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DrugsinPregnancy

DanaG.Carroll,PharmD

Contributionsby:Drs.DougCarroll,ElizabethAnderson,MelissaCarter,MistyClark,ElizabethFlynn,Lindsey
Johnson,ChadHolley,MeghanMorgan,ShelleyOBryan,HemalPatel,JasonSmiley

Pregnancyisauniqueperiodinawomanslife.Manychangesarehappeningtoherbodythatmayaffectthe
pharmacologyofmedications.Duringpregnancy,awomansgastricpHisincreasedandgastricmotilityis
reducedwhichmayinterferewiththerateandextentofmedicationabsorption.Maternalplasmavolumeis
increasedleadingtochangesinthevolumeofdistribution.Inaddition,increasesinprogesteroneand
estradiollevelsmayaffectthehepaticmetabolismofsomemedications.Glomerularfiltrationrateis
increasedduetoincreaserenalbloodflowwhichmayaffectrenallyclearedmedications.Despitethe
changes,thepharmacologyofmostmedicationsisnotalteredenoughtorequiredosingchanges.1

Theplacentaisanorganofexchangeallowingthemothertopassnutrientsandmedicationstothefetus;
therefore,medicationsadministeredtopregnantwomenhavethepotentialtoaffectthegrowingfetus.The
fetusisgenerallyatthegreatestriskofdevelopingteratogeniceffectsfrommedicationsduringthefirst
trimester,butitisdrugspecific.Theuseofmedicationsinpregnancyshouldbeevaluatedforthebenefits
andriskstoboththemotherandfetus.Uponevaluation,somemedicationsmaybeusedsparinglyduring
sometrimestersandcontraindicatedinothers.2Alleffortsshouldbemadetooptimizetheriskbenefitratio.

Drugswithlowmolecularweight,lowmaternalproteinbinding,lowionization,andhighlipophilicityare
morelikelytocrosstheplacentaandcausepharmacologicaffects.1Thedevelopingfetussbodysystemsare
notmature;therefore,thefetusmaylacktheabilitytometabolizemedicationscausingteratogeniceffects.2

TheFDAhascategorizedthepotentialteratogenicriskofmedicationsbyanA,B,C,D,Xsystem.

CategoryA:Controlledstudiesinwomenhavefailedtodemonstratearisktothefetusinthefirsttrimester
andthereisnoevidenceofriskinlatertrimesters.Thepossibilityoffetalharmappearsremote.Medications
inthisclassareconsideredsafetouseinpregnancy.Examplesofmedicationsinthisclassarevitaminsand
levothyroxine.

CategoryB:Eitheranimalreproductionstudieshavenotdemonstratedafetalriskbutthereareno
controlledstudiesinpregnantwomen,oranimalstudieshavedemonstratedrisktothefetusthatwasnot
confirmedincontrolledstudiesinpregnantwomeninthefirsttrimesterandthereisnoevidenceofariskin
latertrimesters.Medicationsinthisclassaregenerallyconsideredsafe.Examplesofmedicationsinthisclass
areacetaminophenandamoxicillin.

CategoryC:Studiesinanimalshaverevealedadverseeffectsonthefetusandtherearenocontrolledstudies
inwomen,orstudiesinwomenandanimalsarenotavailable.Drugsfromthisclasscanbegiventopregnant
womenifthebenefittothemotheroutweighstherisktothefetus.Examplesofmedicationsinthisclassare
diltiazemandspironolactone.

CategoryD:Evidenceofhumanfetalriskhasbeendocumented,butthebenefitstothemothermaybe
acceptabledespitetherisktothefetus.Drugsinthisclassmaybeusedinpregnancyifthebenefitstothe
motheroutweightherisktothefetus(i.e.alifethreateningsituationoraseriousdiseaseforwhichsafer
medicationcannotbeusedorarenotefficacious).Examplesofmedicationsinthisclassarephenytoinand
valproicacid.

CategoryX:Studiesinanimalsorhumanshavedemonstratedteratogeniceffects.Therisktothefetus
clearlyoutweighsanypotentialbenefittothemother.Drugsinthiscategoryarecontraindicatedin
pregnancy.Examplesofmedicationsinthisclassarethalidomideandwarfarin.2
Antibiotics

Generic(Brand) Pregnancy Crosses Reportedadverseeffectstomomor Placeintherapy


Category placenta babyfromuseinpregnancy
Nitrofurantoin(Macrobid) B Yes Fetus:Hemolyticanemia

Sulfamethoxazole(SMX)/ C SMX:Unknown Fetus:SMX:jaundice,hemolyticanemia, Notrecommendedinpregnancy
trimethoprim(TMP) TMP:Yes andpossiblykernicterusTMP:neuraltube
(BactrimDS/SeptraDS) defects(NTD),oralclefts,cardiacdefects,
andurinarytractdefects
Metronidazole(Flagyl) B Yes Fetus:Lowbirthweightbabies, Safeforuseonlyin2ndand3rd
spontaneousabortions,andcarcinogenic trimester
possibilities
Topical(Metrogel) Notmutagenicorteratogenic Contraindicatedin1sttrimester
Clindamycin(Cleocin, B Yes Fetus:Increaseinneonatalinfectionand ForBVasoralalternative,butnot
Clindagel,CleocinT) lowbirthweightseenwithvaginal thetopical
preparation1,12
GroupBstrep.diseaseinpatients
withpenicillinallergy
Tetracyclines D Yes Fetus:Hypospadia(1sttrimesteronly), Notrecommendedinpregnancy
inguinalhernia,limbhypoplasia,teeth
nd rd
discoloration(2 ,3 ) cataracts,cleft
palates,spinabifida,polydactyly

Maternal:livertoxicity,irreversibleshock
Cephalosporins B Yes Nonereported Generallyconsideredsafein
pregnancyunlesspenicillin
allergic

Penicillins+/Beta B Yes Nonereported Safestclassofabxinpregnancyif


lactamaseinhibitor notallergic

Txofchoiceforsyphilis
(desensitizeifpenicillinallergic)
Macrolides Azithro, Yes Fetus:Cardiovascularabnormalitiesand
Erythro:B cleftpalatewithClarithromycin.
Claritro:C

Fluoroquinolones C Yes Erosionofweightbearingcartilageinrats Notrecommendedinpregnancy


anddogs,butnohumanreports

Aminoglycosides D Yes Fetus:ototoxicity/deafness(damageof8th Donotuseinpregnancynot


(Amikacin,Gentamicin,and CN)Neuromuscularweakness,respiratory unlessthebenefitoutweighsthe
Tobramycin) depressionwithconcomitantgentamicin risktothefetus.
andMagsulfate


AntiepilepticDrugs(AEDs)

Pregnancy Crosses Reportedadverseeffectstomomor
Generic(Brand) Placeintherapy
category placenta babyfromuseinpregnancy
Carbamazepine D Yes:levels5080% Fetus:dysmorphicfacialfeatures,cranial CompatibleMaternalBenefit>>
(Tegretol) ofmaternal,highest defects,cardiacdefects,spinabifuda,fingernail Embryo/FetalRiskIfdrugisrequiredduring
infetalliverand hypoplasia,developmentaldelay,mildmental pregnancyitshouldnotbewithheldbecause
kidneys retardation,neuraltubedefects thebenefitsofpreventingseizuresoutweigh
potentialfetalharm
Ethosuximide C Unknown Fetus:spontaneoushemorrhage,patentductus Limitedhumandata.Probablycompatible.
(Zarontin) arteriosus,cleftlip/palate,mongoloidfacies, Succinamideanticonvulsants:DOCfortxof
shortneck,alteredpalmarcreaseandaccessory petitmalepilepsyin1sttrimester
nipple,hydrocephalus
Felbamate(Felbatol) C Unknown Fetus:mentalretardation.Maternal:aplastic LimitedHumanData AnimalDataSuggest
anemia,acuteliverfailure ModerateRisk.Drugcrossesplacentain
animals,notyetdescribedinhumans.But
shouldoccurbecauseofLMW

Phenytoin(Dilantin) D Unknown Fetus:congenitalabnormlaities,hemorrhageat CompatibleMaternalBenefit>>


birth,neurodevelopmentabnormalities Embryo/FetalRisk
Doserelated Maternal:folicaciddeficiency SignificantRisks:major/minorcongenital
teratogenic abnormalities,hemorrhageatbirth,
effect neurodevelopment
Maintainlowestlevelrequiredtoprevent
seizuresinordertolessenriskoffetal
anomalies
Fosphenytoin D Unknown Fetus:congenitalmalformations,orofacialclefts, Benefitsfromuseinpregnantwomenmaybe
(Cerebyx) cardiacdefects,minoranomalies,mental acceptabledespitetherisk(e.g.,ifthedrugis
deficiency neededinalifethreateningsituationorfora
seriousdiseaseforwhichsaferdrugscannotbe
Maternal:Anincreaseinseizurefrequencymay
usedorareineffected)
occurduringpregnancybecauseofaltered
phenytoinpharmacokinetics
Gabapentin C Unknown Limited humandatadoesnotallowan LimitedEvidence:Ifrequired,benefitsappear>
(Neurontin) assessmentastothesafetyofgabapentin fetalrisks

st
Lamotrigine C Yes Fetus:frequencyofmajordefectsamong1 HumanDataSuggestLowRisk;Adjustdoseto
(Lamictal) trimestermonotherapyexposurewas2.9%(12 maintainclinicalresponse
of414)
Levetiracetam C Unknown Risktohumanfetus/embryounknown Risktohumanembryo/fetusisunknown
(Keppra)
Oxcarbamazepine C Yes Fetus:nomajorcongenitalmalformations Noepoxidemetabolites:lowerriskof
(Trileptal) reported,mildfacialdefectsobservedinone teratogenicitycomparedtootheragents,
case Supplementwithfolicacid
Phenobarbital D Yes Fetus: congenitaldefects,hemorrhageatbirth, Benefits>Riskduringatlowesteffectivelevel
(LuminalSodium) addiction,AEofneurobehavioraldevelopment
Maternal:Benefit>Risk

Pregabalin(Lyrica) C Unknown Animalstudies fetalabnormalities,skeletal Useonlyifmaternalbenefit>fetalrisk


malformations,malemediatedteratogenicity
Nohumanstudies
st
Tiagabine(Gabitril) C Unknown Fetus:oneincidencewithunspecified Safestcourse:Avoidin1 trimester ;later
malformations,otherwiseunknown trimestersunknown,

Primidone D Unknown Newborn: neurologicmanifestations Ifbenefits>risks(e.g.,drugneededinlife


(Mysoline) (overactivity/tumor);mechanismfor threateningsituationorseriousdiseasewithno
hemorrhagiceffectsisduetosuppressionof saferdrug)
VitKdependentclottingfactors,recommend
administrationofVitKtoinfantimmediately
afterbirth
st
Topiramate C Yes Hypospadiasinmales(relationshipnot Avoidifpossiblein1 trimester
(Topamax) established);Datatoolimitedtoassess
embryo/fetusrisk
ValproicAcid D Yes Fetus:neuraltubedefects,minorfacialdefects, Benefits>Risks(e.g.,drugneededinlife
(Depakene) defectsofthehead,face,digits,urogenitaltract, threateningsituationorseriousdiseasewithno
mentalandphysicalgrowth saferdrug)
st
Zonisamide C Unknown Congenitalanomaliespossible Avoidifpossiblein1 trimester
(Zonegran)
st 1
Trimethadione D Unknown Fetus:mentalretardation,craniofacialdefects, Contraindicatedin1 trimester
genitourinarydefects,malformedhands,
clubfoot
st
Clonazepam D Unknown Humandatasuggestlowrisk;fetalandneonatal Safestcourseistoavoidduringthe1
(Klonopin) toxicityhasbeenreported trimester;however,ifindicated,itshouldnot
bewithheldbecauseofpregnancy

Lorazepam(Ativan) D Yes Fetus:highIVdosesmaycausefloppyinfant Benefits>Risks(e.g.,drugneededinlife


syndrome,higherincidenceofrespiratory threateningsituationorseriousdiseasewithno
distress saferdrug)
Carbamazepine D Yes Fetus: minorcraniofacialdefects,fingernail Ifrequired,Benefits>risks
(Tegretol) hypoplasia,developmentaldelay,mildmental
retardation


CoughandCold

Generic(Brand) Class Pregnancy Crosses Reportedadverseeffectstomomor Placeintherapy
Category placenta babyfromuseinpregnancy
st
Diphenhydramine Antihistamine B Yes 1 trimester cleftpalate,cardiovascular DOCifparenteralantihistaminesare
(Benadryl) defects,oralclefts,spinabifida, indicated
polydacytly,limbreductiondefectsand
hypospadias.
Maternal:prematurelabor Meclizineandcyclizine:viable
alternatives
Chlorpheniramine Antihistamine B Unknown Fetal: polydactyly,GIdefects,eyeandear Meclizineandcyclizinedonot
(Chlorphen,Aller defects,inguinalhernia,hydrocephaly, requirearestrictiononusein
Chlor) congenitaldislocationofthehipand pregnantwomenandwouldbe
malformationofthefemalegenitalia. viablealternatives
Fexofenadine(Allegra) Antihistamine C Unknown Nowellcontrolledstudiespublished; Considerdiphenhydramineor
avoidinfirsttrimester chlorpheneramine
Loratadine(Alavert, Antihistamine C Unknown Fetal: Cleftpalate,microtia, Considerdiphenhydramineor
Claritin) microphthalmia,deafness,triscuspid chlorpheneramine
dysplia,diaphragmatichernia.
nd st
Bin2 /3rd Notrecommendedin 1 trimester
st
Cetirizine(Zyrtec) Antihistamine C Unknown 1 trimester spontaneousabortion, Considerdiphenhydramineor
ectopickidney,undescendedtestes chlorpheneramine
nd st
Bin2 and Exposuretoolowassesspotentialrisks Notrecommendedinthe1
3rd trimester
Dextromethorphan Antitussive C Unknown generallysafebasedonobservation DOCforcoughduringpregnancy;
(Robitussin,Pediacare) combinationproductscontaining
alcoholshouldbeavoidedduring
pregnancy;avoidliquidalcohol
containingpreparations
Benzonatate(Tessalon Antitussive C Unknown Therehasnotbeensufficientclinical Ifpossible,useofbenzonatate
Perles) experiencetoestablishthesafetyof duringpregnancyshouldbeavoided
benzonatateingeneralduringpregnancy
st
Codeine/ Antitussive C;Dathigher Unknown 1 trimester physicaldependence, Useonlyifclearlyneeded
Hydrocodonerxcough dosesfor withdrawal,growthretardation,
syrups longertime respiratorydepression,cleftlip/palate,
dislocatedhip,musculoskeletaldefects.
nd
2 trimester alimentarytractdefects
st
Guaifenesin(Mucinex, Expectorant C Unknown 1 trimester increasefrequencyof UseonlyifBenefits>Risks
Humibid) inguinalherniasandcardiovascular
defects
SalineNasalSpray A Unknown Noknownadverseeffects Safetouseduringalltrimestersin
pregnancy.
st
Phenylephrine Sympathomimetic C Unknown 1 trimester ear/eyemalformation, Untilmoreinformationisavailable,
(Tannate) syndactyly,preauricularskintag,club useofphenylephrineshouldbe
foot,inguinalhernia. avoidedduringpregnancy
Congenitalhipdislocation,
musculoskeletaldefects,umbilicalhernia
Maternal:uterinevesselvasoconstriction
andreducedbloodflowresultsinfetal
hypoxia
st
Pseudoephedrine Sympathomimetic C Unknown 1 trimester inguinalhernia,clubfoot.
(Sudafed,Dimetapp) Mayresultinfetalhypoxia.Teratogenicis
someanimalspecies
st
NasalSteroids Corticosteroid CBudes:B Unknown 1 trimester orofacialclefts,conotruncal Thebenefitsoftreatmentmustbe
Budesonide Triamcin:Din defects,neuraltubaldefectsandlimb carefullyweighedagainstthe
(Rhinocort) 1sttrimester) abnormalities.Congenitalmalformations, potentialrisksoftherapy.Ofthe
Fluticasone(Flonase) prematurebirth,lowbirthweight,C nasalcorticosteroids,budesonideis
Mometasone section,stillbirthmultiplebirths. thebestchoice.Itistheonlyinhaled
(Nasonex) corticosteroidthatiscategoryB
Triamcinolone
(Nasacort) Budenoside:noincreasedriskoftheseAE.
Triamcinolone:inanimalscleftpalate,
umbilicalhernia,undescendedtestes,
reducedossification,growthretardation.

DiabetesMellitus

Generic(Brand) Class Pregnancy Crosses Reportedadverseeffectstomom Placeintherapy
Category placenta orbabyfromuseinpregnancy
Glyburide(Diabeta, Sulfonylurea C Yes Possibleeardefectsin1sttrimester, Insulinisrecommendedfirstline
Micronase,Glynase) fetalhypoglycemia bytheADA;ACOGrecommends
useofthisagentinD2orGDM

Glipizide(Glucotrol) Sulfonylurea C Yes Possibleeardefectsin1sttrimester,no Notrecommended;limited


teratogenicityinanimalstudies humandata

Glimepiride(Amaryl) Sulfonylurea C Unknown Skeletalmalformationinhighdoses Notrecommended;Nohuman


data
Metformin Biguanide B Unknown Neuraltubedefectsinanimalsathigh Insulinisrecommendedfirstline
(Glucophage, doses.Fewabnormalitiesinhumansat bytheADA;ACOGrecommends
Fortamet,Glumetza) normaldosesandlikelyduetopoorBG useofthisagentinD2orGDM
control

Sitagliptin(Januvia) Dipeptidyl B Unknown Nogoodstudiesinhumans;animal Possible;Nohumandata


peptidaseIV studiesshownodefects/complicationat
inhibitor highdoses
Pioglitazone(Actos) TZD C Unknown Developmentaldelay,decreasedfetal Notrecommended
weightinanimals
Rosiglitazone TZD C Yes Fetaldeath/retardationwasseenin Notrecommended
(Avandia) animalstudies

Exenatide(Byetta) Incretinmimetic C Unknown Decreasedfetalgrowth,skeletal Notrecommended


malformationsinanimalstudies
Pramlintide(Symlin) Amylino C Unknown Animals:neuraltubedefects,cleft Notrecommended
mimetic palateathighdoses
Regularinsulin Shortacting B No Nonereported Drugofchoice
(HumulinR,Novolin insulin
R)

Lisproinsulin Rapidacting B No Casereports:suddenneonataldeath, Recommended


(Humalog) insulin growthretardation;controlledstudies:
asefficaciousasregularinsulin

Glulisineinsulin Rapidacting C Unknown Noavailablestudies Notrecommendedunless


(Apidra) insulin benefits>risks

NPHinsulin(Humulin Intermediate B No Nonereported Recommended


N,NovolinN) actinginsulin

Glargineinsulin Longacting C Unknown Noavailablestudies Notrecommendedunless


(Lantus) insulin benefits>risks

Detemirinsulin Intermediate C Unknown Visceralabnormalitieswereseenin Notrecommended


(Levemir) longacting animals
insulin



Analgesics

Generic(Brand) Class Pregnancy Crosses Reportedadverseeffectsto Placeintherapy
Category placenta maternalorfetusfromusein
pregnancy
Aspirin(Bufferin, NSAID C Yes Fetal:increasedperinatalmortaility, Shouldnotbeusedinpregnancy,
Ecotrin) teratogeniceffects,pulmonaryHTN, consideracetaminophen
bleedingrisk,prematureductus
arteriosisclosure
Maternal:anemia,ante/postpartum
hemorrhage,prolongedlabor
Ibuprofen(Advil, NSAID B Unknown Fetal:ductusarteriosisconstriction, Shouldbeavoidedwhenpossibleand
rd
Midol,) pulmonaryHTNin3 trimester completelyavoidedduringthe3rd
trimester.Consideracetaminophen.
Din3rd Maternal:prolongedlabor,
trimester spontaneousabortion
Naproxen(Aleve, NSAID B;Din3rd Yes Fetal:ductusarteriosisconstriction, Shouldbeavoidedwhenpossibleand
Anaprox,Midol, trimester intracranialhemorrhage,primary completelyavoidedduringthe3rd
Naprosyn,Pamprin) pulmonaryHTN trimester.Consideracetaminophen.
Acetaminophen Analgesic B Yes Fetal:overdosecanleadtoliver Drugofchoiceforanalgesiaand
antipyretic toxicity feverduringpregnancy
Maternal:overdosecanleadtoliver
toxicity
Butorphanol Narcotic C Yes Fetal:sinusoidalfetalheartrate Usedforanalgesiaduringlabor
(Stadol) analgesic pattern,addiction,respiratory
depression
Difprolonged Maternaladdiction
use
Morphine Narcotic C;Dif Yes Fetal:addiction,possiblerelationto Shouldonlybeusedwhenanalgesia
(Duramorph, analgesic prolonged inguinalherniaandrespiratory oranestheticisclearlyindicated
Kadian,MSContin, use depression
OramorphSR, Maternal:addiction
Roxanol)
Fentanyl(Actiq, Narcotic C;Dif Yes Fetal:respiratorydepression, Onlyusewhenbenefits>risks
Duragesic) analgesic prolonged dependenceandlossoffetalheart
use ratevariabilitywithouthypoxia
Hydromorphone Narcotic C Yes Fetal:respiratorydepression Onlyusewhenbenefits>risks
(Dilaudid) analgesic Difprolonged ManufacturerrecommendedCIin
use pregnancy
Meperidine Narcotic C;Dif Yes Fetal:respiratorydepression(time,
(Demerol, analgesic prolonged dosedependant),addiction,inguinal
Meperitab) use hernia
Mom:metabolitebuildupthatcan
causeseizures
Hydrocodone Narcotic C;Dif Yes Fetal:addiction,respiratory
analgesic prolonged depression
use
Oxycodone Narcotic B;Dif Yes Fetal:addiction,respiratory
(OxyContin, analgesic prolonged depression
OxyFast,OxyIR, use
Roxicodone)
Tramadol(Ultram) Central C Yes Fetal:doserelatedfetaltoxicityin Shouldbeavoideduntilfurther
analgesic animals,respiratorydepressionand evidenceconcerningthedoserelated
addiction fetaltoxicityisavailable
Ergotamine Sympatholytic X Yes Fetal:increaseuterinetoneleadingto Donotuseinpregnancy
(Ergomar) fetalhypoxia,teratogenicandfetal
toxicity

Immunizations

Generic(Brand) Class Pregnancy Crosses Reportedadverseeffectstomomor Placeintherapy


Category placenta babyfromuseinpregnancy
Human Inactivated B Unknown Currentlyunderstudy Donotuseduringpregnancy
Papillomavirus vaccine
(Gardasil)

HepatitisB Inactivevaccine Unknown Norisktothemomorbabyhavebeen Giveifindicated


(EngerixB, reported ACOGrecommendsthatvaccineshould
RecombivaxHB) begivenpreorpostexposurein
womenatriskforinfection
Influenza Inactivated C Unknown Studiesofimmunizationofover2000 ACOGrecommendsthevaccinebegiven
(injection)(Afluria, vaccine womenshowednofetaladverse topregnantwomeninthe2ndand3rd
Fluarix,FluLaval, effectsassociatedwithvaccination trimestersduringfluseason.Allatrisk
Fluvirin,Fluzone) forpulmonarycomplicationsshouldbe
vaccinated,regardlessoftrimester

Influenza(nasal) Livevaccine C Unknown Fetalinfectionwithliveattenuated Donotuseduringpregnancy


(FluMist) virusmayoccur
Meningococcal Inactivated C Unknown Riskstothefetusareunknown. Useifindicated
(Menomune vaccine
A/C/Y/W135,
Menactra)
MMR(MMRII) Livevaccine C Unknown Fetalinfectionwithliveattenuated Donotuseduringpregnancy;Avoid
virusmayoccur pregnancyfor12weeksafterinjection
Pneumococcal Inactivated C Maternal Risktothefetusinthe1sttrimesteris Useifindicatedinhighriskpatients
Vaccine vaccine Abyes2 unknown.Noadverseevents
(Pneumovax) reported2
Td(Decavac) Toxoid C Unknown Noevidenceofteratogenicity Useifindicated
TdP(Adacel, Toxoid C Maternal Antibodiesmayalsointerferewiththe Useifathighriskforpertussis
Boostrix) Abyes infantsimmuneresponsetoinfant
dosesofDTaP,soinfantmaynotbe
protected.
VaricellaVaccine Livevaccine C Unknown Fetalinfectionmayoccur Donotuseinpregnancy
(Varivax)


References:

BriggsGG,FreemanRK,YaffeA.DrugsinPregnancyandLactation:7thEdition.Philadelphia:LipppincottWilliams&
Wilkins;2005.

MicromedexHealthcareSeries,(electronicversion).ThomasMicromedex,GreenwoodVillage,Colorado,USA.
Availableathttp://www.thomsonhc.com

GrabensteinJD,Immunfacts2008VaccinesandImmunologicDrugs,Baltimore,MD:Williams&Wilkins,2007.
CentersforDiseaseControlwebsite.Availableat:http://www.cdc.gov/.AccessedonMarch3,2008.

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