Anneke Cranendonk

Optimal growth and lower fat mass in preterm infants fed a protein-enriched postdischarge formula.

Background and Objectives: Postdischarge formulas with extra energy and protein improve short-term growth but may also influence long-term body composition in an unwanted manner. Energy- and protein-enriched formulas with an increased protein-to-energy ratio improves gain of lean mass. The objective of the study was to investigate whether feeding a nutrient-enriched formula without extra energy after term, usually 3 to 4 weeks after discharge, would influence growth and body composition in infancy. Methods: In this randomized controlled trial preterm infants were fed fortified human milk or preterm formula until term. At term, 102 infants were randomized to a nutrient-enriched formula without extra energy or standard formula until 6 months corrected age. Twenty-six infants received unfortified human milk after term. At term and 6 months corrected age, anthropometry and a dual-energy x-ray absorptiometry (DEXA) scan were performed. Lean and fat mass (FM) were corrected for height. Results: There were no differences in growth or body size between the feeding groups. Infants fed the enriched formula gained less FM and had lower FM corrected for body size at 6 months corrected age than infants fed standard formula. Infants fed human milk had lower lean mass and higher FM corrected for body size at 6 months corrected age than formula-fed infants. Conclusions: Feeding nutrient-enriched formula without extra energy after term does not change quantity of growth but does influence type of weight gain and body composition of preterm infants. Infants fed the nutrient-enriched formula had lower FM corrected for body size at 6 months corrected age than infants fed standard formula or human milk.

Clinical pharmacokinetics of phenobarbital in neonates

Demographic and clinical pharmacokinetic data collected from term and preterm neonates who were treated with intravenous phenobarbital have been analysed to evaluate the role of patient characteristics in pharmacokinetic parameters. Significant relationships between total body weight (TBW) or body surface area (BSA) and volume of distribution (Vd) and total body clearance (CL) were found. Coefficients of determination were: 0.55 and 0.59 for Vd, and 0.76 and 0.72 for CL against TBW and BSA, respectively. In addition, significant relationships between height of the infants and volume of distribution of phenobarbital and total body clearance were observed. Coefficients of determination were 0.58 for Vd and 0.56 for CL. A weaker but significant correlation existed between gestational age and Vd or CL of phenobarbital. Coefficients of determination were 0.43 and 0.64, respectively. There was no correlation between volume of distribution per kg body weight or total body clearance per kg body weight and any patient parameter investigated. However, these latter pharmacokinetic parameters tended to decrease with increasing gestational age and height of the neonates. The results obtained were used to develop new loading and maintenance doses for phenobarbital in neonates based on total body weight and body surface area and based on height and gestational age for cases that weight is not available.

Outcome at 4.5 years of children born after expectant management of early-onset hypertensive disorders of pregnancy

OBJECTIVE The objective of the study was to describe neurodevelopmental outcome at the age of 4.5 years in 216 children, born after expectant management of severe early-onset hypertensive complications of pregnancy. STUDY DESIGN This was a prospective follow-up study until age 4.5 years from maternal admission onward. Developmental outcome measurements included child intelligence quotient and behavioral, motor, and neurological outcome. Abnormal composite outcome (perinatal mortality or abnormal developmental outcome) was studied in relation to gestational age (GA), birthweight (BW), and perinatal variables. RESULTS Fetal and neonatal mortality was 9% and 8%, respectively. Of the 178 survivors, 149 (84%) were seen for follow-up. Mean GA was 31.4 weeks and 90% were born growth restricted. Abnormal developmental outcome occurred in 20% and abnormal composite outcome in 37%. CONCLUSION Perinatal mortality or abnormal child development occurs in one third of pregnancies with early-onset and severe hypertensive complications and is highest in the lowest GA and BW ranges.

Neuromotor Function and School Performance in 7 year old children born as high-risk preterm infants

Neuromotor behavior was studied in 63 children at a mean age of 7 years. They were born at a gestational age less than 32 weeks and/or birthweight under 1500 g and were categorized according to their medical history in conformance with the Neonatal Medical Index (from category I to V, from few to serious complications). We included only children considered at high risk as categorized in III to V. The neuromotor behavior study focuses on different subcategories, such as hand function, quality of walking, posture, passive muscle tone, coordination, and diadochokinesia. Hand preference and/or lateralization, the presence of associated movements, and/or asymmetry were noted, as was school performance. Then gender, gestational age, birthweight, and dysmaturity were investigated as confounding factors. The outcome at 7 years was correlated with the Neonatal Medical Index and the neonatal brain ultrasonography classification. None of the children scored 100% on the combined subcategories. Nineteen children (30%) had an overall score between 75 and 99%. Significant relationships between all different subcategories were found. Lack of hand preference, poor lateralization, and male gender were related to poor overall outcome. Poor motor control was correlated to special schooling and education below age level. The Neonatal Medical Index proved to have a significant influence on total outcome and the subcategories at the age of 7 years, with the worst outcome in children formerly classified in category V. Neuromotor behavior at 7 years of age was not related to birthweight, gestational age, dysmaturity, and neonatal brain ultrasonography classification only. (J Child Neurol 2002;17:325-332).

Effects of recombinant human growth hormone treatment in intrauterine growth-retarded preterm newborn infants on growth, body composition and energy expenditure

The effects of recombinant human growth hormone treatment during the early postnatal period on growth, body composition and energy expenditure were studied in seven intrauterine growth‐retarded newborns. Seven infants were studied as controls. No differences were seen in bodyweight or height gain (15.9 ± 1.5g/kg per day and 1.02 ± 0.24cm/week in the treated and 16.3 ± 1.4g/kg per day and 1.11 ± 0.30 cm/week in the control group). Skinfold growth rate was 0.52 ± 0.20 mm/week in the treated vs. 0.56 ± 0.28 mm/week in the control group. Total body water (as a percentage of body‐weight, 80 ± 3.0% vs. 80 ± 4.0%) and energy expenditure (67.5 ± 7.4 vs. 66.7 ± 6.4kcal/kg per day) using 2H218O showed identical results in both groups. We conclude that recombinant human growth hormone treatment directly after birth in intrauterine growth‐retarded newborn infants results neither in an increase in growth rate nor a change in body composition or energy expenditure during the early postnatal period.

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.

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.

The corticotrophin‐releasing hormone test in preterm infants

The developing hypothalamic–pituitary–adrenal axis (HPAA) may be immature and not yet fully functional in preterm infants. This may result in an inappropriate adrenal response to stress. Little is known about the pituitary–adrenal response to corticotrophin‐releasing hormone (CRH) stimulation during the early neonatal period in preterm infants born before 32 weeks of gestation. Therefore, in a first study we investigated the pituitary–adrenal response to 1 µg/kg CRH i.v. in 13 preterm infants born ≤ 32 weeks of gestation. In addition, in a randomized placebo‐controlled study we compared the pituitary–adrenal response of 1 µg/kg CRH to placebo and stimulation with 2 µg/kg CRH.

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.

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.