Karen Harris
Karen Harris is a professional writer and editor with more than two decades of experience in research-driven nonfiction writing. With a background in journalism and a Master's degree in English, she brings a meticulous approach to fact-finding, source evaluation, and clear communication of complex topics. Her work spans health, lifestyle, and consumer education, always with a focus on accuracy and readability.
Context
In the first months of life, many babies spit up after feeds, cry for long stretches, or pass hard stools. These patterns are called functional gastrointestinal disorders (FGID), and the three most common ones are infant regurgitation, infant colic, and functional constipation. They are among the most frequent reasons parents consult a pediatrician. A wide range of infant formulas is marketed to manage these symptoms, and parents often try them before any medical visit.
This position paper from the ESPGHAN Nutrition Committee reviews the current evidence on whether formulas designed for regurgitation, colic, and constipation are safe and effective, and it sets out guidance for clinical use. The authors note that many of these products have altered nutritional compositions compared to standard formula, and that the evidence behind their marketed benefits is often limited.
Study Overview
Design: Position paper and practice guideline of the ESPGHAN Nutrition Committee. It combines a structured literature review with formal expert consensus. Searches ran on PubMed, MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews up to April 30, 2023. Where reliable evidence was available, recommendations are evidence based; where it was lacking, recommendations reflect the authors' consensus (reported as 100% agreement).
Included studies: 752 papers were identified and screened, and 72 were included. Only studies of formula effectiveness that included infants up to 6 months of age and were written in English were eligible.
Comparators: Specialized or modified formulas versus standard infant formula. The specific categories reviewed were thickened (“anti-reflux”) formulas, “anti-colic” formulas (reduced lactose, partially or extensively hydrolyzed protein, added β-palmitate, added pre- or probiotics), formulas for constipation (higher lactose, higher magnesium, higher β-palmitate, partially hydrolyzed protein), and formulas for combined FGID.
Outcomes assessed: Frequency of visible regurgitation, crying and colic symptoms, stool consistency and defecation frequency, weight gain, and safety.
Funding: “No funding was obtained for this study.” However, most authors reported financial ties to infant-nutrition companies (see Neutral Interpretation).
Evidence Certainty (GRADE): Not formally GRADE-rated. The authors describe the overall evidence base as limited and, for several specific interventions (for example, high-magnesium formulas), explicitly rate the certainty of evidence as low because of poor study design and small patient numbers.
Key Findings
Regurgitation
Across four RCTs involving 265 infants, thickened or anti-reflux formula was associated with a statistically significant increase in weight gain, an additional increment of 3.5–3.7 g/d compared with standard formula, which the authors flag as a possible overfeeding risk. An overview of 13 RCTs of anti-reflux formulas (rice, corn starch, and locust bean thickeners) reported a reduction in daily regurgitation from a mean of 5.4 to 2.5 episodes per day over 1 to 4 weeks. The authors caution that these trials differed widely in design, so the roughly 50% reduction is only indicative. Thickened formulas reduce the frequency of visible reflux but do not affect gastric emptying time, and there is no conclusive evidence favoring one thickening agent over another. There was no evidence that protein hydrolyzation or fermentation adds benefit beyond thickening.
Colic
Reported incidence of infantile colic ranges from 8% to 29% in healthy infants. Lactase supplementation drops reduced colic in one RCT of 162 patients, though it did not use the stringent Rome criteria and had a small sample. An industry-driven RCT in 275 infants compared a formula with partially hydrolyzed whey protein, low lactose, prebiotic oligosaccharides, and high β-palmitic acid against standard formula plus simethicone. Crying episodes after 14 days fell from 3.32 (±2.06) per day in the standard group to 1.76 (±1.60) in the study formula group (p < 0.0001), but the combined modifications made it difficult to determine which component was responsible. A later placebo-controlled trial of an alpha-lactalbumin-enriched, probiotic-supplemented formula showed no reduction in crying duration. A single double-blind RCT of isolated SN-2-palmitate reported a significant difference in crying time at 12 weeks of age. A 2018 Cochrane review found the benefits of hydrolyzed protein formulas weak, based on small, industry-driven trials with significant risk of bias, and not large enough to be clinically significant. For probiotics, Lactobacillus reuteri DSM 17938 appeared promising in breastfed infants, but one RCT found no favorable effect when delivered in a partially hydrolyzed, reduced-lactose formula. A goat milk-based formula showed no improvement in fussiness or colic.
Constipation
Prevalence in infancy is reported as up to 27%. In a small crossover trial of 30 infants, tripling the usual lactose content together with a one-third increase in magnesium raised stool water content and eased constipation symptoms. Formulas with elevated magnesium (typically 8–9 mg/100 mL versus about 5 mg/100 mL in conventional formula) showed positive effects on stool frequency and consistency, with no reported or suspected safety issues. A small industry-sponsored RCT in 89 infants using a partially hydrolyzed formula with 25% higher magnesium reported improved stool consistency and frequency, but certainty was low because of study design and patient numbers. For β-palmitate (SN-2-palmitate), data from 21 studies suggested a high SN-2-palmitate fat blend may produce short-term softer stools, though one earlier study found no significant improvement when β-palmitate was combined with hydrolyzed protein and prebiotics.
Combined FGID
The evidence consisted mainly of observational studies with a lack of prospective RCTs, so no definitive assessment of efficacy could be made.
Limitations
The evidence base is the paper's central limitation, and the authors state this repeatedly. Many of the underlying trials had very small sample sizes, were funded or driven by industry, lacked control groups, or carried a significant risk of bias. Several formulas tested multiple compositional changes at once, which makes it impossible to attribute any effect to a single ingredient. Only English-language studies of infants up to 6 months were included, which may leave out relevant data. No formal GRADE rating was applied, and where evidence was absent the recommendations rest on expert consensus rather than trial data. Finally, most authors disclosed financial relationships with infant-formula manufacturers, a relevant consideration given that the paper evaluates those companies' product categories.
Neutral Interpretation
The paper's overall message is cautious: for most infants with regurgitation, colic, or constipation, no special formula is indicated, and breastfeeding should never be stopped in favor of formula. It finds a reasonably consistent (if modest and methodologically shaky) signal that thickened anti-reflux formulas reduce visible spitting up, and a weaker signal that high-magnesium or high-β-palmitate formulas can soften stool in selected constipated infants. For colic, it concludes that specialized formulas are generally not justified by the available evidence. What the paper does not show is that any of these formulas treat the underlying condition, improve long-term outcomes, or outperform reassurance and standard care for the average infant. The document is a consensus position paper rather than a systematic review with pooled effect estimates, and it was not GRADE-rated. It reports that no funding was received, but most authors declared honoraria, advisory-board roles, or research funding from infant-nutrition companies, including several named in the relevant product categories. Readers should weigh that context, though the paper's conclusions are notably restrained about the products involved.
Full Citation
Haiden N, Savino F, Hill S, Kivelä L, De Koning B, Kӧglmeier J, Luque V, Moltu SJ, Norsa L, Saenz De Pipaon M, Verduci E, Bronsky J. Infant formulas for the treatment of functional gastrointestinal disorders: A position paper of the ESPGHAN Nutrition Committee. J Pediatr Gastroenterol Nutr. 2024;79(1):168–180. doi:10.1002/jpn3.12240. PMID: 38766683.
Available at: https://onlinelibrary.wiley.com/doi/10.1002/jpn3.12240
Disclosure
This summary is based on the published position paper. It is provided for informational purposes only and does not constitute medical advice.