Protection against varicella with two doses of combined measles-mumps-rubella-varicella vaccine or one dose of monovalent varicella vaccine: 10-year follow-up of a phase 3 multicentre, observer-blind, randomised, controlled trial.

BACKGROUND: The duration of protection provided by varicella vaccines is unclear. We assessed the 10-year vaccine efficacy of two doses of a combined measles-mumps-rubella-varicella vaccine (MMRV), one live attenuated varicella vaccine (V) dose given after one measles-mumps-rubella vaccine (MMR) dose (MMR + V), versus two MMR doses (control vaccine) for the prevention of confirmed varicella. METHODS: This was a phase 3b follow-up of an observer-blinded, randomised, controlled trial. In phase a, children aged 12-22 months (at first vaccination) from Czech Republic (Czechia), Greece, Italy, Lithuania, Norway, Poland, Romania, Russia, Slovakia, and Sweden were randomly assigned by computer-generated randomisation list (3:3:1) to receive two doses of MMRV, one dose of MMR and one dose of varicella vaccine, or two doses of MMR, 42 days apart. Varicella cases were confirmed by detection of viral DNA, or epidemiological link and clinical assessment, by an independent data monitoring committee; disease severity was based on a modified Vázquez scale. Hazard ratios for MMRV and MMR + V versus MMR estimated in the per-protocol cohort using a Cox proportional hazards regression model were used to calculate vaccine efficacy and 95% CI. Serious adverse events were recorded throughout the study in all vaccinated children. Study objectives were secondary and descriptive. The trial is registered at ClinicalTrials.gov, number NCT00226499. FINDINGS: Between Sept 1, 2005, and May 10, 2006, 5803 children (mean age 14·2 months, SD 2·5) were vaccinated. The per-protocol cohort included 2279 children from the MMRV group, 2266 from the MMR + V group, and 744 from the MMR group. From baseline to a median follow-up of 9·8 years, 76 (3%) children in the MMRV group, 469 (21%) in the MMR + V group, and 352 (47%) in the MMR group had varicella. Vaccine efficacy against all varicella was 95·4% (95% CI 94·0-96·4) for MMRV and 67·2% (62·3-71·5) for MMR + V; vaccine efficacy against moderate or severe varicella was 99·1% (97·9-99·6) for MMRV and 89·5% (86·1-92·1) for MMR + V. During phase b, serious adverse events were reported by 290 (15%) of 1961 children in the MMRV group, 317 (16%) of 1978 in the MMR + V group, and 93 (15%) of 641 in the MMR group. There were no treatment-related deaths. INTERPRETATION: The 10-years vaccine efficacy observed, suggests that a two-dose schedule of varicella vaccine provided optimum long-term protection for the prevention of varicella by offering individual protection against all severities of disease and leading to a potential reduction in transmission, as observed in the US experience with universal mass vaccination. FUNDING: GlaxoSmithKline Biologicals.

Protection against varicella with two doses of combined measles-mumps-rubella-varicella vaccine versus one dose of monovalent varicella vaccine: a multicentre, observer-blind, randomised, controlled trial.

BACKGROUND: Rates of varicella have decreased substantially in countries implementing routine varicella vaccination. Immunisation is possible with monovalent varicella vaccine or a combined measles-mumps-rubella-varicella vaccine (MMRV). We assessed protection against varicella in naive children administered one dose of varicella vaccine or two doses of MMRV. METHODS: This study was done in ten European countries with endemic varicella. Healthy children aged 12-22 months were randomised (3:3:1 ratio, by computer-generated randomisation list, with block size seven) to receive 42 days apart (1) two doses of MMRV (MMRV group), or (2) MMR at dose one and monovalent varicella vaccine at dose two (MMR+V group), or (3) two doses of MMR (MMR group; control). Participants and their parents or guardians, individuals involved in assessment of any outcome, and sponsor staff involved in review or analysis of data were masked to treatment assignment. The primary efficacy endpoint was occurrence of confirmed varicella (by detection of varicella zoster virus DNA or epidemiological link) from 42 days after the second vaccine dose to the end of the first phase of the trial. Cases were graded for severity. Efficacy analyses were per protocol. Safety analyses included all participants who received at least one vaccine dose. This trial is registered with ClinicalTrials.gov, number NCT00226499. FINDINGS: Between Sept 1, 2005, and May 10, 2006, 5803 children (mean age 14·2 months, SD 2·5) were vaccinated. In the efficacy cohort of 5285 children, the mean duration of follow-up in the MMRV group was 36 months (SD 8·8), in the MMR+V group was 36 months (8·5) and in the MMR group was 35 months (8·9). Varicella cases were confirmed for 37 participants in the MMRV group (two moderate to severe), 243 in the MMR+V group, and 201 in the MMR group. Second cases occurred for three participants (all in the MMR+V group). Varicella cases were moderate to severe for two participants in the MMRV group, 37 in the MMR+V group (one being a second case that followed a mild first case); and 117 in the MMR group. Efficacy of two-dose MMRV against all varicella was 94·9% (97·5% CI 92·4-96·6), and against moderate to severe varicella was 99·5% (97·5-99·9). Efficacy of one-dose varicella vaccine against all varicella was 65·4% (57·2-72·1), and against moderate to severe varicella (post hoc) was 90·7% (85·9-93·9). The most common adverse event in all groups was injection-site redness (up to 25% of participants). Within 15 days after dose one, 57·4% (95% CI 53·9-60·9) of participants in the MMRV group reported fever of 38°C or more, by contrast with 44·5% (41·0-48·1) with MMR+V, and 39·8% (33·8-46·1) with MMR. Eight serious adverse events were deemed related to vaccination (three MMRV, four MMR+V, one MMR). All resolved within the study period. INTERPRETATION: These results support the implementation of two-dose varicella vaccination on a short course, to ensure optimum protection from all forms of varicella disease. FUNDING: GlaxoSmithKline Vaccines.

Burden of severe rotavirus disease leading to hospitalization assessed in a prospective cohort study in Sweden.

BACKGROUND: The aim of this prospective cohort study was to estimate the burden of severe disease caused by rotavirus-induced gastroenteritis in Swedish children aged < 5 y. METHODS: Rotavirus-positive children admitted to hospitals serving 3 geographical regions with 155,838 children aged < 5 y, were offered inclusion in this 1-year study. Rotavirus strains identified were genotyped using multiplex PCR. Disease progression was documented through interviews and chart reviews. RESULTS: In total, 604 children with rotavirus-induced gastroenteritis were included in the study. Forty-nine of 604 (8.1%) fulfilled the criteria for nosocomial infection. The minimum incidence was 388 per 100,000, with significant variability between study regions, ranging from 280 to 542 per 100,000. In all regions, the peak season occurred in February-April, but the season start varied, with first cases observed in October in the eastern region and December in the northern region. Genotypes identified differed between the regions: G1[P8] was most prevalent in all regions (77%), while the most varied pattern was observed in the western region, with G1[P8] observed in 61%, G4[P8] in 13%, G9[P8] in 10%, G2[P4] in 8%, and G3[P8] in 8% of the children. The median age of hospitalized children was 14 months and the median total duration of diarrhoea was 6.9 days. Sixty-eight percent reported a temperature > 38.5°C upon admission. Complications occurred in > 10% of the children, with hypertonic dehydration (32/604) and seizures (10/604) occurring most frequently. CONCLUSIONS: Rotaviruses may cause severe febrile acute gastroenteritis leading to dehydration requiring acute rehydration in hospital. In addition, further complications occurred in > 10% of hospitalized children.

Early infections are associated with increased risk for celiac disease: an incident case-referent study.

BACKGROUND: Celiac disease is defined as a 'chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals'. Sweden has experienced an "epidemic" of celiac disease in children below two years of age. Celiac disease etiology is considered multifactorial; however, little is known regarding potential risk- or protecting factors. We present data on the possible association between early infectious episodes and celiac disease, including their possible contribution to the Swedish celiac disease epidemic. METHODS: A population-based incident case-referent study (475 cases, 950 referents) with exposure information obtained via a questionnaire (including family characteristics, infant feeding, and the child's general health) was performed. Celiac disease cases were diagnosed before two years of age, fulfilling the diagnostic criteria of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition. Referents were randomly selected from the national population register after fulfilling matching criteria. The final analyses included 954 children, 373 (79%) cases and 581 (61%) referents, with complete information on main variables of interest in a matched set of one case with one or two referents. RESULTS: Having three or more parental-reported infectious episodes, regardless of type of infection, during the first six months of life was associated with a significantly increased risk for later celiac disease, and this remained after adjusting for infant feeding and socioeconomic status (odds ratio [OR] 1.5; 95% confidence interval [CI], 1.1-2.0; P=0.014). The celiac disease risk increased synergistically if, in addition to having several infectious episodes, infants were introduced to dietary gluten in large amounts, compared to small or medium amounts, after breastfeeding was discontinued (OR 5.6; 95% CI, 3.1-10; P<0.001). CONCLUSION: This study suggests that having repeated infectious episodes early in life increases the risk for later celiac disease. In addition, we found a synergistic effect between early infections and daily amount of gluten intake, more pronounced among infants for whom breastfeeding had been discontinued prior to gluten introduction. Regarding contribution to the Swedish celiac disease epidemic, which partly was attributed to concurrent changes in infant feeding, early infections probably made a minor contribution via the synergistic effect with gluten amount.

Early vaccinations are not risk factors for celiac disease.

OBJECTIVES: To investigate if changes in the national Swedish vaccination program coincided with changes in the celiac disease (CD) incidence rate in infants (ie, the Swedish CD Epidemic), and to assess the potential association between these vaccinations and CD risk. METHODS: All studies were based on the National Swedish Childhood Celiac Disease Register. Using an ecological approach, we plotted changes over time in the national vaccination program in the graph displaying CD incidence rate. A population-based incident case-referent study of invited infants was performed. Exposure information was received through a questionnaire and child health clinic records. Vaccines explored were diphtheria/tetanus, pertussis (acellular), polio (inactivated), Haemophilus influenzae type b (conjugated), measles/mumps/rubella, and live attenuated bacillus Calmette-Guérin (BCG) in children with increased tuberculosis risk. Findings were subjected to a birth cohort analysis. RESULTS: Introduction of pertussis vaccine coincided in time with decreasing CD incidence rates. In the infant case-referent study, however, neither vaccination against pertussis (odds ratio 0.91; 95% confidence interval 0.60-1.4), nor against Haemophilus influenzae type b or measles/mumps/rubella was associated with CD. Coverage for the diphtheria/tetanus and polio vaccines was 99%. BCG was associated with reduced risk for CD (adjusted odds ratio 0.54; 95% confidence interval 0.31-0.94). Discontinuation of general BCG vaccination did not affect the cumulative incidence of CD at age 15 years. CONCLUSIONS: Early vaccinations within the national Swedish program were not associated with CD risk, nor could changes in the program explain the Swedish epidemic. A protective effect by BCG was suggested, which could be subject to further studies.

Robustness of the healthcare utilization results from the Rotavirus Efficacy and Safety Trial (REST) evaluating the human-bovine (WC3) reassortant pentavalent rotavirus vaccine (RV5).

BACKGROUND: The Rotavirus Efficacy and Safety Trial was a placebo-controlled Phase III study that evaluated the safety and efficacy of a three-dose pentavalent rotavirus vaccine (RV5) including its effect on healthcare utilization for rotavirus gastroenteritis (RVGE). The per-protocol (PP) analyses, which counted events occurring 14 days after dose 3 among infants without protocol violations, have already been published. This paper evaluates the consistency of the healthcare utilization results based on the modified intention to treat (MITT) analyses with the PP analyses. The MITT analyses include all infants receiving at least one dose of vaccine or placebo and follow-up begins after dose 1. The paper also explores the consistency of the results for different subgroups of the study population with different types of surveillance. METHODS: Data on healthcare utilization for acute gastroenteritis were collected via telephone interviews after administration of the first dose. Parents were either contacted every 6 weeks or every 2 weeks depending on the substudy in which they were enrolled. Those contacted every 2 weeks were also asked to complete symptom diaries. Poisson regression was used to evaluate the effect of RV5 on the rates of RVGE-associated healthcare encounters in all of the analyses. RESULTS: In the first 2 years after vaccination, RV5 reduced the combined rate of hospitalizations and emergency department (ED) visits 88.9% (95% CI: 84.9, 91.9) for all RVGE regardless of serotype in the MITT analysis compared with a 94.5% (95% CI: 91.2, 96.6) reduction based on the G1-G4 PP analysis. By type of surveillance, the rate reductions for the G1-G4 PP analysis were 91.0% (95% CI: 81.7, 95.5) and 95.9% (95% CI: 92.2, 97.8) among parents contacted every 2 weeks (number evaluable = 4,451) and every 6 weeks (number evaluable = 52,683) respectively. CONCLUSIONS: Our analyses demonstrated that the effect of RV5 on reducing the rate of hospitalizations and ED visits based on the MITT analyses were generally consistent with the PP analyses. The rate of events for subgroups with different intensities of surveillance differed but the effect of RV5 on the relative rate reductions were consistent with the results that have already been published. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00090233.

Impact of community-acquired paediatric rotavirus gastroenteritis on family life: data from the REVEAL study.

BACKGROUND: Rotavirus is the leading cause of acute gastroenteritis (AGE) and the most frequent cause of severe diarrhoea in children aged less than 5 years. Although the epidemiology of rotavirus gastroenteritis (RVGE) is well documented, there are few data on the impact of RVGE on the families of affected children. METHODS: Data associated with the burden of RVGE, including number of working days lost, levels of parental stress, the need for alternative childcare arrangements and additional nappies used, were extracted from questionnaires completed by parents of children participating in a prospective, multicentre, observational study (Rotavirus gastroenteritis Epidemiology and Viral types in Europe Accounting for Losses in public health and society, REVEAL), conducted during 2004-2005 in selected areas of Belgium, France, Germany, Italy, Spain, Sweden, and the United Kingdom to estimate the incidence of RVGE in children aged less than 5 years seeking medical care as a result of AGE. RESULTS: 1102 children with RVGE were included in the present analysis. The proportion of RVGE cases that required at least one parent or other person to be absent from work was 39%-91% in the hospital setting, 44%-64% in the emergency department, and 20%-64% in primary care. Self-reported levels of parental stress were generally high (mean stress levels, > or = 5 on a 10-point visual analogue scale). Additional childcare arrangements were required in up to 21% of RVGE episodes. The mean number of nappies used per day during RVGE episodes was approximately double that used when the child was not ill. CONCLUSIONS: Paediatric RVGE cases cause disruption to families and parental stress. The burden of RVGE on children and their families could be substantially reduced by routine rotavirus vaccination of infants.

RotaTeq, a pentavalent rotavirus vaccine: efficacy and safety among infants in Europe.

A pentavalent human-bovine reassortant oral rotavirus vaccine, RotaTeq, was evaluated among nearly 70,000 infants in the Rotavirus Efficacy and Safety Trial (REST), of which 30,523 were from Europe. All infants were followed for serious adverse events as well as hospitalizations and emergency department (ED) visits. All adverse events, health care utilization, and RVGE regardless of severity were evaluated in the clinical efficacy cohort (N=2686) in Finland. RotaTeq was 98.3% (95% CI, 90.2-100%) and 68.0% (95% CI 60.3-74.4%) efficacious against severe rotavirus gastroenteritis (RVGE) and all RVGE due to any serotype for two rotavirus seasons post-vaccination. The combined rate of hospitalizations and ED visits due to RVGE of any serotype was reduced by 94.5% (95% CI, 91.3-96.8%) for up to 2 years after vaccination. There were no statistically significant differences between RotaTeq and placebo for any of the safety outcomes. In Europe, RotaTeq was highly efficacious and well tolerated.

Effects of feeding probiotics during weaning on infections and antibody responses to diphtheria, tetanus and Hib vaccines.

Microbial exposure is necessary for the development of normal immune function, which has driven the idea of using probiotics for treatment and prevention of immune-mediated diseases in infancy and childhood. Mounting evidence indicates that probiotics have immunomodulatory effects. However, the mechanisms are still poorly understood. Specific antibody response is a valuable proxy for immune system maturation status in infancy. We aimed at determining the impact of Lactobacillus F19 (LF19) during weaning on infections and IgG antibody responses to routine vaccines. In a double-blind, placebo-controlled randomized intervention trial, infants were fed cereals with (n = 89) or without LF19 (n = 90) from 4 to 13 months of age. Infants were immunized with DTaP (diphtheria and tetanus toxoid and acellular pertussis), polio and Hib-conjugate vaccines at (3), 5(1/2) and 12 months of age. We assessed the number of days with infections, antibiotic prescriptions and antibody concentrations to Hib capsular polysaccharide (HibPS), diphtheria toxin (D) and tetanus toxoid (T) before and after the second and third doses. Days with infectious symptoms did not differ between the groups. Days with antibiotic prescriptions were fewer in the LF19 group (p = 0.044). LF19 enhanced anti-D concentrations when adjusting for breastfeeding duration and colonization with LF19 (p = 0.024). There was an interaction of the intervention and colonization with LF19 on anti-T concentrations during the course of vaccination (p = 0.035). The anti-HibPS concentrations were higher after the first and second dose of Hib vaccine in infants breastfed <6 months compared with those breastfed > or =6 months (p < 0.05), with no effect by LF19. In conclusion, feeding LF19 did not prevent infections, but increased the capacity to raise immune responses to protein antigens, with more pronounced effects in infants breastfed <6 months.

Mental health and social competencies of 10- to 12-year-old children born at 23 to 25 weeks of gestation in the 1990s: a Swedish national prospective follow-up study.

OBJECTIVE: We investigated a national cohort of extremely immature children with respect to behavioral and emotional problems and social competencies, from the perspectives of parents, teachers, and children themselves. METHODS: We examined 11-year-old children who were born before 26 completed weeks of gestation in Sweden between 1990 and 1992. All had been evaluated at a corrected age of 36 months. At 11 years of age, 86 of 89 survivors were studied and compared with an equal number of control subjects, matched with respect to age and gender. Behavioral and emotional problems, social competencies, and adaptive functioning at school were evaluated with standardized, well-validated instruments, including parent and teacher report questionnaires and a child self-report, administered by mail. RESULTS: Compared with control subjects, parents of extremely immature children reported significantly more problems with internalizing behaviors (anxiety/depression, withdrawn, and somatic problems) and attention, thought, and social problems. Teachers reported a similar pattern. Reports from children showed a trend toward increased depression symptoms compared with control subjects. Multivariate analysis of covariance of parent-reported behavioral problems revealed no interactions, but significant main effects emerged for group status (extremely immature versus control), family function, social risk, and presence of a chronic medical condition, with all effect sizes being medium and accounting for 8% to 12% of the variance. Multivariate analysis of covariance of teacher-reported behavioral problems showed significant effects for group status and gender but not for the covariates mentioned above. According to the teachers' ratings, extremely immature children were less well adjusted to the school environment than were control subjects. However, a majority of extremely immature children (85%) were functioning in mainstream schools without major adjustment problems. CONCLUSIONS: Despite favorable outcomes for many children born at the limit of viability, these children are at risk for mental health problems, with poorer school results.

Costs of community-acquired pediatric rotavirus gastroenteritis in 7 European countries: the REVEAL Study.

BACKGROUND: Morbidity and resource use due to rotavirus gastroenteritis (RVGE) are substantial in Europe, although comprehensive data on the economic impact of the disease are lacking. METHODS: A cost study was conducted to assess health care resource use data collected during a prospective epidemiologic study of acute gastroenteritis in children <5 years of age in selected areas of Belgium, France, Germany, Italy, Spain, Sweden, and the United Kingdom. We calculated the average cost (direct and indirect) per episode of confirmed RVGE in primary care, emergency department, and hospital settings. RESULTS: The total societal cost (including direct medical, direct nonmedical, and indirect costs) per episode of RVGE ranged from 166 euros to 473 euros in the primary care setting, from 334 euros to 770 euros in the emergency department setting, and from 1525 euros to 2101 euros in the hospital setting. The majority of hospital-related costs were reimbursed by national health care payers, but the percentage of reimbursed costs declined progressively in the emergency department and primary care settings. The mean number of workdays lost by parents and other relatives varied between study areas and settings, ranging from 2.3 to 7.5 days, and this represented the major cost not reimbursed by national health care payers. CONCLUSIONS: RVGE incurs considerable resource utilization in all health care settings and substantial costs for national health care payers, families of patients, and employers. Routine rotavirus vaccination in infants could significantly reduce the health and economic burden of pediatric RVGE.

Clinical consequences of rotavirus acute gastroenteritis in Europe, 2004-2005: the REVEAL study.

BACKGROUND: The availability of comprehensive, up-to-date epidemiologic data would improve the understanding of the disease burden and clinical consequences of rotavirus gastroenteritis (RVGE) in Europe. METHODS: During the 2004-2005 season, a prospective, multicenter, observational study was conducted in children <5 years of age in primary care, emergency department, and hospital settings in selected areas of Belgium, France, Germany, Italy, Spain, Sweden, and the United Kingdom. The clinical consequences of acute gastroenteritis (AGE) and RVGE were estimated. RESULTS: The estimated percentage of children with rotavirus-positive AGE admitted to a hospital was 10.4%-36.0%, compared with 2.1%-23.5% of children with rotavirus-negative AGE. In France, Germany, Italy, Spain, and the United Kingdom, the relative risk of hospitalization was statistically significantly higher for children with rotavirus-positive AGE than for those with rotavirus-negative AGE. Children with rotavirus-positive AGE were more likely to have lethargy, fever, vomiting, and dehydration, and, therefore, more severe disease than were children with rotavirus-negative AGE. Dehydration was up to 5.5 times more likely in children with rotavirus-positive AGE than in those with rotavirus-negative AGE. CONCLUSIONS: Rotavirus-positive AGE is more severe, causes more dehydration, and results in more emergency department consultations and hospitalizations than does rotavirus-negative AGE. Variations in the management of RVGE seen across study areas could be explained by differences in health care systems. Routine rotavirus vaccination of infants could significantly reduce the substantial burden of RVGE and would have major benefits for potential patients, their families, and health care providers.

Multicenter prospective study of the burden of rotavirus acute gastroenteritis in Europe, 2004-2005: the REVEAL study.

BACKGROUND: Rotavirus is recognized as a significant cause of pediatric gastroenteritis worldwide. Comprehensive data on the burden of rotavirus disease in Europe were lacking. METHODS: A prospective, multicenter, observational study was conducted during the 2004-2005 season in selected areas of Belgium, France, Germany, Italy, Spain, Sweden, and the United Kingdom, to estimate the incidence of acute gastroenteritis (AGE) and rotavirus gastroenteritis (RVGE) in children <5 years of age who require medical care in primary care, emergency department, and hospital settings. RESULTS: A total of 2846 children with AGE were included in the study, and, of the 2712 children for whom ELISA results were available, 1102 (40.6%) were found to be rotavirus positive. The estimated annual incidence of RVGE was 2.07-4.97 cases/100 children <5 years of age, and it was highest among children 6-23 months of age, with 56.7%-74.2% of all RVGE cases occurring in children in this age group. Overall, RVGE was estimated to account for 27.8%-52.0% of AGE cases, and it was responsible for up to two-thirds of hospitalizations and emergency department consultations, as well as one-third of primary care consultations for AGE. CONCLUSIONS: Rotavirus infections account for a significant proportion of AGE cases in children <5 years of age in Europe, many of whom require frequent primary care consultations or care in emergency department and/or hospital settings. The results of the present study suggest that routine rotavirus vaccination for infants <6 months of age could significantly reduce the substantial burden of this potentially serious childhood disease.

Growth in 10- to 12-year-old children born at 23 to 25 weeks' gestation in the 1990s: a Swedish national prospective follow-up study.

BACKGROUND: Knowledge of long-term growth of extremely preterm infants in relation to gestational age is incomplete, and there are concerns regarding their poor growth in early childhood. As part of a longitudinal study of a national cohort of infants born at <26 weeks' gestation (extremely immature), growth development from birth to the age of 11 years was examined, and correlates of growth attainment were analyzed. METHODS: Two hundred forty-seven extremely immature children were born alive from April 1990 through March 1992 in the whole of Sweden, and 89 (36%) survived. Growth and neurosensory outcomes of all extremely immature survivors were evaluated at 36 months of age. Eighty-six (97%) extremely immature children were identified and assessed at 11 years of age. In this growth study, 83 extremely immature infants (mean [SD]: birth weight, 772 g [110 g]; gestational age, 24.6 weeks [0.6 weeks]) without severe motor disability were followed up prospectively from birth to 11 years old and compared with a matched group of 83 children born at term. z scores for weight, height, head circumference, and BMI were computed for all children. We also examined gender-specific longitudinal growth measures. Predictors of 11-year growth were studied by multivariate analyses. RESULTS: Extremely immature children were significantly smaller in all 3 growth parameters than the controls at 11 years. Extremely immature children showed a sharp decline in weight and height z scores up to 3 months' corrected age, followed by catch-up growth in both weight and height up to 11 years. In contrast to weight and height, extremely immature children did not exhibit catch-up growth in head circumference after the first 6 months of life. The mean BMI z scores increased significantly from 1 to 11 years in both groups. The mean BMI change between 1 and 11 years of age was significantly larger in extremely immature than in control participants. Extremely immature girls showed a faster weight increase than extremely immature boys, whereas catch-up growth in height and head circumference was similar in these groups. Multiple-regression analyses revealed that preterm birth and parental height were significant predictors of 11-year height, and group status (prematurity) correlated strongly with head circumference. CONCLUSIONS: Children born at the limit of viability attain poor growth in early childhood, followed by catch-up growth to age 11 years, but remain smaller than their term-born peers. Strategies that improve early growth might improve the outcome.

Chronic conditions, functional limitations, and special health care needs in 10- to 12-year-old children born at 23 to 25 weeks' gestation in the 1990s: a Swedish national prospective follow-up study.

BACKGROUND: Children born extremely immature (gestational age < 26 weeks' gestation) increasingly reach school age. Information on their overall functioning and special health care needs is necessary to plan for their medical and educational services. This study was undertaken to examine neurosensory, medical, and developmental conditions together with functional limitations and special health care needs of extremely immature children compared with control subjects born at term. METHODS: We studied 11-year-old children born before 26 completed weeks of gestation in all of Sweden from 1990 through 1992. All had been evaluated at 36 months' corrected age. Identification of children with chronic conditions lasting > or = 12 months was based on a questionnaire administered to parents. Neurosensory impairments were identified by reviewing health records. Information regarding other specific medical diagnoses and developmental disabilities was obtained by standard parent and teacher questionnaires. RESULTS: Of 89 eligible children, 86 (97%) were studied at a mean age of 11 years. An equal number of children born at term served as controls. Logistic-regression analyses adjusting for social risk factors and gender showed that significantly more extremely immature children than controls had chronic conditions, including functional limitations (64% vs 11%, respectively), compensatory dependency needs (59% vs 25%), and services above those routinely required by children (67% vs 22%). Specific diagnoses or disabilities with higher rates in extremely immature children than in controls included neurosensory impairment (15% vs 2%), asthma (20% vs 6%), poor motor skills of > 2 SDs above the mean (26% vs 3%), poor visual perception of > 2 SDs above the mean (21% vs 4%), poor learning skills of > 2 SDs above the mean (27% vs 3%), poor adaptive functioning with T scores of < 40 (42% vs 9%), and poor academic performance with T score < 40 (49% vs 7%). CONCLUSIONS: Children born extremely immature have significantly greater health problems and special health care needs at 11 years of age. However, few children have severe impairments that curtail major activities of daily living.