Supplementation of Vitamin D in the Postdelivery Period of Women with Previous Gestational Diabetes Mellitus: Systematic Review and Meta-Analysis of Randomized Trials

Kron-Rodrigues, Meline Rossetto; Rudge, Marilza Vieira Cunha; Lima, Silvana Andrea Molina

doi:10.1055/s-0041-1734000

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Review Article • Rev. Bras. Ginecol. Obstet. 43 (09) • Sept 2021 • https://doi.org/10.1055/s-0041-1734000 copy

Supplementation of Vitamin D in the Postdelivery Period of Women with Previous Gestational Diabetes Mellitus: Systematic Review and Meta-Analysis of Randomized Trials

Suplementacão da vitamina D no período pós-parto de mulheres com diabetes mellitus gestacional anterior: revisão sistemática de ensaios clínicos randomizados

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective

To evaluate the effects of vitamin D supplementation in the postpartum period of women with previous gestational diabetes mellitus (GDM).

Methods

Randomized clinical trials of pregnant women with GDM of any chronological, gestational age and parity, with no history of previous disease who received vitamin D supplementation in the prenatal and/or postpartum period and were evaluated in the postpartum period were included. The PubMed, EMBASE, Cochrane, and LILACS databases were consulted until July 2019. Serum vitamin D concentration (25- hydroxyvitamin D in nmol/L), fasting blood glucose, glycated hemoglobin, serum calcium concentration, homeostatic model assessment of insulin resistance (HOMAIR), quantitative insulin sensitivity check index (QUICKI), parathyroid hormone (PTH) and body mass index (BMI) were evaluated. Similar results in at least two trials were plotted using the RevMan 5; Cochrane Collaboration, Oxford, Reino Unido. The quality of the evidence was generated according to the classification, development, and evaluation of the classification of the recommendations.

Results

Four studies were included in the present review (200 women). The findings indicate that there is no difference in the postpartum period in women diagnosed with previous GDM who received vitamin D supplementation in the prenatal and/or in the postpartum period, showing only that there was a significant increase in the concentration of vitamin D (relative risk [RR]: 1.85; 95% confidence interval [CI]: 1.02-2.68).

Conclusion

This increase in the concentration of vitamin D should be interpreted with caution, since the assessment of the quality of the evidence was very low. For the other analyzed outcomes, there was no significance between the intervention and control groups, and the outcomes, when analyzed in their strength of evidence, were considered very low and low in their evaluation.

Keywords:
gestational diabetes; vitamin D; meta-analysis; postpartum period; systematic review

First author, year published	Study location	Source of funding	No. of participants	Age (years old), percentiles	Treatment duration	Inclusion criteria	Exclusion criteria	Treatment group	Primary endpoint
Valizadeh et al. (2016)²⁷27 Valizadeh M, Piri Z, Mohammadian F, Kamali K, Amir Moghadami HR. The impact of vitamin D supplementation on post-partum glucose tolerance and insulin resistance in gestational diabetes: a randomized controlled trial. Int J Endocrinol Metab. 2016;14(02): e34312. Doi: 10.5812/ijem.34312 https://doi.org/10.5812/ijem.34312...	Iran	Zanjan University of Medical Sciences and Farir-Teb Company	84	G1: 32.0 (5.5)G2: 32.4 (4.7)	12 weeks after delivery	Pregnant women diagnosed with GDM * – **, maternal age> 16 years, single pregnancy and gestational age between 12 and 32 weeks	Women with type 1 or 2 diabetes known before pregnancy, history of hypertension or thyroid disorders. Women who used assisted reproduction techniques or those with a history of consuming high doses of vitamin D during the previous three months	G1: 200.000 IU of vitamin D3 in the first two days and then 50.000 IU per week, up to 700.000 IU in total.G2: received nothing	Fasting plasma glucose, 2-hour post 75 g glucose load plasma glucose (2-hPLG), fasting serum insulin, homeostasis model assess- ment of insulin resistance (HOMA-IR), HbA1C, and serum 25OHD at 6 - 12 weeks after delivery.
Yeow et al. (2015)²⁸28 Yeow TP, Lim SL, Hor CP, Khir AS, Wan Mohamud WN, Pacini G. Impact of vitamin D replacement on markers of glucose metabo lism and cardio-metabolic risk in women with former gestational diabetes-a double-blind, randomized controlled trial. PLoS One. 2015;10(06):e0129017. Doi: 10.1371/journal.pone.0129017 https://doi.org/10.1371/journal.pone.012...	Malaysia	Penang Medical College and Medical Research Grant from Ministry of Health, Malaysia	26G1:13G2:13	G1:36 (32, 38)G2: 35 (30, 40	6 months after delivery	Women diagnosed with GDM in the last pregnancy, who were between 6 to 48 months after delivery	Women with diabetes, pregnancy, breastfeeding, intolerance to vitamin D supplementation, alcohol dependence, drug use, chronic kidney or liver failure, hypercalcemia, hypocalcemia or concomitant use of calcium supplementation, treatment for tuberculosis or anti-epileptic medications.	G1: 4000 IU of vitamin D3 (cholecalciferol) per day (four capsules of 1000 IU each) for six monthsG2: four corresponding placebo capsules per day for six months	Serum vitamin D level (nmol/L)Intact parathyroid hormone (pg/mL)HbA1C level and glucose metabolism during OGTTFasting glucose (mmol/L)30-minute glucose (mmol/L)2-hour glucose (mmol/L)AUCglucose (mmol/L)ΔAUCglucose (mmol/L)Insulin secretionFasting insulin (pmol/L)Fasting C-peptide (ng/mL)Insulin sensitivityOGIS (ml/ min/ m2)BIGTT-S (10–5(minpmol/L)-1)Disposition index (OGIS* ratio of total AUCinsulin over AUCglucose)
Hosseinzadeh-Shamsi-Anar et al. (2012)²⁹29 Hosseinzadeh-Shamsi-Anar M, Mozaffari-Khosravi H, Salami MA, Hadinedoushan H, Mozayan MR. The efficacy and safety of a high dose of vitamin d in mothers with gestational diabetes mellitus: a randomized controlled clinical trial. Iran J Med Sci. 2012;37(03): 159-165	Iran	NI	45G1:24G2:21	G1: 30.7 ± 6.2G2: 29.5 ± 4	3 months after delivery	Pregnant women diagnosed with GDM, absence of thyroid, kidney and liver diseases, as well as malabsorption	Change in routine treatment and intake of vitamin D, Ca and multivitamin supplements.	G1: 300.000 IU of vitamin D3 administered intramuscularly in the diagnosis of GDMG2: Did not receive placebo	glycosylated hemoglobin A1C (HBA1C), serum 25-OH-D, parathyroid hormone (PTH), serum calcium, phosphorus, BMI (kg/m2) and HBA1C (%)
Mozaffari-Khosravi et al. (2012)³⁰30 Mozaffari-Khosravi H, Hosseinzadeh-Shamsi-Anar M, Salami MA, Hadinedoushan H, Mozayan MR. Effects of a single post-partum injection of a high dose of vitamin D on glucose tolerance and insulin resistance in mothers with first-time gestational diabetes mellitus. Diabet Med. 2012;29(01):36-42. Doi: 10.1111/j.1464-5491.2011.03473.x https://doi.org/10.1111/j.1464-5491.2011...	Iran	NI	45G1:24G2:21	G1: 30.7 ± 6.2G2: 29.5 ± 4	3 months after delivery	Women diagnosed with GDM ** in the last pregnancy, absence of thyroid disease, kidney and liver diseases and absence of malabsorption	NI	G1: 300,000 IU of vitamin D3 administered intramuscularly after deliveryG2: Did not receive placebo	HbA1c, serum 25-hydroxyvitamin D3, fasting insulin and blood glucose, C-peptide, homeostasis model assessment insulin resistance index (HOMA-IR),

Outcomes	Patients (n)	Risk of bias	Inconsistency	Indirectness	Imprecision	Publication bias	Quality of evidence
Serum vitamin D concentration
	200(4 RCTs)	Serious(−1)*	Very serious^a(-2)*	Not serious	Serious^b(-1)*	Probably not	ⴲ◯◯◯very low
Fasting blood glucose
	132(3 RCTs)	Serious(-1)*	Serious^a(-1)	Not serious	Serious^b(-1)*	Probably not	ⴲ◯◯◯very low
Glycated hemoglobin
	200(4RCTs)	Serious (-1)*	Not serious	Not serious	Very serious^b(-2)*	Probably not	ⴲ◯◯◯very low
HOMA-IR
	129(2 RCTs)	Serious (-1)*	Not serious	Not serious	Very serious (-2)*	Probably not	ⴲ◯◯◯very low
QUICKIE
	68(2 ECR's)	Serious (-1)*	Very serious^a(-2)*	Not serious	Not serious	Probably not	ⴲ◯◯◯very low
PTH
	71(2 ECR's)	Grave(-1)*	Very serious^a(-2)*	Not serious	Not serious	Probably not	ⴲ◯◯◯very low

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[1] Address for correspondence Meline Rossetto Kron-Rodrigues, Dra., Praça Teresa Cristina, 229, Guarulhos, SP, 07023-070, Brazil (e-mail: me_kron@hotmail.com).