Ariel Many

Hyperuricemia and xanthine oxidase in preeclampsia, revisited.

Hyperuricemia is associated with the severity of preeclampsia and with fetal outcome. Traditionally the high uric acid concentration in preeclampsia has been attributed soley to renal dysfunction. Preeclampsia is also characterized by increased free radical formation and elevated oxidative stress. Xanthine dehydrogenase/oxidase produces uric acid. Xanthine dehydrogenase/oxidase is present as two isoforms in vivo. Uric acid production is coupled with formation of reactive oxygen species when the enzyme is in the oxidase form. Several factors can increase the holoenzyme activity and the conversion of xanthine dehydrogenase/oxidase to its oxidase form. These factors include hypoxia-reperfusion, cytokines, and increased substrate availability (xanthine and hypoxanthine). Preeclampsia is characterized by hyperuricemia and signs of increased formation of reactive oxygen species and decreased levels of antioxidants. Preeclampsia is also characterized by shallow implantation, producing a relatively hypoxic maternal-fetal interface, and increased turnover of trophoblast tissue, which can result in higher xanthine and hypoxanthine concentrations and higher levels of circulating cytokines. These mechanisms can lead to increased production of uric acid and free radicals and contribute to the hyperuricemia and increased oxidative stress present in preeclampsia.

Pathologic features of the placenta in women with severe pregnancy complications and thrombophilia

OBJECTIVE To compare placental pathology between women with and without thrombophilia who had severe preeclampsia, intrauterine growth retardation, severe abruptio placentae, or stillbirth. METHODS After delivery, 68 women with singleton pregnancies with one of the above complications were evaluated for an inherited thrombophilia: factor V Leiden, methylenetetrahydrofolate reductase and prothrombin gene mutation, and deficiencies of protein S, protein C, and antithrombin III. Thirty‐two women were thrombophilic (group A), and 36 women were not (group B). There was no difference in maternal age, parity, and type of pregnancy complication. A single pathologist examined each placenta. RESULTS The gestational age at delivery, birth weight, and placental weight were significantly lower in group A. Three parameters showed significant differences between the groups: thrombophilic women had a higher number of villous infarcts (P < .01), more multiple infarcts (P < .05), and a higher incidence of placentas with fibrinoid necrosis of decidual vessels (P < .05). CONCLUSION Placentas of women with severe complications and thrombophilia have an increased rate of vascular lesions.

Low-molecular-weight heparin for the prevention of obstetric complications in women with thrombophilias.

OBJECTIVE To evaluate the benefit of combined low-molecular-weight (LMW) heparin and aspirin for prophylaxis in women carriers of thrombophilia who had previously suffered from severe obstetric complications. METHODS The 33 studied women had an earlier pregnancy complicated by severe preeclampsia, abruptio placentae, intrauterine growth retardation, or intrauterine fetal death. All were subsequently diagnosed as carrying inherited thrombophilias. In their subsequent pregnancy, prophylactic therapy consisting of LMW heparin 40 mg/day (Enoxaparin, Rhone-Poulenc-Rorer, France) and aspirin was administered. Patients who were found to be homozygotes for the methylenetetrahydrofolate reductase mutation also received folic acid supplementation throughout their pregnancy. RESULTS Low-molecular-weight heparin was well tolerated and none of the women or the newborns developed any hemorrhagic complications. Only three (9.1%) of the women developed pregnancy complications. The mean gestational age and the mean birth weight at delivery in the previously complicated pregnancies were 32.1 +/- 5.0 weeks and 1175 +/- 590 g, respectively, compared to 37.6 +/- 2.3 weeks and 2719 +/- 526 g, respectively, in the treated pregnancies (p < 0.001). CONCLUSIONS This uncontrolled trial suggests that patients with obstetric complications and an inherited thrombophilia may benefit from treatment with combined LMW heparin and aspirin in subsequent pregnancies. However, this needs to be verified by controlled trials before considering clinical application.

Vascular endothelial growth factor is increased in patients with preeclampsia.

PROBLEM: This study was conducted to determine whether altered levels of vascular endothelial growth factor (VEGF) may play a role in the pathogenesis of preeclampsia.

Neurodevelopmental Outcome in Children With Intrauterine Growth Retardation: A 3-Year Follow-Up

The study was designed to detect early clinical predictors of developmental outcome in children with intrauterine growth retardation. Eighty-five children with intrauterine growth retardation were followed up prospectively to 3 years of age, using biometric parameters, perinatal risk questionnaires, and neurodevelopmental evaluations. Forty-two children served as controls. A significant difference in neurodevelopmental score at 3 years of age was noted between the intrauterine growth retardation and control groups (P < .001). In the intrauterine growth retardation group, the clinical parameters that most significantly correlated with outcome were cephalization index (head circumference:birthweight ratio), neonatal risk score, and birthweight. The best predictor of 3-year outcome was the cephalization index (P < .01). The children with intrauterine growth retardation with neonatal complications had significantly lower IQ scores (P < .05) and a poorer neurodevelopmental outcome (P < .01) than those without complications. Children with intrauterine growth retardation are at higher risk for developmental disabilities than are controls, especially in the presence of neonatal complications and a high cephalization index. (J Child Neurol 1999;14:724-727).

Mid‐trimester severe intrauterine growth restriction is associated with a high prevalence of thrombophilia

Objective To investigate the association between severe mid‐trimester IUGR, whose causes are unknown in most cases, and maternal thrombophilias.

Six-Year Follow-Up of Children With Intrauterine Growth Retardation: Long-Term, Prospective Study

This prospective study was designed to characterize the neurodevelopmental and cognitive difficulties specific to children with intrauterine growth retardation and to detect early clinical predictors of these difficulties. Eighty-one children with intrauterine growth retardation were monitored up to 6 to 7 years of age using biometric parameters, perinatal risk questionnaires, and detailed neurodevelopmental and cognitive assessments. Forty-one children served as age-matched, appropriate for gestational age controls. A significant difference in growth parameters (P < .001), neurodevelopmental score (P < .05), and IQ (P < .05) was found between the children with intrauterine growth retardation and controls. A specific profile of difficulties in coordination, lateralization, spatial and graphomotor skills, and abundance of associated movements is typical of the children with intrauterine growth retardation and hints at possible later learning disabilities. The clinical parameters best predicting neurodevelopmental outcome were the neonatal risk score (P < .05) and the weight and height at 6 years of age (P < .05). The children with intrauterine growth retardation with neonatal complications had lower neurodevelopmental scores than the controls but no difference in IQ. Intrauterine growth retardation children diagnosed prenatally had the same neurodevelopmental and IQ scores as those diagnosed at birth, probably due to the careful perinatal and obstetric care provided. Children with intrauterine growth retardation demonstrate a specific profile of neurodevelopmental disabilities at preschool age. Early diagnosis and intervention could probably reduce these difficulties to a minimum. (J Child Neurol 2000;15:781-786).

Treatment of Patients With Antiphospholipid Antibodies During Pregnancy

ABSTRACT: Most authors agree upon the causal association between antiphosholipid antibodies [lupus anticoagulant (LAC) and/or anticardiolipin antibodies] and adverse pregnancy outcome. Placental insufficiency, caused by thrombosis, infarction and maldevelopment, is thought to be the main cause of fetal loss in patients with LAC. Therapy given thus far to prevent fetal loss can be divided into (1) immunosuppression by corticosteroids, azathioprine, or intravenous gamma globulin (IVGG), (2) anti‐aggregants to overcome imbalance of thromboxane/prostacycline production in patients with LAC, and (3) anticoagulants to neutralize the possible impairment of clotting inhibitor systems. Different therapeutic success rates have been reported by various authors who used the same combination of therapy. We report the results of different therapy regimens in 154 pregnancies in 31 women with LAC. These patients suffered from SLE with LAC or from APLA syndrome and experienced either recurrent miscarriages or thromboembolic phenomena in the past. With no therapy there were seven (6.8%) live births and 95 (93.2%) failures. Various combinations of corticosteroids, anti‐aggregants and anticoagulants were used for treatment. Of 52 treated pregnancies, 27 (51.9%) were successful. Sixteen (69.1%) of 23 pregnancies treated by all three modalities ended in live births. Four of these successful pregnancies occurred after failure of treatment by prednisone and anti‐aggregants only. In order to minimize osteoporosis caused by the combination of steroids and heparin, we have used warfarin in the second trimester and have lately substituted low molecular weight heparin for heparin. In the absence of a therapeutic schedule predicated on a large prospective study, therapy during pregnancy in patients having LAC should be individualized according to their obstetric and medical history. Anticoagulants are indicated in patients who have suffered from thromboembolic phenomena and could be tried after failure of steroids and anti‐aggregants.

Improved accuracy of postpartum blood loss estimation as assessed by simulation

Objective. Caregivers underestimate the amount of blood loss, but this almost five decades‐old assumption has not been validated. We aimed at assessing the accuracy of estimated blood loss by obstetrical teams during a simulated Postpartum hemorrhage (PPH) scenario. Study design. a prospective study conducted as part of the simulation‐based training course, using sophisticated mannequin simulators adapted for obstetrical training by specially designed devices. Setting. Part of the simulation‐based training course. Population. Obstetrical teams consisted of physicians and obstetrical nurses. Methods. Each of the participating obstetrical teams assessed blood loss during PPH scenarios. Their estimates were compared to the actual predefined 3.5‐liter blood loss. An intervention group underwent a similar course in which they recorded their estimations after 1, 2 and 3.5 liters were lost. Outcome measures. Blood loss estimates after completion of the scenario in both groups. Results. Fifty obstetrical teams took part in the study. Eight comprised the interventional group. The average estimated blood loss was 1,780 ml (49% underestimation) for non‐interventional teams. The interventional groups estimated blood loss to be 2,400 ml (32% underestimation). The main method of estimating blood loss was ‘gut feeling’, followed by verbalized guesses of team members and assessments of the ‘patients’ hemodynamic status. Conclusions. Accuracy of blood loss estimations by a simulation‐based PPH scenario was 50–60%. Measurements at predetermined intervals significantly improved accuracy of these estimations. Our study suggests that implementation of periodic estimations of blood loss in the management of PPH might improve clinical judgment.

ACTIVE LABOUR IS ASSOCIATED WITH INCREASED OXIDISIBILITY OF SERUM LIPIDS EX VIVO

Objective As a first step towards evaluating the role of oxidative stress in the process of labour, we tested whether term labour is associated with increased oxidisibility of maternal serum lipids.