Review shows that parental reassurance and nutritional advice help to optimise the management of functional gastrointestinal disorders in infants.

AIM: Regurgitation, infantile colic and functional constipation are common functional gastrointestinal disorders (FGIDs) during infancy. Our aim was to carry out a concise review of the literature, evaluate the impact of these common FGIDs on infants and their families, and provide an overview of national and international guidelines and peer-reviewed expert recommendations on their management.
METHODS: National and international guidelines and peer-reviewed expert recommendations on the management of regurgitation, infantile colic and functional constipation were examined and summarised.
RESULTS: Regurgitation, infantile colic and functional constipation cause frequent parental concerns, lead to heavy personal and economic costs for families and impose a financial burden on public healthcare systems. Guidelines emphasise that the first-line management of these common FGIDs should focus on parental education, reassurance and nutritional advice. Nutritional advice should stress the benefits of continuing breastfeeding, while special infant formulas may be considered for non-breastfed infants with common FGIDs. Drug treatment is seldom required, with the exception of functional constipation.
CONCLUSION: By providing complete and updated parental education, reassurance and nutritional advice, healthcare professionals can optimise the management of FGIDs and related symptoms and reduce the inappropriate use of medication or dietary interventions. ©2018 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.

Functional gastrointestinal disorders

Gastrointestinal

Regurgitation, infantile colic and functional constipation are common functional gastrointestinal disorders (FGIDs) during infancy, cause frequent parental concerns and heavy personal and economic costs for families and public healthcare systems.

This review examined the literature and found that guidelines emphasise that the first‐line management of these common FGIDs should be parental education, reassurance and nutritional advice, including continued breastfeeding.

With the exception of functional constipation, drug treatment is seldom required.

Introduction

Many infants experience at least one symptom of a functional gastrointestinal disorder (FGID) before they reach their first birthday 1. These FGID symptoms are often extremely distressing for the infant and parents, leading to a cascade of infant discomfort and crying, parental anxiety, repeated healthcare consultations and escalating healthcare costs 2. Parents are frequently offered conflicting advice on how to manage FGIDs and their related symptoms, ranging from personal experience, social media exchanges and recommendations for medications that do not have any proven efficacy and could induce adverse reactions, to expert opinions and evidence‐based guidelines.

Despite this, we now recognise that the first‐line management of the most common FGIDs, particularly infantile colic and regurgitation, should focus on parental education and reassurance and nutritional advice. The latter includes recommendations on feeding volume, frequency, techniques for all infants and considering special formulas with proven effects for formula‐fed infants with persisting symptoms. Limiting over‐the‐counter remedies, frequent inappropriate formula changes and the use of extensive protein hydrolysates or amino acid formulas may lead to more favourable outcomes for the infant and parents and relieve the burden on healthcare systems 2 (Fig. 1).

Figure 1

Infants' gastrointestinal symptoms can be distressing for parents and represent a frequent reason for consultations with healthcare professionals.

The aim of this review was to carry out a comprehensive literature overview and evaluate the impact of FGIDs on individuals and society. We also wanted to provide a summary of the international guidelines and expert opinions on nutritional advice that should be offered to parents of both breastfed and formula‐fed infants.

Functional gastrointestinal disorders in early life

During infancy, the structure and function of the gastrointestinal (GI) tract, the nervous system and microbiota are still maturing and this may cause GI signs and symptoms that have no obvious structural or biochemical cause. The occurrence of these principal GI manifestations has been categorised into seven recognised FGIDs (Table 1). The diagnosis of a functional disorder virtually eliminates organic disease as a cause of the symptoms. From birth to 6 months of age, approximately one infant out of two shows at least one FGID or related signs and symptoms 1, 3. Regurgitation, infantile colic and functional constipation are the most common FGIDs in infancy, and it has been shown that more than one FGID often coexist in the same infant 3, 4. Functional diarrhoea, dyschezia, rumination syndrome and cyclic vomiting syndrome occur less frequently 1, 5.

Table 1

Functional gastrointestinal disorders and prevalence 1, 14

Category	Reported worldwide prevalence (%)
1. Infant regurgitation	30–67
2. Infant colic	5–20
3. Functional constipation	3–27
4. Functional diarrhoea	6–7
5. Cyclic vomiting syndrome	3.4
6. Infant dyschezia	2.4
7. Infant rumination syndrome	1.9

Impact on family and society

FGID symptoms vary from mild to extremely distressing for the infant and parents and may lead to parental anxiety, poor quality of life, short‐ and long‐term health consequences, shortened duration of full breastfeeding, numerous formula changes and medical consultations and high associated healthcare costs 1, 2, 6, 7, 8, 9, 10, 11 (Table 2).

Table 2

Impact of functional gastrointestinal disorders and related symptoms on family life, and short‐ and long‐term well‐being

In the first months after birth, FGIDs and related signs and symptoms have been reported in studies to be more frequently associated with: Tiredness and fatigue in mothers 41 Postpartum maternal depressive symptoms 42 Suboptimal social and emotional behaviour of mothers during feeding 43 Premature breastfeeding cessation 7 Frequent infant formula changes 44 Insecure mother–child attachment 13 Suboptimal mother–child, father–child and mother–father interaction 12 Loss of parental working days 10 Infantile abuse and shaken baby syndrome 45, 46

In the long term, FGIDs and related signs and symptoms have been found to be more frequently associated with: Family distress and less satisfactory family life in individual studies with follow‐up to 3 years and school age 6, 47 Children being perceived as fragile by their mothers at 3.5 years of age 48 Abdominal pain, or related FGIDs in individual studies at 4, 8, 10 and 13 years follow‐up, respectively 9, 10, 49, 50 Sleeping problems in individual studies with 3 and 10 years of follow‐up, respectively 6, 50 Behavioural problems such as difficulty with emotional regulation, frequent temper tantrums, or a more impulsive cognitive style in individual studies with 3, 4, 8 and 10 years of follow‐up, respectively 6, 49, 50, 51, 52

For example, one observational study used the Parent Child Early Relational Assessment Scale and the Beavers Scale to examine relationships within 32 families whose children cried excessively 12. The researchers found that parent–child, and particularly father–child, interactions were less than optimal, infants were less competent in interacting with their parents and the interaction between the parents was more likely to be dysfunctional than control families where the infant did not cry excessively. Another study revealed an association between infantile colic, symptoms of postpartum maternal depression and insecure mother–child bonding 13.

Thus, any medical consultation needs to both examine the child and assess the family's experiences, how well they are coping and their level of anxiety 14. Healthcare professionals should appreciate that FGIDs in general, and excessive crying in particular, may be extremely distressing for families and can damage the relationships between parents and their children.

Economic impact

FGIDs and related symptoms have a significant impact on personal and public healthcare expenses. These include the costs of prescribed treatments in countries where residents pay for child healthcare, over‐the‐counter or home remedies, visits to healthcare professionals and loss of income when parents have to take time off work 2.

In the United States, the total national cost for constipation‐related emergency department visits increased by 121% to $1.6 billion between 2006 and 2011 and infants were the most frequent visitors 15. In the United Kingdom, the annual total cost to the National Health Service for infant crying and sleeping problems in the first 12 weeks after birth has been estimated at £65 million 16.

Another study concluded that the total cost of treating FGIDs in infants in England was at least £72.3 million per year in 2014 and 2015 2. The study also concluded that the number of prescribed medications and over‐the‐counter remedies that were purchased indicated gaps between treatment guidelines for FGIDs, which emphasise parental reassurance and nutritional advice, and their implementation 2.

Diagnostic criteria

Internationally agreed diagnostic criteria for FGIDs were first published in 1989 and these Rome criteria have been regularly updated, most recently in 2016 14 (Table 3).

Table 3

Diagnostic criteria for infant regurgitation, infantile colic and functional constipation in infancy

Infant regurgitation	Infant colic	Functional constipation
Must include both of the following in otherwise healthy infants 3 weeks to 12 months of age: Regurgitation 2 or more times per day for 3 or more weeks No retching, haematemesis, aspiration, apnoea, failure to thrive, feeding or swallowing difficulties, or abnormal posturing	Must include all of the following: An infant who is <5 months of age when the symptoms start and stop Recurrent and prolonged periods of infant crying, fussing, or irritability that occur without obvious cause and cannot be prevented or resolved by caregivers No evidence of failure to thrive, fever or illness	Must include 1 month of at least 2 of the following in infants up to 4 years of age: Two or fewer defecations per week History of excessive stool retention History of painful or hard bowel movements History of large‐diameter stools Presence of a large faecal mass in the rectum

Adapted from Benninga et al., 2016 14.

Aetiology at a glance

Most parents request information about the cause of their child's symptoms. Providing parents with an easy to understand and complete explanation of the underlying disorder may reduce their anxiety and reinforce their empathy and confidence. However, to provide proper parental education, we need to clarify the interaction between physiological changes during the maturation of the GI tract, the natural evolution of the specific disorder and the parental coping mechanisms. For example, contributory factors for reflux and regurgitation include feeding large amounts of liquid over a short period of time, a short intra‐abdominal oesophagus, an obtuse angle of His, feeding in horizontal position and the position of the infant after feeding 17.

There are gastrointestinal and behavioural hypotheses for infantile colic 18, 19. Gastrointestinal hypotheses involve immaturity of the gut function, dysmotility, imbalance of the intestinal microbiota, changes in gut hormones and food hypersensitivities or allergies. For example, the behavioural hypotheses include inadequate maternal–infant interaction, maternal anxiety and a difficult infant temperament. Being aware that crying does not always indicate pain would make caregivers feel less inadequate and scared that their child has a disease.

Hypotheses for functional constipation include a family predisposition and dietary factors, such as calcium soaps in the stools and insufficient fibre and liquid intake 20, 21.

Management of regurgitation

Regurgitation is very common in infancy and usually improves spontaneously in the first year after birth. Therefore, the main management goal is to provide effective parental reassurance and symptom relief while avoiding complications (Table 4) 14.

Table 4

Excerpt of current recommendations for the management of infant regurgitation

Recommendation	Reference
Parental education and reassurance as the first line of management
Provide information on: The natural history of regurgitation (even in breastfed infants) Correct formula preparation (in formula‐fed infants) Impact of overfeeding on symptoms	Expert group review 22 NICE (2015) 53
Despite possible benefits of positioning in the treatment of reflux, no position other than supine is recommended for infants due to the risk of sudden infant death syndrome (SIDS)	NASPGHAN/ESPGHAN 54 NICE (2015) 53
Nutritional management
Regurgitation is not a reason to stop breastfeeding Correct the frequency and volume of feeds, if necessary Thickened or anti‐regurgitation formula decreases overt regurgitation and can be considered in persisting and distressing symptoms or in infants with poor growth because of regurgitation	Expert group review 23 NICE (2015) 53
In case of frequent regurgitation associated with marked distress: In breastfed infants: Ensure that a person with appropriate expertise and training carries out a breastfeeding assessment In formula‐fed infants (stepped‐care approach): □ Review the feeding history □ Reduce the feed volumes if excessive for the infant's weight □ Offer a trial of smaller, more frequent feeds (while maintaining an appropriate total daily amount of milk) □ Offer a trial of thickened ‘anti‐regurgitation’ formula (e.g. formula containing rice starch, corn starch, locust bean gum or carob bean gum)	NICE (2015) 53
Modify feeding volumes and frequency according to age and weight to avoid overfeeding Consider thickened feeding (or anti‐regurgitation formula) to treat visible regurgitation/vomiting to improve comfort of the infant and offer additional reassurance to the family In formula‐fed infants who are suspected of gastro‐oesophageal reflux disease but fail to respond to optimal non‐pharmacological treatment, consider a 2–4 week trial of extensively hydrolysed protein‐based (or amino‐acid‐based) formula (as milk protein sensitivity could be the cause)	NASPGHAN/ESPGHAN 54
Pharmacological therapy
No pharmacological recommendation for the treatment of crying/distress or visible regurgitation in otherwise healthy infants Do not recommend antacids/alginates to be used for chronic treatment of infants with gastro‐oesophageal reflux disease Proton pump inhibitors should be prescribed only when there is a clear diagnosis of gastro‐oesophageal reflux disease and, whenever possible, the lowest doses should be prescribed for the shortest length of time possible	NASPGHAN/ESPGHAN 54
There is no indication for drug treatment in ‘happy spitters’ or in infants without troublesome regurgitation Proton pump inhibitors do not decrease infant regurgitation, crying or fussiness and should not be empirically started	Expert group review 22
When frequent regurgitation associated with marked distress continues despite the nutritional management: In breastfed and formula‐fed infants: Consider alginate therapy for a trial period of 1–2 weeks If the alginate therapy is successful continue with it, but try stopping it at intervals to see if the infant has recovered Do not offer acid‐suppressing drugs, such as proton pump inhibitors or Histamine‐2 receptor antagonists, to treat overt regurgitation in infants and children occurring as an isolated symptom Do not offer metoclopramide, domperidone or erythromycin to treat gastro‐oesophageal reflux disease without seeking specialist advice and taking into account their potential to cause adverse events	NICE (2015) 53

If infants have frequent and troublesome regurgitation, a complete medical history and physical examination with anthropometry need to be performed to rule out warning signs of organic disease. Physiological regurgitation should not be diagnosed in infants with vomiting and poor weight gain 22, 23.

Management of infantile colic

Caring for a child with infantile colic can be extremely challenging and in most cases its management should concentrate on helping parents to cope with their child's excessive crying 14 (Table 5). Parents can be reassured that crying peaks at about 4–6 weeks after birth and then steadily diminishes until 12 weeks 4, 24. If there is no evidence of cows’ milk protein allergy or warning signs of organic disease, the feeding technique should be evaluated and the caregivers should be reassured and supported 22.

Table 5

Excerpt of current recommendations for the management of infantile colic

Recommendation	Reference
Parental education and reassurance as the first line of management
Provide information on: Signs of hunger and fatigue Family structure and regularity The self‐limiting nature of the condition There is insufficient evidence to recommend swaddling and other caregiving interventions in all infants Evidence too limited to recommend herbal products such as fennel and peppermint	Expert group review 22
Reassure parent that: Infantile colic is usually a transitory phase Soothing strategies such as holding the baby through the crying episode may be helpful Encourage parent to: Look after their own well‐being, ensuring access of support network Continue breastfeeding where possible	NICE, 2017 55
Nutritional management
Besides parental education and reassurance, nutritional management of infant colic should be the first choice In selected breastfed infants with excessive irritability and crying, lactating mothers may be advised to exclude dairy products for 2–4 weeks and then reintroduce them For selected formula‐fed infants, the use of extensively hydrolysed infant formula may help If cow's milk protein allergy is not a potential cause, partially hydrolysed formula with lactose‐reduced or lactose‐free and containing prebiotics or probiotics may contribute to a reduction in crying time One double‐blind, placebo‐controlled trial showed a significant decrease in infantile colic within 1 week of intervention with a partial hydrolysate, with high beta‐palmitate and a specific prebiotic mixture of galacto‐ and fructo‐oligosaccharides In selected breastfed infants, L. reuteri DSM 17938 may decrease infantile colic although there is insufficient data to recommend L. reuteri DSM 17938 in all colicky infants	Expert group review 22
Pharmacological therapy
Pharmacological therapy (e.g. proton pump inhibitors, simethicone) is not effective, and may cause serious adverse reactions	Expert group review 22

Although food allergies are frequently associated with GI manifestations, the link between food allergies and infantile colic is unlikely in the absence of other symptoms of atopy 24.

A data meta‐analysis of individual participants concluded that Lactobacillus reuteri DSM17938 was effective and could be recommended for breastfed infants with infantile colic, but there were insufficient data to reach conclusions for formula‐fed infants with infantile colic 25.

Management of functional constipation

The goal for treating functional constipation is to restore a regular defecation pattern and to prevent relapses (Table 6). Parental reassurance and follow‐up laxatives may still be required if an organic condition, such as Hirschsprung's disease or cystic fibrosis, is excluded and there are no accompanying signs, such as failure to thrive, intermittent diarrhoea or abdominal distension 22.

Table 6

Excerpt of current recommendations for the management of functional constipation in infants and toddlers

Recommendation	Reference
Parental education and reassurance as the first line of management
Provide information on normal infant defecation patterns	Expert group review 22
Nutritional management
Continue breastfeeding; evaluation after 2–4 weeks Verify proper formula preparation for formula‐fed infants	NASPGHAN/ESPGHAN 56
Harder stools are frequent in infants fed with formulas containing vegetable oil rich in palmitate in the stereospecific numbering (Sn) positions Sn‐1 and Sn‐3, favouring calcium soaps In some infants, constipation is related to the intake of cow's milk protein although there is no consensus that extensively hydrolysed formula is indicated for constipated infants since constipation as single manifestation of cow's milk allergy is extremely rare Juices containing sorbitol, such as prune, pear and apple juices, decrease constipation but may risk unbalanced nutrition and early introduction of complementary foods and lead to diarrhoea or abdominal pain Lactulose may be considered for functional constipation, but may cause flatulence	Expert group review 22
Do not use dietary interventions alone as first‐line treatment for idiopathic constipation Treat constipation with laxatives and a combination of Behavioural interventions Dietary modifications to ensure a balanced diet and sufficient fluids are consumed	NICE (2010)57
Pharmacological therapy
Polyethylene glycol may be considered for functional constipation for infants over 6 months of age Rectal treatment with glycerine suppository should be restricted to provide acute relief in functional constipation Evidence does not support the use of enemas, or (oral) mineral oil as this risks lipoid pneumonia due to aspiration	Expert group review 22
Offer the following oral medication regimen for dis‐impaction if indicated: Polyethylene glycol 3350 + electrolytes, using an escalating dose regimen as the first‐line treatment. Adjust the dose of polyethylene glycol 3350 + electrolytes according to symptoms and response. As a guide for children and young people who have had dis‐impaction, the starting maintenance dose might be half the dis‐impaction dose Add a stimulant laxative if polyethylene glycol 3350 + electrolytes does not work Substitute a stimulant laxative if polyethylene glycol 3350 + electrolytes are not tolerated by the child or young person. Add another laxative such as lactulose or docusate if stools are hard Continue medication at maintenance dose for several weeks after regular bowel habit is established – this may take several months. Children who are not toilet trained should remain on laxatives until toilet training is well established. Do not stop medication abruptly, but gradually reduce the dose over a period of months in response to stool consistency and frequency. Some children may require laxative therapy for several years. A minority may require on‐going laxative therapy	NICE (2010) 57

Pharmacological management of FGIDS in early life

The parents of children with FGIDs are understandably keen to find a quick and easy solution, such as a pill that will lead to rapid symptom relief 26. In addition, changes in society changes have raised parents’ expectations for instant solutions, which results in healthcare professionals being placed under enormous pressure to act and to investigate or prescribe pharmacological products. This often results in infants undergoing unnecessary investigations and medical treatment, which do not offer any significant improvements 22.

A review published in 2016 concluded that there was some evidence to support pharmacological interventions for constipation and rectal dis‐impaction as the first‐line therapy 27. However, pharmacological therapy appears to offer no benefit for other FGIDs that occur early in life 28.

Despite the lack of drug benefits, and the emphasis on parental and nutritional support in the guidelines, there is still widespread overuse of medical management in FGIDs such as regurgitation and infantile colic 26, 27, 29.

A survey among general paediatricians in Italy found little adherence to the guidelines for children with gastro‐oesophageal reflux symptoms issued by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition. The survey reported that 56% of general paediatricians prescribed proton pump inhibitors for infants with unexplained crying and, or, irritability and 38% prescribed them for infants with uncomplicated recurrent regurgitation and vomiting 30. According to a systematic review and meta‐analysis from 2015, there is no benefit in using any kind of proton pump inhibitors for crying and irritable infants 31.

A study from New Zealand published in 2017 concluded that off‐label prescribing of proton pump inhibitors for infants was relatively common. For example, 5.2% of children born in 2012 received a proton pump inhibitor before their first birthday and the majority of infants who received these drugs were not diagnosed with severe gastro‐oesophageal reflux disease 29.

Conversely, the side effects of acid inhibitors have been extensively reported. One review of children up to 18 years of age reported that at least 23% of patients treated with histamine receptor 2 antagonists experienced side effects, as did 34% of those treated with proton pump inhibitors 32. Concerns have been raised with regard to the impact of proton pump inhibitors on the gut microbiome and the association between using proton pump inhibitors and small bowel bacterial overgrowth in children 33, 34. There is sparse evidence for the efficacy of other medication, such as pain relieving agents, prokinetic drugs or over‐the‐counter remedies such as simethicone for treating infantile colic 28, 35, 36, 37, 38. However, parents of infants with colic are very likely to decide what medication they give their children without advice from their doctor 39, 40.

Pragmatically managing FGIDS in early life

Parental education and reassurance are the cornerstones for managing infant colic, constipation and regurgitation. Nutritional advice, such as feeding techniques, volume and frequency, is also recommended.

Based on the current guidelines and expert reviews (Tables 4, 5, 6), the most relevant recommendations for the pragmatic management of FGIDs in primary care can be summarised as follows:

Parental reassurance

Nutritional advice should stress the benefits of breastfeeding and appropriate support should be offered whenever necessary. Parents should be aware that breastfeeding provides the most ideal nutrition for infants.

Overfeeding infants may exacerbate their symptoms and should be avoided.

Colic and regurgitation are temporary problems during the first months of life and then they spontaneously resolve.

Pharmacological approaches are not necessary for infantile colic and regurgitation and could harm infants. Gastric acid inhibitors or prokinetic drugs have been shown to have side effects, such as an increased rate of infection, and are mostly ineffective for these conditions.

Functional regurgitation

Regurgitation is almost never a reason to stop breastfeeding.

A thickened anti‐regurgitation infant formula may reduce persistent regurgitation in non‐exclusively breastfed infants and help to reassure parents. Alginates, extensively hydrolysed protein or amino acid formulas are not indicated for uncomplicated infantile regurgitation.

Infantile colic

Probiotics, specifically Lactobacillus reuteri DSM 17938, have been reported to be of potential benefit for exclusively breastfed infants with infantile colic.

Limited data suggest formula‐fed infants with infantile colic could benefit from a partial hydrolysate with prebiotics and beta‐palmitate or a synbiotic formula with reduced lactose and partially hydrolysed protein. However, there is insufficient evidence to recommend the routine use of these kinds of formula.

Gastric acid inhibitors have been shown to have side effects and have been demonstrated to be ineffective in infantile colic if the crying is unrelated to gastro‐oesophageal reflux disease.

Functional constipation

Constipation is rare in breastfed infants and alternative causes of constipation should be considered. Some breastfed infants defecate less than once a week.

Nutritional advice may not be sufficient for non‐exclusively breastfed infants with functional constipation and laxatives may be required as the first‐line treatment. Limited data suggest infants with hard and infrequent stools could benefit from a formula with a partial whey hydrolysate, a formula containing a mixture of prebiotics and a high level of beta‐palmitate and, or, a formula with high magnesium content, but within normal ranges. However, there is insufficient evidence to recommend the routine use of these formulas.

Conclusion

FGIDs and related symptoms present a common burden in infancy, as they have a negative impact on the short‐term and long‐term health outcomes of the infants, reduce families’ quality of life and increase healthcare system costs. The optimal management of FGIDs in infancy should start with parental education and reassurance, accompanied by proper nutritional guidance. It is unlikely that any pharmacological intervention will be necessary once an organic cause of the symptoms has been excluded. However, pharmacological therapies are often misused, unnecessary and may cause adverse effects. Breastfeeding should be recommended and supported, even when infants display persistent and severe FGIDs. In non‐breastfed infants, special formulas may be considered if reassurance and advice on nutrition, based on the proper volume and frequency of milk intake, fail. FGIDs often lead to a vicious cascade of distressed infants, concerned parents, increased medical consultations, over‐prescribing and use of over‐the‐counter medication, resulting in escalating healthcare costs.

By offering appropriate advice and reassurance to parents, healthcare professionals can help to disrupt this cascade and restore harmony, by reducing infants’ distress, alleviating parental anxiety and improving the quality of life for the family while protecting healthcare budgets.

Competing interests

TL is an employee of Nutricia Research. The other authors have no conflicts of interest to declare.

Funding

This study did not receive any specific funding.