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Hematological toxicity is the most common adverse event after chimeric antigen receptor (CAR) T-cell therapy. Cytopenias can be profound and long-lasting and can predispose for severe infectious complications. In a recent worldwide survey, we demonstrated that there remains considerable heterogeneity in regard to current practice patterns. Here, we sought to build consensus on the grading and management of immune effector cell–associated hematotoxicity (ICAHT) after CAR T-cell therapy. For this purpose, a joint effort between the European Society for Blood and Marrow Transplantation (EBMT) and the European Hematology Association (EHA) involved an international panel of 36 CAR T-cell experts who met in a series of virtual conferences, culminating in a 2-day meeting in Lille, France. On the basis of these deliberations, best practice recommendations were developed. For the grading of ICAHT, a classification system based on depth and duration of neutropenia was developed for early (day 0-30) and late (after day +30) cytopenia. Detailed recommendations on risk factors, available preinfusion scoring systems (eg, CAR-HEMATOTOX score), and diagnostic workup are provided. A further section focuses on identifying hemophagocytosis in the context of severe hematotoxicity. Finally, we review current evidence and provide consensus recommendations for the management of ICAHT, including growth factor support, anti-infectious prophylaxis, transfusions, autologous hematopoietic stem cell boost, and allogeneic hematopoietic cell transplantation. In conclusion, we propose ICAHT as a novel toxicity category after immune effector cell therapy, provide a framework for its grading, review literature on risk factors, and outline expert recommendations for the diagnostic workup and short- and long-term management.

Approximately a quarter of men with metastatic castrate resistant prostate cancer (mCRPC) have alterations in homologous recombination repair (HRR). These patients exhibit enhanced sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. Leveraging the synthetic lethality between PARP inhibition and HRR deficiency, studies have established marked clinical benefit and a survival advantage from PARP inhibitors (PARPi) in mCRPC, most notably in cancers with BRCA1/2 alterations. The role of PARPi is evolving beyond patients with HRR alterations, with studies increasingly focused on exploiting synergistic effects from combination therapeutics. Strategies combining PARP inhibitors with androgen receptor pathway inhibitors, radiation, radioligand therapy, chemotherapy and immunotherapy demonstrate potential additional benefits in mCRPC and these approaches are rapidly moving into the metastatic hormone sensitive treatment paradigm. In this review we summarise the development and expanding role of PARPi in prostate cancer including biomarkers of response, the relationship between the androgen receptor and PARP, evidence for combination therapeutics and the future directions of PARPi in precision medicine for prostate cancer.

Epithelial ovarian cancer (EOC) is a complex disease comprising discrete histological and molecular subtypes, for which survival rates remain unacceptably low. Tailored approaches for this deadly heterogeneous disease are urgently needed. Efflux pumps belonging to the ATP-binding cassette (ABC) family of transporters are known for roles in both drug resistance and cancer biology and are also highly targetable. Here we have investigated the association of ABCC4/MRP4 expression to clinical outcome and its biological function in endometrioid and serous tumors, common histological subtypes of EOC. We found high expression of ABCC4/MRP4, previously shown to be directly regulated by c-Myc/N-Myc, was associated with poor prognosis in endometrioid EOC (P = .001) as well as in a subset of serous EOC with a "high-MYCN" profile (C5/proliferative; P = .019). Transient siRNA-mediated suppression of MRP4 in EOC cells led to reduced growth, migration and invasion, with the effects being most pronounced in endometrioid and C5-like serous cells compared to non-C5 serous EOC cells. Sustained knockdown of MRP4 also sensitized endometrioid cells to MRP4 substrate drugs. Furthermore, suppression of MRP4 decreased the growth of patient-derived EOC cells in vivo. Together, our findings provide the first evidence that MRP4 plays an important role in the biology of Myc-associated ovarian tumors and highlight this transporter as a potential therapeutic target for EOC.

Accurately identifying patients with high-grade serous ovarian carcinoma (HGSOC) who respond to poly(ADP-ribose) polymerase inhibitor (PARPi) therapy is of great clinical importance. Here we show that quantitative BRCA1 methylation analysis provides new insight into PARPi response in preclinical models and ovarian cancer patients. The response of 12 HGSOC patient-derived xenografts (PDX) to the PARPi rucaparib was assessed, with variable dose-dependent responses observed in chemo-naive BRCA1/2-mutated PDX, and no responses in PDX lacking DNA repair pathway defects. Among BRCA1-methylated PDX, silencing of all BRCA1 copies predicts rucaparib response, whilst heterozygous methylation is associated with resistance. Analysis of 21 BRCA1-methylated platinum-sensitive recurrent HGSOC (ARIEL2 Part 1 trial) confirmed that homozygous or hemizygous BRCA1 methylation predicts rucaparib clinical response, and that methylation loss can occur after exposure to chemotherapy. Accordingly, quantitative BRCA1 methylation analysis in a pre-treatment biopsy could allow identification of patients most likely to benefit, and facilitate tailoring of PARPi therapy.Copyright © 2018, The Author(s).

With the current standard of care of the German Hodgkin Study Group (DHSG) consisting of interim positron emission tomography (PET)-guided administration of 4-6 cycles of BEACOPP(escalated) (escalated-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) plus radiotherapy of PET-positive residual lymphoma, the overall survival (OS) of patients with advanced Hodgkin's lymphoma (HL) is in excess of 95%; however, further minimization of acute and delayed toxicities without compromising the tumor-specific outcome of patients is needed, as defining the right balance between efficacy and toxicity remains the most important challenge in HL. The aim of this article is to provide an overview of the current standard of care and recent developments in the treatment of advanced HL. By a systematic literature search, relevant publications as well as reports on new approaches that are being evaluated in current trials were collated and are summarized. Recent comparisons of BEACOPP(escalated) and ABVD (Doxorubicin, Bleomycin, Vinblastin, Dacarbazin) regimens showed a substantial benefit of BEACOPP(escalated) in terms of progression-free survival (PFS) and OS. The interim PET-guided administration of 4-6 cycles of BEACOPP(escalated) can be considered a safe, feasible and highly active approach. This strategy might be improved by the implementation of targeted drugs, such as brentuximab vedotin; therefore, standard BEACOPP(escalated) is currently randomly compared with a variant named Brentuximab Vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone (BrECADD), which was previously shown to be safe and feasible in a phase II study. The major goal in the treatment of advanced HL is the minimization of toxicity without compromising efficacy. Targeted drugs might replace unspecific cytotoxic drugs, which cause systemic toxicity. Hence, the antibody-drug conjugate brentuximab vedotin is currently being investigated as a c

Accurately identifying patients with high-grade serous ovarian carcinoma (HGSOC) who respond to poly(ADP-ribose) polymerase inhibitor (PARPi) therapy is of great clinical importance. Here we show that quantitative BRCA1 methylation analysis provides new insight into PARPi response in preclinical models and ovarian cancer patients. The response of 12 HGSOC patient-derived xenografts (PDX) to the PARPi rucaparib was assessed, with variable dose-dependent responses observed in chemo-naive BRCA1/2-mutated PDX, and no responses in PDX lacking DNA repair pathway defects. Among BRCA1-methylated PDX, silencing of all BRCA1 copies predicts rucaparib response, whilst heterozygous methylation is associated with resistance. Analysis of 21 BRCA1-methylated platinum-sensitive recurrent HGSOC (ARIEL2 Part 1 trial) confirmed that homozygous or hemizygous BRCA1 methylation predicts rucaparib clinical response, and that methylation loss can occur after exposure to chemotherapy. Accordingly, quantitative BRCA1 methylation analysis in a pre-treatment biopsy could allow identification of patients most likely to benefit, and facilitate tailoring of PARPi therapy.

With the current standard of care of the German Hodgkin Study Group (DHSG) consisting of interim positron emission tomography (PET)-guided administration of 4-6 cycles of BEACOPP(escalated) (escalated-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) plus radiotherapy of PET-positive residual lymphoma, the overall survival (OS) of patients with advanced Hodgkin's lymphoma (HL) is in excess of 95%; however, further minimization of acute and delayed toxicities without compromising the tumor-specific outcome of patients is needed, as defining the right balance between efficacy and toxicity remains the most important challenge in HL. The aim of this article is to provide an overview of the current standard of care and recent developments in the treatment of advanced HL. By a systematic literature search, relevant publications as well as reports on new approaches that are being evaluated in current trials were collated and are summarized. Recent comparisons of BEACOPP(escalated) and ABVD (Doxorubicin, Bleomycin, Vinblastin, Dacarbazin) regimens showed a substantial benefit of BEACOPP(escalated) in terms of progression-free survival (PFS) and OS. The interim PET-guided administration of 4-6 cycles of BEACOPP(escalated) can be considered a safe, feasible and highly active approach. This strategy might be improved by the implementation of targeted drugs, such as brentuximab vedotin; therefore, standard BEACOPP(escalated) is currently randomly compared with a variant named Brentuximab Vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone (BrECADD), which was previously shown to be safe and feasible in a phase II study. The major goal in the treatment of advanced HL is the minimization of toxicity without compromising efficacy. Targeted drugs might replace unspecific cytotoxic drugs, which cause systemic toxicity. Hence, the antibody-drug conjugate brentuximab vedotin is currently being investigated as a c

Introduction: DLBCL pts with tumours co-expressing BCL2 and MYC (dual-expressor, DE) or with dual gene translocations (double-hit, DH) have poor outcomes but prognostic relationships between cell-of-origin (COO) subtype (ABC vs GCB) and BCL2/MYC are unclear. We report predefined exploratory analyses of the prognostic effects of BCL2 positivity (+), MYC+, DE and DH, in relation to COO, in the Phase III GOYA study (NCT01287741). Method(s): Pts with previously untreated DLBCL were randomised 1:1 to receive obinutuzumab or rituximab plus 6 or 8 cycles of CHOP. Using a Ventana investigational-use IHC assay (BCL2 antibody clone, 124; c-MYC, Y69), pretreatment tumour samples were analysed at a central laboratory. Samples stained within the limit of BCL2 (<=4 months, 30degreeC) and MYC (<=12 months, 30degreeC) antigen stability were included in primary analyses; sensitivity analyses included all samples. Scoring algorithm incorporated % of tumour cells stained and intensity: BCL2 IHC+, moderate/strong in >=50% of tumour cells; MYC IHC+, >=40% of tumour cells. Vysis LSI Dual Color Break Apart FISH Probes identified BCL2 and MYC translocations: FISH+, >=50%. COO classification of RNA extracts used a NanoString Lymphoma Subtyping gene expression assay. Univariate Cox regression analysis of investigator-assessed PFS was performed. Covariates for multivariate analysis were treatment arm (Tx), IPI score, no. of CHOP cycles and COO. (Figure Presented) Results: Baseline characteristics, including IPI score, were similar for biomarker evaluable and ITT populations. Prevalence of BCL2 IHC+, MYC IHC+, DE and DH was 49%, 83%, 42% and 3.6%, respectively. Prevalence by COO: BCL2 IHC+, 75% in ABC and 38% in GCB; MYC IHC+, 95% in ABC and 76% in GCB; DE, 72% in ABC and 29% in GCB; DH, 7% in GCB and 0% in ABC (19/20 DH pts were GCB; 1 unclassified). In univariate analysis, BCL2 IHC+, DE and DH were associated with poorer prognosis (Table). Multivariate analysis confirm the poor prognosis of

Introduction: DLBCL pts with tumours co-expressing BCL2 and MYC (dual-expressor, DE) or with dual gene translocations (double-hit, DH) have poor outcomes but prognostic relationships between cell-of-origin (COO) subtype (ABC vs GCB) and BCL2/MYC are unclear. We report predefined exploratory analyses of the prognostic effects of BCL2 positivity (+), MYC+, DE and DH, in relation to COO, in the Phase III GOYA study (NCT01287741). Method(s): Pts with previously untreated DLBCL were randomised 1:1 to receive obinutuzumab or rituximab plus 6 or 8 cycles of CHOP. Using a Ventana investigational-use IHC assay (BCL2 antibody clone, 124; c-MYC, Y69), pretreatment tumour samples were analysed at a central laboratory. Samples stained within the limit of BCL2 (<=4 months, 30degreeC) and MYC (<=12 months, 30degreeC) antigen stability were included in primary analyses; sensitivity analyses included all samples. Scoring algorithm incorporated % of tumour cells stained and intensity: BCL2 IHC+, moderate/strong in >=50% of tumour cells; MYC IHC+, >=40% of tumour cells. Vysis LSI Dual Color Break Apart FISH Probes identified BCL2 and MYC translocations: FISH+, >=50%. COO classification of RNA extracts used a NanoString Lymphoma Subtyping gene expression assay. Univariate Cox regression analysis of investigator-assessed PFS was performed. Covariates for multivariate analysis were treatment arm (Tx), IPI score, no. of CHOP cycles and COO. (Figure Presented) Results: Baseline characteristics, including IPI score, were similar for biomarker evaluable and ITT populations. Prevalence of BCL2 IHC+, MYC IHC+, DE and DH was 49%, 83%, 42% and 3.6%, respectively. Prevalence by COO: BCL2 IHC+, 75% in ABC and 38% in GCB; MYC IHC+, 95% in ABC and 76% in GCB; DE, 72% in ABC and 29% in GCB; DH, 7% in GCB and 0% in ABC (19/20 DH pts were GCB; 1 unclassified). In univariate analysis, BCL2 IHC+, DE and DH were associated with poorer prognosis (Table). Multivariate analysis confirm the poor prognosis of

Objectives: To prevent invasive fungal disease (IFD) in adult patients undergoing remission-induction chemotherapy for newly diagnosed acute lymphoblastic leukaemia (ALL). Patients and methods: In a double-blind multicentre Phase 3 study, patients received prophylactic liposomal amphotericin B (L-AMB) at 5 mg/kg intravenously or placebo twice weekly in a 2:1 random allocation during remission-induction treatment. The primary endpoint was the development of proven or probable IFD. Secondary endpoints included those focused on the safety and tolerability of prophylactic L-AMB. Results: Three hundred and fifty-five patients from 86 centres in Europe and South America received at least one dose of L-AMB (n = 237) or placebo (n = 118). Rates of proven and probable IFD assessed independently were 7.9%(18/228) in the L-AMB group and 11.7%(13/111) in the placebo group (P = 0.24). Rates of possible IFD were 4.8% (11/228) in the L-AMB and 5.4% (6/111) in the placebo group (P = 0.82). The remission-induction phase was a median of 22 days for both groups. Overall mortality was similar between the groups: 7.2% (17/237) for L-AMB and 6.8% (8/118) for placebo (P = 1.00). Hypokalaemia and creatinine increase were significantly more frequent with L-AMB. Conclusions: The IFD rate among adult patients undergoing remission-induction chemotherapy for newly diagnosed ALL was 11.7%in the placebo group, andwas not significantly different in patients receiving L-AMB, suggesting that the L-AMB regimen studied is not effective as prophylaxis against IFD. The IFD rate appears higher than previously reported, warranting further investigation. Tolerability of L-AMB was what might be expected. Further studies are needed to determine the optimal antifungal strategy during remission-induction chemotherapy of ALL.

We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20-27%) and a median OS of 3.3 months (95% CI: 2.8-3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36-50%) and a median OS of 6.1 months (95% CI: 4.2-7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67-4.31) and improved OS (HR=0.536, 95% CI: 0.394-0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data.

This book was produced in a Book Sprint at the Senselab, Concordia's Distributing the Insensible event in December 2016. It's an attempt to explain the anarchive in a useful and practical way, for a lot of different contexts outside the academy. NB: there are more authors in the book who aren't on this platform. There are links to landscape and Print-on-Demand versions here: http://senselab.ca/wp2/immediations/upcoming-distributing-the-insensible-dec-10-20-2016/the-go-to-how-to-guide-to-anarchiving/. And all the other books are here: http://senselab.ca/wp2/immediations/upcoming-distributing-the-insensible-dec-10-20-2016

We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20-27%) and a median OS of 3.3 months (95% CI: 2.8-3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36-50%) and a median OS of 6.1 months (95% CI: 4.2-7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67-4.31) and improved OS (HR=0.536, 95% CI: 0.394-0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data.

Next-to-leading order (NLO) QCD predictions for the production of heavy quarks in proton-proton collisions are presented within three different approaches to quark mass, resummation and fragmentation effects. In particular, new NLO and parton shower simulations with POWHEG are performed in the ALICE kinematic regime at three different centre-of-mass energies, including scale and parton density variations, in order to establish a reliable baseline for future detailed studies of heavy-quark suppression in heavy-ion collisions. Very good agreement of POWHEG is found with FONLL, in particular for centrally produced D^0, D^+ and D^*+ mesons and electrons from charm and bottom quark decays, but also with the generally somewhat higher GM-VFNS predictions within the theoretical uncertainties. The latter are dominated by scale rather than quark mass variations. Parton density uncertainties for charm and bottom quark production are computed here with POWHEG for the first time and shown to be dominant in the forward regime, e.g. for muons coming from heavy-flavour decays. The fragmentation into D_s^+ mesons seems to require further tuning within the NLO Monte Carlo approach., Comment: 19 pages, 7 figures

Next-to-leading order (NLO) QCD predictions for the production of heavy quarks in proton-proton collisions are presented within three different approaches to quark mass, resummation and fragmentation effects. In particular, new NLO and parton shower simulations with POWHEG are performed in the ALICE kinematic regime at three different centre-of-mass energies, including scale and parton density variations, in order to establish a reliable baseline for future detailed studies of heavy-quark suppression in heavy-ion collisions. Very good agreement of POWHEG is found with FONLL, in particular for centrally produced D^0, D^+ and D^*+ mesons and electrons from charm and bottom quark decays, but also with the generally somewhat higher GM-VFNS predictions within the theoretical uncertainties. The latter are dominated by scale rather than quark mass variations. Parton density uncertainties for charm and bottom quark production are computed here with POWHEG for the first time and shown to be dominant in the forward regime, e.g. for muons coming from heavy-flavour decays. The fragmentation into D_s^+ mesons seems to require further tuning within the NLO Monte Carlo approach., Comment: 19 pages, 7 figures

Udgivelsesdato: 2001-Aug, Cerebral palsy (CP) is the commonest disabling impairment in childhood, with a prevalence of 2-3 per 1000 live births. The Danish Cerebral Palsy Registry is a research registry that contains cases of CP from birth year 1925 and has estimated the birth prevalence since 1950. Data on children with CP are collected from paediatric departments and one special institution for disabled children. The children are included by a child neurologist and an obstetrician, and information on pregnancy, birth, neonatal period, impairments and demographic data on the child and mother are registered in a standard form. The uptake area is eastern Denmark, covering about 50% of the population, but the rest of Denmark is planned to be included from 2001. The Registry is large, well established and validated, and the definitions and collection procedures have not changed through several decades. It therefore has great research potential. Birth prevalence is estimated continuously, and changes over time are analysed and correlated with pre- and perinatal conditions. A correlation between increased survival of preterm babies and an increased prevalence was found previously, and a decreased prevalence in very preterm infants was later associated with less use of mechanical ventilation. A study correlating CP and maternal infection is ongoing. Collaboration between 14 European CP registries allows the true differences in prevalence between different countries to be studied. Linkage to other individually based registries in Denmark will allow the social consequences of CP to be described.

Udgivelsesdato: 2001-Aug, Cerebral palsy (CP) is the commonest disabling impairment in childhood, with a prevalence of 2-3 per 1000 live births. The Danish Cerebral Palsy Registry is a research registry that contains cases of CP from birth year 1925 and has estimated the birth prevalence since 1950. Data on children with CP are collected from paediatric departments and one special institution for disabled children. The children are included by a child neurologist and an obstetrician, and information on pregnancy, birth, neonatal period, impairments and demographic data on the child and mother are registered in a standard form. The uptake area is eastern Denmark, covering about 50% of the population, but the rest of Denmark is planned to be included from 2001. The Registry is large, well established and validated, and the definitions and collection procedures have not changed through several decades. It therefore has great research potential. Birth prevalence is estimated continuously, and changes over time are analysed and correlated with pre- and perinatal conditions. A correlation between increased survival of preterm babies and an increased prevalence was found previously, and a decreased prevalence in very preterm infants was later associated with less use of mechanical ventilation. A study correlating CP and maternal infection is ongoing. Collaboration between 14 European CP registries allows the true differences in prevalence between different countries to be studied. Linkage to other individually based registries in Denmark will allow the social consequences of CP to be described.

OBJECTIVE: To examine the relation between breech delivery and cerebral palsy, considering the influence of intrauterine growth, low Apgar score at birth, and mode of delivery.DESIGN: Register-based, case-control study.POPULATION: A cohort of infants with cerebral palsy born between 1979 and 1986 in East Denmark, identified by linkage of the cerebral palsy register with the national birth register. Discharge letters from births of breech infants with cerebral palsy were reviewed.MAIN OUTCOME MEASURES: Presentation, mode of delivery, gestational age, birthweight, Apgar score, type of cerebral palsy, severity of handicap.RESULTS: Breech presentation at term was associated with a borderline significantly higher risk of cerebral palsy than vertex presentation (OR 1.56; 95% CI 0.9-2.4). Breech presentation infants more often had a lower Apgar score (< 7 at 5 minutes) and were smaller for gestational age (SGA < 2 SD) than were those with vertex presentation; infants with a low Apgar score, or who were small for gestational age, had a higher risk of cerebral palsy. After stratification by being small for gestational age the risk of cerebral palsy was not related to presentation. There were no differences between breech and vertex infants with cerebral palsy in terms of low Apgar score, being small for gestational age, mode of delivery, and severity of the handicap. Breech presentation infants were more often classified as diplegic (77.8% versus 42.3% in cephalic infants).CONCLUSION: The risk of cerebral palsy among term breech presentation infants does not seem to be related to mode of delivery, but is more likely linked to a higher rate of being small for gestational age in breech infants.

OBJECTIVE: To examine the relation between breech delivery and cerebral palsy, considering the influence of intrauterine growth, low Apgar score at birth, and mode of delivery.DESIGN: Register-based, case-control study.POPULATION: A cohort of infants with cerebral palsy born between 1979 and 1986 in East Denmark, identified by linkage of the cerebral palsy register with the national birth register. Discharge letters from births of breech infants with cerebral palsy were reviewed.MAIN OUTCOME MEASURES: Presentation, mode of delivery, gestational age, birthweight, Apgar score, type of cerebral palsy, severity of handicap.RESULTS: Breech presentation at term was associated with a borderline significantly higher risk of cerebral palsy than vertex presentation (OR 1.56; 95% CI 0.9-2.4). Breech presentation infants more often had a lower Apgar score (< 7 at 5 minutes) and were smaller for gestational age (SGA < 2 SD) than were those with vertex presentation; infants with a low Apgar score, or who were small for gestational age, had a higher risk of cerebral palsy. After stratification by being small for gestational age the risk of cerebral palsy was not related to presentation. There were no differences between breech and vertex infants with cerebral palsy in terms of low Apgar score, being small for gestational age, mode of delivery, and severity of the handicap. Breech presentation infants were more often classified as diplegic (77.8% versus 42.3% in cephalic infants).CONCLUSION: The risk of cerebral palsy among term breech presentation infants does not seem to be related to mode of delivery, but is more likely linked to a higher rate of being small for gestational age in breech infants.

OBJECTIVE: To examine the relation between breech delivery and cerebral palsy, considering the influence of intrauterine growth, low Apgar score at birth, and mode of delivery.DESIGN: Register-based, case-control study.POPULATION: A cohort of infants with cerebral palsy born between 1979 and 1986 in East Denmark, identified by linkage of the cerebral palsy register with the national birth register. Discharge letters from births of breech infants with cerebral palsy were reviewed.MAIN OUTCOME MEASURES: Presentation, mode of delivery, gestational age, birthweight, Apgar score, type of cerebral palsy, severity of handicap.RESULTS: Breech presentation at term was associated with a borderline significantly higher risk of cerebral palsy than vertex presentation (OR 1.56; 95% CI 0.9-2.4). Breech presentation infants more often had a lower Apgar score (< 7 at 5 minutes) and were smaller for gestational age (SGA < 2 SD) than were those with vertex presentation; infants with a low Apgar score, or who were small for gestational age, had a higher risk of cerebral palsy. After stratification by being small for gestational age the risk of cerebral palsy was not related to presentation. There were no differences between breech and vertex infants with cerebral palsy in terms of low Apgar score, being small for gestational age, mode of delivery, and severity of the handicap. Breech presentation infants were more often classified as diplegic (77.8% versus 42.3% in cephalic infants).CONCLUSION: The risk of cerebral palsy among term breech presentation infants does not seem to be related to mode of delivery, but is more likely linked to a higher rate of being small for gestational age in breech infants.

The aim of The Cerebral Palsy Register is to follow the development of cerebral palsy in East Denmark as reported from the children's departments within the area. The prevalence among Danish children born in 1971-1982 is reported. Postnatal cases have been excluded. The live-birth prevalence has increased from 1.7 per 1000 in 1971-1974 to 2.3 per 1000 in 1979-1982. An increased proportion with birthweight under 2500 g and neuroimpairment was found in the latest birth year period. A re-evaluation of diagnostic information confirmed the increasing trend of the prevalence. Preterm births were dominated by perinatal etiology, while term births equally often had a prenatal etiology. It is worrying that the prevalence is rising and that the children have more disabilities. The reason for the increasing trend is most probably due to the decreasing neonatal mortality. Udgivelsesdato: 1995-Feb-6

The aim of The Cerebral Palsy Register is to follow the development of cerebral palsy in East Denmark as reported from the children's departments within the area. The prevalence among Danish children born in 1971-1982 is reported. Postnatal cases have been excluded. The live-birth prevalence has increased from 1.7 per 1000 in 1971-1974 to 2.3 per 1000 in 1979-1982. An increased proportion with birthweight under 2500 g and neuroimpairment was found in the latest birth year period. A re-evaluation of diagnostic information confirmed the increasing trend of the prevalence. Preterm births were dominated by perinatal etiology, while term births equally often had a prenatal etiology. It is worrying that the prevalence is rising and that the children have more disabilities. The reason for the increasing trend is most probably due to the decreasing neonatal mortality. Udgivelsesdato: 1995-Feb-6