Mediating processes underlying the associations between maternal obesity and the likelihood of cesarean birth.

BACKGROUND: Pregnant women with obesity are more likely to experience cesarean birth compared to women without obesity. Yet, little is known about the underlying mechanisms. The objective of this study was therefore to evaluate how mediators contribute to the association between obesity and prelabor/intrapartum cesarean birth. METHODS: We retrospectively analyzed Swiss cohort data from 394,812 singleton, cephalic deliveries between 2005 and 2020. Obesity (BMI ≥ 30 kg/m2 ) was defined as the exposure and prelabor or intrapartum cesarean birth as the outcomes. Hypothesized mediators included gestational comorbidities, large-for-gestational-age infant, pregnancy duration >410/7 weeks, slower labor progress, labor induction, and history of cesarean birth. We performed path analyses using generalized structural equation modeling and assessed mediation by a counterfactual approach. RESULTS: Women with obesity had a cesarean birth rate of 39.36% vs. 24.12% in women without obesity. The path models mainly showed positive direct and indirect associations between obesity and cesarean birth. In the total sample, the mediation models explained up to 39.47% (95% CI 36.92-42.02) of the association between obesity and cesarean birth, and up to 57.13% (95% CI 54.10-60.16) when including history of cesarean birth as mediator in multiparous women. Slower labor progress and history of cesarean birth were found to be the most clinically significant mediators. CONCLUSIONS: This study provides empirical insights into how obesity may increase cesarean birth rates through mediating processes. Particularly allowing for a slower labor progress in women with obesity might reduce cesarean birth rates and prevent subsequent repeat cesarean births in multiparous women.

"Don't add fuel to the fire"- Hyperhemolysis Syndrome in a pregnant woman with compound Sickle cell disease/ß0-thalassemia - Case report and review of the literature.

Hyperhemolysis Syndrome (HHS) is a rare and severe post-transfusion complication characterized by the destruction of both recipient and donor red blood cells (RBC). The underlying mechanism of HHS is not fully understood and proper management can be difficult. Furthermore, there are few reports regarding HHS in pregnancy. We report on the development and management of HHS in a pregnant woman with known compound Sickle cell disease/ß-0-thalassemia after transfusion of not fully compatible packed red blood cells (PRBC). We aim to raise awareness on this diagnostically challenging and life-threatening type of hemolysis with this report, and to stress the need to consider the diagnosis of HHS in SCD patients with progressive anemia despite PRBC administration.

First-trimester glycosylated hemoglobin (HbA1c) and maternal characteristics in the prediction of gestational diabetes: An observational cohort study.

INTRODUCTION: This study aimed to investigate the extent to which gestational diabetes mellitus (GDM) can be predicted in the first trimester by combining a marker of growing interest, glycosylated hemoglobin A1c (HbA1c), and maternal characteristics. MATERIAL AND METHODS: This observational study was conducted in the outpatient obstetric department of our institution. The values of HbA1c and venous random plasma glucose were prospectively assessed in the first trimester of pregnancy. We determined maternal characteristics that were independent predictors from the regression analysis and calculated areas under the receiver-operating curves by combining the maternal age, body mass index, previous history of GDM, and first-degree family history for diabetes mellitus. Moreover we investigated the predictive capability of HbA1c to exclude GDM. Patients with a first-trimester HbA1c level of 6.5% (48 mmol/mol) or more were excluded. The study was registered at ClinicalTrials.gov ID: NCT02139254. RESULTS: We included 785 cases with complete dataset. The prevalence of GDM was 14.7% (115/785). Those who developed GDM had significantly higher HbA1c and random plasma glucose values (p < 0.0001 and p = 0.0002, respectively). In addition, they had a higher body mass index, were more likely to have a history of GDM and/or a first-degree family history of diabetes. When these maternal characteristics were combined with the first-trimester HbA1c and random plasma glucose the combined area under the receiver operating characteristics curve was 0.76 (95% CI 0.70-0.81). CONCLUSIONS: Our results indicate that HbA1c and random plasma glucose values combined with age, body mass index, and personal and family history, allow the identification of women in the first trimester who are at increased risk of developing GDM.

Use of Polynomial Reference Ranges for Atrioventricular Intervals Assessed by Fetal Echocardiography in Anti-Ro/SSA Antibody-Positive Pregnancies to Exclude Fetal Heart Blocks: A Pilot Study.

INTRODUCTION: Maternal anti-Ro/SSA antibodies can cause fetal atrioventricular blocks (AVB). This pilot study aims to apply previously published echocardiographic reference ranges of the fetal atrioventricular (AV) intervals in the setting of anti-Ro/SSA antibody-positive pregnancies in order to exclude a 1° AVB. MATERIALS AND METHODS: Between January 2018 and September 2022, we included all women with known anti-Ro/SSA antibodies followed up at the prenatal ultrasound department of the University Hospital of Bern. AV intervals were serially measured by two previously reported methods and plotted against previously created reference ranges. RESULTS: We included 23 pregnancies from 17 anti-Ro/SSA antibody-positive women with connective tissue diseases. 443 AV interval measurements were recorded between 16+3 and 38+4 weeks of gestation. 14 (3.2%) AV-intervals measured >150 ms, none measured >170 ms and 8 (1.8%) were found to be >95th percentile. In none of the pregnancies, serial AV-prolongations were noted. The postnatal electrocardiograms demonstrated normal sinus rhythm without AVB in all children. CONCLUSION: AV intervals of pregnancies followed up for anti-Ro/SSA antibodies without neonatal AVB lie within our published polynomial reference ranges. While diagnosing a 1° AVB remains controversial, more data are needed to prove that our reference ranges are helpful exclude a 1° AVB.

Implementing Preeclampsia Screening in Switzerland (IPSISS): First Results from a Multicentre Registry.

INTRODUCTION: The Fetal Medicine Foundation (FMF) London developed a first trimester combined screening algorithm for preterm preeclampsia (pPE) that allows a significantly higher detection of pregnancies at risk compared to conventional screening by maternal risk factors only. The aim of this trial is to validate this screening model in the Swiss population in order to implement this screening into routine first trimester ultrasound and to prescribe low-dose aspirin 150 mg (LDA) in patients at risk for pPE. Therefore, a multicentre registry study collecting and screening pregnancy outcome data was initiated in 2020; these are the preliminary results. METHODS: Between June 1, 2020, and May 31, 2021, we included all singleton pregnancies with pPE screening at the hospitals of Basel, Lucerne, and Bern. Multiple of medians of uterine artery pulsatility index (UtA-PI), mean arterial pressure (MAP), placental growth factor (PlGF), and pregnancy-associated plasma protein A (PAPP-A) as well as risks were analysed as calculated by each centre's software and recalculated on the FMF online calculator for comparative reasons. Statistical analyses were performed by GraphPad Version 9.1. RESULTS: During the study period, 1,027 patients with singleton pregnancies were included. 174 (16.9%) had a risk >1:100 at first trimester combined screening. Combining the background risk, MAP, UtA-PI, and PlGF only, the cut-off to obtain a screen positive rate (SPR) of 11% is ≥1:75. Outcomes were available for 968/1,027 (94.3%) of all patients; 951 resulted in live birth. Fifteen (1.58%) developed classical preeclampsia (PE), 23 (2.42%) developed PE according to the International Society for the Study of Hypertension in Pregnancy (ISSHP) definition. CONCLUSION: First trimester combined screening for PE and prevention with LDA results in a low prevalence of PE. The screening algorithm performs according to expectations; however, the cut-off of >1:100 results in a SPR above the accepted range and a cut-off of ≥1:75 should be considered for screening. More data are needed to evaluate, if these results are representative for the general Swiss population.

Postpartum urinary retention: what are the sequelae? A long-term study and review of the literature.

INTRODUCTION AND HYPOTHESIS: Postpartum urinary retention (PUR) may cause long-term urogenital tract morbidity. The incidence ranges from 0.18 to 14.6%, but the importance of prompt diagnosis and appropriate management is often underappreciated. The paucity of data on long-term outcome after PUR contributes to these drawbacks. The aim of this study was to assess long-term persistence of elevated PVR (post-void residual urine) volume after PUR. Pathophysiology, risk factors and management of PUR are reviewed. METHODS: In our tertiary referral urogynecology unit in the University Women's Hospital of Bern, Switzerland, all patients who were referred for PUR were asked to participate in this study. PVR was measured sonographically every 2 days until day 15, then after 6, 12, 24 and 36 months and, if increased, the patients were instructed to perform clean intermittent self-catheterization. If retention persisted longer than the lactation period, multichannel urodynamics was performed. RESULTS: Sixty-two patients were included. The median PVR normalized at day 7. Long-term voiding disorders were found in 8.2%, 6.7%, and 4.9% after 1, 2, and 3 years respectively. Multichannel urodynamics confirmed in all patients with persisting retention an acontractile detrusor and de novo stress urinary incontinence in 4 cases. Quantile regression did not reveal any factor contributing to earlier recovery. Eighty-nine percent of the patients with PUR had operative vaginal deliveries, emphasizing the importance of this risk factor for PUR. CONCLUSIONS: In most cases PUR resolves early, but voiding difficulties persist more often than previously thought, and for these patients the consequences are devastating. Obstetric awareness, early active management, and developing management strategies in the postpartum period might preclude lower urinary tract morbidity.

School-age structural and functional MRI and lung function in children following lung resection for congenital lung malformation in infancy.

BACKGROUND: The management of asymptomatic congenital lung malformations is debated. Particularly, there is a lack of information regarding long-term growth and development of the remaining lung in children following lung resection for congenital lung malformations. In addition to conventional pulmonary function tests, we used novel functional magnetic resonance imaging (MRI) methods to measure perfusion and ventilation. OBJECTIVE: To assess functionality of the remaining lung expanded into the thoracic cavity after resection of congenital lung malformations. MATERIALS AND METHODS: A prospective, cross-sectional pilot study in five children who had surgery for congenital lung malformations during infancy. Participants had structural and functional MRI as well as spirometry, body plethysmography and multiple breath washout at school age. RESULTS: Structural MRI showed an expansion of the remaining lung in all cases. Fractional ventilation and relative perfusion of the expanded lung were locally decreased in functional MRI. In all other parts of the lungs, fractional ventilation and relative perfusion were normal in all children. There was an association between overall impairment of perfusion and elevated lung clearance index. The results of spirometry and body plethysmography varied between patients, including normal lung function, restriction and obstruction. CONCLUSION: Fractional ventilation and relative perfusion maps from functional MRI specifically locate impairment of the remaining lung after lung resection. These changes are not captured by conventional measures such as structural MRI and standard pulmonary function tests. Therefore, following lung resection for congenital lung malformation, children should be investigated more systematically with functional lung MRI.

Differential Diagnosis and Prognosis of Fetuses with Bilateral Enlarged, Hyperechogenic Kidneys: Renal Volume and Amniotic Fluid Volume with Advancing Gestation.

INTRODUCTION: This study's objective was to identify prenatal criteria helping differential diagnosis of bilateral enlarged, hyperechogenic kidneys, especially looking at development of renal volume and amniotic fluid volume with increasing gestational age. METHOD: Retrospective analysis (single-center database) of all bilateral enlarged, hyperechogenic kidneys between 2000-2018. Renal enlargement was defined as renal volume>90th percentile. Evaluation included development of renal and amniotic fluid volume during pregnancy and fetal outcome. RESULTS: 23 cases fulfilled the inclusion criteria. 12 pregnancies were terminated. For 11 continued pregnancies, longitudinal information on amniotic fluid volume and renal volume were available. 4 cases with oligohydramnios showed a progressive reduction; 6 cases with normal/increased amniotic fluid volume remained stable; in 1 case amniotic fluid volume normalized from initially being oligohydramnios. Regarding renal volume, 4 cases showed exponential enlargement, 3 cases linear progression; in 2 cases renal volume stabilized after initial progression; 2 cases showed initial progression and secondary regression. 4 fetuses survived: 3 autosomal dominant polycystic kidney diseases, 1 Bardet-Biedl syndrome. CONCLUSION: Progressive reduction of amniotic fluid volume with exponential increase of renal volume is highly suggestive for autosomal recessive polycystic kidney disease. Cases of autosomal dominant polycystic kidney disease show a linear progression of renal volume>90th percentile and mostly normal amniotic fluid volume.

EULAR recommendations for a core data set for pregnancy registries in rheumatology.

BACKGROUND AND OBJECTIVE: There is an urgent need for robust data on the trajectories and outcomes of pregnancies in women with inflammatory rheumatic diseases (IRD). In particular when rare outcomes or rare diseases are to be investigated, collaborative approaches are required. However, joint data analyses are often limited by the heterogeneity of the different data sources.To facilitate future research collaboration, a European League Against Rheumatism (EULAR) Task Force defined a core data set with a minimum of items to be collected by pregnancy registries in rheumatology covering the period of pregnancy and the 28-day neonatal phase in women with any underlying IRD. METHODS: A stepwise process included a two-round Delphi survey and a face-to-face meeting to achieve consensus about relevant items. RESULTS: A total of 64 multidisciplinary stakeholders from 14 different countries participated in the two rounds of the Delphi process. During the following face-to-face meeting of the EULAR Task Force, consensus was reached on 51 main items covering 'maternal information', 'pregnancy' and 'treatment'. Generic instruments for assessment are recommended for every item. Furthermore, for the five most frequent IRDs rheumatoid arthritis, spondyloarthritis, juvenile idiopathic arthritis, systemic lupus erythematosus and other connective tissue diseases, disease-specific laboratory markers and disease activity measurements are proposed. CONCLUSION: This is the first consensus-based core data set for prospective pregnancy registries in rheumatology. Its purpose is to stimulate and facilitate multinational collaborations that aim to increase the knowledge about pregnancy course and safety of treatment in women with IRDs during pregnancy.

Informal coercion during childbirth: risk factors and prevalence estimates from a nationwide survey of women in Switzerland.

BACKGROUND: In many countries, the increase in facility births is accompanied by a high rate of obstetric interventions. Lower birthrates or elevated risk factors such as women's higher age at childbirth and an increased need for control and security cannot entirely explain this rise in obstetric interventions. Another possible factor is that women are coerced to agree to interventions, but the prevalence of coercive interventions in Switzerland is unknown. METHODS: In a nationwide cross-sectional online survey, we assessed the prevalence of informal coercion during childbirth, women's satisfaction with childbirth, and the prevalence of women at risk of postpartum depression. Women aged 18 years or older who had given birth in Switzerland within the previous 12 months were recruited online through Facebook ads or through various offline channels. We used multivariable logistic regression to estimate the risk ratios associated with multiple individual and contextual factors. RESULTS: In total, 6054 women completed the questionnaire (a dropout rate of 16.2%). An estimated 26.7% of women experienced some form of informal coercion during childbirth. As compared to vaginal delivery, cesarean section (CS) and instrumental vaginal birth were associated with an increased risk of informal coercion (planned CS risk ratio [RR]: 1.52, 95% confidence interval [1.18,1.96]; unplanned CS RR: 1.92 [1.61,2.28]; emergency CS RR: 2.10 [1.71,2.58]; instrumental vaginal birth RR: 2.17 [1.85,2.55]). Additionally, migrant women (RR: 1.45 [1.26,1.66]) and women for whom a self-determined vaginal birth was more important (RR: 1.15 [1.06,1.24]) more often reported informal coercion. Emergency cesarean section (RR: 1.32 [1.08,1.62]), being transferred to hospital (RR: 1.33 [1.11,1.60]), and experiencing informal coercion (RR: 1.35 [1.19,1.54]) were all associated with a higher risk of postpartum depression. Finally, women who had a non-instrumental vaginal birth reported higher satisfaction with childbirth while women who experienced informal coercion reported lower satisfaction. CONCLUSIONS: One in four women experience informal coercion during childbirth, and this experience is associated with a higher risk of postpartum depression and lower satisfaction with childbirth. To prevent traumatic after-effects, health care professionals should make every effort to prevent informal coercion and to ensure sensitive aftercare for all new mothers.

Obstetrician involvement in planned midwife-led births: a cohort study in an obstetric department of a University Hospital in Switzerland.

BACKGROUND: Healthy women with low risk singleton pregnancies are offered a midwife-led birth model at our department. Exclusion criteria for midwife-led births include a range of abnormalities in medical history and during the course of pregnancy. In case of complications before, during or after labor and birth, an obstetrician is involved. The purpose of this study was 1) to evaluate the frequency of and reasons for secondary obstetrician involvement in planned midwife-led births and 2) to assess the maternal and neonatal outcome. METHODS: We analyzed a cohort of planned midwife-led births during a 14 years period (2006-2019). Evaluation included a comparison between midwife-led births with or without secondary obstetrician involvement, regarding maternal characteristics, birth mode, and maternal and neonatal outcome. Statistical analysis was performed by unpaired t-tests and Chi-square tests. RESULTS: In total, there were 532 intended midwife-led births between 2006 and 2019 (2.6% of all births during this time-period at the department). Among these, 302 (57%) women had spontaneous vaginal births as midwife-led births. In the remaining 230 (43%) births, obstetricians were involved: 62% of women with obstetrician involvement had spontaneous vaginal births, 25% instrumental vaginal births and 13% caesarean sections. Overall, the caesarean section rate was 5.6% in the whole cohort of women with intended midwife-led births. Reasons for obstetrician involvement primarily included necessity for labor induction, abnormal fetal heart rate monitoring, thick meconium-stained amniotic fluid, prolonged first or second stage of labor, desire for epidural analgesia, obstetrical anal sphincter injuries, retention of placenta and postpartum hemorrhage. There was a significantly higher rate of primiparous women in the group with obstetrician involvement. Arterial umbilical cord pH < 7.10 occurred significantly more often in the group with obstetrician involvement, while 5' Apgar score < 7 did not differ significantly. The overall transfer rate of newborns to neonatal intensive care unit was low (1.3%). CONCLUSION: A midwife-led birth in our setting is a safe alternative to a primarily obstetrician-led birth, provided that selection criteria are being followed and prompt obstetrician involvement is available in case of abnormal course of labor and birth or postpartum complications.

Soluble fms-like tyrosine kinase 1 (sFlt-1): A novel biochemical marker for acute fatty liver of pregnancy.

INTRODUCTION: Acute fatty liver of pregnancy (AFLP) substantially contributes to maternal and neonatal morbidity and mortality. Other liver-associated pregnancy complications such as preeclampsia-associated HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome may be difficult to differentiate from AFLP as these diseases overlap with regard to multiple clinical and laboratory features. The aim of this study was to investigate angiogenic profiles by measuring soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) in pregnancies compromised by AFLP and to compare them with those complicated by HELLP syndrome. MATERIAL AND METHODS: Pregnant women affected by AFLP or HELLP syndrome were enrolled. The study population of women with HELLP syndrome was part of a larger data collection obtained in our clinic that has been used for previous work. Patients' angiogenic profiles were assessed by measuring sFlt-1 and PlGF serum levels. To assess the diagnostic potential of these angiogenic markers in AFLP, as well as discriminating it from HELLP syndrome, non-parametric tests were used and receiver operating curves were calculated. RESULTS: Six women with AFLP and 48 women with HELLP syndrome were included in the study. Patients with AFLP showed significantly higher sFlt-1 levels (median: 57 570 pg/mL; range 31 609-147 170 pg/mL) than patients with HELLP syndrome (9713 pg/mL; 1348-30 781 pg/mL; p < 0.001). PlGF serum levels were higher in patients with AFLP compared with those with HELLP syndrome (197 pg/mL; 127-487 pg/mL vs. 40 pg/mL; 9-644 pg/mL, respectively; p < 0.01). sFlt-1/PlGF ratios were not significantly different between AFLP and HELLP syndrome patients (192; 157-1159 vs. 232; 3-948, respectively; NS). In our study population, an sFlt-1 cut-off value of 31 100 pg/mL allowed differentiation between these two diseases with a sensitivity and specificity of 100%. A linear correlation was found between the cumulative numbers of Swansea criteria and sFlt-1 serum levels (r = 0.97; p < 0.01). CONCLUSIONS: AFLP is associated with very high sFlt-1 serum levels in particular in women fulfilling eight or more Swansea criteria. Besides the suggested Swansea criteria to diagnose AFLP, an sFlt-1 value above 31 100 pg/mL may be an additional biochemical feature improving discrimination between AFLP and HELLP syndrome. However, because of the small number of pregnancies affected by AFLP included in this work further studies are needed to corroborate our findings.

Changepoint analysis of gestational age and birth weight: proposing a refinement of Diagnosis Related Groups.

BACKGROUND: Although the complexity and length of treatment is connected to the newborn's maturity and birth weight, most case-mix grouping schemes classify newborns by birth weight alone. The objective of this study was to determine whether the definition of thresholds based on a changepoint analysis of variability of birth weight and gestational age contributes to a more homogenous classification. METHODS: This retrospective observational study was conducted at a Tertiary Care Center with Level III Neonatal Intensive Care and included neonate cases from 2016 through 2018. The institutional database of routinely collected health data was used. The design of this cohort study was explorative. The cases were categorized according to WHO gestational age classes and SwissDRG birth weight classes. A changepoint analysis was conducted. Cut-off values were determined. RESULTS: When grouping the cases according to the calculated changepoints, the variability within the groups with regard to case related costs could be reduced. A refined grouping was achieved especially with cases of >2500 g birth weight. An adjusted Grouping Grid for practical purposes was developed. CONCLUSIONS: A novel method of classification of newborn cases by changepoint analysis was developed, providing the possibility to assign costs or outcome indicators to grouping mechanisms by gestational age and birth weight combined.

Cervico-vaginal placental α-macroglobulin-1 combined with cervical length for the prediction of preterm birth in women with threatened preterm labor.

INTRODUCTION: Preterm birth is a major cause of neonatal morbidity and mortality. There is an urgent need to accurately predict imminent delivery to enable necessary interventions such as tocolytic, glucocorticoid, and magnesium sulfate administration. We aimed to evaluate placental α-macroglobulin-1 as a new diagnostic marker in the prediction of preterm birth. MATERIAL AND METHODS: We performed a prospective observational trial in women with intact membranes between 24+0 and 36+6 weeks of gestation. We included both women with and without threatened preterm labor symptoms. We evaluated the test performance of placental α-macroglobulin-1 measurements in cervicovaginal fluid regarding three different presentation-to-delivery intervals: ≤2, ≤7, ≤14 days. In addition, we calculated placental α-macroglobulin-1 performance in combination with other prognostic factors such as ultrasonographic cervical length measurements. RESULTS: We included 126 women in the study. We detected high specificity (97%-98%) and negative predictive value (89%-97%) for placental α-macroglobulin-1 at all time intervals. We assessed placental α-macroglobulin-1 in combination with cervical length measurements (≤15 mm) in the sub-group of women presenting with threatened preterm labor symptoms (n = 63) and detected high positive predictive values (100%) for 7- and 14-day presentation-to-delivery intervals. CONCLUSIONS: Our study provides evidence that placental α-macroglobulin-1 testing in cervicovaginal fluid, in combination with cervical length measurements, accurately predicts preterm birth in women with preterm labor symptoms. This novel test combination may be used clinically to triage women presenting with threatened preterm labor, avoiding overtreatment and unnecessary hospitalizations.

EULAR recommendations for the management of antiphospholipid syndrome in adults.

The objective was to develop evidence-based recommendations for the management of antiphospholipid syndrome (APS) in adults. Based on evidence from a systematic literature review and expert opinion, overarching principles and recommendations were formulated and voted. High-risk antiphospholipid antibody (aPL) profile is associated with greater risk for thrombotic and obstetric APS. Risk modification includes screening for and management of cardiovascular and venous thrombosis risk factors, patient education about treatment adherence, and lifestyle counselling. Low-dose aspirin (LDA) is recommended for asymptomatic aPL carriers, patients with systemic lupus erythematosus without prior thrombotic or obstetric APS, and non-pregnant women with a history of obstetric APS only, all with high-risk aPL profiles. Patients with APS and first unprovoked venous thrombosis should receive long-term treatment with vitamin K antagonists (VKA) with a target international normalised ratio (INR) of 2-3. In patients with APS with first arterial thrombosis, treatment with VKA with INR 2-3 or INR 3-4 is recommended, considering the individual's bleeding/thrombosis risk. Rivaroxaban should not be used in patients with APS with triple aPL positivity. For patients with recurrent arterial or venous thrombosis despite adequate treatment, addition of LDA, increase of INR target to 3-4 or switch to low molecular weight heparin may be considered. In women with prior obstetric APS, combination treatment with LDA and prophylactic dosage heparin during pregnancy is recommended. In patients with recurrent pregnancy complications, increase of heparin to therapeutic dose, addition of hydroxychloroquine or addition of low-dose prednisolone in the first trimester may be considered. These recommendations aim to guide treatment in adults with APS. High-quality evidence is limited, indicating a need for more research.

Shrunken pore syndrome, preeclampsia, and markers of NO metabolism in pregnant women during the first trimester.

Shrunken pore syndrome (SPS) is a condition that manifests itself as the decreased renal clearance of low-molecular-weight proteins but normal clearance of creatinine. Pregnant women with evidence of SPS during the first trimester have an increased risk of developing preeclampsia (PE). The nitric oxide (NO) metabolism markers arginine and ADMA, especially their ratio (Arg/ADMA), are recognized markers of endothelial dysfunction. The aim of this nested case-control study was to establish first-trimester reference intervals (RI) for markers of NO metabolism and to study these markers in women with evidence of SPS at the end of the first trimester. Seventy-four women were stratified in the first trimester according to evidence of SPS (SPS + or SPS-) and the occurrence of PE during subsequent pregnancy (PE + or PE-), as follows: SPS-/PE-, SPS+/PE-, SPS-/PE+, and SPS+/PE+. RIs were determined according to the CLSI EP28-A3c guidelines. Serum Arg and ADMA levels were analyzed. The Arg and ADMA concentrations did not differ among the four groups. However, women in the SPS+/PE + group had a significantly lower Arg/ADMA ratio than those in the other 3 groups (p = .02). In conclusion, we defined the first-trimester RI of Arg, ADMA and the Arg/ADMA ratio as markers of NO metabolism. Our results suggest that SPS in the first trimester predicts a pathophysiological hallmark of subsequent PE, i.e. lower NO production leading to increased vessel tone. Early identification of women at risk for later PE could lead to adaptive prophylactic interventions, such as supplementation with Arg or an NO-donor drug in order to mitigate the risk of developing PE.

Nomograms of the Fetal Sylvian Fissure and Insular Lobe throughout Gestation: A Multicentric, Ultrasonographic Cross-Sectional Study.

INTRODUCTION: Anomalies in cortical development are often associated with an adverse outcome, but prenatal diagnosis is often impeded by the limited knowledge about normal sulci biometries throughout fetal brain development. Our aim was to provide two-dimensional ultrasonographical (2D US) nomograms of the depth of the Sylvian fissure (SF) and insular lobe (IL), as well as of the SF ratio throughout gestation in a large number of fetuses. MATERIALS AND METHODS: This was a prospective cross-sectional study of 329 normal singleton pregnancies. Measurements of the SF, IL, and SF ratio were obtained in a standard transthalamic plane of the fetal head. The SF ratio was defined as SF\SF + IL. All measurements were expressed by regression equations as a function of gestational age (GA) according to the method described by Royston and Wright. The first 38 measurements were repeated twice by 2 examiners to assess the reproducibility through the intraclass correlation coefficient (ICC). RESULTS: A significant correlation was found between GA and SF (r = 0.79; p < 0.0001) as well as IL (r = 0.77; p < 0.0001). Similarly, the SF ratio also showed a significant correlation with GA (r = 0.39; p < 0.0001). When interobserver variability was assessed, ICC was 0.97. CONCLUSIONS: Prenatal 2D US measurements of SF and IL as well as the SF ratio may be feasible and reproducible using a standard view of the fetal head. Our nomograms may be used as a reference for assessing cortical development throughout pregnancy.

The Vermian-Crest Angle: A New Method to Assess Fetal Vermis Position within the Posterior Fossa Using 3-Dimensional Multiplanar Sonography.

BACKGROUND: Normal morphometry of the vermis and its relation to the posterior fossa (PF) rule out most major anomalies of the cerebellum. However, accurate categorization of the position and size of the fetal vermis remains a challenge. OBJECTIVE: Our aim was to test a new method to assess the position and size of fetal vermis on 3-dimensional ultrasound (3D-US). METHODS: We measured the vermian-crest angle (VCA) in normal fetuses using multiplanar 3D-US. We also assessed the diameters (superoinferior, anteroposterior, and horizontal) and volume of the vermis. The Spearman rank test and linear and polynomial regression analyses were used for statistical purposes. RESULTS: We included 126 fetuses. Mean ± SD gestational age (GA) was 26.3 ± 4.6 (range 17-35.5) weeks. Mean ± SD superoinferior, anteroposterior, and horizontal diameters were 16.2 ± 4.9, 11.2 ± 3.6, and 5.6 ± 1.6 mm, respectively. Median (range) vermian volume was 0.50 (0.05-2.9) cm3. The VCA was 64.49° ± 11.45. We found no correlation between GA and VCA (r = 0.15; p = 0.13), a linear correlation between GA and vermian diameters, and a quadratic correlation between GA and vermian volume. CONCLUSIONS: We provide a new method to assess vermian position and size within the PF using 3D-US. The combined information may be of value for screening purposes, particularly to differentiate between the various pathological situations encountered within the PF.