Prevalence and Risk Factors for Post-Discharge Feeding Problems in Children Born Extremely Preterm.

OBJECTIVES: Preterm infants have a high risk of post-discharge feeding problems, but there is a lack of population-based studies in infants born extremely preterm and little is known about underlying mechanisms. The objectives were to assess the incidence of post-discharge feeding problems and underweight in a population-based cohort of infants born extremely preterm in Sweden (EXPRESS) and identify perinatal risk factors. METHODS: Perinatal health data and prenatal/postnatal growth data was prospectively collected in the cohort. Data on clinical diagnoses related to feeding problems were obtained from the Swedish Patient Register and population prevalence data was also obtained. The main outcome was a composite of post-discharge feeding problem diagnosis and/or underweight at 2.5 years of age. RESULTS: In total, 66 children (19%) had post-discharge feeding problems diagnosed before 2 years and/or underweight at 2.5 years of age. The risk of feeding problems when compared to the general population was significantly higher, with an odds ratio (OR) of 193 (95% confidence interval (CI) 137.6-270.9). The strongest risk factors for feeding problems were the number of days on mechanical ventilation during the first 8 postnatal weeks, OR of 1.59 (CI 95% 1.29-1.98), and the Clinical Risk Index for Babies-score, OR of 1.14 (CI 95% 1.03-1.26). CONCLUSIONS: Post-discharge feeding problems and underweight are common in children born extremely preterm. The strongest perinatal risk factor for later feeding problems was early treatment with mechanical ventilation. Identifying infants at risk of post-discharge feeding problems might be useful for targeting of nutritional support.

Higher Parenteral Electrolyte Intakes in Preterm Infants During First Week of Life: Effects on Electrolyte Imbalances.

OBJECTIVES: This study aimed to investigate the effects of a higher intake of electrolytes from parenteral nutrition (PN) on plasma electrolyte concentrations in very low birth weight (VLBW, <1500 g) infants. METHODS: This was a single-center cohort study including all VLBW infants born before (n = 81) and after (n = 53) the implementation of a concentrated PN regimen. Daily nutritional intakes and plasma concentrations of sodium, chloride, potassium, phosphate, and calcium were collected from clinical charts. RESULTS: During the first postnatal week, electrolyte intakes were higher in infants who received concentrated PN compared with infants who received original PN. Infants who received concentrated PN had a lower incidence of hypokalemia (<3.5 mmol/L; 30% vs 76%, P < 0.001) and severe hypophosphatemia (<1.0 mmol/L; 2.2% vs 17%, P = 0.02). While the relatively high prevalence of severe hypophosphatemia in infants who received original PN can be explained by a phosphorus intake below the recommendation, the potassium intake during the first 3 postnatal days (mean ± SD: 0.7 ± 0.2 mmol/kg/d) was within the recommendation. The prevalence of early hypernatremia was not affected by the different sodium intake in the 2 groups. CONCLUSIONS: In VLBW infants, a sodium-containing PN solution (about 2.7 mmol/100 mL) does not cause hypernatremia during the first days of life. Furthermore, providing at least 1 mmol potassium/kg/d during the first 3 postnatal days might be necessary to prevent early hypokalemia.

Mother's Own Milk and Its Relationship to Growth and Morbidity in a Population-based Cohort of Extremely Preterm Infants.

OBJECTIVES: The aim of the study was to evaluate the relationships between intake of mother's own milk (MOM), compared with intake of pasteurized donor milk (DM), and postnatal growth, incidence of retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD), in extremely preterm infants. METHODS: Swedish population-based cohort of surviving extremely preterm infants born 2004 to 2007. Exposure to MOM and DM was investigated from birth until 32 weeks postmenstrual age (PMA) in 453 infants. Primary outcome variables were change in z-score (Δ) from birth to 32 weeks PMA for weight, length, and head circumference (HC). Secondary outcomes were incidence of ROP and BPD. Mixed models adjusting for confounders were used to investigate the association between exposures and outcomes. RESULTS: Infants' mean gestational age (GA) was 25.4 weeks. Unadjusted, MOM (per 10 mL ·â€Škg-1 ·â€Šday-1) was associated with Δweight and ΔHC with beta estimates of 0.03 z-score units (95% CI, 0.02-0.04, P < 0.001) and 0.03 z-score units (95% CI, 0.01-0.05, P = 0.003), respectively. After adjustment for predefined confounders, the association remained significant for Δweight and ΔHC. A similar pattern was found between Δweight and each 10% increase of MOM. Unadjusted, a higher intake of MOM (mL ·â€Škg-1 ·â€Šday-1) was significantly associated to a lower probability of any ROP and severe ROP; however, these associations did not remain in the adjusted analyses. No associations were found between MOM (mL ·â€Škg-1 ·â€Šday-1) and BPD. Moreover, no associations were found between DM and growth or morbidity outcomes. CONCLUSIONS: An increased intake of MOM, as opposed to DM (and not formula feeding), was associated with improved postnatal weight gain and HC growth from birth until 32 weeks PMA in extremely preterm infants. Interventions aiming at increasing early intake of unpasteurized MOM for extremely preterm infants should be encouraged.

Dietitians' perspectives on challenges and prospects for group-based education to adults with type 1 diabetes - a qualitative study.

BACKGROUND: Type 1 diabetes (T1DM) is an autoimmune disorder which can have short- and long-term adverse effects on health. Dietitians in diabetes offer specialist evidence-based advice to people with T1DM and provide education in either individual or group settings. The purpose of this study was to explore dietitians' perception of, and role in, group-based education as well as prospects for development. METHODS: This was a qualitative descriptive study conducted in Sweden using a convenience sampling of dietitians working in adult diabetes care. Semi-structured interviews were conducted with participants and data were analysed using a content analysis approach. RESULTS: Ten dietitians with a median experience of 14.5 years in diabetes care were interviewed. The informants were all appreciative of facilitating group-based education and perceived that it was beneficial for people with T1DM to be part of group processes, but the informants did also suggest that there were challenges for their professional role. The main challenges reported was to adjust the level of depth and complexity to the information provided and the lack of ability to individualize the education-sessions in a heterogenous group. None of the dietitians reported performing pre-assessment or follow-up audits on the group-based education. CONCLUSION: There was a great engagement from the dietitians, but they identified a lack of framework that address challenges regarding group-based education. The dietitians experienced examples of person-centred care while facilitating group-based education, which may benefit people with T1DM. Based on the results, it would be valuable to explore the pedagogic training level of Swedish dietitians and potential barriers in their ability to facilitate group-based education. We suggest that a framework for group-based education should be explored together with patient representatives to optimize the care given to ensure cost-effectiveness, optimize clinical outcomes, quality of life and equally accessible care for people with T1DM.

Sodium supply from administered blood products was associated with severe intraventricular haemorrhage in extremely preterm infants.

AIM: The aim of this study was to investigate the associations between sodium supply, fluid volume, sodium imbalances and severe intraventricular haemorrhage (IVH) in extremely preterm (EPT) infants. METHODS: We used data from the EXtremely PREterm infants in Sweden Study (EXPRESS) cohort consisting of all infants born at 22 to 26 gestational weeks from 2004 to 2007 and conducted a nested case-control study. For every infant with severe IVH (grade 3 or peri-ventricular haemorrhagic infarction), one IVH-free control infant with the birthday closest to the case infant and matched for hospital, sex, gestational age and birth weight was selected (n = 70 case-control pairs). RESULTS: Total sodium supply and fluid volume were higher in infants with severe IVH compared with controls [daily total sodium supply until postnatal Day 2: mean ± SD (mmol/kg/day): 5.49 ± 2.53 vs. 3.95 ± 1.91, p = 0.009]. These differences were accounted for by sodium and fluid from transfused blood products. High plasma sodium concentrations or large sodium fluctuations were not associated with severe IVH. CONCLUSION: Our results suggest a relationship between sodium-rich transfusions of blood products and severe IVH in EPT infants. It is unclear whether this is an effect of sodium load, volume load or some other transfusion-related factor.

Amino acid infusions in umbilical artery catheters enhance protein administration in infants born at extremely low gestational age.

AIM: It is challenging to provide extremely low gestational age neonates (ELGANs) with adequate protein supply. This study aimed to investigate whether amino acid (AA) infusion in the umbilical artery catheter (UAC) in ELGANs is safe and enhances protein supply and growth. METHOD: A before and after study including infants born <27 weeks, treated in Uppsala, Sweden, during 2004-2007, compared those receiving normal saline/10% dextrose in water with those receiving AA infusion in the UAC. Data were retrieved from the Extremely Preterm Infants in Sweden Study, hospital records and the Swedish Neonatal Quality Register. Group comparisons, univariate and multivariate analyses were conducted. RESULTS: AA group (n = 41, females 39%) received on average approximately 0.3 g/kg/day more protein during the first postnatal week, compared to control group (n = 30, females 40%) (unstandardised coefficient (B) 0.26, p .001) but no difference was noted during 8-28 postnatal days. The type of infusion was not associated with growth variables. The incidence of neonatal morbidities and UAC-related thrombosis did not differ between the groups. CONCLUSION: AA infusions in the UACs in ELGANs is safe and enhances protein supply during the first postnatal week. However, this practice is not associated with growth during the first 28 postnatal days.

Erythrocyte transfusions increased the risk of elevated serum ferritin in very low birthweight infants and were associated with altered longitudinal growth.

AIM: There has been a lack of population-based longitudinal data on serum ferritin in very low birthweight (VLBW) infants during hospitalisation. Our aim was to fill this gap in the knowledge and investigate risk factors for elevated serum ferritin and associations between erythrocyte transfusions and longitudinal growth. METHODS: We retrospectively reviewed longitudinal data on 126 VLBW infants treated at Umeå University Hospital, Sweden, between 2010 and 2013. RESULTS: The infants' mean gestational age and birthweight were 26.9 weeks and 899 g. Most (91%) received erythrocyte transfusions, and the majority had multiple erythrocyte transfusions. There was a significant correlation between serum ferritin and the volume of transfusions. Almost two-thirds had at least one serum ferritin measurement of more than 350 µg/L, indicating iron overload. In those with complete anthropometric data (n = 78), there was no significant effect of serum ferritin concentrations in relation to longitudinal growth, but there was a positive association between the erythrocyte transfusion dose and longitudinal growth in VLBW infants born before 25 weeks. CONCLUSION: This is the first population-based study to investigate longitudinal data on serum ferritin in VLBW infants during hospitalisation. The unexpected positive finding in the subgroup born at less than 25 weeks needs further research with a larger cohort.

Postnatal nutritional intakes and hyperglycemia as determinants of blood pressure at 6.5 years of age in children born extremely preterm.

BACKGROUND: Adverse developmental programming by early-life exposures might account for higher blood pressure (BP) in children born extremely preterm. We assessed associations between nutrition, growth and hyperglycemia early in infancy, and BP at 6.5 years of age in children born extremely preterm. METHODS: Data regarding perinatal exposures including nutrition, growth and glycemia status were collected from the Extremely Preterm Infants in Sweden Study (EXPRESS), a population-based cohort including infants born <27 gestational weeks during 2004-2007. BP measurements were performed at 6.5 years of age in a sub-cohort of 171 children (35% of the surviving children). RESULTS: Higher mean daily protein intake (+1 g/kg/day) during postnatal weeks 1-8 was associated with 0.40 (±0.18) SD higher diastolic BP. Higher mean daily carbohydrate intake (+1 g/kg/day) during the same period was associated with 0.18 (±0.05) and 0.14 (±0.04) SD higher systolic and diastolic BP, respectively. No associations were found between infant growth (weight, length) and later BP. Hyperglycemia and its duration during postnatal weeks 1-4 were associated primarily with higher diastolic BP z-scores. CONCLUSIONS: These findings emphasize the importance of modifiable early-life exposures, such as nutrition and hyperglycemia, in determining long-term outcomes in children born extremely preterm.

Validation of the diagnosis of necrotising enterocolitis in a Swedish population-based observational study.

AIM: The definition of necrotising enterocolitis (NEC) is based on clinical and radiological signs that can be difficult to interpret. The aim of the present study was to validate the incidence of NEC in the Extremely Preterm Infants in Sweden Study (EXPRESS) METHODS: The EXPRESS study consisted of all 707 infants born before 27 + 0 gestational weeks during the years 2004-2007 in Sweden. Of these infants, 38 were recorded as having NEC of Bell stage II or higher. Hospital records were obtained for these infants. Furthermore, to identify missed cases, all infants with a sudden reduction of enteral nutrition, in the EXPRESS study were identified (n = 71). Hospital records for these infants were obtained. Thus, 108 hospital records were obtained and scored independently by two neonatologists for NEC. RESULTS: Of 38 NEC cases in the EXPRESS study, 26 were classified as NEC after validation. Four cases not recorded in the EXPRESS study were found. The incidence of NEC decreased from 6.3% to 4.3%. CONCLUSION: Validation of the incidence of NEC revealed over- and underestimation of NEC in the EXPRESS study despite carefully collected data. Similar problems may occur in other national data sets or quality registers.

Hyperglycemia in Extremely Preterm Infants-Insulin Treatment, Mortality and Nutrient Intakes.

OBJECTIVE: To explore the prevalence of hyperglycemia and the associations between nutritional intakes, hyperglycemia, insulin treatment, and mortality in extremely preterm infants. STUDY DESIGN: Prospectively collected data from the Extremely Preterm Infants in Sweden Study (EXPRESS) was used in this study and included 580 infants born <27 gestational weeks during 2004-2007. Available glucose measurements (n = 9850) as well as insulin treatment and nutritional data were obtained retrospectively from hospital records for the first 28 postnatal days as well as 28- and 70-day mortality data. RESULTS: Daily prevalence of hyperglycemia >180 mg/dL (10 mmol/L) of up to 30% was observed during the first 2 postnatal weeks, followed by a slow decrease in its occurrence thereafter. Generalized additive model analysis showed that increasing parenteral carbohydrate supply with 1 g/kg/day was associated with a 1.6% increase in glucose concentration (P < .001). Hyperglycemia was associated with more than double the 28-day mortality risk (P < .01). In a logistic regression model, insulin treatment was associated with lower 28- and 70-day mortality when given to infants with hyperglycemia irrespective of the duration of the hyperglycemic episode (P < .05). CONCLUSIONS: Hyperglycemia is common in extremely preterm infants throughout the first postnatal month. Glucose infusions seem to have only a minimal impact on glucose concentrations. In the EXPRESS cohort, insulin treatment was associated with lower mortality in infants with hyperglycemia. Current practices of hyperglycemia treatment in extremely preterm infants should be reevaluated and assessed in randomized controlled clinical trials.

Sodium supply influences plasma sodium concentration and the risks of hyper- and hyponatremia in extremely preterm infants.

BACKGROUND: Hyper- and hyponatremia occur frequently in extremely preterm infants. Our purpose was to investigate plasma sodium (P-Na) concentrations, the incidence of hyper- and hyponatremia, and the impact of possible predisposing factors in extremely preterm infants. METHODS: In this observational study, we analyzed data from the EXtremely PREterm (< 27 wk.) infants in Sweden Study (EXPRESS, n = 707). Detailed nutritional, laboratory, and weight data were collected retrospectively from patient records. RESULTS: Mean ± SD P-Na increased from 135.5 ± 3.0 at birth to 144.3 ± 6.1 mmol/l at a postnatal age of 3 d and decreased thereafter. Fifty percent of infants had hypernatremia (P-Na > 145 mmol/l) during the first week of life while 79% displayed hyponatremia (P-Na < 135 mmol/l) during week 2. Initially, the main sodium sources were blood products and saline injections/infusions, gradually shifting to parenteral and enteral nutrition towards the end of the first week. The major determinant of P-Na and the risks of hyper- and hyponatremia was sodium supply. Fluid volume provision was associated with postnatal weight change but not with P-Na. CONCLUSION: The supply of sodium, rather than fluid volume, is the major factor determining P-Na concentrations and the risks of hyper- and hyponatremia.

Intakes of Micronutrients Are Associated With Early Growth in Extremely Preterm Infants.

OBJECTIVES: The aim of the study was to describe micronutrient intakes and explore possible correlations to growth during the first 70 days of life in extremely preterm infants. METHODS: Retrospective population-based study including extremely preterm infants (<27 weeks) born in Sweden during 2004-2007. Detailed nutritional and growth data were derived from hospital records. RESULTS: Included infants (n = 531) had a mean gestational age of 25 weeks and 2 days and a mean birth weight of 765 g. Estimated and adjusted intakes of calcium, phosphorus magnesium, zinc, copper, selenium, vitamin D, and folate were lower than estimated requirements, whereas intakes of iron, vitamin K, and several water-soluble vitamins were higher than estimated requirements. High iron intakes were explained by blood transfusions. During the first 70 days of life, taking macronutrient intakes and severity of illness into account, folate intakes were positively associated with weight (P = 0.001) and length gain (P = 0.003) and iron intake was negatively associated with length gain (P = 0.006). CONCLUSIONS: Intakes of several micronutrients were inconsistent with recommendations. Even when considering macronutrient intakes and severity of illness, several micronutrients were independent predictors of early growth. Low intake of folate was associated with poor weight and length gain. Furthermore, high iron supply was associated with poor growth in length and head circumference. Optimized early micronutrient supply may improve early growth in extremely preterm infants.

Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects.

BACKGROUND: Weight loss protects against type 2 diabetes but is hard to maintain with behavioral modification alone. In an analysis of data from a nonrandomized, prospective, controlled study, we examined the effects of bariatric surgery on the prevention of type 2 diabetes. METHODS: In this analysis, we included 1658 patients who underwent bariatric surgery and 1771 obese matched controls (with matching performed on a group, rather than individual, level). None of the participants had diabetes at baseline. Patients in the bariatric-surgery cohort underwent banding (19%), vertical banded gastroplasty (69%), or gastric bypass (12%); nonrandomized, matched, prospective controls received usual care. Participants were 37 to 60 years of age, and the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) was 34 or more in men and 38 or more in women. This analysis focused on the rate of incident type 2 diabetes, which was a prespecified secondary end point in the main study. At the time of this analysis (January 1, 2012), participants had been followed for up to 15 years. Despite matching, some baseline characteristics differed significantly between the groups; the baseline body weight was higher and risk factors were more pronounced in the bariatric-surgery group than in the control group. At 15 years, 36.2% of the original participants had dropped out of the study, and 30.9% had not yet reached the time for their 15-year follow-up examination. RESULTS: During the follow-up period, type 2 diabetes developed in 392 participants in the control group and in 110 in the bariatric-surgery group, corresponding to incidence rates of 28.4 cases per 1000 person-years and 6.8 cases per 1000 person-years, respectively (adjusted hazard ratio with bariatric surgery, 0.17; 95% confidence interval, 0.13 to 0.21; P<0.001). The effect of bariatric surgery was influenced by the presence or absence of impaired fasting glucose (P=0.002 for the interaction) but not by BMI (P=0.54). Sensitivity analyses, including end-point imputations, did not change the overall conclusions. The postoperative mortality was 0.2%, and 2.8% of patients who underwent bariatric surgery required reoperation within 90 days owing to complications. CONCLUSIONS: Bariatric surgery appears to be markedly more efficient than usual care in the prevention of type 2 diabetes in obese persons. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT01479452.).

Perioperative nutrition in extremely preterm infants undergoing surgical treatment for patent ductus arteriosus is suboptimal.

AIM: To evaluate perioperative nutrition in extremely preterm infants undergoing surgery for patent ductus arteriosus (PDA). METHODS: This is a population-based study of extremely preterm infants born in Sweden during 2004-2007 and operated on for PDA. Data on perioperative nutrition were obtained from hospital records. All enteral and parenteral nutrients and blood products were used to calculate daily nutritional intakes, starting 3 days before and ending 3 days after surgery. Data are mean (95% confidence intervals). RESULTS: Study infants (n = 140) had a mean gestational age (GA) of 24.8 weeks, and mean birth weight was 723 g. Energy and macronutrient intakes were below minimal requirements before, during and after PDA surgery. On the day of surgery, energy intake was 78 (74-81) kcal/kg/day, protein 2.9 (2.7-3.2) g/kg/day, fat 2.5 (2.3-2.7) g/kg/day and carbohydrate intake 10.7 (10.2-11.2) g/kg/day. Nutrition did not vary in relation to GA, but infants operated early (0-6 days after birth) received poorer nutrition than infants operated at older age. Fluid intake was 164 (159-169) mL/kg/day, and it did not vary during the week of surgery. CONCLUSION: Perioperative nutrition in extremely preterm infants undergoing PDA surgery in Sweden is suboptimal and needs to be improved. The significance of malnutrition for outcome after PDA surgery remains unclear and requires further investigation.

Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and macrovascular complications.

IMPORTANCE: Short-term studies show that bariatric surgery causes remission of diabetes. The long-term outcomes for remission and diabetes-related complications are not known. OBJECTIVES: To determine the long-term diabetes remission rates and the cumulative incidence of microvascular and macrovascular diabetes complications after bariatric surgery. DESIGN, SETTING, AND PARTICIPANTS: The Swedish Obese Subjects (SOS) is a prospective matched cohort study conducted at 25 surgical departments and 480 primary health care centers in Sweden. Of patients recruited between September 1, 1987, and January 31, 2001, 260 of 2037 control patients and 343 of 2010 surgery patients had type 2 diabetes at baseline. For the current analysis, diabetes status was determined at SOS health examinations until May 22, 2013. Information on diabetes complications was obtained from national health registers until December 31, 2012. Participation rates at the 2-, 10-, and 15-year examinations were 81%, 58%, and 41% in the control group and 90%, 76%, and 47% in the surgery group. For diabetes assessment, the median follow-up time was 10 years (interquartile range [IQR], 2-15) and 10 years (IQR, 10-15) in the control and surgery groups, respectively. For diabetes complications, the median follow-up time was 17.6 years (IQR, 14.2-19.8) and 18.1 years (IQR, 15.2-21.1) in the control and surgery groups, respectively. INTERVENTIONS: Adjustable or nonadjustable banding (n = 61), vertical banded gastroplasty (n = 227), or gastric bypass (n = 55) procedures were performed in the surgery group, and usual obesity and diabetes care was provided to the control group. MAIN OUTCOMES AND MEASURES: Diabetes remission, relapse, and diabetes complications. Remission was defined as blood glucose <110 mg/dL and no diabetes medication. RESULTS: The diabetes remission rate 2 years after surgery was 16.4% (95% CI, 11.7%-22.2%; 34/207) for control patients and 72.3% (95% CI, 66.9%-77.2%; 219/303) for bariatric surgery patients (odds ratio [OR], 13.3; 95% CI, 8.5-20.7; P < .001). At 15 years, the diabetes remission rates decreased to 6.5% (4/62) for control patients and to 30.4% (35/115) for bariatric surgery patients (OR, 6.3; 95% CI, 2.1-18.9; P < .001). With long-term follow-up, the cumulative incidence of microvascular complications was 41.8 per 1000 person-years (95% CI, 35.3-49.5) for control patients and 20.6 per 1000 person-years (95% CI, 17.0-24.9) in the surgery group (hazard ratio [HR], 0.44; 95% CI, 0.34-0.56; P < .001). Macrovascular complications were observed in 44.2 per 1000 person-years (95% CI, 37.5-52.1) in control patients and 31.7 per 1000 person-years (95% CI, 27.0-37.2) for the surgical group (HR, 0.68; 95% CI, 0.54-0.85; P = .001). CONCLUSIONS AND RELEVANCE: In this very long-term follow-up observational study of obese patients with type 2 diabetes, bariatric surgery was associated with more frequent diabetes remission and fewer complications than usual care. These findings require confirmation in randomized trials. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01479452.

Probiotic supplementation and risk of necrotizing enterocolitis and mortality among extremely preterm infants-the Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial: study protocol for a multicenter, double-blinded, placebo-controlled, and registry-based randomized controlled trial.

BACKGROUND: Extremely preterm infants, defined as those born before 28 weeks' gestational age, are a very vulnerable patient group at high risk for adverse outcomes, such as necrotizing enterocolitis and death. Necrotizing enterocolitis is an inflammatory gastrointestinal disease with high incidence in this cohort and has severe implications on morbidity and mortality. Previous randomized controlled trials have shown reduced incidence of necrotizing enterocolitis among older preterm infants following probiotic supplementation. However, these trials were underpowered for extremely preterm infants, rendering evidence for probiotic supplementation in this population insufficient to date. METHODS: The Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial is a multicenter, double-blinded, placebo-controlled and registry-based randomized controlled trial conducted among extremely preterm infants (n = 1620) born at six tertiary neonatal units in Sweden and four units in Denmark. Enrolled infants will be allocated to receive either probiotic supplementation with ProPrems® (Bifidobacterium infantis, Bifidobacterium lactis, and Streptococcus thermophilus) diluted in 3 mL breastmilk or placebo (0.5 g maltodextrin powder) diluted in 3 mL breastmilk per day until gestational week 34. The primary composite outcome is incidence of necrotizing enterocolitis and/or mortality. Secondary outcomes include incidence of late-onset sepsis, length of hospitalization, use of antibiotics, feeding tolerance, growth, and body composition at age of full-term and 3 months corrected age after hospital discharge. DISCUSSION: Current recommendations for probiotic supplementation in Sweden and Denmark do not include extremely preterm infants due to lack of evidence in this population. However, this young subgroup is notably the most at risk for experiencing adverse outcomes. This trial aims to investigate the effects of probiotic supplementation on necrotizing enterocolitis, death, and other relevant outcomes to provide sufficiently powered, high-quality evidence to inform probiotic supplementation guidelines in this population. The results could have implications for clinical practice both in Sweden and Denmark and worldwide. TRIAL REGISTRATION: ( Clinicaltrials.gov ): NCT05604846.

Insulin resistance prior to term age in very low birthweight infants: a prospective study.

OBJECTIVE: To explore the glucose-related hormone profile of very low birthweight (VLBW) infants and assess the association between neonatal hyperglycaemia and insulin resistance during the admission period. DESIGN: A prospective observational study-the Very Low Birth Weight Infants, Glucose and Hormonal Profiles over Time study. SETTING: A tertiary neonatal intensive care unit and four neonatal units in county hospitals in Sweden. PATIENTS: 48 infants born <1500 g (VLBW) during 2016-2019. OUTCOME MEASURES: Plasma concentrations of glucose-related hormones and proteins (C-peptide, insulin, ghrelin, glucagon-like peptide 1 (GLP-1), glucagon, leptin, resistin and proinsulin), insulin:C-peptide and proinsulin:insulin ratios, Homoeostatic Model Assessment 2 (HOMA2) and Quantitative Insulin Sensitivity Check (QUICKI) indices, measured on day of life (DOL) 7 and at postmenstrual age 36 weeks. RESULTS: Lower gestational age was significantly associated with higher glucose, C-peptide, insulin, proinsulin, leptin, ghrelin, resistin and GLP-1 concentrations, increased HOMA2 index, and decreased QUICKI index and proinsulin:insulin ratio. Hyperglycaemic infants had significantly higher glucose, C-peptide, insulin, leptin and proinsulin concentrations, and lower QUICKI index, than normoglycaemic infants. Higher glucose and proinsulin concentrations and insulin:C-peptide ratio, and lower QUICKI index on DOL 7 were significantly associated with longer duration of hyperglycaemia during the admission period. CONCLUSIONS: VLBW infants seem to have a hormone profile consistent with insulin resistance. Lower gestational age and hyperglycaemia are associated with higher concentrations of insulin resistance markers.

Nutrient intakes independently affect growth in extremely preterm infants: results from a population-based study.

AIM: To explore associations between energy and macronutrient intakes and early growth in extremely low gestational age (ELGA) infants. METHODS: Retrospective population-based study of all ELGA infants (<27 weeks) born in Sweden during 2004-2007. Detailed data on nutrition and anthropometric measurements from birth to 70 days of postnatal age were retrieved from hospital records. RESULTS: Study infants (n = 531) had a mean ± SD gestational age of 25.3 ± 1.1 weeks and a birth weight of 765 ± 170 g. Between 0 and 70 days, average daily energy and protein intakes were 120 ± 11 kcal/kg and 3.2 ± 0.4 g/kg, respectively. During this period, standard deviation scores for weight, length and head circumference decreased by 1.4, 2.3 and 0.7, respectively. Taking gestational age, baseline anthropometrics and severity of illness into account, lower energy intake correlated with lower gain in weight (r = +0.315, p < 0.001), length (r = +0.215, p < 0.001) and head circumference (r = +0.218, p < 0.001). Protein intake predicted growth in all anthropometric outcomes, and fat intake was positively associated with head circumference growth. CONCLUSION: Extremely low gestational age infants received considerably less energy and protein than recommended and showed postnatal growth failure. Nutrient intakes were independent predictors of growth even after adjusting for severity of illness. These findings suggest that optimized energy and macronutrient intakes may prevent early growth failure in these infants.

Association between Neonatal Intakes and Hyperglycemia, and Left Heart and Aortic Dimensions at 6.5 Years of Age in Children Born Extremely Preterm.

Survivors of extremely preterm birth (gestational age < 27 weeks) have been reported to exhibit an altered cardiovascular phenotype in childhood. The mechanisms are unknown. We investigated associations between postnatal nutritional intakes and hyperglycemia, and left heart and aortic dimensions in children born extremely preterm. Postnatal nutritional data and echocardiographic dimensions at 6.5 years of age were extracted from a sub-cohort of the Extremely Preterm Infants in Sweden Study (EXPRESS; children born extremely preterm between 2004-2007, n = 171, mean (SD) birth weight = 784 (165) grams). Associations between macronutrient intakes or number of days with hyperglycemia (blood glucose > 8 mmol/L) in the neonatal period (exposure) and left heart and aortic dimensions at follow-up (outcome) were investigated. Neonatal protein intake was not associated with the outcomes, whereas higher lipid intake was significantly associated with larger aortic root diameter (B = 0.040, p = 0.009). Higher neonatal carbohydrate intake was associated with smaller aorta annulus diameter (B = -0.016, p = 0.008). Longer exposure to neonatal hyperglycemia was associated with increased thickness of the left ventricular posterior wall (B = 0.004, p = 0.008) and interventricular septum (B = 0.004, p = 0.010). The findings in this study indicate that postnatal nutrition and hyperglycemia may play a role in some but not all long-lasting developmental adaptations of the cardiovascular system in children born extremely preterm.