Vitamin D insufficiency among Danish pregnant women-Prevalence and association with adverse obstetric outcomes and placental vitamin D metabolism.

INTRODUCTION: In pregnancy, vitamin D deficiency is associated with increased risk of fetal growth restriction and preeclampsia. The underlying mechanisms are not known, but placental dysfunction is believed to play a role. In a Danish population, where health authorities recommend a 10 µg/day vitamin D supplement during pregnancy, we explored current use of vitamin D supplements and vitamin D status. In term placentas, alterations in vitamin D metabolism and placental growth, evaluated by the key placental growth factor pregnancy-associated plasma protein-A (PAPP-A), and their relation to vitamin D insufficiency were investigated. MATERIAL AND METHODS: We included 225 randomly selected pregnant women attending a nuchal translucency scan at gestational weeks 11-14. Information on use of vitamin D supplements and body mass index (BMI) at inclusion was obtained using self-reported questionnaires. Plasma 25-hydroxyvitamin D was measured at inclusion and correlated with pregnancy outcomes and placental biology, as judged by expression of PAPP-A and enzymes involved in vitamin D metabolism (CYP24A1, CYP27B1) in term placentas. RESULTS: Vitamin D supplements were used by 92% of the women, but 42% were vitamin D insufficient (plasma 25-hydroxyvitamin D <75 nmol/L). Eleven women with singleton pregnancies developed fetal growth restriction or preeclampsia. In this small subset, first-trimester mean plasma 25-hydroxyvitamin D was lower in women who developed fetal growth restriction (43 ± 33nmol/L; n = 3; P = .006) and there was a tendency towards lower plasma 25-hydroxyvitamin D among women who developed preeclampsia (65 ± 19 nmol/L; n = 8; P = .08) in third trimester compared with uncomplicated pregnancies (79 ± 22 nmol/L; n = 187). In term placentas, PAPP-A expression was lower among participants with first-trimester vitamin D insufficiency (P = .009; n = 30) but no correlation was found between plasma 25-hydroxyvitamin D and mRNA expression of CYP24A1 (P = .67) and CYP27B1 (P = .34). BMI was negatively correlated with plasma 25-hydroxyvitamin D (P = .03) and positively correlated with placental mRNA expression of CYP24A1 (P = .003; n = 30). CONCLUSIONS: Despite high compliance with official guidelines regarding vitamin D supplements, vitamin D insufficiency was frequent and the findings indicate that vitamin D insufficiency may affect placental growth. High BMI was associated with vitamin D insufficiency and increased placental vitamin D turnover, but further investigations are needed.

Accidental deaths in young people with epilepsy and psychiatric comorbidity-A Danish nationwide cohort study.

OBJECTIVE: The objective of this study was to investigate the accident-related mortality among people younger than 55 years of age with epilepsy compared with the general population and to study how psychiatric comorbidity influences this risk. METHODS: This is a population-based cohort study of individuals born in Denmark between 1960 and 2015 (n = 3, 665 616). Persons diagnosed with epilepsy and psychiatric disorders were identified in the Danish National Patient Register and the Danish Central Psychiatric Central Register. We estimated the hazard ratio (HR) with 95% confidence intervals (CIs) of accidental death in people with epilepsy compared with persons without epilepsy. RESULTS: We identified 61 330 persons (1.7%) diagnosed with epilepsy. Median age at end of follow-up was 27.8 years. In people with epilepsy, 5253 died during follow-up, 480 (9%) of whom died from accidents. Among people without epilepsy, 52 588 died during follow-up, of whom 1280 (2.4%) died from accidents. People with epilepsy had a 3.7-fold (95% CI 3.4-4.1) increased risk of accidental death compared with persons without epilepsy. When we adjusted for psychiatric disorders, the risk remained significantly elevated in people with epilepsy compared to people without epilepsy (adjusted HR [aHR] 2.44, 95% CI 2.22-2.69). When stratifying the analyses on epilepsy and psychiatric disorders, people with epilepsy and psychiatric disorders had an aHR of 4.95 (95% CI 3.82-6.41) when compared with persons without epilepsy and psychiatric disorders. SIGNIFICANCE: The risk of accidental death was increased in people with epilepsy and was particularly high among people with epilepsy with psychiatric comorbidity. The findings highlight the need for awareness and prevention strategies in people with epilepsy, especially in people with comorbid psychiatric disorders.

Use of stimulants, over-the-counter and prescription drugs among Danish pregnant women.

Using self-reports and blood samples from 225 unselected Danish first trimester pregnant women, the purpose of this study was to assess their use of stimulants, for example caffeine and nicotine as well as over-the-counter (OTC) and prescription drugs. According to self-reported information, 24% had used prescription drugs and 48% had used OTC drugs mainly acetaminophen (42%), 9.3% were habitual smokers, 44% stated a daily use of caffeinated beverages, and 1.3% used illegal drugs. Ultra-performance liquid chromatography with high-resolution time-of-flight mass spectrometry (UPLC-HR-TOFMS) analysis was performed on corresponding blood samples applying golden standards for use of UPLC-HR-TOFMS in forensic medicine. Traces of prescription drugs were detected in 5.3% of the samples and 8.9% contained OTC drugs (acetaminophen 7.1%). Traces of smoking were identified in 8.0%, caffeine in 83% and illegal drugs in 0.9%. These results indicate a substantial use of OTC drugs and caffeine among Danish pregnant women. Blood analysis indicated that many women could be unaware of their caffeine intake. As common substances may be associated with adverse pregnancy outcomes, healthcare professionals should inquire about such habits during pregnancy. The results also underline the need for more research into the molecular effects of such drugs on placental function and foetal development.