Medical Illness Medical Illness in Pregnancyin Pregnancy

Beth Harleman, MDBeth Harleman, MDAssistant Clinical Professor of Assistant Clinical Professor of

Medicine and Ob/Gyn and Medicine and Ob/Gyn and Reproductive SciencesReproductive Sciences

SFGH/UCSFSFGH/UCSF

GoalsGoals

At the end of this talk, you will be At the end of this talk, you will be able to: able to: Confidently prescribe needed Confidently prescribe needed

medications in pregnancymedications in pregnancy Order diagnostic imaging safely for your Order diagnostic imaging safely for your

pregnant patientspregnant patients Act on evidence-based recommendations Act on evidence-based recommendations

for management of common medical for management of common medical problems in pregnancyproblems in pregnancy

OutlineOutline

Major physiologic changes in Major physiologic changes in pregnancy and effects on diseasepregnancy and effects on disease

Diagnostic imaging and prescribing in Diagnostic imaging and prescribing in pregnancypregnancy

Cases on commonly encountered Cases on commonly encountered conditionsconditions Diabetes and hypertensionDiabetes and hypertension Asthma and tobacco useAsthma and tobacco use Hypothyroidism and depressionHypothyroidism and depression

National Center for Health Statistics, July 2006

Medical Illness in Pregnancy: Medical Illness in Pregnancy: Changing Trends in Maternal Changing Trends in Maternal

AgeAge

Joseph, K, Obstetrics and Gynecology, 2005

Effects of increased Effects of increased maternal agematernal age

More More preconception preconception chronic diseasechronic disease

More women with More women with severe illnesses of severe illnesses of childhood childhood surviving to surviving to reproductive agereproductive age Congenital heart dzCongenital heart dz Type I DMType I DM

00.5

11.52

2.53

3.54

adjusted rate c/w

ages 20-24

Htn ChrnDz *

Medical conditions in pregnant women in Nova

Scotia 1988-2002

25-2935-39>40

Increasing burden of Increasing burden of chronic diseasechronic disease

Effects of increased Effects of increased maternal agematernal age

Obstetric complicationsObstetric complications Higher rates of placental abruption, Higher rates of placental abruption,

previa, preterm birth and SGA infantsprevia, preterm birth and SGA infants Overall rates of poor outcomes lowOverall rates of poor outcomes low

Kaaja and Greer, JAMA 2006

Pregnancy and chronic Pregnancy and chronic diseasedisease

Pregnancy likely to unmask occult Pregnancy likely to unmask occult chronic diseasechronic disease Glucose intolerance Glucose intolerance Renal dysfunctionRenal dysfunction Hypercoaguable statesHypercoaguable states Valvular heart diseaseValvular heart disease Cerebral aneurysmCerebral aneurysm

Pregnancy as a “stress test for life”Pregnancy as a “stress test for life”

O'Sullivan, J, Diabetes 1991; JAMA 1982; Kaaja, JAMA 2005

Postpartum effectsPostpartum effects

Increased rates of postpartum chronic Increased rates of postpartum chronic diseasedisease Women with GDM have up to 75% Women with GDM have up to 75%

likelihood of developing Type II DM in likelihood of developing Type II DM in subsequent five yearssubsequent five years

Women with preeclampsia more likely to Women with preeclampsia more likely to develop CAD and stroke later in lifedevelop CAD and stroke later in life Higher rates of hypertension, insulin resistance, Higher rates of hypertension, insulin resistance,

dyslipidemia and inflammatory markersdyslipidemia and inflammatory markers Primary prevention could play an important rolePrimary prevention could play an important role

Approach to Medical Illness in Approach to Medical Illness in PregnancyPregnancy

Great need for primary providers to Great need for primary providers to understand medical illness in understand medical illness in pregnancypregnancy Management of medical illness Management of medical illness

including appropriate contraceptionincluding appropriate contraception Preconception counseling and patient Preconception counseling and patient

education education Collaboration with subspecialists, Collaboration with subspecialists,

MFM’sMFM’s

Approach to Medical Illness in Approach to Medical Illness in PregnancyPregnancy

The tools you need:The tools you need: An understanding of the physiologic An understanding of the physiologic

changes of pregnancy and how they changes of pregnancy and how they affect diseaseaffect disease

A basic knowledge of pregnancy A basic knowledge of pregnancy specific illnessesspecific illnesses

A strategy for evaluating drug safety A strategy for evaluating drug safety and diagnostic imaging in pregnancyand diagnostic imaging in pregnancy

Case 1Case 1

23 yo G1 at 9 weeks 23 yo G1 at 9 weeks Immigrant from MexicoImmigrant from Mexico Feeling well with the exception of mild Feeling well with the exception of mild

nauseanausea On examOn exam

BP 105/60, HR 90BP 105/60, HR 90 4/6 systolic murmur at apex4/6 systolic murmur at apexaxillaaxilla

Case 1Case 1

How does the cardiovascular system How does the cardiovascular system change in pregnancy?change in pregnancy?

How might these changes affect a How might these changes affect a patient with cardiac disease?patient with cardiac disease?

What would you do?What would you do?

Key physiologic changes: Key physiologic changes: cardiovascularcardiovascular

Hemodynamic changesHemodynamic changes Blood volume/cardiac output increaseBlood volume/cardiac output increase

50% increase, with half of this by 8 weeks50% increase, with half of this by 8 weeks Maximum blood volume expansion at 28 weeksMaximum blood volume expansion at 28 weeks Labor may increase cardiac output another 50%Labor may increase cardiac output another 50%

10-20% increase in HR10-20% increase in HR 25% decrease in systemic vascular 25% decrease in systemic vascular

resistanceresistance Systolic BP decreases by 5-10mmHg, diastolic Systolic BP decreases by 5-10mmHg, diastolic

by 10-15mmHgby 10-15mmHg

Key physiologic changes: Key physiologic changes: cardiovascularcardiovascular

Oncotic changes:Oncotic changes: Increased plasma volume by 50%Increased plasma volume by 50% Increased red cell mass by 33%Increased red cell mass by 33% Resulting dilutional anemiaResulting dilutional anemia

Effects on valvular heart Effects on valvular heart diseasedisease

Regurgitant lesions improve with lower Regurgitant lesions improve with lower SBPSBP

Stenotic lesions worsen Stenotic lesions worsen Increased HR and CO increase cardiac work Increased HR and CO increase cardiac work Gradient across stenotic valve increasesGradient across stenotic valve increases 25% of women with mitral stenosis present in 25% of women with mitral stenosis present in

pregnancypregnancy Risk factors for decompensationRisk factors for decompensation

Mitral stenosis: increased heart rateMitral stenosis: increased heart rate Aortic stenosis: sudden blood lossAortic stenosis: sudden blood loss Regurgitant lesions: increased preloadRegurgitant lesions: increased preload

Siu, SC, Circulation 2001

Predictors of poor outcome in Predictors of poor outcome in women with heart diseasewomen with heart disease

New York Heart Association Class III New York Heart Association Class III or IVor IV Symptoms with less than ordinary Symptoms with less than ordinary

physical activity or at restphysical activity or at rest History of prior cardiac event or History of prior cardiac event or

arrhythmiaarrhythmia Left sided obstruction in mitral or Left sided obstruction in mitral or

aortic valveaortic valve Ejection fraction less than 40%Ejection fraction less than 40%

Case 1Case 1

Echo shows rheumatic mitral Echo shows rheumatic mitral stenosisstenosis

The cardiologist recommends meds The cardiologist recommends meds to control her heart rateto control her heart rate

How would you decide which How would you decide which medicines are safe to give her in medicines are safe to give her in pregnancy?pregnancy?

Lee R, 2000

Prescribing in pregnancyPrescribing in pregnancy

Do not start any medication unless Do not start any medication unless clearly indicatedclearly indicated

Do not discontinue medicines that Do not discontinue medicines that successfully maintain the maternal successfully maintain the maternal condition unless there are clear condition unless there are clear indications to do soindications to do so

Ask about and document non-Ask about and document non-prescription meds prescription meds

Powrie, R SGIM 2000

Prescribing in pregnancyPrescribing in pregnancy

Have a pregnancy medication reference Have a pregnancy medication reference availableavailable

Favor older medicines with longer record Favor older medicines with longer record of useof use

Check blood levels and consider Check blood levels and consider increased and/or more frequent dosingincreased and/or more frequent dosing Increased volume of distribution, hepatic and Increased volume of distribution, hepatic and

renal clearancerenal clearance Increased production of binding proteins—Increased production of binding proteins—

free drug levels are betterfree drug levels are better

Prescribing in pregnancyPrescribing in pregnancy

Educate and negotiate with your patientEducate and negotiate with your patient Pregnant women more likely to stop needed Pregnant women more likely to stop needed

medsmeds Report adverse outcomesReport adverse outcomes

Add websAdd webs Always consider the effect of not Always consider the effect of not

treatingtreating Remember that few drugs are Remember that few drugs are

absolutely contraindicatedabsolutely contraindicated

Lee, R 2000

Drugs to avoid in Drugs to avoid in pregnancypregnancy

ACE inhibitorsACE inhibitors: renal dysgenesis: renal dysgenesis TetracyclineTetracycline: abnormalities of bone and teeth: abnormalities of bone and teeth FluoroquinolonesFluoroquinolones: abnl cartilage development: abnl cartilage development Systemic retinoidsSystemic retinoids: CNS, craniofacial, CV : CNS, craniofacial, CV

defectsdefects WarfarinWarfarin: skeletal and CNS defects: skeletal and CNS defects Valproic acidValproic acid: neural tube defects: neural tube defects NSAIDSNSAIDS: bleeding, premature closure of the : bleeding, premature closure of the

ductus arteriosisductus arteriosis Live vaccines (MMR, oral polio, varicella, Live vaccines (MMR, oral polio, varicella,

yellow fever)yellow fever):: may cross placentamay cross placenta

Sciali, 2004 accessed from www.reprotox.org

Limits of the FDA Limits of the FDA classificationclassification

Hard to remember Hard to remember May be misleadingMay be misleading

Up to 60% of category X drugs have no Up to 60% of category X drugs have no human datahuman data

No information on degree of riskNo information on degree of risk A drug may end up in category X simply A drug may end up in category X simply

if it has no utility in pregnancyif it has no utility in pregnancy Rarely updatedRarely updated

Good References for Drug Good References for Drug PrescribingPrescribing

Briggs, Freeman, and Yaffe: Drugs in Briggs, Freeman, and Yaffe: Drugs in Pregnancy and Lactation, 2005.Pregnancy and Lactation, 2005.

Lee, Rosene-Montella, Barbour, Garner, Lee, Rosene-Montella, Barbour, Garner, Keely: Medical Care of the Pregnant Keely: Medical Care of the Pregnant Patient, 2000.Patient, 2000.

www.reprotox.orgwww.reprotox.org www.motherisk.orgwww.motherisk.org www.micromedix.comwww.micromedix.com (reprorisk) (reprorisk) www.otispregnancy.orgwww.otispregnancy.org (free) (free) Hale, T: Medications and Mother’s Milk, Hale, T: Medications and Mother’s Milk,

2004. Also www.ibreastfeeding.com2004. Also www.ibreastfeeding.com

Reprotox website 2006

Example from ReprotoxExample from Reprotox Agent Summary—Citalopram (Celexa)Agent Summary—Citalopram (Celexa)

Quick take: Based on experimental animal studies and Quick take: Based on experimental animal studies and limited human reports, standard therapeutic use of limited human reports, standard therapeutic use of citalopram is not expected to increase the risk of citalopram is not expected to increase the risk of congenital anomalies. Use of serotonin reuptake inhibitors congenital anomalies. Use of serotonin reuptake inhibitors late in pregnancy can be associated with a mild transient late in pregnancy can be associated with a mild transient neonatal syndrome of central nervous system, motor, neonatal syndrome of central nervous system, motor, respiratory, and gastrointestinal signs. In a small number respiratory, and gastrointestinal signs. In a small number of cases, the use of other serotonin reuptake inhibitors of cases, the use of other serotonin reuptake inhibitors after 20 weeks gestation has been associated with an after 20 weeks gestation has been associated with an increased risk of neonatal pulmonary hypertension.increased risk of neonatal pulmonary hypertension.

Case #1Case #1

Your patient does well and presents Your patient does well and presents to L&D at 37 weeks in early laborto L&D at 37 weeks in early labor

How do you expect labor to affect How do you expect labor to affect her heart disease?her heart disease?

Labor physiologyLabor physiology

Uterine contractions increase preload Uterine contractions increase preload (equivalent to 1-2 units of blood) and (equivalent to 1-2 units of blood) and cardiac output up to 80%cardiac output up to 80%

Fluid shifts in a C-section can be even Fluid shifts in a C-section can be even more abrupt—>vaginal delivery usually more abrupt—>vaginal delivery usually safersafer

Labor and the period immediately after Labor and the period immediately after delivery represent the period of maximal delivery represent the period of maximal risk for cardiopulmonary risk for cardiopulmonary decompensationdecompensation

Case #1Case #1

Patient developed pulmonary edema Patient developed pulmonary edema in laborin labor

Successfully managed with Successfully managed with metoprolol and low dose lasixmetoprolol and low dose lasix

C-section for fetal distressC-section for fetal distress Mom and baby boy left hospital Mom and baby boy left hospital

doing welldoing well

Case #2Case #2

39 yo G4P2 for new primary care 39 yo G4P2 for new primary care appointment appointment

ObeseObese History of pulmonary embolus in prior History of pulmonary embolus in prior

pregnancypregnancy Upreg positive today, 9 weeks by LMPUpreg positive today, 9 weeks by LMP Complaining of mild shortness of Complaining of mild shortness of

breath, O2 sat is 93%breath, O2 sat is 93%

Case #2Case #2

What are some changes in the What are some changes in the respiratory and hematologic systems respiratory and hematologic systems in pregnancy?in pregnancy?

How might they affect this patient?How might they affect this patient? What would you do next?What would you do next?

Key physiologic changes: Key physiologic changes: pulmonarypulmonary

Increased minute ventilationIncreased minute ventilation Mediated by progesteroneMediated by progesterone Increased tidal volume>>respiratory Increased tidal volume>>respiratory

raterate Compensated respiratory alkalosis Compensated respiratory alkalosis Normal ABG in pregnancy: 7.43/29/100Normal ABG in pregnancy: 7.43/29/100

PaCOPaCO22 of 40mmHg is very abnormal in of 40mmHg is very abnormal in pregnancypregnancy

Fetus relies on high maternal PaOFetus relies on high maternal PaO22

Key physiologic changes: Key physiologic changes: pulmonarypulmonary

Greater tendency to pulmonary Greater tendency to pulmonary edemaedema Increased cardiac outputIncreased cardiac output

Decreased oncotic pressureDecreased oncotic pressure

Leaky capillariesLeaky capillaries

Aggressive IV fluidsAggressive IV fluids

MedsMeds

Sisclone A, Obstetrics and Gynecology, 2003

Causes of non-cardiogenic Causes of non-cardiogenic pulmonary edema in pulmonary edema in

PregnancyPregnancy

PIHtocolyticsfld overldinfection

Key physiologic changes in Key physiologic changes in pregnancy: Hematologicpregnancy: Hematologic

Hematologic/Immunologic:Hematologic/Immunologic: Procoagulant factors increase: factor Procoagulant factors increase: factor

VIII, vWF, fibrinogenVIII, vWF, fibrinogen Protein S levels markedly reducedProtein S levels markedly reduced Increased risk of venous clotsIncreased risk of venous clots

Greatest risk in post-partum periodGreatest risk in post-partum period

Key physiologic changes: Key physiologic changes: endocrineendocrine

Endocrine:Endocrine: Insulin resistance, dyslipidemiaInsulin resistance, dyslipidemia Relative TSH suppression in first Relative TSH suppression in first

trimestertrimester Other thyroid changesOther thyroid changes

Key physiologic changes: Key physiologic changes: renalrenal

Increased glomerular filtration rate Increased glomerular filtration rate Baseline proteinuria increasesBaseline proteinuria increases Drugs metabolized more rapidly by Drugs metabolized more rapidly by

kidneykidney Creatinine fallsCreatinine falls Collecting system dilatesCollecting system dilates

Case #2Case #2

You want to order a chest x-ray for You want to order a chest x-ray for initial evaluationinitial evaluation

She is concerned about the effects She is concerned about the effects on the fetuson the fetus

What would you say?What would you say?

Principles of diagnostic Principles of diagnostic imagingimaging

Greater risk of harm by Greater risk of harm by notnot getting a getting a needed study than getting oneneeded study than getting one

Little evidence that radiation Little evidence that radiation exposures <5 rads have significant exposures <5 rads have significant fetal effects fetal effects

Almost all imaging studies involve Almost all imaging studies involve radiation well below this levelradiation well below this level CXR <0.001 radCXR <0.001 rad Chest CT PE protocol 0.001-0.002 radsChest CT PE protocol 0.001-0.002 rads CT abdomen/pelvis 0.64 radsCT abdomen/pelvis 0.64 rads

How many chest x-rays?How many chest x-rays?

A pregnant woman A pregnant woman could theoretically could theoretically receive receive at leastat least 1,000 chest x-rays 1,000 chest x-rays without negative without negative effectseffects

IV contrastIV contrast

Theoretical concern for effects on Theoretical concern for effects on fetal thyroidfetal thyroid

Case reports of women receiving Case reports of women receiving high dose iodine in pregnancy-->no high dose iodine in pregnancy-->no adverse outcomesadverse outcomes

General advice: avoid if possible, but General advice: avoid if possible, but use contrast when clinically use contrast when clinically necessarynecessary

MRIMRI

Few studiesFew studies Animal evidence shows little riskAnimal evidence shows little risk

NIH consensus statementNIH consensus statement Recommends MRI be reserved for 2Recommends MRI be reserved for 2ndnd

and 3and 3rdrd trimester if possible, but can be trimester if possible, but can be performed in pregnancyperformed in pregnancy

GadoliniumGadolinium Little data—use if clinically warrantedLittle data—use if clinically warranted

Case #2Case #2

CT with PE protocol done: PECT with PE protocol done: PE Managed with treatment dose low Managed with treatment dose low

molecular weight heparin, converted molecular weight heparin, converted to subcutaneous unfractionated to subcutaneous unfractionated heparin at 36 weeksheparin at 36 weeks

Vaginal delivery of healthy baby boyVaginal delivery of healthy baby boy

Medical illness and Medical illness and PregnancyPregnancy

Remember the key physiologic Remember the key physiologic changeschanges

Have prescribing references Have prescribing references available available

Think about what you would do if Think about what you would do if she weren’t pregnantshe weren’t pregnant

Have fun!Have fun!

Case discussionsCase discussions

A 38 yo woman with hypertension A 38 yo woman with hypertension and DM II considering pregnancyand DM II considering pregnancy

A 34 yo woman with hypothyroidism A 34 yo woman with hypothyroidism and depression with a positive upreg and depression with a positive upreg at 6 weeksat 6 weeks

A 25 yo woman with asthma who A 25 yo woman with asthma who smokes in the second trimestersmokes in the second trimester