1. Can colic be attributed to transient lactase deficiency (TLD) ?
Presenter: Jivan Moaddeb, PharmD
Moderator: Robert W. Sears, MD, FAAP

2. Definition of Colic
Colic is a condition where an otherwise healthy infant cries or displays symptoms of distress frequently and for extended periods, without any discernible reason.
Typically appears within the first month of life and usually resolves itself before the infant is three to four months old.
notes;
In 1954, Morris A. Wessel offered a widely accepted definition of “colic” as a healthy infant with periods of intense, unexplained fussing/crying lasting more than 3 hours a day, more than 3 days a week for more than 3 weeks.

3. Typical Symptoms of Colic
Gas
Bloating
Hard belly
Drawing the legs up
Prolonged crying
Appears to be in pain
Symptoms may be triggered after a feeding
Symptoms often happening in the early evening
Failure to respond to normal methods of soothing

4. Colic Patterns Evening only Colic Baby fairly happy most of the day
“Witching hour”
Cries for 3-4 hours
All Day Colic
Baby unhappy much of the day
Prolonged crying periods on and off

5. Impact of Colic on Families
Colic can affect up to 20% of infants Family interactions disrupted by colic. Clinical studies on excessive infant crying have reported:
Colic’s association with problems in family interaction and distress(1), which has been shown to persist at 1 and 3 years (2,3)
Psychological stress and fatigue in both parents (4)
Depression, exhaustion, and anger in mothers (5) and feelings of inadequacy (6)
Impact of Colic on HP
Frequent visits to office
Distressed parents & infant
Turns routine check into prolonged consultation

6. Treatments Lactose-free formulas Change breast feeding mom’s diet
Hypoallergenic formula
Lactose-free formulas
Change breast feeding mom’s diet
Simethicone gas-relieving drops
Probiotics
Consider treatment for GERD
Soothing techniques
Notes:
Some Soothing Techniques are:
Exclude common causes of crying
Walking
Bouncing
Car rides
Gentle music

7. Can colic be attributed to transient lactase deficiency (TLD) ?

8. Transient Lactase Deficiency (TLD)
Inability to fully digest lactose
(breast milk or formula)
Undigested lactose broken down in bowel
Producing lactic acid/hydrogen gas
Bloating and flatulence

9. Lactose broken down into glucose and galactose
Design: insufficient lactase image

10. Categories of Lactose Intolerance
Congenital Lactase Deficiency – rare, autosomal recessive disorder most common in Finland. Begins at birth. Total or near-total lack of lactase enzyme. Extremely rare in most areas of the world
Primary Lactase Deficiency – classic “lactose intolerance.” Normal lactase production early in life, then diminishes during later childhood or adulthood
Secondary, Acquired, or Transient Lactase Deficiency – caused by injury to small intestine, diarrheal illness, or chemotherapy. May also occur in some infants during the first few months of life
It is rare to see true lactose intolerance

11. Diagnosing Transient Lactase Deficiency (TLD)
No practical testing methods (Hydrogen breath test impractical)
Diagnosis made by trial of lactase enzyme drops
Should see improvement within 3 days

12. Breath hydrogen excretion in infants with colic (10)
Miller JJ, et al. Arch Dis Child 1989; 64:
Objective: To assess breath hydrogen excretion in breast and formula-fed infants with and without colic
Design: H2 breath analysis was performed prior to feeding, then 90 and 150 minutes after feeding
Subjects: 118 healthy infants  

13. Breath hydrogen excretion in infants with colic (10)
Miller JJ, et al. Arch Dis Child 1989; 64:
Results: 65 infants (55%) were reported to have colic based on inconsolable crying lasting several hours each day
H2 breath results were higher at all three collection times in colicky infants
Median H2 concentration in colic group was 29 ppm and in the non-colic group was 11 ppm
Positive H2 breath test (>20 ppm) occurred in 62% of infants with colic vs 32% in the control group
Conclusion: Significance of this finding needs to be determined. Incomplete lactose absorption may be either a cause or an effect of colic in infants

14. A Trial of Lactase in the Management of Infant Colic (8)
Kearney PJ, Malone AJ, Hayes T, et al. A trial of lactase in the management of infant colic. J Hum Nutr Diet. 1998;11(4):
Objective: To investigate transient lactose intolerance as a factor in the aetiology of infant colic
Design: A randomised, double-blind, crossover trial of lactase and placebo drops added to milk formula to determine whether this method of reducing lactose intake affected infant colic
Subjects: Infants with colic were referred from clinics in keeping with Wessel's modified criteria

15. A Trial of Lactase in the Management of Infant Colic (8)
Kearney PJ, Malone AJ, Hayes T, et al. A trial of lactase in the management of infant colic. J Hum Nutr Diet. 1998;11(4):
Results: Thirteen babies completed the trial (mean birth weight 3.7kg)
Colic symptoms began in less than 1 month in 12 babies
The effect of the lactase was to reduce crying time by 1.14 h per day
(CI )
The reduction in crying time was significant (t=2.75, d.f.=11,P=0.019)
Note: what is t mean, or d.f.

16. A Trial of Lactase in the Management of Infant Colic (8)
Kearney PJ, Malone AJ, Hayes T, et al. A trial of lactase in the management of infant colic. J Hum Nutr Diet. 1998;11(4):
Conclusion: Transient lactose intolerance may have a role in the aetiology of infant colic Lactase drops require prior incubation with milk formula to be effective The response to lactase in this study supports "colic", i.e. spasm of the large intestine as a factor in these infants' discomfort
The Initial trial showed that the product had a pronounced effect on babies with colic
The trial was small, but results were significant and were published in the Journal of Human Nutrition and Dietetics in 1998
The results showed that by breaking down most of the lactose in a baby’s feed by adding lactase enzyme drops to the milk a number of hours before feeding, the hours of crying were significantly reduced
These results were confirmed by a subsequent, larger trial at a hospital in London, which was published in October 2001

17. Improvement of symptoms in infant colic following reduction of lactose load with lactase(7)
Kanabar D, Randhawa M, Clayton P. Improvement of symptoms in infant colic following reduction of lactose load with lactase. J Hum Nutr Diet. 2001;14(5):
Transient lactose intolerance has been identified as a possible causative factor in infant colic
Design: A double-blind randomised placebo-controlled crossover study to investigate this was undertaken in 53 babies with symptoms of colic 53 infants aged between 3 and 13 weeks were recruited
This study has a larger number of participants.
Insert figure 1
Table

18. Study Results

19. Improvement of symptoms in infant colic following reduction of lactose load with lactase(7)
Kanabar D, Randhawa M, Clayton P. Improvement of symptoms in infant colic following reduction of lactose load with lactase. J Hum Nutr Diet. 2001;14(5):
Treatment goal of study (7)
Reduction in crying time of 45% and
Reduction in the hydrogen breath test of 45%
When treated with Colief compared to placebo
Notes
Breath Hydrogen measurement: Breath Hydrogen was measured using a Micro H2, a portable hydrogen monitor designed for the simple screening of lactose or sucrose malabsorption by automatic sensor drift detection (Peuhkuri et al., 1998)

20. Colief Infant Drops Key Results (7)
45% reduction in 38% of infants who complied properly
45% reduction in 26% of infants who were non-compliant Findings suggest
Colic may have multiple aetiology
In significant number of cases immediate cause is TLD
Pretreatment of feeds with lactase can result in considerable symptomatic benefits
Kanabar trial indicated that 38% of colic cases can be attributed to transient lactase deficiency (TLD)
Natural
Temporary
Insufficiency of lactase enzyme (7)

21. Colief Infant Drops Colief reduces the lactose load by up to 70% (7)
Residual level of lactose helps stimulate the baby’s system to produce endogenous lactase enzyme (7)
At 3-4 months infant will usually produce enough lactase
Added to breast milk or formula before a feeding
If administered directly may denature in the stomach
May work within 3 days, but allow 7 day trial
Image of item

22. Options for Treatment
Image of item

23. Breastfeeding Mom Elimination diet Lactase enzyme drops
Most often cow’s milk products
Lactase enzyme drops
Useful if infant sensitive to milk sugar
Preserving the breastfeeding relationship
Using lactase enzyme drops allows breastfeeding to continue despite colic (if TLD the cause)

24. Formula-fed Infants Available options less than ideal
Most use corn syrup-based sugars instead of healthy and natural lactose
Use elemental proteins and amino acids instead of naturally-occurring milk proteins
Not needed if the infant’s primary problem is TLD
Should be reserved for infants with milk protein allergy / intolerance and as a last resort

25. Formula Choices Soy-based formulas
Good Start soy Corn glucose and sucrose
Similac Soy Corn syrup and sucrose
Prosobee Corn syrup
Galatose lead in
Good

26. Formula Choices Elemental formulas Nutramigen Corn syrup
               
Nutramigen
Corn syrup
Pregestimil Corn syrup
Alimentum Sucrose

27. Formula Choices Lactose-free formulas
Enfamil lactofree Corn syrup (glucose)
Similac lactose free Corn glucose and sucrose

28. Formula Choices Hydrolyzed protein formulas
Enfamil GentleEase Mostly corn syrup and some lactose
Good Start Mostly corn glucose and some lactose
Similac Sensitive Mostly corn syrup and some galactose

29. Formula-fed Infants: A Better Choice
Regular milk based formula with lactase drops added
Benefits include:
Provides infant with the healthiest source of sugar (galactose and glucose combination)
Provides infant milk-based proteins
Won’t work if primary problem is milk protein allergy, but should work if TLD.

30. Instructions Breast feeding
Express a few tablespoons of breast milk into a sterilized container
Add 4 drops of Colief® Infant Drops
Give this to the infant on a sterilized spoon before initiating breastfeeding
Breastfeed as normal Using with formula / ready made formula:
Prepare the infant’s formula as per manufacturer’s instructions
Add 4 drops of Colief® Infant Drops to the warm (not hot) formula
Wait ½ hour (shaking the formula occasionally) then feed the infant as normal making sure that the formula is at the correct temperature
Discard any unused formula

31. Instructions Preparing formula in advance
Prepare the infant’s formula as per manufacturer’s instructions,
Add 2 drops of Colief® Infant Drops to the warm (not hot) formula
Store in the refrigerator for a minimum of 4 hours before use and use within twelve hours
Feed the infant as normal making sure that the formula is at the correct temperature
Discard any unused formula
* When infants consume formula treated with Colief Infant Drops, there may be a change in stool pattern. The stools may resemble those of a breast fed infant – looser and more frequent. If this occurs, try reducing the number of drops used in the formula.

32. Instructions
Colief can be used from birth onwards until infant is 3-4 months old
Gradually withdraw from use
Halve the drops used per feeding
Then use at alternative feedings
Finally, reduce to once a day until withdrawal is complete
If at any stage discomfort returns revert to the previous dosage level listed above
It can be used onward

33. Summary Proven Natural Product Diagnostic Continue breastfeeding
Colief has been on the market in UK and Ireland for over 15 years
Natural Product
Contains lactase enzyme, glycerol and water
Diagnostic
Rule TLD in /out as cause of colic
Continue breastfeeding
No need to move to hypoallergenic formula

34. References
1) Raiha H, Lehtonen L, Huhtala V, et al. Excessively crying infant in the family: mother-infant, father-infant, and mother-father interactions. Child Care Health Dev. 2002;28(5):
(2) Rautava P, Lehtonen L, Helenius H et al. Infantile colic: child and family three years later. Pediatrics. 1995;96(1, pt1):43-47.
(3) Lehtonen L. From colic to toddlerhood. In: Barr RG, St. James-Roberts I, Keefe MR, eds. New Evidence on unexplained Early Infant Crying: Its Origins, Nature and Management. Skillman, NJ: Johnson and Johnson Pediatric Institute; 2001:
(4)Papousek M, von Hofacker N. Persistent crying in early infancy: a non-trivial condition of risk for the developing mother-infant relationship. Child Care Health Dev. 1998;24(5):
(5) Pinyerd B. Infant colic and maternal mental health: nursing research and practice concerns. Issues Compr Pediatric Nurs. 1992;15(3):
(6) Stifter CA, Bono MA. The effect of infant colic on maternal self-perceptions and mother-infant attachment. Child Care Health Dev 1998;24(5):
(7) Kanabar D, Randhawa M, Clayton P. Improvement of symptoms in infant colic following reduction of lactose load with lactase. J Hum Nutr Diet. 2001;14(5): (8) Kearney PJ, Malone AJ, Hayes T, et al. A trial of lactase in the management of infant colic. J Hum Nutr Diet. 1998;11(4):
(9) Moore DJ, et al. Breath hydrogen response to milk containing lactose in colicky and non-colicky infants. The Journal of Pediatrics Dec 1988, 113(6):
(10) Miller JJ, et al. Breath hydrogen excretion in infants with colic. Arch Dis Child 1989; 64: