Complications of Pregnancy ebooksclub.org Tobacco or Health Physiological and Social Damages Caused by Tobacco Smoking Second Edition

Remarkably,฀the฀rate฀of฀pre-eclampsia฀has฀been฀reported฀to฀be฀lower฀in฀heavy฀smokers฀ than฀in฀non-smokers฀11.3฀vs.฀13.0;฀OR฀=฀0.85;฀CI:฀0.73–0.99.฀However,฀smokers฀ with฀pre-eclampsia฀had฀higher฀rates฀of฀infants฀with฀very฀low฀birth฀weight฀OR฀=฀1.85;฀ CI:฀1.55–2.20฀and฀higher฀rates฀of฀placental฀abruption฀OR฀=฀3.49;฀CI:฀1.65–7.28฀ [43] . More฀discriminating฀information฀on฀malformations฀is฀provided฀by฀a฀study฀from฀the฀ USA฀in฀which฀3,284฀live฀births฀of฀women฀who฀smoked฀were฀compared฀with฀4,500฀live฀ births฀of฀non-smokers.฀When฀all฀malformations฀were฀considered฀as฀a฀group,฀no฀increased฀ risk฀was฀associated฀with฀maternal฀smoking.฀However,฀when฀speciic฀malformations฀were฀ considered฀ separately,฀ signiicant฀ associations฀ with฀ maternal฀ smoking฀ were฀ found฀ for฀ microcephalus,฀cleft฀defects฀and฀clubfoot,฀but฀not฀for฀Down฀syndrome฀Table฀ 8.5 ฀ [48] .฀ Atrial฀septal฀defects฀are฀reported฀not฀to฀be฀attributable฀to฀smoking฀during฀pregnancy฀ [52] . One฀survey฀of฀12,914฀pregnancies฀and฀10,523฀live฀births฀has฀shown฀that฀the฀risks฀of฀spon- taneous฀abortion฀and฀congenital฀abnormality฀in฀smoking฀mothers฀are฀1.7-฀and฀2.3-fold฀higher,฀ respectively,฀than฀in฀non-smokers฀ [62] .฀Similar฀indings฀were฀reported฀in฀another฀study฀pub- lished฀in฀the฀same฀year฀showing฀that฀smokers฀20฀cigarettesday฀had฀a฀1.6-fold฀increased฀ risk฀of฀giving฀birth฀to฀an฀infant฀with฀congenital฀malformations฀ [63] .฀The฀infants’฀birth฀weight฀ is฀reduced฀ [64–67] ,฀and฀preterm฀deliveries฀are฀more฀common฀ [68] ,฀because฀of฀the฀possibility฀ of฀disturbances฀of฀placental฀maturation฀resulting฀from฀intrauterine฀O 2 ฀deiciency.฀As฀demon- strated฀in฀a฀group฀of฀770,744฀babies฀born฀in฀Germany฀in฀1999,฀154,149฀of฀them฀were฀born฀of฀ smoking฀ mothers฀ [2] .฀ A฀ dose-dependent฀ and฀ age-dependent฀ reduction฀ of฀ the฀ mean฀ birth฀ weight฀was฀calculated฀Fig.฀ 8.1 .฀It฀has฀also฀been฀suggested฀in฀this฀context฀that฀the฀infants฀ affected฀have฀a฀lower฀IQ฀ [69,฀70] ,฀as฀substantiated฀by฀a฀prospective฀study฀in฀19,117฀children.฀ Low฀IQ฀values฀were฀detected฀when฀no฀other฀neurological฀abnormalities฀were฀present.฀In฀a฀UK฀ study฀conducted฀in฀children฀aged฀9.4฀years฀whose฀mothers฀had฀smoked฀during฀pregnancy,฀no฀ adverse฀effects฀on฀IQ฀or฀cognitive฀development฀were฀detected฀compared฀with฀controls฀ [71] . A฀study฀conducted฀in฀227,791฀live฀births฀in฀Westphalia฀clearly฀showed฀an฀association฀ between฀ LBW฀ and฀ cigarette฀ consumption฀ during฀ pregnancy฀ 10฀ cigarettesday฀ [72] ฀ see฀Table฀ 8.4 .฀Similarly,฀smoking฀African฀American฀women฀from฀low-income฀groups฀ were฀reported฀to฀be฀more฀likely฀to฀have฀LBW฀2,500฀g฀and฀preterm฀37฀weeks’฀gesta- tion฀births.฀When฀lightsmokers฀were฀compared฀with฀non-smokers,฀the฀odds฀ratios฀were฀ 1.89฀CI:฀1.15–3.13฀for฀LBW฀births฀and฀1.74฀CI:฀1.00–3.02฀for฀preterm฀births.฀When฀ heavy฀smokers฀were฀compared฀with฀non-smokers,฀the฀odds฀ratios฀were฀3.03฀CI:฀1.90–4.86฀ for฀LBW฀births฀and฀2.60฀CI:฀1.55–4.35฀for฀preterm฀births฀ [74] .฀According฀to฀a฀Swedish฀ study฀ in฀ pregnant฀ women฀ who฀ smoked,฀ male฀ foetuses฀ were฀ affected฀ signiicantly฀ more฀ Enzyme฀system Genetic฀variant n Birth฀weight฀ reduction฀g OR฀95฀CI CYP1A1 None −377฀±฀89 2.1฀1.2–3.7 CYP1A1 AA 75฀AA −252฀±฀111 1.3฀0.6–2.6 CYP1A1 AAaa 43฀Aa,฀6฀aa −520฀±฀124 3.2฀1.6–6.4 GSTT1 Present −285฀±฀99 1.7฀0.9–3.2 GSTT1 Absent −642฀±฀154 3.5฀1.5–8.3 CYP1A1฀–฀GSTT1 AAaa฀+฀absent −1,285฀±฀234 p฀฀0.001 Table 8.3 ฀฀฀Inluence฀of฀genetic฀variants฀of฀CYP1A1฀and฀GSTT1฀on฀the฀birth฀weight฀of฀infants฀born฀ to฀174฀smoking฀and฀567฀non-smoking฀pregnant฀women฀ [42] frequently฀and฀severely฀than฀female฀foetuses฀in฀terms฀of฀growth฀retardation฀assessed฀in฀ utero฀biparietal฀diameter,฀subscapular฀fat฀accretion.฀In฀boys฀but฀not฀girls฀born฀to฀smok- ers,฀head฀circumference฀was฀also฀signiicantly฀smaller฀ [81] . During฀a฀prospective฀cohort฀study฀of฀30,681฀pregnancies฀of฀at฀least฀28฀weeks’฀gesta- tion,฀307฀women฀ca.฀1฀had฀placental฀abruptions.฀Each฀pack฀of฀cigarettes฀smoked฀per฀ day฀increased฀the฀risk฀of฀placental฀abruption฀by฀40฀OR฀=฀1.39;฀CI:฀1.09–1.79,฀with฀a฀ 3800 3600 3400 3200 3000 2800 2600 Birth Weight [g] 16 20 24 28 32 36 40 Age [years] of the para Difference: −252 g −341g −456 g Fig. 8.1 ฀฀฀Mean฀ birth฀ weight฀ of฀ children฀ of฀ non-smoking฀ upper฀ line฀ and฀ of฀ smoking฀ pregnant฀ women฀ 6–10฀ cigarettesday;฀ middle฀ line;฀ or฀ 21–60฀ cigarettesday;฀ lower฀ line.฀ The฀ data฀ were฀ calculated฀in฀dependence฀of฀the฀para’s฀age฀ [2] Risks OR References Premature฀placental฀abruption฀ 30,681฀pregnancies In฀ca.฀1;฀OR฀1.39 [42,฀73] Reduction฀in฀birth฀weight −200–300฀g [2,฀42,฀64,฀65,฀74–78] LBW฀227,791฀live฀births −239฀g;฀−1.41฀cm;฀ BMI฀−0.6฀kgm 2 [72] LBW฀1,011฀pregnancies −205฀g;฀−1.28฀cm;฀−0.38฀cm฀ head฀circumference฀ 10฀cigarettesday [79] Sudden฀infant฀death฀syndrome฀ SIDS Risk฀increased฀by฀2.2-฀to฀ 8.4-fold,฀depending฀on฀ study,฀also฀depending฀on฀ the฀number฀of฀cigarettes฀ smoked [80] Spontaneous฀abortions฀Sp฀and฀ malformationsMF฀12,914฀ pregnancies.฀+10,523฀live฀births 1.7-fold฀Sp฀and฀2.3-fold฀ MF฀increase [62] Table 8.4 ฀฀฀Risks฀to฀pregnancy฀associated฀with฀cigarette฀smoking concomitant฀ increase฀ in฀ perinatal฀ mortality.฀ Placental฀ abruption฀ was฀ also฀ signiicantly฀ associated฀with฀intrauterine฀growth฀retardation฀and฀foetal฀malformations฀ [82] . The฀commonly฀detected฀presence฀of฀O 2 ฀deiciency฀in฀the฀blood฀of฀women฀who฀smoke฀ is฀attributable฀to฀the฀elevated฀CO฀levels฀ [83] ,฀a฀phenomenon฀that฀is฀associated฀with฀the฀ increased฀formation฀of฀CO–haemoglobin.฀The฀pathogenetic฀importance฀of฀CO฀is฀indicated฀ by฀cases฀of฀CO฀poisoning฀during฀pregnancy฀culminating฀in฀the฀delivery฀of฀malformed฀ infants฀see฀Sect.฀ 8.5 . According฀to฀other฀investigations,฀the฀risk฀of฀spontaneous฀abortion฀ [84] ฀and฀perinatal฀ mortality฀are฀increased฀in฀pregnant฀women฀who฀smoke฀ [85] .

8.3 Malformations Possibly Caused by Smoking

Women฀ who฀ smoke฀ during฀ pregnancy฀ must฀ expect฀ their฀ neonates฀ to฀ display฀ signs฀ of฀ embryotoxic฀and฀fetotoxic฀damage,฀even฀though฀the฀possibility฀of฀malformations,฀such฀as฀ those฀known฀to฀occur฀with฀various฀medicinal฀products,฀was฀initially฀dismissed.฀Tables฀ 8.4 ฀ and฀ 8.5 ฀summarise฀the฀risks฀of฀cigarette฀smoking฀during฀pregnancy,฀although฀the฀number฀ of฀abortions฀may฀be฀subject฀to฀considerable฀variation฀ [40] .฀In฀a฀study฀in฀more฀than฀86,000฀ live฀births,฀negative฀associations฀were฀found฀between฀maternal฀smoking฀during฀pregnancy฀ and฀increased฀risk฀for฀a฀number฀of฀malformations,฀including฀ventricular฀septal฀defects,฀ hydroceles,฀clubfoot,฀pigmented฀naevi,฀haemangiomas฀and฀Down฀syndrome฀ [44] .฀Similarly,฀ following฀analysis฀of฀288,067฀live฀births฀during฀the฀period฀from฀1980฀to฀1983฀in฀Missouri,฀ no฀association฀was฀detected฀between฀congenital฀malformations฀and฀maternal฀smoking฀dur- ing฀pregnancy฀OR฀=฀0.98฀ [45] . One฀problem฀frequently฀discussed฀in฀the฀literature฀is฀the฀possibility฀that฀maternal฀smok- ing฀during฀pregnancy฀may฀increase฀the฀occurrence฀of฀Down฀syndrome.฀Several฀studies฀ [86–88] ฀have฀failed฀to฀indicate฀any฀increased฀frequency฀among฀smokers฀compared฀with฀ non-smokers฀ see฀ Table฀ 8.5 .฀ However,฀ heavy฀ smoking฀ does฀ increase฀ co-morbidity฀ in฀ terms฀of฀additional฀malformations฀tetralogy฀of฀Fallot,฀atrial฀septal฀defects฀without฀ven- tricular฀septal฀defects฀ [89] .฀These฀data฀have฀been฀conirmed฀by฀further฀studies฀in฀which฀ maternal฀a-fetoprotein฀AFP฀and฀human฀chorionic฀gonadotrophin฀hCG฀were฀included฀ as฀markers฀ [90] .฀Slight฀changes฀in฀AFP,฀unconjugated฀oestriol฀uE3฀and฀hCG฀were฀reported฀ in฀smokers฀in฀a฀population฀of฀23,668฀pregnant฀women:฀compared฀with฀non-smokers,฀AFP฀ was฀raised฀by฀3฀while฀uE3฀and฀hCG฀were฀reduced฀by฀3฀and฀23,฀respectively฀ [91,฀92] .฀ Smoking฀has฀also฀been฀shown฀to฀affect฀the฀triple฀test฀AFP,฀E3฀and฀b-hCG฀used฀to฀screen฀ for฀trisomy฀21,฀with฀b-hCG฀in฀particular฀being฀lowered฀by฀smoking฀ [93–95] .฀However,฀the฀ measured฀ changes฀ were฀ inadequate฀ to฀ establish฀ a฀ prevalence฀ for฀ Down฀ syndrome,฀ and฀ consequently฀it฀is฀not฀justiiable฀to฀use฀measurements฀of฀this฀type฀to฀predict฀a฀harmful฀ effect฀ [91] .฀Other฀investigators฀have฀reported฀opposite฀results฀with฀AFP฀determinations฀ 21฀increase฀ [96] .฀According฀to฀a฀Swedish฀study฀in฀1,117,021฀liveborn฀infants,฀an฀asso- ciation฀was฀not฀found฀in฀multiparous฀women,฀but฀could฀not฀be฀ruled฀out฀totally฀in฀primipa- rous฀women฀ [54] .฀The฀fact฀that฀somewhat฀fewer฀Down฀syndrome฀children฀are฀born฀to฀ smoking฀mothers฀than฀to฀non-smoking฀mothers฀should฀therefore฀probably฀be฀interpreted฀as฀ a฀chance฀event฀ [86] .฀The฀development฀of฀neural฀tube฀defects฀is฀a฀controversial฀topic฀ [97,฀98] ฀ but฀the฀association฀with฀maternal฀smoking฀during฀pregnancy฀is฀less฀likely. The฀risk฀of฀oral฀clefts฀cleft฀lip฀and฀palate฀has฀been฀considered฀repeatedly฀in฀the฀con- text฀of฀maternal฀smoking฀Table฀ 8.5 ฀ [97,฀99] .฀Studies฀rejecting฀such฀an฀association฀have฀ occasionally฀appeared:฀for฀example,฀one฀recently฀published฀study฀has฀reported฀higher฀odds฀ ratios฀1.09–1.85฀for฀oral฀clefts฀with฀increasing฀cigarette฀consumption,฀but฀no฀associations฀ were฀identiied฀between฀clefting฀type฀and฀smoking฀habits฀ [100] . The฀association฀between฀maternal฀smoking฀during฀pregnancy฀and฀the฀development฀of฀ cleft฀lip฀and฀palate฀in฀infants฀has฀been฀demonstrated฀elsewhere฀ [97,฀99] .฀One฀case฀-control฀ study฀conducted฀in฀Maryland฀between฀1992฀and฀1996฀revealed฀no฀statistically฀signiicant฀ association฀between฀maternal฀smoking฀and฀oral฀cleft฀development,฀although฀there฀was฀a฀ slight฀increase฀in฀the฀C2฀allele฀on฀the฀TGFa฀genotype฀among฀cases฀of฀oral฀cleft฀ [46] .฀In฀con- trast,฀another฀US฀study฀showed฀increased฀risks฀for฀isolated฀cleft฀lip฀OR฀=฀2.1฀and฀for฀iso- lated฀ cleft฀ palate฀ OR฀ =฀ 2.2฀ when฀ the฀ mothers฀ smoked฀ 20฀ or฀ more฀ cigarettesday.฀ This฀ corresponds฀to฀a฀3-฀to฀11-fold฀risk฀increase฀compared฀with฀non-smokers฀ [101] .฀In฀a฀study฀ Malformations Study฀population฀n Risk฀or฀odds฀ratio฀OR References Malformations 86,000฀and฀288,067฀ live฀births No฀association฀with฀smoking฀ OR฀0.98 [44,฀45] Cleft฀palatecleft฀lip 3-and฀11-fold฀increased฀risk [46,฀47] Microcephalus,฀cleft฀ defects,฀clubfoot 3,284฀live฀births฀+฀ 4,500฀controls Association฀conirmed [48] Cleft฀lippalate 6.16-fold฀and฀8.69-fold฀risk฀ increase฀in฀smokers [49] Cleft฀lippalate 1,002,742฀live฀births OR฀1.16฀cleft฀lip,฀1.29฀ cleft฀palate [50] Cleft฀lippalate Meta-analysis฀ 1966–1996 OR฀1.29฀cleft฀lip฀+฀palate฀ and฀1.32฀cleft฀palate [51] Atrial฀septal฀defects No฀association฀with฀smoking [52] Down฀syndrome 1,117,021฀live฀births No฀association฀in฀multiparous฀ women,฀but฀cannot฀be฀ ruled฀out฀in฀primiparous฀ women [53] Limb฀defects฀and฀limb฀ reduction฀defects 1,575,904฀and฀ 1,109,299฀live฀ births฀610฀infants OR฀1.26–1.70 [54–56] Urinary฀tract฀ malformations฀and฀ polycystic฀kidneys 118฀live฀births฀+฀369฀ controls,฀and฀ 1,117,021฀live฀ births OR฀2.3฀and฀1.22฀respectively [57,฀58] Aortopulmonary฀ septal฀defects OR฀1.9 [56] Craniosynostosis Increased฀risk฀with฀higher฀ antenatal฀maternal฀ altitude [59,฀60] Gastroschisis Children฀born฀to฀ mothers฀below฀25฀ years฀of฀age OR฀2.0 [61] Table 8.5 ฀฀฀Malformations฀possibly฀caused฀by฀cigarette฀smoking