Table 1 Description of the studies selected according to the inclusion and exclusion criteria and included in the systematic review
Authors | Study Design | Country | Sample Size | Study Participants | Aim of the Study | FA supplementation evaluation Y/N | Dietary folate intake Y/N | FA dosage (mg) | FA supplementation protocol | FA supplementation related to BMI | FA timing of supplementation | FA Recommendation | Folate Blood Level (if available) | Fortification Policy |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Cawley et al. [28] | Prospective Cohort Study | Ireland | n = 587 | Pregnant women in the 1rst trimester: - BMI < 18.5 kg/m2: 1.9% (n = 11) - 18.5 < BMI < 25 kg/m2: 50.7% (n = 296) - 25 < BMI < 30 kg/m2: n = 171 (29,3%) - BMI > 30 kg/m2: n = 106 (18,1%) | To analyse folic acid supplementation among women seeking antenatal care at a large maternity hospital in Ireland | Y | N | - 0,4 mg of FA; - 5 mg as high-dose | na | - 0.4 mg FA (n = 549) - 5 mg (2 of them with obesity) (n = 15) | -Preconceptionally; - > 12 weeks preconceptionally; - Post conception | - 12 weeks of 400 mg folic acid (FA) supplementation is needed to reach the target RCF level of 906 nmols[38]; - International guidelines suggest that women with obesity should take high-dose (5 mg) FA around the time of conception to lower their risk of neural tube defects (NTDs)[38] | na | Northern Ireland: Mandatory fortification of wheat flour [35].The NCFAFF recommends the mandatory fortification with FA of most white, brown and wholemeal breads on sale in Ireland [36] |
Linell et al. [29] | Prospective Cohort Study | Ireland | n = 328 | Pregnant women at ≤ 18 weeks’ gestation: - BMI < 18.5 kg/m2: 1,2% (n = 4) - 18.5 < BMI < 25 kg/m2: 41,2% (n = 135) - 25 < BMI < 30 kg/m2: 33,8% (n = 111) - BMI > 30 kg/m2: 23,8% (n = 78) | To assess the use of folic acid supplementation among pregnant women, based on their obesity status | Y | N | - 0,4 mg of FA; - 5 mg as high-dose | na | - 0.4 mg FA; n = 216 (65,9%) - 5 mg; n = 22 (6,7%) out of the 78 women with obesity | - 30.2% (n = 99) commenced FA < 12 weeks prior to conception; - 30.5% (n = 100) commenced FA > 12 weeks prior to conception; - 61% (n = 199) commenced FA when found out they were pregnant | -Women of childbearing age should take 400 μg of folic acid daily, alongside dietary sources, for at least 12 weeks before conception - Women with obesity are recommended a higher dose of 5 mg of folic acid to reduce the risk of neural tube defects (NTDs) - The 5 mg dosage of FA should be taken before conception and continued through the first trimester of pregnancy[39] | na | Northern Ireland: Mandatory fortification of wheat flour [35].The NCFAFF recommends the mandatory fortification with FA of most white, brown and wholemeal breads on sale in Ireland [36] |
Malvasi A. et al. [30] | Prospective, randomized, double- blind, placebo controlled clinical trial, pilot study | Italy, Greece, Russia | n = 48 | - Uniparous healthy pregnant women between 13 and 24th week of pregnancy - 25 < BMI < 30 kg/m2 | To assess biochemical parameters during the second trimester of pregnancy in women who received Inositol supplementation | N (preconception not mentioned) | N | - 0,4 mg of FA | Formulation of Supplement (MDFN)—Daily | - n = 24 (treated group): 0,4 mg - n = 24 (control group): NA | Between 13 and 24th week of pregnancy | na | na | No official food fortification policy [35] |
Mohd-Shukri N. et al. [31] | Prospective case–control study | UK | n = 241 | - BMI > 40 kg/m2: n = 148 - BMI < 25 kg/m2: n = 93 | To compare dietary habits and physical activity levels during pregnancy between women with very severe obesity and those of normal weight | Y | Y | - 0,4 mg of FA; - 5 mg as high-dose | na | BMI < 25 kg/m2: - 0.4 mg FA; n = 84 -5 mg of FA; n = 2 BMI > 40 kg/m2: - 0.4 mg FA; n = 129 (96%) -5 mg of FA; n = 5 (4%) | - Early pregnancy (16 weeks of gestation); - Late pregnancy (28 weeks of gestation) | na | Early pregnancy measurements (16 weeks), (mcg/mL)(SD) - Women with BMI > 40 kg/m2, (n = 25): 7.9 mcg/mL (4.2) - Women with BMI < 25 kg/m2, (n = 25): 15.0 mcg/mL (2.7) Late pregnancy (28 weeks), (mcg/mL)(SD) - Women with BMI > 40 kg/m2, (n = 25): 3.9 mcg/mL (2.8) - Women with BMI < 25 kg/m2, (n = 25): 10.6 mcg/mL (5.7) | Mandatory fortification of wheat flour [35] New legislation (effective November 2024) mandates FA fortification of non-wholemeal wheat flour by late 2026 [37] |
Redfern K. et al. [32] | Prospective observational study | UK | n = 66 | Pregnant women with obesity: a BMI ≥ 30 kg/m2 and < 40 kg/m2, at 12 and 14 weeks of gestation | To examine the intake of key micronutrients (iodine, vitamin D, folate) among pregnant women with obesity in the UK, considering relevant demographic characteristics | Y | Y | - 0,4 mg of FA; - 5 mg as high-dose | - Within pregnancy multivitamin; - FA | 5 mg of FA, n = 17 (26%) - n = 5 women supplement 5 mg of FA (2/5 with GDM) - n = 12 women supplement 5 mg + 0,4 mg (6/12 with GDM) 0.4 mg FA, n = 24 (36%) | 1st trimester | - Women should supplement with 400 μg of folic acid daily from pre-conception until 12 weeks of gestation [40]; - The RCOG, advises that women with obesity who are planning to become pregnant or are already pregnant should take a higher dose of 5 mg of folic acid daily until the end of the first trimester [40] | na | Mandatory fortification of wheat flour [35] New legislation (effective November 2024) mandates FA fortification of non-wholemeal wheat flour by late 2026 [37] |
Santamaria A. et al. [33] | Randomized Controlled Trial | Italy | n = 220 | - 25 < BMI < 30 kg/m2 | To assess whether myo-inositol supplementation can reduce the rate of gestational diabetes mellitus (GDM) in overweight women | N (preconception not mentioned) | N | 0,4 mg of FA | - Treated group received: 2 g myo-inositol + 0.2 mg of FA twice a day, - Placebo group received: 0.2 mg of FA twice a day | n = 220 supplemented with 0.2 mg of FA twice a day | 12th–13th week of gestation | na | na | No official food fortification policy [35] |
Vitale S. et al. [34] | Randomized and Open-Label, placebo Controlled clinical Trial | Italy | n = 223 | - 25 < BMI < 30 kg/m2 | To examine the effects of myo-inositol supplementation on GDM rates and body water distribution in women with overweight | N (preconception not mentioned) | N | 0,4 mg of FA | - Treated group received: 2 g myo-inositol + 0.2 mg of FA twice a day, - Placebo group received: 0.2 mg of FA twice a day | n = 223 supplemented with 0.2 mg of FA twice a day | 12th–13th week of gestation The treatment lasted until 3 weeks after delivery | na | na | No official food fortification policy [35] |
O'Malley E. et al. [27] | Prospective observational study | Ireland | n = 496 | - 18.5 < BMI < 25 kg/m2: n = 269 - BMI > 30 kg/m2: n = 97 | To investigate the association between maternal BMI in early pregnancy and serum and RBC folate and plasma vitamin B12 levels | Y | Y | - 0.4 mg of FA; - 5 mg as high-dose | na | Higher dose of FA (5 mg): - BMI > 30 kg/m2: 9.5% (n = 8); - 18.5 < BMI < 25 kg/m2: 7.1% (n = 19) 0.4 mg of FA: - BMI > 30 kg/m2: 90.4% (n = 76); | Women were asked about their FA supplementation - at enrollment ( first visit: 12,1 weeks) - pre-pregnancy (retrospectively) | The RCOG [39], RANZCOG[41] and Irish guideline[42] recommendations for obese women advise a dose of 5 mg daily | There was no statistical difference in the mean values of RBC folate between BMI categories: - BMI < 25.0 kg/m2: 139.8 nmol/L (SD 413.5) - BMI > 30 kg/m2: 1184.0 nmol/L (SD 476.7) (p = 0.18) | Northern Ireland: Mandatory fortification of wheat flour [35].The NCFAFF recommends the mandatory fortification with FA of most white, brown and wholemeal breads on sale in Ireland [36] |