Human Milk Oligosaccharide Profiles and the Secretor and Lewis Gene Status of Indonesian Lactating Mothers / 대한소아소화기영양학회지

Purpose@#Human milk oligosaccharides (HMOs) may be genetically determined based on the secretor and Lewis status of the mother. This study aims to determine the HMO profile and the secretor and Lewis gene status of Indonesian lactating mothers. @*Methods@#Baseline data of 120 mother-infant pairs between 0-4 months post-partum obtained from a prospective longitudinal study was used. The concentrations of 2'-fucosyllactose (2’FL), lacto-N-fucopentaose I (LNFP I), lacto-N-tetraose (LNT), lactoN-neotetraose (LNnT), 3'-sialyllactose (3’SL), and 6'-sialyllactose (6’SL) were measured.Genetic analysis was performed for mothers using targeted next-generation sequencing and Sanger sequencing. Wild-type AA with the rs1047781 (A385T) polymorphism was categorized as secretor positive, while heterozygous mutant AT was classified as a weak secretor. The presence of rs28362459 (T59G) heterozygous mutant AC and rs3745635 (G508A) heterozygous mutant CT genes indicated a Lewis negative status, and the absence of these genes indicated a positive status. Subsequently, breast milk was classified into various groups, namely Group 1: Secretor+Lewis+ (Se+Le+), Group 2: Secretor−Lewis+ (Se−Le+), Group 3: Secretor+Lewis− (Se+Le−), and Group 4: Secretor−Lewis− (Se−Le−). Data were analyzed using the Mann–Whitney and Kruskal–Wallis rank tests, and a p-value of 0.05 indicated statistical significance. @*Results@#A total of 58.3% and 41.7% of the samples had positive and weak secretor statuses, respectively. The proportion of those in Group 1 was 85%, while 15% were Group 3.The results showed that only 2'FL significantly differed according to the secretor status (p-value=0.018). @*Conclusion@#All Indonesian lactating mothers in this study were secretor positive, and most of them had a Lewis-positive status.

Association Between Pediatric Gastroesophageal Reflux Disease Symptom and Quality of Life Questionnaire Score, Endoscopy and Biopsy in Children with Clinical Gastroesophageal Reflux Disease: A Prospective Study / 대한소아소화기영양학회지

Purpose@#Gastro esophageal reflux disease (GERD) is a burdensome disease affecting many children. A clinical examination is reported to be unreliable to diagnose GERD in children.This study aimed to investigate the relationship between the Pediatric Gastroesophageal Reflux Disease Symptom and Quality of Life Questionnaire (PGSQ) and endoscopic and histopathological findings in children with symptoms suggesting GERD. Changes in the PGSQ score in children with esophagitis as response to one month therapy were recorded as secondary outcome. @*Methods@#This is a prospective cohort study in the pediatric outpatient clinic in an Indonesian tertiary hospital. Children aged 2–17 years old with clinical symptoms suspected of GERD are included in the study. Blinded endoscopic and histopathological examination was performed in all patients before one month proton pump inhibitors (PPI) therapy. The PGSQ information was collected at inclusion and after one month PPI treatment. @*Results@#Fifty-eight subjects were included. Esophagitis was found in 60.9% of subjects according to endoscopy and 58.6% according to histology. There was no significant relationship between the PGSQ score and endoscopic (p=0.781) nor biopsy (p=0.740) examinations. The PGSQ showed a low diagnostic value compared to endoscopy and biopsy (area under the curve [AUC] 0.477, p=0.477, 95% confidence interval [CI] 0.326–0.629 and AUC 0.474, p=0.740 (95% CI 0.321–0.627 respectively). The PGSQ improved significantly post one month of PPI treatment. @*Conclusion@#The PGSQ cannot be used to diagnose esophagitis in children with clinical symptoms suggesting GERD. However, the PGSQ can be used to monitor the treatment response in children with esophagitis.

Association between milk consumption and lactose malabsorption in Indonesian children / 中国当代儿科杂志

OBJECTIVES@#To study the association between milk consumption and lactose malabsorption in Indonesian children aged 3-12 years.@*METHODS@#This cross sectional study was conducted in randomly selected presumed healthy children with good nutritional status aged 3-12 years in Central Jakarta, Indonesia (@*RESULTS@#The prevalence of lactose malabsorption in children aged 3-5 years and children aged 6-12 years was 20.8% (15/72) and 35.3% (36/102), respectively. There was no association between milk or milk product consumption and lactose malabsorption (@*CONCLUSIONS@#There is no association between milk consumption and lactose malabsorption in Indonesian children aged 3-12 years, suggesting that genetic predisposition may be more important than adaptive mechanisms to lactose consumption.

Human Milk Oligosaccharides as a Missing Piece in Combating Nutritional Issues during Exclusive Breastfeeding / 대한소아소화기영양학회지

Extensive studies have shown that breast milk is the best source of nutrition for infants, especially during the first six months, because it fulfills almost all of their nutritional needs. Among the many functional building blocks in breast milk, human milk oligosaccharides (HMOs) have been receiving more attention recently. Furthermore, it is the third most common group of compounds in human milk, and studies have demonstrated the health benefits it provides for infants, including improved nutritional status. HMOs were previously known as the ‘bifidus factor’ due to their ‘bifidogenic’ or prebiotic effects, which enabled the nourishment of the gastrointestinal microbiota. Healthy gastrointestinal microbiota are intestinal health substrates that increase nutrient absorption and reduce the incidence of diarrhea. In addition, HMOs, directly and indirectly, protect infants against infections and strengthen their immune system, leading to a positive energy balance and promoting normal growth. Non-modifiable factors, such as genetics, and modifiable factors (e.g., maternal health, diet, nutritional status, environment) can influence the HMO profile. This review provides an overview of the current understanding of how HMOs can contribute to the prevention and treatment of nutritional issues during exclusive breastfeeding.

Effect of Supplementation of Zinc, Glutamine, Fiber, and Prebiotics in Presumed Healthy Indonesian Children Aged 1–3 Years / 대한소아소화기영양학회지

Purpose@#Impaired intestinal mucosal integrity may affect the gastrointestinal function, especially in relation to nutrition, absorption, and barrier function. The purpose of this study was to measure the prevalence of impaired intestinal mucosal integrity in presumed healthy children aged 1–3 years and assess the effects of zinc, glutamine, fiber, and prebiotic supplementation in them. @*Methods@#A cross-sectional study was conducted in 200 children aged 1–3 years in Pasar Minggu, South Jakarta, Indonesia. A randomized double-blind parallel group method clinical trial was then performed to assess the effects of zinc, glutamine, fiber, and prebiotic supplementation. @*Results@#Elevated calprotectin was found in 91/200 subjects (45.5%) at the onset of the study. After 10 months, 144 subjects completed the study: 72 subjects received the trial formula, whereas the other 72 received the standard formula. A transitory decrease in fecal calprotectin (FC) was observed after 6 months in the subgroup with normal FC levels, who were fed the test formula (p=0.012). @*Conclusion@#The prevalence of impaired intestinal mucosal integrity in this group of Indonesian children aged 1–3 years was high. Supplementation with zinc, glutamine, fiber, and prebiotics during 6 months reduced FC only in those who had low levels at baseline but not in those with impaired integrity.

Dosage-Related Prebiotic Effects of Inulin in Formula-Fed Infants / 대한소아소화기영양학회지

PURPOSE: The aim of this study was to identify the minimally meaningful dosage of inulin leading to a prebiotic effect in Indonesian infants. METHODS: In a randomized controlled double-blinded, parallel, 3-arm intervention study, 164 healthy formula-fed infants aged 3 to 5 months first obtained formula-A (without inulin) during a 4-week adaptation period. Subsequently, 142 subjects were subjected to a 4-week feeding period by administering either formula-A (no inulin), formula-B (0.2 g/100 mL inulin) or formula-C (0.4 g/100 mL inulin). The primary outcome parameter was %-bifidobacteria in faecal samples determined using quantitative polymerase chain reaction analyses. Secondary outcome parameters were faecal %-lactobacilli, pH and stool frequency, and consistency. Growth and tolerance/adverse effects were recorded as safety parameters. RESULTS: Typical %-bifidobacteria and %-lactobacilli at the end of the adaptation period in the study population were 14% and 2%, respectively. For faecal pH, significant differences between formula groups A vs. C and A vs. B were found at the end of the intervention period. Testing for differences in faecal %-bifidobacteria and %-lactobacilli between groups was hampered by non-normal data set distributions; no statistically significant differences were obtained. Comparisons within groups revealed that only in formula group C, all the three relevant parameters exhibited a significant effect with an increase in faecal %-bifidobacteria and %-lactobacilli and a decrease in pH. CONCLUSION: A consistent prebiotic effect along with a decrease in pH and increase in %-bifidobacteria and %-lactobacilli was found only in the group administered 0.4 g inulin/100 mL.

A perspective on partially hydrolyzed protein infant formula in nonexclusively breastfed infants / 소아과

The World Health Organization recommends that infants should be exclusively breastfed for the first 6 months of life to provide optimal nutrition in this critical period of life. After this, infants should receive nutritionally adequate and safe complementary foods while breastfeeding continues for up to 2 years of age or beyond. For nonbreastfed infants, infant formula is an available option to provide the nutrition needed. Infant formula is usually prepared from industrially modified cow's milk and processed to adjust for the nutritional needs of infants. However, cow's milk is one of the most common causes of food allergy, affecting 2%–5% of all formula-fed infants during their first year of life. One strategy to prevent cow's milk allergy in nonbreastfed infants is the use of partially hydrolyzed formula (pHF) in high-risk infants, which are infants born in families with atopic disease. However, based on an epidemiological study, approximately half of the infants who develop allergy are not part of the at-risk group. This is because the non-at-risk group is significantly larger than the at-risk group and the non-at-risk infants have approximately 15% risk of developing allergies. This study aimed to evaluate the effects of partially hydrolyzed whey formula (pHF-W) in nonbreastfed infants and determine whether pHF-W can prevent atopic disease in high-risk infants and can be used as routine starter formula regardless of the allergy risk status.

Lactobacillus reuteri DSM 17938 Improves Feeding Intolerance in Preterm Infants / 대한소아소화기영양학회지

PURPOSE: Feeding tolerance is extremely important in preterm infants. This study aimed to evaluate whether preterm infants receiving Lactobacillus reuteri DSM 17938 would develop fewer symptoms of feeding intolerance. Secondary outcomes were duration of parenteral nutrition, time to reach full feeding, length of hospital stay, sepsis, necrotizing enterocolitis (NEC), diarrhea, and mortality. METHODS: This double-blind randomized controlled trial of L. reuteri DSM 17938 versus placebo included 94 neonates with a gestational age of 28–34 weeks and birth weight of 1,000–1,800 g. RESULTS: Feeding intolerance (vomiting and/or distension) was less common in the probiotic group than in the placebo group (8.5% vs. 25.5%; relative risk, 0.33; 95% confidence interval, 0.12–0.96; p=0.03). No significant intergroup differences were found in proven sepsis, time to reach full feeding, length of hospital stay, or diarrhea. The prevalence of NEC (stages 2 and 3) was 6.4% in the placebo group vs. 0% in the probiotic group (relative risk, 1.07; 95% confidence interval, 0.99–1.15; p=0.24). Mortality rates were 2.1% in the probiotic group and 8.5% in the placebo group, p=0.36). CONCLUSION: The administration of L. reuteri DSM 17938 to preterm infants was safe and significantly reduced feeding intolerance. No significant differences were found in any other secondary outcomes.

The Role of Two Human Milk Oligosaccharides, 2′-Fucosyllactose and Lacto-N-Neotetraose, in Infant Nutrition / 대한소아소화기영양학회지

Human breast milk contains numerous biomolecules. Human milk oligosaccharides (HMOs) are the third most abundant component of breast milk, after lactose and lipids. Amongst the synthetized HMOs, 2′-fucosyllactose (2′-FL) and lacto-N-neotetraose (LNnT) are widely studied and are considered safe for infant nutrition. Several studies have reported the health benefits of HMOs, which include modulation of the intestinal microbiota, anti-adhesive effect against pathogens, modulation of the intestinal epithelial cell response, and development of the immune system. The amount and diversity of HMOs are determined by the genetic background of the mothers (HMO secretors or non-secretors). The non-secretor mothers secrete lower HMOs than secretor mothers. The breastfed infants of secretor mothers gain more health benefit than those of non-secretor mothers. In conclusion, supplementation of infant formula with 2′-FL and LNnT is a promising innovation for infant nutrition.

The Gastroesophageal Reflux Disease Questionnaire in Adolescents: What Is the Best Cutoff Score? / 대한소아소화기영양학회지

BACKGROUND: A self-assessment questionnaire, the GERD-Questionnaire (GERD-Q) was used to determine the prevalence of GERD in adolescents, describe the related factors, and determine the impact on quality of life (QoL). METHODS: The incidence of GERD was evaluated using the GERD-Q in adolescents aged 12–18 years. The Pediatric Gastroesophageal Reflux Disease Symptom Questionnaire and Quality of Life Questionnaire (PGSQ-A) for adolescents were additionally administered. Some factors considered related to GERD were also evaluated. RESULTS: The 520 adolescents were included. The prevalence of suspected GERD, according to a GERD-Q cutoff score of ≥7 was 32.9%, and those drinking soda were 1.7 times more likely to have GERD (95% confidence interval, 1.3–2.2; p<0.001). However, soda consumption was not a risk factor for development of GERD symptoms. Applying a cutoff score of ≥8, only 10.9% of the participants had a positive GERD score, but the association with soda consumption persisted. The median PGSQ-A score in subjects suspected of GERD was 8 (range 0–37) on weekends and 1 (range 0–17) during weekdays (p<0.001) compared to those not suspected of GERD, with a median of 2 (range 0–27) during weekends and 0 (range 0–10) during weekdays. Heartburn, regurgitation, and extraesophageal symptoms correlated significantly with QoL (p<0.001). CONCLUSION: The prevalence of suspected GERD in adolescents was 32.9% or 10.9%, depending on the cutoff score used. There was a statistically significant difference in PGSQ-A scores between the subjects suspected or not of GERD, indicating an impaired QoL.

An Electronic Questionnaire Survey Evaluating the Perceived Prevalence and Practices of Lactose Intolerance in 1 to 5 Year Old Children in South East Asia / 대한소아소화기영양학회지

PURPOSE: Lactose intolerance (LI) is perceived to be frequent in Asia and has been reported to have considerable impact on dietary intake, nutritional status and the quality of life. We aimed to gather information from healthcare professionals on the perceived incidence, diagnosis and management of LI in 1 to 5 year old children in Southeast Asia. METHODS: An anonymous electronic survey was sent randomly among healthcare professionals registered in the database of the pediatric societies in Thailand, Indonesia, and Singapore between June and October 2016. RESULTS: In total, 259 health care professionals responded of which 45.5% (n=118) were from Thailand, 37.4% (n=97) from Indonesia and 16.9% (n=44) from Singapore. Of the participants who responded (n=248), primary LI prevalence among children 1 to 3 years of age was estimated to be less than 5% by 56.8%. However, about 18.9% (n=47) answered they did not know/unsure. Regarding secondary LI, 61.6% of respondents (n=153) estimated the prevalence to be less than 15%. But again, 10.8% (n=27) answered they did not know or unsure. Rotavirus gastroenteritis was ranked as the top cause for secondary LI. There was considerable heterogeneity in the diagnostic methods used. The majority of respondents (75%) recommended lactose-free milk to manage primary and secondary LI. CONCLUSION: More education/training of pediatricians on this topic and further epidemiological studies using a more systematic approach are required.

Regurgitation and Gastroesophageal Reflux Disease in Six to Nine Months Old Indonesian Infants / 대한소아소화기영양학회지

PURPOSE: Regurgitation is known to peak at the age of 3-4 months, with a sharp decrease around the age of 6 months. Little is known about the natural evolution of infants who still regurgitate after the age of 6 months. METHODS: Hundred thirty-one infants older than 6 months regurgitating more than once a day were followed for a period of 3 months. RESULTS: According to our data, gastroesophageal reflux disease (GERD) is seldom at this age. Most of the infants regurgitated 3 or more times/day and spit up an estimated volume of more than 15 mL. Eighty-five parents were educated regarding frequency of feeding. There were only 6 infants that still had frequent regurgitation (>3 times/day) despite an appropriate feeding schedule. The Infant GER Questionnaire score reached a score of 0 in 50% of the infants after one month of follow-up and in 81.9% at the third month of follow-up. There was an increase of the "weight for age z-score" trends in infants that still regurgitated at the end of follow-up and a declining z-score in infants that no longer regurgitated. An explanation may be that infants that regurgitate drink larger volumes than infants who do not regurgitate. Conservative treatment (reassurance, dietary treatment, behavioral advice) resulted in a significant better outcome than natural evolution. CONCLUSION: Regurgitation that persisted after the age of 6 months, strongly decreased during a 3-month follow-up with conservative treatment. GERD is rare in this age group; therefore, anti-reflux medication is only seldom needed.

Glass and antimony electrodes for oesophageal pH monitoring in distressed infants: how different are they?

OBJECTIVE: Although antimony electrodes are by far the most popular for performing oesophageal pH monitoring, there are few data comparing the accuracy of glass and antimony electrodes. Therefore, we tested the accuracy of both electrodes in the prediction of oesophagitis. METHOD: pH monitoring using a glass electrode and an antimony electrode was performed in 60 distressed infants, aged between 1 and 6 months. An upper endoscopy with oesophageal biopsies was also performed in all infants. RESULTS: A reflux index (percentage of the total time with pH < 4.0) greater than 5% was considered to be abnormal and was found in 40/60 patients. Histological oesophagitis was present in 26/60 infants. The reflux index was > 5% with the glass electrode in 18/26 children with histological oesophagitis and with the antimony electrode in 10/26 children with histological oesophagitis. Histology of the oesophagus was normal in 22/40 children with abnormal pH monitoring. With the glass electrode, the mean reflux index in the group with oesophagitis was significantly higher than in the group with normal histology, although there was an important overlap. With the antimony electrode, the mean reflux indices in the groups with and without oesophagitis were not different. Regarding normal/abnormal, there was discordance in 35% of the pH studies. No reflux index could be related to a clinically useful sensitivity and specificity to predict oesophagitis. CONCLUSION: The reflux index does not accurately predict oesophagitis. Oesophageal pH monitoring and endoscopy provide complementary information.

Oesophageal pH monitoring and reflux oesophagitis in irritable infants.

UNLABELLED: Acid reflux and/or oesophagitis may be responsible for inconsolable crying in infants. We evaluated prospectively the presence of acid reflux disease, oesophagitis and the accuracy of pH monitoring in the prediction of oesophagitis in a population of irritable infants. A 24-h oesophageal pH monitoring with a glass electrode and an upper gastro-intestinal tract endoscopy with grasp biopsies were performed in 60 irritable infants, aged 1 to 6 months, not responding to cow's milk elimination. The 24-h oesophageal pH monitoring was considered abnormal in 40/60 (66%) babies and histological oesophagitis was present in 26/60 (43%). In the infants with histological oesophagitis, the reflux index (% of the investigation time with a pH < 4.0) was > 5% in 18/26 (69%). Histology of the oesophagus was normal in 22 of the 40 (55%) infants with an abnormal pH monitoring. The mean reflux index in the group with oesophagitis (12.20%) was significantly higher than in the group with normal histology (8.74) (P = 0.036), although there was an important overlap. The sensitivity and specificity to predict oesophagitis with a reflux index of 5.0% or more was 69.2 and 35.3, respectively. There was not a reflux index which could be related to a clinically useful sensitivity and specificity to predict oesophagitis. CONCLUSION: Acid gastro-oesophageal reflux disease and/or histological oesophagitis were diagnosed in 66% and 43% of irritable infants, respectively. There was no relation between symptoms and abnormal pH metry or oesophagitis; however, the reflux index does not accurately predict oesophagitis and normal histology does not accurately exclude acid gastro-oesophageal reflux disease. Oesophageal pH monitoring and endoscopy provide additional information.

Pharmacotherapy of gastro-oesophageal reflux disease in children: focus on safety.

Gastro-oesophageal reflux (GOR) disease is very common and, in the majority of infants, is physiological. However, untreated GOR disease in infants and children is associated with a decrease in quality of life for the child and their parents. It may also cause sometimes more severe complications, such as oesophagitis, and causing, in rare cases, failure to thrive, oesophageal stricture, apnoea and even death. Every therapeutic intervention (non-drug treatment, medical treatment and surgery) is associated with morbidity and even mortality. Moreover, efficacy data of many medications in children are non-existing, limited or disappointing. The safety profile of cisapride is comparable to that of other therapeutic interventions or to the risk of non-treatment. Therefore, the therapeutic approach of GOR disease in infants and children needs to be well-balanced, considering therapeutic efficacy and side effects. This review will focus on the side effects of the different therapeutic options.