Preeclampsia and Eclampsia Vincenzo Berghella, M.D. Professor Department of Obstetrics and...

Preeclampsia Preeclampsia and Eclampsiaand Eclampsia

Vincenzo Berghella, M.D.Vincenzo Berghella, M.D.ProfessorProfessor

Department of Obstetrics and GynecologyDepartment of Obstetrics and GynecologyDirector, Division of Maternal-Fetal MedicineDirector, Division of Maternal-Fetal Medicine

Jefferson Medical College of Thomas Jefferson UniversityJefferson Medical College of Thomas Jefferson University

January 4th, 2016

CLASSof

1990

““Obstetrics”: what does it mean?Obstetrics”: what does it mean?

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25% 25%25%25%1.1. To stand byTo stand by

2.2. To help reproductionTo help reproduction

3.3. To deliver a babyTo deliver a baby

4.4. To ‘obstruct’To ‘obstruct’

ObstetricsObstetrics

• ‘‘Ob-stare’: to stand by, or in front Ob-stare’: to stand by, or in front ofof

• To review the obstetrician To review the obstetrician safest safest and most effectiveand most effective way to stand by way to stand by

• PreventionPrevention of complications of complications

Objective

‘‘I have my own opinion, I have my own opinion, do not confuse it with the facts’do not confuse it with the facts’

George Bernard ShawGeorge Bernard Shaw

‘‘Those of you who think you know Those of you who think you know everything are annoying to those of us everything are annoying to those of us

who do’who do’

What is Evidence Based Medicine?What is Evidence Based Medicine?

Bes

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Clin

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exp

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Pat

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and

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All

the

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25% 25%25%25%1.1. Best medical evidence from Best medical evidence from researchresearch

2.2. Clinical expertiseClinical expertise

3.3. Patient’s value and Patient’s value and expectationsexpectations

4.4. All the aboveAll the above

Evidence-based Evidence-based medicinemedicine

• Best available Best available

clinical evidence from clinical evidence from

systematic researchsystematic research

• Individual clinicalIndividual clinical

expertiseexpertise

• Patient’s values and expectationsPatient’s values and expectations

Best clinical evidence from Best clinical evidence from researchresearch

• All randomized controlled All randomized controlled trials (RCTs)trials (RCTs)

• Meta-analysesMeta-analyses

• Cochrane databaseCochrane database

• Level I evidenceLevel I evidence

• Science vs Religion/ArtScience vs Religion/Art

130 million births /yr130 million births /yr

What can go wrong in my What can go wrong in my pregnancy?pregnancy?

• 15-20% (up to 60%) miscarriage (pregnancy loss)15-20% (up to 60%) miscarriage (pregnancy loss)

• 13% preterm birth13% preterm birth– 500,000 / yr in USA500,000 / yr in USA– Question: how many of you born preterm?Question: how many of you born preterm?– How many twins?How many twins?

• Infant mortality: 17% births in AfghanistanInfant mortality: 17% births in Afghanistan

• Maternal deaths: 500,000 / yr worldwideMaternal deaths: 500,000 / yr worldwide

The Last Century in ObstetricsThe Last Century in Obstetrics1900-19991900-1999

• ‘‘Obstetrics rate of progress – its success in reducing the risk of Obstetrics rate of progress – its success in reducing the risk of childbirth – puts other fields to shame’childbirth – puts other fields to shame’

The New Yorker Oct 9, 2006The New Yorker Oct 9, 2006

• Infant mortality Infant mortality 90% 90%– <1/500 (full term)<1/500 (full term)

• Maternal mortality Maternal mortality 99% 99%– <1/10,000<1/10,000

– Leading causes:Leading causes:

•Venous thromboembolism•Infection•Hypertensive disorders

•Hemorrhage•Infection•Impacted labor

Incidence: 1 - 5%Incidence: 1 - 5%• Incidence of superimposed preeclamsia: 20%Incidence of superimposed preeclamsia: 20%

• Incidence: 7-10%Incidence: 7-10%

CHN HTNCHN HTN

PreeclampsiaPreeclampsia

Renal

Chronic HTN

Gestational HTN

Lupus

Preeclampsia

Eclampsia HELLP

Severe Preeclampsia

Chronic Hypertension Chronic Hypertension DefinitionDefinition

• Sustained BP Sustained BP >> 140/90 prior to 20 weeks gestation 140/90 prior to 20 weeks gestation

• Hx HTN (before pregnancy)Hx HTN (before pregnancy)

What’s the definition of What’s the definition of preeclampsia?preeclampsia?

Edem

a

Ele

vate

d BP

Pro

tein

uria

1+2+

3 2

+3

20% 20% 20%20%20%1.1. EdemaEdema

2.2. Elevated BPElevated BP

3.3. ProteinuriaProteinuria

4.4. 1+2+31+2+3

5.5. 2+32+3

Preeclampsia Preeclampsia DefinitionDefinition

• Sustained BP Sustained BP >> 140/90 140/90

• Proteinuria Proteinuria [ [ >> 1+(0.1g/L) or 300mg/24 hrs] 1+(0.1g/L) or 300mg/24 hrs]

• Gestational HTN (Pregnancy-induced HTN)Gestational HTN (Pregnancy-induced HTN)– sustained BP > 140/90 after 20 weekssustained BP > 140/90 after 20 weeks

• Superimposed preeclampsiaSuperimposed preeclampsia– Proteinuria after 20 weeks in a woman with chronic HTNProteinuria after 20 weeks in a woman with chronic HTN

• HELLP syndromeHELLP syndrome– Hemolysis, Elevated Liver enzymes, Low PlateletsHemolysis, Elevated Liver enzymes, Low Platelets

• EcclampsiaEcclampsia– SeizuresSeizures

Other DefinitionsOther Definitions

PreeclampsiaPreeclampsiaRisk FactorsRisk Factors

• NulliparityNulliparity

• Age > 40 y.o.Age > 40 y.o.

• African-American African-American

• Family HistoryFamily History

• HTNHTN

• Renal diseaseRenal disease

• APA syndrome

• Diabetes MellitusDiabetes Mellitus

• TwinTwin

• ObesityObesity• Low socioecon. statusLow socioecon. status

• SmokingSmoking

PreeclampsiaPreeclampsiaPathophysiologyPathophysiology

• Endothelial disease (vasospasm; sympathetic overactivity?)Endothelial disease (vasospasm; sympathetic overactivity?)

– failure of the second wave of trophoblastic invasion into the spiral arteries of the uterusfailure of the second wave of trophoblastic invasion into the spiral arteries of the uterus

– reduced perfusionreduced perfusion

– hypoxia, free radicals, oxidative stress, activation of endothelium, clinical diseasehypoxia, free radicals, oxidative stress, activation of endothelium, clinical disease

– vasospasm, capillary leakvasospasm, capillary leak

cardiac output, cardiac output, plasma volume, plasma volume, SVR SVR

Preeclampsia Preeclampsia PathophysiologyPathophysiology

• Systemic diseaseSystemic disease

• ??????????????????????????

• Hemostatic - systemic vasospasm, endothelial injuryHemostatic - systemic vasospasm, endothelial injury

• Uteroplacental Uteroplacental

• Prostanoid Prostanoid

• Symphatetic stateSymphatetic state

• Not ‘toxemia’Not ‘toxemia’

Clinical DiagnosisClinical Diagnosis

• BPBP• ProteinProtein• Hx: HA, blurred vision; abdominal painHx: HA, blurred vision; abdominal pain• PE: Edema; ReflexesPE: Edema; Reflexes• Labs: LFTs; platelets; creatinine-uric acid; Labs: LFTs; platelets; creatinine-uric acid;

coagulation studiescoagulation studies• Must know your baselineMust know your baseline

Severe PreeclampsiaSevere Preeclampsia

• SBP SBP >> 160mm Hg or DBP 160mm Hg or DBP >> 110 mm Hg 110 mm Hg

• HELLP syndromeHELLP syndrome

• Creatinine >1.1 mg/dLCreatinine >1.1 mg/dL

• Pulmonary edemaPulmonary edema

• CNS/visual symptomsCNS/visual symptoms

• Proteinuria Proteinuria >> 5g/24h 5g/24h

• Oliguria < 500 ml/24hOliguria < 500 ml/24h

• Epigastric painEpigastric pain

• EclampsiaEclampsia

PreeclampsiaPreeclampsiaComplicationsComplications

• SeizuresSeizures• Cerebral hemorrhageCerebral hemorrhage• Abruptio PlacentaeAbruptio Placentae• DICDIC• Pulmonary edemaPulmonary edema• Renal failureRenal failure• Liver hemorrhageLiver hemorrhage• DeathDeath

MaternalMaternal

PreeclampsiaPreeclampsiaComplicationsComplications

• Growth restriction (IUGR)Growth restriction (IUGR)• HypoxemiaHypoxemia• AcidosisAcidosis• PrematurityPrematurity• DeathDeath

FetusFetus

Internal Medicine ConsultInternal Medicine Consult

• Understand these are ‘healthy’ patientsUnderstand these are ‘healthy’ patients

• Temporary diseaseTemporary disease

• Only true cure is deliveryOnly true cure is delivery

• Two patients in one: Delivery always good for mother, Two patients in one: Delivery always good for mother, not always for babynot always for baby

• Maternal physiology is different than nonpregnant adult Maternal physiology is different than nonpregnant adult physiologyphysiology

• TJUH: critical care obstetrical teamTJUH: critical care obstetrical team

How many gestational How many gestational weeks-old was the earliest weeks-old was the earliest

neonate to survive? neonate to survive?

19w

21w

23w

25w

25% 25%25%25%

1.1. 19w19w

2.2. 21w21w

3.3. 23w23w

4.4. 25w25w

When does When does intactintact neonatal neonatal survival reach survival reach ≥≥90%? 90%?

(weeks)(weeks)

20w

24w

28w

32w

25% 25%25%25%

1.1. 20w20w

2.2. 24w24w

3.3. 28w28w

4.4. 32w32w

Neonatal Morbidity and Mortality by Gestational Neonatal Morbidity and Mortality by Gestational AgeAge

0

20

40

60

80

100

120

23 24 25 26 27 28 29 30 31 32 33 34 35 36

RDS

IVH (3,4)

Sepsis

NEC

Survival

Robinson AJOG 92

PreeclampsiaPreeclampsiaTreatmentTreatment

MildMild

Delivery if Delivery if >> 36 weeks 36 weeks

SevereSevere

Delivery if Delivery if >> 32 weeks 32 weeks

““Preeclamptic Labs”Preeclamptic Labs”

• CBC (platelets)CBC (platelets)

• SMA-12 (AST, ALT, Uric Acid, creatinine)SMA-12 (AST, ALT, Uric Acid, creatinine)

• 24 hour urine (total protein)24 hour urine (total protein)

• Fibrinogen, fibrin split productsFibrinogen, fibrin split products

PreeclampsiaPreeclampsiaExpectant ManagementExpectant Management

• Counseling (symptoms)Counseling (symptoms)

• Bed restBed rest

• BP, I+O, weightBP, I+O, weight

• CBC, SMA-12, 24 hr urineCBC, SMA-12, 24 hr urine

• Fetal monitoring (NST, BPP, U/S)Fetal monitoring (NST, BPP, U/S)

• MgSOMgSO44 x 24 hours x 24 hours

• SteroidsSteroids

Severe Preeclampsia < 32 WeeksSevere Preeclampsia < 32 WeeksDeliver for:Deliver for:

• Uncontrollable BPUncontrollable BP• Uncontrollable CNS/visual symptomsUncontrollable CNS/visual symptoms• Epigastric painEpigastric pain• Vaginal bleedingVaginal bleeding• Persistent oliguriaPersistent oliguria• Preterm laborPreterm labor• Rupture of membranesRupture of membranes• Platelets < 100,000Platelets < 100,000• Fetal distress/severe oligohydramniosFetal distress/severe oligohydramnios

(exclude renal disease, IDDM , lupus, bleeding, ROM, multiple gestation, PTL)(exclude renal disease, IDDM , lupus, bleeding, ROM, multiple gestation, PTL)

Sibai, AJOG, 1994; 171:818Sibai, AJOG, 1994; 171:818

MagnesiumMagnesiumBest Agent for:Best Agent for:

• Eclampsia Eclampsia treatmenttreatment

• Eclampsia prophylaxis in severe preeclampsiaEclampsia prophylaxis in severe preeclampsia

(Start with labor, end 24 hours postpartum)(Start with labor, end 24 hours postpartum)

Lancet, 1995; 345:1455Lancet, 1995; 345:1455Lucas, NEJM, 1995; 333:201Lucas, NEJM, 1995; 333:201

EclampsiaEclampsia

• MagnesiumMagnesium

• Delivery once stableDelivery once stable

• Fetal in-utero resuscitationFetal in-utero resuscitation

• Team effortTeam effort

Post-partumPost-partum

• Short-term VigilanceShort-term Vigilance

–Preeclamspia can worsenPreeclamspia can worsen

–Edema always worsensEdema always worsens

–EclamsiaEclamsia

• Long-term CounselingLong-term Counseling

–RecurrenceRecurrence

–PreventionPrevention

Pregnancy for the Non-obstetricianPregnancy for the Non-obstetrician

• Not a good reason to stop ‘all medicines’Not a good reason to stop ‘all medicines’

• Not a good reason to stop treating diseasesNot a good reason to stop treating diseases

• Ask your friendly obstetricianAsk your friendly obstetrician

• Prevent panic: get patient ready for a healthy Prevent panic: get patient ready for a healthy pregnancy before contraception stoppedpregnancy before contraception stopped

• Mother: different physiologyMother: different physiology

• Fetus: your ‘other’ patientFetus: your ‘other’ patient

Benefits of Benefits of Preconception CounselingPreconception Counseling

• Improved cooperation with patientImproved cooperation with patient

• Increased planned pregnanciesIncreased planned pregnancies

• Decreased terminationsDecreased terminations

• Overall care - smoking, ETOH, obesity, etcOverall care - smoking, ETOH, obesity, etc

• Consultation with others (Maternal-Fetal Medicine, Consultation with others (Maternal-Fetal Medicine, etc)etc)

• Cost saving - fewer hospitalizations for mother, Cost saving - fewer hospitalizations for mother, fewer fewer anomalies for fetusanomalies for fetus

Life as an Obstetrician-Life as an Obstetrician-GynecologistGynecologist

• Life-style Life-style

• LiabilityLiability

• GenderGender

• SatisfactionSatisfaction

Relationships/Social ties Doing what you like to doGoalsMeaningHard work/Engagement Recognition/Accomplishments

Happiness

Martin Seligman; PERMA

[email protected]@jefferson.edu

MotherMother Worsening HTNWorsening HTNPreeclampsiaPreeclampsia

FetalFetal IUGR/OligohydramniosIUGR/OligohydramniosPlacental AbruptioPlacental AbruptioDeathDeath

CHN HTNCHN HTNCounselingCounseling

ComplicationsComplications

• Hx (antiHTN drug), PE (BP)Hx (antiHTN drug), PE (BP)

• CBC (platelets)CBC (platelets)

• SMA-12 (ALT, AST, Uric Acid, creatinine)SMA-12 (ALT, AST, Uric Acid, creatinine)

• 24 hour urine for Total Protein and Cr. Cl.24 hour urine for Total Protein and Cr. Cl.

• EKGEKG

• Ophthalmologic examOphthalmologic exam

• ANA, ACA, DRVVTANA, ACA, DRVVT

CHN HTNCHN HTNInitial EvaluationInitial Evaluation

• Anti HTN med if SBP Anti HTN med if SBP >> 160 ± DBP 160 ± DBP >> 100 on 2 occasions 100 on 2 occasions (lower threshold if DM,end organ damage)(lower threshold if DM,end organ damage)

• Rationale: Rationale: CVA and CV complications in CVA and CV complications in

pregnancies with such high BPspregnancies with such high BPs

• No evidence for BP Rx at lower thresholdsNo evidence for BP Rx at lower thresholds

CHN HTNCHN HTNBP ControlBP Control

CHN HTNCHN HTNAvoidAvoid

• Angiotensin converting enzyme (ACE) inhibitorsAngiotensin converting enzyme (ACE) inhibitors

–OligohydramniosOligohydramnios

–Neonatal renal failureNeonatal renal failure

• DiureticsDiuretics maternal plasma vol. may cause oligohydramniosmaternal plasma vol. may cause oligohydramnios

• Atenolol (Tenormin)Atenolol (Tenormin)

–IUGRIUGR

Butters, BMJ 1990; 301:587Butters, BMJ 1990; 301:587

• Aldomet 250 mg po tidAldomet 250 mg po tid

• up to 2gr/dayup to 2gr/day

• If not enough, add another agentIf not enough, add another agent

• Rationale: best documentation of fetal safetyRationale: best documentation of fetal safety

• Contraindication: liver damageContraindication: liver damage

CHN HTNCHN HTNChoice of Anti HTN MedChoice of Anti HTN Med

• LabetalolLabetalol– or other beta blockeror other beta blocker

• NifedipineNifedipine– or other calcium channel blockeror other calcium channel blocker

CHN HTNCHN HTNOther Choices of Anti HTN MedOther Choices of Anti HTN Med

Q 2-4 weeks, first visit-24 weeksQ 2-4 weeks, first visit-24 weeks

Q 2 weeks, 24-36 weeksQ 2 weeks, 24-36 weeks

Q 1 weeks, 36-40 weeksQ 1 weeks, 36-40 weeks

CHN HTNCHN HTN

Prenatal visitsPrenatal visits

• DatingDating

• 18-20 weeks18-20 weeks


CHN HTNCHN HTN

Fetal UltrasoundsFetal Ultrasounds

Non-stress TestsNon-stress Tests

q week between 34-40 weeksq week between 34-40 weeks

CHN HTNCHN HTN

• Na intake?Na intake?

CHN HTNCHN HTNMGMMGM

Br J Ob Gyn 1991; 98:980Br J Ob Gyn 1991; 98:980

CHN HTNCHN HTNProphylaxis for PreeclampsiaProphylaxis for Preeclampsia

• Low dose ASA (81 mg/qD)Low dose ASA (81 mg/qD)

• Calcium (2 g/qd)Calcium (2 g/qd)

• Omega 3 fatty acidsOmega 3 fatty acids

Sibai, NEJM, 1993; 329:1213Sibai, NEJM, 1993; 329:1213CLASP, Lancet 1994; 343:619CLASP, Lancet 1994; 343:619ECPPA, Br J OG, 1996; 103:39ECPPA, Br J OG, 1996; 103:39NICHD, SPO 1997NICHD, SPO 1997

Belizan, NEJM, 1991; 325:1399Belizan, NEJM, 1991; 325:1399Carroli, Br J OG, 1994; 101:753Carroli, Br J OG, 1994; 101:753Bucher, JAMA, 1996; 275:1113Bucher, JAMA, 1996; 275:1113CPEP, SPO 1997CPEP, SPO 1997

Adair, AJOG, 1993; 175:688Adair, AJOG, 1993; 175:688

Gestational HTNGestational HTN

• Sustained BP > 140/90 after 20 weeks Sustained BP > 140/90 after 20 weeks without proteinuriawithout proteinuria

• NoneNone

DefinitionDefinition

TherapyTherapy

Blood Pressure ControlBlood Pressure Control

• Hydralazine 5-10 mg IV q 20 min or dripHydralazine 5-10 mg IV q 20 min or drip

• Labetalol 20 mg IV q 10 min or dripLabetalol 20 mg IV q 10 min or drip

(alternatives: nifedipine, verapamil, sodium nitroprusside)(alternatives: nifedipine, verapamil, sodium nitroprusside)

Diabetes mellitus in pregnancyDiabetes mellitus in pregnancyRisksRisks

• Spontaneous abortionsSpontaneous abortions• Congenital anomaliesCongenital anomalies• Macrosomic/polyhydramnios, Macrosomic/polyhydramnios,

Shoulder dystocia, birth traumaShoulder dystocia, birth trauma• IUGR (growth restriction)IUGR (growth restriction)• Neonatal RDSNeonatal RDS• Perinatal deathPerinatal death• Long term obesity, DM, low IQLong term obesity, DM, low IQ

Fetal/NeonatalFetal/Neonatal MaternalMaternal

• Operative deliveryOperative delivery• HTN/preeclampsiaHTN/preeclampsia• UTI/UTI/pyelonephritispyelonephritis• Preterm labor/deliveryPreterm labor/delivery• KetoacidosisKetoacidosis• NephropathyNephropathy• RetinopathyRetinopathy• NeuropathyNeuropathy• Future DMFuture DM

Uncover undiagnosed DIABETESUncover undiagnosed DIABETES

• Screen Screen preconceptionallypreconceptionally Family History DM/GDMFamily History DM/GDM ObesityObesity Chronic steroid useChronic steroid use Age > 35Age > 35 GlycosuriaGlycosuria Prior unexplained stillbirthPrior unexplained stillbirth Prior infant with cardiac/NTD anomalyPrior infant with cardiac/NTD anomaly Prior macrosomia infantPrior macrosomia infant Prior unexplained polyhydramniosPrior unexplained polyhydramnios Prior Gestational DMPrior Gestational DM

FastingFasting < 115< 115 < 140< 140 >> 140 140 ~~

1/2, 1, 1 1/2h1/2, 1, 1 1/2h All < 200All < 200 1 value 1 value >> 200 200 1 value 1 value >> 200 200

2 h2 h < 140< 140 140-199140-199 >> 200 200

GDMGDMNonpregnant - Postpartum EvaluationNonpregnant - Postpartum Evaluation

Plasma Glucose LevelPlasma Glucose Level** (mg/dl) in (mg/dl) in

Time Time TestedTested

NoNoDiabetesDiabetes

ImpairedImpairedGlucoseGlucoseToleranceTolerance

DiabetesDiabetesMellitusMellitus

* * 2-h, 75g oral glucose tolerance test 2-h, 75g oral glucose tolerance test

~~ Fasting plasma glucose determinations of Fasting plasma glucose determinations of >> 140 on two occasions establish the diagnosis 140 on two occasions establish the diagnosis

DM in pregnancyDM in pregnancy

White’s ClassificationWhite’s Classification– A1A1 Gestational, diet controlledGestational, diet controlled

– A2A2 Gestational, insulin controlledGestational, insulin controlled

– BB > 20 yo, < 10 yrs duration> 20 yo, < 10 yrs duration

– CC 10-20 yo, 10-20 yrs duration10-20 yo, 10-20 yrs duration

– DD < 10 yo, > 20 yrs duration< 10 yo, > 20 yrs duration

– RR Retinal Retinal

– HH HeartHeart

– TT TransplantTransplant

– FF RenalRenalClinics in Perinatology 1974Clinics in Perinatology 1974

Pregestational DMPregestational DMPrepregnancy CounselingPrepregnancy Counseling

• Patient education Patient education prior toprior to conception conception

–discuss risks according to classdiscuss risks according to class

–pregnancy does not worsen DM, except bad renalpregnancy does not worsen DM, except bad renal

– importance of euglycemiaimportance of euglycemia

• TeratogenicityTeratogenicity

– importance of euglycemiaimportance of euglycemia

• Folic acid supplementation Folic acid supplementation prior toprior to conception conception

• Rubella, Thyroid functionRubella, Thyroid function

Benefits of Benefits of Preconceptional CounselingPreconceptional Counseling

• Improved cooperation with patientImproved cooperation with patient

• Increased planned pregnanciesIncreased planned pregnancies

• Decreased terminationsDecreased terminations

• Overall care - smoking, ETOH, obesity, etcOverall care - smoking, ETOH, obesity, etc

• Consultation with others (Maternal-Fetal Consultation with others (Maternal-Fetal Medicine, etc)Medicine, etc)

• Cost saving - fewer hospitalizations for mother, Cost saving - fewer hospitalizations for mother, fewer anomalies for fetusfewer anomalies for fetus

Factors predicting Factors predicting bad outcome in DMbad outcome in DM

• Renal diseaseRenal disease

– Massive proteinuria (>3g/24hrs)Massive proteinuria (>3g/24hrs)

– Creatinine >1.5mg/dlCreatinine >1.5mg/dl

• HypertensionHypertension

• RetinopathyRetinopathy

– proliferative -untreated, 89% progressesproliferative -untreated, 89% progresses

• GI - gastropathyGI - gastropathy

• Cardiac - CADCardiac - CAD

• Anemia - Hct < 25%Anemia - Hct < 25%

Contraindications to Contraindications to Pregnancy with DiabetesPregnancy with Diabetes• Ischemic heart diseaseIschemic heart disease

• Untreated proliferative retinopathyUntreated proliferative retinopathy

• Creatinine clearance < 50Creatinine clearance < 50

• Proteinuria > 2g/24hrsProteinuria > 2g/24hrs

• Creatinine > 2mg/dlCreatinine > 2mg/dl

• Uncontrolled HTNUncontrolled HTN

• GI gastropathyGI gastropathyADA 1993

HgbA1C and HgbA1C and Congenital MalformationsCongenital Malformations

• < 7 = no increased risk< 7 = no increased risk

• 7-9 = 15%7-9 = 15%

• 9-11 = 23%9-11 = 23%

• > 11 = 25%> 11 = 25%

Lucas AJOG 1989

Poorly controlled DM -Poorly controlled DM -Congenital anomaliesCongenital anomalies

• CardiacCardiac

• Neural tubeNeural tube

• Caudal regressionCaudal regression

• RenalRenal

• GI - rectum, anusGI - rectum, anus

Pregestational DMPregestational DMDetection of Congenital AnomaliesDetection of Congenital Anomalies

• 10-12 weeks hemoglobin A1C10-12 weeks hemoglobin A1C

• 16 weeks triple screen16 weeks triple screen

(lower cutoff for MSAFP)(lower cutoff for MSAFP)

• 20 week ultrasound, including 20 week ultrasound, including echocardiographyechocardiography

Pregestational DMPregestational DMEvaluationEvaluation

• History an Physical ExamHistory an Physical Exam

• Laboratory TestsLaboratory Tests– Hemoglobin A1C (First Trimester)Hemoglobin A1C (First Trimester)

– SMA-12 (Chol, Creat)SMA-12 (Chol, Creat)

– Urine Cx (Monthly)Urine Cx (Monthly)

– EKGEKG

• Ophthalmology consultOphthalmology consult

Pregestational DMPregestational DMDietDiet

• 2000-2400 kcal/day2000-2400 kcal/day

• 3 meals, 3 snacks3 meals, 3 snacks

• CompositionComposition– Carbohydrates (complex)Carbohydrates (complex) 50-60%50-60%

– ProteinProtein 10-20%10-20%

– Fat (< 10% saturated)Fat (< 10% saturated) 20-30%20-30%

Ney, DM Care, 1981; 4:647Ney, DM Care, 1981; 4:647

Pregestational DMPregestational DMGlucose MonitoringGlucose Monitoring

• Fasting Fasting

• 2 hours postprandial2 hours postprandial• Occasionally preprandial ± 3 amOccasionally preprandial ± 3 am

Pregestational DMPregestational DMTarget ValuesTarget Values

• Fasting < 105 mg/dlFasting < 105 mg/dl

• 2 hr postprandial < 120 mg/dl2 hr postprandial < 120 mg/dl

Pregestational DMPregestational DMInsulin RequirementsInsulin Requirements

11 0.70.7

22 0.80.8

33 1.01.0

TrimesterTrimester Units/kg/dayUnits/kg/day

Pregestational DMPregestational DMInsulin RegimenInsulin Regimen

AMAM

2/3 total dose2/3 total dose

1/3 regular1/3 regular

AMAM


2/3 NPH2/3 NPH 1/3 regular1/3 regular

PMPM


1/2 NPH1/2 NPH 1/2 regular1/2 regular

hshs dinnerdinner

• No oral hypoglycemic agentsNo oral hypoglycemic agents– Fetal hyperinsulinemiaFetal hyperinsulinemia

• Continue pump in pregestational diabetics already in good control with this therapyContinue pump in pregestational diabetics already in good control with this therapy

• Hospitalization PRNHospitalization PRN

Pregestational DMPregestational DM

Coustan, JAMA 1986; 255:631Coustan, JAMA 1986; 255:631


Glucagon available at homeGlucagon available at home

MGM of DKAMGM of DKA

• InsulinInsulin

• Normal SalineNormal Saline

Seizure DisordersSeizure Disorders• Drug levels decreased in pregnancy: follow levels, adjust dose, avoid Drug levels decreased in pregnancy: follow levels, adjust dose, avoid

high doseshigh doses

• No contraindication to pregnancyNo contraindication to pregnancy

• Congenital anomalies X2Congenital anomalies X2

• All antisz meds teratogenicAll antisz meds teratogenic

– use best med for specific dx/patientuse best med for specific dx/patient

– no poly rxno poly rx

– avoid change in antisz med post first trimesteravoid change in antisz med post first trimester

– take antisz med regularly, sleep welltake antisz med regularly, sleep well

– if only one sz, no rxif only one sz, no rx

– if no sz > 4-5yrs, consider d/c antisz medif no sz > 4-5yrs, consider d/c antisz med

Seizure DisordersSeizure DisordersSpecific MedicationsSpecific Medications

• Trimethadione - absolute contraindicationTrimethadione - absolute contraindication

• All antisz meds: CHD, cleft lip/palate, developmental All antisz meds: CHD, cleft lip/palate, developmental delay, coagulopathydelay, coagulopathy

• Carbamazepine: NTD, fingers hypoplasiaCarbamazepine: NTD, fingers hypoplasia

• Phenytoin: hypertelorism, hypoplastic nails, limb Phenytoin: hypertelorism, hypoplastic nails, limb anomalies, IUGR, microcephaly, mental deficienciesanomalies, IUGR, microcephaly, mental deficiencies

• Valproic acid: NTDValproic acid: NTD

• Phenobarbital: neonatal withdrawal (no anom. when Phenobarbital: neonatal withdrawal (no anom. when taken for other indic.)taken for other indic.)

Seizure DisordersSeizure DisordersManagementManagement

• Folic acid 1-4mg preconceptionallyFolic acid 1-4mg preconceptionally

• Drug levels qtrimDrug levels qtrim

• MSAFP, amniocentesis, fetal MSAFP, amniocentesis, fetal ultrasound/echocardiographyultrasound/echocardiography

• Vitamin K 10mg po qd last 4 weeks of Vitamin K 10mg po qd last 4 weeks of pregnancypregnancy

• breastfeeding ok (stop if infant overly sedated)breastfeeding ok (stop if infant overly sedated)

GDMGDMRisksRisks

• Macrosomia/polyhydramnios, Macrosomia/polyhydramnios, Shoulder dystocia, birth traumaShoulder dystocia, birth trauma

• Neonatal hypoglycemiaNeonatal hypoglycemia

• Neonatal RDSNeonatal RDS

• Perinatal deathPerinatal death

• Long term obesity, DM, low IQLong term obesity, DM, low IQ


• Operative deliveryOperative delivery

• HTN/preeclampsiaHTN/preeclampsia

• UTIUTI

• Preterm labor/deliveryPreterm labor/delivery

• KetoacidosisKetoacidosis

• Future DMFuture DM

GDMGDM

Screen Screen ALLALL women for glucose women for glucose

intolerance between 24-28 weeks intolerance between 24-28 weeks

gestationgestation

GDMGDMScreen (1 Hour GCT)Screen (1 Hour GCT)

• 50 grams one hour Glucose Challenge Test (GCT)50 grams one hour Glucose Challenge Test (GCT)

• Abn venous plasma glucoseAbn venous plasma glucose < 135 mg/dl < 135 mg/dl no GDM no GDM 135 mg/dl 135 mg/dl 3 hour GTT 3 hour GTT 200 mg/dl 200 mg/dl GDM GDM

GDMGDMDiagnosisDiagnosis ((3 Hour GTT)3 Hour GTT)

• 100 gram glucose after 8-14 hours fast100 gram glucose after 8-14 hours fast

• GDM if 2 abn venous plasma glucose values:GDM if 2 abn venous plasma glucose values:

FastingFasting 105 mg/dl105 mg/dl

1 hour1 hour 190 mg/dl190 mg/dl



GDMGDM

3 Hour GTT3 Hour GTT• If only one abn value If only one abn value

nutrition consult nutrition consult repeat 3 hour GTT in 4 weeksrepeat 3 hour GTT in 4 weeks

GDMGDMDietDiet

• ~ 2000 kcal/day~ 2000 kcal/day

• Lean Lean

– 35 kcal/kg of ideal prepregnancy body weight35 kcal/kg of ideal prepregnancy body weight

• Obese Obese

– 25 kcal/kg of ideal prepregnancy body weight25 kcal/kg of ideal prepregnancy body weight

• CarbohydratesCarbohydrates 50-60%50-60%

• ProteinProtein 10-20%10-20%

• Fat (< 10% saturated)Fat (< 10% saturated) 20-30%20-30%

• No concentrated sweetsNo concentrated sweets

• Nutrition consultNutrition consult

• ExerciseExercise

GDMGDMGlucose MonitoringGlucose Monitoring

• Fasting and 2 hour postprandial Fasting and 2 hour postprandial

• Fasting < 105, 2 hour postprandial < 120Fasting < 105, 2 hour postprandial < 120

GDMGDMFetusFetus

• U/S for EFWU/S for EFW

• Non-stress tests at 40 weeksNon-stress tests at 40 weeks

• Induction if macrosomia with or Induction if macrosomia with or without a favourable cervixwithout a favourable cervix

GDMGDMA2 A2 (Insulin Requiring)(Insulin Requiring)

• DietDiet

• Fasting and 2 hour postprandialsFasting and 2 hour postprandials

• Insulin Insulin

AM: NPH 20 u., Regular 10u; AM: NPH 20 u., Regular 10u;

PM: NPH 8u, Regular 8uPM: NPH 8u, Regular 8u

• Fasting < 105, 2 hour postprandial < 120Fasting < 105, 2 hour postprandial < 120

De Veciana NEJM 1995; 333:1237De Veciana NEJM 1995; 333:1237

GDMGDMA2 A2 (Insulin Requiring)(Insulin Requiring)

• U/S for EFWU/S for EFW

• Non-stress test at 34 weeks (weekly)Non-stress test at 34 weeks (weekly)

• Induce by EDCInduce by EDC

Pregestational DMPregestational DMRisksRisks

• Spontaneous abortionsSpontaneous abortions• Congenital anomaliesCongenital anomalies• Macrosomic/polyhydramnios, Macrosomic/polyhydramnios,

Shoulder dystocia, birth traumaShoulder dystocia, birth trauma• IUGR (growth restriction)IUGR (growth restriction)• Neonatal RDSNeonatal RDS• Perinatal deathPerinatal death• Long term obesity, DM, low IQLong term obesity, DM, low IQ


• Operative deliveryOperative delivery• HTN/preeclampsiaHTN/preeclampsia• UTI/UTI/pyelonephritispyelonephritis• Preterm labor/deliveryPreterm labor/delivery• KetoacidosisKetoacidosis• NephropathyNephropathy• RetinopathyRetinopathy• NeuropathyNeuropathy• Future DMFuture DM

Pregestational DMPregestational DMUltrasoundUltrasound

• First trimesterFirst trimester


• 20-22 weeks (echocardiogram)20-22 weeks (echocardiogram)

• 28 weeks28 weeks

• 34 weeks34 weeks


Non stress tests (NST) twice weekly and Non stress tests (NST) twice weekly and amniotic fluid indexes (AFI) weekly amniotic fluid indexes (AFI) weekly starting at 34 weeks (good control)starting at 34 weeks (good control)


•Delivery by due dateDelivery by due date> 2% > 2%

(or 2 of other FLM tests)(or 2 of other FLM tests)

Pregestational DMPregestational DMIntrapartum Glucose ControlIntrapartum Glucose Control

< 100< 100 00 Dextrose/Lactated Dextrose/Lactated Ringer’s injectionRinger’s injection

100-140100-140 1.01.0 Dextrose/Lactated Dextrose/Lactated Ringer’s injectionRinger’s injection

141-180141-180 1.51.5 Normal SalineNormal Saline

181-220181-220 2.02.0 Normal SalineNormal Saline

> 220> 220 2.52.5 Normal SalineNormal Saline

Blood GlucoseBlood Glucose(mg/100ml)(mg/100ml)

Insulin DosageInsulin Dosage(U/h)(U/h)

FluidsFluids(125 ml/h)(125 ml/h)

Pregestational DMPregestational DMPostpartum Glucose ControlPostpartum Glucose Control

• Lower insulin drip with boluses or Lower insulin drip with boluses or nothingnothing

• Resume SQ insulin when back or ADA Resume SQ insulin when back or ADA regulate dietregulate diet

Preeclampsia and Eclampsia Vincenzo Berghella, M.D. Professor Department of Obstetrics and...

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