Factors affecting early-life intestinal microbiota development.

OBJECTIVES: This paper reviews the published evidence on early-life intestinal microbiota development, as well as the different factors influencing its development before, at, and after birth. A literature search was done using PubMed, Cochrane and EMBASE databases. A growing body of evidence indicates that the intrauterine environment is not sterile as once presumed, but that maternal-fetal transmission of microbiota occurs during pregnancy. The consecutive order of bacteria with which the gastrointestinal tract is colonized will influence the outcome of community assembly and the ecological success of individual colonizers. The genetic background of the infant may also strongly influence microbial colonization of the gastrointestinal tract. The composition and development of infant gut microbiota can be influenced by many prenatal factors, such as maternal diet, obesity, smoking status, and use of antibiotic agents during pregnancy. Mode of delivery is generally accepted as a major factor determining the initial colonization. Breast milk stimulates the most balanced microbiome development for the infant, mainly because of its high content of unique oligosaccharides. Feeding is another important factor to determine intestinal colonization. Compared with breastfed infants, formula-fed infants have an increased richness of species. Initial clinical studies show that infant formulas supplemented with specific human milk oligosaccharides (HMOs) -2´-fucosyllactose alone or in combination with lacto-n-neotetraose are structurally identical to those in breast milk. HMOs increase the proportion of infants with a high bifidobacterial-dominated gut microbiota typical of that observed in breastfed infants, lead to plasma immune marker profiles similar to those of breast-fed infants and to lower morbidity and antibiotics use. Further clinical studies with the same, others or more HMOs are needed to confirm these clinical effects. A growing number of studies have reported on how the composition and development of the microbiota during early life will affect risk factors related to health up to and during adulthood. If exclusive breastfeeding is not possible, the composition of infant formula should be adapted to stimulate the development of a bifidobacterial-dominated gut microbiota typical of that observed in breastfed infants. The main components in breast milk that stimulate the growth of specific bifidobacteria are HMOs.

Parenteral nutrition in childhood and consequences for dentition and gingivae.

AIM: Assessment of dentition in children under parenteral nutrition, risk factors for caries, and dental developmental abnormalities. MATERIALS AND METHODS: The study involved 63 patients (aged 2.25-16.6 years), i.e. 32 subjects receiving parenteral nutrition for a mean period of 5.6±2.94 years, and 31 healthy control subjects. Oral hygiene (OHI-S, PL-I), gingival (GI), and dentition status (caries, DMFT/dmft, enamel defects, shape alterations), frequency of oral meals and frequency of cariogenic snacks consumption were evaluated. Medical records provided information on parenteral meals per week, age parenteral nutrition started, birth body mass, Apgar score, weight deficiency, and antibiotic therapy until aged 1 year. The Mann-Whitney test, chi-squared test, and Spearman rank correlation coefficient were used (p≤0.05). RESULTS: Dental developmental abnormalities occurred more often in PN subjects (71.87% vs. 25.80%). The prevalence of caries in PN (56.25% vs. 90.32%) and dmft (2.00±3.30 vs. 4.21±3.33) and DMFT (2.47±4.08 vs. 3.33±3.50) were lower. Positive caries Spearman's rank correlation coefficients: frequency of oral meals and frequency of cariogenic snacks consumption, and GI. Negative correlation coefficients: low birth body mass, antibiotic therapy, and low body mass in the first year of life. Positive dental developmental abnormality Spearman's coefficients: low birth body mass, Apgar score < 7, parenteral nutrition duration, low body mass and antibiotic therapy in the first year of life. Beta- lactam, aminoglycoside, glycopeptide and nitroimidazole treatments were related to enamel hypoplasia. CONCLUSION: Parenteral nutrition in childhood is related to the risk of dental developmental abnormalities, promoted by malnutrition and antibiotic therapy in infancy. Limiting the number of meals and cariogenic snacks, and most probably administration of antibiotics, decreases the risk of caries.

Difficulties in recognition of pyruvate dehydrogenase complex deficiency on the basis of clinical and biochemical features. The role of next-generation sequencing.

Pyruvate dehydrogenase complex (PDHc) defect is a well-known cause of mitochondrial disorders (MD) with at least six responsible genes (PDHA1, PDHB, DLAT, DLD, PDHX, PDP1). The aim of this work was to assess the diagnostic value of biochemical methods in recognition of PDHc defect in Polish patients with suspicion of MD. In the first step, Western blot of the E1α subunit was performed on 86 archive muscle bioptates with suspicion of MD. In the second step, Sanger PDHA1 sequencing was performed in 21 cases with low E1α expression. In the third step, 7 patients with negative results of PDHA1 sequencing were subjected to whole-exome sequencing (WES). This protocol revealed 4 patients with PDHA1 and one with DLD mutations. Four additional probands were diagnosed outside the protocol (WES or Sanger sequencing). The molecular characterization of PDHc defect was conducted in a total of 9 probands: 5 according to and 4 off the protocol. Additionally, two affected relatives were recognized by a family study. Altogether we identified seven different PDHA1 changes, including two novel variants [c.464T > C (p.Met155Thr) and c.856_859dupACTT (p.Arg288Leufs*10)] and one DLD variant. The lactate response to glucose load in the PDHA1 subset was compared to a subset of non PDHc-related MD. Opposite responses were observed, with an increase of 23% and decrease of 27%, respectively. The results show that determining lactate response to glucose load and muscle E1α expression may contribute to distinguishing PDHc-related and other MD, however, WES is becoming the method of choice for MD diagnostics.

Neonatal short bowel syndrome as a model of intestinal failure: physiological background for enteral feeding.

Intestinal failure (IF) is a well identified clinical condition, which is characterised by the reduction of functional gut capacity below the minimum needed for adequate digestion and absorption of nutrients for normal growth in children. Short bowel syndrome (SBS) is the leading cause of IF in neonates, infants and young children usually as a result of extensive intestinal resection during the neonatal period. Simultaneously maintaining optimal nutritional status and achieving intestinal adaptation is a clinical challenge in short bowel patients. Both growth and development of the child as well as gut adaptation should be considered synergistically as primary outcome parameters. Enteral nutrition (EN) can be introduced orally and/or by tube feeding (TF). Several controversies over nutritional treatment of children with SBS related intestinal failure remain. As reported from different centres around the world, most practices are more "experienced based" rather than "evidence based". This is partly due to the small number of patients with this condition. This review (based on a consensus) discusses the physiological principles and nutritional management, including the type of diet and route of delivery. Perspectives in optimizing intestinal adaptation and reducing the consequences of small intestinal bacterial overgrowth are also discussed.

[Influence of hiatal hernia of the diaphragm of the intensity of gastroesophageal reflux in children]. / Wplyw przepukliny rozworu przelykowego przepony na nasilenie refluksu zoladkowoprzelykowego u dzieci.

The aim of the study was to evaluate how the hiatal hernia acts on the gastroesophageal reflux (GER). We observed 52 children (31 boys, and 21 girls) aged from 2 months to 12 years (mean age 14,3 months), who were diagnosed as having GER by clinical symptoms and 24-hr oesophageal pH monitoring. All patients underwent barium radiological examination. According to the absence or presence of hiatal hernia diagnosed by barium radiology, subjects were divided into two groups: I- without hernia, II-with hernia. In both groups 24-hr oesophageal pH monitoring was analyzed. We found that patients with sliding hiatal hernia had significantly higher median percent total time when oesophageal pH was below 4, significantly higher median total number of reflux episodes and higher median time of duration of oesophageal episodes. Median number of episodes greater than five minutes did not significantly differ in both groups. We conclude that hiatal hernia increases the GER.

[Evaluation of resting energy expenditure in children with cystic fibrosis]. / Ocena spoczynkowego wydatku energetycznego u dzieci chorych na mukowiscydoze.

UNLABELLED: The aim of the investigation was to assess resting energy expenditure (REE) and substrate utilisation rate in children with cystic fibrosis. Body mass coefficient was below normal limits in 2 out of 14 controls and in 9 out of 10 patients with cystic fibrosis (p < 0.001). REE and basal energy expenditure (BEE) in the patient group were respectively 52.2 +/- 8.7 kcal/kg and 45.7 +/- 8.9 kcal/kg (p < 0.006). REE/BEE ratios in relation to total body mass were 115.34 +/- 12.27% and 93.54 +/- 4.47% (p < 0.001). REE / BEE ratio in relation to lean body mass 102.95 +/- 11.5% and 92.94 +/- 5.74% (p < 0.007). Substrate oxidation rate in the patient group and control group (g/kg) were: glycogen: 4.13 +/- 2.32 and 1.91 +/- 0.81 (p < 0.004); fat: 2.76 +/- 1.39 and 1.51 +/- 0.59 (p < 0.006); protein: 1.98 +/- 0.45 and 1.32 +/- 0.40 (p < 0.001). IN CONCLUSION: In children with cystic fibrosis, malnutrition was found with increase REE which resulted from higher substrate utilisation rate as compared with the control group.

Balloon aortic valvotomy through a carotid cutdown in infants with severe aortic stenosis: results of the multi-centric registry.

OBJECTIVES: The purpose of this study was to evaluate the short and intermediate term results of infants who have undergone balloon aortic valvotomy from the carotid arterial approach, and to identify risk factors in those infants who had a poor outcome. METHODS: Between 1988 and 1999, balloon aortic valvotomy was attempted at four centres in 95 infants with severe aortic stenosis. Echocardiographic and hemodynamic data, and outcome, were analysed retrospectively. RESULTS: Valvotomy was accomplished in 92 of the 95 infants, with a median age of 5 days, a range from 0 to 191 days, and weighing 3.4 kg, with a range from 1.0 to 6.5 kg. Major procedural complications occurred in 10 infants. Post-procedural aortic regurgitation was severe in 5 patients. There were 13 early deaths, and 4 late deaths. The period of mean follow-up has been 2.1 years, with a range from 0 to 9.3 years. The actuarial survival at 3 years was 76 +/- 6%. Further interventions were needed in 19 patients, giving a 3-year freedom from reintervention of 67 +/- 6%. The 51 infants who were duct-dependent were further analyzed, and found to have a higher mortality (38%) compared to those infants not dependent on the arterial duct (5%). Risk factors for a poor outcome in the duct-dependent infants were mitral stenosis (p<0.005), a left ventricle which did not form the cardiac apex (p<0.005), and an aortic valve with a diameter of less than 6 mm (p<0.05). CONCLUSIONS: This multi-centric registry shows good results in the intermediate term for treating infants with severe aortic valvar stenosis with balloon valvotomy through a carotid arterial cutdown. Infants dependent on prostaglandin had a worse outcome, especially if they had any of the identified risk factors.

[Current views on requirements for vitamin D, calcium and phosphorus, particularly in formula fed infants]. / Wspólczesne poglady na zapotrzebowanie na witamine D oraz wapn i fosfor ze szczególnym uwzglednieniem niemowlat karmionych sztuczie.

Calcium (Ca) and phosphorus (P) absorption depends on vitamin D. Vitamin deficiency in children results in rickets and osteoporosis in adults. Prematurely born infants are at risk of osteopenia and rickets. Skin synthesis of vitamin D can obtain the level of 10 000 IU (250 ug) when the whole body is exposed to the sun. Recent opinion on vitamin D requirement establishes the level of more than 80 nmol/L of 25(OH)D. There are no recommendations for children but it seems that due to the risk of skin cancer, exposure to the sun in children will be limited and as a result higher dose of vitamin D will be needed. Calcium and phosphorus are the most common minerals of the human body. Calcium concentration in human milk is not related to the intake. Calcium intake of calcium in premature infants is 70-140 mg/100 kcal. Phosphorus content in breast milk, even as low as 15 mg%, can maintain the optimal Ca/P ratio of 2/1. Prolonged breast feeding without additional Ca and P, may result in reduced bone mineralisation. Higher content of calcium in infant formula in comparison to human milk is due to the fact that Ca absorption from breast milk is 60% in comparison to 40% absorption from the formula.

[Influence of feeding long-chain polyunsaturated fatty acids on children's health]. / Wplyw podazy dluglancuchowych wielonienasyconych kwasów tluszczowych na stan zdrowia dzieci.

Milk formulae for term-born infants supplemented with docosahexaenoic acid (DHA) resulted in DHA concentration in the red cells comparable to values observed in breast-fed infants without influence on visual acuity. Prematurely born infants fed with DHA supplemented formulae achieved visual acuity faster than the non-supplemented control group. The influence of long-chain polyunsaturated fatty acids (LC-PUFA) on visual and cognitive functions may justify their use if the safety criteria are met. LC-PUFA formulae for low birth weigh infants must contain appropriate concentration of the fatty acids with antyoxidative factors: vitamin E and vitamin C.

[Influence of child nutrition on health status during adult years]. / Wplyw zywienia dzieci na stan zdrowia w wieku doroslym.

The problem of safety of child's nutrition should be considered from the moment of his conception because intrauterine growth may be related to the diseases in adult life: atherosclerosis and coronary heart disease. Strict vegetarian diets are not appropriate for children. The task of proper nutrition in childhood is to prevent adult life diseases and to promote potentially highest quality of life and development of cognitive and intellectual functions, and proper growth. The role of microelements - iron and zinc - is also discussed.

Stent implantation for aortic coarctation and recoarctation.

OBJECTIVE: To determine the early results of balloon expandable stent implantation for aortic coarctation or recoarctation. DESIGN: Prospective observational study. SETTING: Two paediatric cardiology tertiary referral centres. PATIENTS: 17 patients, median age 17 years (range 4.4 to 45) and median weight 61 kg (17 to 92). Six had native aortic coarctation and 11 had aortic recoarctation; 14 had upper limb systolic hypertension. Of those with recoarctation, eight had had at least one previous balloon dilatation attempt and two of these patients also had further surgical interventions. INTERVENTION: Balloon expandable Palmaz iliac stent implantation. MAIN OUTCOME MEASURES: Systolic pressures gradients, minimum aortic diameter, upper limb blood pressures, and incidence of aneurysm formation. RESULTS: 18 stents were implanted during 18 procedures in the 17 patients. Mean peak systolic pressure gradient fell from 26 mm Hg (95% confidence interval (CI), 21 to 31 mm Hg) before to 5 mm Hg (2 to 8 mm Hg) after stent implantation (p < 0.001), and mean minimum aortic diameter increased from 7 mm (95% CI, 6 to 8 mm) before to 11.3 mm (10 to 12.6 mm) after implantation (p < 0.001). Complications occurred in five patients (bleeding in two, stent migration in two, and aneurysm formation in one). Two patients remained borderline hypertensive and eight were receiving antihypertensive treatment at most recent assessment. CONCLUSIONS: Stent implantation for aortic recoarctation and native coarctation gives good immediate results. Careful follow up is necessary to evaluate complications and the long term effect on blood pressure.

Aluminum contamination of parenteral nutrition additives, amino acid solutions, and lipid emulsions.

Contamination of parenteral nutrition solutions with aluminum may result in accumulation of this element in bones and, in premature infants, may inhibit bone calcium uptake and induce cholestasis. We measured the aluminum concentration of small-volume parenterals, amino acid solutions, lipid emulsions, and special solutions containing glucose, amino acids, electrolytes, and trace elements (standard I for children with a body weight of 3-5 kg, standard II for children with a body weight of 5-10 kg). The method used was graphite furnace atomic absorption spectrometry GTA-AAS (SpectrAA-400 Plus, Varian, PtY Ltd., Mulgrave, Australia). Quality control was run with the use of control serum (Seronorm, Nycomed, Oslo, Norway). The aluminum contents of parenterally administered solutions were: pediatric trace elements, 130 micrograms/L, and pediatric trace elements, 3000 micrograms/L; phosphorus salts: K-phosphates, 9800 micrograms/L, and Na/K phosphates, 13,000 micrograms/L; 10% calcium gluconate, 4400 micrograms/L; 6.5% amino acids, 30 micrograms/L; 10% amino acids, 120 micrograms/L; 12.5% amino acids, 121 micrograms/L; 20% lipid emulsion, 30 micrograms/L; 20% lipid emulsion, 180 micrograms/L; water-soluble vitamins, 12 micrograms/L; lipid soluble vitamins, 360 micrograms/L; standard I, 55 micrograms/L; standard II, 90 micrograms/L; The aluminum intake from parenteral nutrition was 6.6-10.8 micrograms.kg-1.d-1--a dose exceeding the safety limit of 2 micrograms.kg-1.d-1. The possible association of aluminum not only with metabolic bone disease, but also with encephalopathy, dictates caution when dealing with the pediatric population on long-term parenteral nutrition. In the absence of reliable label information, it seems proper to monitor the aluminum concentration in parenteral nutrition products and to report it in professional journals.

Home parenteral nutrition in children: the Polish experience.

BACKGROUND: Home parenteral nutrition has become routine for management of intestinal failure in patients. In Poland the main obstacle to widespread use of home parenteral nutrition is the lack of interest of commercial companies in delivering feedings and ancillaries to patients. METHODS: Twenty-five home parenteral nutrition patients aged from 4 months to more than 13 years were reviewed. The mother or both parents were trained in home parenteral nutrition techniques for 4 to 6 weeks and compounded the nutrients themselves at home. RESULTS: The mean duration of home parenteral nutrition was 10,117 patient days. Hospital stays of patients receiving parenteral feedings were significantly shorter than the duration of administration of home parenteral nutrition (p < 0.001). Eleven children are continuing the home parenteral nutrition program. Eighty-three catheters were used in these patients. The rate of catheter occlusion decreased within the observation period, and in 1997 not one case of occlusion was observed. In 1997 only three catheters were removed during 7.8 patient years, and the overall incidence of catheter-related complications was 0.38 per patient year. The overall occurrence of septicemia was one case in 516 days and of catheter infection was one in 459 days. In 1997 a catheter was infected on average of once every 1419 days. There was significant improvement in the z score for weight during therapy. The average monthly cost of nutrients and ancillary items was approximately $1200 (4200 Polish zlotys [PLN]). These costs are 1.6 to 3 times lower than those recorded in other studies. CONCLUSION: Home parenteral nutrition in children with nutrients mixed by caregivers in the home setting is a safe and appropriate method of treatment that can be used in countries where home parenteral nutrition solutions are not manufactured or where commercial home parenteral nutrition is not economically feasible.

Middle aortic syndrome treated by stent implantation.

OBJECTIVES: To determine outcome of stent implantation in patients with middle aortic syndrome. DESIGN: Prospective study, case series. SETTING: A tertiary paediatric cardiology centre in a children's hospital. PATIENTS: Five patients, aged 4 to 17 years (mean 11.4 years), with upper limb hypertension due to middle aortic syndrome. INTERVENTION: Stents were implanted in the mid/lower thoracic/upper abdominal aorta. MAIN OUTCOME MEASURE: Satisfactory deployment of stents and blood pressure control. RESULTS: In all patients, angiocardiography showed long segment stenosis in the mid or lower thoracic/upper abdominal aorta. The pressure gradient was between 40 and 90 mm Hg (mean 63.2 mm Hg). Seven Palmaz stents were implanted. Immediately after implantation, the gradient decreased to between 0 and 35 mm Hg (mean 13.6 mm Hg). Angiography showed a satisfactory result with widely patent stents in all. In one patient, thrombosis of the stent occurred six days after implantation. This was successfully treated with infusion of alteplase, further balloon dilatation, and implantation of a second stent overlapping the first, both dilated to 10 mm diameter. One patient had elective redilatation of the stent six months after implantation, with further reduction of the gradient from 35 mm Hg to 10 mm Hg. At the latest follow up between three and 20 months (mean 12.2 months) after stent implantation, in four patients blood pressure was better controlled with antihypertensive drugs. One patient was normotensive without drugs. Computed tomography showed no aneurysm formation in the region of the stents. CONCLUSIONS: Stent implantation is a preferable alternative to surgery in the treatment of patients with middle aortic syndrome and merits further evaluation.

[Standard parenteral solutions for children up to 3 years of age]. / Standardy plynów w zywieniu pozajelitowym dzieci do 3 roku zycia.

Standard parenteral solutions for children up to 3 years of age and body weight 3-15 kg are presented and mixing procedure under laminar flow is described.

Is growth hormone a feasible adjuvant in the treatment of children after small bowel resection?

The aim of our study was to assess the metabolic consequences of short-term administration of growth hormone in children after gut resection and influence on polyamine production in red blood cells (RBC). Twelve children aged 4-60 months were studied. All children remained on parenteral nutrition and 11 also received oral feeding. Total non-protein energy intake was 429 +/- 86 kJ/kg body weight (BW)/day. Recombinant growth hormone (GH) was administered subcutaneously at a dose of 0.3 IU/kg BW/day for 10 days. Resting energy expenditure (REE; kJ/kg BW/day) was: 316.07 +/- 54.08 before and 346.04 +/- 54.40 during GH administration (P < 0.02), but daily weight gain before GH administration was significantly lower than during treatment. A significant increase of polyamine concentrations was observed in the RBC (spermidine: 30.1 +/- 15.1 and 43.8 +/- 24.9 nmol/ml packed RBC, P < 0.003; spermine: 15.6 +/- 5.1 and 19.6 +/- 10.6 nmol/ml packed RBC, P < 0.02) and in jejunal mucosa (spermidine: 172.10 +/- 142.35 nmol/g tissue and 193.92 +/- 108.15 nmol/g tissue). The authors concluded that increased polyamine concentrations in the RBC and jejunal mucosa reflect a cellular response to GH administration. The anabolic effect of GH results in higher weight gain, although increased REE may indicate increased energy requirements during GH treatment.

Energy metabolism in portal hypertension in children.

This study was designed to assess resting energy expenditure (REE) and nutritional status in children with hepatic and prehepatic portal hypertension in comparison with healthy controls. Twenty-five patients with portal hypertension (PHT) and a history of variceal bleeding were compared with 14 healthy volunteers selected after matching for age and sex. PHT patients were allocated to one of two groups: 11 children with liver cirrhosis and/or chronic hepatitis, aged 14.0 +/- 3.3 y (means +/- SD) or 14 children with extrahepatic portal vein obstruction, aged 12.3 +/- 2.8 y. The control group consisted of 14 healthy children, aged 14.0 +/- 1.8 y. REE (indirect calorimetry) assessed after an overnight fast was significantly higher in PHT patients than in controls when related to body mass (143.7 +/- 29.5 and 116.1 +/- 5.9 kJ/kg, respectively; p < 0.004), lean body mass (168.0 +/- 28.9 and 146.4 +/- 14.1 kJ/kg, respectively; p < 0.02), and body surface area (7480 +/- 736 and 6590 +/- 567 kJ/1.73 m2, respectively; p < 0.001). The ratios of measured REE to basal energy expenditure calculated from standard equations (Schofield equations) indicated higher REE in PHT patients (102.24 +/- 6.90% and 93.54 +/- 4.47%, respectively; p < 0.001). Fat was the predominant source of energy in both PHT patients and controls; the percentage of nonprotein energy derived from carbohydrate oxidation was equaled: 36.04 +/- 18.84% and 37.15 +/- 15.71%, respectively. Analysis of percentage of undernutrition in PHT patients and controls revealed significant differences (44% and 21%, respectively; p < 0.001). Children with PHT are susceptible to malnutrition and have elevated REE compared with healthy controls. Fat is the principal basal state oxidative substrate for patients with PHT and healthy children.