Table 22. The effect of maternal vitamin D status in gestation on risk of Type 1 Diabetes Mellitus (DM) in the offspring – Observational studies.
| First Author and year |
Bias score |
Study details |
Study type |
Confounders/ adjustments |
Number of weeks gestation when 25(OH)D was measured | Maternal mean (SD) 25(OH)D concentration (nmol/l) in cases of offspring DM | Maternal mean (SD) 25(OH)D concentration (nmol/l) in offspring without DM | Odds ratio (95% CI) of offspring developing Type 1 Diabetes from univariate analysis | Odds ratio (95% CI) of offspring developing Type 1 Diabetes from multivariate analysis | Conclusion | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Stene, 2003 122 | 2 (med) | Norway Cases of offspring Type 1 DM=545 (mean age 10.9 (3.4) years) Controls=1668 |
Case-control | Controls matched for period of birth (between 1/1/1985 – 31/12/1999) Maternal use of cod liver oil in pregnancy, child’s use of cod liver oil or other vitamin D supplement during the first year of life, duration of exclusive breastfeeding, child’s age at introduction of solids, maternal education, smoking in pregnancy, maternal age at delivery, child number of siblings, type 1 DM amongst child’s siblings or parents, child’s age, child’s sex |
Not measured. Retrospective questionnaire of maternal use of vitamin D supplements during pregnancy. Grouped into either ,no supplements-; ,yes, 1-4 times per week- or ,yes, 5+ times per week- |
Not measured | Not measured | Vit D suppl. in pregnancy | OR (95% CI) | Vit D suppl in pregnancy | Adjusted OR (95% CI) | Maternal use of vitamin D supplements in pregnancy were not associated with an increased risk of type 1 DM in the offspring | |
| No | 1 (ref) | No | 1 (Ref) | ||||||||||
| Yes, 1-4 times per week | 0.86 (0.63, 1.18) | Yes, 1-4 times per week | 1.09 (0.77, 1.56) | ||||||||||
| Yes, 5+ times per week | 0.89 (0.69, 1.13) | Yes, 5+ times per week | 0.98 (0.73, 1.31) | ||||||||||
| p for trend | 0.28 | p for trend | 0.94 | ||||||||||
| Marjamaki, 2010 123 | 6 (low) | Diabetes Prediction and Prevention study (DIPP), Finland Cohort size=3723 women and their children with increased genetic risk of diabetes* Cases of offspring Type 1 DM=74 (children observed for mean 4.3 (range 0.2-8.9) years |
Prospective cohort |
2 models: HR1 adjusted for genetic risk and familial type 1 DM HR2 adjusted for genetic risk, familial Type 1 diabetes, sex, gestational age,maternal age, maternal education, delivery hospital, route of delivery, number of earlier deliveries, smoking during pregnancy |
Not measured. Estimated from FFQ completed 1-3 months after delivery – focused on food taken in the 8th month of pregnancy and the use of supplements |
Not given | Not given | Not given | HR given HR1=1.18 (0.74 p=0.187) p=0.49 HR2=1.08 (0.65 p=1.79) p=0.77 |
Maternal intake of vitamin D, either from food or supplements is not associated with type 1 DM or advanced B cell autoimmunity in the offspring | |||
| Sorensen, 2012 121 | 8 (low) | Norway Overall cohort=29072 women Cases of offspring type 1 DM= 109 (mean age at diagnosis 9.0 (3.6) years Controls=219 |
Nested case-control |
No significant difference between cases and controls in terms of maternal age, parity, gestational week of blood sample, frequency of C-section or maternal diabetes pre-pregnancy. Significantly more female offspring in cases than controls. Adjustments: 2 models: OR1 adjusted for sex of child and season of blood sample OR2 adjusted for age of child at diagnosis, offspring sex, mothers age at delivery, parity, gestational week of blood sample, pregestational diabetes, season of blood sample, region of residence, percentage undergoing C-section |
Median (IQR) cases=37 (22-38) wks Median (IQR) controls=37(24-38) wks |
65.8 (26.5)) | 73.1 (27.2) | 25(OH)D conc | OR | 25(OH)D conc | OR1 | OR2 | Trend towards higher risk of type 1 diabetes in the offspring with lower levels of maternal 25(OH)D in late pregnancy, especially in those with 25(OH)D under 54 nmol/l |
| >89 | 1.0 (ref) | >89 | 1.0 (ref) | 1.0 (ref) | |||||||||
| >69-89 | 1.32 (0.63, 2.76) | >69-89 | 1.35 (0.63, 2.89) | Not given | |||||||||
| >54-69 | 1.73 (0.86, 3.48) | >54-69 | 1.78 (0.85, 3.74) | Not given | |||||||||
| ≤54 | 2.25 (114, 4.46) | ≤54 | 2.38 (1.12, 5.07) | 2.39 (1.07-5.11 | |||||||||
| Test for trend Cont. | P=0.022 | Test for trend Cont. | 0.031 | 0.032 | |||||||||
*
Increased genetic risk defined by genotype HLA DQB1*02*0302 for high risk and HLA-DQB1*0302/x, where x=other than *03, *0301 or *0602 for moderate risk