Date Published: April 25, 2019
Publisher: Public Library of Science
Author(s): Shruti Murthy, Myron Anthony Godinho, Vasudeva Guddattu, Leslie Edward Simon Lewis, N. Sreekumaran Nair, Wisit Cheungpasitporn.
The incidence of neonatal sepsis in India is the highest in the world. Evidence regarding its risk factors can guide clinical practice and prevention strategies.
To review, assess and synthesize the available literature from India on the risk factors of sepsis among neonates.
A systematic review was conducted. We searched PubMed, CINAHL, Scopus, Web of Science, Popline, IndMed, Indian Science Abstracts and Google Scholar from inception up to March 23, 2018 to identify observational analytical studies reporting on risk factors of laboratory-confirmed neonatal sepsis in India. Two authors independently screened studies (title, abstract and full-text stages), extracted data, and assessed quality. A random-effects meta-analysis was performed as substantial heterogeneity was anticipated. Subgroup and sensitivity analyses were additionally performed. Effect size in our review included odds ratio and standardized mean difference.
Fifteen studies were included from 11,009 records, of which nine were prospective in design. Birthweight and gestational age at delivery were the most frequently reported factors. On meta-analyses, it was found that male sex (OR: 1.3, 95% CI: 1.02, 1.68), out born neonates (OR: 5.5, 95% CI: 2.39, 12.49), need for artificial ventilation (OR: 5.61; 95% CI: 8.21, 41.18), gestational age <37 weeks (OR: 2.05; 95% CI:1.40, 2.99) and premature rupture of membranes (OR:11.14, 95% CI: 5.54, 22.38) emerged as risk factors for neonatal sepsis. Included studies scored lowest on exposure assessment and confounding adjustment, which limited comparability. Inadequacy and variation in definitions and methodology affected the quality of included studies and increased heterogeneity. Male neonates, outborn admissions, need for artificial ventilation, gestational age <37 weeks and premature rupture of membranes are risk factors for sepsis among neonates in India. Robustly designed and reported research is urgently needed to confirm the role of other risk factors of neonatal sepsis in India.
Sepsis is the second major cause of mortality among neonates, killing more than one million neonates annually. Neonatal sepsis, pneumonia and meningitis together result in up to a quarter of all newborn deaths. Globally, of the three million annual neonatal sepsis cases (2202/ 1,00,000 live births), India has the highest incidence of clinical sepsis (17,000/ 1,00,000 live births). The case fatality rate of sepsis among neonates ranges between 25% to 65% in India.[4, 5] These rates are likely to be underestimated, and more accurate data is expected from the ‘Global Maternal and Neonatal Sepsis Initiative’.[6–8]
This review will be used to inform, a larger mixed-methods study addressing the burden of neonatal systemic infection in India. This systematic review and meta-analysis has been reported in accordance with the ‘Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) guidelines (see S1 PRISMA Checklist). A protocol was developed for our review (see S1 File) and registered on the ‘International prospective register of systematic reviews PROSPERO’ (ID: PROSPERO 2017 CRD42017053721), which can be accessed on their website (http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42017053721).
A total after 10,567 titles were screened, after excluding 442 duplicate records. Of these, 9085 titles were excluded and 1482 abstracts were screened. Of these, 340 full text records were screened and 15 full texts met the inclusion criteria in our review, after discussion and consensus. Reasons for exclusion of 325 full-text records were lack of a comparison group/ wrong study design (n = 148), population not neonates/ no subgroup analysis (n = 77), infection not sepsis (n = 52), no risk factors studied (n = 34) and unclear/ wrong diagnostic criteria (n = 14). The study selection process is illustrated in Fig 1.
In a “time-critical clinical course” like that of sepsis,1 knowledge of risk factors aids in early prediction, identification and timely empirical antibiotic therapy, which are key to reducing neonatal morbidity and mortality.[7, 15] Male gender, outborn admissions, need for artificial ventilation, gestational age <37 weeks and PROM were found to significantly increase the odds of neonatal sepsis in our meta-analysis. Due to limited number of studies, we were unable to find conclusive evidence for the timing of onset of the systemic infection, and for systemic infections other than sepsis in neonates (e.g. pneumonia, meningitis). Our meta-analysis found three neonatal (male gender, out born admissions, need for artificial ventilation) and two maternal (gestational age <37 weeks and PROM) factors to significantly increase the risk for sepsis among neonates. Evidence on other important risk factors of neonatal sepsis from India, including for community-acquired and neonatal systemic infections other than neonatal sepsis, is lacking. Robust research and improved reporting on risk factors is required from India, which has the highest global incidence of neonatal sepsis, for improved preventive efforts to reduce the burden of neonatal sepsis in India. Source: http://doi.org/10.1371/journal.pone.0215683