Risk factors for neonatal mortality: an umbrella review of systematic reviews and meta-analyses
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Date
2025
Authors
Kefale, B.
Jancey, J.
Gebremedhin, A.T.
Belay, D.G.
Nyadanu, S.D.
Pereira, G.
Tessema, G.A.
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EClinicalMedicine, 2025; 88:103525-1-103525-14
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Bereket Kefale, Jonine Jancey, Amanuel T. Gebremedhin, Daniel Gashaneh Belay, Sylvester Dodzi Nyadanu, Gavin Pereira, Gizachew A. Tessema
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Background Neonatal mortality (NM) remains a persistent global public health challenge, necessitating a comprehensive understanding of its associated risk factors to guide effective interventions. Despite multiple systematic reviews and meta-analyses varying in quality, scope, and conclusions, an umbrella review synthesising this evidence was lacking. Methods We conducted an umbrella review using six major databases: Embase, Medline, Global Health, CINAHL, Web of Science, and Scopus, along with regional databases, systematic review repositories, and grey literature sources. Eligible studies were systematic reviews and meta-analyses published from 1990 to 22 July 2025 reporting associations between risk factors and all-cause NM based on at least two primary studies. The quality of the reviews was assessed using a measurement tool to assess systematic reviews (AMSTAR-2). Evidence on risk factors was summarised and graded. The review protocol was registered with PROSPERO (CRD42023455542). Findings Of 10,610 retrieved records, 64 systematic reviews and meta-analyses were included, five of which were systematic reviews without meta-analyses. We identified 54 unique risk factors across 73 outcome–exposure associations. Probable evidence indicated an increased risk of NM associated with maternal age ≥35 years, low occupational status, arsenic exposure, prenatal opioid exposure, maternal overweight and obesity, history of stillbirth, maternal death, severe maternal morbidity, hypertensive disorders of pregnancy, haemorrhagic disorders, anaemia in pregnancy, preterm birth, low birth weight and delayed initiation of breastfeeding (≥24 h). Probable evidence also supported the protective effects of antenatal care uptake and health facility delivery. Evidence for most other factors was graded as limited-suggestive or limited and non-conclusive. Interpretation This umbrella review identified probable evidence for several modifiable maternal and perinatal risk factors associated with NM, emphasising the critical need to improve access to high-quality antenatal, delivery and neonatal care, prevent preterm birth, promote timely initiation of breastfeeding, and address other identified risk factors. However, further high-quality research is required to strengthen the evidence base on these risk factors.
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© 2025 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).