Optimal care during pregnancy and delivery Professor Catherine - - PowerPoint PPT Presentation

Oxford Inflammatory Bowel Disease MasterClass

Optimal care during pregnancy and delivery

Professor Catherine Nelson-Piercy, London, UK

Oxford Inflammatory Bowel Disease MasterClass

Therapeutic goals in IBD: Optimal care during pregnancy and delivery

Professor Catherine Nelson-Piercy Guy‟s & St Thomas‟ Foundation Trust Imperial College Healthcare Trust London, UK

Disclosures

 I HAVE RECEIVED LECTURING FEES FROM WARNER CHILCOTT

Concerns in pregnancy

 Effect of IBD on fertility  Effect of IBD on pregnancy outcome  Effect of pregnancy on IBD  Drugs

 In pregnancy  While breast feeding

 Mode of delivery

 Which women need CS?

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Effect of pregnancy on UC

 Little effect on the course of UC.  Risk of exacerbation  50% (i.e. similar to the annual risk in non-pregnant patients)  30% if colitis is quiescent at the time of conception.  Exacerbations of UC are usually mild and occur during the first two trimesters.

Effect of pregnancy on CD

 Remains quiescent in ¾  Improves in 1/3 of those whose disease is active at the time of conception.  Most exacerbations of inactive CD occur during the first trimester.

IBD has same risk of flare whether pregnant or not So maintenance therapy should be continued

Effect of IBD on pregnancy

 Fertility may be decreased in active CD

 Inflammation and adhesions may affect tubes and ovaries  Prior surgical intervention

 Quiescent disease at the time of conception no increased rate of

 miscarriage, stillbirth, fetal abnormality

 Majority (80–90%) of women have full-term normal pregnancies.  Active disease at the time of conception associated with

 an increased miscarriage rate (35%).  an increased rate of preterm delivery.

Management in pregnancy

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Drug Safety

• C. J van der Woude, S Kolacek, I Dotan, T Øresland, S Vermeire, P Munkholm, U Mahadevan, L Mackillop, A Dignass. European

evidenced-based consensus on reproduction in inflammatory bowel disease for the European Crohn's Colitis Organisation (ECCO). Journal of Crohn's and Colitis (2010) 4, 493–510

Management continued

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Management continued

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Risks of major congenital anomalies in children born to women with IBD: a UK population-based cohort study

UK primary care database 1990-2010 1703 children born to women with IBD Rate of congenital malformations:

• 2.8% without IBD
• 2.7% with IBD
• 3.7% CD
• 1.9% UC

Exposure to: 5ASA 32.4% Steroids 12.3% Azathioprine 8.7% Lu Ban, Laila J Tata and Tim Card Division of Epidemiology & Public Health, University of Nottingham

 In pregnancy maternal antibodies are transported across placenta by the neonatal Fc receptor  Immunoglobulin concentrations increase in fetal blood from early second trimester until delivery  IgG1 is the most efficiently transported Ig subclass  Infliximab and adalimumab are IgG1 subclass anti TNFα antibodies that are actively transported across the placenta  Certolizumab pegol is pegylated Fab fragment of humanized anti TNFα monoclonal antibody without an Fc portion. Therefore any transport across the placenta is by passive diffusion

Biologics in pregnancy

Biologics in pregnancy

• Animal data reassuring
• Vinet et al. Arthritis & Rheumatism 2009;61:587
• – 663 pregnancies RA & CD
• 403 Etanercept
• 225 Infliximab
• 35 Adalimumab
• No increased risk of congenital malformations
• Manufacturer has data on >131 cases of infliximab exposure in

pregnancy for RA or IBD – no diff in pregnancy outcomes.

Adalimumab

 Adalimumab (recombinant human monoclonal antibody (IgG1) to TNF)  116 women enrolled (Jan 2003- May 2007)  27 exposed to adalimumab during pregnancy with RA  47 had adalimumab during pregnancy treated for conditions

• ther than RA including Crohn's disease, psoriatic arthritis,

ankylosing spondylitis and non-specific auto-immune disorder.  Outcomes for 26 exposed human pregnancies included 2 children with congenital malformations (undescended testes and microcephaly).  Six other case reports of pregnancy exposure resulting in normal outcomes.

Johnson et al. Pregnancy outcomes in women exposed to adalumimab:the OTIS autoimmune diseases in pregnancy project. Ann Rheum Dis 2008;67(Suppl. 2):FR10053

INFLIXIMAB

Mouse – Human chimeric monoclonal antibody Blocks action of pro- infammatory TNF- ½ life 9-10 days Contains human IgG1 constant

Crosses placenta (2nd and 3rd trimesters) Does not cross into breast milk

Evidence for transplacental transfer of maternally administered infliximab. Longterm affect on neonate not known Avoid after 30 weeks if possible Vasiliauskas et al. Clin Gastroenterol Hepatol 2006

Management of flare in pregnancy

 Medical management with

• 5-ASA derivatives
• Steroids +/- Azathioprine
• Biologics
• (metronidazole for pouchitis)

 Address nutritional deficiencies

• Emotional and psychological support
• Increased fetal surveillance
• TPN
• Surgery reserved for: obstruction, perforation, hemorrhage,

abscess in the severely ill patient when continued illness is a greater risk to the fetus

Previous surgery

 Pregnancy (and vaginal delivery) well tolerated with

 Ileostomy  Proctocolectomy  Ileoanal anastomosis  pouch surgery

 Ileostomies

 Stomas with quiescent disease can have full-term NVD  Ileostomy dysfunction may occur in the second trimester  intermittent intestinal obstruction  peristomal cracking and bleeding may result from stretching of the abdominal wall

Indications for CS

 Only required for obstetric indications  Severe peri-anal Crohn’s disease (role of MRI)

 deformed or scarred rectum and perineum  perineal inelasticity

 Some pouches

 Discuss with individual surgeon

Risk of venous thromboembolism

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Drugs in breast feeding

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• 31 breast milk samples from 10 women
• Low levels (2-10% therapeutic) of 6MP in 2

samples from 1 woman

• No detectable 6MP or 6TGN in any of the

neonatal blood samples

BJOG 2007; 114: 498-501.

Is Infliximab safe to use while breast feeding?

 22yo fistulizing ileocolonic CD  10mg/kg (1000mg) infliximab x 6 doses in pregnancy  Last dose 2 weeks prior to delivery  CS 39/40; BW 7lb 6 oz  Fully breast fed  Breast milk spiked with 40 ng/ml infliximab  Infliximab detected in all spiked samples (1:2, 1:4, 1:8) but not her unspiked breast milk  Usual dose (10mg/kg) of infliximab given, breast milk collected daily for 30 days. NO INFLIXIMAB DETECTED

Stengel et al. W J Gastroenterol 2008;14:3085

Drug Safety in lactation

• C. J van der Woude, S Kolacek, I Dotan, T Øresland, S Vermeire, P Munkholm, U Mahadevan, L Mackillop, A Dignass. European

evidenced-based consensus on reproduction in inflammatory bowel disease for the European Crohn's Colitis Organisation (ECCO). Journal of Crohn's and Colitis (2010) 4, 493–510

Biologics in pregnancy

Mahadevan U et al. Clin Gastroenterol Hepatol. 2013 Mar;11(3):286-92; quiz e24. doi: 10.1016/j.cgh.2012.11.011. Epub 2012 Nov 28.

Infliximab detectable in infants up to 2-6 months of age

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Mahadevan U et al. Clin Gastroenterol Hepatol. 2013 Mar;11(3):286-92; quiz e24. doi: 10.1016/j.cgh.2012.11.011. Epub 2012 Nov 28.

Adalimumab detectable up to 3 months of age

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Mahadevan U et al. Clin Gastroenterol Hepatol. 2013 Mar;11(3):286-92; quiz e24. doi: 10.1016/j.cgh.2012.11.011. Epub 2012 Nov 28.

 >1000 women with IBD  Interim analysis  896 completed pregnancies  326 unexposed

 204 immunomodulator  291 biologic  75 combination biologic + immunomodulator

 No increase in congenital abnormalities by drug exposure  Increased risk of infections (OR 1.35 [95%CI 1.01-1.8]) by age 1 in infants exposed to ADA / IFX (but not CZP) + immunomodulator vs monotherapy

PIANO (Pregnancy IBD And Neonatal Outcomes) Registry

Mahadevan et al. Gastroenterologist 2012; 142

12/18 discontinued IFX < 30 /40; all stayed in remission 13/13 discontinued ADA < 30/40; 2 relapsed

Zelinkova Z et al. Clin Gastroenterol Hepatol. 2013 Mar;11(3):318-21. doi: 10.1016/j.cgh.2012.10.024. Epub 2012 Oct 25.

Neonatal vaccinations

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 3 cases of fatal disseminated BCG infection in neonate  No live vaccines for first 6-12 months.

Vaccinations

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Indications for Surgery

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Indications for surgery

 Obstruction  Haemorrhage  Perforation  Toxic megacolon  Surgery should not be delayed because of the pregnancy

Nutrition

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Oxford Inflammatory Bowel Disease MasterClass

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