Abstract
Purpose
Methods
Results
Conclusions
Figures and Tables
Fig. 2
The relationship between MTHFR C677T polymorphism and asthma risk. (A) CT vs CC; (B) TT vs CC. OR, odds ratio; CI, confidence intervals.
![aair-7-538-g002](/upload/SynapseData/ArticleImage/0166aair/aair-7-538-g002.jpg)
Fig. 3
The relationship between maternal folic acid supplementation during early pregnancy and risk of wheeze in childhood. *Four weeks before conception until 8 weeks after conception and/or during the first trimester of pregnancy. RR, risk ratio; CI, confidence intervals.
![aair-7-538-g003](/upload/SynapseData/ArticleImage/0166aair/aair-7-538-g003.jpg)
Table 1
Effects of folate status on the development of asthma, wheeze, or other allergic diseases
![aair-7-538-i001](/upload/SynapseData/ArticleImage/0166aair/aair-7-538-i001.jpg)
Outcome | Exposure timing types of folic acid | Timing of assessment | Folic acid use, RR (95% CI)* | Heterogeneity (I2, %) |
---|---|---|---|---|
Asthma | Any use101112 | At 6 yr10, 3-8 yr11, at 6-7 yr12 | 1.04 (0.94-1.16) | 0.0 |
Pre-pregnancy910 | At 3.5 yr and 5.5 yr9, at 6 yr10 | 0.98 (0.73-1.33) | 0.0 | |
Early pregnancy91012 | At 3.5 yr and 5.5 yr9, at 6 yr10, at 6-7 yr12 | 0.98 (0.78-1.23) | 0.0 | |
Other period in pregnancy1112 | 3-8 yr11, at 6-7 yr12 | 1.03 (0.92-1.16) | 0.0 | |
Wheeze | Any use1112 | 1-8 yr11, until 6-7 yr12 | 1.05 (0.95-1.15) | 0.0 |
Early pregnancy81213 | 6-18 mo8, until 6-7 yr12, up to 4 yr13 | 1.06 (1.02-1.09)† | 0.0 | |
Other period in pregnancy81112 | 6-18 mo8, 1-8 yr11, until 6-7 yr12 | 1.01 (0.98-1.03) | 0.0 | |
Atopic Dermatitis | Early pregnancy1213 | at 2 yr12, up to 4 yr13 | 1.15 (0.91-1.45) | 0.0 |
Eczema | Other period in pregnancy1112 | 1-8 yr11, until 6-7 yr12 | 0.99 (0.89-1.10) | 0.0 |
Sensitization | Other period in pregnancy1112 | At 8 yr11, at 2 yr12 | 0.88 (0.75-1.03) | 0.0 |
Table 2
The relationship between MTHFR C677T polymorphism and the risk of asthma or other allergic diseases
![aair-7-538-i002](/upload/SynapseData/ArticleImage/0166aair/aair-7-538-i002.jpg)
Outcome | Genotypes | OR (95% CI)* | Heterogeneity (I2, %) |
---|---|---|---|
Asthma | CT genotype1520 | 0.98 (0.82-1.17) | 0.0 |
TT genotype1520 | 1.41 (1.07-1.86)† | 21.5 | |
Atopy | CT genotype1527 | 1.05 (0.92-1.19) | 0.0 |
TT genotype1527 | 0.93 (0.76-1.14) | 0.0 | |
Sensitization | CT genotype1520 | 0.99 (0.89-1.10) | 0.0 |
TT genotype1520 | 1.03 (0.86-1.23) | 0.0 |
Table 3
The quality of evidence assessment of association between maternal folic acid supplementation and asthma/wheeze in childhood by the GRADE approach
![aair-7-538-i003](/upload/SynapseData/ArticleImage/0166aair/aair-7-538-i003.jpg)
Outcomes | Exposure timing | Relative effect (95% CI) | No. of participants (studies) | Quality of evidence (GRADE) |
---|---|---|---|---|
Asthma in childhood | ||||
Pregnancy101112 | RR=1.04 (0.94-1.16) | 7,925 (n=3) | ⊕⊕⊖⊖Low 1 | |
Pre-pregnancy910 | RR=0.98 (0.73-1.33) | 2,056 (n=2) | ⊕⊖⊖⊖Very Low 2 | |
Early pregnancy91012 | RR=0.98 (0.78-1.23) | 4,696 (n=3) | ⊕⊕⊖⊖Low 3 | |
Other period in pregnancy1112 | RR=1.03 (0.92-1.16) | 6,426 (n=2) | ⊕⊕⊖⊖Low 4 | |
Wheeze in childhood | ||||
Pregnancy1112 | RR=1.05 (0.95-1.15) | 6,426 (n=2) | ⊕⊕⊖⊖Low 5 | |
Early pregnancy81213 | RR=1.06 (1.02-1.09) | 43,459 (n=3) | ⊕⊕⊖⊖Low 6 | |
Other period in pregnancy81112 | RR=1.01 (0.98-1.03) | 38,503 (n=3) | ⊕⊕⊖⊖Low 7 | |
Atopic Dermatitis | Early pregnancy1213 | RR=1.15 (0.91-1.45) | 11,382 (n=2) | ⊕⊖⊖⊖Very Low 8 |
Eczema | Other period in pregnancy1112 | RR=0.99 (0.89-1.10) | 6,426 (n=2) | ⊕⊕⊖⊖Low 9 |
Sensitization | Other period in pregnancy1112 | RR=0.88 (0.75-1.03) | 6,426 (n=2) | ⊕⊕⊖⊖Low 10 |
1 No factors exist that can reduce or increase the quality of evidence.
2 (-1 imprecision) 95% CI overlaps no effect (CI includes RR of 1.0) and CI fails to exclude 0.75 and 1.25 though the sample size is very large.
3 No factors exist that can reduce or increase the quality of evidence.
4 No factors exist that can reduce or increase the quality of evidence.
5 No factors exist that can reduce or increase the quality of evidence.
6 No factors exist that can reduce or increase the quality of evidence.
7 No factors exist that can reduce or increase the quality of evidence.
8 (-1 imprecision) 95% CI overlaps no effect (CI includes RR of 1.0) and CI fails to exclude 1.25 though the sample size is very large.
9 No factors exist that can reduce or increase the quality of evidence.
10 No factors exist that can reduce or increase the quality of evidence.
RR, risk ratio; CI, confidence intervals.
Table 4
The quality of evidence assessment of association MTHFR C667T polymorphisms and asthma risk by the GRADE Approach
![aair-7-538-i004](/upload/SynapseData/ArticleImage/0166aair/aair-7-538-i004.jpg)
Outcomes | Comparisons | Relative effect (95% CI) | No. of participants (studies) | Quality of evidence (GRADE) |
---|---|---|---|---|
Asthma | CT vs CC1520 | OR=0.98 (0.82-1.17) | 7,991 (n=2) | ⊕⊕⊖⊖Low 1 |
TT vs CC1520 | OR=1.41 (1.07-1.86) | 7,991 (n=2) | ⊕⊕⊖⊖Low 2 | |
Atopy | CT vs CC1527 | OR=1.05 (0.92-1.19) | 6,571 (n=2) | ⊕⊕⊖⊖Low 3 |
TT vs CC1527 | OR=0.93 (0.76-1.14) | 6,571 (n=2) | ⊕⊕⊖⊖Low 4 | |
Sensitization | CT vs CC1520 | OR=0.99 (0.89-1.10) | 7,991 (n=2) | ⊕⊕⊖⊖Low 5 |
TT vs CC1520 | OR=1.03 (0.86-1.23) | 7,991 (n=2) | ⊕⊕⊖⊖Low 6 |