Postoperative orthostatic intolerance following fast-track unicompartmental knee arthroplasty: incidence and hemodynamics-a prospective observational cohort study.

BACKGROUND: Early postoperative mobilization is essential for early functional recovery but can be inhibited by postoperative orthostatic intolerance (OI). Postoperative OI is common after major surgery, such as total knee arthroplasty (TKA). However, limited data are available after less extensive surgery, such as unicompartmental knee arthroplasty (UKA). We, therefore, investigated the incidence of OI as well as cardiovascular and tissue oxygenation responses during early mobilization after UKA. METHODS: This prospective single-centre observational study included 32 patients undergoing primary UKA. Incidence of OI and cardiovascular and tissue oxygenation responses during mobilization were evaluated preoperatively, at 6 and 24 h after surgery. Perioperative fluid balance, bleeding, surgery duration, postoperative hemoglobin, pain during mobilization and opioid usage were recorded. RESULTS: During mobilization at 6 h after surgery, 4 (14%, 95%CI 4-33%) patients experienced OI; however, no patients terminated the mobilization procedure prematurely. Dizziness and feeling of heat were the most common symptoms. OI was associated with attenuated systolic and mean arterial blood pressure responses in the sitting position (all p < 0.05). At 24 h after surgery, 24 (75%) patients had already been discharged, including three of the four patients with early OI. Only five patients were available for measurements, two of whom experienced OI; one terminated the mobilization procedure due to intolerable symptoms. We observed no statistically significant differences in perioperative fluid balance, bleeding, surgery duration, postoperative hemoglobin, pain, or opioid usage between orthostatic intolerant and tolerant patients. CONCLUSIONS: The incidence of orthostatic intolerance after fast-track unicompartmental knee arthroplasty is low (~ 15%) and is associated with decreased orthostatic pressure responses. Compared to the previously described orthostatic intolerance incidence of ~ 40% following total knee arthroplasty, early orthostatic intolerance is uncommon after unicompartmental knee arthroplasty, suggesting a procedure-specific component. TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov; registration number: NCT04195360, registration date: 13.12.2019.

Orthostatic intolerance after acute mild hypovolemia: incidence, pathophysiologic hemodynamics, and heart-rate variability analysis-a prospective observational cohort study.

PURPOSE: Early postoperative mobilization can be hindered by orthostatic intolerance (OI). Postoperative OI has multifactorial pathogenesis, possibly involving both postoperative hypovolemia and autonomic dysfunction. We aimed to investigate the effect of mild acute blood loss from blood donation simulating postoperative hypovolemia, on both autonomic function and OI, thus eliminating confounding perioperative factors such as inflammation, residual anesthesia, pain, and opioids. METHODS: This prospective observational cohort study included 26 blood donors. Continuous electrocardiogram data were collected during mobilization and night sleep, both before and after blood donation. A Valsalva maneuver and a standardized mobilization procedure were performed immediately before and after blood donation, during which cardiovascular and tissue oxygenation variables were continuously measured by LiDCOrapid™ and Massimo Root™, respectively. The incidence of OI, hemodynamic responses during mobilization and Valsalva maneuver, as well as heart rate variability (HRV) responses during mobilization and sleep were compared before and 15 min after blood donation. RESULTS: Prior to blood donation, no donors experienced OI during mobilization. After blood donation, 6/26 (23%; 95% CI, 9 to 44) donors experienced at least one OI symptom. Three out of 26 donors (12%; 95% CI, 2 to 30) terminated the mobilization procedure prematurely because of severe OI symptoms. Cardiovascular and cerebral tissue oxygenation responses were reduced in patients with severe OI. After blood loss, HRV indices of total autonomic power remained unchanged but increased sympathetic and decreased parasympathetic outflow was observed during mobilization, but also during sleep, indicating a prolonged autonomic effect of hypovolemia. CONCLUSION: We describe a specific hypovolemic component of postoperative OI, independent of postoperative autonomic dysfunction, inflammation, opioids, and pain. STUDY REGISTRATION: ClinicalTrials.gov (NCT04499664); registered 5 August 2020.

RéSUMé: OBJECTIF: La mobilisation postopératoire précoce peut être entravée par une intolérance orthostatique (IO). L'IO postopératoire a une pathogenèse multifactorielle, impliquant peut-être à la fois une hypovolémie postopératoire et un dysfonctionnement autonome. Notre objectif était d'étudier l'effet d'une légère perte de sang aiguë due au don de sang simulant une hypovolémie postopératoire, à la fois sur la fonction autonome et sur l'IO, éliminant ainsi les facteurs périopératoires confondants tels que l'inflammation, l'anesthésie résiduelle, la douleur et les opioïdes. MéTHODE: Cette étude de cohorte observationnelle prospective comprenait 26 personnes ayant donné leur sang. Des données d'électrocardiogramme continu ont été recueillies pendant la mobilisation et le sommeil nocturne, avant et après le don de sang. Une manœuvre de Valsalva et une procédure de mobilisation standardisée ont été réalisées immédiatement avant et après le don de sang, au cours desquelles les variables d'oxygénation cardiovasculaire et tissulaire ont été mesurées en continu avec les moniteurs LiDCOrapid™ et Massimo Root™, respectivement. L'incidence d'IO, les réponses hémodynamiques pendant la mobilisation et la manœuvre de Valsalva, ainsi que les réponses de variabilité de la fréquence cardiaque (VFC) pendant la mobilisation et le sommeil ont été comparées avant et 15 minutes après le don de sang. RéSULTATS: Avant le don de sang, aucune personne ayant fait un don de sang n'a ressenti d'IO pendant la mobilisation. Après le don de sang, 6/26 (23 %; IC 95 %, 9 à 44) des donneurs et donneuses ont manifesté au moins un symptôme d'IO. Trois personnes sur 26 (12 %; IC 95 %, 2 à 30) ont interrompu prématurément la procédure de mobilisation en raison de symptômes graves d'IO. Les réponses d'oxygénation des tissus cardiovasculaires et cérébraux ont été réduites chez les personnes atteintes d'IO sévère. Après la perte de sang, les indices de VFC de la puissance totale autonome sont demeurés inchangés, mais une augmentation du flux sympathique et une diminution du flux parasympathique ont été observées pendant la mobilisation, mais également pendant le sommeil, indiquant un effet autonome prolongé de l'hypovolémie. CONCLUSION: Nous décrivons une composante spécifique hypovolémique de l'IO postopératoire, indépendante du dysfonctionnement autonome postopératoire, de l'inflammation, des opioïdes et de la douleur. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT04499664); enregistrée le 5 août 2020.

Elevated blood pressure in pregnant women with gestational diabetes according to the WHO criteria: importance of overweight.

OBJECTIVE: Hypertension before and during early pregnancy has been associated with an increased risk of gestational diabetes mellitus (GDM) in retrospective analyses. We aimed to investigate the prospective blood pressure trackings in a population-based cohort of pregnant women, who were stratified according to their metabolic status in early third trimester. METHODS: We recorded blood pressure longitudinally during pregnancy in 1230 women from the Odense Child Cohort, Denmark. Fasting glucose and insulin were measured at gestational weeks 28-30. Metabolic status was evaluated according to the WHO 2013 threshold for GDM (GDM-WHO: fasting plasma glucose ≥5.1 mmol/l), insulin and homeostatic model assessment of insulin resistance (HOMA-IR). Relationships between metabolic status in third trimester and blood pressure trajectories were evaluated with adjusted linear mixed models. Trajectory was defined as blood pressure records in pregnancy per 4 weeks interval. RESULTS: Prevalence of GDM-WHO was 40% (498/1230). GDM-WHO was associated with 1.46 (0.22-2.70) mmHg higher SBP and 1.04 (0.07-2.01) mmHg higher DBP trajectories in the overall cohort. The associations were driven by differences in the overweight group, with 3.14 (1.05-5.25) mmHg higher SBP and 1.94 (0.42-3.47) mmHg higher DBP per 4 weeks in women with GDM-WHO compared with women without GDM-WHO. GDM-WHO was not associated with blood pressure in women with normal weight. Blood pressure trajectories were elevated across quartiles of insulin resistance. CONCLUSION: GDM-WHO is associated with higher blood pressure in pregnancy, and there appears to be a stronger effect in overweight women.

Orthostatic intolerance after fast-track knee arthroplasty: Incidence and hemodynamic pathophysiology.

BACKGROUND: Early postoperative mobilization can be hindered by orthostatic intolerance (OI) due to failed orthostatic cardiovascular regulation. The underlying mechanisms are not fully understood and specific data after total knee arthroplasty (TKA) are lacking. Therefore, we evaluated the incidence of OI and the cardiovascular response to mobilization in fast-track TKA. METHODS: This prospective observational cohort study included 45 patients scheduled for primary TKA in spinal anesthesia with a multimodal opioid-sparing analgesic regime. OI and the cardiovascular response to sitting and standing were evaluated with a standardized mobilization procedure preoperatively, and at 6 and 24 h postoperatively. Hemodynamic variables were measured non-invasively (LiDCO™ Rapid). Perioperative bleeding, fluid balance, surgery duration, postoperative hemoglobin, opioid use, and pain during mobilization were recorded. RESULTS: Eighteen (44%) and 8 (22%) patients demonstrated OI at 6 and 24 h after surgery, respectively. Four (10%) and 2 (5%) patients experienced severe OI and terminated the mobilization procedure prematurely. Dizziness was the most common OI symptom during mobilization at 6 h. OI was associated with decreased orthostatic responses in systolic, diastolic, mean arterial pressures, and heart rate (all p < .05), while severe OI patients demonstrated impaired diastolic, mean arterial pressures, heart rate, and cardiac output responses (all p < .05). No statistically significant differences in perioperative bleeding, fluid balance, surgery duration, postoperative hemoglobin, pain, or opioid use were observed between orthostatic tolerant and intolerant patients. CONCLUSION: Early postoperative OI is common following fast-track TKA. Pathophysiologic mechanisms include impaired orthostatic cardiovascular responses. The progression to severe OI symptoms appears to be primarily due to inadequate heart rate response.

Early pregnancy vitamin D status is associated with blood pressure in children: an Odense Child Cohort study.

BACKGROUND: Blood pressure in childhood tracks into later life. Vitamin D status in adults is associated with blood pressure, but the impact of vitamin D status in pregnancy and childhood on blood pressure still needs investigation. OBJECTIVE: We investigated whether fetal rather than current vitamin D status is associated with blood pressure in children. METHODS: In a prospective observational study within the population-based Odense Child Cohort (OCC), we examined serum 25-hydroxyvitamin D2+3 [s-25(OH)D] in early and late pregnancy, cord blood, and at 5 y age, and the associations with systolic and diastolic blood pressure (SBP/DBP) in the 5-y-old children (n = 1,677). Multiple regression models were adjusted for maternal country of origin, parity, smoking during pregnancy, 5-y height, and weight. Two-stage mixed effect modeling was performed, integrating all s-25(OH)D data from pregnancy and cord blood. RESULTS: The median (IQR) s-25(OH)D in early pregnancy, late pregnancy, the umbilical cord, and at 5 y was 65.5 (50.7-78.5), 78.5 (60.3- 95.8), 45.4 (31.1- 60.7), and 71.9 (54.6- 86.5) nmol/L, respectively. The mean ±SD 5-y SBP/DBP was 101.0/63.8 (7.1/5.9) mmHg. In adjusted analyses, a 10 nmol/L increase of s-25(OH)D in early pregnancy associated with a 0.3/0.2 mmHg lower SBP/DBP at 5 y (P < 0.05). Optimal s-25(OH)D (>75 nmol/L) in early pregnancy was associated with lower 5-y SBP and DBP, ß (95% CI) -1.45 (-2.6, -0.3), and -0.97 (-1.9, -0.1), compared with reference s-25(OH)D (50-74.9 nmol/L). Two-stage analysis combining early pregnancy, late pregnancy, and cord s-25(OH)D data showed an inverse association with 5-y SBP and DBP for boys (P < 0.025) with significant sex-difference for DBP (Pinteraction = 0.004). No associations were found between s-25(OH)D and 5-y BP above the 90th percentile. CONCLUSION: Early pregnancy s-25(OH)D concentrations, especially >75 nmol/L, were inversely associated with 5-y blood pressure in the offspring. A novel identified protective effect of optimal vitamin D levels in early pregnancy on offspring BP is suggested.

Validation and development of models using clinical, biochemical and ultrasound markers for predicting pre-eclampsia: an individual participant data meta-analysis.

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk is needed to plan management. OBJECTIVES: To assess the performance of existing pre-eclampsia prediction models and to develop and validate models for pre-eclampsia using individual participant data meta-analysis. We also estimated the prognostic value of individual markers. DESIGN: This was an individual participant data meta-analysis of cohort studies. SETTING: Source data from secondary and tertiary care. PREDICTORS: We identified predictors from systematic reviews, and prioritised for importance in an international survey. PRIMARY OUTCOMES: Early-onset (delivery at < 34 weeks' gestation), late-onset (delivery at ≥ 34 weeks' gestation) and any-onset pre-eclampsia. ANALYSIS: We externally validated existing prediction models in UK cohorts and reported their performance in terms of discrimination and calibration. We developed and validated 12 new models based on clinical characteristics, clinical characteristics and biochemical markers, and clinical characteristics and ultrasound markers in the first and second trimesters. We summarised the data set-specific performance of each model using a random-effects meta-analysis. Discrimination was considered promising for C-statistics of ≥ 0.7, and calibration was considered good if the slope was near 1 and calibration-in-the-large was near 0. Heterogeneity was quantified using I2 and τ2. A decision curve analysis was undertaken to determine the clinical utility (net benefit) of the models. We reported the unadjusted prognostic value of individual predictors for pre-eclampsia as odds ratios with 95% confidence and prediction intervals. RESULTS: The International Prediction of Pregnancy Complications network comprised 78 studies (3,570,993 singleton pregnancies) identified from systematic reviews of tests to predict pre-eclampsia. Twenty-four of the 131 published prediction models could be validated in 11 UK cohorts. Summary C-statistics were between 0.6 and 0.7 for most models, and calibration was generally poor owing to large between-study heterogeneity, suggesting model overfitting. The clinical utility of the models varied between showing net harm to showing minimal or no net benefit. The average discrimination for IPPIC models ranged between 0.68 and 0.83. This was highest for the second-trimester clinical characteristics and biochemical markers model to predict early-onset pre-eclampsia, and lowest for the first-trimester clinical characteristics models to predict any pre-eclampsia. Calibration performance was heterogeneous across studies. Net benefit was observed for International Prediction of Pregnancy Complications first and second-trimester clinical characteristics and clinical characteristics and biochemical markers models predicting any pre-eclampsia, when validated in singleton nulliparous women managed in the UK NHS. History of hypertension, parity, smoking, mode of conception, placental growth factor and uterine artery pulsatility index had the strongest unadjusted associations with pre-eclampsia. LIMITATIONS: Variations in study population characteristics, type of predictors reported, too few events in some validation cohorts and the type of measurements contributed to heterogeneity in performance of the International Prediction of Pregnancy Complications models. Some published models were not validated because model predictors were unavailable in the individual participant data. CONCLUSION: For models that could be validated, predictive performance was generally poor across data sets. Although the International Prediction of Pregnancy Complications models show good predictive performance on average, and in the singleton nulliparous population, heterogeneity in calibration performance is likely across settings. FUTURE WORK: Recalibration of model parameters within populations may improve calibration performance. Additional strong predictors need to be identified to improve model performance and consistency. Validation, including examination of calibration heterogeneity, is required for the models we could not validate. STUDY REGISTRATION: This study is registered as PROSPERO CRD42015029349. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 72. See the NIHR Journals Library website for further project information.

WHAT IS THE PROBLEM?: Pre-eclampsia, a condition in pregnancy that results in raised blood pressure and protein in the urine, is a major cause of complications for the mother and baby. WHAT IS NEEDED?: A way of accurately identifying women at high risk of pre-eclampsia to allow clinicians to start preventative interventions such as administering aspirin or frequently monitoring women during pregnancy. WHERE ARE THE RESEARCH GAPS?: Although over 100 tools (models) have been reported worldwide to predict pre-eclampsia, to date their performance in women managed in the UK NHS is unknown. WHAT DID WE PLAN TO DO?: We planned to comprehensively identify all published models that predict the risk of pre-eclampsia occurring at any time during pregnancy and to assess if this prediction is accurate in the UK population. If the existing models did not perform satisfactorily, we aimed to develop new prediction models. WHAT DID WE FIND?: We formed the International Prediction of Pregnancy Complications network, which provided data from a large number of studies (78 studies, 25 countries, 125 researchers, 3,570,993 singleton pregnancies). We were able to assess the performance of 24 out of the 131 models published to predict pre-eclampsia in 11 UK data sets. The models did not accurately predict the risk of pre-eclampsia across all UK data sets, and their performance varied within individual data sets. We developed new prediction models that showed promising performance on average across all data sets, but their ability to correctly identify women who develop pre-eclampsia varied between populations. The models were more clinically useful when used in the care of first-time mothers pregnant with one child, compared to a strategy of treating them all as if they were at high-risk of pre-eclampsia. WHAT DOES THIS MEAN?: Before using the International Prediction of Pregnancy Complications models in various populations, they need to be adjusted for characteristics of the particular population and the setting of application.

External validation of prognostic models predicting pre-eclampsia: individual participant data meta-analysis.

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-eclampsia using individual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting. METHODS: IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-eclampsia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-eclampsia as an outcome were included for validation. We reported the model predictive performance as discrimination (C-statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis. RESULTS: Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C-statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model's calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions appeared small and limited to probability thresholds between 5 and 7%. CONCLUSIONS: The evaluated models had modest predictive performance, with key limitations such as poor calibration (likely due to overfitting in the original development datasets), substantial heterogeneity, and small net benefit across settings. The evidence to support the use of these prediction models for pre-eclampsia in clinical decision-making is limited. Any models that we could not validate should be examined in terms of their predictive performance, net benefit, and heterogeneity across multiple UK settings before consideration for use in practice. TRIAL REGISTRATION: PROSPERO ID: CRD42015029349 .

Validation of hospital discharge diagnoses for hypertensive disorders of pregnancy.

INTRODUCTION: A correct diagnosis of preeclampsia and gestational hypertension is important for treatment and epidemiological studies. Changes in diagnostic criteria and underreporting in certain subsets of patients may hamper validity of the diagnoses. MATERIALS AND METHODS: We validated the discharge diagnoses of preeclampsia and gestational hypertension, which are reported to the Danish National Patient Registry, in a cohort of 2163 pregnant women by retrospective evaluation of electronic hospital data. RESULTS: A preeclampsia discharge diagnosis was found in 113 (5.2%) of the participants. After validation, significantly more patients fulfilled criteria for diagnosis of preeclampsia (n = 163, 7.5%, p = 0.002); more had severe preeclampsia, 14 (0.6%) vs. 70 (3.2%), p < 0.001 and gestational hypertension, 62 (2.9%) vs. 46 (2.1%), p = 0.12. The diagnostic sensitivity for preeclampsia by discharge diagnosis was 55.8%; severe preeclampsia 18.6%; gestational hypertension 39.1%. Corresponding positive predictive values were 80.5, 92.9 and 29.0%. Misclassification occurred in 4.3, 2.7 and 3.3%, respectively. Misclassification was more prevalent in obese compared to lean women (10% vs. 3.6%, p < 0.0001). CONCLUSIONS: Discharge diagnoses substantially underestimated the prevalence of preeclampsia, especially severe preeclampsia. Misclassification was most common in obese preeclamptic women. These findings depict the limitations associated with the direct use of discharge diagnoses of hypertensive disorders in pregnancy for research purposes.

Infant Gut Microbiota Development Is Driven by Transition to Family Foods Independent of Maternal Obesity.

The first years of life are paramount in establishing our endogenous gut microbiota, which is strongly affected by diet and has repeatedly been linked with obesity. However, very few studies have addressed the influence of maternal obesity on infant gut microbiota, which may occur either through vertically transmitted microbes or through the dietary habits of the family. Additionally, very little is known about the effect of diet during the complementary feeding period, which is potentially important for gut microbiota development. Here, the gut microbiotas of two different cohorts of infants, born either of a random sample of healthy mothers (n = 114), or of obese mothers (n = 113), were profiled by 16S rRNA amplicon sequencing. Gut microbiota data were compared to breastfeeding patterns and detailed individual dietary recordings to assess effects of the complementary diet. We found that maternal obesity did not influence microbial diversity or specific taxon abundances during the complementary feeding period. Across cohorts, breastfeeding duration and composition of the complementary diet were found to be the major determinants of gut microbiota development. In both cohorts, gut microbial composition and alpha diversity were thus strongly affected by introduction of family foods with high protein and fiber contents. Specifically, intake of meats, cheeses, and Danish rye bread, rich in protein and fiber, were associated with increased alpha diversity. Our results reveal that the transition from early infant feeding to family foods is a major determinant for gut microbiota development. IMPORTANCE The potential influence of maternal obesity on infant gut microbiota may occur either through vertically transmitted microbes or through the dietary habits of the family. Recent studies have suggested that the heritability of obesity may partly be caused by the transmission of "obesogenic" gut microbes. However, the findings presented here suggest that maternal obesity per se does not affect the overall composition of the gut microbiota and its development after introduction of complementary foods. Rather, progression in complementary feeding is found to be the major determinant for gut microbiota establishment. Expanding our understanding of the influence of complementary diet on the development and establishment of the gut microbiota will provide us with the knowledge to tailor a beneficial progression of our intestinal microbial community.

Early pregnancy angiogenic markers and spontaneous abortion: an Odense Child Cohort study.

BACKGROUND: Spontaneous abortion is the most commonly observed adverse pregnancy outcome. The angiogenic factors soluble Fms-like kinase 1 and placental growth factor are critical for normal pregnancy and may be associated to spontaneous abortion. OBJECTIVE: We investigated the association between maternal serum concentrations of soluble Fms-like kinase 1 and placental growth factor, and subsequent spontaneous abortion. STUDY DESIGN: In the prospective observational Odense Child Cohort, 1676 pregnant women donated serum in early pregnancy, gestational week <22 (median 83 days of gestation, interquartile range 71-103). Concentrations of soluble Fms-like kinase 1 and placental growth factor were determined with novel automated assays. Spontaneous abortion was defined as complete or incomplete spontaneous abortion, missed abortion, or blighted ovum <22+0 gestational weeks, and the prevalence was 3.52% (59 cases). The time-dependent effect of maternal serum concentrations of soluble Fms-like kinase 1 and placental growth factor on subsequent late first-trimester or second-trimester spontaneous abortion (n = 59) was evaluated using a Cox proportional hazards regression model, adjusting for body mass index, parity, season of blood sampling, and age. Furthermore, receiver operating characteristics were employed to identify predictive values and optimal cut-off values. RESULTS: In the adjusted Cox regression analysis, increasing continuous concentrations of both soluble Fms-like kinase 1 and placental growth factor were significantly associated with a decreased hazard ratio for spontaneous abortion: soluble Fms-like kinase 1, 0.996 (95% confidence interval, 0.995-0.997), and placental growth factor, 0.89 (95% confidence interval, 0.86-0.93). When analyzed by receiver operating characteristic cut-offs, women with soluble Fms-like kinase 1 <742 pg/mL had an odds ratio for spontaneous abortion of 12.1 (95% confidence interval, 6.64-22.2), positive predictive value of 11.70%, negative predictive value of 98.90%, positive likelihood ratio of 3.64 (3.07-4.32), and negative likelihood ratio of 0.30 (0.19-0.48). For placental growth factor <19.7 pg/mL, odds ratio was 13.2 (7.09-24.4), positive predictive value was 11.80%, negative predictive value was 99.0%, positive likelihood ratio was 3.68 (3.12-4.34), and negative likelihood ratio was 0.28 (0.17-0.45). In the sensitivity analysis of 54 spontaneous abortions matched 1:4 to controls on gestational age at blood sampling, the highest area under the curve was seen for soluble Fms-like kinase 1 in prediction of first-trimester spontaneous abortion, 0.898 (0.834-0.962), and at the optimum cut-off of 725 pg/mL, negative predictive value was 51.4%, positive predictive value was 94.6%, positive likelihood ratio was 4.04 (2.57-6.35), and negative likelihood ratio was 0.22 (0.09-0.54). CONCLUSION: A strong, novel prospective association was identified between lower concentrations of soluble Fms-like kinase 1 and placental growth factor measured in early pregnancy and spontaneous abortion. A soluble Fms-like kinase 1 cut-off <742 pg/mL in maternal serum was optimal to stratify women at high vs low risk of spontaneous abortion. The cause and effect of angiogenic factor alterations in spontaneous abortions remain to be elucidated.

The effects of water and dairy drinks on dietary patterns in overweight adolescents.

The aim was to investigate the effects of increased water or dairy intake on total intake of energy, nutrients, foods and dietary patterns in overweight adolescents in the Milk Components and Metabolic Syndrome (MoMS) study (n=173). Participants were randomly assigned to consume 1l/d of skim milk, whey, casein or water for 12 weeks. A decrease in the dietary pattern called Convenience Food, identified by principal component analysis, was observed during the intervention both in the water and dairy groups. Total energy intake decreased by 990.9 kJ/d (236.8 kcal/d) in the water group but was unchanged in the dairy group during intervention. To conclude, an extra intake of fluid seems to favourably affect the rest of the diet by decreasing the intake of convenience foods, including sugar-sweetened beverages. A low energy drink, such as water, seems advantageous considering the total energy intake in these overweight adolescents. This study is registered at clinicaltrials.gov (NCT00785499).

Prostasin and matriptase (ST14) in placenta from preeclamptic and healthy pregnant women.

OBJECTIVE: Preeclampsia is characterized by disturbed placentation, hypertension, proteinuria, and suppression of plasma renin, angiotensin II, and aldosterone. Regulated activity of tissue serine proteases, prostasin, and matriptase is necessary for normal placental development in mice. Prostasin activates the renal epithelial sodium channel. We hypothesized that preeclampsia is associated with low prostasin expression in placenta and spillover of prostasin into urine across the defect glomerular barrier. METHODS: In a cross-sectional study, 20 healthy pregnant women and 20 patients suspected of preeclampsia were included. Plasma and urine was obtained before delivery, and placental biopsies were taken immediately after delivery (mean gestational age: control 39 and preeclampsia 38 weeks). RESULTS: Patients with preeclampsia displayed lower levels of aldosterone in plasma and in spot urine normalized for creatinine (P = 0.0001). Prostasin, matriptase, hepatocyte growth factor activator inhibitor type 1 (HAI-1) and 2, and nexin-1 mRNA abundances were not different in placental tissue between groups. Prostasin mRNA in placenta correlated directly with nexin-1 and HAI-1 mRNA, but not with matriptase mRNA. Plasma prostasin and placental homogenate prostasin and nexin-1 protein levels did not differ between groups. Activated, arginine 614 (Arg614)-cleaved matriptase was not detectable in placentas. Western blotting showed significant elevated levels of prostasin in urine from preeclamptic patients that correlated with urine albumin. Placenta and plasma prostasin did not correlate to aldosterone or placental weight. CONCLUSION: Preeclampsia is not associated with altered prostasin in placenta or plasma at term, but with increased prostasin in urine. An impact of prostasin-matriptase on placental development is likely to be at the level of activity and not protein abundance.

It's harder for boys? Children's representations of their HIV/AIDS-affected peers in Zimbabwe.

This study examines whether children in rural Zimbabwe have differing representations of their HIV/AIDS-affected peers based on the gender of those peers. A group of 128 children (58 boys, 70 girls) aged 10-14 participated in a draw-and-write exercise, in which they were asked to tell the story of either an HIV/AIDS-affected girl child, or an HIV/AIDS-affected boy child. Stories were inductively thematically coded, and then a post hoc statistical analysis was conducted to see if there were differences in the themes that emerged in stories about girls versus stories about boys. The results showed that boys were more often depicted as materially deprived, without adult and teacher support, and heavily burdened with household duties. Further research is needed to determine whether the perceptions of the children in this study point to a series of overlooked challenges facing HIV/AIDS-affected boys, or to a culture of gender inequality facing HIV/AIDS-affected girls - which pays more attention to male suffering than to female suffering.

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

BACKGROUND: Miscarriage 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. OBJECTIVE: We investigated whether 25-hydroxyvitamin D serum concentration was a modifiable risk factor for early miscarriage. DESIGN: In 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). RESULTS: The 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. CONCLUSIONS: We 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.

Indicators of dietary patterns in Danish infants at 9 months of age.

BACKGROUND: It is important to increase the awareness of indicators associated with adverse infant dietary patterns to be able to prevent or to improve dietary patterns early on. OBJECTIVE: The aim of this study was to investigate the association between a wide range of possible family and child indicators and adherence to dietary patterns for infants aged 9 months. DESIGN: The two dietary patterns 'Family Food' and 'Health-Conscious Food' were displayed by principal component analysis, and associations with possible indicators were analysed by multiple linear regressions in a pooled sample (n=374) of two comparable observational cohorts, SKOT I and SKOT II. These cohorts comprised infants with mainly non-obese mothers versus infants with obese mothers, respectively. RESULTS: A lower Family Food score indicates a higher intake of liquid baby food, as this pattern shows transition from baby food towards the family's food. Infants, who were younger at diet registration and had higher body mass index (BMI) z-scores at 9 months, had lower Family Food pattern scores. A lower Family Food pattern score was also observed for infants with immigrant/descendant parents, parents who shared cooking responsibilities and fathers in the labour market compared to being a student, A lower Health-Conscious Food pattern score indicates a less healthy diet. A lower infant Health-Conscious Food pattern score was associated with a higher maternal BMI, a greater number of children in the household, a higher BMI z-score at 9 months, and a higher infant age at diet registration. CONCLUSIONS: Associations between infant dietary patterns and maternal, paternal, household, and child characteristics were identified. This may improve the possibility of identifying infants with an increased risk of developing unfavourable dietary patterns and potentially enable an early targeted preventive support.

Risk factors for developing post-traumatic stress disorder following childbirth: a systematic review.

BACKGROUND: Approximately 1-2% of women suffer from post-traumatic stress disorder (PTSD) postnatally. This review aims to elucidate how women at risk can be identified. METHODS: A systematic search of the published literature was carried out using the MEDLINE database (November 2003 to 29 October 2010) with both MeSH terms and free text. Thirty-one studies were considered appropriate for qualitative synthesis. Articles were included on the basis of (a) publication pertaining to PTSD following childbirth, (b) study carried out in Western Europe and (c) publication written in English. The results were primarily based on observational studies. The literature was thoroughly read and results were compiled. Furthermore, a novel quality rating system was employed to minimize the impact of bias. RESULTS: Subjective distress in labor and obstetrical emergencies were the most important risk factors. Infant complications, low support during labor and delivery, psychological difficulties in pregnancy, previous traumatic experiences, and obstetrical emergencies were identified as risk factors. CONCLUSIONS: We have identified factors both strongly associated and non-associated with PTSD following childbirth. While the literature is limited by methodological shortcomings, a hypothesis regarding the development of PTSD is outlined, and recommendations with respect to screening and future research are provided.