The Care of the Pregnant Patient with GI Diseases

1. The Care of the Pregnant Patient with GI Diseases Mary Pat Pauly, MD FACP AGAF Kaiser Permanente Clinical Professor of Internal Medicine and Gastroenterology at UC Davis

2. Outine • Management of common GI diseases in pregnancy • GERD • PUD • Constipation • Special considerations for pregnancy patients requiring endoscopy • Special considerations for patients with IBD • Management of the pregnant patient with liver disease.

3. GERDHeartburn • Heartburn occurs in 30 – 50% of pregnancies • Usually mild symptoms • Life style modifications • Dietary modifications

4. 35 yo female calls for advice. She is about 3 months pregnant and having severe heart burn. • She has tried life style changes without success. • Her obstetrician advised her to take antacids. • Her mother has her taking tums • and her neighbor recommended sodium bicarbonate. • Her mother in law takes pepcid. • Her husband insists omeprazole is the drug of choice. • What should she do?

5. Treatment of Reflux in pregnancy • Antacids • In general OK , short term – but • AVOID • Magnesium trisilicates (Gaviscon) • Fetal nephrolithiasis, hyponatremia and respiratory distress • Excessive calcium carbonate • Milk alkali syndrome • Hypercalcemia, renal impairment and metabolic alkalosis • Avoid -Na HCO3 • fetal metabolic alkalosis • Fluid overload

6. FDA classification for the use of Medications in pregnancy

7. H2 Blockers Category B Tagamet Ranitidine Many studies available supporting safety Pepcid Less data available…makes “choice of another agent prudent.”* PPI Category C Omeprazole Animal toxicity: embryonic toxicity and fetal mortality in preg rats and rabbits. Multiple cohort studies suggest low risk of human toxicity Slightly Increased risk of cardiac malformations Category B Esomeprazole, pantoprazole lansoprazole Limited data: low risk What about H2 Blockers and proton pump inhibitors? * AGA review of used of GI meds in pregnancy 2006

8. She is doing better on ranitidine twice daily and has changed to eating her main meal at noon and small dinner • She reminds you that her father had history of GERD and Barrett’s esophagus and died of Esophageal cancer at age 40. • She asks if she should have Endoscopy to check for Barrett’s?

9. Endoscopy in the Pregnant patient • The need for procedure has to be driving force • Must have good indication • Elective procedures should be deferred • Endoscopy is usually safe during pregnancy • – during second and third trimesters • Risks include • Risk of sedation • Risk of hypoxemia • Risk of aspiration

10. 35 year old G2 P1 female 32 weeks pregnant comes in with hematemesis and melena. • BP 80/60 with pulse 120 and Hb 5.8 • Conservative therapy is initially recommended. She is resussitated with fluids and given blood. BP 90/70 P 100. • NGT shows BRB • not clearing with lavage • What do you recommend?

11. Endoscopy in pregnancy • Be certain good indication for EGD • For 2nd and third trimester • Ob consultation • Ob anesthesia consultation • Fetal heart tone monitoring • Either before and after the procedure or during the procedure if it may be prolonged. • Position patient on left side laterally • To avoid compression of vena cava by gravid uterus • Sedation • Minimize sedative drugs • Topical anesthesia • Recommendation is to “Gargle and spit”

12. Endoscopy in patient with active GI Bleed - preferred modes of intervention • Endoclips • Intervention of choice • Bipolar cautery • Minimizes chance of stray currents going through fetus • Injection of epinephrine • FDA pregnancy category C • Can be associated with decreased uterine blood flow • A note about Monopolar cautery • Avoid having the uterus between the catheter and grounding pad • Consider grounding pad in upper right arm if this mode is necessary

13. Hospital coures • FHT were normal after the procedure • She recovered from sedation • Was kept on side with HOB elevated after procedure • She was started on IV Pantoprazole • …and the Clotest was positive for HP !! • What would you recommend now?

14. Gall stone pancreatitis with Cholangitis • Can be associated with sepsis, end-organ failure and death. • Can lead to pre term labor and fetal loss • Charcot’s triad – • RUQ pain, jaundice and fever • Reynold’s pentad – • add hypotension and confusion • Treatment of choice - ERCP • But in general • Best avoided until after first trimester when organogenesis is complete • Wait until second or third trimester when possible

15. 28 year old pregnant female at 34 weeks gestation presents to ER at 11pm with severe RUQ pain,N,V,T and shaking chills. • These sx are similar to sx that resolved spontaneously when she was 8 weeks pregnant with gall stones pancreatitis • and recovered with conservative medical therapy. • Plan was to have cholecystectomy after delivery. • But the pain recurred 2 days ago and progressed • she noticed dark colored urine the day of presentation. Temp 102

16. Initial vs: • T 101, BP 100/70 P 120 O2 sat 1--% on 2 L with resp 16 • RUQ tenderness • Labs: ALP 456 • AST/ALT 468/502 • Bilirubin 3.1 • Amylase and lipase nl • Creatinine 1.3, • Initial management included IV fluids, O2,NPO, admission to ICU and antibiotics • Which antibiotics are safe to be used in pregnancy?

17. Antibiotics inidcated and contraindicated in pregnancy • Safe in pregnancy • Cephalosporins • Penicillins • Clindamycin • Gentamycin • Contraindicated in pregnancy • Quinolones • Tetracyclines • streptomycin • Avoid during the first trimester metronidazole (flagyl) Avoid during second and third trimester sulfonamides nitrofurantoin

18. The patient was placed on Zosyn • The next day the patient was still in pain requiring IV pain medications. • VS 110/40 100 resp 20 and O2 sat 100% on 2L O2 • Labs: ALT and AST still >450 • Bilirubin 5.9 • US – 8 mm stone in 11 mm distal CBD – • What is the best management at this point?

19. ERCP in pregnancy • Pre op Antibiotics • Ampicillin (B) and gentamycin (B) • Positioning of pt • Prone is difficult • On back increases compression of aorta and/or vena cava • Preferably left lateral position • Head up a little to avoid aspiration • Radiation • Shield the baby • Lead between patient and table • radiation comes from below • Keep procedure and fluoro time to minimum

20. What about sedation? • Use as little sedation as possible • Propofol and demerol are drugs of choice. • Small amounts of IV versed are OK if needed • Fentanyl crosses BBB more quickly • Many recommend • FHT monitored during procedure or at least prior to and after procedure • OB consult and preferably OB Anesthesia to assist • Esp if case may be long • Cetacaine or hurricane spray is OK but most recommend “gargle and spit.” • If breast feeding, pump and dump.

21. What about cautery Sphincterotomy requires • Monopolar cautery • Put grounding pad on right arm • Never allow uterus to be between the cautery and the grounding pad. • Amniotic fluid is good conducting medium

22. She was evaluated by OB • FHT checked just prior to sedation • Our most experienced and expert endoscopist did ERCP • Cannulated and aspirated bile • Made a sphincterotomy and extracted stone • OB returned to check FHT 30 minutes later. • Uneventful recovery • Cholecystectomy scheduled for later …after delivery.

23. 24 yo Hmong female 25 weeks pregnant with Hepatitis B asks for advice. • She has had HBV since she was born and transmission at birth as her mother had HBV and now has cirrhosis. • She in HBeAg positive, HBeAb negative • persistently normal ALT 17 – 19. • High viral load 6 x 10 (9) • What is my chance of transmission to my baby? • Is there anything that can be done to decrease the chance of transmission

24. Anti- viral therapy decreases rate of transmission of HBV • Active and passive immunization has decreased transmission rates of HBV • 90% effective • HBIG and vaccination within 12 hours of birth • Followed by additional 2 doses of vaccination • If HBV viral load >10 (8) chances of transmission is higher • Up to 38% in some studies • Lamivudine100 mg daily in third trimester decreases rate of transmission

25. 28 year old female with Hepatitis C asks for advice. • She has hepatitis C • genotype 2 • viral load 392,000 IU/ml • normal ALT • no signs of chronic liver disease • INR, bilirubin, and platelet count are normal • No medical problems • Contemplating pregnancy • Effect of pregnancy on disease? • Effect of disease on pregnancy? • Chance of passing disease on to baby?

26. HCV - Modes of Transmission • Blood • Blood transfusions – before 1992 • Intra venous Drug abuse • Dialysis • Tattoos, piercing, razors, toothbrush • Other • Intranasal cocaine • Sexual • Mother to baby (< 5 %) • Associated with higher viral load • HIV co-infection

27. Pregnancy in patients with Inflammatory Bowel Disease • The highest age adjusted incidence of IBD overlap the peak productive years • Newer medications allow patients to be healthier and disease free • For longer periods of time • And this …leads to • Increased opportunity of successful conception

28. AGE AND SEX DISTRIBUTION OF IBD

29. 32 year old woman newly diagnosed with Crohn’s disease • Moderate to severe ileo-colonic CD • She has questions about the most effective therapies • After complete review with physician she is placed on budesonide 9 mg daily • She has concerns about the impact on pregnancy • Disease • medications

30. Treatment of Crohn’s Disease Surgery Bowel rest Cyclosporine Anti TNF agents Infliximab Adalimumab certolizumab 6MP, AZA, MTX Corticosteroids Antibiotics mesalamine

31. Before pregnancy • Be sure disease under good control • Preferably in remission • Active disease associated with • Decreased ability to conceive • Increased risk of spontaneous abortion • Ideally healthcare maintenance up to date • Check iron, B12, folate, vitamin D leve • Vitamin D deficiency is associated with infertility • Identify high risk obstetrician • Counseling regarding medications during • Pregnancy • Breast feeding

32. Common questions • Inheritance? • Fertility ? • Effect of pregnancy on disease activity? • Effect of disease on pregnancy outcomes? • Safety of medications? • Management of flares?

33. Inheritance • Multifactorial • One parent with CD • 5% chance for offspring • One parent with UC • 1.6% • If both parents have IBD a child’ risk of IBD is higher • Pregnancy should not be discouraged for this reason

34. Fertility • With either UC of CD, the risk of infertility prior to surgery is probably similar to the general population • In UC patients there seems to be decreased fertility after IPAA (J pouch) • As much as 40-80% • One study from Scotland * • fertility was only 1/5th of those with UC prior to IPAA. *Olsen KO et al. Gastro 2002;122:15-19

35. Effect of Pregnancy on Disease Activity in IBD • Chances of flare • Same as non pregnant patient • 33%per year • Postpartum flares • Usually associated with medication discontinuation

36. Pregnancy outcome in IBD • In general Healthy pregnancies • Healthy babies • Even with disease in remission Higher rates of adverse outcomes • preterm birth • Spontaneous abortion • Low birth weight • Complications of labor and delivery

37. Medications in IBDuse during pregnancy • Stopping medications during pregnancy can be harmful • Increased risk of flare • Harmful to pregnancy • Impair ability of mother to care for child after delivery • Most medications are low risk and compatible with pregnancy and lactation • Except METHOTREXATE (X) • Teratogenic • Discontinue 3-6 months prior to pregnancy

38. Medications in IBDuse during pregnancy • Mesalamine (B) • Safe for use in preg • Sulfasalazine • Folate 2 gm daily • ASACOL (C) • Recently reclassified to class “C” • Due to presence of dibutyl phthalate in the coating • Azothioprine and 6-mercaptopurine (D) • controversial • Consider risks and benefits • Teratogenic in animals • Increased rate of VSD and ASD* • Increased rated of • Premature birth • Low birth weight • Probably disease related * Swedish Medical Birth Register Cleary Birth Defects Research 2009;85: 647-54

39. Corticosteroids ( C) • Prednisone • Considered low risk during pregnancy • Can be used for flare up • Risk in mother • Gestational Diabetes • Risk to baby • Overall risk of malformations is low • Increased risk of cleft palate • Use in first trimester

40. Anti –TNF agents • Inlfiximab and adalimumab • Low risk, can be used in pregnancy • IgG1 antibodies • Cross placenta • Can be detected in infant for up to 6 m after delivery • Last dose at 30 -32 w • Avoid live vaccines for 6 m • Certolizumab • Low risk • Can be used in pg • Fab fragment • Minimal placental transfer by passive diffusion • Continue through pg • No change in vaccination schedule

41. The same 32 year old woman recently diagnosed with Crohn’s disease and currently being treated with Budesonide returns 16 weeks pregnant with problems. • Remember • Moderate to severe ileo-colonic CD • Presentation pain, distention, n,v, and obstipation. • T 102, palpable mass in LQ. • ESR 64, CRP 6.8, WBBC 17,800 • Admitted and placed on Antibiotics and underwent imaging study to rule out abscess.

42. Antibiotics indicated and contraindicated in pregnancy • Safe in pregnancy • Cephalosporins • Penicillins • Clindamycin • Gentamycin • Contraindicated in pregnancy • Quinolones • Tetracyclines • streptomycin • Avoid during the first trimester metronidazole flagyl Avoid during second and third trimester sulfonamides nitrofurantoin

43. Imaging studies in CD • CT should be avoided in pregnancy • US • No contraindications • MRI • OK if imaging study is needed but • Avoid gadolinium – especially in first trimester • Teratogen

44. She was treated with Zosyn and underwent MRI • There was inflammatory mass in RLQ • Ileum • She improved clinically • Afebrile, no distention, good BMs, • Steroids were added and she was started on a taper • She was switched to anti TNF agent • certiluzimab

45. One more consideration… • Modes of delivery • Usually at discretion of high risk Obstetrician • C-section preperred • Active perianal diseae • Ileal-pouch anal anastomosis • Preserves sphincter continence

46. Pregnancy in patients with cirrhosis • Pregnancy is usually NOT encouraged in patients with cirrhosis • Pregnancy is rare in patients with cirrhosis • Advanced liver disease does not typically occur until later in life • Until after most patients have completed their reproductive years. • Higher incidence of anovulation and amenorrhea • Due to metabolic and hormonal derangements • Maternal mortality is higher in cirrhosis

47. Pregnancy in cirrhosis – effects on the fetus • Data is sparse • Increased spontaneious abortin rate • Increased risk of prematurity • Increased perinatal death rate

48. Effects of cirrhosis and portal hypertension • Esophageal variceal bleeding – varices get worse during pregnancy • Reported in 18 – 32% with cirrhosis • Up to 50% of those with known portal hypertension • Up to 78% in those with pre-existing varices. • Most commonly in 2nd and 3rd trimester • Blood volume highest • Fetus compreses IVC • Mortality rates are high

49. Treatment of variceal bleeding • Endoscopic variceal band ligation • Superior to sclerotherapy – no chemicals instilled into blood stream. -Expert opinion • Octreotide (B) • Safety in pg not determined • Could cause arterolar vasospasm • Decreased placental perfusion and increased risk of placental abruption as well as • HTN, MI, peripheral ischemia • Endoscopy • Safe when done with caution

50. Prophylactic treatment of varices in cirrhosis • Screening EGD • Before pregnancy • Or at beginning of second trimester* • Blood volume increased • Gravid uterus compressing IVC • Prophylaxis – • options • non selective beta blockers • Or variceal band ligation * AASLD recommendations