Table 1 Systematic reviews that evaluated the effect of FA on CLP formation in humans
From: Effect of folic acid on animal models, cell cultures, and human oral clefts: a literature review
Author, year of publication | Study population | Study conclusion | Authors’ judgment |
|---|---|---|---|
Johnson and Little, 2008 [6] | 8.303 cases 119.468 controls | There is no strong evidence of the association between oral clefts and FA intake alone. However, the use of multivitamins early in pregnancy can protect against the formation of oral clefts, specifically CLP. | Most of the investigations included were case–control studies and their quality was not formally assessed, probably affecting the results of the present systematic review. |
De-Regil et al. 2015 [1] | 2033 cases 5.359 controls | FA, alone or in combination with vitamins and minerals, prevents NTD; however, its effect on other birth defects is not as evident. | Inferior quality of studies conducted on CL and CP may have influenced the results. |
Blanco et al. 2017 [2] | 928 cases 2.390 controls | High level of HCY in the maternal plasma is a risk factor for non-syndromic orofacial clefts in children. | Blanco et al. performed additional analyzes to resolve heterogeneity and small size in study samples. Results of the meta-analysis help in explaining the complex etiology of orofacial clefts. |
Millacura et al. 2017 [3] | 61.355 cases 59.586.433 controls | Fortification with FA produces a beneficial effect on non-syndromic CLP. | This multi-ethnic meta-analysis provides robust evidence of the beneficial effect of FA on CLP. |
Jahanbin et al. 2018 [4] | 27.045 cases 1.150.186 controls | FA supplements during the early stages of pregnancy mitigate the risk of non-syndromic CLP and CP in children. | Results are statistically robust based on a large sample size and thus eliminated heterogeneity. |