AFP Review NEIMEF Shanna Elliott, DO R1 Infantile Colic Recognition and Treatment October 1, 2015 Vol 92, No 7, p577 AFP Review NEIMEF Shanna Elliott, DO R1

What is it? Episodes of inconsolable and unprovoked crying “Rule of 3” criteria - crying for: > 3 hours per day > 3 days per week > 3 weeks 10-40% infants worldwide Benign Self-limited, resolves at 3-6 mo. Peaks at 6 weeks Infantile colic is a benign, self-limited process where healthy infants have paroxysms of inconsolable crying. Often accompanied by significant parental guilt and frustration, as well as multiple physician visits. Parents often reports episodes occur most frequently in the evening. The standard diagnostic criteria known as “the rule of 3” is crying more than 3 hours per day, more than 3 days per week, and for longer than 3 weeks. Symptoms usually resolve by 3-6 months of age. Colic affects approximately 10-40% of infants worldwide, typically peaks at around 6 weeks of age. The incidence between sexes is equal. There is no correlation with breast vs bottle feeding, gestational age, socioeconomic status, or season of the year.

Etiology No known cause Proposed causes: Altered fecal microflora Cow’s milk protein / lactose intolerance GI immaturity GI inflammation ↑ fecal calprotectin Increased serotonin secretion Poor feeding technique Maternal smoking / nicotine replacement therapy Shaken baby syndrome Post-partum depression Despite decades of research there is no known cause for infantile colic. Proposed etiologies include alterations to the fecal microflora, intolerance to cow’s milk protein, lactose intolerance, gastrointestinal immaturity or inflammation (there have been 2 studies demonstrating higher fecal calprotectin (a marker of colonic inflamamtion) in infants with colic, increased serotonin secretion, poor feeding technique, and maternal smoking or nicotine replacement therapy. Also associated with post-partum depression and shaken baby syndrome.

Evaluation: Red flags Finding Possible cause Distended abdomen Mass, hepatosplenomegaly, Hirschprung disease, intestinal malrotation with volvulus, necrotizing enterocolitis Fever AOM, appendicitis, bacteremia, endocarditis, meningitis, osteomyelitis, pneumonia, sepsis, UTI, viral respiratory infection Lethargy Hydrocephalus, meningitis, sepsis, subdural hematoma

Symptoms persist and parents desire treatment Meets criteria H&P Organic causes ruled out Reassurance and support Symptoms persist and parents desire treatment Because colic is benign the mainstay of treatment is parental reassurance and support, providing education to caregivers about the course of the condition.

Treatment Continue breastfeeding Maternal allergen restricted diet (A) Breastfed infant Bottle-fed infant Continue breastfeeding Maternal allergen restricted diet (A) Cow’s milk Eggs Peanuts / tree nuts Wheat Soy Fish Lactobacillus probiotic 5 drops daily (B) Transition to hydrolyzed formula for 2 week trial (A) The prevalence of colic between breast-fed and formula fed infants is similar and as such breast feeding mothers should be encouraged to continue. A randomized controlled trial showed significant reductions in colic symptoms among breastfed infants whose mothers followed a low-allergen diet, averaging 137 minutes less crying per day compared to 51 less minutes per day in the control group, recommended as an option. Should be accompanied by dietary counseling to ensure adequate nutrition. Return to a normal diet can be considered after the infant reaches 3-6 months of age. Probiotics (such as Lactobacillus reuteri) were shown to reduce coli symptoms in 4 out of 5 clinical trials, no adverse effects were reported. 2 recent meta-analysis and 1 systematic review found that administration of 5 drops of Lactobacillus per day significantly decreased colic in infants who are breastfed (average of 61 minutes per day less crying time per day at 21 days) and recommended as an option for treatment. 1 trial found a significant increase in crying or fussing in bottle fed infants who received lactobacillus and as such cannot be recommended for formula fed infants. Parents of formula fed infants with colic often consider switching formulas. A systematic review of 13 studies found a statistically significant decrease in crying time among infants who switched to partially, extensively, or completely hydrolyzed formulas suggesting a 2 week trial of a different formula may be considered for treatment of colic. They are expensive and may not be covered by assistance programs. Parents can transition to new formula by mixing the hydrolyzed formula and regular formula incrementally over 3-4 days. If successful, can be continued until 3-6 months of age when they can be switched to regular formula. Studies showed the use of soy formula for treatment of colic had insufficient evidence to support this recommendation. The American Academy of Pediatrics recommends against the regular use of soy formula as this can be an allergen. Evidence Rating: A = consistent, good quality patient oriented evidence; B = inconsistent or limited quality patient oriented evidence; C = consensus, disease oriented evidence

Hydrolyzed infant formulas Type Brand Formula Cost Partially hydrolyzed Enfamil Gentlease $1.41 Gerber Good Start Gentle $1.30 Good Start Soothe $1.37 Similac Similac Total Comfort $1.58 Extensively hydrolyzed Nutramigen $1.97 Pregestimil $2.06 Alimentum $1.87 Completely hydrolyzed Elecare $3.05 Enfamily Nutramigen AA $2.34 Nutricia Neocate $3.19

Other treatment options 12% sucrose solution BID “Gripe water” Herbal supplements Peppermint, teas Not recommended: Simethicone Dicyclomine PPI Infants in 1 small study who received 2mL of 12% sucrose at 5pm and 8pm daily had reduced colic symptoms. “Gripe water” consisting of dill seed oil, bicarbonate and hydrogenated glucose has also been used but there are no trials demonstrating effectiveness or possible harm. Herbal supplements including peppermint and teas (fennel, chamomile, vervain, lemon balm, licorice) have decreased crying time in some studies, but further research is required before recommending these treatments. 2 small poorly designed studies suggested possible used of a vented bottle. Swaddling has been proposed as a method for reducing crying in infants, but show no statistically significant benefit. Simethicone drops, while readily available and often sued to treat colic, were found to be not better than placebo in a systematic review of 3 randomized controlled trials. Dicyclomine was found to be significantly better than placebo for the treatment of colic, but is contraindicated in infants younger than 6 months due to adverse effects of drowsiness, constipation, diarrhea, and apnea. Proton pump inhibitors (Prilosec) were found to be no more effective than placebo at reducing crying or fussing time in a trial of 30 infants with colic symptoms, reflux, or esophagitis. Physical therapies including chiropractic and osteopathic manipulation studied under a Cochrane review were found to have insufficient evidence to support their use in treating colic. However, many of these studies were small and had a high likelihood of bias. Acupuncture and infant massage have had conflicting results and further studies needed to assess harm vs benefit.

CME quiz questions During a 2mo check-up for a healthy breast-fed infant, parents ask if there is anything they can do to reduce his lengthy nighttime crying spells. The child spits up occasionally after feedings but does not seem to be in distress, which one of the following treatments should you recommend? Simethicone Dicyclomine Lactobacillus Omperazole

CME quiz questions During a 2mo check-up for a healthy breast-fed infant, parents ask if there is anything they can do to reduce his lengthy nighttime crying spells. The child spits up occasionally after feedings but does not seem to be in distress, which one of the following treatments should you recommend? Simethicone Dicyclomine Lactobacillus Omperazole

CME quiz questions Which of the following interventions reduces crying times in formula-fed infants with colic? Switching to soy formula Switching to hydrolyzed formula Osteopathic manipulation Infant massage

CME quiz questions Which of the following interventions reduces crying times in formula-fed infants with colic? Switching to soy formula Switching to hydrolyzed formula Osteopathic manipulation Infant massage