Characterization of a new BRCA1 rearrangement in an Italian woman with hereditary breast and ovarian cancer syndrome.

BACKGROUND: We report a novel BRCA1 LGR, involving the complete duplication of exon 3, in an Italian patient with a strong family history of breast and ovarian cancer. Our purpose is to provide an effective characterization of this LGR using a combination of different methods able to establish the exact breakpoints of the duplication. METHODS: MAQ assay was used as primary screening method in LGRs detection. Array CGH, RT-PCR, and Long-PCR were used for a careful characterization of rearrangement and breakpoint regions. The Repeat Masker program was employed to identify Alu sequences at breakpoint junctions. RESULTS: RNA analysis showed that this in tandem duplication of exon 3 causes an in frame insertion of 18 amino acids within the protein. Array CGH and Long-PCR strategies revealed that the duplication (g.100411_102863dup) involves exactly 2.452 nucleotides between intron 2 and intron 3 of the gene. In addition, while an Alu Sx sequence was identified at upstream breakpoint, no Alu repeats were found at downstream junction. This supports the hypothesis that the new duplication was the result of a non-homologous recombination event between Alu and Non-Alu sequences. CONCLUSION: Our strategy, which combines a comprehensive set of methodologies, has been able to characterize the new BRCA1 duplication confirming, as previously reported, that MAQ assay represents a reliable and effective method for a primary screening of BRCA rearrangements. We underline the relevance of incorporating quantitative methods for BRCA genes dosage testing into routine diagnostic practice.

Fecal but not serum calprotectin is a potential marker of GVHD after stem cell transplantation.

Gastrointestinal graft-versus-host disease (GvHD) represents a life-threatening complication after stem cell transplantation. Differential diagnosis between gut GvHD and other causes of diarrhea after HSCT is still subjected to endoscopy and histological findings. The research for a reliable biomarker for gut GvHD might allow an early diagnosis of this condition and a consequent prompt treatment that could reduce unfavorable outcomes. Recently, fecal calprotectin was reported as reliable marker of gut involvement. We would evaluate if serum instead of fecal calprotectin could be considered a possible biomarker of gut GvHD. Serum calprotectin was measured in a cohort of 54 patients submitted to allogeneic stem cell transplantation using ELISA assay. For a subset of 21 patients, calprotectin serum levels were compared with fecal calprotectin detection. Contrary to fecal calprotectin, we found only a trend to high level of serum calprotectin for GvHD development and gut involvement, but statistical difference was not reached. Fecal but not serum calprotectin could be considered as possible biomarker for gut GvHD.

Comparison of Fully Automated and Semiautomated Systems for Protein Immunofixation Electrophoresis.

BACKGROUND: In order to establish a diagnosis of monoclonal gammopathy, it is necessary to detect and identify monoclonal components. To confirm the immunological nature of the proteins, the next step is to define their composition in heavy and light chains using immunofixation. The purpose of this study was to compare two different instruments, one semiautomated and the other fully automated for serum and urine immunofixation. METHODS: We selected 150 sera and 100 urines from patients admitted for routine analysis, which were analyzed by immunofixation to characterize monoclonal components. RESULTS AND CONCLUSION: Comparison study showed a difference in the identification of small monoclonal components and hypogammaglobulinemia, in serum and urine, between the two analyzers. We also observed a difference in the length of the electrophoretic pattern that is of considerable importance as it leads to a better resolution of the gamma region, allowing to identify even the smallest monoclonal component that can be easily hide in an oligoclonal pattern. For this reason, there is need to ameliorate commercial immunofixation assays. It is essential to improve data harmonization and standardize measurement procedures in order to guarantee a correct diagnosis for the right patient care.

Urinary Albumin Detection: Comparison of Two Different Methods.

BACKGROUND: Monitoring urinary albumin is a useful method in clinical practice for the management of diabetic nephropathy, chronic kidney disease, and hypertension. Currently there are neither standardized methods nor reference material for the determination of urinary albumin; for this reason it is useful to compare different assays used in clinical laboratory. OBJECTIVES: The aim of this study is to verify analytical performance of an immunoturbidimetric assay on Roche Cobas 8000 platform and to compare urinary albumin results with those obtained by immunonephelometry on Siemens Dade Behring BN II Nephelometer. RESULTS: The method comparison showed a good linear relationship, confirmed by Passing-Bablok and Bland-Altman plots. The turbidimetric assay meets the requirements of accuracy and precision for the practice of medical diagnostics and clinical use. CONCLUSIONS: The present study can contribute to the methods standardization and harmonization of urinary albumin assay.

Is intraoperative calcitonin monitoring useful to modulate the extension of neck dissection in patients with medullary thyroid carcinoma?

BACKGROUND: The extension of the compartment-oriented neck dissection at primary surgery in medullary thyroid carcinoma (MTC) is controversial. Because a <50 % decrease in intraoperative calcitonin levels (IO-CT) after total thyroidectomy plus central neck dissection (TT-CND) has been associated with residual disease, IO-CT monitoring has been proposed to predict the completeness of surgery. The goal of the present prospective study was to verify the accuracy of IO-CT monitoring. METHODS: All patients scheduled for primary surgery for suspected or proven MTC between November 2010 and January 2013 were included. Calcitonin was measured pre-incision (basal level), after tumor manipulation, at the time TT-CND was accomplished (ablation level), 10 and 30 min after ablation. A decrease >50 % with respect to the highest IO-CT level 30 min after ablation was considered predictive of cure. RESULTS: Twenty-six patients were included, and IO-CT monitoring identified 18 of 23 cured patients (true negative results) and 2 of 3 patients with persistent disease (true positive result). In 5 patients with normal basal and stimulated postoperative calcitonin levels, a decrease <50 % was observed (false positive results). In one of three patients with persistent disease a >50 % decrease in IO-CT was observed (false negative results). Specificity, sensitivity, and accuracy of IO-CT were 78.2, 66.6, and 76.9 %, respectively. CONCLUSIONS: Intraoperative calcitonin monitoring is not highly accurate in predicting the completeness of surgical resection. In the present series, relying on IO-CT would result in limited resection in about one third of the patients with residual neck disease and in unnecessary lateral neck dissection in about 20 % of the cured patients.

Evaluation of the diagnostic and predictive power of PCA3 in the prostate cancer. A different best cut-off in each different scenario. Preliminary results.

INTRODUCTION: Aim of this study is to evaluate the diagnostic performance of PCA3 in patients with indication to perform a new biopsy, according to the histological doubt such as High Grade Prostatic Intraepithelial Neoplasia (HGPIN) or Atypical Small Gland Proliferation (ASAP) or the clinical suspicion. MATERIALS AND METHODS: One hundred men were enrolled. We used the PCA3 - PROGENSA™ procedure. After the PCA3 test a repeated prostate biopsy was proposed. The histological findings were correlated to the PCA3 scores. We calculated the positive predictive value (PPV), the sensibility, the specificity, the Youden's index, the ROC curves, the area under the curve (AUC) for each cut-off value of PCA3 score. RESULTS: These results are preliminary, because at present only 50 of the 100 enlisted men were subjected to rebiopsy. We calculated the best cut-off PCA3 score 20 at the first diagnosis; for patients with HGPIN or ASAP at first biopsy the best sensitivity cut-off is 45; the best cutoff is 45 when you already have a diagnosis of HGPIN, and 35 for ASAP. If we normalize the PCA3 score to the prostate volume, the best cut-off would be 20, with 100% sensitivity with a prostate volume of 65 ml. All results are statistically significant. The real problem, also present in literature, is the constant presence of not diagnosed prostate cancers, for any cut-off value. CONCLUSIONS: Our preliminary results suggest that, to get the best diagnostic performance, it would be wrong to maintain a single cut-off, but it should be chosen according to the scenario of the patients subgroup. It is to explore the possibility to search for the PCA3 in the serum to bridge the gap of the aggressive PCa missed by the urinary test.

Gilbert and Crigler Najjar syndromes: an update of the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene mutation database.

UGT1A1 enzyme defects are responsible of both Gilbert syndrome (GS) and Crigler-Najjar syndrome (CNS). GS depends on a variant TATAA element (which contains two extra TA nucleotides as compared to the wild type genotype) in the UGT1A1 gene promoter resulting in a reduced gene expression. On the contrary, CNS forms are classified in two types depending on serum total bilirubin concentrations (STBC): the more severe (CNS-I) is characterized by high levels of STBC (342-684µmol/L), due to total deficiency of the UGT1A1 enzyme, while the milder one, namely CNS-II, is characterized by partial UGT1A1 deficiency with STBC ranging from 103 to 342µmol/L. GS and CNS are caused by genetic lesions involving a complex locus encoding the UGT1A1 gene. The present report provides an update of all reported UGT1A1 gene mutations associated to GS and CNS.

Myocardial performance index and biochemical markers for early detection of doxorubicin-induced cardiotoxicity in children with acute lymphoblastic leukaemia.

BACKGROUND: Despite significant improvements in the prognosis of childhood acute lymphoblastic leukaemia (ALL), the risk of anthracycline-induced cardiovascular disease remains a major concern. This study was designed to investigate the role of the myocardial performance index (MPI) and serum concentrations of biomarkers (cTnT and NT-pro-BNP) in the early detection of subclinical anthracycline-induced functional alterations in children with ALL. METHODS: All children consecutively admitted to our Pediatric Oncologic Department from January 2009 to October 2010 with a diagnosis of ALL were enrolled in this study. cTnT and NT-pro-BNP were evaluated in all patients at diagnosis, before doxorubicin therapy and 2 and 24 h following each anthracycline administration. ECG and echocardiography were performed at diagnosis and 24 h after each anthracycline course. RESULTS: Nineteen children with standard-risk ALL were evaluated. The mean age was 6 years. The cumulative doxorubicin dosage was 240 mg/m(2) according to the AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) ALL 2000 protocol. None of the 19 patients developed congestive heart failure. With increasing cumulative dosages of anthracyclines a significant increase was observed in MPI. This increase was statistically significant starting from the cumulative dosage of 120 mg/m(2) compared to baseline, while the median NT-pro-BNP level did not change significantly during treatment and cTnT levels never exceeded the cut-off value for cardiac injury. CONCLUSION: MPI value is a sensitive and accurate parameter, allowing subclinical cardiac dysfunction to be detected in children receiving anthracyclines. Lifelong cardiac surveillance of these patients is warranted in order to determine the clinical implications of increased MPI on long-term cardiac status.

Potential usefulness of CTC detection in follow up of prostate cancer patients. A preliminary report obtained by using Adnagene platform.

OBJECTIVE: Prostate cancer (PCa) represents one of the most important medical problems for males, being the second major cause of cancer death. Routinely, PCa patients are followed up with both periodic evaluation of serum PSA levels and imaging. Recently, alternative laboratory methods were proposed for PCa patients' monitoring, with contrasting results. Aim of the present study was to evaluate the usefulness of a new commercially CE-IVD kit for detection of prostate circulating tumour cells. Our intention was to verify the Adnagene platform usefulness to identify patients with disease progression, whatever treatment ongoing, in order to modify the therapeutic process even before treatment failure is evident with imaging methods. MATERIALS AND METHODS: Twenty-one patients were enrolled and subdivided into three groups: n = 10 high risk tumor PCa patients; n = 6 low risk PCa patients; n = 5 sbjects without any signs of PCa. AdnaTest Prostate Cancer kit was used for enrichment and molecular characterization of prostate circulating tumour cells. RESULTS: Healthy subjects (with BPH) and patients without metastases resulted as negative, while 3 out of 10 high risk PCa patients were positive at least for one molecular marker like PSA, while only two showed positivity for PSMA mRNA. Our results indicate that the test specificity is 100% and the sensitivity is 100%; of course the sample is too small to give it statistical validity. In detail we verified that only the "not responder" patients resulted positive for AdnaTest. CONCLUSIONS: The present preliminary report provides evidence that isolation and detection of circulating tumour cells (CTCs) is feasible and it may be useful in the follow-up of patients with advanced prostate cancer. If the results of this preliminary study would be confirmed by a large prospective cohort study, it could be demonstrated that this test is a rapid diagnostic method, based on the analysis of a blood sample and useful to the clinician to decide when to change therapy for patients resistant to castration or able to confirm that, at that time, the therapy is effective.

Glucose-6-phosphate dehydrogenase (G6PD) mutations database: review of the "old" and update of the new mutations.

In the present paper we have updated the G6PD mutations database, including all the last discovered G6PD genetic variants. We underline that the last database has been published by Vulliamy et al. [1] who analytically reported 140 G6PD mutations: along with Vulliamy's database, there are two main sites, such as http://202.120.189.88/mutdb/ and www.LOVD.nl/MR, where almost all G6PD mutations can be found. Compared to the previous mutation reports, in our paper we have included for each mutation some additional information, such as: the secondary structure and the enzyme 3D position involving by mutation, the creation or abolition of a restriction site (with the enzyme involved) and the conservation score associated with each amino acid position. The mutations reported in the present tab have been divided according to the gene's region involved (coding and non-coding) and mutations affecting the coding region in: single, multiple (at least with two bases involved) and deletion. We underline that for the listed mutations, reported in italic, literature doesn't provide all the biochemical or bio-molecular information or the research data. Finally, for the "old" mutations, we tried to verify features previously reported and, when subsequently modified, we updated the specific information using the latest literature data.

A vascular endothelial growth factor deficiency characterises scleroderma lung disease.

OBJECTIVES: Vascular endothelial growth factor (VEGF) is thought to play an important role in systemic sclerosis (SSc) pathogenesis. It was found to be upregulated in the serum and in the affected skin of scleroderma patients. However, its involvement in scleroderma lung disease is not clear. This study aimed to evaluate VEGF concentration in the bronchoalveolar lavage fluid (BALF) of scleroderma patients with interstitial lung disease, to correlate the cytokine levels in plasma and in the lung with pulmonary functional, radiological and cellular parameters, and with the progression of lung disease. METHODS: BALF and plasma VEGF concentrations were analysed by ELISA in 55 SSc patients with lung disease and 17 controls. Cytokine real-time PCR messenger RNA expression in alveolar macrophages was assessed. Lung involvement progression was evaluated after a 1-year follow-up. RESULTS: VEGF was found to be significantly lower in the BALF of scleroderma patients compared with controls. The lowest concentrations were observed in SSc patients with alveolitis. A decreased VEGF expression in alveolar macrophages was found in SSc patients with alveolitis. VEGF concentration in BALF correlated inversely with the ground glass score on high-resolution CT and with BALF neutrophil cell count. Moreover, SSc patients with a lower VEGF concentration showed a worsening in the interstitial score at follow-up. CONCLUSIONS: Scleroderma interstitial lung disease is characterised by a VEGF deficiency. Lower concentrations were found in patients with progression of lung disease.

Reactive oxygen metabolites (ROMs) are associated with cardiovascular disease in chronic hemodialysis patients.

BACKGROUND: The aim of our study was to measure reactive oxygen metabolites (ROMs) in chronic hemodialysis (HD) patients and evaluate the possible association with cardiovascular disease (CVD) and mortality. METHODS: We measured ROMs in 76 HD patients and correlated with CVD, cardiovascular (CV) events in the follow-up and all-cause and CVD-related mortality. RESULTS: The levels of ROMs presented a median value of 270 (238.2-303.2) CARR U (interquartile range). We created a ROC curve (ROMs levels vs. CVD) and we identified a cut-off point of 273 CARR U. Patients with ROMs levels ≥273 CARR U were significantly older, had higher C-reactive protein levels and lower creatinine concentrations. The prevalence of CVD was higher in patients with ROMs levels ≥273 (87.1%) than in those with ROMs levels <273 CARR U (17.7%; p<0.0001). ROMs levels were significantly higher in patients with CVD (317±63.8) than in those without (242.7±49.1; p<0.0001). At multiple regression analysis, age, creatinine and C-reactive protein were independent factors associated with ROMs. At multiple logistic regression analysis the association between ROMs and CVD was independent (OR: 1.02, 95% CI: 1.00-1.05; p=0.03). Twenty six patients developed cardiovascular (CV) events during the follow-up. Of these, seven were in the group with ROMs levels <273 CARR U and 19 in the group with ROMs levels ≥273 CARR U. The logistic regression analysis showed that both age (OR: 1.06, 95% CI: 1.01-1.12; p=0.013) and ROMs levels (OR: 1.10, 95% CI: 1.00-1.02; p=0.045) were independently associated with CV events in the follow-up. CONCLUSIONS: ROMs are independently associated with CVD and predict CV events in chronic HD patients.

Rapid detection of CFH (p.Y402H) and ARMS2 (p.A69S) polymorphisms in age-related macular degeneration using high-resolution melting analysis.

BACKGROUND: Age-related macular degeneration (AMD) is a complex disorder causing irreversible central vision loss. Complement Factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) are now widely accepted as important AMD susceptibility genes. In particular, two specific variants, CFH p.Y402H and ARMS2 p.A69S, have been reported as strongly AMD associated. In order to perform the genetic screening of these single nucleotide polymorphisms (SNPs), we describe a high resolution melting analysis (HRM) as a rapid closed tube mutation scanning assay. METHODS: To validate HRM genotyping, 94 DNA samples from AMD patients (previously genotyped by sequence analysis) were analyzed. PCR amplification and melting curve analysis were performed in the LightCycler 480 Real-Time PCR System. In order to evaluate the accuracy of the HRM assay, we performed a blinded study of 20 unknown independent samples. RESULTS: We correctly genotyped all samples. In fact, all samples corresponded to the previous genotype assignments. CONCLUSIONS: Early identification of individuals with genetic risk variants CFH p.Y402H and ARMS2 p.A69S is clinically important for the definition of AMD status. High-resolution DNA melting is homogenous, accurate and rapid method for CFH and ARMS2 genotyping.

Blood presence of circulating oncofetal fibronectin mRNA, by RT-PCR, does not represent a useful specific marker for the management and follow-up of thyroid cancer patients.

BACKGROUND: Recent studies strongly suggest the use of oncofetal fibronectin (onfFN) mRNA in diagnostic follow-up and staging due to its very high specificity for thyroid cancers. Since the use of this marker has not been well established yet, particularly in the monitoring of minimal residual disease, we have tried to verify the diagnostic power of onfFN and its usefulness as a prognostic molecular marker. For this reason, we evaluated (by RT-PCR) the presence of onfFN mRNAs, not only in blood samples and thyroid tissues (both normal and neoplastic), but also in different biological fluids (such as K3-EDTA blood samples, saliva and urine) belonging to healthy individuals. METHODS: Molecular investigations, such as RT-PCR protocol, and sequencing of onfFN cDNAs evaluation of the above-mentioned samples were performed. RESULTS: The onfFN transcript was largely expressed in all benign and malignant thyroid tissues [differentiated thyroid carcinomas (DTCs)] tested as well as in a large number of biological fluids; in particular, 100% urine samples were positive for onfFN transcript as compared to the thyroglobulin (Tg) mRNA (75%), while saliva was always positive for onfFN and never for Tg. These findings indicate that onfFN cannot be considered a marker specific for thyroid cancer presence. Finally, Tg results were positive in a large part of the samples, but not always in concomitance with onfFN. CONCLUSIONS: We underline how the complexity of onfFN transcripts could affect the RT-PCR procedure. In addition, the presence of onfFN transcripts in several normal and cancer tissues, along with non-thyroid biological fluids or cells, does not allow the use of this marker for cancer monitoring.

Combining early postoperative parathyroid hormone and serum calcium levels allows for an efficacious selective post-thyroidectomy supplementation treatment.

BACKGROUND: Optimal treatment protocol to prevent symptomatic hypocalcemia following total thyroidectomy is still matter of debate. We prospectively evaluated the efficacy of a selective supplementation protocol based on both early postoperative intact parathyroid hormone (iPTH) and serum calcium levels. METHODS: Two hundred thirty consecutive patients were divided in three different groups of treatment according to iPTH levels 4 h after total thyroidectomy (4 h-iPTH) and serum calcium levels in the first postoperative day (1PO-Ca): group A (4 h-iPTH > 10 pg/ml, 1PO-Ca ≥ 8.5 mg/dl), no treatment; group B (4 h-iPTH > 10 pg/ml, 1PO-Ca < 8.5 mg/dl), oral calcium (OC) 3 g per day; and group C (4 h-iPTH ≤ 10 pg/ml), OC 3 g + calcitriol (VD) 1 µg per day. Development of biochemical and/or symptomatic hypocalcemia was evaluated. RESULTS: Fifty-nine patients (25.6%) had subnormal 4 h-iPTH levels (≤10 pg/ml) (group C). Among patients with normal 4 h-iPTH levels, 25 (10.9%) had subnormal 1PO-Ca (<8.5 mg/dl) (group B). The remaining 146 patients (63.5%) had normal 4 h-iPTH and 1PO-Ca levels (group A). One patient in group A, 2 in group B, and 18 in group C developed biochemical hypocalcemia. Only one patient in group C experienced major symptoms. Treatment was discontinued within 1 month in all the patients in group B. At a mean follow-up of 303 days, five patients in group C were still under supplementation treatment. CONCLUSION: The proposed supplementation protocol seems efficacious in preventing symptomatic hypocalcemia. It could allow a safe and early discharge of most patients, thus avoiding the constraints and the costs of routine supplementation.

Human growth hormone (GH) immunoassay: standardization and clinical implications.

BACKGROUND: The poor comparability of growth hormone (GH) results obtained using commercially available methods, is partly due to standard preparations used in calibration. The system relies on the use of the International Reference Preparation (IRP) international standard (IS) 80/505, of human pituitary origin, containing all GH isoforms. Recently, a 22K recombinant GH isoform IRP IS 98/574 was commercialized. Our aim was to evaluate the influence of both calibrators on GH results. METHODS: GH concentration in 97 serum samples from children undergoing a growth hormone releasing hormone+arginine stimulation test was measured using Siemens IMMULITE electro-chemiluminescence method, calibrated with both IS 80/505 and IS 98/574 (GRH Growth hormone-Recombinant 98/574-kit). RESULTS: Comparison of our results obtained with the two sets of calibrators showed good correlation, although we found higher percentage variation (var%) than that stated by Siemens. The mean var% value was confirmed when all results were sub-divided into subgroups based on both high and low GH concentrations. CONCLUSIONS: Since the GH assay is influenced by a variety of binding proteins, isoforms and conversion factors, standardization of the assay is strongly required. In Italy, the Agenzia Italiana del Farmaco 39 note provides GH laboratory values which are useful for therapy. On the basis of our results, we therefore propose to adjourn these GH values in order to ensure better management of patients with GH-related disorders.

Determination of asymmetric dimethyl arginine in human serum by liquid chromatography-tandem mass spectrometry: clinical application in hypertensive subjects.

BACKGROUND: Asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase plays an important role in endothelial dysfunction processes. Recent studies have linked high ADMA levels with several pathological conditions. The interest as a marker of endothelial dysfunction has increased in the last few years. In this paper, a method for serum ADMA quantification by liquid chromatography tandem mass spectrometry has been described. To test the utility in a pathological condition ADMA levels in hypertensive subjects have been measured. METHODS: HPLC separation was performed by hydrophilic interaction chromatography using acetonitrile/water containing 0.1% formic acid and 20 mmol/L ammonium formate. Selected reaction monitoring was performed following the transitions m/z 203.1→46.4 for ADMA and 210.1→46.3 for the internal standard [2H7]ADMA. RESULTS: The method was linear up to 10 µmol/L, limit of detection and limit of quantification were 0.005 µmol/L and 0.01 µmol/L, respectively. Recovery was higher than 96%. Intra- and inter-assay imprecision were lower than 6%. The accuracy, expressed as bias %, was <2.5. ADMA in "healthy" subjects ranged from 0.343 to 0.608 µmol/L and resulted significantly lower than that measured in hypertensive subjects (p<0.001). CONCLUSIONS: The method developed is selective and sensitive, thus suitable not only for research purposes, but also for routinely work.

Cardiovascular risk factors in healthy women with previous small for gestational age infants.

AIM: To investigate whether healthy women with a previous pregnancy complicated by a small for gestational age (SGA) infant have normal endothelial function, carbohydrate and lipid metabolism, and normal inflammation parameters. MATERIAL AND METHODS: Brachial artery flow-mediated dilatation (FMD, endothelium-dependent) was measured in 16 subjects with previous SGA, and in 15 controls (CTR) with previous normal pregnancies. Lipid panel, glucose, insulin, tumor necrosis factor alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (s-ICAM), soluble vascular (s-VCAM-1) adhesion molecule-1 (s-VCAM-1), and androgens were also measured. RESULTS: FMD was reduced in women with previous SGA compared to controls (P < 0.0001). SGA women showed increased insulin resistance (P < 0.0001), s-ICAM-1 (P = 0.008), TNF-alpha (P = 0.02), testosterone (P = 0.03), and diastolic blood pressure (P = 0.01) than CTR. CONCLUSION: Endothelial dysfunction, reduced insulin sensitivity and subclinical inflammation are present in otherwise healthy women with previous SGA. These abnormalities show that the presence of a SGA infant in the obstetric history should be considered as a risk factor for cardiovascular disease later in life.