18.06.

2017 MaternalDiabetesMellitus:OvidMD

ClohertyandStark'sManualofNeonatalCare
8th_Edition
LippincottWilliams&Wilkins,
2017

2
MaternalDiabetesMellitus
AvivaLeeParritz

KEYPOINTS

Withappropriatemanagementofpregnantwomenwithdiabetes,womenwithgoodglycemiccontrolandminimalmicrovascular
diseasecanexpectpregnancyoutcomescomparabletothegeneralpopulation.

Womenwithtype1andtype2diabetesareatsignificantlyincreasedriskforhypertensivedisorders,suchaspreeclampsia,which
ispotentiallydeleterioustobothmaternalandfetalwellbeing.

Routeofdeliveryofafetusaffectedbymaternaldiabetesisdeterminedbyultrasonographyestimatedfetalweight,maternaland
fetalconditions,andpreviousobstetrichistory.

Preconceptionglucosecontrolforwomenwithpregestationaldiabetescanreducetheriskofcongenitalanomaliestonearthatof
thegeneralpopulation.

Strictglycemiccontrolcanreducefetalmacrosomiainbothpregestationalandgestationaldiabetes.Targetingpostmealglycemia
ismoreeffectivethansolelypremealmeasurementtoreducefetalovergrowth.

Womenwithpregestationaldiabetesandmicrovasculardiseaseareatriskforindicatedpretermdeliveryduetoworsening
maternalorfetalstatus.

Tightintrapartumglucosecontrolisimportanttoreducefetaloxidativestressandneonatalhypoglycemia.

Womenwithpregestationaldiabetesmayhavereducedglycemicprofilesandinsulinrequirementspostpartum,especiallyin
womenbreastfeeding.

http://ovidmd.ovid.com.am.enformation.ro/Chapter?ovidid=ovid:/fts/bookdb/01965279/8th_Edition/2/OVIDBOOK[1]/TXTBKBD[1]/DIVISIONA[1]/CHAPTER[2]&q=mullerian+duct 1/6
18.06.2017 MaternalDiabetesMellitus:OvidMD

I.DIABETESANDPREGNANCYOUTCOME.Improvedmanagementofdiabetesmellitusandadvancesinobstetricshavereducedthe
incidenceofadverseperinataloutcomeinpregnanciescomplicatedbydiabetesmellitus.Withappropriatemanagement,womenwith
goodglycemiccontrolandminimalmicrovasculardiseasecanexpectpregnancyoutcomescomparabletothegeneralpopulation.
Womenwithadvancedmicrovasculardisease,suchashypertension,nephropathy,andretinopathy,havea25%riskofpretermdelivery
becauseofworseningmaternalconditionorpreeclampsia.Pregnancydoesnothaveasignificantimpactontheprogressionofdiabetes.
Inwomenwhobeginpregnancywithmicrovasculardisease,diabetesoftenworsens,butinmost,thediseasereturntobaseline.
Preconceptionglucosecontrolmayreducetherateofcomplicationstoaslowasthatseeninthegeneralpopulation.

II.DIABETESINPREGNANCY

A.Generalprinciples

1.Diabetesthatantedatesthepregnancycanbeassociatedwithadversefetalandmaternaloutcomes.Themostimportantcomplication
isdiabeticembryopathyresultingincongenitalanomalies.Congenitalanomaliesareassociatedwith50%ofperinataldeathsamong
womenwithdiabetescomparedto25%amongnondiabeticwomen.Theriskofcongenitalanomaliesisrelatedtotheglycemicprofileat
thetimeofconception.Themostcommontypesofanomaliesincludecardiacmalformationsandneuraltubedefects.Womenwithtype
1andtype2diabetesareatsignificantlyincreasedriskforhypertensivedisorders,suchaspreeclampsia,whichispotentiallydeleterious
tobothmaternalandfetalwellbeing.Gestationaldiabetesmellitus(GDM)isdefinedascarbohydrateintoleranceofvariableseverity
firstdiagnosedduringpregnancy,anditaffects6%to8%ofpregnancies.

2.Epidemiologyofgestationaldiabetes.Approximately3%to5%ofpatientswithGDMactuallyhaveunderlyingtype1ortype2
diabetes,butpregnancyisthefirstopportunityfortesting.RiskfactorsforGDMincludeadvancedmaternalage,multifetalgestation,
increasedbodymassindex,andstrongfamilyhistoryofdiabetes.Certainethnicgroups,suchasNativeAmericans,SoutheastAsians,
andAfricanAmericans,haveanincreasedriskofdevelopingGDM.

3.Physiologyuniquetowomenwithdiabetesantedatingpregnancy.Inthefirsthalfofpregnancy,asaresultofnauseaandvomiting,
hypoglycemiacanbeasmuchofaproblemashyperglycemia.Hypoglycemia,followedbyhyperglycemiafromcounterregulatory
hormones,maycomplicateglucosecontrol.Maternalhyperglycemialeadstofetalhyperglycemiaandfetalhyperinsulinemia,which
resultsinfetalovergrowth.Gastroparesisfromlongstandingdiabetesmaybeafactoraswell.Theredoesnotappeartobeadirect
relationshipbetweenhypoglycemiaaloneandadverseperinataloutcome.Throughoutpregnancy,insulinrequirementsincreasebecause
oftheincreasingproductionofplacentalhormonesthatantagonizetheactionofinsulin.Thisismostprominentinthemidthird
trimesterandrequiresintensivebloodglucosemonitoringandfrequentadjustmentofmedicationstocontrolbloodglucose.

B.Complicationsoftype1andtype2diabetesduringpregnancy

1.Ketoacidosisisanuncommoncomplicationduringpregnancy.However,ketoacidosiscarriesa50%riskoffetaldeath,especiallyifit
occursbeforethethirdtrimester.Ketoacidosiscanbepresentinthesettingofevenmildhyperglycemia(200mg/dL)andshouldbe
excludedineverypatientwithtype1diabeteswhopresentswithhyperglycemiaandsymptomssuchasnausea,vomiting,orabdominal
pain.

http://ovidmd.ovid.com.am.enformation.ro/Chapter?ovidid=ovid:/fts/bookdb/01965279/8th_Edition/2/OVIDBOOK[1]/TXTBKBD[1]/DIVISIONA[1]/CHAPTER[2]&q=mullerian+duct 2/6
18.06.2017 MaternalDiabetesMellitus:OvidMD

2.Stillbirthremainsanuncommoncomplicationofdiabetesinpregnancy.Itismostoftenassociatedwithpoorglycemiccontrol,fetal
anomalies,severevasculopathy,andintrauterinegrowthrestriction(IUGR)aswellasseverepreeclampsia.Shoulderdystociathat
cannotberesolvedcanalsoresultinfetaldeath.

3.Polyhydramniosisnotanuncommonfindinginpregnanciescomplicatedbydiabetes.Itmaybesecondarytoosmoticdiuresisfrom
fetalhyperglycemia.Carefulultrasonographicexaminationisrequiredtoruleoutstructuralanomalies,suchasesophagealatresia,asan
etiology,whenpolyhydramniosispresent.

4.Severematernalvasculopathy,especiallynephropathyandhypertension,isassociatedwithuteroplacentalinsufficiency,whichcan
resultinIUGR,fetalintoleranceoflabor,andneonatalcomplications.

III.MANAGEMENTOFDIABETESDURINGPREGNANCY

A.Generalprinciplesfortype1ortype2diabetes.Managementoftype1ortype2diabetesduringpregnancybeginsbeforeconception.
Tightglucosecontrolisparamountduringthepericonceptionalperiodandthroughoutpregnancy.Optimalglucosecontrolrequires
coordinatedcarebetweenendocrinologists,maternalfetalmedicinespecialists,diabetesnurseeducators,andnutritionists.
Preconceptionglycemiccontrolhasbeenshowntodecreasetheriskofcongenitalanomaliestoclosetothatofthegeneralpopulation.
However,<30%ofpregnanciesareplanned.Physiciansshoulddiscusspregnancyplanningorrecommendcontraceptionforalldiabetic
womenofchildbearingageuntilglycemiccontrolisoptimized.

B.Generalprinciplesforgestationaldiabetes.IntheUnitedStates,mostwomenarescreenedforGDMbetween24and28weeks'
gestationbya50g,1hourglucosechallenge.Apositiveresultofabloodglucose140mg/dLisfollowedbyadiagnostic100g,3hour
oralglucosetolerancetest(GTT).ApositivetestisdefinedastwoormoreelevatedvaluesontheGTT.Thereisacurrentmovementto
movetoasinglediagnostictest,consistingofa75g,2hourGTT,amethodthatisuseduniformlyoutsideoftheUnitedStates.
Uncontrolledpregestationalandgestationaldiabetescanleadtofetalmacrosomiaandconcomitantriskoffetalinjuryatdelivery.GDM
sharesmanyfeatureswithtype2diabetes.WomendiagnosedwithGDMhavea60%lifetimeriskofdevelopingoverttype2diabetes.

1.Testing(firsttrimester)fortype1andtype2diabetes

a.Measurementofglycosylatedhemoglobininthefirsttrimestercangiveariskassessmentforcongenitalanomaliesbyreflecting
ambientglucoseconcentrationsduringtheperiodoforganogenesis.

b.Accuratedatingofthepregnancyisobtainedbyultrasonography.

c.Ophthalmologicexaminationismandatorybecauseretinopathymayprogressbecauseoftherapidnormalizationofglucose
concentrationinthefirsttrimester.Womenwithretinopathyneedperiodicexaminationsthroughoutpregnancy,andtheyare
candidatesforlaserphotocoagulationasindicated.

d.Renalfunctionisassessedbyeitheraspotprotein/creatinineratioorspoturinemicroalbumin,followedbya24hoururinecollection
forproteinexcretionandcreatinineclearanceifabnormal.Serumcreatinineshouldalsobeassessedinpatientswithlongstanding
http://ovidmd.ovid.com.am.enformation.ro/Chapter?ovidid=ovid:/fts/bookdb/01965279/8th_Edition/2/OVIDBOOK[1]/TXTBKBD[1]/DIVISIONA[1]/CHAPTER[2]&q=mullerian+duct 3/6
18.06.2017 MaternalDiabetesMellitus:OvidMD

pregestationaldiabetes.Becausetheincidenceofpreeclampsiaissignificantlyelevatedinwomenwithdiabetes,identificationof
baselineproteinuriacanimpactthediagnosisofpreeclampsialaterinpregnancy.

e.Thyroidfunctionshouldbeevaluated.

f.Nuchaltranslucencyandserumscreeningforaneuploidy.Althoughdiabetesinandofitselfisnotariskfactorforaneuploidy,thisis
partofroutinepregnancycare.Nuchaltranslucencyassessmentisparticularlyimportantbecauseanabnormalmeasurementisalso
associatedwithstructuralabnormalities,theriskofwhichisincreasedinthisgroupofpatients.

2.Testing(secondtrimester)fortype1andtype2diabetes

a.Maternalserumscreeningforneuraltubedefectsisperformedbetween15and19weeks'gestation.Womenwithdiabeteshavea10
foldincreasedriskofneuraltubedefectscomparedtothegeneralpopulation.

b.Allpatientsundergoathoroughultrasonographicsurvey,includingfetalechocardiographyforstructuralanomalies.

c.Womenolderthan35yearsofageorwithotherriskfactorsforfetalaneuploidyareofferednoninvasiveprenataltestingor
karyotypingviachorionicvillussamplingoramniocentesis.

3.Testing(thirdtrimester)fortype1andtype2diabetes,GDM

a.Ultrasonographicexaminationsareperformedmonthlythroughthethirdtrimesterforfetalgrowthmeasurement.

b.Weeklyortwiceweeklyfetalsurveillanceusingnonstresstestingorbiophysicalprofilesareimplementedbetween28and32weeks'
gestation,dependingonglycemiccontrolandothercomplications.

C.Treatmentforalltypesofglucoseintolerance

Strictdiabeticcontrolisachievedwithnutritionalmodification,exerciseandmedications,withthetraditionalgoalsoffastingglucose
concentration<95mg/dLandpostprandialvalues<140mg/dLfor1hourand120mg/dLfor2hours.Recentdatahavesuggestedthat
inpregnantwomen,euglycemiamaybeevenlower,withfastingglucoselevelsinthe60mg/dLrangeandpostmealglucoselevels<105
mg/dL.Insulintherapyhasthelongestrecordofaccomplishmentofperinatalsafety.Ithasbeendemonstratedthathumaninsulin
analogsdonotcrosstheplacenta.Morerecently,theoralhypoglycemicagentssuchasglyburideandmetforminhavebeenshowntobe
aseffectiveasinsulininthemanagementofGDMandmaybeappliedtowomenwithpregestationaldiabetes.

IV.MANAGEMENTOFLABORANDDELIVERYFORWOMENWITHDIABETES

A.Generalprinciples.Theriskofspontaneouspretermlaborisnotincreasedinpatientswithdiabetes,althoughtheriskofiatrogenic
pretermdeliveryisincreasedforpatientswithmicrovasculardiseaseasaresultofIUGR,nonreassuringfetaltesting,andmaternal
hypertension.Antenatalcorticosteroidsforinductionoffetallungmaturity(FLM)shouldbeemployedfortheusualobstetric

http://ovidmd.ovid.com.am.enformation.ro/Chapter?ovidid=ovid:/fts/bookdb/01965279/8th_Edition/2/OVIDBOOK[1]/TXTBKBD[1]/DIVISIONA[1]/CHAPTER[2]&q=mullerian+duct 4/6
18.06.2017 MaternalDiabetesMellitus:OvidMD

indications.Corticosteroidscancausetemporaryhyperglycemiatherefore,patientsmayneedtobemanagedwithcontinuous
intravenous(IV)insulininfusionsuntiltheeffectofthesteroidswearoff.Deliveryisplannedfor39to40weeks,unlessotherpregnancy
complicationsdictateearlierdelivery.Electivedeliveryafter39weeksdoesnotrequireFLMtesting.Indicateddeliverybefore39weeks'
gestationshouldbecarriedoutwithoutFLMtesting.Routeofdeliveryisdeterminedbyultrasonographyestimatedfetalweight,
maternalandfetalconditions,andpreviousobstetrichistory.Theultrasonographyestimatedweightatwhichanelectivecesarean
deliveryisrecommendedisacontroversialissue,withtheAmericanCollegeofObstetriciansandGynecologistsrecommending
discussionofcesareandeliveryatanestimatedfetalweightof>4,500gduetotheincreasedriskofshoulderdystocia.

B.Treatment.Bloodglucoseconcentrationistightlycontrolledduringlaboranddelivery.Ifaninductionoflaborisplanned,patients
areinstructedtotakeonehalfoftheirusualbasalinsulinonthemorningofinduction.Duringspontaneousorinducedlabor,blood
glucoseconcentrationismeasuredevery1to2hours.Bloodglucoseconcentrationhigherthan120to140mg/dListreatedwithan
infusionofIVshortactinginsulin.IVinsulinisveryshortacting,allowingforquickresponsetochangesinglucoseconcentration.
Activelabormayalsobeassociatedwithhypoglycemiabecausethecontractinguterususescirculatingmetabolicfuels.Continuousfetal
monitoringismandatoryduringlabor.Cesareandeliveryisperformedforobstetricindications.Theriskofcesareansectionforobstetric
complicationsisapproximately50%.Patientswithadvancedmicrovasculardiseaseareatincreasedriskforcesareandeliverybecauseof
theincreasedincidenceofIUGR,preeclampsia,andnonreassuringfetalstatus.Ahistoryofretinopathythathasbeentreatedinthepast
isnotnecessarilyanindicationforcesareandelivery.Patientswithactiveproliferativeretinopathythatisunstableoractivehemorrhage
maybenefitfromelectivecesareandelivery.Postpartum,patientsareatincreasedriskforhypoglycemia,especiallyinthepostoperative
settingwithminimaloralintake.Patientswithpregestationaldiabetesmayalsoexperienceahoneymoonperiodimmediatelyafter
delivery,withgreatlyreducedinsulinrequirementsthatcanlastuptoseveraldays.Lactationisalsoassociatedwithsignificantglucose
utilizationandpotentialhypoglycemiaespeciallyintheimmediatepostpartumperiod.Forwomenwithtype2diabetes,theuseof
metforminandglyburidearecompatiblewithbreastfeeding.

SuggestedReadings

AmericanCollegeofObstetriciansandGynecologists.ACOGPracticeBulletin.Clinicalmanagementguidelinesforobstetricians
gynecologists.Number60,March2005.Pregestationaldiabetesmellitus.ObstetGynecol2005105(3):675685.
OvidFullText|BibliographicLinks
AmericanCollegeofObstetriciansandGynecologists.PracticeBulletinNo.137:gestationaldiabetesmellitus.OstetGynecol
2013122(2,Pt1):406416.
CrowtherCA,HillerJE,MossJR,etal.Effectoftreatmentofgestationaldiabetesmellitusonpregnancyoutcomes.NEnglJMed
2005352(24):24772486.
BuyNow|BibliographicLinks
deVecianaM,MajorCA,MorganMA,etal.Postprandialversuspreprandialbloodglucosemonitoringinwomenwithgestational
diabetesmellitusrequiringinsulintherapy.NEnglJMed1995333(19):12371241.
BuyNow|BibliographicLinks
KitzmillerJL,GavinLA,GinGD,etal.Preconceptioncareofdiabetes.Glycemiccontrolpreventscongenitalanomalies.JAMA
1991265:731736.

http://ovidmd.ovid.com.am.enformation.ro/Chapter?ovidid=ovid:/fts/bookdb/01965279/8th_Edition/2/OVIDBOOK[1]/TXTBKBD[1]/DIVISIONA[1]/CHAPTER[2]&q=mullerian+duct 5/6
18.06.2017 MaternalDiabetesMellitus:OvidMD

BibliographicLinks
LandonMB,LangerO,GabbeSG,etal.Fetalsurveillanceinpregnanciescomplicatedbyinsulindependentdiabetesmellitus.Am
JObstetGynecol1992167:617621.
BibliographicLinks
LandonMB,SpongCY,ThomE,etal.Amulticenter,randomizedtrialoftreatmentformildgestationaldiabetes.NEnglJMed
2009361(14):13391348.
BuyNow|BibliographicLinks
LangerO,ConwayDL,BerkusMD,etal.Acomparisonofglyburideandinsulininwomenwithgestationaldiabetesmellitus.N
EnglJMed2000343(16):11341138.
BuyNow|BibliographicLinks
MetzgerBE,LoweLP,DyerAR,etal.Hyperglycemiaandadversepregnancyoutcomes.NEnglJMed2008358(19):19912002.
BuyNow|BibliographicLinks
MillerEM,HareJW,ClohertyJP,etal.ElevatedmaternalhemoglobinA1cinearlypregnancyandmajoranomaliesininfantsof
diabeticmothers.NEnglJMed1981304:13311334.
BibliographicLinks
MooreLE,ClokeyD,RappaportVJ,etal.Metformincomparedwithglyburideingestationaldiabetes:arandomizedcontrolled
trial.ObstetGynecol2010115(1):5559.
OvidFullText|BibliographicLinks
NaylorCD,SermerM,ChenE,etal.Cesareandeliveryinrelationtobirthweightandgestationalglucosetolerance:
pathophysiologyorpracticestyle?TorontoTrihospitalGestationalDiabetesInvestigators.JAMA1996275(15):11651170.
BuyNow|BibliographicLinks
ParrettiE,MecacciF,PapiniM,etal.Thirdtrimestermaternalglucoselevelsfromdiurnalprofilesinnondiabeticpregnancies:
correlationwithsonographicparametersoffetalgrowth.DiabetesCare200124(8):13191323.
BibliographicLinks
PhilippsAF,PortePJ,StabinskyS,etal.Effectsofchronicfetalhyperglycemiauponoxygenconsumptionintheovineuterusand
conceptus.JClinInvest198474(1):279286.
FullText|BibliographicLinks
StarikovR,BohrerJ,GohW,etal.HemoglobinA1cinpregestationaldiabeticgravidasandtheriskofcongenitalheartdiseasein
thefetus.PediatrCardiol201334(7):17161722.
BibliographicLinks
Copyright20112017

OvidisaregisteredtrademarkofOvidTechnologies,Inc.andcannotbereproducedwithoutpermission.

http://ovidmd.ovid.com.am.enformation.ro/Chapter?ovidid=ovid:/fts/bookdb/01965279/8th_Edition/2/OVIDBOOK[1]/TXTBKBD[1]/DIVISIONA[1]/CHAPTER[2]&q=mullerian+duct 6/6