Sarah Towner Wright, MLS

Evidence summary

Cradle cap is a form of seborrheic dermatitis that manifests as greasy patches of scaling on the scalp of infants between the second week and sixth month of life.^1,2 Untreated, it usually resolves at 8 months.¹ It’s generally nonpruritic and doesn’t bother the infant, though it can be a stressor for parents.¹

Researchers have noted a potential link with increased concentrations of the yeast Malassezia furfur (formerly Pityrosporum ovale), but a causative mechanism has not been identified.^1,2 Overnight use of emollients such as mineral oil to soften scales followed by gentle brushing and washing with baby shampoo is an accepted treatment, although no trials could be found to show its efficacy for infants.^1,3

Numerous treatments for seborrheic dermatitis with proven efficacy for adults have been adopted for use for infants. These include topical antifungals, anti-dandruff shampoos with zinc pyrithione or selenium sulfide, coal tar preparations, and episodic topical corticosteroids.^1,4 Although each of these agents is used for infants with cradle cap, significantly sized randomized controlled trials in this age group are essentially absent.

Although limited evidence exists for seborrhea treatment in any age group, ketoconazole shampoo appears to be backed by the strongest evidence. For example, an uncontrolled multicenter trial with 575 adults found ketoconazole shampoo was superior to placebo for treatment of scalp seborrheic dermatitis with an 88% “excellent response” rate (P<.0001, no relative risk or confidence intervals given).⁴

Based on small studies, ketoconazole appears safe and effective for infants. A small (n=13) phase I safety trial of infants demonstrated that ketoconazole shampoo applied twice weekly for 1 month resulted in no detectable serum ketoconazole levels or elevation in liver function tests.⁵ In another small (n=19) uncontrolled study of once-daily ketoconazole 2% cream, 79% of infants affected with seborrheic dermatitis of the scalp and diaper area showed good response by day 10 (no statistical methods reported). Peak plasma ketoconazole levels in this study were only 1% to 2% of those documented after systemic administration.⁶

Studies conducted on topical steroids have also shown weak data. An unblinded uncontrolled comparative study of 2% ketoconazole cream and 1% hydrocortisone cream in the treatment of infantile seborrheic dermatitis revealed no statistical difference (31% vs 35%) in severity for 48 infants. All skin lesions in both treatment groups were cleared by the end of the second week of treatment.²

Multiple authors note safety concerns when considering treatment for mild and self-limited conditions such as cradle cap. Several studies have demonstrated systemic absorption and, in some cases, adrenocortical suppression when using mild topical steroids such as 1% hydrocortisone cream in pediatric populations.^1,3,7

Recommendations from others

The guidance from PRODIGY (the UK’s National Health Service primary care database) recommends regular washing with baby shampoo followed by gentle brushing. Alternatively, softening the scale with mineral oil, followed by gentle brushing and shampooing is an alternative approach. Ketoconazole 2% shampoo or cream once a day has been shown to be effective; PRODIGY recommends avoiding topical corticosteroids.¹

A review article recommends daily shampooing with an unmedicated shampoo. If this doesn’t work, the authors recommend trying a dandruff shampoo and softening the scales with mineral oil before washing.⁸ While the American Academy of Dermatology has no official guidelines on this subject, their patient-oriented pamphlet Dermatology Insights suggests that “cradle cap is treated with anti-dandruff or baby shampoo, with or without hydrocortisone lotion or cream, depending on the severity.”⁹

Acknowledgments

The opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

Cradle cap is a form of seborrheic dermatitis that manifests as greasy patches of scaling on the scalp of infants between the second week and sixth month of life.^1,2 Untreated, it usually resolves at 8 months.¹ It’s generally nonpruritic and doesn’t bother the infant, though it can be a stressor for parents.¹

Researchers have noted a potential link with increased concentrations of the yeast Malassezia furfur (formerly Pityrosporum ovale), but a causative mechanism has not been identified.^1,2 Overnight use of emollients such as mineral oil to soften scales followed by gentle brushing and washing with baby shampoo is an accepted treatment, although no trials could be found to show its efficacy for infants.^1,3

Numerous treatments for seborrheic dermatitis with proven efficacy for adults have been adopted for use for infants. These include topical antifungals, anti-dandruff shampoos with zinc pyrithione or selenium sulfide, coal tar preparations, and episodic topical corticosteroids.^1,4 Although each of these agents is used for infants with cradle cap, significantly sized randomized controlled trials in this age group are essentially absent.

Although limited evidence exists for seborrhea treatment in any age group, ketoconazole shampoo appears to be backed by the strongest evidence. For example, an uncontrolled multicenter trial with 575 adults found ketoconazole shampoo was superior to placebo for treatment of scalp seborrheic dermatitis with an 88% “excellent response” rate (P<.0001, no relative risk or confidence intervals given).⁴

Based on small studies, ketoconazole appears safe and effective for infants. A small (n=13) phase I safety trial of infants demonstrated that ketoconazole shampoo applied twice weekly for 1 month resulted in no detectable serum ketoconazole levels or elevation in liver function tests.⁵ In another small (n=19) uncontrolled study of once-daily ketoconazole 2% cream, 79% of infants affected with seborrheic dermatitis of the scalp and diaper area showed good response by day 10 (no statistical methods reported). Peak plasma ketoconazole levels in this study were only 1% to 2% of those documented after systemic administration.⁶

Studies conducted on topical steroids have also shown weak data. An unblinded uncontrolled comparative study of 2% ketoconazole cream and 1% hydrocortisone cream in the treatment of infantile seborrheic dermatitis revealed no statistical difference (31% vs 35%) in severity for 48 infants. All skin lesions in both treatment groups were cleared by the end of the second week of treatment.²

Multiple authors note safety concerns when considering treatment for mild and self-limited conditions such as cradle cap. Several studies have demonstrated systemic absorption and, in some cases, adrenocortical suppression when using mild topical steroids such as 1% hydrocortisone cream in pediatric populations.^1,3,7

Recommendations from others

The guidance from PRODIGY (the UK’s National Health Service primary care database) recommends regular washing with baby shampoo followed by gentle brushing. Alternatively, softening the scale with mineral oil, followed by gentle brushing and shampooing is an alternative approach. Ketoconazole 2% shampoo or cream once a day has been shown to be effective; PRODIGY recommends avoiding topical corticosteroids.¹

A review article recommends daily shampooing with an unmedicated shampoo. If this doesn’t work, the authors recommend trying a dandruff shampoo and softening the scales with mineral oil before washing.⁸ While the American Academy of Dermatology has no official guidelines on this subject, their patient-oriented pamphlet Dermatology Insights suggests that “cradle cap is treated with anti-dandruff or baby shampoo, with or without hydrocortisone lotion or cream, depending on the severity.”⁹

Acknowledgments

The opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

Cradle cap is a form of seborrheic dermatitis that manifests as greasy patches of scaling on the scalp of infants between the second week and sixth month of life.^1,2 Untreated, it usually resolves at 8 months.¹ It’s generally nonpruritic and doesn’t bother the infant, though it can be a stressor for parents.¹

Researchers have noted a potential link with increased concentrations of the yeast Malassezia furfur (formerly Pityrosporum ovale), but a causative mechanism has not been identified.^1,2 Overnight use of emollients such as mineral oil to soften scales followed by gentle brushing and washing with baby shampoo is an accepted treatment, although no trials could be found to show its efficacy for infants.^1,3

Numerous treatments for seborrheic dermatitis with proven efficacy for adults have been adopted for use for infants. These include topical antifungals, anti-dandruff shampoos with zinc pyrithione or selenium sulfide, coal tar preparations, and episodic topical corticosteroids.^1,4 Although each of these agents is used for infants with cradle cap, significantly sized randomized controlled trials in this age group are essentially absent.

Although limited evidence exists for seborrhea treatment in any age group, ketoconazole shampoo appears to be backed by the strongest evidence. For example, an uncontrolled multicenter trial with 575 adults found ketoconazole shampoo was superior to placebo for treatment of scalp seborrheic dermatitis with an 88% “excellent response” rate (P<.0001, no relative risk or confidence intervals given).⁴

Based on small studies, ketoconazole appears safe and effective for infants. A small (n=13) phase I safety trial of infants demonstrated that ketoconazole shampoo applied twice weekly for 1 month resulted in no detectable serum ketoconazole levels or elevation in liver function tests.⁵ In another small (n=19) uncontrolled study of once-daily ketoconazole 2% cream, 79% of infants affected with seborrheic dermatitis of the scalp and diaper area showed good response by day 10 (no statistical methods reported). Peak plasma ketoconazole levels in this study were only 1% to 2% of those documented after systemic administration.⁶

Studies conducted on topical steroids have also shown weak data. An unblinded uncontrolled comparative study of 2% ketoconazole cream and 1% hydrocortisone cream in the treatment of infantile seborrheic dermatitis revealed no statistical difference (31% vs 35%) in severity for 48 infants. All skin lesions in both treatment groups were cleared by the end of the second week of treatment.²

Multiple authors note safety concerns when considering treatment for mild and self-limited conditions such as cradle cap. Several studies have demonstrated systemic absorption and, in some cases, adrenocortical suppression when using mild topical steroids such as 1% hydrocortisone cream in pediatric populations.^1,3,7

Recommendations from others

The guidance from PRODIGY (the UK’s National Health Service primary care database) recommends regular washing with baby shampoo followed by gentle brushing. Alternatively, softening the scale with mineral oil, followed by gentle brushing and shampooing is an alternative approach. Ketoconazole 2% shampoo or cream once a day has been shown to be effective; PRODIGY recommends avoiding topical corticosteroids.¹

A review article recommends daily shampooing with an unmedicated shampoo. If this doesn’t work, the authors recommend trying a dandruff shampoo and softening the scales with mineral oil before washing.⁸ While the American Academy of Dermatology has no official guidelines on this subject, their patient-oriented pamphlet Dermatology Insights suggests that “cradle cap is treated with anti-dandruff or baby shampoo, with or without hydrocortisone lotion or cream, depending on the severity.”⁹

Acknowledgments

The opinions and assertions contained herein are the private views of the authors and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Evidence summary

Colic has been described using the “rule of 3”: crying for at least 3 hours per day on at least 3 days per week for at least 3 weeks.¹ The distinction can be subtle; a normal infant can cry more than 2 hours per day. This syndrome has its onset typically in the first few weeks of life. It spontaneously resolves by age 4 to 6 months. Prevalence depends on the definition used for colic; approximately 5% to 25% of infants meet some reasonable definition of colic.² The cause of infantile colic is poorly understood. Although clinicians tend to focus on a likely gastrointestinal cause, neuropsychological issues, food allergy, and parenting misadventures are also potential contributing factors.

There are myriad strategies—ranging from craniosacral osteopathic manipulation to car ride simulation—offered for dealing with infantile colic. Although none of these treatments has been validated in rigorous studies, the available evidence offers tentative support for 3 strategies: (1) a trial of a hypoallergenic (protein hydrolysate) formula (for formula fed infants), (2) a low-allergen maternal diet (for breastfeeding mothers), and (3) reduced stimulation of the infant.

A systematic review analyzed controlled clinical trials lasting at least 3 days involving infants less than 6 months of age who cried excessively.³ Twenty-seven studies were included; the outcome measure was colic symptoms, typically reported as duration of crying. Two reports studying hypoallergenic (protein hydrolysate) formula in nearly 130 infants found an effect size of 0.22 (95% confidence interval [CI], 0.10–0.34) for the hypoallergenic formula. Additionally, 3 behavioral trials (involving nearly 200 infants) revealed the benefits of reduced stimulation of the colicky infant (effect size of 0.48; 95% CI, 0.23–0.74).

A more recent systematic review⁴ followed a similar high-quality search strategy and identified 22 articles, and reported a number needed to treat (NNT) of 6 for the 2 hypoallergenic formula studies identified in the previous review.⁴ Because of concern regarding the quality of the behavioral studies involving infants with colic, the authors of this second review only included 1 small (42 patients) trial of decreased stimulation, which resulted in a relative risk (RR) of 1.87 (95% CI, 1.04–3.34) and a NNT of 2. There was some inconclusive evidence to suggest benefit to dietary adjustment for breastfeeding mothers (specifically, the avoidance of cow’s milk and other potential allergens like nuts, eggs, and wheat).

A recent randomized controlled trial confirmed the value of this approach by showing significant improvement in distress scores of infants whose mothers followed a low-allergen diet (excluding dairy, soy, wheat, eggs, peanuts, tree nuts, and fish) for 7 days.⁵ This well-designed study included 107 patients (a relatively large sample in the published research about colic), and showed an absolute risk reduction of 37% (NNT=3) for those mothers following the challenge.

A small RCT (43 patients) suggested efficacy in the substitution of a whey hydrolysate formula in place of cow’s milkbased formula for infants with colic (casein hydrolysate formula has been more widely studied), but there continues to be controversy regarding the preferred protein hydrolysate formula (whey vs casein) in the treatment of colic.³

Several medications have been tested in RCTs; only dicyclomine has shown an effect in a few small RCTs.^3,4 However, there have been reports of apnea and other serious, although infrequent, adverse effects. For that reason, the manufacturer has contraindicated the use of this medication in infants aged <6 months.

A small (n=68) study of an herbal tea showed reduced symptoms (RR=0.57 favoring the active tea), although the mean volume of tea consumption (32 mL/kg/d) is a nutritional concern in this age group.⁶ No adverse events were noted, but the small sample size limits the ability to detect any but the most common events.

Recommendations from others

The American Gastroenterological Association recommends a hypoallergenic, protein hydrolysate formula for formula fed infants or a maternal low-allergen diet as an initial strategy for infant struggling with colic symptoms if the clinician is considering a diagnosis of (cow’s milk) allergy.⁷

The American Academy of Family Physicians on their familydoctor.org web site makes no specific formula or diet adjustment recommendations.⁸ The web site does list some techniques (eg, massage or warm compress of abdomen, swing or car rides) not supported by the available evidence. The National Library of Medicine and the National Institutes of Health web site Medline Plus presents similar information.⁹ The American Academy of Pediatrics does not address the topic on its public web site.

Evidence summary

Colic has been described using the “rule of 3”: crying for at least 3 hours per day on at least 3 days per week for at least 3 weeks.¹ The distinction can be subtle; a normal infant can cry more than 2 hours per day. This syndrome has its onset typically in the first few weeks of life. It spontaneously resolves by age 4 to 6 months. Prevalence depends on the definition used for colic; approximately 5% to 25% of infants meet some reasonable definition of colic.² The cause of infantile colic is poorly understood. Although clinicians tend to focus on a likely gastrointestinal cause, neuropsychological issues, food allergy, and parenting misadventures are also potential contributing factors.

There are myriad strategies—ranging from craniosacral osteopathic manipulation to car ride simulation—offered for dealing with infantile colic. Although none of these treatments has been validated in rigorous studies, the available evidence offers tentative support for 3 strategies: (1) a trial of a hypoallergenic (protein hydrolysate) formula (for formula fed infants), (2) a low-allergen maternal diet (for breastfeeding mothers), and (3) reduced stimulation of the infant.

A systematic review analyzed controlled clinical trials lasting at least 3 days involving infants less than 6 months of age who cried excessively.³ Twenty-seven studies were included; the outcome measure was colic symptoms, typically reported as duration of crying. Two reports studying hypoallergenic (protein hydrolysate) formula in nearly 130 infants found an effect size of 0.22 (95% confidence interval [CI], 0.10–0.34) for the hypoallergenic formula. Additionally, 3 behavioral trials (involving nearly 200 infants) revealed the benefits of reduced stimulation of the colicky infant (effect size of 0.48; 95% CI, 0.23–0.74).

A more recent systematic review⁴ followed a similar high-quality search strategy and identified 22 articles, and reported a number needed to treat (NNT) of 6 for the 2 hypoallergenic formula studies identified in the previous review.⁴ Because of concern regarding the quality of the behavioral studies involving infants with colic, the authors of this second review only included 1 small (42 patients) trial of decreased stimulation, which resulted in a relative risk (RR) of 1.87 (95% CI, 1.04–3.34) and a NNT of 2. There was some inconclusive evidence to suggest benefit to dietary adjustment for breastfeeding mothers (specifically, the avoidance of cow’s milk and other potential allergens like nuts, eggs, and wheat).

A recent randomized controlled trial confirmed the value of this approach by showing significant improvement in distress scores of infants whose mothers followed a low-allergen diet (excluding dairy, soy, wheat, eggs, peanuts, tree nuts, and fish) for 7 days.⁵ This well-designed study included 107 patients (a relatively large sample in the published research about colic), and showed an absolute risk reduction of 37% (NNT=3) for those mothers following the challenge.

A small RCT (43 patients) suggested efficacy in the substitution of a whey hydrolysate formula in place of cow’s milkbased formula for infants with colic (casein hydrolysate formula has been more widely studied), but there continues to be controversy regarding the preferred protein hydrolysate formula (whey vs casein) in the treatment of colic.³

Several medications have been tested in RCTs; only dicyclomine has shown an effect in a few small RCTs.^3,4 However, there have been reports of apnea and other serious, although infrequent, adverse effects. For that reason, the manufacturer has contraindicated the use of this medication in infants aged <6 months.

A small (n=68) study of an herbal tea showed reduced symptoms (RR=0.57 favoring the active tea), although the mean volume of tea consumption (32 mL/kg/d) is a nutritional concern in this age group.⁶ No adverse events were noted, but the small sample size limits the ability to detect any but the most common events.

Recommendations from others

The American Gastroenterological Association recommends a hypoallergenic, protein hydrolysate formula for formula fed infants or a maternal low-allergen diet as an initial strategy for infant struggling with colic symptoms if the clinician is considering a diagnosis of (cow’s milk) allergy.⁷

The American Academy of Family Physicians on their familydoctor.org web site makes no specific formula or diet adjustment recommendations.⁸ The web site does list some techniques (eg, massage or warm compress of abdomen, swing or car rides) not supported by the available evidence. The National Library of Medicine and the National Institutes of Health web site Medline Plus presents similar information.⁹ The American Academy of Pediatrics does not address the topic on its public web site.

Evidence summary

Colic has been described using the “rule of 3”: crying for at least 3 hours per day on at least 3 days per week for at least 3 weeks.¹ The distinction can be subtle; a normal infant can cry more than 2 hours per day. This syndrome has its onset typically in the first few weeks of life. It spontaneously resolves by age 4 to 6 months. Prevalence depends on the definition used for colic; approximately 5% to 25% of infants meet some reasonable definition of colic.² The cause of infantile colic is poorly understood. Although clinicians tend to focus on a likely gastrointestinal cause, neuropsychological issues, food allergy, and parenting misadventures are also potential contributing factors.

There are myriad strategies—ranging from craniosacral osteopathic manipulation to car ride simulation—offered for dealing with infantile colic. Although none of these treatments has been validated in rigorous studies, the available evidence offers tentative support for 3 strategies: (1) a trial of a hypoallergenic (protein hydrolysate) formula (for formula fed infants), (2) a low-allergen maternal diet (for breastfeeding mothers), and (3) reduced stimulation of the infant.

A systematic review analyzed controlled clinical trials lasting at least 3 days involving infants less than 6 months of age who cried excessively.³ Twenty-seven studies were included; the outcome measure was colic symptoms, typically reported as duration of crying. Two reports studying hypoallergenic (protein hydrolysate) formula in nearly 130 infants found an effect size of 0.22 (95% confidence interval [CI], 0.10–0.34) for the hypoallergenic formula. Additionally, 3 behavioral trials (involving nearly 200 infants) revealed the benefits of reduced stimulation of the colicky infant (effect size of 0.48; 95% CI, 0.23–0.74).

A more recent systematic review⁴ followed a similar high-quality search strategy and identified 22 articles, and reported a number needed to treat (NNT) of 6 for the 2 hypoallergenic formula studies identified in the previous review.⁴ Because of concern regarding the quality of the behavioral studies involving infants with colic, the authors of this second review only included 1 small (42 patients) trial of decreased stimulation, which resulted in a relative risk (RR) of 1.87 (95% CI, 1.04–3.34) and a NNT of 2. There was some inconclusive evidence to suggest benefit to dietary adjustment for breastfeeding mothers (specifically, the avoidance of cow’s milk and other potential allergens like nuts, eggs, and wheat).

A recent randomized controlled trial confirmed the value of this approach by showing significant improvement in distress scores of infants whose mothers followed a low-allergen diet (excluding dairy, soy, wheat, eggs, peanuts, tree nuts, and fish) for 7 days.⁵ This well-designed study included 107 patients (a relatively large sample in the published research about colic), and showed an absolute risk reduction of 37% (NNT=3) for those mothers following the challenge.

A small RCT (43 patients) suggested efficacy in the substitution of a whey hydrolysate formula in place of cow’s milkbased formula for infants with colic (casein hydrolysate formula has been more widely studied), but there continues to be controversy regarding the preferred protein hydrolysate formula (whey vs casein) in the treatment of colic.³

Several medications have been tested in RCTs; only dicyclomine has shown an effect in a few small RCTs.^3,4 However, there have been reports of apnea and other serious, although infrequent, adverse effects. For that reason, the manufacturer has contraindicated the use of this medication in infants aged <6 months.

A small (n=68) study of an herbal tea showed reduced symptoms (RR=0.57 favoring the active tea), although the mean volume of tea consumption (32 mL/kg/d) is a nutritional concern in this age group.⁶ No adverse events were noted, but the small sample size limits the ability to detect any but the most common events.

Recommendations from others

The American Gastroenterological Association recommends a hypoallergenic, protein hydrolysate formula for formula fed infants or a maternal low-allergen diet as an initial strategy for infant struggling with colic symptoms if the clinician is considering a diagnosis of (cow’s milk) allergy.⁷

The American Academy of Family Physicians on their familydoctor.org web site makes no specific formula or diet adjustment recommendations.⁸ The web site does list some techniques (eg, massage or warm compress of abdomen, swing or car rides) not supported by the available evidence. The National Library of Medicine and the National Institutes of Health web site Medline Plus presents similar information.⁹ The American Academy of Pediatrics does not address the topic on its public web site.

TABLE 1
Interventions that affect vomiting or regurgitation

TABLE 2
Interventions that affect pH probe/measured reflux

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° 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 1 trial of drugs used to treat infant reflux measured clinical symptoms. This large manufacturer-sponsored RCT found that sodium alginate⁹ 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 metoclopramide¹⁰ and omeprazole¹¹ 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.

TABLE 1
Interventions that affect vomiting or regurgitation

TABLE 2
Interventions that affect pH probe/measured reflux

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° 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 1 trial of drugs used to treat infant reflux measured clinical symptoms. This large manufacturer-sponsored RCT found that sodium alginate⁹ 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 metoclopramide¹⁰ and omeprazole¹¹ 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.

TABLE 1
Interventions that affect vomiting or regurgitation

TABLE 2
Interventions that affect pH probe/measured reflux

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° 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 1 trial of drugs used to treat infant reflux measured clinical symptoms. This large manufacturer-sponsored RCT found that sodium alginate⁹ 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 metoclopramide¹⁰ and omeprazole¹¹ 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.