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Alginic acid (algine, alginate) is a viscous gum that is abundant in the cell walls of brown algae. more...

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Structure

Chemically, it is a linear copolymer with homopolymeric blocks of (1-4)-linked ß-D-mannuronate (M) and its C-5 epimer α-L-guluronate (G) residues, respectively, covalently linked together in different sequences or blocks.

The monomers can appear in homopolymeric blocks of consecutive G-residues (G-blocks), consecutive M-residues (M-blocks), alternating M and G-residues (MG-blocks) or randomly organized blocks. The relative amount of each block type varies both with the origin of the alginate. Alternating blocks form the most flexible chains and are more soluble at lower pH than the other blocks. G-blocks form stiff chain elements, and two G-blocks of more than 6 residues each form stable cross-linked junctions with divalent cations (e.g. Ca²⁺, Ba²⁺, Sr²⁺ among others) leading to a three-dimensional gel network. At low pH, protonized alginates will form acidic gels. In these gels, it is mostly the homopolymeric blocks that form the junctions, where the stability of the gel is determined by the relative content of G-blocks.

Forms

Commercial varieties of alginate are extracted from seaweed, including the giant kelp Macrocystis pyrifera, Ascophyllum Nodosum and various types of Laminaria.

Alginate absorbs water quickly, which makes it useful as an additive in dehydrated products such as slimming aids, and in the manufacture of paper and textiles. It is also used for waterproofing and fireproofing fabrics, for thickening drinks, ice cream and cosmetics, and as a detoxifier that can absorb poisonous metals from the blood. Alginate is also produced by certain bacteria, notably Azotobacter species. Attempts to produce bacterial alginate have not yet been commercially successful.

Alginate ranges from white to yellowish brown, and takes filamentous, grainy, granular, and powdered forms. It is insoluble in water and organic solvents, and dissolves slowly in basic solutions of sodium carbonate, sodium hydroxide and trisodium phosphate.

Uses

Purified forms of alginate are used in antacid preparations such as Gaviscon®, Bisodol®, Asilone®, and Boots Own® tablets. Alginate is used extensivly as a mold-making material in dentistry and prosthetics, and in textiles. It is also used in the food industry, for thickening soups and jellies. Calcium alginate is used in burn dressings that promote healing and can be removed painlessly.

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What is the best treatment for gastroesophageal reflux and vomiting in infants?
From Journal of Family Practice, 4/1/05 by Vanessa McPherson

* Evidence-Based Answer

The literature on pediatric reflux can be divided into studies addressing clinically apparent reflux (vomiting or regurgitation) and reflux as measured by pH probe or other methods (TABLES 1 AND 2). Sodium alginate reduces vomiting and improves parents' assessment of symptoms (strength of recommendation [SOR]: B, small randomized controlled trial [RCT]). Formula thickened with rice cereal decreases the number of postprandial emesis episodes in infants with gastroesophageal reflux disease (GERD) (SOR: B, small RCT).

There are conflicting data on the effect of carob bean gum as a formula thickener and its effect on regurgitation frequency (SOR: B, small RCTs). Metoclopramide does not affect vomiting or regurgitation, but is associated with greater weight gain in infants over 3 months with reflux (SOR: B, low-quality RCTs).

Carob bean gum used as a formula thickener decreases reflux as measured by intraluminal impedance but not as measured by pH probe (SOR: B, RCT). Omeprazole and metoclopramide each improve the reflux index as measured by esophageal pH probe (SOR: B, RCT).

Evidence is conflicting for other commonly used conservative measures (such as positional changes) or other medications for symptomatic relief of infant GERD. There is very limited evidence or expert opinion regarding breastfed infants, particularly with regard to preservation of breastfeeding during therapy.

* Evidence Summary

Regurgitation ("spitting up") and gastroesophageal reflux are common in infants. In a cross-sectional survey of 948 parents of healthy infants aged 0 to 13 months, regurgitation occurred daily in half of infants from birth to 3 months old, peaked to 67% at age 4 months, and was absent in 95% by age 12 months. (1) Gastroesophageal disease (GERD) is characterized by refractory symptoms or complications (pain, irritability, vomiting, failure to thrive, dysphagia, respiratory symptoms, or esophagitis) and occurs in the minority of infants with reflux. (2) This distinguishes the "happy spitter," whose parents may simply require reassurance, from infants who require treatment.

Unfortunately, most of the available studies do not make this distinction in their subjects. Also, available data primarily regard formula-fed infants, and are insufficient to make recommendations for breastfed infants. Esophageal pH probe monitoring is the gold standard for measuring reflux in research; however, its correlation with symptoms is questionable and it is infrequently used in clinical practice. (3) Therefore, recommendations are focused primarily on treating only clinically-evident reflux (emesis and regurgitation).

Five small RCTs studied the practice of using formula thickeners (TABLES 1 AND 2). In 1 study, formula thickened with rice cereal decreased emesis episodes. (4) Two studies of carob bean gum-thickened formula vs plain formula yielded conflicting results. (5,6) In the study showing improvement with carob bean gum, the parents were not blinded to the treatment, which may have led to bias favoring the treatment. (5) An uncontrolled, comparative trial of carob bean gum vs rice cereal suggested superiority of carob bean gum as a thickener, although both treatments yielded improvement. (7) Carob bean gum is available in the UK as a powder (Instant Carobel) but is not widely available in the US.

Three trials studied the effects of other conservative therapies such as positional changes and pacifiers on reflux measured by pH probe; unfortunately, none assessed clinical outcomes such as emesis or regurgitation. (3) Reflux by pH probe was worsened in a trial studying the infant seat for positioning. In the trial studying elevating the head of the bed to 30 [degrees] in the prone position, reflux measured by pH probe was also unchanged; prone positioning is no longer recommended due to the risk of Sudden Infant Death Syndrome (SIDS). (8) The trial of pacifier use showed improvement of reflux by pH probe when used in the seated position, but worsening in the prone position. Since pH probe does not necessarily reflect clinical symptoms, the utility of the information from these studies is limited.

Only I trial of drugs used to treat infant reflux measured clinical symptoms. This large manufacturer-sponsored RCT found that sodium alginate (9) significantly reduced emesis episodes in treated infants. Sodium alginate is marketed in the UK as Gaviscon Infant. While this trial included breastfed infants, it did not report the numbers of breastfed infants in the 2 treatment groups or present data separately for breastfed infants. Small RCTs of metoclopramide (10) and omeprazole (11) show significant improvement in reflux index measured by pH probe. However, metoclopramide yielded no improvement in symptom counts, and the omeprazole study resulted in no differences in "cry-fuss time" between treatment groups.

* Recommendations from Others

The North American Society for Pediatric Gastroenterology and Nutrition recommends thickening agents or a trial of hypoallergenic formula for vomiting infants. (2) They caution against prone positioning and favor proton pump inhibitors over H2 blockers for symptomatic relief and healing of esophagitis. They found insufficient evidence to recommend surgery over medication.

REFERENCES

(1.) Nelson SP, Chen EH., Syniar GM, Christoffel KK. Prevalence of symptoms of gastroesophageal reflux during infancy. A pediatric practice-based survey. Pediatric Practice Research Group. Arch Pediatr Adolesc Med 1997; 151:569-572.

(2.) Rudolph CD, Mazur LJ, Liptak GS, et al; North American Society for Pediatric Gastroenterology and Nutrition. Guidelines for evaluation and treatment of gastroesophageal reflux in infants and children: Recommendations of the North American Society for Pediatric Gastroenterology and Nutrition. J Pediatr Gastroenterol Nutr 2001; 32 Suppl 2:S1-S31.

(3.) Carroll AE, Garrison, MM, Christakis DA. A systematic review of nonpharmacological and nonsurgical therapies for gastroesophageal reflux in infants. Arch Pediatr Adolesc Med 2002; 156:109-113.

(4.) Orenstein, SR, Magill, HL, Brooks, R Thickening of infant feedings for therapy of gastroesophageal reflux. J Pediatr 1987; 110:181-186.

(5.) Wenzl TG, Schneider S, Scheele F, Silny J, Heimann G, Skopnik H. Effects of thickened feeding on gastroesophageal reflux in infants: a placebo-controlled crossover study using intraluminal impedance. Pediatrics 2003; 111(4 Pt 1): e355-359.

(6.) Vandemplas Y, Hachimi-Idrissi S, Casteels A, Mahler T, Loeb. A clinical trial with an "anti-regurgitation" formula. Eur J Pediatr 1994; 153:419-423.

(7.) Borelli O, Salvia G, Campanozzi A. Use of a new thickened formula for treatment of symptomatic gastroesophageal reflux in infants. Ital J Gastroenterol Hepatol 1997, 29:237-242.

(8.) Orenstein, SR. Prone positioning in infant gastroesophageal reflux: Is elevation of the head worth the trouble? J Pediatr 1990; 117:184-187.

(9.) Miller S. Comparison of the efficacy and safety of a new aluminum-free paediatric alginate preparation and placebo in infants with recurrent gastro-oesophageal reflux. Curr Med Res Opin 1999; 15:160-168.

(10.) olia V, Calhoun J, Kuhns L, Kauffman RE. Randomized, prospective double-blind trial of metoclopramide and placebo for gastroesophageal reflux in infants. J Pediatr 1989; 115: 141-145.

(11.) Moore, D J, Tao BS, Lines DR, Hirte C, Heddle ML, Davidson GR Double-blind placebo-controlled trial of omeprazole in irritable infants with gastroesophageal reflux. J Pediatr 2003; 143:219-223.

* Clinical Commentary

Lack of age-appropriate RCTs make evidence-based treatment difficult

Gastroesophageal reflux, defined as the passage of gastric contents into the esophagus, is one of the most common gastroesophageal problems in infants. GERD is a pathological process in infants manifested by poor weight gain, signs of esophagitis, persistent respiratory symptoms or complications, and changes in neurologic behavior. Gastroesophageal reflux generally resolves within the first year of life, as the lower esophageal sphincter mechanism matures. Traditionally, these infants have been managed conservatively with feeding schedule modifications, thickened feeds, changes in positions after feeding, and formula changes. Depending on the history and clinical presentation of an infant with GERD, more detailed evaluation and treatment may be necessary.

As per the North American Society for Pediatric Gastroenterology and Nutrition, if an upper gastrointestinal series has ruled out anatomic causes of gastroesophageal reflux, and nonpharmacologic interventions have failed, an acid suppressive agent is usually the first line of therapy. The lack of age-appropriate case definitions and randomized controlled trials, however, make it difficult for those practitioners who treat infants to have a evidence-based protocol for managing GERD.

Alfreda L. Bell, MD, Kelsey-Seybold Clinic, Houston, Tex

Vanessa McPherson, MD, Carolinas Medical Center and University of North Carolina-Chapel Hill, Charlotte, NC

Sarah Towner Wright, MLS, Health Sciences Library, University of North Carolina at Chapel Hill

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