Unplanned cesarean sections in advanced maternal age: A predictive model.

INTRODUCTION: As maternal age during pregnancy is rising all over the world, there is a growing need for prognostic factors that determine maternal and perinatal outcomes in older women. MATERIAL AND METHODS: This study is a retrospective cohort study of women aged 40 years or older at the time of delivery in four Santeon hospitals across the Netherlands between January 2016 and December 2019. Outcomes were compared between women of 40-44 years (advanced maternal age) and 45 years and older (very advanced maternal age). Primary outcome was unplanned cesarean section, secondary outcomes included postpartum hemorrhage and neonatal outcomes. Multivariate regression analysis was performed to analyze predictive factors for unplanned cesarean sections in women who attempted vaginal delivery. Subsequently, a predictive model and risk scores were constructed to predict unplanned cesarean section. RESULTS: A cohort of 1660 women was analyzed; mean maternal age was 41.4 years, 4.8% of the women were 45 years and older. In both groups, more than half of the women had not delivered vaginally before. Unplanned cesarean sections were performed in 21.1% of the deliveries in advanced maternal age and in 29.1% in very advanced maternal age. Four predictive factors were significantly correlated with unplanned cesarean sections: higher body mass index (BMI), no previous vaginal delivery, spontaneous start of delivery and number of days needed for cervical priming. A predictive model was constructed from these factors with an area under the curve of 0.75 (95% confidence interval 0.72-0.78). A sensitivity analysis in nulliparous women proved that BMI, days of cervical priming, age, and gestational age were risk factors, whereas spontaneous start of delivery and induction were protective factors. There was one occurrence of neonatal death. CONCLUSIONS: Women of advanced maternal age and those of very advanced maternal age have a higher chance of having an unplanned cesarean section compared to the general obstetric population in the Netherlands. Unplanned cesarean sections can be predicted through use of our predictive model. Risk increases with higher BMI, no previous vaginal delivery, and increasing number of days needed for cervical priming, whereas spontaneous start of labor lowers the risk. In nulliparous women, age and gestational age also increase risk, but induction lowers the risk of having an unplanned cesarean section.

Perinatal Outcome and Long-Term Neurodevelopment after Intracranial Haemorrhage due to Fetal and Neonatal Alloimmune Thrombocytopenia.

OBJECTIVES: To evaluate the perinatal and long-term neurodevelopmental outcome in a cohort of children with intracranial haemorrhage (ICH) due to fetal and neonatal alloimmune thrombocytopenia (FNAIT) and to clearly outline the burden of this disease. SUBJECTS AND METHODS: We performed an observational cohort study and included all consecutive cases of ICH caused by FNAIT from 1993 to 2015 at Leiden University Medical Centre. Neurological, motor, and cognitive development were assessed at a minimum age of 1 year. The primary outcome was adverse outcome, defined as perinatal death or severe neurodevelopmental impairment (NDI). Severe NDI was defined as any of the following: cerebral palsy (Gross Motor Function Classification System [GMFCS] level ≥II), bilateral deafness, blindness, or severe motor and/or cognitive developmental delay (<-2 SD). RESULTS: In total, 21 cases of ICH due to FNAIT were included in the study. The perinatal mortality rate was 10/21 (48%). Long-term outcome was assessed in 10 children (n = 1 lost to follow-up). Severe and moderate NDI were diagnosed in 6/10 (60%) and 1/10 (10%) of the surviving children. The overall adverse outcome, including perinatal mortality or severe NDI, was 16/20 (80%). CONCLUSIONS: The risk of perinatal death or severe NDI in children with ICH due to FNAIT is high. Only screening and effective preventive treatment can avoid this burden.

Fetal and Neonatal Alloimmune Thrombocytopenia: Management and Outcome of a Large International Retrospective Cohort.

OBJECTIVE: To evaluate the management and outcome of a large international cohort of cases of pregnancies complicated by fetal and neonatal alloimmune thrombocytopenia (FNAIT). METHODS: This was an observational prospective and retrospective cohort study of all cases of FNAIT entered into the international multicentre No IntraCranial Haemorrhage (NOICH) registry during the period of 2001-2010. We evaluated human platelet antigen (HPA) specificity, the antenatal and postnatal interventions performed, and clinical outcome. RESULTS: A total of 615 pregnancies complicated by FNAIT from 10 countries were included. Anti-HPA-1a was the most commonly implicated antibody. Antenatal treatment was administered in 273 pregnancies (44%), varying from intrauterine platelet transfusion to maternal administration of immunoglobulins, steroids, or a combination of those. Intracranial haemorrhage was diagnosed in 23 fetuses or neonates (3.7%). Overall perinatal mortality was 1.14% (n = 7). CONCLUSION: This study presents the largest cohort of cases of FNAIT published. Our data show that antenatal treatment for FNAIT results in favourable perinatal outcome. Over time, in most centres, treatment for FNAIT changed from an invasive to a complete non-invasive procedure.

Lower-dose intravenous immunoglobulins for the treatment of fetal and neonatal alloimmune thrombocytopenia: a cohort study.

BACKGROUND: Intravenous immunoglobulins (IVIGs) are the cornerstone in the treatment of pregnancies at risk for fetal and neonatal alloimmune thrombocytopenia (FNAIT). The most commonly used dose is 1.0 g/kg/week, not based on any dose-finding study. IVIG is an expensive multidonor human blood product with dose-related side effects. Our aim was to describe the amount of severe thrombocytopenia according to two different doses of IVIG. STUDY DESIGN AND METHODS: We performed a cohort study, where two dosage regimes of IVIG were evaluated in the treatment of pregnant women suffering from FNAIT with a previous affected child without intracranial hemorrhage (ICH). Cases, treated with 0.5 or 1.0 g/kg/week, were selected from the international multicenter No IntraCranial Hemorrhage (NOICH) registry. Outcome was neonatal platelet (PLT) count at birth and amount of severe thrombocytopenia. Furthermore the appearance of ICH was analyzed. RESULTS: A total of 109 women were included in the study, 46 in the 0.5 IVIG group and 63 in the 1.0 IVIG group. There was no difference in PLT count at birth (mean, 112 vs. 119; crude difference, 7; confidence interval [CI], -37.4 to 23.7]) and incidence of severe thrombocytopenia (<30 × 10(9) /L; n = 7/46 vs. n = 7/63; odds ratio, 1.43 [CI, 0.46-4.42]). No ICH occurred. CONCLUSION: In pregnancies with FNAIT with a previous affected child without ICH, treatment with IVIG in a weekly dose of 0.5 or 1.0 g/kg results in comparable neonatal PLT count at birth and degree of thrombocytopenia.

Severe bleeding complications other than intracranial hemorrhage in neonatal alloimmune thrombocytopenia: a case series and review of the literature.

BACKGROUND: The most feared bleeding complication in fetal and neonatal alloimmune thrombocytopenia (FNAIT) is an intracranial hemorrhage (ICH). However, FNAIT may also lead to other severe bleeding problems. The aim was to analyze this spectrum and evaluate the occurrence of severe hemorrhages other than ICH in fetuses or neonates with FNAIT. STUDY DESIGN AND METHODS: A retrospective chart analysis of cases of FNAIT presenting with severe bleeding complications other than ICH at our institution from 1990 to 2015 was conducted. Additionally, a review of the literature was performed to identify case reports and case series on FNAIT presenting with extracranial hemorrhage. RESULTS: Of 25 fetuses or neonates with severe bleeding due to FNAIT, three had isolated severe internal organ hemorrhage other than ICH, two pulmonary hemorrhages and one gastrointestinal hemorrhage. Two of these three neonates died due to this bleeding. Eighteen cases of extracranial bleeding complications as a first presentation of FNAIT were found in the literature, including ocular, gastrointestinal, spinal cord, pulmonary, renal, subgaleal, and genitourinary hemorrhages. CONCLUSION: Bleeding complications other than ICH may be more extensive, and the presentation of FNAIT may have a greater spectrum than previously described. A high index of suspicion on the possible diagnosis of FNAIT with any bleeding complication in a fetus or neonate may enable adequate diagnostics, adequate treatment, and appropriate follow-up in future pregnancies, as is especially relevant for FNAIT.

Accuracy and workflow of navigated spinal instrumentation with the mobile AIRO(®) CT scanner.

PURPOSE: Current solutions for navigated spine surgery remain hampered by restrictions in surgical workflow as well as a limited versatility and applicability. Against this background, we report the first experience of navigated spinal instrumentation with the mobile AIRO(®) intraoperative computed tomography (iCT) scanner. METHODS: AIRO(®) iCT was used for navigated posterior spinal instrumentation of 170 screws in 23 consecutive patients operated on in our Department between the first use of the system in May 2014 and August 2014. The indications for AIRO(®) were based on the surgical region, anatomical complexity and the need for >3 segment instrumentation. Following navigated screw insertion, screw positions were confirmed intraoperatively by a second iCT scan. CT data on screw placement accuracy were retrospectively reviewed and analyzed by an independent observer. RESULTS: AIRO(®)-based spinal navigation was easy to implement and successfully accomplished in all patients, adding around 18-34 min to the net surgery time. A systematic description of the authors' approach, setup in the OR and workflow integration of the AIRO(®) is presented. Analysis of screw placement accuracy revealed 9 (5.3%) screws with minor pedicle breaches (<2 mm). A total of 7 screws (4.1%) were misplaced >2 mm, resulting in an accuracy rate of 95.9%. CONCLUSIONS: The AIRO(®) system is an easy-to-use and versatile iCT for navigated spinal instrumentation and provides high pedicle screw accuracy rates. Although the authors' experience suggests that the learning curve associated with AIRO(®)-based spinal navigation is steep, a systematic user-based approach to the technology is required.

Low-Dose versus Standard-Dose Intravenous Immunoglobulin to Prevent Fetal Intracranial Hemorrhage in Fetal and Neonatal Alloimmune Thrombocytopenia: A Randomized Trial.

OBJECTIVE: Pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia (FNAIT) are commonly treated using weekly intravenous immunoglobulin (IVIG) at 1 g/kg maternal weight. IVIG is an expensive multidonor human blood product with dose-related side effects. Our aim was to evaluate the effectiveness of IVIG at a lower dose, i.e., 0.5 g/kg. METHODS: This was a randomized controlled multicenter trial conducted in Sweden, the Netherlands and Australia. Pregnant women with human platelet antigen alloantibodies and an affected previous child without intracranial hemorrhage (ICH) were enrolled. The participants were randomized to IVIG at 0.5 or 1 g/kg per week. The analyses were per intention to treat. The primary outcome was fetal or neonatal ICH. Secondary outcomes were platelet count at birth, maternal and neonatal IgG levels, neonatal treatment and bleeding other than ICH. RESULTS: A total of 23 women were randomized into two groups (low dose: n = 12; standard dose: n = 11). The trial was stopped early due to poor recruitment. No ICH occurred. The median newborn platelet count was 81 × 10(9)/l (range 8-269) in the 0.5 g/kg group versus 110 × 10(9)/l (range 11-279) in the 1 g/kg group (p = 0.644). CONCLUSION: The risk of adverse outcomes in FNAIT pregnancies treated with IVIG at 0.5 g/kg is very low, similar to that using 1 g/kg, although our uncompleted trial lacked the power to conclusively prove the noninferiority of using the low dose.

Development of a dynamic myocardial perfusion phantom model for tracer kinetic measurements.

BACKGROUND: Absolute myocardial perfusion imaging (MPI) is beneficial in the diagnosis and prognosis of patients with suspected or known coronary artery disease. However, validation and standardization of perfusion estimates across centers is needed to ensure safe and adequate integration into the clinical workflow. Physical myocardial perfusion models can contribute to this clinical need as these can provide ground-truth validation of perfusion estimates in a simplified, though controlled setup. This work presents the design and realization of such a myocardial perfusion phantom and highlights initial performance testing of the overall phantom setup using dynamic single photon emission computed tomography. RESULTS: Due to anatomical and (patho-)physiological representation in the 3D printed myocardial perfusion phantom, we were able to acquire 22 dynamic MPI datasets in which 99mTc-labelled tracer kinetics was measured and analyzed using clinical MPI software. After phantom setup optimization, time activity curve analysis was executed for measurements with normal myocardial perfusion settings (1.5 mL/g/min) and with settings containing a regional or global perfusion deficit (0.8 mL/g/min). In these measurements, a specific amount of activated carbon was used to adsorb radiotracer in the simulated myocardial tissue. Such mimicking of myocardial tracer uptake and retention over time satisfactorily matched patient tracer kinetics. For normal perfusion levels, the absolute mean error between computed myocardial blood flow and ground-truth flow settings ranged between 0.1 and 0.4 mL/g/min. CONCLUSION: The presented myocardial perfusion phantom is a first step toward ground-truth validation of multimodal, absolute MPI applications in the clinical setting. Its dedicated and 3D printed design enables tracer kinetic measurement, including time activity curve and potentially compartmental myocardial blood flow analysis.

Development of a dedicated 3D printed myocardial perfusion phantom: proof-of-concept in dynamic SPECT.

We aim to facilitate phantom-based (ground truth) evaluation of dynamic, quantitative myocardial perfusion imaging (MPI) applications. Current MPI phantoms are static representations or lack clinical hard- and software evaluation capabilities. This proof-of-concept study demonstrates the design, realisation and testing of a dedicated cardiac flow phantom. The 3D printed phantom mimics flow through a left ventricular cavity (LVC) and three myocardial segments. In the accompanying fluid circuit, tap water is pumped through the LVC and thereafter partially directed to the segments using adjustable resistances. Regulation hereof mimics perfusion deficit, whereby flow sensors serve as reference standard. Seven phantom measurements were performed while varying injected activity of 99mTc-tetrofosmin (330-550 MBq), cardiac output (1.5-3.0 L/min) and myocardial segmental flows (50-150 mL/min). Image data from dynamic single photon emission computed tomography was analysed with clinical software. Derived time activity curves were reproducible, showing logical trends regarding selected input variables. A promising correlation was found between software computed myocardial flows and its reference ([Formula: see text]= - 0.98; p = 0.003). This proof-of-concept paper demonstrates we have successfully measured first-pass LV flow and myocardial perfusion in SPECT-MPI using a novel, dedicated, myocardial perfusion phantom. This proof-of-concept study focuses on the development of a novel, dedicated myocardial perfusion phantom, ultimately aiming to contribute to the evaluation of quantitative myocardial perfusion imaging applications.

A Multimodality Myocardial Perfusion Phantom: Initial Quantitative Imaging Results.

This proof-of-concept study explores the multimodal application of a dedicated cardiac flow phantom for ground truth contrast measurements in dynamic myocardial perfusion imaging with CT, PET/CT, and MRI. A 3D-printed cardiac flow phantom and flow circuit mimics the shape of the left ventricular cavity (LVC) and three myocardial regions. The regions are filled with tissue-mimicking materials and the flow circuit regulates and measures contrast flow through LVC and myocardial regions. Normal tissue perfusion and perfusion deficits were simulated. Phantom measurements in PET/CT, CT, and MRI were evaluated with clinically used hardware and software. The reference arterial input flow was 4.0 L/min and myocardial flow 80 mL/min, corresponding to myocardial blood flow (MBF) of 1.6 mL/g/min. The phantom demonstrated successful completion of all processes involved in quantitative, multimodal myocardial perfusion imaging (MPI) applications. Contrast kinetics in time intensity curves were in line with expectations for a mimicked perfusion deficit (38 s vs. 32 s in normal tissue). Derived MBF in PET/CT and CT led to under- and overestimation of reference flow of 0.9 mL/g/min and 4.5 mL/g/min, respectively. Simulated perfusion deficit (0.8 mL/g/min) in CT resulted in MBF of 2.8 mL/g/min. We successfully performed initial, quantitative perfusion measurements with a dedicated phantom setup utilizing clinical hardware and software. These results showcase the multimodal phantom's potential.

Fetal and neonatal alloimmune thrombocytopenia: prenatal interventions.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a potentially devastating condition, which may lead to intracranial haemorrhage (ICH) in the fetus or neonate, often with death or major neurological damage as consequence. In the absence of screening, preventive measures are only possible in the next pregnancy of women with an affected child. Controversy exists on the best intervention to minimise the risk of ICH. Most centres have abandoned treatment with serial fetal blood sampling (FBS) and platelet transfusions, because of a high rate of complications and the availability of quite effective non-invasive alternatives. In pregnancies with FNAIT and a previous affected child without ICH, weekly intravenous administration of immunoglobulins to the mother appears close to 100% effective to prevent fetal or neonatal ICH. Some centres add prednisone; this combination leads to slightly higher platelet counts at birth. In pregnant women with a previous child with ICH, the recurrence risk seems particularly high, and more aggressive maternal medical treatment is recommended, starting earlier with immunoglobulins. Whether a higher intravenous immunoglobulin dose or the addition of prednisone is really necessary is unclear. What does seem to be clear is that the use of FBS should be minimised, possibly even abandoned completely.

Quantitative imaging: systematic review of perfusion/flow phantoms.

BACKGROUND: We aimed at reviewing design and realisation of perfusion/flow phantoms for validating quantitative perfusion imaging (PI) applications to encourage best practices. METHODS: A systematic search was performed on the Scopus database for "perfusion", "flow", and "phantom", limited to articles written in English published between January 1999 and December 2018. Information on phantom design, used PI and phantom applications was extracted. RESULTS: Of 463 retrieved articles, 397 were rejected after abstract screening and 32 after full-text reading. The 37 accepted articles resulted to address PI simulation in brain (n = 11), myocardial (n = 8), liver (n = 2), tumour (n = 1), finger (n = 1), and non-specific tissue (n = 14), with diverse modalities: ultrasound (n = 11), computed tomography (n = 11), magnetic resonance imaging (n = 17), and positron emission tomography (n = 2). Three phantom designs were described: basic (n = 6), aligned capillary (n = 22), and tissue-filled (n = 12). Microvasculature and tissue perfusion were combined in one compartment (n = 23) or in two separated compartments (n = 17). With the only exception of one study, inter-compartmental fluid exchange could not be controlled. Nine studies compared phantom results with human or animal perfusion data. Only one commercially available perfusion phantom was identified. CONCLUSION: We provided insights into contemporary phantom approaches to PI, which can be used for ground truth evaluation of quantitative PI applications. Investigators are recommended to verify and validate whether assumptions underlying PI phantom modelling are justified for their intended phantom application.

HIP (HPA-screening in pregnancy) study: protocol of a nationwide, prospective and observational study to assess incidence and natural history of fetal/neonatal alloimmune thrombocytopenia and identifying pregnancies at risk.

INTRODUCTION: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) may lead to severe fetal or neonatal bleeding and/or perinatal death. Maternal alloantibodies, targeted against fetal human platelet antigens (HPAs), can result thrombocytopenia and bleeding complications. In pregnancies with known immunisation, fetal bleeding can be prevented by weekly maternal intravenous immunoglobulin infusions. Without population-based screening, immunisation is only detected after birth of an affected infant. Affected cases that might have been prevented, when timely identified through population-based screening. Implementation is hampered by the lack of knowledge on incidence, natural history and identification of pregnancies at high risk of bleeding. We designed a study aimed to obtain this missing knowledge. METHODS AND ANALYSIS: The HIP (HPA-screening in pregnancy) study is a nationwide, prospective and observational cohort study aimed to assess incidence and natural history of FNAIT as well as identifying pregnancies at high risk for developing bleeding complications. For logistic reasons, we invite rhesus D-negative or rhesus c-negative pregnant women, who take part in the Dutch population-based prenatal screening programme for erythrocyte immunisation, to participate in our study. Serological HPA-1a typing is performed and a luminex-based multiplex assay will be performed for the detection of anti-HPA-1a antibodies. Results will not be communicated to patients or caregivers. Clinical data of HPA-1a negative women and an HPA-1a positive control group will be collected after birth. Samples of HPA-1a immunised pregnancies with and without signs of bleeding will be compared with identify parameters for identification of pregnancies at high risk for bleeding complications. ETHICS AND DISSEMINATION: Ethical approval for this study has been obtained from the Medical Ethical Committee Leiden-The Hague-Delft (P16.002). Study enrolment began in March 2017. All pregnant women have to give informed consent for testing according to the protocol. Results of the study will be disseminated through congresses and publication in relevant peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04067375.

Assessing Exercise-Induced Bronchoconstriction in Children; The Need for Testing.

Objective: Exercise-induced bronchoconstriction (EIB) is a specific morbidity of childhood asthma and a sign of insufficient disease control. EIB is diagnosed and monitored based on lung function changes after a standardized exercise challenge test (ECT). In daily practice however, EIB is often evaluated with self-reported respiratory symptoms and spirometry. We aimed to study the capacity of pediatricians to predict EIB based on information routinely available during an outpatient clinic visit. Methods: A clinical assessment was performed in 20 asthmatic children (mean age 11.6 years) from the outpatient clinic of the MST hospital from May 2015 to July 2015. During this assessment, video images were made. EIB was measured with a standardized ECT performed in cold, dry air. Twenty pediatricians (mean years of experience 14.4 years) each evaluated five children, providing 100 evaluations, and predicted EIB severity based on their medical history, physical examination, and video images. EIB severity was predicted again after additionally providing baseline spirometry results. Results: Nine children showed no EIB, four showed mild EIB, two showed moderate, and five showed severe EIB. Based on clinical information and spirometry results, pediatricians detected EIB with a sensitivity of 84% (95% CI 72-91%) and a specificity of 24% (95% CI 14-39%).The agreement between predicted EIB severity classifications and the validated classifications after the ECT was slight [Kappa = 0.05 (95% CI 0.00-0.17)]. This agreement still remained slight when baseline spirometry results were provided [Kappa = 0.19 (95% CI 0.06-0.32)]. Conclusion: Pediatricians' prediction of EIB occurrence was sensitive, but poorly specific. The prediction of EIB severity was poor. Pediatricians should be aware of this in order to prevent misjudgement of EIB severity and disease control.

Neonatal outcome in alloimmune thrombocytopenia after maternal treatment with intravenous immunoglobulin.

BACKGROUND: Weekly maternal intravenous immunoglobulin (IVIG) is the cornerstone of antenatal treatment of foetal and neonatal alloimmune thrombocytopenia (FNAIT). The aim of this study was to describe the neonatal outcome and management in neonates with FNAIT treated antenatally with IVIG. MATERIALS AND METHODS: All neonates treated antenatally and delivered at our centre between 2006 and 2012 were included in the study. We assessed the neonatal outcome and management, including the occurrence of intracranial haemorrhage, platelet count at birth and need for postnatal platelet transfusions or postnatal IVIG treatment. RESULTS: A total of 22 neonates were included of whom 12 (55%) had severe thrombocytopenia at birth (platelet count ≤50×10(9)/L). Most neonates (67%, 8/12) with severe thrombocytopenia received a platelet transfusion after birth. None of the neonates required postnatal treatment with IVIG. Three neonates had petechiae and haematomas, without clinical consequences. One foetus suffered from intracranial haemorrhage, which was detected just before the planned start of antenatal IVIG at 28 weeks' gestation. DISCUSSION: Our results suggest that antenatal maternal IVIG and, if necessary, postnatal matched platelet transfusions, are effective and safe for the treatment of FNAIT.

Incidence and consequences of neonatal alloimmune thrombocytopenia: a systematic review.

BACKGROUND: Neonatal alloimmune thrombocytopenia (NAIT) is a potentially devastating disease that may lead to intracranial hemorrhage in the fetus or neonate, often with death or major neurologic damage. There are no routine screening programs for NAIT, preventive measures are taken only in a subsequent pregnancy. To estimate the population incidence of NAIT and its consequences, we conducted a review of the literature. Our results may aid in the design of a screening program. METHODS: An electronic literature search included Medline, Embase, Cochrane database and references of retrieved articles. Eligible for inclusion were all prospective studies aimed at diagnosing NAIT in a general, nonselected newborn population, with sufficient information on platelet count at birth, bleeding complications, and treatment. Titles and abstracts were reviewed, followed by review of full text publications. Studies were independently assessed by 2 reviewers for methodologic quality. Disagreements were resolved by consensus, including a third reviewer. RESULTS: From the initial 768 studies, 21 remained for full text analysis, 6 of which met the inclusion criteria. In total, 59,425 newborns were screened, with severe thrombocytopenia in 89 cases (0.15%). NAIT was diagnosed in 24 of these 89 newborns (27%). In 6 (25%) of these cases, an intracranial hemorrhage was found, all likely of antenatal origin. CONCLUSIONS: NAIT is among the most important causes of neonatal thrombocytopenia. Intracranial hemorrhage due to NAIT occurs in 10 per 100 000 neonates, commonly before birth. Screening for NAIT might be effective but should be done antenatally.

Differences in delineation guidelines for head and neck cancer result in inconsistent reported dose and corresponding NTCP.

PURPOSE: To test the hypothesis that delineation of swallowing organs at risk (SWOARs) based on different guidelines results in differences in dose-volume parameters and subsequent normal tissue complication probability (NTCP) values for dysphagia-related endpoints. MATERIALS AND METHODS: Nine different SWOARs were delineated according to five different delineation guidelines in 29 patients. Reference delineation was performed according to the guidelines and NTCP-models of Christianen et al. Concordance Index (CI), dosimetric consequences, as well as differences in the subsequent NTCPs were calculated. RESULTS: The median CI of the different delineation guidelines with the reference guidelines was 0.54 for the pharyngeal constrictor muscles, 0.56 for the laryngeal structures and 0.07 for the cricopharyngeal muscle and esophageal inlet muscle. The average difference in mean dose to the SWOARs between the guidelines with the largest difference (maxΔD) was 3.5±3.2Gy. A mean ΔNTCP of 2.3±2.7% was found. For two patients, ΔNTCP exceeded 10%. CONCLUSIONS: The majority of the patients showed little differences in NTCPs between the different delineation guidelines. However, large NTCP differences >10% were found in 7% of the patients. For correct use of NTCP models in individual patients, uniform delineation guidelines are of great importance.

Fetal intracranial haemorrhages caused by fetal and neonatal alloimmune thrombocytopenia: an observational cohort study of 43 cases from an international multicentre registry.

OBJECTIVE: To characterise pregnancies where the fetus or neonate was diagnosed with fetal and neonatal alloimmune thrombocytopenia (FNAIT) and suffered from intracranial haemorrhage (ICH), with special focus on time of bleeding onset. DESIGN: Observational cohort study of all recorded cases of ICH caused by FNAIT from the international No IntraCranial Haemorrhage (NOICH) registry during the period 2001-2010. SETTING: 13 tertiary referral centres from nine countries across the world. PARTICIPANTS: 37 mothers and 43 children of FNAIT pregnancies complicated by fetal or neonatal ICH identified from the NOICH registry was included if FNAIT diagnosis and ICH was confirmed. PRIMARY AND SECONDARY OUTCOME MEASURES: Gestational age at onset of ICH, type of ICH and clinical outcome of ICH were the primary outcome measures. General maternal and neonatal characteristics of pregnancies complicated by fetal/neonatal ICH were secondary outcome measures. RESULTS: From a total of 592 FNAIT cases in the registry, 43 confirmed cases of ICH due to FNAIT were included in the study. The majority of bleedings (23/43, 54%) occurred before 28 gestational weeks and often affected the first born child (27/43, 63%). One-third (35%) of the children died within 4 days after delivery. 23 (53%) children survived with severe neurological disabilities and only 5 (12%) were alive and well at time of discharge. Antenatal treatment was not given in most (91%) cases of fetal/neonatal ICH. CONCLUSIONS: ICH caused by FNAIT often occurs during second trimester and the clinical outcome is poor. In order to prevent ICH caused by FNAIT, at-risk pregnancies must be identified and prevention and/or interventions should start early in the second trimester.

Implementation of routine screening for Kell antibodies: does it improve perinatal survival?

BACKGROUND: In 1998 a national program for first-trimester screening for red cell (RBC) antibodies in all pregnant women was implemented. The aim of our study was to assess the impact on perinatal mortality caused by Kell alloimmunization STUDY DESIGN AND METHODS: Prospectively collected data on all pregnant women referred to our center from 1988 until 2005 for intrauterine transfusion (IUT) for fetal anemia due to Kell alloantibodies were analyzed. The cohort was divided into two groups, those treated before 1998 and those treated after 1998. The primary outcome was fetal and neonatal survival. Secondary outcome variables were gestational age, fetal hemoglobin (Hb) levels at first IUT, severity of hydrops, and total number of IUTs per pregnancy. Causes for mortality were analyzed in detail. RESULTS: A total of 43 pregnancies were included, 18 before introduction of screening and 25 thereafter. Perinatal survival increased from 61 percent in the first period to 100 percent after introduction of screening. After 1998, fetal hydrops was generally less severe at first IUT, while gestational age and fetal Hb levels at first IUT were similar. CONCLUSION: Implementation of routine screening for Kell antibodies in pregnancy was associated with an increased referral rate for suspected fetal anemia, more timely referrals, and a higher perinatal survival rate after intrauterine treatment.