Maternal Serum Levels of 25-Hydroxy-Vitamin D During Pregnancy and Risk of Type 1 Diabetes in the Offspring

Ingvild M. Sørensen; Geir Joner; Pål A. Jenum; Anne Eskild; Peter A. Torjesen; Lars C. Stene


Diabetes. 2012;61(1):175-178. 

In This Article

Research Design and Methods

We designed a case-control study nested within a cohort of 35,940 women who gave birth in Norway between 1992 and 1994. All pregnant women in 11 of 19 counties in Norway participated. The purpose of the original cohort was to study Toxoplasma gondii infection in pregnancy.[13] One to four blood samples was collected from each woman throughout pregnancy in their respective primary health care centers at regular maternity check-ups. All samples were sent to the Norwegian Institute of Public Health in Oslo. After testing for T. gondii antibodies, in accordance with the original study objective, the sera were stored at −20°C. Subsequent to the toxoplasmosis study, all women were asked by mail to participate in additional research, of whom 29,072 women consented. We obtained information on the pregnancy outcomes by linkage to the Medical Birth Registry of Norway. This registry includes information on all deliveries in Norway after 16 weeks of gestation since 1967.[14]

To identify children born within the cohort who developed type 1 diabetes, linkage to the Norwegian Childhood Diabetes Registry was performed. Linkages were conducted using the unique 11-digit personal identification number given to every person in Norway. Children with newly diagnosed type 1 diabetes are reported to the Norwegian Childhood Diabetes Registry after a written consent from their parents, and 92% of all children with type 1 diabetes in Norway younger than 15 years of age are included.[15] In total, the offspring of 119 pregnancies were identified to have type 1 diabetes. Serum samples from 109 of these pregnancies were available for analysis (case subjects). Among 280 control subjects, in a computer-generated random sample among the non–case subjects in the cohort, 219 subjects had an available serum sample of sufficient quality for 25-OH D analysis. We analyzed the latest available serum sample taken during pregnancy from each woman in both case and control subjects, mainly from the last trimester (Table 1).

The study was approved by the regional committee for medical and health research ethics and by the data inspectorate.

Laboratory Analyses of 25-OH D

Sera were analyzed at the Hormone Laboratory at Oslo University Hospital, Aker, Norway, using a radioimmunoassay (DiaSorin, Stillwater, MN). The serum levels of 25-OH D are expressed as nanomoles per liter, and the reference range for the normal adult population is 37–131 nmol/L. The intra-assay coefficient of variation is 6%. The total coefficient of variation is 13% at low levels (38 nmol/L), 16% at middle levels (75 nmol/L), and 14% at high levels (148 nmol/L). The Hormone Laboratory participates in the following external quality assessment schemes that include 25-OH D determination: the Vitamin D External Quality Assessment Scheme and Labquality.

Statistical Analyses

Before initiating this study, we estimated (based on the expected number of cases in the cohort) that we would have at least 80% power to obtain a significant result with a two-tailed test for trend assuming a logit-linear dose response, if the true odds ratio (OR) comparing the upper and lower quartiles of 25-OH D was ≤0.3. Statistical analyses were carried out using SPSS version 15.0 (SPSS, Chicago, IL) and Stata version 11.0 (Stata, College Station, TX). The main analysis was conducted using logistic regression, with the 25-OH D divided into quartiles (derived from the values in the control group), and test for trend was obtained by including 25-OH D as a continuous variable. A 95% CI for the OR excluding 1.00 or a P value <0.05 was considered statistically significant. We adjusted for potential confounders by including these factors in the logistic regression model. As an additional analysis to assess the dose-response relationship, we plotted predicted values from logistic regression models with fractional polynomials with default settings in Stata version 11.[16]


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