Safe and efficient practice of parenteral nutrition in neonates and children aged 0-18 years - The role of licensed multi-chamber bags.

Parenteral nutrition (PN) is recognized as a complex high-risk therapy. Its practice is highly variable and frequently suboptimal in pediatric patients. Optimizing care requires evidence, consensus-based guidelines, audits of practice, and standardized strategies. Several pediatric scientific organizations, expert panels, and authorities have recently recommended that standardized PN should generally be used over individualized PN in the majority of pediatric patients including very low birth weight premature infants. In addition, PN admixtures produced and validated by a suitably qualified institution are recommended over locally produced PN. Licensed multi chamber bags are standardized PN bags that comply with Good Manufacturing Practice and high-quality standards for the finished product in the frame of their full manufacturing license. The purpose of this article is to review the practical aspects of PN and the evidence for using such multi-chamber bags in pediatric patients. It highlights the safety characteristics and the limitations of the different PN practices and provides some guidance for ensuring safe and efficient therapy in pediatric patients.

Actual electrolyte intake during the first week of life and morbidity in very-low-birthweight infants.

AIM: To describe sodium and potassium intake, their sources and plasma concentrations, and the association between intake and morbidity in very-low-birthweight (VLBW, <1500 g) infants during the first week of life. METHODS: This retrospective cohort study comprised 951 VLBW infants born at <32 weeks. Infants were divided into three groups according to gestational age: 23-26 (n = 275), 27-29 (n = 433) and 30-31 (n = 243) weeks. Data on fluid management and laboratory findings were acquired from an electronic patient information system. RESULTS: The median sodium intake was highest in the 23-26 week group, peaking at 6.4 mmol/kg/day. A significant proportion of sodium derived from intravascular flushes; it reached 27% on day 1 in the 23-26 week group. High cumulative sodium intake in the first postnatal week was associated with weight gain from birth to day 8 in the 23-26 week group. High intake of sodium associated with an increased risk of surgically ligated patent ductus arteriosus (PDA), bronchopulmonary dysplasia and intraventricular haemorrhage, whereas low intake of potassium associated with an increased risk of PDA. CONCLUSION: Sodium intake in the most premature infants exceeded recommendations during the first postnatal week. Saline flushes accounted for a significant proportion of the sodium load.

Very low birthweight infants receive less enteral feeding than what is prescribed.

AIM: Feeding a very low birthweight (VLBW, <1500 g) infant is challenging. Our aims were to study how prescribed enteral feeding is implemented in VLBW infants and to identify factors associating with slow enteral feeding progression. METHODS: Our retrospective cohort included 516 VLBW infants born before 32 weeks of gestation during 2005-2013 and admitted to Children's Hospital, Helsinki, Finland, for at least the two first weeks of life. Nutritional data were collected from birth until the age of 14-28 days, depending on the length of stay. RESULTS: We found that enteral feeding progressed slower than recommended and implementation differed from the prescriptions, especially during the parenteral nutrition phase (milk intake 10-20 mL/kg/day): 71% [40-100], median [IQR], of the prescribed enteral milk was administered. The full prescribed amount was less likely administered if a higher volume of gastric residual was aspirated or if the infant did not pass stool during the same day. Longer opiate use, patent ductus arteriosus, respiratory distress syndrome and slower passage of the first meconium associated with slower enteral feeding progression. CONCLUSION: Enteral feeding of a VLBW infant is often not administered as prescribed, which possibly plays a significant role in the slow progression of enteral feeding.

Length of Nutritional Transition Associates Negatively with Postnatal Growth in Very Low Birthweight Infants.

Very low birthweight (VLBW, <1500 g) infants may be predisposed to undernutrition during the nutritional transition phase from parenteral to enteral nutrition. We studied the associations among the length of the transition phase, postnatal macronutrient intake, and growth from birth to term equivalent age in VLBW infants. This retrospective cohort study included 248 VLBW infants born before 32 weeks of gestation and admitted to the Children's Hospital, Helsinki, Finland during 2005-2013. Daily nutrient intakes were obtained from computerized medication administration records. The length of the transition phase correlated negatively with cumulative energy, protein, fat, and carbohydrate intake at 28 days of age. It also associated negatively with weight and head circumference growth from birth to term equivalent age. For infants with a long transition phase (over 12 d), the estimates (95% CI) for weight and head circumference z-score change from birth to term equivalent age were -0.3 (-0.56, -0.04) and -0.44 (-0.81, -0.07), respectively, in comparison to those with a short transition phase (ad 7 d). For VLBW infants, rapid transition to full enteral feeding might be beneficial. However, if enteral nutrition cannot be advanced, well-planned parenteral nutrition during the transition phase is necessary to promote adequate growth.

Blood pressure changes during the first 24 hours of life and the association with the persistence of a patent ductus arteriosus and occurrence of intraventricular haemorrhage.

Very low birthweight (VLBW) infants are at risk of intraventricular haemorrhage (IVH) and delayed closure of ductus arteriosus. We investigated mean arterially recorded blood pressure (MAP) changes during the first day of life in VLBW infants as potential risk factors for a patent ductus arteriosus (PDA) and IVH. This retrospective cohort study exploring MAP changes during adaption and risk factors for a PDA and IVH comprised 844 VLBW infants admitted to the Helsinki University Children's Hospital during 2005-2013. For each infant, we investigated 600 time-points of MAP recorded 4-24 hours after birth. Based on blood pressure patterns revealed by a data-driven method, we divided the infants into two groups. Group 1 (n = 327, mean birthweight = 1019 g, mean gestational age = 28 + 1/7 weeks) consisted of infants whose mean MAP was lower at 18-24 hours than at 4-10 hours after birth. Group 2 (n = 517, mean birthweight = 1070 g, mean gestational age = 28 + 5/7 weeks) included infants with a higher mean MAP at 18-24 hours than at 4-10 hours after birth. We used the group assignments, MAP, gestational age at birth, relative size for gestational age, surfactant administration, inotrope usage, invasive ventilation, presence of respiratory distress syndrome or sepsis, fluid intake, and administration of antenatal steroids to predict the occurrence of IVH and use of pharmacological or surgical therapy for a PDA before 42 weeks of gestational age. Infants whose mean MAP is lower at 18-24 hours than at 4-10 hours after birth are more likely to undergo surgical ligation of a PDA (odds ratio = 2.1; CI 1.14-3.89; p = 0.018) and to suffer from IVH (odds ratio = 1.83; CI 1.23-2.72; p = 0.003).

A triple-chamber parenteral nutrition solution was associated with improved protein intake in very low birthweight infants.

AIM: We evaluated the nutrient intakes of very low birthweight (VLBW) infants weighing less than 1500 g and tested the hypothesis that using a triple-chamber parenteral nutrition (PN) solution, containing lipids, glucose and amino acids, would improve protein intake. METHODS: This retrospective cohort study comprised 953 VLBW infants born in 2005-2013 at a gestational age of less than 32 + 0/7 weeks and admitted to the neonatal care unit at Helsinki Children's Hospital, Finland. The infants were divided into four groups according their birth year and PN regime. Nutrient intakes were obtained from computerised medication administration records. RESULTS: In 2012-2013, when a triple-chamber PN solution was used, infants were more likely to reach the target parenteral protein intake of 3.5 g/kg/d, and reach it 3-7 days earlier, compared with infants who received individual PN or standard two-in-one PN solutions in 2005-2011. In addition, infants in the triple-chamber group had the highest median energy intake (90 kcal/kg/d) during the first week. They also had higher median protein intakes in weeks one, two and three (3.1, 3.4 and 3.7 g/kg/d) than infants born in 2005-2011 (P < .05). CONCLUSION: Using a triple-chamber PN solution was associated with improved protein intake, and the protein target was more likely to be achieved.

Hidden sources like saline flushes make a significant contribution to the fluid intake of very low birthweight infants during the first postnatal week.

AIM: We examined actual fluid intake, and routes of administration, in very low birthweight (VLBW) infants during the first week of life in a neonatal intensive care unit. METHODS: This retrospective cohort study comprised 953 infants born at <32 weeks and 1500 g and treated at Helsinki University Children's Hospital from 2005 to 2013. All parenterally and enterally administered fluids, and their sources, were obtained from our patient information system. Infants were divided into three groups according to their gestational age: 23-26, 27-29 and 30-31 weeks. RESULTS: Fluid intake exceeded European guidelines during the first 3 days. On days 1-7, total fluid intake was highest in the most premature group (P < .001) and the median total fluid intake in this group peaked at 177 mL/kg/d (IQR 154-209) on day three. Intravascular flushes provided a considerable source of fluids, with the median intake in the most preterm group peaking at 26.4 mL/kg/d, which represented 15.6% of total fluid intake. CONCLUSION: During the first 3 days of life, our VLBW infants had a higher total fluid intake than the European guidelines. A considerable percentage came from hidden sources, such as saline flushes, which should be taken into account when prescribing fluids.

Eliminating cows' milk, but not wheat, barley or rye, increases the risk of growth deceleration and nutritional inadequacies.

AIM: Our study examined the growth and nutritional intake of children on milk and/or wheat, barley or rye elimination diets. METHODS: This was a nested case-control study within the Finnish Type 1 Diabetes Prediction and Prevention Study. It investigated 295 children born in the Tampere University Hospital area between 1997 and 2004 on a diet without cows' milk and/or wheat, barley or rye due to food allergies and 265 matched controls. Nutritional intake was recorded with three-day food records at the ages of one, two and three years. Serial growth measurements were recorded annually up to the age of five years. RESULTS: Despite consuming a balanced diet with sufficient energy and protein, the children on milk elimination diets grew slower than the control children (p = 0.009). Wheat, barley or rye elimination was not associated with growth. The intakes of protein and calcium were lower in children in the milk elimination group than the controls, at p < 0.05 for all. However, children on elimination diets consumed less saturated fats and sugar and more vitamin C and iron than the control children. CONCLUSION: Children on elimination diets faced an increased risk of growth deceleration and suboptimal intake of several micronutrients.

Maternal dietary folate, folic acid and vitamin D intakes during pregnancy and lactation and the risk of cows' milk allergy in the offspring.

Maternal nutrient intake during pregnancy and lactation potentially influences the development of allergic diseases. Cows' milk allergy (CMA) is often the first manifestation of atopic diseases, but the impact of early nutritional influences on CMA has not been explored. The associations between maternal intakes of folate, folic acid and vitamin D during pregnancy and lactation were addressed in a prospective, population-based birth cohort within the Finnish Type 1 Diabetes Prediction and Prevention Study. Mothers of 4921 children during pregnancy and 2940 children during lactation provided information on maternal dietary intake during the 8th month of pregnancy and the 3rd month of lactation using a detailed, validated FFQ. Information on diagnosed CMA in the offspring was obtained from a medical registry as well as queried from the parents. The Finnish food composition database was used to calculate nutrient intake. Logistic regression was applied for statistical analyses. Folate intake and folic acid and vitamin D supplement use were associated with an increased risk of CMA in the offspring, whereas vitamin D intake from foods during pregnancy was associated with a decreased risk of CMA. Thus, maternal nutrient intake during pregnancy and lactation may affect the development of CMA in offspring. Supplementation with folic acid may not be beneficial in terms of CMA development, especially in children of allergic mothers. The association between dietary supplement use and CMA risk can at least partly be explained by increased health-seeking behaviour among more educated mothers who also use more dietary supplements.

The effect of elimination diet on the growth of a child with milk allergy - a systematic review.

BACKGROUND: Cow's milk is the most common food allergen in children under 3 years of age. Milk allergy is treated by eliminating milk from the diet. METHODS: The present study was conducted according to international guidelines for systematic reviews. RESULTS: In all three articles included in the current study, children with milk allergy were of lower weight than the controls. Furthermore, in one of the studies included, growth of the children with mild allergy was stunted. DISCUSSION: The current review shows that milk allergy is associated with stunted growth in childhood. The reasons for this growth retardation are unclear.

Food consumption and risk of childhood asthma.

BACKGROUND: The consumption of foods rich in n-3 polyunsaturated fatty acids has been proposed to protect against childhood asthma. This study explores the association of food consumption (including cow's milk (CM)-free diet) in early life and the risk of atopic and non-atopic asthma. METHODS: Food intake of 182 children with asthma and 728 matched controls was measured using 3-day food records, within the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study cohort. The diagnoses of food allergies came both from the written questionnaire and from the registers of the Social Insurance Institution. Conditional logistic regression with generalized estimating equations framework was used in the analyses. RESULTS: The diagnosis of cow's milk allergy (CMA) led to multiple dietary restrictions still evident at 4 yr of age. Even after adjusting for CMA, higher consumption of CM products was inversely associated with the risk of atopic asthma and higher consumption of breast milk and oats inversely with the risk of non-atopic asthma. Early consumption of fish was associated with a decreased risk of all asthma. CONCLUSIONS: Dietary intake in early life combined with atopy history has a clear impact on the risk of developing asthma. Our results indicate that CM restriction due to CMA significantly increases and mediates the association between food consumption and childhood asthma risk.

Two intrauterine rescue transfusions in treatment of severe fetomaternal hemorrhage in the early third trimester.

KEY CLINICAL MESSAGE: When massive fetomaternal hemorrhage is diagnosed in the early third trimester of pregnancy, serial fetal intravascular transfusion may be an alternative to immediate delivery.

Dietary fatty acid composition during pregnancy and the risk of asthma in the offspring.

BACKGROUND: Fatty acids (FA) modulate the immune system, and it has been proposed that they affect the incidence of IgE-mediated allergic diseases. We explored the association of maternal dietary FA composition during pregnancy with the risk of asthma in the offspring. METHODS: We analyzed data from the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study. Maternal dietary intake during pregnancy (8th month) was assessed by a validated 181-item food frequency questionnaire. The occurrence of asthma was assessed at the age of 5 yr with a questionnaire modified from the International Study of Asthma and Allergies in Childhood (ISAAC). Cox proportional hazards regression was used for the statistical analyses. RESULTS: Low maternal intakes of α-linolenic acid (18:3n-3) [lowest quarter vs. mid-half HR 1.67 (95% CI 1.12-2.48)] and total n-3-polyunsaturated fatty acids (PUFA) [HR 1.66 (95% CI 1.11-2.48)] during pregnancy were associated with an increased risk of asthma in the offspring, while a low intake of arachidonic acid (20:4n-6) [HR 0.52 (95% CI 0.32-0.84)] and high intake of total saturated fatty acids [highest quarter vs. mid-half HR 0.55 (95% CI 0.34-0.90)] and palmitic acid (16:0) [HR 0.51 (95% CI 0.31-0.83)] were associated with a decreased risk of asthma. The ratios of n-6 to n-3-PUFA and 18:2n-6 to 18:3n-3, and the maternal intake of oils, fish and fish products, showed no association with the risk of asthma. The associations found were independent of several perinatal and clinical confounders. CONCLUSION: Maternal intake of FA during pregnancy was associated with childhood asthma. Maternal α-linolenic acid, total n-3 PUFA and palmitic acid intake may decrease, while arachidonic acid intake may increase the risk of asthma in the offspring.

Validation of the Finnish ISAAC questionnaire on asthma against anti-asthmatic medication reimbursement database in 5-year-old children.

BACKGROUND: Valid identification of childhood asthma at the population level for epidemiological purposes remains a challenge. We aimed at validating the Finnish version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire based on parental-reported childhood asthma. MATERIALS AND METHODS: The ISAAC questionnaire has been validated against anti-asthmatic medication reimbursement data of the Finnish Social Insurance Institution, being the gold standard, among 2236 5-year-old consecutively born children (1996-2004) carrying human leukocyte antigen (HLA)-conferred susceptibility to type 1 diabetes. Two combined questionnaire questions (any wheezing symptom or use of asthma medication during the preceding 12 months plus ever asthma; any wheezing symptom or use of asthma medication during the preceding 12 months plus ever doctor-diagnosed asthma) were validated against valid reimbursement with purchase of at least one anti-asthmatic medication during a 12-month period. The validity of the questionnaire was estimated as the sensitivity, specificity, positive predictive value, negative predictive value, and Youden's index. RESULTS: The sensitivity 0.98 [95% confidence interval (CI) = 0.92-0.99]; specificity 0.98 (95% CI = 0.97-0.98); negative predictive value 1.00 (95% CI = 1.00-1.00); and Youden's index 0.96 (95% CI = 0.96-0.96) were the same for each of the two sets of combined questions. The positive predictive value for the first combined question was 0.63 (95% CI = 0.55-0.71), while it was 0.64 (95% CI = 0.57-0.72) for the second combined question. CONCLUSION: The Finnish ISAAC questionnaire was highly valid and is an acceptable instrument for the survey of the prevalence of parental-reported childhood asthma for epidemiological purposes.

Hydrocortisone and indomethacin negatively modulate EGF-R signaling in human fetal intestine.

Concomitant use of hydrocortisone and the nonspecific cyclo-oxygenase (COX)-inhibitor indomethacin increases the risk for intestinal perforations in preterm infants. We determined whether this was associated with insufficient epidermal growth factor receptor (EGF-R) signaling. We tested the effect of EGF, hydrocortisone, and indomethacin on its activation, cell proliferation and migration, COX-2 expression, and prostaglandin E2 (PGE2) production. Human small intestine epithelial cell line FHsInt74 and EGF-R-deficient mice [EGF-R (-/-)] were used as models. The data revealed that EGF-R signaling had a bimodal positive effect on fetal enterocyte: 1) it increased cell proliferation and migration synergistically with hydrocortisone and 2) up-regulated COX-2 mRNA expression and subsequent PGE2 production. Correlating with this, COX-2 protein expression was down-regulated in EGF-R (-/-) intestine. Despite a positive effect on cell proliferation with EGF, hydrocortisone blunted the stimulatory effect of EGF on COX-2 expression and PGE2 production. Addition of indomethacin even further inhibited the EGF-stimulated PGE2 synthesis. The data suggest that concomitant use of indomethacin and hydrocortisone on preterm infants, who physiologically synthesize only low levels of EGF-R ligands, may lead to intestinal problems related to failure in cytoprotective and regenerative events.

Emergence of fluconazole resistance in a Candida parapsilosis strain that caused infections in a neonatal intensive care unit.

Candida parapsilosis is an increasing cause of bloodstream infections (BSIs) in neonatal intensive care units (NICUs). It has been a persistent problem in the NICU of Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland, since 1987. Fluconazole prophylaxis has been used to control the problem. The number of new infections has, however, increased markedly since September 2000. We assessed fluconazole consumption and occurrence of all Candida species in the NICU from 1991 to 2002. C. parapsilosis bloodstream isolates obtained in the NICU from 1990 to 2002 (n = 26) were genotyped and their fluconazole susceptibility was defined. A low rate of C. parapsilosis BSIs was correlated with high rates of consumption of fluconazole. No emergence of Candida species with primary resistance to fluconazole was detected. However, genotyping with a complex DNA fingerprinting probe revealed that a single strain of C. parapsilosis with decreasing susceptibility to fluconazole was responsible for cross-infections that caused BSIs in the NICU over a 12-year period. The emergence of fluconazole resistance in that strain was observed after more than 10 years of fluconazole prophylaxis.

Clustering of Serratia marcescens infections in a neonatal intensive care unit.

OBJECTIVES: To study clusters of infections caused by Serratia marcescens in a neonatal intensive care unit (NICU) and to determine risk factors for S. marcescens infection or colonization. DESIGN: Genotyping of S. marcescens isolates was performed by pulsed-field gel electrophoresis (PFGE). A retrospective case-control study was conducted. SETTING: A tertiary-care pediatric hospital with a 16-bed NICU. PATIENTS: All neonates with at least one culture positive for S. marcescens in the NICU during December 1999 to July 2002. Case-patients (n = 11) treated in the NICU during December 1999 to February 2000 were included in the case-control study. Neonates treated in the NICU for at least 72 hours during the same period with cultures negative for S. marcescens were used as control-patients (n = 27). RESULTS: S. marcescens was cultured from 19 neonates; 9 were infected and 10 were colonized. PFGE analysis identified three epidemic strains; each cluster consisted of identical isolates, except one isolate in the first cluster that was different. The risk factors identified were low birth weight, prematurity, prolonged respiratory therapy, prolonged use of antibiotics, and maternal infection prior to delivery. Overcrowding and understaffing were recorded simultaneously with the clusters. CONCLUSIONS: PFGE analysis showed three independent clusters. Several factors contributed to spread of the epidemic strains: (1) there were many severely premature and susceptible neonates, (2) the NICU was overcrowded during the clusters, and (3) transmission was likely to occur via the hands of staff. Cohorting and improvement of routine infection control measures led to the cessation of each cluster.