Moorkath Nandakumaran

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.

Hormone profile of Kuwaiti women with hyperemesis gravidarum

Abstract Objective: To evaluate the incidence of hyperemesis gravidarum among pregnant women in Kuwait and the status of HCG, TSH, Total T4 and Free T4 in the serum of patients with hyperemesis gravidarum compared with a control group of women. Methodology: During a 6-month period all patients admitted to Maternity Hospital with features of hyperemesis gravidarum (excessive vomiting and ketonuria) were enlisted into the study. In fifty of these patients and their fifty normal controls, the status of serum total βhCG, TSH, total T4 and freeT4 were evaluated with AXSYM micro particle enzyme immunoassay. Results: The incidence of hyperemesis in the maternity population was 45 per 1000 deliveries. Total βhCG and Total T4 and FreeT4 were significantly higher in the hyperemesis patients than in the normal controls (p<0.0001, p=0.004 and p=0.01 respectively). TSH levels were significantly lower in hyperemesis patients than in their normal controls (p<0.0001). There was a strong positive correlation between the total βhCG and the gestational age (r=0.8). Conclusion: There is a high incidence of hyperemesis gravidarum in the Kuwaiti population. Total βhCG, Total T4 and Free T4 titers were significantly higher in patients with hyperemesis gravidarum, but none of the patients showed signs of hyperthyroidism.

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.

Assessment of Transport Dynamics in the Perfused Human Placental Lobule: In vitro Study

Transport dynamics in the human placental lobule have been investigated in vitro using a dual perfusion technique. Buffered oxygenated Earle’s salt solution was used as the perfusate. Dynamic transpor

Effect of insulin on transport kinetics of alpha-aminoisobutyric acid in the perfused human placental lobule in vitro.

Abstract Background : The limited data available on the role of insulin on maternal‐fetal transport of amino acids prompted us to undertake this study.

Kinetics of palmitic acid transport in insulin‐dependent diabetic pregnancies: In vitro study

Abstract Backgound: The paucity of data relating to transport kinetics of free fatty acids (FFA) in pregnant diabetic women prompted the undertaking of the present study.

Maternal–fetal transport kinetics of manganese in perfused human placental lobule in vitro

Abstract Objective: There have been no detailed reports relating to maternal–fetal transport kinetics of manganese, an essential trace element in the human pregnancies, and hence we have attempted to study the transport kinetics of this trace element in the human placenta in vitro. Methods: Human placentae from normal uncomplicated pregnancies were collected postpartum. Manganese chloride solution (GFS Chem Inc., Columbus, OH), 10 times the physiological concentrations, along with antipyrine (Sigma Chem Co., St. Louis, MO) as reference marker were then injected as a single bolus (100 µl) into the maternal arterial circulation of perfused placental lobules and perfusate samples collected from maternal and fetal circulations over a period of five minutes. National Culture and Tissue Collection medium, diluted with Earle’s buffered salt solution was used as the perfusate and serial perfusate samples from fetal venous perfusate collected for a period of 30 min. Concentration of manganese in perfusate samples was assessed by atomic absorption spectrophotometry, while that of antipyrine was assessed by spectrophotometry. Transport kinetics of substances studied were computed using established permeation parameters. Results: Differential transport rates of manganese and antipyrine in 12 perfusions differed significantly for 25.75, 90% efflux fractions (ANOVA test, p < 0.05), while those of 10 and 50% efflux fractions were not significantly different between the study and reference substances. Transport fraction (TF) of manganese averaged 54.9% of bolus dose in 12 perfusions, whereas that of antipyrine averaged 89% of bolus dose, representing 61.80% of reference marker TF. The difference observed in TF values of manganese and antipyrine was statistically significant (Student’s t-test, p < 0.05). Pharmacokinetic parameters such as area under the curve, clearance, absorption rate, elimination rate of manganese compared to reference marker were significantly different (ANOVA test, p < 0.05) between the study and reference substances. Conclusions: Our studies show for the first time maternal–fetal transport kinetics of manganese in human placenta in vitro. Considering the restricted transfer of this essential trace element despite its small molecular weight, we hypothesize possibility of active transport of manganese across the human placental membrane. Further studies relating to manganese placental transport in “diabetic model” placental perfusions are in progress.

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.