consumptionduringpregnancy,theriskofSIDSwasreduced.Causaldifferenceshave been reported, depending on age at death before or after 120 days
[128] . Late SIDS
occurredpredominantlyinwinter,andavarietyofriskconditionslowparentalsocialand educationallevel,smokingstatus,andthepronesleepingpositionwereimportantinboth
earlyandlateSIDS.TheriskofSIDSwasincreased8.4-foldinpretermbabies,3.4-foldin low-birth-weightbabies2,500gand2.2-foldwhenthemotherssmokedduringpreg-
nancy [129,130]
.Thesefactorsunderlineamultiple-causehypothesisforSIDS [126]
.The SIDSratewasreducedwheninfantswerechangedtosleepingontheirbacks
[131] .Apart
fromsmoking,numerousothersocioculturalfactorsyoungmaternalage,loweducational levelofmotherandfather,frequentpregnanciesetc.increasetheriskforSIDS,asdem-
onstratedbyastudyrecentlyconductedinNorway [132]
.Infurtherstudies,theinfants’ risk level for SIDS was reported to be increased 6.2-fold
[133] and 5.01-fold
[127] .
AccordingtotheWestphaliastudy,theSIDSriskincreaseddose-dependentlyfrom2.4- 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 similarriskassessmentshavealsobeenpublishedbyresearchersintheUSA
[134] and
Scotland [135]
.Aplasmacotininelevel30ngmlhasbeenrecordedinabout25of SIDSchildren
[124] ,evidencethattobaccosmokeandhencetheinhalednicotineistrans-
ferredtothefoetus. LBWisanimportantriskfactor,giventheprovenethnicdifferencesinthesubsequent
occurrenceofSIDS.AnassociationbetweeninfantLBWandSIDShasbeenreported amongwhitesandAmericanIndians,andtoalesserextentamongblacks,butnotamong
AsiansorHispanics [136]
. Investigationshaverecentlybeenconductedintotheinetissuechangesinthebrain-
stemofSIDSvictims [137]
.ItwasfoundthatinSIDSvictimstherewas41probability thatthemorethemotherssmokedduringpregnancy,themoregliosisinthenucleusoliva-
risinferiorwasfoundintheirinfantsp0.01.Similarly,associationswerefoundbetween gliosisinthenucleusolivarisinferiorandhypoxic-ischaemiceventsduringpregnancy,
birthandtheperinatalperiod [137]
. ChildrenofwomensufferingfromschizophreniaareatincreasedriskforSIDSRR=2.76;
CI:1.67–4.56andforcongenitalmalformationsamongtheirchildrenRR=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
ResultsofaSIDScase-controlstudyfromtheUSA.Smokersinthehouseholdincluded thechildren’sparentsandotherliveinadults
[125]
1.04–2.77.Theseindingsshouldbeinterpretednotmerelyinthelightofincreaseddrug consumption,includingsmoking,butalsoinsocio-economicterms
[138] .
Overall,30–40ofallcasesofSIDSwouldbepreventableifwomenweretocom- pletelyceasesmokingduringandafterpregnancy
[139] .
8.5 Foetotoxic Effects of CO
Animal experiments in pregnant rats conirm that inhalation of high concentrations of smokeleadstochangesinthefoetusthatarerelectedamongotherthingsinLBW,depend-
ingonthedurationandextentofexposure [140]
.FindingsfollowingCOinhalationinmice andrabbitsconirmtheLBWsoftheanimalsandslightchangesintheskeletalsystem
[141] ,
butdonotsupportateratogeniceffectofCO.Studiesinpregnant,CO-exposedguinea- pigs200ppmfor10hconirmreducedtyrosinehydroxylase-immunoreactivityinthe
medulla oblongata and increased choline acetyltransferase-immunoreactivity [142]
. Consequently,moreextensivechangesmaybeassumedtooccurinthecholinergicand
adrenergic system in the medulla, with particular implications for the cardiorespiratory centres,regionsthoughttobecompromisedinSIDS
[142] .Inexperimentsofsimilardesign,
changesweredetectedfollowingexposuretoacombinationofsulphurdioxideSO
2
and CO,butnottoSO
2
alone [143]
.Inmice,COlevelsof180ppminairmarkedlyreduced oxyhaemoglobinlevelswhilecarboxyhaemoglobinlevelswereincreased.Thisresultedin
increasesintheincidenceofresorbedembryosandofcleftlippalate [144]
.Inadifferent experimentaldesign,pregnantCD-1miceunderwentexposuretoincreasingconcentrations
ofCO0–500ppmCOandwerefeddietswithdifferingproteincontents4,8and16. FoetalweightswerereducedintheCO-exposedgroupsreceivingprotein-deicientdiets.
Therewasalsoanincreasedincidenceofbrachygnathia,microstomia,microcephalus,open mouth,openeyes,skullandjawmalformations,scoliosisandlimbunossiications
[145] .
Theprotein-deicientdiethadasynergisticeffectwithchronicCOintoxicationontheani- mals’development.
Accordingtorecentlypublishedresearch,maternalsmokingduringpregnancyreduces foetalheartrateandtheregulationofheartraterange.Thischangemaybeattributedto
chronichypoxaemia [146]
.End-tidalCOmeasurementsinneonatesrevealdifferingval- ues,followingcorrectionforinhaledair:10.0±7.7ppminneonatesborntosmokers,2.51±
1.4ppminneonatesofpassivelyexposedmothersand1.74±0.98ppminneonatesof non-smokingmothersp0.0001
[147] .Thus,neonatalCOexposurecanbedemon-
stratedasaresultofmaternalsmokingimmediatelybeforedelivery. ImportantevidencefortheteratogeniceffectofCOcanbededucedfromreportsofCO
intoxicationinpregnantwomen:forexample,womenwhoexperiencedCOintoxication duringpregnancyhavegivenbirthtochildrenwithtelencephalicdysgenesis
[148] .
Casereport:Owingtodefectivehouseholdappliances,apregnantwomanwasexposed onseveraloccasionstoraisedambientCOconcentrationsupto100ppm.Inweek41of
pregnancyshegavebirthtoanunderdevelopedinfantwithbilateralcleftformation,ear dysplasia,micropenisandgeneralmuscleweakness.Thechilddiedonday12incardiogenic
shock and post-mortem examination revealed multiple brain malformations [149]
. The mother’sCO–Hblevelwas14,andshealsosmokedabout15cigarettesday.
SixtycasesofCOpoisoninginpregnantwomenwerecollectedinaretrospectivesurvey: adequateinformationconcerningtheseverityofCOexposurewasavailablefor42ofthese
casesTable 8.6
.Overall,tencasesofCOpoisoningsubsequentlyledtomalformationsin the children absent or malformed extremities, brachycephaly, craniosynostosis, multiple
contracturesoftheextremities,hypoplasticlungs,hydrocephalus,earanomaliesetc. [148,
150–152] andahighproportionofthemothersn=26gavebirthtostillborninfants
[150] .
MaternalCO–Hblevelsareparticularlyimportantinthiscontext.Oneprospectivestudy conductedbetween1985and1989examinedfoetaloutcomesin32womenfollowingacci-
dentalCOpoisoningduetoavarietyofcauses.ThesourcesofCOweremalfunctioningfur- naces,hot-waterheaters,carexhaustfumesandmethylenechlorideinhalation.Pregnancy
outcomewasadverselyaffectedin3outof5pregnancieswithseveretoxicity:twostillbirths andonecerebralpalsybecauseofischaemicdamage.Thewomenreceivedhyperbaricoxygen
therapyimmediatelyafterpoisoning,withtheresultthat31neonatesshowednormalphysical developmentdespitemildormoderateCOpoisoninginutero.SeverematernalCOtoxicity
wasassociatedwithsigniicantlymoreadversefoetaleffects [153]
.Inafurthersixwomen withCOpoisoning,thereweretwoabortionsandonepretermdeliverywithnumerousmor-
phologicalanomalies [151]
.Severalstudiesindicatethathyperbaricoxygenventilationisthe treatmentofchoiceforreversingtheeffectsofCOtoxicity
[153,154] .
Inwomenwithpregnancy-inducedhypertensionandpre-eclampsia,endogenousCO formationissomewhatlowerthaninnormotensivepregnantcontrols1.17±0.35vs.1.70±
0.54ppm [153]
,withCObeingaccordedacontributoryroleintheparadoxoftheseem- inglyprotectiveeffectofsmokingtodecreasetheriskofpre-eclampsia
[155] .
8.6 Effects of Nicotine on the Foetus
Littlehasbeenpublishedconcerningtheteratogenicorembryotoxicandfetotoxiceffectsof nicotine.Insteadofpurenicotine,afewanimalexperimentshaveusedaqueousextractsof
chewingtobacco,involvingpre-andpostconceptionalintragastricadministrationofdoses of4,12and20mgkgbodyweightthreetimesdailytoCD-1mice.Theplasmanicotine
levelsmeasured30minafteradministrationrangedfrom99to623ngml.Thisoverdosing ledtothedeathof18and31ofthedamsinthetwohighestdosagegroups.Following
Outcomeforthefoetus SeverityofmaternalCOexposure
Minimal Moderate
Severedeath Nosequelae
4 2
– Survivedwithmalformations
andorfunctionalimpairment –
10 –
Death –
15 11
Table 8.6
MaternalCOpoisoningandimplicationsforthefoetusorchild;summaryof42outof60 casesofCOexposurefromtheliteratureforwhichadequateinformationwasavailable
[150]