Novel Associations of Early Pregnancy Vitamin B12 and Folate Levels with Gestational Diabetes: Results from a Large, Prospective, Multi-Ethnic UK Cohort (PRiDE Study)

Abstract

Background: Women from certain ethnic groups are at higher risk of Gestational Diabetes Mellitus (GDM). While altered methylation potential due to low vitamin B12 and/or imbalance of B12 and folate levels may be potential contributing factors, there is conflicting evidence. Methods: In a prospective multi-ethnic UK cohort study (n=4746), maternal first trimester B12, folate and total homocysteine (tHcy) levels were measured, and GDM status was assessed at 26-28 weeks of gestation. Findings: GDM rates were 12·5% by NICE and 14·7% by International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria. Early pregnancy median B12 levels were lower, and folate levels higher, in women who have diagnosed with GDM. B12 was negatively associated with fasting (FPG)(1-SD: -0·06mmol/l; p<0·0001) and 2-hour plasma glucose levels (2hr-PG)(-0·07mmol/l, p=0·004); associations were stronger in South Asians (FPG: -0·07mmol/l, p=0·001; 2hr-PG: -0·14mmol/l, p=0·02). Higher B12 was associated with lower odds of GDM [aOR(95%CI): NICE-GDM: 0·888(0·80,0·985), p=0·02; IADPSG-GDM: 0·838(0·758,0·927), p=0·0006]. Approximately half of this association was mediated through BMI. Folate was positively associated with 2hr-PG (0·08mmol/l, p=0·0005) but its relationship with FPG was U-shaped (quadratic b:0·011; p=0·05). Low B12-high folate combination was associated with higher glycaemia and risk of GDM. tHcy was inversely associated with glycaemia and GDM risk. Interpretation: Low B12 and high folate levels in early pregnancy were associated with subsequent hyperglycaemia but do not explain the higher risk of GDM in ethnic minority groups. There is a need to investigate the effect of optimising early pregnancy or pre-conception B12 and folate levels on subsequent hyperglycaemia. Trial Registration: (PRiDE) study (clinicaltrials.gov number: NCT03008824). Funding: Medical Research Council, UK (MR/94/1). Declaration of Interests: All authors declare no conflict of interest. Ethics Approval Statement: Ethical approval was obtained from the National Research Ethics Committee (12/WM/0010).