"Association of Breast-feeding and AsthmaWord Count- 1520 words1. Authors have followed the PRISMA method for their systematic review which shows that theprotocol is registered. They gave the flowchart, introduction as per the PRISMA guidelines.2. Authors had clearly describedthe effect of breastfeeding on the occurrence of asthma in theintroduction. There were certain studies which show that the breastfeeding will reduce thechances of asthma. At the same time author also mentioned about certain studies which showsthat either there is no impact or increase the chances of asthma in children (5-18 years). Theyalso evaluated that the difference in the method was the reason of getting different results.3. Authors tried to give the explanation related to the previous studies conducted between theassociation of breastfeeding and asthma. They tried to cover interventions, participants,comparisons, outcomes and study design. It was clearly captured in the introduction that moststudies have shown to be a protective way of breastfeeding against the asthma, while some haveno association or have increased chances of asthma in children. Differences in the results couldbe due to the different methods followed by them. Combination of factors could be the reason onwhich the results can be directly impacted. This was not covered in the earlier studies.Breastfeeding duration, cultural practices are some of the factors which were not captured.Breastfeeding guidelines, study designs, cultural beliefs, financial status of the family are otherfactors which can impact on the results. 4. Yes, anyone can repeat the method followed by the authors. They used Pubmed, CINAHL andEMBASE electronic databases. A standard form for the data collection was used to collect all therelevant information from all the selected articles. Newcastle-Ottawa scale and GRADEguidelines were used for quality assessment in the studies. Funnel plots and Egger’s test wereused to perform the analysis. Studies of different types were pooled together to get theheterogenous data. This was done to combine the factors which can be the reason of asthmaattack. They tried to reduce the chances of selection bias by pooling the different studies. Forestplots were used to evaluate the pooled studies.5. Total studies included in case of Asthma were 42 whereas studies included in the meta-analysiswere 29 for Asthma. This was done to exclude the multiple similar records. Finally, 17 recordsof cohort study and 12 cross sectional study were taken for meta-analysis. An adjusted measurewith 95% confidence intervals was also measured for the effect of breastfeeding on allergicoutcomes like asthma. It was also considered while selecting the studies for meta-analysis. I2statistic was used to assess the heterogeneity of the estimated pool.6. Biasness which is introduced by selecting the individuals or groups in a manner whererandomization cannot be achieved in a proper way is known as Selection bias. In this way, wecannot ensure that the sample data obtained is of good quality for the purpose of the study.Type of study Items that should be included Was the item included? (Yes/No/Partially)Cohort Risk factor YesCause of disease NoHealth outcome Yes Cross-sectional Data analysis of results obtained from Nodifferent groupsCase-control Individuals-with or without disease Yes7. Biasness which has raised as a result of error in measurement is known as Information bias. It isalso known as misclassification and observational bias.Measurement of: Items that should be Was the item included?included (Yes/No/Partially)OutcomeCohort studies Results No Cross-sectional studies Data for analysis Yes Case-control studies Results NoAge YesExposure Cohort studies Cause of disease NoRisk factor YesCross-sectional studies Different groups NoCase-control studies Retrospective data,No Individuals with and Yeswithout the disorder 8. To prevent the risk of confounding, reader must know the other factors which can also be thecause for the disease. Supplementary Table 2 has clearly indicated the other factors which canact as a confounder. For e.g. In the study conducted by Brew et al, Birth weight, the gender ofthe child and the maternal age were the confounders at age 5, while the education and asthmahistory of patients, smoking at the early age or during pregnancy were also reported as theconfounders.9. Newcastle-Ottawa scale was used for the quality assessment of the risk of bias in case ofindividual studies.10. A design-specific-scale-cross sectional vs. case–control vs. cohort study) and theGRADE guidelines were used to evaluate the overall quality of the studies11. As per the studies, protective effect seemed to decrease with the age. The weaker methodologyshown to have a more protective effect during the meta-regression studies which suggests thatone should be remain cautious while considering these results as the qualitative evidence.According to the study of Dogaru et al., recent studies have shown to have more protectiveeffects which can be due to the better methodology followed recently or it can be due to theincreased publication bias. Brew et al. restricted the outcome for atleast 3 months breastfeedingwhich can be the reason of their different conclusion from others. As per the systematic review,classification of breastfeeding appeared to have less influence on the pooled risk during subgroup analysis. All the above statements are sufficient to say that the quality evidence are of low grade whichstates that longer breastfeeding can help to reduce the asthma risk in children having age groupbetween 5-18 years.12. The authors reached this conclusion due to the pipeline publication bias and multiple publicationbiases. These are the primary evidences of publication biasedness. 13. A) No, it does not make me feel less comfortable about including cross-sectional studies in theoverall meta-analysis. This is because it provides new dimensions and perceptions to the study. Italso provides an opportunity to look beyond the direct things. Hence, it offers directions for newresearch work and processes by which the studies can be further explored. B) In the case of lesser methodological quality, small biasedness may lead to major variations inthe results and also the chances of biasedness become high. Therefore, the author is pointingtowards the biasedness which may have followed in studies of lesser methodological quality andthis would have resulted into the different odds ratios for cohort and cross-sectional studies.14. The evidence is not completely consistent as there is protective effect in the case of everbreastfeeding and more breastfeeding. At the same time, there is no significant effect in the caseof exclusive breastfeeding for more than 3-4 months and in a case of family history of asthma.During the conclusion, authors stated that the classification of breastfeeding has little impact onthe pooled analysis of asthma risk. They concluded that there was more protective effect in the "