Smoking and Sudden Infant Death Syndrome SIDS

consumption฀during฀pregnancy,฀the฀risk฀of฀SIDS฀was฀reduced.฀Causal฀differences฀have฀ been฀ reported,฀ depending฀ on฀ age฀ at฀ death฀ before฀ or฀ after฀ 120฀ days฀ [128] .฀ Late฀ SIDS฀ occurred฀predominantly฀in฀winter,฀and฀a฀variety฀of฀risk฀conditions฀low฀parental฀social฀and฀ educational฀level,฀smoking฀status,฀and฀the฀prone฀sleeping฀position฀were฀important฀in฀both฀ early฀and฀late฀SIDS.฀The฀risk฀of฀SIDS฀was฀increased฀8.4-fold฀in฀preterm฀babies,฀3.4-fold฀in฀ low-birth-weight฀babies฀2,500฀g฀and฀2.2-fold฀when฀the฀mothers฀smoked฀during฀preg- nancy฀ [129,฀130] .฀These฀factors฀underline฀a฀multiple-cause฀hypothesis฀for฀SIDS฀ [126] .฀The฀ SIDS฀rate฀was฀reduced฀when฀infants฀were฀changed฀to฀sleeping฀on฀their฀backs฀ [131] .฀Apart฀ from฀smoking,฀numerous฀other฀sociocultural฀factors฀young฀maternal฀age,฀low฀educational฀ level฀of฀mother฀and฀father,฀frequent฀pregnancies฀etc.฀increase฀the฀risk฀for฀SIDS,฀as฀dem- onstrated฀by฀a฀study฀recently฀conducted฀in฀Norway฀ [132] .฀In฀further฀studies,฀the฀infants’฀ risk฀ level฀ for฀ SIDS฀ was฀ reported฀ to฀ be฀ increased฀ 6.2-fold฀ [133] ฀ and฀ 5.01-fold฀ [127] .฀ According฀to฀the฀Westphalia฀study,฀the฀SIDS฀risk฀increased฀dose-dependently฀from฀2.4- fold฀ in฀ moderate฀ smokers฀ 10฀ cigarettesday฀ to฀ 7.2-fold฀ in฀ heavy฀ smokers20฀ ciga- rettesday฀ [70] .฀ Only฀ preterm฀ babies฀ had฀ an฀ even฀ higher฀ risk฀ 16-fold฀ increase.฀ Very฀ similar฀risk฀assessments฀have฀also฀been฀published฀by฀researchers฀in฀the฀USA฀ [134] ฀and฀ Scotland฀ [135] .฀A฀plasma฀cotinine฀level฀30฀ngml฀has฀been฀recorded฀in฀about฀25฀of฀ SIDS฀children฀ [124] ,฀evidence฀that฀tobacco฀smoke฀and฀hence฀the฀inhaled฀nicotine฀is฀trans- ferred฀to฀the฀foetus. LBW฀is฀an฀important฀risk฀factor,฀given฀the฀proven฀ethnic฀differences฀in฀the฀subsequent฀ occurrence฀of฀SIDS.฀An฀association฀between฀infant฀LBW฀and฀SIDS฀has฀been฀reported฀ among฀whites฀and฀American฀Indians,฀and฀to฀a฀lesser฀extent฀among฀blacks,฀but฀not฀among฀ Asians฀or฀Hispanics฀ [136] . Investigations฀have฀recently฀been฀conducted฀into฀the฀ine฀tissue฀changes฀in฀the฀brain- stem฀of฀SIDS฀victims฀ [137] .฀It฀was฀found฀that฀in฀SIDS฀victims฀there฀was฀41฀probability฀ that฀the฀more฀the฀mothers฀smoked฀during฀pregnancy,฀the฀more฀gliosis฀in฀the฀nucleus฀oliva- ris฀inferior฀was฀found฀in฀their฀infants฀p฀฀0.01.฀Similarly,฀associations฀were฀found฀between฀ gliosis฀in฀the฀nucleus฀olivaris฀inferior฀and฀hypoxic-ischaemic฀events฀during฀pregnancy,฀ birth฀and฀the฀perinatal฀period฀ [137] . Children฀of฀women฀suffering฀from฀schizophrenia฀are฀at฀increased฀risk฀for฀SIDS฀RR฀=฀2.76;฀ CI:฀1.67–4.56฀and฀for฀congenital฀malformations฀among฀their฀children฀RR฀=฀1.70;฀CI:฀ 100 10 1 3 1 2 3 5.3 5.1 2.4 3.6 22.7 20 11−20 1−10 Total Daily Cigarette Exposure Number of Household Smokers Odds Ratio Adjusted ORs for Nonsmokers = 1.0 Fig. 8.2 ฀฀฀Results฀of฀a฀SIDS฀case-control฀study฀from฀the฀USA.฀Smokers฀in฀the฀household฀included฀ the฀children’s฀parents฀and฀other฀live฀in฀adults฀ [125] 1.04–2.77.฀These฀indings฀should฀be฀interpreted฀not฀merely฀in฀the฀light฀of฀increased฀drug฀ consumption,฀including฀smoking,฀but฀also฀in฀socio-economic฀terms฀ [138] . Overall,฀30–40฀of฀all฀cases฀of฀SIDS฀would฀be฀preventable฀if฀women฀were฀to฀com- pletely฀cease฀smoking฀during฀and฀after฀pregnancy฀ [139] .

8.5 Foetotoxic Effects of CO

Animal฀ experiments฀ in฀ pregnant฀ rats฀ conirm฀ that฀ inhalation฀ of฀ high฀ concentrations฀ of฀ smoke฀leads฀to฀changes฀in฀the฀foetus฀that฀are฀relected฀among฀other฀things฀in฀LBW,฀depend- ing฀on฀the฀duration฀and฀extent฀of฀exposure฀ [140] .฀Findings฀following฀CO฀inhalation฀in฀mice฀ and฀rabbits฀conirm฀the฀LBWs฀of฀the฀animals฀and฀slight฀changes฀in฀the฀skeletal฀system฀ [141] ,฀ but฀do฀not฀support฀a฀teratogenic฀effect฀of฀CO.฀Studies฀in฀pregnant,฀CO-exposed฀guinea- pigs฀200฀ppm฀for฀10฀h฀conirm฀reduced฀tyrosine฀hydroxylase-immunoreactivity฀in฀the฀ medulla฀ oblongata฀ and฀ increased฀ choline฀ acetyltransferase-immunoreactivity฀ [142] .฀ Consequently,฀more฀extensive฀changes฀may฀be฀assumed฀to฀occur฀in฀the฀cholinergic฀and฀ adrenergic฀ system฀ in฀ the฀ medulla,฀ with฀ particular฀ implications฀ for฀ the฀ cardiorespiratory฀ centres,฀regions฀thought฀to฀be฀compromised฀in฀SIDS฀ [142] .฀In฀experiments฀of฀similar฀design,฀ changes฀were฀detected฀following฀exposure฀to฀a฀combination฀of฀sulphur฀dioxide฀SO 2 ฀and฀ CO,฀but฀not฀to฀SO 2 ฀alone฀ [143] .฀In฀mice,฀CO฀levels฀of฀180฀ppm฀in฀air฀markedly฀reduced฀ oxyhaemoglobin฀levels฀while฀carboxyhaemoglobin฀levels฀were฀increased.฀This฀resulted฀in฀ increases฀in฀the฀incidence฀of฀resorbed฀embryos฀and฀of฀cleft฀lippalate฀ [144] .฀In฀a฀different฀ experimental฀design,฀pregnant฀CD-1฀mice฀underwent฀exposure฀to฀increasing฀concentrations฀ of฀CO฀0–500฀ppm฀CO฀and฀were฀fed฀diets฀with฀differing฀protein฀contents฀4,฀8฀and฀16.฀ Foetal฀weights฀were฀reduced฀in฀the฀CO-exposed฀groups฀receiving฀protein-deicient฀diets.฀ There฀was฀also฀an฀increased฀incidence฀of฀brachygnathia,฀microstomia,฀microcephalus,฀open฀ mouth,฀open฀eyes,฀skull฀and฀jaw฀malformations,฀scoliosis฀and฀limb฀unossiications฀ [145] .฀ The฀protein-deicient฀diet฀had฀a฀synergistic฀effect฀with฀chronic฀CO฀intoxication฀on฀the฀ani- mals’฀development. According฀to฀recently฀published฀research,฀maternal฀smoking฀during฀pregnancy฀reduces฀ foetal฀heart฀rate฀and฀the฀regulation฀of฀heart฀rate฀range.฀This฀change฀may฀be฀attributed฀to฀ chronic฀hypoxaemia฀ [146] .฀End-tidal฀CO฀measurements฀in฀neonates฀reveal฀differing฀val- ues,฀following฀correction฀for฀inhaled฀air:฀10.0฀±฀7.7฀ppm฀in฀neonates฀born฀to฀smokers,฀2.51฀±฀ 1.4฀ppm฀in฀neonates฀of฀passively฀exposed฀mothers฀and฀1.74฀±฀0.98฀ppm฀in฀neonates฀of฀ non-smoking฀mothers฀p฀฀0.0001฀ [147] .฀Thus,฀neonatal฀CO฀exposure฀can฀be฀demon- strated฀as฀a฀result฀of฀maternal฀smoking฀immediately฀before฀delivery. Important฀evidence฀for฀the฀teratogenic฀effect฀of฀CO฀can฀be฀deduced฀from฀reports฀of฀CO฀ intoxication฀in฀pregnant฀women:฀for฀example,฀women฀who฀experienced฀CO฀intoxication฀ during฀pregnancy฀have฀given฀birth฀to฀children฀with฀telencephalic฀dysgenesis฀ [148] . Case฀report:฀Owing฀to฀defective฀household฀appliances,฀a฀pregnant฀woman฀was฀exposed฀ on฀several฀occasions฀to฀raised฀ambient฀CO฀concentrations฀up฀to฀100฀ppm.฀In฀week฀41฀of฀ pregnancy฀she฀gave฀birth฀to฀an฀underdeveloped฀infant฀with฀bilateral฀cleft฀formation,฀ear฀ dysplasia,฀micropenis฀and฀general฀muscle฀weakness.฀The฀child฀died฀on฀day฀12฀in฀cardiogenic฀ shock฀ and฀ post-mortem฀ examination฀ revealed฀ multiple฀ brain฀ malformations฀ [149] .฀ The฀ mother’s฀CO–Hb฀level฀was฀14,฀and฀she฀also฀smoked฀about฀15฀cigarettesday. Sixty฀cases฀of฀CO฀poisoning฀in฀pregnant฀women฀were฀collected฀in฀a฀retrospective฀survey:฀ adequate฀information฀concerning฀the฀severity฀of฀CO฀exposure฀was฀available฀for฀42฀of฀these฀ cases฀Table฀ 8.6 .฀Overall,฀ten฀cases฀of฀CO฀poisoning฀subsequently฀led฀to฀malformations฀in฀ the฀ children฀ absent฀ or฀ malformed฀ extremities,฀ brachycephaly,฀ craniosynostosis,฀ multiple฀ contractures฀of฀the฀extremities,฀hypoplastic฀lungs,฀hydrocephalus,฀ear฀anomalies฀etc.฀ [148,฀ 150–152] ฀and฀a฀high฀proportion฀of฀the฀mothers฀n฀=฀26฀gave฀birth฀to฀stillborn฀infants฀ [150] . Maternal฀CO–Hb฀levels฀are฀particularly฀important฀in฀this฀context.฀One฀prospective฀study฀ conducted฀between฀1985฀and฀1989฀examined฀foetal฀outcomes฀in฀32฀women฀following฀acci- dental฀CO฀poisoning฀due฀to฀a฀variety฀of฀causes.฀The฀sources฀of฀CO฀were฀malfunctioning฀fur- naces,฀hot-water฀heaters,฀car฀exhaust฀fumes฀and฀methylene฀chloride฀inhalation.฀Pregnancy฀ outcome฀was฀adversely฀affected฀in฀3฀out฀of฀5฀pregnancies฀with฀severe฀toxicity:฀two฀stillbirths฀ and฀one฀cerebral฀palsy฀because฀of฀ischaemic฀damage.฀The฀women฀received฀hyperbaric฀oxygen฀ therapy฀immediately฀after฀poisoning,฀with฀the฀result฀that฀31฀neonates฀showed฀normal฀physical฀ development฀despite฀mild฀or฀moderate฀CO฀poisoning฀in฀utero.฀Severe฀maternal฀CO฀toxicity฀ was฀associated฀with฀signiicantly฀more฀adverse฀foetal฀effects฀ [153] .฀In฀a฀further฀six฀women฀ with฀CO฀poisoning,฀there฀were฀two฀abortions฀and฀one฀preterm฀delivery฀with฀numerous฀mor- phological฀anomalies฀ [151] .฀Several฀studies฀indicate฀that฀hyperbaric฀oxygen฀ventilation฀is฀the฀ treatment฀of฀choice฀for฀reversing฀the฀effects฀of฀CO฀toxicity฀ [153,฀154] . In฀women฀with฀pregnancy-induced฀hypertension฀and฀pre-eclampsia,฀endogenous฀CO฀ formation฀is฀somewhat฀lower฀than฀in฀normotensive฀pregnant฀controls฀1.17฀±฀0.35฀vs.฀1.70฀±฀ 0.54฀ppm฀ [153] ,฀with฀CO฀being฀accorded฀a฀contributory฀role฀in฀the฀paradox฀of฀the฀seem- ingly฀protective฀effect฀of฀smoking฀to฀decrease฀the฀risk฀of฀pre-eclampsia฀ [155] .

8.6 Effects of Nicotine on the Foetus

Little฀has฀been฀published฀concerning฀the฀teratogenic฀or฀embryotoxic฀and฀fetotoxic฀effects฀of฀ nicotine.฀Instead฀of฀pure฀nicotine,฀a฀few฀animal฀experiments฀have฀used฀aqueous฀extracts฀of฀ chewing฀tobacco,฀involving฀pre-฀and฀postconceptional฀intragastric฀administration฀of฀doses฀ of฀4,฀12฀and฀20฀mgkg฀body฀weight฀three฀times฀daily฀to฀CD-1฀mice.฀The฀plasma฀nicotine฀ levels฀measured฀30฀min฀after฀administration฀ranged฀from฀99฀to฀623฀ngml.฀This฀overdosing฀ led฀to฀the฀death฀of฀18฀and฀31฀of฀the฀dams฀in฀the฀two฀highest฀dosage฀groups.฀Following฀ Outcome฀for฀the฀foetus Severity฀of฀maternal฀CO฀exposure Minimal Moderate Severe฀death No฀sequelae 4 ฀ 2 – Survived฀with฀malformations฀ andor฀functional฀impairment – 10 – Death – 15 11 Table 8.6 ฀฀฀Maternal฀CO฀poisoning฀and฀implications฀for฀the฀foetus฀or฀child;฀summary฀of฀42฀out฀of฀60฀ cases฀of฀CO฀exposure฀from฀the฀literature฀for฀which฀adequate฀information฀was฀available฀ [150]