Bowel Dysfunction in Pregnancy

RCP London December 2017 Anton Emmanuel

National Hospital for Neurology & Neurosurgery - epidemiology

Commonest bowel complaint of pregnancy

- 25% of pregnancies (modified Rome III) (Bradley Obstet Gynecol 2007)

st nd Especially likely in 1 and 2 trimester (Zielinski J Perinat Neonat Nurs 2015) Especially likely if constipated in prior pregnancies Constipation - aetiopathogenesis Motility Healthy vs. constipated motor activity1

Bowel action

1. Dinning et al. World J. Gastroenterol 2010;16(41):5162-5172. 4 The relationship between transit, bowel frequency and stool consistency Higher number of SCBMs and looser stools are associated with a shorter colonic transit time

Correlation between transit time Correlation between transit time and number of SCBM/week and stool consistency

Emmanuel, et al. Am J Gastroenterol. 2014 Jun;109(6):887-94 SCBM, spontaneous complete bowel movements Transit and function are related

Dinning et al 2004;127(1):49-56 Dyssynergic Defaecation • Normal pattern for defaecation • Dyssynergic defaecation* – Increased intrarectal pressure – Failure to coordinate abdominal – Simultaneous relaxation of anal musculature and pelvic floor sphincters – Failure to coordinate pelvic floor – Descent of pelvic floor and anal sphincters1

At rest During straining

Pubis

Puborectalis Coccyx Anorectal angle Anorectal angle External anal Internal anal *Also termed: Anismus, Paradoxical anal contraction, Pelvic Descent of the sphincter sphincter pelvic floor floor , Obstructed constipation, Functional outlet obstruction.

7 1. Rao et al. Gastroenterol Clin North Am. 2003;32:659-683; Image developed for programme Digital Excruciating pain suggests an Assess resting sphincter tone Elevated tone (70–80% internal sphincter) Palpate the rectal walls Rectal mass, anterior Assess for pain on palpation

Assess for anal sphincteric and puborectalis contraction on squeezing

Talley NJ. Am J Gastroenterol 2008; 103: 820–822. Digital rectal examination

Ask the patient to strain and try to push out your finger (normal perineal descent <3.5 cm) Tightening of muscles is suggestive of paradoxical and puborectalis contraction, impeding Assess for excessive anterior abdominal wall contraction with straining DRE in the identification of dyssynergia in chronic constipation: Sensitivity = 75%; specificity = 87%; positive predictive value = 97%

Talley NJ. Am J Gastroenterol 2008; 103: 820–822. Tantiphlachiva K, et al. Clin Gastroenterol Hepatol 2010; 8: 955–960. Three overlapping pathogenic features to classify the patient  Evacuatory dysfunction (structural or physiological) NO or YES

+ IBS-C

 Abdominal pain Normal Slow Transit (Time) Transit (Time)

–

 Disordered motility

11 1. Eoff & Lembo. J Manag Care Pharm 2008;14(9):S1-S17 2. Mertz et al. Am J Gastroenterol 1999;94:609-615 Dissatisfaction with current treatment is common in chronic constipation patients US web-based community-based panel (n=557)

Proportion of dissatisfied patients (%) Reason for dissatisfaction

80 Ineffective relief of bloating 52 67

79 Lack of predictability 75 71

66 Ineffective relief of multiple 50 symptoms 60 Fibre (n=268)

50 Prescription (n=42) Ineffective relief of constipation 50 44 OTC Laxatives (n=146) *Respondents classified as having chronic constipation according to Rome II criteria using a 45-question web-based survey 557 eligible participants from a panel of >24,000: 243 men and 314 women, ≥18 years old; 385 were taking medication at the time of the survey OTC = over-the-counter

1. Johanson & Kralstein. Aliment Pharmacol Ther 2007;25:599-608 Effect of diet Nurses Health Study: 62,036 women aged 36-61 years 3327 (5.4%) constipated ( <3 BM/wk)

Risk factors: Younger, lower BMI Protective factors: High fibre intake, regular exercise, coffee drinking, smoking, alcohol intake >7.7gm/day

Dukas et al Am J Gastroenterol 2003;98(8):1790-6 Effect of exercise • Several studies link exercise with reduced risk – Community survey of 1,699 Japanese – >4h /day walking reduces risk OR 0.46(0.2-1.0) • Nakaji et al Eur J Nutr 2002;41(6):244-8 • One RCT of exercise in IBS-C – 56 IBS randomised to usual care or 12 weeks exercise programme – Recruitment low (18%) – Primary endpoint : QOL showed no change – Significant improvement in constipation • Daley et al Int J Sports Med 2008;29(9):778-82 Effect of fluid intake

7% develop constipation in 3 mo after nursing home admission Risk factors: race, decreased fluid intake, pneumonia and Parkinson’s Robson et al Dis Colon 2000;43(7):940-3

Severe water restriction reduces stool weight • RCT in volunteers reducing fluid intake from 2500ml to <500ml • Results: Stool weight fell from 1,290 to 940 g/wk, p<0.05 • Klauser et al Z Gastroenterol 1990;28(11):606-9 No evidence of benefit with additional water if already well hydrated: • RCT of 108 children with CC randomised to: • No change • 50% increase in fluid intake with water • 50% increase in total fluid intake as soft drinks • Results: No change in stool frequency of consistency • Young et al Gastroenterol Nurs 1998;21(4):156-61 Laxatives for chronic constipation: Luminal mechanism of action1

GUT WALL Salts, Sugars and Osmotic agents Water binding in stool

Fibre and Bulking agents Stool softening & lowers surface tension of stool Docusate and Stool softeners

Peristalsis Senna and Stimulant agents

1Tack & Müller-Lissner. Clin Gastroenterol Hepatol 2009;7:502 Therapeutic strategies for chronic constipation Current therapeutic options for chronic constipation

Agent and mechanism of action Example Therapeutic response Bulking agent • Methylcellulose • Decreased gut transit time and increased stool • Increase stool volume making it easier to • frequncy1,2 pass • Takes >1 week Stool softener • Docusate • Less effective than psyllium in improving bowel • Soften stool making it easier to pass movements and stool output3 Osmotic• Although 16–40% of patients •useLactulose laxatives, current• Decreased laxative transit andoptions reduced for fecal impaction4 • Increasechronic fluids withinconstipation the intestine are making ineffective 8 • Lactulose causes flatulence stools softer and easier to pass • Symptoms persist despite laxative• Polyethylene use in up to 70%• ofIncreased patients stool8 frequency and decreased glycol straining5 Stimulant laxative • Bisacodyl • Increased frequency of bowel movement6 • Stimulate muscles helping them to move • Sennoside stools and waste products along the

1. Ashraf et al. Aliment Pharmacol Ther. 1995;9(6):639-47: 2. Cheskin et al. J Am Geriatr Soc. 1995;43(6):666-9: 3. McRorie et al. Aliment Pharmacol Ther. 1998;12(5):491-7: 4. Sanders. J Am Geriatr Soc. 1978; 26(5):236-9: 5. Attar et al. Gut. 1999.44.226-30: 6. Kamm et al. Clin Gastroenterol Hepatol. 2011;9(7):577-83: 7. Kinnunen et al. Pharmacology. 1993;47 Suppl 1253-5: 8. Wald et al. Aliment Pharmacol Ther 2008;28:917 Are current laxative options effective for chronic constipation? 16–40% of those with constipation use laxatives Symptoms persist despite laxative use

Patients with ongoing constipation symptoms (%) 100 Use laxative Do not use laxative 80

60

40

20

0 US UK FR GE IT BR SK Country Approximately 2000 adults each from: United States, US; United Kingdom, UK; France, FR; Germany, GE; Italy, IT; Brazil, BR; South Korea, SK Emmanuel et al. U Eur Gastro J 2013;1:375 Wald et al. Aliment Pharmacol Ther 2008;28:917 Emerging treatments

Basolateral membrane Tight junction Apical membrane Gut flora in colon lumen 5-HT4 receptor Lumen Epithelial cell layer Chloride channel Mucosa Cl–

Enteric nervous system

Muscularis mucosa

Submucosa Circular muscle layer Guanylate cyclase Myenteric nerve plexus receptor

Longitudinal muscle layer + Cl–

Prucalopride μ-opioid receptor

Lubiprostone Linaclotide Suppositories and enemas

Mainly for patients with normal urge sensation where rectal evacuation is problem1 Typically glycerine suppositories first-line followed by bisacodyl suppositories1 Only weak evidence supporting their use in chronic constipation2 WGO Practice Guideline (2007) recommends suppositories as an osmotic laxative option (glycerin) or where a fast-acting stimulant laxative is needed3 Enemas are used when suppositories fail 4

20 WGO, World Gastroenterology Organisation

1. Emmanuel Ther Adv Gastronenterol 2011; 4(1):37-48 2. Pare et al. Can J Gastroenterol. 2007;21(Suppl B):3B-22B 3. World Gastroenterology Organisation. Practice Guideline: constipation. 2007 4. World Gastroenterology Organisation Global Guideline. J Clin Gastroenterol. 2011;45(6):483-7 therapy

Rectal Electrodes Feedback Patients balloon On an anal plug Information Are trained to Expansion of record motor conveyed to achieve balloon mimics activity of EAS patient via maximal sensation of contractions visual or contraction of rectal filling auditory the EAS feedback

1. Berman et al. Yale J Biol Med. 2005;78(4):211-21 Biofeedback for constipation Evidence Large amount of short- and long-term data from RCTs for biofeedback as an effective treatment for chronic constipation1-5 – Greatest effect in patients with pelvic floor dyssynergia:5

Stool frequency Whole gut transit time 6 20 * * * * 5 16 4 * * * * 12 3

8 on Day 5 on Day

per per week 2

1 4 Bowel movements movements Bowel 0 Number of Sitzmarks 0

Slow transit (n=12) Pelvic floor disorder (n=34)

*For each follow-up interval, P<0.001

1. Rao. Gastroenterol Clin North Am. 2008;37(3).569-86 4. Gadel Hak et al. Arab J Gastroenterol. 2011;12(1):15-9 22 2. Rao et al. Clin Gastroenterol Hepatol. 2007;5(3):331-8 5. Chiarioni et al. Gastroenterology. 2005;129(1)86-97 3. Rao et al. Am J Gastroenterol. 2010;105(4)890-6 Biofeedback for constipation

% improvement biofeedback bisacodyl

RCT BF vs bisacodyl need to strain (Rao et al AJG 2007)

51 patients, all with dyssinergia Biofeedback for slow transit

Emmanuel et al Gut 2001 The other biofeedback…to address this What is biofeedback?

Habit training and talking therapy

Sphincter Balloon EMG biofeedback biofeedback

Acute diarrhoea

Flexible sigmoidoscopy safe

Can precede onset of labour Diarrhoea - treatment

Loperamide recently reclassified to C due to reports of hypospadias, large-for-dates, placenta previa Lomotil and peptobismol – contraindicated (teratogens) Antibiotics – most contraindicated, can use erythromycin

IBS treatments – avoid tricyclics, SSRIs: dicycloverine OK Inflammatory Bowel Disease

IBD affects pregnancy … pregnancy affects IBD course

Pre-term birth: OR 1.85 (1.67-2.05) Still birth: OR 1.57 (1.03-2.38) *controversial Small-for-dates: OR 1.36 (1.16-1.60) Foetal abnormality: OR 1.29 (1.05-1.58) Pregnancy complications (thromboembolism, preclampsia)

O’Toole et al Dig Dis Sci 2015 Recommendation for Disease activity minimum 3 months remission before conceiving

Increase risk Increase risk spontaneous abortion & preterm birth, still birth preterm birth and low birth weight (Crohn’s >UC) Bortoli et al APT 2011 Aetiopathogenesis

Disease activity Recommendation for specialist care and 3rd trimester surveillance Maternal Medicine weight exposure Pregnancy risks

Anaemia Malnutrition

Reddy et al Am J Gastro 2008 Impact of pregnancy on IBD

If in remission at conception Crohn’s 20% chance of flare in pregnancy UC 35% chance of flare in pregnancy (less maintenance) Pedersen et al APT 2013

If not in remission at conception 46-55% risk of IBD relapse Julsgaard et al Scan J Gastro 2014 Method of delivery

Perianal Crohn’s disease } Caesarean does not alter Ileoanal pouch } natural history

Caesarean: prevention of symptomatic obstetric sphincter injury - unproven Therapy – balance drug safety with influence of disease Therapy Optimising care

Restart biologics 24hrs after vaginal, 48 hrs LSCS Infant – no live vaccines 6mo

Reduce biologics, last dose wks 32-36 Maintain medication Educate patient Update vaccines Optimise remission Treating IBD relapses in pregnancy

Investigation Rule out C difficile Unsedated flexi sigmoidoscopy OK in any trimester – avoid colonoscopy MRI preferred to CT Treatment 5ASA first line for flare Corticosteroids – least amount and shortest course Budesonide > prednisolone (may need stress dose during labour) Biologics may be needed If need antibiotics – co-amoxiclav is safe If need surgery, 2nd term is best Thank you