28 ]. It is postulated that similar to term gestation, ANC exposure at late preterm gestation accelerates coordinated organ development sequence in response to endogenous rise in fetal glucocorticoids [ 29 , 30 ].

Experimental studies show that the improvement in lung function after ANC exposure are due to an increase in the absorption of fetal lung fluid, thinning of alveolar septae, and synthesis of surfactant proteins and phospholipids [ 30 , 31 ]. The benefits of ANC need to be considered in the context of their potential adverse effects.

ANC exposure is associated with reduced brain mass, delayed myelination, decreased maturation of peripheral nerves, increased impairment of hypothalamopitutory axis and impaired programmed apoptosis in animal studies [ 30 , 32 — 34 ]. A follow-up study of participants from ASTECS trial reported two-fold increase in teacher-reported low academic ability in children age 8—15 years exposed to betamethasone as term infants born by an elective caesarean section.

There were no significant differences in general health, behaviour and academic achievements between exposed vs. A recent population-based study from Finland using nationwide registries of all term and preterm singleton live births found that ANC exposure was associated with a significant increase [adjusted hazard ratio aHR : 1.

The incidence of these disorders was high in term neonates exposed to ANC vs. The incidence of these adverse outcomes was higher It is important to consider the implications of our results for clinical practice. The NNT to prevent one case of any respiratory support and need for resuscitation at birth was 20 and 16 respectively. In comparison, the NNT for harm was 13 for neonatal hypoglycaemia.

LPNs are at high risk of hypoglycaemia due to poor substrate and underdeveloped compensatory response. The increased risk of neonatal hypoglycaemia might be due to transient hyperinsulinemia following maternal hyperglycaemia in response to ANC [ 37 ].

The definition of neonatal hypoglycaemia varied in the RCTs included in our review. Hypoglycaemia is an independent predictor of poor neurodevelopmental outcomes in neonates. Inability to predict spontaneous preterm birth means inevitable unwarranted exposure to ANC in a significant number of late preterm pregnancies, which do not result in late preterm delivery.

Overall, potential long-term neurodevelopmental adverse effects of ANC must receive due attention considering that none of the included trials till date have reported such data. The limitations of using Apgar scores as a primary outcome need to be discussed. Apgar score at 1 minute does not correlate with mortality and long-term neurodevelopmental outcomes [ 40 ].

Apgar scores can be low in otherwise well preterm neonates with no evidence of perinatal asphyxia [ 40 — 42 ]. Moreover, being a continuous measure, it is much more likely that differences would be noted regardless of their clinical importance. The strengths of our review include its robust methodology, inclusions of only RCTs, large sample size and use of GRADE guidelines for summarizing the level of evidence.

We conducted sensitivity analysis excluding the studies with high ROB. The provision of the NNT for both, benefit and harm, is important for guiding research and clinical practice. The limitations of our review include the fact that the pooled results are still influenced by the large ALPS trial [ 10 ]. The included RCTs differ in the definitions of various outcomes, type of steroids, and their dosage.

Furthermore, analysis stratified by gestation, mode of delivery or maternal diabetic status was not possible. Our systematic review showed that exposure to ANC was beneficial in reducing the need for respiratory support but with an increased risk of hypoglycemia in neonates born at late preterm gestation. In summary, moderate to low-quality evidence indicates that ANC exposure reduced the need for respiratory support and increased the risk of neonatal hypoglycaemia in LPNs.

The increased risk of neonatal hypoglycaemia is a serious concern. Pragmatic and adequately powered multicentre RCTs with long-term follow up assessing neonatal neurodevelopmental outcomes are needed to assess the efficacy and safety of ANC. Stratification by gestation, mode of delivery, maternal diabetes and other risk factors for respiratory distress is desirable in such trials.

Pending results of such trials rigorous monitoring, treatment, and follow up of LPNs exposed to ANC is critical, more so in the context of hypoglycemia. Submission declaration : All authors declare that the work submitted has not been published previously, that it is not under consideration for publication elsewhere, that its publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere including electronically in the same form, in English or in any other language, without the written consent of the copyright-holder.

Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Abstract Background Administration of antenatal corticosteroids ANC for impending preterm delivery beyond 34 weeks of gestation continues to be a controversial issue despite various guidelines for obstetricians and gynaecologists. Conclusions Moderate quality evidence indicates that ANC exposure reduced need for respiratory support, and increased the risk of hypoglycaemia in late preterm neonates.

Funding: The authors received no specific funding for this work. Participants Inclusion criteria. Exclusion criteria. Major chromosomal and congenital anomalies. Search strategy. Study selection. Data extraction and management. Data synthesis. Assessment of publication bias. Grading the evidence and summary of findings. Results The literature search retrieved potentially relevant citations Fig 1.

Download: PPT. Fig 1. Flow chart of study selection process after screening of electronic search. Table 1. Need for any respiratory support was significantly less in the ANC vs. The number needed to treat NNT for preventing one case of respiratory support was 20 Fig 3.

Hypoglycaemia : Four studies that reported this outcome included neonates ANC: , Control: [ 10 , 20 , 21 , 25 ]. Incidence of hypoglycaemia was significantly high in the ANC vs. Control: The number needed for harm for hypoglycemia was 13 Fig 4. Secondary outcomes Need for resuscitation at birth [only in delivery room immediately after birth not in NICU ]: The data for this outcome was available from 6 studies that included neonates ANC: , Control: [ 10 , 21 — 25 ].

Need for resuscitation at birth was significantly less in the ANC vs. S1 Fig NNT for this outcome was Mortality was similar in the ANC vs. S5 Fig Need for mechanical ventilation : The data for this outcome was available from 4 studies that included neonates ANC: , Control: [ 10 , 20 — 22 ].

S6 Fig Need for Surfactant : The data for this outcome was available from 3 studies that included neonates ANC: , Control: [ 10 , 20 , 22 ]. Need for surfactant was 1. S7 Fig Developmental follow up : None of the included studies reported data on this outcome. Adverse effects : Apart from neonatal hypoglycaemia none of the included studies reported any other adverse effects such as neonatal sepsis, and seizures. Sensitivity analysis. Subgroup analysis. Analysis using fixed effect model. Summary of findings table and publication bias.

Table 2. Discussion Our systematic review showed that exposure to ANC was beneficial in reducing the need for respiratory support but with the increased risk of hypoglycemia in neonates born at late preterm gestation. Conclusions Our systematic review showed that exposure to ANC was beneficial in reducing the need for respiratory support but with an increased risk of hypoglycemia in neonates born at late preterm gestation.

Supporting information. S1 Fig. Effect of ANC on need for resuscitation at birth. S2 Fig. Effect of ANC on admission to nursery. S3 Fig. S4 Fig. S5 Fig. Effect of ANC on mortality. S6 Fig. Effect of ANC on mechanical ventilation. S7 Fig. Effect of ANC on need for surfactant. S1 Table. Results of sensitivity analysis based on ROB. Results of analysis by fixed and random effects model.

S3 Table. S1 File. References 1.

80 MG STEROID INJECTION

Both reviewers MD and SP independently selected studies for inclusion in the review. First, the records were screened according to the titles and abstracts. Full texts of the selected articles were then retrieved and assessed for inclusion according to the pre-specified selection criteria. Reviewers MD and SP extracted the data independently, using a data collection form. We included the information about authors, year of publication, the country where the study was conducted, setting, inclusion and exclusion criteria, participants characteristics, type of steroids betamethasone or dexamethasone used, outcome measures need for respiratory support, hypoglycaemia, RDS, TTN, neonatal resuscitation, admission to neonatal unit, mortality and developmental follow up and their definitions.

We checked the number of participants allocated to each arm, methods of analysis, loss to follow up and reasons for the same. For dichotomous outcomes, the number of patients with the event and the number of patients analysed in each treatment group was recorded. For continuous outcomes, we recorded the mean and standard deviations. Both reviewers verified the information about study design and outcomes. Discrepancies were resolved by discussion and consensus. Both reviewers MD and SP assessed the ROB in each included trial for the following seven components: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective outcome reporting and other biases.

For each of these components, they assigned ratings of high, low or unclear ROB [ 16 ]. Differences in judgements were resolved by discussion. Meta-analysis was conducted using Review Manager 5. Heterogeneity between trials was assessed by visual examination of the forest plot to check for overlapping of confidence intervals CI , Chi 2 test and I 2 statistics. We used random-effects model REM assuming high heterogeneity. However, results were also compared using fixed-effect model FEM.

Categorical and continuous measures of effect size were expressed as risk difference RR Mantel Haenszel method and mean difference MD Inverse Variance method respectively. Sensitivity analysis was planned for studies with low ROB. Subgroup analyses were planned by neonatal gestation at birth 34, 35, 36 weeks , mode of delivery vaginal or caesarean section and presence of maternal gestational diabetes.

We planned to assess publication bias using a funnel plot [ 17 ]. Evidence from RCTs was considered as high quality. We graded the evidence in the following domains: ROB, inconsistency, indirectness, imprecision and publication bias. The evidence was downgraded one level for serious and two levels for very serious limitation. The literature search retrieved potentially relevant citations Fig 1. Total of citations removed as duplicate. After carefully reviewing the abstracts and titles citations were excluded.

Total 29 citations were read in details and 22 were excluded for reasons mentioned in the flow chart. Five studies provided data for the primary outcome of need for any respiratory support [ 10 , 20 — 22 , 25 ] whereas only 4 reported on hypoglycemia [ 10 , 20 , 21 , 25 ]. The characteristics of the included studies are shown in Table 1. Results of the sensitivity analysis including only studies with low ROB Gyamifi- Bannerman and Porto et al showed no difference in any respiratory support between ANC vs.

This was not possible due to lack of stratified data based on gestational age, mode of delivery and maternal diabetes. The results of this comparative analysis showed that majority of the outcomes including both primary outcomes were similar with both models. S2 Table. For the primary outcome of need for any respiratory support, the evidence was graded as moderate whereas it was deemed high for hypoglycaemia.

For secondary outcomes the evidence was deemed as very low to moderate. Our systematic review showed that exposure to ANC was beneficial in reducing the need for respiratory support but with the increased risk of hypoglycemia in neonates born at late preterm gestation. Exposure to ANC also reduced the need for resuscitation at birth. None of the included trials reported long term follow up data.

Respiratory morbidities in LPNs relate to developmental immaturity of the lungs. The mechanisms for benefits of ANC include enhanced alveolar differentiation with the induction of type 2 pneumocytes and activation of endothelial nitric oxide synthase [ 27 , 28 ].

It is postulated that similar to term gestation, ANC exposure at late preterm gestation accelerates coordinated organ development sequence in response to endogenous rise in fetal glucocorticoids [ 29 , 30 ]. Experimental studies show that the improvement in lung function after ANC exposure are due to an increase in the absorption of fetal lung fluid, thinning of alveolar septae, and synthesis of surfactant proteins and phospholipids [ 30 , 31 ]. The benefits of ANC need to be considered in the context of their potential adverse effects.

ANC exposure is associated with reduced brain mass, delayed myelination, decreased maturation of peripheral nerves, increased impairment of hypothalamopitutory axis and impaired programmed apoptosis in animal studies [ 30 , 32 — 34 ]. A follow-up study of participants from ASTECS trial reported two-fold increase in teacher-reported low academic ability in children age 8—15 years exposed to betamethasone as term infants born by an elective caesarean section.

There were no significant differences in general health, behaviour and academic achievements between exposed vs. A recent population-based study from Finland using nationwide registries of all term and preterm singleton live births found that ANC exposure was associated with a significant increase [adjusted hazard ratio aHR : 1. The incidence of these disorders was high in term neonates exposed to ANC vs. The incidence of these adverse outcomes was higher It is important to consider the implications of our results for clinical practice.

The NNT to prevent one case of any respiratory support and need for resuscitation at birth was 20 and 16 respectively. In comparison, the NNT for harm was 13 for neonatal hypoglycaemia. LPNs are at high risk of hypoglycaemia due to poor substrate and underdeveloped compensatory response. The increased risk of neonatal hypoglycaemia might be due to transient hyperinsulinemia following maternal hyperglycaemia in response to ANC [ 37 ]. The definition of neonatal hypoglycaemia varied in the RCTs included in our review.

Hypoglycaemia is an independent predictor of poor neurodevelopmental outcomes in neonates. Inability to predict spontaneous preterm birth means inevitable unwarranted exposure to ANC in a significant number of late preterm pregnancies, which do not result in late preterm delivery. Overall, potential long-term neurodevelopmental adverse effects of ANC must receive due attention considering that none of the included trials till date have reported such data. The limitations of using Apgar scores as a primary outcome need to be discussed.

Apgar score at 1 minute does not correlate with mortality and long-term neurodevelopmental outcomes [ 40 ]. Apgar scores can be low in otherwise well preterm neonates with no evidence of perinatal asphyxia [ 40 — 42 ]. Moreover, being a continuous measure, it is much more likely that differences would be noted regardless of their clinical importance. The strengths of our review include its robust methodology, inclusions of only RCTs, large sample size and use of GRADE guidelines for summarizing the level of evidence.

We conducted sensitivity analysis excluding the studies with high ROB. The provision of the NNT for both, benefit and harm, is important for guiding research and clinical practice. The limitations of our review include the fact that the pooled results are still influenced by the large ALPS trial [ 10 ]. The included RCTs differ in the definitions of various outcomes, type of steroids, and their dosage.

Furthermore, analysis stratified by gestation, mode of delivery or maternal diabetic status was not possible. Our systematic review showed that exposure to ANC was beneficial in reducing the need for respiratory support but with an increased risk of hypoglycemia in neonates born at late preterm gestation. In summary, moderate to low-quality evidence indicates that ANC exposure reduced the need for respiratory support and increased the risk of neonatal hypoglycaemia in LPNs.

The increased risk of neonatal hypoglycaemia is a serious concern. Pragmatic and adequately powered multicentre RCTs with long-term follow up assessing neonatal neurodevelopmental outcomes are needed to assess the efficacy and safety of ANC. Stratification by gestation, mode of delivery, maternal diabetes and other risk factors for respiratory distress is desirable in such trials.

Pending results of such trials rigorous monitoring, treatment, and follow up of LPNs exposed to ANC is critical, more so in the context of hypoglycemia. Submission declaration : All authors declare that the work submitted has not been published previously, that it is not under consideration for publication elsewhere, that its publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere including electronically in the same form, in English or in any other language, without the written consent of the copyright-holder.

Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Abstract Background Administration of antenatal corticosteroids ANC for impending preterm delivery beyond 34 weeks of gestation continues to be a controversial issue despite various guidelines for obstetricians and gynaecologists.

Conclusions Moderate quality evidence indicates that ANC exposure reduced need for respiratory support, and increased the risk of hypoglycaemia in late preterm neonates. Funding: The authors received no specific funding for this work. Participants Inclusion criteria. Exclusion criteria. Major chromosomal and congenital anomalies.

Search strategy. Study selection. Data extraction and management. Data synthesis. Assessment of publication bias. Grading the evidence and summary of findings. Results The literature search retrieved potentially relevant citations Fig 1. Download: PPT. Fig 1. Flow chart of study selection process after screening of electronic search. Table 1. Need for any respiratory support was significantly less in the ANC vs.

The number needed to treat NNT for preventing one case of respiratory support was 20 Fig 3. Hypoglycaemia : Four studies that reported this outcome included neonates ANC: , Control: [ 10 , 20 , 21 , 25 ]. Incidence of hypoglycaemia was significantly high in the ANC vs. Control: The number needed for harm for hypoglycemia was 13 Fig 4. Secondary outcomes Need for resuscitation at birth [only in delivery room immediately after birth not in NICU ]: The data for this outcome was available from 6 studies that included neonates ANC: , Control: [ 10 , 21 — 25 ].

Need for resuscitation at birth was significantly less in the ANC vs. S1 Fig NNT for this outcome was Mortality was similar in the ANC vs. S5 Fig Need for mechanical ventilation : The data for this outcome was available from 4 studies that included neonates ANC: , Control: [ 10 , 20 — 22 ].

S6 Fig Need for Surfactant : The data for this outcome was available from 3 studies that included neonates ANC: , Control: [ 10 , 20 , 22 ]. Need for surfactant was 1. S7 Fig Developmental follow up : None of the included studies reported data on this outcome.

Adverse effects : Apart from neonatal hypoglycaemia none of the included studies reported any other adverse effects such as neonatal sepsis, and seizures. Sensitivity analysis. Subgroup analysis. The presence of RDS is the main foetal outcome in this study. Respiratory distress in evidence of dyspnoea grunting, sternal, subcostal and intercostal retraction. Chest X-ray changes homogenous reticulogranular [ 16 ].

IVH is diagnosed by cranial ultrasound on day three of life and graded according to the classification by Papile et al. NEC is diagnosed according to Bell staging criteria [ 18 ]. Neonatal outcomes were compared between the group of neonates that were delivered within 7 days and those delivering beyond 7 days of first dose of ACS.

Pearson Chi-square test was performed for categorical variables. For continuous variables, normality was checked using Kolmogorov—Smirnov test. For normally distributed variables, T test was performed. For non-normally distributed variables, Mann—Whitney U test was performed. Adjusted analysis was not performed for individual morbidities with low frequencies, less than 10 observations for category for other outcomes. A total of infants were delivered prematurely to women in the study period with singleton, 50 twins and one triplet deliveries.

All records were available and retrieved within the study period. As seen from Fig. Out of which, only 51 There were no infants who received a rescue dose or a repeat course of ACS. Proportion of neonates who was exposed to Dexamethasone Dexa antenatally and the duration between ACS exposure and delivery. There was a significant association between birth weight and ACS exposure to delivery among the 3 groups within 48 h, 48 h to 7 days and beyond 7 days.

There were no statistically significant difference between the groups in terms of gestational age, type of preterm birth, gestation, mode of delivery and indication for ACS Table 1. The overall incidence of RDS in our study is Multivariate analysis of the association between neonatal characteristics with incidence of RDS, independent of ACS exposure.

A total of three 0. There were no cases of NEC among neonates who received steroids. There were 16 4. Mortality rate inclusive of stillborn and neonatal death within the 3 months study period was 4. There was no statistically significant difference in NEC, IVH and mortality rate among neonates who received ACS within 48 h, within window of efficacy or beyond a week. Table 3 shows the incidence of RDS for neonates who were exposed to ACS within 48 h, from 48 h to 7 days and beyond 7 days.

Those with ACS exposure beyond 7 days were 7. When compared with neonates with ACS exposure within the window of efficacy 48 h to 1 week , neonates given within 48 h were 0. Administration of antenatal corticosteroids ACS is a widely accepted practice for preterm deliveries to decrease the incidence of neonatal respiratory distress syndrome RDS.

However, the timing of ACS administration in relation to the delivery is controversial. It remains unknown if the efficacy of ACS beyond a week from initial exposure is indeed limited, necessitating a repeat dose of ACS. It also begs the question of how important is it for obstetricians to judge the timing of ACS administration relative to the likelihood of preterm delivery within the next 7 days.

Our results showed that ACS exposure in preterm neonates significantly reduce the incidence of RDS and oxygen therapy requirement. There was a benefit of administrating corticosteroids IM Dexamethasone 12 mg 12 h apart within 7 days of delivery as infants with ACS exposure beyond 7 days are seven times more likely to have RDS as those with ACS exposure within this window period.

This result is similar to that in some other studies as well. In a retrospective cohort study performed by Ring et al. Waters et al. Our results also suggested benefit of administering ACS within 48 h of delivery. Strengths of our study include a large number of preterm deliveries with a significant incidence of RDS for analysis, from a clinically diverse cohort of women presenting at the largest obstetric centre and perinatal unit in Singapore.

We acknowledge that there are several limitations to our study. Our study is a retrospective review which limits the analysis on cause and effect relationship between the factors and outcomes. The low incidence of severe complications: stillbirth, neonatal death, IVH and NEC within the study period did not allow us to examine them.

Both Peaceman et al. Peaceman et al. It is hypothesised that ACS aids in the maturation of organs with glucocorticoid receptors such as the brain, thyroid and gastrointestinal tract, thus reducing the incidence of IVH and NEC [ 20 , 21 , 22 ].

Hence, it may be worthwhile to analyse these correlations in future larger studies. It is possible that the results of this study may be partly due to the different ACS regime in our centre and the inclusion of late preterm neonates.

Previous studies mentioned above involved an ACS regime of hourly dosage instead of a hourly one. There are, however, evidence to suggest that a h interval may be equivalent to standard h interval [ 14 ]. A recent study by Gyamfi-Bannerman et al.

The study showed significantly lower risk of the composite primary outcome stillbirth or neonatal death before 72 h or need for respiratory support by 72 h of age in the betamethasone group than in the placebo group. In summary, our study reinforced the rationale behind the common practice of giving antenatal corticosteroids in preterm birth and also demonstrated significant decrease in RDS for those who were delivered within 7 days of ACS.

This supports the current practice among obstetricians to aim to administer ACS within the window of efficacy. There may also be added benefit to the infant to administer at least a dose of ACS in late preterm labour. Our study also revealed that only It is imperative to keep a regular audit of this intervention for preterm birth, educate patients to allow earlier presentation, and encourage the timely administration of ACS before preterm delivery occurs in order to benefit. Eveline Gan Premature births on the rise in Singapore.

TODAY in press. Roberts D, Dalziel SR Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. Google Scholar. Liggins GC, Howie RN A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics — PubMed Google Scholar. Arch Gynecol Obstet — J Matern Fetal Neonatal Med — Am J Perinatol — Article PubMed Google Scholar.

J Matern Fetal Neonatal Med 27 5 — Am J Obstet Gynecol Crowther CA, Harding JE Repeat doses of prenatal corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease. Lancet — Preterm labour and birth. Accessed Nov Greenough A Respiratory distress syndrome. In: Rennie JM ed Textbook of neonatology.

GOLDEN DRAGON NEWHAM

The NNT to prevent one case of any respiratory support and need for resuscitation at birth was 20 and 16 respectively. In comparison, the NNT for harm was 13 for neonatal hypoglycaemia. LPNs are at high risk of hypoglycaemia due to poor substrate and underdeveloped compensatory response. The increased risk of neonatal hypoglycaemia might be due to transient hyperinsulinemia following maternal hyperglycaemia in response to ANC [ 37 ].

The definition of neonatal hypoglycaemia varied in the RCTs included in our review. Hypoglycaemia is an independent predictor of poor neurodevelopmental outcomes in neonates. Inability to predict spontaneous preterm birth means inevitable unwarranted exposure to ANC in a significant number of late preterm pregnancies, which do not result in late preterm delivery. Overall, potential long-term neurodevelopmental adverse effects of ANC must receive due attention considering that none of the included trials till date have reported such data.

The limitations of using Apgar scores as a primary outcome need to be discussed. Apgar score at 1 minute does not correlate with mortality and long-term neurodevelopmental outcomes [ 40 ]. Apgar scores can be low in otherwise well preterm neonates with no evidence of perinatal asphyxia [ 40 — 42 ]. Moreover, being a continuous measure, it is much more likely that differences would be noted regardless of their clinical importance. The strengths of our review include its robust methodology, inclusions of only RCTs, large sample size and use of GRADE guidelines for summarizing the level of evidence.

We conducted sensitivity analysis excluding the studies with high ROB. The provision of the NNT for both, benefit and harm, is important for guiding research and clinical practice. The limitations of our review include the fact that the pooled results are still influenced by the large ALPS trial [ 10 ]. The included RCTs differ in the definitions of various outcomes, type of steroids, and their dosage. Furthermore, analysis stratified by gestation, mode of delivery or maternal diabetic status was not possible.

Our systematic review showed that exposure to ANC was beneficial in reducing the need for respiratory support but with an increased risk of hypoglycemia in neonates born at late preterm gestation. In summary, moderate to low-quality evidence indicates that ANC exposure reduced the need for respiratory support and increased the risk of neonatal hypoglycaemia in LPNs.

The increased risk of neonatal hypoglycaemia is a serious concern. Pragmatic and adequately powered multicentre RCTs with long-term follow up assessing neonatal neurodevelopmental outcomes are needed to assess the efficacy and safety of ANC. Stratification by gestation, mode of delivery, maternal diabetes and other risk factors for respiratory distress is desirable in such trials.

Pending results of such trials rigorous monitoring, treatment, and follow up of LPNs exposed to ANC is critical, more so in the context of hypoglycemia. Submission declaration : All authors declare that the work submitted has not been published previously, that it is not under consideration for publication elsewhere, that its publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere including electronically in the same form, in English or in any other language, without the written consent of the copyright-holder.

Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Abstract Background Administration of antenatal corticosteroids ANC for impending preterm delivery beyond 34 weeks of gestation continues to be a controversial issue despite various guidelines for obstetricians and gynaecologists.

Conclusions Moderate quality evidence indicates that ANC exposure reduced need for respiratory support, and increased the risk of hypoglycaemia in late preterm neonates. Funding: The authors received no specific funding for this work. Participants Inclusion criteria. Exclusion criteria. Major chromosomal and congenital anomalies. Search strategy. Study selection. Data extraction and management.

Data synthesis. Assessment of publication bias. Grading the evidence and summary of findings. Results The literature search retrieved potentially relevant citations Fig 1. Download: PPT. Fig 1. Flow chart of study selection process after screening of electronic search.

Table 1. Need for any respiratory support was significantly less in the ANC vs. The number needed to treat NNT for preventing one case of respiratory support was 20 Fig 3. Hypoglycaemia : Four studies that reported this outcome included neonates ANC: , Control: [ 10 , 20 , 21 , 25 ]. Incidence of hypoglycaemia was significantly high in the ANC vs.

Control: The number needed for harm for hypoglycemia was 13 Fig 4. Secondary outcomes Need for resuscitation at birth [only in delivery room immediately after birth not in NICU ]: The data for this outcome was available from 6 studies that included neonates ANC: , Control: [ 10 , 21 — 25 ]. Need for resuscitation at birth was significantly less in the ANC vs. S1 Fig NNT for this outcome was Mortality was similar in the ANC vs. S5 Fig Need for mechanical ventilation : The data for this outcome was available from 4 studies that included neonates ANC: , Control: [ 10 , 20 — 22 ].

S6 Fig Need for Surfactant : The data for this outcome was available from 3 studies that included neonates ANC: , Control: [ 10 , 20 , 22 ]. Need for surfactant was 1. S7 Fig Developmental follow up : None of the included studies reported data on this outcome. Adverse effects : Apart from neonatal hypoglycaemia none of the included studies reported any other adverse effects such as neonatal sepsis, and seizures.

Sensitivity analysis. Subgroup analysis. Analysis using fixed effect model. Summary of findings table and publication bias. Table 2. Discussion Our systematic review showed that exposure to ANC was beneficial in reducing the need for respiratory support but with the increased risk of hypoglycemia in neonates born at late preterm gestation.

Conclusions Our systematic review showed that exposure to ANC was beneficial in reducing the need for respiratory support but with an increased risk of hypoglycemia in neonates born at late preterm gestation. Supporting information. S1 Fig. Effect of ANC on need for resuscitation at birth. S2 Fig. Effect of ANC on admission to nursery. S3 Fig. S4 Fig. S5 Fig. Effect of ANC on mortality. S6 Fig.

Effect of ANC on mechanical ventilation. S7 Fig. Effect of ANC on need for surfactant. S1 Table. Results of sensitivity analysis based on ROB. Results of analysis by fixed and random effects model. S3 Table. S1 File. References 1. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth.

Cochrane Database Syst Rev. Practice CoO. Committee Opinion No. Obstetrics and gynecology. Journal of Obstetrics and Gynaecology Canada. Delnord M, Zeitlin J. Epidemiology of late preterm and early term births—An international perspective. Semin Fetal Neonatal Med. Raju T. Neonatal outcomes and delivery of care for infants born late preterm or moderately preterm: a prospective population-based study.

Archives of disease in childhood Fetal and neonatal edition. Effect of late-preterm birth and maternal medical conditions on newborn morbidity risk. Barfield W LK. Late Preterm Infants. Persistence of morbidity and cost differences between late-preterm and term infants during the first year of life. N Engl J Med. Saccone G, Berghella V. Antenatal corticosteroids for maturity of term or near term fetuses: systematic review and meta-analysis of randomized controlled trials.

Antenatal corticosteroids: an assessment of anticipated benefits and potential risks. Am J Obstet Gynecol. Antenatal corticosteroids beyond 34 weeks gestation: What do we do now? Searching for studies. Cochrane handbook for systematic reviews of interventions New York: Wiley. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.

Annals of internal medicine. View Article Google Scholar Table 3 shows the incidence of RDS for neonates who were exposed to ACS within 48 h, from 48 h to 7 days and beyond 7 days. Those with ACS exposure beyond 7 days were 7. When compared with neonates with ACS exposure within the window of efficacy 48 h to 1 week , neonates given within 48 h were 0. Administration of antenatal corticosteroids ACS is a widely accepted practice for preterm deliveries to decrease the incidence of neonatal respiratory distress syndrome RDS.

However, the timing of ACS administration in relation to the delivery is controversial. It remains unknown if the efficacy of ACS beyond a week from initial exposure is indeed limited, necessitating a repeat dose of ACS.

It also begs the question of how important is it for obstetricians to judge the timing of ACS administration relative to the likelihood of preterm delivery within the next 7 days. Our results showed that ACS exposure in preterm neonates significantly reduce the incidence of RDS and oxygen therapy requirement.

There was a benefit of administrating corticosteroids IM Dexamethasone 12 mg 12 h apart within 7 days of delivery as infants with ACS exposure beyond 7 days are seven times more likely to have RDS as those with ACS exposure within this window period. This result is similar to that in some other studies as well. In a retrospective cohort study performed by Ring et al.

Waters et al. Our results also suggested benefit of administering ACS within 48 h of delivery. Strengths of our study include a large number of preterm deliveries with a significant incidence of RDS for analysis, from a clinically diverse cohort of women presenting at the largest obstetric centre and perinatal unit in Singapore. We acknowledge that there are several limitations to our study.

Our study is a retrospective review which limits the analysis on cause and effect relationship between the factors and outcomes. The low incidence of severe complications: stillbirth, neonatal death, IVH and NEC within the study period did not allow us to examine them. Both Peaceman et al. Peaceman et al. It is hypothesised that ACS aids in the maturation of organs with glucocorticoid receptors such as the brain, thyroid and gastrointestinal tract, thus reducing the incidence of IVH and NEC [ 20 , 21 , 22 ].

Hence, it may be worthwhile to analyse these correlations in future larger studies. It is possible that the results of this study may be partly due to the different ACS regime in our centre and the inclusion of late preterm neonates. Previous studies mentioned above involved an ACS regime of hourly dosage instead of a hourly one. There are, however, evidence to suggest that a h interval may be equivalent to standard h interval [ 14 ].

A recent study by Gyamfi-Bannerman et al. The study showed significantly lower risk of the composite primary outcome stillbirth or neonatal death before 72 h or need for respiratory support by 72 h of age in the betamethasone group than in the placebo group. In summary, our study reinforced the rationale behind the common practice of giving antenatal corticosteroids in preterm birth and also demonstrated significant decrease in RDS for those who were delivered within 7 days of ACS.

This supports the current practice among obstetricians to aim to administer ACS within the window of efficacy. There may also be added benefit to the infant to administer at least a dose of ACS in late preterm labour. Our study also revealed that only It is imperative to keep a regular audit of this intervention for preterm birth, educate patients to allow earlier presentation, and encourage the timely administration of ACS before preterm delivery occurs in order to benefit.

Eveline Gan Premature births on the rise in Singapore. TODAY in press. Roberts D, Dalziel SR Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. Google Scholar. Liggins GC, Howie RN A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics — PubMed Google Scholar. Arch Gynecol Obstet — J Matern Fetal Neonatal Med — Am J Perinatol — Article PubMed Google Scholar.

J Matern Fetal Neonatal Med 27 5 — Am J Obstet Gynecol Crowther CA, Harding JE Repeat doses of prenatal corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease. Lancet — Preterm labour and birth. Accessed Nov Greenough A Respiratory distress syndrome.

In: Rennie JM ed Textbook of neonatology. Churchill Livingstone, London, pp — Papile LA, Burstein J, Koffier H Incidence and evolution of sub- ependymal and intraventricular hemorrhage: a study of infants with birth weights less than g. J Pediatr — Am J Obstet Gynaecol — Proc Nutr Soc. Mol Endocrinol 29 5 — N Engl J Med — Download references. Hester C. Lau, Janice S. You can also search for this author in PubMed Google Scholar.

JSZT and HCQL: Development of the research design, analysis strategy, data collection, statistical analysis, interpretation of results, manuscript writing; co-first authors of this manuscript. TTCW: Data collection, statistical analysis, and manuscript writing.

TPL: Development of research study and analysis strategy. ST: Development of research design and analysis strategy, editorial guidance. All authors approved this version of manuscript for submission. Correspondence to Hester C. Reprints and Permissions. Lau, H. Timing of antenatal steroids exposure and its effects on neonates. Arch Gynecol Obstet , — Download citation.

Received : 21 May Accepted : 11 September Published : 25 September Issue Date : December

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Although most premature infants survive without major sequelae, some require rehospitalization and special services. Corticosteroid treatment of pregnant women delivering prematurely was first introduced in to enhance fetal lung maturity.

A recent meta-analysis concluded that corticosteroid administration prior to anticipated preterm delivery is associated with a large reduction in the incidence of early neonatal death, RDS, IVH, and NEC. Despite evidence of beneficial effects from both experimental models and randomized controlled trials in humans, a minority of women delivering prematurely receive antenatal corticosteroid treatment.

In reports from approximately perinatal centers, only 12 to 18 percent of women who deliver preterm infants of to 1, grams birthweight are treated with antenatal corticosteroids. Clinicians are not treating many patients who might benefit because of concerns about the efficacy of corticosteroids and the potential complications of treatment in certain conditions.

Use of this therapy is further impeded by lack of access to prenatal care and to appropriate delivery services. After a year of study and preparation concluding with a day and a half of presentations by experts in the relevant fields and discussion from the audience, an independent consensus panel composed of representatives from the medical and related scientific disciplines, as well as representatives from the public, considered the evidence and formulated a consensus statement in response to the following key questions: For what conditions and purposes are antenatal corticosteroids used, and what is the scientific basis for that use?

What are the short-term and long-term benefits of antenatal corticosteroid treatment? What are the short-term and long-term adverse effects for the infant and mother? What is the influence of the type of corticosteroid, dosage, timing and circumstances of administration, and associated therapy on treatment outcome? What are the economic consequences of this treatment? What are the recommendations for use of antenatal corticosteroids? What research is needed to guide clinical care?

Animal studies conducted in the 's and 's showed that the pituitary adrenal system affected differentiation of the intestine and lung. Later studies found physiologic surges in corticosteroids just before term or preterm delivery, and a relationship between fetal cortisol levels at delivery and lung maturity. Since then, randomized controlled trials in women have confirmed the maturational effects of corticosteroids on fetal organ systems such as the cardiovascular, respiratory, nervous, and gastrointestinal systems.

As a result, antenatal corticosteroids are now administered for the purpose of hastening maturation of the preterm infant's organs and tissues, thus reducing morbidity and mortality related to prematurity. The clinical conditions under which antenatal corticosteroid administration has been investigated are those associated with threatened or inevitable preterm delivery.

These include 1 preterm labor, which accounts for 30 to 50 percent of all preterm deliveries; 2 preterm premature rupture of membranes, which accounts for 20 to 50 percent of all preterm deliveries; 3 preeclampsia, which is associated with 10 to 25 percent of preterm deliveries; and 4 other conditions, such as diabetes mellitus, third trimester bleeding, fetal distress, or isoimmunization necessitating preterm delivery, which account for up to 10 percent of preterm deliveries.

The use of antenatal corticosteroid therapy has been studied in relatively few pregnancies less than 24 weeks' or greater than 34 weeks' gestation. Additional issues that have been investigated include duration of the "treatment window," the gender and race of the fetus, the relationship of gestational age to the risks and benefits of treatment, and the use of antenatal corticosteroids along with other treatments, such as postnatal pulmonary surfactant and tocolytic administration.

Studies of antenatal corticosteroid treatment were evaluated with the grading system developed by the Canadian Task Force on the Periodic Health Examination and adapted by the U. Preventive Services Task Force Table 1.

The ratings reflect both the quality of evidence and the strength of the recommendations that can be based on that evidence. For most of these conditions or outcomes, at least some data were available from randomized controlled trials. For some outcomes, such as RDS, data were extensive. For other maternal conditions or neonatal outcomes, though derived from randomized controlled trials, data were limited. Hence, for some conditions or outcomes, although grade I evidence was available, this evidence was judged insufficient to allow a recommendation concerning the use of corticosteroids.

Antenatal corticosteroid therapy in the preterm fetus in many randomized controlled trials has reduced neonatal mortality and the incidence of the respiratory distress syndrome RDS. A meta-analysis based on 15 such trials showed a reduction in the incidence of RDS with a typical odds ratio of 0.

These data are not only statistically significant, but also clinically compelling. In subgroup analysis these benefits were confirmed regardless of the infant's gender or race. One recent randomized controlled trial showed a significant reduction in IVH with antenatal corticosteroid treatment.

Secondary outcome variables reported in the meta-analysis of randomized controlled trials also showed a significant reduction in the incidence of IVH with an odds ratio of 0. This reduction in IVH is supported by the results of the observational database, information prospectively collected in five registries involving more than 30, low-birthweight infants.

Since IVH is an important contributor to mortality and serious long-term neurodevelopmental disability, this reduction is a major benefit. Improved circulatory stability and reduced requirements for oxygen and ventilatory support were additional benefits identified in randomized controlled trials. The meta-analysis of the randomized controlled trials revealed a reduction of the incidence of NEC, however, this finding was not corroborated by the observational database.

Conversely, the incidence of PDA was not found to be reduced in the meta-analysis, but was significantly reduced in the observational database. Several studies have followed infants from the randomized trials for as long as 12 years. The increased survival of treated infants has not resulted in the appearance of adverse long-term effects. Short-term adverse effects of antenatal corticosteroid administration of greatest concern in the neonate include infection and adrenal suppression.

The evidence presented to date shows no increase in infection in treated infants, no clinically important adrenal suppression, and rapid return of adrenal function when antenatal corticosteroids are discontinued. Some animal studies have suggested that antenatal corticosteroid treatment might promote maladaptive responses to hypoxia. Other animal studies have shown that corticosteroids in doses similar to those used in humans antenatally provide protection against hypoxic-ischemic brain injury.

More data are needed from human studies in this area of research. Studies initiated in the 's, which followed the development of children treated antenatally with corticosteroids up to the age of 12 years, showed no adverse outcomes in the areas of motor skills, language, cognition, memory, concentration or scholastic achievement. The possibility of adverse, long-term neurodevelopmental outcomes has been suggested by studies of corticosteroid administration in animals.

These studies were conducted using doses approximately 10 times the doses used in human clinical trials. There does not seem to be an increased risk in children of long-term neurodevelopmental impairment as reflected in any greater prevalence of learning, behavioral, motor, or sensory disturbances. Long-term effects of antenatal corticosteroids on growth and the onset of puberty are not fully known.

Maternal pulmonary edema can occur when antenatal corticosteroids are used in combination with tocolytic agents. This complication is more commonly associated with maternal infection, fluid overload, and multiple gestation. Pulmonary edema has not been reported when antenatal corticosteroids are used alone. The risk of maternal infection may be increased when corticosteroids are used in preterm premature rupture of membranes PPROM , however, the degree of this effect, if any, is unclear.

Furthermore, there is no evidence that antenatal corticosteroid treatment interferes with the ability to diagnose maternal infection. When corticosteroids are administered to pregnant diabetic women, diabetic control may become more difficult and insulin may have to be adjusted accordingly. Screening for gestational diabetes may similarly be affected.

In serious maternal medical conditions that necessitate premature delivery, the delay necessary to demonstrate maximal corticosteroid effects for the fetus may worsen the maternal medical status. A subgroup analysis in the first randomized trial suggested that antenatal corticosteroid administration might predispose to fetal death in hypertensive women.

Subsequent trials failed to demonstrate this effect. No long-term maternal adverse effects have been reported. Dexamethasone and betamethasone are the preferred corticosteroids for antenatal therapy. These two compounds are identical in biological activity and readily cross the placenta in their biologically active forms.

They are devoid of mineralocorticoid activity, relatively weak in immunosuppressive activity, and exert longer duration of action than cortisol and methylprednisolone. They also are the most extensively studied antenatal corticosteroids for accelerating fetal maturation.

Treatment of two doses of 12 mg of betamethasone given intramuscularly 24 hours apart or four doses of 6 mg of dexamethasone given intramuscularly 12 hours apart has been shown to be effective. Although these regimens were arbitrarily selected, subsequently they have been shown to deliver concentrations to the fetus that are comparable to physiologic stress levels of cortisol occurring after birth in untreated premature infants who develop RDS. These regimens result in an estimated 75 percent occupancy of available corticosteroid receptors, which should provide a near maximal induction of antenatal corticosteroid receptor-mediated response in fetal target tissues.

Higher or more frequent doses do not increase the benefits of antenatal corticosteroid therapy and may increase the likelihood of adverse effects. Strong evidence exists for neonatal benefits from a complete course of antenatal corticosteroids starting at 24 hours and lasting up to 7 days after treatment. Evidence suggests a reduction in mortality, RDS, and IVH even with treatment initiated less than 24 hours prior to delivery. Both clinical and in vitro evidence suggest that the corticosteroid biological effects persist up to 7 days following initial treatment.

Data are inadequate to establish the clinical benefit beyond 7 days after antenatal corticosteroid therapy. The potential benefits or risks of repeated administration after 7 days are unknown. In vitro experiments in human fetal lung explants show that inducible biochemical effects have dissipated by 7 days although structural changes persist. For infants born at 29 to 34 weeks' gestation, treatment with antenatal corticosteroids clearly reduces the incidence of RDS and overall mortality.

While antenatal corticosteroids do not clearly decrease the incidence of RDS in infants born at 24 to 28 weeks' gestation, they reduce its severity. More important, antenatal corticosteroids clearly reduce mortality and the incidence of IVH in this age group.

All fetuses between 24 and 34 weeks' gestation threatened with premature delivery are candidates for treatment with antenatal corticosteroids. The evidence for significant improvement in outcomes in these infants with antenatal corticosteroid use is limited. Alternatively, an observational study reported less-frequent adverse neurological outcome at 18—22 months after betamethasone exposure These inconsistent and limited data are not considered sufficient to recommend one corticosteroid regimen over the other.

Treatment should consist of either two mg doses of betamethasone given intramuscularly 24 hours apart or four 6-mg doses of dexamethasone administered intramuscularly every 12 hours Because treatment with corticosteroids for less than 24 hours is still associated with significant reduction in neonatal morbidity and mortality, a first dose of antenatal corticosteroids should be administered even if the ability to give the second dose is unlikely, based on the clinical scenario 11 The benefit of corticosteroid administration is greatest at 2—7 days after the initial dose.

Therefore, corticosteroids should not be administered unless there is substantial clinical concern for imminent preterm birth. Specific data on the use of corticosteroids in the periviable period are supported by a combination of laboratory data on the response of lung tissue and clinical observational studies 1 2 17 The use of antenatal corticosteroid administration after preterm PROM has been evaluated in a number of clinical trials and has been shown to reduce neonatal mortality, respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis 6 12 19 Current data suggest that antenatal corticosteroids are not associated with increased risks of maternal or neonatal infection regardless of gestational age.

Whether to administer a repeat or rescue course of corticosteroids with preterm PROM is controversial, and there is insufficient evidence to make a recommendation for or against see Single Rescue Course. A Cochrane review concluded that although antenatal corticosteroids are beneficial in singleton gestations, further research is required to demonstrate an improvement in outcomes for multifetal gestations 21 More recently, a well-designed retrospective cohort study concluded that administration of a complete course of antenatal corticosteroids 1—7 days before birth in twin pregnancies is associated with a clinically significant decrease in neonatal mortality, short-term respiratory morbidity, and severe neurological injury that is similar in magnitude to that observed among singletons The Maternal Fetal Medicine Units MFMU Network Antenatal Late Preterm Steroids trial 24 was a double-blind, placebo-controlled, randomized clinical trial designed to evaluate the use of antenatal betamethasone for pregnant women at high risk of delivery in the late preterm period.

Women were identified to be at high risk if they presented in preterm labor, had preterm PROM, or if they had a planned delivery in the late preterm period, with the indication at the discretion of the obstetrician—gynecologist or other health care provider. Tocolysis was not employed as a part of this trial, and delivery was not delayed for obstetric or medical indications.

The study found that the administration of betamethasone led to a significant decrease in the primary outcome, which was the need for respiratory support. A larger decrease was demonstrated for severe respiratory complications, from There were also significant decreases in the rates of transient tachypnea of the newborn; bronchopulmonary dysplasia; a composite of respiratory distress syndrome RDS , transient tachypnea of the newborn and RDS; and the need for postnatal surfactant.

Infants exposed to betamethasone were less likely to require immediate postnatal resuscitation. There was no increase in proven neonatal sepsis, chorioamnionitis, or endometritis with late preterm betamethasone. Hypoglycemia was more common in the infants exposed to betamethasone The rates of hypoglycemia found in the trial are similar to what is reported in the general population of late preterm infants Although not studied in this trial, long-term adverse outcomes of prolonged and persistent neonatal hypoglycemia have been described 26 The American Academy of Pediatrics recommends the monitoring of neonatal blood sugars for late preterm infants because late preterm birth is a known risk factor for hypoglycemia.

There are important considerations specific to the administration of late preterm corticosteroids that should be noted and are derived from the methodology used by the trial. Late preterm administration of antenatal corticosteroids is not indicated in women diagnosed with clinical chorioamnionitis intrauterine infection Furthermore, tocolysis should not be used in an attempt to delay delivery in order to administer antenatal corticosteroids in the late preterm period, nor should an indicated late preterm delivery such as for preeclampsia with severe features be postponed for corticosteroid administration Groups not studied by the Antenatal Late Preterm Steroids trial include women with multiple gestations, women with pregestational diabetes, women who previously had received a course of corticosteroids, and women who gave birth by cesarean at term.

Whether or not late preterm corticosteroids provide benefit in these populations is unknown. Because of concerns for maternal and fetal harm, and the balance of risk and benefits, planned multiple courses are not recommended. In a randomized trial of single versus serial courses of antenatal corticosteroids, a reduction in birth weight and an increase in the number of infants who were small for gestational age were found, especially after four courses of corticosteroids Although not consistent, six studies found decreased birth weight and head circumference with repeat courses 29 30 31 32 33 34 35 and three studies did not 36 37 Follow-up of children at 2 years of age who were exposed to repeat courses of antenatal corticosteroids showed no significant difference in physical or neurocognitive measures in two studies 39 40 , and the same outcome was found in younger children in a third study Although not statistically significant, the relative risk of cerebral palsy in infants exposed to serial courses of antenatal corticosteroids RR, 5.

Maternal effects include increased risk of infection and suppression of the hypothalamic—pituitary—adrenal axis 31 Regularly scheduled repeat courses or serial courses more than two are not currently recommended Although the initial data 43 suggested the benefit of corticosteroids may decrease after 7 days, the duration of corticosteroid benefit remains controversial No increase in newborn complications or intrauterine growth restriction was identified, although the power to evaluate these individual outcomes was low.

There was no difference in bronchopulmonary dysplasia, and long-term outcome developmental data are not available for these patients. The Crowther Cochrane meta-analysis 10 trials, 4, women and 5, infants included trials with a repeat course of corticosteroids as early as 7 days from initial course. The results of the meta-analysis showed reduction in RDS and there was noted an associated small reduction in size at birth, but no significant adverse outcomes.

Rescue course corticosteroids could be provided as early as 7 days from the prior dose, if indicated by the clinical scenario, given the Cochrane meta-analysis results 11 Whether to administer a rescue course of corticosteroids with PROM is controversial, and there is insufficient evidence to make a recommendation for or against 6 The concern that corticosteroids may have the potential to adversely affect neurodevelopmental outcomes is largely based on animal data and from studies of multiple course corticosteroids The MFMU study of repeat course corticosteroids suggested that four or more courses may be associated with the development of cerebral palsy This single signal does not lead us to caution against corticosteroid use, particularly as it refers to term exposure, but continued surveillance of long-term outcomes should be supported.

The year neurodevelopmental follow-up of this cohort were exposed to corticosteroids from Cognitive functioning as measured by the Weschler scales, working memory and attention, and other neurocognitive assessments were not different between exposure groups. The MFMU Antenatal Late Preterm Steroids study has not yet obtained long-term outcome data but doing so would add significantly to limited available literature.

A final additional consideration regarding corticosteroid risks is that in the context of maternal critical care, antenatal corticosteroids are not contraindicated, even in the setting of sepsis 1 Perinatal Quality Collaboratives, such as the Ohio Perinatal Quality Collaborative, California Perinatal Quality Care Collaborative, and the March of Dimes Big 5 State Perinatal Collaborative have worked to improve use of antenatal corticosteroids through a focus on the identification of missed opportunities and use of quality improvement strategies to optimize appropriate and timely antenatal corticosteroid administration.

Implementation of preterm labor assessment toolkits, standardized order sets for women at risk of early delivery, timely availability of medication in settings where pregnant women are cared for, maternal transfer protocols that indicate corticosteroids should be given before transport, and appropriate documentation of first course and rescue course antenatal corticosteroids in inpatient and outpatient health records, have been among the proposed strategies to improve appropriate and timely antenatal corticosteroid use.

One study reported qualitative focus group data describing conditions that enable delivery of antenatal corticosteroids with high reliability at hospitals that participated in the Ohio Perinatal Quality Collaborative antenatal corticosteroid project Six major themes supporting reliable implementation of antenatal corticosteroids were described, including 1 presence of a high reliability culture, 2 processes that emphasize high reliability, 3 timely and efficient administration process, 4 involvement of multiple disciplines, 5 evidence of benefit supports antenatal corticosteroid use, and 6 benefit is recognized at all levels of the care team.

Participating obstetrician—gynecologists or other health care providers and staff described that these key processes and supports were needed to ensure appropriate and timely delivery of antenatal corticosteroids with high reliability A collaborative of 54 hospitals from across the Big 5 States has been convened to pilot the new resources to standardize the identification of eligible patients and to improve the appropriate timing of corticosteroid therapy.

The Ohio Perinatal Quality Collaborative reported that antenatal corticosteroid rates increase and are maintained at high levels when hospitals are aware that antenatal corticosteroid use is monitored, and missed opportunities are identified and reviewed. The collaborative worked with Ohio vital records to add antenatal corticosteroid administration to the Ohio birth certificate registry.

Monitoring hospital rates provided incentive for hospitals to improve appropriate administration and documentation. This work by state and regional collaboratives demonstrates that quality improvement strategies to optimize appropriate and timely antenatal corticosteroid administration are effective and should be encouraged. Therefore, the administration of antenatal corticosteroids should be monitored and missed opportunities reviewed.

Overuse of antenatal corticosteroids was recently addressed at the Society for Maternal—Fetal Medicine conference in In view of this, it is critical to have ongoing development of strategies that encourage timely corticosteroid administration to women at risk of preterm delivery within 7 days and avoid overuse of corticosteroids for low risk women. Collecting measures that track antenatal corticosteroids use for infants born before 34 weeks of gestation and timing of corticosteroids in relation to delivery will support quality improvement efforts to optimize appropriate and timely antenatal corticosteroid administration.

The American College of Obstetricians and Gynecologists has identified additional resources on topics related to this document that may be helpful for ob-gyns, other health care providers, and patients.

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As a result, maternal steroids decrease the incidence and severity of respiratory distress in premature babies. Premature babies have an increased risk of death. That risk increases as gestational age at birth decreases. Premature babies are at risk of developing intraventricular hemorrhage. Due to fragile blood vessels in the brain and fluctuations in blood pressure, some babies develop bleed in the areas of the brain called ventricles. The presence of intraventricular hemorrhage increases the risk of future developmental problems in the baby.

Necrotic enterocolitis NEC is a severe inflammatory and infectious disease of the GI tract that may affect some premature babies. Affected babies frequently need prolonged antibiotic treatments, sometimes surgery. Some of the babies do not survive it. Giving steroids to mothers who are at risk of delivering a premature baby is reasonably safe but is not entirely free of any side effects.

The majority of mothers given antenatal steroids tolerate it well. An extensive review of several trials in which antenatal steroids were administered to pregnant women, did not find any increased incidence of maternal death or chorioamnionitis infection of the amniotic sac. Transient elevation in glucose levels may occur in women starting 12 hours after the first dose of steroids and may last for several days. Diligent monitoring of glucose levels is essential, so an intervention can be instituted if needed.

Therefore, the diagnosis of infections may be more difficult in those cases. Rare case reports of pulmonary edema have been described in women who received steroids while having chorioamnionitis and also receiving tocolysis treatment to slow down uterine contractions. Pulmonary edema is a condition in which a patient retains too much fluid in the lungs, and that, in turn, leads to breathing problems.

Sometimes it can be a very serious condition. We know that the administration of steroids to babies after birth may be associated with a neurodevelopmental impairment such as cerebral palsy. At this time, we do not have useful data on long term neurodevelopmental outcomes of children who were exposed to steroids at more than 34 weeks of gestational age. For premature babies exposed to antenatal steroids and born at less than 34 weeks, the general consensus is that steroids do not have a significant negative impact on their development.

Doctors monitoring babies in-utero after steroid administration need to be aware that steroids may affect fetal heart rate variability decrease it and also may increase blood flow in umbilical arteries during ultrasound studies. Antenatal steroid treatment is a powerful tool allowing us to improve health outcomes in premature babies. Even though this treatment has been around for more than four decades, there is still a lot we need to learn regarding its positive and negative effects on women and babies.

If you would like to learn about the causes of premature birth, you may be interested in reading my article on this topic here. This article is only for general information purposes. It should not be viewed as any medical advice. There is a chance that information here may be inaccurate. It would be best if you always discussed all health-related matters with your doctor before making any decisions that may affect your health or health of your family members.

Wisniewski is a board-certified pediatrician and neonatologist with over 20 years of clinical experience in the USA. Wisniewski loves educating parents on various health conditions affecting their newborn babies and children. If you just gave birth to a premature baby, you may be asking what you should do now?

That is a great question. Nobody and nothing could prepare you for such eventuality unless you had previously The majority of mothers and doctors prefer natural birth over the operative one. Secondary outcome variables reported in the meta-analysis of randomized controlled trials also showed a significant reduction in the incidence of IVH with an odds ratio of 0.

This reduction in IVH is supported by the results of the observational database, information prospectively collected in five registries involving more than 30, low-birthweight infants. Since IVH is an important contributor to mortality and serious long-term neurodevelopmental disability, this reduction is a major benefit. Improved circulatory stability and reduced requirements for oxygen and ventilatory support were additional benefits identified in randomized controlled trials.

The meta-analysis of the randomized controlled trials revealed a reduction of the incidence of NEC, however, this finding was not corroborated by the observational database. Conversely, the incidence of PDA was not found to be reduced in the meta-analysis, but was significantly reduced in the observational database.

Several studies have followed infants from the randomized trials for as long as 12 years. The increased survival of treated infants has not resulted in the appearance of adverse long-term effects. Short-term adverse effects of antenatal corticosteroid administration of greatest concern in the neonate include infection and adrenal suppression. The evidence presented to date shows no increase in infection in treated infants, no clinically important adrenal suppression, and rapid return of adrenal function when antenatal corticosteroids are discontinued.

Some animal studies have suggested that antenatal corticosteroid treatment might promote maladaptive responses to hypoxia. Other animal studies have shown that corticosteroids in doses similar to those used in humans antenatally provide protection against hypoxic-ischemic brain injury.

More data are needed from human studies in this area of research. Studies initiated in the 's, which followed the development of children treated antenatally with corticosteroids up to the age of 12 years, showed no adverse outcomes in the areas of motor skills, language, cognition, memory, concentration or scholastic achievement.

The possibility of adverse, long-term neurodevelopmental outcomes has been suggested by studies of corticosteroid administration in animals. These studies were conducted using doses approximately 10 times the doses used in human clinical trials. There does not seem to be an increased risk in children of long-term neurodevelopmental impairment as reflected in any greater prevalence of learning, behavioral, motor, or sensory disturbances.

Long-term effects of antenatal corticosteroids on growth and the onset of puberty are not fully known. Maternal pulmonary edema can occur when antenatal corticosteroids are used in combination with tocolytic agents. This complication is more commonly associated with maternal infection, fluid overload, and multiple gestation. Pulmonary edema has not been reported when antenatal corticosteroids are used alone.

The risk of maternal infection may be increased when corticosteroids are used in preterm premature rupture of membranes PPROM , however, the degree of this effect, if any, is unclear. Furthermore, there is no evidence that antenatal corticosteroid treatment interferes with the ability to diagnose maternal infection. When corticosteroids are administered to pregnant diabetic women, diabetic control may become more difficult and insulin may have to be adjusted accordingly.

Screening for gestational diabetes may similarly be affected. In serious maternal medical conditions that necessitate premature delivery, the delay necessary to demonstrate maximal corticosteroid effects for the fetus may worsen the maternal medical status. A subgroup analysis in the first randomized trial suggested that antenatal corticosteroid administration might predispose to fetal death in hypertensive women. Subsequent trials failed to demonstrate this effect.

No long-term maternal adverse effects have been reported. Dexamethasone and betamethasone are the preferred corticosteroids for antenatal therapy. These two compounds are identical in biological activity and readily cross the placenta in their biologically active forms.

They are devoid of mineralocorticoid activity, relatively weak in immunosuppressive activity, and exert longer duration of action than cortisol and methylprednisolone. They also are the most extensively studied antenatal corticosteroids for accelerating fetal maturation. Treatment of two doses of 12 mg of betamethasone given intramuscularly 24 hours apart or four doses of 6 mg of dexamethasone given intramuscularly 12 hours apart has been shown to be effective.

Although these regimens were arbitrarily selected, subsequently they have been shown to deliver concentrations to the fetus that are comparable to physiologic stress levels of cortisol occurring after birth in untreated premature infants who develop RDS. These regimens result in an estimated 75 percent occupancy of available corticosteroid receptors, which should provide a near maximal induction of antenatal corticosteroid receptor-mediated response in fetal target tissues.

Higher or more frequent doses do not increase the benefits of antenatal corticosteroid therapy and may increase the likelihood of adverse effects. Strong evidence exists for neonatal benefits from a complete course of antenatal corticosteroids starting at 24 hours and lasting up to 7 days after treatment. Evidence suggests a reduction in mortality, RDS, and IVH even with treatment initiated less than 24 hours prior to delivery. Both clinical and in vitro evidence suggest that the corticosteroid biological effects persist up to 7 days following initial treatment.

Data are inadequate to establish the clinical benefit beyond 7 days after antenatal corticosteroid therapy. The potential benefits or risks of repeated administration after 7 days are unknown. In vitro experiments in human fetal lung explants show that inducible biochemical effects have dissipated by 7 days although structural changes persist.

For infants born at 29 to 34 weeks' gestation, treatment with antenatal corticosteroids clearly reduces the incidence of RDS and overall mortality. While antenatal corticosteroids do not clearly decrease the incidence of RDS in infants born at 24 to 28 weeks' gestation, they reduce its severity.

More important, antenatal corticosteroids clearly reduce mortality and the incidence of IVH in this age group. All fetuses between 24 and 34 weeks' gestation threatened with premature delivery are candidates for treatment with antenatal corticosteroids. The evidence for significant improvement in outcomes in these infants with antenatal corticosteroid use is limited. There is no convincing evidence from any of the clinical trials that either gender or race of the fetus affects the response to therapy with antenatal corticosteroids.

The use of antenatal corticosteroids to reduce infant morbidity in the presence of PPROM remains controversial. Antenatal corticosteroids reduced the risk of RDS in PPROM in randomized controlled trials, although the magnitude of the reduction was not as great as when the membranes were intact.

Strong evidence from observational studies suggests that, even in the presence of PPROM, the incidence of neonatal mortality and IVH is reduced when antenatal corticosteroids are used. Although the risk of neonatal infection associated with antenatal corticosteroid use in the face of PPROM may be increased, the magnitude of the increase is small.

Because of the effectiveness of antenatal corticosteroids in reducing mortality and IVH in fetuses of less than 30 to 32 weeks' gestation, antenatal corticosteroid use is appropriate in the absence of chorioamnionitis. Data are insufficient to assess the effectiveness of antenatal corticosteroid use in certain maternal high-risk conditions such as hypertension and diabetes.

In the absence of evidence of adverse effects, it may be reasonable to treat these women as one would others with threatened premature delivery. Similarly, in the presence of high-risk fetal conditions, such as multiple gestation, intrauterine growth retardation, and hydrops, it is reasonable to treat these patients as one would others with threatened premature delivery. Antenatal administration of corticosteroids acts additively with postnatal administration of surfactant to reduce mortality, RDS, and IVH.

For these reasons the decision to use antenatal corticosteroids should not be altered by availability of surfactant replacement therapy. Thyroid hormones accelerate fetal lung maturation in animal studies. However, T 3 ; and T 4 ; do not cross the placenta. This problem has been circumvented by maternal administration of thyrotropin-releasing hormone TRH.

The combination of TRH plus antenatal corticosteroids was more effective than corticosteroids alone in two randomized studies. Women who received both drugs had infants with fewer adverse outcomes, fewer days on the ventilator, and a lower incidence of BPD. The use of TRH to accelerate fetal pulmonary maturation currently is experimental and randomized studies are in progress.

Beta-mimetic agents such as ritodrine and terbutaline are frequently administered in an attempt to arrest preterm labor. Women receiving tocolytic therapy are candidates for antenatal corticosteroids to accelerate fetal maturation in the face of threatened premature delivery. Several studies have examined the outcomes of infants born prematurely to mothers who received both ritodrine and dexamethasone or betamethasone.

Although there are flaws in the design of each of these studies, they all showed a significant decrease in incidence of RDS. In addition, one study demonstrated a decrease in ventilator dependency and incidence of PDA. There is evidence that beta-mimetic agents may be associated with increased risk of IVH.

However, the use of antenatal corticosteroids may reduce this risk. Neonatal intensive care is expensive, but is more cost-effective in terms of years of life gained than many other accepted medical interventions. Because the costs of caring for infants with RDS are so high, interventions that may reduce its incidence, such as antenatal corticosteroids or prophylactic surfactant, have the potential of producing large cost savings, in addition to improving health.

The net economic consequences include the costs of initial treatment, changes in treatment made to allow the corticosteroids to work, the costs of any harmful side effects of treatment, the savings resulting from reduced length of stay and intensity of treatment, and the long-term costs of the burden of chronic diseases in surviving infants. Because the direct costs of corticosteroid treatment are so low and differential extra long-term burden has not been well quantified, net cost estimates were derived from the balance of costs of the health outcomes of initial treatment.

Costs of infant care are relatively low for both uncomplicated preterm infants and early neonatal deaths. For any proposed clinical situation, costs are decreased to the extent that corticosteroids reduce illness in survivors, and increased for infants that would have died quickly without them. Data on costs from randomized trials are scant, but length of stay was reduced by about one-third in corticosteroid-treated infants in the four trials for which these data were collected.

To estimate costs or savings from increased use, data on efficacy from all corticosteroid trials can be applied to data on current costs of caring for infants with and without disease. Of the 4,, babies born in the United States each year, , weigh less than 2, grams at birth. Currently 15 percent of these babies are treated with corticosteroids.