Risk Factors for Developing Inflammatory Bowel Disease Within and Across Families with a Family History of IBD.

INTRODUCTION: A family history of inflammatory bowel disease [IBD] is the strongest risk factor for disease. However, some first-degree relatives (FDRs) will develop disease, while others will not. METHODS: Using the nationwide Danish National Patient Register, we examined risk factors in families with two or more affected FDRs. First, we compared exposures between siblings with and without IBD within the same family [within-family analysis]. Second, we compared exposures between individuals with and without IBD across all families [across-family analysis]. Exposures included sex, birth order, mode of delivery, antibiotics, personal and family history of immune-mediated diseases, gastrointestinal infections, and surgical history preceding diagnosis. Uni- and multivariable conditional logistic regression analyses were conducted. RESULTS: In the 'within-family analysis', 1669 families were included [1732 cases, 2447 controls]. Female sex (adjusted odds ratio [aOR]: 1.40, 95% confidence interval [CI] 1.23, 1.59), history of ankylosing spondylitis [aOR: 2.88, 95% CI 1.05, 7.91] and exposure to antibiotics [aOR: 1.28, 95% CI 1.02, 1.61] increased the risk for IBD. In the 'across-family analysis', 1254 cases and 37 584 controls were included, confirming an association with prior ankylosing spondylitis [aOR: 3.92, 95% CI 1.38, 11.12] and exposure to antibiotics [aOR: 1.29, 95% CI 1.04, 1.60]. Having two or more relatives [aOR: 6.26, 95% CI 1.34, 29.29] or a sibling with IBD [aOR: 1.36, 95% CI 1.18, 1.57] increased the risk of IBD. Appendectomy reduced the risk of ulcerative colitis [aOR: 0.32, 95% CI 0.14, 0.72]. CONCLUSION: In families with IBD, we identified risk factors for the unaffected FDR to develop disease. These findings provide an opportunity for counselling IBD relatives.

Metformin use is not associated with reduced risk of older onset inflammatory bowel disease: a Danish nationwide population-based study.

BACKGROUND: Metformin has pleiotropic effects including anti-inflammatory properties and effects on the gut microbiome. It is primarily used in the older population, where the occurrence of inflammatory bowel disease (IBD) is increasing. The aim of this study was to examine whether metformin protects against development of IBD. METHODS: In the setting of a Danish nationwide population-based cohort, we conducted a nested case-control study using a new-user active comparator design. For each patient with IBD, we selected 10 IBD-free individuals matched on age, sex, and duration of follow-up. Conditional logistic regression was used to estimate odds ratios (ORs) of IBD. Adjustment included educational level, other immune-mediated inflammatory diseases, and use of dipeptidyl peptidase (DPP)-4 inhibitors and statins. RESULTS: Among 302,863 IBD-free new users of oral glucose-lowering drugs, we identified 1271 patients who developed IBD and 12,676 matched IBD-free individuals. Mean age at IBD diagnosis was 66 (SD, 11) years. We found no association between ever use of metformin and risk of IBD, Crohn's disease or ulcerative colitis, adjusted OR 0.95 (95% CI 0.78-1.15), 0.87 (95% CI 0.60-1.26), and 1.04 (95% CI 0.83-1.31), respectively. Neither was the cumulative dose of metformin or the treatment duration with metformin associated with risk of IBD. CONCLUSIONS: In this population-based study, we report that despite anti-inflammatory effects and a notable impact on the gut microbiome, metformin use is not associated with reduced risk of older onset IBD.

Socioeconomic inequalities in the incidence of alcohol-related liver disease: A nationwide Danish study.

BACKGROUND: There is socio-economic inequality in total alcohol-related harm, but knowledge of inequality in the incidence of specific alcohol-related diseases would be beneficial for prevention. Registry-based studies with nationwide coverage may reveal the full burden of socioeconomic inequality compared to what can be captured in questionnaire-based studies. We examined the incidence of alcohol-related liver disease (ALD) according to socioeconomic status and age. METHODS: We used national registries to identify patients with an incident diagnosis of ALD and their socioeconomic status in 2009-2018 in Denmark. We computed ALD incidence rates by socioeconomic status (education and employment status) and age-group (30-39, 40-49, 50-59, 60-69 years) and quantified the inequalities as the absolute and relative difference in incidence rates between low and high socioeconomic status. FINDINGS: Of 17,473 patients with newly diagnosed ALD, 78% of whom had cirrhosis, 86% had a low or medium-low educational level and only 20% were employed. ALD patients were less likely to be employed in the 10 years prior to diagnosis than controls. The incidence rate of ALD correlated inversely with educational level, from 181 (95% CI, 167-197) to 910 (95% CI, 764-1086) per million person-years from the highest to the lowest educational level. By employment status, the incidence rate per million person-years was 211 (95% CI, 189-236) for employed and 3449 (95% CI, 2785-4271) for unemployed. Incidence rates increased gradually with age leading to larger inequalities in absolute numbers for older age-groups. Although ALD was rare in the younger age-groups, the relative differences in incidence rates between high and low socioeconomic status were large for these ages. The pattern of socioeconomic inequality in ALD incidence was similar for men and women. INTERPRETATION: This study showed substantial socioeconomic inequalities in ALD incidence for people aged 30-69 years. FUNDING: The study was supported by grants from the Novo Nordisk Foundation (NNF18OC0054612) and the Research Fund of Bispebjerg Hospital.

Risk of pancreatitis in patients with inflammatory bowel disease - a meta-analysis.

INTRODUCTION: Patients with inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are believed to be at increased risk of pancreatitis. The objective of the present study was to investigate the association between IBD and risk of pancreatitis in a systematic review and meta-analysis. METHODS: We conducted a systematic literature search in the PubMed and Embase databases. Data were extracted using predefined data fields, and risk of bias was assessed using the Risk of Bias Assessment tool for Non-randomized Studies. Random-effects meta-analyses were conducted. RESULTS: Four studies with acute pancreatitis as outcome met the eligibility criteria. The overall estimated risk ratio revealed an increased risk for acute pancreatitis in patients with IBD of 2.78 (95% confidence interval (CI): 2.40-3.22). The risk ratio was increased for both CD and UC, with estimated risk ratios of 3.62 (95% CI: 2.99-4.38) and 2.24 (95% CI: 1.85-2.71), respectively. No studies meeting the eligibility criteria had chronic pancreatitis as outcome. CONCLUSIONS: The risk of acute pancreatitis is increased in patients with IBD and higher for patients with CD. Due to the observational design of the studies included in our meta-analysis, the mechanisms underlying the increased risk of pancreatitis are unknown and remain to be investigated. Studies of the risk of chronic pancreatitis among patients with IBD are warranted. FUNDING: This work was supported by a grant from the Novo Nordisk Foundation (NNF16OC0022586). The funder had no role in the study design, collection, analysis, interpretation of the data, or the writing of the manuscript. TRIAL REGISTRATION: not relevant.

Anti-tumour necrosis factor-α therapy and recurrent or new primary cancers in patients with inflammatory bowel disease, rheumatoid arthritis, or psoriasis and previous cancer in Denmark: a nationwide, population-based cohort study.

BACKGROUND: Safety of anti-tumour necrosis factor-α (TNFα) therapy in people with a history of cancer and with an immune-mediated disease is unknown. We aimed to assess the risk of recurrence of initial cancer or development of a new primary cancer after treatment with anti-TNFα therapy. METHODS: In this Danish, population-based cohort study we recruited adults (≥18 years) with inflammatory bowel disease (IBD), rheumatoid arthritis, or psoriasis and a primary cancer diagnosed between Jan 1, 1999 and Dec 31, 2016. Patients were recruited from the prospectively recorded Danish National Patient Registry and the Danish Cancer Registry. Participants were matched 1:10 between the treatment group who received anti-TNFα therapy and the control group (no anti-TNFα therapy) and we excluded individuals with a cancer diagnosed before their first anti-TNFα treatment (or before matching date for controls), individuals diagnosed with IBD, rheumatoid arthritis, or psoriasis after anti-TNFα initiation (or respective match date for controls), and individuals who received anti-TNFα with fewer than five matched controls. Using adjusted Cox proportional hazards regression, we estimated the primary outcome of development of recurrent or new primary cancer in patients who received anti-TNFα therapy compared with patients who did not receive this therapy, matched by sex, immune-mediated disease type, cancer type, and time from initial cancer diagnosis to first anti-TNFα registration. FINDINGS: Overall, 25 738 patients with immune-mediated disease and a history of cancer were identified. 434 patients who received anti-TNFα therapy after their initial cancer were matched to 4328 patients in the control group. During 18 752 person-years (median 5·6 years [IQR 2·8-7·9]) of follow up, 635 individuals developed recurrent or new primary cancer, 72 of whom had received anti-TNFα therapy and 563 of whom were in the control group. The median time between anti-TNFα treatment and recurrent or new primary cancer diagnosis was 2·8 years (IQR 1·7-5·4). The incidence of recurrent or new primary cancer development was 30·3 cases (95% CI 24·0-38·2) per 1000 person-years in the anti-TNFα treatment group and 34·4 cases (31·7-37·3) per 1000 person-years in the control group, yielding an adjusted hazard ratio of 0·82 (95% CI 0·61-1·11). INTERPRETATION: Use of anti-TNFα therapy was not associated with recurrent or new primary cancer development in patients with previous cancer. Timing of anti-TNFα therapy after an initial cancer diagnosis did not influence recurrent or new primary cancer development. This observation might guide clinical decision making among providers treating immune-mediated diseases with anti-TNFα medications. FUNDING: None.

Childhood growth and risk of inflammatory bowel disease: a population-based study of 317,030 children.

Background: Growth in childhood is associated with later development of autoimmune diseases and cancer, but the impact of growth on risk of inflammatory bowel disease (IBD) remains unknown. We conducted a population-based cohort study to examine whether birth weight, childhood height, or changes in height associated with later risk of IBD. Methods: Our cohort consisted of 317,030 children from the Copenhagen School Health Records Register (born 1930-1989) with height repeatedly measured from age 7 to 13 and with data on birth weight on a subset. Through linkage to the Danish National Patients Register, cases of IBD were identified. Cox proportional hazard regression was used to examine associations between measures of childhood growth and risk of IBD. Results: During more than 9 million years of follow-up, 1612 individuals were diagnosed with Crohn's disease (CD) and 2,640 with ulcerative colitis (UC). Birth weight and childhood heights were not associated with subsequent risk of CD or UC (HRs close to 1.00). Childhood growth from 7 to 10 years (CD: HR, 1.00; 95% CI, 0.85-1.18; UC: HR, 0.92; 95% CI, 0.81-1.05) and 10 to 13 years (CD: HR, 1.02; 95% CI, 0.89-1.17; UC: HR, 0.95; 0.85-1.05) did not associate with risk of IBD either. Conclusion: In this large population-based cohort study, birth weight and childhood growth did not influence risk of IBD, which contrasts with observations in other chronic diseases. Thereby, the study also suggests that pre-clinical effects of adult IBD are not measurable in childhood and that childhood risk factors for IBD do not influence growth.

Body mass index in young men and risk of inflammatory bowel disease through adult life: A population-based Danish cohort study.

Body mass index (BMI) is associated with increased future risk of inflammatory bowel disease(IBD) particularly Crohn's disease(CD), where associations with high and low BMI have been observed. Most studies are based on adult women. We aimed to explore the impact of BMI in men entering adult life on their long-term risk of developing IBD. A total of 377,957 men born during 1939-1959, with BMI measured at draft boards at mean age 19, were followed from 1977, or time of examination, to end of 2015. Risk of IBD was assessed using Cox regression. During 13 million person-years of follow-up, 1,523 developed CD and 3,323 UC. Using normal weight as reference, for CD the following HRs were observed: BMI < 18.5, 1.35; 95% CI, 1.12-1.62, BMI 25-29.9; 0.83; 95% CI, 0.68-1.02. and BMI > 30 1.20; 95% CI, 0.75-1.90). The increased risk of CD in underweight was maintained up until age 60 not explained by known effects of smoking. For UC, minor inverse associations were observed. Restricted cubic splines revealed a U-shape association between BMI and CD, but not UC. Low BMI of men entering adult life is associated with an increased incidence of CD and UC up to 40 years later.

Childhood body mass index and risk of inflammatory bowel disease in adulthood: a population-based cohort study.

BACKGROUND: The increasing incidence of inflammatory bowel disease (IBD) in western countries has led to the hypothesis that obesity-related inflammation could play a role in the etiology of IBD. However, this hypothesis lacks confirmation in studies of individuals prior to the typical onset of IBD in young adulthood. METHODS: In a cohort of 316,799 individuals from the Copenhagen School Health Records Register (CSHRR), we examined whether BMI at ages 7 through 13 years was associated with later IBD. Linking the CSHRR to the Danish National Patient Register, we identified cases of Crohn's disease (CD) and ulcerative colitis (UC) diagnosed during follow-up. Cox regression was used to estimate the hazard ratios (HR) with 95% confidence intervals. RESULTS: During 10 million person-years of follow-up, 1500 individuals were diagnosed with CD and 2732 with UC. At all examined ages, a 1 unit increase in BMI z-score was associated with a significantly decreased risk of UC (HRs = 0.9) and with a significantly increased risk of CD when diagnosed before age 30 (HRs = 1.2). We observed no associations between changes in BMI z-score between 7 and 13 years and later risk of CD or UC. CONCLUSION: We found a direct association between childhood BMI and CD diagnosed before 30 years of age, and an inverse association between childhood BMI and UC irrespective of age. Our results support the previous hypotheses of obesity being a risk factor for CD, and suggest that childhood underweight might be a risk factor for UC.

Neonatal Vitamin D Levels in Relation to Risk of Overweight at 7 Years in the Danish D-Tect Case-Cohort Study.

BACKGROUND: Vitamin D level in pregnancy may be associated with risk of overweight in the offspring later in life. METHODS: In a case-cohort study based on Danish biobanks and registers we examined the association between 25-hydroxy-vitamin D (25(OH)D) level at birth and overweight at 7 years. Cases of overweight (n = 871) were randomly selected among 7-year-old children from the Copenhagen School Health Records Register (CSHRR) with a BMI above the 90th percentile. The cohort (n = 1,311) was a random sample selected among all Danish children born during the same period. Neonatal 25(OH)D was measured in dried blood spots. RESULTS: 25(OH)D3 exhibited the expected seasonal variation. Median level of 25(OH)D3 was 20.6 (11.9-33.3) nmol/l in the overweight group and 23.4 (13.5-34.3) nmol/l in the cohort. We found no association between neonatal 25(OH)D3 level and risk of overweight at age 7 years, neither in the crude model (OR (CI) 1.00 (0.99; 1.00)) nor in a model adjusted for maternal ethnicity, educational level, civil status, parity, season and year of birth, and offspring ponderal index (OR (CI) 1.00 (0.99; 1.01)). CONCLUSION: Risk of overweight at 7 years of age was not associated with vitamin D level at birth.

No evidence of seasonality of birth in adult type 2 diabetes in Denmark.

AIMS/HYPOTHESIS: The season of birth might influence prenatal circumstances, which may influence the risk of developing type 2 diabetes. The aim of this study was to determine whether the diagnosis of type 2 diabetes in Denmark changed with the season of birth. METHODS: This study used data from the population-based Copenhagen School Health Records Register (CSHRR) that includes schoolchildren born between 1930 and 1989. Via a personal identification number, the CSHRR was linked to the National Patient Register containing hospital discharge diagnoses since 1977. The effect of seasonal variation in birth on the risk of type 2 diabetes was assessed using Cox regression, with month or season of birth as the predictor. The underlying time variable was age, and follow-up started in 1977 or at age 30 years. RESULTS: The study population consisted of 223,099 people, of whom 12,486 developed adult type 2 diabetes. Using January as the reference month, the risk of type 2 diabetes by month of birth was not statistically different for any of the 11 comparative birth months. Grouping month of birth into seasons (spring was the reference) gave essentially similar results, showing no difference in the risk of type 2 diabetes for any season. Repeating the analysis by sex, birth cohort and birthweight categories revealed no associations. CONCLUSIONS/INTERPRETATION: The risk of adult type 2 diabetes was not associated with month of birth in a large Danish population-based study. The results suggest that the causes of seasonality in birthweight are not causes of type 2 diabetes.

Secular trends in seasonal variation in birth weight.

BACKGROUND: Many environmental factors have been shown to influence birth weight (BW) and one of these are season of birth. AIM: The aim of the present study was to investigate the seasonal variation in BW in Denmark during 1936-1989, and to see if the variation could be explained by sunshine exposure during pregnancy. METHODS: The study population was selected from the Copenhagen School Health Records Register and included 276 339 children born between 1936 and 1989. Seasonal variation was modeled using a non-stationary sinusoidal model that allowed the underlying trend in BW and the amplitude and phase of the yearly cycles to change. RESULTS: There was a clear seasonal pattern in BW which, however, changed gradually across the study period. The highest BWs were seen during fall (September - October) from 1936 to 1963, but a new peak gradually grew from the early 1940s during early summer (May - June) and became the highest from 1964 to 1989. The amplitude of the fall peak started at 25.5 (95%CI 24.6; 25.9) grams and gradually disappeared. The amplitude of the early summer peak gradually arose from nothing to a peak of 18.6 (95%CI 17.7; 19.6) grams in the mid 1980s where it started to decrease again. Sunshine did not explain the seasonal variation in BW. CONCLUSION: There was a clear seasonal pattern in BW in Denmark 1936-1989, which however changed across the study period. Throughout the study period we observed a peak in BW during the fall, but gradually, starting in the early 1940s, an additional early summer peak emerged and became the highest from 1964 and onwards.

Predicted vitamin D status in mid-pregnancy and child allergic disease.

BACKGROUND: Vitamin D deficiency in pregnancy may be a risk factor for child allergic disease. However, less is known about disease risk across different levels of vitamin D. OBJECTIVE: We aimed to examine the relation between a maternal vitamin D prediction score and child allergic disease. METHODS: A total of 32,456 pregnant women were enrolled in the Danish National Birth Cohort (1996-2003) and had data on a validated vitamin D prediction score based on 1497 mid-pregnancy plasma 25(OH)D samples. Child allergic disease was assessed at 18 months and at 7 years using questionnaire data and national registry extracts. We used multivariable log-binomial models to quantify risk ratios (RR) and 95% CI. Plasma 25(OH)D was examined in a stability analysis. RESULTS: Median (IQR) vitamin D prediction score was 58.7 (49.2-69.0) nmol/l. In main analysis, there was no association between vitamin D prediction score examined in quintiles or by restricted categories (≥75 nmol/l and <25 nmol/l vs. 25-74.9 nmol/l) and child allergic disease. However, maternal vitamin D prediction score ≥100 nmol/l(vs. 50-79.9 nmol/l) was associated with increased risks of child asthma at 18 months (RR: 1.36, 95% CI: 1.02, 1.80) and asthma by hospital admission (RR: 1.65, 95% CI: 1.04, 2.62). For vitamin D prediction score <25-30 nmol/l, there were increased risks of child asthma at 18 months and by hospital admission and medication prescription at age 7, although these findings were not robust to covariate adjustment. Similar results were found for plasma 25(OH)D. CONCLUSIONS: Our study provided little evidence for an association between maternal vitamin D prediction score and child allergic disease for scores ≥75 nmol/l. However, increased risks were observed for vitamin D prediction score ≥100 nmol/l. These associations are hypothesis generating and would need to be replicated in other cohorts.

Does prenatal exposure to vitamin D-fortified margarine and milk alter birth weight? A societal experiment.

The present study examined whether exposure to vitamin D from fortified margarine and milk during prenatal life influenced mean birth weight and the risk of high or low birth weight. The study was based on the Danish vitamin D fortification programme, which was a societal intervention with mandatory fortification of margarine during 1961-1985 and voluntary fortification of low-fat milk between 1972 and 1976. The influence of prenatal vitamin D exposure on birth weight was investigated among 51 883 Danish children, by comparing birth weight among individuals born during 2 years before or after the initiation and termination of vitamin D fortification programmes. In total, four sets of analyses were performed. Information on birth weight was available in the Copenhagen School Health Record Register for all school children in Copenhagen. The mean birth weight was lower among the exposed than non-exposed children during all study periods (milk initiation - 20·3 (95 % CI - 39·2, - 1·4) g; milk termination - 25·9 (95 % CI - 46·0, - 5·7) g; margarine termination - 45·7 (95 % CI - 66·6, - 24·8) g), except during the period around the initiation of margarine fortification, where exposed children were heavier than non-exposed children (margarine initiation 27·4 (95 % CI 10·8, 44·0) g). No differences in the odds of high (>4000 g) or low ( < 2500 g) birth weight were observed between the children exposed and non-exposed to vitamin D fortification prenatally. Prenatal exposure to vitamin D from fortified margarine and milk altered birth weight, but the effect was small and inconsistent, reaching the conclusion that vitamin D fortification seems to be clinically irrelevant in relation to fetal growth.

Vitamin D intake in mid-pregnancy and child allergic disease - a prospective study in 44,825 Danish mother-child pairs.

BACKGROUND: Past studies suggest that maternal vitamin D intake during pregnancy may protect against child wheeze but studies on asthma are limited. Our objective was to examine the relation between intake of vitamin D in mid-pregnancy and child asthma and allergic rhinitis at 18 months and 7 years. METHODS: We examined data from 44,825 women enrolled during pregnancy in the longitudinal Danish National Birth Cohort (1996-2002). We estimated vitamin D intake from diet and supplements based on information from a validated food frequency questionnaire completed in gestational week 25. At 18 months, we evaluated child asthma using data from phone interviews. We assessed asthma and allergic rhinitis by self-report at age 7 and asthma by using records from national registries. Current asthma at age 7 was defined as lifetime asthma diagnosis and wheeze in the past 12 months. We calculated multivariable risk ratios with 95% CIs comparing highest vs. lowest quintile of vitamin D intake in relation to child allergic disease outcomes. RESULTS: The median (5%-95%ile) intake of total vitamin D was 11.7(3.0-19.4) µg/day (68% from supplements). In multivariable analysis, mothers in the highest (vs. lowest) quintile of total vitamin D intake were less likely to have children classified with current asthma at 7 years (Q5 vs. Q1: 0.74, 95% CI: 0.56, 0.96, P = 0.02) and they were less likely to have children admitted to the hospital due to asthma (Q5 vs. Q1: 0.80, 95% CI: 0.64, 1.00, P = 0.05). We found no associations with child asthma at 18 months or with allergic rhinitis at 7 years. CONCLUSIONS: Our findings suggest a weak inverse relationship between high total vitamin D and asthma outcomes in later, but not early, childhood. The data did not suggest a clear threshold of vitamin D intake above which risk of asthma was reduced.

The influence of early exposure to vitamin D for development of diseases later in life.

BACKGROUND: Vitamin D deficiency is common among otherwise healthy pregnant women and may have consequences for them as well as the early development and long-term health of their children. However, the importance of maternal vitamin D status on offspring health later in life has not been widely studied. The present study includes an in-depth examination of the influence of exposure to vitamin D early in life for development of fractures of the wrist, arm and clavicle; obesity, and type 1 diabetes (T1D) during child- and adulthood. METHODS/DESIGN: The study is based on the fact that in 1961 fortifying margarine with vitamin D became mandatory in Denmark and in 1972 low fat milk fortification was allowed. Apart from determining the influences of exposure prior to conception and during prenatal life, we will examine the importance of vitamin D exposure during specific seasons and trimesters, by comparing disease incidence among individuals born before and after fortification. The Danish National databases assure that there are a sufficient number of individuals to verify any vitamin D effects during different gestation phases. Additionally, a validated method will be used to determine neonatal vitamin D status using stored dried blood spots (DBS) from individuals who developed the aforementioned disease entities as adults and their time and gender-matched controls. DISCUSSION: The results of the study will contribute to our current understanding of the significance of supplementation with vitamin D. More specifically, they will enable new research in related fields, including interventional research designed to assess supplementation needs for different subgroups of pregnant women. Also, other health outcomes can subsequently be studied to generate multiple health research opportunities involving vitamin D. Finally, the results of the study will justify the debate of Danish health authorities whether to resume vitamin D supplementation policies.

Sources and determinants of vitamin D intake in Danish pregnant women.

Vitamin D deficiency during pregnancy has been associated with the development of several adverse health outcomes, e.g., pre-eclampsia, gestational diabetes mellitus, preterm delivery, low birth weight, birth length, and bone mineral content. The aims of the present study were to estimate the intake and sources of vitamin D in Danish pregnant women and to examine potential determinants of vitamin D intake of the recommended level (10 µg per day). In 68,447 Danish pregnant women the mean ± SD for vitamin D intake was 9.23 ± 5.60 µg per day (diet: 3.56 ± 2.05 µg per day, supplements: 5.67 ± 5.20 µg per day). 67.6% of the women reported use of vitamin D supplements but only 36.9% reported use of vitamin D supplements of at least 10 µg. Supplements were the primary source of vitamin D for the two higher quartiles of total vitamin D intake, with diet being the primary source for the two lower quartiles. Determinants of sufficient total vitamin D intake were: high maternal age, nulliparity, non-smoking, and filling out of the Food Frequency Questionnaire (FFQ) during summer or fall. We propose that clinicians encourage vitamin D supplementation among pregnant women, with special focus on vulnerable groups such as the young, smokers and multiparous women, in order to improve maternal and fetal health both during and after pregnancy.