studies showed similar association between neonatal sepsis and NDI, however, the magnitude of this effect was less (relative risk 1.43; 95% CI 1.22 to 1.67). The fact that the studies in our systematic review have differently adjusted for one or more of the potential confounding factors including gestational age, birth weight, sex, cesarean delivery, multiple birth, antenatal and postnatal steroid exposure, intrauterine growth restriction, bronchopulmonary dysplasia, necrotizing enterocolitis and chorioamnionitis required us to use the unadjusted ORs when pooling the data on neurodevelopmental outcomes, therefore, we could not assess the impact of these confounding factors. However, the available adjusted ORs from studies reporting them14,15,22,27 were consistent with our results. The presence of publication bias must not be forgotten as the small studies elucidate a higher risk for NDI. Neonatal meningitis is frequently accompanied with bacteremia. In all, 19.8 to 55% of affected neonates could have NDI.43–45 Included studies in our systematic review did not exclude babies with meningitis from the analysis. Thus, the impact of sepsis without meningitis on long-term outcome could not be assessed separately and represents a limitation to our meta-analysis. Recent biological studies suggest that sepsis-causing pathogens in neonates have the ability to stimulate microglia (brain’s resident immune cells) resulting in excitotoxicity and activation to free radical attack by reactive oxygen and nitrogen species, leading to the death of the vulnerable pre-myelinating oligodendrocytes.46–50 Table 1. Characteristics of the included studies Study Year Design Population Birth year Survivors total no. Follow up rate/ total no. Proven sepsis no. Comparison group no. Age at assessment, months Blinding of outcome assessors Cohort Schlapbach et al.14 2multicenter; NA, not available; NS, not specified; SC, single center; VLBW, very low birth weight. Neurodevelopmental outcomes of VLBW infants with neonatal sepsis B Alshaikh et al 560 Journal of Perinatology (2013), 558 – 564 & 2013 Nature America, Inc. Table 2. Methods of assessment and definitions of NDI and CP Study Scale Definitions Cohort Schlapbach et al.14 BSID II NDI: X1of the following: CP; MDIp 70; PDIp70; deafness or blindness. CP: a nonprogressive motor disorder characterized by abnormal tone in at least 1 extremity and abnormal control of movement and posture. Blindness: not defined but bilateral. Deafness: severe hearing loss requiring auditory amplification. Jang et al.15 BSID II Non-CP NDI: 46 month of motor or mental development including cognitive impairment, psychomotor impairment or neurosensory impairment. CP: a permanent, but not unchanging, disorder of movement or posture and of motor function, caused by a non-progressive interference, lesion or abnormality of the developing premature brain. Blindness and deafness: not assessed. Kono et al.16 KSPD test31 Cognitive delay: developmental quotient on KSPD scale o70 CP: non-progressive central nervous system disorder characterized by abnormal muscle tone in at least one extremity and abnormal control of movement and position. Blindness: unilateral or bilateral based on diagnosis of ophthalmologist. Deafness: severe impairment required hearing aids. Gocer et al.17 DDST32 NDI (severe): CP, mental retardation, blindness, deafness, hydrocephalus or convulsion,33 balance disorders, myopia, mild hearing loss, perception difficulties, behavioral problem. Blindeness and deafness: not defined. Addison et al.18 BSID II NDI: Either CP or a BSID MDI or PDIo70 CP: a non-progressive central nervous system disorder characterized by abnormal muscle tone in at least one extremity and abnormal control of movement and posture resulting in impaired motor function Chen et al.19 BSID II MDI or PDI o84 (mild and moderate: 70–83, severe: o70) CP, blindness and deafness: not assessed. Shah et al.20 BSID II MDI or PDI o70 (mean of 100 and s.d. of 15) CP: not defined Blindness and deafness: not assessed. Saw et al.21 Hearing only Deafness: absent of reliable hearing response to a sound pulse