Table 4.
Summary of causal approaches which demonstrates multivariate regression was commonly applied whilst all other approaches were infrequently used.
| Study | Design | Sample Size Cases/Controls or Children (Cases) |
Multivariate Regression/GEE | Causal Diagram | Propensity Score | Sibling Study | Negative Control | Genetic Studies |
|---|---|---|---|---|---|---|---|---|
| Folic acid/multivitamins | ||||||||
| Desoto and Hitlan, 2012 (taking supplements) | Case-control | 256/752 | ▼ | |||||
| DeVilbiss et al., 2017 (taking supplements) | Cohort | 273,107 (1064) | ▲ | ▲ | Δ | |||
| Levine et al., 2018 (taking supplements) | Cohort | 45,300 (572) | ▲ | ▲ b | ||||
| Li et al., 2018 (taking supplements) | Case-control | 354/374 | ▲ | |||||
| Moser et al., 2019 (taking supplements) | Case-control | 2009/19,886 | Δ | |||||
| Nilsen et al., 2013 (taking supplements) | Cohort | 507,856 (2072) | ▲ | |||||
| Raghavan et al., 2017 a (taking supplements < twice/week or taking supplements > five times/week) | Cohort | 1257 (86) | ▼ | |||||
| Schmidt et al., 2019 (taking supplements) | Cohort | 241 (55) | ▲ | |||||
| Schmidt et al., 2012 (taking supplements) | Case-control | 429/278 | ▲ | ▲ c | ||||
| Suren et al., 2013 (taking supplements) | Cohort | 85,176 (114) | ▲ | ∇ d | ||||
| Strom et al., 2017 (taking supplements) | Cohort | 87,210 (1234) | ∇ | |||||
| Tan et al., 2020 (not taking supplements) | Case-control | 416/201 | ▲ |
Effect direction: ▲ indicates a positive health impact, ▼ indicates a negative health impact. Significance association indicated with a black arrow, no association is indicated with an unshaded arrow (Δ, ∇); The nutrient source is supplements/fortified food (reference group: no/low intake); a Raghavan et al. reference group is 3–5/week compared to low and high supplements intakes; b negative control was two years pre-pregnancy and had a stronger association with autism; c Beneficial effects of folic acid supplements were only detected if the child or mother had at least one T allele which reduces the efficiency of folate metabolism; d negative control was fish oils, which showed no association with autism.