9. Results by individual review: nutritional interventions.
| Folic acid supplementation (De‐Regil 2015) | |||
| Comparison | Outcome | No. of studies, no. of women | Results |
| Supplementation with any folate vs no intervention, placebo or other micronutrients without folate | Stillbirth | 4 studies, 6597 women | RR 1.05, 95% CI 0.54 to 2.05, no evidence of a difference GRADEa: very low |
| Supplementation with any folate vs no intervention, placebo or other micronutrients without folate | LBW | 2 studies, 5048 women | RR 1.13, 95% CI 0.84 to 1.52, no evidence of a difference |
| Supplementation with any folate vs no intervention, placebo or other micronutrients without folate | SGA | Outcome not reported | |
| Supplementation with any folic acid vs no intervention, placebo or other micronutrients without folate | NICU admission | Outcome not reported | |
| Vitamin A supplementation (McCauley 2015) | |||
| Comparison | Outcome | No. of studies, no. women | Results |
| Vitamin A alone vs placebo or no treatment | Stillbirth | 2 studies, 122,850 women | RR 1.04, 95% CI 0.98 to 1.10, evidence of no difference GRADEa: moderate |
| Vitamin A alone vs placebo or no treatment | Perinatal death | 1 study, 76,176 women | RR 1.01, 95% CI 0.95 to 1.07, evidence of no difference GRADEb: high |
| Vitamin A alone vs placebo or no treatment | LBW | 4 studies, 14,599 women | RR 1.02, 95% CI 0.89 to 1.16, no evidence of a difference |
| Vitamin A alone vs placebo or no treatment | SGA | Outcome not reported | |
| Vitamin A alone vs placebo or no treatment | NICU admission | Outcome not reported | |
| Vitamin A with other micronutrients vs micronutrient supplements without vitamin A | Stillbirth | 2 studies, 866 women | RR 1.41, 95% CI 0.57 to 3.47, no evidence of a difference GRADEa: very low |
| Vitamin A with other micronutrients vs micronutrient supplements without vitamin A | Perinatal death | 1 study, 179 women | RR 0.51, 95% CI 0.10 to 2.69, no evidence of a difference GRADEa: moderate |
| Vitamin A with other micronutrients vs micronutrient supplements without vitamin A | LBW | 1 study, 594 women | RR 0.67, 95% CI 0.47 to 0.96 (P = 0.03), reduction in LBW for women receiving vitamin A with other micronutrients |
| Vitamin A with other micronutrients vs micronutrient supplements without vitamin A | SGA | Outcome not reported | |
| Vitamin A with other micronutrients vs micronutrient supplements without vitamin A | NICU admission | Outcome not reported | |
| Vitamin C supplementation (Rumbold 2015a) | |||
| Comparison | Outcome | No. of studies, no. women | Results |
| Vitamin C supplementation alone or in combination with other supplements (all trials) | Stillbirth | 11 studies, 20,038 women | RR 1.15, 95% CI 0.89 to 1.49, no evidence of a difference GRADEb: moderate |
| Vitamin C supplementation alone or in combination with other supplements (all trials) | Perinatal death | 7 studies, 17,271 women | RR 1.07, 95% CI 0.77 to 1.49, no evidence of a difference GRADEa: very low |
| Vitamin C supplementation alone or in combination with other supplements (all trials) | IUGR | 12 studies, 20,361 women | RR 0.98, 95% CI 0.91 to 1.06, evidence of no difference |
| Vitamin C supplementation alone or in combination with other supplements (all trials) | NICU admission | 9 studies, 18,371 women | RR 1.02, 95% CI 0.96 to 1.09, evidence of no difference |
| Vitamin C supplementation alone or in combination with other supplements (all trials) | LBW | Outcome not reported | |
| Vitamin C supplementation alone or in combination with other supplements (all trials) | SGA | Outcome not reported | |
| Vitamin D supplementation (Palacios 2019) | |||
| Comparison | Outcome | No. of studies, no. women | Results |
| Vitamin D alone vs no treatment/placebo (no vitamins or minerals) | Stillbirth | 3 studies, 584 women | RR 0.35, 95% CI 0.06 to 1.98, no evidence of a difference GRADEa: very low |
| Vitamin D alone vs no treatment/placebo (no vitamins or minerals) | LBW | 5 studies, 697 women | RR 0.55, 95% CI 0.35 to 0.87 (P = 0.01), reduction in LBW for women receiving vitamin D alone |
| Vitamin D alone vs no treatment/placebo (no vitamins or minerals) | SGA | Outcome not reported | |
| Vitamin D alone vs no treatment/placebo (no vitamins or minerals) | NICU admission | Outcome not reported | |
| Vitamin E supplementation (Rumbold 2015b) | |||
| Comparison | Outcome | No. of studies, no. women | Results |
| Any vitamin E supplementation | Stillbirth | 9 studies, 19,023 women | RR 1.17, 95% CI 0.88 to 1.56, no evidence of a difference GRADEb: moderate |
| Any vitamin E supplementation | Perinatal death | 6 studies, 16,923 women | RR 1.09, 95% CI 0.77 to 1.54, no evidence of a difference GRADEa: very low |
| Any vitamin E supplementation | IUGR | 11 studies, 20,202 women | RR 0.98, 95% CI 0.91 to 1.06, evidence of no difference |
| Any vitamin E supplementation | NICU admission | 8 studies, 17,594 women | RR 1.01, 95% CI 0.95 to 1.08, evidence of no difference |
| Any vitamin E supplementation | LBW | Outcome not reported | |
| Any vitamin E supplementation | SGA | Outcome not reported | |
| Vitamin supplementation for preventing miscarriage (Balogun 2016) | |||
| Comparison | Outcome | No. of studies, no. women | Results |
| Multivitamin vs control | Stillbirth | 1 study, 5021 women | RR 0.83, 95% CI 0.58 to 1.17, no evidence of a difference GRADEa: low |
| Multivitamin vs control | Total fetal loss | 1 study, 5021 women | RR 0.83, 95% CI 0.58 to 1.17, no evidence of a difference GRADEa: low |
| Multivitamin plus vitamin E vs multivitamin without vitamin E or control | Stillbirth | 1 study, 823 women | RR 0.88, 95% CI 0.39 to 1.98, no evidence of a difference GRADEa: low |
| Multivitamin plus vitamin E vs multivitamin without vitamin E or control | Total fetal loss | 1 study, 823 women | RR 0.92, 95% CI 0.46 to 1.83, no evidence of a difference GRADEa: low |
| Folic acid plus iron vs iron | Stillbirth | 1 study, 75 women | RR 0.38, 95% CI 0.02 to 9.03, no evidence of a difference GRADEa: low |
| Folic acid plus iron vs iron | Total fetal loss | 1 study, 75 women | RR 0.23, 95% CI 0.01 to 4.59, no evidence of a difference GRADEa: low |
| Folic acid plus iron and antimalarials vs iron and antimalarials | Total fetal loss | 1 study, 160 women | RR 13.0, 95% CI 0.74 to 226.98, no evidence of a difference GRADEa: low |
| Any comparison | LBW | Outcome not reported | |
| Any comparison | SGA | Outcome not reported | |
| Any comparison | NICU admission | Outcome not reported | |
| Calcium supplementation commencing before or early in pregnancy, for preventing hypertensive disorders of pregnancy (Hofmeyr 2019) | |||
| Comparison | Outcome | No. of studies, no. women | Results |
| Calcium supplementation vs placebo (before and/or early pregnancy only) | Stillbirth | 1 study, 579 women | RR 0.78, 95% CI 0.48 to 1.27, no evidence of a difference GRADEa: low |
| Calcium supplementation vs placebo (before and/or early pregnancy only) | Pregnancy loss, stillbirth or neonatal death before discharge | 1 study, 632 women | RR 0.82, 95% CI 0.61 to 1.10, no evidence of a difference GRADEb: low |
| Calcium supplementation vs placebo (before and/or early pregnancy only) | Perinatal death and/or NICU admission for > 24 h | 1 study, 508 women | RR 1.11, 95% CI 0.77 to 1.60, no evidence of a difference GRADEb: low |
| Calcium supplementation vs placebo (before and/or early pregnancy only) | LBW | Outcome not reported | |
| Calcium supplementation vs placebo (before and/or early pregnancy only) | SGA | Outcome not reported | |
| Calcium supplementation (preventing hypertensive disorders) (Hofmeyr 2018) | |||
| Comparison | Outcome | No. of studies, no. women | Results |
| Routine high‐dose calcium supplementation in pregnancy by baseline dietary calcium | Stillbirth or death before discharge from hospital | 11 studies, 15,665 women | RR 0.90, 95% CI 0.74 to 1.09, no evidence of a difference GRADEa: very low |
| Routine high‐dose calcium supplementation in pregnancy by baseline dietary calcium | LBW | 9 studies, 14,883 women | RR 0.85, 95% CI 0.72 to 1.01 (P = 0.06), evidence of no difference |
| Routine high‐dose calcium supplementation in pregnancy by baseline dietary calcium | SGA | 4 studies, 13,615 women | RR 1.05, 95% CI 0.86 to 1.29, no evidence of a difference |
| Routine high‐dose calcium supplementation in pregnancy by baseline dietary calcium | NICU admission | 4 studies, 13,406 women | RR 1.05, 95% CI 0.94 to 1.18, no evidence of a difference |
| Low‐dose calcium supplementation (< 1 g/d) with or without co‐supplements vs placebo or no treatment | Stillbirth or death before discharge from hospital | 5 studies, 1025 women | RR 0.48, 95% CI 0.14 to 1.67, no evidence of a difference GRADEa: very low |
| Low‐dose calcium supplementation (< 1 g/d) with or without co‐supplements vs placebo or no treatment | LBW | 2 studies, 134 women | RR 0.20, 95% CI 0.05 to 0.88 (P = 0.033), reduction in LBW for women receiving low‐dose calcium supplementation during pregnancy |
| Low‐dose calcium supplementation (< 1 g/d) with or without co‐supplements vs placebo or no treatment | SGA | 4 studies, 854 women | RR 0.81, 95% CI 0.54 to 1.21, no evidence of a difference |
| Low‐dose calcium supplementation (< 1 g/d) with or without co‐supplements vs placebo or no treatment | NICU admission | 1 study, 422 women | RR 0.44, 95% CI 0.20 to 0.99 (P = 0.047), reduction in NICU admission for women receiving low‐dose calcium supplementation during pregnancy |
| Calcium supplementation (other than for preventing or treating hypertension) (Buppasiri 2015) | |||
| Comparison | Outcome | No. of studies, no. women | Results |
| Calcium supplementation vs placebo or no treatment | Stillbirth or fetal death | 6 studies, 15,269 women | RR 0.91, 95% CI 0.72 to 1.14, no evidence of a difference GRADEa: low |
| Calcium supplementation vs placebo or no treatment | LBW | 6 studies, 14,162 women | RR 0.93, 95% CI 0.81 to 1.07, evidence of no difference |
| Calcium supplementation vs placebo or no treatment | IUGR | 6 studies, 1701 women | RR 0.83, 95% CI 0.61 to 1.13, no evidence of a difference |
| Calcium supplementation vs placebo or no treatment | NICU admission | 4 studies, 14,062 women | RR 1.05, 95% CI 0.94 to 1.18, evidence of no difference |
| Iodine supplementation (Harding 2017) | |||
| Comparison | Outcome | No. of studies, no. women | Results |
| Any supplement containing iodine vs same supplement without iodine or no intervention/placebo | Perinatal death | 2 studies, 457 women | RR 0.66, 95% CI 0.42 to 1.03, no evidence of a difference GRADEb: low |
| Any supplement containing iodine vs same supplement without iodine or no intervention/placebo | LBW | 2 studies, 377 women | RR 0.56, 95% CI 0.26 to 1.23, no evidence of a difference |
| Any supplement containing iodine vs same supplement without iodine or no intervention/placebo | SGA | 2 studies, 377 women | RR 1.26, 95% CI 0.77 to 2.05, no evidence of a difference |
| Any supplement containing iodine vs same supplement without iodine or no intervention/placebo | Stillbirth | Outcome not reported | |
| Any supplement containing iodine vs same supplement without iodine or no intervention/placebo | NICU admission | Outcome not reported | |
| Magnesium supplementation (Makrides 2014) | |||
| Comparison | Outcome | No. of studies, no. women | Results |
| Magnesium supplementation vs no magnesium | Stillbirth | 4 studies, 5526 women | RR 0.73, 95% CI 0.43 to 1.25, no evidence of a difference GRADEa: low |
| Magnesium supplementation vs no magnesium | LBW | 5 studies, 5577 women | RR 0.95, 95% CI 0.83 to 1.09, evidence of no difference |
| Magnesium supplementation vs no magnesium | SGA | 3 studies, 1291 women | RR 0.76, 95% CI 0.54 to 1.07, no evidence of a difference |
| Magnesium supplementation vs no magnesium | NICU admission | 3 studies, 1435 women | RR 0.74, 95% CI 0.50 to 1.11, no evidence of a difference |
| Zinc supplementation (Ota 2015b) | |||
| Comparison | Outcome | No. of studies, no. women | Results |
| Zinc supplementation vs no zinc (with or without placebo) | Stillbirth or neonatal death | 8 studies, 5100 women | RR 1.12, 95% CI 0.86 to 1.46, no evidence of a difference GRADEb: low |
| Zinc supplementation vs no zinc (with or without placebo) | LBW | 14 studies, 5643 women | RR 0.93, 95% CI 0.78 to 1.12, evidence of no difference |
| Zinc supplementation vs no zinc (with or without placebo) | SGA | 8 studies, 4252 women | RR 1.02, 95% CI 0.94 to 1.11, evidence of no difference |
| Zinc supplementation vs no zinc (with or without placebo) | NICU admission | Outcome not reported | |
| Multiple micronutrient supplementation (Keats 2019) | |||
| Comparison | Outcome | No. of studies, no. women | Results |
| Multiple micronutrients with iron and folic acid vs iron with or without folic acid | Stillbirth | 17 studies, 97,927 women | RR 0.95, 95% CI 0.86 to 1.04, evidence of no difference GRADEb: high |
| Multiple micronutrients with iron and folic acid vs iron with or without folic acid | Perinatal mortality | 15 studies, 63,922 women | RR 1.00, 95% CI 0.90 to 1.11, evidence of no difference GRADEb: high |
| Multiple micronutrients with iron and folic acid vs iron with or without folic acid | LBW | 18 studies, 68,801 women | RR 0.88, 95% CI 0.85 to 0.91 (P < 0.00001), reduction in LBW for women receiving multiple micronutrient supplementation vs iron with or without folic acid |
| Multiple micronutrients with iron and folic acid vs iron with or without folic acid | SGA | 17 studies, 57,348 women | RR 0.92, 95% CI 0.88 to 0.97 (P = 0), reduction in SGA for women receiving multiple micronutrient supplementation vs iron with or without folic acid |
| Multiple micronutrients with iron and folic acid vs iron with or without folic acid | NICU admission | Outcome not reported | |
| Energy and protein intake (Ota 2015a) | |||
| Comparison | Outcome | No. of studies, no. women | Results |
| Nutritional advice during pregnancy | Stillbirth | 1 study, 431 women | RR 0.37, 95% CI 0.07 to 1.90, no evidence of a difference GRADEb: low |
| Nutritional advice during pregnancy | LBW | 1 study, 300 women | RR 0.04, 95% CI 0.01 to 0.14 (P < 0.00001), reduction in LBW for women receiving nutritional advice during pregnancy |
| Nutritional advice during pregnancy | SGA | 1 study, 404 women | RR 0.97, 95% CI 0.45 to 2.11, no evidence of a difference |
| Nutritional advice during pregnancy | NICU admission | Outcome not reported | |
| Balanced protein/energy supplementation in pregnancy | Stillbirth | 5 studies, 3408 women | RR 0.60, 95% CI 0.39 to 0.94 (P = 0.024), reduction in stillbirth for women receiving balanced protein/energy supplementation in pregnancy GRADEb: moderate |
| Balanced protein/energy supplementation in pregnancy | SGA | 7 studies, 4408 women | RR 0.79, 95% CI 0.69 to 0.90 (P = 0.0004), reduction in SGA for women receiving balanced protein/energy supplementation in pregnancy |
| Balanced protein/energy supplementation in pregnancy | LBW | Outcome not reported | |
| Balanced protein/energy supplementation in pregnancy | NICU admission | Outcome not reported | |
| High protein supplementation in pregnancy | Stillbirth | 1 study, 529 women | RR 0.81, 95% CI 0.31 to 2.15, no evidence of a difference GRADEb: low |
| High protein supplementation in pregnancy | SGA | 1 study, 505 women | RR 1.58, 95% CI 1.03 to 2.41, (P = 0.04), increase in SGA for women receiving high protein supplementation during pregnancy |
| High protein supplementation in pregnancy | LBW | Outcome not reported | |
| High protein supplementation in pregnancy | NICU admission | Outcome not reported | |
| Isocaloric balanced protein supplementation in pregnancy | Stillbirth | Outcome not reported | |
| Isocaloric balanced protein supplementation in pregnancy | LBW | Outcome not reported | |
| Isocaloric balanced protein supplementation in pregnancy | SGA | Outcome not reported | |
| Isocaloric balanced protein supplementation in pregnancy | NICU admission | Outcome not reported | |
| Omega‐3 fatty acid addition during pregnancy (Middleton 2018) | |||
| Comparison | Outcome | No. of studies, no. women | Results |
| Omega‐3 vs no omega‐3 | Stillbirth | 16 studies, 7880 women | RR 0.94, 95% CI 0.62 to 1.42, no evidence of a difference GRADEa: very low |
| Omega‐3 vs no omega‐3 | Perinatal death | 10 studies, 7416 women | RR 0.75, 95% CI 0.54 to 1.03, no evidence of a difference GRADEb: low |
| Omega‐3 vs no omega‐3 | LBW | 15 studies, 8449 women | RR 0.90, 95 % CI 0.82 to 0.99 (P = 0.034), decrease in LBW for women receiving omega‐3 fatty acids during pregnancy |
| Omega‐3 vs no omega‐3 | SGA/IUGR | 8 studies, 6907 women | RR 1.01, 95% CI 0.90 to 1.13, evidence of no difference |
| Omega‐3 vs no omega‐3 | NICU admission | 9 studies, 6920 women | RR 0.92, 95% CI 0.83 to 1.03, evidence of no difference |
| Lipid‐based nutrient supplements (LNS) (Das 2018) | |||
| Comparison | Outcome | No. of studies, no. women | Results |
| Lipid‐based nutrient supplements vs iron folic acid | Stillbirth | 3 studies, 5575 women | RR 1.14, 95% CI 0.52 to 2.48, no evidence of a difference GRADEa: low |
| Lipid‐based nutrient supplements vs iron folic acid | LBW | 3 studies, 4826 women | RR 0.87, 95% CI 0.72 to 1.05, possible reduction, but also slight increase |
| Lipid‐based nutrient supplements vs iron folic acid | SGA | 3 studies, 4823 women | RR 0.94, 95% CI 0.89 to 0.99 (P = 0.015), decrease in SGA for women receiving LNS during pregnancy |
| Lipid‐based nutrient supplements vs iron folic acid | NICU admission | Outcome not reported | |
| CI: confidence interval; CTG: cardiotocography; IUGR: interuterine growth restriction; LBW: low birthweight; LNS: lipid‐based nutrient supplements; NICU: neonatal intensive care unit; RR: risk ratio; SGA: small‐for‐gestational age | |||
aGRADE assessed by review overview authors because it was not reported in the original review; bGRADE rating reported in the original review.