Screening For Metabolic Disorders Research Articles

Clinical feasibility of dried blood spots: Analytics, validation, and applications

Dried blood spots (DBS) sampling and their specific advantages are becoming common in analytical and clinical routine. Being first established for metabolic disorder screening in neonates, its use emerged to a broad spectrum of clinical applications. Although DBS are easily generated, the conduction of specific analytical and clinical validation procedures should be obligatory when implementing DBS for clinical purposes, e.g. therapeutic drug monitoring or clinical drug trials. A respective recommendation has already been published by the European Bioanalysis Forum. Since no official guidelines are present, investigators are currently free in DBS procedure development and validation. This review summarizes and discusses published clinical validation procedures in relation to their applications to highlight the clinical feasibility of DBS.

An Overview of Biochemical Genetics.

Biochemical genetics focuses on the pathophysiology, diagnosis, and treatment of inherited metabolic disorders. While individually rare, the combined incidence of these diseases makes them a significant source of morbidity and mortality, particularly among infants and young children, and new conditions continue to be identified. Inherited metabolic disorders may present as an acute, life-threatening illness or with more chronic, progressive symptoms. Population-scale newborn screening allows for early detection and treatment for >40 different metabolic disorders. This introductory unit is intended to provide an overview of the different clinical categories of metabolic disorders, including a description of modern diagnostic methods and treatment options.

NON PHARMACOLOGICAL METHODS TO REDUCE PAIN IN NEWBORNS; SYSTEMATIC REVIEW

newborns require diagnostic and preventive procedures since the early days of life, such as the heel prick screening for metabolic disorders, intramuscular injection of vaccines and, in some cases, channeling venous route. Which are often associated with a painful sensation. The evaluation of the intensity of painful stimuli in newborns has been studied in recent years. Various scales that collect physiological and behavioral parameters have been used. This somewhat has allowed us to get closer to the intensity of pain perceived by the child, and to decide if analgesia is necessary. In regards of methods of pain relief, the most important ones are the nonpharmacological approaches due to their safety, effectiveness and low cost. Therefore, we analyze the studies that evaluate the effectiveness of nonpharmacological interventions for painful procedures (IFN) in reducing pain in neonates. a systematic search would be performed and 21 specific articles on the subject would be selected, following the PRISMA guidelines. numerous studies have proven the effectiveness of nonpharmacological interventions in relieving pain in term and preterm infants. It highlights a methodological choice, especially in the measuring of painful stimulus. It requires greater involvement on the part of health workers due to the negative consequences that entails the feeling of pain at an early age, including sleep disturbances. we conclude that some of the nonpharmacological interventions are most commonly used oral administration of sweet solutions, breastfeeding and kangaroo, which have proven effective, as it involves numerous benefits for the baby. However, further studies are required in this regard, and the implementation of a universal evaluation method for the subsequent evaluation of results in the medium and long term.

Current and future perspective of newborn screening: an Indian scenario.

Newborn screening comprises a paramount public health program seeking timely detection, diagnosis, and intervention for genetic disorders that may otherwise produce serious clinical consequences. Today newborn screening is part of the health care system of developed countries, whereas in India, newborn screening is still in the toddler stage. We searched PubMed with the keywords newborn screening for metabolic disorders, newborn screening in India, and congenital disorder in neonates, and selected publications that seem appropriate. In India, in spite of the high birth rate and high frequency of metabolic disorders, newborn screening programs are not part of the health care system. At Union Territory, Chandigarh in 2007, newborn screening was initiated and is currently ongoing for three disorders, that is, congenital hypothyroidism, congenital adrenal hyperplasia, and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Prevalence of these disorders is found to be 1:1400 for congenital hypothyroidism, 1:6334 for congenital adrenal hyperplasia, and 1:80 for G6PD deficiency. Mandatory newborn screening for congenital hypothyroidism should be implemented in India, and other disorders can be added in the screening panel on the basis of region-wise prevalence. The objective of this review is to provide insight toward present scenario of newborn screening in India along with recommendations to combat the hurdles in the pathway of mandatory newborn screening.

Analysis of benzodiazepines and their metabolites using DBS cards and LC–MS/MS

Dried Blood Spot (DBS) has been used a blood extraction method for inherited metabolic disorder screening since 1960s. With introduction of LC–MS/MS, not only DBS could be used to analysis drugs in small blood volume, but in various fields, such as toxicology, drug therapeutic monitoring, drug diagnostic screening, and illicit drugs. In toxicology field, many drugs (e.g. benzodiazepines, acetaminophen, small molecule drugs) have been tested with DBS. Compared with earlier blood extraction methods (SPE and LLE), DBS has lots of advantages; lower blood volume (less than 50μL), shorter analysis time caused by a more concise analysis procedure and lower cost. We optimized the DBS procedure and LC–MS/MS conditions for 18 benzodiazepines, seven benzodiazepine metabolites, and one z-drug (zolpidem) analysis in blood. 30μL of whole blood was spotted on FTA DMPK card C and dried for 2h in a desiccator. A 6-mm disk was punched and vortexed for 1min in a centrifuge tube with 300μL methanol/acetonitrile mixture (1:1, v/v). After evaporation, redissolved in 100μL mobile phase of LC–MS/MS and 5μL was injected. In the analysis for 26 target compounds in blood, all of the method validation parameters – LLOD, LLOQ, accuracy (intra- and inter-assay), and precision (intra- and inter-assay) – were satisfied with method validation criteria, within 15%. The results of matrix effect, recovery, and process efficiency were good. We developed a fast and reliable sample preparation method using DBS for 26 benzodiazepines, benzodiazepine metabolites, and z-drug (zolpidem).

The Big Screen Difference

The Big Screen Difference

Fifteen years experience: Egyptian metabolic lab

BackgroundInborn errors of metabolism (IEM) are single gene disorders responsible for abnormalities in the synthesis or catabolism of proteins, carbohydrates and fats by means of defective enzymes or transport proteins which results in a block of the metabolic pathway and accumulation of metabolites in different tissues. This study shows the most common diagnosed inherited inborn errors of metabolism among the Egyptian population. Prior to 1995, the diagnosis of inherited metabolic disorders in Egypt was very limited and diagnosed mainly on clinical suspicion. In 1995, The Biochemical Genetics Unit at The National Research Centre has been established as a part of The Human Genetics Department and later on in 2003 it was developed into The Biochemical Genetics Department by applying advanced techniques and equipments and providing early diagnosis for the metabolic disorders which led to better outcome in our patients. Material and methodsWe have retrospectively reviewed a total of 12,148 cases suspected to have inborn errors of metabolism (IEM) with different age groups. They had been referred from several diagnostic centers and hospitals in Egypt to The Department of Biochemical Genetics at The National Research Centre. The diagnosis of these disorders was confirmed by qualitative determination of amino acid profile, quantitative determination of phenylalanine and galactose levels using dried blood spots (DBSs), quantitative determination of urinary glycosaminoglycans (GAGs), two-dimensional electrophoretic separation of GAGs in urine and the assay for lysosomal enzymes activities in plasma and leukocytes. ResultsOut of the total number of cases; 1041 (8.6%) patients were proved to have metabolic disorders. Those patients were classified as: 722 patients (69.4%) with lysosomal storage disorders, 302 patients (29%) with amino acid disorders and 17 patients (1.6%) with galactosemia. ConclusionThis study illustrates the experience of the reference metabolic lab in Egypt over 15years. The lab began metabolic disorder screening by using simple diagnostic techniques like thin layer chromatography and colored tests in urine which by time updated and upgraded the methods to diagnose a wide range of disorders. This study shows the most common diagnosed inherited inborn errors of metabolism among the Egyptian population.

Cyclization‐Induced Turn‐On Fluorescence System Applicable to Dicarboxylate Sensing

A novel tetraphenylethene-based fluorescence (FL) chemosensor exhibits nonlinear turn-on FL switching though cooperative binding of L-tartarate, where its convergent binding to form cyclic substructures is responsible for the FL increase. This binding scheme achieves selective detection of dicarboxylates over monocarboxylates, thus is potentially applicable to the preliminary screening for metabolic disorders.

Selective newborn screening of inborn errors of amino acids, organic acids and fatty acids metabolism in the Kingdom of Bahrain

Mandatory newborn screening for metabolic disorders has not been implemented in most Middle Eastern countries. Early detection and treatment of inborn errors of metabolism can reduce mortality and minimize morbidity. Preliminary studies conducted in some parts of Middle East suggest that the incidences of inborn errors of metabolism are reported to be higher in the region than anywhere else in the world due to the consanguinity.In this study the incidence of inborn errors of amino acids, organic acids and fatty acids oxidation disorders was investigated from the results of blood spot analysis of 1986 symptomatic children from 1st January 2008 to 31st of December 2011. Out of 1986 newborns screened 25 infants were diagnosed and confirmed with amino acids (n=11), organic acids (n=9) and fatty acids oxidation (n=5) disorders. Overall incidences based on number of live birth between 2008 and 2011 inclusive were 1:6000, 1:8000 and 1:14,000 for amino acids, organic acids and fatty acids oxidation disorders; respectively. Out of 25 infants diagnosed, 21 were the children of first cousin marriages. Results from this study suggest high incidence of inborn errors of amino acids, organic acids and fatty acids oxidation metabolism in Bahrain and significant contribution of consanguinity in inherited metabolic disorders. Mandatory screening for inborn errors of metabolism in Bahrain is highly recommended.

Assessment of cardiovascular disease risk in patients with schizophrenia spectrum disorders in German psychiatric hospitals: results of the pharmacoepidemiologic CATS study

Patients with severe mental illness are at high risk for metabolic and cardiac disorders. Thus, monitoring of cardiovascular risks is imperative and schedules for screening for lipids, glucose, body mass index (BMI), waist-hip ratio and blood pressure have been developed. We intended to analyze screening for metabolic disorders in German patients with schizophrenia spectrum disorders in routine psychiatric care. We included 674 patients with any F2 diagnosis in out- and inpatient settings and analyzed metabolic screening procedures as practiced under conditions of usual care. Except BMI (54%), all other values were documented only in a minority of patients: waist circumference (23%), cholesterol (28%), fasting glucose (19%), triglycerides (25%) and blood pressure (37%). We found evidence for less than perfect quality of blood pressure measures. The group of patients who met the individual metabolic syndrome ATPIII criteria was comparable to the US CATIE trial. We conclude that frequency and quality of metabolic monitoring in German in- and outpatients settings are not in accordance with the respective recommendations. Similar to previous reports we found evidence for a high prevalence of metabolic disturbances in German patients with schizophrenia spectrum disorders.

Unique acyl-carnitine profiles are potential biomarkers for acquired mitochondrial disease in autism spectrum disorder

Autism spectrum disorder (ASD) has been associated with mitochondrial disease (MD). Interestingly, most individuals with ASD and MD do not have a specific genetic mutation to explain the MD, raising the possibility of that MD may be acquired, at least in a subgroup of children with ASD. Acquired MD has been demonstrated in a rodent ASD model in which propionic acid (PPA), an enteric bacterial fermentation product of ASD-associated gut bacteria, is infused intracerebroventricularly. This animal model shows validity as it demonstrates many behavioral, metabolic, neuropathologic and neurophysiologic abnormalities associated with ASD. This animal model also demonstrates a unique pattern of elevations in short-chain and long-chain acyl-carnitines suggesting abnormalities in fatty-acid metabolism. To determine if the same pattern of biomarkers of abnormal fatty-acid metabolism are present in children with ASD, the laboratory results from a large cohort of children with ASD (n=213) who underwent screening for metabolic disorders, including mitochondrial and fatty-acid oxidation disorders, in a medically based autism clinic were reviewed. Acyl-carnitine panels were determined to be abnormal if three or more individual acyl-carnitine species were abnormal in the panel and these abnormalities were verified by repeated testing. Overall, 17% of individuals with ASD demonstrated consistently abnormal acyl-carnitine panels. Next, it was determined if specific acyl-carnitine species were consistently elevated across the individuals with consistently abnormal acyl-carnitine panels. Significant elevations in short-chain and long-chain, but not medium-chain, acyl-carnitines were found in the ASD individuals with consistently abnormal acyl-carnitine panels—a pattern consistent with the PPA rodent ASD model. Examination of electron transport chain function in muscle and fibroblast culture, histological and electron microscopy examination of muscle and other biomarkers of mitochondrial metabolism revealed a pattern consistent with the notion that PPA could be interfering with mitochondrial metabolism at the level of the tricarboxylic-acid cycle (TCAC). The function of the fatty-acid oxidation pathway in fibroblast cultures and biomarkers for abnormalities in non-mitochondrial fatty-acid metabolism were not consistently abnormal across the subgroup of ASD children, consistent with the notion that the abnormalities in fatty-acid metabolism found in this subgroup of children with ASD were secondary to TCAC abnormalities. Glutathione metabolism was abnormal in the subset of ASD individuals with consistent acyl-carnitine panel abnormalities in a pattern similar to glutathione abnormalities found in the PPA rodent model of ASD. These data suggest that there are similar pathological processes between a subset of ASD children and an animal model of ASD with acquired mitochondrial dysfunction. Future studies need to identify additional parallels between the PPA rodent model of ASD and this subset of ASD individuals with this unique pattern of acyl-carnitine abnormalities. A better understanding of this animal model and subset of children with ASD should lead to better insight in mechanisms behind environmentally induced ASD pathophysiology and should provide guidance for developing preventive and symptomatic treatments.

A rapid UPLC–MS/MS method for simultaneous separation of 48 acylcarnitines in dried blood spots and plasma useful as a second-tier test for expanded newborn screening

Acylcarnitine profiling in dried blood spots (DBS) is a useful method for high-throughput newborn screening of metabolic disorders, but differentiation of isobaric and isomeric compounds is not achievable. Chromatographic methods for separation have already been reported but are specific for short-chain acylcarnitines or time-consuming. The aim of this work was to develop a fast ultraperformance liquid chromatography (UPLC)-tandem mass spectrometry (MS/MS) method for separation and quantification of a large number of acylcarnitines, including dicarboxylic acylcarnitines and hydroxyacylcarnitines, in DBS and plasma samples. Acylcarnitines from DBS and plasma were converted to their butyl esters and analyzed by electrospray ionization MS/MS. Chromatographic separation was achieved using a UPLC system equipped with an ethylene-bridged hybrid C(18) column. The correlation coefficients of the calibration curves (r(2)) ranged from 0.990 to 0.999. The limit of detection ranged from 0.002 and 0.063 μM for all compounds, and the limit of quantification ranged from 0.004 and 0.357 μM. Precision ranged from 0.8 to 8.8% and the mean recovery was 103%. Profiles of acylcarnitine isomers were investigated in specimens obtained from patients diagnosed with different inborn errors of metabolism. Acylcarnitine concentrations were also measured in 58 term newborns and compared with flow injection analysis measurements. With this newly developed UPLC-MS/MS method, the simultaneous detection of 61 (13 of these labeled) acylcarnitines in DBS and plasma can be achieved in 15 min including postrun equilibration. The method has been validated and can be used as an important component of newborn screening methods as a second-tier test for discrimination and to confirm diagnosis.

Newborn Screening for Metabolic Disorders

Positive newborn screening (NBS) results cause significant parental distress, but little is known about how parents find out about children's screening results and what they are told. This qualitative, exploratory study reports on parents' perceptions of the initial communication of NBS results. Participants included the parents of 75 infants referred to a metabolic clinic in California over a 3-year period (2007-2010). Parents provided information about the initial communication of NBS results during audiotaped clinical encounters and open-ended interviews. Transcripts were analyzed inductively using thematic coding. Responses fell into 3 primary themes: sources of news delivery, providing information, and mitigation strategies. The findings suggest that health care providers have access to a range of communicative resources to buffer the impact of positive screening results that may be mobilized in future interventions. Recommendations for improving the communication process and future research directions are discussed.

Psychological Effects of False-Positive Results in Expanded Newborn Screening in China

ObjectivesAs more families participate expanded newborn screening for metabolic disorders in China, the overall number of false positives increases. Our goal was to assess the potential impact on parental stress, perceptions of the child's health, and family relationships.MethodsParents of 49 infants with false-positive screening results for metabolic disorders in the expanded newborn screening panel were compared with parents of 42 children with normal screening results. Parents first completed structured interview using likert scales, closed and open questions. Parents also completed the parenting stress index.ResultsA total of 88 mothers and 41 fathers were interviewed. More mothers in the false-positive group reported that their children required extra parental care (21%), compared with 5% of mothers in the normal-screened group (P<0.001). 39% of mothers in the false-positive group reported that they worry about their child's future development, compared with 10% of mothers in the normal-screened group (P<0.001). Fathers in the false-positive group did not differ from fathers in the normal-screened group in reporting worry about their child's extra care requirements, and their child's future development. Children with false-positive results compared with children with normal results were triple as likely to experience hospitalization (27%vs 9%, respectively; P<0.001).ConclusionsThe results showing false-positive screening results may affect parental stress and the parent-child relationship. Parental stress and anxiety can be reduced with improved education and communication to parents about false-positive results.

Methionine Synthase Deficiency (cblG): A Rare Cause of Adult Onset Leukoencephalopathy with Reversible Neurological Deficit (P01.124)

Objective: To describe a very rare cause of leucoencepahlopathy with adult onset. Background The presentation of cobalamin (cbl) metabolism disorders has usually been in the first 2 years of life. Design/Methods: A woman complained of pain of the lower limbs at the age of 23. A severe macrocytosis without anemia was observed few years before neurological complain with normal serum folate and vitamin B12 concentrations. At 24 years of age, mild paraparesis appeared subacutely then worsened progressively. Brain MRI showed periventricular leukoencephalopathy. She was considered as having possible multiple sclerosis but cerebrospinal fluid analysis was normal without oligoclonal bands. Results: At the age of 27, a second brain and spinal cord MRI showed moderate cerebral atrophy with periventricular leukoencephalopathy and cervical thinning of spinal cord. Neuro-ophthalmologic examination showed bilateral optic neuropathy. Extensive metabolic analyses in search for metabolic leukodystrophies were negative. Further screening for metabolic disorders revealed hyperhomocysteinemia with hypomethioninemia in the absence of methylmalonic acid upon chromatography. The abnormalities were thought to be due to a defect in homocysteine remethylation. Complementation studies upon cultured fibroblasts indicated a cblG defect rather than a cblE defect. Therapy with intra-muscular hydroxycobalamine and oral betaine was started resulting in normalization of plasma and urine homocysteine concentrations and MCV. Neurological improvement became significant at 3 months. Brain MRI performed respectively at 6 months, 5 years and 7 years of treatment showed an overall stabilization of T2 lesion load but with a slight posterior reduction of periventricular leucopathy. After a review of the literature, we only found 1 case of methionine synthase cblG deficiency with adult onset. Conclusions: In the diagnosis work-up of a adult-leukoencephalopathy, association of homocystinuria and hypomethionemia in the absence of methylmalonic aciduria, should make consider methylcobalamin deficiency due to cobalamin E (cblE) or G (cblG). Disclosure: Dr. Outteryck has received personal compensation for activities with Biogen Idec, Bayer Schering, Teva Neuroscience, Merck & Co., Inc., and Sanofi-Aventis Pharmaceuticals, Inc. Dr. De Seze has received personal compensation for activities with Bayer Schering, Biogen Idec, LFB, Merck Serono, Novartis, Sanofi-Aventis, and Teva Neuroscience.Dr. De Seze has received personal compensation in an editorial capacity for Elsevier. Dr. Stojkovic has received personal compensation for activities with Biogen Idec, Bayer Schering Pharma, Teva, Merck, Sanofi, and LFB. Dr. Delalande has nothing to disclose. Dr. Lacour has received personal compensation for activities with LFB, Genzyme, Biogenidec, Merck, Bayer Schering Pharma, Teva, and Sanofi as a consultant. Dr. Fowler has nothing to disclose. Dr. Vermersch has received personal compensation for activites with Merck Serono, Bayer Schering, Teva-Aventis, Biogen Idec, Allmirall, and Novartis as a consultant and/or speaker.

Newborn Screening for Metabolic Disorders: How Are We Doing, and Where Are We Going?

Owing to technological advances during the last decade, there has been a paradigm shift in the way that we diagnose patients with inherited metabolic disease. The introduction of tandem mass spectrometry (MS/MS),7 a technology with sufficient analytical sensitivity to measure metabolic biomarkers in small blood spot samples, has allowed us to shift from what was initially a diagnosis made after or during acute metabolic decompensation into an era in which diagnosis is made immediately in the newborn period. In this environment, the diagnosis of certain metabolic diseases frequently precedes the onset of symptoms, giving physicians an opportunity to prevent many of the catastrophic events that used to occur. To this point, disorders such as medium-chain acyl-CoA dehydrogenase (MCAD) deficiency now rarely initially present as the acute-onset liver failure that was previously seen in unscreened and consequently undiagnosed patients. Clinical outcomes for MCAD deficiency are now excellent, and data on some of the other screened disorders are starting to show the benefit of early diagnosis. Diagnostic technology continues to increase in its capability to provide early diagnosis of increasing numbers of these metabolic diseases as more biomarkers become identified. In this Q&A, 5 leading thinkers in the field provide their insights into where we presently stand in this area and where we might be headed in the future. Has there been a positive impact on patient care as a result of early diagnosis and implementation of the American College of Medical Genetics (ACMG) recommended-screening disorders? Piero Rinaldo: The implementation of the ACMG uniform panel has had a positive impact at multiple levels. The consistency of the panel has virtually eliminated the discrepancies between neighboring states, often a cause of heartbreaking events where parents have experienced significant morbidity and mortality of their child that would not have happened if their child …

Postmortem tandem mass spectrometry profiling for detection of infection in unexpected infant death

Numerous hypotheses have been suggested to explain the cause of sudden unexpected infant death, including infection. As part of the autopsy, routine ancillary investigations are performed, including blood/bile tandem mass spectrometry (TMS) primarily for detection of metabolic disease. The aim of this study was to evaluate and assess TMS derived acylcarnitine profiles to determine whether infectious deaths were associated with characteristic profiles. As part of a retrospective study including >2,500 pediatric autopsies at a single specialist centre over a 14 year period, acylcarnitine profiles were reviewed. Using multiple linear regression, standardised residuals were prepared and findings compared between different cause of death groups, including unexplained, focal infection, microbiological infection and accidental injuries. 415 blood samples from SUDI autopsies were identified. Statistically significant differences in TMS profiles were identified between those dying of infection and the unexplained SUDI group, including changes in free carnitine, short chain acylcarnitines and octanoylcarnitine. Cases with microbiological infection diagnosed only from postmortem cultures did not show any significant difference from the unexplained group. Postmortem TMS profiling identifies SUDI deaths which are associated with histological evidence of infection, and an acylcarnitine profile suggesting perturbation of oxidative metabolism. Such findings raise the possibility that more comprehensive TMS profiling may offer additional diagnostic clues beyond screening for metabolic disorders, and may contribute to determination of mode of death.

P1-S2.71 Sexually transmitted infections in Mexico-City's penitentiary centers: the Ponte a Prueba: put yourself to the test “study”

BackgroundSocial and behavioural risk factors, as well as the conditions within penitentiary centers, place incarcerated people at high risk for infectious diseases. Few data exist for penitentiary health in Latin...

Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: A worldwide collaborative project

PurposeTo achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort. MethodsCumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25–30 million normal newborns and 10,742 deidentified true positive cases are compared to assign clinical significance, which is achieved when the median of a disorder range is, and usually markedly outside, either the 99th or the 1st percentile of the normal population. The cutoff target ranges of analytes and ratios are then defined as the interval between selected percentiles of the two populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity taking all available factors into consideration. ResultsAs of December 1, 2010, 130 sites in 45 countries have uploaded a total of 25,114 percentile data points, 565,232 analyte results of true positive cases with 64 conditions, and 5,341 cutoff values. The average rate of submission of true positive cases between December 1, 2008, and December 1, 2010, was 5.1 cases/day. This cumulative evidence generated 91 high and 23 low cutoff target ranges. The overall proportion of cutoff values within the respective target range was 42% (2,269/5,341). ConclusionAn unprecedented level of cooperation and collaboration has allowed the objective definition of cutoff target ranges for 114 markers to be applied to newborn screening of rare metabolic disorders. Genet Med 2011:13(3):230–254.

Strengthening preventive care programs: a permanent challenge for healthcare systems; lessons from PREVENIMSS México.

BackgroundIn 2001, the Instituto Mexicano del Seguro Social (IMSS) carried out a major reorganization to provide comprehensive preventive care to reinforce primary care services through the PREVENIMSS program. This program divides the population into programmatic age groups that receive specific preventive services: children (0-9 years), adolescents (10-19 years), men (20-59 years), women (20-59 years) and older adults (> = 60 years). The objective of this paper is to describe the improvement of the PREVENIMSS program in terms of the increase of coverage of preventive actions and the identification of unmet needs of unsolved and emergent health problems.MethodsFrom 2003 to 2006, four nation-wide cross-sectional probabilistic population based surveys were conducted using a four stage sampling design. Thirty thousand households were visited in each survey. The number of IMSS members interviewed ranged from 79,797 respondents in 2003 to 117,036 respondents in 2006.ResultsThe four surveys showed a substantial increase in coverage indicators for each age group: children, completed schemes of vaccination (> 90%), iron supplementation (17.8% to 65.5%), newborn screening for metabolic disorders (60.3% to 81.6%). Adolescents, measles - rubella vaccine (52.4% to 71.4%), hepatitis vaccine (9.3% to 46.2%), use of condoms (17.9% to 59.9%). Women, measles-rubella vaccine (28.5% to 59-2%), cervical cancer screening (66.7% to 75%), breast cancer screening (> 2.1%). Men, type 2 diabetes screening (38.6% to 57.8%) hypertension screening (48-4% to 64.0%). Older adults, pneumococcal vaccine (13.2% to 24.9%), influenza vaccine (12.6% to 52.9) Regarding the unmet needs, the prevalence of anemia in children was 30% and a growing prevalence of overweight and obesity, type 2 diabetes, and hypertension was found in men, women and older adults.ConclusionPREVENIMSS showed an important increase in the coverage of preventive services and stressed the magnitude of the old and new challenges that this healthcare system faces. The unsolved problems such as anemia, and the emerging ones such as overweight, obesity, among others, point out the need to strength preventive care through designing and implementing innovative programs aimed to attain effective coverage for those conditions in which prevention obtains substandard results.