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closeAntenatal corticosteroids in low-resource settings
Posted by R.Mooij on 23 Mar 2018 at 20:07 GMT
We would like to congratulate the authors on the positive results of their bundle of interventions to improve neonatal outcome after preterm birth. However, the advice to implement this bundle in smaller (district) hospitals after the success of this study in larger hospitals has risks. The large study of Althabe et al. found opposite results of antenatal corticosteroid therapy (ACT) [1]. Massawe and colleagues suggest the negative effect can be explained by a difference in location of birth, but a secondary analysis of the data does not support this theory [2]. This is why the World Health Organization (WHO) advises against ACT in low-resource settings when certain conditions cannot be met [3]. Research in a district-size hospital in Tanzania by our group also found a negative effect of ACT. More importantly, we found that the WHO criteria could not be met and that the setting of the hospital is more similar to the setting of the study of Althabe et al than that of studies with a positive effect of ACT [4]. We would suggest implementation of ACT in smaller hospitals only in the context of scientific research.
Rob Mooij, Jeroen van Dillen, Jelle Stekelenburg
References
1. Althabe F, Belizan JM, McClure EM, Hemingway-Foday J, Berrueta M, Mazzoni A, et al. A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: the ACT cluster-randomised trial. Lancet. 2015;385(9968):629-39. Epub 2014/12/03. doi: 10.1016/s0140-6736(14)61651-2. PubMed PMID: 25458726.
2. Althabe F, Thorsten V, Klein K, McClure EM, Hibberd PL, Goldenberg RL, et al. The Antenatal Corticosteroids Trial (ACT)'s explanations for neonatal mortality - a secondary analysis. Reprod Health. 2016;13(1):62. Epub 2016/05/26. doi: 10.1186/s12978-016-0175-3. PubMed PMID: 27220987; PubMed Central PMCID: PMCPMC4878056.
3. Vogel JP, Oladapo OT, Manu A, Gulmezoglu AM, Bahl R. New WHO recommendations to improve the outcomes of preterm birth. The Lancet Global health. 2015. Epub 2015/08/28. doi: 10.1016/s2214-109x(15)00183-7. PubMed PMID: 26310802.
4. Mooij R, Lugumila J, Mwashambwa MY, Mwampagatwa IH, van Dillen J, Stekelenburg J. Characteristics and outcomes of patients with eclampsia and severe pre-eclampsia in a rural hospital in Western Tanzania: a retrospective medical record study. BMC Pregnancy Childbirth. 2015;15(1):213. Epub 2015/09/10. doi: 10.1186/s12884-015-0649-2. PubMed PMID: 26350344.
RE: Antenatal corticosteroids in low-resource settings
jperlman replied to R.Mooij on 30 Mar 2018 at 13:40 GMT
We appreciate the interest by R Mooij et al in our manuscript entitled “A care bundle including antenatal corticosteroids reduces preterm infant mortality in Tanzania a low resource country” [1]. The authors apparently missed the fundamental aspect of the paper. Specifically the study was focused on the use of a care bundle (maternal antibiotics, antennal corticosteroids (ACT), avoidance of moderate hypothermia and early neonatal antibiotics) rather than the singular use of ACS. The greatest impact on neonatal mortality was noted with a combination of ACT and antibiotics. Indeed ACT when used alone was associated with increased risk of mortality Table 6 in the manuscript (Odds Ratio 1.79 (95% Confidence Interval (0.95-3.39), (p=0.07) and similarly in Table 8[1]. Moreover there was a dose dependent reduction in neonatal mortality with ACS use, with the highest mortality with no ACS (18.9%), 1 to 2 doses (12.6%) and a full course (7.6%). (Table 5) [1]. Our findings regarding ACS administration only, are consistent with those of Althabe et al. [2]. Thus we consider the use of ACS alone to be an ineffective method of trying to reduce premature infant mortality. Importantly the primary pathways leading to premature infant mortality include respiratory distress/ insufficiency, infection and moderate hypothermia (temperature < 36OC) with secondary downstream end organ consequences. Notably Tanzania has limited capacity for applying continuous positive airway pressure (CPAP) or the ability to intubate and ventilate an infant. Thus our approach had to be very basic and utilize elements that are standard in a resource replete country. First we choose an estimated gestational age of 28 to 34 6/7 weeks where survival is considered feasible in Tanzania. Second we empowered the midwife to work under protocols to administer maternal antibiotics and ACS. Third upon delivery the midwives have been trained in the basic steps of HBB with an additional focus on avoiding moderate hypothermia. Finally we have placed an important focus on the early administration of neonatal antibiotics. And all this at a cost of $6 to $7 dollars. How Tanzania or other low resource countries rollout the care bundle beyond the referral hospitals will depend on a multitude of factors, and is beyond prescription. We will always advocate implementation be carried out in the context of scientific research.
Augustine Massawe, Hussein Kidanto, Jeffrey Perlman
1. 1. Massawe A, Kidanto HL, Moshiro R, Majaliwa E, Chacha F, Shayo A, Mdoe P, Ringia P, Azayo M, Msemo G Mduma E, Ersdal HE, Perlman Jm. (2018) A care bundle including antenatal corticosteroids reduces preterm infant mortality in Tanzania a low resource country. PLoS ONE 13(3): e0193146. https://doi. org/10.1371/journal.pone.0193146
2. Althabe F, Belizan JM, McClure EM, Hemingway-Foday J, Berrueta M, Mazzoni A, et al. A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: the ACT cluster-randomised trial. Lancet. 2015;385(9968):629-39. Epub 2014/12/03. doi: 10.1016/s0140-6736(14)61651-2. PubMed PMID: 25458726.
3. Vogel JP, Oladapo OT, Manu A, Gulmezoglu AM, Bahl R. New WHO recommendations to improve the outcomes of preterm birth. The Lancet Global health. 2015. Epub 2015/08/28. doi: 10.1016/s2214-109x(15)00183-7. PubMed PMID: 26310802.