Fetal sex dependency of maternal vascular adaptation to pregnancy: a prospective population-based cohort study.

OBJECTIVE: To investigate fetal sex dependency of maternal vascular adaptation to pregnancy as assessed by uteroplacental vascular resistance and maternal blood pressure. DESIGN: Prospective population-based cohort study. SETTING: Rotterdam, the Netherlands. POPULATION: In total, 8224 liveborn singleton pregnancies were included. METHODS: Maternal vascular adaptation was assessed in all trimesters of pregnancy. Pregnancies were stratified into being either complicated by the placental syndrome (i.e. pre-eclampsia, fetal growth restriction or preterm birth, n = 1229) or uncomplicated (n = 6995). MAIN OUTCOME MEASURES: First trimester: blood pressures. Second trimester: blood pressures, pulsatility index of the uterine artery (PI-UtA). Third trimester: blood pressures, PI-UtA, presence of notching in the uterine artery. RESULTS: In women carrying a male fetus PI-UtA was higher than in women with a female fetus in the total group (second trimester P < 0.001, third trimester P = 0.005). Effect estimates differed between women with or without the placental syndrome. In the total group, women with a male fetus more often showed notching in the Doppler resistance pattern (odds ratio 1.42, 95% confidence interval 1.17-1.72). Different blood pressure patterns were observed between pregnant women with a male fetus and pregnant women with a female fetus and between complicated pregnancies and uncomplicated pregnancies. CONCLUSION: Fetal sex is significantly associated with maternal vascular adaptation to pregnancy with differential effects in uncomplicated pregnancies and in pregnancies complicated by the placental syndrome. TWEETABLE ABSTRACT: Fetal sex is significantly associated with maternal vascular adaptation to pregnancy.

Determining differentially expressed miRNAs and validating miRNA--target relationships using the SPRET/Ei mouse strain.

Micro RNAs (miRs) are involved in many biological processes. The challenge of identifying genes influenced by miRs is evidenced by the relatively few validated miR-target interactions. In this work, we used the Mus spretus SPRET/Ei strain as an in vivo system to identify new miR-target relations. Mus spretus diverged from Mus musculus over one million years ago, making it genetically and phenotypically divergent. SPRET/Ei mice are resistant to inflammation and several cancers, making them attractive for different research fields. Their phenotype is unique and is considerably different from that of almost all other laboratory mouse strains. We exploited the characteristics of SPRET/Ei mice as a tool to identify miR-target relationships. Hepatic genes and miRs differentially expressed between C57BL/6 and SPRET/Ei mice at basal levels were identified with an Affymetrix microarray and a multiplex qPCR, respectively. A total of 955 genes and 38 miRs were identified as differentially expressed. Increased miR expression might result in downregulation of its target mRNA and vice versa. Subsequently, we used our miR and mRNA data to identify possible in vivo miR-target interactions. Ingenuity pathway analysis (IPA) analysis revealed 380 possible miR-target interactions. Five miRs were selected for experimental validation by in vivo overexpression of the miRs. This resulted in the confirmation of six previously unknown miR-target interactions: miR-146a, Zdhhc2; miR-150, Elovl3, Kcnk5, and Nrd1d2; miR-155, Camta1; and miR-592, Steap2. In conclusion, we show that SPRET/Ei mice can be used as a platform for miR-target identification in vivo, and we used this platform to identify and experimentally confirm miR-target interactions.

AOX removal from industrial wastewaters using advanced oxidation processes: assessment of a combined chemical-biological oxidation.

In this paper, the abatement of adsorbable halogenated organic compounds (AOX) from an industrial wastewater containing relatively high chloride concentrations by a combined chemical and biological oxidation is assessed. For chemical oxidation, the O(3)/UV, H(2)O(2)/UV and photo-Fenton processes are evaluated on pilot scale. Biological oxidation is simulated in a 4 h respirometry experiment with periodic aeration. The results show that a selective degradation of AOX with respect to the matrix compounds (expressed as chemical oxygen demand) could be achieved. For O(3)/UV, lowering the ratio of O(3) dosage to UV intensity leads to a better selectivity for AOX. During O(3)-based experiments, the AOX removal is generally less than during the H(2)O(2)-based experiments. However, after biological oxidation, the AOX levels are comparable. For H(2)O(2)/UV, optimal operating parameters for UV and H(2)O(2) dosage are next determined in a second run with another wastewater sample.

Reference ranges of anti-Müllerian hormone and interaction with placental biomarkers in early pregnancy: the Generation R Study, a population-based prospective cohort study.

Objective: The primary objective of this study is to establish maternal reference values of anti-Müllerian hormone (AMH) in a fertile multi-ethnic urban pregnant population and to evaluate the effect of gestational age. The secondary objective of this study is to explore the association between AMH and placental biomarkers. Design: This study was embedded in the Generation R Study, an ongoing population-based prospective cohort study from early pregnancy onwards. Setting: City of Rotterdam, the Netherlands, out of hospital setting. Patients: In 5806 women, serum AMH levels were determined in early pregnancy (median 13.5 weeks; 95% range 10.5-17.2). Intervention(s): None. Main outcome measures: Maternal AMH levels in early pregnancy and its association with placental biomarkers, including human chorionic gonadotrophin (hCG), soluble fms-like tyrosine kinase-1 (sFLT), and placental growth factor (PLGF). Results: A nomogram of AMH in early pregnancy was developed. Serum AMH levels showed a decline with advancing gestational age. Higher AMH levels were associated with a higher level of the placental biomarkers hCG and sFLT in early pregnancy. This last association was predominantly mediated by hCG. AMH levels were negatively associated with PLGF levels. Conclusion: In this large study, we show that AMH levels in early pregnancy decrease with advancing gestational age. The association between AMH and the placental biomarkers hCG, sFLT, and PLGF suggests a better placental development with lower vascular resistance in mothers with higher AMH levels. Hence, AMH might be useful in predicting adverse pregnancy outcomes due to impaired placental development.

Homocysteine and folate concentrations in early pregnancy and the risk of adverse pregnancy outcomes: the Generation R Study.

OBJECTIVE: To investigate associations between early pregnancy homocysteine, folate and vitamin B12 concentrations and placental weight, birthweight and adverse pregnancy outcomes. DESIGN: Population-based birth cohort study. SETTING: Rotterdam, the Netherlands. POPULATION: Cohort of 5805 pregnant women. METHODS: To analyse homocysteine, folate and vitamin B12 concentrations, blood was drawn in early pregnancy. These concentrations were divided into quintiles. Information on birth outcomes was retrieved from medical records. Multivariate regression analyses were used. MAIN OUTCOME MEASURES: Placental weight, birthweight, small for gestational age at birth (SGA) (<5th centile), prematurity and pre-eclampsia. RESULTS: High homocysteine concentrations (highest quintile) were associated with lower placental weight (difference 30 g; P < 0.001) and birthweight (difference 110 g; P < 0.001), and increased risk of SGA [odds ratio (OR) 1.7; P = 0.006] compared with lowest quintile (reference). Low folate concentrations (lowest quintile) were associated with lower placental weight (difference 26 g; P = 0.001) and birthweight (difference 125 g; P < 0.001), and increased risks of SGA (OR 1.9; P = 0.002), prematurity (OR 2.2; P = 0.002) and pre-eclampsia (OR 2.1; P = 0.04) compared with highest quintile (reference). The risk of developing SGA and pre-eclampsia was substantially higher in women who had higher homocysteine and lower folate concentrations. No associations were found with vitamin B12. CONCLUSIONS: Higher homocysteine and lower folate concentrations in early pregnancy are associated with lower placental weight and birthweight, and higher risk of adverse pregnancy outcomes. These findings suggest that high homocysteine and low folate concentrations in early pregnancy may adversely influence placentation and subsequently affect the success of pregnancy and birth outcomes.

Folic acid is positively associated with uteroplacental vascular resistance: the Generation R study.

BACKGROUND AND AIMS: Periconception folic acid supplementation may influence early placentation processes and thereby the occurrence of hypertensive pregnancy disorders. For this reason we examined the associations between periconception folic acid supplementation and uteroplacental vascular resistance, blood pressure, and the risks of gestational hypertension and preeclampsia, in 5993 pregnant women, participating in a population-based cohort study. METHODS AND RESULTS: Folic acid supplementation was assessed by questionnaire. Mean pulsatility index (PI) and resistance index (RI) of the uterine (UtA) and umbilical arteries (UmA) were measured by Doppler ultrasound in mid- and late pregnancy. Systolic and diastolic blood pressures (SBP, DBP) were measured in early, mid- and late pregnancy. Compared to women who did not use folic acid, preconception folic acid users had a slightly lower UtA-RI in mid-pregnancy [ß -0.02, 95% confidence interval (CI) -0.03, -0.01] and late pregnancy [ß -0.02, 95% CI -0.03, -0.001], a lower UtA-PI in mid-pregnancy [ß -0.06, 95% CI -0.1, -0.03] and late pregnancy [ß -0.03, 95% CI -0.05, -0.01], as well as tendencies towards a lower UmA-PI in mid-pregnancy [ß -0.02, 95% CI -0.04, -0.001] and late pregnancy [ß -0.01, 95% CI -0.02, 0.01]. Additionally, these women had slightly higher SBP and DBP throughout pregnancy. Neither the patterns of blood-pressure change during pregnancy, nor the risk of gestational hypertension and preeclampsia differed between the folic acid categories. CONCLUSION: Periconception folic acid supplementation is associated with lower uteroplacental vascular resistance and higher blood pressures during pregnancy. The effects are small and within physiologic ranges and seem not associated with the risk of hypertensive pregnancy disorders.

The diagnostic value of contrast-enhanced 2D mammography in everyday clinical use.

Contrast-enhanced mammography (CEM) has shown to be superior to full-field digital mammography (FFDM), but current results are dominated by studies performed on systems by one vendor. Information on diagnostic accuracy of other CEM systems is limited. Therefore, we aimed to evaluate the diagnostic performance of CEM on an alternative vendor's system. We included all patients who underwent CEM in one hospital in 2019, except those with missing data or in whom CEM was used as response monitoring tool. Three experienced breast radiologists scored the low-energy images using the BI-RADS classification. Next, the complete CEM exams were scored similarly. Histopathological results or a minimum of one year follow-up were used as reference standard. Diagnostic performance and AUC were calculated and compared between low-energy images and the complete CEM examination, for all readers independently as well as combined. Breast cancer was diagnosed in 23.0% of the patients (35/152). Compared to low-energy images, overall CEM sensitivity increased from 74.3 to 87.6% (p < 0.0001), specificity from 87.8 to 94.6% (p = 0.0146). AUC increased from 0.872 to 0.957 (p = 0.0001). Performing CEM on the system tested, showed that, similar to earlier studies mainly performed on another vendor's systems, both sensitivity and specificity improved when compared to FFDM.

Ten-year disease progression in multiple sclerosis: walking declines more rapidly than arm and hand function.

BACKGROUND AND AIMS: From a clinical perspective there is a difference in the decline of arm and hand function and leg function in patients with multiple sclerosis (PwMS). Therefore, this study investigated the course of walking and arm and hand functions in PwMS over the first 10 years after diagnosis, including whether any function declined earlier or faster. METHODS: A long-term prospective follow-up study of an incidence cohort of 156 patients with a definite diagnosis of MS, either non-relapse onset (n=28) or relapse onset (n=128) type. Participants were systematically examined immediately after definite diagnosis, at 6 months, and at 1, 2, 3, 6 and 10 years. Walking was determined with the fast 10-meter timed walk test (10mTWT), arm and hand function with the Action Research Arm test (ARAT) and the nine-hole peg test (9HPT). The 10-year trajectories of walking and arm and hand functions were compared using standardized z-scores. RESULTS: From 3 years onwards the z-scores of the arm and leg function were visually diverging, with a trend towards significance at 6 years, and at 10 years the 10mTWT z-score is significantly higher than the 9HPT. This difference is more pronounced in non-relapse onset patients than in patients with relapse onset type MS, but present in both groups over the first 10 years. In the non-relapse onset group a difference in z-scores at 10 years post-diagnosis between the 10m TWT and 9HPT was found of -12.94 (95% confidence interval (CI) -20.2 to -5.73) for the right and -10.14 (95% CI -17.3 to -2.93) for the left hand. In the relapse onset group there was a difference at 10 years post-diagnosis of -2.17 (95% CI -3.75 to -0.59) for the right and a difference of -2.29 (95% CI -3.87 to -0.71) for the left hand. CONCLUSION: This is the first longitudinal study that shows that walking declines earlier and more rapidly than arm and hand function in patients with MS. These results give important insights that can be linked to the pathophysiological disease process regarding the ascending order of deterioration in patients with MS.

Eliciting Help-Seeking Behaviors in Patients With Fecal Incontinence: Supporting Timely Access to Treatment.

People with fecal incontinence (FI) symptoms often do not report their symptoms to their care providers, which may adversely impact their quality of life. Although the differential diagnosis for the cause of an individual's FI symptoms can be done by a family doctor, nurse practitioner, or a specialist, many other healthcare professionals have the training and education to competently screen patients for FI risk factors. Those individuals identified with FI symptoms can be supported to disclose this information to their healthcare professional in a timely manner. Healthcare professionals have a responsibility to encourage patients to seek medical treatment in order to ensure an accurate diagnosis for their FI symptoms, and to support clients through the process of managing symptoms including adhering to care plans to mitigate modifiable causes of FI. When clients actively seek medical help, it is referred to as help-seeking behavior. Given the sensitive nature of FI, with the associated stigma and taboo surrounding the topic, healthcare providers must conscientiously work to support each client with sensitivity and self-awareness.

Endothelial progenitor cells are differentially impaired in ANCA-associated vasculitis compared to healthy controls.

BACKGROUND: Endothelial progenitor cells (EPC) are of major importance in vascular repair under healthy circumstances. Vascular injury in need of repair occurs frequently in ANCA-associated vasculitis (AAV). A specialized T cell subset enhancing EPC function and differentiation has recently been described. These angiogenic T cells (Tang) may have an important impact on the vascular repair process. Therefore, the aim of our study was to investigate EPC and Tang in AAV. METHODS: Fifty-three patients suffering from AAV and 29 healthy controls (HC) were enrolled in our study. Forty-four patients were in remission, nine patients were in active state of disease. Patients were either untreated or were under monotherapy with low-dose steroids (max. 5 mg/day) at the time of sampling. Circulating EPC and Tang were determined by flow cytometry (FACS). The functional capacity of EPC was assessed by established cell culture methods. RESULTS: Circulating EPC were significantly decreased in AAV as compared to HC. The capacity of EPC to differentiate and proliferate was differentially impaired in patients as compared to HC. The outgrowth of endothelial colony-forming cells (ECFC) was severely decreased in patients whereas colony-forming units-endothelial cell (CFU-EC) outgrowth was unaffected. ECFC and CFU-EC differentiation was strictly T cell-dependent. Patients with a relapsing disease course had an impaired ECFC outgrowth and expansion of Tang as compared to patients with a stable, nonrelapsing disease. CONCLUSIONS: The differentiation process of EPC is impaired in AAV. This may favor insufficient vascular repair promoting a relapsing disease course. Finally, these factors may explain a higher cardiovascular morbidity as has been previously documented in AAV.

Longitudinal analysis of factor VIII inhibitors in a previously untreated mild haemophilia A patient with an Arg593-->Cys substitution.

Recent studies suggest that certain missense mutations associated with mild to moderate haemophilia A predispose to inhibitor development. In this study, we present a longitudinal analysis of the epitope specificity of an inhibitor that developed in a mild haemophiliac with an Arg593-->Cys mutation. Immunoprecipitation studies revealed the presence of antibodies directed towards the light chain and A2 domain of factor VIII. Limited reactivity was observed with metabolically labelled C2 domain. Almost complete inhibitor neutralization was achieved upon addition of A2 domain. Binding of the inhibitor was not affected by the presence of the Arg593-->Cys substitution in the recombinant A2 fragment. Evaluation of the epitope specificity of anti-factor VIII antibodies in plasma samples obtained at different time-points of inhibitor development revealed initial development of a low titre inhibitor directed towards the A2 domain and factor VIII light chain. A second period of factor VIII replacement therapy resulted in a dramatic rise in factor VIII inhibitor titre, which maintained their original epitope specificity. Based on the results of this and previous studies (Fijnvandraat et al., 1997; Thompson et al., 1997) it is argued that inhibitor development in patients with the Arg593-->Cys mutation may proceed via a similar mechanism.

Evidence-based medicine, clinical uncertainty, and learning to doctor.

For the past two decades, evidence-based medicine (EBM), or the reliance on current scientific evidence to reach medical decisions, has been embraced as a new paradigm to standardize clinical care. Drawing from in-depth interviews with seventeen pediatric residents in two residency programs, we evaluate the extent to which the medical sociology scholarship on uncertainty analytically elucidates the recent influx of EBM during residency training. Our findings suggest that residents interpret EBM in varying ways to match their work practices: "Librarians" consult the literature while "researchers" evaluate it critically. For both groups, EBM might generate new uncertainties due to the increased reliance on information technologies and epidemiology. Whether EBM reduces uncertainty depends upon the residents' understanding of standardized knowledge and consequent incorporation of EBM in their clinical practice. Contrary to the predictions of some sociologists, EBM does not lead to a diminishment of humanitarian values in medical care. Nor does EBM lead to a science-based meritocracy on the patient ward, as claimed by some EBM advocates. Our conceptual updating of uncertainty emphasizes the continuous management of uncertainty during the medical socialization process. We argue that managing uncertainty develops along with what we term evidence-based clinical judgment.

[Highly active antiretroviral therapy (HAART) in HIV-positive pregnant women in the Netherlands, 1997-2003: safe, effective and with few side effects]. / Krachtige antiretrovirale therapie (HAART) bij HIV-positieve zwangeren in Nederland, 1997-2003: veilig, effectief en met weinig bijwerkingen.

OBJECTIVE: To assess the side effects, safety and efficacy of highly active antiretroviral therapy (HAART) in a cohort of HIV-infected pregnant women in the Netherlands. DESIGN: Retrospective. METHOD: Data were collected from the medical records of HIV-infected pregnant women who received HAART during pregnancy in the period 1 January 1997-1 June 2003 at 14 HIV-specialized centres in the Netherlands. The inclusion criteria were at least a triple drug regimen and birth at 20 or more weeks of gestation. Information was collected about patient characteristics, HAART prescribed, side effects, viral load response, mode of delivery and HIV-status of the neonate. RESULTS: A total of 267/413 women satisfied the inclusion criteria. Most women (n = 199) had not previously received anti-retroviral therapy and started HAART between weeks 21 and 28 of the pregnancy. The two most frequently used regimens contained nelfinavir (57%) or nevirapine (31%). Gastrointestinal side effects were more frequently observed in the nelfinavir group, while rash and hepatotoxicity were more frequently reported in the nevirapine group. Efficacy and pregnancy outcome were similar in both groups. Two infants (0.7%) were HIV-infected. CONCLUSION: HAART regimens containing nelfinavir or nevirapine in HIV-infected pregnant women were safe, effective and well tolerated.

The redemption of thalidomide: standardizing the risk of birth defects.

In this paper we examine how a standardized drug distribution system contributed to a therapeutic and symbolic make-over of thalidomide. In the 1960s, thalidomide was seen as a horror drug that caused severe birth defects among over 10,000 babies who were exposed to it in utero. Currently, thalidomide is viewed as a potentially life-saving drug which is being distributed in the USA. We discuss this transformation from a social worlds perspective, showing how the standardized drug distribution system normalized the risk of foetal birth defects, while preserving the autonomy of health care professionals. The distribution system accomplished this transformation by focusing on the risk associated with female reproductive behavior, and by providing close reproductive surveillance of female patients. This standardized system solidified social inequalities and professional power relationships, revealing assumptions about trust, responsibility and risk.

Maternal smoking during pregnancy and childhood overweight and fat distribution: the KOALA Birth Cohort Study.

UNLABELLED: What is already known about this subject There is an association between maternal smoking during pregnancy and higher body mass index (BMI) and overweight in childhood. What this study adds The association between maternal smoking during pregnancy and childhood overweight develops with age, starting with a lower birth weight, followed by weight catch-up in the first year after birth, finally leading to overweight at school age. Children of mothers who had smoked during pregnancy had a higher risk of exceeding the 85th percentile of BMI, waist circumference and total skinfold thickness at school age. BACKGROUND: Maternal smoking during pregnancy is associated with childhood overweight, but the association with fat distribution is not clear. OBJECTIVE: To explore the longitudinal association between smoking during pregnancy and childhood overweight and fat distribution. METHODS: In the KOALA Birth Cohort Study, repeated questionnaires were administered to 2698 mother-child pairs, including questions on smoking at 14 and 34 weeks of pregnancy. Main outcomes were birth weight, weight gain in the first year, body mass index (BMI) z-scores and overweight (BMI ≥85th percentile) at 1, 2, 4-5 and 6-7 years (n = 1730) and waist circumference and four skinfold thicknesses measured at home visits at age 6-7 years in a subgroup (n = 418). We used multivariable linear and logistic regression, with generalized estimating equations (GEE) for repeated measurements. RESULTS: Maternal smoking was associated with lower birth weight, higher weight gain in the first year and increasing overweight after infancy (change with age P = 0.02 in the GEE). Maternal smoking vs. non-smoking during pregnancy was associated with a higher risk of the child exceeding the 85th percentile of BMI (adjusted odds ratio [aOR] 3.72; 95% CI 1.33-10.4), waist circumference (aOR 2.65; 95% CI 1.06-6.59) and sum of skinfold thicknesses (aOR 4.45; 95% CI 1.63-12.2) at the age of 6-7 years. CONCLUSIONS: Maternal smoking during pregnancy is associated with lower birth weight, weight catch-up and development of overweight into childhood.

Fetal sex specific differences in human placentation: a prospective cohort study.

INTRODUCTION: Our objective was to assess fetal sex specific differences in first trimester placental biomarkers of both physiological and pathological pregnancies and their interaction with environmental influences. This study is embedded in the Generation R Study, a prospective cohort study. METHODS: Only live singleton births were included. Linear regression was performed to assess the effect of sex on first trimester placental biomarkers. Interaction analyses were performed to assess interaction of fetal sex with environmental influences. First trimester soluble fms-like tyrosine kinase (s-Flt1), placental growth factor (PLGF), plasminogen activator inhibitor (PAI-2) and homocysteine levels were assessed. RESULTS: Significant fetal sex specific differences in placental biomarkers were observed. S-Flt1, PAI-2 and PLGF log transformated concentrations were 0.08 ng/mL (95% CI 0.05; 0.11), 0.07 ng/mL (95% CI 0.06; 0.09) and 0.04 pg/mL (95% CI 0.01; 0.06) higher in case of female as compared to male placentas. In pregnancies complicated by pre-eclampsia (PE), preterm birth (PTB) or a newborn being small for gestational age (SGA) no fetal sex specific differences were observed. Interaction analyses suggest that concentrations of s-Flt1, PLGF and PAI-2 decrease in male placentas in the case of hyperhomocysteinemia but remain equal in female placentas. DISCUSSION: Fetal sex affects early placentation processes with discrepancies regarding pregnancies complicated by PE, PTB or a newborn being SGA. This suggests that other mechanisms causing these complications may dominate the fetal sex effect. The differences concerning homocysteine suggest that fetal sex dependent placental gene-environment interactions exist. CONCLUSION: Fetal sex specific differences in placental biomarkers exist.

Keep an eye out for tubulo-interstitial nephritis.

Acute tubulo-interstitial nephritis and uveitis syndrome (TINU) is a rare disease, generally presenting in young women. We describe a 16-year-old Turkish girl with aspecific symptoms and elevated serum creatinine. Further, she complained about a burning pain in her left eye. Renal biopsy revealed acute TIN. Other conditions were excluded and TINU was diagnosed.

Maternal circulating PlGF concentrations and placenta-related pregnancy complications: First results from the CoLab AngF Study.

INTRODUCTION: Circulating angiogenic factors are potential markers for preeclampsia, but heterogeneous studies have failed to identify precise predictive/diagnostic properties. The Global CoLaboratory is investigating how to merge published data of angiogenic factors for meta-analysis on an individual sample basis. OBJECTIVE: To amalgamate pregnancy angiogenic factor studies, investigate diagnostic and predictive properties of these markers in preeclampsia and placenta-related pregnancy complications, and to test if measures from disparate platforms can be standardised. This is the first report using PlGF measures to diagnose preeclampsia. METHODS: Data were derived from 15 cohorts, within and outside the CoLaboratory network. Women were classified as either case (confirmed diagnosis of preeclampsia at sampling) or non-case (no preeclampsia at sampling). Individual PlGF measurements from four different analytical platforms were used, along with transformations of the data (e.g. log-transformations, transformations to a baseline platform). Transformed measurements were standardised both for specific platforms and globally, stratifying on gestational age. Different statistical techniques were compared. RESULTS: The database currently contains 1442 cases and 11,512 non-cases, which were used to define an algorithm to merge PlGF measurements from different platforms. Non-case distributions were used to standardise case results. Diagnostic PlGF measurements in relation to preeclampsia will be presented and confirm feasibility. CONCLUSIONS: Future studies can extend this approach to other angiogenic factors, prediction as well as diagnosis and to other placenta-related disorders.