Factors Predicting Statin Initiation During Childhood in Familial Hypercholesterolemia: Importance of Genetic Diagnosis.

OBJECTIVE: To identify childhood and parental factors associated with initiation of statin therapy in children with heterozygous familial hypercholesterolemia (HeFH), including underlying genetic diagnosis or parental premature atherosclerotic cardiovascular disease (ASCVD). STUDY DESIGN: This multicenter cohort study included 245 HeFH child-parent pairs from the REFERCHOL national register (2014-2020). Demographic and clinical characteristics at the last visit were collected. Vascular disease in parents was defined as a history of ASCVD, and/or a coronary artery calcium score >100, and/or stenosis of >50% in at least carotid artery. Statistical analyses included descriptive analysis, logistic regression for univariate and multivariate effects of statins, and a sensitivity analysis combining the characteristics of children and parents. RESULTS: Among the 245 children in the study cohort, 135 (58%), with a mean age of 14 ± 3 years, were treated with a statin. In multivariable analysis, the predictive childhood factors associated with statin treatment were genetic diagnosis (OR, 2.5; 95% CI, 1.3 to 4.9; P = .01), older age (OR, 4.4; 95% CI, 1.8-10.6; P = .01), more than 2 visits (OR, 2.36; 95% CI, 1.18-4.73; P = .015), and longer duration of follow-up (OR, 1.3; 95% CI, 1.1-1.6; P < .001). The predictive parental factor associated with childhood treatment was the presence of vascular disease (OR, 2.4; 95% CI, 1.0-5.7; P = .04). CONCLUSIONS: HeFH confirmed by DNA testing during childhood and a history of vascular disease in parents were independently associated with statin treatment in children with HeFH. Genetic diagnosis may be useful for cardiovascular prevention in children.

Prevalence and Etiologies of Renal and Urinary Manifestations in a Large Cohort of Children With Inflammatory Bowel Disease.

BACKGROUND AND OBJECTIVES: Renal and/or urinary manifestations (RUM) have been reported in pediatric patients with inflammatory bowel disease (IBD) but their incidence is unknown. The aims of this study were to assess the prevalence and causes of these manifestations in children with IBD and determine the causal link with 5-aminosalicylic acid (5-ASA) treatment. METHODS: A retrospective observational study was performed with children with diagnosis of IBD. All children with RUM during follow-up and/or impaired renal function [estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m 2 ] were identified. RESULTS: Of 228 included patients, 9 (3.9%) had a RUM during follow-up [follow-up: 5 years (1-12 years)] at a median age of 16 years (8-17 years). It concerned 7 of 171 patients with Crohn disease and 2 of 57 with ulcerative colitis. Seven patients were taking 5-ASA at the time of the RUM. Only 1 of them had an iatrogenic renal complication related to this treatment. Patients with RUM had a more severe disease with increased anti-tumor necrosis factor-α use ( P = 0.031), more abscesses ( P = 0.003), and a higher rate of digestive surgery ( P = 0.04). For the whole cohort, a significant decrease in eGFR was found during follow-up (121 vs 107 mL/min/1.73 m 2 , P < 0.001). At the end of follow-up, 38 of 202 (19%) patients had an eGFR < 90 mL/min/1.73 m 2 . CONCLUSION: In children with IBD, RUM can occur, independently of treatment with 5-ASA. During follow-up, a significant decrease in eGFR was observed. We suggest monitoring renal function in all patients with IBD.

Complementary bottles during the first month and risk of cow's milk allergy in breastfed infants.

AIM: To assess the impact of complementary feeding bottles given at maternity hospital and/or over the first month after discharge from the maternity ward on cow's milk allergy (CMA) risk in breastfed infants. METHODS: Case-control study involving infants aged 6-9 months and who were breastfed for at least 1 month. RESULTS: In 554 cases with a diagnosis of CMA and 211 controls, feeding bottles at maternity hospital, feeding bottles during the first month of life, avoidance of dairy products during pregnancy or breastfeeding, family history of allergy, intake of antibiotics and consumption of proton-pump inhibitors or antacids by the infant during the first month of life were associated with increased risk of CMA in a univariate model. In a multivariate model, only feeding bottle at maternity hospital (OR = 1.81 [1.27; 2.59]), family history of allergy (OR = 2.83 [2.01; 3.99]) and avoidance of dairy products during pregnancy or breastfeeding (OR = 5.62 [1.99; 15.87]) were independent risk factors of CMA. CONCLUSION: Complementary bottles given at maternity hospital to newborns who will be exclusively breastfed increases the later risk of CMA. Similarly, avoidance of dairy products during pregnancy or breastfeeding should be discouraged.

Multichamber Dysfunction in Children and Adolescents With Severe Obesity: A Cardiac Magnetic Resonance Imaging Myocardial Strain Study.

BACKGROUND: In severe obesity, left ventricular (LV) and right ventricular (RV) remodeling and contractile dysfunction have been documented, but less is known regarding left atrial (LA) dysfunction and its association with LV/RV remodeling, especially in children. PURPOSE: To assess the effects of severe childhood obesity on cardiac function by using multichamber strain analysis with MRI. STUDY TYPE: Prospective. SUBJECTS: Forty-five children aged 7-18 years (including 20 with severe obesity, defined as a body mass index values above the 99th percentile). FIELD STRENGTH: 5 T. SEQUENCE: Steady-state-free-precession (SSFP) images in short-axis views and longitudinal two- and four-chamber views. ASSESSMENT: Cardiac strain measurements were derived from standard SSFP cine images by using a dedicated MR imaging feature tracking software. Inter- and intra-rater reliability were evaluated. STATISTICAL TESTS: Independent sample t test, Spearman's correlation coefficient, principal component analysis, Bland-Altman analysis, and intra-class correlation coefficients (ICC). A P value <0.05 was considered statistically significant. RESULTS: As compared to children without obesity, those with obesity showed significantly reduced LA reservoir function (22.2% ± 6.4% vs. 33.8% ± 9.0%) and contractile function (5.4% ± 3.2% vs. 13.3% ± 8.0%) as well as significantly decreased absolute values for LA longitudinal strain in reservoir and contraction phases and LA radial motion fraction in reservoir and contraction phases. Children with severe obesity showed significantly reduced absolute RV radial motion fraction (-10.6% ± 2.9% vs. -18.2% ± 2.9%) and circumferential strain (-10.6% ± 2.9% vs. -16% ± 2.5%) as well as higher LV mass index (28.7% ± 5.1% vs. 21.7 ± 4.6 g/m2 ) along with significantly reduced LV ejection fraction (56.4% ± 3.9% vs. 60% ± 4.1%), LV radial strain (56% ± 6% vs. 61.8% ± 11.3%), and longitudinal strain (-17.8% ± 1.8% vs. -20.3% ± 3.2%). Reliability was good to excellent, with ICC ranging from 79.1% to 97.7%. DATA CONCLUSION: MR feature-tracking strain analysis revealed multichamber dysfunction in severely obese children with impaired LA reservoir and atrial contraction phases, which suggest an early loss in the compensatory ability of atrial contraction with severe obesity. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

Antiretroviral Prophylaxis: A Digestive Complication to Know.

ABSTRACT: An 8-year-old child experienced abdominal pain and melena due to duodenal and ileal ulcerations throughout antiretroviral prophylactic treatment after a needlestick injury. Mild to moderate adverse effects often occur with lamivudine and zidovudine, but more severe adverse effects such as intestinal ulcers resulting in melena after a prophylactic antiretroviral treatment may question the safety of the current guidelines.

Intermediate-Term Efficacy and Tolerance of Statins in Children.

OBJECTIVES: To evaluate the intermediate-term efficacy and tolerance of statins in children and adolescents with familial hypercholesterolemia. STUDY DESIGN: A total of 131 children or adolescents treated with statins for familial hypercholesterolemia were prospectively included. The efficacy of treatment was established by the percentage of children who achieved low density lipoprotein-cholesterol (LDL-C) levels <160 mg/dL during treatment. Treatment tolerance was evaluated by the occurrence of clinical or laboratory side effects, regularity of increases in height and weight, and pubertal development. RESULTS: The median duration of treatment with statins was 4 years. A median decrease of 32% in LDL-C levels was observed (P < .0001). The therapeutic target (LDL-C <160 mg/dL) was achieved in 67% of cases. Increases in height and weight and sexual maturation were not affected by the treatment. Minor side effects were reported for 24 (18.4%) patients including 3 cases of a clinically asymptomatic increase in creatine phosphokinase (CPK) levels, 2 cases of an increase in CPK levels with muscular symptoms, 14 cases of myalgia without an increase in CPK levels, 3 cases of abdominal pain, 1 case of dysuria, and 1 case of diffuse pain. None of these side effects led to the discontinuation of statin therapy, although a change of statin was required in 7 cases. This new statin was tolerated in all cases. No patients had abnormal liver function during treatment. CONCLUSIONS: The results of this large cohort confirm the intermediate-term safety and efficacy of statin therapy in children with familial hypercholesterolemia.

Effect of Cyproheptadine on Weight and Growth Velocity in Children With Silver-Russell Syndrome.

OBJECTIVES: Nutritional management of children with Silver-Russell syndrome (SRS) is crucial, especially before initiating growth hormone therapy. Since cyproheptadine (CYP) has been reported to be orexigenic, we retrospectively investigated the effects of CYP on changes in weight and height in patients with SRS. METHODS: Anthropometric parameters (weight [W], length or height [H], weight on expected weight for height [W/H], and body mass index) were recorded for 34 children with SRS receiving CYP. We specifically analyzed the anthropometric parameters (expressed in median) in a group of 23 patients treated with CYP at baseline (M0-CYP) and every 3 months (M3 to M12-CYP) after the initiation of CYP treatment. RESULTS: The 23 children with SRS treated by CYP only had weight stagnation during the months preceding the start of treatment. Anthropometric parameters, especially the weight, differed significantly between M0-CYP and all other times (M3, M6, M9, M12-CYP). After 1 year of treatment, a gain in overall length/height and weight was observed (W: +1.1 standard deviations from the mean [SDS]; H: +0.5 SDS). At M3, significant improvements in W/H (74.9% vs 79.3% [P = 0.01]) and body mass index (-3.4 vs -2.4 SDS [P = 0.001]) were also observed. Twenty-one patients (91%) improved their weight by at least +0.5 SDS, and 12 (52%) by at least +1 SDS. CONCLUSIONS: Our results show that CYP can be effective in patients with SRS with significant improvements in growth velocity and nutritional status before initiation of growth hormone therapy. Further prospective studies are required to confirm these results.

Global molecular analysis and APOE mutations in a cohort of autosomal dominant hypercholesterolemia patients in France.

Autosomal dominant hypercholesterolemia (ADH) is a human disorder characterized phenotypically by isolated high-cholesterol levels. Mutations in the low density lipoprotein receptor (LDLR), APOB, and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes are well known to be associated with the disease. To characterize the genetic background associated with ADH in France, the three ADH-associated genes were sequenced in a cohort of 120 children and 109 adult patients. Fifty-one percent of the cohort had a possible deleterious variant in LDLR, 3.1% in APOB, and 1.7% in PCSK9. We identified 18 new variants in LDLR and 2 in PCSK9. Three LDLR variants, including two newly identified, were studied by minigene reporter assay confirming the predicted effects on splicing. Additionally, as recently an in-frame deletion in the APOE gene was found to be linked to ADH, the sequencing of this latter gene was performed in patients without a deleterious variant in the three former genes. An APOE variant was identified in three patients with isolated severe hypercholesterolemia giving a frequency of 1.3% in the cohort. Therefore, even though LDLR mutations are the major cause of ADH with a large mutation spectrum, APOE variants were found to be significantly associated with the disease. Furthermore, using structural analysis and modeling, the identified APOE sequence changes were predicted to impact protein function.

Ultrasonography and Computed Tomographic Manifestations of Abdominal Sarcoidosis in Children.

OBJECTIVES: Sarcoidosis is a multisystem, granulomatous inflammatory disease affecting both pediatric and adult patients. So far in children, very few radiological descriptions of abdominal sarcoidosis manifestations have been reported. The present study describes the frequency and the appearance of abdominal radiologic manifestations in pediatric patients with histologically proven sarcoidosis. METHODS: We reviewed retrospectively all of the radiological examinations of 22 patients ages 1 to 15 years at diagnosis with proven sarcoidosis evaluated in a university pediatric hospital between 1994 and 2014. The locations of biopsies and the angiotensin-converting enzyme level were reported. The size, shape, and parenchymal homogeneity of the liver and spleen, the presence of abdominal lymph nodes, and abnormalities of the gastrointestinal tract were tabulated. RESULTS: The study included 22 children (mean age: 9.9 ±â€Š2.8 years). The liver was the most frequent location of biopsy (12/22), even without radiological involvement. Abdominal manifestations were present in 11 of 22 children with sarcoidosis. Hepatomegaly was the most frequent abnormality, reported in 8 of 11 cases either homogeneous (n = 7) or nodular (n = 1). Homogeneous lymph node enlargement was noted in 6 of 11 cases and splenomegaly in 4 of 11 cases. No calcification was observed. All patients with initial abdominal sarcoidosis had simultaneous thoracic involvement. CONCLUSIONS: Abdominal manifestations in children sarcoidosis are frequent but often nonspecific. Nodular hepatosplenomegaly is rare. All of our patients with abdominal abnormalities had a more specific associated thoracic involvement. Awareness of this association could assist the clinicians in assessing the initial diagnosis of abdominal sarcoidosis in children.

Genetic characterization of congenital tufting enteropathy: epcam associated phenotype and involvement of SPINT2 in the syndromic form.

Congenital tufting enteropathy (CTE) is a rare and severe enteropathy recently ascribed to mutations in the epcam gene. Here we establish SPINT2, previously ascribed to congenital sodium diarrhea, as a second gene associated with CTE and report molecular and immunohistochemistry data in 57 CTE patients. Inclusion criteria were early onset diarrhea and intestinal insufficiency with the typical histological CTE abnormalities. The clinical phenotype was registered, the entire coding regions of epcam and SPINT2 sequenced, and immunostaining of EpCAM and SPINT2 performed on intestinal biopsies. An epcam mutation was involved in 41 patients (73 %) who mainly displayed isolated digestive symptoms. Mutations severely affected gene expression since the EpCAM signal on intestinal tissues was either undetectable or low and irregular. Twelve other patients (21 %) carried mutations in SPINT2, and were phenotypically characterized by systematic association with keratitis (p < 10(-4)) and, for half of them, with choanal atresia (p < 10(-4)). Dependency on parenteral nutrition (PN) was comparable in patients with epcam or SPINT2 mutations, but the frequent epcam mutation c.556-14A>G (abnormal splicing) was significantly associated with a better outcome (p = 0.032) with milder PN dependency to weaning in some cases. Finally, four patients (7 %) with isolated digestive symptoms had no detectable epcam or SPINT2 mutation. Two candidate genes, Elf3 and Claudin7, were excluded from this population. Our study allows us to separate CTE patients into at least three genetic classes, each with specific phenotypes. The genetics approach raises the question of the distinction between two congenital enteropathies. Our findings should help improve the diagnosis of CTE, guide toward strategies of long-term PN management, and limit indications for intestinal transplantation to life-threatening PN complications.

Variants of ENPP1 are associated with childhood and adult obesity and increase the risk of glucose intolerance and type 2 diabetes.

We identified a locus on chromosome 6q16.3-q24.2 (ref. 1) associated with childhood obesity that includes 2.4 Mb common to eight genome scans for type 2 diabetes (T2D) or obesity. Analysis of the gene ENPP1 (also called PC-1), a candidate for insulin resistance, in 6,147 subjects showed association between a three-allele risk haplotype (K121Q, IVS20delT-11 and A-->G+1044TGA; QdelTG) and childhood obesity (odds ratio (OR) = 1.69, P = 0.0006), morbid or moderate obesity in adults (OR = 1.50, P = 0.006 or OR = 1.37, P = 0.02, respectively) and T2D (OR = 1.56, P = 0.00002). The Genotype IBD Sharing Test suggested that this obesity-associated ENPP1 risk haplotype contributes to the observed chromosome 6q linkage with childhood obesity. The haplotype confers a higher risk of glucose intolerance and T2D to obese children and their parents and associates with increased serum levels of soluble ENPP1 protein in children. Expression of a long ENPP1 mRNA isoform, which includes the obesity-associated A-->G+1044TGA SNP, was specific for pancreatic islet beta cells, adipocytes and liver. These findings suggest that several variants of ENPP1 have a primary role in mediating insulin resistance and in the development of both obesity and T2D, suggesting that an underlying molecular mechanism is common to both conditions.

Hyperphagia and impulsivity: use of self-administered Dykens' and in-house impulsivity questionnaires to characterize eating behaviors in children with severe and early-onset obesity.

BACKGROUND: The determinants of early-onset obesity (< 6 years) are not completely elucidated, however eating behavior has a central role. To date no study has explored eating behavior in children with severe, early-onset obesity. Self-administered questionnaire data from these children were examined to evaluate eating behavior and the etiology of early-onset obesity. METHODS: Children with severe, early-onset obesity (body mass index [BMI] > International Obesity Task Force [IOTF] 30) of different etiologies (hypothalamic obesity [HO], intellectual disability with obesity [IDO], common polygenic obesity [CO]) were prospectively included. BMI history and responses from the Dykens' Hyperphagia Questionnaire and an in-house Impulsivity Questionnaire at first visit were compared between groups. RESULTS: This cohort of 75 children (39 girls; mean age ± standard deviation [SD] 10.8 ± 4.4 years) had severe, early-onset obesity at an age of 3.8 ± 2.7 years, with a BMI Z-score of 4.9 ± 1.5. BMI history varied between the 3 groups, with earlier severe obesity in the HO group versus 2 other groups (BMI > IOTF40 at 3.4 ± 1.6 vs. 4.6 ± 1.6 and 8.4 ± 4.1 years for the IDO and CO groups, respectively [P < 0.01]). Absence of adiposity rebound was more prevalent in the HO group (87% vs. 63% and 33% for the IDO and CO groups, respectively [P < 0.01]). The Dykens' mean total score for the cohort was 22.1 ± 7.2 with no significant between-group differences. Hyperphagia (Dykens' score > 19) and impulsivity (score > 7) were found in 50 (67%) and 11 children (15%), respectively, with no difference between the HO, IDO and CO groups regarding the number of patients with hyperphagia (10 [67%], 14 [74%], and 26 [63%] children, respectively) or impulsivity (2 [13%], 1 [7%], and 8 [19%] children, respectively). Children with food impulsivity had significantly higher total and severity scores on the Dykens' Questionnaire versus those without impulsivity. CONCLUSION: The Dykens' and Impulsivity questionnaires can help diagnose severe hyperphagia with/without food impulsivity in children with early-onset obesity, regardless of disease origin. Their systematic use can allow more targeted management of food access control in clinical practice and monitor the evolution of eating behavior in the case of innovative therapeutic targeting hyperphagia.

Indications for extensively hydrolyzed cow's milk protein in the neonatal period.

A large proportion of prescriptions for extensively hydrolyzed cow's milk protein (CMP) in newborns are not based on any scientific data justifying the indication. Many of these prescriptions are old habits or are based on incomplete data. The aim of this article is to analyze these practices and propose recommendations. The following points are covered: (a) indications for extensively hydrolyzed formula based on studies demonstrating their benefits in these situations-newborns with a proven allergy to CMP and occasional prescription of supplements to breastfeeding; (b) possible indications not based on a high level of evidence-re-initiation of feeding due to necrotizing enterocolitis, short bowel syndrome, re-initiation of feeding of newborns following intestinal surgery, and laparoschisis if neither the mother's own milk nor milk from a lactarium is available; (c) unjustified indications-newborns at risk of atopy, prematurity, severe neurological pathologies, newborns who are hemodynamically unstable and/or have congenital cardiopathy, neonatal hypoxic-ischemic encephalopathy treated with hypothermia, and newborns with esophageal atresia or diaphragmatic hernia. By following this classification, the prescriber will be guided to use the milk best suited to the pathology, bearing in mind that each situation must be adapted individually and the tolerance and effectiveness of the food reassessed from a nutritional and functional point of view.

Treatment of pediatric heterozygous familial hypercholesterolemia 7 years after the EAS recommendations: Real-world results from a large French cohort.

BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) predisposes to premature cardiovascular diseases. Since 2015, the European Atherosclerosis Society has advocated initiation of statins at 8-10 years of age and a low-density lipoprotein cholesterol (LDL-C) target of <135 mg/dL. Longitudinal data from large databases on pharmacological management of pediatric HeFH are lacking. OBJECTIVE: Here, we describe treatment patterns and LDL-C goal attainment in pediatric HeFH using longitudinal real-world data. METHODS: This was a retrospective and prospective multicenter cohort study (2015-2021) of children with HeFH, diagnosed genetically or clinically, aged <18 years, and followed up in the National French Registry of FH (REFERCHOL). Data on the study population as well as treatment patterns and outcomes are summarized as mean±SD. RESULTS: We analyzed the data of 674 HeFH children (age at last visit: 13.1 ± 3.6 years; 82.0 % ≥10 years; 52.5 % females) who were followed up for a mean of 2.8 ± 3.5 years. Initiation of lipid-lowering therapy was on average at 11.8 ± 3.0 years of age for a duration of 2.5 ± 2.8 years. At the last visit, among patients eligible for treatment (573), 36 % were not treated, 57.1 % received statins alone, 6.4 % statins with ezetimibe, and 0.2 % ezetimibe alone. LDL-C was 266±51 mg/dL before treatment and 147±54 mg/dL at the last visit (-44.7 %) in treated patients. Regarding statins, 3.3 %, 65.1 %, and 31.6 % of patients received high-, moderate-, and low-intensity statins, respectively. Overall, 59 % of children on statin therapy alone and 35.1 % on bitherapy did not achieve the LDL-C goal; fewer patients in the older age group did not reach the treatment goal. CONCLUSION: Pediatric patients with FH followed up in specialist lipid clinics in France receive late treatment, undertreatment, or suboptimal treatment and half of them do not reach the therapeutic LDL-C goal. Finding a more efficient framework for linking scientific evidence to clinical practice is needed.

Rare melanocortin-3 receptor mutations with in vitro functional consequences are associated with human obesity.

In contrast to the melanocortin 4 receptor, the possible role of the melanocortin 3 receptor (MC3R) in regulating body weight is still debated. We have previously reported three mutations in the MC3R gene showing association with human obesity, but these results were not confirmed in a study of severe obese North American adults. In this study, we evaluated the entire coding region of MC3R in 839 severely obese subjects and 967 lean controls of Italian and French origin. In vitro functional analysis of the mutations detected was also performed. The total prevalence of rare MC3R variants was not significantly different in obese subjects when compared with controls (P= 0.18). However, the prevalence of mutations with functional alterations was significantly higher in the obese group (P= 0.022). In conclusions, the results of this large study demonstrate that in the populations studied functionally significant MC3R variants are associated with obesity supporting the current hypothesis that rare variants might have a stronger impact on the individual susceptibility to gain weight. They also underline the importance of detailed in vitro functional studies in order to prove the pathogenic effect of such variants. Further investigations in larger cohorts will be needed in order to define the specific phenotypic characteristics potentially correlated with reduced MC3R signalling.

Pre-, pro-, syn-, and Postbiotics in Infant Formulas: What Are the Immune Benefits for Infants?

The first objective of infant formulas is to ensure the healthy growth of neonates and infants, as the sole complete food source during the first months of life when a child cannot be breastfed. Beyond this nutritional aspect, infant nutrition companies also try to mimic breast milk in its unique immuno-modulating properties. Numerous studies have demonstrated that the intestinal microbiota under the influence of diet shapes the maturation of the immune system and influences the risk of atopic diseases in infants. A new challenge for dairy industries is, therefore, to develop infant formulas inducing the maturation of immunity and the microbiota that can be observed in breastfed delivered vaginally, representing reference infants. Streptococcus thermophilus, Lactobacillus reuteri DSM 17938, Bifidobacterium breve (BC50), Bifidobacterium lactis Bb12, Lactobacillus fermentum (CECT5716), and Lactobacillus rhamnosus GG (LGG) are some of the probiotics added to infant formula, according to a literature review of the past 10 years. The most frequently used prebiotics in published clinical trials are fructo-oligosaccharides (FOSs), galacto-oligosaccharides (GOSs), and human milk oligosaccharides (HMOs). This review sums up the expected benefits and effects for infants of pre-, pro-, syn-, and postbiotics added to infant formula regarding the microbiota, immunity, and allergies.

Digestive Tolerance and Safety of an Anti-Regurgitation Formula Containing Locust Bean Gum, Prebiotics and Postbiotics: A Real-World Study.

Purpose: Infant regurgitation is associated with other functional gastrointestinal disorders and signs and symptoms that have a major impact on the quality of life of infants and their families. This study evaluated the safety, tolerance, and real-world effectiveness of an anti-regurgitation formula containing locust bean gum (LBG), prebiotics, and postbiotics to alleviate digestive symptoms beyond regurgitation. Methods: This 3-month study involved infants with regurgitation requiring the prescription of an anti-regurgitation formula according to usual clinical practice. Outcomes included evaluation of the evolution of stool consistency and frequency; occurrence of colic, constipation, and diarrhea; and assessment of regurgitation severity. Infant crying, parental assessment of infant well-being, and parental satisfaction with the stool consistency were also evaluated. Results: In total, 190 infants (average age: 1.9±1.1 months) were included. After three months, stool frequency and consistency remained within the normal physiological range, with 82.7% of infants passing one or two stools per day and 90.4% passing loose or formed stools. There was no significant increase in the number of infants with diarrhea, whereas a decrease was observed in the number of infants with constipation after 1 month (p=0.001) and with colic after both 1 and 3 months (p<0.001). Regurgitation severity and crying decreased and parental satisfaction with stool consistency, formula acceptability, infant well-being, and sleep quality increased. Monitoring of adverse events did not reveal any safety concerns. Conclusion: Formulas containing LBG, prebiotics, and postbiotics were well tolerated and provided an effective strategy for managing infant regurgitation and gastrointestinal discomfort.