Introduction
Functional constipation (FC) is a common gastrointestinal disorder in children aged 0-5. It is identified by unusual bowel movements, struggle with passing stool, and/or excessive retention of stool without an identifiable primary cause [1-3]. The condition significantly affects a child’s physical health and emotional well-being and imposes stress on families [4, 5]. Studies have reported varied prevalence of FC in children, ranging from about 0.7% to 29.6% globally, due to the differences in geographical location, diagnostic criteria, and study methods [1, 6]. Children aged 5 years and below are particularly vulnerable to FC due to rapid physiological and behavioral changes, such as switching from breastmilk to formula or starting solid foods, beginning toilet training, and adapting to structured routines. These developmental milestones often coincide with changes in bowel habits, making this age group vulnerable [1, 6]. While FC does not pose an immediate threat to life, its continuation may result in complications including fecal incontinence, abdominal pain, and reduced quality of life (QoL) [1, 2]. For correct diagnosis and identifying the complications of FC in children within this age group, the Rome IV criteria are often used [7-9]. These criteria are specifically made to define FC based on the pattern of symptoms. In children, diagnostic criteria are met by the presence of two or fewer bowel movements per week, a history of painful or hard stools, passage of large-diameter stools that may cause toilet blockage, and, in toilet-trained children, episodes of fecal incontinence, sustained for a minimum of one month in infants and toddlers and two months in older children [7-9]. 
Current guidelines recommend both drug and behavioral therapies for FC. Polyethylene glycol (PEG) and lactulose are frequently prescribed drug treatments for quick relief and improved stool consistency [10-13], while behavioral approaches, including toilet training, dietary changes, and positive reinforcement, have proven useful in treating the underlying causes and improving long-term bowel health [1, 12-14]. Among these, PEG is generally tolerated well and is a safe drug [8, 15]. However, there are concerns regarding possible dependence and the need for continuous treatment due to reliance only on medications [10, 16]. Similarly, the effectiveness of behavioral interventions alone in sustaining bowel health remains unclear.
While treatment guidelines exist, there is a lack of consolidated evidence that compares the outcomes of drug treatment versus behavioral therapies, especially in children under five. Further research that sufficiently explores the most effective combined and age-specific strategies and assesses how severity or duration of treatment influences outcomes is required. This review study aims to identify and compare the efficacy of drug treatment and behavioral therapies for FC in early childhood, including assessment of their impact on health-related QoL (HRQoL) and prevention of recurrence. 

Materials and Methods
This systematic review was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and was registered in PROSPERO. The methodology included protocol development, systematic literature search, study selection, data extraction, risk of bias assessment, and synthesis of findings. The review focused on various study designs, with a particular focus on randomized controlled trials (RCTs) comparing drug treatments and behavioral therapies for FC in children aged 0-5 years. 

Search strategy
A comprehensive literature search was conducted in PubMed, Web of Science (WoS), CINAHL, EBSCO, and Cochrane CENTRAL. These databases were selected because they index a broad range of high-quality studies in pediatrics, gastroenterology, clinical, nursing, and behavioral research literature. The search was limited to studies published from 2014 to June 2025 to ensure it included studies that incorporated updated diagnostic criteria (such as Rome IV), evolving treatment recommendations, and clinical practices in managing pediatric constipation. The keywords used in describing constipation were “pediatric constipation” OR “childhood FC”. The study participants were identified using the keywords “infant” OR “child” OR “toddlers” OR “preschoolers”. The keywords used in searching for treatment approaches were “pharmacological therapy” OR “laxatives” OR “drug therapy” AND “non-pharmacological therapy” OR “behavioral therapy”. 

Inclusion and exclusion criteria
We included various study designs, particularly RCTs. The selection process followed the population, intervention, comparison, and outcome (PICO) framework. The population included children aged 0-5 diagnosed with FC according to the Rome IV criteria. The study interventions included drug treatments (e.g. PEG, Lactulose), compared with behavioral therapies, such as toilet training, changes in diet, structured programs for behavior, and positive encouragement. The study outcomes included frequency of bowel movements, consistency of stool, occurrence of fecal incontinence, and HRQoL. The exclusion criteria were specifically focusing on constipation caused by organic medical conditions like Hirschsprung’s disease or spina bifida or by preexisting conditions, publishing in a non-English language, not focusing on children within the defined age group, and publishing >10 years ago. 

Study selection
A total of 111 studies were yielded after the initial search. Ten duplicate records were removed using reference management software (EndNote software, version X9) and verified manually based on titles, authors, DOIs, and publication metadata. After removing 10 inaccessible articles with limited access or studies with no relevance, 91 articles were thoroughly screened. Forty-three more records were excluded after screening the abstracts and full texts. The remaining 48 studies were evaluated again using the inclusion and exclusion criteria, which led to the exclusion of 17 articles. Disagreements between reviewers were resolved through discussion and consensus. Based on these evaluations, 31 studies, including three RCTs, were included in the final review. Figure 1 shows the article selection process.



Assessing the quality of articles
Two reviewers carefully and systematically examined the articles to judge their trustworthiness, value, and relevance based on the research methodology. The articles were critically reviewed to maintain consistency and reliability. Discrepancies were resolved through consensus, ensuring analyses are thorough and unbiased. 

Risk of bias assessment
The risk of bias assessment was conducted only in 13 studies that specifically focused on children aged 0-5 years, using the Cochrane risk-of-bias tool. A visual summary of the risk of bias assessment is provided in Figure 2. Although most studies had low risk of bias in several domains, there were some concerns regarding overall bias and in the randomization process, deviations from intended interventions, and the measurement of outcomes. 



The results of the risk of bias judgment based on five domains for 13 studies are presented in Figure 3. The randomization process, which involved the allocation of participants to intervention groups, was appropriately allocated in four out of 13 studies [15, 17-19]. A low risk of bias for sequence generation was indicated in these studies. There were insufficient details regarding the randomization process of the remaining nine studies included in this systematic review. Blinding of participants and personnel was described and considered to be appropriate in one of the studies [18]. A low risk of bias for blinding was indicated in this study [18]. In two studies, an open-label design was used. The participants and personnel were not blinded in one study [20]. The use of the blinding method was not reported in other studies, which were rated as unclear risk of bias. 



There were no reports of deviation from the intended interventions in any studies that were judged low risk of bias, except for one study [15] due to deviation from the intended interventions that was rated as unclear risk of bias. In the study, 51 participants were switched due to intolerance or lack of effect of lactulose, which may have affected the outcome. All thirteen studies were judged to be at low risk of bias for incomplete outcome data because of a few dropouts that were similar to the reasons for withdrawal. In one study [18], outcome assessors were blinded to the intervention provided to the participants, indicating its low risk of bias. Reports regarding blinding of outcome assessors were not stated in 11 studies. Eight out of these 11 studies [16, 17, 19-24] were judged to be at low risk of bias because the measurement of outcomes was appropriate, and three studies [1, 10, 25] were considered to be at unclear risk of bias because there were no reports about the measurement of outcomes. In one study [15], outcome assessors were also not blinded, but the assessment of outcomes could not have been influenced by the awareness of the received intervention. It was judged to be at a low risk of bias.
In three studies [17-19], the risk of bias was low across all domains, suggesting that these studies were conducted well. In the remaining studies, a low risk of bias was observed in most domains. However, there were some moderate concerns regarding the process due to unclear intentions regarding the process, and the deviation from the intended interventions was reported in one study [15], which may have affected the outcome.

Data synthesis
The characteristics (author name, year of study, study design, sample size, age of participants, interventions, outcomes, and key findings) of the included articles were extracted (Table 1). In synthesizing the data, differences in treatment effectiveness were explored based on specific factors such as participants’ age, severity of constipation, treatment duration, and the type of intervention (drug treatment and behavioral therapy).







Results

Characteristics of studies
A total of 13 studies, representing a variety of interventions, participant groups, and settings, were included in the final analysis. The RCTs were conducted in Türkiye [17], the USA [18], and Poland [15]. The sample size of studies ranged from 56 [19] to 2604 [20], with one study not specifying the number of participants [1]. Four studies (38.46%) included a higher number of males [15, 19-21] than females.

Epidemiological findings
According to a systematic review of functional gastrointestinal disorders (FGIDs) in infants and toddlers, based on the Rome III criteria, the prevalence of FC at 3 months of age was 11.6% [10]. Findings of a study showed that the prevalence of FC in China was approximately 3% in infants (0-12 months) and 7% in children aged 1-4 years which indicates that FC is a major public health concern [20]. A cohort study conducted in Italy reported the prevalence of FC in infants with 3, 6, and 12 months of age as 11.6%, 13.7%, and 10.7%, respectively [23]. In a recent study conducted in the United States, approximately 4.7% of infants and 9.4% of toddlers were experiencing FC [23]. The prevalence of FC in children is influenced by different factors, including age, diet, and psychology [10]. Huang et al. [20] reported that in the child with vaginal birth, the risk of experiencing FC was significantly lower (OR=0.005, 95% CI, <0.001%, 0.17%, P=0.003) [21]. In another cross-sectional study, FC was seen in 8% of underweight infants and toddlers [22]. Regarding the geographic area, a study in China showed that the rate of FC in rural areas was higher (4.6%) than in urban areas (2.9%) [20]. In Asia, a lower prevalence of FC was observed. Walter et al. reported that according to the Rome IV criteria, the prevalence of FC in Asia was approximately 0.5-29.6%, with a pooled estimate of about 6.2% [22]. 

Comparison of drug treatment and behavioral therapy
Eight of 31 studies (46.15%) focused on the treatment outcomes of both drug therapies. In one study (14.28%), PEG 3350 plus electrolytes was used to assess the implementation, efficiency, and safety in treating critically ill children with FC [19]. Two studies (15.38%) compared the effectiveness of PEG with lactulose in managing FC [16, 18]. One study (7.69%) highlighted the importance of using behavioral approaches and drug treatments in effective management of childhood FC [1]. Drug treatment, particularly with PEG and lactulose, for softening stools, increasing stool frequency, and improving stool consistency until the child can comfortably pass stools, is usually recommended. Studies indicated that drug therapies are particularly useful for short-term management of FC, especially in cases where a fast reduction of symptoms is required [1, 8, 15]. However, potential side effects, such as abdominal discomfort, diarrhea, and the risk of developing a dependency on laxatives are quite concerning and are important for clinicians to decide on the duration of drug treatments. The side effects of lactulose mentioned by Jarzebicka et al. were bloating and abdominal pain, when compared to PEG [15]. 
Behavioral therapies, on the other hand, which involve hydration, changes in diet, physical activity, psychoeducation, and toilet training, showed effectiveness in the promotion of long-term regularity of the bowel and the prevention of FC recurrence. Başaran’s study highlighted that while the increase in the frequency of defecation may not be notably observed in a short period using behavioral therapy, compared to drug treatment, improvement in emotional well-being and reduction in anxiety related to the movements of the bowel can be observed [17]. An open-label controlled study by Benninga et al. suggested that magnesium can positively affect the pattern of defecation in children. İn their study, the effectiveness of a formula rich in magnesium was examined on 286 infants <6 months of age. The consistency of softer stool and a noticeably higher frequency of defecation were reported in infants receiving formula rich in magnesium compared to infants who were given formula that was not rich in magnesium [21].
Administration of laxatives is not enough to completely resolve FC. Taking a combined approach which involves the use of both drug treatment and behavioral therapy, is effective. This combined approach offers the best outcomes by using drug treatments to address the physiological symptoms and behavioral therapies to manage the behavioral causes. The implementation of both strategies not only provides immediate relief but also promotes the health of the bowel for a longer duration by reducing the likelihood of recurring constipation and minimizing the need to use medications for a longer period [8, 13]. PEG can relieve symptoms quickly and help disimpact stool. Implementing behavioral strategies such as toilet training and changes in diet regimen can help with maintaining these improvements and promote bowel movements regularly, eventually improving the child’s QoL [13]. In younger children, improving constipation management outcomes is achieved by individualized treatment plans that prioritize safety, efficiency, and the preferences of pediatric patients. 

Impact on QoL
The QoL in children under the age of 5 with FC received drug therapy is greatly affected. Drug therapy provides quick relief from symptoms, eases discomfort physically, and reduces stress psychologically, which can improve a child’s overall well-being. In children above 4 years, when FC is effectively managed with medication, improvements in QoL are noticed. However, possible adverse events such as abdominal pain, diarrhea, and the possibility of developing a dependency on laxatives for regularity of the bowel are associated with drug therapy. It is important to consider the drug therapy’s immediate advantages alongside the long-term potential risks carefully when deciding on the best treatment approach for younger children with FC. For effective relief of symptoms and increased QoL, finding the right balance is a key.
The effect of behavioral therapy on the QoL in younger children dealing with FC can be significant and diverse. It focuses on the underlying habits and routines, which are both physical and psychological causes of FC in younger children. Both drug and behavioral therapies significantly affect the child’s QoL. The mood, appetite, sleep, and participation in daily activities in children experiencing FC are positively affected when there is an improvement in bowel habits, which enhances the QoL generally. Physical discomfort, pain, and psychosocial issues such embarrassment or social withdrawal can be prevented by addressing FC early. Improvement in children’s emotional well-being and social interaction can lead to a better QoL. The immediate relief of FC symptoms with drug therapies and the long-term impact of behavioral strategies on emotional and functional abilities in children have been highlighted by different studies. A more comprehensive management strategy that involves the combination of drug treatments with behavioral therapies is more effective than using either of the interventions alone in improving the QoL of children experiencing FC. Both therapies address symptoms and underlying behavioral factors, such as anxiety associated with bowel movements that contribute to constipation. When a combined approach is used, less discomfort is experienced in children, promoting overall well-being.

Variations in treatment outcomes 
Treatment outcomes for FC in children aged 0-5 years varied based on age, severity of constipation, and duration of treatment. Drugs such as PEG and lactulose have been proven to be effective in providing disimpaction and short-term relief for young children, especially those under three years of age. For mild cases in infants, adjustments to their diet (such as changing the formula or introduction of solid foods) were sufficient. However, due to the development of their systems, it was recommended that they should be more cautious regarding the dosage. In contrast, preschool-aged children (3-5 years) were more receptive to the implementation of behavioral interventions such as regular pooping and eating foods high in fiber, due to their ability to follow and understand instructions. Combined therapy (drug and behavioral) was found to be more effective across all age groups, supporting both physiological and behavioral aspects of FC. 
Mild to moderate cases of FC were effectively managed with changes in diet and osmotic laxatives. For severe cases, higher doses of medication or the combination of drug and behavioral therapies were necessary. Individualized treatment methods based on the constipation severity, habits, and preferences in pediatric patients produced better outcomes and improved patient adherence. Their specific needs, such as dietary habits, hydration, and toileting behaviors, should be considered while developing the management plans. 
Prolonged treatment duration, especially with behavioral interventions, was associated with more sustained improvement in relieving symptoms and overall QoL. Although drug therapies may offer temporary relief, they often lack long-term effectiveness and can result in dependency or relapse when used alone. In comparison, despite the delayed outcomes of behavioral therapy, a higher success rate in the sustenance of optimal bowel health over an extended duration was seen when implemented consistently.

Discussion
Studies on the drug treatment of FC in children (0-5 years) showed that PEG was the most effective and safe drug in increasing the frequency of stool and improving the consistency of stool. Further research is needed to clarify the mechanisms responsible for variances in treatment outcomes and the role of demographic factors. Başaran’s cross-sectional study on children aged 8 months to 4 years revealed that PEG 4000 led to better outcomes compared to lactulose after 3 months of treatment. It improved frequency of bowel movements per day and reduced presence of pain during defecation [17]. The observed results are consistent with the established osmotic mechanism of PEG, which facilitates hydration of the colon and stool softening, while maintaining electrolyte equilibrium. In contrast to lactulose, which is fermented in the colon by bacteria, leading to gas and possible cramping, PEG acts as a non-absorbable osmotic agent without fermentation, resulting in fewer gastrointestinal complications. The observed reduction in adverse reactions following PEG administration is likely due to its different mechanism of action. 
An RCT comparing PEG 3350 with lactulose provided additional evidence for the higher efficacy of PEG, where the PEG group achieved 7.9 defecations per week compared to 5.7 in the lactulose group. The clinical success rate after 12 weeks of the treatment period was achieved in about 98% of the PEG group compared to that of the lactose group, which was approximately 90%. An increase in the frequency of stools and a reduction in encopresis were observed in both treatments. Fewer adverse reactions and better tolerance were seen in PEG 3350 compared to lactulose [15]. Although an 8% difference may seem negligible, it is a clinically meaningful improvement, especially considering the chronic nature of pediatric constipation and its effects on QoL. 
Demographic factors such as age, dietary patterns, stage of development, and independence in toileting also affect the success of treatment across different populations. The different patterns of response observed across different age groups probably indicate developmental variations in the colon function and drug metabolism. Children under the age of three show greater sensitivity to osmotic agents due to their larger surface area-to-volume ratio and increased permeability of the intestine. This clarifies why lower PEG doses are required in younger children to achieve effectiveness similar to that in older children. In contrast, preschool-aged children (3-5 years) show improved behavioral therapy responsiveness, which relates to their developing independence and cognitive abilities for the formation of habits. 
Magnesium-based treatment is another effective intervention. For children aged 2-5 years, the recommended daily dosage is 0.4–1.2 g or 5 mg, administered once at night. However, the use of magnesium has unique risks and benefits. The small therapeutic range between beneficial effects and adverse reactions, particularly diarrhea and abdominal cramping, indicates that magnesium may be suitable for children who do not respond to first-line osmotic treatments or have particular contraindications to PEG. Benninga et al. study on 286 infants under the age of six months demonstrated that the use of formula rich in magnesium led to softer stools and a noticeably higher frequency of defecation [21]. However, the focus of this study on formula modification rather than providing direct supplementation limits its relevance and applicability to older children or those who are not fed with formula. In Walter et al.’s study, only 32% of children received advice on toilet training [22], indicating the gap in the comprehensive management of FC. The effectiveness of behavioral interventions, especially in toilet training, is closely related to the developmental readiness of the child. Starting these strategies too early might trigger anxiety and cause stool withholding behaviors, which can worsen symptoms [22, 31]. This concern is particularly relevant for children younger than 4 years, who often do not have the cognitive, motor, or emotional skills needed for consistent compliance with organised toileting schedules. In such cases, drug therapy is the most suitable approach. 
PEG remains the primary choice for increasing the frequency of defecation and rates of treatment success and should remain the first line of treatment for children with FC [26, 27], whereas magnesium-based treatment can be beneficial but requires careful dosage [26]. Behavioral therapy was found to be effective in reducing behavioral problems in children, which suggests possible benefits beyond the management of symptoms [28]. To optimize outcomes based on individual needs and circumstances for long-term maintenance, combination with drug therapy is recommended [12, 14, 29]. Additional studies are required to determine ideal treatment protocols that consider age-related responses, long-term outcomes, and the role of combined therapies in cases resistant to treatment.
The FC affect important aspects of QoL, including sleep patterns, eating behaviors, and developmental milestones. Vandenplas et al. highlighted the significant impact of FC on the physical, emotional, and social well-being of children experiencing FC, who showed feeding difficulties and sleep problems, potentially leading to more developmental delays. The need for outcome measures that go beyond stool frequency and consistency, including developmental and behavioral health, is important [24]. Turco et al. reported the FC prevalence rates of 11.6%, 13.7%, and 10.7% in infants aged 3, 6, and 12 months, respectively, indicating that infancy is an essential period for timely intervention. Moreover, the observed association of increased rate of FC with female gender and acetaminophen use provides opportunities for risk assessment and preventive measures. These suggest that improving QoL may require early individualized treatment strategies rather than a standard approach for all children [25]. Therefore, a combined approach can provide the best benefit. Drug treatments manage acute symptoms, while behavioral strategies focus on underlying causes and help in developing sustainable habits. The importance of implementing the appropriate treatment strategies that manage the physiological and psychological aspects of FC at the right time cannot be underrated. The combined approach can support both immediate relief and lasting behavioral transformation, ultimately promoting better health outcomes and minimizing recurrence [25, 30].
The review of studies showed the variability in treatment outcomes based on factors such as age, severity of constipation, and duration of treatment. The variation in response to treatment among age groups indicates the importance of developmental stage, in addition to chronological age. Individualized treatment strategies should consider factors such as the child’s motor skills, communication skills, emotional management, and independence level. These personalized approaches ensure that interventions are suitable for developmental stages and applicable practically, improving adherence to treatment, therapeutic outcomes, and overall QoL. A randomized, multicenter study conducted by Jarzebicka et al. [15] demonstrated the superior effectiveness of PEG across varying severities of FC, supporting its role as a fundamental component in treatment guidelines. However, the 12-week follow-up duration of the study might be insufficient to thoroughly evaluate outcomes in severe or chronic situations, where alleviating symptoms and adjusting behavior can take several months of consistent intervention. 
In more severe cases, combination therapy is frequently required. Immediate resolution of fecal impaction requires higher doses of PEG, which can resolve urgent fecal impaction, whereas thorough behavioral interventions such as modification of dietary habits, toilet schedules, and educating caregivers are essential for dealing with underlying behavioral factors. Although there is clinical agreement on the benefits of a holistic approach, the ideal timing, duration, and prioritization of these interventions represent an important area for future research. The observed reduction in adverse reactions over time in several studies indicates the presence of adaptive physiological or behavioral mechanisms that contribute to long-term treatment success. This suggests that early intolerance to treatment, especially with PEG or magnesium therapies, may not indicate long-term failure, and that immediate side effects should not lead to hasty discontinuation. These findings support the importance of extended treatment durations before modifying or discontinuing a selected intervention [3]. For children with ongoing or severe FC, the need for prolonged treatment duration also raises important inquiries regarding the ideal treatment goals and ongoing management approaches [29]. Current evidence indicates that discontinuation of treatment should rely on consistent symptom improvement and normalized bowel habits, rather than following a timeframe of weeks or months. Establishing clear criteria for maintenance therapy and gradual reduction can be essential in reducing the rate of relapse and ensuring long-term QoL improvement.
A major strength of this review study is its specific focus on children aged 0-5 years, a developmental period that is often underrepresented in clinical studies on FC. This study presents a comprehensive comparison of both pharmacological and behavioral treatment interventions by providing a holistic overview of current treatment options. This study promotes the applicability of the findings to a practical environment and provides clinicians with scientific evidence required in making individualized treatment decisions. Furthermore, the emphasis on individualized treatment approaches aligns with best pediatric care practices and recognizes the variability in presentation of symptoms and response to treatment in the 0-5 age groups. In addition to informing clinical management, this study identifies the vital critical gaps in existing literature, thereby providing a clear direction for future research in pediatric gastroenterology. Despite these advantages, there were several limitations. The insufficiency of high quality RCTs that compare both drug and behavioural approaches, focusing specifically on children aged 0-5 was a major limitation of this study. The age for the implementation of behavioral therapy in the management of FC was not consistent across all studies. Some authors suggested Kegel exercises in the management of FC, but they were not included due to age limitations. This review study only considered research studies published in English and available in certain databases, which may have resulted in the exclusion of studies published in different languages or in journals not included in the databases that were relevant to this review. This limitation may lead to an incomplete collection of data. Databases such as Scopus and Embase were not included for search. Furthermore, the inclusion of some studies published only until the first six months of 2025, may result in certain limitations. 

Conclusion
This systematic review provides an important contribution to literature by comparing the effectiveness of drug treatments, especially PEG, and behavioral therapies for managing FC in children aged 0-5 years. The developmental and physiological factors that affect the treatment responses in early childhood, by focusing on outcomes such as symptom relief, preventive strategies, and QoL improvement, were highlighted in this study. Combining short-term drug treatment and behavioral strategies can provide a holistic approach for clinical practice. While previous studies have investigated pediatric FC, further RCTs should be conducted to determine the most effective behavioral techniques, optimal timing, and the best methods for their implementation for children <5 years of age, particularly those with more severe FC. This will facilitate evidence-based guidelines to improve clinical outcomes and QoL for children suffering from FC.

Ethical Considerations

Compliance with ethical guidelines
This study does not contain any human or animal subjects. This study was registered by PROSPERO (ID: CRD42024573684). 

Funding
This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors. 

Authors contributions
Conceptualization, literature search, data extraction, and writing: Moyosore Omotola Afolayan; Supervision, review & editing: Candan Ozturk; Final approval: All authors.

Conflict of interest
The authors declared no conflict of interest. 

Acknowledgements
The authors sincerely appreciate the library and academic staff at Cyprus Aydin University and Near East University for their support during this research.





References