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Medical Illness in Pregnancy Beth Harleman, MD Assistant Clinical Professor of Medicine and Ob/Gyn and Reproductive Sciences SFGH/UCSF.

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Presentation on theme: "Medical Illness in Pregnancy Beth Harleman, MD Assistant Clinical Professor of Medicine and Ob/Gyn and Reproductive Sciences SFGH/UCSF."— Presentation transcript:

1 Medical Illness in Pregnancy Beth Harleman, MD Assistant Clinical Professor of Medicine and Ob/Gyn and Reproductive Sciences SFGH/UCSF

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3 Goals At the end of this talk, you will be able to: At the end of this talk, you will be able to: Confidently prescribe needed medications in pregnancy Confidently prescribe needed medications in pregnancy Order diagnostic imaging safely for your pregnant patients Order diagnostic imaging safely for your pregnant patients Act on evidence-based recommendations for management of common medical problems in pregnancy Act on evidence-based recommendations for management of common medical problems in pregnancy

4 Outline Major physiologic changes in pregnancy and effects on disease Major physiologic changes in pregnancy and effects on disease Diagnostic imaging and prescribing in pregnancy Diagnostic imaging and prescribing in pregnancy Cases on commonly encountered conditions Cases on commonly encountered conditions Diabetes and hypertension Diabetes and hypertension Asthma and tobacco use Asthma and tobacco use Hypothyroidism and depression Hypothyroidism and depression

5 National Center for Health Statistics, July 2006 Medical Illness in Pregnancy: Changing Trends in Maternal Age

6 Joseph, K, Obstetrics and Gynecology, 2005 Effects of increased maternal age More preconception chronic disease More preconception chronic disease More women with severe illnesses of childhood surviving to reproductive age More women with severe illnesses of childhood surviving to reproductive age Congenital heart dz Congenital heart dz Type I DM Type I DM

7 Increasing burden of chronic disease

8 Effects of increased maternal age Obstetric complications Obstetric complications Higher rates of placental abruption, previa, preterm birth and SGA infants Higher rates of placental abruption, previa, preterm birth and SGA infants Overall rates of poor outcomes low Overall rates of poor outcomes low

9 Kaaja and Greer, JAMA 2006 Pregnancy and chronic disease Pregnancy likely to unmask occult chronic disease Pregnancy likely to unmask occult chronic disease Glucose intolerance Glucose intolerance Renal dysfunction Renal dysfunction Hypercoaguable states Hypercoaguable states Valvular heart disease Valvular heart disease Cerebral aneurysm Cerebral aneurysm Pregnancy as a stress test for life Pregnancy as a stress test for life

10 O'Sullivan, J, Diabetes 1991; JAMA 1982; Kaaja, JAMA 2005 Postpartum effects Increased rates of postpartum chronic disease Increased rates of postpartum chronic disease Women with GDM have up to 75% likelihood of developing Type II DM in subsequent five years Women with GDM have up to 75% likelihood of developing Type II DM in subsequent five years Women with preeclampsia more likely to develop CAD and stroke later in life Women with preeclampsia more likely to develop CAD and stroke later in life Higher rates of hypertension, insulin resistance, dyslipidemia and inflammatory markers Higher rates of hypertension, insulin resistance, dyslipidemia and inflammatory markers Primary prevention could play an important role Primary prevention could play an important role

11 Approach to Medical Illness in Pregnancy Great need for primary providers to understand medical illness in pregnancy Great need for primary providers to understand medical illness in pregnancy Management of medical illness including appropriate contraception Management of medical illness including appropriate contraception Preconception counseling and patient education Preconception counseling and patient education Collaboration with subspecialists, MFMs Collaboration with subspecialists, MFMs

12 Approach to Medical Illness in Pregnancy The tools you need: The tools you need: An understanding of the physiologic changes of pregnancy and how they affect disease An understanding of the physiologic changes of pregnancy and how they affect disease A basic knowledge of pregnancy specific illnesses A basic knowledge of pregnancy specific illnesses A strategy for evaluating drug safety and diagnostic imaging in pregnancy A strategy for evaluating drug safety and diagnostic imaging in pregnancy

13 Case 1 23 yo G1 at 9 weeks 23 yo G1 at 9 weeks Immigrant from Mexico Immigrant from Mexico Feeling well with the exception of mild nausea Feeling well with the exception of mild nausea On exam On exam BP 105/60, HR 90 BP 105/60, HR 90 4/6 systolic murmur at apex axilla 4/6 systolic murmur at apex axilla

14 Case 1 How does the cardiovascular system change in pregnancy? How does the cardiovascular system change in pregnancy? How might these changes affect a patient with cardiac disease? How might these changes affect a patient with cardiac disease? What would you do? What would you do?

15 Key physiologic changes: cardiovascular Hemodynamic changes Hemodynamic changes Blood volume/cardiac output increase Blood volume/cardiac output increase 50% increase, with half of this by 8 weeks 50% increase, with half of this by 8 weeks Maximum blood volume expansion at 28 weeks Maximum blood volume expansion at 28 weeks Labor may increase cardiac output another 50% Labor may increase cardiac output another 50% 10-20% increase in HR 10-20% increase in HR 25% decrease in systemic vascular resistance 25% decrease in systemic vascular resistance Systolic BP decreases by 5-10mmHg, diastolic by mmHg Systolic BP decreases by 5-10mmHg, diastolic by mmHg

16 Key physiologic changes: cardiovascular 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 anemia Resulting dilutional anemia

17 Effects on valvular heart disease Regurgitant lesions improve with lower SBP Regurgitant lesions improve with lower SBP Stenotic lesions worsen Stenotic lesions worsen Increased HR and CO increase cardiac work Increased HR and CO increase cardiac work Gradient across stenotic valve increases Gradient across stenotic valve increases 25% of women with mitral stenosis present in pregnancy 25% of women with mitral stenosis present in pregnancy Risk factors for decompensation Risk factors for decompensation Mitral stenosis: increased heart rate Mitral stenosis: increased heart rate Aortic stenosis: sudden blood loss Aortic stenosis: sudden blood loss Regurgitant lesions: increased preload Regurgitant lesions: increased preload

18 Siu, SC, Circulation 2001 Predictors of poor outcome in women with heart disease New York Heart Association Class III or IV New York Heart Association Class III or IV Symptoms with less than ordinary physical activity or at rest Symptoms with less than ordinary physical activity or at rest History of prior cardiac event or arrhythmia History of prior cardiac event or arrhythmia Left sided obstruction in mitral or aortic valve Left sided obstruction in mitral or aortic valve Ejection fraction less than 40% Ejection fraction less than 40%

19 Case 1 Echo shows rheumatic mitral stenosis Echo shows rheumatic mitral stenosis The cardiologist recommends meds to control her heart rate The cardiologist recommends meds to control her heart rate How would you decide which medicines are safe to give her in pregnancy? How would you decide which medicines are safe to give her in pregnancy?

20 Lee R, 2000 Prescribing in pregnancy Do not start any medication unless clearly indicated Do not start any medication unless clearly indicated Do not discontinue medicines that successfully maintain the maternal condition unless there are clear indications to do so Do not discontinue medicines that successfully maintain the maternal condition unless there are clear indications to do so Ask about and document non-prescription meds Ask about and document non-prescription meds

21 Powrie, R SGIM 2000 Prescribing in pregnancy Have a pregnancy medication reference available Have a pregnancy medication reference available Favor older medicines with longer record of use Favor older medicines with longer record of use Check blood levels and consider increased and/or more frequent dosing Check blood levels and consider increased and/or more frequent dosing Increased volume of distribution, hepatic and renal clearance Increased volume of distribution, hepatic and renal clearance Increased production of binding proteinsfree drug levels are better Increased production of binding proteinsfree drug levels are better

22 Prescribing in pregnancy Educate and negotiate with your patient Educate and negotiate with your patient Pregnant women more likely to stop needed meds Pregnant women more likely to stop needed meds Report adverse outcomes Report adverse outcomes Add webs Add webs Always consider the effect of not treating Always consider the effect of not treating Remember that few drugs are absolutely contraindicated Remember that few drugs are absolutely contraindicated

23 Lee, R 2000 Drugs to avoid in pregnancy ACE inhibitors: renal dysgenesis ACE inhibitors: renal dysgenesis Tetracycline: abnormalities of bone and teeth Tetracycline: abnormalities of bone and teeth Fluoroquinolones: abnl cartilage development Fluoroquinolones: abnl cartilage development Systemic retinoids: CNS, craniofacial, CV defects Systemic retinoids: CNS, craniofacial, CV defects Warfarin: skeletal and CNS defects Warfarin: skeletal and CNS defects Valproic acid: neural tube defects Valproic acid: neural tube defects NSAIDS: bleeding, premature closure of the ductus arteriosis NSAIDS: bleeding, premature closure of the ductus arteriosis Live vaccines (MMR, oral polio, varicella, yellow fever): may cross placenta Live vaccines (MMR, oral polio, varicella, yellow fever): may cross placenta

24 Sciali, 2004 accessed from Limits of the FDA classification Hard to remember Hard to remember May be misleading May be misleading Up to 60% of category X drugs have no human data Up to 60% of category X drugs have no human data No information on degree of risk No information on degree of risk A drug may end up in category X simply if it has no utility in pregnancy A drug may end up in category X simply if it has no utility in pregnancy Rarely updated Rarely updated

25 Good References for Drug Prescribing Briggs, Freeman, and Yaffe: Drugs in Pregnancy and Lactation, Briggs, Freeman, and Yaffe: Drugs in Pregnancy and Lactation, Lee, Rosene-Montella, Barbour, Garner, Keely: Medical Care of the Pregnant Patient, Lee, Rosene-Montella, Barbour, Garner, Keely: Medical Care of the Pregnant Patient, (reprorisk) (reprorisk) (free) (free) Hale, T: Medications and Mothers Milk, Also Hale, T: Medications and Mothers Milk, Also

26 Reprotox website 2006 Example from Reprotox Agent SummaryCitalopram (Celexa) Quick take: Based on experimental animal studies and limited human reports, standard therapeutic use of citalopram is not expected to increase the risk of congenital anomalies. Use of serotonin reuptake inhibitors late in pregnancy can be associated with a mild transient neonatal syndrome of central nervous system, motor, respiratory, and gastrointestinal signs. In a small number of cases, the use of other serotonin reuptake inhibitors after 20 weeks gestation has been associated with an increased risk of neonatal pulmonary hypertension. Agent SummaryCitalopram (Celexa) Quick take: Based on experimental animal studies and limited human reports, standard therapeutic use of citalopram is not expected to increase the risk of congenital anomalies. Use of serotonin reuptake inhibitors late in pregnancy can be associated with a mild transient neonatal syndrome of central nervous system, motor, respiratory, and gastrointestinal signs. In a small number of cases, the use of other serotonin reuptake inhibitors after 20 weeks gestation has been associated with an increased risk of neonatal pulmonary hypertension.

27 Case #1 Your patient does well and presents to L&D at 37 weeks in early labor Your patient does well and presents to L&D at 37 weeks in early labor How do you expect labor to affect her heart disease? How do you expect labor to affect her heart disease?

28 Labor physiology Uterine contractions increase preload (equivalent to 1-2 units of blood) and cardiac output up to 80% Uterine contractions increase preload (equivalent to 1-2 units of blood) and cardiac output up to 80% Fluid shifts in a C-section can be even more abrupt>vaginal delivery usually safer Fluid shifts in a C-section can be even more abrupt>vaginal delivery usually safer Labor and the period immediately after delivery represent the period of maximal risk for cardiopulmonary decompensation Labor and the period immediately after delivery represent the period of maximal risk for cardiopulmonary decompensation

29 Case #1 Patient developed pulmonary edema in labor Patient developed pulmonary edema in labor Successfully managed with metoprolol and low dose lasix Successfully managed with metoprolol and low dose lasix C-section for fetal distress C-section for fetal distress Mom and baby boy left hospital doing well Mom and baby boy left hospital doing well

30 Case #2 39 yo G4P2 for new primary care appointment 39 yo G4P2 for new primary care appointment Obese Obese History of pulmonary embolus in prior pregnancy History of pulmonary embolus in prior pregnancy Upreg positive today, 9 weeks by LMP Upreg positive today, 9 weeks by LMP Complaining of mild shortness of breath, O2 sat is 93% Complaining of mild shortness of breath, O2 sat is 93%

31 Case #2 What are some changes in the respiratory and hematologic systems in pregnancy? What are some changes in the respiratory and hematologic systems in pregnancy? How might they affect this patient? How might they affect this patient? What would you do next? What would you do next?

32 Key physiologic changes: pulmonary Increased minute ventilation Increased minute ventilation Mediated by progesterone Mediated by progesterone Increased tidal volume>>respiratory rate Increased tidal volume>>respiratory rate Compensated respiratory alkalosis Compensated respiratory alkalosis Normal ABG in pregnancy: 7.43/29/100 Normal ABG in pregnancy: 7.43/29/100 PaCO 2 of 40mmHg is very abnormal in pregnancy PaCO 2 of 40mmHg is very abnormal in pregnancy Fetus relies on high maternal PaO 2 Fetus relies on high maternal PaO 2

33 Key physiologic changes: pulmonary Greater tendency to pulmonary edema Greater tendency to pulmonary edema Increased cardiac output Increased cardiac output Decreased oncotic pressure Decreased oncotic pressure Leaky capillaries Leaky capillaries Aggressive IV fluids Aggressive IV fluids Meds Meds

34 Sisclone A, Obstetrics and Gynecology, 2003 Causes of non-cardiogenic pulmonary edema in Pregnancy

35 Key physiologic changes in pregnancy: Hematologic Hematologic/Immunologic: Hematologic/Immunologic: Procoagulant factors increase: factor VIII, vWF, fibrinogen Procoagulant factors increase: factor VIII, vWF, fibrinogen Protein S levels markedly reduced Protein S levels markedly reduced Increased risk of venous clots Increased risk of venous clots Greatest risk in post-partum period Greatest risk in post-partum period

36 Key physiologic changes: endocrine Endocrine: Endocrine: Insulin resistance, dyslipidemia Insulin resistance, dyslipidemia Relative TSH suppression in first trimester Relative TSH suppression in first trimester Other thyroid changes Other thyroid changes

37 Key physiologic changes: renal Increased glomerular filtration rate Increased glomerular filtration rate Baseline proteinuria increases Baseline proteinuria increases Drugs metabolized more rapidly by kidney Drugs metabolized more rapidly by kidney Creatinine falls Creatinine falls Collecting system dilates Collecting system dilates

38 Case #2 You want to order a chest x-ray for initial evaluation You want to order a chest x-ray for initial evaluation She is concerned about the effects on the fetus She is concerned about the effects on the fetus What would you say? What would you say?

39 Principles of diagnostic imaging Greater risk of harm by not getting a needed study than getting one Greater risk of harm by not getting a needed study than getting one Little evidence that radiation exposures <5 rads have significant fetal effects Little evidence that radiation exposures <5 rads have significant fetal effects Almost all imaging studies involve radiation well below this level Almost all imaging studies involve radiation well below this level CXR <0.001 rad CXR <0.001 rad Chest CT PE protocol rads Chest CT PE protocol rads CT abdomen/pelvis 0.64 rads CT abdomen/pelvis 0.64 rads

40 How many chest x-rays? A pregnant woman could theoretically receive at least 1,000 chest x-rays without negative effects

41 IV contrast Theoretical concern for effects on fetal thyroid Theoretical concern for effects on fetal thyroid Case reports of women receiving high dose iodine in pregnancy-->no adverse outcomes Case reports of women receiving high dose iodine in pregnancy-->no adverse outcomes General advice: avoid if possible, but use contrast when clinically necessary General advice: avoid if possible, but use contrast when clinically necessary

42 MRI Few studies Few studies Animal evidence shows little risk Animal evidence shows little risk NIH consensus statement NIH consensus statement Recommends MRI be reserved for 2 nd and 3 rd trimester if possible, but can be performed in pregnancy Recommends MRI be reserved for 2 nd and 3 rd trimester if possible, but can be performed in pregnancy Gadolinium Gadolinium Little datause if clinically warranted Little datause if clinically warranted

43 Case #2 CT with PE protocol done: PE CT with PE protocol done: PE Managed with treatment dose low molecular weight heparin, converted to subcutaneous unfractionated heparin at 36 weeks Managed with treatment dose low molecular weight heparin, converted to subcutaneous unfractionated heparin at 36 weeks Vaginal delivery of healthy baby boy Vaginal delivery of healthy baby boy

44 Medical illness and Pregnancy Remember the key physiologic changes Remember the key physiologic changes Have prescribing references available Have prescribing references available Think about what you would do if she werent pregnant Think about what you would do if she werent pregnant Have fun! Have fun!

45 Case discussions A 38 yo woman with hypertension and DM II considering pregnancy A 38 yo woman with hypertension and DM II considering pregnancy A 34 yo woman with hypothyroidism and depression with a positive upreg at 6 weeks A 34 yo woman with hypothyroidism and depression with a positive upreg at 6 weeks A 25 yo woman with asthma who smokes in the second trimester A 25 yo woman with asthma who smokes in the second trimester


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