Question: Can we do anything about Colic?

1. Question: Can we do anything about Colic? Lactobacillus reuteri (ATCC Strain 55730) Versus Simethicone in the Treatment of Infantile Colic: A prospective Randomized Study Fancesco Savino, Emanuela Pelle, Elisabetta Palumeri, Roberto Oggero and Roberto Miniero Pediatrics 2007;119;124-130 Presented by Daniel Imler, MD

2. Case Presentation • A distressed mother and father comes into your practice complaining that they cannot get a wink of sleep with the new baby. Mom is now becoming very depressed and Dad is having problems with his constituents approval at work. • “Doctor is there anything that you can do to help?” Baby: 2 ½ mo ex FT female, no PMHx, did fine for the first few months, but cries for 4-5 hours a day often in the middle of the night. The parents are now so haggard and depressed that they state they cannot take care of their child. Feeds: Maternal Breast Milk only

3. Case Presentation • You explain to the family that the patient is suffering from Colic. • “What’s that doctor? How did she catch it?” • You begin your explanation • Colic is commonly described as a behavioral syndrome characterized by excessive, paroxysmal crying. Colic is most likely to occur in the evenings, and it occurs without any identifiable cause. During episodes of colic, an otherwise healthy neonate or infant aged 2 weeks to 4 months is difficult to console. They stiffen, draw up their legs, and pass flatus.

4. Definition of Colic • The most widely used definition of colic is by Wessel et al. Their definition is based on the amount of crying, ie, paroxysms of crying lasting longer than 3 hours of a day and occurring on more than 3 days in any week for a period of 3 weeks.

5. The Hypothesis • Because some feeding practices and crying may result in large amounts of air entering the gastric lumen physicians have assumed that excessive aerophagia may be associated with colic • Colonic fermentation is the second proposed source of excessive intestinal gas in infants. However, no experimental evidence supports either theory.

6. The Evidence (where it exists) • There is an association between low birth weight and increased incidence of colic. • It is equally likely to occur in both breastfed and formula-fed infants. • Increased levels of certain biochemical markers, such as motilin, alpha lactalbumin, and urinary 5-hydroxy-3-indole acetic acid (5-OH HIAA) have been associated in infants with colic. • Psychosocial stress during pregnancy is associated with colicky babies. • Colic affects 10-30% of infants worldwide. • Some evidence that there is an increased susceptibility to recurrent abdominal pain, allergic disorders and certain psychological disorders may be seen in some colicky babies in their childhood.

7. Classic Treatment • Recommend that the parents not exhaust themselves, and encourage them to consider leaving their baby with other caretakers for short respites. • Bentyl (Dicyclomine hydrochloride) is an anticholinergic drug that has been proven in clinical trials to be effective in the treatment of colic. However, because of serious, although rare, adverse effects (eg, apnea, breathing difficulty, seizures, syncope), its use cannot be recommended. • Wessel and colleagues suggested an association between family and infantile tension. Families with colicky infants may have more problems in their family structure, family functioning, and affective state, compared with families with noncolicky infants. • Commercial products, including car-ride simulators, infant swings, lambskin or sheepskin blankets, and womb-sound recordings, have not been proven effective and may be very expensive. • Remind parents about the importance of feeding a hungry baby, changing wet diapers, and comforting a baby who is cold and crying as a result of these factors. Soothing music accompanied with parental attention (including eye contact, talking, touching, rocking, walking, and playing) may be effective in some infants and is never harmful. • Encourage parents to discuss their feelings and concerns with each other to obtain support. Emphasize the responsibility of the whole family in the care of a colicky baby.

8. Cuddle Cure (only $25.95) • Premise: Babies need a “Fourth Trimester” since we are all born “premature” due to the fact that our heads are growing too fast to fit through the birth canal. • Parents' job is to trigger the baby's "calming reflex" • THE CUDDLE CURE 5 S's • Swaddle • Side or Stomach • Shhh… • Swing • Suck

9. Case Presentation • You explain to the parents the classic treatment of colic and recommend they attempt your suggestions. • The parents, wearily accept your advice and stumble out of your office towards Barns & Noble. • One week later they’re back looking worse. • “The baby keeps on crying doctor despite everything that we do. Isn’t there something wrong with here, isn’t their some sort of medicine that we can give her?”

10. Simethicone • You decide to recommend Simethicone to you family. • “What’s that Doc? Finally a Cure!” • Simethicone is a mixture of polydmethylsiloxanes that works by reducing the surface tension of gas bubbles, causing them to combine into larger bubbles that can be passed more easily by belching or flatulence. • However Simethicone has been shown to be no better than placebo in randomized control trials PEDIATRICS Vol. 94 No. 1 July 1994, pp. 29-34

11. Case Presentation • Another week goes by and the parents are back and can hardly talk to you they are so exhausted! • “Doc, the medicine didn’t work! Please help us, we find ourselves imaging that we are suffocating our daughter just to get relief!” • “We were searching the internet and read something about bacteria helping with colic. Is that true?”

12. Lactobacillus reuteri • L. reuteri is a gram-positive bacterium that usually inhabits mice and pigs, but is also considered and endogenous species in humans. • It is not commonly used in yogurt • Previous Reports • A Human Lactobacillus Strain (Lactobacillus Casei sp strain GG) Promotes Recovery From Acute Diarrhea in Children Pediatrics, Jul 1991; 88: 90 - 97. • Lactobacillus Therapy for Acute Infectious Diarrhea in Children: A Meta-analysisPediatrics, Apr 2002; 109: 678 - 684. • The Efficacy and Safety of Heat-Killed Lactobacillus paracasei for Treatment of Perennial Allergic Rhinitis Induced by House-Dust Mite • Lactobacillus paracasei Strain ST11 Has No Effect on Rotavirus but Ameliorates the Outcome of Nonrotavirus Diarrhea in Children From Bangladesh • Lactobacillus Sepsis Associated With Probiotic Therapy

13. Can Probiotics effect Colic?

14. Background • Past investigations included: • Inadequate or inappropriate mother-infant interaction • Mother’s anxiety • Abnormal Gastrointestinal Function • Transient Relative Lactase Deficiency • Exposure to Cow’s Milk Proteins

15. Background • Now: Intestinal Microflora • Lower counts of intestinal lactobacilli observed in colicky infants • Increased colic in children who went on to develop atopic disease. • Intestinal microflora are considered the major external driving force in maturation of the immune system after birth.

16. Methods • Dates: April 2004 – May 2005 • 90 infants with inclusion criteria • Exclusively Breastfeed • 21-90 days of age • 2400g to 4000g • Colic symptoms (>3 hours crying on >3 days in the week) • Exclusion Criteria • Clinical evidence of chronic illness • Gastrointestinal disorders • Received antibiotics of probiotics for week prior to the study • Patients received either Lactobacillus x 28 days or Simethicone (30mg PO BID) x 28 days • Mothers were asked to follow a cow’s milk-free diet (milk, yogurt, fresh cheese, cream, butter and biscuits) with diet diaries. • Follow-up was done on days 1, 7, 14, 21, 28

17. Results • Primary Outcome • Reduction of the daily average crying time, from baseline to the end of the treatment period, to <3 hours/day • Secondary Outcome • Number of responders vs. nonresponders in each group at the end of treatment • Responders = a decrease in the daily average crying time of 50% during the study.

18. Results • 90 breastfeed colicky infants enrolled • 45 randomly assigned to L. reuteri • 45 randomly assigned to simethicone • 7 patients were excluded • Interrupted breastfeeding (2) • Presentation of GERD and treated (2) • Failure to complete diet diary (1) • Missing data (2) • 83 completed the trial • 41 assigned to L. reuteri • 42 assigned to simethicone

22. In regards to Atopy • The authors also analyzed their data with regard to family history of atopy and found that there was no significant difference between the two groups (n=39 & n=44)

23. Discussion • Authors showed that there was a significant response to L. reuteri within 7 days of treatment with a response rate of 95%. • Their thought about why this treatment would be effective is that inappropriate bowel microflora has a tendency to initiate receptors to release cytokines which have a direct effect on the neruomusculatur of the bowel. This would possibly lead to abdominal dysmotility and colicky behavior. • There is also a recent study which showed that L. reuteri has inhibitory effects on visceral pain, modulating the inflammation-associated visceral hypersensitivity response through a more-direct action on enteric nerves.

24. Limitations • In regards to atopy, there was no response shown in the study even though in previous studies with L. rhamnosus combined with L. reuteri there was benefit show. The authors attributed this to their small population size. • Non-blinded trial (difference in dosage and administration of the two medications. • Non Placebo controlled (the authors chose simethicone as it is the best available and most commonly used treatment for colicky infants.) • They study group had a high incidence of atopic patients

25. “It worked Doc!” • The happy family comes back to your office 2 weeks later and tells you that their little girl is quiet, content and pain free. They thank you profusely and complement you on your decision to keep your practice evidence-based!