TABLE 2.
Summary of studies of folate exposure and asthma or wheezing by pregnancy stage, outcome, and exposure1
| Exposure | Periconceptional or first trimester
|
Second and third trimesters
|
Any/throughout pregnancy
|
||||||
|---|---|---|---|---|---|---|---|---|---|
| Outcome (timing) | Change in risk | Ref | Outcome (timing) | Change in risk | Ref | Outcome (timing) | Change in risk | Ref | |
| Folic acid–containing supplement use (yes or no) | |||||||||
| W (6–18 mo) | ▲ | 24 | W (6–18 mo) | ▬ | 24 | W (6–18 mo) | ▲ | 24 | |
| PC: A (3.5 y, 5.5 y) | ▬ ▬ | 25 | A (3, 4, 5, 6, 7, 8 y) | ▬ ▬ ▬ ▬ ▬ ▬ | 22 | A, W (6–7 y) | ▬ ▬ | 232 | |
| A, W (6–7 y) | ▬ ▬ | 232 | W (1, 2, 3, 4, 5, 6, 7, 8 y) | ▲ ▬ ▬ ▬ ▬ ▬ ▬ ▬ | 22 | ||||
| Peri, 10 wk: W (to 4 y) (to 4 y) | ▬ ▬ | 26 | |||||||
| PC, 1, 2, 3 mo: A (6 y) | ▬ ▬ ▬ ▬ | 272 | |||||||
| Folic acid intake (other than supplement (yes or no) | |||||||||
| W (2 y) | ▬ | 28 | A (3.5 y, 5.5 y) | ▲ ▬ | 25 | ||||
| A (3.5 y, 5.5 y) | ▬ ▬ | 25 | W (1 y) | ▬ | 31 | ||||
| A (6 y), W (1 y) | ▼▼ | 29 | |||||||
| PC, 1, 2, 3 mo: A (6 y) | ▬ ▬ ▬ ▬ | 272 | |||||||
| Dietary folate intake | |||||||||
| A (3.5 y, 5.5 y) | ▬ ▬ | 25 | A (3.5 y, 5.5 y) | ▬ ▬ | 25 | W (16–24 mo) | ▬ | 35 | |
| A, W (5 y) | ▬ ▬ | 32 | |||||||
| Blood folate concentration | |||||||||
| PF Qr4:Qr1: W (to 4 y) | ▬ | 26 | PF Qn5:Qn1: A (3 y) | ▲ | 332 | ||||
| CBF T3:T2, T1:T2: W (1 y) | ▬ ▬ | 31 | |||||||
| RBC Qn5:Qn1: A, W (6–7 y) | ▬ ▬ | 232 | |||||||
Studies that reported multiple associations within a time period for different subsets of the time period (eg, periconceptional and at 10 wk of gestation) or variations of the same outcomes (eg, asthma and wheeze at 1 y or asthma and wheeze at 5 y) have multiple findings denoted to avoid bias of only reporting positive findings. However, if there are findings that group individual outcomes (eg, asthma at 3.5, 5.5, and both 3.5 and 5.5 y), only individual findings are shown. We included only findings that fell within the denoted exposure time frames. See Supplemental Table 1 under “Supplemental data” in the online issue for all reported findings. Symbols are defined as follows: ▲, significant increased risk; ▬, no association; ▼, significant decreased risk. A, asthma; CBF, cord blood folate; PC, preconception; Peri, periconceptional; PF, plasma folate; Qn, quintile; Qr, quartile; RBC, red blood cell folate; Ref, reference; T, tertile; W, wheeze.
Nested case-control studies.