4. Medical Complications of Pregnancy: A Brief Review for the Internal Medicine Resident Kristen Amann, MD July 9, 2010

5. Quick Reminders Give all pregnant women folate to prevent neural tube defects (most effective in the 1 st trimester) Treat asymptomatic bacteruria (20% will develop cystitis and/or pyelonephritis) hCG doubles every 2 days in the first trimester –Home pregnancy tests: positive ~ 2 weeks after conception Gravid uterus: abdomen at 12 weeks, umbilicus at 20 weeks GP nomenclature: –G (gravida): # of times pregnant –P (para): # births >20 weeks gestation (term), (preterm), (abortions), (living children)

6. Some Pertinent Teratogens Acyclovir ACE Inhibitors Diazepam Fluconazole Lithium Warfarin Aminoglycosides Isotretinoin (Accutane) Antineoplastic agents Carbamazepine Methotrexate Trimethoprim Tetracycline Phenytoin (Dilantin)

8. Sheehan’s Syndrome (Postpartum Pituitary Necrosis) Major obstetric hemorrhage resulting in hypovolemic shock and subsequent anterior pituitary ischemia and necrosis Most common cause of anterior pituitary insufficiency in females –Total: 0.5% of all hypopituitarism cases Clinical presentation: –Severe (recognized within the first days to weeks): lethargy, anorexia, fatigue, agalactorrhea –Less severe (weeks, months, or even years after delivery): agalactorrhea, failure to resume menses, lethargy Physiology: –Hypertrophy and hyperplasia of lactotrophs during pregnancy resulting in enlargement of the anterior pituitary –Anterior pituitary supplied by low pressure venous system (versus posterior pituitary having direct arterial supply). –Major hormones secreted: TSH, ACTH, LH, FSH, GH, prolactin If blood loss is severe, immediately treat for presumed adrenal insufficiency

9. Diabetes Mellitus Optimization of pre-conceptional DM and during key periods of organogenesis can reduce risk for fetal malformations –Sacral agenesis, caudal dysplasia, renal agenesis, VSD, hypertrophic cardiomyopathy, etc. Increased risk for preeclampsia DM + microvascular disease: higher risk for IUGR Fasting glucose goals: 105-140 Treatment: diet, insulin –ADA and ACOG do not endorse oral hypoglycemic agents

10. HELLP Hemolysis, Elevated Liver enzymes, Low Platelets Develops in 10-20% of patients with severe preeclampsia/eclampsia Overall occurrence: 1-2 per 1,000 pregnancies Usually occurs in 3 rd trimester but can occur in 2 nd and post- partum Clinical: –RUQ/epigastric pain, nausea, vomiting, malaise –MAHA, Plt 70, LDH >600 Significant morbidity: DIC, AKI, ARDS, subcapsular liver hematoma, etc. Treatment: delivery, supportive management, HTN control, magnesium (seizure prevention), platelet transfusion for <20,000 or for significant bleeding

11. Acute Fatty Liver of Pregnancy Usually in the 3 rd trimester but may occur in the 2 nd Maternal mortality: <3% More common with male fetus Etiology hypothesis: Disordered metabolism of fatty acids in the patient’s mitochondria caused by LCHAD (long-chain-3- hydroxyl acyl DH) deficiency Clinical: –Liver is typically small –Transaminitis (<500 IU/L), elevated bilirubin, elevated ammonia, hypoglycemia, prolonged INR Usually necessitates termination of pregnancy due to fetal distress Treatment: supportive care, fetal delivery Recurrence is rare

12. Thromboembolic Disease Hypercoagulable state: stasis, changes in venous capacitance, increase in factor levels, decrease in protein S, progressive protein C resistance in 2 nd and 3 rd trimesters, Pulmonary embolism = most common cause of maternal death in the US DVT: more common in LLE versus RLE (left iliac vein compression) –25%: carriers of the factor V Leiden allele (activated protein C resistance) –Additional genetic mutations: prothrombin G20210A mutation (hetero- and homozygotes), methylenetetrahydrofolate reductase C677T mutation (homozygotes) Treatment: heparin (or LMWH) –Warfarin contraindicated during pregnancy, but not in breast-feeding mothers

13. Gestational Trophoblastic Neoplasia Spectrum of lesions arising from the trophoblastic epithelium of the placenta: –Hydatidiform mole (complete or partial) –Invasive mole –Placental-site trophoblastic tumor Cytotrophoblast cells arising from placental implantation site –Choriocarcinoma Anaplastic trophoblastic tissue with both cytotrophoblastic and syncytiotrophoblastic components, no villi Elevated  -hCG without an existing pregnancy Incidence: 1 per 1,500 pregnancies (10-fold higher in Asia) –Choriocarcinoma: 1 in 25,000 pregnancies Approximately 50% of patients had a prior molar pregnancy Frequently metastasizes (lung, brain, vagina) Think about this in females of child-bearing age with multiple pulmonary nodules Add to differential for premenopausal women with irregular vaginal bleeding

14. Thanks for listening! (See next slide for sources)

15. Sources Dunaif, A. Women’s Health. Harrison’s Principles of Internal Medicine, 16 th edition. McGraw-Hill, New York. 2005. Snyder, P. Causes of Hypopituitarism. www.uptodate.com. Teratogens. http://sis.nlm.nih.gov. The American College of Obstetrics and Gynecology. www.acog.org. Young, D. Gynecologic Malignancies. Harrison’s Principles of Internal Medicine, 16 th edition. McGraw-Hill, New York. 2005.