Cortisol and Cortisone in Early Childhood in Very-Low-Birthweight Infants and Term-Born Infants.

INTRODUCTION: Besides programming of the hypothalamic-pituitary-adrenal (HPA) axis, changes in the activity of 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) could contribute to the later metabolic and cardiovascular consequences of preterm birth. OBJECTIVE: We compared serum cortisol, cortisone, and cortisol/cortisone ratio in early childhood in very-low-birthweight (VLBW) infants and term appropriate for gestational age (AGA) born infants. METHODS: We included 41 VLBW infants, participating in the randomized controlled Neonatal Insulin Replacement Therapy in Europe trial, and 64 term AGA-born infants. Cortisol and cortisone were measured in blood samples taken at 6 months and 2 years corrected age (VLBW children) and at 3 months and 1 and 2 years (term children). At 2 years of (corrected) age (HDL) cholesterol, triglycerides, glucose, and insulin were also measured. RESULTS: During the first 2 years of life, cortisol/cortisone ratio is higher in VLBW children compared to term children. In the total group of children, cortisol/cortisone ratio is positively related to triglycerides at 2 years of (corrected) age. In VLBW children, over the first 2 years of life both cortisol and cortisone are higher in the early-insulin group compared to the standard care group. CONCLUSIONS: In VLBW infants, lower 11ß-HSD2 activity probably contributes to the long-term metabolic and cardiovascular risks. In VLBW infants, early insulin treatment could affect programming of the HPA axis, resulting in higher cortisol and cortisone levels during early childhood.

IGF-I and relation to growth in infancy and early childhood in very-low-birth-weight infants and term born infants.

BACKGROUND: In very-low-birth-weight infants IGF-I plays an important role in postnatal growth restriction and is probably also involved in growth restriction in childhood. We compared IGF-I and its relation to growth in early childhood in very-low-birth-weight infants and term appropriate for gestational age born infants. METHODS: We included 41 very-low-birth-weight and 64 term infants. Anthropometry was performed at all visits to the outpatient clinic. IGF-I and insulin were measured in blood samples taken at 6 months and 2 years corrected age (very-low-birth-weight children) and at 3 months, 1 and 2 years (term children). RESULTS: Over the first 2 years of life growth parameters are lower in very-low-birth-weight children compared to term children, but the difference in length decreases significantly. During the first 2 years of life IGF-I is higher in very-low-birth-weight children compared to term children. In both groups there is a significant relationship between IGF-I and (change in) length and weight over the first 2 years of life and between insulin and change in total body fat. CONCLUSIONS: Considering the relation of IGF-I to growth and the decrease in difference in length, higher IGF-I levels in very-low-birth-weight infants in early childhood probably have an important role in catch-up growth in length.

Salivary and serum cortisol and relation to blood pressure in infancy and early childhood in very-low-birth-weight infants.

BACKGROUND: Programming of the hypothalamic-pituitary-adrenal (HPA) axis possibly explains the relation between intrauterine growth restriction (IUGR) and/or preterm birth and elevated blood pressure in later life. Very-low-birth-weight infants (birth weight <1,500 g) have high prevalence of raised blood pressure, already in early childhood. We investigated cortisol levels, relation to blood pressure and reliability of salivary cortisol in infancy and early childhood in very-low-birth-weight infants. METHODS: We included 41 children, participating in the randomized controlled Neonatal Insulin Replacement Therapy in Europe (NIRTURE) trial. Serum and salivary samples for cortisol measurement (immunoassay) were taken simultaneously at 6 mo and separately at 2 y corrected age. Blood pressure was measured at 2 y corrected age. RESULTS: Serum cortisol was significantly correlated to systolic and diastolic blood pressure in boys and in the early-insulin treated group. At 2 y corrected age serum cortisol was significantly higher in the early-insulin group compared to the standard care group. At 6 mo corrected age salivary cortisol was significantly correlated to serum cortisol. CONCLUSION: In very-low-birth-weight boys, the positive correlation between cortisol and blood pressure is present at 2 y corrected age. Early insulin therapy could affect programming of the HPA axis. Salivary cortisol mirrors serum levels at 6 mo corrected age.

Components of the metabolic syndrome in early childhood in very-low-birth-weight infants and term small and appropriate for gestational age infants.

BACKGROUND: Term small-for-gestational-age (SGA) and preterm born infants have an increased prevalence of metabolic syndrome components already in childhood. Our recent study in 2-y-old very-low-birth-weight (VLBW) infants was limited by the absence of a control group of term born children. We compared the metabolic syndrome components in early childhood in VLBW and term SGA infants to term appropriate for gestational age (AGA) infants. METHODS: We included 38 VLBW children and 82 term born children (64 AGA/18 SGA). HDL cholesterol, triglycerides, glucose, and insulin were measured in blood samples taken at 1 y (term children) and 2 y (all children) of (corrected) age. RESULTS: At 2 y corrected age, VLBW children have lower BMI and higher glucose level compared to AGA children. SGA children have lower BMI at 1 and 2 y of age and a high prevalence of high triglyceride levels at 1 y of age compared to AGA children. Total body fat is a significant determinant of HDL cholesterol and triglycerides and birth weight is a significant determinant of glucose at 2 y corrected age. CONCLUSION: In early childhood, VLBW and term SGA children already have a high prevalence of some metabolic syndrome components compared to term AGA children.

Relationship between insulin-like growth factor I levels, early insulin treatment, and clinical outcomes of very low birth weight infants.

OBJECTIVES: Insulin regulates the secretion of insulin-like growth factor I (IGF-I) in the newborn, and low levels of IGF-I have been linked to neonatal morbidity. As part of the Neonatal Insulin Replacement Therapy in Europe Trial, we investigated the impact of early insulin treatment on IGF-I levels and their relationship with morbidity and growth. STUDY DESIGN: Prospective cohort analyses of data collected as part of an international randomized controlled trial. Blood samples (days 1, 3, 7, and 28), were taken for IGF-I bioassay from 283 very low birth weight infants (<1500 g). RESULTS: Early insulin treatment led to a late increase in IGF-I levels between day 7 and 28 (P = .028). In the first week of life IGF-I levels were lower in infants with early hyperglycemia; mean difference -0.10 µg/L (95% CI -0.19, -0.02, P = .02). Lower levels of IGF-I at day 28 were independently associated with an increased risk of chronic lung disease, OR 3.23 (95% CI, 1.09-9.10), and greater IGF-I levels were independently associated with better weight gain, 0.10 kg (95% CI, 0.03-0.33, P = .02). CONCLUSIONS: Early intervention with insulin is related to increased IGF-I levels at 28 days. Low IGF-I levels are associated with hyperglycemia, increased morbidity, and reduced growth. Increasing IGF-I levels may improve outcomes of very low birth weight infants.

Components of the metabolic syndrome in early childhood in very-low-birth-weight infants.

BACKGROUND/AIMS: Term small-for-gestational-age and preterm born infants have an increased prevalence of metabolic syndrome components already in childhood. Data in very-low-birth-weight (VLBW) children are limited. We investigated the prevalence of metabolic syndrome components in VLBW infants at 2 years of corrected age. METHODS: We included 38 children, participating in the Neonatal Insulin Replacement Therapy in Europe (NIRTURE) trial, a randomized controlled trial of early insulin therapy in VLBW infants. Metabolic syndrome components were defined as: body mass index SDS >2; blood pressure (systolic and/or diastolic) ≥ 90th percentile; triglycerides ≥ 0.98 mmol/l; high-density lipoprotein (HDL) cholesterol ≤ 1.03 mmol/l; glucose ≥ 5.6 mmol/l. RESULTS: Two children (5%) had three metabolic syndrome components, 13 children (34%) had two components, and 11 children (29%) one component. 63% had raised blood pressure (prevalence higher in boys), 32% low HDL, and 30% high triglycerides (prevalence lower in early insulin group). In children with body mass index SDS <0, insulin-treated children had higher HDL than children with standard care. Systolic blood pressure was correlated with growth between term and 2 years of corrected age. CONCLUSIONS: VLBW infants already have a high prevalence of metabolic syndrome components at 2 years of corrected age. Early insulin treatment could have long-term benefits for some of these components.

Urine gonadotropin and estradiol levels in female very-low-birth-weight infants.

BACKGROUND: The postnatal activation of the hypothalamic-pituitary-gonadal axis is more exaggerated in preterm than in full-term born infants and may be important for future reproductive function. AIM: The objective of this study was to investigate the postnatal activation of the hypothalamic-pituitary-gonadal axis in female very-low-birth-weight infants. STUDY DESIGN: We performed serial measurements of gonadotropin and estradiol levels in urine samples of female very-low-birth-weight infants collected at 1 and 4weeks postnatal age, at 32weeks postmenstrual age, at expected date of delivery and at the corrected age of three and six months. SUBJECTS: Twenty-two very-low-birth-weight infants (gestational age 25.4-30.1weeks), participating in the Neonatal Insulin Replacement Therapy in Europe trial, were included in this study. OUTCOME MEASURES: Gonadotropin and estradiol levels were measured in serial urine samples. RESULTS: Longitudinal analysis shows that after birth FSH and LH levels increase until 32weeks postmenstrual age (4weeks postnatal age) and then decrease until 3months corrected age (26weeks postnatal age). Estradiol levels decrease from 28weeks postmenstrual age (1week postnatal age) until 6months corrected age (39weeks postnatal age). CONCLUSIONS: Serial urine sampling for measurement of gonadotropin and estradiol levels provides an accurate description of the postnatal activation of the hypothalamic-pituitary-gonadal axis in very-low-birth-weight girls. Levels of FSH and LH peak at a mean postmenstrual age of 32weeks (postnatal age of 4weeks) whereas estradiol levels are highest shortly after birth.

Characteristics of suitable work from the perspective of patients with fibromyalgia.

OBJECTIVES: The evaluation of work ability of patients with FM is difficult. Our aim was to investigate the characteristics of suitable work from the perspective of patients with FM. METHODS: Interviews with patients yielded statements about characteristics of suitable work. Patients individually sorted these statements according to similarity. Hierarchical cluster analysis was applied to these sortings. RESULTS: The hierarchical structure included 74 characteristics of suitable work. The 10 clusters at the lowest level included (i) recovery opportunities, (ii) pace of work, (iii) not too high workload, (iv) keeping energy for home and free time, (v) match between work and capabilities, (vi) development opportunities, (vii) understanding from colleagues, (viii) help from colleagues, (ix) support from management and (x) work agreements with management. CONCLUSIONS: According to patients with FM, suitable work is paced in such a way that one can perform the job well and with satisfaction while keeping energy for home and free time and having acknowledgement and help from management and colleagues. The brief suitable work checklist that is provided can help patients with FM to negotiate with employers and job professionals to improve the match between job demands and capabilities.

Prevalence and determinants of hyperglycemia in very low birth weight infants: cohort analyses of the NIRTURE study.

OBJECTIVES: To investigate the prevalence and determinants of hyperglycemia in the preterm population, as part of the Neonatal Insulin Therapy in Europe (NIRTURE) Trial. STUDY DESIGN: We conducted prospective cohort analyses of continuous glucose monitoring data from control infants participating in an international randomized controlled trial. Data were collected from 188 very low birth weight infants (<1500 g). RESULTS: In the first week of life, 80% of infants had evidence of glucose levels >8 mmol/L, and 32% had glucose levels >10 mmol/L >10% of the time. Independent risk factors for hyperglycemia included increasing prematurity, small size at birth, use of inotropes, lipid infusions, and sepsis. There was a lack of association between rate of dextrose infused and risk of hyperglycemia. CONCLUSION: The prevalence of hyperglycemia in the very low birth weight infant is high, with marked variability in prevalence between infants, not simply related to rates of glucose infused, but to other potentially modifiable risk factors.

Early insulin therapy in very-low-birth-weight infants.

BACKGROUND: Studies involving adults and children being treated in intensive care units indicate that insulin therapy and glucose control may influence survival. Hyperglycemia in very-low-birth-weight infants is also associated with morbidity and mortality. This international randomized, controlled trial aimed to determine whether early insulin replacement reduced hyperglycemia and affected outcomes in such neonates. METHODS: In this multicenter trial, we assigned 195 infants to continuous infusion of insulin at a dose of 0.05 U per kilogram of body weight per hour with 20% dextrose support and 194 to standard neonatal care on days 1 to 7. The efficacy of glucose control was assessed by continuous glucose monitoring. The primary outcome was mortality at the expected date of delivery. The study was discontinued early because of concerns about futility with regard to the primary outcome and potential harm. RESULTS: As compared with infants in the control group, infants in the early-insulin group had lower mean (+/-SD) glucose levels (6.2+/-1.4 vs. 6.7+/-2.2 mmol per liter [112+/-25 vs. 121+/-40 mg per deciliter], P=0.007). Fewer infants in the early-insulin group had hyperglycemia for more than 10% of the first week of life (21% vs. 33%, P=0.008). The early-insulin group had significantly more carbohydrate infused (51+/-13 vs. 43+/-10 kcal per kilogram per day, P<0.001) and less weight loss in the first week (standard-deviation score for change in weight, -0.55+/-0.52 vs. -0.70+/-0.47; P=0.006). More infants in the early-insulin group had episodes of hypoglycemia (defined as a blood glucose level of <2.6 mmol per liter [47 mg per deciliter] for >1 hour) (29% in the early-insulin group vs. 17% in the control group, P=0.005), and the increase in hypoglycemia was significant in infants with birth weights of more than 1 kg. There were no differences in the intention-to-treat analyses for the primary outcome (mortality at the expected date of delivery) and the secondary outcome (morbidity). In the intention-to-treat analysis, mortality at 28 days was higher in the early-insulin group than in the control group (P=0.04). CONCLUSIONS: Early insulin therapy offers little clinical benefit in very-low-birth-weight infants. It reduces hyperglycemia but may increase hypoglycemia (Current Controlled Trials number, ISRCTN78428828.)

Therapeutic total plasma exchange in a child with neuroblastoma-related anti-Hu syndrome.

A 5-year-old boy underwent total plasma exchange to remove anti-neuronal anti-Hu autoantibodies as a complication of neuroblastoma, leading to autonomic bowel dysfunction. Total plasma exchange (TPE) resulted eventually in a reduction of autoantibody levels, but, more importantly, led to improvement of bowel function. TPE proved to be a safe and effective treatment option in neuroblastoma-related anti-Hu syndrome in a child.