Transport kinetics of chromium in perfused human placental lobule in late gestation: in vitro study.

Objective: Reports relating to maternal-fetal transport kinetics of chromium, an essential trace element in the human pregnancies are scanty. Hence, we thought it interesting to investigate the transport kinetics of this trace element in the human placenta in late gestation in vitro. Methods: Human placentae were collected immediately after delivery from normal uncomplicated pregnancies. Chromium chloride solution (GFS Chem Inc, Ohio, USA) at 10 times the physiological concentrations and antipyrine (Sigma Chem Co., St. Louis, USA) as internal reference marker was injected as a single bolus (100 µl) into the maternal arterial circulation of perfused placental lobules and perfusate samples were collected from maternal and fetal circulations over a study period of 5 minutes. National culture and Tissue collection medium, diluted with Earle's buffered salt solution was used as the perfusate. Serial perfusate samples were collected from fetal venous perfusate for a period of 30 minutes. Chromium concentration in perfusate samples was determined using atomic absorption spectrophotometry and the concentration of reference marker, antipyrine was measured by spectrophotometry. Transport kinetics and transport parameters of study and reference markers were assessed using well-established parameters. Results: Differential transport rates of chromium and antipyrine in 10 perfusions differed significantly for 10 and 50% efflux fractions (ANOVA test, p < .05) while those of 25, 75, and 90% efflux fractions were not significantly different between the study and reference substances. Chromium transport fraction (TF) averaged 54.9% of bolus dose in 10 perfusions while that of antipyrine averaged 89% of bolus dose, representing 61.80% of reference marker TF. The difference observed in TF values of chromium and antipyrine was statistically significant (Student's t-test, p < .05). Pharmacokinetic parameters such as area under the curve, clearance, absorption rate, elimination rate of chromium compared to reference marker was significantly different (ANOVA test, p < .05) between the study and reference substances. Conclusions: Our studies report for the first time maternal-fetal transport kinetics of chromium in human placenta in vitro. Considering the restricted transfer of this essential trace element from maternal to fetal circulation despite its small molecular weight, we hypothesize an active transport of chromium across the human placental membrane. Further studies relating to placental transport kinetics of this trace element in various pregnancy-related disease states are in progress.

Effect of methotrexate administration on status of some essential trace elements and antioxidant enzymes in pregnant rats in late gestation.

OBJECTIVE: Folate antagonists are widely used in the treatment of various cancerous states. Paucity of data on effect of administration of one such widely used drug, methotrexate (MTX), on the status of essential trace elements and antioxidant enzymes in pregnant women or in pregnant animals prompted us to undertake this study. METHODS: MTX at a concentration of 5 mg/kg body weight was administered intraperitoneally as single dose to pregnant Sprague-Dawley rats for three consequitive days from day 17 of pregnancy. Control group of pregnant rats received single dose of saline instead of the anti-cancer drug on all the 3 days. After receiving the third dose of drug, the treated rats and control group rats were sacrificed, 1 h after intraperitoneal injection of a cocktail of essential trace elements namely, Cu, Se and Zn administered as a single bolus dose. Blood samples were collected 30 min of trace element cocktail injection, after decapitation and concentrations of trace elements in serum samples were determined by atomic absorption spectrophotometry. Concentrations of antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase and total antioxidant status were determined by specific analytical kits, using spectrophotometry. RESULTS: In control group(n = 6), serum concentrations of Cu, Se and Zn averaged 2330.5, 614.8 and 2773.2 microg/l, while in study group (n = 6) the concentrations of trace elements averaged 2294, 596 and 2713 microg/l, respectively. Student's t-test did not show any statistical significance (p > 0.05) between various trace element concentrations in control and treated groups. Cu:Zn ratios of control and treated group of rats did not vary significantly as well. Concentrations of superoxide dismutase, glutathione peroxidase in whole blood samples in control rats averaged 165 and 43,260 U/ml, respectively, while in MTX-treated group of animals the corresponding antioxidant enzymes averaged 330.6 and 67,101 U/ml respectively. SOD and GPX values were significantly higher in drug-treated animals compared to controls (Student's t-test, p < 0.05) However, total antioxidant activity was shown to be significantly lower (Student's t-test; p < 0.05) in the drug-treated group compared to control. CONCLUSIONS: We report for the first time that effect of MTX administration in pregnancy is not associated with significant alteration in disposition of essential trace elements. However, the effect of drug administration on antioxidant enzyme status in pregnant women cannot be excluded while using the drug in clinical states.

Magnesium sulphate therapy in women with pre-eclampsia and eclampsia in Kuwait.

OBJECTIVE: To evaluate the outcome of the use of MgSO4 therapy in women with severe pre-eclampsia in Kuwait from January 2002 to December 2004. SUBJECTS AND METHODS: The study involved 450 women managed at the Maternity Hospital in Kuwait with a blood pressure of 160/110 mm Hg and proteinuria of >0.3-5 g/24 h. A loading dose of 4 g MgSO4 was administered intravenously over 20 min and then the maintenance dose continued at 1 g/h for 24 h postpartum. Magnesium sulphate toxicity was monitored by urine output, deep tendon reflexes and serum magnesium levels and managed with an infusion of 10 ml of 10% calcium gluconate and cessation of magnesium infusion. Adjunct therapy included intravenous hydralazine 10 mg and labetalol 100 mg. The mode of delivery was determined after stabilizing the patient. RESULTS: The women included Kuwaitis (n = 200, 44.4%), Asians (n = 129, 28.7%) and other Arabs (n = 116, 25.8%) with a mean age of 29.7 +/- 6.7 years (primigravida: n = 233, 51.8%; other parities: n = 217, 48.2%). Antenatal complications included intra-uterine growth restriction (n = 136, 30.2%), oliguria (n = 39, 8.7%), haemolysis, elevated liver enzymes and low platelet count syndrome (n = 30, 6.6%), abruptio placentae (n = 20, 4.4%), eclampsia (n = 15, 3.3%), and preterm birth (n = 253, 55.2%). Caesarean section (n = 241, 53.6%) was the main mode of delivery. The perinatal mortality rate was 27 per 1,000. Magnesium sulphate toxicity observed as reduced tendon reflexes occurred in 14 (3.1%) patients and flushing, nausea and vomiting and blocked nostrils in 86 (19.1%). There was no association between adverse outcomes and maternal serum magnesium concentrations and no maternal mortality occurred. CONCLUSION: Magnesium sulphate was effective in preventing recurrence of eclamptic fits and safe for both mother and fetus.

Maternal-foetal status of copper, iron, molybdenum, selenium and zinc in obese gestational diabetic pregnancies.

Obesity is well known to be a contributory risk factor for several disease states, including diabetes mellitus. Paucity of data on maternal-foetal status of essential trace elements in obese diabetic pregnancies prompted us to undertake this study. Maternal venous and umbilical arterial and venous blood samples were collected from obese gestational diabetic patients (Body Mass Index (BMI) >30) and control obese pregnant women (BMI>30) at time of spontaneous delivery or caesarean sections and concentrations of essential trace elements such as Cu, Fe, Mo, Se and Zn were determined in various samples by atomic absorption spectrophotometry. Activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPX) and total antioxidant (TAO) in maternal and umbilical blood were assessed using appropriate reagent kits. Maternal-foetal disposition and exchange parameters of elements studied were assessed using established criteria. Concentrations of Cu, Fe, Mo, Se and Zn in serum of control obese pregnant women (n=10) averaged 2404, 2663, 11.0, 89.0 and 666 microg/l respectively, while in the obese diabetic group (n=11), the corresponding values averaged 2441, 2580, 13.3, 85.1 and 610 microg/l respectively. Activities of antioxidant enzymes such as SOD, GPX and TAO were not significantly different in maternal veins of control and diabetic groups. Varying differences were noted in the case of antioxidant enzyme activities in umbilical blood samples of control and study groups. We conclude that obesity is not associated with significant alterations in antioxidant enzyme status in gestational diabetes and only with relatively minor alterations in status of some essential trace elements.

Birthweight percentiles by gestational age in Kuwait.

Our aim is develop a curve for singleton birthweight based on accurately calculated gestational age. A retrospective analysis of all singleton live births from 22-44 completed weeks of gestation during the period from September 1998 to December 2000 in the two largest birth birth centers in Kuwait was conducted. Neonates with major congenital anomalies and those with unrecorded gestational age were excluded from the study population. Total population and gender-specific birthweight percentiles according to gestational age were developed after smoothening of growth curves. A total of 35768 births were included in the development of the birthweight curve. Percentiles of birthweight for all population and by gender are presented. There was significant difference in birthweight among different ethnic groups in this population. At term, 9.8% of births are smaller than the 10th percentile and 10.0% are larger than the 90th percentile. Plotting birthweight in our population on percentile curves derived from the United States or United Kingdom would generally overestimate small for gestational age newborns and underestimate large for gestational age newborns. We conclude that the diagnosis of clinically significant birthweight abnormalities depends on the fetal growth curve used. A population specific curve of fetal growth dated by ultrasonography would provide a reliable reference for birthweight distribution.

Prediction of fetal anemia by middle cerebral artery peak systolic velocity in pregnancies complicated by rhesus isoimmunization.

OBJECTIVES: To study the correlation of peak systolic velocity in the middle cerebral artery with hemoglobin concentration in fetuses at risk of anemia due to Rhesus isoimmunization. DESIGN: Peak systolic velocity of middle cerebral artery (MCA-PSV) was measured before 66 cordocentesis procedures in 20 isoimmunized fetuses. Reference values were derived from a study of 300 control fetuses. MCA-PSV values and hemoglobin concentrations were expressed as multiples of the median (MoM) for gestational age. The following hemoglobin concentration MoM thresholds defined degrees of anemia: mild, between 0.83 and 0.65; moderate, between 0.64 and 0.55; and severe, less than 0.55. Regression analysis was performed and receiver-operator-characteristic curves were constructed to determine the diagnostic accuracy of different thresholds of MCA-PSV for the prediction of moderate to severe anemia, either at the initial or repeat cordocentesis procedures. RESULTS: The mean (+/-SD) gestational age at cordocentesis was 28.5+/-4.6 weeks. Moderate to severe anemia was observed on 29 (44%) and hydrops on 27 (41%) occasions. MCA-PSV correlated weakly with hemoglobin concentrations. At threshold values 1.50 MoM, the sensitivity, specificity, and negative predictive value for moderate to severe anemia were 9.0, 100, and 48.0% at the initial cordocentesis procedures, and 44.0, 96.0, and 73.0% at repeat cordocentesis procedures, respectively. CONCLUSIONS: Although MCA-PSV is highly specific, negative values do not rule out fetal anemia. Further research is required before it can be recommended in clinical practice.

Treatment of ectopic pregnancy with a single intramuscular dose of methotrexate.

This study evaluates the outcome of unruptured ectopic pregnancies treated with single-dose intramuscular methotrexate injection. There were 77 women with unruptured non-laparoscopically diagnosed ectopic pregnancies who were prospectively followed after receiving a single dose of 50 mg/m2 intramuscular methotrexate. Diagnosis required transvaginal ultrasound and serial quantification of beta subunit of human chorionic gonadotropin (betahCG). A repeat dose was given if the weekly drop of betahCG was less than 30%. Therapy was considered successful if complete resolution of betahCG to a level below 25 IU/L was achieved without surgical intervention. Treatment in 73 (95%) cases was successful. The mean pre-treatment level of betahCG was 2592 +/- 3771 IU/L (177-15000 IU/L), the mean diameter of ectopic mass was 2.4 +/- 1.0 cm (1.7-3.5 cm). The average resolution period was 3.2 +/- 1.0 weeks (1-6 weeks) and this significantly correlated with the pre-treatment betahCG level. With strict criteria of inclusion and follow-up, single-dose intramuscular methotrexate is a successful method for the treatment of selected cases of ectopic pregnancy.

Pro-inflammatory maternal cytokine profile in preterm delivery.

PROBLEM: The objective of this study was to determine the levels of cytokines produced by maternal peripheral blood mononuclear cells (PBMC) upon stimulation with a mitogen, with autologous placental cells and with a trophoblast antigen extract. METHOD OF STUDY: Peripheral blood mononuclear cells from 54 women with a history of successful pregnancy and 30 women undergoing preterm delivery (PTD) were stimulated with the mitogen and antigens, and the cytokine levels in mitogen-stimulated culture supernatants assessed. RESULTS: Significantly higher levels of the type 1 cytokines, interferon (IFN)-gamma and interleukin (IL)-2, were produced by the PTD group than by the normal pregnancy group, which on the contrary showed significantly greater production of the type 2 cytokines, IL-4, IL-5 and IL-10. A comparison of the ratios of type 2 to type 1 cytokines is indicative of a type 1 cytokine bias in PTD. CONCLUSIONS: These data are suggestive of a maternal type 1 cytokine bias in PTD.

Placental pathology in relation to the White's classification of diabetes mellitus.

The objective of this study was to investigate various macroscopic and microscopic features of the placenta in pregnancies complicated by diabetes according to White's classification. A total of 148 placentas were studied. Sixty-five were from control patients and 83 from diabetic mothers. The diabetic mothers were further divided into three groups according to White's classification. There were 40 cases in White's group A and 36 cases in White's group B. There were 7 cases in White's groups C and D combined. Advanced maternal age and grandmultiparity were significantly higher in White A, White B and White C&D compared to the normal group. Mean weight of the mother was higher in White group A and group B compared to the control group and group C&D. The placental weight and neonatal weight were increased provided the diabetes was not complicated by vascular disease. With accompanying vascular disease the placental weight and neonatal weight were reduced compared to the controls. As a result of increased perinatal jeopardy the rate of operative delivery was higher in diabetic mothers. No major difference was observed in microscopic changes of placentas in different groups according to White's classification and the normal group.