Antenatal corticosteroids for neonates born before 25 Weeks—A systematic review and meta-analysis

RESEARCH ARTICLE Antenatal corticosteroids for neonates born before 25 Weeks—A systematic review and meta-analysis Mangesh Deshmukh1,2*, Sanjay Patole3,4 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 1 Department of Neonatal Pediatrics, St. John of God Hospital, Subiaco, Perth, Western Australia, 2 Department of Neonatal Pediatrics, Fiona Stanley Hospital, Perth, Western Australia, 3 Department of Neonatal Pediatrics, King Edward Memorial Hospital, Perth, Western Australia, 4 Centre for Neonatal Research and Education, University of Western Australia, Perth, Western Australia * Abstract Background OPEN ACCESS Citation: Deshmukh M, Patole S (2017) Antenatal corticosteroids for neonates born before 25 Weeks —A systematic review and meta-analysis. PLoS ONE 12(5): e0176090. https://doi.org/10.1371/ journal.pone.0176090 Efficacy of antenatal corticosteroids before 25 weeks of gestation is unclear. Objective To assess and compare neonatal outcomes following ANC exposure at 22, 23 and 24 weeks of gestation by conducting systematic review and meta- analysis. Editor: Olivier Baud, Hopital Robert Debre, FRANCE Received: December 16, 2016 Accepted: April 5, 2017 Published: May 9, 2017 Copyright: © 2017 Deshmukh, Patole. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: We have used mainly published data from the studies. We have also procured additional data from three authors which we have mentioned in the manuscript (page no- 9, line no-183- 184) in Results section. We have mentioned their email addresses which we have used to request the data in the covering letter as follows (1) Rintaro Mori: (2) Nadia Bajwa: (3) Ruth Guinsburg: We can confirm that future interested readers may contact these same authors in the same manner as us (email correspondence) to obtain the additional data used in our study. We can also confirm that Methods A systematic review of randomised controlled trials (RCT) and non-RCTs reporting on neonatal outcomes after exposure to ANC up to 246 weeks of gestation using the Cochrane systematic review methodology. Databases Pubmed, CINAHL, Embase, Cochrane Central library, and online abstracts of conference proceedings including the Pediatric Academic Society (PAS) were searched in Feb 2017. Primary outcome was in-hospital mortality defined as death before discharge during the first admission. Secondary outcomes included severe intraventricular hemorrhage (IVH> grade III and IV)/or periventricular leukomalacia (PVL), necrotising enterocolitis (NEC >stage II) and chronic lung disease (CLD). Meta-analysis was performed using a random-effects model. The level of evidence (LOE) was summarised using the GRADE guidelines. Main results There were no RCTs; 8 high quality non-RCTs were included in the review. Meta-analysis showed reduction in mortality [N = 10109; OR = 0.47(0.39–0.56), p<0.00001; LOE: Moderate] and severe IVH and PVL [N = 5084; OR = 0.71(0.61–0.82), p<0.00001; LOE: Low] after exposure to ANC in neonates born <25 weeks. There was no significant difference in CLD [N = 4649; OR = 1.19(0.85–1.65) p = 0.31; LOE: Low] and NEC [N = 5403; OR = 0.95 (0.76– 1.19) p = 0.65; LOE: Low]. Mortality was comparable in neonates born at 22, 23 or 24 weeks. PLOS ONE | https://doi.org/10.1371/journal.pone.0176090 May 9, 2017 1 / 15 Antenatal corticosteroids for neonates born before 25 weeks we didn’t have any special access privileges to obtain additional data from these authors. We identified email addresses of corresponding authors from their published manuscripts. Conclusion Moderate to low quality evidence indicates that exposure to ANC is associated with reduction in mortality and IVH/or PVL in neonates born before 25 weeks. Funding: The authors received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. Introduction Administering antenatal corticosteroids (ANC) for impending preterm delivery before 34 weeks’ of gestation is a standard practice. A systematic review of randomised controlled trials (RCT) indicates that exposure to ANC significantly reduces neonatal mortality and morbidity such as respiratory distress, cerebrovascular haemorrhage, and necrotising enterocolitis (NEC).[1] The guidelines of Obstetric and Gynaecological Colleges/Societies recommend ANC between 24–34 weeks of gestation. [2–5] The updated guidelines of the Royal College of Obstetricians and Gynaecologist (RCOG), the consensus statement from the American College of Obstetricians and Gynaecologist (ACOG), and the New Zealand-Australia guidelines suggest ANC should be considered from 23 weeks’ gestation after careful evaluation of the benefit and risks with parenteral consultation. [2, 4, 5] There is a broad consensus for not offering active management including ANC and neonatal resuscitation for delivery <23 weeks’.[6]A review of the international guidelines for management of extremely preterm births showed an agreement for offering ANC, neonatal resuscitation, and intensive care after 25 weeks’ gestation. [6] On the other hand the consensus statement from New South Wales, Australia suggests that it is acceptable not to initiate intensive care in neonates born at 22−256 weeks’ gestation if parents wish so after appropriate counselling. [7] It is important to note that the evidence supporting ANC at <26 weeks’ gestation is based mainly on laboratory studies and non-RCTs. The only RCT (n = 49) in this field is from the pre-surfactant era. [8] The RCOG and ACOG guidelines acknowledge this limitation. [2, 4] Given the lack of clarity on guidelines for ANC at extremely preterm gestations there is significant variation in clinical practice for managing such pregnancies. [9, 10] For example in the Express cohort study from Sweden, a high percentage of neonates (23 weeks: 85%, 24 and 25 weeks: > 95%) were exposed to ANC, whereas in the EPIPAGE-2 cohort study from France only 12.3% of neonates at 23 weeks, 56.7% at 24 weeks and 78.4% at 25 weeks gestation were given ANC. [11] A recent systematic review has addressed the issue of ANC for impending deliveries at 22 and 236 weeks’ gestation.[10] Meta-analysis of 4/17 included non-RCTs indicated that the adjusted odds of mortality to discharge (Primary outcome) were reduced by 52% in the ANC vs. control group. Severe morbidity was not significantly different between the two groups.[12] Overall, the data supporting ANC are scarce for neonates born at 22–26 weeks’ gestation. At 25 weeks of gestation most will offer ANC after parental counselling. However, controversy continues about ANC not only at 22 and 23 weeks, but also at 240−6 weeks of gestation. Comparing neonatal outcomes between 22, 23, and 24 weeks’ gestation following ANC exposure is im (...truncated)