Glucose-regulatory hormones and growth in very preterm infants fed fortified human milk.

BACKGROUND: Bovine colostrum (BC) contains a range of milk bioactive components, and it is unknown how human milk fortification with BC affects glucose-regulatory hormones in very preterm infants (VPIs). This study aimed to investigate the associations between hormone concentrations and fortification type, birth weight (appropriate/small for gestational age, AGA/SGA), milk intake, postnatal age, and body growth. METHODS: 225 VPIs were randomized to fortification with BC or conventional fortifier (CF). Plasma hormones were measured before, one and two weeks after start of fortification. ΔZ-scores from birth to 35 weeks postmenstrual age were calculated. RESULTS: Compared with CF, infants fortified with BC had higher plasma GLP-1, GIP, glucagon, and leptin concentrations after start of fortification. Prior to fortification, leptin concentrations were negatively associated with growth, while IGF-1 concentrations associated positively with growth during fortification. In AGA infants, hormone concentrations generally increased after one week of fortification. Relative to AGA infants, SGA infants showed reduced IGF-1 and leptin concentrations. CONCLUSION: Fortification with BC increased the plasma concentrations of several glucose-regulatory hormones. Concentrations of IGF-1 were positively, and leptin negatively, associated with growth. Glucose-regulatory hormone levels were affected by birth weight, milk intake and postnatal age, but not closely associated with growth in VPIs. IMPACT: Little is known about the variation in glucose-regulatory hormones in the early life of very preterm infants (VPIs). This study shows that the levels of glucose-regulatory hormones in plasma of VPIs are highly variable and modified by birth weight (appropriate or small for gestational age, AGA or SGA), the type of fortifier, enteral nutritional intake, and advancing postnatal age. The results confirm that IGF-1 levels are positively associated with early postnatal growth in VPIs, yet the levels of both IGF-1 and other glucose-regulatory hormones appeared to explain only a small part of the overall variation in growth rates.

Insulin-like growth factor 1 associated with altered immune responses in preterm infants and pigs.

BACKGROUND: Preterm infants show low blood levels of insulin-like growth factor 1 (IGF-1), known to be negatively correlated with Interleukin-6 (IL-6). We hypothesized that circulating IGF-1 is associated with systemic immune-markers following preterm birth and that exogenous IGF-1 supplementation modulates immune development in preterm pigs, used as model for preterm infants. METHODS: Plasma levels of IGF-1 and 29 inflammatory markers were measured in very preterm infants (n = 221). In preterm pigs, systemic immune development, assessed by in vitro challenge, was compared between IGF-1 treated (2.25 mg/kg/day) and control animals. RESULTS: Preterm infants with lowest gestational age and birth weight showed the lowest IGF-1 levels, which were correlated not only with IL-6, but a range of immune-markers. IGF-1 supplementation to preterm pigs reduced plasma IL-10 and Interferon-γ (IFN-γ), IL-2 responses to challenge and reduced expression of genes related to Th1 polarization. In vitro addition of IGF-1 (100 ng/mL) further reduced the IL-2 and IFN-γ responses but increased IL-10 response. CONCLUSIONS: In preterm infants, plasma IGF-1 correlated with several immune markers, while supplementing IGF-1 to preterm pigs tended to reduce Th1 immune responses. Future studies should document whether IGF-1 supplementation to preterm infants affects immune development and sensitivity to infection. IMPACT: Supplementation of insulin-like growth factor 1 (IGF-1) to preterm infants has been proposed to promote postnatal growth, but its impact on the developing immune system is largely unknown. In a cohort of very preterm infants, low gestational age and birth weight were the primary predictors of low plasma levels of IGF-1, which in turn were associated with plasma immune markers. Meanwhile, in immature preterm pigs, experimental supplementation of IGF-1 reduced Th1-related immune responses in early life. Supplementation of IGF-1 to preterm infants may affect the developing immune system, which needs consideration when evaluating overall impact on neonatal health.

NON-pharmacological Approach Less Invasive Surfactant Administration (NONA-LISA) trial: protocol for a randomised controlled trial.

INTRODUCTION: Using pre-procedure analgesia with the risk of apnoea may complicate the Less Invasive Surfactant Administration (LISA) procedure or reduce the effect of LISA. METHODS: The NONA-LISA trial (ClinicalTrials.gov, NCT05609877) is a multicentre, blinded, randomised controlled trial aiming at including 324 infants born before 30 gestational weeks, meeting the criteria for surfactant treatment by LISA. Infants will be randomised to LISA after administration of fentanyl 0.5-1 mcg/kg intravenously (fentanyl group) or isotonic saline solution intravenously (saline group). All infants will receive standardised non-pharmacological comfort care before and during the LISA procedure. Additional analgesics will be provided at the clinician's discretion. The primary outcome is the need for invasive ventilation, meaning mechanical or manual ventilation via an endotracheal tube, for at least 30 min (cumulated) within 24 h of the procedure. Secondary outcomes include the modified COMFORTneo score during the procedure, bronchopulmonary dysplasia at 36 weeks, and mortality at 36 weeks. DISCUSSION: The NONA-LISA trial has the potential to provide evidence for a standardised approach to relief from discomfort in preterm infants during LISA and to reduce invasive ventilation. The results may affect future clinical practice. IMPACT: Pre-procedure analgesia is associated with apnoea and may complicate procedures that rely on regular spontaneous breathing, such as Less Invasive Surfactant Administration (LISA). This randomised controlled trial addresses the effect of analgesic premedication in LISA by comparing fentanyl with a placebo (isotonic saline) in infants undergoing the LISA procedure. All infants will receive standardised non-pharmacological comfort. The NONA-LISA trial has the potential to provide evidence for a standardised approach to relief from discomfort or pain in preterm infants during LISA and to reduce invasive ventilation. The results may affect future clinical practice regarding analgesic treatment associated with the LISA procedure.

Mineral supplementation for very preterm infants fed fortified human milk.

OBJECTIVES: The safety and feasibility of human milk fortification with bovine colostrum (BC) were investigated in very preterm infants (FortiColos trial, NCT03537365). The BC product contained lower calcium, phosphate, and iron levels compared to the conventional fortifier (CF). We tested whether fortification with BC plus extra phosphate was sufficient to support the infants' mineral status assessed by blood biochemistry. METHODS: In a randomised controlled trial (FortiColos, NCT03537365), mineral status was compared after fortification with BC versus CF. Blood calcium, phosphate, and haemoglobin were determined before and up to 3 weeks after the start of fortification (at the mean age of 8-9 days). The maximum supplemental doses of calcium, phosphate, and iron given were retrieved from patient medical records. Results were adjusted for gestational age, birth weight, and enteral nutrition with the mother's own milk and/or donor human milk. RESULTS: Blood values of calcium, phosphate, and haemoglobin were similar between groups. Infants in both groups required supplementation with calcium and phosphate, but infants fed BC required higher maximum doses of phosphate and calcium (p < 0.05) to maintain acceptable blood values. Regardless of fortification groups, the most immature (<29 weeks of gestation) and small for gestational age infants showed a higher risk for requiring additional phosphate (odds ratio [OR]: 3.9, p < 0.001; OR: 2.14, p = 0.07, respectively). CONCLUSIONS: The use of BC as a fortifier for human milk requires additional phosphate and calcium relative to a CF. Regardless of the fortification product, the most immature and small infants require additional mineral supplementation.

The ASQ did not predict low IQ scores when children born VPT were six years.

AIM: There is a need for methods that can provide valid assessment tools in a follow-up programme without great financial costs. This study assessed the accuracy of the 60-month Ages and Stages Questionnaire as a screening tool to predict a low intelligence quotient score at 6 years in children born very preterm. METHODS: Totally, 54 children participated in a six-year follow-up study, which included an intelligence quotient test at 6 years of age and a 60-month Ages and Stages Questionnaire at four and a half or 5 years of age at respond. We used the receiver operating characteristic curve and evaluated the optimal cut-off score to predict a low intelligence quotient score. RESULTS: At four and a half years, the optimal cut-off value for predicting a low intelligence quotient score was 242, with a sensitivity of 67% and a specificity of 59%. At 5 years, only one child had a low intelligence quotient score, and the analysis was not performed. CONCLUSION: Our results did not support the use of the 60-month Ages and Stages Questionnaire as a valuable screening tool to predict a low intelligence quotient score in children born very preterm at 6 years of age.

Enteral Nutrition in Preterm Infants (2022): A Position Paper From the ESPGHAN Committee on Nutrition and Invited Experts.

OBJECTIVES: To review the current literature and develop consensus conclusions and recommendations on nutrient intakes and nutritional practice in preterm infants with birthweight <1800 g. METHODS: The European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee of Nutrition (CoN) led a process that included CoN members and invited experts. Invited experts with specific expertise were chosen to represent as broad a geographical spread as possible. A list of topics was developed, and individual leads were assigned to topics along with other members, who reviewed the current literature. A single face-to-face meeting was held in February 2020. Provisional conclusions and recommendations were developed between 2020 and 2021, and these were voted on electronically by all members of the working group between 2021 and 2022. Where >90% consensus was not achieved, online discussion meetings were held, along with further voting until agreement was reached. RESULTS: In general, there is a lack of strong evidence for most nutrients and topics. The summary paper is supported by additional supplementary digital content that provide a fuller explanation of the literature and relevant physiology: introduction and overview; human milk reference data; intakes of water, protein, energy, lipid, carbohydrate, electrolytes, minerals, trace elements, water soluble vitamins, and fat soluble vitamins; feeding mode including mineral enteral feeding, feed advancement, management of gastric residuals, gastric tube placement and bolus or continuous feeding; growth; breastmilk buccal colostrum, donor human milk, and risks of cytomegalovirus infection; hydrolyzed protein and osmolality; supplemental bionutrients; and use of breastmilk fortifier. CONCLUSIONS: We provide updated ESPGHAN CoN consensus-based conclusions and recommendations on nutrient intakes and nutritional management for preterm infants.

Trial-related blood sampling and red blood cell transfusions in preterm infants.

AIM: To determine if trial-related blood sampling increases the risk of later red blood cell (RBC) transfusion in very preterm infants, we compared the volume of clinical- and trial-related blood samples, in a specific trial and correlated to subsequent RBC transfusion. METHODS: For 193 very preterm infants, participating in the FortiColos trial (NCT03537365), trial-related blood volume drawn was in accordance with ethical considerations established by the European Commission. Medical records were reviewed to assess the number and accumulated volume (mL/kg) of blood samples (both clinical- and trial-related). Data were compared with the need of RBC transfusions during the first 28 days of life. RESULTS: Mean (SD) gestational age and birth weight was 28 ± 1 weeks and 1168 ± 301 g. In total, 11% of total blood volume was drawn for sampling (8.1 ± 5.1 mL/kg) and trial-related sampling accounted for 1.6 ± 0.6 mL/kg. Trial-related blood sampling had no impact on RBC transfusion (p = 0.9). CONCLUSION: Clinical blood sampling in very preterm infants is associated with blood loss and subsequent need for RBC transfusions. In a specific trial requiring blood samples, we found no additional burden of trial-related blood sampling. The study suggests that trial-related sampling is safe if European criteria are followed.

Preterm birth rates were slightly lower in Denmark during the first year of the COVID-19 pandemic compared with the previous 4 years.

AIM: Our aim was to investigate the rates of preterm births, live births and stillbirths in Denmark during the first year of the COVID-19 pandemic. METHODS: This was a national, cross-sectional registry-based study that used the Danish Newborn Quality database, which covers all births in Denmark. The proportions of preterm births were compared between the COVID-19 pandemic period of 1 March 2020 to 28 February 2021 and the preceding 4-year pre-pandemic period. RESULTS: We studied 60 323 and 244 481 newborn infants from the pandemic and pre-pandemic periods, respectively. The proportion of preterm live births and stillbirths declined slightly, from 6.29% during the pre-pandemic period to 6.02% during the pandemic period. This corresponded to a relative risk (RR) of 0.96, with a 95% confidence interval (CI) of 0.93-0.99 during the pandemic. The RRs for extremely preterm, very preterm and moderately preterm infants were 0.88 (95% CI 0.76-1.02), 0.91 (95% CI 0.82-1.02) and 0.97 (95% CI 0.93-1.01), respectively. CONCLUSION: This comparative study showed a small reduction in just over 4%, from 6.29 to 6.02% in the proportion of all preterm births during the pandemic period, compared with the previous four pandemic-free years. There were no differences between subcategories of preterm births.

Cytomegalovirus Transmitted From Mother's Own Milk to a Growth-Restricted Extremely Preterm Infant: A Case Report.

BACKGROUND: Mother's own milk (MOM) is considered the optimal nutrition for preterm infants. Unfortunately, MOM can contain human cytomegalovirus (HCMV), which can be transmitted to the infants. Postnatal HCMV infection in very preterm infants can lead to organ failure. CLINICAL FINDINGS: In this case we report cholestasis possibly associated to HCMV transmitted through MOM in a very growth-restricted extremely preterm infant. PRIMARY DIAGNOSIS: The primary diagnosis is postnatal HCMV infection. INTERVENTIONS: The infant was too preterm to be treated with antiviral medication. Instead, he was treated with a diet with no fresh MOM but only freeze-thawed MOM to reduce the viral load. OUTCOMES: Conjugated bilirubin values normalized after the infant was fed freeze-thawed MOM with a reduced viral load and formula. PRACTICE RECOMMENDATIONS: The awareness of HCMV-positive mothers giving birth to extremely preterm infants should be increased. Feeding only freeze-thawed MOM or in combination with fresh MOM should be considered prophylactically to avoid transmission of high viral loads of HCMV to these vulnerable infants.

Nutrient Restriction has Limited Short-Term Effects on Gut, Immunity, and Brain Development in Preterm Pigs.

BACKGROUND: Extrauterine growth restriction (EUGR) in preterm infants is associated with higher morbidity and impaired neurodevelopment. Early nutrition support may prevent EUGR in preterm infants, but it is not known if this improves organ development and brain function in the short and long term. OBJECTIVE: Using pigs as models for infants, we hypothesized that diet-induced EUGR impairs gut, immunity, and brain development in preterm neonates during the first weeks after birth. METHODS: Forty-four preterm caesarean-delivered pigs (Danish Landrace × Large White × Duroc, birth weight 975 ± 235 g, male:female ratio 23:21) from 2 sows were fed increasing volumes [32-180 mL/(kg·d)] of dilute bovine milk (EUGR group) or the same diet fortified with powdered bovine colostrum for 19 d (CONT group, 50-100% higher protein and energy intake than the EUGR group). RESULTS: The EUGR pigs showed reduced body growth (-39%, P < 0.01), lower plasma albumin, phosphate, and creatine kinase concentrations (-35 to 14%, P < 0.05), increased cortisol and free iron concentrations (+130 to 700%, P < 0.05), and reduced relative weights of the intestine, liver, and spleen (-38 to 19%, all P < 0.05). The effects of EUGR on gut structure, function, microbiota, and systemic immunity were marginal, although EUGR temporarily increased type 1 helper T cell (Th1) activity (e.g. more blood T cells and higher Th1-related cytokine concentrations on day 8) and reduced colon nutrient fermentation (lower SCFA concentration; -45%, P < 0.01). Further, EUGR pigs showed increased relative brain weights (+19%, P < 0.01), however, memory and learning, as tested in a spatial T-maze, were not affected. CONCLUSION: Most of the measured organ growth, and digestive, immune, and brain functions showed limited effects of diet-induced EUGR in preterm pigs during the first weeks after birth. Likewise, preterm infants may show remarkable physiological adaptation to deficient nutrient supply during the first weeks of life although early life malnutrition may exert negative consequences later.

Impact of Early Exposure to Cefuroxime on the Composition of the Gut Microbiota in Infants Following Cesarean Delivery.

OBJECTIVES: To assess in mothers giving birth by cesarean delivery if prophylactic antibiotics administered either before skin incision or immediately after cutting the umbilical cord influences gut microbiota colonization and antibiotic susceptibility of the gut bacteria in the newborn. STUDY DESIGN: Forty-two pregnant women scheduled for elective cesarean delivery were recruited at Odense University Hospital, Denmark, and randomly assigned to receive cefuroxime either before skin incision or immediately after the umbilical cord was cut. Fecal samples were collected from all infants at age 10 days and 9 months. Composition of the gut microbiota was determined by 16S ribosomal RNA gene amplicon high-throughput sequencing. Gram-positive cocci and Enterobacteriaceae were isolated and identified before antimicrobial susceptibility tests were performed by disk diffusion. RESULTS: No clear difference in the composition of the gut microbiota was observed between infants whose mothers received cefuroxime before or after cesarean delivery at neither time point, though surprisingly at 9 months of age, but not at 10 days of age, the number of observed species was higher in infants where mothers received cefuroxime after cord clamping. No differences in antimicrobial susceptibility of Enterobacteriaceae, Enterococcus spp, and Staphylococcus spp were seen at 10 days. CONCLUSIONS: Timing of cefuroxime administration to mothers undergoing cesarean delivery does not have a major effect on the gut microbiota and bacterial antibiotic resistance traits in infants. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02072798.

Improved lung function at age 6 in children born very preterm and fed extra protein post-discharge.

BACKGROUND: In very preterm-born children, alveolar maturation is challenged and lung function is often compromised during childhood. So far, very few studies have focused on type of early nutrition and lung function in children born preterm. METHODS: This study is a 6 years follow-up of 281 very preterm-born infants (VPI) with a gestational age (GA) <32 + 0 weeks. Infants breastfed at discharge from hospital were randomized to unfortified (UHM) or fortified (FHM) mother's (human) milk, whereas those not breastfed received a preterm formula (PF). The intervention lasted until 4 months corrected age. At 6 years of age fractional exhaled nitric oxide (FeNO), airway resistance and occlusion measurements with reversibility were performed. Data on predisposition to asthma and allergy as well as possible allergic symptoms of the child were obtained with questionnaires. RESULTS: Outcome data was fully or partially available on 160 (66.9%) of 239 children. This included 49 (30.6%) children fed UHM, 58 (36.3%) fed FHM and 53 (33.1%) fed PF. Successful FeNO measurements were obtained in 119 (74.4%) children and airway resistance measurements in 160. FeNO results were not significantly different between feeding groups. Children fed a protein-enriched diet (FMH/PF) had the lowest, for example, best, airway resistance; FHM-fed had lower values than UHM-fed (P = 0.042) before, and PF-fed had significantly lower values than UHM-fed after beta-2-agonist inhalation (P = 0.050). The tendency of lower airway resistance when protein enriched were the same in gender-specific analyses. In SGA children, the same tendency was found between PF- and UHM-fed (P = 0.007 before and P = 0.046 after beta-2-agonist inhalation). All values were within reference limits. CONCLUSIONS: Lung function in very preterm-born children may improve when fed a protein-enriched nutrition post-discharge.

Differences in Current Procedures for Handling of Expressed Mother's Milk in Danish Neonatal Care Units.

BACKGROUND: Mother's own milk (MOM) is preferred when feeding preterm infants. When expressed mother's milk is stored and handled, there is a risk of bacterial contamination, decreased immunological activity, and less nutritional potential. PURPOSE: The aim of this study was to investigate current routines when handling MOM in Danish neonatal intensive care units (NICUs). METHODS: A survey was sent to all 17 NICUs in Denmark in which current practices regarding human milk handling, storage, and preparation were evaluated. Furthermore, one question sought to establish when mother's milk was believed to be colostrum. Respondents of the survey were neonatal nurses. RESULTS: All 17 units responded to the survey. Only 5 of 17 units answered that human colostrum was defined as milk from the first week after birth. Refrigerator storage time varied between 24 and 72 hours. In 6 of 17 units, parents were in charge of mixing milk and fortifier. Heating of human milk was done by using microwave ovens in 4 of 17 of the units. IMPLICATIONS FOR PRACTICE: This national survey established that there is significant variability in the way mother's milk is handled. Some of the procedures performed may affect the quality of the milk. It is important to implement evidence-based practice regarding storage and handling of expressed mother's milk to ensure that the quality of the milk is the best possible alternative for all preterm infants. IMPLICATIONS FOR RESEARCH: Prospective studies are needed to examine the association between handling of human milk and changes in composition and nutritional potential of the milk.

Osteopontin Levels in Human Milk Vary Across Countries and Within Lactation Period: Data From a Multicenter Study.

OBJECTIVES: Osteopontin (OPN) is a multifunctional protein expressed in many cell types, tissues and body fluids with the highest concentrations found in milk; significantly higher in human than in bovine milk. Intervention studies have indicated beneficial effects of supplementing infant formula with bovine OPN. In this multicenter study, we determined the OPN content in human milk samples from 629 Chinese, Danish, Japanese and Korean mothers. METHODS: At each study site, milk samples were collected and analyzed for OPN and protein concentration using ELISA and infrared spectroscopy, respectively. RESULTS: A total of 829 milk samples from 629 women were included. When delivering the first sample, mean maternal age was 31.4 years (SD 4.0), and median infant age was 13.4 weeks (interquartile range 4.6-17.9). The median OPN concentration varied across sites; from 99.7 mg/L in Danish, 185.0 mg/L in Japanese, 216.2 mg/L in Korean to 266.2 mg/L in Chinese mothers (P < 0.001), corresponding to 1.3%, 2.4%, 1.8% and 2.7% of the total protein content (OPN/protein%) (P < 0.05), respectively. Based on 75 Chinese and 33 Japanese mothers delivering more than 1 sample, multilevel (mixed model) linear regression analysis showed a decrease in OPN concentration with infant age (ß = (-11.3), 95% confidence interval (CI) = (-13.9) to (-8.8) and ß = (-2.1), 95% CI = (-3.2) to (-0.9), respectively). CONCLUSIONS: In this large multicenter study, we observed statistically significant differences in the OPN concentration and the OPN/protein% in human milk samples between countries. Based on mothers delivering more than 1 sample, a significant decrease within the lactation period was observed.

Free Amino Acids in Human Milk and Associations With Maternal Anthropometry and Infant Growth.

OBJECTIVES: Free glutamic acid has an appetite-regulating effect and studies with infant formula have suggested that free amino acids (FAA), especially glutamic acid, can downregulate intake. The content of glutamic acid and glutamine is high in breast milk but varies considerably between mothers. The aim was to investigate whether maternal anthropometry was associated with the content of the FAA glutamic acid or glutamine in breast milk and whether there was a negative association between these FAA and current size or early infant growth in fully breastfed infants. METHODS: From a subgroup of 78 mothers, of which 50 were fully breast feeding, from the Odense Child Cohort breast milk samples were collected 4 months after birth and analyzed for FAA. Information regarding breastfeeding status and infant weight and length was also recorded. RESULTS: There was a large variation in the concentration of the FAAs between mothers. Glutamic acid was positively correlated with mother's prepregnancy weight and height (P ≤ 0.028), but not body mass index. There was no negative correlation between the 2 FAA and infant weight or body mass index. Infant length at 4 months was, however, positively associated with glutamine, (P = 0.013) but the correlation was attenuated when controlling for birth length (P = 0.089). CONCLUSIONS: The hypothesis that a high content of glutamic acid and glutamine in breast milk could downregulate milk intake to a degree affecting early growth could not be confirmed. Maternal factors associated with the level of these FAA in milk and the potential effect on the infant should be investigated further.

Using text messaging to obtain weekly data on infant feeding in a Danish birth cohort resulted in high participation rates.

AIM: Our aim was to use text message questions to obtain prospective, real-time data on exclusive and partial breastfeeding and introduction to complementary foods in a Danish birth cohort. We also wanted to identify factors influencing breastfeeding initiation and cessation. METHODS: This study formed part of the Odense Child Cohort and focused on mothers who gave birth to full-term singletons between April and October 2012. They received the same three to five questions, about breastfeeding, infant formula and introduction to complementary food, three days after birth and then at weekly intervals. RESULTS: We recruited 499 mothers, and the response rate to the first of the weekly questions was ≥89.4% during the study. Three days after birth, 96.7% of mothers were breastfeeding, 61.2% exclusively and 30.2% partially, and 26 weeks after birth 60.2% of mothers were breastfeeding, 1.1% exclusively. Complementary food was introduced at an average age of 20 weeks. Breastfeeding cessation was associated with maternal smoking, lower maternal age and supplementation with infant formula in the first days after birth (all p < 0.05). CONCLUSION: Most mothers initiated breastfeeding, but only 1.1% were exclusively breastfeeding at 26 weeks. Text messaging resulted in high response rates and was a feasible data collection method.

Having older siblings is associated with gut microbiota development during early childhood.

BACKGROUND: Evidence suggests that early life infections, presence of older siblings and furred pets in the household affect the risk of developing allergic diseases through altered microbial exposure. Recently, low gut microbial diversity during infancy has also been linked with later development of allergies. We investigated whether presence of older siblings, furred pets and early life infections affected gut microbial communities at 9 and 18 months of age and whether these differences were associated with the cumulative prevalence of atopic symptoms of eczema and asthmatic bronchitis at 3 years of age. Bacterial compositions and diversity indices were determined in fecal samples collected from 114 infants in the SKOT I cohort at age 9 and 18 months by 16S rRNA gene sequencing. These were compared to the presence of older siblings, furred pets and early life infections and the cumulative prevalence of diagnosed asthmatic bronchitis and self-reported eczema at 3 years of age. RESULTS: The number of older siblings correlated positively with bacterial diversity (p = 0.030), diversity of the phyla Firmicutes (p = 0.013) and Bacteroidetes (p = 0.004) and bacterial richness (p = 0.006) at 18 months. Further, having older siblings was associated with increased relative abundance of several bacterial taxa at both 9 and 18 months of age. Compared to the effect of having siblings, presence of household furred pets and early life infections had less pronounced effects on the gut microbiota. Gut microbiota characteristics were not significantly associated with cumulative occurrence of eczema and asthmatic bronchitis during the first 3 years of life. CONCLUSIONS: Presence of older siblings is associated with increased gut microbial diversity and richness during early childhood, which could contribute to the substantiation of the hygiene hypothesis. However, no associations were found between gut microbiota and atopic symptoms of eczema and asthmatic bronchitis during early childhood and thus further studies are required to elucidate whether sibling-associated gut microbial changes influence development of allergies later in childhood.

Administering different levels of parenteral phosphate and amino acids did not influence growth in extremely preterm infants.

AIM: When a new high amino acid parenteral nutrition (PN) solution was introduced to our hospital, a design error led to decreased phosphate levels. This prompted us to examine the effect of three different PN solutions on plasma phosphate, plasma calcium and weight increases on extremely preterm infants. METHOD: This was a retrospective study of 186 infants with a gestational age of <28 weeks during their first month of life. They were divided into three groups based on the PN they received during hospitalisation. Group one received high levels of phosphate and low levels of amino acids. Group two received low levels of phosphate and high levels of amino acids. Group three received high levels of both phosphate and amino acids. RESULTS: The lowest plasma phosphate values varied significantly between groups one (1.80 ± 0.46 mmol/L), two (1.05 ± 0.48 mmol/L) and three (1.40 ± 0.37 mmol/L) (p < 0.001), but no significant difference in weight increase was seen (p = 0.497). CONCLUSION: The phosphate content of the PN influenced plasma phosphate and plasma calcium levels, but increasing the levels of both phosphate and amino acids did not improve weight gain during the first month of life.

Benign bloody milk secretion in pregnancy.

Rusty pipe syndrome (RPS) is a benign, self-limiting condition characterized by bloody milk secretion, and is primarily seen among primiparous women. This case report highlights the clinical presentation of a 31-year-old primiparous woman with bloody milk secretion from gestational week 31. This persisted throughout pregnancy until seven days after birth. RPS should be considered in pregnant women with painless bilateral bloody milk secretion during pregnancy and/or the early days post-partum. The milk can safely be provided to the infant, and RPS is not an indication for formula feeding.