Paul M. Kuhnert

Cadmium levels in maternal blood, fetal cord blood, and placental tissues of pregnant women who smoke.

Previous studies have reported that cigarette smoking is a major source of exposure to cadmium (Cd). This study was carried out to determine the degree of exposure to Cd of pregnant women who smoke and to determine the degree of exposure to Cd of pregnant women who smoke and to determine the disposition of the Cd in the maternal-fetoplacental unit. Our data reveal that pregnant women who smoke expose themselves and their placentas to levels of Cd higher than those to which they would normally be exposed. The percentage increase in Cd due to smoking was 32% in the placenta and 59% in maternal blood; these increases are statistically significant. The mean levels of Cd in maternal blood, cord blood, and placental tissues of pregnant women who smoked were all higher than the mean levels of Cd in the same tissues and blood of pregnant women who did not smoke. In addition, the levels of Cd in the maternal blood of smokers were significantly higher than levels of Cd in the cord blood of their infants; this relationship was not found in nonsmokers. On the basis of the Cd data on cord blood and placental tissues, the fetuses found in nonsmokers. On the basis of the Cd data on cord blood and placental tissues, the fetuses of pregnant women who smoke apparently receive very little additional exposure to Cd; however, this does not lessen concern for the fetus. The presently reported increase in exposure to Cd of pregnant women due to smoking must be viewed as undesirable because Cd has been shown to alter placental function in animals, and because Cd has no known biologic function.

The relationship between cadmium zinc and birth weight in pregnant women who smoke

It is universally accepted that smoking during pregnancy results in decreased infant birth weight. However, the mechanism for decreased birth weight is not completely understood. This study tested the hypothesis that the cadmium/zinc interaction in the maternal-fetal-placental unit of the mother who smokes could be related to birth weight. Thiocyanate was used as the index of smoking status and atomic absorption spectroscopy was used to determine trace elements. Results show that cord vein red blood cell zinc and maternal whole blood cadmium levels are significant predictors of infant birth weight when variance that is due to clinical factors and thiocyanate is controlled with stepwise multiple regression techniques (n = 202). Bivariate correlation techniques showed that the factors affecting birth weight were different in the smoking and nonsmoking groups. For example, in nonsmokers (n = 125), the cord vein red blood cell zinc level was positively related to birth weight. In smokers (n = 77), maternal whole blood cadmium, placental cadmium, and placental zinc levels were negatively related to birth weight; the ratio of placental zinc to placental cadmium and the cord vein red blood cell zinc level were positively related to birth weight. The results suggest that increased maternal cadmium and decreased cord vein red blood cell zinc levels in infants of smokers may be significant clinically since increased maternal whole blood cadmium and decreased cord vein red blood cell zinc levels are both significantly related to decreased birth weight.

The effect of smoking on placental and fetal zinc status

Previous studies have reported a cadmium/zinc interaction in cadmium-exposed pregnant animals that results in (1) increased placental cadmium levels, (2) increased placental zinc levels, and (3) decreased placental zinc transport. This study was carried out to determine whether zinc status would be affected in pregnant women exposed to cadmium through cigarette smoke. Atomic absorption spectroscopy was used to determine the levels of cadmium and zinc; 65 pregnant women who smoke and 84 who do not smoke were studied. Our data reveal that increased cadmium levels in pregnant women as the result of smoking increase placental zinc levels and decrease cord red blood cell zinc levels. Significantly higher levels of both cadmium and zinc were found in the placentas of pregnant women who smoke; moreover, stepwise multiple regression showed that maternal whole blood cadmium levels predicted placental zinc levels. In regard to cord blood, a significant 9% decrease in the red blood cell zinc level was observed in infants of mothers who smoke and this decrease was correlated with smoking activity, as evaluated by measuring plasma levels of thiocyanate. Also cord red blood cell zinc levels were found to correlate with placental zinc levels in nonsmokers but not in smokers. Overall, our data show that a cadmium/zinc interaction does take place in the maternal-fetal-placental unit of pregnant women who smoke and results in less favorable zinc status in the infants.

Effects of low doses of meperidine on neonatal behavior.

: After meperidine administration during labor, meperidine reaches its highest level in fetal tissues within 2-3 hr. The highest levels of normeperidine, the active metabolite of meperidine, are, on the other hand, determined in fetal tissues by the time between administration of meperidine to the mother and delivery: the greater the drug-to-delivery interval (DDI), the higher the fetal levels of normeperidine. Because of the different times to peak fetal levels of meperidine and normeperidine, it may be possible to partially separate the effects of meperidine and its metabolite on the neonate using the DDI. The purpose of this study was to determine whether low doses of meperidine affected performance on the Brazelton Neonatal Behavioral Assessment Scale (BNBAS), and whether this performance is related to the DDI or to levels of meperidine or to normeperidine. Sixteen control neonates whose mothers received no meperidine and 41 study infants whose mothers received 25-100 mg meperidine intravenously (mean 39 +/- 19 mg) were studied. Comparisons of BNBAS scores of control and study infants measured at less than 12 hr, again at 3 days of age, and the effect of DDI were made using repeated measures analyses of variance (ANOVA). Correlation techniques were used to examine relationships between BNBAS performance and clinical and pharmacological variables related to drug administration. The BNBAS cluster scores representing regulation of state and number of abnormal reflexes were significantly different in study neonates from control neonates. Performance depended upon test day. Further analysis showed that longer DDIs resulted in less optimal BNBAS performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal passive smoking and fetal serum thiocyanate levels.

Passive smoking, exposure of the nonsmoker to air contaminated with tobacco smoke, has been reported to have several adverse consequences for health. However, its effects on the fetus are unknown. Detailed smoking histories and fetal SCN (thiocyanate) levels were obtained in 107 low-risk pregnancies in order to evaluate fetal exposure to this metabolic byproduct of tobacco smoke. Among nonsmokers, fetal SCN levels were increased in association with passive smoking in the home (p less than 0.05). Significant differences in clinical characteristics were associated with passive smoking, but none of these differences were accounted for a significant increase in fetal SCN levels. These findings suggest that maternal passive smoking exposes the fetus to SCN, which is reported to be an effective biochemical marker of overall exposure to smoking, and which is known to be toxic in higher doses.

Comparison of mercury levels in maternal blood, fetal cord blood, and placental tissues

Previous studies have reported that mercury accumulates in cord blood during pregnancy. This study was carried out to determine where in cord blood the mercury accumulates, i.e., in cord erythrocytes, in cord plasma, or in both, and to determine whether the predominant form of mercury which accumulates is methyl or inorganic mercury. From our data it is clear that methyl mercury accumulates in cord erythrocytes: A total of 30% more methyl mercury was found in fetal erythrocytes than in maternal erythrocytes. Also correlation analysis of the methyl mercury levels in maternal and fetal erythrocytes showed a strong correlation (r = 0.87). In regard to inorganic mercury, the highest concentration was found in the placenta, suggesting a barrier role, but a significant correlation (r = 0.62) was also found between the maternal and fetal plasma levels of inorganic mercury. Moreover, the inorganic mercury concentration per gram of plasma was higher in fetal cord plasma than in maternal plasma. Overall, the relative levels of methyl and inorganic mercury reported here varied considerably in materrnal and fetal erythrocytes, plasma, and in the placenta, but all of the levels were low (<6 ng Hg/gm of tissue) and in agreement with Øtotal¿ mercury levels reported by others.

Meperidine and normeperidine levels following meperidine administration during labor: II. Fetus and neonate☆

The time interval between the administration of meperidine to laboring patients and delivery may affect neonatal status, but sophisticated analytic techniques have not been used to determine the exposure of the fetus to meperidine at various drug-delivery intervals. By means of gas chromatography and mass spectrometry, the concentrations of meperidine and normeperidine (the principle metabolite of meperidine) were quantitated in the umbilical cord venous and arterial plasma at delivery and in the urine of the neonate for three days postpartum. Following 50 mg. of meperidine administered intravenously during labor, fetal exposure to meperidine was highest two to three hours after maternal medication while fetal exposure to normeperidine was highest four hours or more after medication. We conclude from this study that there is a definite but nonlinear relationship between the drug-delivery interval and the amount of meperidine and normeperidine an infant receives; and that the drug-delivery intervals resulting in maximum fetal exposure reported here correspond with those resulting in maximum neonatal depression reported by others.

Meperidine and normeperidine levels following meperidine administration during labor

The time interval between the administration of meperidine to laboring patients and delivery may affect neonatal status, but sophisticated analytic techniques have not been used to determine the exposure of the fetus to meperidine at various drug-delivery intervals. By means of gas chromatography and mass spectrometry, the concentrations of meperidine and normeperidine (the principle metabolite of meperidine) were quantitated in the umbilical cord venous and arterial plasma at delivery and in the urine of the neonate for three days postpartum. Following 50 mg. of meperidine administered intravenously during labor, fetal exposure to meperidine was highest two to three hours after maternal medication while fetal exposure to normeperidine was highest four hours or more after medication. We conclude from this study that there is a definite but nonlinear relationship between the drug-delivery interval and the amount of meperidine and normeperidine an infant receives; and that the drug-delivery intervals resulting in maximum fetal exposure reported here correspond with those resulting in maximum neonatal depression reported by others.

Disposition of meperidine and normeperidine following multiple doses during labor: II. Fetus and neonate

It has been suggested that continued diffusion gradients from mother to fetus would exist and that both meperidine and normeperidine would accumulate in the fetus following multiple doses of meperidine to the mother during labor. However, no pharmacokinetic data are available. Therefore, the purpose of this study was to document the disposition of meperidine and normeperidine in the fetus and neonate following multiple doses of meperidine to the mother over long time periods. Twelve infants were studied. The results show surprisingly high concentrations of both meperidine and normeperidine in fetal blood at delivery. In addition, the amount of normeperidine increased with time in umbilical cord blood, the ratio of normeperidine to meperidine increased with time, and the umbilical artery-to-vein ratio of meperidine (but not normeperidine) was greater than one following long drug-to-delivery intervals. The data also suggest that with long drug-to-delivery intervals the levels of normeperidine may become clinically important and that the elimination of both compounds by the neonate is prolonged. The study suggests that multiple doses to the mother over long time periods result in maximum accumulation of both meperidine and normeperidine in fetal tissues.

Transient tachypnea of the newborn: The relationship to preterm delivery and significant neonatal morbidity☆☆☆

Early studies suggest that transient tachypnea of the newborn is a benign disease of uncertain etiology. Consequently, prevention of this complication has not been a primary concern of obstetricians. In this study of amniotic fluid phospholipids, 55 pregnancies in which the neonate developed transient tachypnea were compared to 355 pregnancies after which respiratory distress did not occur. Thirteen neonatal complications and procedures, often associated with prematurity, were significantly increased in the infants who developed transient tachypnea. Potential risk factors for transient tachypnea were examined by stepwise discriminant analysis. Negative amniotic fluid phosphatidylglycerol, prematurity (less than 38 weeks), and 1-minute Apgar score less than 7 all made an independent contribution to the overall characterization of infants at increased risk for transient tachypnea. These findings suggest that mild fetal lung immaturity may be a factor in the pathophysiology of this syndrome, and that the relationship of perinatal factors associated with transient tachypnea of the newborn in previous studies, including maternal diabetes mellitus and cesarean birth, may be partially mediated through a neonatal surfactant deficiency.