Malte Cremer

Platelet transfusions in neonates: practices in the United States vary significantly from those in Austria, Germany, and Switzerland.

BACKGROUND: Thrombocytopenia affects 20% to 35% of patients admitted to neonatal intensive care units (NICUs). Platelet (PLT) transfusions are usually administered to neonates with thrombocytopenia at higher thresholds than those used for older children or adults, although there is a paucity of evidence to guide these decisions.

Immature platelet fraction as novel laboratory parameter predicting the course of neonatal thrombocytopenia

Thrombocytopenia occurs in up to 30% of neonates admitted to neonatal intensive care units (NICUs). In preterm neonates, severe thrombocytopenia is associated with increased risk of intracerebral bleeding. Thus, diagnosis of thrombocytopenia often leads to repeated subsequent analysis of blood cell counts and transfusion of platelets. However, no evidence has been provided that current practice for platelet transfusion prevents bleeding complications and improves clinical outcome. A rapid automated method to assess reticulated platelets, the immature platelet fraction (IPF), is available (Briggs et al, 2000). The aim of this study was to investigate the diagnostic value of IPF as a marker for megakaryopoietic activity in neonates. All 612 neonates admitted to our NICUs over a 6-month period were included in the study. Written parental consent and organisational approval were obtained. During the first postnatal week, blood samples were obtained as clinically indicated. To generate reference values for the IPF, patients were divided in two groups: The control group (n = 456) always displayed normal platelet counts (150–450 · 10/l). In the thrombocytopenic group (n = 156), platelet counts dropped below 150 · 10/l at least once. Blood samples obtained after platelet transfusion were excluded from analysis. Platelet counts were optically measured with the automated analyser XE-2100 (Sysmex, Kobe, Japan) equipped with the software xe-ipf-master. Determination of IPF is based on fluorescence flow cytometry using a nucleic acid specific dye that stains RNA in erythrocytic and platelet reticulocytes. The computed algorithm discriminates mature and immature platelet populations applying a preset gate (fluorescent intensity = RNA-content; forward scatter = cell volume). The IPF is normally expressed as a percentage of the platelet count to indicate the rate of platelet production; additionally, absolute values may be used to differentiate between insufficient platelet production and increased consumption as cause of thrombocytopenia. Regression analysis was used to calculate the correlation between platelet counts and IPF. Student’s t-test was applied to compare group means. Statistical analysis was performed using the software statgraphics (Manugistics Inc., Rockville, MD, USA). A P-value < 0Æ05 was considered to indicate statistical significance. In 1045 out of 1339 blood specimens IPF was routinely determined in addition to platelet counts. Four hundred and fifty-six patients (838 specimens) were assigned to the control group, 25Æ5% of patients (n = 156; 501 specimens) to the thrombocytopenic group. The mean [standard deviation (SD)] birth weight in the control group was significantly higher than in the thrombocytopenic group [2717 g, (SD ± 849) vs. 2188 g, (SD ± 105), P < 0Æ001]; this also refers to mean gestational age [36Æ3 weeks, (SD ± 3Æ7) vs. 34Æ2 weeks, (SD ± 5Æ0), P < 0Æ001]. In controls, the mean IPF value was 4Æ3% [95% confidence interval (CI) 0Æ7–7Æ9%] during the first postnatal week. In the thrombocytopenic group, the mean IPF (SD) during the first postnatal week was always significantly higher than in the control group [e.g. day 1: IPF 8Æ7% (9Æ3) vs. 4Æ53% (1Æ8); P < 0Æ001; Fig 1). 36% of thrombocytopenic neonates displayed an IPF above 7Æ9%. We found no significant correlation between gestational age and IPF. Using simultaneous IPF and platelet measurements of both groups, a significant negative correlation between IPF and platelet counts was found with an exponential decay (r = )0Æ62, P < 0Æ001). Increasing platelet counts were anticipated by an increased IPF, reflecting enhanced platelet production (Fig 1). According to the study aim, we analysed whether the platelet counts on the following day were somehow predicted by means of previous IPF values. In patients whose blood samples were analysed on two subsequent days, the difference in platelet counts was plotted against the corresponding IPF value (Fig 2). In this scatter plot, specimens (n = 398) were divided in to four quadrants according to IPF (>8%, which is outside CI > 95% of controls) and difference in platelet counts (severe

Human birth observed in real-time open magnetic resonance imaging

OBJECTIVE Knowledge about the mechanism of labor is based on assumptions and radiographic studies performed decades ago. The goal of this study was to describe the relationship between the fetus and the pelvis as the fetus travels through the birth canal, using an open magnetic resonance imaging (MRI) scanner. STUDY DESIGN The design of the study used a real-time MRI series during delivery of the fetal head. RESULTS Delivery occurred by progressive head extension. However, extension was a very late movement that was observed when the occiput was in close contact with the inferior margin of the symphysis pubis, occurring simultaneously with gliding downward of the fetal head. CONCLUSION This observational study shows, for the first time, that birth can be analyzed with real-time MRI. MRI technology allows assessment of maternal and fetal anatomy during labor and delivery.

Longitudinal thrombopoietin plasma concentrations in fetuses with alloimmune thrombocytopenia treated with intrauterine PLT transfusions

BACKGROUND:  The purpose of this study was to describe longitudinal thrombopoietin (TPO) plasma concentrations in fetuses with fetomaternal alloimmune thrombocytopenia (FMAIT).

Neonatal outcome in infants of patients with radical vaginal trachelectomy

Abstract Objective: Radical vaginal trachelectomy (RVT) as a fertility-preserving surgery in patients with early-stage cervical cancer is proven to be oncologically safe. After RVT, pregnancy rates vary between 40% and 80%. Outcome of infants is complicated by a preterm delivery rate of 30–50%. We investigated pregnancy and neonatal outcome after RVT. Methods: A total of 154 patients with cervical cancer underwent RVT between March 1995 and February 2008. Desire to conceive, pregnancy data, and neonatal outcome were prospectively recorded. Infants’ data were pair-matched to data of a control group according to weeks of gestation. Bayley scales of infant development scores were recorded in the group of preterm-delivered infants. Results: Fifty-five women who underwent RVT gave birth to 58 children. Twenty-five (43%) pregnancies were complicated by preterm rupture of membranes. Thirty infants (52%) were born preterm, of with 17 (29%) were <32 gestational weeks (GW) and seven (12%) were <28 GW. There were significantly more premature rupture of membranes in pregnancies after RVT. Despite a higher occurrence of postnatal infections in newborns of mothers who underwent RVT, long-term outcomes are not affected negatively. Regarding overall morbidity, a trend to fewer postnatal complications, compared with the control group, was found. Conclusion: Postnatal morbidity in infants of women who underwent RVT, based on trend, is decreased compared with controls. Intense medical observation and treatment during pregnancy, birth, and neonatal period may explain this finding. Neonates in the RVT group have a non-significantly elevated risk for postnatal infections. They do not show an additional risk due to the maternal operation. Their long-term postnatal outcome is not affected negatively.

Granularity Index of the SYSMEX XE-5000 hematology analyzer as a replacement for manual microscopy of toxic granulation neutrophils in patients with inflammatory diseases.

Abstract Background: When certain inflammatory processes occur, toxic granulation neutrophils (TGNs) appear in the blood showing prominent cytoplasmic granules. Currently, the granularity of TGNs is analyzed by manual microscopy of blood smears. The SYSMEX XE-5000 is an automated hematology analyzer, which can measure toxic granulation of TGNs by calculating the Granularity (GI) Index. In this study we investigated if the GI-Index is suitable as a parameter for the TGN granularity in inflammatory diseases. Methods: An evaluation of the toxic granulation neutrophil (TGN) granularity by manual microscopy, the GI-Index and the C-reactive protein (CRP) concentrations of 158 patients were determined. Blood samples from 40 healthy individuals were incubated with lipopolysaccharide (LPS) for in vitro kinetic measurements of the GI-Index. Furthermore, time course measurements of the GI-Index and CRP concentrations of 100 intensive care unit patients were performed. Results: The GI-Index correlated with the microscopic rating of TGNs (n=158; rs=0.839; p<0.0001). When incubating the blood samples with LPS, the neutrophils displayed hypogranulation 30 min after incubation and a hypergranulation after 90 min. In vivo, the GI-Index indicated changes of the bacterial infection status 1 day earlier than the CRP concentration. The correlation of CRP and GI-Index varied between the patient cohorts (n=158; rs=0.836) (n=100; r=0.177), depending on the cause and extent of inflammation. Conclusions: The GI-Index is suited to quantify the granularity of TGNs. The GI-Index is an automated, standardized parameter available on a 24 h basis. We suggest that it replace the time-consuming, subjective and semiquantitative microscopic procedure.

Selenium status in neonates with connatal infection

Infectious diseases impair Se metabolism, and low Se status is associated with mortality risk in adults with critical disease. The Se status of neonates is poorly characterised, and a potential impact of connatal infection is unknown. We hypothesised that an infection negatively affects the Se status of neonates. We conducted an observational case-control study at three intensive care units at the Charité-Universitätsmedizin Berlin, Germany. Plasma samples were collected from forty-four neonates. On the basis of clinical signs for bacterial infection and concentrations of IL-6 or C-reactive protein, neonates were classified into control (n 23) and infected (n 21) groups. Plasma Se and selenoprotein P (SePP) concentrations were determined by X-ray fluorescence and ELISA, respectively, at day of birth (day 1) and 48 h later (day 3). Se and SePP showed a positive correlation in both groups of neonates. Se concentrations indicative of Se deficit in adults (500 ng/l). During antibiotic therapy, SePP increased significantly from day 1 (1·03 (sd 0·10) mg/l) to day 3 (1·34 (sd 0·10) mg/l), indicative of improved hepatic Se metabolism. We conclude that both Se and SePP are suitable biomarkers for assessing Se status in neonates and for identifying subjects at risk of deficiency.

Copper to Zinc Ratio as Disease Biomarker in Neonates with Early-Onset Congenital Infections

Copper (Cu) and zinc (Zn) are essential trace elements for regular development. Acute infections alter their metabolism, while deficiencies increase infection risks. A prospective observational case-control study was conducted with infected (n = 21) and control (n = 23) term and preterm newborns. We analyzed trace element concentrations by X-ray fluorescence, and ceruloplasmin (CP) by Western blot. Median concentration of Cu at birth (day 1) was 522.8 [387.1–679.7] μg/L, and Zn was 1642.4 ± 438.1 μg/L. Cu and Zn correlated positively with gestational age in control newborns. Cu increased in infected newborns from day 1 to day 3. CP correlated positively to Cu levels at birth in both groups and on day 3 in the group of infected neonates. The Cu/Zn ratio was relatively high in infected newborns. Interleukin (IL)-6 concentrations on day 1 were unrelated to Cu, Zn, or the Cu/Zn ratio, whereas C-reactive protein (CRP) levels on day 3 correlated positively to the Cu/Zn -ratio at both day 1 and day 3. We conclude that infections affect the trace element homeostasis in newborns: serum Zn is reduced, while Cu and CP are increased. The Cu/Zn ratio combines both alterations, independent of gestational age. It may, thus, constitute a meaningful diagnostic biomarker for early-onset infections.

Nucleated red blood cells as marker for an increased risk of unfavorable outcome and mortality in very low birth weight infants.

BACKGROUND Nucleated red blood cells (NRBC) are normoblastic cells that failed to extrude their nuclei before exiting from bone marrow or liver. While NRBC are frequently found in umbilical cord blood after fetal distress, NRBC counts drop rapidly after birth. AIMS To determine the predictive value of the NRBC count during the first 120h after birth as marker for later risk of unfavorable outcome in very preterm infants. STUDY DESIGN This cohort study investigated the association between absolute count of NRBC on admission (day 1), the mean NRBC count between day 2 to 5, and outcome (mortality or the composite outcome of mortality and severe morbidity). RESULTS 438 infants with a gestational age<32weeks and a birth weight<1500g were included within a five-year period, of whom 46 patients died and 65 suffered from severe morbidity. Nonsurvivors had significantly higher NRBC counts between day 2 and 5, as compared to survivors. This finding was observed in infants both appropriate and small for gestational age. An increase of 10/nL of the mean NRBC count on postnatal day 2 to 5 had an odds ratio for mortality of 6.95 (95% CI 2.21-21.86) and an odds ratio for the composite outcome mortality and severe morbidity of 3.43 (95% CI 1.43-8.24). The optimal cut-off value for prediction of death was NRBC >2/nL with a sensitivity of 85% and a specificity of 75%. CONCLUSIONS Elevation of NRBC on postnatal day 2 to 5 is an independent predictor of mortality in preterm infants.

Diagnosis and treatment of maternal acute myeloid leukemia during pregnancy imitating HELLP syndrome

No abstract available