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BACKGROUND: Epidural-related maternal fever (ERMF) has been reported in ∼26% of labouring women. The underlying mechanisms remain unclear. We hypothesised that ERMF is promoted by bupivacaine disrupting cytokine production/release from mononuclear leucocytes [mononuclear fraction (MNF)]. We examined whether bupivacaine (i) reduces caspase-1 activity and release of the anti-pyrogenic cytokine interleukin (IL)-1 receptor antagonist (IL-1ra), and (ii) is pro-inflammatory through mitochondrial injury/IL-1ß. METHODS: In labouring women, blood samples were obtained before/after epidural analgesia was implemented. Maternal temperature was recorded hourly for the first 4 h of epidural analgesia. Time-matched samples/temperatures were obtained from labouring women without epidural analgesia, pregnant non-labouring, and non-pregnant women. The primary clinical outcome was change in maternal temperature over 4 h after the onset of siting epidural catheter/enrolment. The secondary clinical outcome was development of ERMF (temperature ≥ 38°C). The effect of bupivacaine/saline on apoptosis, caspase-1 activity, intracellular IL-1ra, and plasma IL-1ra/IL-1ß ratio was quantified in MNF from labouring women or THP-1 monocytes (using flow cytometry, respirometry, or enzyme-linked immunosorbent assay). RESULTS: Maternal temperature increased by 0.06°C h-1 [95% confidence interval (CI): 0.03-0.09; P=0.003; n=38] after labour epidural placement. ERMF only occurred in women receiving epidural analgesia (five of 38; 13.2%). Bupivacaine did not alter MNF or THP-1 apoptosis compared with saline control, but reduced caspase-1 activity by 11% (95% CI: 5-17; n=10) in MNF from women in established labour. Bupivacaine increased intracellular MNF IL-1ra by 25% (95% CI: 10-41; P<0.001; n=10) compared with saline-control. Epidural analgesia reduced plasma IL-1ra/IL-1ß ratio (mean reduction: 14; 95% CI: 7-30; n=30) compared with women without epidural analgesia. CONCLUSIONS: Impaired release of anti-pyrogenic IL-1ra might explain ERMF mechanistically. Immunomodulation by bupivacaine during labour could promote ERMF.

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A decreased antioxidant activity for superoxide dismutases (SODs) in the placenta was reported in preeclampsia (PE). However, it is unclear if this reduced enzymatic activity can be attributed to a specific SOD isoform. Moreover, the specific spatial SOD expression in the placenta and the impact of the mode of delivery on the latter are still lacking. There are three known SOD isoforms: SOD1 (cytosolic), SOD2 (mitochondrial) and SOD3 (extracellular). Our main objective was to characterize by RT-PCR, western blot and immunolocalization, the expression of SOD1, SOD2, and SOD3 in placentas of normotensive (n = 23) and PE pregnancies (n = 25) according to the presence or absence of labor, the sampling site (peri-insertion, mid-disc and periphery) and the placental layer: amnion-chorion, villi, and maternal side layer (MS). In absence of labor (cesarean), SOD1 expression in the placental villi and MS was lower in PE than in controls (p < 0.049). In presence of labor (vaginal deliveries), SOD1 expression in the amnion-chorion only was higher in PE than controls (p = 0.014). Additionally, SOD2 and SOD3 expression in presence of labor were higher in all three layers in PE than controls, with a strong positive correlation between these two SODs (mRNA; r > 0.65, p < 0.008). The sampling site and gestational age had no effect on SOD expression within the placenta. In this study, we showed that the reported decrease for SOD activity in PE may be attributed to SOD1 in absence of labor. Also, this is the first study characterizing specific SOD isoforms according to the mode of delivery. We demonstrated in PE that labor upregulates SOD1 in fetal membranes as well as SOD2 and SOD3 in the whole placenta.

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This study compared the activity of matrix metalloproteinases (MMP-2 and MMP-9) in retained and non-retained bovine placenta. The activities of MMPs and their zymogens were measured in fetal and maternal placental tissues from control cows (group B) and animals affected with retention of fetal membranes (group A) using a zymography technique on 10 per cent SDS polyacrylamide gels. The activity of proMMP-9 detected only in the maternal part of the placenta was lower in group A than in group B. ProMMP-2 activity was higher in group A than in group B in both tissues. The active forms of MMP-2 were observed in the maternal and fetal part of placenta in group B, but only the 68-kDa form was detected in the placental tissues of group A. The differences in enzyme activity between the groups and the lack of 64- and 60-kDa active forms of MMP-2 in the maternal and fetal parts of the retained placenta may have influenced the hydrolysis of collagen and the proper release of fetal membranes.

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BACKGROUND: Chest pain or discomfort are infrequent complaints among women during labor and early puerperium, but when present they raise the suspicion of myocardial ischemia. The diagnosis of the latter is based upon serum elevatIon of certain enzymes, such as aspartate amino transferase, lactate dehydrogenase and creatine phosphokinase. Nevertheless, the normal patterns of these enzymes in the serum during labor and early puerperium have not been characterized well. OBJECTIVE: To determine serum creatine phosphokinase, lactate dehydrogenase and aspartate amino transferase levels in late pregnancy, and throughout labor and early puerperium. METHODS: Fifty women having normal pregnancies followed by uneventful vaginal deliveries were prospectively studied for serum lactate dehydrogenase, aspartate amino transferase and creatine phosphokinase including its MB isoenzyme before, during and after labor. Cardiac status was evaluated in all women using serial electrocardiographic and physical examinations. RESULTS: All women were found to have low to normal antepartum serum enzymes levels. However, during labor total creatine phosphokinase increased markedly, reaching a peak of 2-4 fold baseline levels 24 hours postpartum. It then declined gradually back to baseline. Nulliparous women reached substantially higher levels than multiparous women. The MB or so-called cardio-specific isoenzyme was found to be an important contributor to creatine phosphokinase surge in most women. Correlation was demonstrated between length of the active phase of labor and both total and MB creatine phosphokinase activity. There was no clinical or electrocardiographic evidence for cardiac muscle damage in any of the study patients. Serum lactate dehydrogenase and aspartate amino transferase were not altered during or after labor. CONCLUSIONS: Serum total creatine phosphokinase and its MB isoenzyme increase substantially during normal vaginal labor without evidence of myocardial ischemia. The uterus and placenta, two organs which were reported to embody substantial amounts of these enzymes, and which participate actively in the process of labor, are thought to release these enzymes to the circulation during labor. Knowing the normal patterns of these enzymes in the serum during labor and puerperium may prevent erroneous diagnoses of myocardial ischemia or infarction. Lack of electrocardiographic abnormalities and low lactate dehydrogenase and aspartate amino transferase levels may assist in excluding such diagnoses.

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At the Kiel University Department of Gynaecology, 21 patients between the 21th and 39th week of gestation were treated in 1987 and 1988 following diagnosis of HELLP syndrome. At the time of diagnosis all patients presented an advanced gestosis/eclampsia. 9 patients developed the classical signs and symptoms, while hospitalised. The typical signs of gestosis, hypertension, proteinurea, oedema and hypoproteinaemia preceded the changes in laboratory values caused by the HELLP syndrome. Upper abdominal pain and increase in transaminase values occurred on the average 3.4 or 2.7 days prior to the decrease of, thrombocyte count. In 19 of the 21 cases, pregnancy was terminated by caesarean section. Severe peripartal complications occurred in 7 cases e.g. foetal death in utero (n = 3), eclampsia (n = 5), renal failure (n = 2), cerebral oedema (n = 1), intracerebral haemorrhage (n = 1), disseminated intravascular coagulation (n = 1), abdominal wall haematoma (n = 1). 6 of these patients were admitted after complications had occurred prior to admittance. All 18 infants born alive survived the neonatal period. The average birth weight was 1,571 g. 11 infants were discharged clinically normal. The remaining infants included 5 cases pointing to retinopathy and 3 cases of cerebral palsy. One infant developed post-haemorrhagic hydrocephalus.

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The activity of aminopeptidases and cathepsins was determined in placentoma homogenates; placentomas of cows were extirpated immediately after parturition and in four and eight hours. In cows with afterbirth retention (a. r.) following induced parturition, the activity of these enzymes was always higher than in cows without a. r., no matter if after induced and spontaneous parturitions; it was at a similar or slightly higher level than in the eighth month of pregnancy. The content of total proteins in placentomas of cows with a. r. was also higher. These findings point to the insufficient ripening, or aging of placental tissue, which is related to a release of lysosomal enzymes. The enzymes are active through hydrolysis in the separation of foetal placenta from the maternal one and in the modification of proteins participating in intercellular linkages.

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Maternal plasma zinc levels, red blood cell levels, and serum alkaline phosphatase activity were used as indices of zinc status in 279 pregnant women at delivery and were compared with the incidence of complications during the antenatal period and major dysfunctional labor patterns. The median values for plasma zinc, red blood cell zinc, and alkaline phosphatase were used as cutoff points to subdivide the patient population into "low" and "high" groups. Low levels of maternal plasma zinc were associated with more complications in the antenatal or intrapartum periods than maternal levels of either alkaline phosphatase or red blood cell zinc. Plasma zinc levels less than the median value were more commonly associated with mild toxemia (p = 0.02), vaginitis (p = 0.01), and postdates (p = 0.01) in the antenatal period. During the intrapartum period, low plasma zinc levels were associated with a prolonged latent phase (p = 0.05), a protracted active phase (p = 0.04), labor greater than 20 hours (p = 0.03), second stage greater than 2.5 hours (p = 0.01), and cervical and vaginal lacerations (p = 0.02). Low levels of maternal alkaline phosphatase were strongly associated with a history of previous stillbirth (p = 0.0005). A low maternal red blood cell zinc level was not associated with complications during either period. Since a low plasma zinc level is a valid predictor of pregnancy complications and abnormal labor, the results suggest that plasma zinc screening, as part of the patient's antenatal workup should be evaluated.

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Concentrations of the enzymes creatine kinase (CK) and aspartate aminotransferase (ASAT/GOT) were determined in plasma of 100 gilts and 175 sows at the 112. day of pregnancy and one day after parturition. Gilts and sows were divided into a stress resistant (n = 146) and a stress susceptible group (n = 129) following the creatine-kinase-test carried out after the performance test period at a body weight of 90 kg (CK-90). Stress susceptible gilts and sows showed higher CK-values before and especially after parturition than stress resistant ones. Significant correlations were demonstrable between CK-90 and the CK values before and after parturition (r = 0.5). Regarding body temperature, respiration rate and heart frequency as well as the percentage of stillborn piglets, the two groups of sows did not differ from each other. The increase of enzyme activities after parturition was not influenced by prophylactic treatment with prostaglandin-F2-alpha or beta receptor blocking agent. The beta blocking agent Carazolol, however, caused a transient depression of heart rate after parturition.

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The total CK-, CK-B- and CK-M-activity was determined in 48 newborns from the first to the third day of life by use of the "CK-Monotest" (Boehringer Mannheim). Opposite to a very small decrease of the total CK-activity a significant decrease of the CK-B is evident in the same time. At the first day the detection of CK-B was impossible in only 1 of 27 patients, but at the third day a low CK-B level was detectable in only 5 of 11 test persons. The activities of total CK and the CK-B were determined based upon these investigations in 245 newborns at the first day of life by use of the "CK-Monotest NAC activated" (Boehringer Mannheim). There was no significant difference of total CK- and CK-B-activity dependent on the mode of delivery (spontaneous vertex presentation, forceps delivery, caesarean section, breech presentation.) The proportion of the CK-B varied between 8 and 11% of the total creatine kinase in dependence on the mode of delivery.

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Total serum lactic acid dehydrogenase activity (LDH) and the levels of LDH isoenzymes were investigated in 14 women during early pregnancy (8--16th week), in 28 women during late pregnancy (29--37th week), in 73 at term (38--42nd week) and in 27 during labor (38--42nd week). LDH activity was found to be elevated in severe pre-eclampsia and in chronic hypertensive women during pregnancy as well as during normal and dysfunctional labor. No change was established in total serum LDH during normal pregnancy. LDH 1 was increased during late pregnancy and at term. In severe pre-eclampsia and during normal labor it was decreased. LDH 2 was also decreased in severe pre-eclampsia and during dysfunctional labor. LDH 3 was decreased during late pregnancy but increased in severe pre-eclampsia. No change was observed in LDH 4 during pregnancy, or in labor. LDH 5 was increased in normal and dysfunctional labor.

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The activity of some enzymes of indirect metabolic rate in maternal and umbilical blood were measured in the cases of normal and complicated by the severe intrauterine foetal asphyxia labours. It is concluded that the severe foetal asphyxia caused by the umbilical conflict is reflecting in the changed levels of the majority of examined enzymes in the umbilical blood.

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