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 T homas‟ 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?
Page 367
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. So maintenance therapy should be continued IBD has same risk of flare whether pregnant or not
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 Page 371
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 Page 373
Management continued Page 374
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
Biologics in pregnancy 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 • 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 other 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 Evidence for transplacental transfer of constant maternally administered infliximab. Crosses placenta (2 nd and 3 rd trimesters) Longterm affect on neonate not known Does not cross into breast Avoid after 30 weeks if possible milk 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 Page 383
Drugs in breast feeding Page 384
BJOG 2007; 114: 498-501. • 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
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 Page 389 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 Page 390 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.
PIANO (Pregnancy IBD And Neonatal Outcomes) Registry >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 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 Page 394
Vaccinations Page 395 3 cases of fatal disseminated BCG infection in neonate No live vaccines for first 6-12 months.
Indications for Surgery Page 396
Indications for surgery Obstruction Haemorrhage Perforation Toxic megacolon Surgery should not be delayed because of the pregnancy
Nutrition Page 398
Oxford Inflammatory Bowel Disease MasterClass Thank you for your attention!
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