Surveillance of Surgical Site Infections following Major Hip and Knee Surgery in Finland

Background and aims. Since 1999, hospitals in the Finnish Hospital Infection Program (SIRO) have reported data on surgical site infections (SSI) following major hip and knee surgery. The purpose of this study was to obtain detailed information to support prevention efforts by analyzing SIRO data on SSIs, to evaluate possible factors affecting the surveillance results, and to assess the disease burden of postoperative prosthetic joint infections in Finland. Methods. Procedures under surveillance included total hip (THA) and total knee arthroplasties (TKA), and the open reduction and internal fixation (ORIF) of femur fractures. Hospitals prospectively collected data using common definitions and written protocol, and also performed postdischarge surveillance. In the validation study, a blinded retrospective chart review was performed and infection control nurses were interviewed. Patient charts of deep incisional and organ/space SSIs were reviewed, and data from three sources (SIRO, the Finnish Arthroplasty Register, and the Finnish Patient Insurance Centre) were linked for capture-recapture analyses. Results. During 1999-2002, the overall SSI rate was 3.3% after 11,812 orthopedic procedures (median length of stay, eight days). Of all SSIs, 56% were detected after discharge. The majority of deep incisional and organ/space SSIs (65/108, 60%) were detected on readmission. Positive and negative predictive values, sensitivity, and specificity for SIRO surveillance were 94% (95% CI, 89-99%), 99% (99-100%), 75% (56-93%), and 100% (97-100%), respectively. Of the 9,831 total joint replacements performed during 2001-2004, 7.2% (THA 5.2% and TKA 9.9%) of the implants were inserted in a simultaneous bilateral operation. Patients who underwent bilateral operations were younger, healthier, and more often males than those who underwent unilateral procedures. The rates of deep SSIs or mortality did not differ between bi- and uni-lateral THAs or TKAs. Four deep SSIs were reported following bilateral operations (antimicrobial prophylaxis administered 48-218 minutes before incision). In the three registers, altogether 129 prosthetic joint infections were identified after 13,482 THA and TKA during 1999-2004. After correction with the positive predictive value of SIRO (91%), a log-linear model provided an estimated overall prosthetic joint infection rate of 1.6% after THA and 1.3% after TKA. The sensitivity of the SIRO surveillance ranged from 36% to 57%. According to the estimation, nearly 200 prosthetic joint infections could occur in Finland each year (the average from 1999 to 2004) after THA and TKA. Conclusions. Postdischarge surveillance had a major impact on SSI rates after major hip and knee surgery. A minority of deep incisional and organ/space SSIs would be missed, however, if postdischarge surveillance by questionnaire was not performed. According to the validation study, most SSIs reported to SIRO were true infections. Some SSIs were missed, revealing some weakness in case finding. Variation in diagnostic practices may also affect SSI rates. No differences were found in deep SSI rates or mortality between bi- and unilateral THA and TKA. However, patient materials between these two groups differed. Bilateral operations require specific attention paid to their antimicrobial prophylaxis as well as to data management in the surveillance database. The true disease burden of prosthetic joint infections may be heavier than the rates from national nosocomial surveillance systems usually suggest.

The effects of low-intensity ultrasound in bioabsorbable self-reinforced poly-L-lactide -fixed cancellous bone fracture

The purpose of the present study was to investigate the effects of low-intensity ultrasound on bioabsorbable self-reinforced poly-L-lactide (SR-PLLA) screws and on fracture healing after SR-PLLA device fixation in experimental and clinical cancellous bone fracture. In the first experimental study, the assessment of the mechanical strengths of the SR-PLLA screws was performed after 12 weeks of daily 20-minute ultrasound exposure in vitro. In the second experimental study, 32 male Wistar rats with an experimental distal femur osteotomy fixed with an SR-PLLA rod were exposed for daily low-intensity ultrasound treatment for 21 days. The effects on the healing bone were assessed. The clinical studies consist of three prospective, randomized, and placebo-controlled series of dislocated lateral malleolar fractures fixed with one SR-PLLA screw. The total number of the patients in these series was 52. Half of the patients were provided randomly with a sham ultrasound device. The patients underwent ultrasound therapy 20 minutes daily for six weeks. Radiological bone healing was assessed both by radiographs at two, six, nine, and 12 weeks and by multidetector computed tomography (MDCT) scans at two weeks, nine weeks, and 18 months. Bone mineral density was assessed by dual-energy X-ray absorptiometry (DXA). The clinical outcome was assessed by both Olerud-Molander scoring and clinical examination of the ankle. Low-intensity ultrasound had no effects on the mechanical properties and degradation behaviour of the SR-PLLA screws in vitro. There were no obvious signs of low-intensity ultrasound-induced enhancement in the bone healing in SR-PLLA-rod-fixed metaphyseal distal femur osteotomy in rats. The biocompatibility of low-intensity ultrasound treatment and SR-PLLA was found to be good. In the clinical series low-intensity ultrasound was observed to have no obvious effects on the bone mineral density of the fractured lateral malleolus. There were no obvious differences in the radiological bone healing times of the SR-PLLA-screw-fixed lateral malleolar fractures after low-intensity ultrasound treatment. Low-intensity ultrasound did not have any effects on radiological bone morphology, bone mineral density or clinical outcome 18 months after the injury. There were no obvious findings in the present study to support the hypothesis that low-intensity pulsed ultrasound enhances bone healing in SR-PLLA-rod-fixed experimental metaphyseal distal femur osteotomy in rats or in clinical SR-PLLA-screw-fixed lateral malleolar fractures. It is important to limit the conclusions of the present set of studies only to lateral malleolar fractures fixed with an SR-PLLA screw.

Bone Health in Children and Adolescents with Juvenile Idiopathic Arthritis and Solid Organ Transplant

Osteoporosis is a skeletal disorder characterized by compromised bone strength that predisposes to increased fracture risk. Childhood and adolescence are critical periods for bone mass gain. Peak bone mass is mostly acquired by the age of 18 years and is an important determinant of adult bone health and lifetime risk for fractures. Medications, especially glucocorticoids (GCs), chronic inflammation, decreased physical activity, hormonal deficiencies, delayed puberty, and poor nutrition may predispose children and adolescents with a chronic disease to impaired bone health. In this work, we studied overall bone health, the incidence and prevalence of fractures in children and adolescents who were treated for juvenile idiopathic arthritis (JIA) or had undergone solid organ transplantation. The first study cohort included 62 patients diagnosed with JIA and treated with GCs. The epidemiology of fractures after transplantation was investigated in 196 patients and a more detailed analysis of bone health determinants was performed on 40 liver (LTx) and 106 renal (RTx) transplantation patients. Bone mineral density (BMD) and vertebral morphology were assessed by dual-energy x-ray absorptiometry. Standard radiographs were obtained to detect vertebral fractures and to determine bone age; BMD values were adjusted for skeletal maturity. Our study showed that median BMD values were subnormal in all patient cohorts. The values were highest in patients with JIA and lowest in patients with LTx. Age at transplantation influenced BMD values in LTx but not RTx patients; BMD values were higher in patients who had LTx before the age of two years. BMD was lowest during the immediate posttransplantation years and increased subnormally during puberty. Delayed skeletal maturation was common in all patient groups. The prevalence of vertebral fractures ranged from 10% to 19% in the cohorts. Most of the fractures were asymptomatic and diagnosed only at screening. Vertebral fractures were most common in LTx patients. Vitamin D deficiency was common in all patient groups, and only 3% of patients with JIA and 25% of transplantation patients were considered to have adequate serum vitamin D levels. The total cumulative weight-adjusted dose of GC was not associated with BMD values in JIA or LTx patients. The combination of female gender and age over 15 years, parathyroid hormone concentration over 100 ng/L, and cumulative weight-adjusted methylprednisolone dose over 150 mg/kg during the three preceding years were found to be important predictors for low lumbar spine BMD in RTx patients. Based on the high prevalence of osteoporosis in the study cohorts more efforts should be put to prevention and early diagnosis of osteoporosis in these pediatric patients.

Shwachman-Diamond syndrome : Clinical, genetic and radiological study

Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder in which the cardinal symptoms arise from exocrine pancreatic insufficiency and bone marrow dysfunction. Previous studies have suggested increased risk of fatal complications among Finnish SDS infants. The genetic defect responsible for the disease was recently identified; the SBDS gene is located at chromosome 7q11 and encodes a protein that is involved in ribosome biosynthesis. The discovery of the SBDS gene has opened new insights into the pathogenesis of this multi-organ disease. This study aimed to assess phenotypic and genotypic features of Finnish patients with SDS. Seventeen Finnish patients with a clinical diagnosis of SDS were included in the study cohort. Extensive clinical, biochemical and imaging assessments were performed to elucidate the phenotypic features, and the findings were correlated with the SBDS genotype. Imaging studies included abdominal magnetic reso-nance imaging (MRI), brain MRI, cardiac echocardiography including tissue Doppler examination, and cardiac MRI. The skeletal phenotype was assessed by dual-energy X-ray absorptiometry and bone histomorphometry. Twelve patients had mutations in the SBDS gene. In MRI, a characteristic pattern of fat-replaced pancreas with occasional enhancement of scattered parenchymal foci and of pancreatic duct was noted in the SBDS mutation-positive patients while the mutation-negative patients did not have pancreatic fat accumulation. The patients with SBDS mutations had significantly reduced bone mineral density associated with low-energy peripheral fractures and vertebral compression fractures. Bone histomorphometry confirmed low-turnover osteoporosis. The patients with SBDS mutations had learning difficulties and smaller head size and brain volume than control subjects. Corpus callosum, cerebellar vermis, and pos-terior fossa structures were significantly smaller in SDS patients than in controls. Patients with SDS did not have evidence of clinical heart disease or myocardial fibrosis. However, subtle diastolic changes in the right ventricle and exercise-induced changes in the left ventricle contractile reserve were observed. This study expanded the phenotypic features of SDS to include primary low-turnover osteoporosis and structural alterations in the brain. Pancreatic MRI showed characteristic changes in the SBDS mutation-positive patients while these were absent in the mutation-negative patients, suggesting that MRI can be used to differentiate patients harbouring SBDS mutations from those without mutations. No evidence for clinical cardiac manifestations was found, but imaging studies revealed slightly altered myocardial function that may have clinical implications. These findings confirm the pleiotropic nature of SDS and underscore the importance of careful multidisciplinary follow-up of the affected individuals.

Bone health and vitamin D status in children with motor disability and adults with intellectual disability

Osteoporosis is not only a disease of the elderly, but is increasingly diagnosed in chronically ill children. Children with severe motor disabilities, such as cerebral palsy (CP), have many risk factors for osteoporosis. Adults with intellectual disability (ID) are also prone to low bone mineral density (BMD) and increased fractures. This study was carried out to identify risk factors for low BMD and osteoporosis in children with severe motor disability and in adults with ID. In this study 59 children with severe motor disability, ranging in age from 5 to 16 years were evaluated. Lumbar spine BMD was measured with dual-energy x-ray absorptiometry. BMD values were corrected for bone size by calculating bone mineral apparent density (BMAD), and for bone age. The values were transformed into Z-scores by comparison with normative data. Spinal radiographs were assessed for vertebral morphology. Blood samples were obtained for biochemical parameters. Parents were requested to keep a food diary for three days. The median daily energy and nutrient intakes were calculated. Fractures were common; 17% of the children had sustained peripheral fractures and 25% had compression fractures. BMD was low in children; the median spinal BMAD Z-score was -1.0 (range -5.0 – +2.0) and the BMAD Z-score <-2.0 in 20% of the children. Low BMAD Z-score and hypercalciuria were significant risk factors for fractures. In children with motor disability, calcium intakes were sufficient, while total energy and vitamin D intakes were not. In the vitamin D intervention studies, 44 children and adolescents with severe motor disability and 138 adults with ID were studied. After baseline blood samples, the children were divided into two groups; those in the treatment group received 1000 IU peroral vitamin D3 five days a week for 10 weeks, and subjects in the control group continued with their normal diet. Adults with ID were allocated to receive either 800 IU peroral vitamin D3 daily for six months or a single intramuscular injection of 150 000 IU D3. Blood samples were obtained at baseline and after treatment. Serum concentrations of 25-OH-vitamin D (S-25-OHD) were low in all subgroups before vitamin D intervention: in almost 60% of children and in 77% of adults the S-25-OHD concentration was below 50 nmol/L, indicating vitamin D insufficiency. After vitamin D intervention, 19% of children and 42% adults who received vitamin D perorally and 12% of adults who received vitamin D intramuscularly had optimal S-25-OHD (>80 nmol/L). This study demonstrated that low BMD and peripheral and spinal fractures are common in children with severe motor disabilities. Vitamin D status was suboptimal in the majority of children with motor disability and adults with ID. Vitamin D insufficiency can be corrected with vitamin D supplements; the peroral dose should be at least 800 IU per day.

Primary Dislocation of the Patella : A Clinical Study

A total of 177 patients with primary dislocation of the patella (PDP) were admitted to two trauma centers in Helsinki, Finland during 1991 to 1992. The inclusion criteria were: 1. Acute (≤14 days old) first-time lateral dislocation of the patella. 2. No previous knee operations or major knee injuries. 3. No ligament injuries to be repaired. 4. No osteochondral fractures requiring fixation. 50 patients were excluded. 30 of these excluded patients would have met the inclusion criteria, 19 patients received treatment by consultants not involved in the study, 7 refused to participate and 4 had an erroneous randomization. 127 patients including, 82 females, were then randomized to have either tailor-made operative procedure (group O) or conservative treatment (group C). The aftercare was similar for both groups. The mean age of the patients was 20 (9-47) years. All patients were subjected to analysis of trauma history (starting position and knee movement during the dislocation), examination under anesthesia (EUA) and arthroscopy. 70 patients (52 females) were randomized by their odd year of birth to operative group O and 57 patients (30 females) by their even year of birth to conservative group C. The diagnosis of PDP was based on locked dislocation in 68 patients, on dislocatability in EUA in 47 patients, and on subluxation in EUA combined with typical intra-articular lesions in 12 patients. In group O, 63 patients had exploration of the injuries on the medial side of the knee and tailor made reconstruction added with lateral release in 54 cases. The medial injury was operated by suturing in 39 patients, by duplication in 18 patients and by additional augmentation of the medial patellofemoral ligament (MPFL) with adductor magnus tenodesis in 6 patients. 7 patients, without locking in trauma history and only subluxation in EUA had only lateral release for realignment. In adductor magnus tenodesis the proximal end of the distal tendinous part was rerouted to the upper medial border of the patella. In the conservative group C, the treatment was adjusted to the extent of patellar displacement in EUA. Patients with dislocation in EUA had 3 weeks’ immobilization with the knee in slight flexion. Mobilization was started with a soft patellar stabilizing orthosis (PSO) used for additional three weeks. The patients with subluxation in EUA wore an orthosis for six weeks. The aftercare was similar in group O. The outcome was similar in both groups. After an average of 25 (20-45) months´ follow-up, the subjective result was better in group C in respect of the mean Hughston VAS knee score (87 for group O and 90 for group C, p=0.04, visual analog scale), but similar in terms of the patient’s own overall opinion and the mean Lysholm II knee score. Recurrent instability episodes occurred in 18 patients in group O and in 20 patients in group C. After an average of 7 (6-9) years´ follow-up, the groups did not show statistical difference either in respect of the patient’s own overall opinion, or the mean Hughston VAS and Kujala knee scores. The proportions of stable patellae was 25/70 (36%) in group O and 17/57 (30%) in group O (p=0.5). In a multivariate risk analysis, there was a correlation between low Kujala score (<90) as dependent parameter and female gender (OR: 3.5; 95% CI: 1.4-9.0), and loose body on primary radiographs (OR: 4.1; 95% CI: 1.2-15). Recurrent instability correlated with young age at the time of PDP (OR: 0.9; 95% CI: 0.8-1.0/year). Girls with open tibial apophysis had the worst prognosis for instability (88%; 95% CI: 77-98). The most common mechanisms in trauma history of the patients were movement to flexion from a straight start (78%) and movement to extension from a well-bent start (8%). Spontaneous relocation of the patella had taken place in 13/39 of girls, in 11/21 of boys, in 26/42 of women and in 17/24 of men with skeletal maturity of the tibia. The dislocation in EUA was non-rotating in 96/126 patients followed by outward rotating dislocation in 14/126 patients. Operative treatment policy in PDP is not recommended. Locking tendency of the patella in PDP depended on the skeletal maturation. Recurrence rate after PDP was higher than expected.

Bioabsorbable materials for osteosynthesis and small joint arthroplasty in the hand

Fractures and arthritic joint destruction are common in the hand. A reliable and stable fracture fixation can be achieved by metal implants, which however, become unnecessary or even harmful after consolidation. The silicone implant arthroplasty is the current method of choice for reconstruction of metacarpophalangeal joints in rheumatoid patients. However, the outcome tends to worsen with long-term follow-up and implant-related complications become frequent. To address these problems, bioabsorbable implants were designed for the hand area. Aims of the studies were: 1) to evaluate the biomechanical stabilities provided by self- reinforced (SR) bioabsorbable implants in a transverse and an oblique osteotomy of small tubular bones and to compare them with those provided by metal implants; 2) to evaluate the SR poly-L/DL-lactide 70/30 plate for osteosynthesis in a proof-of-principle type of experiment in three cases of hand injuries; and 3) to evaluate the poly-L/D-lactide (PLA) 96/4 joint scaffold, a composite joint implant with a supplementary intramedullary Polyactive® stem and Swanson silicone implant in an experimental small joint arthroplasty model. Methods used were: 1) 112 fresh frozen human cadaver and 160 pig metacarpal bones osteotomised transversally or obliquely, respectively, and tested ex vivo in three point bending and in torsion; 2) three patient cases of complex hand injuries; and 3) the fifth metacarpophalangeal joints reconstructed in 18 skeletally-mature minipigs and studied radiologically and histologically. The initial fixation stabilities provided by bioabsorbable implants in the tubular bones of the hand were comparable with currently-employed metal fixation techniques, and were sufficient for fracture stabilisation in three preliminary cases in the hand. However, in torsion the stabilities provided by bioabsorbable implants were lower than that provided by metal counterparts. The bioabsorbable plate enhanced the bending stability for the bioabsorbable fixation construct. PLA 96/4 joint scaffolds demonstrated good biocompatibility and enabled fibrous tissue in-growth in situ. After scaffold degradation, a functional, stable pseudarthrosis with dense fibrous connective tissue was formed. However, the supplementary Polyactive® stem caused a deleterious tissue reaction and therefore the stem can not be applied to the composite joint implant. The bioabsorbable implants have potential for use in clinical hand surgery, but have to await validation in clinical patient series and controlled trials.

Genetic variation in the LDL receptor-related protein 5 (LRP5) gene : Association with bone health and metabolic parameters

Bone mass accrual and maintenance are regulated by a complex interplay between genetic and environmental factors. Recent studies have revealed an important role for the low-density lipoprotein receptor-related protein 5 (LRP5) in this process. The aim of this thesis study was to identify novel variants in the LRP5 gene and to further elucidate the association of LRP5 and its variants with various bone health related clinical characteristics. The results of our studies show that loss-of-function mutations in LRP5 cause severe osteoporosis not only in homozygous subjects but also in the carriers of these mutations, who have significantly reduced bone mineral density (BMD) and increased susceptibility to fractures. In addition, we demonstrated for the first time that a common polymorphic LRP5 variant (p.A1330V) was associated with reduced peak bone mass, an important determinant of BMD and osteoporosis in later life. The results from these two studies are concordant with results seen in other studies on LRP5 mutations and in association studies linking genetic variation in LRP5 with BMD and osteoporosis. Several rare LRP5 variants were identified in children with recurrent fractures. Sequencing and multiplex ligation-dependent probe amplification (MLPA) analyses revealed no disease-causing mutations or whole-exon deletions. Our findings from clinical assessments and family-based genotype-phenotype studies suggested that the rare LRP5 variants identified are not the definite cause of fractures in these children. Clinical assessments of our study subjects with LPR5 mutations revealed an unexpectedly high prevalence of impaired glucose tolerance and dyslipidaemia. Moreover, in subsequent studies we discovered that common polymorphic LRP5 variants are associated with unfavorable metabolic characteristics. Changes in lipid profile were already apparent in pre-pubertal children. These results, together with the findings from other studies, suggest an important role for LRP5 also in glucose and lipid metabolism. Our results underscore the important role of LRP5 not only in bone mass accrual and maintenance of skeletal health but also in glucose and lipid metabolism. The role of LRP5 in bone metabolism has long been studied, but further studies with larger study cohorts are still needed to evaluate the specific role of LRP5 variants as metabolic risk factors.

Magnetic resonance imaging and ultrasonography in brachial plexus birth injury

Brachial plexus birth injury (BPBI) is caused by stretching, tearing or avulsion of the C5-C8 or Th1 nerve roots during delivery. Foetal-maternal disproportion is the main reason for BPBI. The goal of this study was to find out the incidence of posterior subluxation of the humeral head during first year of life in BPBI and optimal timing of the ultrasonographic screening of the glenohumeral joint. The glenohumeral congruity and posterior subluxation of the humeral head associated to muscle atrophy were assessed and surgical treatment of the shoulder girdle as well as muscle changes in elbow flexion contracture were evaluated. The prospective, population based part of the study included all neonates born in Helsinki area during years 2003-2006. Patients with BPBI sent to the Hospital for Children and Adolescents because of decreased external rotation, internal rotation contracture or deformation of the glenohumeral joint as well as patients with elbow flexion contracture were also included in this prospective study. The incidence of BPBI was calculated to be 3.1/1000 newborns in Helsinki area. About 80% of the patients with BPBI recover totally during the follow-up within the first year of life. Permanent plexus injury at the age of one year was noted in 20% of the patients (0.64/1000 newborns). Muscle imbalance resulted in sonographically detected posterior subluxation in one third of the patients with permanent BPBI. If muscle imbalance and posterior subluxation are left untreated bony deformities will develop. All patients with internal rotation contracture of the glenohumeral joint presented muscle atrophy of the rotator cuff muscles. Especially subscapular and infraspinous muscles were affected. A correlation was found particularly between greatest thickness of subscapular muscle and subluxation of the humeral head, degree of glenoid retroversion, as well as amount of internal rotation contracture. Supinator muscle atrophy was evident among all the studied patients with elbow flexion contracture. Brachial muscle pathology seemed to be an important factor for elbow flexion contracture in BPBI. Residual dysfunction of the upper extremity may require operative treatment such as tendon lengthening, tendon transfers, relocation of the humeral head or osteotomy of the humerus. Relocation of the humeral head improved the glenohumeral congruency among patients under 5 years of age. Functional improvement without remodeling of the glenohumeral joint was achieved by other reconstructive procedures. In conclusion: Shoulder screening by US should be done to all patients with permanent BPBI at the age of 3 and 6 months. Especially atrophy of the subscapular muscle correlates with glenohumeral deformity and posterior subluxation of the humeral head, which has not been reported in previous studies. Permanent muscle changes are the main reason for diminished range of motion of the elbow and forearm. Relocation of the humeral head, when needed, should be performed under the age of 5 years.

Preterm birth and risk factors for chronic disease : Helsinki Study of Very Low Birth Weight Adults

Background: The improved prognosis of early preterm birth has created a generation of surviving very low birth weight (< 1500 g, VLBW) infants whose health risks in adulthood are poorly known. Of every 1000 live-born infants in Finland, about 8 are born at VLBW. Variation in birth weight, even within the normal range, relates to considerable variation in the risk for several common adult disorders, including cardiovascular disease and osteoporosis. Small preterm infants frequently exhibit severe postnatal or prenatal growth retardation, or both. Much reason for concern thus exists, regarding adverse health effects in surviving small preterm infants later lives. We studied young adults, aiming at exploring whether VLBW birth and postnatal events after such a birth are associated with higher levels of risk factors for cardiovascular disease or osteoporosis. Subjects and Methods: A follow-up study for VLBW infants began in 1978; by the end of 1985, 335 VLBW survivors at Helsinki University Central Hospital participated in the follow-up. Their gestational ages ranged from 24 to 35 weeks, mean 29.2 and standard deviation 2.2 weeks. In 2004, we invited for a clinic visit 255 subjects, aged 18 to 27, who still lived in the greater Helsinki area. From the same birth hospitals, we also invited 314 term-born controls of similar age and sex. These two study groups underwent measurements of body size and composition, function of brachial arterial endothelium (flow-mediated dilatation, FMD) and carotid artery intima-media thickness (cIMT) by ultrasound. In addition, we measured plasma lipid concentrations, ambulatory blood pressure, fasting insulin, glucose tolerance and, by dual-energy x-ray densitometry, bone-mineral density. Results: 172 control and 166 VLBW participants underwent lipid measurements and a glucose tolerance test. VLBW adults fasting insulin (adjusted for body mass index) was 12.6% (95% confidence interval, 0.8 to 25.8) higher than that of the controls. The glucose and insulin concentrations 120 minutes after 75 g glucose ingestion showed similar differences (N=332) (I). VLBW adults had 3.9 mmHg (1.3 to 6.4) higher office systolic blood pressure, 3.5 mmHg (1.7 to 5.2) higher office diastolic blood pressure (I), and, when adjusted for body mass index and height, 3.1 mmHg (0.5 to 5.5) higher 24-hour mean systolic blood pressure (N=238) (II). VLBW birth was associated neither with HDL- or total cholesterol nor triglyceride concentrations (N=332) (I), nor was it associated with a low FMD or a high cIMT (N=160) (III). VLBW adults had 0.51-unit (0.28 to 0.75) lower lumbar spine Z scores and 0.56-unit (0.34 to 0.78) lower femoral neck Z scores (N=283). Adjustments for size attenuated the differences, but only partially (IV). Conclusions: These results imply that those born at VLBW, although mostly healthy as young adults, already bear several risk factors for chronic adult disease. The significantly higher fasting insulin level in adults with VLBW suggests increased insulin resistance. The higher blood pressure in young adults born at VLBW may indicate they later are at risk for hypertension, although their unaffected endothelial function may be evidence for some form of protection from cardiovascular disease. Lower bone mineral density around the age of peak bone mass may suggest increased risk for later osteoporotic fractures. Because cardiovascular disease and osteoporosis are frequent, and their prevention is relatively cheap and safe, one should focus on prevention now. When initiated early, preventive measures are likely to have sufficient time to be effective in preventing or postponing the onset of chronic disease.

Preterm birth and risk factors for chronic disease : Helsinki Study of Very Low Birth Weight Adults

Background: The improved prognosis of early preterm birth has created a generation of surviving very low birth weight (PIENEMPI KUIN 1500 g, VLBW) infants whose health risks in adulthood are poorly known. Of every 1000 live-born infants in Finland, about 8 are born at VLBW. Variation in birth weight, even within the normal range, relates to considerable variation in the risk for several common adult disorders, including cardiovascular disease and osteoporosis. Small preterm infants frequently exhibit severe postnatal or prenatal growth retardation, or both. Much reason for concern thus exists, regarding adverse health effects in surviving small preterm infants later lives. We studied young adults, aiming at exploring whether VLBW birth and postnatal events after such a birth are associated with higher levels of risk factors for cardiovascular disease or osteoporosis. Subjects and Methods: A follow-up study for VLBW infants began in 1978; by the end of 1985, 335 VLBW survivors at Helsinki University Central Hospital participated in the follow-up. Their gestational ages ranged from 24 to 35 weeks, mean 29.2 and standard deviation 2.2 weeks. In 2004, we invited for a clinic visit 255 subjects, aged 18 to 27, who still lived in the greater Helsinki area. From the same birth hospitals, we also invited 314 term-born controls of similar age and sex. These two study groups underwent measurements of body size and composition, function of brachial arterial endothelium (flow-mediated dilatation, FMD) and carotid artery intima-media thickness (cIMT) by ultrasound. In addition, we measured plasma lipid concentrations, ambulatory blood pressure, fasting insulin, glucose tolerance and, by dual-energy x-ray densitometry, bone-mineral density. Results: 172 control and 166 VLBW participants underwent lipid measurements and a glucose tolerance test. VLBW adults fasting insulin (adjusted for body mass index) was 12.6% (95% confidence interval, 0.8 to 25.8) higher than that of the controls. The glucose and insulin concentrations 120 minutes after 75 g glucose ingestion showed similar differences (N=332) (I). VLBW adults had 3.9 mmHg (1.3 to 6.4) higher office systolic blood pressure, 3.5 mmHg (1.7 to 5.2) higher office diastolic blood pressure (I), and, when adjusted for body mass index and height, 3.1 mmHg (0.5 to 5.5) higher 24-hour mean systolic blood pressure (N=238) (II). VLBW birth was associated neither with HDL- or total cholesterol nor triglyceride concentrations (N=332) (I), nor was it associated with a low FMD or a high cIMT (N=160) (III). VLBW adults had 0.51-unit (0.28 to 0.75) lower lumbar spine Z scores and 0.56-unit (0.34 to 0.78) lower femoral neck Z scores (N=283). Adjustments for size attenuated the differences, but only partially (IV). Conclusions: These results imply that those born at VLBW, although mostly healthy as young adults, already bear several risk factors for chronic adult disease. The significantly higher fasting insulin level in adults with VLBW suggests increased insulin resistance. The higher blood pressure in young adults born at VLBW may indicate they later are at risk for hypertension, although their unaffected endothelial function may be evidence for some form of protection from cardiovascular disease. Lower bone mineral density around the age of peak bone mass may suggest increased risk for later osteoporotic fractures. Because cardiovascular disease and osteoporosis are frequent, and their prevention is relatively cheap and safe, one should focus on prevention now. When initiated early, preventive measures are likely to have sufficient time to be effective in preventing or postponing the onset of chronic disease.