Jehad Al-Harmi

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-fetal status of copper, iron, molybdenum, selenium, and zinc in obese pregnant women in late gestation

Obesity is well known to be a contributory risk factor for several disease states, including diabetes mellitus. Further, obese women are more prone to have babies born with congenital abnormalities. Paucity of data on maternal-fetal disposition of essential trace elements in obese pregnancies prompted us to undertake this study. Maternal venous and umbilical arterial and venous samples were collected from obese patients (body mass index >30) and control pregnant women (body mass index <25) at time of spontaneous delivery or cesarean sections and concentrations of essential trace elements such as Cu, Fe, Mo, Se, and Zn determined in various samples by atomic absorption spectrophotometry. Activities of antioxidant enzymes, superoxide dismutase, glutathione peroxidase, and total antioxidant activity in maternal and umbilical blood were assessed using appropriate reagent kits. Maternal-fetal disposition and exchange parameters of elements studied were assessed using established critieria. Concentrations of Cu, Fe, Mo, Se, and Zn in the serum of control pregnant women at time of delivery averaged 2232.6, 2398.1, 10.9, 108.9, and 661.9 μg/L, respectively, whereas in the obese group, the values of the above elements averaged 2150.3, 2446.8, 12.6, 96.8, and 838.9 μg/L, respectively. Umbilical vein/maternal vein ratios of Cu, Fe, Mo, Se, and Zn in the control group averaged 0.29, 1.93, 1.06, 0.76, and 1.12, respectively, whereas in the obese group, their fetal-maternal ratios averaged 0.32, 2.23, 1.06, 0.78, and 1.53, respectively. The Cu:Zn ratio in the maternal vein of the obese group (3.60±0.20) was significantly lower (Students t-test; p<0.05) than that of the controls (2.50±0.19); however, Cu:Fe ratio (1.04±0.08 vs 1.02±0.09) was not significantly different (Students t-test; p>0.05) in the two groups. Varying differences were noted in the case of antioxidant enzyme activities between the control and study groups. We conclude that obesity is associated with alterations in maternal-fetal disposition of some essential trace elements and antioxidant enzyme status and that these alterations could pose a potential health risk for the mother as well as the fetus.

Motor–vehicle injury in pregnancy and subsequent feto-maternal outcomes: of grave concern

Abstract Objectives: (1) To evaluate maternal and fetal outcome after motor-vehicle injury during pregnancy. (2) To determine if there was prenatal care provider counseling for seat belt use. Methods: Retrospective chart analysis of materno-fetal outcome following motor vehicle injury in 728 pregnant women between 2009 and 2012. Women attending antenatal clinics over these years were asked if they were counseled regarding correct seat belt use by prenatal health care providers during their antenatal visits. Results: In these pregnant women, 80 (11%) sustained minor injuries/sprains. 648 women (89%) had severe adverse materno-fetal pregnancy outcomes. Important causes being: (1) placental abruption 58.8%; (2) preterm labor (40%); and (3) uterine rupture (1.6%). There were 100 (13.7%) maternal and 78 (10.7%) fetal deaths. 91 (12.5%) perimortem cesarean deliveries were performed and 74 (81%) fetus survived, as did 31 women. Prenatal care provider counseling for seat belt use occurred in 44.8% of prenatal visit. Only 125 (21%) were using seat belt during the accident. Conclusion: Important causes of adverse pregnancy outcome were: abruptio placenta, preterm labor and uterine rupture. There were 100 maternal and 78 fetal deaths with 97 preterm births. Counseling occurred in 44.8% of women. Those using seat belts during the accidents sustained minor injuries.

Viral load of human papillomavirus in women with normal and abnormal cervical cytology in Kuwait.

INTRODUCTION Human papillomaviruses (HPV) are the most commonly known sexually transmitted agents. Almost all cases of cervical cancer are caused by persistent infection. This study was conducted to ascertain whether there is a difference in HPV load in cervical samples with normal and abnormal cervical cytology reports in Kuwait. METHODOLOGY HPV-positive abnormal ThinPrep samples (n = 206) and normal ThinPrep samples (n = 120) were taken from women attending gynecology clinics. Real-time PCR was used to measure the viral load for all HPV genotypes. RESULTS The median normalized viral load in samples with normal and abnormal cytology reports was 0.86 × 10-7 and 4.66 × 10-7, respectively (p = 0.001). Median normalized viral load of high-risk (HR), intermediate-risk (IR) and low-risk (LR) HPV was 4.04 × 10-7, 0.71 × 10-7 and 2.38 × 10-7, respectively, (p = 0.002). CONCLUSIONS The findings suggest that, in the absence of a proper screening programme in Kuwait, quantification of HPV viral load could be considered as a surrogate virology test to identify women with abnormal cytology. Further population-based prospective studies are needed to include more women with high-grade and invasive carcinoma reports.

Maternal-fetal transport kinetics of carboplatin in the perfused human placental lobule: in vitro study.

Objective. Platinum-containing drugs are widely used in the treatment of various malignancies in humans. There is a paucity of data on maternal–fetal transport characteristics of one such widely used drug, carboplatin, and this prompted us to study its permeation characteristics in the human placenta in vitro. Methods. Placentae from uncomplicated, normal pregnancies were collected postpartum. Carboplatin, along with antipyrine as internal reference marker were injected as a single bolus (100 ul) into the maternal arterial circulation of isolated perfused placental lobules and perfusate samples collected from both maternal and fetal circulations over a period of 5 minutes. National Culture and Tissue Collection medium, diluted with Earles buffered salt solution was used as the perfusate. Carboplatin concentration in various samples was determined by atomic absorption spectrophotometry, while antipyrine concentration was assayed by spectrophotometry. Transport and pharmacokinetic data of study and reference substances were computed using appropriate parameters. Results. The differential transport rate of carboplatin for 10, 25, 50, 75, and 90% efflux fractions in fetal venous effluent averaged 0.60, 1.35, 2.52, 3.72, and 4.49 minutes in 12 perfusions, representing 1.16 ± 0.10, 1.06 ± 0.06, 1.00 ± 0.02, 0.98 ± 0.01, and 0.99 ± 0.01, respectively, times the antipyrine reference value. Students t-test did not show any significant difference (p > 0.05) between the control and study group data. The transport fraction (TF) of carboplatin, expressed as the fraction of the drug appearing in the fetal vein during a study period of 5 minutes, averaged 9.00 ± 0.52% of bolus dose, while antipyrine TF averaged 68.60 ± 2.01% of injected bolus dose, representing 13.1% of reference marker value. Students t-test showed carboplatin and reference marker TF values to be significantly different (p < 0.05). Pharmacokinetic parameters such as area under the curve, clearance, time for maximum response, and absorption and elimination rates of study and reference substances showed varying differences. Conclusions. We report for the first time that carboplatin transport from the maternal to the fetal circulation is relatively small in the human placenta at term. It is reasonable to assume that the risk for the neonate from carboplatin use in pregnancy is minimal when used in emergency clinical situations.

Maternal-fetal transport kinetics of methotrexate in perfused human placenta: in vitro study.

Objective. Folate antagonists are widely used in the treatment of diverse cancerous states. A paucity of data on transport characteristics of one such widely used drug, methotrexate, in the human placenta, prompted us to study its permeation characteristics in vitro. Methods. Placentas from normal pregnancies were collected post-partum. Methotrexate, along with antipyrine as reference marker were injected as a single bolus (100 μL) into the maternal arterial circulation of isolated perfused placental lobules; perfusate samples were collected from both maternal and fetal circulations over a study period of five minutes. National Culture and Tissue Collection medium, diluted with Earles buffered salt solution was used as the perfusate. The concentration of methotrexate in various samples was determined by high performance liquid chromatography, while antipyrine concentration was assayed by spectrophotometry. Transport and pharmacokinetic data of study and reference substances were computed using standard parameters. Results. Differential transport rate of methotrexate for 10, 25, 50, 75 and 90% efflux fractions in fetal venous effluent averaged 0.52, 1.30, 2.37, 3.57 and 4.43 minutes in 12 perfusions, representing 1.01 + 0.08, 1.03 + 0.06, 0.95 + 0.03, 0.93 + 0.03, 0.93 + 0.03 respectively times antipyrine reference value. Students t-test showed varying differences between the control and study group data. Transport Fraction (TF) of methotrexate, expressed as fraction of the drug appearing in fetal vein, during study period of 5 minutes averaged 24.00 + 2.50% of bolus dose while antipyrine TF averaged 68.73 + 2.01% of injected bolus dose, representing 24.00 percent of reference marker value. Students t-test showed methotrexate and reference marker TF values to be significantly different (p < 0.05). Pharmacokinetic parameters such as area under the curve, clearance, time for maximum response, absorption and elimination rates of study and reference substances showed varying differences. Conclusions. We report for the first time that the transport of methotrexate from maternal to fetal circulation is not negligible in human placenta at term. It is reasonable to assume that a direct risk for the fetus from methotrexate use in pregnancy cannot be excluded, and caution is warranted when it is used in emergency clinical situations.

Transport kinetics of cisplatin in the perfused human placental lobule in vitro

Objective. Platinum-containing drugs are used extensively in the treatment of various malignancies in humans. Data are scarce on the maternal–fetal transport characteristics in humans of one such widely used drug, cisplatin, and this prompted us to study its transport characteristics in the human placenta in vitro. Methods. Placentae from normal pregnancies were collected after delivery. Cisplatin, along with antipyrine as an internal reference marker, was injected as a single bolus (100 μL) into the maternal arterial circulation of isolated perfused placental lobules and perfusate samples collected from both maternal and fetal circulations over a period of 5 minutes. National Culture and Tissue Collection medium, diluted with Earles buffered salt solution, was used as the perfusate. The concentration of cisplatin in various samples was determined by atomic absorption spectrophotometry, while antipyrine concentration was quantified by spectrophotometry. Transport and pharmacokinetic data of study and reference substances were computed using appropriate parameters. Results. The differential transport rate of cisplatin for 10, 25, 50, 75, and 90% efflux fractions in fetal venous effluent averaged 0.49 ± 0.02, 1.23 ± 0.03, 2.41 ± 0.04, 3.67 ± 0.03, and 4.48 ± 0.07 minutes in 12 perfusions, while corresponding rates for antipyrine, for above mentioned efflux fractions averaged 0.51 ± 0.01, 1.26 ± 0.05, 2.52 ± 0.01, 3.78 ± 0.01, and 4.52 ± 0.01 minutes, respectively. Cisplatin transport rates averaged 0.97, 0.97, 0.96, 0.97, and 0.99 times the antipyrine reference value. Analysis of variance (ANOVA) did not show any significant difference (p > 0.05) between the control and study group data. The transport fraction (TF) of cisplatin, expressed as a fraction of the drug appearing in the fetal vein during a study period of 5 minutes, averaged 9.00 ± 0.52% of bolus dose, while antipyrine TF averaged 68.6 ± 2.01% of injected bolus dose, representing 13.10% of reference marker value. The Students t-test showed cisplatin and reference marker TF values to be significantly different (p < 0.05). Pharmacokinetic parameters such as area under the curve, clearance, absorption rate, and elimination rate of study and reference substances also varied significantly (p < 0.05). Conclusions. We report for the first time that cisplatin transport is negligible in the human placenta at term. It is reasonable to assume that the risk for the neonate from cisplatin use in pregnancy is minimal when it is used in emergency clinical situations.

Is membrane sweeping beneficial at the initiation of labor induction

Abstract Objective: To determine whether cervical membrane sweeping during labor induction is beneficial. Methods: Outcomes of labor after induction in pregnant women at term were compared in a randomized trial. Women were assigned to having their membranes “swept” or “not swept” at the initiation of labor induction. Results: We recruited a total of 870 women of which 70 were excluded. There were 400 nullipara (Group A) [198 “swept”, 202 “not swept”] and 400 multiparas (Group B) (201 “swept” and 199 “not swept”]. Among group A who received intravaginal prostaglandin (PG) E2, those who had simultaneous sweeping had significantly shorter mean induction-labor interval (12.9 ± 1.3 versus 16.2 ± 1.1 hours, p = 0.046), lower mean dose of oxytocin (6.6 ± 0.6 versus 10.11 ± 1.4 mU/minute, p = 0.01), and increased normal delivery rates (vaginal delivery 82.8% versus 58.6%, p = 0.01). Sweeping also had a favorable effect on nulliparas who had ARM and received oxytocin alone (mean induction-labor interval 5.9 ± 2.9 versus 10.9 ± 2.6 hours p = 0.04, mean maximum dose of oxytocin 9.8 ± 1.1 versus 15.2 ± 1.1 mU/min, p = 0.01). These results were restricted to women with unfavorable cervix in Group A those who had membrane sweeping. Conclusion: Membrane sweeping, has beneficial effects on labor and delivery, which is limited to nulliparas with unfavorable cervix requiring PGE2 or Oxytocin alone.

Prevalence of Cytomegalovirus DNA in Cord Blood and Voided Urine Obtained from Pregnant Women at the End of Pregnancy

Objective: This study was undertaken to determine the prevalence of congenital cytomegalovirus (CMV) infection in pregnant women at the end of pregnancy in Kuwait using cord blood and maternal urine. Subjects and Methods: Urine samples were collected prior to childbirth, and cord blood was collected immediately after delivery from 983 women. Anti-CMV IgG and IgM antibodies were determined using ELISA; CMV DNA was detected using nested PCR, and viral load was calculated using real-time PCR. CMV concentration in samples was categorized as low when the viral load ≤103 copies/µl, intermediate when the viral load = 103–104 copies/µl, and high when the viral load >104 copies/µl. The cord blood serology outcome was compared to cord blood PCR, cord blood viral load, maternal urine PCR and viral load analyses. Results: Serology showed that of the 983 cord blood samples, 89 (9%) were positive for anti-CMV IgM antibodies; PCR test showed 44 (4.5%) contained CMV DNA, and there was a high viral load in all. Maternal urine PCR showed that 9 (10.11%) women had CMV DNA, and there was a high viral load in 7 (78%). The kappa test for measures of agreement showed a reasonable agreement (0.45) between cord blood PCR and urine PCR. Conclusion: This study showed that CMV infection in the cord blood sera of pregnant women is common in Kuwait and highlights the need for more clinically based studies to follow up newborns with congenital CMV infection.

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

Abstract 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.