Bone Mineral Content in Preterm Infants at Age 4 to 16

Using photon absorptiometry the forearm bone mineral content (BMC) was determined in 75 children aged 4 to 16, who all had a low birth weight. Forty-five of them were born preterm AGA (27 boys, 18 girls, mean weight 1580 g; range 920-2060 g) and 30 preterm SGA (17 boys, 13 girls, mean weight 1510; range 940-2130 g). The results were compared with a control group of children of the same age, and analyses of covariance with age, height and weight as the covariant factors were performed. The BMC, weight and height did not differ between the children born AGA or SGA. Irrespective of AGA or SGA, the BMC was significantly decreased in boys but the difference was less pronounced and less significant when height and weight were used as covariant factors. Boys who had been born preterm had a less BMC than the control boys for their age but the were also somewhat shorter and lighter than expected with regard to their age.     

Bone mineral content in preterm infants at age 4 to 16

Using photon absorptiometry the forearm bone mineral content (BMC) was determined in 75 children aged 4 to 16, who all had a low birth weight. Forty-five of them were born preterm AGA (27 boys, 18 girls, mean weight 1 580 g; range 920-2 060 g) and 30 preterm SGA (17 boys, 13 girls, mean weight 1510; range 940-2130 g). The results were compared with a control group of children of the same age, and analyses of covariance with age, height and weight as the covariant factors were performed. The BMC, weight and height did not differ between the children born AGA or SGA. Irrespective of AGA or SGA, the BMC was significantly decreased in boys but the difference was less pronounced and less significant when height and weight were used as covariant factors. Boys who had been born preterm had a less BMC than the control boys for their age but they were also somewhat shorter and lighter than expected with regard to their age.     

Peripheral blood lymphocyte subpopulations in schoolchildren born very preterm.

AIM: To investigate whether lymphocytes or serum inflammatory markers are associated with obstructive lung disease and bronchial lability in schoolchildren born very preterm. METHOD: Lymphocyte subsets were studied in the peripheral venous blood of 29 such children (median age 8.8 years). Serum eosinophil cationic protein (ECP) and myeloperoxidase (MPO) concentrations and the association between them, lymphocyte subsets, and lung function were studied. Fourteen healthy children born at term, median age 9.1 years, served as controls. T lymphocytes (CD3), T lymphocyte subpopulations (CD4 and CD8), B lymphocytes (CD19), natural killer cells (CD16+56) and activation markers of T and B lymphocytes (CD23 and CD25) were determined using flow cytometry. Lung function was measured in all children both in the clinic and at home (Vitalograph Data Storage Spirometer). RESULTS: Compared with the controls, schoolchildren born very preterm had significantly lower CD4(+) T cell percentages and CD4:CD8 ratios (p < 0.05 for both), whereas natural killer cell percentages and serum ECP values were significantly higher (p < 0. 05). The very preterm schoolchildren had significantly lower spirometric values than the control group (p < 0.05)-except forced vital capacity. When all the subjects were considered together, a weak, but significant, negative association was observed between the bronchial responsiveness in peak expiratory flow, after a beta(2) agonist during home monitoring, and the CD4(+) T cell percentage (r = -0.45; p = 0.008) and the CD4:CD8 ratio (r = -0.50; p = 0.003), indicating a relation between bronchial lability and imbalance of T cell subpopulations. CONCLUSIONS: These results suggest that there is an inflammatory basis for lung function abnormalities in schoolchildren born very preterm.     

The ontogeny of serum immunoreactive pancreatic lipase and cationic trypsinogen in the premature human infant

We evaluated the development of the exocrine pancreas in 16 healthy preterm infants (29.3 +/- 1.6 weeks). The infants were fed breast milk with formula supplements (n = 8) or formula alone (n = 8). Growth was monitored weekly for 12 weeks then at 3, 6, 9, 12 months. At the same intervals sera were determined for pancreatic lipase and cationic trypsinogen. In addition, cord blood samples were analysed from another 33 preterm (27.6 +/- 5.2 weeks) and 75 healthy full-term infants. Serum pancreatic lipase in the cord blood of term (3.7 +/- 0.4 micrograms/l) and preterm infants (1.8 +/- 0.2 micrograms/l) was significantly below values reported for older children (10.5 +/- 0.9 micrograms/l; p less than 0.001). In the preterm infant, serum lipase was also significantly lower than values obtained at term (p less than 0.001). At birth, serum trypsinogen for preterm (16.8 +/- 1.3 micrograms/l) and term infants (23.3 +/- 1.9 micrograms/l) were below those for older children (31.4 +/- 3.7 micrograms/l; p less than 0.05). Over the first 3 weeks of life, serum lipase and trypsinogen increased significantly. From 3 weeks to 12 months of age, serum trypsinogen values remained unchanged, but serum lipase increased dramatically after 10 weeks of age. Thus, at 6 and 12 months of age, the preterm infants had significantly higher serum lipase values than infants of the same age born at term. These two pancreatic enzymes appear to show independent age-related maturation in infants born before term. The rate of maturation of lipase appears to be accelerated by exposure to the extrauterine environment.     

Very preterm children who do not cooperate with assessments at three years of age: skill differences at five years

This study examined skill differences at 5 years of age for very preterm children who were or were not cooperative with developmental testing at 3 years of age. All children born between 1986 and 1991 who were less than 30 weeks of gestation were followed prospectively. Two hundred one children were seen at both the 3- and 5-year assessments. Of the 201 children, 24 (11.9%) who had been uncooperative in the assessment at 3 years were seen at 5 years. Uncooperative children were matched to a group of cooperative children for sex, gestation, and/or birth weight. Nonparametric analyses revealed that scores on the Binet Pattern Analysis (p < .01) and the Bead Memory (p < .01) subtests were significantly different between the groups. The uncooperative children scored significantly more often in the at-risk range for tests of minor neurological dysfunction (MND; p < .01) compared with cooperative matched controls. The authors speculate that in very preterm children, uncooperative behavior shown at 3 years of age associated with poor visual/spatial skills and a high level of MND at 5 years of age may reveal children at risk for the development of nonverbal learning disabilities.     

Differences in insulin resistance markers between children born small for gestational age or born preterm appropriate for gestational age

Aim: To evaluate the impact of prenatal or postnatal compromised environment on glucose homoeostasis in children born preterm and appropriate for gestational age or small for gestational age (SGA) at term. Method: Seventy-seven children (median 9.9 years, range 8.5–10) born at Karolinska Hospital were allocated to three groups: 21 subjects born before 30 weeks of gestational age (preterm), 26 SGA at term and 30 at term with appropriate birth weight (control). Anthropometric measurements were taken, and fasting blood samples for haemoglobin A1c, glucose, insulin, IGFBP-1, IGF-1 and lipid profile were taken. Glucose, insulin and IGFBP-1 samples were taken at 0, 30 and 120 min during an oral glucose tolerance test (OGTT). Results: Subjects born preterm or SGA were shorter and thinner compared with Controls. After adjustment for body mass index (BMI), the SGA group had higher basal insulin levels (p = 0.029), higher homoeostasis model assessment—insulin resistance (p = 0.012) and lower whole-body insulin sensitivity index (p = 0.007) than Controls. IGFBP-1 decrease during OGTT was attenuated in the Preterm group compared with the Control (p = 0.045) and SGA groups (p = 0.007). Conclusion: The higher fasting insulin level in the SGA children, adjusted for BMI, could indicate peripheral insulin resistance. Preterm born children had reduced suppression of IGFBP-1 during OGTT, suggesting hepatic insulin resistance.     

Large variability in performance IQ associated with postnatal morbidity,and reduced verbal IQ among school-aged children born preterm

Aim: To assess cognitive ability in a population-based group of prematurely born school-aged children and to relate these findings to postnatal morbidity. Method: The study group consisted of a cohort of 51 children born preterm, 43 (26 boys, 17 girls) of whom were available for psychological evaluation At evaluation, their median age was 10 y (range 8-11 y). They were all born between 1988 and 1991, with gestational age less than 29 wk (median 27, range 24-28). Their median birthweight was 1060 g (range 450-1450). The Wechsler Intelligence Scale for Children (WISC-III) was used, and the test results were compared with those of a standardized, age-matched, normative group of children. Results: Thirteen children (30%) performed below average [intelligence quotient (IQ) 380] for Full Scale IQ (FSIQ). Thirty-six children had a Verbal IQ (VIQ) below the mean value of 100 [84%, 95% confidence interval 73-95%], p 3 0.0001. The Performance IQ (PIQ) was within the expected range of a normal population, although a large variability was observed. Discrepancies between VIQ and PIQ of more than 15 IQ units were found in 42% of the children. High postnatal morbidity (days with assisted ventilation, number of blood transfusions) and low birthweight standard deviation scores (SDS) were associated with lower PIQ than VIQ, while low postnatal morbidity and high birthweight were associated with higher PIQ than VIQ. Conclusion: This cohort of preterm children had reduced overall verbal capacity independent of morbidity, and a large variability in performance capacity that was associated with postnatal morbidity. The findings suggest that there are different mechanisms influencing the outcome of verbal and performance capacity in preterm children.     

Lung function in children born after foetal growth restriction and very preterm birth

Aims: To assess lung function at early school age in children delivered at very early gestation owing to intrauterine growth restriction and abnormal foetal blood flow (IUGR). Methods: Spirometry was performed at median age 8.4 (range 6.5–10.7) years in 31 children born preterm with IUGR (PT‐IUGR) with a median (range) birth weight (BW) of 650 (395–976) g and median (range) gestational age 27 (24–29) weeks. Control groups were matched for gender and age and had BW appropriate for gestational age (AGA); 31 children born preterm (PT‐AGA) with BW of 1010 (660–1790) g matched for gestational age at birth, and 31 children born at term (T‐AGA) with BW of 3530 (3000–4390) g. Results: The PT‐IUGR group had lower mean (SD) values of z‐scores for FEV₁, FEV₁/FVC and forced mid‐expiratory flow rate (FEF_25–75%) compared to the T‐AGA group, p = 0.003, p = 0.032 and p < 0.001, respectively, but did not differ from the PT‐AGA group. PT‐IUGR children delivered at ≥26 gestational weeks (GW) had lower FEF_25–75% than PT‐AGA children of corresponding GA, p = 0.014. Conclusion: Lung function was reduced in the PT‐IUGR group at early school age compared to controls born at term. The influence of IUGR on later lung function was only apparent in children born preterm after 26 GW.     

Improvement of developmental outcome between 24 and 36 months corrected age in very preterm infants

Aim: To study early developmental course in preschool‐aged very preterm infants and its association with perinatal risk factors and test‐taking behaviour. Methods: Children born <30 weeks gestation and/or <1000 g in the Academic Medical Center of Amsterdam were assessed at 24 and 36 months corrected age with the Dutch Bayley Scales of Infant Development‐II (BSID‐II‐NL) and neurological examination. Linear regression analyses for developmental change were performed with perinatal risk factors. Results: One hundred and forty‐six children, mean GA 28 weeks and mean birth weight 1043 g, participated. Mental and psychomotor scores improved significantly with 6 and 7 points, respectively, from 24 to 36 months (p < 0.01). Mild to severe problems on at least one domain occurred less often at 36 (32%) compared to 24 months (63%) (p < 0.01), using corrected scores. Mental improvement was associated with being born very small for gestational age or <28 weeks; psychomotor improvement was associated with not being treated with indomethacin. Difficult test behaviour occurred mostly at 24 months and was associated with non‐optimal development at 36 months. Conclusion: Improved developmental outcome and test behaviour were found at 36 compared to 24 months in a cohort of very preterm children. Long‐term outcome studies and retesting of behaviourally difficult children are recommended.     

Is it correct to correct? Developmental milestones in 555 "normal" preterm infants compared with term infants

To determine whether correction for preterm birth should be applied during developmental assessment, we conducted a prospective national survey of very premature infants (born at less than 32 weeks of gestation); neurodevelopment in the first 2 years was studied with the Dutch child health care developmental assessment. In 555 preterm children who had no evidence of handicap at 2 years of age, the age at which developmental milestones were reached was established. The results were compared with the results of the same assessment in Dutch children born at term. During the first year, the development of the very premature children equaled the development of normal children when full correction was applied. At 2 years of age, development was equal to or better than normal children's development without correction. We conclude that full correction for prematurity should be applied in the first year to avoid overreferral for developmental stimulation, whereas at 2 years of age correction is not necessary.     

Neurodevelopment of children born very preterm and free of severe disabilities: the Nord‐Pas de Calais Epipage cohort study

Aim: To describe the development of very preterm children free of cerebral palsy or severe sensory impairment in the domains of gross and fine motor functions, language and sociability at a corrected age of 2 years; to identify factors associated with performances in each domain. Methods: A total of 347 children born in 1997 before 33 weeks of gestation, part of the EPIPAGE population‐based cohort study, had their psychomotor development assessed with the Brunet‐Lezine scale. Results: The study population had a mean gestational age of 30.1 ± 2.0 weeks. Lower developmental quotients (DQ) were observed in the study group compared to the reference sample (96 ± 13 vs 104 ± 8, p < 0.01). Fine motor function, language and sociability were all affected with a p value <0.01. Multivariate analysis showed that duration of intubation and parents’ educational and occupational levels were the only variables significantly related to each developmental domain (p < 0.01). Conclusions: Children very preterm and free of severe disabilities had mild delays in multiple areas of development. The mechanisms by which neonatal factors played a role need further investigation. However socioeconomic status had a great impact on development and our results underline the need for improved support of socioeconomically disadvantaged parents after a preterm birth.     

Longitudinal assessment of infant lung function following pregnancies complicated by prolonged and preterm rupture of the membranes

Serial measurements of functional residual capacity (FRC) were made in 22 infants (median gestational age at delivery 32 weeks, range 25–40) during the first 2 years of life. All infants had been delivered from pregnancies complicated by prolonged and preterm rupture of the membranes (PPROM) of at least 1 week in duration. The onset of membrane rupture was at a median of 26 weeks (range 15–32) with a median duration of 5.5 weeks (range 1–21). The mean FRC at all postnatal ages studied: 25 ml/kg at 6 and 12 months and 24ml/kg at 18 and 24 months did not differ significantly from the control population (mean 24ml/kg). There was, however, a wider scatter of results in the study population: four infants born very preterm consistently had FRC results above the 95% confidence limits of the controls but only two infants had FRCs consistently below this range. These results suggest PPROM may not be an invariable association of abnormal antenatal lung growth.     

Pulmonary follow-up of moderately low birth weight infants with and without respiratory distress syndrome

Pulmonary function was measured in 18 children aged 6 to 9 years who had been born prematurely (mean birth weight 1760 +/- 555 g) and who had each received greater than 100 hours (mean 177 +/- 74 hours) of mechanical ventilation for respiratory distress syndrome (RDS). We used as controls 26 children aged 6 to 7 years who had been born prematurely (mean birth weight 1636 +/- 554 g) but who had required no treatment for pulmonary disease. Results for total lung capacity, FEV1, ratios of functional residual capacity and residual volume to total lung capacity, specific airway conductance, and alveolar plateau slope did not differ in the RDS and control groups. Eight of the 18 children in the RDS group had had radiologic evidence of bronchopulmonary dysplasia at 30 days and oxygen dependence at 30 days, but did not differ from the control group for any of the indices of pulmonary function. However, FEV1 and specific airway conductance were significantly reduced in the premature control group compared with children born at term. Therefore, factors associated with prematurity rather than combined effects of RDS and its treatment determined pulmonary function at age 6 to 9 years.     

Intrapartum magnesium sulfate exposure attenuates neutrophil function in preterm neonates

BACKGROUND: Prenatal exposure to magnesium sulfate, a drug that is frequently used for attempted tocolysis in preterm labor, could alter neutrophil functional activity in infants born preterm. OBJECTIVES: To determine the association between maternal tocolysis with magnesium sulfate and the cord blood neutrophil functional activity of preterm neonates. METHODS: The chemotaxis, random motility, and chemiluminescence of neutrophils were compared in the cord blood of 10 preterm neonates born to mothers tocolysed with magnesium sulfate, 10 preterm infants whose mothers had not received any tocolysis, and 10 term infants. Data regarding the maternal and neonatal magnesium and calcium levels were collected and analyzed in association with the cord blood neutrophil functional activity of the preterm infants. RESULTS: Neutrophil functional activity in the cord blood of the preterm neonates was significantly lower than in term neonates. However, the alteration of neutrophil chemotaxis, random motility and chemiluminescence was more noticeable in neonates with intrapartum exposure to magnesium sulfate as compared to preterm infants whose mothers received no tocolysis (30.9 +/- 2.3 vs. 36.7 +/- 2.7 microm, p < 0.01; 26.6 +/- 1.9 vs. 33.1 +/- 3.1 microm, p < 0.01; and 74.3 +/- 6.5 vs. 89.9 +/- 6.25 x 10(3) counts per min (cpm), p < 0.01, respectively). Furthermore, the reduction in neutrophil functional activity of preterm infants with intrapartum exposure to magnesium was directly correlated with the maternal serum magnesium levels (r = -0.90 to -0.85, p < 0.01). CONCLUSION: In infants born preterm, intrapartum exposure to magnesium sulfate is a risk factor contributing to the alteration in neutrophil motility and post-phagocytic bactericidal capacity.     

Chronic lung disease of prematurity and respiratory outcome at eight years of age

AIM: The study aimed to determine the respiratory outcome of children who had chronic lung disease of prematurity (CLD) compared with a preterm control group of children at school age. METHODS: Fifty-two preterm infants with CLD born between 26 and 33 weeks gestation were assessed regarding respiratory illness with 47 having lung function testing. Information regarding respiratory illness was obtained from 52 children in the birthweight-matched control group of whom 45 had lung function testing. The results were compared between the CLD and control groups. RESULTS: There was no difference in respiratory symptomatology between CLD groups and control preterm infants. On lung function testing, a significantly lower mean forced expiratory flow at 25-75% of vital capacity was identified compared with the preterm controls (P=0.024). This significant difference did not persist after bronchodilator therapy. There was no evidence of increased air trapping or bronchial hyper-reactivity in the CLD children compared with the controls. CONCLUSION: Lung function in CLD children is largely normal in comparison with preterm controls, apart from some evidence of reversible small airway obstruction. Respiratory symptomatology is not increased in chronic disease children in comparison with control preterm children.     

Mild prematurity and respiratory functions

Pulmonary function tests and bronchial reactivity to methacholine (MCH) were measured in 34 randomly selected prematures (21 males, 13 females; mean age 11.6 years; mean gestational age 34.9 weeks; mean birth weight 1980 g) and in 34 siblings (22 males, 12 females; mean age 12.5 years; mean gestational age 39.5 weeks; mean birth weight 3030 g). None had suffered neonatal respiratory distress syndrome or had been artificially ventilated. Prematurely born children had a residual volume (RV) and residual volume/total lung capacity (RV/TLC) significantly (P<0.01) increased compared to controls, although the mean values of both groups were still within the upper limits of normal. Furthermore, an increase of closing volume/vital capacity and closing capacity/total lung capacity (CC/TLC) was observed in most patients with increased RV and RV/TLC. No significant difference was observed for bronchial responsiveness to MCH between prematurely born and control children (11.8% and 5.9% of hyperreactive subjects, respectively). Maternal smoking during pregnancy was prevalent in prematures with impaired respiratory functions. In conclusion clinically normal children of smoking mothers who have survived prematurity but present some respiratory function impairment compared to their born-at-term siblings, should be fully informed and protected from risk factors for chronic obstructive pulmonary disease (COPD) in adult life.     

Ten-year follow-up of children born before 29 gestational weeks: health, cognitive development, behaviour and school achievement

Since the mid-1990s several studies have reported poor school performance in extremely preterm infants. The necessity to provide a full picture of the child's situation has been indicated. In a southern Swedish population 32,120 infants were born during the 2-y period 1985-1986. In total, 121 infants (0.4%) were reported liveborn before the 29th gestational wk and 12 (0.04%) were reported stillborn. Only 65 infants (50%) survived to the age of 10 y. The aim of this study was to evaluate the situation of extremely preterm (EPT) children at school, compared with that of full-term (FT) control children, at the age of 10 y. Health, cognitive development, school achievement and behaviour were measured. Ninety-two percent of the preterm children had no major neurological disability and most were in good health. The EPT children had an IQ of 90 +/- 15 vs 106 +/- 15 (mean +/- SD) for the FT children (p <0.001), and on the test of Visual-Motor Integration, the EPT children had 93.3 +/- 12.2 vs 109.6 +/- 14.2 for FT peers (p < 0.001). On both tests the differences between the groups corresponded to approximately one standard deviation. Thirty-eight percent of the EPT children performed below grade level at school. Thirty-two percent had general behavioural problems and 20% had attention deficit hyperactivity disorder, compared with 10% and 8%, respectively, in the FT group. EPT children require interventions to support their development and reduce behavioural problems.     

Childhood sequelae of infant lung disease: exercise and pulmonary function abnormalities after bronchopulmonary dysplasia

To determine the long-term pulmonary sequelae and effect on exercise tolerance of bronchopulmonary dysplasia (BPD), we studied 10 children at a mean age of 10.4 years, who had been born prematurely, survived respiratory distress syndrome, and subsequently developed BPD, and compared them with eight age-matched normal children born at term. Pulmonary function tests and graded exercise stress tests were performed. Residual volume, the ratio between residual volume and total lung capacity, vital capacity, forced expiratory volume in 1 second, forced expiratory flow between 25% and 75% of vital capacity, and maximal expiratory flows at 80%, 70%, and 60% of total lung capacity were all abnormal (P less than 0.02) in the children with BPD, compared with control values. Pre-exercise transcutaneous CO2 tension was higher (P less than 0.05) in the BPD group than in the control group. At maximal workload, tcPCO2 remained high in patients with BPD compared with control values (P less than 0.05). Arterial oxygen saturation at maximal workload fell below pre-exercise levels in the BPD group (P less than 0.05) but not in control children. There were no differences in maximal oxygen consumption between the BPD group and control children. Exercise-induced bronchospasm occurred in 50% of the BPD group, but not in the control group. We conclude that long-term survivors of BPD have evidence of airway obstruction, hyperinflation, and airway hyperreactivity, compared with a control group. Aerobic fitness was not significantly different in the BPD and control groups, but was achieved in the BPD group at the expense of a fall in SaO2 and a rise in tcPCO2.     

The influence of gestational age, size for dates, and prenatal steroids on cord transferrin levels in newborn infants

Serum transferrin levels assess protein status in older children and adults. To generate standards for its use in newborn infants, we measured umbilical cord serum transferrin levels in 161 appropriate (AGA), 25 large (LGA) and 16 small (SGA) for gestational age infants between 25 and 43 weeks' gestation. We also assessed the effects of intrauterine growth, exposure to prenatal steroids, and presence of pulmonary maturity on neonatal transferrin levels. Cord transferrin levels in AGA infants were significantly correlated with increasing gestational age (r = 0.60; p less than 0.001). Infants born before 37 weeks' gestation had significantly lower transferrin levels, when compared with those born at term (p less than 0.001). LGA infants had significantly higher levels than age-matched AGA infants (253 +/- 75 vs. 214 +/- 53 mg/dl; p less than 0.025). Despite significantly lower mean birth weights (p less than 0.001), SGA infants also had significantly higher levels than gestational age-matched AGA controls (227 +/- 63 vs. 167 +/- 40 mg/dl; p less than 0.005). For infants less than 35 weeks' gestation, neither the 20 preterm infants with exposure to prenatal steroids (maternal betamethasone), nor the 26 infants with pulmonary maturity had significantly elevated transferrin levels, when compared with gestational age-matched control infants. Newborn transferrin levels correlate well with gestational age and are significantly affected by size for dates, but not by a brief course of prenatal steroids or by pulmonary maturity.     

Serum Immunoglobulin Levels and Incidence of Infection During the First Year of Life in Full-term and Preterm Infants

IgG, IgM, and IgA concentrations from birth to 12 months of age, and the incidence of acute infectious processes were determined in 25 full-term and in 26 preterm infants by the single radioimmunodiffusion technique in a prospective study. Infants born at term showed significantly higher IgG levels than preterm babies up to 2 months of age (P less than 0.05) and the frequency of preterm babies with one or more acute infectious episodes during the same period of time was higher, mainly owing to pulmonary, oral mucosa, and ocular infections. The frequency of children with six or seven infectious episodes was also higher in the preterm group (P less than 0.05). IgM and IgA levels did not differ between groups. Even though preterm infants did not show serious bacterial disease or inability to produce antibodies, the incidence of infectious processes was higher in this group up to 2 months of age, a period during which serum IgG levels were lower than in the group of children born at term.