Objective: Preeclampsia is a major cause of morbidity and mortality in pregnancy and still lacking an early prediction. Oxylipins, auto- and paracrine signaling molecules derived from polyunsaturated fatty acids (PUFAs), are implicated in the pathogenesis. We performed oxylipin profiling and developed a novel prediction model for preeclampsia. Design and method: We measured eighty-one free circulating oxylipins derived from linoleic-, eicosapentaenoic-, docosahexaenoic- and arachidonic acids by Triple-Quad-Tandem mass spectrometry in serum collected at gestational week (GW) 7-12 in a cohort study (total, 90 cases, 608 matched controls) before clinical onset of maternal syndrome. The later arising preeclampsia phenotype was heterogeneous with predominantly mild, late-onset disease. Using a machine learning regression-decision tree approach, prediction models incorporated clinical data, angiogenic markers and oxylipins, compared with a model including only standard clinical variables in combination with sFlt-1 and PlGF, bio markers used to diagnose PE late in pregnancy. Results: A regression tree approach for predicting preeclampsia in first trimester including X (number) specific oxylipins demonstrated good predictive capacity in early pregnancy with sensitivity 71, specificity 99 and AUC 87. Conclusions: Placentally derived PUFA metabolites (oxylipins) substantially add to the known clinical and biochemical predictive parameters for preeclampsia. A regression-tree based approach including known clinical and biochemical parameters, blood pressure and key oxylipins is a promising tool for predicting preeclampsia already in the first trimester.

Abstract 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.

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. 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. Prior to blood donation, no donors experienced OI during mobilization. After blood donation, 6/26 (23

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.

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, beta (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 (P-interaction = 0.004). No associations were found between s-25(OH)D and 5-y BP above the 90(th) 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.

Objective: Hypertension before and during early pregnancy has been associated with an increased risk of gestational diabetes mellitus (GDM) in retrospective analyses. We investigated the prospective blood pressure patterns in a population-based cohort of pregnant women, who were stratified according to their metabolic status in early 3rd trimester. Research Design and Methods: We recorded blood pressure longitudinally during pregnancy in 1,230 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 World Health Organization (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 3rd trimester and blood pressure trajectories throughout pregnancy were evaluated with adjusted linear mixed models. Results: GDM-WHO prevalence was high, 40% (498/1,230). Significant associations between GDM-WHO and blood pressure were seen only in overweight women, with 2.48 (1.08; 3.88) mmHg higher systolic and 1.58 (0.57; 2.58) mmHg higher diastolic trajectories in women with GDM-WHO compared with differences of -0.38 (-1.51; 0.75) and 0.03 (-0.83; 0.89) mmHg in lean women with GDM-WHO. The associations were independent of progression to gestational hypertension. Blood pressure trajectories in pregnancy were elevated across insulin and HOMA-IR quartiles. Conclusions: GDM-WHO was associated with moderate elevations of blood pressure troughout pregnancy. The relationships were independent of progression to overt gestational hypertension, but largely modified by overweight status. Disclosure A. Birukov: None. R. Dechend: None. M. S. Andersen: None. D. Glintborg: None. M. B. Schulze: None. T. K. Jensen: None. L. B. Andersen: None. K. Kräker: None. E. Polemiti: None. B. L. Jensen: None. J. S. Joergensen: None. Funding German Ministry of Education and Research; State of Brandenburg (82DZD00302)

Abstract Background Nasal tracheal aspiration (NTA) is a frequently used diagnostic method to assess of infections in the lower airways. However, the validity of the method has not previously been compared to bronchoalveolar lavage (BAL) in non-intubated children with a lung disease. We hypothesised that NTA performed by health professionals using the nares vocal cord distance to be placed at the entrance of the trachea, will result in same finding of bacteria in the lower airways as the gold standard of BAL. Methods In a prospective study, 173 paired samples of NTA and BAL were obtained between June 2016 to August 2018. Samples were collected from all patients undergoing bronchoscopy with spontaneous breathing during general anaesthesia. This study compares the microbiological results from the cultures obtained by investigating complete concordance i.e. identical pathogenic bacteria and coherence i.e. absence or presence of pathogenic bacteria growth between NTA and BAL. Results Samples were collected in 164 patients, 158 children between 21 days and 18 years of age and six young adults still treated at the paediatric department. The overall similarity (complete agreement) was found in 49% [41–56], sensitivity was 35% [27–45], specificity was 66% [55–76], positive predictive value was 36% [27–46] and negative predictive value was 64% [54–64] concerning complete pathogenic bacteria concordance. If we only considered coherence growth of pathogenic bacteria, similarity was 71% [63–79], sensitivity was 74% [64–81], specificity was 66% [55–76], positive predictive value was 75% [65–82] and negative predictive value was 65% [54–75]. Patients with cystic fibrosis showed a similarity of 88% [73–95], a sensitivity of 92% [76–99], a specificity of 71% [36–95], a positive predictive value of 92% [76–99] and a negative predictive value of 71% [36–95] concerning coherence growth of pathogenic bacteria. Conclusion The study indicates that NTA compared to BAL as the gold standard is not clinically useful to assess positive findings of specific bacteria in the lower airway tract. Statistically significantly increased sensitivity and positive predictive value were found in cystic fibrosis patients concerning coherence growth. The clinical usage of NTA remains important as negative findings are of clinical value. However, BAL continues to be preferred as a significantly superior diagnostic tool.

Background: Exercise-induced laryngeal obstruction (EILO) is a common cause of exertional breathlessness and wheeze yet is frequently misdiagnosed as asthma. Insight regarding the demographic characteristics, laryngeal abnormalities and impact of EILO is currently limited, with data only available from individual centre reports. The aim of this work was to provide a broader perspective from a collaboration between multiple international expert centres. Methods: Five geographically distinct clinical paediatric and adult centres (3 Denmark, 1 UK, 1 USA) with an expertise in assessing unexplained exertional breathlessness completed database entry of key characteristic features for all cases referred with suspected EILO over a 5-year period. All included cases completed clinical asthma workup and continuous laryngoscopy during exercise (CLE) testing for EILO. Results: Data were available for 1007 individuals (n=713 female (71%)) with a median (range) age of 24 (8-76) years, and of these 586 (58%) were diagnosed with EILO. In all centres, EILO was frequently misdiagnosed as asthma; on average there was a 2-year delay to diagnosis of EILO, and current asthma medication was discontinued in 20%. Collapse at the supraglottic level was seen in 60%, whereas vocal cord dysfunction (VCD) was only detected/visualised in 18%. Nearly half (45%) of individuals with EILO were active participants in recreational-level sports, suggesting that EILO is not simply confined to competitive/elite athletes. Conclusion: Our findings indicate that key clinical characteristics and the impact of EILO/VCD are similar in globally distinct regions, facilitating improved awareness of this condition to enhance recognition and avoid erroneous asthma treatment.

Background: Previous studies of association between exposure to poly-and perfluoroalkyl substances (PFAS) and gestational hypertension (GH) and preeclampsia (PE) have shown conflicting results, but most dichotomized outcome and did not study continuous blood pressure (BP) changes. Objectives: To study the association between PFAS exposure in early pregnancy and maternal BP trajectories in pregnancy, gestational hypertension and preeclampsia. Methods: 1436 women were enrolled in the Odense Child Cohort in early pregnancy and had a serum sample drawn, from which perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) were measured using LC-MS/MS. Repeated BP measurements through pregnancy and information on PE were obtained from hospital files. Adjusted linear mixed models were used to investigate association between PFAS exposure and BP trajectory. Associations between PFAS and PE and GH were assessed by Cox proportional hazards model. Results: All women had measurable concentrations of PFAS. In all of many comparisons higher PFAS exposure (apart from PFHxS) was associated with higher systolic (SBP) and diastolic (DBP) blood pressures, although not all were significant, which is unlikely to be due to chance. After adjustment, each doubling in PFOS or PFOA exposure was associated with 0.47 mmHg (95% CI:-0.13; 1.08) and 0.36 mmHg (-0.19; 0.92) higher SBP; and 0.58 mmHg (0.13; 1.04) and 0.37 mmHg (-0.05; 0.79) higher DBP. No clear associations between PFAS exposure and PE or GH were found. Discussion: The magnitude of the association between PFAS exposure and BP might appear small, statistically non-significant and the possible clinical importance low. However, at a population level this may slightly shift the distribution of BP towards an increased incidence of GH. If BP increases in pregnancy, it may have long-term impact on health not only of the pregnant woman but also of her offspring.

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 I 2 and τ 2 . 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.

Background: Exercise-induced laryngeal obstruction (EILO) is an important cause of exertional breathlessness and wheeze. Epidemiological understanding of EILO remains unclear and arises largely from Scandinavian countries. We provide the first international perspective on the demographic characteristics, laryngeal abnormalities and impact of EILO. Methods: Retrospective database review (from 5 expert centres in Denmark, UK, & USA), for patients undergoing clinical asthma and EILO work-up with continuous laryngoscopy during exercise (CLE) testing between 2014–2018. Results: A total of 1,007 individuals completed CLE, of these 586 (58%) demonstrated EILO. Demographic characteristics for cases with EILO were similar across centres; median age of 21 (80% were ≤ 34), a female preponderance (76%) and median 2-year delay to diagnosis; 20% were found to not have asthma despite prescription of inhalers. Half (49%) of subjects were elite athletes. Supraglottic EILO (i.e. collapse of the arytenoid structures) was the predominant form and only 18% had glottic level (i.e. vocal cord dysfunction [VCD]) closure. Conclusion: This international collaboration reveals similarities in the clinical characteristics of EILO highlighting delay to diagnosis, inappropriate asthma treatment and that exercise induced VCD is a misnomer. These findings help to further define this condition and improve clinician’s recognition.

Albuminuria in the pathological range is a significant predictor of preeclampsia. In healthy persons, high normal urinary albumin predicts a later incidence of hypertension and is associated with salt sensitivity of blood pressure. We hypothesized that in pregnancy urinary albumin in the normal range associates with blood pressure through activation of distal Na+ reabsorption and renal salt retention by plasma factors cofiltered with albumin. We analyzed 24-h urine collections and plasma samples from gestational week 29 of 560 pregnant women from the Odense Child Cohort, a Danish population-based cohort. Plasma and urinary aldosterone were measured by ELISA. Plasma and urinary Na+, K+, Cl−, and creatinine were also determined. Predictive values of urinary albumin were assessed by linear mixed, multiple, and Cox regression analyses. Primary outcomes were blood pressure and renal electrolyte handling. Twenty-four-hour urinary albumin excretion at gestational week 29 associated with gestational blood pressure trajectory, with adjusted β coefficients (95% confidence intervals) for each 10-fold increase in urinary albumin as follows: 5.71 (1.60 to 9.81) mmHg for systolic blood pressure and 4.39 (1.41 to 7.38) mmHg for diastolic blood pressure. Urinary albumin was inversely associated with fractional excretion rates of Na+, K+, and Cl−, with adjusted β coefficients (95% confidence intervals) for each 10-fold increase in urine albumin as follows: −0.25 (−0.35 to −0.14), −5.06 (−6.81 to −3.30), and −0.28 (−0.41 to −0.15), respectively. In conclusion, at gestational week 29, urinary albumin excretion in the normal range associated with blood pressure and renal electrolyte handling independent of potential confounders.

Background & aims: The susceptibility to overweight in adults born during winter season may suggest foetal programming of prenatal vitamin D levels on adiposity. We investigated whether cord or pregnancy serum 25-hydroxyvitamin D (s-25OHD) was associated with infant and child body fat measures in a Danish population-based prospective cohort. Methods: In the Odense Child Cohort, 1905 singletons had cord s-25OHD and data on waist circumference (WC), weight, body mass index (BMI), and sum of skin folds (SSF) at median 3.7 months, 18.9 months and three years' age. Early and late pregnancy samples of s-25OHD (mean gestational age 12 and 29 weeks) were chosen as secondary exposures. Multiple linear and logistic regression as well as linear mixed models was applied testing the relation between cord and pregnancy s-25OHD and body fat outcomes and their Z-scores by use of updated national reference populations. Models were adjusted for maternal educational level, maternal ethnicity, pre-gestational BMI and season of birth, a priori stratified by sex. Results: The median [IQR] cord s-25OHD was 45.5 [31.1; 60.9] nmol/L. Cord s-25OHD <50 nmol/L was found in 57.5%; values < 25 nmol/L in 16.3%. The mean Z-scores of body fat measures at all ages were in the range of -0.32 to +0.42. No consistent associations were found between s-25OHD in cord, early pregnancy or late pregnancy and WC, weight, BMI, SSF, or their Z-scores at ages 3.7 months, 18.9 months, or 3 years. Neither did a computed composite outcome (WC, SSF, BMI, or weight >90th vs. <= 90 percentile) associate with cord or pregnancy s-25OHD. Conclusion: Cord or pregnancy s-25OHD was not associated with measures of body fat or adiposity in children up to three years of age. Our data suggested no programming effect of maternal s-25OHD on offspring obesity in a relatively lean and healthy population of mothers. (C) 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Pregnancy-induced hypertension is a severe pregnancy complication, increasing risk of long-term cardiovascular disease in mothers and offspring. We hypothesized that maternal blood pressure in pregnancy associated with offspring blood pressure; that the associations were sex-specific; and that maternal circulating placental angiogenic markers (PlGF [placental growth factor] and sFlt-1 [soluble fms-like tyrosine kinase-1]) mediated this relationship. We analyzed data from 2434 women and 2217 children from the Odense Child Cohort, a prospective Danish cohort study. Offspring blood pressure trajectory from 4 months to 5 years was highly associated to maternal first, second, and third trimester blood pressure, and mean blood pressure in pregnancy, independent of maternal and offspring covariates. There were offspring sex-specific associations: Girls from mothers in the highest quartile of first and third trimester blood pressure had significantly higher systolic blood pressure at 5 years than the rest of the cohort (mean difference±SEM: 1.81±0.59 and 2.11±0.59 mm Hg, respectively, all P<0.01); whereas boys had significantly higher diastolic blood pressure at 5 years (mean difference±SEM: 1.11±0.45 and 1.03±0.45, respectively, all P<0.05). Concentrations of PlGF at gestational week 28 correlated inversely to maternal gestational blood pressure trajectory, independent of the diagnosis of pregnancy-induced hypertension, adjusted β coefficients (95% CI) for predicting systolic blood pressure (SBP): −3.18 (−4.66 to −1.70) mm Hg, for predicting diastolic blood pressure (DBP): −2.48 (−3.57 to −1.40) mm Hg. In conclusion, maternal gestational blood pressure predicted offspring blood pressure trajectory until 5 years in a sex-differential manner. Furthermore, subtle alterations in blood pressure in early pregnancy preceded hypertension or preeclampsia, and PlGF was a mediator of cardiovascular health in pregnancy.

The mineralocorticoid aldosterone increases in plasma in healthy pregnancy along with renin and angiotensin II and plays a key role in the physiological plasma volume expansion. In mice, aldosterone contributes to an optimal fetal development by enhancing PlGF (placental growth factor) expression and trophoblast cell proliferation. In preeclampsia, there is coincident suppression of aldosterone and impaired placental development. We hypothesized that aldosterone independently contributes to placental and birth weight in humans, and high dietary sodium and low potassium intakes affect this relationship adversely. We analyzed 24-hour urine collections and plasma samples from gestational week 29 in a subsample of 569 pregnant women from the Odense Child Cohort-a Danish population-based longitudinal cohort study. Plasma and urinary aldosterone were measured by ELISA, sodium and potassium excretions by flame photometer. Predictive values of aldosterone levels and sodium and potassium intakes were assessed by multiple and Cox regression analyses. Primary outcomes were placental weight and birth weight. Secondary outcome was preeclampsia. Urinary aldosterone excretion at gestational week 29 independently contributed to placental and birth weights (adjusted β-coefficients [95% CI], 24.50 [9.66-39.35] and 9.59 [4.57-14.61], respectively). Aldosterone levels were not associated to preeclampsia incidence. Salt intake >6 g/d was associated with development of preeclampsia (hazard ratio [95% CI], 5.68 [1.51-21.36]). At gestational week 29, urinary aldosterone excretion is an independent predictor of placental and birth weights. High salt intake is a risk factor for preeclampsia. In perspective, suppression of aldosterone in pregnancy has adverse trophic effects.