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

4. 35 yo female calls for advice
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
FDA pregnancy category
Interpretation A
Controlled studies in animals and women show no risk in 1st trimester, and possible fetal harm is remote. B
Either animal studies have not shown fetal risk but no controlled studies in pregnant women, or animal studies have shown an adverse effect that was not confirmed in women in 1st trimester. C
No controlled studies in humans have been performed, and animal studies have shown AE, or studies in humans and animals are not available: give if potential benefit outweighs risk D
Positive evidence of fetal risk is available, but the benefits may outweigh the risk if life threatening or serious disease. X
Studies in animals or humans show fetal abnormalities: drug contraindicated

7. What about H2 Blockers and proton pump inhibitors?
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
* 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. But the pain recurred 2 days ago and progressed
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. Which antibiotics are safe to be used in pregnancy?
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/ 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 Keep procedure and fluoro time to minimum
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. What is my chance of transmission to my baby?
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
Crohn’s disease and ulcerative colitis can have their onset at any age, but the peak incidence is in late adolescence and early adulthood. In some studies there is a second peak of Crohn’s colitis in women during their 6th and 7th decades of life. In general, the frequency of ulcerative colitis and Crohn’s disease is similar in males and females with a very slight female predominance in some studies. Multiple studies demonstrate a correlation of proximal Crohn’s disease (gastric, duodenal and small bowel location) with early onset disease and of colonic inflammation with late onset Crohn’s disease.
• Rogers BH, Clark LM, Kirsner JB. The epidemiologic and demographic characteristics of inflammatory bowel disease: an analysis of a computerized file of 1400 patients. Journal of Chronic Disease 1971;24:743.

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 IBD use 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 IBD use 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:

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 Certolizumab Low risk
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 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 MRI
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
Reports up to 18 – 50% mortality in cirrhosi with PHTN – and only about 2-6% in pateints with non cirrhotic portalhypertension

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

51. Pregnancy and cirrhosis
Review of data from 1984 – 2009
Kings College Hospital
62 pregnancies in 29 women
Median MELD was 7 (range 6 – 17)
Median CPS was 5 ( range 5-8)
Live birth rate was 58%
Median gestational age 36 w
Westbrook RH et al ClinGastroHep 2011;9: 694-9

52. Pregnancy and cirrhosis
Maternal complications occurred in 10%
Ascites
Encephaolpathy
Variceal hemorrhage
Associated with MELD > 10
MELD predicted which patients were to have liver related complications
AUC 0.8
83% sensitivity and 83% specificity
No one with MELD <6 had any liver related complications
Westbrook RH et al ClinGastroHep 2011;9: 694-9

53. Constipation in pregnancy
Fiber is first line therapy
Lactulose (B)
Magnesium containing products (B)
Senna (C)*
Lubiprostone (C)*
PEG (C)*
Do not use
Castor oil (X) – associated with uterine rupture
*Low risk if used short term

54. In summary
Many young women who are pregnant have GI problems and will seek care from gastroenterologists
It is very important for the mother to be as healthy as possible
Treat the disease in mother so she will be able to have a healthy baby
When treating patients you must consider the effects of the medications on the baby as well as the mother
No drugs that we routinely use are class A
Use class B or C drugs when the benefit outweighs the risk

55. Remember special concerns when performing endoscopy
And special considerations for sedation
Propofol when available and position pt appropriately
Patients with IBD and cirrhosis have higher rates of complications when pregnant
Patients with IBD need extra special care and follow up
Get disease under control with as safe a medication as possible
Patients with cirrhosis have high risk of variceal bleeding and other complications
Pregnancy is strongly discouraged
Screen for varices and treat prophylactically when possible.