ETS and Drug Metabolism

The฀study฀population฀comprised฀183฀women฀consecutively฀enrolled฀at฀20–24฀weeks฀of฀ pregnancy฀at฀the฀two฀antenatal฀care฀units฀and฀ultrasound฀biometric฀measurements฀of฀foetal฀ bi-parietal฀diameter฀BPD,฀abdominal฀circumference฀AC฀and฀femur฀length฀FL฀were฀ performed.฀Also,฀serum฀cotinine฀concentration฀was฀determined฀at฀20–24฀weeks฀of฀gesta- tion฀ by฀ gas฀ chromatography฀ with฀ mass฀ spectrometry฀ detector฀ GCMS฀ to฀ assess฀ ETS฀ exposure฀during฀the฀previous฀evening฀and฀the฀morning฀of฀the฀same฀day฀blood฀collection฀ at฀1,200–1,300฀h.฀ETS฀exposure฀passive฀smoking฀was฀assumed฀to฀occur฀when฀the฀level฀ of฀serum฀cotinine฀ranged฀from฀2฀to฀10฀ngml.฀The฀authors฀demonstrated฀that฀a฀statistically฀ signiicant฀negative฀association฀was฀present฀between฀the฀BPD฀and฀serum฀cotinine฀concen- tration.฀A฀similar฀association฀was฀identiied฀for฀subjects฀with฀serum฀cotinine฀concentra- tions฀below฀10฀ngml฀corresponding฀to฀passive฀smoking฀฀p฀=฀0.06.฀After฀controlling฀for฀ pregnancy฀duration,฀maternal฀pre-pregnancy฀weight฀and฀infant’s฀gender,฀we฀found฀that฀ serum฀cotinine฀levels฀at฀20–24฀weeks฀of฀gestation฀was฀inversely฀associated฀with฀infant฀ birth฀weight฀฀p฀=฀0.004.฀For฀the฀subjects฀with฀serum฀cotinine฀levels฀below฀10฀ngml,฀a฀ borderline฀association฀฀p฀=฀0.09฀with฀infant฀birth฀weight฀was฀found.฀It฀was฀concluded฀that฀ maternal฀exposure฀to฀tobacco฀smoke฀in฀early฀pregnancy,฀as฀measured฀by฀serum฀cotinine฀ concentrations฀at฀20–24฀weeks฀of฀gestation,฀adversely฀affects฀foetal฀BPD฀ [75] . In฀children฀with฀low฀birth฀weight฀following฀ETS฀exposure,฀the฀vasodilator฀response฀ following฀forearm฀cuff฀occlusion฀and฀release฀was฀still฀reduced฀at฀age฀9–11฀years฀compared฀ with฀that฀in฀normal฀birth฀weight฀children฀born฀to฀non-smoking฀mothers.฀The฀physiological฀ vasodilator฀response฀is฀triggered฀by฀NO฀release฀from฀endothelial฀cells฀ [76] .฀Among฀other฀ things,฀this฀harmful฀effect฀has฀its฀origins฀in฀the฀prenatal฀period฀and฀is฀related฀to฀the฀smok- ing฀behaviour฀of฀the฀mother-to-be฀during฀pregnancy;฀it฀manifests฀itself฀as฀early฀as฀the฀irst฀ decade฀of฀life฀as฀a฀prelude฀to฀later฀atherogenic฀changes.฀Evidently,฀in฀the฀developmental฀ phases฀characterised฀by฀rapid฀growth฀such฀as฀the฀foetal฀period,฀the฀endothelial฀cells฀also฀ undergo฀adverse฀changes฀which฀limit฀physiological฀function฀ [77] . Urinary฀cotinine฀levels฀were฀determined฀in฀199฀ETS-exposed฀children฀between฀the฀ages฀ of฀4฀months฀and฀4฀years฀with฀obstructive฀bronchitis.฀Compared฀with฀healthy฀children฀of฀the฀ same฀age,฀urinary฀cotinine฀levels฀were฀found฀to฀be฀5.7฀µgl,฀instead฀of฀4.4฀µgl.฀The฀risk฀of฀ developing฀bronchitis฀was฀increased฀in฀line฀with฀the฀extent฀of฀passive฀smoking฀and฀the฀rise฀ in฀urinary฀cotinine.฀This฀risk฀was฀increased฀threefold฀at฀a฀urinary฀cotinine฀concentration฀of฀ 20฀ µgl฀ [78] .฀ Similar฀ results฀ have฀ been฀ reported฀ in฀ 69฀ children฀ [79] .฀ The฀ incidence฀ of฀ Nicotine฀ngml Cotinine฀ngml฀ Active฀smoking฀women฀n฀=฀36 19.2 4.9 6.3 4.0 Newborns฀of฀active฀smoking฀women ฀ 2.4 0.9 2.8 0.8 Passive฀smoking฀women a ฀n฀=฀23 ฀ 3.2 0,8 0.9 0.3 b Newborns฀of฀passive฀smoking฀women ฀ 0.28 0.05 0.6 0.15 Non-smoking฀women฀n฀=฀35 ฀ 1.2 0.4 0.3 0.06 Newborns฀of฀non-smoking฀women ฀ 0.4 0.09 0.26 0.04 Table 9.4 ฀฀฀Hair฀concentrations฀mean฀±฀SEM฀of฀nicotine฀and฀cotinine฀in฀women฀and฀their฀newborn฀ infants฀ [56] a฀ Deined฀as฀regular฀and฀steady฀gestational฀exposure฀to฀other฀person’s฀cigarette฀smoke,฀either฀at฀ home฀or฀in฀the฀workplace b p฀฀0.01฀when฀compared฀to฀newborns฀of฀active฀smoking฀women฀and฀newborns฀of฀non-smokers