Pre-pregnancy Evaluation and Planning: Optimizing Outcome in High-Risk Women

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Pre-pregnancy Evaluation and Planning Optimizing
Outcome in High-Risk Women

• Siri L. Kjos, MD
• Harbor-UCLA Medical Center

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Preconception Care Basics
Medical History Review of Systems
Obstetrical History Previous pregnancy outcomes
Medications Teratogenicity
Family History Genetic medical diseases
Social Drugs, smoking, alcohol
Health Lifestyle Diet, ideal weight,
Environmental Work, travel, toxic exposure
Contraception When to discontinue?
Use complete history and physical form
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Preconception CareThe Goal

• What factors can be positively changed to improve
  
• perinatal outcome?
• Maternal
• Neonatal

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Preconception CareGenetic Screening

• Identification of inheritable disorders in family
• Determine if patient and/or partner should be
  screened for carrier status
• Genetic referral?
• Ever-expanding molecular genetic testing
• Counseling for identified disorders

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Preconception CareGenetic Screening

• Common inheritable/genetic disorders
• Tay-Sachs
• Thalassemia
• Sickle cell anemia
• Cystic fibrosis
• Mental retardation (Fragile x)
• Muscular dystrophy, Huntingtons Chorea
• Fetal erythroblastosis (Rh disease)
• Chromosomal anomalies

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Preconception Care Medications

• Prescription
• Daily and irregularly used medication
• Treatment for chronic conditions
• Pain killers, tranquilizers
• Weight loss medication
• Over-the counter
• Alternative or herbal medicines

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FDA Classification for Teratogenicity
Category Type of data Relative risk
A Human studies No risk
B Animal studies Little risk
C No good studies Uncertain risk
D Animal studies Some risk
X Human studies Definite risk
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Known Teratogens
Aminopterin Methotrexate (X) SAb, IUGR, hydrocephalus, cleft palate, ossification defects
Diethylstilbestrol (X) Genital tract malformations Malignancy
Isotretinoin (X) NTD and CNS defects, skull, external ear, cardiovascular, thymus defects, cleft palate
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Known Teratogens
Thalidomide (X) Limb reduction, girdle hypoplasia, olic defects
Warfarin (X) Nasal hypoplasia, stippled epiphysis, CNS abnormalities
Lithium (X) Cardiac defects, Epsteins anomaly
ACE Inhibitors (D) Fetal demise, oligohydramnios, hypoplastic lung, IUGR
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Known Teratogens
Phenytoin (D) Cleft lip/palate, FHS (SGA, microcephaly) Vit K deficiency
Trimethadione (D) FTS (IUGR, mental deficiency, abnormal facies)
Phenobarbitol (D) Similar to phenytoin
Valproic Acid (D) NTD (1-2), cardiac defects
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Preconception Care Drugs

• Alcohol
• Pattern of use?
• Questionnaires CAGE, TACE, TWEAK
• TERATOGENIC Fetal alcohol syndrome (abnormal
  facies, mental retardation, IUGR, microcephaly)
• Cigarette Smoking
• Amount smoked
• IUGR (25), LBW, PTD, Sudden infant Death
• STOP SMOKING!
• Smoking cessation programs, nicotine patches
• Illicit Drug use

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Preconception Care Hepatitis B

• Transmission
• parenteral and sexual contact
• Vertical mother to newborn
• Infected newborns (HbSAg)
• Complete resolution 85-90
• Chronically infected 10-15
• Of these 15-30 develop chronic active dz
  (persisent hepatitis, cirrhosis, hepatocellular
  carcinoma)

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Preconception Care Hepatitis B

• Maternal HbSAg
• 10-20 vertical transmission
• HBeAg and HbSAg 80-90
• Timing of maternal infection
• 1st trimester 10 transmission
• 3rd trimester 80-90 transmission
• Passive active immunization at birth
• 85-90 protection
• ACOG recommend preconception testing
• Immunize high-risk (recombinant DNA)

MMW 1991 40(r13)1-25 ACOG Technical Bulletin
July 1998 No 248
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Preconception Care Immunization
Rubella (live attenuatedMMR or MR) Vaccinate all childbearing non-immune women, avoid pregnancy for 3 Mo (category C no known fetal risk)
Tetanus-diptheria (toxiod) Vaccinate all non-immune or if last booster gt10 yr, OK in pregnancy (category C no known fetal risk)
Hepatitis B (recombinant) High-risk individuals (category C no known fetal risk)
Influenza (inactivated) 3rd Tri pregnancy, Immunosuppressed, chronic dz (diabetes, sickle dz, renal dz, SLE, HIV), health care workers (category C no known fetal risk)
Varicella (live-attenuated) Vaccinate all childbearing non-immune women, avoid pregnancy for 3 Mo (category C no known fetal risk Engerix-B)
Pneumo-coccal High-risk individuals
ACOG Committee Opinion Dec 2000 No 246
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Preconception Care HIV testing

• Maternal Rx during pregnancy reduces vertical
  transmission
• AZT prophylaxis ? from 26 to 8
• Combination Rx transmission rare
• US Public Health, ACOG, IOM
• Recommend Universal testing in pregnancy
• Recommend offering all women testing as part of
  preconception care and counseling

ACOG Statement of Policy May 1999
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(No Transcript)
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http//www.mypyramid.gov/downloads/MyPyramid_Anato
my.pdf
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http//www.mypyramid.gov/downloads/MiniPoster.pdf
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http//www.mypyramid.gov/downloads/worksheets/Work
sheet_1800_18.pdf
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Recommended Weight Gain during Pregnancy based on
Pre-pregnancy BMI
BMI Category Kg lb
Low lt19.8 Kg/m2 12.5-18 28-40
Normal 19.826.0 Kg/m2 11.5-16 25-35
High 26.0-29.0 Kg/m2 7-11.5 15-25
Obese gt 29.0 Kg/m2 7 15
Nutrition During Pregnancy National Academy of
Sciences, 1990
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Nutrition Prescription of a Balanced Diet
Daily Calories 30 Kcal/Kg based on IBW
Fat calories 20 - 30
Saturated fat lt 10
Cholesterol lt 300 mg
Protein 1.6 g/kg
Committee on Diet and Health of the National
Research Council, 1989
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Preconception Care Exercise

• Cardiovascular Fitness
• Ability to maintain prolonged period of physical
  activity
• Low intensity program 30-60 minutes
• 3-4 times per week
• Goal ?aerobic capacity (VO2 max)
• Measure HR (220-age) x 60-80 target HR
• All exercise should be encouraged
• Walking, cycling, swimming, dance

ACOG Technical Bulletin No 173 Oct 1992
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1996 NIH Recommendations for Exercise

• 50 of people do not exercise at all or
  sporadically
• Goal EVERY DAY
• 30 minutes of moderate-intensity exercise
• Yard work, brisk walking, cycling, swimming
• Minutes may be accumulated as long as individuals
  maintained moderate exertion for no less than
  10-15 minutes at a time
• Get sedentary people into daily exercise
• Those already exercising moderately exercise
  more rigorously and more frequently

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Risk of NTD from Heat Exposure
1st Trimester exposure Adjusted RR (CI) Risk 1 exposure
Hot tub Sauna Fever Electric Blanket 2.8 (1.2-6.5) 1.8 (0.4-7.9) 1.8 (0.8-4.1) 1.2 (0.5-2.6) 1.9 (0.9-3.7) Risk 2 exposures 6.2 (2.2-17.2)
Study Population 23,491 women at time of
amniocentesis or MSAFP Adjusted for folate
supplement, family history of NTD, maternal age
other heat source Milunsky, JAMA 1992, 268882-6
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Folic Acid Prevention of NTD
Folic acid Gestational weeks NTD RR (CI)
Yes 1-6 0.09 0.27 (0.1-0.6)
No 1-6 0.32 0.93 (0.3-3.3)
Yes 7-12 0.32 0.92 (0.5-1.9)
No gt12 0.35 1
Milunsky, JAMA 1989, 2622847
n22,591
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Recommendation for Folic Acid Supplementation in
Reproductive-age Women

• All women of childbearing age capable of becoming
  pregnant
• Should consume 0.4 mg/d of folic acid
• Total consumption should be lt 1.0 mg/d
• High-risk women (with prior infant with NTD)
  should consult MD
• General population risk of NTD 1/1,000
• MMWR 1992, Sept 11, 41 (R-14)1-7

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Folic Acid Prevention of NTDMRC Vitamin Study
Research Group Multi-center Double-blind
Randomized Trial in Women with a History of
Infant with Prior Neural Tube Defect
Folic Acid cases of NTD NTD RR (CI)
4.0 mg/d 6/593 1 0.28 (0.32-0.71)
0.1 mg/d 21/602 3.5 1
Lancet 1991, 338131
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Prevention of Recurrent NTD

• General risk of recurrent NTD 2-3
• Recommend folic acid 4.0 mg/d
• Prior to conception
• Continue until the 12th week of pregnancy
• Other high-risk groups
• Epilepsy on AED Diabetes
• Lancet 1991 338131

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Preconception Care Folic Acid
? Requirement Accelerated eythropoiesis for placental fetal DNA synthesis
RDA for folic acid 0.8 mg/d
Multivitamins 0.2 0.4 mg/d
Prenatal vitamins 1.0 mg/d (requires Rx)
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Preconception Care Past Obstetrical History

• History of prior fetal loss after documented
  cardiac motion
• Thrombophilic disease (History of
  hypercoagulopathy)
• Anti-phospholipid syndrome
• Anti-cardiolipin Ab (aCL)
• Lupus anti-coagulant (LAC aPTT, KCT (Exner),
  RVVT)
• Anti-thrombin III deficiences
• Activated Protein C Resistence
• Protein S Protein C deficiencies
• Incompetent cervix (painless loss, PTD)
• Uterine anomaly
• Coexisting medical disease
• Prior cesarean deliveries ?risk of previa/accreta

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Preconception CareWomen with Medical Disease

• Establish pregnancy risk
• Complete medical evaluation/therapy
• Diagnostic evaluation/ consultation
• Surgery or procedures
• Determine optimal medical control of preexisting
  disease
• Titrate medicine to lowest dose, safest Rx
• Effective contraception until
• Completed health evaluation
• Optimal health status

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Preconception care DiabetesEuglycemic Control
Major anomaly Diabetic diet Education Insulin Glycemic GOAL type 1 2 6-12 Poor control 25-30 Based on IBW, teach exchange system Recognize/treat hypo- hyperglycemia type 1 Titrate insulin to achieve euglycemia type 2 2-3 months oral meds/diet/ exercise/ weight loss before insulin Self-monitor blood glucose HbA1c lt 7.0 (lt6.0)
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Preconception Care Diabetes
Co-manage Health Obesity Exercise Vitamins Hypertension Nephropathy Retinopathy Neuropathy Obstetrician internist (diabetes team) Pneumococcal Influenza vaccine Diabetes diet, achieve IBW Daily cardiovascular exercise Prenatal vitamins (1.0 mg/d folate) Control BP (ACEI), EKG Evaluate microalbuminuria, CrCl, Cr, BUN Opthalmology examination and therapy Complete evaluation
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Preconception Care Epilepsy
Consult Major anomaly Counseling History Vitamins Medication With Neurologist assess need for anti-epileptic Rx With anti-epileptic Rx up to 10 (?2-3 xs) Do not stop meds unless instructed by neurologist Last seizure, compliance with medication Obtain serum levels of medication Prenatal vitamins (folate 1.0 mg) Lowest dose of monotherapy which controls seizure, select least-risk med if possible
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Preconception Care Cardiac Disease
Co-manage Counseling Newborn risk Evaluation With Cardiologist Assess pregnancy risk 1) type of lesion 2) Functional cardiac status (NYHAC) Maternal mortality (lt1 to 50) May have complicated pregnancy, Prolonged hospitalization, mortality risk Prematurity, IUGR History, record review, ECG, echo, stress test, cardiac catherization, surgery
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Preconception Care Cardiac Disease
Medication GOAL Nutrition Exercise Most cardiac meds not teratogenic Exceptions ACEI and warfarin Optimize health prior to pregnancy Titrate medication, Corrective surgery before pregnancy if indicated Lifestyle (weight, smoking, etc) Special needs (salt restriction, IBW) Program per cardiologist
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Preconception Care Mitral Valve Prolapse
Prevalence Work-up Counseling High-risk lesion Antibiotics Frequently over-diagnosed New studies suggest prevalence of 2.4, occurring equally in females males Consult with cardiologist Echocardiograph (if not recently done) Majority are asymptomatic Left atrial enlargement, mitral insufficiency Serious arrhythmia, prior thrombosis? Treat as functional cardiac disease Prophylaxis may not be necessary
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Preconception Care Chronic Anticoagulation
Candidates for Anticoagulation Consult Mechanical prosthetic valves Cardiac arrhythmias at risk for embolism Antithrombin III deficiency, Protein C and Protein S deficiency Antiphospholipid syndrome Prior DVT or thromboembolism associated With pregnancy, oral contraceptives or At high risk of recurrence With internist Assess need for anti-coagulation
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Preconception Care Chronic Anticoagulation
Counseling Preconception Treatment Nutrition If on warfarin therapy Teratogenic exposure 6-9 weeks GA ?CNS abnormalities in 2nd 3rd trimester (10 risk) Stop warfarin if possible ? initiate heparin or low-dose heparin Alternative discontinue warfarin when late for menses Calcium supplementation on heparin
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Preconception Care Chronic Hypertension
Consult Counsel Evaluation With Internist Pregnancy risk depends on BP control, coexisting disease, renal function May have complicated and prolonged hospitalization, ? preeclampsia risk, ? preterm delivery, ?IUGR For cardiovascular or peripheral disease EKG, CXR, symptoms of angina Opthalmologic exam of fundi Renal function Cr BUN, CrCL, 24H urine for protein, microalbuminuria
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Preconception Care Chronic Hypertension
Nutrition Exercise Treatment goal Low-salt, balanced diet for IBW Daily cardiovascular exercise (per MD) Control of BP (lt130/85) Switch to antihypertensive therapy acceptable in pregnancy Stop ACE-I, AIIRA medications
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Preconception Care Systemic Lupus Erythematous
Comanage Counseling Neonatal Pregnancy Prognosis Complications With internist, rheumatologist May have complicated prolonged hospitalization, ? bedrest, ?preeclampsia ?SAb, ?prematurity, ?IUGR, ?stillbirth Inactive dz (gt6 mo) 66 stay in remission 92 perinatal survival Active dz High risk complications 55 with ?Platelets (with aCL) and preeclampsia Hypertension, proteinuria Rare Classic SLE flare (13) pleursy, fever, rash, arthritis
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Preconception Care Systemic Lupus Erythematous
Examination Vaccination Medications Goal CBC (platelets), Complement level-C3/C4 Antibodies ANA, aCL, LAC, anti-SSA (Rh), anti-SSB (La) Renal function Cr BUN, CrCL, 24H urine for protein, microalbuminuria Pneumococcal Influenza Prednisone, NSAIDs, Cytotoxics (cyclophosphamide) Avoid pregnancy until in remission gt6 mo Control BP, proteinuria
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Preconception Care Chronic Renal Failure
Co-manage High-risk Triad (any 2) Severe CRF Moderate CRF With internist Chronic renal failure (Cr gt1.5) Nephrotic syndrome (gt3.0 g/d proteinuria) Hypertension (diastolic BP gt 90 mmHg) Cr gt3.0 mg/dl Pregnancy inadvisible End-stage renal disease likely Cr 1.5-3.0 mg/dl 25-30 irreversible acceleration to ESRD
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Preconception Care Renal Disease on Dialysis
Fertility Preconception Care Perinatal Pregnancy course Complications Recommend Sporadic ovulation, require contraception ?unexpected, late dx of pregnancy Control hypertension Anti-coagulation (shunt) stop warfarin ? heparinize PNM up to 80, ?2nd tri loss, ?PIH 40IUGR (40), 60PTD (lt32 wk) Dialysis 3-5 xs/wk (BUN lt70 mg/dl) ? ?intrauterine azotemia, Anemia (epoeitin a injection), calcium Pregnancy after transplant
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Preconception Care Sickle Cell Disease
Counseling Genetic Pregnancy Prognosis Examination Consult, co-manage with internist ?SAb, ?PTD, ?IUGR, ?stillbirth, ?PIH Perinatal mortality up to 15 Autosomal recessive offer partner testing Depends on sequelae Vascular occulsive crisis ?with infection, dehydration, hypoxia ?UTI, ?pulmonary infection CBC, Ferritin Iron levels, Urine culture
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Preconception Care Sickle Cell Disease
Coexisting Dz Medication Vaccination Treatment goal Evaluation of pulmonary renal function cardiac status (EKG, CXR), BP Folate (1 mg/d) Pneumococcal Influenza Optimize health
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Preconception Care

• Minimize the risk
• Optimize maternal health
• Use contraception until evaluation complete and
  health optimized
• Stress the positive steps your patient can do to
  improve her outcome
• Share control/responsibility for her health