Jan Stener Jørgensen

Vitamin D insufficiency is associated with increased risk of first-trimester miscarriage in the Odense Child Cohort

BACKGROUNDnMiscarriage is the most common negative outcome of pregnancy, and identification of modifiable risk factors is potentially of great importance for public health. Low vitamin D concentrations in pregnancy are widespread worldwide, and vitamin D deficiency is implicated in immune cell regulation at the feto-maternal interface and several diseases of pregnancy.nnnOBJECTIVEnWe investigated whether 25-hydroxyvitamin D serum concentration was a modifiable risk factor for early miscarriage.nnnDESIGNnIn a prospective cohort study of 1683 pregnant women donating serum before gestational week 22, we investigated the association between maternal serum concentrations of serum 25-hydroxyvitamin D [25(OH)D] and the risk of subsequent miscarriage (n = 58).nnnRESULTSnThe adjusted hazard of first-trimester miscarriage was lower with higher 25(OH)D concentrations (HR: 0.98; 95% CI: 0.96, 0.99). Concentrations of 25(OH)D <50 nmol/L were associated with a >2-fold increased adjusted HR for miscarriage (HR: 2.50; 95% CI: 1.10, 5.69). Concentrations of 25(OH)D were not associated with an increased risk of second-trimester miscarriage.nnnCONCLUSIONSnWe found an association between 25(OH)D and first-trimester miscarriages, suggesting vitamin D as a modifiable risk factor for miscarriage. To test this hypothesis, randomized controlled trials should investigate the possible effect of vitamin D supplementation to increase 25(OH)D concentrations in early pregnancy, or before conception, to decrease risk of miscarriage. This trial was registered at clinicaltrials.gov as NCT02434900.

The Odense Child Cohort: Aims, Design, and Cohort Profile

BACKGROUNDnThe importance of the environment on the development of the fetus and infant throughout early life is increasingly recognised. To study such effects, biological samples and accurate data records are required. Based on multiple data collection from a healthy pregnant population, the Odense Childhood Cohort (OCC) study aims to provide new information about the environmental impact on child health by sequential follow-up to 18 years of age among children born between 2010 and 2012.nnnMETHODSnA total of 2874 of 6707 pregnancies (43%) were recruited between January 2010 and December 2012. Three hundred seventy-four have since left the study, leaving 2500 active families. The non-participants act as controls contributing data through local registries. Biological material, questionnaires, and registry data were compiled. Anthropometric data and other physical data were collected.nnnRESULTSnTwo thousand five hundred families actively participated in the study with 2549 children. Sixty-four peru2009cent of the fathers and 60% and 58% of the mothers, respectively, donated a blood sample at 10 and 28 weeks of gestation. On average, 69% completed questionnaires, 78% of the children were regularly examined, and had a blood sample taken (46%). The participating pregnant women differed from the non-participants in several respects: age, body mass index, smoking, parity, education, and ethnicity. The infants were comparable with respect to gender and mode of delivery.nnnCONCLUSIONSnThe OCC provides material for in-depth analysis of environmental and genetic factors that are important for child health and disease. Registry data from non-participating women and infants are available which ensures a high degree of comparable data.

Diagnosis of preeclampsia with soluble Fms–like tyrosine kinase 1/placental growth factor ratio: an inter–assay comparison

The angiogenic factor ratio soluble Fms-kinase 1 (sFlt-1)/placental growth factor (PlGF) is a novel diagnostic tool for preeclampsia. We compared the efficacy of the KRYPTOR (BRAHMS) automated assays for sFlt-1 and PlGF with the Elecsys (Roche) assays in a routine clinical setting. Preeclamptic women (nxa0=xa039) were included shortly after the time of diagnosis. Normotensive control pregnancies were matched by gestational age (nxa0=xa076). The KRYPTOR assays performed comparably or superior to Elecsys (sFlt-1/PlGF area under the curve 0.746 versus 0.735; Pxa0=xa0.09; for non-obese 0.820 versus 0.805, Pxa0=xa0.047). For early-onset preeclampsia, KRYPTOR area under the curve increased to 0.929 with a 100% specificity for preeclampsia at cut-off 85 and an 88.9% sensitivity for preeclampsia at cut-off 33. For women with preeclampsia and preterm delivery or Hemolysis, Elevated Liver enzymes, Low Platelet count (HELLP) syndrome, the KRYPTOR sFlt-1/PlGF ratio was manifold increased (Pxa0<xa0.01). The sFlt-1/PlGF ratio proved especially useful in early-onset preeclampsia, preeclampsia with preterm delivery or HELLP, and among non-obese women.

Metabolic effects of lifestyle intervention in obese pregnant women. Results from the randomized controlled trial 'Lifestyle in Pregnancy' (LiP).

The Lifestyle in Pregnancy intervention in obese pregnant women resulted in significantly lower gestational weight gain compared with the control group, but without improvement in rates of clinical pregnancy complications. The impact of the lifestyle intervention on metabolic measurements in the study participants is now reported.

Vitamin D depletion aggravates hypertension and target-organ damage.

Background We tested the controversial hypothesis that vitamin D depletion aggravates hypertension and target‐organ damage by influencing renin. Methods and Results Four‐week‐old double‐transgenic rats (dTGR) with excess angiotensin (Ang) II production due to overexpression of the human renin (hREN) and angiotensinogen (hAGT) genes received vitamin D‐depleted (n=18) or standard chow (n=15) for 3 weeks. The depleted group had very low serum 25‐hydroxyvitamin D levels (mean±SEM; 3.8±0.29 versus 40.6±1.19 nmol/L) and had higher mean systolic BP at week 5 (158±3.5 versus 134.6±3.7 mm Hg, P<0.001), week 6 (176.6±3.3 versus 162.3±3.8 mm Hg, P<0.01), and week 7 (171.6±5.1 versus 155.9±4.3 mm Hg, P<0.05). Vitamin D depletion led to increased relative heart weights and increased serum creatinine concentrations. Furthermore, the mRNAs of natriuretic peptides, neutrophil gelatinase‐associated lipocalin, hREN, and rRen were increased by vitamin D depletion. Regulatory T cells in the spleen and in the circulation were not affected. Ang metabolites, including Ang II and the counter‐regulatory breakdown product Ang 1 to 7, were significantly up‐regulated in the vitamin D‐depleted groups, while ACE‐1 and ACE‐2 activities were not affected. Conclusions Short‐term severe vitamin D depletion aggravated hypertension and target‐organ damage in dTGR. Our data suggest that even short‐term severe vitamin D deficiency may directly promote hypertension and impacts on renin‐angiotensin system components that could contribute to target‐organ damage. The findings add to the evidence that vitamin D deficiency could also affect human hypertension.

Mental disorders in motherhood according to prepregnancy BMI and pregnancy-related weight changes—A Danish cohort study

BACKGROUNDnPrevious studies have shown an association between prepregnancy BMI and postpartum depression, but little is known about this association beyond one year postpartum and the influence of postpartum weight retention (PPWR).nnnMETHODSnWe used data from 70355 mothers from the Danish National Birth Cohort to estimate the associations between maternal prepregnancy BMI and PPWR, respectively, and incident depression/anxiety disorders until six years postpartum. Outcome was depression or anxiety diagnosed clinically or filling a prescription for an antidepressant. Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Follow-up started at the day of delivery. For the analysis regarding PPWR, follow-up started six months postpartum.nnnRESULTSnUnderweight, overweight and obesity were associated with depression and/or anxiety disorders when compared to normal-weight, though the associations were attenuated after adjustments (HR 1.24 [95% CI 1.06-1.45], 1.05 [95% CI 0.96-1.15] and 1.07 [95% CI 0.95-1.21] for underweight, overweight and obese, respectively). Compared to mothers who had returned to their prepregnancy BMI, risk of depression/anxiety disorders was increased for mothers, who from prepregnancy to 6 months postpartum experienced either weight loss >1 BMI unit (HR 1.19 [95% CI 1.06-1.25]), weight gain of 2-3 BMI units (HR 1.23 [95% CI 1.08-1.40]), or weight gain of ≥3 BMI units (HR 1.21 [95% CI 1.05-1.40]).nnnLIMITATIONnCausal direction and mechanisms behind the associations are largely unknown.nnnCONCLUSIONSnLow prepregnancy body weight and postpartum weight gain or loss are associated with occurrence of depression and anxiety disorders.

Providing information about prenatal screening for Down syndrome: a systematic review

In recent decades there have been advances in the options for prenatal screening. Screening programmes for Down syndrome are well established in many countries. It is important that pregnant women are well informed about the benefits and risks of screening. A variety of interventions has been introduced to support pregnant women in their choice of prenatal screening.

Prevalence of substance abuse in pregnancy among Danish women

There are few recent data on the prevalence of substance abuse among Danish pregnant women. During 2013, in the Region of Southern Denmark, a cross‐sectional, anonymous, screening‐based study was conducted among pregnant women attending for routine ultrasound scan at 12 weeks gestation. The women submitted a urine sample and completed a short questionnaire. Urine samples were tested for opiates, cannabis, benzodiazepines, cocaine, methadone, amphetamine and methamphetamine. Positive samples underwent repeat analysis for confirmation. Of 690 pregnant women, 88.1% participated. Overall, 3.6% of women had a positive urine sample confirmed by repeated analysis. The age distribution in women with positive samples did not differ from the entire cohort. Our findings indicate a larger prevalence than anticipated, and that a substantial number of pregnant women with substance abuse are not appropriately referred to the focused specialist center for such women at risk.

The safety of tocolytics used for the inhibition of preterm labour

ABSTRACT Introduction: Preterm birth is the major cause of neonatal mortality and morbidity worldwide and a huge cost burden on healthcare. Between 22 and 26 completed weeks of gestation, for every day that delivery is delayed, survival increases by 3%. Areas covered: Following a systematic review of the literature, we have provided an overview of the use of tocolytics for the prevention of preterm birth and have examined the fetal and maternal adverse effects of the various tocolytic agents currently in use. Expert opinion: No tocolytic currently in use was developed specifically to treat preterm labour so most have multi-organ side effects. β2-agonists are relatively safe for the fetus but have rare and potentially serious maternal adverse effects. In contrast, prostaglandin synthetase inhibitors have potentially serious side effects for the fetus and neonate but have mild maternal gastrointestinal side effects. In Europe, the choice of first line therapy is either atosiban or nifedipine. The evidence base for atosiban is much more robust than for nifedipine. While their efficacy is similar, atosiban has placebo level side effects and is safer than nifedipine but is much more expensive.

The association between angiogenic markers and fetal sex: implications for preeclampsia research

OBJECTIVEnCurrent research suggests sexual dimorphism between the male and female fetoplacental units, but with unknown relevance for preeclampsia. We investigated the association between fetal sex and concentrations of the angiogenic markers soluble Fms-like kinase 1 (sFlt-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio in first and second-third trimester in women with/without preeclampsia, and the impact of fetal sex on the prognostic value of angiogenic markers for preeclampsia.nnnSTUDY DESIGNnObservational study in a prospective, population-based cohort of 2110 singleton pregnancies with 150 preeclampsia cases.nnnRESULTSnHigher sFlt-1 concentrations were observed for women carrying female fetuses in first trimester (all, 1107.65 vs. 992.27pg/ml; preeclampsia cases, 1118.79 vs. 934.49pg/ml, p<0.05) and in second-third trimester (all, 1130.03 vs. 1043.15pg/ml; preeclampsia, 1480.30 vs. 1152.86pg/ml, p<0.05), with similar findings for the sFlt-1/PlGF ratio concentrations in first (29.67 vs. 27.39 p<0.05) and second-third trimester (3.56 vs. 3.22, p<0.05). In first trimester, log transformed concentrations of PlGF, sFlt-1 and sFlt-1/PlGF (all participants) and sFlt-1 (preeclampsia cases) associated with fetal sex in adjusted analyses (p<0.05). In second-third trimester, only log(sFlt-1) associated with fetal sex (all, p=0.028; preeclampsia, p=0.067) In receiver operating curve analysis, prediction of early-onset preeclampsia by sFlt-1/PlGF tended to be superior in pregnancies with female vs. male fetuses (p=0.06).nnnCONCLUSIONnSexual dimorphism was observed for concentrations of angiogenic markers. Female fetal sex was associated to higher sFlt-1 and sFlt-1/PlGF ratio concentrations in both healthy pregnancies and women developing preeclampsia. Fetal sex should be considered in research and clinical use of angiogenic markers.