Uwe Töllner

Parental Smoking and Neonatal Serum Levels of Polychlorinated Biphenyls and Hexachlorobenzene

Polychlorinated biphenyls (PCB) and hexachlorobenzene (HCB) are ubiquitous compounds that have tumor-promoting properties if applied together with tobacco-specific carcinogens. It was the purpose of the present study to investigate whether parental smoking by itself will increase the prenatal uptake of such organochloric compounds. With the informed consent of the parents, blood samples were taken from 80 full-term neonates before the first oral feeding. Six PCB congeners (PCB 28, 52, 101, 138, 153, and 180) and HCB were analyzed with capillary gas chromatography. Information about parental smoking behavior, the geographic origin of the parents, and their actual and previous working places was recorded. We composed three study groups for statistical analyses: active smoking mothers (n = 12), passive smoking mothers (n = 33), and nonsmoking families (n = 35). Neonates born to active smoking mothers had the highest PCB and HCB concentrations compared with children of passive or nonsmoking mothers. These differences were statistically significant (p < 0.01) in the cases of PCB 138, total PCB, and HCB. Newborns of passive smoking mothers had higher PCB and HCB concentrations than children of nonsmoking families but lower values than those of active smoking mothers. These differences were statistically significant for all compounds with the exception of PCB 180. It is concluded that active and passive maternal smoking increases the neonatal burden with PCB and HCB.

Influence of Maternal Age and Duration of Pregnancy on Serum Concentrations of Polychlorinated Biphenyls and Hexachlorobenzene in Full-Term Neonates

Polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) are ubiquitous carcinogenic and teratogenic compounds that are transplacentally transferred from mother to fetus during pregnancy. It was the aim of the present study to evaluate the possible influence of maternal age and duration of pregnancy on the neonatal burden with these substances. Blood samples were taken from 80 full-term German neonates within the first 12 h of life, before the first oral feeding. The serum concentrations of six PCB congeners (28, 52, 101, 138, 153, and 180) and HCB were determined with capillary gas chromatography with electron capture detection. The concentrations of the lower chlorinated PCB congeners (28, 52, and 101) were below the detection limit. PCB 153 showed the highest serum concentration (median 0.42 μg/l), followed by PCB 138 (0.34 μg/l) and PCB 180 (0.17 μg/l). Total PCB concentration was 0.96 μg/l, HCB concentration 0.61 μg/l. All detectable PCB congeners and the total PCB concentration correlated significantly with the gestational age of the newborns (r = 0.2639; p < 0.01), with 50–140% higher serum levels in children born at 42 weeks of gestation as compared with neonates born in the 38th week. HCB concentration correlated with maternal age (r = 0.249; p < 0.01), with 2.7-fold higher serum levels in offspring of 40-year-old as compared with 20-year-old women. It is concluded that the neonatal burden with organochlorine compounds depends on maternal age and duration of pregnancy, thereby reflecting the increase in body pollution with these substances during human life as well as a continuous transplacental transfer from mother to fetus during pregnancy.

Serum enzyme activities in full-term asphyxiated and healthy newborns : enzyme kinetics during the first 144 hours of life

Little is known about the kinetics of most serum enzymes during the first hours of life, and even less about the effect on such enzyme activities of perinatal hypoxia-ischaemia. It was the aim of the present study to evaluate the serum kinetics of seven differently located cell enzymes in healthy and asphyxiated newborns during the 1st week of life. The serum activities of cytoplasmic and mitochondrial [aspartate aminotransferase (ASAT), creatine kinase (CK), glutamate dehydrogenase (GLDH), lactate dehydrogenase (LDH), and hydroxybutyrate dehydrogenase (HBDH)] and membrane-bound (gamma-glutamyl-transferase and leucine arylaminidase) enzymes were prospectively measured in full-term asphyxiated (n = 49) and healthy (n = 87) newborns during the first 144 h of life. The blood samples were taken serially at five fixed times: 0 (cord), 12, 24, 72, and 144 h postpartum. The asphyxiated newborns had significantly increased serum activities of ASAT, LDH, and HBDH up to 72 h postpartum, whereas healthy newborns showed higher CK and GLDH activities. Only the activities of ASAT, LDH, and HBDH seemed to depend on the oxygen supply of the fetus or newborn. If other causes of increased serum enzyme activities, e.g. liver diseases, haemolytic disorders, tumours, or inborn errors of metabolism, are excluded, elevated serum activities of ASAT, LDH, and HBDH should draw ones attention to a perinatal hypoxic-ischaemic insult of the newborn.

Pränatale Belastung mit Organochlorverbindungen Vergleichende Untersuchung zwischen einem ländlichen Kleinstadtbereich und einem Großstadtballungszentrum in Deutschland

ZusammenfassungFragestellung. Geographische Unterschiede in der Belastung mit polychlorierten Biphenylen (PCB) und Hexachlorbenzol (HCB) liegen angesichts ihrer Verbreitung als Industrieemissionen und Fungizide nahe und konnten tierexperimentell sowie im globalen Rahmen auch beim Menschen nachgewiesen werden. Ziel der vorliegenden Untersuchung war es, an einem Kollektiv gesunder Neugeborener etwaige regionale Unterschiede in der pränatalen Belastung mit PCB und HCB zwischen einem ländlichen Kleinstadtbereich und einem Großstadtballungszentrum in Deutschland zu untersuchen. Patienten und Methode. Es wurden jeweils 100 reife, gesunde Neugeborene erfasst, die im Untersuchungszeitraum (1998) in Fulda bzw. Düsseldorf geboren wurden. Allen Kindern wurde innerhalb der ersten Lebensstunden, in jedem Fall vor der ersten oralen Nahrungsaufnahme, eine Blutprobe entnommen. Im Serum wurden sodann die 6 PCB-Kongenere 28, 52, 101, 138, 153 und 180 sowie HCB kapillar-gaschromatographisch mit ECD-Detektion bestimmt. Die Untersuchungsgruppen wurden mit dem Wilcoxon-Test für unabhängige Stichproben auf Mittelwertunterschiede untersucht. Ergebnisse. Bezüglich Gestationsalter, Geburtsgewicht und Alter der Mütter bestand kein statistisch signifikanter Unterschied zwischen den beiden Untersuchungsgruppen aus Fulda und Düsseldorf. Das Gleiche galt für die 3 nachweisbaren, höher chlorierten PCB-Kongenere 138, 153 und 180. Dagegen wiesen die Düsseldorfer Neugeborenen signifikant höhere HCB-Konzentrationen auf (Median: 0,26 vs. 0,16 μg/l) als die Kinder aus Fulda. Schlussfolgerungen. Es gibt in den von uns untersuchten Regionen Deutschlands derzeit keine nachweisbaren Unterschiede in der pränatalen PCB-Belastung, die auf einen Unterschied im Wohnumfeld (Stadt vs. Land) zurückgeführt werden könnten. Dafür zeigen Neugeborene aus einem Großstadtballungszentrum signifikant höhere HCB-Belastungen. Mögliche Ursachen hierfür werden aufgezeigt. Insgesamt ist jedoch zu erwarten, dass sich – parallel zur allgemeinen Abnahme der Schadstoffbelastung in Deutschland – auch die Unterschiede in der HCB-Belastung in den nächsten Jahren ausgleichen werden.AbstractQuestion. In face of the global distribution of polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB), regional differences in the human burden with these substances are anticipated and could be demonstrated in animal research as well as in humans in a global context. It was the aim of the present study to investigate whether there are any regional differences in the prenatal burden with PCBs and HCB in a rural vs. metropolitan area in Germany. Patients and methods. Each 100 full-term healthy newborns were recruited who were born in Fulda and Düsseldorf, respectively, in 1998. A blood sample was taken from each newborn within the first hours of life, in every case before the first oral feeding. Six PCB congeners (28, 52, 101, 138, 153, and 180) as well as HCB were determined in serum with capillary gaschromatography with ECD-detection. The results of both study groups were tested on mean differences with Wilcoxons test for independent samples. Results. There were no statistically significant differences between both study groups with regard to gestational age, birth weight and maternal age. The same applied to the three detectable, higher-chlorinated PCB congeners 138, 153, and 180. Only HCB concentration was significantly higher in the newborns from Düsseldorf as compared with those from Fulda (0.26 vs. 0.16 μg/l). Conclusions. We could not demonstrate evidence for obvious differences in the prenatal burden with PCBs in two defined regions of Germany today. On the other hand, neonates born in a metropolitan area have significantly higher HCB concentrations than newborns from a rural area. Possible explanations for this finding are discussed. It is suggested that these differences will be evened out in the next years according to the general decline in the neonatal burden with these organochlorine compounds in Germany.

Tabakspezifische transplazentare Kanzerogene, Nikotin und Cotinin im Urin von Neugeborenen rauchender Mütter

ZusammenfassungHintergrund: Obwohl viele Frauen während der Schwangerschaft rauchen und so der sich entwickelnde Fetus transplazentaren Kanzerogenen ausgesetzt werden kann, ist bislang wenig über die fetale Aufnahme solcher Verbindungen bekannt. Ziel der vorliegenden Untersuchung war es, den Urin von Neugeborenen rauchender und nichtrauchender Mütter auf Metaboliten des tabakspezifischen Kanzerogens 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanon (NNK) sowie Nikotin und Cotinin zu untersuchen. Methode: Die erste Urinprobe reifer Neugeborener wurde gesammelt und auf die NNK-Metaboliten 4-(Methylnitrosamino)- 1-(3-Pyridyl)-1-Butanol (NNAL) und dessen Glukuronid, NNAL-Gluc, untersucht. Die Analysen erfolgten mittels Gaschromatographie mit einem Nitrosamin-selektiven Detektor und wurden durch Massenspektrometrie bestätigt. Nikotin und Cotinin wurden gaschromatografisch-massenspektrometrisch analysiert. Ergebnisse: NNAL-Gluc wurde in 22 von 31 Urinproben (71%) von Neugeborenen rauchender Mütter nachgewiesen. In 4 Fällen wurde zusätzlich NNAL entdeckt. Keine dieser Verbindungen war in den 17 Proben von Neugeborenen nichtrauchender Mütter nachweisbar. Die mittlere Konzentration von NNAL plus NNAL-Gluc betrug in den quantifizierbaren Proben 0,19±0,14 pmol/ml Urin, ungefähr 10% des Werts, den man bei erwachsenen Aktivrauchern findet. Die Konzentration von NNAL plus NNAL-Gluc korrelierte mit der Anzahl der Zigaretten, die pro Tag während der Schwangerschaft geraucht worden waren (r=0,55; P<0,005). Auch die Nikotin- und Cotininkonzentrationen waren bei den Neugeborenen rauchender Mütter signifikant gegenüber der Kontrollgruppe erhöht und korrelierten mit den NNAL- und NNAL-Gluc-Konzentrationen. Schlußfolgerung: Die Ergebnisse zeigen, daß 2 Metaboliten des tabakspezifischen, transplazentaren Kanzerogens NNK im Urin von Neugeborenen rauchender Mütter nachweisbar sind.SummaryBackground: Cigarette smoking is common during pregnancy and can expose the developing fetus to transplacental carcinogens, but relatively little information is available on fetal uptake of such compounds. It was the aim of the present study to analyze the first urine of newborns of mothers who did or did not smoke for metabolites of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) as well as nicotine and cotinine. Methods: First urine of newborns was collected and analyzed for two metabolites of NNK. The metabolites are 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide, NNAL-Gluc. The analyses were carried out by gas chromatography and nitrosamine-selective detection with confirmation by mass spectrometry. Nicotine and cotinine were analyzed by gas chromatography-mass spectrometry. Results: NNAL-Gluc was detected in 22 of 31 (71%) of the urine samples from newborns of smoking mothers; in 4 cases, NNAL was also detected. Neither of these analytes was detected in the 17 samples from newborns of mothers who did not smoke. NNAL plus NNAL-Gluc levels in the positive quantified newborn urine samples were 0.19±0.14 pmol/ml urine, about 10% of that seen in adult smokers. NNAL plus NNAL-Gluc levels correlated with the number of cigarettes smoked per day during pregnancy (r=0.55; p<0.005). Nicotine and cotinine levels in the urine of newborns of smoking mothers were also significantly higher than in the urine of newborns of non-smoking mothers and correlated well with levels of NNAL plus NNAL-Gluc. Conclusions: The results demonstrate that two metabolites of the tobacco-specific transplacental carcinogen NNK are present in the urine of newborns born to mothers who smoke cigarettes.