Table 3. The quality of evidence assessment of association between maternal folic acid supplementation and asthma/wheeze in childhood by the GRADE approach.

Outcomes	Exposure timing	Relative effect (95% CI)	No. of participants (studies)	Quality of evidence (GRADE)
Asthma in childhood
	Pregnancy10,11,12	RR=1.04 (0.94-1.16)	7,925 (n=3)	⊕⊕⊖⊖Low 1
	Pre-pregnancy9,10	RR=0.98 (0.73-1.33)	2,056 (n=2)	⊕⊖⊖⊖Very Low 2
	Early pregnancy9,10,12	RR=0.98 (0.78-1.23)	4,696 (n=3)	⊕⊕⊖⊖Low 3
	Other period in pregnancy11,12	RR=1.03 (0.92-1.16)	6,426 (n=2)	⊕⊕⊖⊖Low 4
Wheeze in childhood
	Pregnancy11,12	RR=1.05 (0.95-1.15)	6,426 (n=2)	⊕⊕⊖⊖Low 5
	Early pregnancy8,12,13	RR=1.06 (1.02-1.09)	43,459 (n=3)	⊕⊕⊖⊖Low 6
	Other period in pregnancy8,11,12	RR=1.01 (0.98-1.03)	38,503 (n=3)	⊕⊕⊖⊖Low 7
Atopic Dermatitis	Early pregnancy12,13	RR=1.15 (0.91-1.45)	11,382 (n=2)	⊕⊖⊖⊖Very Low 8
Eczema	Other period in pregnancy11,12	RR=0.99 (0.89-1.10)	6,426 (n=2)	⊕⊕⊖⊖Low 9
Sensitization	Other period in pregnancy11,12	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.