Vitale 2019.

Study characteristics
Methods	Study type: prospective, open‐label, placebo‐controlled RCT
Participants	250 pregnant women from Italy Inclusion criteria: pre‐pregnancy BMI > 25 and < 30 kg/m2, first‐trimester fasting plasma glucose ≤ 126 mg/dl and/or random glycaemia <200 mg/dl, single pregnancy, and Caucasian ethnicity. Exclusion criteria: women who had a pre‐pregnancy BMI < 25 and ≥ 30 kg/m2, previous gestational diabetes, pre‐gestational diabetes, first‐trimester glycosuria, and in treatment with corticosteroids. Location: Gynaecology and Obstetrics of the Department of Human Pathology in Adulthood and Childhood, University of Messina, Italy Timeframe: started at the beginning of 2016 and lasted 2 years
Interventions	Intervention: 4 g myo‐inositol plus 400 mg folic acid (2 g myo‐inositol plus 200 mg folic acid twice/day—InofolicVR ; Loli Pharma, Rome, Italy), and followed the same diet according to the ADA recommendations (N = 125) Duration: the treatment lasted until three weeks after delivery Comparison: 400 mg folic acid only (200 mg twice/day), and followed the same diet according to the ADA recommendations (N = 125)
Outcomes	Maternal: occurrence of gestational diabetes and body water distribution, changes in lipid metabolism (total cholesterol, HDL, LDL and triglycerides serum levels), rate of caesarean section in emergency, pregnancy induced hypertension (PIH) and pre‐eclampsia Criteria used to diagnose gestational diabetes: IADPSG Infant: prevalence of fetal macrosomia (fetal birth weight >4500 g at delivery),  preterm delivery (< 37 weeks), , the occurrence of shoulder dystocia, neonatal hypoglycaemia, the need for transfer to the Neonatal Intensive Care Unit (NICU)
Notes	Sample size calculation: yes   Funding source: not reported Conflict of interest: none reported The trial is registered with the number NCT01047982, the same as D’Anna 2015 The ethical was approval by the Ethical Committee of Messina University Hospital(E347/2008) No response was received following email contact with the authors.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	A computer‐generated random sampling method with a 1:1 ratio was used.
Allocation concealment (selection bias)	Unclear risk	A nurse sealed and randomly numbered the allocations in white envelopes according to the computer‐generated scheme. Sealed envelopes should be opaque and sequentially numbered.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open label trial. Blinding not carried out
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open label trial. Blinding not carried out
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	10.8% lost to follow up overall
Selective reporting (reporting bias)	Unclear risk	Not all outcomes specified in the methodology section have been reported.
Other bias	Low risk	Appears free of other bias. The authors do not report any potential conflicts of interest.

ADA: American Diabetes Assocation
BMI: body mass index
GDM: gestational diabetes 
HbA1c: glycated haemoglobin
HDL: high density lipoprotein
IADPSG: International Association of Diabetes and Pregnancy Study Groups
LDL: low density lipoprotein
OGTT: oral glucose tolerance test
PCOS: polycystic ovary syndrome
RCT: randomised controlled trial