Summary of findings 4.

Darbe or EPO (ESA) compared with sham injection for neuro protection ‐ long‐term outcomes
Patient or population: neonates born preterm with low birth weight Settings: NICU Intervention: Darbe or EPO (ESA) Comparison: sham injection
Outcomes	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No. of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Sham injection	ESA
BSID‐III composite cognitive scores at 18 to 22 months The Bayley‐III has 3 main sub tests: the Cognitive Scale, which includes items such as attention to familiar and unfamiliar objects, looking for a fallen object, and pretend play; the Language Scale, which taps understanding and expression of language, for example, recognising objects and people, following directions, and naming objects and pictures; and the Motor Scale, which assesses gross and fine motor skills such as grasping, sitting, stacking blocks, and climbing stairs.	Mean BSID‐III in the control group was 88.7 units (SD 13.5).	Mean BSID‐III in the intervention group was 7.80 units higher.	MD 7.80 (95% CI 1.65 to 13.95)	80 (1)	⊕⊕⊕⊝ moderate	Bias: Risk of bias was low, but the sample followed was small. We did not reduce the quality of evidence. Heterogeneity/Consistency: Only 1 study was included, so the test for heterogeneity was N/A. Directness of evidence: The study was conducted in the target population. Precision: Because of the small sample size (n = 80), the point estimate had a wide 95% CI. We downgraded the quality of evidence by 1 step. Presence of publication bias: N/A, as only 1 study was included.
WPPSI‐III FSIQ at 3.5 to 4 years of age Composite scores have a mean of 100 and a standard deviation of 15. Average is 90 to 109.	Mean WPPSI‐III FSIQ in the control group was 79.2 units (SD 18,5).	Mean WPPSI‐III FSIQ in the intervention group was 11.90 units higher.	MD 11.90 (95% CI 0.76 to 23.04)	53 (1)	⊕⊕⊝⊝ low	Bias: Risk of bias was low, but the sample followed was even smaller than at 18 to 22 months of age (n = 53). We did reduce the quality of evidence by 1 step. Heterogeneity/Consistency: Only 1 study was included, so the test for heterogeneity was N/A. Directness of evidence: The study was conducted in the target population. Precision: Because of the small sample size (n = 53), the point estimate had a large 95% CI. We downgraded the quality of evidence by 1 step. Presence of publication bias: N/A, as only 1 study was included,
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). BSID‐III: Bayley Scales of Infant Development ‐ Third Edition; CI: confidence interval; EPO: erythropoietin; ESA: erythropoiesis‐stimulating agent; MD: mean difference; N/A: not applicable; NICU: neonatal intensive care unit; RR: risk ratio; SD: standard deviation; WPPSI‐III FSIQ: Wechsler Preschool and Primary Scale of Intelligence ‐ Third Edition.
GRADE Working Group grades of evidence. High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.