Does delayed cord clamping result in higher maternal blood loss in primary cesarean sections? A retrospective comparative study.

OBJECTIVES: The University Hospital Basel implemented delayed umbilical cord clamping of 30-60 s in all laboring women on April 1, 2020. This practice has been widely researched showing substantial benefit for the neonate. Few studies focused on maternal blood loss. The objective of our retrospective comparative study was to assess the impact of immediate vs. delayed cord clamping on maternal blood loss in primary scheduled cesarean sections. METHODS: We analyzed data of 98 women with singleton gestations undergoing primary scheduled cesarean section at term. Data from procedures with early cord clamping (ECC) were compared to those after implementation of delayed cord clamping (DCC). Primary outcomes were perioperative change in maternal hemoglobin levels, estimated and calculated blood loss. Secondary outcomes included duration of cesarean section and neonatal data. RESULTS: There was a statistically significant difference in the mean perioperative decline of hemoglobin of 10.4 g/L (SD=7.92) and 18.7 g/L (SD=10.4) between the ECC and DCC group, respectively (p<0.001). The estimated (482 mL in ECC vs. 566 mL in DCC (p=0.011)) and the calculated blood loss (438 mL in ECC vs. 715 mL in DCC (p=0.002)) also differed significantly. Secondary outcomes showed no significant differences. CONCLUSIONS: In our study DCC resulted in a statistically significant higher maternal blood loss. In our opinion the widely researched neonatal benefit of DCC outweighs the risk of higher maternal blood loss in low-risk patients. However, maternal risks must be minimized, improvements to preoperative blood management and operative techniques are required.

Interventional study to improve pertussis and influenza vaccination uptake in pregnant women.

OBJECTIVES: Pertussis and influenza are endemic infections and associated with relevant morbidity and mortality in newborns and young infants. The Swiss Federal Office of Public Health has recommended influenza vaccination since 2011 and pertussis vaccination in pregnancy (ViP) since 2013 and expanded to repetition in each pregnancy since 2017. ViP is safe and effective in preventing severe diseases, but implementation is a challenge. We hypothesized that the proportion of women receiving ViP is persistently low despite existing national recommendations. Our primary objective was to compare the proportion of pertussis and influenza vaccine recommendations for and its acceptance by pregnant women before and after an information campaign tailored to obstetricians. Secondly, we aimed to identify reasons for missing or declining ViP. STUDY DESIGN: We conducted a prospective, single-center, single-arm implementation study in the maternity ward at the University Women's Hospital Basel. We performed standardized interviews with women hospitalized for postpartum care before (October to December 2019, Phase 1, n = 262) and after an information campaign (October to December 2020, Phase 2, n = 233) and compared categorical variables using chi-squared or Fisher's exact test and continuous variables using Whitney Mann U test. RESULTS: We found no significant differences in the proportion of recommendation for pertussis ViP (80 % vs. 84 %, p = 0.25) and implementation (76 % vs. 78 %, p = 0.63) between Phase 1 and 2. Main reasons for missing or declining vaccinations were lack of recommendation (62.8 %) and safety concerns regarding the unborn child (17.7 %). In contrast, the proportion of recommendation for influenza ViP (45 % vs. 63 %, p < 0.001) and implementation (29 % vs. 43 %, p < 0.001) increased significantly. CONCLUSION: Proactive recommendations by obstetricians play a key role in the implementation of ViP but is still insufficient in our setting. We believe that future efforts should aim to explore possible hurdles that impede recommendations by obstetricians for ViP. The focus should be on the needs and experiences of obstetricians in private practice, but also other health care professionals involved in care of pregnant women. Local campaigns do not seem effective enough, therefore national campaigns with new strategies are desirable.

Circulatory Neutrophils Exhibit Enhanced Neutrophil Extracellular Trap Formation in Early Puerperium: NETs at the Nexus of Thrombosis and Immunity.

Pregnancy is associated with elevated maternal levels of cell-free DNA of neutrophil extracellular trap (NET) origin, as circulatory neutrophils exhibit increased spontaneous NET formation, mainly driven by G-CSF and finely modulated by sex hormones. The postpartum period, on the other hand, involves physiological alterations consistent with the need for protection against infections and fatal haemorrhage. Our findings indicate that all relevant serum markers of neutrophil degranulation and NET release are substantially augmented postpartum. Neutrophil pro-NETotic activity in vitro is also upregulated particularly in post-delivery neutrophils. Moreover, maternal puerperal neutrophils exhibit a strong pro-NETotic phenotype, associated with increased levels of all key players in the generation of NETs, namely citH3, MPO, NE, and ROS, compared to non-pregnant and pregnant controls. Intriguingly, post-delivery NET formation is independent of G-CSF in contrast to late gestation and complemented by the presence of TF on the NETs, alterations in the platelet activity status, and activation of the coagulation cascade, triggered by circulating microparticles. Taken together, our results reveal the highly pro-NETotic and potentially procoagulant nature of postpartum neutrophils, bridging an overt immune activation with possible harmful thrombotic incidence.

Diagnostic accuracy of an interdisciplinary tertiary center evaluation in children referred for suspected congenital anomalies of the kidney and urinary tract on fetal ultrasound - a retrospective outcome analysis.

BACKGROUND: Fetal ultrasound organ screening has become a standard of care in most high-income countries. This has resulted in increased detection of congenital abnormalities, which may lead to major uncertainty and anxiety in expectant parents, even though many of them are of minor relevance. In order to optimize prenatal counselling, we introduced an interdisciplinary approach for all pregnant women referred to our center by private obstetricians for a co-assessment of suspected relevant fetal abnormalities of the kidney or urinary tract, involving both experienced prenatal ultrasound specialists and a pediatric nephrologist or urologist. METHODS: In a retrospective analysis, we evaluated reports of intrauterine evaluation and postnatal follow-up in order to assess accuracy of explicit intrauterine diagnoses and outcome of hydronephroses according to their severity in this setting. RESULTS: A total of 175 fetuses were examined between 2012 and 2019 and followed postnatally at our Pediatric Nephrology or Urology Department. There was a high concordance (85.9%) between explicit intrauterine and final diagnoses. Resolution rate of hydronephrosis was higher in patients with intrauterine low-grade than high-grade hydronephrosis (61.8% versus 11.9%). An etiological diagnosis was found in 62.5%, 52.0%, and 11.1% of patients with intrauterine bilateral high-grade, unilateral high-grade, and unilateral high-grade with contralateral low-grade hydronephrosis, respectively, but in none of the patients with intrauterine low-grade hydronephrosis. CONCLUSIONS: The results of our study demonstrate that, through interdisciplinary teamwork, intrauterine assessment of the fetal kidneys and urinary tract is highly accurate and allows a good discrimination between relevant and transient/physiological hydronephroses. A higher resolution version of the Graphical abstract is available as Supplementary information.

Preeclampsia in Switzerland: a cost analysis in two hospitals.

Aim: Preeclampsia is a serious complication of pregnancy that occurs in approximately 2.3% of all pregnancies in Switzerland. The aim of this study was to determine inpatient costs based on actual services in suspected and confirmed cases of preeclampsia in two Swiss hospitals (University Hospital Basel, Lucerne Cantonal Hospital) for the year 2016.Methods: Costs for patients with suspected or diagnosed preeclampsia were determined based on the databases of the finance and controlling departments. The cases were identified according to ICD-10 codes and were divided into three main categories: (1) patients with suspected preeclampsia who were discharged without delivering; (2) patients with diagnosed preeclampsia followed by vaginal induction; (3) patients with diagnosed preeclampsia followed by cesarean delivery.Results: A total of 301 cases were included in the analysis, of which 36 (12%) were hospitalized with suspected preeclampsia and discharged after a few days without delivering. Costs for cases of suspected preeclampsia were the lowest, averaging CHF 7,159/EUR 6,658 (95% CI: CHF 5,361/EUR 4,986; CHF 8,958/EUR 8,331), followed by CHF 12,124/EUR 11,275 (95% CI: CHF 10,401/EUR 9,673; CHF 13,950/EUR 12,974) for cases of preeclampsia with vaginal delivery, and CHF 19,352/EUR 17,997 (95% CI: CHF 17,342/EUR 16,128; CHF 21,507/EUR 20,002) for preeclampsia with cesarean section. Overall medical costs were CHF 4.7 (EUR 4.4) million. In all patient groups, the actual patient costs exceeded the DRG revenue that inpatient care providers receive from payers for providing services. The budget deficit was seen in both hospitals, although the magnitude of the deficit was different.Limitation and conclusion: This is the first study to analyze costs for preeclampsia in Switzerland. It would be desirable if this cost analysis was to be performed in other hospitals in order to achieve greater representativity for Switzerland.

Placental Protein 13 (Galectin-13) Polarizes Neutrophils Toward an Immune Regulatory Phenotype.

Termed as galectin-13, placental protein 13 (PP13) is exclusively expressed in the placenta of anthropoid primates. Research on PP13 in normal and pathologic pregnancies show alteration of PP13 concentrations in pregnancy affected by preeclampsia or gestational diabetes. Galectins are also described as potent immunomodulators, and PP13 regulates T cell function in the placenta. Therefore, this study aims to investigate the effects of PP13 on neutrophils; a cell type often ignored in pregnancy, but present in the uterus and placenta from the early stages of pregnancy. Since neutrophil function is dysregulated during pathologic pregnancies, a link between PP13 and neutrophil activity is possible. We determined that PP13 reduces the apoptosis rate in neutrophils. Also, PP13 increases the expression of PD-L1 and production of HGF, TNF-α, reactive oxygen species (ROS), and MMP-9 in these cells. This phenotype resembles one observed in permissive tumor neutrophils; able to sustain tissue and vessel growth, and inhibit T cell activation. At the same time, PP13 does not alter all neutrophil functions, i.e., extrusion of neutrophil extracellular traps, degranulation, phagocytosis, and ROS production following bacterial exposure. PP13 seems to play an essential role in regulating the activity of neutrophils in the placenta by polarizing them toward a placental-growth-permissive phenotype.

Maternal serum glycosylated fibronectin as a short-term predictor of preeclampsia: a prospective cohort study.

BACKGROUND: Preeclampsia is a major pregnancy complication that results in significant maternal and infant mortality, most of which occurs in low and middle-income countries. The accurate and timely diagnosis of preeclampsia is critical in management of affected pregnancies to reduce maternal and fetal/neonatal morbidity and mortality, yet difficulties remain in establishing the rigorous diagnosis of preeclampsia based on clinical parameters alone. Biomarkers that detect biochemical disease have been proposed as complements or alternatives to clinical criteria to improve diagnostic accuracy. This cohort study assessed the performance of several biomarkers, including glycosylated fibronectin (GlyFn), to rule-in or rule-out preeclampsia within 4 weeks in a cohort of women at increased risk for preeclampsia. METHODS: 151 women with risk factors for or clinical signs and symptoms of preeclampsia were selected from a prospective cohort. Maternal serum samples were collected between 20 and 37 weeks of gestation. Clinical suspicion of preeclampsia was defined as presence of new-onset proteinuria, or clinical symptoms of preeclampsia. Subjects with a clinical diagnosis of preeclampsia at the time of enrollment were excluded. GlyFn, pregnancy-associated plasma protein-A2 (PAPPA2), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured by immunoassay. GlyFn was also determined using a rapid point-of care (POC) test format. Receiver-operating characteristic (ROC) curves derived from logistic regression analysis were used to determine the classification performance for each analyte. RESULTS: 32 of 151 (21%) women developed a clinical diagnosis of preeclampsia within 4 weeks. All biomarkers exhibited good classification performance [GlyFn (area under the curve (AUROC) = 0.94, 91% sensitivity, 86% specificity); PAPPA2 AUC = 0.92, 87% sensitivity, 77% specificity; PlGF AUC = 0.90, 81% sensitivity, 83% specificity; sFlt-1 AUC = 0.92, 84% sensitivity, 91% specificity. The GlyFn immunoassay and the rapid POC test showed a correlation of r = 0.966. CONCLUSIONS: In this prospective cohort, serum biomarkers of biochemical disease were effective in short-term prediction of preeclampsia, and the performance of GlyFn in particular as a POC test may meet the needs of rapid and accurate triage and intervention.

Significance of isolated borderline ventriculomegaly.

PURPOSE: Foetal ventriculomegaly (VM) is one of the most commonly diagnosed brain abnormalities. The aims of this study were to assess cases with isolated VM, describe the prenatal course and assess short- and long-term follow-up at the age of 2 years. METHODS: We performed a retrospective analysis from our prenatal data base and included all children that were prenatally diagnosed with VM in our unit between 2008 and 2013 (n = 250). Prenatal management, postnatal outcome and neurologic development at the age of 2 years were evaluated. RESULTS: A total of 106 children were born at our institution and were diagnosed prenatally with isolated borderline VM. A total of 1.9% (n = 2/106) was transferred to the neonatal unit. A total of 0.9% (n = 1/106) showed abnormal findings in postnatal brain ultrasound. A total of 1.9% (n = 2/106) showed mild neurologic abnormalities after birth, but none had to be seen by a neuropediatrician. At the follow-up at 2 years, 2.5% (n = 1/40) had an insertion of a shunt. CONCLUSION: Based on our analysis, the majority of isolated borderline VM do not show short- or long-term neurological abnormalities. However, all cases of VM should be referred to a detailed prenatal ultrasound exam by a specialist.

Impact of parturition on maternal cardiovascular and neuronal integrity in a high risk cohort - a prospective cohort study.

BACKGROUND: To better understand the profound multisystem changes in maternal physiology triggered by parturition, in particular in the underexplored neuronal system, by deploying a panel of pre- vs post-delivery maternal serum biomarkers, most notably the neuronal cytoskeleton constituent neurofilament light chain (NfL). This promising fluid biomarker is not only increasingly applied to investigate disease progression in numerous brain diseases, particularly in proteopathies, but also in detection of traumatic brain injury or monitoring neuroaxonal injury after ischemic stroke. METHODS: The study was nested within a prospective cohort study of pregnant women at risk of developing preeclampsia at the University Hospital of Basel. Paired ante- and postpartum levels of progesterone, soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), mid-regional pro-atrial natriuretic peptide (MR-proANP), copeptin (CT-proAVP), and NfL were measured in 56 women with complete clinical data. RESULTS: Placental delivery significantly decreased all placental markers: progesterone 4.5-fold, PlGF 2.2-fold, and sFlt-1 1.7-fold. Copeptin and MR-proANP increased slightly (1.4- and 1.2-fold, respectively). Unexpectedly, NfL levels (median [interquartile range]) increased significantly post-partum: 49.4 (34.7-77.8) vs 27.7 (16.7-31.4) pg/ml (p < 0.0001). Antepartum NfL was the sole independent predictor of NfL peri-partum change; mode of delivery, duration of labor, clinical characteristics and other biomarkers were all unrelated. Antepartum NfL levels were themselves independently predicted only by maternal age. CONCLUSIONS: Parturition per se increases maternal serum NfL levels, suggesting a possible impact of parturition on maternal neuronal integrity.

sFlt-1/PlGF Ratio as a Predictive Marker in Women with Suspected Preeclampsia: An Economic Evaluation from a Swiss Perspective.

In Switzerland, 2.3% of pregnant women develop preeclampsia. Quantification of the soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio has shown a diagnostic value in the second and third trimesters of pregnancy, in particular in ruling out preeclampsia within one week. We estimated the economic impact of implementing sFlt-1/PlGF ratio evaluation, in addition to the standard of care (SOC), for women with suspected preeclampsia from a Swiss healthcare system's perspective. A decision tree model was developed to estimate direct medical costs of diagnosis and management of a simulated cohort of Swiss pregnant women with suspected preeclampsia (median week of gestation: 32) until delivery. The model compared SOC vs. SOC plus sFlt-1/PlGF ratio, using clinical inputs from a large multicenter study (PROGNOSIS). Resource use data and unit costs were obtained from hospital records and public sources. The assumed cost for sFlt-1/PlGF evaluation was €141. Input parameters were validated by clinical experts in Switzerland. The model utilized a simulated cohort of 6084 pregnant women with suspected preeclampsia (representing 7% of all births in Switzerland in 2015, n = 86,919). In a SOC scenario, 36% of women were hospitalized, of whom 27% developed preeclampsia and remained hospitalized until birth. In a sFlt-1/PlGF test scenario, 76% of women had a sFlt-1/PlGF ratio of ≤38 (2% hospitalized), 11% had a sFlt-1/PlGF ratio of >38-<85 (55% hospitalized), and 13% had a sFlt-1/PlGF ratio of ≥85 (65% hospitalized). Total average costs/pregnant woman (including birth) were €10,925 vs. €10,579 (sFlt-1/PlGF), and total costs were €66,469,362 vs. €64,363,060 (sFlt-1/PlGF). Implementation of sFlt-1/PlGF evaluation would potentially achieve annual savings of €2,105,064 (€346/patient), mainly due to reduction in unnecessary hospitalization. sFlt-1/PlGF evaluation appears economically promising in predicting short-term absence of preeclampsia in Swiss practice. Improved diagnostic accuracy and reduction in unnecessary hospitalization could lead to significant cost savings in the Swiss healthcare system.

Prevention of pre-eclampsia after infertility treatment: Preconceptional minimalisation of risk factors.

Although an increased risk of pre-eclampsia in pregnancies conceived after infertility treatment has been reported, it remains unknown whether preconceptional minimalisation of known risk factors would help in preventing pre-eclamsia. Obesity and preconceptional blood pressure are discussed as major risks for the development of pre-eclampsia and low doses of aspirins, folic acid, statins and metformin are discussed as potential preventive treatments to decrease the risk of pre-eclampsia. In the present review we discuss whether present-day reproductive medicine could progress towards complication-free pregnancy.

Feto-Maternal Microchimerism: The Pre-eclampsia Conundrum.

Feto-maternal microchimerism (FMM) involves bidirectional cross-placental trafficking during pregnancy, leading to a micro-chimeric state that can persist for decades. In this manner a pregnant woman will harbor cells from her mother, as well as, cells from her child. Historically, eclampsia, a severe disorder of pregnancy provided the basis for FMM following the detection of trophoblast cells in the lungs of deceased women. Bi-directional cell trafficking between mother and fetus is also altered in pre-eclampsia and has been suggested to contribute to the underlying etiology. FMM has been implicated in tolerance promotion, remission of auto-inflammatory disorders during pregnancy, or the development of autoimmune conditions post-partum. The underlying mechanism whereby the host immune system is modulated is unclear but appears to involve HLA class II molecules, in that incompatibility between mother and fetus promotes remission of rheumatoid arthritis, whereas feto-maternal HLA compatibility may assist in the post-partum initiation of scleroderma. Couples having a high degree of HLA class II compatibility have an increased risk for pre-eclampsia, while the occurrence of scleroderma and rheumatoid arthritis is greater in pre-eclamptic cases than in women with normal pregnancies, suggesting a long term autoimmune predisposition. Since pregnant women with pre-eclampsia exhibit significantly lower levels of maternally-derived micro-chimerism, the question arises whether pre-eclampsia and post-partum development of autoimmune conditions occur due to the failure of the grandmothers cells to adequately regulate an inappropriate micro-chimeric constellation.

Exome sequencing of fetal anomaly syndromes: novel phenotype-genotype discoveries.

The monogenic etiology of most severe fetal anomaly syndromes is poorly understood. Our objective was to use exome sequencing (ES) to increase our knowledge on causal variants and novel candidate genes associated with specific fetal phenotypes. We employed ES in a cohort of 19 families with one or more fetuses presenting with a distinctive anomaly pattern and/or phenotype recurrence at increased risk for lethal outcomes. Candidate variants were identified in 12 families (63%); in 6 of them a definite diagnosis was achieved including known or novel variants in recognized disease genes (MKS1, OTX2, FGFR2, and RYR1) and variants in novel disease genes describing new fetal phenotypes (CENPF, KIF14). We identified variants likely causal after clinical and functional review (SMAD3, KIF4A, and PIGW) and propose novel candidate genes (PTK7, DNHD1, and TTC28) for early human developmental disease supported by functional and cross-species phenotyping evidence. We describe rare and novel fetal anomaly syndromes and highlight the diagnostic utility of ES, but also its contribution to discovery. The diagnostic yield of the future application of prenatal ES will depend on our ability to increase our knowledge on the specific phenotype-genotype correlations during fetal development.

Personalized weight change prediction in the first week of life.

BACKGROUND & AIMS: Almost all neonates show physiological weight loss and consecutive weight gain after birth. The resulting weight change profiles are highly variable as they depend on multiple neonatal and maternal factors. This limits the value of weight nomograms for the early identification of neonates at risk for excessive weight loss and related morbidities. The objective of this study was to characterize weight changes and the effect of supplemental feeding in late preterm and term neonates during the first week of life, to identify and quantify neonatal and maternal influencing factors, and to provide an educational online prediction tool. METHODS: Longitudinal weight data from 3638 healthy term and late preterm neonates were prospectively recorded up to 7 days of life. Two-thirds (n = 2425) were randomized to develop a semi-mechanistic model characterizing weight change as a balance between time-dependent rates of weight gain and weight loss. The dose-dependent effect of supplemental feeding on weight gain was characterized. A population analysis applying nonlinear mixed-effects modeling was performed using NONMEM 7.3. The model was evaluated on the remaining third of neonates (n = 1213). RESULTS: Key population characteristics (median [range]) of the whole sample were gestational age 39.9 [34.4-42.4] weeks, birth weight 3400 [1980-5580] g, maternal age 32 [15-51] years, cesarean section 26%, and girls 50%. The model demonstrated good predictive performance (bias 0.01%, precision 0.56%), and is able to accurately predict individual weight change (bias 0.15%, precision 1.43%) and the dose-dependent effects of supplemental feeding up to 1 week after birth based on weight measurements during the first 3 days of life, including birth weight, and the following characteristics: gestational age, gender, delivery mode, type of feeding, maternal age, and parity. CONCLUSIONS: We present the first mathematical model not only to describe weight change in term and late preterm neonates but also to provide an educational online tool for personalized weight prediction in the first week of life.

Diagnostic Accuracy of Different Soluble fms-Like Tyrosine Kinase 1 and Placental Growth Factor Cut-Off Values in the Assessment of Preterm and Term Preeclampsia: A Gestational Age Matched Case-Control Study.

Introduction: The objective was to investigate the diagnostic accuracy of different thresholds of the soluble vascular endothelial growth factor receptor-1 (sFlt-1) and the placental growth factor (PlGF) in preterm (≤37 weeks) and term (>37 weeks) preeclampsia (PE). Materials and Methods: A nested case-control study was performed from a high-risk Swiss cohort. Only blood samples on the day of PE diagnosis were included. The primary outcome was to verify the diagnosis using the recently proposed cut-off values for PE (sFlt-1:PlGF ratio of ≥85 in ≤ 34 weeks or ≥110 in >34 weeks), and the gestational age dependent centiles. Results: Thirty-four women with preterm PE were matched with 64 controls and 25 women with term PE with 45 controls. The test performance of the sFlt-1:PlGF ratio in preterm PE was very good (AUROCC of 0.95). The sFlt-1:PlGF ratio could adequately predict adverse fetal or neonatal outcome. In term PE, sFlt-1 alone showed a slightly better diagnostic accuracy with an AUROCC of 0.84. Almost all women with a sFlt-1:PlGF ratio above threshold delivered during the following week. Discussion: In pregnant women with high risk of developing PE, the sFlt-1:PlGF ratio and sFlt-1 levels help clinicians to confirm the diagnosis of imminent preterm PE and can additionally be used to rule out PE at term.

Excessive Neutrophil Activity in Gestational Diabetes Mellitus: Could It Contribute to the Development of Preeclampsia?

Gestational diabetes mellitus is a transient form of glucose intolerance occurring during pregnancy. Pregnancies affected by gestational diabetes mellitus are at risk for the development of preeclampsia, a severe life threatening condition, associated with significant feto-maternal morbidity and mortality. It is a risk factor for long-term health in women and their offspring. Pregnancy has been shown to be associated with a subliminal degree of neutrophil activation and tightly regulated generation of neutrophil extracellular traps (NETs). This response is excessive in cases with preeclampsia, leading to the presence of large numbers of NETs in affected placentae. We have recently observed that circulatory neutrophils in cases with gestational diabetes mellitus similarly exhibit an excessive pro-NETotic phenotype, and pronounced placental presence, as detected by expression of neutrophil elastase. Furthermore, exogenous neutrophil elastase liberated by degranulating neutrophils was demonstrated to alter trophoblast physiology and glucose metabolism by interfering with key signal transduction components. In this review we examine whether additional evidence exists suggesting that altered neutrophil activity in gestational diabetes mellitus may contribute to the development of preeclampsia.

Performance of a Blood Pressure Smartphone App in Pregnant Women: The iPARR Trial (iPhone App Compared With Standard RR Measurement).

Hypertensive disorders are one of the leading causes of maternal death worldwide. Several smartphone apps claim to measure blood pressure (BP) using photoplethysmographic signals recorded by smartphone cameras. However, no single app has been validated for this use to date. We aimed to validate a new, promising smartphone algorithm. In this subgroup analysis of the iPARR trial (iPhone App Compared With Standard RR Measurement), we tested the Preventicus BP smartphone algorithm on 32 pregnant women. The trial was conducted based on the European Society of Hypertension International Protocol revision 2010 for validation of BP measuring devices in adults. Each individual received 7 sequential BP measurements starting with the reference device (Omron-HBP-1300) and followed by the smartphone measurement, resulting in 96 BP comparisons. Validation requirements of the European Society of Hypertension International Protocol revision 2010 were not fulfilled. Mean (±SD) systolic BP disagreement between the test and reference devices was 5.0 (±14.5) mm Hg. The number of absolute differences between test and reference device within 5, 10, and 15 mm Hg was 31, 53, and 64 of 96, respectively. A Bland-Altman plot showed an overestimation of smartphone-determined systolic BP in comparison with reference systolic BP in low range but an underestimation in medium-range BP. The Preventicus BP smartphone algorithm failed the accuracy criteria for estimating BP in pregnant women and was thus not commercialized. Pregnant women should be discouraged from using BP smartphone apps, unless there are algorithms specifically validated according to common protocols. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02552030.

Neurofilament as Neuronal Injury Blood Marker in Preeclampsia.

Preeclampsia has been shown to be associated with changes in cerebral structure and cognitive function later in life. Nf (neurofilaments) are specific scaffolding proteins of neurons, and their quantification in serum has been proposed as a biomarker for neuroaxonal injury. We performed a prospective, longitudinal, single-center study at the University Hospital of Basel to determine serum Nf concentrations in pregnant women with singleton pregnancies and with high risk of preeclampsia or with early signs of preeclampsia. Enrollment started at 21 weeks of gestation, followed up with multiple visits until delivery. Sixty out of 197 women developed preeclampsia (30.5%). NfL (Nf light chain) was measured with a highly sensitive single molecule array (Simoa) assay, in addition to the established preeclampsia markers sFlt-1 (soluble fms-like tyrosine kinase-1) and PlGF (placental growth factor). The most important independent predictors of NfL were maternal age, number of pregnancies, and proteinuria. NfL levels increased during pregnancy and were significantly higher in women developing preeclampsia. The discriminatory accuracy of NfL, PlGF, and sFlt-1 in receiver operating characteristic curves analysis (area under the curve) of the overall group was 0.68, 0.81, and 0.84, respectively, and in women older than 36 years 0.7, 0.62, and 0.79, respectively. We conclude that increased axonal injury serum marker NfL predicts preeclampsia particularly in older women, with an accuracy similar to the established angiogenic factors. NfL may serve as an early indicator of preeclampsia-induced changes in cerebral structure and may help to stratify disease management.

Impact of nationwide health insurance coverage for non-invasive prenatal testing.

OBJECTIVE: To describe the changes in women's choices for prenatal testing after the introduction of nationwide health insurance coverage for non-invasive prenatal testing (NIPT) in Switzerland. METHODS: The present retrospective study reviewed data from all women with singleton pregnancies who presented at the prenatal unit of Basel University Hospital, Switzerland, for first-trimester screening between July 15, 2014, and December 31, 2015. Women were divided into three categories according to their risk for aneuploidy, and the uptake of NIPT in the period before and after the introduction of the nationwide coverage for NIPT was compared. RESULTS: Overall, 887 women were included in the study: 573 screens were carried out before (group 1) and 314 after (group 2) the introduction of insurance coverage for NIPT. In group 1, 53 (9.2%) had NIPT as compared with 72 (22.9%) in group 2. Among women with intermediate risk for aneuploidies and basic insurance coverage, NIPT increased by 56% (12/88 [14%] vs 32/46 [70%]; P<0.001). CONCLUSION: There was a notable increase in the uptake of NIPT; uptake was most significant among women with basic health insurance and intermediate risk for aneuploidy.