Eyad Al-Saleh

Assessment of maternal–fetal status of some essential trace elements in pregnant women in late gestation: relationship with birth weight and placental weight

Objective: The status of the essential trace elements copper (Cu), iron (Fe), zinc (Zn), selenium (Se) and molybdenum (Mo) has been investigated in maternal and umbilical cord blood in control, uncomplicated pregnancies at term, and the possibility assessed of a relationship between blood levels of these trace elements and newborn weight and placental weight. Fetal–maternal ratios of the elements were also computed to establish baseline values for the Kuwaiti obstetric population. Methods: Blood samples were collected from a maternal vein, the umbilical artery and umbilical vein of normal pregnant women at the time of spontaneous delivery or Cesarean section, and the concentrations of various trace elements determined by atomic absorption spectrophotometry. Results: The concentration of Cu, Fe, Mo, Se and Zn averaged 2406.1, 3252.1, 11.6, 107.3 and 696.2 μg/l, respectively, in maternal venous blood in the pregnant women (n = 39) at term. Umbilical venous/maternal venous ratios of Cu, Fe, Mo, Se and Zn averaged 0.32, 1.96, 1.03, 0.83 and 1.55, respectively. Neonatal birth weight did not correlate with maternal blood levels of the trace elements (p > 0.05) in the mother–child pairs studied. However, neonatal weight correlated negatively (p < 0.05) with umbilical venous Cu level. Placental weight correlated positively (p < 0.05) with Fe and Mo levels and negatively with Zn level in umbilical venous blood. Conclusions: Our results indicate an active placental transport for Fe and Zn, while Cu, Mo and Se appear to be exchanged passively between mother and fetus. Evaluation of Fe, Mo, Se and Zn levels in maternal and umbilical cord blood does not appear to be useful in the assessment of fetal growth.

Maternal-fetal status of copper, iron, molybdenum, selenium and zinc in patients with gestational diabetes.

Objective: The status of essential trace elements such as copper, iron, zinc, selenium and molybdenum was investigated in gestational diabetic pregnancies at term, and data were compared to control pregnancies. Fetal/maternal ratios of the elements and copper/zinc ratio were also computed in control and study populations. Methods: Samples from maternal venous, umbilical artery and umbilical vein were collected from gestational diabetic and control pregnant women, at the time of spontaneous delivery or Cesarean section, and concentrations of various trace elements were determined by atomic absorption spectrophotometry. Results: The concentrations of copper, iron, molybdenum, selenium and zinc averaged 2156.2 μg/l, 2020.1 μg/l, 13.1 μg/l, 102.3 μg/l and 656.2 μg/l, respectively, in maternal venous blood in control pregnant women at term (n = 15) while in the corresponding gestational diabetic group (n = 15), concentrations of the trace elements averaged 2345.8 μg/l, 2061.6 μg/l, 15.0 μg/l, 75.2 μg/l and 610.3 μg/l, respectively. Students t test showed that the selenium concentration was significantly lower (p < 0.05)in the diabetic group compared to controls. Values of other elements were not significantly different. Umbilical blood/maternal blood ratios of the trace elements showed varying differences. The Cu/Zn ratio was found to be significantly different between umbilical and maternal samples of control and study groups, indicating a possibility of compromised antioxidant function in diabetic pregnancies. Conclusions: We speculate that altered maternal–fetal status of some essential trace elements in gestational diabetes patients could have deleterious influences on the health of the mother as well as the fetus and newborn.

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.

A 26-Year Review of Emergency Peripartum Hysterectomy in a Tertiary Teaching Hospital in Kuwait - Years 1983-2011

Objective: To identify the risk factors and study the incidence, indications and complications of emergency peripartum hysterectomy (EPH). Materials and Methods: This was a retrospective case-control study. The cases consisted of all women who underwent EPH between January 1983 and January 2011. Two controls per case were randomly selected from the remaining deliveries by using a random number table. Case records were retrieved from the medical records. Results: Among 150,993 deliveries, there were 59 EPHs (cases), giving a rate of 0.390 per 1,000. Of the 59 cases, only 56 were analysed because 3 files were unavailable. These women were older (mean age 36 ± 5.7 vs. 22 ± 5.3 years, p < 0.01) and had delivered more than 1 child (p = 0.02). Thirty-seven (66%) cases had had previous caesarean sections (CSs) and the number of CSs in this group was greater than in the controls (21%, p < 0.01). More index cases had a history of atonic postpartum haemorrhage (46 vs. 4%, p < 0.001) and placenta praevia (34 vs. 4%, p < 0.01). More cases than controls were delivered by CS (73 vs. 29%; p = 0.003). The leading indications for EPH were haemorrhage due to uterine atony and placenta praevia. Independent risk factors were older age, multiparity, history of one or more CSs and placenta praevia. There were 2 maternal deaths from coagulopathy following massive obstetric haemorrhage. The main complications of EPH were febrile morbidity: 12 (21%), wound infection: 8 (14%) and bladder or ureteric injury: 8 (14%). Conclusions: CSs, especially repeat CSs in women with placenta praevia and persistent uterine atony, significantly increased the risks of peripartum hysterectomy.

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.

Trends in maternal mortality over 29 years in a Kuwait Tertiary Teaching Hospital: signs of progress?

This study aims at (1) Assessing trends in maternal mortality in kuwait (2) Define strategies for prevention. Methods: Retrospective analysis of maternal deaths that occurred among, 55,979 live births at a tertiary hospital, between 1980 and 2009. Results: There were 14 maternal deaths, and 55,979 live births, giving a maternal mortality rate of 25 per 100,000 live birth. In terms of decades maternal mortality declined from 54.8 in 1980–90 to 28.4 in 1990–2000 and continued to decline to 12.2 in 2000–2009. Thromboembolism (28.6%), Obstetric haemorrhage (21.5%) and Eclampsia (14.3%) were the leading causes of direct deaths. Cardiac disease is the most common cause of indirect deaths (14.3%) followed by H1N1 pneumonia 7.1%. Eclampsia contributed to 40% of deaths, only in the 1980s. Thromboembolism caused 28.6% of deaths, 50% of which were in the last 9 years. Indirect deaths from cardiomyopathies (66.7%) gained prominence in the 1990s. No deaths from puerperal sepsis were reported after the 1980s (14.3%). Conclusions: Maternal mortality rates are decreasing significantly (p < 0.01) at our institution over the last 29 years. Obstetric haemorrhage and thromboembolism remain important causes of maternal mortality. Substandard care was identified in 70% of Direct and 55% of indirect deaths.

Influence of coconut oil administration on some hematologic and metabolic parameters in pregnant rats

Objective. Data on the effect of coconut oil intake on various hematologic and metabolic parameters in pregnant women or animals are scanty. Hence we attempted to assess the effect of oral administration of graded doses of this edible oil during pregnancy, on various hematologic and metabolic parameters in rats. Methods. Groups of pregnant Sprague Dawley rats were given oral doses of 1 ml, 2 ml, and 4 ml coconut oil twice per day, respectively. Control group of rats were given tap water. Oral feeding of oil was done continuously for a period of 20 days and at the end of the study period the animals were lightly anaesthetized with ether and sacrificed to collect blood samples for analysis. Various hematologic parameters such as red blood cell (RBC) count, white blood cell (WBC) count, hemoglobin (Hg), platelets, lymphocytes, and mean corpuscular hemoglobin concentration (MCHC) were analyzed by a hematology blood analyzer, while metabolic parameters such as cholesterol, triglycerides, urea, uric acid, creatinine, and protein were analyzed by specific analytical kits. Activities of antioxidant enzyme, superoxide dismutase (SOD), glutathione peroxidase (GPX), and total antioxidant activity (TAO) were assessed by specific analytical kits. Statistical analysis of data was performed using a SPSS data analytical package. Results. Oral administration of coconut oil for 20 continuous days of pregnancy did not significantly alter any of the hematologic parameters studied, compared to control group even when the oil was administered at a relatively massive dose of 4 ml/day. Administration of coconut oil appeared to decrease WBC, Hg, platelet, and lymphocyte blood concentrations in treated rats, but the difference, however, was not statistically significant (ANOVA test; p > 0.05). However, platelet concentration was significantly lower (p < 0.05) in rats receiving 1 ml/day of coconut oil compared to control group rats. Administration of coconut oil did not alter the concentrations of protein, cholesterol, urea, triglycerides, uric acid, and creatinine in treated groups of rats significantly (Student’s t-test, p > 0.05) compared to those of control rats. SOD, GPX, and TAO levels in control and treated groups were not significantly different (ANOVA test, p > 0.05) than controls. Conclusions. We conclude that oral administration of coconut oil during pregnancy in rats, even in massive doses, does not cause any significant alterations in hematologic and metabolic parameters. More detailed studies, however, are warranted before extrapolating these results to human 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.