Common Medical Complications in Pregnancy

1. Common Medical Complications in Pregnancy Susan M Cox, MD 4.27.2014

2. Milestone 1 • Basic understanding of the pathophysiology and management of gestational hypertensive diseases • Basic understanding and management of Diabetes Mellitus complicating pregnancy

3. Objectives • Review the diagnosis and treatment of common medical conditions seen in pregnancy • Hypertension • Diabetes • Hyperthyroidism • Recognize the maternal and fetal complications of each

4. Case 1 • A 23-year-old G1P0 presents at 39 weeks with concerns for swelling in her face and hands over the last 3 days. Her blood pressure is 155/99. A 24-hour urine collection shows 440mg of protein. What is the treatment for her disease? • Delivery • Furosemide • Hydralazine • Magnesium sulfate • Management of fluids

5. Epidemiology and Risk Factors • First Pregnancies • Multiple Gestations • Maternal Vascular Disorders • Diabetes Mellitus (Types 1 And 2) • Lupus Erythematosus • Renal Disease • Antiphospholipid Antibody Syndrome • Obesity • Advanced Maternal Age • African-American Race • Chronic Hypertension. Complicates 8% of pregnancies

7. Terminology • Chronic hypertension • Chronic hypertension with superimposed preeclampsia • Gestational hypertension • Preeclampsia and eclampsia

8. Hypertensive Disorders in Pregnancy • Chronic Hypertension • Dx: BP >140/90 • Prior pregnancy or • Noted prior to 20th week EGA or • Persists beyond 12 weeks postpartum

9. Hypertensive Disorders in Pregnancy • Chronic HTN • Treatment Goal: DBP <100 (<90 if end organ damage) • Treatment options (starting dose) • Methyldopa 250 mg PO bid • Labetalol 100 mg PO bid • Nifedipine 30 mg PO q day • Hydralazine 10 mg PO qid

10. Hypertensive Disorders in Pregnancy • Chronic hypertension with superimposed preeclampsia • Gestational age > 20 weeks • Proteinuria >300 mg / 24 hours (when it didn’t exist at gestational age < 20 weeks) OR • BP >160 / 110 (when it was under control at earlier gestational age )

11. Hypertensive Disorders in Pregnancy • Gestational Hypertension • Dx >140/90 on two occasions • Gestational age >20 weeks and normal BP earlier in pregnancy • No proteinuria (<300 mg / 24 hours on spot urine estimation)

12. Hypertensive Disorders in Pregnancy • Gestational Hypertension • Treatment Goal: DBP <100 ( <90 with end organ damage) • Treatment options • Methyldopa • Labetalol • Nifedipine • Hydralazine

13. Hypertensive Disorders in Pregnancy • Pre-eclampsia • Hypertension >140/90 on two readings • Proteinuria >300 mg / 24 hours on spot estimation • Gestational age > 20 weeks • Normal blood pressures earlier in pregnancy

14. Hypertensive Disorders in Pregnancy • Pre-eclampsia • Treatment options • Depends of gestational age and severity criteria

15. Hypertensive Disorders of Pregnancy • Criteria for severe pre-eclampsia • SBP >160 or DBP >110 • Proteinuria > 5 grams / 24 hours • Oliguria <500 ml / 24 hours • Pulmonary edema • Thrombocytopenia (<100,000) • Liver dysfunction (AST or ALT > 2x normal) or liver distention (RUQ pain / N/V ) • Neurologic dysfunction • IUGR • Eclampsia

16. HELLP Syndrome • Hemolysis • Elevated Liver Enzymes • Low Platelets Deliver the baby! Dexamethasone not effective (Am J of Obstet Gynecol 2005 Nov; 193(5):1591-1598)

17. Clinical Management Pearls • Pre-eclampsia • Preterm • Betamethasone 12 mg IM q 24 hours x 2 doses (EGA < 34 weeks) • Observation if BPP reassuring and no severe criteria • Term • Expedite delivery

18. Clinical Management Pearls • Eclampsia prevention • Magnesium Sulfate • 4 gram load IV then 2 gram/hr IV • Monitor for • Oliguria • Loss of reflexes • Somnolence • Respiratory depression • Continue Mag SO4 for 24 hours post-partum

19. Maternal Cardiovascular Consequences

20. Case 2 • A 34 year old G2 P1 presents for her first prenatal visit at 25 weeks’ gestation. She had no prenatal care during her first pregnancy which ended in a term stillborn whose birth weight was 10.5 pounds.   • Past medical history is negative for hypertension, diabetes, and substance abuse. She denies alcohol use, smoking, or trauma. Her previous pregnancy was via Caesarean delivery because of failed induction times 3 and CPD. • Physical Examination is unremarkable except for a gravid uterus at 26 cm height with fetal heart tones: 144/min. • Routine Prenatal Labs: • Hemoglobin: 12.6 g/dL • WBC: 7800 • Creatinine: 0.6 mg/dL • Random blood sugar: 130 • One-hour glucola: 165

21. What is the next step in her work-up? 100 gram glucola (3 hr GTT)

22. GDM Risk Factors • Traditional risk factors • Family history • Previous macrosomic infant • Poor obstetric history • Glycosuria identify only 40-60% of cases of GDM

23. Gestational Diabetes Mellitus • Criteria for no screening: • Age <25 • No history of GDM / DM 2 • No first degree relative with DM 2 • Pre-pregnancy body weight normal • No history of poor obstetrical outcome • Not a member of higher risk ethnic group (Hispanic / African American / Pacific Islander / Native American / South or East Asian) Fifth International Workshop Conference on GDM certain features place women at low risk of GDM, and it may not be cost-effective to screen this group of women. Represents only 10% of population.

24. Gestational Diabetes MellitusScreening • 50 gram Glucola (1 hour glucola) • 24-28 weeks EGA (+/- 1st trimester screen) • No fasting required • Nurse can give drink at beginning of encounter • Single lab draw 1 hour after drinking glucola • Screening cut-off • 130 = 23% require 30 GTT and identifies additional 10% of GDM cases • 140 = 14% require 30 GTT

25. GDM Diagnostic Test • Confirmation with a 100 gram glucola (3 hr GTT) • Fasting for 8 – 10 hours • Draw fasting glucose level • Drink glucola • Draw 1, 2 and 3 hour PP values

26. 3 hour GTT cutoffs • Carpenter and Coustan Criteria • Fasting <95 • 1 hour <180 • 2 hour <155 • 3 hour <140 A positive test for GDM is 2 of 4 values abnormal

27. GDM Goals of Treatment Fasting < 95 AND One hour PP < 130 OR Two hour PP < 120

28. Treatment for GDM • Diet (medical nutritional therapy) • Insulin • Glyburide • Metformin

29. Oral therapy for GDM • Glyburide 1. No difference in maternal / neonatal outcomes • Most authorities still cautious about recommending due to placenta crossing, but gaining acceptance • Start Glyburide 2.5 mg PO q day • Titrate to maximum dose 20 mg PO q day

30. Oral Therapy for GDM • Metformin • No randomized trials (i.e. insulin vs. metformin) • Data comes from cohorts treated into pregnancy for infertility / PCOS / etc. • No significant safety concerns at this point

31. Antepartum Monitoring of GDM • GDM A1 NST / AFI >38 weeks • GDM A2 NST / AFI >32 weeks

32. Risk of future DM 2 • GDM = Pre-Diabetes • 75 gram glucola at PP visit and yearly thereafter

33. Maternal And Fetal Consequences • Current pregnancy • Future prognosis for mom • Future prognosis for baby

34. Case 3 34-year-old G4 P3 at 19 weeks presents to the emergency department with chest pain, palpitations and sweating, which began 4 hours ago. She notes that she has been very anxious lately and is not sleeping well, which she attributes to the pregnancy. She reports that she has lost 30 pounds in the last year while not dieting. She denies significant medical problems.

35. Case 3 Examination: patient appears diaphoretic and anxious, her eyes are wide open, prominent, and you can easily see the sclera surrounding the pupil. Her temperature is 38.1; pulse is 132; and her blood pressure is 162/84. Height is 1.75 meters (70”) and weight is 58 kg (128 lb.). Her thyroid is palpably enlarged, with an audible bruit. Electrocardiogram shows sinus tachycardia. Remaining labs are pending.

36. Case 3 • What is the most likely diagnosis? • Anxiety • Heatstroke • Serotonin Syndrome • Thyroid Storm • Anticholinergic toxicity  

37. Hyperthyroidism • Affects 0.2% of pregnancies • Prevalence 0.1% to 0.4%, with 85% Graves’ disease • Single toxic adenoma, multinodular toxic goiter, and subacute thyroiditis • gestational trophoblastic disease, viral thyroiditis and tumors of the pituitary gland or ovary (Struma Ovarii)

38. Physiologic Changes in Thyroid Function During Pregnancy

39. Graves’ disease • 95% of thyrotoxicosis during pregnancy • Activity level fluctuate during gestation • exacerbation during the first trimester • gradual improvement during the latter half • exacerbation shortly after delivery • Clinicalscenarios • stable Graves’ disease receiving thionamidetherapy with exacerbation during early pregnancy. • in remission with a relapse of disease. • without prior history diagnosed with Graves’ disease de novo duringpregnancy.

40. Graves’ disease • Diagnosis • difficult: hypermetabolic symptoms in normal pregnancy • thyroid examination: goiter (with or without bruit) • suppressed serum TSH level and usually elevated free and total T4 serum concentrations • TSH receptor antibodies • complications related to the duration and control of maternal hyperthyroidism • autoantibodies mimic TSH and can cross the placenta and cause neonatal Graves’ disease

41. Graves’ disease • Pregnancy outcome • preterm labor • untreated (88%)/partially treated(25%) /adequately treated (8%) • preeclampsia • untreated twice the risk • stillbirth • untreated (50%) /partially treated (16%) /adequately treated (0%) • small for gestational age • congenital malformations

42. Thyroid storm • Obstetric emergency • Extreme metabolic state • 10% of pregnant women with hyperthyroidism • High risk of maternal cardiac failure. • Fever, change in mental status, seizures, nausea, diarrhea, and cardiac arrhythmias. • Inciting event (e.g., infection, surgery, labor/delivery) and a source of infection • Treatment immediately, even if serum free t4, free t3, and TSH levels are not known. • Untreated thyroid storm can cause shock, stupor, and coma.

43. Treatment of Hyperthyroidism • Goal is to maintain FT4/FTI in high normal range using lowest possible dose (minimize fetal exposure) • Measure FT4/FTI q2-4 weeks and titrate • Thioamides (PTU/methimazole) -> • decrease thyroid hormone synthesis blocks I organification • PTU also reduces T4->T3 and may work more quickly • PTU traditionally preferred (methimazole crossed placenta and associated with fetal aplasia cutis; newer studies refute this)

44. Treatment of Hyperthyroidism • Median time to normalization of maternal thyroid function • 7 weeks with PTU • 8 weeks with methimazole • Breastfeeding safe when taking PTU/ methimazole

45. Treatment of Hyperthyroidism • Beta-blockers can be used for symptomatic relief (usually Propanolol) • Reserve thyroidectomy for women in whom thioamide treatment unsuccessful • Iodine 131 contraindicated (risk of fetal thyroid ablation especially if exposed after 10 weeks); avoid pregnancy/breastfeeding for 4 months after radioactive ablation

46. Maternal Complications • Increased risk of stillbirth • Preterm delivery • Intrauterine growth restriction • Preeclampsia • Heart failure • Spontaneous abortion • Increased maternal mortality

47. Fetal Complications • Fetal thyroid hyperfunction or hypofunction caused by TSH abs • Fetal goiter from excessive antithyroid drug treatment • Neonatal thyrotoxicosis • Increased perinatal maternal mortality • Decreased IQ of offspring because of excessive use of antithyroid drugs

48. Good Luck!