1. Breeding Trouble Early Complications & Diabetes Jennifer K. McDonald

2. Spontaneous Abortion u Delivery before the 20 th completed week of gestation u Implies fetus less than 500 grams

3. Incidence u 15% clinically evident pregnancies u 60% chemically evident pregnancies u 80% occur prior to 12 weeks gestation

4. Etiology

5. Genetic Abnormalities Aneuploidy = abnormal number of chromosomes u Autosomal trimsomies 50% losses u Trisomy 16 most common autosomal trisomy u Monosomy X (Turners) = most common aneuploidy (20%) u Polyploidy found in 20% miscarriages Typically results in blighted ovum

6. Terminology u Complete abortion u Incomplete abortion u Inevitable abortion u Missed abortion u Septic abortion

7. Threatened vs Inevitable Threatened Abortion 20% pregnancies experience 1 st trimester bleeding Cervix remains closed Inevitable Abortion Abdominal or back pain and bleeding with an open cervix. Abortion is inevitable when cervical dilation, effacement, and/or rupture of membranes is present

8. Complete vs Incomplete Complete Abortion Passage of the entire conceptus. Bleeding continues for short time and pain usually ceases. Incomplete Abortion Products of conception have partially passed from the uterine cavity. Cramping usually present. Bleeding can be severe. Missed Abortion Pregnancy has been retained after the death of the fetus.

9. Blighted ovum u Anembryonic pregnancy u Fertilization without subsequent development of embryonic tissue

11. Maternal Factors u Maternal infection u Congenital uterine defects (25-50% risk) u Acquired uterine defects (fibroids) u Immunologic disorders u Severe malnutrition u Toxic factors (radiation, alcohol, antineoplastic drugs) u Trauma

12. Diagnosis u Vaginal bleeding u Abdominal pain u Need to rule out ectopic pregnancy u Decreased symptoms of pregnancy u Abnormally rising  hCG u Abnormal ultrasound findings

13. Treatment u Expectant management u D&C u Important to know blood type & Rh u Rhogam for Rh - blood types

14. Recurrent Abortion u 3 or more consecutive losses before 20 weeks gestation u Incidence 0.4-1% Recurrence risk higher if the embryo has a normal karyotype

15. Ectopic Pregnancy u Leading cause of pregnancy related death in the 1st trimester u 9% of all pregnancy related deaths u 1% of pregnancies u Increasing over past 10 years

16. Sites of Ectopic Pregnancy 95% occur in the fallopian tube

17. Ampullary

18. Ampullary 80-90% of ectopics Tubal damage minimal since usually growing outside lumen Can open tube to remove contents (linear salpingostomy)

19. Isthmic 5-15% of ectopics Grow within tubal lumen Usually tube needs to be resected (salpingectomy)

20. Fimbrial 5% of ectopics Partially extruded ectopic that stays at the end of the tube

21. Cornual/Interstitial 1-2% of ectopics Growing within muscular wall of uterus Removal very difficult

22. Ovarian <1% of ectopics Abundant blood supply Difficult to save the ovary

23. Abdominal

24. Abdominal Ectopic that has been extruded from tube and implants in the abdomen 20x higher maternal mortality Often placental tissue left in situ

25. Cervical <1% of ectopics Abundant blood supply (uterine vessels) Non-surgical methods employed

26. Heterotopic Pregnancy u An ectopic in combination with an intrauterine pregnancy u 1 in 15,000-40,000 u 1% of patients undergoing IVF

27. Risk Factors u History of sexually transmitted diseases or PID u Prior ectopic pregnancy u Previous tubal surgery u Prior pelvic or abdominal surgery resulting in adhesions u Endometriosis u In vitro fertilization or other ART u Congenital abnormalities of the fallopian tubes u Use of an IUD

28. Diagnosis u Abdominal pain (90-100%) u Vaginal bleeding (75%) u No evidence of intra-uterine pregnancy on ultrasound (  hCG 1500-2000 mIU/mL) u Abnormally rising  hCG u Abnormal hematocrit

29. Timing of Rupture u Isthmic pregnancies rupture earliest 6-8 weeks u Ampullary 8-12 weeks u Interstitial pregnancies 12-16 weeks

30. Treatment Unstable u Stabilize with IV fluids, blood products u Immediate laparotomy Stable u Laparoscopy or u Methotrexate injection

31. Methotrexate u Folate antagonist u Destroys proliferating trophoblastic tissue u May be useful in small unruptured ectopics u Relative contraindications u Adnexal mass > 3.5 cm u Fetus with cardiac activity

32. Teratogenesis u Effect of a teratogen is dependent on when the drug is given during the pregnancy u Incidence of major structural anomalies ~6% Pre-implantation = conception to week 20 Embryogenic period = week 3 to week 8 Fetal period = week 21 to term

34. Pregnancy Categories A Controlled studies fail to demonstrate risk B Animal reproductive studies failed to identify a risk but there are no controlled studies in pregnant women or animal studies showed an effect that was not confirmed in human studies C Studies in animals showed an adverse effect or no controlled studies available in women. Use when benefit justifies potential risk to the fetus D Positive evidence of human fetal risk. May be acceptable in a life threatening situation if better options not available X Studies have confirmed fetal abnormalities. Risk always outweighs benefit

35. Diabetes in Pregnancy Chapter 18

36. Statistics u Pre-gestational diabetes 1-3/1000 births u Gestational diabetes = any degree of glucose intolerance with first recognition during pregnancy u Complicates 4% of pregnancies u Diabetic women 4x more likely to develop pre-eclampsia u Twice as likely to have an SAB

37. Metabolism u HPL and cortisol normally lower glucose levels, promote fat deposition and stimulate appetite u Rising estrogen & progesterone increase insulin production and tissue sensitivity u Overall result is lowered glucose levels u 70-80 mg/dL by 10th week u Also decrease in postprandial glucose levels

38. 2 nd Trimester u Fasting and post-prandial levels rise u Facilitates transfer of glucose across the placenta (facilitated diffusion) u Fetal levels 80% of maternal levels u HPL rises steadily through 2 nd & 3 rd trimesters u Cortisol levels rise stimulating endogenous glucose production & glycogen storage

39. Type 1 Diabetes u Cellular mediated autoimmune destruction of the  cells of the pancreas u Incidence 0.1-0.4% u One of most common maternal disorders resulting in anomalous offspring u 6-10% (2-3x general population) u Incidence of malformations directly related to level of glucose over embryonic period

40. Anomalies

41. Common Anomalies u Caudal regression u Neural tube defects u Transposition of the great vessels u Ventricular septal defects u Renal agenesis u Duodenal atresia

42. Approach to Prenatal Care u Ideally pre-conceptual care u Normalization of blood sugars u Initiation of prenatal vitamins with 400  g folic acid u Dilated eye exam u Baseline labs: HbA1C, thyroid studies, 24 hour urine

43. Glucose Goals u Fasting glucose 80-95 mg/dL u One hour post-prandial < 130 mg/dL u Two hour post-prandial < 120 mg/dL

44. Retinopathy u Diabetic retinopathy leading cause of blindness between ages 24-64 u Some form in 100% of patients with Type 1 DM for 25 years or more u 5% of patients with background retinopathy experienced worsening during pregnancy with improvements following delivery

45. Nephropathy u Peak incidence of nephropathy after 16 years of DM u Renal blood flow and GFR increase 30-50% u 3rd trimester mean arterial pressure and PVR increase u Women with microvascular disease experience worsening renal function

46. Gestational Diabetes Screening u ~28 weeks u 50 gram glucose load followed by 1 hour glucose measurement u > 130 requires diagnostic test

47. Diagnosis GDM 8 hour overnight fast 100 gram glucose load Need 2 or more abnormal values

48. Risk Factors GDM u > 25 years of age u Obesity u Family history u Previous infant > 4000 grams u Previous stillborn u Previous polyhydramnios u History of recurrent SABs