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.

The 185delAG* BRCA1 mutation is encountered primarily in Jewish Ashkenazi and Iraqi individuals, and sporadically in non-Jews. Previous studies estimated that this is a founder mutation in Jewish mutation carriers that arose before the dispersion of Jews in the Diaspora B2500 years ago. The aim of this study was to assess the haplotype in ethnically diverse 185delAG* BRCA1 mutation carriers, and to estimate the age at which the mutation arose. Ethnically diverse Jewish and non-Jewish 185delAG*BRCA1 mutation carriers and their relatives were genotyped using 15 microsatellite markers and three SNPs spanning 12.5 MB, encompassing the BRCA1 gene locus. Estimation of mutation age was based on a subset of 11 markers spanning a region of B5 MB, using a previously developed algorithm applying the maximum likelihood method. Overall, 188 participants (154 carriers and 34 noncarriers) from 115 families were included: Ashkenazi, Iraq, Kuchin-Indians, Syria, Turkey, Iran, Tunisia, Bulgaria, non-Jewish English, non-Jewish Malaysian, and Hispanics. Haplotype analysis indicated that the 185delAG mutation arose 750-1500 years ago. In Ashkenazim, it is a founder mutation that arose 61 generations ago, and with a small group of founder mutations was introduced into the Hispanic population (conversos) B650 years ago, and into the Iraqi-Jewish community B450 years ago. The 185delAG mutation in the non-Jewish populations in Malaysia and the UK arose at least twice independently. We conclude that the 185delAG* BRCA1 mutation resides on a common haplotype among Ashkenazi Jews, and arose about 61 generations ago and arose independently at least twice in non-Jews.

ObjectiveTo assess the associations between neonatal hyperglycaemia and insulin treatment, versus long-term neurodevelopmental outcomes in children born extremely preterm.Design and settingObservational national cohort study (Extremely Preterm Infants in Sweden Study) using prospectively and retrospectively collected data. Neurodevelopmental assessment was performed at 6.5 years of age.Patients533 infants born <27 gestational weeks during 2004–2007; 436 survivors were assessed at 6.5 years.Outcome measuresNeurodevelopmental disability (NDD), survival without moderate to severe NDD, Wechsler Intelligence Scale for Children IV Full scale intelligence quotient (WISC-IV FSIQ) and Movement Assessment Battery for Children 2 (MABC-2) total score.ResultsDuration of neonatal hyperglycaemia >8 mmol/L was associated with WISC-IV scores—for each day with hyperglycaemia there was a decrease of 0.33 points (95% CI 0.03 to 0.62) in FSIQ. Neonatal hyperglycaemia >8 mmol/L occurring on 3 consecutive days was associated with lower MABC-2 scores (adjusted mean difference: −4.90; 95% CI −8.90 to −0.89). For each day with hyperglycaemia >8 mmol/L, there was a decrease of 0.55 points (95% CI 0.17 to 0.93) in MABC-2 total score. Insulin treatment was not associated with any of the outcome measures.ConclusionNeonatal hyperglycaemia >8 mmol/L was associated with lower intelligence scores and worse motor outcomes at 6.5 years of age. Insulin treatment was not associated with either worsened or improved neurodevelopmental outcomes. Randomised controlled trials are needed to clarify the role of insulin in treating hyperglycaemia in extremely preterm infants.

BackgroundAdverse 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.MethodsData 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).ResultsHigher 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.ConclusionsThese findings emphasize the importance of modifiable early-life exposures, such as nutrition and hyperglycemia, in determining long-term outcomes in children born extremely preterm.

Background Evidence showing the beneficial effects of enhanced parenteral nutrition (PN) to very low‐birth‐weight (VLBW, <1500 g) infants is accumulating. However, PN composition and its impact on growth outcomes are questioned. This study aimed to investigate the associations between administration of a concentrated PN regime and intakes of energy and macronutrients as well as postnatal growth in VLBW infants. Methods We compared 2 cohorts of VLBW infants born before (n = 74) and after (n = 44) a concentrated PN regime was introduced into clinical use. Daily nutrition and fluid intake during the first 28 postnatal days and all available growth measurements during hospitalization were retrospectively collected from clinical charts. Results Infants who received concentrated PN compared with original PN had higher parenteral intakes of energy (56 vs 45 kcal/kg/d, P < 0.001), protein (2.6 vs 2.2 g/kg/d, P = 0.008), and fat (1.5 vs 0.7 g/kg/d, P < 0.001) during the first postnatal week. Changes in standard deviation scores for weight and length from birth to postnatal day 28 were more positive in the concentrated PN group (mean [95% CI]; weight change: –0.77 [–1.02 to –0.52] vs –1.29 [–1.33 to –1.05], P = 0.005; length change: –1.01 [–1.36 to –0.65] vs –1.60 [–1.95 to –1.25], P = 0.025). There were no significant differences in fluid intake and infant morbidity between the groups. Conclusion Our results suggest that concentrated PN is useful and seems to be safe for improving early nutrition and growth in VLBW infants.

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.

Objective To assess the associations between neonatal hyperglycaemia and insulin treatment, versus longterm neurodevelopmental outcomes in children born extremely preterm. Design and setting Observational national cohort study (Extremely Preterm Infants in Sweden Study) using prospectively and retrospectively collected data. Neurodevelopmental assessment was performed at 6.5 years of age. Patients 533 infants born <27 gestational weeks during 2004-2007; 436 survivors were assessed at 6.5 years. Outcome measures Neurodevelopmental disability (NDD), survival without moderate to severe NDD, Wechsler Intelligence Scale for Children IV Full scale intelligence quotient (WISC-IV FSIQ) and Movement Assessment Battery for Children 2 (MABC-2) total score. Results Duration of neonatal hyperglycaemia >8 mmol/L was associated with WISC-IV scores-for each day with hyperglycaemia there was a decrease of 0.33 points (95% CI 0.03 to 0.62) in FSIQ. Neonatal hyperglycaemia >8 mmol/L occurring on 3 consecutive days was associated with lower MABC-2 scores (adjusted mean difference: −4.90; 95% CI −8.90 to −0.89). For each day with hyperglycaemia >8 mmol/L, there was a decrease of 0.55 points (95% CI 0.17 to 0.93) in MABC-2 total score. Insulin treatment was not associated with any of the outcome measures. Conclusion Neonatal hyperglycaemia >8 mmol/L was associated with lower intelligence scores and worse motor outcomes at 6.5 years of age. Insulin treatment was not associated with either worsened or improved neurodevelopmental outcomes. Randomised controlled trials are needed to clarify the role of insulin in treating hyperglycaemia in extremely preterm infants. What this study adds?► Both magnitude and duration of neonatal hyperglycaemia were associated with worse motor outcomes at 6.5 years of age and might be associated with lower intelligence scores. ► These associations were observed at glucose concentrations >8 mmol/L. ► Insulin treatment was not associated with either worsened or improved neurodevelopmental outcomes at 6.5 years of age, but further studies are required.