Passive Smoking During and After Pregnancy

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 spastic฀ bronchitis฀ increased฀ by฀ 14฀ where฀ maternal฀ tobacco฀ consumption฀ was฀ 4฀ ciga- rettesday,฀and฀by฀49฀at฀14฀cigarettesday฀ [80] . ETS-induced฀hypoxia฀causes฀chronic฀pulmonary฀hypoventilation฀in฀children฀at฀the฀risk฀ of฀SIDS฀ [81] .฀In฀response฀to฀hypoxia,฀a฀decline฀in฀mitochondrial฀cytochrome฀oxidase฀has฀ been฀ observed฀ in฀ conjunction฀ with฀ reduced฀ succinate฀ oxidase฀ and฀ palmitoyl฀ carnitine฀ capacity฀during฀circulatory฀collapse.฀The฀brown฀mitochondria฀of฀adipose฀tissue฀were฀acti- vated฀in฀response฀to฀increased฀blood฀low,฀causing฀the฀tissue฀apparently฀to฀take฀on฀a฀brown฀ discolouration฀ [82] .฀The฀hypoxia฀hypothesis฀is฀thus฀a฀more฀likely฀starting฀point฀for฀foetal฀ and฀postpartum฀harmful฀effects,฀ahead฀of฀nicotine฀and฀its฀metabolites. Although฀so฀far฀demonstrated฀only฀in฀animal฀experiments฀rats,฀exposure฀of฀pregnant฀ animals฀to฀smoke฀causes฀the฀development฀of฀hypoplastic฀lungs฀with฀fewer฀or฀larger฀sacculi฀ and฀a฀reduced฀lung฀surface฀area฀for฀gas฀exchange.฀Transposed฀to฀the฀situation฀in฀humans,฀ this฀would฀mean฀that฀the฀pulmonary฀changes฀have฀their฀origin฀in฀utero฀and฀are฀thus฀consis- tent฀with฀reduced฀respiratory฀capacity฀at฀birth฀ [52] . Overall,฀ETS฀exposure฀is฀harmful฀for฀paediatric฀development,฀starting฀with฀the฀smok- ing฀behaviour฀of฀the฀mother฀and฀to฀a฀lesser฀extent,฀of฀the฀father฀before฀birth,฀but฀of฀both฀ parents฀ after฀ birth.฀ Exposure฀ of฀ children฀ to฀ ETS฀ in฀ rooms฀ where฀ smokers฀ are฀ actively฀ smoking฀should฀be฀viewed฀as฀similarly฀harmful. Maternal฀smoking฀during฀and฀after฀pregnancy฀exerts฀substantial฀harmful฀effects฀on฀the฀ health฀of฀the฀neonate฀or฀infant฀ [83] :฀smoking฀cessation฀should฀therefore฀be฀encouraged฀in฀ the฀mother฀either฀before฀she฀becomes฀pregnant฀or฀during฀the฀early฀weeks฀of฀pregnancy.

9.4 Cardiovascular Disease

9.4.1 Coronary Heart Disease

CHD฀is฀the฀leading฀cause฀of฀death฀in฀various฀industrialised฀countries.฀In฀1995,฀a฀total฀of฀ 481,287฀people฀in฀the฀USA฀alone฀died฀from฀the฀consequences฀of฀CHD฀ [76] ,฀and฀active฀ smoking฀is฀one฀of฀the฀key฀risk฀factors฀for฀its฀development.฀Studies฀have฀also฀been฀published฀ to฀indicate฀that฀ETS฀is฀implicated฀in฀CHD฀ [84] ,฀and฀plasma฀or฀serum฀levels฀of฀cotinine฀are฀a฀ useful฀index฀of฀smoke฀exposure฀ [85,฀86] .฀One฀comprehensive฀meta-analysis฀of฀ten฀prospec- tive฀cohort฀studies฀and฀eight฀case-control฀studies฀involving฀between฀513฀ [87] ฀and฀479,680฀ subjects฀ [88] ฀used฀myocardial฀infarction฀or฀death฀from฀CHD฀as฀endpoints.฀The฀follow-up฀ observation฀period฀ranged฀from฀6฀to฀20฀years.฀Even฀though฀the฀assessment฀criteria฀for฀inclu- sion฀in฀the฀meta-analysis฀were฀varied,฀ETS฀exposure฀was฀associated฀with฀a฀25฀increase฀ in฀the฀risk฀of฀acquiring฀CHD฀with฀all฀its฀sequelae฀Table฀ 9.5 .฀Another฀meta-analysis฀has฀ shown฀that฀the฀risk฀of฀CHD฀in฀non-smokers฀was฀higher฀when฀their฀spouses฀continued฀to฀ smoke฀RR,฀1.16;฀CI,฀1.06–1.28฀than฀when฀their฀spouses฀were฀former฀smokers฀RR,฀0.98;฀ CI,฀0.89–1.08฀ [89] .฀When฀the฀number฀of฀passively฀smoked฀cigarettes฀and฀the฀duration฀of฀expo- sure฀years฀were฀taken฀into฀account,฀there฀was฀a฀slight฀increase฀in฀CHD฀risk฀compared฀with฀ non-smokers฀Fig.฀ 9.5 ฀ [84] .฀The฀relative฀risk฀for฀the฀development฀of฀CHD฀in฀ETS-exposed฀ non-smokers฀ has฀ been฀ estimated฀ at฀ 1.30฀ California฀ Environmental฀ Protection฀ Agency,฀ CAEPA฀and฀1.23฀Scientiic฀Committee฀on฀Tobacco฀and฀Health,฀SCOTH฀ [90] .฀Platelet฀ aggregation฀ induced฀ by฀ tobacco฀ smoke฀ products฀ has฀ been฀ proposed฀ as฀ the฀ mechanism฀ responsible฀for฀this฀non-linear฀dose–response฀anomaly฀ [90] . The฀purpose฀of฀studies฀by฀Pitsavos฀et฀al.฀performed฀in฀Greece฀was฀to฀investigate฀the฀ association฀between฀passive฀smoking฀and฀the฀risk฀of฀acute฀coronary฀syndromes฀ACS฀ among฀non-smokers฀ [91] .฀In฀total,฀848฀patients฀with฀the฀irst฀event฀of฀ACS฀and฀1,078฀car- diovascular฀disease-free฀matched฀controls฀completed฀a฀detailed฀questionnaire฀regarding฀ 1.5 1.0 P = 0.006 for linear trend 1.23 95 CI, 1.13−1.34 1.29 95 CI, 1.21−1.42 1.00 0.5 Level of Exposure to cigarettes [cpd] Relative Risk 1 − 19 20 1.00 P = 0.01 for linear trend 1.18 95 CI, 0.98 − 1.42 1.31 95 CI, 1.11 − 1.55 1.29 95 CI, 1.16 − 1.43 1.5 1.0 0.5 Duration of Exposure to Smoking [years] 1 − 9 10 − 19 20 Fig. 9.5 ฀฀฀Relative฀risk฀of฀ coronary฀heart฀disease฀ associated฀with฀passive฀ smoking฀among฀non-smokers฀ [84] .฀Number฀of฀cigarettes฀ smoked฀above฀and฀duration฀ of฀exposure฀below.฀95฀CI฀ 95฀conidence฀interval Studies฀included฀in฀the฀meta-analysis฀ Number฀ Relative฀risk฀95฀CI฀ p-value All฀studies 18 1.25฀1.17–1.32 0.001 Peer-reviewed฀studies 15 1.25฀1.17–1.33 0.001 Studies฀using฀death฀from฀AMI฀or฀CHD฀฀ as฀an฀outcome฀measure 14 1.24฀1.17–1.32 ฀ 0.001 Studies฀controlling฀for฀important฀risk฀฀ factors฀for฀CHD 10 1.26฀1.16–1.38 ฀ 0.001 Table 9.5 ฀฀฀Relative฀risk฀of฀coronary฀heart฀disease฀associated฀with฀passive฀smoking฀among฀non- smokers฀ [84]