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Plasminogen activator inhibitor-1 promoter activity in adipocytes is not influenced by the 4 G/5 G promoter polymorphism and is regulated by a USF-1/2 binding site immediately preceding the polymorphic region.

Plasminogen activator inhibitor-1 (PAI-1) levels were found to be associated with obesity indicating that adipocytes influence PAI-1 plasma levels. In addition, the 4 G/5 G promoter polymorphism of the PAI-1 gene may modulate PAI-1 transcription. We investigated the transcriptional regulation of the human PAI-1 gene in adipocytes and analyzed the genetic contribution of the 4 G/5 G polymorphism. The PAI-1 promoter was analyzed using electrophoretic mobility shift assays (EMSAs) and luciferase reporter gene assays. A putative binding site for the upstream stimulatory factor-1/2 (USF-1/2) at the polymorphic region of the PAI-1 promoter was identified. The binding of USF-1/2 was studied using nuclear extracts prepared from adipocytes and was similar in all the promoter variants as analyzed by EMSA. A 257 bp PAI-1 promoter fragment including the 4 G/5 G site was transcriptionally active in adipocytes and was not influenced by the polymorphism. The present data indicate for the first time that USF-1/2 is transcriptionally active in differentiated adipocytes. However, USF-1/2 binding activity and PAI-1 transcription are not influenced by the 4 G/5 G-allele. These data possibly explain the observation that PAI-1 secretion from adipose tissue is not influenced by the PAI-1 promoter polymorphism.

3T3-L1 Cells↗

Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) and hepatocyte nuclear factor 4gamma (HNF-4gamma) and HNF-4alpha regulate the bovine growth hormone receptor 1A promoter through a common DNA element.

The growth hormone receptor (GHR) 1A promoter is responsible for transcription of the liver-specific GHR mRNA variant 1A in several mammalian species. We previously found that the region between nucleotide -218 and nucleotide -151 (relative to the major transcription start site) of the bovine GHR 1A promoter contained a binding site between -196 and -178 for the liver-enriched transcription factor hepatocyte nuclear factor 4alpha (HNF-4alpha) and that the same region might also interact with additional transcription factors in the liver. Using the -218/-151 region as bait to screen a bovine liver cDNA library in a yeast one-hybrid analysis, we identified chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) and HNF-4gamma, as well as HNF-4alpha, as binding proteins to the -218/-151 region. These binding proteins were also identified in a second yeast one-hybrid analysis using the -196/-178 region as bait, suggesting that COUP-TFII, HNF-4gamma and HNF-4alpha all bind to the -196/-178 region. Electrophoretic mobility shift assays confirmed the ability of these three transcription factors in bovine liver nuclear extracts to interact with the -196/-178 region. These interactions also appeared to exist in vivo, as the GHR 1A promoter containing the -196/-178 region could be recovered by immunoprecipitation of the bovine liver chromatin with antibody against COUP-TFII, HNF-4gamma or HNF-4alpha. In co-transfection analyses, each of these three transcription factors could activate GHR 1A promoter and the activation was dependent on the -196/-178 region. These results together identify COUP-TFII, HNF-4gamma and HNF-4alpha as transcription factors regulating GHR 1A promoter activity through binding to a common DNA element.

Amino Acid Sequence↗

[A study of factors influencing on health promoting lifestyle in the elderly--application of Pender's health promotion model].

PURPOSE: The purpose of this study was to investigate the factors influencing health promoting lifestyle in the elderly. METHOD: The subject of this study was 305 elderly person over the age of 60, living in rural and urban, Korea. For the analysis of collected data, descriptive statistics, t-test, analysis of variance and stepwise multiple regression were used for statistical analysis with SPSS statistical program. RESULTS: The average item score for the health promoting lifestyle was 2.46. The higher score on the subscale was nutrition(2.65). The lowest score on the subscale were physical activity(2.36) and stress management(2.36). General characteristics showing statistically significant difference in health promoting lifestyle were age, residential district, live together spouse, education, religion and pocket money in the elderly. Stepwise multiple regression analysis revealed that the most powerful predictor of health promoting lifestyle in the elderly was prior related behavior(R2=.554). A combination of prior related behavior, perceived benefits of action, perceived self-efficacy, commitment to a plan of action, and interpersonal influences accounted for 64.3% of the variance in health promoting lifestyle in the elderly. CONCLUSION: The factors influencing on health promoting lifestyle for elderly were prior related behavior, perceived benefits of action, perceived self-efficacy, commitment to a plan of action, and interpersonal influences.

Aged↗

HS1,2 enhancer regulation of germline epsilon and gamma2b promoters in murine B lymphocytes: evidence for specific promoter-enhancer interactions.

During an immune response, activated B cells develop into high rate Ig-secreting plasma cells. They also switch from production of IgM to IgG, IgA, or IgE. This process requires a DNA recombination event, which is regulated at the transcriptional level by the production of isotype-specific, sterile germline (GL) transcripts. Induction of these transcripts is controlled by GL promoters and, possibly, by IgH 3' enhancers. We investigated the interaction of the GL epsilon and gamma2b promoters with the HS1,2 enhancer using transiently transfected mouse primary B cells and cell lines. The constructs used for the transfections contained a GL promoter upstream and HS1,2 downstream of a luciferase reporter gene. Both GL epsilon and gamma2b promoters synergized strongly with the HS1,2 enhancer in activated primary B cells, a mature B cell line, and a plasma cell line. We show that the major activity of HS1,2 in activated primary B cells occurs within a 310-bp fragment that includes NF-kappaB, OCT, and NF of activated B cells (Ets/AP-1) sites. By mutating the consensus sequences for various transcription factors, we have determined which sites in HS1,2 are important for synergy with the GL epsilon and gamma2b promoters. Our findings indicate that different sites in HS1,2 might selectively interact with the GL epsilon and gamma2b promoters. We also provide evidence that B cell-specific activator protein is not an absolute suppressor of HS1,2 activity.

Animals↗

Characterization of an oxygen-dependent inducible promoter, the nar promoter of Escherichia coli, to utilize in metabolic engineering.

The nar promoters, whose transcription is maximally induced under microaerobic conditions in the presence of nitrate ion, were characterized in fed-batch culture to determine whether they can be used for metabolic engineering, by which overall production of valuable chemicals can be increased. For this purpose, we tested whether the expression level of a reporter gene, the lacZ gene from the nar promoter, could be maintained constant throughout the induction period by manipulation of dissolved oxygen (DO) levels at a given nitrate ion concentration. First, E. coli was grown under aerobic conditions (DO 80%) to absorbance at 600 nm (OD(600)) of 35, then the nar promoter was induced by reduction of DO to different levels, combined with different frequencies and duration of alternating microaerobic and aerobic conditions throughout the entire induction period. For a wild-type nar promoter (pMW61) in a mutant host E. coli with a mutation in the narG gene on the chromosome of the host (RK5265), it was possible to maintain production of beta-galactosidase activity per cell (specific beta-galactosidase activity) at a constant rate at 5000, 10,000, 15,000, and 20,000 Miller units, using different combinations of nitrate ion concentrations (0.1%, 0.5%, and 1%) and DO levels. In addition, it was possible to maintain production of specific beta-galactosidase activity at a constant rate at about 10,000 Miller units in the absence of nitrate ion when a nitrate-independent nar promoter (pMW618) in the narL(-) mutant of the W3110 E. coli strain (W3110narL(-)) was used. Based on these results, we conclude that the nar promoter system provides a convenient expression system for metabolic engineering as well as for maximal production of recombinant proteins under conditions of fed-batch culture.

Chromosomes, Bacterial↗

Analysis of polymorphism of the GLUT2 promoter in NIDDM patients and its functional consequence to the promoter activity.

Glucose transporter type 2 (GLUT2), along with glucokinase, has been implicated to participate in glucose-induced insulin secretion in pancreatic beta-cells. Recently, several sequence variations in the promoter of GLUT2 have been identified in patients with non-insulin dependent diabetes mellitus (NIDDM), but the functional effects of these polymorphisms on promoter activity have not previously been studied. We compared the incidence of sequence variations in the GLUT2 promoter in 100 normal subjects and 100 NIDDM patients. Sequencing of the promoter region (-294 to +301) revealed that an A --> G variant at position -44 was found in 45 of 100 NIDDM patients, but only in 23 of 100 normal subjects. In addition, -269 A --> C and + 103 A --> G mutations were identified in a single diabetic patient. Electrophoretic mobility shift assays using double-stranded oligonucleotide containing -44A as a probe showed a clearly shifted band of DNA-protein. To examine whether the sequence variation at position -44 affects the promoter activity, we carried out in vitro transfection experiments. Site-specific mutagenesis at position -44 region from A to C, T, or G resulted in reductions of CAT activity by 52.3%, 63.8%, and 63.6%, respectively. The -269 A --> C and + 103 A --> G mutations also decreased the promoter activity. These results suggest that polymorphisms at positions -269, -44, or + 103 may affect GLUT2 gene transcription, possibly associated with reduced expression of the GLUT2 gene in NIDDM patients.

Cell Line↗

Characterization of the promoter region of the c-yes proto-oncogene: the importance of the GC boxes on its promoter activity.

In this study we cloned the 5' flanking sequence of the human c-yes gene and identified its promoter region. A 0.53 kilobase pair (kbp) fragment containing the 5' terminus of the c-yes gene showed strong promoter activity when placed upstream of the bacterial chloramphenicol acetyltransferase (CAT) gene and transfected into monkey CV-1 cells. By nuclease S1 mapping multiple transcriptional start sites were detected within the promoter region. Nucleotide sequence analysis revealed that the c-yes promoter region had high G + C contents (64%) and contained six GC box-like sequences (one at the 5' distal region and five in a cluster at the 5' proximal region), but not a TATA box. These features of the c-yes promoter region are similar to those of other protooncogenes, ras-family genes and c-raf-1, and some house-keeping genes. Deletion analysis suggested that the most downstream 0.21 kbp region is primarily important for the promoter activity. This 0.21 kbp region contains one major and another minor transcriptional start site. Five GC box-like sequences were located within this region, and four of them were shown to bind with purified Sp1 transcription factor. Furthermore, using the base-substituted mutants of the Sp1-binding sites, each GC box in the cluster (GC1 to GC4) was shown to affect the c-yes gene expression.

Animals↗

Substitution of 2 base pairs (1 base pair per DNA half-site) within the Escherichia coli lac promoter DNA site for catabolite gene activator protein places the lac promoter in the FNR regulon.

The consensus DNA site for Escherichia coli catabolite gene activator protein (CAP) is 5'-AAATGTGATCTAGATCACATTT-3'. The proposed consensus DNA site for E. coli FNR is 5'-AAATTTGATATATATCAAATTT-3'. In this report, we show that substitution of 2 base pairs (1 base pair per DNA half-site) within the E. coli lac DNA site for CAP suffices to remove the lac promoter from the CAP regulon and to place the lac promoter in the FNR regulon. FNR stimulates transcription of the derivative of the lac promoter having G:C----T:A substitutions at base pair 5 each DNA half-site (13-fold stimulation). FNR does not stimulate transcription of the wild-type lac promoter, or of derivatives of the lac promoter having G:C----A:T or G:C----C:G substitutions at base pair 5 of each DNA half-site. Stimulation of transcription is strictly dependent on anaerobiosis. FNR-stimulated transcription initiates at the same base pair as does CAP-dependent transcription of the wild-type lac promoter.

Aerobiosis↗

A transcription factor required for promoter recognition by human mitochondrial RNA polymerase. Accurate initiation at the heavy- and light-strand promoters dissected and reconstituted in vitro.

Faithful transcription of human mitochondrial DNA has been reproduced in vitro, using a fraction of mitochondrial proteins capable of accurate initiation at both the heavy- and light-strand promoters. Here we report the initial dissection of this system into two nonfunctional components which, upon mixing, reconstitute promoter-specific transcriptional capacity in vitro. One of these components copurifies with the major nonspecific RNA polymerase activity, suggesting its identity. The other component lacks significant polymerase activity, but contains a protein or proteins required for accurate initiation at the two individual promoters by isolated mitochondrial RNA polymerase. This factor facilitates specific transcription, but has little or no effect on nonspecific transcription of a synthetic copolymer (poly(dA-dT)), indicating a positive role in proper promoter recognition. The transcription factor markedly stimulates light-strand transcription, but only moderately enhances transcription initiation at the heavy-strand promoter, suggesting different or additional factor requirements for heavy-strand transcription. These requirements may reflect the functional differences between heavy- and light-strand transcription in vivo and, in particular, the role of the light-strand promoter in priming of heavy-strand DNA replication.

Carcinoma↗

E1BF/Ku interacts physically and functionally with the core promoter binding factor CPBF and promotes the basal transcription of rat and human ribosomal RNA genes.

We have previously characterized an RNA polymerase (pol) I transcription factor, E1BF, from rat cells. This protein is immunologically related to Ku autoantigen and is required in pol-I directed transcription of rodent ribosomal RNA gene (rDNA). Glycerol density gradient fractionation and in situ UV cross-linking analysis of the purified factor showed directly that it consists of a heterodimer of 85 and 72 kDa polypeptides. E1BF also interacted with the human core promoter and augmented transcription of human rDNA as much as fivefold in HeLa nuclear extract, whereas transcription from adenovirus major late promoter, CMV or SV40 early promoters by pol II and of U6 and 5S RNA genes by pol III were either unaffected or minimally inhibited by the antibodies. Purified rat E1BF partially restored the suppression of human rDNA transcription by anti-Ku antibodies. Immunoprecipitation of rat cell extract with the anti-Ku antibodies followed by SDS-PAGE of the precipitated proteins and Southwestern analysis showed that E1BF interacts with CPBF, a core promoter binding factor. When the majority of CPBF and E1BF was removed from the reaction mixture by preincubation with a core promoter oligo nucleotide fragment, rDNA transcription was severely impaired. Addition of exogenous CPBF or E1BF to such a reaction resulted in significant restoration of the transcription, whereas inclusion of both factors caused further enhancement of rDNA transcription. These data demonstrate that E1BF is a basal pol I transcription factor that interacts with a core promoter binding factor both physically and functionally, and that is not a general pol II or pol III transcription factor.

Adenoviridae↗

[Health promotion. Planning process of health promotion programs for individuals with arthritis].

Based on the health conception viewed from the literature on nursing and by the clients, health is defined as a living experience, or as a perception of wellness in this study. That is, it is the perceived wellness that the individual obtains by wholistically integrating all dimensions of health where ever the individual stands in the health continuum. Thus health exists independently, regardless of illness or disability, because the individual is able to perceive the wellness within limitations imposed to him/her. Also, based on the health conception defined in this study and the literature review on health promotion, health promotion is defined as the process of enhancing the perception of wellness (i.e., living experience), where ever the individual stands in the health continuum. Therefore, health promotive care represents the process of making client help himself to improve health experience/perception of wellness by selecting and/or integrating the individual or social health parameters (determinants) based on his reality. After analyzing the data which is provided from the related literature and the results from the descriptive/exploratory research on this group of clients, and then applying those analysis results to the PRECEDE model, planning process for health promotion program is established. However, as planning process is only based on data from literature in the first stage, it will be modified appropriately according to the assessment feedback from the direct participation of client in the following study. Based on the planning model refined through this assessment process, health promotion program is to be developed, implemented and evaluated. Planning process of health promotion for clients with arthritis is begun from the assessment of health outcome as the first phase. It is analyzed from this study that clients with arthritis indicates lower quality of life/satisfaction than the other groups from the several research findings indicate. In the second phase, according to the analysis results in the first phase, clients' health problems (perceived seriousness about illness, uncertainty in illness, helplessness, difficulty of movement), which affect the low quality of life, are identified and then program objective for each problem is demonstrated. As an objective for the perceived seriousness about illness, relief of the mistrust on the general effects of treatment for illness is determined through appropriate data analysis. And clients' accumulation of accurate knowledge on the nature of illness is determined as an objective, for reducing uncertainty in the illness. Also enhancement of distraction ability and self-efficacy perception is defined as objectives for reducing physical, psychological and social helplessness.(ABSTRACT TRUNCATED AT 400 WORDS)

Arthritis↗

RNA polymerase II promoter strength in vitro may be reduced by defects at initiation or promoter clearance.

We have measured the ability of three TATA box promoters, adenovirus 2 major late (Ad 2 ML), Ad 2 ML with a point mutation in the TATA box, and mouse beta-globin, to support abortive and productive RNA synthesis in vitro. We have also measured the ability of these promoters to direct the assembly of preinitiation complexes using a nuclease protection assay. The relative strengths in productive transcription, determined from the synthesis of RNAs 10 nucleotides or longer, were 12:6:1 for Ad 2 ML, mouse beta-globin, and the TATA mutant of Ad 2 ML. However, the TATA mutant was reduced only 4-fold in its ability to assemble preinitiation complexes, compared to Ad 2 ML. Complexes formed on the Ad 2 ML TATA mutant may therefore also be reduced in their ability to initiate transcription. The mouse beta-globin promoter directed assembly and initiation as well as Ad 2 ML, but the beta-globin transcription complexes were less able to clear the promoter, resulting in an increase in aborted transcripts at the expense of productive RNA synthesis. We have thus shown that the transcriptional strength of eukaryotic promoters may be determined not only at the step of transcription complex assembly but also at the level of promoter clearance and possibly at transcription initiation as well.

Adenoviruses, Human↗

All 4 bases of both strands at -9 and -8 in T7 promoter are needed to be substituted by SP6-specific bases to switch promoter specificity.

It has previously been shown that a substitution of two base pairs at -9 and -8 in T7 promoter by SP6 promoter-specific base pairs alone is sufficient to make the T7 variant become an SP6 promoter, abolishing T7 promoter activity [Lee, S. S., and Kang, C. (1992) Biochem. Int. 26, 1-5]. In order to determine which of the 4 bases on both strands at the two positions is involved in the discriminative specificity, each base or each pair of bases was substituted by SP6-specific base(s), allowing one or two mismatches. The results show that all-four-base substitution only is capable of switching promoter specificity, and that all the four bases are substantially involved in T7 promoter activity.

Bacteriophage T7↗

Deletional analysis of the human renin promoter: transcriptional activation by the SV40 enhancer enables identification of promoter regulatory elements in non-renin-expressing cells.

Identification of regulatory elements in the human renin gene promoter has been hindered by the lack of suitable renin-expressing cell lines. In this paper, the SV40 viral enhancer is coupled to a human renin promoter/chloramphenicol acetyltransferase (CAT) reporter gene construct, to determine whether promoter regulatory elements can be identified in the context of enhanced transcription in the normally non-renin-expressing HeLa cell line. The present results indicate that the SV40 enhancer can overcome tissue-specificity of the human renin promoter, and confer correctly initiated transcriptional activity to HeLa cells. Analysis of a series of 5'-end deletions of the human renin promoter linked to the CAT gene and SV40 enhancer identified negative regulatory elements between positions-275 and -225, and between-142 and -102 of the human renin promoter, as well as a positive regulatory element between -225 and -142. Thus, studies of renin promoter regulatory elements need not be limited to renin-expressing cells, but can be performed in non-renin-expressing cells with the addition of an enhancer. This strategy can be generally applicable to the study of tissue-specific gene regulation in cases where there are no specific cell lines available.

Chloramphenicol O-Acetyltransferase↗

Analysis of the promoter elements necessary for IL-4 and anti-CD40 antibody induction of murine Fc epsilon RII (CD23): comparison with the germline epsilon promoter.

IL-4 and CD40 ligand stimulate transcription of CD23 (Fc epsilonRII) in B cells and are necessary for the expression of germline epsilon mRNA and production of IgE. Because in vivo studies have shown that the Fc epsilonRII is involved in the regulation of IgE, a study was initiated to compare how IL-4 and engagement of CD40 up-regulate the Fc epsilonRII and epsilon genes. Herein, we describe the preparation of a series of linker-scanning mutants that cover the IL-4 response region in the murine Fc epsilonRII promoter, and their function when transfected into M12.4.5 and M12.4.1 B lymphoma cell lines. Several discrete elements were found to be necessary for IL-4 induction of the Fc epsilonRII gene, some of which have homology with the binding sites of known transcription factors, including NF-IL-4 and NF-kappaB. In contrast, the response element for anti-CD40 (plus IL-4) mapped to a single discrete sequence, a NF-kappaB-like site. Aligning the Fc epsilonRII and germline epsilon promoters in the region that is highly conserved between the human and mouse homologues of both genes reveals a high degree of identity, particularly within discrete clusters. Comparing the function of linker-scanning mutants of the Fc epsilonRII promoter with a similar report for germline epsilon shows that both genes require at least two homologous and similarly located DNA elements in their promoters for a full IL-4 induction. Moreover, the similar response of Fc epsilonRII and epsilon promoter-driven chloramphenicol acetyl transferase plasmids to several cytokines and other agents suggests that the two proximal promoter regions are activated by a similar cassette of factors.

Animals↗

Promoting health through schools. Report of a WHO Expert Committee on Comprehensive School Health Education and Promotion.

Education confers the ability to combine knowledge, attitudes, and skills and use them to shape one's life and the lives of others. A higher educational level correlates with greater competence in decision-making, a better economic situation, and a higher degree of awareness concerning the benefits of and risks to health--indeed, education can be said to be a prerequisite for health. However, education cannot achieve its potential if young people do not attend school because of poor health and related conditions. Moreover, if children are ill, hungry, or malnourished, or suffer from undue stress, they cannot learn effectively in school. Likewise, early or unintended pregnancy, violence, infectious diseases, alcohol or drug abuse, and other health problems can limit the learning potential of adolescents. Therefore, the extent to which schools can become instruments of health promotion for children and adolescents is fundamental in determining whether they will be both educated and healthy, and whether they can lead fulfilling lives and contribute to building a better world. This report of a WHO Expert Committee considers how best to make schools truly health promoting. It presents the rationale for school health promotion, cites significant features of the status of school health promotion worldwide, reviews existing research, notes common barriers to effective school health promotion, and offers a set of strategies to overcome these barriers. Many strategies are illustrated with concrete examples demonstrating success. Priority areas for research are also outlined. The report concludes with a set of recommendations that can serve as a charter for guiding the actions of educational and health professionals at different levels--local, national, and international--to advance the common cause of promoting health through schools.

Adolescent↗

Cloning of human telomerase catalytic subunit (hTERT) gene promoter and identification of proximal core promoter sequences essential for transcriptional activation in immortalized and cancer cells.

Telomerase activation is thought to be a critical step in cellular immortalization and carcinogenesis. Of the three major subunits comprising human telomerase, human telomerase catalytic subunit (hTERT) has been shown to be a rate-limiting determinant of the enzymatic activity of human telomerase. However, little is known concerning how expression of hTERT is regulated in human cells. To identify the regulatory elements controlling hTERT gene expression, approximately 3.5 kb of the 5'-flanking sequence of hTERT was cloned and characterized. The promoter of hTERT was GC rich and lacked both TATA and CAAT boxes. The CapSite Hunting method identified transcription start site 19 bp upstream of the first nucleotide of the published cDNA sequence. Transient expression assays revealed that transcription of hTERT was significantly activated in cancer cell lines but repressed in normal primary cells. Using the fibroblast lineage at various stages of transformation, we found that transcription occurred in strains that had overcome replicative senescence and expressed telomerase activity. Deletion analysis of hTERT promoter identified the 181-bp core promoter region upstream of the transcription start site. Gel shift analysis revealed two major factors binding to core promoter, an E box (CACGTG) binding factor and Sp1. Overexpression of c-Myc resulted in a significant increase in transcriptional activity of the core promoter. These findings suggest that hTERT expression is strictly regulated at the transcription machinery, and that the proximal core promoter containing an E box and Sp1 sites is required for transactivation of hTERT.

Base Sequence↗

Developmental care for promoting development and preventing morbidity in preterm infants.

BACKGROUND: Preterm infants experience a range of morbidity related to the immaturity of their organ systems and to concurrent disease states. An unfavourable environment in the neonatal intensive care unit (NICU) may compound this morbidity. Modification of the environment could minimize the iatrogenic effects. Developmental care is a broad category of interventions designed to minimize the stress of the NICU environment. These interventions may include one or more elements such as control of external stimuli (vestibular, auditory, visual, tactile), clustering of nursery care activities, and positioning or swaddling of the preterm infant. Individual strategies have also been combined to form programs, such as the 'Neonatal Individualized Developmental Care and Assessment Program' (NIDCAP) (Als 1986). OBJECTIVES: In preterm infants, do developmental care interventions reduce neurodevelopmental delay, poor weight gain, length of hospital stay, length of mechanical ventilation, physiological stress and other clinically relevant adverse outcomes? SEARCH STRATEGY: The Neonatal Review Group search strategy was utilized. Searches were made of Medline from 1966 to July, 2000, and of CINAHL, The Cochrane Library, and conference and symposia proceedings in the English language from 1990 to July, 2000. A list of all relevant articles was sent to two experts in the field to identify any omissions or additional unpublished studies. SELECTION CRITERIA: Randomized trials in which elements of developmental care are compared to routine nursery care for infants < 37 weeks gestation and that measured clinically relevant outcomes. Reports were in English or a language for which a translator was available. Computerized searches were conducted and all potentially relevant titles and abstracts were extracted. Retrieved articles were assessed for relevance independently by two reviewers, based on predetermined criteria. Articles that met all criteria for relevance were assessed for methodological quality based on predetermined criteria. Articles judged to have the appropriate quality by both reviewers were included in the analysis. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the two authors. Meta-analyses were conducted for each intervention where the same outcome measures and/or instruments were used within comparable time points. MAIN RESULTS: This review detected 31 eligible randomized controlled trials involving four major groups of developmental care interventions, 19 sub-groups and multiple clinical outcomes. The results of the review indicate that developmental care interventions demonstrate some benefit to preterm infants with respect to: improved short-term growth outcomes, decreased respiratory support, decreased length and cost of hospital stay, and improved neurodevelopmental outcomes to 24 months corrected age. These findings were based on two or three small trials for each outcome, and did not involve meta-analyses of more than two trials for any one outcome. Although a number of other benefits were demonstrated, those results were from single studies with small sample sizes. The lack of blinding of the assessors was a significant methodological flaw in half of the studies. The cost of the interventions and personnel was not considered in any of the studies. REVIEWER'S CONCLUSIONS: Because of the inclusion of multiple interventions in most studies, the determination of the effect of any single intervention is difficult. Although there is evidence of some benefit of developmental care interventions overall, and no major harmful effects reported, there were a large number of outcomes for which no or conflicting effects were demonstrated. The single trials that did show a significant effect of an intervention on a major clinical outcome were based on small sample sizes, and the findings were often not supported in other small trials. Before a clear direction for practice can be supported, evidence demonstrating more consistent effects of developmental care interventions on important short- and long-term clinical outcomes is needed. The economic impact of the implementation and maintenance of developmental care practices should be considered by individual institutions.

Developmental Disabilities↗