Paediatric Lactose Intolerance

Infantile Colic

Infant colic is common in the first 3- 4 months of life. Infant colic affects 10- 30% of babies on breast- or formula-fed. About one in five infants develop colic in the first three months of life. Colicky babies cry hard and continuously, at about the same time each day, at least 3 days a week.¹Kanabar D, Randhawa M, Clayton P. Improvement of symptoms in infant colic following reduction of lactose load with lactase. J Hum Nutr Diet. 2001 Oct;14(5):359- 63.  ²Bahrami H, Ali Kiani M, Noras M. Massage for Infantile Colic: Review and Literature. Int J Pediatr. 2016;4(6):1953- 58.   There is a definite pattern in the 1 manifestation of colic, so called the rule of three :¹Kanabar D, Randhawa M, Clayton P. Improvement of symptoms in infant colic following reduction of lactose load with lactase. J Hum Nutr Diet. 2001 Oct;14(5):359- 63.  

• Colic starts by the 3^rd week of life
• Colic lasts about three hours a day
• Predominantly colic is seenduringfirst threemonthsofbaby’s life

Aetiology

Although a lot of research has been done to find what makes colicky babies cry, the answer remains elusive. Underlying organic causes of excessive crying must be considered during the evaluation. Organic causes account for less than 5% of infants presenting with excessive crying. The possible causes of infantile 3,4 colic are as follows :³Roberts DM, Ostapchuk M, O’Brien JG, Infantile Colic. Am Fam Physician. 2004 Aug 15;70(4):735- 740.  ⁴Data on file.  

• Trapped intestinal gas
• Gastroesophageal reflux (GER)
• Milk protein allergy
• Lactose intolerance
• Food allergy
• Bacterial imbalance

Clinical Manifestation

Colicky babies show the following symptoms⁵Understanding Colic. Available from: http://www.coliccalm.com/baby_infant_rd newborn_ articles/understanding-colic.htm [Accessed on 3 Feb 2017].   :

• Bouts of irritability, restlessness and crying, which start and stop for no apparent reason
• Bouts of abdominal pain that occur abruptly during or immediately after feeding, repeated many times throughout the day, intensifying by the evening
• During colic, baby begins to cry, pulls legs to the tummy and clenches fists
• Sometimes flatulence and constipation are observed

Outcomes of Infant Colic

Infantile colic can be distressing to parents whose infant is inconsolable during crying episodes. Although it is considered to be a self-limiting and benign affection, it is a stressful condition for parents.²Bahrami H, Ali Kiani M, Noras M. Massage for Infantile Colic: Review and Literature. Int J Pediatr. 2016;4(6):1953- 58.  ³Roberts DM, Ostapchuk M, O’Brien JG, Infantile Colic. Am Fam Physician. 2004 Aug 15;70(4):735- 740.   Colic can lead to :¹Kanabar D, Randhawa M, Clayton P. Improvement of symptoms in infant colic following reduction of lactose load with lactase. J Hum Nutr Diet. 2001 Oct;14(5):359- 63.  

• Failure to thrive and in extreme cases dehydration and electrolyte imbalance
• More commonly, it may contribute to impaired parent-child bonding
• Increases the risk of child abuse
• Contributes to maternal depression.

Link Between Infantile Colic and Lactose Indigestion

Lactose, a disaccharide molecule, is the main carbohydrate found in milk and dairy products like cheese, yogurt, nonfat dry milk powder and evaporated milk. Lactose is exclusively present in mammalian milk and is composed of glucose and galactose units joined by a chemical bond.⁶Heyman MB. Lactose Intolerance in infants, children and adolescents. Pediatrics.2006; 118(3):1279- 1286.  ⁷Noble R, Bovey A. Resolution of Lactose Intolerance and Colic in Breastfed Babies.Available from: http://www.health-e-learning.com/articles/Lactose.htm [Accessed on rd 23 September 2016].  ⁴Data on file.  

Lactose makes up around 7% of breast milk and it provides around 40% of the baby’s energy needs, helps in absorption of calcium and 8 iron and ensures healthy development.⁸Raising Children Network. Lactose Intolerance. Available from http://raisingchildren.rd net.au/articles/lactose_intolerance.html/context/644 [Accessed on 23 September 2016].   Furthermore, various dairy 6,9 products contain lactose and calcium as shown in Table 1.⁶Heyman MB. Lactose Intolerance in infants, children and adolescents. Pediatrics.2006; 118(3):1279- 1286.  ⁹Lami F, Callegari C, Tatali M, et al. Efficacy of addition of exogenous lactase to milk in adult lactase deficiency. Am J Gastroenterol. 1988 Oct;83(10):1145- 9.  

Failure to break down lactose in the small intestine results in significant quantities of undigested lactose entering the large intestine, where bacterial fermentation produces lactic acid, carbon dioxide, and result in colicky abdominal pain. This may be further compounded by an influx of water due to the osmotic effect of lactose and lactic acid in the colon that can lead to further 10 distension and acidic diarrhoea (Figure 1).¹⁰Kanabar D. Current treatment options in the management of infantile colic. Prescriber.2008;19(7):24-8.   Lactose content varies among species and individuals. Lactose content in human milk is 11 6.9 g per 100 g of milk.¹¹Food and Agriculture Organization of the United Nations. Milk and dairy product in human nutrition. 2013. Available from: http://www.fao.org/docrep/018/i3396e/ i3396e.th pdf [Accessed on 25 Jan 2017].  

Lactase Deficiencies in Paediatric Population

The term lactase deficiency is widely used to indicate a low or absent level of lactase enzyme in the small intestine, leading to 12 lactose intolerance.¹²Rings EH, Grand RJ, Büller HA. Lactose intolerance and lactase deficiency in children. Curr Opin Pediatr. 1994 Oct;6(5):562- 7.  

Absorption of lactose requires lactase activity to split the bond linking the two monosaccharides, as it cannot be digested by 7 humans in its disaccharide form.⁷Noble R, Bovey A. Resolution of Lactose Intolerance and Colic in Breastfed Babies.Available from: http://www.health-e-learning.com/articles/Lactose.htm [Accessed on rd 23 September 2016].   Lactase enzyme deficiency is an important contributing factor in paediatric lactose intolerance.There are four types of lactase deficiencies observed in the 6 paediatric population.⁶Heyman MB. Lactose Intolerance in infants, children and adolescents. Pediatrics.2006; 118(3):1279- 1286.   The four types are described below.

Primary Lactase Deficiency

Primary lactase deficiency is caused due to relative or total lactase inexistence. It develops in childhood at various ages in different racial groups. It is the most common cause of lactose malabsorption and lactose intolerance. Lactase deficiency is prevalent in all age groups & generally increases with age. There is 6 decline in expression of lactase enzyme after 5 years of age.⁶Heyman MB. Lactose Intolerance in infants, children and adolescents. Pediatrics.2006; 118(3):1279- 1286.  

Secondary Lactase Deficiency

Small bowel injuries such as acute gastroenteritis, persistent diarrhoea, small bowel overgrowth, cancer chemotherapy, or other causes of injury to the small intestinal mucosa give rise to secondary lactase deficiency. It is observed at any age but during infancy the occurrence is more common. Aetiologies include acute infection (e.g., rotavirus) causing small intestinal injury with loss of 1 the lactase-containing epithelial cells from the tips of the villi.¹Kanabar D, Randhawa M, Clayton P. Improvement of symptoms in infant colic following reduction of lactose load with lactase. J Hum Nutr Diet. 2001 Oct;14(5):359- 63.   Crohn’s disease and coeliac disease are the other causative factors.¹³American College of Gastroenterology. Lactose Intolerance in Children. Available from: nd http://patients.gi.org/topics/lactose-intolerance-in-children/ [Accessed on 22 September 2016].   The underlying cause needs to be treated instead of lactose elimination in such cases. After treatment completion, there can be normal consumption of lactose containing products which 6 are excellent sources of calcium and other nutrients in the diet.⁶Heyman MB. Lactose Intolerance in infants, children and adolescents. Pediatrics.2006; 118(3):1279- 1286.  

Developmental (neonatal) Lactase Deficiency

It is defined as the relative lactase deficiency observed among preterm infants of less than 34 week’s gestation. This is due to the immature gastrointestinal tract which is deficient in lactase and 6 other disaccharides.⁶Heyman MB. Lactose Intolerance in infants, children and adolescents. Pediatrics.2006; 118(3):1279- 1286.   Transient lactose intolerance is prevalent in the first 3 months of life. It has been identified as a possible causative factor in infant colic. According to a study conducted by Kanabar D et al., in most cases the immediate cause of infantile 1 colic is transient lactose intolerance.¹Kanabar D, Randhawa M, Clayton P. Improvement of symptoms in infant colic following reduction of lactose load with lactase. J Hum Nutr Diet. 2001 Oct;14(5):359- 63.  

Congenital Lactase Deficiency

It is a rare disorder with only few infants being affected. Intractable diarrhoea occurs due to the introduction of human milk or lactosecontaining formula in affected infants. Small intestinal biopsies reveal normal histologic characteristics but low or completely absent lactase concentrations. If not for quick recognition and treatment, the condition becomes life-threatening due to dehydration and electrolyte losses. Lactose in the diet needs to be 6 removed and substituted with a commercial lactose-free formula.⁶Heyman MB. Lactose Intolerance in infants, children and adolescents. Pediatrics.2006; 118(3):1279- 1286.  

Correlation between Lactase Deficiency and Lactose Intolerance

Lactase deficiency leads to lactose malabsorption that manifests as lactose intolerance (Figure 2). Lactose malabsorption is caused due to an imbalance between the quantity of lactose ingested and 6 the capacity for lactase to hydrolyse the disaccharide.⁶Heyman MB. Lactose Intolerance in infants, children and adolescents. Pediatrics.2006; 118(3):1279- 1286.  

Lactose Intolerance in Paediatric Population

More than 1/3^rd of Indians suffers from lactase deficiency. Lactase deficiency is prevalent in all age groups and generally increases with age. There is decline in expression of lactase enzyme after 5 years of age. Lactose intolerance plays a causal role in recurrent abdominal pain in children. Studies have shown that abdominal pain in children due to lactose intolerance can be up to 25%.¹⁴Frequency of lactose malabsorption among healthy southern and northern Indian populations by genetic analysis and lactose hydrogen breath and tolerance tests. Am J Clin Nutr. 2010 Jan;91(1):140-6.   ¹⁵Liebman WM. Recurrent abdominal pain in children: Lactose and sucrose intolerance,a prospective study. Pediatrics. 1979 Jul;64(1):43-5.  Lactose intolerance is defined as a clinical syndrome which causes symptoms like abdominal pain, diarrhoea, flatulence, nausea, and/or bloating after intake of lactose or lactose-containing food substances. The quantity of lactose that give rise to symptoms differs from infant to infant (or child to child). It depends on the following factors :⁶Heyman MB. Lactose Intolerance in infants, children and adolescents. Pediatrics.2006; 118(3):1279- 1286.  

• Amount of lactose consumed
• The degree of lactase deficiency
• The form of food substance in which lactose ingestion occurs
• Sensitivity of colon to lactose

Transient lactose intolerance has been identified as a probable causative factor in infant colic (Figure 3).¹Kanabar D, Randhawa M, Clayton P. Improvement of symptoms in infant colic following reduction of lactose load with lactase. J Hum Nutr Diet. 2001 Oct;14(5):359- 63.   In a study conducted by Moore DJ et al., on 122 healthy newborn infants, up to 78% of colicky infants show signs of lactose intolerance (positive breath H2 tests) at 6 weeks and 89% at 12 weeks (Figure 4).¹⁶Moore DJ, Robb TA, Davidson GP. Breath hydrogen response to milk containing lactose in colicky and noncolicky infants. J Pediatr. 1988 Dec;113(6):979- 84.  

Prevalence

Certain populations are more likely to be lactose intolerant than others.¹⁷Scrimshaw NS, Murray EB. The acceptability of milk and milk products in populations with a high prevalence of lactose intolerance. Am J Clin Nutr. 1988;48(4 Suppl):1079- 159.   Lactose intolerance occurs more often in people of Asian,African and South American descent than among people of European descent. According to experts, there is a greater chance of lactasedeficiency in those ethnicities that have not consumedlactose in their ancestral diet.¹⁸Healthwise Staff. Who is affected by Lactose Intolerance? Available from: http://www.rd healthlinkbc.ca/healthtopics/content.asp?hwid=ue5392 [Accessed on 23 September 2016].   According to American Academy of Pediatrics there is a variation among ethnicities on the prevalence of primary lactase deficiency. It depends on the consumption of dairy products in their diets. The incidence of primary lactase deficiency in populations is inversely proportional to the amount of dietary dairy products consumed. Only 2% of the Northern European population hasprimary lactasedeficiency.⁶Heyman MB. Lactose Intolerance in infants, children and adolescents. Pediatrics.2006; 118(3):1279- 1286.  

There is evidence of lactase deficiency in approximately 20% of Hispanic, Asian and African children below 5 years of age, whereas development of lactose intolerance symptoms is not seen in white children until after 4 or 5 years of age.⁶Heyman MB. Lactose Intolerance in infants, children and adolescents. Pediatrics.2006; 118(3):1279- 1286.  

Worldwide only 35% of the human population can digest lactose beyond the age of about seven or eight.¹⁹Leonardi M, Gerbault P, Thomas MG, Burger J. The evolution of lactase persistence in Europe. A synthesis of archaeological and genetic evidence. Int Dairy J. 2012;22:88–97. doi: 10.1016/j.idairyj.2011.10.010   Studies on Indian population report lactose intolerance in 27.4% of North Indians and 66.6% in South Indians.²⁰RK, Joshi YK, Singh DS, et al. Lactose intolerance in North and South Indians. Am J Clin Nutr. 1981;34(5):943- 946.  

Pathophysiology

There is uniformity of pathophysiology that results in manifestations of lactose intolerance. The pathophysiology does not vary according to the type or nature of lactase deficiency.²¹Sreedharan R, Tung J. Lactose Intolerance. In: Liacouras CA, Piccoli DA (eds.).Pediatric Gastroenterology. Philadelphia, USA; 2008.p. 146- 151.   The enzyme lactase is found in the microvilli of the small intestine. It breaks down and hydrolyses dietary lactose (a disaccharide sugar) into glucose and galactose (monosaccharide sugars) which are then transported across the cell membrane. When lactase is absent or deficient, unabsorbed lactose causes an influx of fluid into the bowel lumen, due to osmotic pressure. Gas and short-chain fatty acids are produced via fermentation as the unabsorbed lactose enters the colon and is used by the intestinal bacteria as a substrate. The colonic mucosa cannot absorb the fatty acids; this causes more fluid to be drawn into the bowel. The overall result is a marked increase of fluid and gas in the bowel leading to symptoms of lactose intolerance.²²Wyeth J, Steele R, Chin S. Lactose Intolerance. BPJ. 2007; 9:30- 35.  

Manifestations

In lactose intolerant individuals, lactose passes whole into the large intestine or colon, as it is not digested properly in the small intestine. The normal colon bacteria break it down after it reaches the colon.Hence, carbon dioxide and hydrogen gases are produced (Figure 5). The followingcommonsymptomsarisedue to gas production :⁸Raising Children Network. Lactose Intolerance. Available from http://raisingchildren.rd net.au/articles/lactose_intolerance.html/context/644 [Accessed on 23 September 2016].  ¹⁶Moore DJ, Robb TA, Davidson GP. Breath hydrogen response to milk containing lactose in colicky and noncolicky infants. J Pediatr. 1988 Dec;113(6):979- 84.  

Older children and adolescent

• Abdominal pain
• Abdominal distension
• Diarrhoea
• Borborygmi
• Flatulence
• Nausea
• Vomiting

Infants

• Colic symptoms and excessive crying
• Abdominal distension
• Loose stool
• Nappy rashes

Lactose intolerance symptoms start during childhood or adolescence and with age it tends to get worse. The severity of symptoms is proportional to the amount of the milk sugar ingested (more symptoms are observed after a meal that contains higher milk sugar). Although lactose intolerant individuals will experience discomfort after consuming lactose-containing products, the risk of developing more serious intestinal disease does not arise due to long-term lactose malabsorption.¹⁶Moore DJ, Robb TA, Davidson GP. Breath hydrogen response to milk containing lactose in colicky and noncolicky infants. J Pediatr. 1988 Dec;113(6):979- 84.  

Diagnosis

Diagnosis of lactase deficiency in infants and children is done through various tests. Diagnosis of lactase deficiency in infants,older children and adolescents can be done by below mentioned test, whereas diagnosis of lactose intolerance can be easily done by proper history taking and symptoms.

In Infants

The infant’s and the family’s accurate history is essential with detailed information about the feeding patterns and bowel habits. A thorough physical examination (hydration and nutrition status) is mandated to determine the infant’s overall condition. Other than this, baseline observations of temperature, pulse, respirations and blood pressure, together with growth and development measurements in relation to weight, height and head circumference, are required.²³Taylor C. Lactose Intolerance in infants. Nursing Times. 2006;102(17):43.   The following methods are used to diagnose lactase deficiency in infants.

• Checking for stool pH: The amount of lactic acid is measured in the infant’s stools. A stool pH of 5.5 indicates lactose intolerance.²³Taylor C. Lactose Intolerance in infants. Nursing Times. 2006;102(17):43.  
• Checking for faecal sugar: The baby’s faeces is tested for sugar.²⁴Department of Health Government of Western Australia. Available from: http:// healthnd ywa.wa.gov.au/Articles/J_M/Lactose-intolerance-in-babies [Accessed on 22 November 2016].  
• Lactose tolerance test: Fasting glucose levels are measured.Lactose malabsorption is detected when the increase in blood sugar is less than 20 mg/dL. Although the test is invasive in nature, it can be used to detect lactase enzyme deficiency in infants.²⁵Liu J, Chang J, Yao A, et al. Diagnosis and clinical observation of lactose-free milk powder on treatment of neonatal diarrhoea. Pak J Pharm Sci. 2016;29(1):309- 314.  
• Urine galactose detection: Urine galactose is detected after taking loaded lactose. Infants evacuate urine, and then consume breast milk or lactose-containing milk.²⁵Liu J, Chang J, Yao A, et al. Diagnosis and clinical observation of lactose-free milk powder on treatment of neonatal diarrhoea. Pak J Pharm Sci. 2016;29(1):309- 314.  
• Lactose rapid detection: Lactose rapid detection is a relatively new diagnostic method which involves detection of small intestinal epithelium mucosa cells through an endoscopic device.²⁵Liu J, Chang J, Yao A, et al. Diagnosis and clinical observation of lactose-free milk powder on treatment of neonatal diarrhoea. Pak J Pharm Sci. 2016;29(1):309- 314.  

In Children

• The faecal pH test: Due to physiologic overload of lactose in their diets, the faecal pH will normally be lower (5.0-5.5) in infants compared with older children and adolescents. This favours growth of Lactobacillus species in the colon. Faecal reducing substances can also be measured; excretion of a reducing sugar (lactose, glucose, fructose, and galactose but not sucrose) in the stools makes it positive.⁶Heyman MB. Lactose Intolerance in infants, children and adolescents. Pediatrics.2006; 118(3):1279- 1286.  
• Lactose challenge test: Take 500 Figure 5: Clinical Features of Lactose Overload mL of milk (25 grams of Lactose), followed by fasting till 1-3 hours. If individual has symptoms such as abdominal pain, gas, cramps, bloating or diarrhoea; he/she is likely to be lactose intolerant.
• Lactose intolerance test: This test was used as the primary test of lactose malabsorption before the availability of breath hydrogen test. The diagnosis of lactose intolerance was done on the onset of symptoms and/or positive test results after a standard lactose dose was ingested (2 g/kg of body weight or 250 g/m of body surface area; maximum 50 g in a 20% water solution). Lactose malabsorption was diagnosed if the maximum increase in blood glucose concentration was less than 26 mg/dL after a lactose-tolerance test dose.⁶Heyman MB. Lactose Intolerance in infants, children and adolescents. Pediatrics.2006; 118(3):1279- 1286.  
• Hydrogen breath test: This is the least invasive and most helpful test to diagnose lactose malabsorption. A standardised amount of lactose is administered (2 g/kg, up to a maximum of 25 g of milk) after an overnight fast. The amount of hydrogen in expired air over a 2- to 3-hour period is measured afterwards. An increase (>20 ppm) in the hydrogen expired after approximately 60 minutes is consistent with lactose malabsorption.⁶Heyman MB. Lactose Intolerance in infants, children and adolescents. Pediatrics.2006; 118(3):1279- 1286.  
• Stool examination: If an underlying cause for secondary lactose intolerance is suspected, testing for intestinal aetiologies include stool examination, particularly for parasites that affect the upper gastrointestinal tract such as Giardia lamblia and Cryptosporidia species, and blood tests for coeliac disease (i.e., total immunoglobulin A concentration and anti-tissue transglutaminase antibody) or immunodeficiency (quantitative immunoglobulins).⁶Heyman MB. Lactose Intolerance in infants, children and adolescents. Pediatrics.2006; 118(3):1279- 1286.  
• Intestinal biopsy: To detect an underlying gastrointestinal mucosal problem causing lactose malabsorption, intestinal 6 biopsy is required.⁶Heyman MB. Lactose Intolerance in infants, children and adolescents. Pediatrics.2006; 118(3):1279- 1286.  
• [¹³C] lactose breath test: Additional detailed information about the prevalence and significance of lactose intolerance can be 13 obtained from the newer tests. For example, the [¹³C] lactose breath test is still primarily an investigational tool. It could be used to augment the accuracy of the breath hydrogen test.⁶Heyman MB. Lactose Intolerance in infants, children and adolescents. Pediatrics.2006; 118(3):1279- 1286.  
• Dietary challenge: The American Academy of Pediatrics recommends that a lactose-free diet should be trialled for 2 weeks when lactose intolerance is suspected. All sources of lactose should be eliminated by studying food labelling closely. Lactose intolerance can be diagnosed if symptoms resolve over this 2-week period and then return when lactose containing foods are subsequently reintroduced.²²Wyeth J, Steele R, Chin S. Lactose Intolerance. BPJ. 2007; 9:30- 35.  

Consequences of Lactase Deficiency

Milk and dairy consumption is an essential part of our modern & traditional diets, especially for children and adolescents. It is deep rooted in our Indian culture. Milk and dairy are important for growing children as they provide protein, calcium, vitamin D and riboflavin.Moreover, the lactose in milk contains glucose and galactose.Galactose is essential for neurodevelopment and IQ. Lactose intolerance has been linked to malabsorption of the essential amino acid L-tryptophan. L-tryptophan deficiencies have been linked to serotonin deficiencies, clinical depression and anxiety.²⁶EFSA panel on Dietetic Products, Nutrition and Allergies; Scientific Opinion on Lactose thresholds in lactose intolerance and galactosaemia. EFSA Journal. 2010;8(9):1777.Available from: www.efsa.europa.eu/efsajournal.htm  

Management

Various options are available to manage lactose intolerance in children and infants. In children lactose can be managed by dietary restriction, lactose-free milks, dairy products with naturally lower levels of lactose, calcium and vitamin D.⁶Heyman MB. Lactose Intolerance in infants, children and adolescents. Pediatrics.2006; 118(3):1279- 1286.  ²²Wyeth J, Steele R, Chin S. Lactose Intolerance. BPJ. 2007; 9:30- 35.  ²⁷Berry J, Freeborn D. Lactose Intolerance in Children. Available from https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=90&contentid=p02003 th [Accessed on 24 September 2016].   In infants, formulas like term formulas, preterm and enriched formulas, soy formulas and lactose-free formulas are used for the management of lactose intolerance.²⁷Berry J, Freeborn D. Lactose Intolerance in Children. Available from https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=90&contentid=p02003 th [Accessed on 24 September 2016].  

The formulas developed for term infants-do not fulfill the growth and development requirements of the preterm infant. The lactose content of milk often influences, correctly or not, the ultimate decision about the use or continuation of milk in the diet. Apart from that milk and dairy-product avoidance has a negative effect on calcium and vitamin D intake in infants and children.⁶Heyman MB. Lactose Intolerance in infants, children and adolescents. Pediatrics.2006; 118(3):1279- 1286.  

In order to overcome these issues lactose malabsorption is often treated with commercial lactase preparations i.e. crushed tablet or drops of liquid.²⁹Tan-Dy CRY, Ohlsson A. Lactase treated feeds to promote growth and feeding tolerance in preterm infants. Available from: https:// www.nichd.nih.gov/ cochrane_nd data/tandyc_01/tandyc_01.html [Accessed on 22 November 2016].   In Infants WHO recommends exclusive breast feeding.

Milk/dairy avoidance is not recommended by Guidelines like European Food Safety Authority (EFSA) and National Institute of Health (NIH) (US), as it can lead to conditions like nutritional deficiency, poor bone health and depression.²⁶EFSA panel on Dietetic Products, Nutrition and Allergies; Scientific Opinion on Lactose thresholds in lactose intolerance and galactosaemia. EFSA Journal. 2010;8(9):1777.Available from: www.efsa.europa.eu/efsajournal.htm   Source of lactase impacts the pH stability of final preparation which decides the dosage, efficacy, safety & cost. The best source is Aspergillus oryzae.EFSA & United States food drug administration (USFDA), both approve & recommend Aspergillus oryzae. Lactase from Aspergillus oryzae source is considered Generally Recognised As Safe (GRAS) by USFDA and EFSA.²⁶EFSA panel on Dietetic Products, Nutrition and Allergies; Scientific Opinion on Lactose thresholds in lactose intolerance and galactosaemia. EFSA Journal. 2010;8(9):1777.Available from: www.efsa.europa.eu/efsajournal.htm   ³⁰U.S. Food and Drug Administration. Enzyme Preparations used in food (Partial list).Available from: http://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/th Enzyme Preparations/default.htm [Accessed on 19 Feb 2017].   Lactase preparations from Aspergillus oryzae are stable in an acidic environment and are practically pH independent. High activity throughout the GI tract, even in lower stomach where pH is less than 3.5 (Independent of pH), unlike other formulationswhichareunstableatpHof less than3.5.³¹Park YK, De Santi MSS, Pastore GM. Production and characterization of bgalactosidase from aspergillus oryzae. J Food Sci. 1979; 44: 100-103.  

The National Institute for Health and Care Excellence clinical Knowledge summary for infantile colic suggests a one-week trial of lactase as an option for infants of parents who feel unable to cope despite advice and reassurance for infantile colicky pain. Trials have also showed that there is 45% reduction in total crying time in infants by use of lactase enzyme.¹Kanabar D, Randhawa M, Clayton P. Improvement of symptoms in infant colic following reduction of lactose load with lactase. J Hum Nutr Diet. 2001 Oct;14(5):359- 63.   Figure 6 describes the treatment algorithm for infantile colic.³²Kanabar D. J Fam Health Care. 2004;14(2).  

Lactase Drops use in Infants

The last of the major intestinal disaccharidases to develop in preterm infants is lactase. Preterm infants are unable to digest lactose adequately due to inadequate lactase activity. There is potential for lactase preparations to be used to hydrolyse lactose in formulas and breast milk to minimise lactose malabsorption in preterm infants.²⁹Tan-Dy CRY, Ohlsson A. Lactase treated feeds to promote growth and feeding tolerance in preterm infants. Available from: https:// www.nichd.nih.gov/ cochrane_nd data/tandyc_01/tandyc_01.html [Accessed on 22 November 2016].  

Lactase drops should be used before each feeding during the first 3- 4 months of the baby’s life. After 3- 4 months of life of the newborn, lactase enzyme is produced in sufficient quantities. After this period use of lactase drops should be gradually tapered off.⁴Data on file.   Advantages associated with lactase drops are as follows :⁴Data on file.  

• It is a highly potent, biologically active and stable enzyme formulation that ensures efficacy at any level of lactose intolerance.
• The clinical symptoms associated with lactose intolerance are significantly reduced.
• It helps mothers to continue breastfeeding in lactose intolerant infants.

Storage of Lactase Drops

Lactase has a temperature of saturation, temperature above which the enzyme denatures, or loses its activity; the denaturation is an irreversible process. The melting temperature of lactase is 58℃ so it is not advisable to add lactase to hot milk. It should be warm.Lactase should be stored at 20-25℃, at which there is no risk of denaturation.⁴Data on file.  

In India lactase enzyme drops have recently become available.Each 1 mL contains lactase enzyme 600 FCC units.

Dosage of Drops in Infants

Direction I (for Breast-fed): Add 4 to 5 drops of lactase drops to few mL of expressed breast milk. The foremilk contains most of the lactose. Wait a few minutes, give this mixture to the baby and then breast feed as normal.⁴Data on file.  

Direction II (for formula/animal’s milk feed): Add 4 to 5 drops of 0 lactase drops per 50 mL of infant formula, when it is warm (30℃ to 40℃). Wait for 30 minutes, shake the formula occasionally and then feed the baby.⁴Data on file.  

Lactase Tablets use in Children

In India lactase tablet is now available. One tablet of lactase contains 4500 FCC lactase enzyme. Dosage of Tablets in children/adolescents is ½ to 1 tablet immediately before or with first bite/sip of dairy (lactose) containing meal/drink. The tablet has to be chewed thoroughly before swallowing. In case the person consumes more foods/drinks containing dairy after 20 to 45 minutes, another tablet has to be taken.⁴Data on file.   Beta-galactosidase tablets have been used in the treatment of lactose intolerance in children. Medow et al., conducted a study on 18 lactose intolerant children who were previously identified as being lactose intolerant and having no underlying organic gastrointestinal disease.Hydrogen production was significantly greater following placebo ingestion (maximum hydrogen excretion, approximately 60 ppm)compared with lactase-containing tablets (maximum hydrogen excretion, 7 ppm). The clinical symptoms observed in patients following placebo ingestion were abdominal pain (89% of the subjects), bloating (83%), diarrhoea (61%) and flatulence (44%).

This demonstrated that coingestion of lactose and lactase-containing tablets significantly reduce both breath hydrogen excretion and clinical symptoms associated with lactose intolerance.³³Medow MS, Thek KD, Newman LJ, et al. Beta-galactosidase tablets in the treatment of lactose intolerance in pediatrics.Am J Dis Child 1990 Nov;144(11):1261- 4.  Administration of lactase enzyme in children reduces the symptoms of lactose intolerance, thereby enabling them to consume dairy products. Thus, preventing complications such as rickets which arises due to calcium deficiency in lactose intolerant children.³⁴Guandalini S. Paediatric Lactose Intolerance. Available from: http://misc.medscape.th com/pi/iphone/medscapeapp/html/A930971-business.html[Accessed on 15 November 2016].   In lactose intolerant children, it is recommended to restrict lactose or supplement the enzyme that digests the sugar (lactase) as lactose sugar cantrigger symptomsof irritablebowel syndrome.³⁵Stanford Children’s Health. Irritable Bowel Syndrome in Children. Available from: http://www.stanfordchildrens.org/en/topic/default?id=irritable-bowel-syndrome-inth children-90-P01983 [Accessed on 15 November 2016].  

Clinical Trials

Few clinical trials have reported effectiveness of lactase in reducing symptoms of lactose intolerance in paediatric population. Two studies conducted on infants are given in Table 2.An open-challenged study conducted by Biller et al., on children -16 years of age (n = 16), who were given lactase enzyme,reported reduction in clinical symptoms.⁴Data on file.  

An another open-challenged study conducted by Barillas & Solomons on 27 school children (2.5-6 years),who were given lactase enzyme, reported reduction in hydrogen excretion.⁴Data on file.  

Conclusion

Lactose intolerance rises due to lactose malabsorption. There is imbalance between the quantity of lactose ingested and the capacity for lactase to hydrolyse the disaccharide. Infantile colic,common problem in infancy, could be due to lactose intolerance.

Management of lactose intolerance in infants by the use of lactase enzyme in the first 3 to 4months of the infant’s life could be used as a therapeutic oral lactase enzyme supplement for aweek in infantswith lactose intolerance. In those where there is a response to this, it may be continued for 3- 4months. Thiswould help themother to continue breast feeding normally. Lactase drops can be easily stored at room temperature with no risk of denaturation. Beta-galactosidase tablets coingested with lactose result in reduction of clinical symptoms,mainly inchildrenwithsuspectedlactose intolerance.

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