BackgroundHyperglycemia in premature infants is associated with increased morbidity and mortality, but data on long-term outcome are limited. We investigated the effects of neonatal hyperglycemia (blood glucose ≥ 10 mmol/l, treated with insulin for ≥ 12 hours) on growth and neurobehavioral outcome at 2 years of age.MethodsRetrospective follow-up study at 2 years of age among 859 infants ≤32 weeks of gestation admitted to a tertiary neonatal center between January 2002 and December 2006. Thirty-three survivors treated with insulin for hyperglycemia and 63 matched controls without hyperglycemia were evaluated at a corrected age of 2 years. Outcome measures consisted of growth (weight, length, and head circumference) and neurological and behavioural development.Results66/859 (8%) infants ≤ 32 weeks of gestation developed hyperglycemia. Mortality during admission was 27/66 (41%) in the hyperglycemia group versus 62/793 (8%) in those without hyperglycemia (p < 0.001). Mortality was higher in infants with hyperglycemia with a birth weight ≤1,000 gram (p = 0.005) and/or gestational age of 24-28 weeks (p = 0.009) than in control infants without hyperglycemia. Sepsis was more prominent in infants with hyperglycemia and a birth weight of >1,000 gram (p = 0.002) and/or gestational age of 29-32 weeks (p = 0.009) than in control infants without hyperglycemia. Growth at 2 years of age was similar, but neurological and behavioural development was more frequently abnormal among those with neonatal hyperglycemia (p = 0.036 and 0.021 respectively).ConclusionsMortality was higher in very preterm infants with hyperglycemia treated with insulin during the neonatal period. At 2 years of age survivors showed normal growth, but a higher incidence of neurological and behavioural problems. Better strategies to manage hyperglycemia may improve outcome of very preterm infants.

Nephrocalcinosis in preterm neonates can have long-term sequelae for glomerular and tubular function. Furthermore, prematurity per se is associated with high blood pressure, relatively small kidneys, and (distal) tubular dysfunction. Long-term follow-up of blood pressure and renal glomerular and tubular function of preterm neonates, especially with neonatal nephrocalcinosis, seems warranted.

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Etiology of nephrocalcinosis in preterm neonates: AssociationNephrocalcinosis (NC) occurs frequently in preterm of nutritional intake and urinary parameters.neonates. The incidence varies between 17 and 64%, de-Background. Nephrocalcinosis (NC) in preterm neonates pending on different study populations, ultrasonographic has been described frequently, and small-scale studies suggest nates receive a high intake of calcium, phosphorus, and vs. 2.3 mmol/mmol, P Ͻ 0.05) and a lower mean urinary citrate/ vitamin D in the first months of life in order to prevent calcium ratio (1.1 vs. 1.7 mmol/mmol, P ϭ 0.005). rickets of prematurity. In a prospective study, we exam-Conclusions. NC develops as a result of an imbalance beined the association of stone-promoting and stone-inhibtween stone-inhibiting and stone-promoting factors. A high intake of calcium, phosphorus, and ascorbic acid, a low urinary iting factors with the development of NC in preterm citrate/calcium ratio, a high urinary calcium/creatinine ratio, neonates.immaturity, and medication to prevent or treat chronic lung disease with hypercalciuric side effects appear to contribute to the high incidence of NC in preterm neonates. METHODS Patients

The aim of the study was to evaluate the natural course of nephrocalcinosis (NC) in preterm neonates and the effect of NC on blood pressure and renal glomerular and tubular function. In a prospective observational study of 201 preterm neonates (gestational age <32 weeks) NC was present at term in 83 patients (41%), who were subsequently examined at 6, 12, and 24 months, and until August 2000 annually (with a maximum of 4 years) if NC persisted. Examination consisted of blood pressure measurement, renal ultrasonography, and glomerular and tubular function tests. The probability that NC, when present at term, would persist for 15 and 30 months was 34% [21-45, 95% confidence interval (CI)] and 15% (5-25, 95% CI) (Kaplan-Meier), respectively. Urinary tract infection did not occur more frequently in patients with NC (2.5%) than patients without NC at term (4.4%). Systolic and diastolic blood pressures above the 95th percentile were found in 39% and 48% of patients at 1 year and 30% and 34% at 2 years ( P<0.001). Mean glomerular filtration rate (GFR) (inulin clearance) at 1 and 2 years was 92 and 102 ml/min per 1.73 m(2), respectively. TP/GFR and excretion of alpha(1)-microglobulin were normal. The desmopressin test was impaired in 4 of 30 patients at 1 year and 2 of 25 at 2 years. It was concluded that while proximal tubular function is unaffected in children with neonatal NC, high blood pressure and impaired glomerular and distal tubular function might occur more frequently than in healthy children. Although no relationship can be proven between NC and hypertension or diminished renal function in this study, these results justify a large follow-up study with matched controlled study groups.

Mortality and neonatal morbidity were higher in infants with GA <27 weeks compared with infants born between 27 and 32 weeks. The high adverse outcome of infants <25 weeks suggests that one should carefully weigh whether or not to aggressively resuscitate and treat these extremely premature infants.

Nephrocalcinosis (NC) in preterm neonates has been reported frequently and small studies suggest an unfavourable effect on renal function. Data on ultrasonic features are limited and the reproducibility of ultrasonography (US) in detecting NC in preterm neonates is unknown. In this study, interobserver and intraobserver agreement of US was determined through videotape recordings of US examinations of preterm neonates. Furthermore, a prospective US study was performed in 215 preterm neonates (gestational age < 32 weeks) to evaluate ultrasonic characteristics, incidence, time course and effect on kidney length of NC. Patients were studied at 4 weeks after birth and at term. Patients with NC were followed for 2 years. NC was defined as bright reflections in the medulla or cortex seen in both transverse and longitudinal direction. The length of the kidneys was noted. The kappa value was 0.84 for intraobserver and 0.46 for interobserver agreement, whereas the overall agreement was 73%. NC was found in 50 of 150 (33%) patients at 4 weeks and in 83 of 201 patients (41%) at term. NC was localized mainly in the medulla. At 1 and 2 years, NC had persisted in 36% and 26%, respectively, of the patients with NC at term. Kidney length was comparable with normal values. In conclusion, US has a very good intraobserver agreement but a moderate interobserver agreement in detecting NC. Medullary NC is common among preterm neonates. During the first 2 years of life, the incidence decreases spontaneously and NC does not influence kidney length.

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