TY - JOUR
T1 - Need for more evidence in the prevention and management of perinatal asphyxia and neonatal encephalopathy in low and middle-income countries
T2 - A call for action
AU - Newborn Brain Society Guidelines and Publications Committee
AU - Krishnan, Vaisakh
AU - Kumar, Vijay
AU - Variane, Gabriel Fernando Todeschi
AU - Carlo, Waldemar A.
AU - Bhutta, Zulfiqar A.
AU - Sizonenko, Stéphane
AU - Hansen, Anne
AU - Shankaran, Seetha
AU - Thayyil, Sudhin
N1 - Funding Information:
VKr and VKu are funded by an NIHR Research and Innovation for Global Health Transformation (RIGHT) program grant , and ST is supported by an NIHR advanced fellowship. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health, UK.
Funding Information:
Emotional support (e.g., reassurance and praise), comforting measures (e.g., touch, massage, warm baths/showers, promoting fluid intake), encouragement and provision of information (e.g., coping methods, update on progress of labor) provided by birth companions improves the labor experience and reduces birth asphyxia (low Apgar scores). The Cochrane meta-analysis of 26 studies, of which 13 were from HICs and 13 were from LMICs, showed labor support by birth companions reduces the need for a caesarean section (RR 0.75; 95 % CI, 0.64–0.88) or instrumental delivery (RR 0.90; 95 % CI, 0.85–0.96), and the chances of having a neonate with a low five‐minute Apgar score (RR 0.62; 95%CI, 0.46–0.85) [26]. In another systematic review, a continuous one-to-one support during labor reduced the number of neonates with low 5-min Apgar score (13 trials, n = 12,515, RR 0.69; 95 % CI, 0.50–0.95) [27]. Although these studies have been underpowered to examine a reduction in NE, the benefits on maternal outcomes are convincing. While the presence of birth companions, particularly male partners during delivery is the standard practice in HICs, this is not often the case in LMICs, particularly in Africa and South Asia where considerable cultural and logistic barriers still exist.Limited data are available on supportive care in NE in LMICs to make definitive recommendations. Almost all interventions used in neonatal units in LMICs are based on evidence from HICs which overlooks population differences, and at times these could have disastrous consequences. In high income country cooling trials, early hypocarbia was associated with adverse outcome at 18–22 months [OR 2.0; 95%CI, 1.1–3.4)][45,46]. Nadeem et al. reported moderate hypocarbia in 69 % of neonates with NE on ventilator support compared to the 31 % not on respiratory support [47]. Klinger et al. reported that severe hyperoxia (pO2 > 200 mm of Hg) during the first 2 h after birth was independently associated with adverse outcome. Neonates with a combination of hyperoxia and hypocapnia (<20 mmHg) were more likely to be have a poor outcome at 18–20 months of age (OR 3.07; 95%CI, 1.31–7.18; p = 0.001) [48].Given the sub-acute nature of brain injury in LMICs [5], it is likely that drugs with neuroregenerative properties are more effective than acute neuroprotective therapies, until the underlying mechanisms are known. A recent systematic review of five small studies of erythropoietin monotherapy in LMICs, involving 348 neonates from tertiary neonatal intensive care units, showed a significant reduction in death or disability (RR 0.56; 95 % CI, 0.42–0.75), when administered within 24 h after birth [72]. Erythropoietin monotherapy needs to be evaluated in well designed and adequately powered randomized control trials in LMICs before clinical use, irrespective of the results of high-income country erythropoietin trials where erythropoietin is evaluated as an adjunct to cooling therapy, particularly as cerebral iron depletion may negate the effects of erythropoietin neuroprotection. The EMBRACE (Erythropoietin Monotherapy for Brain Regeneration in NE) funded by Thrasher foundation recruiting over 800 neonates from South Asian neonatal intensive care units is expected to start recruitment soon.VKr and VKu are funded by an NIHR Research and Innovation for Global Health Transformation (RIGHT) program grant, and ST is supported by an NIHR advanced fellowship. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health, UK.
Publisher Copyright:
© 2021
PY - 2021/10
Y1 - 2021/10
N2 - Although low- and middle-income countries (LMICs) shoulder 90 % of the neonatal encephalopathy (NE) burden, there is very little evidence base for prevention or management of this condition in these settings. A variety of antenatal factors including socio-economic deprivation, undernutrition and sub optimal antenatal and intrapartum care increase the risk of NE, although little is known about the underlying mechanisms. Implementing interventions based on the evidence from high-income countries to LMICs, may cause more harm than benefit as shown by the increased mortality and lack of neuroprotection with cooling therapy in the hypothermia for moderate or severe NE in low and middle-income countries (HELIX) trial. Pooled data from pilot trials suggest that erythropoietin monotherapy reduces death and disability in LMICs, but this needs further evaluation in clinical trials. Careful attention to supportive care, including avoiding hyperoxia, hypocarbia, hypoglycemia, and hyperthermia, are likely to improve outcomes until specific neuroprotective or neurorestorative therapies available.
AB - Although low- and middle-income countries (LMICs) shoulder 90 % of the neonatal encephalopathy (NE) burden, there is very little evidence base for prevention or management of this condition in these settings. A variety of antenatal factors including socio-economic deprivation, undernutrition and sub optimal antenatal and intrapartum care increase the risk of NE, although little is known about the underlying mechanisms. Implementing interventions based on the evidence from high-income countries to LMICs, may cause more harm than benefit as shown by the increased mortality and lack of neuroprotection with cooling therapy in the hypothermia for moderate or severe NE in low and middle-income countries (HELIX) trial. Pooled data from pilot trials suggest that erythropoietin monotherapy reduces death and disability in LMICs, but this needs further evaluation in clinical trials. Careful attention to supportive care, including avoiding hyperoxia, hypocarbia, hypoglycemia, and hyperthermia, are likely to improve outcomes until specific neuroprotective or neurorestorative therapies available.
KW - Hypothermia
KW - Low- and middle-income countries
KW - Neonatal encephalopathy
KW - Neonate
KW - Newborn infant
UR - http://www.scopus.com/inward/record.url?scp=85111152879&partnerID=8YFLogxK
U2 - 10.1016/j.siny.2021.101271
DO - 10.1016/j.siny.2021.101271
M3 - Review article
C2 - 34330679
AN - SCOPUS:85111152879
SN - 1744-165X
VL - 26
JO - Seminars in Fetal and Neonatal Medicine
JF - Seminars in Fetal and Neonatal Medicine
IS - 5
M1 - 101271
ER -