Figure 2:

Results of the risk of bias and methodological quality indicators for all included studies. The items in the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) Risk of Bias assessment (Q1–Q10) were scored with “yes” indicating low risk of bias, “no” indicating high risk of bias, or “unclear” indicating that the item was not reported, resulting in an unknown risk of bias (Hooijmans et al. 2014). Q1–Q3 consider selection bias, Q4–Q5 consider performance bias, Q6–Q7 consider detection bias, Q8 considers attrition bias, Q9 considers reporting bias, and Q10 considers other biases. The overall study quality indicators (Q11–Q12) were scored with “yes” when reported or “no” when not reported. The methodological quality indicators focusing on potential intralitter correlation (Q13–Q14) were scored with “yes,” “no,” or “unclear.” Q, question. Q1: Was the allocation sequence adequately generated and applied?; Q2: Were the groups similar at baseline or were they adjusted for confounders in the analysis?; Q3: Was the allocation to the different groups adequately concealed?; Q4: Were the animals randomly housed during the experiment?; Q5: Were the caregivers and/or investigators blinded from knowledge which intervention each animal received during the experiment?; Q6: Were animals selected at random for outcome assessment?; Q7: Was the outcome assessor blinded?; Q8: Were incomplete outcome data adequately addressed?; Q9: Are reports of the study free of selective outcome reporting?; Q10: Was the study apparently free of other problems that could result in high risk of bias?; Q11: Was it stated that the experiment was randomized at any level?; Q12: Was it stated that the experiment was blinded at any level?; Q13: Was intralitter correlation controlled for by using the litter as statistical unit (instead of offspring)?; Q14: Was the study free of potential intralitter correlation caused by effects on litter size?