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Transplacental passage of fluorides
The Journal o f Pediatrics Volume 123, Number 1
screening of meconium samples has been proposed. 11 A t present, however, urine testing is the only method available for large screening programs at many institutions. Our institution is a large inner city hospital serving predominantly patients without private insurance (68.6% of patients), and the screening criteria used in the targeted screening program were developed for use in this population. Other institutions might find it necessary to modify these criteria. We conclude that a targeted screening program would have identified 97% of the infants in our neonatal nursery who h a d u r i n e screens during the first 24 hours of life with positive results for drugs of abuse. The program of universal screening identified only two infants who were missed by the targeted screening but resulted in the ordering of 881 additional tests, an incremental yield of 0.23%. The cost of these additional tests, both monetary and in time spent by the nursery staff, is considerable. The advantages of universal urine screening of all infants admitted to a regular neonatal nursery over a careful targeted screening program are limited. On the basis of the results of this study, we have abandoned universal screening in favor of a targeted screening program. REFERENCES
Gupta et al.
139
2. Neerhof MG, MacGregor SN, Retzky SS, Sullivan TP. Cocaine abuse during pregnancy: peripartum prevalence and perinatal outcome. Am J Obstet Gynecol 1989; l 61:633-8. 3. Kaye K, Elkind L, Goldberg D, Tytun A. Birth outcomes for infants of drug abusing mothers. NY State J Med 1989;89:25661. 4. Mastrogiannis DS, Decavalas GO, Verma U, Tejani N. Perinatal outcome after recent cocaine usage, Obstet Gyneeol 1990;76:8-11. 5. Handler A, Kistin N, Davis F, Ferre C. Cocaine use during pregnancy: perinatal outcomes. Am J Epidemiol 1991; 133:81825. 6. Singer LT, Garber R, Kliegman R. Neurobehavioral sequelae of fetal cocaine exposure. J PEDIATR 1991;119:667-72. 7. Chasnoff I J, Griffith DR, Freier C, Murray J. Cocaine/polydrug use in pregnancy: two year follow-up. Pediatrics 1992; 89:284-9. 8. Dusick AM, Covert RF, Tebbett IR, Yee GT, Schreiber MD. Prenatal cocaine exposure and intracranial hemorrhage in very low birthweight babies [Abstract]. Pediatr Res 1991 ;29:212A. 9. Ostrea EM, Brady M J, Parks PM, Asensio DC, Naluz A. Drug screening of meconium in infants of drug-dependent mothers: an alternative to urine testing. J PEDIATR 1989;115:474-7. 10. Ostrea EM, Brady M, Gause S, Raymundo AL, Stevens M. Drug screening of newborns by meeonium analysis: a largescale, prospective, epidemiologic study. Pediatrics 1992;89: 107-13. l 1. Ostrea EM, Romero A, Yee H. Adaptation of the meconium drug test for mass screening. J PEDIATR 1993;122:152-4.
1. Chasnoff I J, Burns W J, Schnoll SH, Burns KA. Cocaine use in pregnancy. N Engl J Med. 1985;313:666-9. 9
Transplacental passage of fluorides Sunil G u p t a , MD, A. K. Seth, MTech, Alka G u p t a , MS, a n d A. G. G a v a n e , MSc From the Satellite Hospital,Sethi Colony; the National Environmental Engineering Research Institute Zonal Laboratory; and Mahila Chikltsalaya, Jaipur, India Transplacental p a s s a g e of fluorides was studied in 25 r a n d o m l y s e l e c t e d neonates. Blood samples c o l l e c t e d simultaneously from the mother a n d the umbilical cord showed that a v e r a g e fluoride c o n c e n t r a t i o n in the cord b l o o d was 60% of that in mother's blood. When c o n c e n t r a t i o n in the mother's b l o o d e x c e e d e d 0.4 p p m , the p l a c e n t a a c t e d as a s e l e c t i v e barrier. (J PEDIATR1993;123:139741 )
Fluorosis is endemic in several parts of India. Despite the efforts of the local governments, a large population has no alternative but to drink water with a high fluoride content. Submitted for publication Dec. 30, 1992; accepted Feb. 11, 1993. Reprint requests: Sunil Gupta, MD, 15, Burmese Colony, Jaipur 302004, India. Copyright | 1993 by Mosby-Year Book, Inc. 0022-3476/93/$1.00 + .10 9/24/46458
New areas are being discovered in which water contains fluoride concentrations ranging from 4.5 to 8.5 ppm. Gardner et al. 1 observed that fluoride levels in maternal blood and in the placental tissues of pregnant women were increased in areas in which the drinking water contained 1 ppm of fluoride. Feltman and Kosel, 2 Shen and Taves, 3 and Gedalia et al. 4'5 reported that the placenta passively permits fluorides to pass to the fetus. Armstrong et al. 6 measured fluorides in maternal uterine vessels and in the
140
Gupta et al.
The Journal of Pediatrics July 1993 a
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Figure. Correlation of maternal and fetal blood fluoride concentrations (CONCN) (in parts per million).
umbilical vein and artery at cesarean section but found no significant gradient between maternal and fetal blood fluoride levels; however, Gedalia 7 suggested that the placenta may provide a partial barrier at higher blood fluoride levels. In view of this conflicting evidence, we conducted a study to determine whether correlation existed in fluoride levels between maternal blood and cord blood that would indicate transplacental passage of fluoride. METHODS The study was conducted at Mahila Chikitsalaya, a hospital in Jaipur, India. The subjects were chosen randomly from those coming to the hospital for delivery. The study was restricted to a sample size of 25. Immediately after delivery, we collected 5 ml samples of maternal blood and of cord blood under aseptic conditions. The blood samples were stored in a vial of ethylenediaminetetraacetic acid (EDTA) and immediately transferred to the laboratory. Fluoride concentrations were estimated with the ion selective electrode method. 8 The data were subjected to statistical analysis by the Pearson method to determine the coefficient of correlation. R E S U L T S AND D I S C U S S I O N In two cases in which maternal blood fluoride concentrations were 0.4 and 0.15 ppm, the cord blood values were
similar. In all other cases the fluoride concentration in cord blood was less than that in the maternal blood. At the maximum observed value of 2.4 ppm, the cord blood contained 1.0 ppm of fluoride, only 41.7% of the maternal blood level. There was a considerable spread in the difference between maternal and fetal values. As the fluoride concentration in maternal blood increased beyond 0.4 ppm, the pattern changed significantly. When the entire sample was considered, the coefficient of correlation, r, was 0.736, indicating a fairly high positive correlation; that is, cord blood fluoride levels increased with maternal blood fluoride levels (Figure). On average, the cord blood fluoride concentration was about 60% of that in maternal blood. Because the relationship changed significantly when the fluoride level in maternal blood exceeded 0.4 ppm, the observations were divided into two parts, one having fluoride levels less than 0.4 ppm and the other having higher values. Two sets of regression analyses were carried out. For the lower fluoride values, r = 0.568, indicating a slightly lower positive correlation than that for the full sample (Figure). On average, cord blood fluoride concentration was about 64% of the maternal value, similar to that for the full sample. For the higher fluoride values, r = 0.87, indicating a higher positive correlation (Figure). Thus, at a maternal fluoride level greater than 0.4 ppm, the cord blood fluoride
The Journal o f Pediatrics Volume 123, Number 1
Gupta el al.
concentration increased by only about 12%; in this range the placenta apparently acted as a more effective barrier. Conclusions. Fluoride concentration in fetal blood is of significance because formation and calcification of primary teeth occur during the intrauterine period. Several studies have indicated a passive role of the placenta in the passage of fluoride from maternal blood to fetal blood. However, our study has confirmed the suggestion of Gedalia 7 that the placenta may provide a partial barrier at higher blood fluoride levels. A fluoride concentration of about 0.4 ppm in the maternal blood seems to be a level beyond which the placenta acts as a selective barrier for the passage of fluoride.
REFERENCES 1. Gardner DE, Smith FA, Hodge HC, Overton DE, Feltman R. The fluoride content of placental tissue as related to the fluoride content of drinking water. Science 1952;115:208-9.
14 1
2. Feltman R, Kosel G. Prenatal ingestion of fluorides and their transfer to the fetus. Science 1955;122:560-1. 3. Shen YW, Tares DR. Fluoride concentration in the human placenta and maternal and cord blood. Am J Obstet Gynecol 1974;119:205-7. 4. Gedalia I, Brezezinski A, Zukerman H, Mayersdorf A. Fluoride concentration in placental tissue, fetal blood and maternal blood at low and elevated fluoride intake. J Dent Res 1964;43:669-71. 5. Gedalia I, Brezezinski A, Bercovici B, Lazarov E. Placental transfer of fluoride in the human fetus. Proc Soc Exp Biol Med 1961;106:147-9. 6. Armstrong WD, Singer L, Makowski WL. Placental transfer of fluoride and calcium. Am J Obstet Gynecol 1970; 107:432-4. 7. Gedalia I. Distribution in placenta and fetus. In: Fluoride and human health. (WHO Monograph Series No. 59.) Geneva: World Health Organization, 1970:128-34. 8. Fuchs C, Dom D, Fuchs CA, Henning HV, Meintosh C, Scheler F. Fluoride determination in plasma by ion selective electrode: a simplified method for the clinical laboratory. Clin Chim Acta 1975;60:157-67.
FELLOWSHIPS Fellowships available in pediatric subspecialties and those for general academic pediatric training are listed once a year, in January, in THE JOURNAL OF PEDIATRICS. Each June, forms for listing fellowships available for the academic year beginning 18 months after publication are sent to the Chairman of the Department of Pediatrics at major hospitals in the United States and Canada. In addition, a copy of the application form appears in the July, August, and September issues of THE JOURNAL (please use the current form). Should you desire to list fellowships, a separate application must be made each year for each position. All applications must be returned to Mosby by October 15 preceding the listing year to ensure publication. Additional forms will be supplied on request from the Journal Editing Department, Mosby, 11830 Westline Industrial Drive, St. Louis, M O 63146-3318/800-325-4177, ext. 4317, or 314-453-4317.
screening of meconium samples has been proposed. 11 A t present, however, urine testing is the only method available for large screening programs at many institutions. Our institution is a large inner city hospital serving predominantly patients without private insurance (68.6% of patients), and the screening criteria used in the targeted screening program were developed for use in this population. Other institutions might find it necessary to modify these criteria. We conclude that a targeted screening program would have identified 97% of the infants in our neonatal nursery who h a d u r i n e screens during the first 24 hours of life with positive results for drugs of abuse. The program of universal screening identified only two infants who were missed by the targeted screening but resulted in the ordering of 881 additional tests, an incremental yield of 0.23%. The cost of these additional tests, both monetary and in time spent by the nursery staff, is considerable. The advantages of universal urine screening of all infants admitted to a regular neonatal nursery over a careful targeted screening program are limited. On the basis of the results of this study, we have abandoned universal screening in favor of a targeted screening program. REFERENCES
Gupta et al.
139
2. Neerhof MG, MacGregor SN, Retzky SS, Sullivan TP. Cocaine abuse during pregnancy: peripartum prevalence and perinatal outcome. Am J Obstet Gynecol 1989; l 61:633-8. 3. Kaye K, Elkind L, Goldberg D, Tytun A. Birth outcomes for infants of drug abusing mothers. NY State J Med 1989;89:25661. 4. Mastrogiannis DS, Decavalas GO, Verma U, Tejani N. Perinatal outcome after recent cocaine usage, Obstet Gyneeol 1990;76:8-11. 5. Handler A, Kistin N, Davis F, Ferre C. Cocaine use during pregnancy: perinatal outcomes. Am J Epidemiol 1991; 133:81825. 6. Singer LT, Garber R, Kliegman R. Neurobehavioral sequelae of fetal cocaine exposure. J PEDIATR 1991;119:667-72. 7. Chasnoff I J, Griffith DR, Freier C, Murray J. Cocaine/polydrug use in pregnancy: two year follow-up. Pediatrics 1992; 89:284-9. 8. Dusick AM, Covert RF, Tebbett IR, Yee GT, Schreiber MD. Prenatal cocaine exposure and intracranial hemorrhage in very low birthweight babies [Abstract]. Pediatr Res 1991 ;29:212A. 9. Ostrea EM, Brady M J, Parks PM, Asensio DC, Naluz A. Drug screening of meconium in infants of drug-dependent mothers: an alternative to urine testing. J PEDIATR 1989;115:474-7. 10. Ostrea EM, Brady M, Gause S, Raymundo AL, Stevens M. Drug screening of newborns by meeonium analysis: a largescale, prospective, epidemiologic study. Pediatrics 1992;89: 107-13. l 1. Ostrea EM, Romero A, Yee H. Adaptation of the meconium drug test for mass screening. J PEDIATR 1993;122:152-4.
1. Chasnoff I J, Burns W J, Schnoll SH, Burns KA. Cocaine use in pregnancy. N Engl J Med. 1985;313:666-9. 9
Transplacental passage of fluorides Sunil G u p t a , MD, A. K. Seth, MTech, Alka G u p t a , MS, a n d A. G. G a v a n e , MSc From the Satellite Hospital,Sethi Colony; the National Environmental Engineering Research Institute Zonal Laboratory; and Mahila Chikltsalaya, Jaipur, India Transplacental p a s s a g e of fluorides was studied in 25 r a n d o m l y s e l e c t e d neonates. Blood samples c o l l e c t e d simultaneously from the mother a n d the umbilical cord showed that a v e r a g e fluoride c o n c e n t r a t i o n in the cord b l o o d was 60% of that in mother's blood. When c o n c e n t r a t i o n in the mother's b l o o d e x c e e d e d 0.4 p p m , the p l a c e n t a a c t e d as a s e l e c t i v e barrier. (J PEDIATR1993;123:139741 )
Fluorosis is endemic in several parts of India. Despite the efforts of the local governments, a large population has no alternative but to drink water with a high fluoride content. Submitted for publication Dec. 30, 1992; accepted Feb. 11, 1993. Reprint requests: Sunil Gupta, MD, 15, Burmese Colony, Jaipur 302004, India. Copyright | 1993 by Mosby-Year Book, Inc. 0022-3476/93/$1.00 + .10 9/24/46458
New areas are being discovered in which water contains fluoride concentrations ranging from 4.5 to 8.5 ppm. Gardner et al. 1 observed that fluoride levels in maternal blood and in the placental tissues of pregnant women were increased in areas in which the drinking water contained 1 ppm of fluoride. Feltman and Kosel, 2 Shen and Taves, 3 and Gedalia et al. 4'5 reported that the placenta passively permits fluorides to pass to the fetus. Armstrong et al. 6 measured fluorides in maternal uterine vessels and in the
140
Gupta et al.
The Journal of Pediatrics July 1993 a
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0"0297
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L
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IN MOTHER'Ir
0:7 BLOOD
Figure. Correlation of maternal and fetal blood fluoride concentrations (CONCN) (in parts per million).
umbilical vein and artery at cesarean section but found no significant gradient between maternal and fetal blood fluoride levels; however, Gedalia 7 suggested that the placenta may provide a partial barrier at higher blood fluoride levels. In view of this conflicting evidence, we conducted a study to determine whether correlation existed in fluoride levels between maternal blood and cord blood that would indicate transplacental passage of fluoride. METHODS The study was conducted at Mahila Chikitsalaya, a hospital in Jaipur, India. The subjects were chosen randomly from those coming to the hospital for delivery. The study was restricted to a sample size of 25. Immediately after delivery, we collected 5 ml samples of maternal blood and of cord blood under aseptic conditions. The blood samples were stored in a vial of ethylenediaminetetraacetic acid (EDTA) and immediately transferred to the laboratory. Fluoride concentrations were estimated with the ion selective electrode method. 8 The data were subjected to statistical analysis by the Pearson method to determine the coefficient of correlation. R E S U L T S AND D I S C U S S I O N In two cases in which maternal blood fluoride concentrations were 0.4 and 0.15 ppm, the cord blood values were
similar. In all other cases the fluoride concentration in cord blood was less than that in the maternal blood. At the maximum observed value of 2.4 ppm, the cord blood contained 1.0 ppm of fluoride, only 41.7% of the maternal blood level. There was a considerable spread in the difference between maternal and fetal values. As the fluoride concentration in maternal blood increased beyond 0.4 ppm, the pattern changed significantly. When the entire sample was considered, the coefficient of correlation, r, was 0.736, indicating a fairly high positive correlation; that is, cord blood fluoride levels increased with maternal blood fluoride levels (Figure). On average, the cord blood fluoride concentration was about 60% of that in maternal blood. Because the relationship changed significantly when the fluoride level in maternal blood exceeded 0.4 ppm, the observations were divided into two parts, one having fluoride levels less than 0.4 ppm and the other having higher values. Two sets of regression analyses were carried out. For the lower fluoride values, r = 0.568, indicating a slightly lower positive correlation than that for the full sample (Figure). On average, cord blood fluoride concentration was about 64% of the maternal value, similar to that for the full sample. For the higher fluoride values, r = 0.87, indicating a higher positive correlation (Figure). Thus, at a maternal fluoride level greater than 0.4 ppm, the cord blood fluoride
The Journal o f Pediatrics Volume 123, Number 1
Gupta el al.
concentration increased by only about 12%; in this range the placenta apparently acted as a more effective barrier. Conclusions. Fluoride concentration in fetal blood is of significance because formation and calcification of primary teeth occur during the intrauterine period. Several studies have indicated a passive role of the placenta in the passage of fluoride from maternal blood to fetal blood. However, our study has confirmed the suggestion of Gedalia 7 that the placenta may provide a partial barrier at higher blood fluoride levels. A fluoride concentration of about 0.4 ppm in the maternal blood seems to be a level beyond which the placenta acts as a selective barrier for the passage of fluoride.
REFERENCES 1. Gardner DE, Smith FA, Hodge HC, Overton DE, Feltman R. The fluoride content of placental tissue as related to the fluoride content of drinking water. Science 1952;115:208-9.
14 1
2. Feltman R, Kosel G. Prenatal ingestion of fluorides and their transfer to the fetus. Science 1955;122:560-1. 3. Shen YW, Tares DR. Fluoride concentration in the human placenta and maternal and cord blood. Am J Obstet Gynecol 1974;119:205-7. 4. Gedalia I, Brezezinski A, Zukerman H, Mayersdorf A. Fluoride concentration in placental tissue, fetal blood and maternal blood at low and elevated fluoride intake. J Dent Res 1964;43:669-71. 5. Gedalia I, Brezezinski A, Bercovici B, Lazarov E. Placental transfer of fluoride in the human fetus. Proc Soc Exp Biol Med 1961;106:147-9. 6. Armstrong WD, Singer L, Makowski WL. Placental transfer of fluoride and calcium. Am J Obstet Gynecol 1970; 107:432-4. 7. Gedalia I. Distribution in placenta and fetus. In: Fluoride and human health. (WHO Monograph Series No. 59.) Geneva: World Health Organization, 1970:128-34. 8. Fuchs C, Dom D, Fuchs CA, Henning HV, Meintosh C, Scheler F. Fluoride determination in plasma by ion selective electrode: a simplified method for the clinical laboratory. Clin Chim Acta 1975;60:157-67.
FELLOWSHIPS Fellowships available in pediatric subspecialties and those for general academic pediatric training are listed once a year, in January, in THE JOURNAL OF PEDIATRICS. Each June, forms for listing fellowships available for the academic year beginning 18 months after publication are sent to the Chairman of the Department of Pediatrics at major hospitals in the United States and Canada. In addition, a copy of the application form appears in the July, August, and September issues of THE JOURNAL (please use the current form). Should you desire to list fellowships, a separate application must be made each year for each position. All applications must be returned to Mosby by October 15 preceding the listing year to ensure publication. Additional forms will be supplied on request from the Journal Editing Department, Mosby, 11830 Westline Industrial Drive, St. Louis, M O 63146-3318/800-325-4177, ext. 4317, or 314-453-4317.