Perinatal dioxin exposure, cytochrome P-450 activity, liver functions and thyroid hormones at follow-up after 7-12 years.
OBJECTIVE
Prenatal and lactational exposure to Dutch "background" dioxin levels may cause health effects spanning many years. In addition, perinatal studies have shown a relationship between dioxin exposure and thyroid disturbance. To assess the later health effects of prenatal and lactational dioxin exposure on liver function we measured plasma ALAT and ASAT levels amongst our longitudinal cohort, as was done perinatally and at 2(1/2) years. The children underwent a caffeine loading test to determine CYP1A2 activity. To assess the later effects on thyroid function we measured plasma TSH and FT4.


METHODS
A longitudinal cohort of 37 healthy children (age 7-12, mean 8.2 years), with documented prenatal and lactational dioxin exposure, ingested 3mg caffeine/kg BW 6h prior to blood withdrawal. Paraxanthine/caffeine molar ratio, ALAT, ASAT, TSH and FT4 were determined in venous blood.


RESULTS
Linear regression of ASAT and ALAT revealed no relation with prenatal and lactational dioxin exposure. No correlation was found between the paraxanthine/caffeine molar ratio and prenatal and lactational dioxin exposure. Linear regression of TSH and FT4 revealed no relation with prenatal and lactational dioxin exposure.


CONCLUSIONS
This follow-up has shown a normalisation of previously abnormal ALAT and ASAT levels, indicating a transient effect. CYP1A2 activity, measured by means of a caffeine-loading test, revealed no correlation with the prenatal and lactational exposures. A normalisation of previously abnormal thyroid hormone homeostasis was seen, also possibly indicating a transient effect. This study provides new data on long-term follow-up after perinatal dioxin exposure to background levels of dioxins.
ten Tusscher
Gavin W
GW
Department of Paediatrics and Neonatology, Westfriesgasthuis, Maelsonstraat 3, 1624 NP Hoorn, The Netherlands. g.w.ten.tusscher@planet.nl
Guchelaar
Henk-Jan
HJ
Koch
Joost
J
Ilsen
Adri
A
Vulsma
Thomas
T
Westra
Matthijs
M
van der Slikke
Johannes W
JW
Olie
Kees
K
Koppe
Janna G
JG
D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D002110:Caffeine / Q000097:blood / Q000493:pharmacokinetics; D002648:Child; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D004147:Dioxins / Q000633:toxicity*; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007774:Lactation; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008431:Maternal-Fetal Exchange; D009426:Netherlands / Q000453:epidemiology; D011247:Pregnancy; D013806:Theophylline / Q000097:blood; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood
D004147:Dioxins; D004785:Environmental Pollutants; D002110:Caffeine; D013972:Thyrotropin; D013806:Theophylline; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C021183:1,7-dimethylxanthine; D013974:Thyroxine