3 Goals At the end of this talk, you will be able to: Confidently prescribe needed medications in pregnancyOrder diagnostic imaging safely for your pregnant patientsAct on evidence-based recommendations for management of common medical problems in pregnancy
4 Outline Major physiologic changes in pregnancy and effects on disease Diagnostic imaging and prescribing in pregnancyCases on commonly encountered conditionsDiabetes and hypertensionAsthma and tobacco useHypothyroidism and depression
5 Medical Illness in Pregnancy: Changing Trends in Maternal Age National Center for Health Statistics, July 2006
6 Effects of increased maternal age More preconception chronic diseaseMore women with severe illnesses of childhood surviving to reproductive ageCongenital heart dzType I DMAll women in Nova Scotia Canada who delivered bet Adjusted rates c/w reference rate of 1 for ages Chronic disease includes cardiac arrhythmia, congenital heart disease, CAD, endocarditic, mi, CM, plum htn, RHD, thyroid dz, renal dz, IBD, etc.Joseph, K, Obstetrics and Gynecology, 2005
8 Effects of increased maternal age Obstetric complicationsHigher rates of placental abruption, previa, preterm birth and SGA infantsOverall rates of poor outcomes low
9 Pregnancy and chronic disease Pregnancy likely to unmask occult chronic diseaseGlucose intoleranceRenal dysfunctionHypercoaguable statesValvular heart diseaseCerebral aneurysmPregnancy as a “stress test for life”Kaaja and Greer, JAMA 2006
10 O'Sullivan, J, Diabetes 1991; JAMA 1982; Kaaja, JAMA 2005 Postpartum effectsIncreased rates of postpartum chronic diseaseWomen with GDM have up to 75% likelihood of developing Type II DM in subsequent five yearsWomen with preeclampsia more likely to develop CAD and stroke later in lifeHigher rates of hypertension, insulin resistance, dyslipidemia and inflammatory markersPrimary prevention could play an important roleO'Sullivan, J, Diabetes 1991; JAMA 1982; Kaaja, JAMA 2005
11 Approach to Medical Illness in Pregnancy Great need for primary providers to understand medical illness in pregnancyManagement of medical illness including appropriate contraceptionPreconception counseling and patient educationCollaboration with subspecialists, MFM’s
12 Approach to Medical Illness in Pregnancy The tools you need:An understanding of the physiologic changes of pregnancy and how they affect diseaseA basic knowledge of pregnancy specific illnessesA strategy for evaluating drug safety and diagnostic imaging in pregnancy
13 Case 1 23 yo G1 at 9 weeks Immigrant from Mexico Feeling well with the exception of mild nauseaOn examBP 105/60, HR 904/6 systolic murmur at apexaxilla
14 Case 1 How does the cardiovascular system change in pregnancy? How might these changes affect a patient with cardiac disease?What would you do?
15 Key physiologic changes: cardiovascular Hemodynamic changesBlood volume/cardiac output increase50% increase, with half of this by 8 weeksMaximum blood volume expansion at 28 weeksLabor may increase cardiac output another 50%10-20% increase in HR25% decrease in systemic vascular resistanceSystolic BP decreases by 5-10mmHg, diastolic by 10-15mmHg
16 Key physiologic changes: cardiovascular Oncotic changes:Increased plasma volume by 50%Increased red cell mass by 33%Resulting dilutional anemia
17 Effects on valvular heart disease Regurgitant lesions improve with lower SBPStenotic lesions worsenIncreased HR and CO increase cardiac workGradient across stenotic valve increases25% of women with mitral stenosis present in pregnancyRisk factors for decompensationMitral stenosis: increased heart rateAortic stenosis: sudden blood lossRegurgitant lesions: increased preload
18 Predictors of poor outcome in women with heart disease New York Heart Association Class III or IVSymptoms with less than ordinary physical activity or at restHistory of prior cardiac event or arrhythmiaLeft sided obstruction in mitral or aortic valveEjection fraction less than 40%Siu, SC, Circulation 2001
19 Case 1 Echo shows rheumatic mitral stenosis The cardiologist recommends meds to control her heart rateHow would you decide which medicines are safe to give her in pregnancy?
20 Prescribing in pregnancy Do not start any medication unless clearly indicatedDo not discontinue medicines that successfully maintain the maternal condition unless there are clear indications to do soAsk about and document non-prescription medsLee R, 2000
21 Prescribing in pregnancy Have a pregnancy medication reference availableFavor older medicines with longer record of useCheck blood levels and consider increased and/or more frequent dosingIncreased volume of distribution, hepatic and renal clearanceIncreased production of binding proteins—free drug levels are betterPowrie, R SGIM 2000
22 Prescribing in pregnancy Educate and negotiate with your patientPregnant women more likely to stop needed medsReport adverse outcomesAdd websAlways consider the effect of not treatingRemember that few drugs are absolutely contraindicated
23 Drugs to avoid in pregnancy ACE inhibitors: renal dysgenesisTetracycline: abnormalities of bone and teethFluoroquinolones: abnl cartilage developmentSystemic retinoids: CNS, craniofacial, CV defectsWarfarin: skeletal and CNS defectsValproic acid: neural tube defectsNSAIDS: bleeding, premature closure of the ductus arteriosisLive vaccines (MMR, oral polio, varicella, yellow fever): may cross placentaLee, R 2000
24 Limits of the FDA classification Hard to rememberMay be misleadingUp to 60% of category X drugs have no human dataNo information on degree of riskA drug may end up in category X simply if it has no utility in pregnancyRarely updatedSciali, 2004 accessed from
25 Good References for Drug Prescribing Briggs, Freeman, and Yaffe: Drugs in Pregnancy and Lactation, 2005.Lee, Rosene-Montella, Barbour, Garner, Keely: Medical Care of the Pregnant Patient, 2000.(reprorisk)(free)Hale, T: Medications and Mother’s Milk, Also
26 Example from ReprotoxAgent Summary—Citalopram (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.Reprotox website 2006
27 Case #1Your patient does well and presents to L&D at 37 weeks in early laborHow do you expect labor to affect her heart disease?
28 Labor physiologyUterine 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 saferLabor and the period immediately after delivery represent the period of maximal risk for cardiopulmonary decompensation
29 Case #1 Patient developed pulmonary edema in labor Successfully managed with metoprolol and low dose lasixC-section for fetal distressMom and baby boy left hospital doing well
30 Case #2 39 yo G4P2 for new primary care appointment Obese History of pulmonary embolus in prior pregnancyUpreg positive today, 9 weeks by LMPComplaining of mild shortness of breath, O2 sat is 93%
31 Case #2What are some changes in the respiratory and hematologic systems in pregnancy?How might they affect this patient?What would you do next?
32 Key physiologic changes: pulmonary Increased minute ventilationMediated by progesteroneIncreased tidal volume>>respiratory rateCompensated respiratory alkalosisNormal ABG in pregnancy: 7.43/29/100PaCO2 of 40mmHg is very abnormal in pregnancyFetus relies on high maternal PaO2
33 Key physiologic changes: pulmonary Greater tendency to pulmonary edemaIncreased cardiac outputDecreased oncotic pressureLeaky capillariesAggressive IV fluidsMeds
34 Causes of non-cardiogenic pulmonary edema in Pregnancy Sisclone A, Obstetrics and Gynecology, 2003
35 Key physiologic changes in pregnancy: Hematologic Hematologic/Immunologic:Procoagulant factors increase: factor VIII, vWF, fibrinogenProtein S levels markedly reducedIncreased risk of venous clotsGreatest risk in post-partum period
36 Key physiologic changes: endocrine Insulin resistance, dyslipidemiaRelative TSH suppression in first trimesterOther thyroid changes
37 Key physiologic changes: renal Increased glomerular filtration rateBaseline proteinuria increasesDrugs metabolized more rapidly by kidneyCreatinine fallsCollecting system dilates
38 Case #2 You want to order a chest x-ray for initial evaluation She is concerned about the effects on the fetusWhat would you say?
39 Principles of diagnostic imaging Greater risk of harm by not getting a needed study than getting oneLittle evidence that radiation exposures <5 rads have significant fetal effectsAlmost all imaging studies involve radiation well below this levelCXR <0.001 radChest CT PE protocol radsCT 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 Case reports of women receiving high dose iodine in pregnancy-->no adverse outcomesGeneral advice: avoid if possible, but use contrast when clinically necessary
42 MRI Few studies NIH consensus statement Gadolinium Animal evidence shows little riskNIH consensus statementRecommends MRI be reserved for 2nd and 3rd trimester if possible, but can be performed in pregnancyGadoliniumLittle data—use if clinically warranted
43 Case #2 CT with PE protocol done: PE Managed with treatment dose low molecular weight heparin, converted to subcutaneous unfractionated heparin at 36 weeksVaginal delivery of healthy baby boy
44 Medical illness and Pregnancy Remember the key physiologic changesHave prescribing references availableThink about what you would do if she weren’t pregnantHave fun!
45 Case discussionsA 38 yo woman with hypertension and DM II considering pregnancyA 34 yo woman with hypothyroidism and depression with a positive upreg at 6 weeksA 25 yo woman with asthma who smokes in the second trimester