L. Pereira-Leite

Evaluation of interobserver agreement of cardiotocograms.

Objective: To evaluate interobserver agreement in visual analysis of each cardiotocographic event. Methods: Three experts independently divided 16 antepartum and 17 intrapartum cardiotocograms into baseline segments, accelerations and decelerations, according to the FIGO guidelines. Baseline segments were further classified as having normal, reduced or increased variability and decelerations as early, late and variable. Uterine activity was divided into tonus and contractions. Agreement was assessed by the proportions of agreement (pa) with 95% confidence intervals. Results: Reproducibility in assessment of baseline segments with normal variability, accelerations and uterine activity was acceptable (pa = 0.56–0.71) whereas that of other segments was not (pa = 0.14–0.45). Conclusions: Analysis of most cardiotocographic events is poorly reproducible, even when experts use the FIGO guidelines. This may be explained by some still ambiguous guidelines, by eyeball limitations in evaluation of subtle events, and by the incapacity of busy clinicians to assess complex and multiple cardiotocographic events in a systematic and disciplined fashion.

Inconsistencies in classification by experts of cardiotocograms and subsequent clinical decision

Inter‐observer agreement in the interpretation according to the FIGO guidelines of 33 cardiotocographic tracings by experts and subsequent clinical decision was evaluated, using the kappa statistic (K) and the proportions of agreement (Pa). Overall agreement in the classification of tracings was fair (K = 0.48) and was better for normal (Pa = 0.62), than for suspicious (Pa = 0.42) or pathologic tracings (Pa = 0.25). Overall agreement on clinical decision was slightly higher (K = 0.59), but mostly was centred on the decision to take ‘no action’ (Pa = 0.79). Experts especially disagreed over the decisions to ‘monitor closely’ (Pa = 0.14) or to ‘intervene immediately’ (Pa = 0.38). These limitations should be taken into account in clinical audits and in medical jurisprudence.

Neutrophil Activation and C‐Reactive Protein Concentration in Preeclampsia

Preeclamptic pregnancies seem to be associated with a higher extent of inflammation compared with normal ones. We intended to test this proposal and also to clarify the contribution of some variables in such inflammatory process. We measured total and differential leukocyte count, serum C‐reactive protein (CRP), and plasma levels of lactoferrin, elastase, and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). Uric acid was also evaluated and used as an indicator of the severity of the disease. A cross‐sectional study was performed by evaluating healthy and preeclamptic women in the third trimester of gestation (n = 67 and n = 51, respectively) and 24 to 48 h postpartum (n = 32 and n = 26, respectively). When comparing the third trimester of normal and preeclamptic pregnancies, we found significantly higher levels of uric acid, CRP, and elastase, and a significantly higher elastase to neutrophil ratio in the pathologic group. However, for CRP, statistical significance was lost after adjustment for maternal weight. No significant differences were found in total leukocyte count, plasma levels of GM‐CSF, and lactoferrin between groups. In preeclampsia, a significant positive correlation was found between elastase and lactoferrin and these neutrophil activation products correlated positively with uric acid level. Considering the analysis of all variables in the postpartum period, only CRP and uric acid levels were significantly elevated in the pathologic group. However, CRP differences obtained in the puerperium seem to be influenced by the increased number of dystocic deliveries in the preeclamptic group. In conclusion, our data suggest that inflammation is further pronounced in preeclampsia and that the extent of neutrophil activation correlates with the severity of this syndrome.

Elevated tissue plasminogen activator as a potential marker of endothelial dysfunction in pre-eclampsia: correlation with proteinuria

Objective To clarify the role played by endothelial cell production of fibrinolytic factors in normal pregnancy and pre‐eclampsia.

Objective computerized fetal heart rate analysis.

Objective: To assess the validity of a computerized methodology for cardiotocogram analysis based on a recently described reproducible visual estimation of the baseline. Methods: Forty‐two antepartum and 43 intrapartum cardiotocograms (CTGs) acquired by a personal computer were selected. Antepartum tracings were performed in the 48 h that preceded an elective cesarean section, and intrapartum tracings were performed until delivery. FHR baselines were estimated by an expert, according to an objective and reproducible methodology. Using these baselines, automated detection of accelerations and decelerations and estimation of variability was performed by the personal computer. A quantitative adaptation of the FIGO guidelines for fetal monitoring was used to classify tracings. Perinatal outcome was classified according to the Apgar score and umbilical arterial pH. Validity was then assessed by the proportions of agreement (PA), kappa statistic (κ), sensitivity and specificity, with 95% confidence intervals (95% CI). Cases showing a disagreement between CTG and perinatal classification were reviewed and an adjustment in baseline definition was tested. Results: The initial overall PA and κ between CTG and perinatal classification were, respectively, 0.79 (95% CI: 0.69–0.87) and 0.62 (95% CI: 0.41–0.83). The overall PA and κ, after baseline adjustment were, respectively, 0.89 (95% CI: 0.81–0.95) and 0.78 (95% CI: 0.58–0.98). Sensitivities and specificities ranged between 79% (95% CI: 60–92%) and 100% (95% CI: 95–100%). Conclusions: Good clinical prediction may be possible with an objective methodology for cardiotocogram analysis based on a recently described reproducible baseline estimation.

Comparative study of lactoferrin and other blood markers of inflammatory stress between preeclamptic and normal pregnancies

OBJECTIVE To test lactoferrin as a blood discriminator of neutrophil activation between normal and preeclamptic pregnancy. DESIGN Comparative study between normal (n = 40) and preeclamptic women receiving treatment (n = 42) in the third trimester of pregnancy and in the post partum period (30 women with normal pregnancy and 22 with preeclampsia). METHODS Blood, serum or plasma measurements of neutrophils, lactoferrin, vitamin C, vitamin E, lipid peroxidation products, elastase, C-reactive protein (CRP), gamma-glutamyltranspeptidase (gamma GT), haptoglobin, osmotic fragility, urea, creatinine, uric acid, transaminases (ASAT, ALAT), lactic dehydrogenase (LDH), platelets, red and white blood cells. RESULTS In preeclamptic women the ratios of lactoferrin per neutrophil or per erythrocyte are higher before delivery than in normal women but decrease after delivery. Delivery induces a greater inflammatory response in normal pregnancy as detected by blood concentrations of inflammatory markers and hepatic and renal parameters. CONCLUSION Whereas in normal pregnant women neutrophil activation increases with delivery, in preeclamptic women the opposite occurs.

Lactoferrin as a sensitive blood marker of neutrophil activation in normal pregnancies

OBJECTIVE To test lactoferrin as a marker of neutrophil activation during pregnancy. DESIGN Cross-sectional study in normal pregnant (n = 100), nonpregnant (n = 11) and post partum women (n = 30). METHODS Serum or plasma measurements of neutrophils, lactoferrin, vitamin C, vitamin E, lipid peroxide, elastase, C-reactive protein gamma-glutamyltranspeptidase, haptoglobin and osmotic fragility. RESULTS During normal pregnancy all markers of neutrophil-activation increase. CONCLUSION Neutrophil-activation compromises the antioxidant defense mechanism during normal pregnancy.

Apolipoprotein E and cholesteryl ester transfer protein polymorphisms in normal and preeclamptic pregnancies

OBJECTIVES To evaluate the association of apolipoprotein (apo) E polymorphism and a cholesteryl ester transfer protein (CETP) polymorphism (CETP/TaqIB) with preeclampsia and with lipid/lipoprotein profile in pregnancy. MATERIALS AND METHODS A group of 144 normal pregnant women (67 in the third trimester) were compared with 51 cases of preeclampsia in the third trimester of gestation. Apo E and CETP genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. Serum lipids, lipoproteins and apolipoproteins were evaluated using commercially available kits. LDL size was assessed by gradient gel electrophoresis. RESULTS No differences were found in the distribution of subjects with respect to genotypes, in the apo E and CETP polymorphisms, between control and pathologic groups. In the third trimester of gestation (both control and case groups considered), apo E polymorphism, but not CETP polymorphism, was associated with different lipid and lipoprotein levels. Patients carrying the E2 allele (E2+) presented with significantly lower values of LDL cholesterol (LDLc) compared with carriers of E4 (E4+) and E3/3 individuals. E2+ also presented with the highest triglyceride (TG) level, although this was not statistically significant. On the other hand, HDL cholesterol (HDLc) and apo A-I levels were significantly reduced in E4+, compared with E3/3. Furthermore, E4+ presented with the highest total cholesterol and LDL and therefore LDLc/HDLc and apo B/apo A-I ratios were significantly higher in this group compared with the other two. CONCLUSIONS Neither of our candidate genes showed association with preeclampsia. However, apo E genotype was associated with changes in lipid and lipoprotein profiles in pregnant women.

Band 3 as a marker of erythrocyte changes in pregnancy

Abstract:  Modifications in the erythrocyte membrane protein band 3 seem to mark the cell for death. A decrease in band 3 high molecular weight aggregates (HMWAg) and a rise in its proteolytic fragments (Pfrag) were described for younger erythrocytes. The aim of this work was to study the band 3 profile as a marker of erythrocyte changes in pregnancy and postpartum. We performed a cross‐sectional study in non‐pregnant controls (n = 24), in women in the first (n = 64), second (n = 48) and third (n = 67) trimesters of gestation, and also in the puerperium (24–48 h after delivery; n = 32); we also carried out a longitudinal study (n = 23) during the three trimesters of normal pregnancy. We evaluated the band 3 profile (% of band 3 monomer, HMWAg, and Pfrag) and the membrane‐bound haemoglobin. Total serum bilirrubin, glutathione peroxidase activity, red blood cell (RBC) count, haematocrit (Ht), haemoglobin (Hb) concentration, the haematimetric indices, and red cell distribution width were also evaluated. Similar results were found in pregnancy in both the cross‐sectional and longitudinal studies. We found that the RBC count, Hb, and Ht decreased significantly in pregnancy and in puerperium. Band 3 profile in the first trimester of pregnancy, when compared with controls, presented significantly reduced HMWAg and increased Pfrag. Comparing the first with the third trimester, we found a significant reduction in band 3 and a significant rise in Pfrag. However, between these same periods, HMWAg did not decrease. Our data suggest band 3 profile as a marker of erythrocyte changes in pregnancy, which are independent of the ‘physiological anaemia’ of pregnancy. These changes suggest an increase in damaged RBCs, but also an increase in younger RBCs in the maternal circulation.