Meta-Analysis
Copyright ©The Author(s) 2022.
World J Methodol. May 20, 2022; 12(3): 164-178
Published online May 20, 2022. doi: 10.5662/wjm.v12.i3.164
Table 1 Salient features of the reviewed trials
Ref.
Design
Participants
Interventions
Outcomes
Jamilian et al[37], 2016Randomized, double-blind, placebo-controlled clinical trial; Intervention arms: Two; Single-centered trialTrial duration: 6 wk. Trial conducted in: Iran; Obtained ethical clearance and participant consent. Funding information provided. Clinical trial registration number: IRCT201509115623N52Participants diagnosed with GDM (used ADA criteria); 60 participants randomized into different treatment arms (vitamin D3 and evening primrose oil: n = 30, placebo: n = 30); Mean age of participants: -Vitamin D3 and evening primrose oil receiving group: 28.4 ± 6.2 yr; -Placebo receiving group: 29.6 ± 4.3 yrTwo intervention arms: (1) 1000 IU of vitamin D and 1000 mg of evening primrose oil daily for 6 wk; and (2) PlaceboAttrition from vitamin D supplemented arm: n = 3; Other outcomes reported: Fasting plasma glucose
Jamilian et al[17], 2017Randomized, double blinded, placebo-controlled clinical trial; Intervention arms: four; Single centered trial; Trial duration: 6 wk. Trial conducted in: Iran; Obtained ethical clearance and participant consent. Funding information provided. Clinical trial registration number: IRCT201605135623N78Participants diagnosed with GDM (used ADA criteria); 140 participants randomized into different treatment arms (vitamin D and omega-3 fatty acid receiving group: n = 35, vitamin D receiving arm: n = 35, omeag-3 fatty acid receiving arm: n = 35, placebo receiving arm: n = 35); Mean age of participants: -Vitamin D and omega-3 fatty acid receiving group: 31.2 ± 4.3 yr; -Vitamin D receiving group: 31.5 ± 7.0 yr; -Omega-3 receiving group: 30.7 ± 3.5 yr; -Placebo receiving group: 30.7 ± 4.1 yrFour intervention arms: (1) Vitamin D and omega-3 fatty acid: 50000 IU of vitamin D two weekly and 1000 mg omega-3 fatty acid twice daily; (2) Vitamin D: 50000 IU vitamin D every 2 wk; (3) Omega-3 fatty acid: 1000 mg omega-3 fatty acids two times a day; and (4) PlaceboNo attrition from vitamin D supplemented arm; Other outcomes reported: Fasting plasma glucose
Jamilian et al[33], 2019a Randomized, double-blind, placebo-controlled; Intervention arms: 3; Trial conducted in: Iran; Single centered trial; Trial duration: 6 wk; Obtained ethical clearance and participant consent. Funding information provided. Trial ID: IRCT201706075623N119Participants diagnosed with GDM (used ADA criteria); 90 participants randomized into different treatment arms (probiotic arm: n = 30, vitamin D and probiotic arm: n = 30, placebo arm: n = 30); Mean age of participants: -Probiotic arm: 31.2 ± 5.9 yr; -Vitamin D and probiotic arm: 28.9 ± 6.1 yr; -Placebo arm: 29.9 ± 3.7 yrThree intervention arms: (1) Probiotic: 8 × 109 CFU/g; (2) Vitamin D3 (50,000 IU) every 2 wk plus 8 × 109 CFU/g probiotic; PlaceboNo attrition from vitamin D supplemented arm; Other outcomes reported: (1) Newborn hyperbilirubinemia; (2) Newborn hospitalization; (3) Macrosomia; and (4) Cesarean section. Fasting plasma glucose
Jamilian et al[36], 2019b Randomized, double-blind, placebo-controlled. Intervention arms: 2; Trial conducted in: IranSingle centered trialTrial duration: 6 wkObtained ethical clearance and participant consent. Funding information provided.Trial ID: IRCT201704225623N109Participants diagnosed with GDM (used ADA criteria); 60 participants randomized into different treatment arms (vitamin D-magnesium-zinc-calcium arm: n = 30, placebo arm: n = 30). Mean age of participants: -Vitamin D-magnesium-zinc-calcium arm: 27.7 ± 4.0 yr; -Placebo arm: 29.1 ± 4.1 yrTwo intervention arms: (1) Vitamin D (200 IU) along with 100 mg magnesium, 4 mg zinc, 400 mg calcium twice daily; and (2) PlaceboNo attrition from vitamin D supplemented armOther outcomes reported: (1) Newborn hyperbilirubinemia; (2) Newborn hospitalization; (3) Macrosomia; and (4) Cesarean section. Fasting plasma glucose
Asemi et al[31], 2014aRandomized, double-blind, placebo-controlled trial. Intervention arms: 2; Trial conducted in: Iran; Single centered trial; Trial duration: 6 wk; Obtained ethical clearance and participant consent. Funding information provided.Trial ID: IRCT201305115623N7Participants diagnosed with GDM (used ADA criteria); 50 participants randomized into different treatment arms (vitamin D arm: n = 25, placebo arm: n = 25). Mean age of participants: -Vitamin D arm: 31.1 ± 5.5 yr; -Placebo arm: 30.8 ± 6.2 yrTwo intervention arms: (1) Vitamin D: 50,000 IU vitamin D3 pearl two times during the trial period (at baseline and day 21); and (2) PlaceboAttrition from vitamin D supplemented arm: n = 3; Other outcomes reported: (1) Newborn hyperbilirubinemia; (2) Newborn hospitalization; (3) Macrosomia; and (4) Cesarean section
Asemi et al[16], 2014bRandomized, placebo-controlled clinical trial. Intervention arms: TwoMulti-centric trial. Trial duration: 6 wk. Trial conducted in: IranObtained ethical clearance and participant consent. Funding information provided. Clinical trial registration number: IRCT201311205623N11Participants diagnosed with GDM (used ADA criteria); 56 participants randomized into different treatment arms (vitamin D and calcium: n = 28, placebo receiving group: n = 28). Mean age of participants: -Vitamin D and calcium receiving arm: 28.7 ± 6.0 yr; -Placebo receiving arm: 30.8 ± 6.6 yrTwo intervention arms: (1) 1000 mg calcium carbonate daily and 50000 U vitamin D3 at the baseline and day 21 of the study; and (2) PlaceboAttrition from vitamin D supplemented arm: n = 3. Other outcomes reported: Fasting plasma glucose
Karamali et al[32], 2016 Randomized, double-blind, placebo-controlled trial; Intervention arms: 2; Trial conducted in: Iran; Multicentric trialTrial duration: 6 wk; Obtained ethical clearance and participant consent. Funding information provided. Trial ID: IRCT201407115623N23Participants diagnosed with GDM (used ADA criteria); 60 participants randomized into different treatment arms (vitamin D and calcium arm: n = 30; placebo arm: n = 30). Mean age of participants: -Vitamin D and calcium arm: 28·7 ± 6·1 yr; -Placebo arm: 31·6 ± 6·3 yrTwo intervention arms: (1) Vitamin D3 (50000 IU) at baseline and day 21 along with 1000 mg calcium carbonate daily; and (2) PlaceboNo attrition from vitamin D supplemented arm; Other outcomes reported: (1) Newborn hyperbilirubinemia; (2) Newborn hospitalization; (3) Macrosomia; and (4) Cesarean section
Karamali et al[14], 2018 Randomized, double-blind, placebo-controlled trial; Intervention arms: 2; Single centered trial. Trial duration: 6 wk; Trial conducted in: Iran; Obtained ethical clearance (participant consent information unclear). Funding information provided. Trial registration details: UnclearParticipants diagnosed with GDM (used ADA criteria); 60 participants randomized into different treatment arms; (Magnesium, zinc, calcium and vitamin D supplements arm: n = 30; Placebo arm: n = 30); Mean age of participants: -Magnesium, zinc, calcium and vitamin D: 30.0 ± 4.5 yr; -Placebo arm: 31.1 ± 4.2 yrTwo intervention arms: (1) 100 mg magnesium, 4 mg zinc, 400 mg calcium and 200 IU vitamin D two times a day for 6 wk; and (2) PlaceboNo attrition from vitamin D supplemented arm; Other outcomes reported: Fasting plasma glucose
Razavi et al[35], 2017 Randomized, double-blind, placebo-controlled, Intervention arms: 4; Trial conducted in: Iran. Single centered trial. Trial duration: 6 wk; Obtained ethical clearance and participant consent. Funding information provided. Trial ID: IRCT201701305623N106Participants diagnosed with GDM (used ADA criteria); 120 participants randomized into different treatment arms (vitamin D and omega-3 arm: n = 30; omega-3 arm: n = 30; vitamin D arm: n = 30; placebo: n = 30); Mean age of participants: -Vitamin D and omega-3 arm: 29.9 ± 4.0 yr; -Omega-3 arm: 29.7 ± 3.6 yr; -Vitamin D arm: 29.9 ± 5.0 yr; -Placebo: 29.2 ± 3.4 yrFour intervention arms: (1) Vitamin D (50000 IU): Two weekly two times a day; (2) Vitamin D (50000 IU) two weekly plus 1000 mg omega-3 fatty acids two times a day; (3) 1000 mg omega-3 fatty acids two times a day; and (4) PlaceboNo attrition from vitamin D supplemented arm; Other outcomes reported: (1) Newborn hyperbilirubinemia; (2) Newborn hospitalization; (3) Macrosomia; and (4) Cesarean section
Valizadeh et al[34], 2016 Randomized controlled trial. Investigators and patients were not blinded. Intervention arms: 2; Single centered trial; Trial conducted in: Iran; Trial duration: Until delivery; Obtained ethical clearance and participant consent. Funding information provided. Trial ID: IRCT2012101611144N1Participants diagnosed with GDM (used ADA criteria); 96 participants randomized into different treatment arms (vitamin D arm: n = 48; no supplement arm: n = 48); Mean age of participants: -Vitamin D arm: 32.0 ± 5.5 yr; -No supplement arm: 32.4 ± 4.7 yrTwo intervention arms: (1) 700000 IU vitamin D3 in total (regimen differed by gestational age of GDM patients); and (2) Comparison group did not receive any supplementationAttrition from vitamin D supplemented arm: n = 4; Other outcomes reported: (1) Newborn hyperbilirubinemia; (2) Macrosomia; (3) Cesarean section; and (4) Fasting plasma glucose
Yazdchi et al[15], 2016Randomized, double-blinded placebo-controlled clinical trial; Intervention arms: 2; Multi-center trial; Trial duration: 8 wk. Trial conducted in: Iran; Obtained ethical clearance and participant consent. Funding information provided. Clinical trial registration number: IRCT201306253140N11Participants diagnosed with GDM (used International Association of Diabetes and Pregnancy Study Groups criteria); 76 participants randomized into different treatment arms: Vitamin D arm: n = 38; placebo arm: n = 38; Mean age of participants: -Vitamin D arm: 31.64 ± 4.40 yr; -Placebo arm: 32.11 ± 3.61 yrTwo intervention arms:(1) 50000 IU vitamin D3 oral capsules two weekly for 8 wk; and (2) PlaceboAttrition from vitamin D supplemented arm: n = 4; Other outcomes reported: Fasting plasma glucose
Zhang et al[38], 2016 Randomized, double-blind, placebo-controlled trial. Intervention arms: 4; Single centered trial. Trial duration: 24-28 wk of pregnancy to delivery; Trial conducted in: China; Obtained ethical clearance and participant consent. Funding information provided. Clinical trial registration details: UnclearParticipants diagnosed with GDM (criteria unclear). 133 participants randomized into different treatment arms (low dose vitamin D: n = 38; medium dose vitamin D: n = 38; high dose vitamin D: n = 37; placebo: n = 23); Mean age of participants: -Placebo arm: 29.8 ± 4.7; -Low dose vitamin D arm: 30.3 ± 5.1; -Medium dose vitamin D arm: 29.4 ± 4.9; -High dose vitamin D arm: 30.1 ± 4.5Four intervention arms: (1) Low dose vitamin D: 200 IU daily; (2) Medium dose vitamin D: 2000 IU monthly; and (3) High dose vitamin D: 50000 IU every 2 wk. PlaceboAttrition from vitamin D supplemented arm: n = 4
Li and Xing[13], 2016Randomized, double-blinded clinical trial. Intervention arms: 2. Multi-centric trial. Trial duration: 16 wk. Trial conducted in: China; Obtained ethical clearance and participant consent. Funding information provided. Clinical trial registration details: UnclearParticipants diagnosed with GDM (used ADA criteria)103 participants randomized into different treatment arms (yoghurt with vitamin D: n = 52, plain yoghurt: n = 51); Mean age of participants: -Yoghurt supplemented with vitamin D receiving arm: 29.0 ± 5.3 yr; -Plain yoghurt arm: 28.3 ± 4.1 yrTwo intervention arms: (1) Yoghurt was supplemented with 500 IU of vitamin D3 twice daily for 16 wk; and (2) plain yoghurt: Twice daily for 16 wkAttrition from vitamin D supplemented arm: n = 4. Other outcomes reported: Fasting plasma glucose
Table 2 Risk of bias assessment of respective trial included in the review[23]
Ref.Random sequence generation (selection bias)Allocation concealment (selection bias)Blinding of participants and personnel (performance bias); All outcomesBlinding of outcome assessment (detection bias); All outcomesIncomplete outcome data (attrition bias); All outcomesSelective reporting (reporting bias)Other bias
Jamilian et al[37], 2016LowUnclear; Comment: Precise mechanism unclearUnclear; Comment: Precise mechanism unclearLowLowLowLow
Jamilian et al[17], 2017LowUnclear; Comment: Precise mechanism unclearUnclear; Comment: Precise mechanism unclearUnclearLowLowLow
Jamilian et al[33], 2019a Low riskUnclear risk; Comment: Precise mechanism unclearLow riskLow riskLow riskLow riskLow risk
Jamilian et al[36], 2019b Low riskUnclear risk; Comment: Precise mechanism unclearLow riskLow riskLow riskLow riskLow risk
Asemi et al[31], 2014aLow riskUnclear risk; Comment: Precise mechanism unclearLow riskLow riskLow riskLow riskLow risk
Asemi et al[16], 2014bLowLowLowLowLowLowLow
Karamali et al[32], 2016 Low riskUnclear risk; Comment: Precise mechanism unclearLow riskLow riskLow riskLow riskLow risk
Karamali et al[14], 2018 LowUnclear; Comment: Precise mechanism unclearUnclear; Comment: Precise mechanism unclearLowLowLowLow
Razavi et al[35], 2017 Low riskUnclear risk; Comment: It’s unclear if the bottles were sequentially numbered and identical in appearanceLow riskLow riskLow riskLow riskLow risk
Valizadeh et al[34], 2016Low riskUnclear riskHigh risk; Comment: Both investigators and participants were not blindedLow riskLow riskLow risk
Yazdchi et al[15], 2016LowUnclearUnclearLowLowLowLow
Zhang et al[38], 2016 LowUnclear; Comment: Precise mechanism unclearUnclear; Comment: Precise mechanism unclearUnclear; Comment: Precise mechanism unclearLowLowLow
Li and Xing[13], 2016 LowUnclear; Comment: Precise mechanism unclearUnclear; Comment: Precise mechanism unclearLowLowLowLow
Table 3 League table. Outcomes: cesarean section (left lower triangle) and newborn hyperbilirubinemia (right upper triangle). Interventions of interest: represented in diagonal cells
Interventions and effect sizes
Vitamin D and probiotic1.14 (0.22, 5.92)10.79 (0.19, 3.27)0.59 (0.16, 2.20)0.73 (0.18, 2.96)0.28 (0.09, 0.91)20.34 (0.09, 1.32)0.42 (0.10, 1.69)
0.76 (0.27, 2.19)Vitamin D and omega-3 fatty acid0.70 (0.17, 2.79)0.52 (0.16, 1.75)0.64 (0.14, 2.99)0.25 (0.08, 0.77)0.30 (0.09, 0.98)0.37 (0.09, 1.44)
1.48 (0.52, 4.21)1.94 (0.71, 5.28)Vitamin D and calcium0.75 (0.29, 1.96)0.91 (0.25, 3.35)0.35 (0.16, 0.77)0.43 (0.16, 1.19)0.53 (0.18, 1.55)
0.69 (0.29, 1.68)0.91 (0.44, 1.90)0.47 (0.21, 1.07)Vitamin D1.22 (0.37, 3.96)0.47 (0.27, 0.83)0.57 (0.27, 1.22)0.71 (0.28, 1.78)
0.68 (0.30, 1.54)0.89 (0.34, 2.35)0.46 (0.17, 1.20)0.97 (0.45, 2.13)Probiotic0.39 (0.14, 1.09)0.47 (0.14, 1.60)0.58 (0.16, 2.07)
0.54 (0.25, 1.18)0.71 (0.35, 1.46)0.37 (0.18, 0.74)0.78 (0.52, 1.19)0.80 (0.42, 1.56)Placebo1.22 (0.64, 2.33)1.50 (0.72, 3.14)
0.68 (0.24, 1.90)0.89 (0.40, 1.99)0.46 (0.17, 1.22)0.98 (0.49, 1.96)1.00 (0.39, 2.58)1.24 (0.63, 2.45)Omega-3 fatty acid1.23 (0.46, 3.28)
1.23 (0.33, 4.57)1.61 (0.45, 5.79)0.83 (0.23, 2.97)1.76 (0.56, 5.53)1.81 (0.52, 6.33)2.25 (0.78, 6.52)1.81 (0.51, 6.37)Magnesium, zinc, calcium, and vitamin D
Table 4 League table: Outcomes: Macrosomia (left lower triangle) and newborn hospitalization (right upper triangle). Interventions of interest: Represented in diagonal cells
Interventions and effect sizes
Vitamin D and probiotic1.27 (0.24, 6.66)10.88 (0.21, 3.69)0.66 (0.18, 2.49)0.97 (0.21, 4.41)0.31 (0.09, 1.03)0.38 (0.10, 1.49)0.47 (0.11, 1.91)
0.94 (0.11, 8.45)Vitamin D and omega-3 fatty acid0.70 (0.17, 2.79)0.52 (0.16, 1.75)0.76 (0.15, 4.02)0.25 (0.08, 0.77)20.30 (0.09, 0.98)0.37 (0.09, 1.44)
3.36 (0.13, 88.67)3.56 (0.14, 93.17)Vitamin D and calcium0.75 (0.29, 1.96)1.10 (0.26, 4.59)0.35 (0.16, 0.77)0.43 (0.16, 1.19)0.53 (0.18, 1.55)
0.98 (0.13, 7.29)1.03 (0.18, 6.09)0.29 (0.01, 6.77)Vitamin D1.46 (0.39, 5.50)0.47 (0.27, 0.83)0.57 (0.27, 1.22)0.71 (0.28, 1.78)
1.93 (0.19, 20.18)2.05 (0.15, 27.32)0.58 (0.02, 20.11)1.98 (0.17, 22.68)Probiotic0.32 (0.10, 1.07)0.39 (0.10, 1.53)0.48 (0.12, 1.97)
0.37 (0.08, 1.77)0.40 (0.08, 1.85)0.11 (0.01, 1.98)0.38 (0.11, 1.36)0.19 (0.02, 1.55)Placebo1.22 (0.64, 2.33)1.50 (0.72, 3.14)
0.63 (0.08, 4.84)0.67 (0.12, 3.71)0.19 (0.01, 4.45)0.64 (0.13, 3.13)0.33 (0.03, 3.83)1.69 (0.45, 6.30)Omega-3 fatty acid1.23 (0.46, 3.28)
1.87 (0.14, 25.22)1.98 (0.15, 26.45)0.56 (0.02, 19.45)1.91 (0.17, 21.96)0.97 (0.05, 18.42)5.00 (0.62, 40.28)2.96 (0.25, 34.96)Magnesium, zinc, calcium, and vitamin D
Table 5 The surface under the cumulative ranking curve values. Outcomes: Newborn hyperbilirubinemia, newborn hospitalization, and cesarean section
InterventionOutcomes
Newborn hyperbilirubinemia
Newborn hospitalization
Cesarean section
SUCRA
Mean rank
SUCRA
Mean rank
SUCRA
Mean Rank
Vitamin D and omega-3 fatty acid81.82.3181.12.3146.44.8
Vitamin D and probiotic76.22.770.73.066.33.4
Probiotic62.23.669.53.136.65.4
Vitamin D and calcium67.93.367.23.387.61.91
Vitamin D52.84.352.44.339.05.3
Magnesium, zinc, calcium, and vitamin D32.45.732.25.773.82.8